4	Catheterization laboratory events and hospital outcome with direct angioplasty for acute myocardial infarction To assess the safety of direct infarct angioplasty without antecedent thrombolytic therapy, catheterization laboratory and hospital events were assessed in consecutively treated patients with infarctions involving the left anterior descending (n = 100 patients), right (n = 100), and circumflex (n = 50) coronary arteries. The groups of patients were similar for age (left anterior descending coronary artery, 59 years; right coronary artery, 58 years; circumflex coronary artery, 62 years), patients with multivessel disease (left anterior descending coronary artery, 55%; right coronary artery, 55%; circumflex coronary artery, 64%), and patients with initial grade 0/1 antegrade flow (left anterior descending coronary artery, 79%; right coronary artery, 84%; circumflex coronary artery, 90%). Cardiogenic shock was present in eight patients with infarction of the left anterior descending coronary artery, four with infarction of the right coronary artery, and four with infarction of the circumflex coronary artery. Major catheterization laboratory events (cardioversion, cardiopulmonary resuscitation, dopamine or intra-aortic balloon pump support for hypotension, and urgent surgery) occurred in 10 patients with infarction of the left anterior descending coronary artery, eight with infarction of the right coronary artery, and four with infarction of the circumflex coronary artery (16 of 16 shock and six of 234 nonshock patients, p less than 0.001). There was one in-laboratory death (shock patient with infarction of the left anterior descending coronary artery). 
5	Renal abscess in children. Three cases of renal abscesses in children are described to illustrate the variable presenting features. An additional 23 pediatric cases, reported over the past ten years, were reviewed for clinical features and therapy. Fever, loin pain, and leukocytosis were common presenting features, but less than half of all abscesses were associated with either an abnormal urinalysis or a positive urine culture. The presenting features were sometimes confused with appendicitis, peritonitis, or a Wilms tumor. An organism was identified in 17 cases--Escherichia coli in 9 children and Staphylococcus aureus in 8 children. The majority of E. coli infections occurred in girls and the majority of S. aureus infections occurred in boys. Reflux was documented in 5 patients, and 2 children had a possible extrarenal source of infection. Antibiotics alone produced a cure in 10 children (38%), but 16 children (62%) required a surgical procedure. 
2	Hyperplastic polyps seen at sigmoidoscopy are markers for additional adenomas seen at colonoscopy. Asymptomatic individuals undergoing screening flexible sigmoidoscopy were prospectively studied. Polyps were found in 185 subjects. The endoscopist recorded an opinion on the polyps' histology based on endoscopic appearance. No polyps were removed at sigmoidoscopy. All subjects with rectosigmoid polyps then underwent colonoscopy and polypectomy. Of them, 99 subjects (54%) had at least one rectosigmoid adenoma, 69 (37%) had only hyperplastic polyps, and 17 (9%) had other findings. The endoscopists' opinion of the histopathology of polyps at sigmoidoscopy was correct for 61% of the lesions. Of subjects with adenomatous rectosigmoid polyps, 29% had additional adenomas at more proximal sites. Proximal adenomas were found in 28% of patients with hyperplastic rectosigmoid polyps. Patients with rectosigmoid hyperplastic polyps had the same risk for additional proximal adenomas as patients with rectosigmoid adenomatous polyps. 
5	Subclavian artery to innominate vein fistula after insertion of a hemodialysis catheter. Insertion of hemodialysis catheters for temporary use is now preferentially performed by percutaneous infraclavicular subclavian vein catheterization. This method involves passage of a stiff dilator and a peel-away sheath over a guide wire, and is usually carried out without fluoroscopy. For the most part this has proved to be a valuable and safe approach. However, a small incidence of major complications occurs, which needs to be emphasized. Sixteen cases of arteriovenous fistulas between the subclavian artery or its branches and the subclavian vein have been reported so far in the literature. To date only one case of subclavian artery to innominate vein fistula has been reported. We report the second case with this complication and suggest possible preventive measures. 
4	Effect of local inhibition of gamma-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of gamma-aminobutyric acid and on stress-induced tachycardia: a study using microdialysis. Previous studies involving local microinjection of drugs that interfere with gamma-aminobutyric acid (GABA)A receptor-mediated synaptic inhibition have led to the suggestion that endogenous GABA suppresses the activity of a sympatho-excitatory mechanism in the dorsomedial hypothalamus in rats. In this study, microdialysis was used to assess and to alter pharmacologically extracellular-levels of GABA within this region while simultaneously monitoring heart rate and blood pressure. In anesthetized rats, local microdialysis for 15 min with 2.5, 10 and 40 mM nipecotic acid, an inhibitor of GABA uptake, caused concentration-related increases in GABA and taurine in the extracellular space, but no significant change in heart rate or arterial pressure. Similar perfusion with 37.5, 75 and 150 mM KCl caused concentration-related increases in GABA as well as aspartate, glutamate, taurine, glycine and alanine. Only modest, variable increases in heart rate and no effect on arterial pressure were observed during the perfusions with high potassium. In conscious rats, unilateral microdialysis of the dorsomedial hypothalamus with 0.5 mM nipecotic acid for 2 to 2.5 hr before stress coupled with contralateral microinjection of muscimol (88 pmol/250 nl) 5 min before stress significantly reduced air stress-induced tachycardia; this reduction in tachycardia was associated with markedly elevated levels of GABA in dialysates collected from the dorsomedial hypothalamus. Neither treatment alone significantly influenced stress-induced increases in heart rate, although perfusion with nipecotic acid alone evoked similar elevations in extracellular GABA. These results suggest that extracellular levels of endogenous GABA in the dorsomedial hypothalamus may regulate the cardiovascular response to stress. 
1	Infection during chronic epidural catheterization: diagnosis and treatment. A potentially serious complication of long-term epidural catheterization in cancer patients is infection. The early signs of infection were studied in 350 patients in whom long-term epidural catheters were inserted. Three areas of the catheter track were found to be involved; exit site and superficial catheter track infection, and epidural space infection. The authors identified the early signs of infection in each area and the progress of the infection from the deep track to include the epidural space in four of these patients. All 19 patients who developed deep track or epidural infections were successfully treated with antibiotics and catheter removal. None of the patients required surgery for spinal cord decompression. Catheters were replaced in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. It was concluded that use of long-term epidural catheterization is associated with a definable epidural infection rate. The use of epidural opioid analgesia is an effective and safe means of obtaining pain relief for terminally ill patients when patients are monitored for possible infection and receive prompt treatment when the diagnosis is established. 
5	Mediastinal tracheostomy using a pectoralis major myocutaneous flap after resection of carcinoma of the esophagus involving the proximal part of the trachea. An operative procedure of mediastinal tracheostomy using a pectoralis major myocutaneous flap is presented. In this procedure, the terminal portion of the trachea penetrates through the center of a pectoralis major myocutaneous flap and the tracheal wall is completely wrapped with the muscular portion of the flap. Between 1981 and 1988, eight patients with carcinoma in the cervicothoracic segment of the esophagus underwent mediastinal tracheostomy after laryngoesophagectomy and extended resection of the proximal part of the trachea through sternal manubrectomy, because of invasion into the trachea. In five of eight patients, a pectoralis major myocutaneous flap was used to construct a tracheal stoma. A skin flap only, or both a skin flap and a muscle flap, was used in the other three. In four of eight patients, tracheal necrosis occurred, and rupture of the brachiocephalic artery occurred in one patient when the tracheal stoma had been constructed using both a skin flap and a muscle flap. However, neither skin breakdown nor bleeding from the major vessels occurred when using the myocutaneous flap. Therefore, it is concluded that the construction of the tracheal stoma using a pectoralis major myocutaneous flap is recommended for mediastinal tracheostomy after laryngoesophagectomy with extended resection of the proximal part of the trachea. 
5	Tumefactive fibroinflammatory lesion of the extremity. Report of a case and review of the literature. Tumefactive fibroinflammatory lesion is an idiopathic fibroinflammatory process of the head and neck region. Although benign histopathologically, it is invasive, destructive, and locally recurrent, leading to uncertainty regarding its proper management; as the disease is rare, determining optimal treatment is difficult, given the anecdotal nature of reports. We report the first case of a tumefactive fibroinflammatory lesion occurring outside the head and neck region. Our patient was treated with corticosteroids and had a favorable response, supporting this approach as initial treatment. Immunohistochemical studies performed on a pretreatment specimen were consistent with a secondary inflammatory component because no monoclonal nor aberrant phenotypes were detected. The tumefactive fibroinflammatory lesion appears to be indistinguishable from the other known idiopathic fibroinflammatory processes; patients presenting with any one of these should be evaluated for the others. 
3	Multiple representations contribute to body knowledge processing. Evidence from a case of autotopagnosia. Body schema disturbances were studied in a 62-yr-old woman with Alzheimer's disease. She was severely impaired in verbal and nonverbal tasks requiring her to localize body parts (on her own body, the examiner's body or a doll's body) even though she correctly named the same parts when pointed at by the examiner. Pointing responses were misdirected mainly to parts contiguous with the target area and, to a lesser extent, to functionally equivalent body parts. We also found that the patient was able to define body part names functionally but not spatially. In another series of tasks, and in contrast to the above results, performances were normal when small objects, attached to the patient's body, served as pointing targets. Furthermore, on subsequent testing she pointed correctly at the remembered position of these objects. The fact that the same point in 'body space' is localized correctly when it corresponds to an external object and erroneously when it corresponds to a body part contradicts the idea of the body schema as a unitary function. Learning the position of objects on the body surface requires access to some form of body-reference system on which this information can be mapped. We argue that such a system can be available in autotopagnosia and is independent from the visuospatial representations of the body structure that are postulated to be damaged or inaccessible in this syndrome. An integrated account of the present results and of those reported by other authors suggests that multiple levels of representation (e.g., sensorimotor, visuospatial, semantic) are involved in the organization of body knowledge. 
5	Increasing asthma prevalence in a rural New Zealand adolescent population: 1975-89. A survey of asthma symptoms and spirometry in 435 adolescent schoolchildren was undertaken in 1989 in a rural, largely Maori population. The survey questionnaires were identical to those used in a 1975 survey at the same school. The prevalence of reported asthma or wheeze significantly increased from 26.2% to 34.0%. This increase occurred in groups reporting asthma, and also those reporting wheeze unassociated with colds, but without a previous diagnosis of asthma. There was a tendency for a rise in reported wheeze in Europeans (24.3% to 27.4%) and a significant rise in Maoris (27.1% to 36.2%). The reclassification of other respiratory problems did not account for the increase. Data from this study provides evidence that there has been a rise in the prevalence of asthma in this New Zealand population over a time period of 14 years. 
5	Usefulness of the automatic implantable cardioverter defibrillator in improving survival of patients with severely depressed left ventricular function associated with coronary artery disease. Clinical outcome was analyzed among a group of 39 consecutive patients with coronary artery disease, left ventricular (LV) ejection fractions less than 30% and arrhythmias that required an automatic implantable cardioverter defibrillator (AICD) in an attempt to better define the role of the device in patients with severely depressed LV function. Twenty-nine (74%) were survivors of out-of-hospital cardiac arrest and 10 (26%) had ventricular tachycardia that was refractory to electrophysiologically guided antiarrhythmic therapy. The study group had the following demographic characteristics: 90% were men, mean age was 64 years (range 41 to 79) and mean LV ejection fraction was 21 +/- 4%. Concomitant pharmacotherapy included antiarrhythmic drugs 31 (79%), vasodilators in 22 (56%) and digoxin in 20 (51%). There was no statistical difference in baseline characteristics between survivors and nonsurvivors. Patients were followed for a mean of 24 months (range 2 to 72) from implantation. The difference between actuarial survival--77% at 1 year and 72% at 2 years--and projected survival without the AICD (patients who survive without appropriate device discharge)--30% at 1 year and 21% at 2 years--was significant (p less than 0.01 and less than 0.05 at 1 and 2 years, respectively). This study suggests that the AICD improves survival in patients with coronary artery disease despite severely depressed LV function. 
5	Stress-related mucosal damage: review of drug therapy. The increased awareness of stress-related mucosal damage (SRMD) that accompanied the widespread use of fiberoptic endoscopy and the increased incidence of SRMD that accompanied the advances in caring for critically ill patients resulted in the recognition that the majority of patients in the intensive care unit (ICU) setting wil develop mucosal damage. Complications of gastrointestinal hemorrhage in these patients may contribute significantly to their morbidity and mortality, and the consequences of this bleeding may be more severe than the underlying predisposing conditions. Because of the importance of gastric acid in the pathogenesis of SRMD, therapy has focused on reduction of the intraluminal acid concentration. Acid neutralization, while effective, is laborious and associated with side effects. H2-receptor antagonists have been used successfully in the prophylaxis and treatment of SRMD and offer the potential for an effective parenteral as well as oral agent. They obviate the need for frequent antacid administration and eliminate some of the troubles and side effects that accompany an intensive antacid regimen. Of the available H2-receptor antagonists, cimetidine has been the most thoroughly evaluated. It is equivalent to antacids in the prevention of overt bleeding and offers the advantage of dosing flexibility, ease of administration, and a remarkable safety profile. Cimetidine has also been shown to be effective when administered by intermittent bolus infusions given every 8, 6, or 4 h or by primed continuous infusion, which has proven to be the most successful method of controlling intragastric pH. 
2	A biphasic pattern of anti-pre-S responses in acute hepatitis B virus infection. The clinical relevance of the immune response to the translation products of the pre-S1 and pre-S2 regions of hepatitis B virus was examined by testing sequential serum samples from 17 patients with acute self-limited hepatitis B and from two patients in whom chronic liver disease developed. Anti-pre-S antibodies were determined by enzyme immunoassays based on the inhibition of binding of monoclonal antibodies to epitopes in the pre-S1 and pre-S2 sequence. In acute, self-limited infection, anti-pre-S antibodies appeared in a biphasic pattern. The early antibodies were detected at the time of clinical signs of acute disease when HBsAg and often HBeAg were present, but hepatitis B virus DNA was no longer detectable in serum. Anti-pre-S levels then fell, but subsequently reappeared as the late antibody during the recovery phase, after development of anti-HBe, but before anti-HBs. Anti-pre-S responses were detected in 15 of 17 patients who recovered (88.2%) and in both patients with acute hepatitis B virus infection evolving to chronic liver disease. Although the early antibodies to pre-S1 and pre-S2 proteins appeared at the time of decreasing levels of infectious virus in serum in cases of self-limited infection, these antibodies also were transiently or continuously present with high levels of serum hepatitis B virus DNA in patients in whom chronic hepatitis B infection developed. Thus the anti-pre-S response in acute hepatitis is not a prognostic marker for clinical resolution. 
5	A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. BACKGROUND. Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. METHODS. Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). RESULTS. After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. CONCLUSIONS. In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease. 
5	Pentostatin induces durable remissions in hairy cell leukemia. Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia. 
5	Cytologic features of poorly differentiated 'insular' carcinoma of the thyroid, as revealed by fine-needle aspiration biopsy. The authors report on the cytologic features of six cases of poorly differentiated "insular" carcinoma (IC) of the thyroid, a recently described variety of thyroid tumor intermediate between well-differentiated and anaplastic neoplasms. It is characterized by trabecular and/or alveolar growth patterns, merging with follicular areas, and by the absence of pleomorphism in the tumor cells. Fine-needle aspiration biopsy (FNAB) materials (both smears and cell-block preparations) from six patients were reviewed after the diagnosis of IC was confirmed on the surgical specimen. The following cytologic features were consistently found: high cellularity and necrotic background; low grade of atypia; trabeculae and/or clusters, possibly associated with microfollicles, of cells with poorly defined cytoplasm; and cytoplasmic vacuoles containing thyroglobulin. Nuclear inclusions and grooving of the nuclear surface were additional features. Preoperative diagnosis suggestive of IC might be of value for planning surgical treatment and subsequent therapy. 
1	Cutaneous manifestations of multiple myeloma. We report the cutaneous manifestations of multiple myeloma, using a retrospective review of 115 patients' records obtained from tumor registry files. Five patients were found to have biopsy-proved extramedullary plasmacytomas without extension from an underlying bony focus. Twelve patients had ecchymoses without thrombocytopenia; two of them had biopsy-proved amyloidosis. One patient presented with pyoderma gangrenosum and was subsequently diagnosed with multiple myeloma. The last patient initially presented with what clinically appeared to be leukocytoclastic vasculitis, and, in the course of a standard workup, he was diagnosed with multiple myeloma. These findings are discussed with regard to the current literature on the cutaneous manifestations of multiple myeloma. 
5	Steal-prone coronary anatomy and myocardial ischemia associated with four primary anesthetic agents in humans. To examine the relationship between myocardial ischemia in patients with steal-prone coronary anatomy and the administration of isoflurane anesthesia, we reviewed coronary angiograms of 955 patients who had participated in a randomized trial of the use of one of four primary anesthetics for coronary artery bypass operations. Steal-prone anatomy was found in 31.8% of patients who had received enflurane; 40.0%, halothane; 32.6%, isoflurane; and 31.7%, sufentanil. Detected by greater than or equal to 0.1 mV ST segment displacement, ischemia during anesthesia occurred in 290 (30.4%) of all patients with no difference in the incidence among the four primary anesthetics (27.5%-32.9%). Patients with steal-prone anatomy did not suffer more ischemia than patients who needed coronary artery bypass surgery but with other varieties of coronary anatomy. In patients with steal-prone coronary anatomy, the incidence of myocardial ischemia by primary anesthetic was 24.0% with enflurane, 34.4% with halothane, 32.1% with isoflurane, and 38.2% with sufentanil. Systolic blood pressure less than 90 mm Hg during anesthesia occurred in 416 (45.6%) patients and was twice as common during administration of volatile anesthetics than during that of sufentanil. Hypotension did not increase ischemia frequency in patients with steal-prone anatomy with use of any of the four primary anesthetics including isoflurane. Ischemia was temporally related to hypotension in only 9 patients (0.9%). In none of the 42 patients who had steal-prone anatomy and hypotension during isoflurane anesthesia was ischemia temporally related to hypotension. 
1	Ewing's sarcoma. Radiotherapy versus surgery for local control. Significant strides in the treatment of Ewing's sarcoma, the second most common bone tumor of childhood, have resulted in cure for approximately 50% of patients. Successful therapy requires systemic chemotherapy for the eradication of microscopic or overt metastatic disease and surgery or irradiation therapy for control of the primary lesion. The article debates the controversy over the extent to which surgical resection should play a role in the local management of this disease. 
3	Tethered cord syndrome from a choristoma of mullerian origin. Case report. The authors report a case of tethered cord syndrome due to a choristoma of mullerian origin located in the spinal cord at the lumbosacral junction. Two similar cases were found upon review of the literature. The embryology of this lesion is discussed. 
1	Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma. P-glycoprotein (Pgp) has emerged as the central mediator in classic multidrug resistance in model systems in vitro. High levels of Pgp also have been detected in many normal human tissues and tumors; and its role in clinical drug resistance is currently under investigation. Recently significant levels of Pgp were localized to gravid and secretory endometrium; and it was demonstrated that the combination of estrogen and progesterone is sufficient to induce high levels of both Pgp mRNA and Pgp in uterine secretory epithelium. These findings suggest that increased Pgp expression also may be present in hormone-responsive malignancies such as endometrial adenocarcinoma. To determine whether Pgp is expressed in endometrial adenocarcinoma, 36 endometrial adenocarcinomas (grade I [n = 17]; grade II [n = 6]; grade III [n = 13]) were investigated retrospectively by the avidin-biotin-complex immunohistochemical procedure using three murine monoclonal antibodies (MAb) MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Seventy-two percent of the tumors showed positive immunostaining with at least one MAb; 67% showed immunostaining with MAb C219, 50% with MAb C494, and 62% with MAb JSB-1. Forty-six percent of tumors were immunoreactive to two and 29% to all three antibodies. Membranous and Golgi/paranuclear type staining patterns were observed. Overall the intensity of immunostaining varied from one sample to another for a given tumor type, and considerable heterogeneity of expression was commonly seen within a given tumor. Strong to moderate immunoreactivity was seen in diffusely infiltrating, adenosquamous, and serous papillary carcinomas. In general, immunoreactivity to MAb C494 was weaker than MAb C219 or MAb JSB-1. Adenomatous and non-neoplastic endometrium adjacent to the tumors displayed strong membranous immunostaining with MAb JSB-1. Endometrial capillaries showed weak-to-moderate immunostaining to all three antibodies. It is concluded that Pgp is commonly expressed in endometrial adenocarcinoma and may be a significant factor responsible for their drug-resistant nature subject to modulation by progesterone. 
3	Acute phase reactants and risk of bacterial meningitis among febrile infants and children. STUDY OBJECTIVE: To test the hypothesis that quantitation of either C-reactive protein (CRP) or the total peripheral WBC count can improve clinical detection of underlying bacterial meningitis among young febrile children. DESIGN: Cross-sectional survey of selected symptoms of central nervous system infection, signs of meningeal irritation and/or elevated intracranial pressure, levels of CRP in serum, and total peripheral WBC counts among unselected pediatric patients undergoing lumbar punctures for evaluation of acute febrile illnesses. SETTING: Emergency department and acute care "walk-in" clinic of an urban, university-affiliated general hospital. PARTICIPANTS: 160 previously well, acutely febrile infants and children (median age, 6 months). RESULTS: The prevalence of bacterial meningitis was 6%. Sensitivity of symptoms was 1.00 and specificity was 0.17. Sensitivity of signs was 0.70 and specificity was 0.81. Of the acute phase reactants, sensitivity of a CRP level of more than 1.0 mg/dL was 0.80, while that of a total peripheral WBC count of more than 15,000/mm3 was 0.40. The presence of signs and/or a CRP level of more than 1.0 mg/dL correctly identified all children with bacterial meningitis (sensitivity, 1.00). The absence of signs and a CRP level of 1.0 mg/dL or less correctly identified 71 of 150 children without bacterial meningitis (specificity, 0.47). Of 125 children without meningeal signs, the combination of symptoms and a CRP level of more than 1.0 mg/dL correctly identified all three children with bacterial meningitis (sensitivity, 1.00). The absence of these symptoms and/or a CRP level of 1.0 mg/dL or less correctly identified 80 of 122 children without bacterial meningitis (specificity, 0.66). CONCLUSION: Quantitation of CRP but not the total peripheral WBC count can increase the sensitivity of physical examination findings and the specificity of symptoms for the diagnosis of bacterial meningitis. Measurement of CRP in serum is useful as an adjunct to history and physical examination for the detection of acute bacterial meningitis in the acutely febrile child. 
1	Follicular thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome We retrospectively analyzed the outcome of all patients who received their primary treatment for follicular thyroid cancer at the Mayo Clinic between 1946 and 1970. The diagnosis was confirmed by reexamination of preserved tissue specimens. The 57 female and 43 male patients (mean age, 53 years) underwent follow-up for a maximum of 32 years (mean, 17.4 years). All patients were treated surgically, and total removal of primary tumor was thought to have been accomplished in all but three. Only 2 of the 88 patients without distant metastatic lesions at the time of initial diagnosis underwent ablation of the thyroid remnant. At the conclusion of the study, 52 patients had died, thyroid cancer being the cause of death in 19. On the basis of univariate survival analysis, age more than 50 years, tumor size that exceeded 3.9 cm, higher tumor grade, presence of marked vascular invasion, adjacent tissue invasion, and distant metastatic involvement at the time of initial diagnosis were associated with increased cancer mortality. Multivariate analysis (by Cox proportional hazards model), however, identified only age greater than 50 years, marked vascular invasion, and metastatic disease at the time of diagnosis to be independent predictors of follicular thyroid cancer-related mortality. Patients with two or more of these predictors were classified as being high risk. These patients had 5- and 20-year survival rates of 47% and 8%, respectively; the corresponding survival data for the low-risk group were 99% at 5 years and 86% at 20 years. The identification of these risk groups may facilitate a more rational approach to treatment of follicular thyroid cancer. 
5	Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and surgery. A prospective, consecutive series of 307 patients with aneurysmal subarachnoid hemorrhage ranging from Grades 1 to V according to the classification of Hunt and Hess on admission were evaluated to determine the incidence of epilepsy 1 to 3 years (mean, 1.4 years) after aneurysmal subarachnoid hemorrhage (SAH) and surgery. Sixty-three patients had died and one patient was lost to follow-up. Twenty-nine patients developed epileptic seizures after the SAH and surgery. The mean time from the SAH to epileptic seizure varied from 0 days (day of the SAH) to 2 years (mean, 6.7 months). The seizures were classified as focal in 9 patients (31%) and as generalized in 20 patients (69%). All patients received anticonvulsant medication after more than one seizure. The risk factors for development of posthemorrhagic/postoperative epilepsy were, in order of importance: a history of hypertension; an infarct on late computed tomographic scan; and the duration of coma after the ictus. Of the 85 patients with histories of hypertension, 17 (20.0%) developed epilepsy. Only 12 (5.4%) of the 222 nonhypertensive patients developed epileptic seizures. The difference between the groups was significant (P = 0.0001). Computed tomographic scans were undertaken in 237 patients 1 to 3 years (mean, 1.4 years) after the SAH and surgery. Postoperative epilepsy was significantly associated with infarcts visualized on computed tomographic scan (P = 0.0005). 
3	Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group. We compared 211 consecutive patients who had acute ischemic hemispheric stroke and atrial fibrillation with 837 consecutive patients who had stroke without atrial fibrillation. The atrial fibrillation group included a higher frequency of women, older subjects, and those with a severe neurologic deficit, abnormal computed tomogram, and elevated heart rate. The 1-month case-fatality rate in the atrial fibrillation group was 27% while that in the group without atrial fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40% and 20%, respectively. The risk of death attributable to atrial fibrillation, adjusted for the effect of other prognostic factors, was significant at 1 month (relative risk = 1.55) and at 6 months (relative risk = 1.74). The causes of death were equally distributed in the two groups during both the acute and subacute phases. We conclude that atrial fibrillation is a negative prognostic factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism alone does not completely explain the increase in mortality for stroke patients with atrial fibrillation. Other associated pathogenetic mechanisms must also be taken into account. 
5	Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88. OBJECTIVES--To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN--Retrospective study of clinical case notes. SETTING--Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS--All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES--Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS--1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS--Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure. 
5	Acute urinary retention secondary to Herpes simplex meningitis. We report a case of acute urinary retention in a 24-year-old man with Herpes simplex meningitis without genital lesions. Since the differential diagnosis in young patients who present with acute urinary retention also includes multiple sclerosis, lumbosacral disk herniation, rheumatological disorders and drug intoxication, a thorough history and careful neurological examination are of paramount importance in distinguishing these syndromes. As part of a directed neurological evaluation prompt performance of lumbar puncture is indicated; a lymphocytic pleocytosis is suggestive of herpetic meningitis. Culture of Herpes simplex virus from the cerebrospinal fluid should be attempted. We recommend conservative management only, typically with intermittent catheterization, since bladder function usually normalizes within 10 to 14 days. 
5	Indications for computed tomography in children with blunt abdominal trauma. This investigation was undertaken to identify clinical variables, alone or in combination, that could be used to assign children to high- and low-risk categories for intra-abdominal injury following blunt trauma. Six hundred consecutive children who were examined with computed tomography (CT) following blunt trauma were enrolled. Complete data sets were available on 375 children. Stepwise logistic regression was used to identify predictor variables for the presence of abdominal injury. There were 174 children with abdominal injury detected by CT. Of these, 95 were classified as having significant injury. Indicators associated with significantly higher risk of abdominal injury included the following: more than three clinical indications given (odds likelihood ratio [OLR] = 4.60, 95% confidence interval [95% Cl] = 2.29, 9.21, p less than 0.001); gross hematuria (OLR = 5.80, 95% Cl = 2.51, 13.4, p less than 0.001); lap belt injury (OLR = 12.2, 95% Cl = 2.22, 66.8, p less than 0.01); assault or abuse as the mechanism of injury (OLR = 5.08, 95% Cl = 1.07, 24.2, p less than 0.05); abdominal tenderness (OLR = 2.73, 95% Cl = 1.296, 5.82, p less than 0.01); and Trauma Score less than or equal to 12 (OLR = 2.27, 95% Cl = 1.006, 5.13, p less than 0.01). No child with asymptomatic hematuria (n = 56), regardless of grade or neurologic impairment in the absence of abdominal findings (n = 15), had an abnormal CT examination. These data are useful as an adjunct to clinical judgment in triage when the availability of CT equipment is limited or there are competing extra-abdominal injuries. 
3	Lexical organization of nouns and verbs in the brain. The analysis of neuropsychological disorders of lexical processing has provided important clues about the general organization of the lexical system and the internal structure of the processing components. Reports of patients with selective dysfunction of specific semantic categories such as abstract versus concrete words, living things versus inanimate objects, animals, fruits and vegetables, proper names and so forth, support the hypothesis that the neural organization of the semantic processing component is organized in these categories. There are reports of selective dysfunction of the grammatical categories noun and verb, suggesting that a dimension of lexical organization is the grammatical class of words. But the results reported in these studies have not provided unambiguous evidence concerning two fundamental questions about the nature and the locus of this organization within the lexical system. Is the noun-verb distinction represented in the semantic or in the phonological and orthographic lexicons? Is grammatical-class knowledge represented independently of lexical forms or is it represented separately and redundantly within each modality-specific lexicon? Here we report the performance of two brain-damaged subjects with modality-specific deficits restricted principally (H.W.) or virtually only (S.J.D) to verbs in oral and written production, respectively. The contrasting performance suggests that grammatical-class distinctions are redundantly represented in the phonological and orthographic output lexical components. 
5	Vitamin B6 in the treatment of the premenstrual syndrome--a review [published erratum appears in Br J Obstet Gynaecol 1991 Mar;98(3):329-30] A search of the literature yielded 12 controlled trials on vitamin B6 in the treatment of the premenstrual syndrome. These are discussed with emphasis on methodological aspects. A major drawback of the trials is the limited number of patients included. The existing evidence of positive effects of vitamin B6 is weak, and some well-designed trials with positive results would be needed to change this view. 
3	Ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities. A total of 111 amniotic fluid samples, clear or blood stained, with elevated levels of alpha-fetoprotein and acetylcholinesterase was analysed by immunoassays specific for acetylcholinesterase and butyrylcholinesterase and the acetylcholinesterase/butyrylcholinesterase-ratios determined. Samples from 40 pregnancies associated with anencephaly, 47 pregnancies associated with open spina bifida or encephalocele and six pregnancies with fetal intrauterine death or miscarriage all had ratios of greater than 0.14. All 11 pregnancies with fetal ventral wall defects had ratios less than 0.14 as had four pregnancies with normal outcome and elevated levels of alpha-fetoprotein and acetylcholinesterase. Three fetuses with both open spina bifida and ventral wall defects were associated with ratios above 0.14. These results suggest that immunochemical determination of acetylcholinesterase and butyrylcholinesterase can be used to distinguish pregnancies complicated by anencephaly, open spina bifida, encephalocele and miscarriage from those with ventral wall defects and samples with false positive elevated levels of alpha-fetoprotein and acetylcholinesterase. The procedure is accurate and simple to carry out and well suited to routine use in a clinical chemistry laboratory. 
5	Colonic motor activity in acute colitis in conscious dogs. The changes in motor activity of the colon during acute colitis were investigated in six conscious dogs. The motor activity was recorded with seven strain-gauge transducers. Colitis was induced in the entire colon by luminal perfusion of acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. The mucosa was diffusely erythematous and friable and there were scattered ulcerations over the mucosal surface. The motor activity of the colon changed in several ways during colitis: (a) the total duration per hour and the mean duration of contractile states decreased significantly; (b) the cycle length of colonic migrating motor complexes was significantly prolonged, and the nonmigrating motor complexes were almost completely absent; and (d) the incidence of giant migrating contractions increased significantly. About half of the giant migrating contractions were followed by defecation. The remaining expelled mucus or gas. Sometimes, a migrating motor complex in the colon was also followed by defecation; this was never observed in the normal state. The motor activity of the colon was still decreased and the cycle length prolonged 21 days after induction of colitis. However, the dogs were asymptomatic at this time and the mucosa looked normal at colonoscopy. The incidence of giant migrating contractions was also normal at this time. It was concluded that the dog is a good model for the study of colitis because of the similarity of symptoms with human ulcerative colitis. The phasic contractions of the colon decreases during colitis but the incidence of giant migrating contractions is increased. The diarrhea in colitis may primarily be due to the large number of giant migrating contractions in the middle and the distal colon. 
1	Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. In a prospective study of 148 consecutive breast adenocarcinomas, proliferative indices of the same surgical tumor sample were performed by immunohistologic staining (Ki67 index) with the use of the Ki67 monoclonal antibody, which binds to a nuclear antigen only expressed in cycling cells, and by flow cytometry-derived S-phase fraction (SPF). Measurable Ki67 and SPF indices were obtained in 142 cases and 99 cases, respectively, and in 96 cases by both methods. In aneuploid tumors, a significant but low (P less than 0.05, r = 0.3) relationship was observed between Ki67 index and SPF. When compared with clinical, pathologic, and biochemical parameters these two proliferative indices were shown to be associated with nuclear grading and mitotic index. Additionally, correlations were observed between Ki67 index and node involvement (P less than 0.02) and between SPF and estrogen receptors (P = 0.002). These results show that (1) proliferative indices are obtained in 96% of surgical samples with Ki67 versus 67% with SPF and that (2) Ki67 index and SPF may provide complementary data with respect to prognosis. 
5	Effects of menstrual phase and amenorrhea on exercise performance in runners. There are few well controlled studies in terms of subject selection, menstrual classification, and exercise protocol that have examined both maximal and submaximal exercise responses during different phases of the menstrual cycle in eumenorrheic runners and compared these runners to amenorrheic runners. Thus, the purpose of this study was to measure selected physiological and metabolic responses to maximal and submaximal exercise during two phases of the menstrual cycle in eumenorrheic runners and amenorrheic runners. Eight eumenorrheic runners (29.0 +/- 4.2 yr) and eight amenorrheic runners (24.5 +/- 5.7 yr) matched for physical, gynecological, and training characteristics were studied. The eumenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run during both the early follicular (days 2-4) and midluteal (6-8 d from LH surge) phases. The amenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run. Cycle phases were documented by urinary luteinizing hormone and progesterone assays and by plasma estradiol and progesterone assays. No differences were observed in oxygen uptake, minute ventilation, heart rate, respiratory exchange ratio, rating of perceived exertion, time to fatigue (maximal), and plasma lactate (following the maximal and submaximal exercise tests) between the follicular and luteal phases in the eumenorrheic runners and the amenorrheic runners. We conclude that neither menstrual phase (follicular vs luteal) nor menstrual status (eumenorrheic vs amenorrheic) alters or limits exercise performance in female athletes. 
4	Radiographic manifestations of anomalies of the lung. Congenital nonvascular anomalies of the lung can be subdivided into those affecting the bronchial tree and those affecting parenchymal abnormalities. Embryologic development of the lung is briefly reviewed to facilitate an understanding of developmental pulmonary anomalies. Clinical, radiographic, and therapeutic aspects of these anomalies are discussed. 
3	Clarifying confusion: the confusion assessment method. A new method for detection of delirium OBJECTIVE: To develop and validate a new standardized confusion assessment method (CAM) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk settings. DESIGN: Prospective validation study. SETTING: Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University (site 1) and in general medicine wards at the University of Chicago (site 2). PATIENTS: The study included 56 subjects, ranging in age from 65 to 98 years. At site 1, 10 patients with and 20 without delirium participated; at site 2, 16 patients with and 10 without delirium participated. MEASUREMENTS AND MAIN RESULTS: An expert panel developed the CAM through a consensus building process. The CAM instrument, which can be completed in less than 5 minutes, consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). An a priori hypothesis was established for the diagnostic value of four criteria: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion. At both sites, the diagnoses made by the CAM were concurrently validated against the diagnoses made by psychiatrists. At sites 1 and 2 values for sensitivity were 100% and 94%, respectively; values for specificity were 95% and 90%; values for positive predictive accuracy were 91% and 94%; and values for negative predictive accuracy were 100% and 90%. The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium. The CAM was shown to have convergent agreement with four other mental status tests, including the Mini-Mental State Examination. The interobserver reliability of the CAM was high (kappa = 0.81 - 1.0). CONCLUSIONS: The CAM is sensitive, specific, reliable, and easy to use for identification of delirium. 
1	The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10. Two new morphs (F and G) detected by the centromeric alpha satellite probe p alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong linkage disequilibrium with each other but were in weak linkage disequilibrium with the A and B morphs defined in PstI digests. Data for haplotypes formed by using the A and F morphs improved the lod score for linkage between the disease locus for multiple endocrine neoplasia type 2A (MEN2A) and D10Z1 (Z = 14.06 at theta = 0) in the six large families studied by Wu et al. Furthermore, the locus that codes for a distinct phenotype, medullary thyroid carcinoma (MTC) with parathyroid tumors (PTs) and no pheochromocytomas (PHEOs) (referred to as MTC with PTs), in one of the families was closely linked to two markers, D10Z1 and RBP3, with lodscores of 2.86 and 3.54, respectively, at theta = 0. A possible allelic association was noted between disease phenotypes and centromeric haplotypes. The phenotype MTC and PHEOs with and without PTs was associated with the same relatively common centromeric haplotype (A + B-F-G-) in the four families in which all four morphs could be determined, while the phenotype MTC with PTs was associated with the rare centromeric haplotype (A-B-F-G+) in one family. 
4	The Mansfield Scientific Aortic Valvuloplasty Registry: overview of acute hemodynamic results and procedural complications. Between December 1, 1986 and October 30, 1987, balloon aortic valvuloplasty was performed in 492 patients with aortic stenosis (mean age 79 +/- 8.4 years) enrolled in the Mansfield Scientific Aortic Valvuloplasty Registry. All procedures were performed from a femoral approach (92%), brachial approach (6%) or transseptal approach (2%) and utilized either a single balloon technique (72%) or a double balloon technique (28%). Valvuloplasty resulted in a significant improvement in aortic valve area (0.50 +/- 0.18 cm2 to 0.82 +/- 0.30 cm2), mean aortic valve gradient (60 +/- 23 mm Hg to 30 +/- 13 mm Hg) and cardiac output (3.86 +/- 1.26 to 4.05 +/- 1.31 liters/min). Serial aortography demonstrated a moderate or severe increase in aortic insufficiency in only 2.1% of patients. Statistical analysis of the procedural factors affecting acute valvuloplasty results demonstrated significant correlations of single versus double balloon technique, total number of balloon inflations and total number of balloon exchanges with respect to the absolute change in mean aortic valve gradient occurring during the valvuloplasty procedure. In addition, there was a significant correlation between the maximal time of valvuloplasty balloon inflation with aortic valve area measured after valvuloplasty, and there were significant correlations of the total number of balloon inflations and total number of balloon exchanges with the aortic valve mean gradient measured after valvuloplasty. The overall complication rate for the procedure was 20.5%, including vascular injury in 11%, embolic phenomenon in 2.2%, ventricular perforation resulting in tamponade in 1.8%, massive aortic insufficiency in 1%, nonfatal arrhythmia in 0.8% and myocardial infarction in 0.2%. 
3	Meralgia paresthetica after coronary bypass surgery. Meralgia paresthetica is a neurologic disorder characterized by localized paresthesia and numbness on the anterolateral aspect of the thigh and involving the lateral femoral cutaneous nerve. It involves no motor deficits. Meralgia paresthetica, which may result from a variety of causes, has been observed as a rare complication in heart operations. Its cause when associated with such operations is uncertain but may be prolonged relaxed positioning on the operating table and recovery room stretcher. Another possible cause of meralgia paresthetica after heart operations is the "frog-leg" position of the legs during vein harvesting. Patients with this condition should be advised of its untreatable, but benign and self-limiting, nature. 
1	Modified anterior compartment resection. In the majority of patients with soft tissue sarcomas of the anterior compartment of the thigh, it is possible to preserve a small portion of the quadriceps with intact nerve supply without compromising on the radicality of the procedure or the local control rate. The distal one-third of the vastus medialis can usually be spared with a long, slender branch providing its innervation. Dissection of the femoral nerve below the inguinal ligament and its branch(es) to an uninvolved area of the quadricepts the farthest from the location of the tumor is essential. This modified anterior compartment resection improves dramatically the function of the extremity. 
1	Pheochromocytoma in the pediatric age group: the prostate--an unusual location. Pheochromocytomas of the prostate are rare, with only 3 cases in adults reported in the literature. We present the case of an 8-year-old boy with a pheochromocytoma of the prostate and a second tumor in the region of the left internal iliac artery. 
1	Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas. Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation. 
5	Neonatal repair of tetralogy of Fallot with and without pulmonary atresia. Our experience with the arterial switch operation for transposition of the great arteries has confirmed the attainability of excellent results with elective neonatal surgery. Up to this time, we have repaired tetralogy of Fallot during the neonatal period only when symptoms, either severe persistent cyanosis or cyanotic spells, have been present. This review assesses the results of such nonelective neonatal correction of tetralogy between 1973 and 1988. Twenty-seven neonates with either symptomatic tetralogy of Fallot or symptomatic tetralogy of Fallot with valvar pulmonary atresia underwent repair. Mean age at repair was 8 +/- 8.4 days and mean weight was 3.0 +/- 0.7 kg. Unsatisfactory palliative shunts had previously been placed elsewhere in four patients. Twenty-five transannular patches and two conduits were used for reconstruction of the right ventricular outflow tract. There were five deaths in the hospital, three of which were due to avoidable technical problems. All deaths occurred in patients with pulmonary artery (Nakata) index less than 150 mm2/m2. One premature child weighing 2.3 kg displayed an absent pulmonary valve-like syndrome after repair and died late of respiratory complications caused by aneurysmal branch pulmonary arteries. Actuarial survival at 5 years was 74%. There was a single rapidly declining hazard phase for death, with the hazard approaching zero at 1 1/2 years after repair. Actuarial freedom from need for reoperation was 76% at 5 years. Postoperative catheterization of 15 long-term survivors showed right ventricular pressure less than 70% systemic in 13 cases. All patients are symptomatically well and functioning in sinus rhythm 1 to 15 years after repair (mean, 5 +/- 4 years). This experience with neonates with symptoms suggests that, if mortality is lower in the absence of symptoms, elective repair of tetralogy of Fallot could be reasonably undertaken during the first months of life. 
4	Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. To precisely define the incidence, type and consequences of cardiac arrhythmias early after heart transplantation, 25 cardiac transplant recipients were monitored continuously for 728 days from the day of surgery to discharge or death. A subset of 15 patients had sinus node function studies with overdrive suppression performed weekly at the time of endomyocardial biopsy. Results revealed sinus bradycardia in 10 patients (40%) and junctional bradycardia in 6 (24%). Supraventricular tachycardia in the form of atrial tachycardia, atrial fibrillation and atrial flutter occurred in 11 patients (44%). Ventricular tachycardia occurred in 15 patients (60%) and was nonsustained in all. Cardiac pacing for 1,403 h was used in nine patients with a pulse rate less than 50 beats/min; seven recovered and permanent pacing was instituted in two. In the subgroup that had sinus node function studies, seven patients were identified with clinical bradyarrhythmia; each had abnormal sinus node recovery time (greater than 1,400 ms) and abnormal corrected sinus node recovery time (greater than 525 ms) in at least one study. These seven patients also had a significantly prolonged ischemic time (236 +/- 26 versus 159 +/- 68 min, p less than 0.01). In conclusion, cardiac arrhythmias, particularly ventricular tachycardia and bradyarrhythmia, occur more commonly early after orthotopic heart transplantation than has previously been reported. Sinus node dysfunction due to prolonged organ ischemic time, antiarrhythmic drug use or surgical trauma, alone or in combination, may contribute to these arrhythmias. 
2	Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: support for the intact-hepatocyte theory. Hepatic drug metabolism is decreased in patients with severe liver disease, but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity. In this study we quantitated in needle-biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease (n = 36), chronic active hepatitis (n = 16) and cirrhosis (n = 15) to metabolize two model compounds in vitro. Hydroxylation of the low-extraction drug bufuralol resulted in the formation of 251 +/- 25 nmol 1'OH-bufuralol/gm wet wt/hr in mildly diseased liver tissue and was significantly (p less than 0.01) reduced in liver tissue exhibiting chronic active hepatitis (166 +/- 23 nmol/gm wet wt/hr) and cirrhosis (124 +/- 21 nmol/gm wet wt/hr). The formation rates of monoethylglycinexylidide, the main metabolite of the high-extraction drug lidocaine, varied widely and were not significantly different among the three groups. To relate the drug-metabolizing capacity to the hepatocyte content of liver tissue, morphometrical study was performed in the biopsy pieces originally submitted. The metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain. In mildly diseased liver tissue 355 +/- 35 nmol 1'OH-bufuralol/ml hepatocytes x hr or 12.4 +/- 1.0 mumol monoethylglycinexylidide/ml hepatocytes x hr- and in cirrhotic liver tissue 306 +/- 49 nmol 1'OH-bufuralol/ml hepatocytes x hr or 15.3 +/- 3.0 mumol monoethylglycinexylidide/ml hepatocytes x hr--were formed, respectively, and these differences were not significant. 
5	Carotid artery resection and replacement in patients with head and neck malignant tumors. Tumor involvement of the carotid artery with head and neck cancers may be present either simultaneously with the primary lesion or more often appears at a later date following resection of the primary tumor. Management of the secondary tumor consists of its resection together with the involved carotid artery with or without carotid artery reconstruction. The Authors are convinced that the best chance for cure of patients with advanced head and neck squamous cell cancers involving the carotid artery is radical extirpation with ablative surgery in the form of en block resection of the primary lesion, the secondary tumor, and the involved carotid artery followed by immediate revascularization. This bold approach was carried out in two male patients, 48 and 61 years of age, followed by chemotherapy and radiation therapy in one and radiation therapy alone in the other, with excellent results. Dermal grafts were placed over the entire length of the arterialized veins to protect them from radiation injury. Based on this limited experience and excellent results, we recommend this one-stage surgical ablative procedure in well selected patients. However, cooperation between the ENT and vascular surgeons, strict adherence to the principles and techniques of vascular surgery, and coverage of the arterialized vein with a dermal graft is absolutely essential. 
5	The treatment of chondrodermatitis nodularis with cartilage removal alone. Fifty-eight patients with chondrodermatitis nodularis on the antihelix in 24 ears (16 women and eight men) and the helix in 40 ears (six women and 34 men) were studied. Twelve ears responded to intralesional steroid therapy. Under local anesthetic, 46 operations were performed to remove cartilage without skin excision. On the helix, a longitudinal incision was made; on the antihelix, a flap was raised and the underlying cartilage was excised, taking care to leave no rough cartilage edges. Follow-up (mean, 16 months; range, 4.5 to 34 months) showed that 10 of 17 antihelix lesions and 24 of 29 helix lesions healed completely with excellent cosmetic results. Recurrences, requiring further treatment, occurred at cartilage-excision margins in seven ears, and further cartilage excision alone was successful in four ears. This study demonstrates that only cartilage needs to be removed in the surgical treatment of chondrodermatitis nodularis. 
3	The influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral edema, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery. Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group. The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window. The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach. Five hours after circulation was reestablished in the middle cerebral artery, Evans blue dye was injected intravenously: 30 minutes later, the animal was killed. Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment. Induced hypertension was produced by administration of dopamine during the occlusion. Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and infarction were evaluated from histological findings. They were most prominent in the control group: the extent of hemisphere affected was as follows (mean +/- standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction, 35.5 +/- 9.6%. On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in the former; 17.0 +/- 6.2 in the latter). 
1	Heffalumps, jagulars, and cheshire cats. A commentary on cytokeratins and soft tissue sarcomas. Historically, antibodies to cytokeratin intermediate filaments have been models of target specificity. In most diagnostic settings, the utility of these antibodies was unquestioned; reactivity for cytokeratin was dogmatically equated with epithelial differentiation. Recently, however, the diagnostic importance of these antibodies has been challenged, prompted by the demonstration of cytokeratin reactivity in a variety of "nonepithelial" neoplasms. In this review, the evolving literature on this topic is explored, and the practical implications of these findings are discussed. 
3	The distribution of muscle weakness in upper motoneuron lesions affecting the lower limb. To determine the distribution of weakness in the lower limb after upper motoneuron lesions the strength of 8 muscle groups was measured. Four groups of patients were studied: 22 control subjects, 16 patients with unilateral leg paresis, 4 patients with severe unilateral paralysis and 5 patients with paraparesis. In the testing posture (seated), patients with cerebral upper motoneuron lesions showed no selective loss of power in flexors or extensors on the contralateral side. Gravitational torques were included in the measurements. However, proximal muscles (acting at hip and knee) were significantly less severely affected than more distal muscles (acting at ankle and hallux). At any particular joint, physiological flexors and extensors were affected equally in both the hemiparetic and paraparetic subjects. As in the upper limb (Colebatch and Gandevia, 1989), the strength of muscles on the clinically unaffected side was reduced compared with control subjects, although no muscle groups were especially affected. 
1	Role of percutaneous fine-needle aspiration biopsy in suspected intrathoracic malignancy. Percutaneous fine-needle aspiration (PFNA) biopsy is an accepted technique for the diagnosis of suspected intrathoracic malignancy, but the appropriate indications for its use have not been clearly defined. To help establish guidelines, we performed a retrospective analysis of 188 patients who underwent PFNA biopsy for suspected intrathoracic malignancy. Biopsy led to a diagnosis in 72% (135/188) of the patients, but in 27% (50/188) samples were inadequate for cytological diagnosis, and in 2% (3/188) samples were adequate but failed to yield a diagnosis. Fifty-three patients underwent surgical intervention, thus allowing histological confirmation of the cytological diagnosis. In patients with a diagnosis from PFNA biopsy, operation confirmed malignancy in 97% (37/38) and a specific cell type in 79% (30/38). In patients without a diagnosis after biopsy, a malignancy was found in 73% (11/15) at the time of operation. This suggests a high rate of accuracy when PFNA biopsy provides a diagnosis. However, it also illustrates that a substantial percentage of PFNA biopsy attempts fail to yield a diagnosis in patients ultimately found to have malignancies. This implies that PFNA biopsy might best be reserved for patients who are not surgical candidates. 
5	Delayed brachial artery occlusion owing to a dog bite of the upper extremity. We report a case of delayed presentation of vascular injury from a superficial dog bite of the upper extremity in a five-year-old male. This example of a significant arterial injury, in the setting of seemingly minor trauma, is the first known report of blunt arterial trauma owing to a dog bite in any age group. Blunt arterial trauma in children is rare unless associated with fractures, dislocations, or massive crush injuries. Additionally, persistent pulses following arterial occlusion are rare and can potentially lead to misdiagnosis of a serious arterial injury. A brief review of pediatric blunt vascular injuries is presented with implications for diagnosis and management of such cases. 
5	Effect of amiodarone on erythrocyte shape and membrane properties. 1. Amiodarone is a potent anti-arrhythmic drug with lipophilic properties. The intercalation of such a drug into the membrane of erythrocytes may alter their shape and have an impact on the flow properties of blood. We therefore studied the influence of amiodarone on erythrocyte shape and deformability in vitro and in vivo. 2. Incubation in vitro with increasing amiodarone concentrations led to a progressive stomatocytic shape transformation and a decreased deformability of the erythrocytes. 3. Amiodarone treatment in eight patients did not affect erythrocyte morphology and deformability. However, an increase in the membrane cholesterol/phospholipid ratio was found. 4. The stomatocytic shape transformation of erythrocytes in vitro indicates that amiodarone intercalates in the inner hemileaflet of the lipid bilayer leading to membrane internalization. These results shed light on the interaction of amiodarone with biomembranes. 
5	Comparison of frequency of late potentials in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy with advanced congestive heart failure and their usefulness in predicting sudden death. Signal-averaged electrocardiograms were obtained in 62 consecutive patients with advanced congestive heart failure (CHF) undergoing evaluation for possible heart transplantation to determine if late potentials: (1) provide unique information compared to assessment of ventricular ectopic activity on ambulatory electrocardiogram, and (2) identify a subgroup of CHF patients with higher sudden death risk. Patients with a history of cardiac arrest or sustained ventricular tachycardia were excluded. CHF was due to old myocardial infarction in 40 patients and idiopathic dilated cardiomyopathy in 22 patients. Late potentials were present in 16 of 40 (40%) patients with old infarction but in only 3 of 22 (14%) patients with nonischemic CHF (p = 0.03). Twenty-four-hour ambulatory electrocardiograms were obtained in 34 patients (55%). Total ventricular ectopic activity and repetitive forms of ectopy were similar in patients with and without late potentials. Nine patients died suddenly, 9 had nonsudden death, 15 underwent heart transplantation and 29 were alive and well after a mean follow-up of 218 +/- 154 days. At 1 year, the actuarial risk of death was 37% and of sudden death was 20%. Sudden death risk was 12% in patients with late potentials versus 21% in those without (p = 0.73). Thus, the incidence of the arrhythmia substrate producing late potentials depends on the CHF etiology. The signal-averaged electrocardiogram and ambulatory electrocardiogram provide independent information for possible risk assessment in CHF. However, late potentials are poor predictors of sudden death risk when CHF is advanced, possibly due to the heterogeneity of causes of sudden death--ventricular tachycardia being only 1 of many possible mechanisms. 
5	Premature menopause because of an inherited deletion in the long arm of the X-chromosome. A family is described in which both a mother and an infertile daughter had premature menopause at the ages of 31 and 28 years, respectively. Initially, an extensive investigation revealed no apparent cause for their conditions. However, when cytogenetic analysis in the daughter was performed, a terminal deletion in the long arm of one of the X-chromosomes was found. The karyotype was: 46,Xdel(X),(q25-qter). Chromosomal investigation in the mother showed an identical deletion. The karyotype of the patient's 35-year-old sister is normal. She has a normal menstrual cycle and two normal children. The presence of such familial cases suggests that chromosomal investigation should be considered in young women with oligomenorrhea, especially those whose mothers have experienced a premature menopause. 
3	Shunt surgery for hydrocephalus in tuberculous meningitis: a long-term follow-up study. Hydrocephalus is a common complication of tuberculous meningitis. Case studies of 114 patients with tuberculous meningitis and hydrocephalus, who underwent shunt surgery between July, 1975, and June, 1986, were reviewed to evaluate the long-term outcome and to outline a management protocol for these patients based on the results. Seven factors were studied in each case: 1) age at admission; 2) grade on admission (I to IV, classified by the authors; Grade I being the best and Grade IV being the worst); 3) duration of alteration of sensorium; 4) cerebrospinal fluid (CSF) cell content at initial examination; 5) CSF protein levels at initial examination; 6) number of shunt revisions required; and 7) the necessity for bilateral shunts. During a long-term follow-up period ranging from 6 months to 13 years (mean 45.6 months), the mortality rate was 20% for patients in Grade I; 34.7% for patients in Grade II; 51.9% for patients in Grade III; and 100% for patients in Grade IV. Only the grade at the time of admission was found to be statistically significant in determining final outcome (p less than 0.001). Based on these results, the authors advocate early shunt surgery for Grade I and II patients. For patients in Grade III, surgery may be performed either if external ventricular drainage causes an improvement in sensorium or without selection. All patients in Grade IV should undergo external ventricular drainage and only those who show a significant change in their neurological status within 24 to 48 hours of drainage, should have shunt surgery. 
5	Genetic diagnosis of Lynch syndrome II in an extended colorectal cancer-prone family. Knowledge of colon cancer genetics, with particular attention to precision in hereditary cancer syndrome diagnosis, can often enable highly targeted surveillance and management strategies for patients at high genetic risk. Unfortunately, the patient's family history of cancer is often given minimal attention, and knowledge of hereditary cancer syndromes is frequently limited. Indeed, many physicians still consider familial adenomatous polyposis (FAP) as the only genetic risk factor for colorectal cancer. This concern with FAP was noted in a colorectal cancer-prone kindred which for decades had been thought to manifest that syndrome. However, after meticulous genetic, medical, and pathologic studies, the cardinal phenotypic characteristics of Lynch syndrome II were observed. The potential for cancer control in current and future generations of families like this one clearly mandates the need for computerized registries which could transmit current information about hereditary colon cancer syndrome diagnosis, surveillance, and management. 
4	Underestimation of treatment effect in crossover trials. In crossover trials each subject serves as his own control. For the study of cardiovascular diseases such as hypertension and angina pectoria, properly designed crossover studies are preferred to parallel studies. There is a considerable between-subject variability of symptoms in some of these conditions. Bias due to this is eliminated by the use of a crossover design. However, a problem is the so-called treatment-by-period interaction. The present study analyzes the potential influences of this on the outcome of the trial. Physical carryover effect, defined as a physical effect of the first treatment period carrying on into the second, tends to minimize differences between two consecutive treatment periods. So does the frustrating experience of an inactive agent in the first treatment period. Outside influences such as the change of the seasons may affect lengthy crossover trials in a similar way. The author concludes that the treatment effect in a crossover trial tends to be underestimated. The current concept that reports of clinical trials are generally biased toward an exaggeration of treatment effects does not seem to apply to crossover trials. 
3	AAEM case report #1: ulnar neuropathy at the elbow. A patient with bilateral cubital syndrome complicated by anomalous innervation is presented. The electrodiagnostic approach to patients with this neuropathy is reviewed emphasizing new developments. The interpretation of the findings in this patient centers around issues of pathophysiology and methodology. 
1	Intracranial tumor in infants: characteristics, management, and outcome of a contemporary series. Since 1980, 22 patients less than 2 years of age have been treated for intracranial tumors at our institution. The most common presentation was elevated intracranial pressure associated with ventriculomegaly (73%). The diagnosis was made by computed tomography or magnetic resonance imaging and confirmed surgically in every case. In 68% of cases, the tumor involved midline structures in the central nervous system. Tumors were infratentorial in 29% of patients less than 1 year of age and in 60% of those more than 1 year of age. Most tumors were either primitive neuroectodermal tumors (41%, 7 of 9 located in midline posterior fossa structures) or astrocytomas (27%, 5 of 6 located in the hypothalamus, chiasm, or optic nerve). Twenty patients had gross or subtotal tumor resection. Surgical mortality and neurological morbidity were 10% and 5%, respectively. Of 5 patients who underwent a second operation for tumor recurrence, 3 demonstrated a change in the pathological features of the tumor from those of the original diagnosis. Of 10 surgical survivors with malignant tumors, 8 received chemotherapy and 5 radiation therapy. Radiation was not administered before 1 year of age. The overall 1-year survival was 70%, and 2-year survival was 58%. Two-year survival for benign and malignant tumors was not significantly different. We think that the interdisciplinary efforts directed toward the treatment of these tumors has improved survival and that all children should be offered entry to a research protocol and aggressive treatment. 
3	Aspiration in bilateral stroke patients. Seventy patients with bilateral strokes underwent neurologic and videofluoroscopic barium swallowing examinations; 34 (48.6%) aspirated. Patients with aspiration were more likely to have posterior circulation strokes, abnormal cough, abnormal gag, and dysphonia. However, patients likely to aspirate can be identified best by the presence of an abnormal voluntary cough, an abnormal gag reflex, or both. The prediction of patients at risk for aspiration was not improved by additional clinical information (ie, presence of dysphonia or bilateral neurologic signs). 
3	Prognostic factors in the treatment of alopecia areata with diphenylcyclopropenone. One hundred thirty-nine patients with alopecia areata were treated with diphenylcyclopropenone. Before treatment, 85 patients had subtotal or total hair loss (greater than 90% bald area) and in the remaining patients scalp involvement was between 40% and 90%. The following three factors were found to be of prognostic significance: type of alopecia areata as documented before treatment, duration of the disease before therapy, and presence of nail changes. Other factors such as age at onset, sex, presence of atopic features, the extent of variation in the range of diphenylcyclopropenone concentrations during treatment, and sleep disturbances caused by pruritus did not influence the prognosis significantly. 
5	Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV. Ehlers-Danlos syndrome type IV (EDS IV) is an autosomal dominant condition characterized by extreme fragility of skin, blood vessels, intestine, gravid uterus, and lungs. The phenotype is accounted for by mutations affecting the integrity and/or synthesis of the precursor procollagen molecules of type III collagen. In this article, we report the elucidation of the molecular defect in an EDS IV patient whose type III collagen was previously found to be structurally abnormal. We utilized PCR in a two-step process involving first the localization of the mutation in the mRNA and then the characterization of the defect in the gene. The results established the patient's heterozygosity for a genomic deletion of about 7.5 kb which eliminates 1,026 nucleotides of coding sequences in the message. The mutation arose as a result of an exon-to-intron recombination. The deleted segment extends from the 13th nucleotide of exon 9 to within a DNA sequence of intron 24, which is composed of a series of dinucleotide repeats. Using PCR, we tested the polymorphic nature of this DNA element on several unrelated individuals. Analysis of amplified genomic products of 45 chromosomes recognized at least four distinct allelic forms that display frequencies ranging from 5% to 61%. Mendelian segregation of three of the four alleles was established by the same method in a 3-generation family. 
5	Cheilitis granulomatosa: report of six cases and review of the literature. Six cases of cheilitis granulomatosa, a rare inflammatory disorder of unknown origin, are reported. The condition produces nontender, persistent swelling of one or both lips and affects primarily young adults. Histologically, nonnecrotizing granulomatous inflammation is seen. The clinical findings and results of therapy in these six cases are presented. One patient was treated with hydroxychloroquine sulfate (Plaquenil) that stabilized the process. One of our patients had vesicular-appearing lesions. Microscopic examination showed the lesions to be dilated superficial lymphatic channels, a finding that to our knowledge has not been previously described. 
3	Stereotactic investigation of limbic epilepsy using a multimodal image analysis system. Technical note. A methodology has been developed for stereotactic investigation of limbic epilepsy using an image-analysis system that simultaneously displays different structural and functional images of the brain. The validity and accuracy of this system were established with phantom studies. Surgical planning and electrode implantation are guided by stereotactic magnetic resonance imaging, digital subtraction angiography, and position emission tomography. This methodology provides the spatiotemporal relationship of cerebral structure and function necessary to identify seizure onset and propagation in human limbic system epilepsy. 
5	Does indomethacin alter the hemodynamic response to magnesium sulfate infusion and hemorrhage in gravid ewes? The purpose of this study was to determine whether indomethacin alters the maternal and fetal hemodynamic response to magnesium sulfate (MgSO4) infusion and hemorrhage in gravid ewes. We studied seven chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) at time 0, indomethacin, 2 mg/kg, or vehicle only intravenously (IV) over 5 minutes; 2) at 60 minutes, MgSO4 4 g IV over 5 minutes; 3) at 65 minutes, MgSO4 infusion at 4 g/hour; 4) at 150 minutes, maternal hemorrhage, 20 mL/kg, over 60 minutes; and 5) at 215 minutes, reinfusion of maternal blood over 60 minutes. Each animal was studied with and without indomethacin. Indomethacin, but not vehicle only, transiently increased maternal and fetal mean arterial pressure (MAP), decreased maternal and fetal heart rate, and decreased maternal cardiac output. Magnesium sulfate significantly decreased uterine vascular resistance and increased uterine blood flow both with and without indomethacin. Hemorrhage significantly decreased maternal MAP, heart rate, cardiac output, and uterine blood flow in both groups. The magnitude of each change was similar between the groups. For example, at the end of hemorrhage, maternal MAP was 36 +/- 7% below baseline (P = .0001) with indomethacin and 41 +/- 2% below baseline (P = .0001) in the vehicle-only group (P = not significant between groups). Hemorrhage significantly decreased fetal heart rate, pH, and PO2, and increased fetal MAP and PCO2 in both groups. We conclude that indomethacin did not alter the maternal or fetal hemodynamic response to MgSO4 infusion and hemorrhage in gravid ewes. 
1	Intracerebral solitary plasmacytoma. We report a rare occurrence of intraparenchymal plasmacytoma and review the literature. The clonal nature of the neoplasm is demonstrated by immunohistochemical and molecular techniques. The importance of the latter techniques in ruling out other pathological entities is stressed. 
3	Excitatory amino acids in the developing brain: ontogeny, plasticity, and excitotoxicity. Besides their role as neurotransmitters, excitatory amino acids (EAAs) in the developing brain are crucially involved in plasticity and excitotoxicity which are modified by their distinct ontogeny. Along with incomplete neuritogenesis and synaptogenesis, presynaptic markers of the EAA system are immature in the developing brain; however, postsynaptic EAA system activities, particularly of the N-methyl-D-aspartate and quisqualate receptors, are transiently enhanced early in life. This transient enhancement is presumably beneficial to the immature brain because physiologic activation of the EAA system plays a critical role in plasticity of early learning and morphogenesis. At the same time, this transient hypersensitivity renders the immature brain vulnerable to pathologic excitation of the EAA system (excitotoxicity) as observed during neonatal hypoxia-ischemia. 
4	Alarm reaction and serum K+ in hypertensive patients. The effect of serum K+ of the alarm reaction induced by the participation to an experimental noninvasive study was evaluated in 35 subjects with borderline hypertension and in 18 essential hypertensives. A group of 44 inpatients undergoing routine blood sampling served as a control. Serum K+, blood pressure and heart rate were measured before (casual) and after (baseline) 20 min of rest in the recumbent position. Baseline serum K+ values were significantly higher than casual values in patients participating to the experimental protocol while no change was observed in inpatients undergoing routine blood sampling. The increase in serum K+ induced by relaxation was significantly related to heart rate decrease (r = 0.73). After relaxation 75% of patients had an increase in serum K+ with a change greater than 10% in about 35% of patients. In a subgroup of patients who repeated the same test three times, the alarm reaction was still evident and not reproducible within each patient. These data suggest that when potassium levels are measured in outpatients undergoing diagnostic or experimental procedures falsely reduced levels can be found in a large proportion of subjects. 
5	Acute myocardial infarction and chest pain syndromes after cocaine use. Seventy patients hospitalized with chest pain after cocaine use were retrospectively evaluated to define the risk and clinical course of acute myocardial infarction (AMI). AMI developed in 22 patients (31%) and transient myocardial ischemia was seen in an additional 9 patients (13%). Coronary risk factors did not distinguish those who developed AMI from those who did not. The presenting electrocardiogram was abnormal in 20 of 22 patients who evolved AMI and in 19 of 48 of those who did not. Creatine kinase levels were elevated in 75% of the patients, including 65% of those who did not develop AMI, but creatine kinase-MB elevations were only observed in the AMI group. The route of cocaine administration did not predict AMI and there was no predilection for a particular coronary vascular bed. The length of time between drug use and onset of AMI pain was often quite prolonged (median interval, 18 vs 1 hour in the non-AMI group). Eight of the patients with AMI underwent cardiac catheterization and 4 had significant coronary narrowing. 
4	A rheolytic system for percutaneous coronary and peripheral plaque removal. A method for plaque dissolution has been identified that percutaneously delivers a pulsatile high-velocity stream of saline to the site of an atheromatous lesion within a coronary or peripheral artery. In vitro evaluation and in vivo canine and porcine testing were performed using this 'rheolytic' system to determine its feasibility in ablating calcified plaque and soft thrombotic tissue. A prototype rheolytic guidewire capable of providing 30,000 psi of internal pressure was designed to fit within the guidewire lumen of a standard percutaneous transluminal coronary angioplasty catheter. An additional over-the-wire rheolytic catheter was fabricated to follow a standard .014-inch guidewire. The rheolytic devices were tested in vitro with simulated atheromatous and thrombotic lesions to evaluate the size and quantity of the particulate effluent. The particulate was then sterilized, mixed with saline, and introduced percutaneously into the animal kidney and heart for evaluation. The in vitro studies demonstrated that the rheolytic catheter and guidewire were able to follow both a coronary and femoral arterial model and successfully ablate the simulated lesions. The particle size for osseous, muscular, and cartilagenous tissue ranged from 2 to 6 micrometers; for fresh human plaque the particles ranged from 2 to 15 micrometers. Injection of cartilagenous and plaque particles into the animal model caused very slight regions of necrosis but no clinical sequelae. Applications of the rheolytic devices to the animal femoral artery demonstrated that both devices could ablate and cross calified or soft thrombosed lesions without damage to the vessel wall; the rheolytic catheter provided a debulking of the plaque. 
4	Epidemiology of heart failure. Analysis of 34 years of follow-up of Framingham Study data provides clinically relevant insights into the prevalence, incidence, secular trends, prognosis, and modifiable risk factors for the occurrence of heart failure in a general population sample. Heart failure was found to be highly prevalent, affecting about 1% of persons in their 50s and rising progressively with age to afflict 10% of persons in their 80s. The annual incidence also increased with age, from about 0.2% in persons 45 to 54 years, to 4.0% in men 85 to 94 years, with the incidence approximately doubling with each decade of age. Women lagged slightly behind men in incidence at all ages. Male predominance was because of a higher rate of coronary heart disease, which confers a fourfold increased risk of heart failure. Heart failure, once manifest, was highly lethal, with 37% of men and 33% of women dying within 2 years of diagnosis. The 6-year mortality rate was 82% for men and 67% for women, which corresponded to a death rate fourfold to eightfold greater than that of the general population of the same age. Sudden death was a common mode of exitus and accounted for 28% of the cardiovascular deaths in men and 14% in women with heart failure. Hypertension and coronary disease were the predominant causes for heart failure and accounted for more than 80% of all clinical events. Factors reflecting deteriorating cardiac function were associated with a substantial increase in risk of overt heart failure. These include low vital capacity, sinus tachycardia, and ECG evidence of left ventricular hypertrophy. 
3	Ubiquitin immunoreactivity in kuru plaques in Creutzfeldt-Jakob disease. Cerebellar kuru plaques in 2 cases of Creutzfeldt-Jakob disease were studied immunohistochemically. Similar to cerebellar senile plaques in Alzheimer's disease, many kuru plaques contained ubiquitin-positive, tau-negative small granular elements, presumably representing dystrophic neurites. Our results suggest that similar mechanisms are involved in neuritic changes in cerebellar plaques in Creutzfeldt-Jakob and Alzheimer's diseases despite differences of amyloid proteins in the plaques. 
1	Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix. The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3-year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases. 
1	Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results. 
2	Carcinoma of the gallbladder. Gallbladder cancer remains difficult to diagnose preoperatively. However, recent work suggests that ultrasound may be effective. Gallbladder cancer remains highly lethal despite aggressive therapy. Extension of the disease beyond the mucosa predicts a poor chance of long-term survival. 
4	Microscopic pulmonary tumor embolism causing subacute cor pulmonale: a difficult antemortem diagnosis [published erratum appears in Mayo Clin Proc 1991 Apr;66(4):439] Microscopic pulmonary tumor embolism is difficult to diagnose. The most common initial clinical symptom is subacute progressive dyspnea, and the initial laboratory evaluation typically shows hypoxemia in a patient with clear lung fields on a chest roentgenogram. Another distinguishing feature may be hepatic abnormalities. In general, pulmonary angiography discloses no evidence of emboli, but multiple subsegmental peripheral perfusion defects are noted on ventilation-perfusion lung scans. The diagnosis of microscopic pulmonary tumor embolism can be confirmed by open-lung or transbronchial lung biopsy or by microvascular pulmonary cytology, a less invasive procedure that could be performed at the time of pulmonary angiography. Herein we describe two patients with unsuspected microscopic pulmonary tumor embolism that eventuated in subacute cor pulmonale and death. These cases illustrate the characteristic findings of this entity and emphasize the need for early diagnosis. 
5	Obstructed total anomalous pulmonary venous return. Toward neutralization of a major risk factor. Among 57 neonates undergoing repair of total anomalous pulmonary venous return with severe pulmonary venous obstruction from 1980 through 1989, date of operation (1980 to 1984), preoperative hemodynamic instability, and failure to monitor pulmonary artery pressure postoperatively were risk factors for death. Thus, among the 30 patients having repair between 1985 and 1989, the 55-month survival rate including hospital deaths was 83%. 
4	The association between Type A behavior and change in coronary risk factors among young adults. The association of Type A/B behavior pattern and changes in blood pressure, total serum cholesterol, serum triglyceride, body mass, and smoking was estimated in a cohort of 375 young Black and White men and women from a rural county in Central Kentucky between 1978-79 and 1985-88. Type A participants experienced significant increases in systolic (2.90 +/- 1.29 mmHg) and diastolic (3.80 +/- 1.17 mmHg) blood pressure and in cigarette smoking (3.26 +/- 0.89 cigarettes per day) over the eight-year follow-up period, but Type B participants experienced no change. Type A and B individuals showed similar changes in total serum cholesterol, serum triglyceride, or body mass. Differences between behavioral types in blood pressure were present for women but not men, and for Blacks but not for Whites. These findings suggest a possible significance of the Type A pattern for the development of cardiovascular risk of young adults. 
5	Is liver transplantation justified for the treatment of hepatic malignancies? Twenty-eight patients received orthotopic liver transplants for malignant disease between February 1, 1984, and December 31, 1989. Preoperative diagnoses included hepatocellular carcinoma (n = 16), cholangiocarcinoma (n = 3), other primary hepatic tumors (n = 6), and metastatic diseases to the liver (n = 3). Overall actuarial survivals at 6 months, 1 year, and 5 years were 67.3%, 51%, and 31%, respectively. Long-term survival longer than 5 years was achieved in 3 patients. The recurrence rate in patients surviving longer than 3 months is 48% (median, 7 months). Hepatocellular carcinoma and cholangiocarcinoma had the poorest survival and highest recurrence rates. Specific prognostic factors correlating with survival or recurrence could not be elucidated. These results indicate that orthotopic liver transplants can provide long-term cure and palliation for malignant disease; however, patient selection is extremely important in predicting outcome. 
2	A chronic granulomatous syndrome of unknown origin. A small clinically distinct group of patients with widespread tissue granulomata are described. The principal presenting symptoms are malaise, fever, and weight loss, although a wide variety of complaints are documented. Pulmonary involvement is uncommon. The granulomata are noncaseating with a few multinucleate giant cells and some surrounding chronic inflammatory infiltrate. There is no evidence of an associated arteritis. The disease has a relapsing and remitting course and although it may require treatment with immunosuppressive drugs, particularly if the kidneys are involved, the prognosis is relatively good. We propose that this entity be called granulomatous syndrome of unknown origin. The characteristics that set this syndrome apart from the other granulomatous vasculitides are discussed. The current limited understanding of granuloma formation does not allow us to propose a definite etiology for this condition. It is emphasized that it is not helpful to encompass it within a label of sarcoidosis. First, it may only serve to confuse the doctor in assessing and treating this very particular group of patients. Secondly, it may hinder future attempts to understand the different pathogenetic mechanisms underlying the various conditions in which granulomata may arise. 
1	Removal of large symptomatic intrauterine growths by the hysteroscopic resectoscope. Fifty-three patients underwent 55 procedures with a resectoscope for the removal of large symptomatic intrauterine growths. The presenting complaint was menorrhagia, menometrorrhagia, or heavy postmenopausal bleeding in 38 patients; excessive menses plus infertility in 13 patients; and infertility alone in two patients. Forty-three patients had pedunculated or sessile submucous myomas and ten patients had large endometrial polyps. The long-term results are based on 45 patients followed for longer than 1 year. Excessive bleeding was controlled in 40 of the 43 women (93%). Failure to control abnormal bleeding was apparent within the first year. Seven of the 12 infertility patients (58%) delivered live-born infants. Five patients have undergone subsequent hysterectomies (9%). Two patients had repeat resectoscopic removal of myomas and two had subsequent non-resectoscope myomectomies. No major complications were encountered. 
3	Apneic oxygenation in apnea tests for brain death. A controlled trial. We performed a prospective controlled study of apneic oxygenation on 15 patients undergoing apnea tests for brain death. All patients were preoxygenated with 100% oxygen at existing respirator settings. During the 10-minute apnea tests, nine patients were given continuous apneic oxygenation by tracheal cannula. The other six patients had tracheal tubes open to room air. The patients given apneic oxygenation had little or no hypoxia by the end of the test. The patients given room air during the test became hypoxic. Many neurologists perform apnea tests with no oxygenation or with preoxygenation alone. This is the first prospective controlled study (to our knowledge) of apneic oxygenation; it shows that preoxygenation alone does not prevent hypoxia during apnea tests for brain death. We recommend that all apnea tests be performed with apneic oxygenation. 
1	Therapeutic dilemmas associated with antenatally detected ovarian cysts. Fifteen instances of ovarian cysts detected antenatally are reported. Seven cysts more than 5 centimeters in diameter were treated surgically because of clinical signs, such as palpable abdominal mass, vomiting and abdominal distension. Seven cysts less than 5 centimeters in diameter, and one cyst more than 5 centimeters in diameter began to regress spontaneously within six months after birth. Because the pathophysiologic nature of neonatal ovarian cysts has not been elucidated and because the borderline between physiologic and pathologic factors is still unclear, we propose a more conservative approach in the management of neonatal ovarian cysts to avoid unnecessary operations. 
2	Hyposensitivity to vasopressin in patients with hepatitis B-related cirrhosis during acute variceal hemorrhage. It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18 +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p greater than 0.05). 
5	Seismic communication in a blind subterranean mammal: a major somatosensory mechanism in adaptive evolution underground. Seismic communication, through low-frequency and patterned substrate-borne vibrations that are generated by head thumping, and which travel long distances underground, is important in the nonvisual communication of subterranean mole rats of the Spalax ehrenbergi superspecies (2n = 52, 54, 58, and 60) in Israel. This importance pertains both intraspecifically in adaptation and interspecifically in speciation. Neurophysiologic, behavioral, and anatomic findings in this study suggest that the mechanism of long-distance seismic communication is basically somatosensory and is independent of the auditory mechanism. Seismic communication thus appears to be a channel of communication important in the evolution of subterranean mammals that display major adaptation to life underground. 
5	Age effects susceptibility to pulmonary barotrauma in rabbits. OBJECTIVE: We studied the effect of age on the development of pulmonary barotrauma after mechanical ventilation with high peak inspiratory pressures (PIP). DESIGN: Young (4 to 6 wk old) and adult rabbits were ventilated for 1 hr at PIPs of 15, 30, and either 45 cm H2O (young group) or 55 cm H2O (adult group). MEASUREMENTS AND MAIN RESULTS: The pulmonary capillary filtration coefficient (Kf,c) was measured in an isolated lung perfusion system after the animals were killed. In young rabbits, Kf,c increased significantly from the 15 cm H2O PIP value in both the 30 cm H2O (55%) and 45 cm H2O (507%) PIP groups, whereas Kf,c was increased in adult rabbits only in the 55 cm H2O (113%) PIP group. Kf,c was significantly (p less than .01) higher in young rabbits than in adult rabbits after ventilation, with every level of PIP being 91% higher at 15 cm H2O PIP and 440% higher at 45 to 55 cm H2O PIP. Also, a greater incidence of pneumothorax and airleaks was observed in the young rabbits. Pressure-volume loops demonstrated that the young rabbits had more compliant lungs and chest wall than adult rabbits. CONCLUSIONS: These data indicate that the lungs of young rabbits had a higher baseline microvascular permeability and were more susceptible to the development of ventilator-induced increased microvascular permeability. More compliant lungs and chest wall and the larger distending volumes attained at each peak airway pressure appear to be the mechanisms. 
5	Pulmonary hypertension five years after left pneumonectomy for adenoid cystic carcinoma. We report the findings in a patient with shortness of breath due to pulmonary hypertension five years after left pneumonectomy. Mediastinal recurrence of an incompletely resected and slowly growing adenoid cystic carcinoma of the left main bronchus had encased the right main pulmonary artery. 
4	Effect of Bay U 3405, a new thromboxane antagonist, on collagen-induced thromboembolism in rabbits. Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2-induced contraction of smooth muscles, and coronary artery thrombosis. We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405. The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen. Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits. Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia. In the vehicle-treated group, 100% of the animals died. One of the most prominent parameters was the massive fall in blood pressure. All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect. Tracings of the electrocardiogram and heart rate were unchanged. Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases. 
1	Gastric duplication cyst communicating with the pancreatic duct: a rare cause of recurrent abdominal pain. A 41-year-old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct. Celiotomy demonstrated a noncontiguous gastric duplication cyst. Internal drainage was curative. 
5	Recurrent herpes gestationis with postpartum flare: a case report. A case of herpes gestationis recurring in each pregnancy, with a postpartum flare-up in the last pregnancy, is described. The diagnosis was confirmed by skin biopsy. The first pregnancy ended in a term stillbirth, but there were favorable outcomes in four subsequent pregnancies. Histopathologic examination of the placentas of the last three pregnancies revealed varying grades of villositis. Symptoms improved with oral corticosteroids. 
5	Clinical efficacy of oral-transdermal clonidine combinations during the perioperative period. In an attempt to maintain stable levels of an alpha 2-adrenergic agonist throughout the perioperative period, two different oral-transdermal clonidine dosage regimens were administered according to a randomized, double-blind, placebo-controlled study in patients undergoing abdominal surgery. We determined the clinical efficacy of a high- and a low-dose clonidine regimen on sedation, hemodynamic parameters, anesthesia, and analgesia. The low-dose clonidine group of patients (n = 14) received a 7-cm2 clonidine transdermal patch (Catapres-TTS #2), which was supplemented with oral doses of clonidine approximately 3 micrograms.kg-1 on the evening prior to surgery and on the morning of surgery. The high-dose clonidine group (n = 14) received a 10.5-cm2 clonidine transdermal patch (Catapres-TTS #3) with oral clonidine approximately 4.5 micrograms.kg-1 at bedtime and 6.0 micrograms.kg-1 on the morning of surgery. Placebo-treated (control) patients received the same occlusive patch without active ingredient and oral placebo tablets at bedtime and on the morning of surgery. Preanesthetic medication included midazolam 50 micrograms.kg-1 intramuscularly (im). Anesthesia was induced with alfentanil 30 micrograms.kg-1 intravenously (iv), thiopental 3 mg.kg-1 iv, and vecuronium 0.1 mg.kg-1 iv, and was maintained with 70% nitrous oxide in oxygen and a continuous infusion of alfentanil 0.5 microgram.kg-1.min-1. Isoflurane was added when the blood pressure exceeded 110% of the patient's prestudy value. For pain relief postoperatively, the patients received morphine, 1-2-mg iv boluses, via a patient-controlled analgesia pump. The low-dose clonidine patient group had mean plasma clonidine concentrations that varied from 1.47 ng.ml-1 (preoperative) to 1.32 ng.ml-1 (postoperative day 2). 
3	Richner-Hanhart's syndrome. Electron microscopic study of the skin lesion. The plantar hyperkeratotic skin lesion in a case of Richner-Hanhart's syndrome was investigated using ultrastructural examination. Light microscopic examination showed remarkable hyperkeratosis and some aberrant keratinocytes with multiple nuclei. On ultrastructural examination, some abnormal structures were seen in the affected keratinocytes: aggregations of tonofilaments and intracytoplasmic inclusions. The inclusions were needle shaped and were considered to be "crystal ghosts," presumably of tyrosine. The formation of tyrosine crystalline inclusions seems to be an important factor in the pathogenesis of the cutaneous lesions in Richner-Hanhart's syndrome. 
2	Frequency of recovery of Blastocystis hominis in clinical practice. We examined the frequency of isolation of Blastocystis hominis from stools of patients seen in an indigent-care teaching hospital. Over a 2-year period, 2,744 stool specimens were examined prospectively. B. hominis was found in 262 stools (9.5% of all stool specimens and 53.5% of the positive specimens). Clinical data were obtained from 80 patients with stools positive for B. hominis. B. hominis was the only parasite isolated in 39 of 47 (83%) of the adults, compared with 17 of 33 (52%) of the children (p = 0.006). All but 2 of 52 patients without concomitant parasitic infection or bacterial pathogens in stool had gastrointestinal symptoms (41 abdominal pain, 26 diarrhea, and 5 vomiting), but no association was seen with fever, peripheral leukocytosis, stool occult blood, fecal leukocytes, or endoscopic or radiologic evidence of colitis. Therefore, B. hominis was frequently recovered from stools examined in a hospital clinical parasitology laboratory. The clinical presentations of patients in our series did not suggest that B. hominis was invasive. Most patients with B. hominis probably do not require treatment since they will either have spontaneous resolution of symptoms or will be found to have an alternative explanation for their problem. 
4	Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. OBJECTIVE--To examine the association between the serum lipoprotein (a) concentration and subsequent coronary heart disease. DESIGN--Prospective case-control study based on a six year follow up of a general population sample of men aged 50 at baseline in 1983-4. Serum samples were frozen at the time of the baseline examination and kept at -70 degrees C for six years, after which the lipoprotein (a) concentrations in the samples were measured in cases and controls. SETTING--City of Gothenburg, Sweden. SUBJECTS--26 Men, from a general population sample of 776 men, who had sustained a myocardial infarction or died of coronary heart disease during the six years and 109 randomly selected controls from the same sample who had remained free of myocardial infarction. In neither cases nor controls was there a history of myocardial infarction at baseline. MAIN OUTCOME MEASURES--Proportion of myocardial infarction or deaths from coronary heart disease, or both, in relation to the serum lipoprotein (a) concentration. RESULTS--Men who suffered coronary heart disease had significantly higher serum lipoprotein (a) concentrations than controls (mean difference 105 mg/l; 95% confidence interval 18 to 192 mg/l). Men with the highest fifth of serum lipoprotein (a) concentrations (cut off point 365 mg/l) suffered a coronary heart disease rate which was more than twice that of men with the lowest four fifths of concentrations. Logistic regression analysis showed the serum lipoprotein (a) concentration to be significantly associated with coronary heart disease independently of other risk factors. CONCLUSION--The serum lipoprotein (a) concentration in middle aged men is an independent risk factor for subsequent myocardial infarction or death from coronary heart disease. 
1	Primary carcinoma of the upper urinary tract. Effect of primary and secondary therapy on survival. The pathologic material and medical records of 76 patients with primary upper urinary tract carcinomas were reviewed to identify the role of grade and stage in predicting survival; to determine any differences in survival between ureteral and renal pelvic carcinoma; to understand the role of local therapy in low grade, low stage tumors; and to establish the usefulness of adjuvant therapies in metastatic disease. Kaplan-Meier survival curves with Cox-Mantel analysis for statistical significance revealed both grade and stage to be excellent predictors of survival. No differences in survival were noted between renal pelvic and ureteral carcinomas for equivalent stage tumors. For low grade, low stage tumors, although there was an increased risk of local recurrence with local therapy, there were no differences in survival between patients treated with local therapy or radical surgery. Finally, cisplatin-based chemotherapy seemed to improve survival in patients with metastatic disease. 
5	Drop attacks with Meniere's syndrome. We report the clinical features of 12 patients with drop attacks associated with Meniere's syndrome. Each described a sensation of being pushed, thrown, or knocked to the ground or a sudden illusion of movement of the environment that led to a fall. These episodes were not accompanied by symptoms of their typical attacks of Meniere's syndrome. The drop attacks occurred early and late in the course of the disease; they were the initial manifestation in 1 patient. In the majority the episodes spontaneously remitted, although Meniere's syndrome continued to progress. These attacks probably result from a sudden mechanical deformation of the otolithic membrane of the utricle or saccule due to pressure gradients within the inner ear. They are important to recognize because their prognosis is relatively benign compared to other causes of drop attacks. 
1	The oncologic risks of skin preservation at mastectomy when combined with immediate reconstruction of the breast. Most oncologic surgeons agree that removal of the nipple, the areola and any recent scar at the site of the biopsy is necessary during a mastectomy for treatment of carcinoma of the breast. There is less agreement about what should be done with the remaining uninvolved mammary skin. Its preservation facilitates the performance of immediate reconstruction of the breast and can lead to improved aesthetic results, but many oncologists fear that this practice could lead to an increased incidence of local tumor recurrence. To determine if that fear was justified, 87 patients who had undergone unilateral or bilateral mastectomy with immediate reconstruction for treatment of early carcinoma of the breast were studied. Preservation of uninvolved skin was used in all instances. All patients had a documented follow-up study of 12 months or more; the average follow-up time was 23.1 months. One peripheral local recurrence was observed. This 1.2 per cent rate of early local recurrence is lower than that reported from several series using modified radical mastectomy without skin preservation or immediate reconstruction, and suggests that skin preservation does not confer additional risks of local recurrence of carcinoma of the breast in properly selected patients. 
3	Thrombocytosis after pneumonia with empyema and other bacterial infections in children. Thrombocytosis is seen in association with many conditions, including infectious diseases. We studied thrombocytosis after severe bacterial infections, particularly pneumonia with empyema in children. A systematic survey of the phenomenon was conducted. Twenty-seven children admitted for pneumonia with empyema were studied. Thrombocytosis (platelet counts greater than 500 x 10(3)/microliters) was present in 92.5%. Platelet counts reached their maximum at 15.1 +/- 3.7 days (range, 7 to 25) and declined to normal after 3 weeks of illness. Compared with a healthy control group, significant thrombocytosis, but of lower incidence, was also noted in children with lobar pneumonia without pleural effusion, bacterial meningitis and osteomyelitis. Platelet functions were examined in seven of the children but no abnormalities were observed. Bone marrow aspiration of three children with pneumonia and empyema showed megakaryocytic hyperplasia. We found no correlation between thrombocytosis, neutrophilia, fever, the clinical course, complications, prognosis or treatment. Neither thromboembolic nor hemorrhagic phenomena were observed. 
4	Discrepancies in the measurement of isovolumic relaxation time: a study comparing M mode and Doppler echocardiography. Mitral valve cusp separation on M mode echogram, the mitral valve opening artefact, and the onset of forward transmitral flow recorded by Doppler echocardiography have all been taken to mark the end of isovolumic relaxation, while its onset has been taken either as the aortic closure sound (A2) recorded phonocardiographically or the aortic closure artefact determined by Doppler technique. Possible differences in the measurement of the isovolumic relaxation time were studied when these landmarks were used in 44 healthy people, 14 patients with mitral stenosis, 21 patients with left ventricular hypertrophy, and 24 patients with dilated cardiomyopathy by recording M mode echograms of the mitral valve, and pulsed and continuous wave Doppler spectra of transmitral flow, with simultaneous electrocardiograms and phonocardiograms. A2 was effectively synchronous with the aortic artefact. However, when the onset of Doppler flow was regarded as the end of isovolumic relaxation, the interval was significantly longer than when mitral cusp separation on M mode echograms was used: by 25 (10) ms in healthy individuals, by 25 (15) ms in patients with left ventricular hypertrophy, and by 50 (35) ms in patients with dilated cardiomyopathy. In patients with mitral stenosis the interval was only 5 (5) ms longer. The mitral valve opening artefact consistently followed the onset of flow and corresponded much more closely to the E point on the M mode echogram. This shows that it occurred during the rapid filling period and well beyond isovolumic relaxation by any definition. Thus isovolumic relaxation time measured from A2 to the onset of transmitral flow or the mitral valve opening artefact differs from that derived from A2 to mitral valve cusp separation. These intervals cannot be used interchangeably to measure "isovolumic relaxation time". 
1	Reviewing the unicystic ameloblastoma: report of two cases. Classification of ameloblastoma into solid, multicystic, unicystic, and peripheral types based on clinical appearance and effects has gained recent recognition. The unicystic ameloblastoma is a less encountered variant of the ameloblastoma. It appears more frequently in the second or third decade with no sexual or racial predilection. It is almost exclusively encountered asymptomatically in the posterior mandible. The following report of two cases discusses the pathophysiology, demographics, histology, and prognosis of the unicystic ameloblastoma. 
1	Radical prostatectomy and adjuvant radioactive gold seed placement: results of treatment at 5 and 10 years for clinical stages A2, B1 and B2 cancer of the prostate. Between 1977 and 1988, 131 patients with adenocarcinoma of the prostate underwent combined radical prostatectomy and intraoperative radioactive gold seed placement. Of these 131 patients 80 were clinically assessed as having stage A2 (12), B1 (43) or B2 (25) cancer and they are the subject of this review. The average dose of radioactivity administered to each patient was 96.6 mCi, and mean followup was 65 months (median 64 months). No patient in this series received any other form of adjuvant therapy until disease recurrence was demonstrated. Local recurrences were observed in 2 patients (2.5%) in this series while distant recurrences were observed in 10 (12.5%). Cancer specific survival free of disease at 5 years was 100% for clinical stage A2, 91% for B1 and 75% for B2 cancers. The 10-year survival free of disease was 100% for clinical stage A2, 82% for B1 and 68% for B2 cancers. Covariants of clinical stage and seminal vesicle involvement influenced survival free of disease in a statistically significant manner (p less than 0.05) while pathological stage and degree of tumor differentiation did not. Mild to severe complications were observed in 12 patients (15%). Intraoperative placement of radioactive gold seeds into unresected pelvic tissues surrounding the site of prostatectomy offers a theoretical advantage in treatment by delivering tumoricidal levels of irradiation to residual foci of cancer not appreciated at the time of surgery. Our results suggest that increases in cancer specific survival free of disease over that previously reported for prostatectomy alone may be achieved through this combined treatment regimen. Furthermore, it is our opinion that therapeutic gains can be achieved without the attendant increases in morbidity and treatment delay often associated with adjuvant external beam radiotherapy. 
2	Postoperative pancreatic abscess due to Plesiomonas shigelloides. Plesiomonas shigelloides is being recognized with increasing frequency as a human pathogen. The organism is ubiquitous in fresh and brackish water, and clinical illness has been associated with foreign travel and ingestion of inadequately cooked seafood. We describe a 64-year-old Filipino woman who presented 2 weeks after elective cholecystectomy and pancreatic biopsy with left upper quadrant pain, abdominal distention, and fever. Computerized tomography of the abdomen revealed an abscess in the tail of the pancreas with fluid accumulation in the lesser omental sac. Percutaneous aspiration yielded purulent material, and P. shigelloides was recovered in pure culture. To our knowledge, this is the first reported case of pancreatic abscess due to P. shigelloides. 
5	Rhodopsin mutants that bind but fail to activate transducin. Rhodopsin is a member of a family of receptors that contain seven transmembrane helices and are coupled to G proteins. The nature of the interactions between rhodopsin mutants and the G protein, transduction (Gt), was investigated by flash photolysis in order to monitor directly Gt binding and dissociation. Three mutant opsins with alterations in their cytoplasmic loops bound 11-cis-retinal to yield pigments with native rhodopsin absorption spectra, but they failed to stimulate the guanosine triphosphatase activity of Gt. The opsin mutations included reversal of a charged pair conserved in all G protein-coupled receptors at the cytoplasmic border of the third transmembrane helix (mutant CD1), replacement of 13 amino acids in the second cytoplasmic loop (mutant CD2), and deletion of 13 amino acids from the third cytoplasmic loop (mutant EF1). Whereas mutant CD1 failed to bind Gt, mutants CD2 and EF1 showed normal Gt binding but failed to release Gt in the presence of guanosine triphosphate. Therefore, it appears that at least the second and third cytoplasmic loops of rhodopsin are required for activation of bound Gt. 
1	Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1. Mesangial cell (MC) proliferation is an early pathologic alteration characteristic of many forms of immune mediated glomerulonephritis. The intracapillary position, contractile capacity, and production of cytokines and other inflammatory molecules place MC in a pivotal position to initiate, mediate, and direct glomerular damage. We as well as others have noted increased levels of cytokines including IFN gamma, TNF, and IL-1 and the cell surface MHC class II and ICAM-1 molecules in the kidneys of mice with lupus nephritis. MHC class II and ICAM-1 molecules are central to the interaction of T cells with antigen presenting cells (APC). Since cytokines can increase both MHC class II and ICAM-1 molecules, we investigated whether mesangial cells could function as APC or accessory cells after cytokine stimulation. For these studies we established a permanent MC line through transformation with origin-deficient SV40 DNA. Surface expression of ICAM-1 was similar in untransformed MC as well as SV40 transformed MC from normal mice and in untransformed cells from mice with lupus nephritis. Basal expression of ICAM-1 was upregulated rapidly by IFN gamma, TNF, and IL-1. MHC class II expression could not be induced with TNF or IL-1 alone but required prolonged stimulation with IFN gamma. MC adhered and presented antigen to an antigen specific IaK restricted T cell hybridoma. Anti-ICAM-1 mAb decreased adhesion and antigen presentation of cytokine stimulated MC. By comparison, MHC class II mAb abrogated antigen presentation by MC bearing MHC class II but did not block adhesion. 
2	A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club. BACKGROUND AND METHODS. The Southern Surgeons Club conducted a prospective study of 1518 patients who underwent laparoscopic cholecystectomy for treatment of gallbladder disease in order to evaluate the safety of this procedure. RESULTS. Seven hundred fifty-eight operations (49.9 percent) were performed at academic hospitals, and 760 (50.1 percent) at private hospitals. In 72 patients (4.7 percent) the operation was converted to conventional open cholecystectomy; the most common reason for the change was the inability to identify the anatomy of the gallbladder as a result of inflammation in the region of this organ. A total of 82 complications occurred in 78 (5.1 percent) of the patients; this is comparable with the rates of 6 to 21 percent that have been reported for conventional cholecystectomy. Overall, the most common complication was superficial infection of the site of insertion of the umbilical trocar. A total of seven injuries to the common bile duct or the hepatic duct occurred during the operation, for a rate of 0.5 percent. Four of the seven injuries were simple lacerations, which were repaired after conversion to conventional cholecystectomy. The incidence of bile-duct injury in the first 13 patients operated on by each surgical group was 2.2 percent, as compared with 0.1 percent for subsequent patients. No complications were attributed directly to either cautery or laser-surgical technique, and similar numbers of complications occurred in academic and private hospitals. The mean hospital stay for the entire group was 1.2 days (range, 6 hours to 30 days). CONCLUSIONS. The results of laparoscopic cholecystectomy compare favorably with those of conventional cholecystectomy with respect to mortality, complications, and length of hospital stay. A slightly higher incidence of biliary injury with the laparoscopic procedure is probably offset by the low incidence of other complications. 
1	Percutaneous fine-needle aspiration cytologic study of main pancreatic duct stenosis under pancreatographic guidance. When pancreatography shows a stenosis of the main pancreatic duct in patients with normal or inconclusive ultrasound and computed tomography, the exact nature of such stenosis is sometimes difficult to precise before surgical exploration. In such cases, the authors systematically performed a percutaneous fine-needle aspiration cytologic study of the stenosis under pancreatographic guidance. Fifteen patients were referred because of suspected pancreatic malignancy. The tumor markers, carcinoembryonic antigen (CEA) and CA 19-9 were normal in 11 patients and elevated in one patient, whereas only CA 19-9 was elevated in three others. In 14 cases, both the ultrasound and computed tomography did not show any obvious pancreatic mass. The pancreatography was done through endoscopic retrograde cholangiopancreatography (ERCP) (12 patients) or percutaneously in case of failure at ERCP3 and showed a main pancreatic duct stenosis that underwent aspiration by percutaneous fine needle precisely positioned using biplane fluoroscopy. The aspirated material was then smeared on glass slides, air-dried, and stained by Giemsa. In nine of the 15 patients, cytologic study revealed adenocarcinoma. This was confirmed by surgery in five and by progressive deterioration followed by death in four. In six patients, cytologic study gave a nonmalignant result. Chronic pancreatitis was found in five of them, confirmed at surgery in three and based on uneventful follow-up of at least 12 months in two others. In one case, a pancreatic adenocarcinoma not detected by cytologic study was found at surgery. Thus, the sensitivity and specificity of this diagnostic approach were 90% and 100%, respectively. No serious complication was noticed. The authors conclude that when ultrasound and computed tomography are inconclusive, percutaneous fine-needle aspiration cytologic study of main pancreatic duct stenosis under pancreatographic guidance is a safe, simple, and helpful procedure in the investigation of patients with suspected pancreatic malignancy. 
5	Allograft tympanoplasty: predictive value of preoperative status. The functional and anatomical results of a series of 181 consecutive allograft tympanoplasties for ears with drum perforation and an intact ossicular chain were retrospectively reviewed and related to preoperative factors. Drum closure was realized in 92% (166 of 181 cases evaluated 1 year after surgery), and 96.6% of the reconstructed drums were still intact 3 years after surgery (118 cases evaluated). An air-bone gap of less than 21 dB was reached in 79.6% (of a total of 162 cases) 1 year after surgery, and in 78% (of a total of 118 cases) 3 years after surgery. Age, contralateral pathology, the wet or dry status of the ear preoperatively, and the preoperative air-bone gap had no influence on anatomical results. The preoperative air-bone gap did not predict the postoperative air-bone gap. The influence of age and existence of contralateral pathology on hearing gain was only visible in some of the strictly defined patient groups. The wet preoperative status of the ear generally predicted lower functional gain. 
3	Intrathecal baclofen for spasticity in cerebral palsy Seventeen patients with congenital spastic cerebral palsy and six patients with other forms of spasticity were injected intrathecally with doses of placebo or baclofen, 25 micrograms, 50 micrograms, or 100 micrograms, in a randomized, double-blind manner. Muscle tone in the upper and lower extremities was assessed by Ashworth scores both before the injections and every 2 hours afterward for 8 hours. Function of the upper extremities was evaluated before the injections and 4 hours afterward. Muscle tone in the lower extremities was significantly decreased within 2 hours after baclofen injection and remained lower than baseline 8 hours afterward. Upper extremity tone and function were not significantly affected by these single doses. Confusion and drowsiness occurred in two of the youngest children in the study after the 50-micrograms dose, but cleared within 2 hours. Our findings indicate that intrathecal baclofen reduces spasticity in children with cerebral palsy, as it does in adults with spasticity of spinal origin. 
2	Interleukin 1 beta is expressed predominantly by enterocytes in experimental colitis. The cytokine interleukin 1 beta is an important mediator of inflammatory processes capable of inducing eicosanoid production, T-cell activation, and increased vascular permeability. In this study, in situ hybridization techniques were used to delineate the kinetics and cellular source of induced interleukin 1 beta in acute experimental colitis. The induction of interleukin 1 beta messenger RNA was an early phenomenon and occurred predominantly in undifferentiated cells located in the basal part of the mucosal crypts but not in differentiated enterocytes. The undifferentiated enterocytes retained the messenger RNA during differentiation and migration to more apical parts of the crypts. These results suggest that induction of interleukin 1 beta messenger RNA in enterocytes is causally related to the subsequent inflammatory changes seen in acute experimental colitis. 
3	Embolism of cerebral tissue: a cause of coagulopathy and cerebral infarction? Report of a case. We report a case of potentially survivable closed head injury, which was complicated by disseminated intravascular coagulation and bilateral cerebral infarction. Autopsy disclosed pulmonary emboli composed of cerebral tissue. We suggest that the entry of brain tissue into the systemic blood circulation caused severe disseminated intravascular coagulation, with consequent thrombosis of cerebral veins and spreading infarction. 
5	Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed. 
4	Endothelin family in human plasma and cerebrospinal fluid. To clarify whether endothelin may be present in human cerebrospinal fluid (CSF) and, if it exists, to compare its molecular forms with those of endothelin in human plasma, we analyzed pooled human CSF and plasma by high performance liquid chromatography with specific enzyme immunoassays for each endothelin peptide. Of the four human endothelin peptides hitherto identified, big endothelin-1 was the major molecular form of endothelin present in human CSF. In addition, there was a small but significant amount of endothelin-1 and endothelin-3 in CSF, while endothelin-2 was not detectable. Similarly, big endothelin-1, endothelin-1, and endothelin-3 were identified in human plasma. Although big endothelin-1 was the most abundant, a substantial amount of endothelin-1 and endothelin-3 was found in plasma with a resultant lower molar ratio of big endothelin-1 to endothelin-1 than in CSF. In all CSF samples from 17 patients requiring diagnostic lumbar puncture or lumbar anesthesia, endothelin was detectable, with a preponderance of big endothelin-1 relative to endothelin-1 and endothelin-3. The mean concentrations of endothelin-1 and endothelin-3 in simultaneously collected plasma were significantly (P less than 0.01) higher than those in CSF, while there was no significant difference between the mean big endothelin-1 concentration in plasma and that in CSF. There was no significant correlation among concentrations of big endothelin-1, endothelin-1, and endothelin-3 in each paired sample. These results indicate that endothelin is present in human CSF that is differently processed from endothelin in vascular endothelial cells and suggest a possible role for endothelin as a modulator of neuronal functions. 
1	Gastric lymphoma causing granulocytopenia and cold intolerance, with recovery after treatment. A 34-year-old man was found to have granulocytopenia with a white blood count of 2.3 x 10(9) l-1, consisting of 10% segmented neutrophils, 50% monocytes and 40% lymphocytes. A bone marrow aspirate showed 20% promyelocytes and 10% blasts with monoblastic features, and a smouldering myelomonocytic leukaemia was considered to be a possible diagnosis. In cold weather the patient experienced cold intolerance with acrocyanosis and small ulcerations on the ears. The test for heparin-precipitable protein ('cryofibrinogen') was strongly positive. During the following year, these signs and symptoms persisted, and the patient also developed constant moderate pain in the epigastric region. Gastroscopy revealed a large lymphoma of the stomach, which was a high-grade malignant centroblastic type of non-Hodgkin's lymphoma. After successful removal of the tumour, and six courses of potent cytostatic combinations, the patient recovered completely, and the granulocytopenia and cold intolerance disappeared. 
4	Angiotensin II levels in hypertensive and normotensive pregnancies. We measured circulating angiotension II by radioimmunoassay in women with pregnancy-induced hypertension (n = 54), and compared these values with those obtained in women with normal pregnancy (n = 18) and in non pregnant women (n = 20). Pregnant women had statistically significantly higher plasma angiotensin II [mean (SD): 41.3 (12.6) pg/ml] than non-pregnant women [29.2 (11.3) pg/ml; P less than 0.004]. Angiotensin II concentrations in women with pregnancy-induced hypertension [mean (SD): 31.7 (16.2) pg/ml] were, on average, 25% lower than in normal pregnancy (P less than 0.003) and resembled those obtained in non-pregnant women. The lowest angiotensin II levels were found in women with more severe forms of pregnancy-induced hypertension, such as proteinuric or superimposed pregnancy-induced hypertension. Review of the published studies on angiotensin II and our data suggest that the conflict among studies on angiotensin II levels in pregnancy-induced hypertension is largely due to the heterogeneity of the study populations in the various reports. 
1	Role of ultrasound guided fine needle aspiration biopsy in the diagnosis of hepatocellular carcinoma. In 170 cases of hepatocellular carcinoma, ultrasound showed a high sensitivity in identifying focal liver lesions. Fine needle aspiration biopsy guided by ultrasound yielded a pathological diagnosis in the majority of cases. The advantages of this technique, its high diagnostic yield and low cost, render the older technique of blind percutaneous biopsy using a coarse needle obsolete. Laparoscopy retains its essential role in selected cases. Complementary use of fine needle aspiration biopsy under ultrasound guidance and laparoscopy assures the highest rate of diagnostic accuracy in hepatocellular carcinoma. We confirm the poor sensitivity of alpha fetoprotein. 
3	Low plasma iron status and akathisia. Thirty patients were examined to test the hypothesis that a depletion of iron levels is associated with symptoms of akathisia. Fifteen akathisic patients were pair-matched with 15 non-akathisic patients. Plasma ferritin levels were significantly decreased in the akathisic patients, and there was a significant inverse correlation between plasma iron levels and akathisia rating. In addition, akathisia ratings were found to be correlated with a scale measuring symptoms of tardive dyskinesia. 
5	Hepatic oxygen and lactate extraction during stagnant hypoxia. As O2 delivery falls, tissues must extract increasing amounts of O2 from blood to maintain a normal O2 consumption. Below a critical delivery threshold, increases in O2 extraction cannot compensate for the falling delivery, and O2 uptake falls in a supply-dependent fashion. Numerous studies have identified a critical delivery in whole animals, but the regional contributions to the critical O2 delivery are less fully understood. In the present study, we explored the limits of O2 extraction in the isolated liver, seeking to determine 1) the normal relationship between O2 consumption and delivery in the liver and 2) the relationship of hepatic lactate extraction to the drop in hepatic O2 consumption at low O2 deliveries. To answer these questions, using support dogs as a source for oxygenated metabolically stable blood, we studied eight pump-perfused canine livers. By lowering the blood flow in a model of stagnant hypoxia, we explored the relationship between O2 consumption and delivery over the entire physiological range of O2 delivery. The critical O2 delivery was 28 +/- 5 (SD) ml.kg-1.min-1; the livers extracted 68 +/- 9% of the delivered O2 before reaching supply dependence. This suggests that the liver has an O2 extraction capacity quite similar to the body as a whole and not different from other tissues that have been isolated. At high blood flows, the livers extracted approximately 10% of the lactate delivered by the blood, but the arteriovenous lactate differences were small. At low blood flows, however, the livers changed from lactate consumption to production. The O2 delivery coinciding with the dropoff in lactate extraction did not differ significantly from the critical O2 delivery. We conclude that reductions in lactate uptake by the liver do not precede the transition to O2 supply dependence. 
5	The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias. The t(1;19)(q23;p13) chromosomal translocation is observed cytogenetically in 25% of children with pre-B-cell acute lymphoblastic leukemia (ALL) and is associated with an adverse treatment outcome. The t(1;19) juxtaposes the E2A gene from chromosome 19 with the PBX1 gene on chromosome 1, leading to the production of fusion transcripts and resultant chimeric proteins that contain the transcriptional-activating motif of E2A and the DNA-binding homeodomain of PBX1. To investigate the molecular nature of E2A/PBX1 fusion in patients with t(1;19) ALL we used an RNA-based polymerase chain reaction (PCR) procedure to amplify a portion of the chimeric transcript. We detected E2A/PBX1 fusion transcripts in cells from 97% (37 of 38) of cases in which the t(1;19) had been observed cytogenetically. Molecular evidence of E2A/PBX1 fusion transcripts was also observed in a patient in whom a t(1;19) was not detected cytogenetically and in one patient with subclinical levels of minimal residual disease before overt clinical relapse. In all PCR-positive cases the junction of E2A and PBX1 coding sequences occurred at precisely the same location as demonstrated by hybridization of PCR products with a fusion site-specific detection oligonucleotide. These findings demonstrate the consistent fusion of E2A and PBX1 coding sequences resulting from t(1;19) and suggest that site-specific fusion of E2A and PBX1 is an important pathogenic event in t(1;19) ALL. 
4	Role of ultrasonic tissue characterization to distinguish reversible from irreversible myocardial injury. Tissue characterization reflects structural and functional integrity of tissues. Inasmuch as reversible ischemia causes no structural damage and irreversible ischemia results in persistent structural myocardial damage, we postulated that ultrasonic tissue characterization can distinguish the two types of injuries. Anesthetized open chest dogs underwent 15 minutes (group 1, n = 5) and 90 minutes (group 2, n = 8) of acute total occlusion of the left anterior descending coronary artery, followed by 3 hours of reperfusion. Myocardial ischemia-infarction was confirmed with segment shortening, electronmicroscopic examination, and triphenyl tetrazolium chloride staining. Integrated backscatter Rayleigh 5 (IBR5), a measure of ultrasonic backscatter, and Fourier coefficient of amplitude modulation (FAM), an index of cardiac cycle dependent variation in backscatter, were measured at baseline, during ischemia, and after reperfusion. Group 1 (reversible ischemia) showed an increase in IBR5 from -48 +/- 1.2 dB at control to -45 +/- 1.0 dB (p less than 0.01) during ischemia, which returned to baseline after reperfusion (-47 +/- 1.3 dB). FAM was blunted during ischemia (6.2 +/- 1.0 dB during control versus 1.2 +/- 1.0 dB during ischemia, p less than 0.01) and recovered completely during reperfusion. Segment shortening was abolished during ischemia (18% +/- 3% during control versus -12% +/- 5% during ischemia, p less than 0.01) and recovered partially during reperfusion (4% +/- 5%). The group 2 animals with irreversible myocardial injury showed an increase in IBR5, from -49 +/- 1.2 dB during control to -44 +/- 1.0 dB during ischemia (p less than 0.01) and paradoxical bulging of the ischemic region (17% +/- 3% to -7% +/- 3%, p less than 0.01) during ischemia. 
5	Neurodevelopmental performance of very-low-birth-weight infants with mild periventricular, intraventricular hemorrhage. Outcome at 5 to 6 years of age. The neurodevelopmental outcome of 38 very-low-birth-weight neonates (birth weight, less than 1501 g) was followed up prospectively from birth to 5 to 6 years of age to assess the neurodevelopmental sequelae of mild periventricular, intraventricular hemorrhage (grades I and II). All neonates were screened for periventricular, intraventricular hemorrhage at 5 to 10 days of age. Eleven incurred a mild periventricular, intraventricular hemorrhage (group 1) and 27 had no periventricular, intraventricular hemorrhage (group 2). Each of the infants was neurodevelopmentally normal at 1 to 2 years of age. The 38 children were matched by race, age, sex, and socioeconomic status with control children (group 3) who had been born at term. On outcome measurements at 5 to 6 years of age, groups 1 and 2 scored significantly lower than group 3 on the combined test measurements and on three of the four individual measurements. Group 1 scored significantly lower than group 2 on the combined test measurements only. These data indicate that very-low-birth-weight infants are at risk for learning problems. Although children with mild periventricular, intraventricular hemorrhage did not demonstrate a significant deficit on individual test scores, the significant difference on the combined battery suggests that mild periventricular, intraventricular hemorrhage has an adverse effect on global performance. 
3	The effect of quinidine and mexiletine on the adaptation of ventricular refractoriness to an increase in rate. The purpose of this study was to determine the effects of quinidine and mexiletine on the adaptation of ventricular refractoriness to a change in heart rate. The ventricular effective refractory period was measured at a basic drive cycle length of 500 msec with basic drive train durations of two beats, eight beats, 20 beats and 3 minutes. The ventricular refractory periods were measured in the baseline state and after oral treatment with quinidine or mexiletine in 20 subjects each. In the baseline state, there was progressive shortening of the ventricular refractory period as the drive train duration increased from two beats to 3 minutes. Quinidine prolonged refractoriness by 5% (p less than 0.001) at each drive train duration. Mexiletine did not affect the ventricular effective refractory period at any of the drive train durations. In a control group of 20 subjects, there were no significant differences between two determinations of refractoriness at each basic drive train duration. In conclusion, neither quinidine nor mexiletine affect the adaptation of ventricular refractoriness to an increase in rate. Although the ventricular effective refractory period measured with a conventional basic drive train duration of eight beats is often more than 20 msec longer than the actual ventricular effective refractory period measured with a drive train duration of 3 minutes, the effects of quinidine and mexiletine on the conventionally measured ventricular effective refractory period accurately reflect the effects of these drugs on the actual ventricular effective refractory period. 
4	Mechanical factors in large artery disease and antihypertensive drugs. Hypertension may induce early alterations in large arteries by 2 mechanical stresses: one related to intravascular pressure, the other to blood flow dynamics. Distending pressure force acts in a circumferential direction, inducing decreased arterial distensibility. Arterial distensibility can be evaluated in humans by measurement of arterial compliance and pulse-wave velocity. It is well established that in chronic hypertension age and elevated pressure act together to increase arterial rigidity. Blood flow dynamics induce frictional forces in the endothelial surfaces of arteries. These forces, expressed by shear stress, are proportional to the viscosity of the blood and to the velocity gradient at the arterial wall. Measurement of blood viscosity and evaluation of velocity profile in the brachial arteries of hypertensive subjects have shown a reduction in wall shear rate and stress despite the elevation in blood viscosity. Several studies have shown that drug therapy that successfully reduces blood pressure does not necessarily improve arterial compliance. In contrast, few data are available on the effects of antihypertensive medication on arterial wall shear in humans. Arterial compliance and wall shear stress are 2 main therapeutic targets of potential importance in the physiopharmacologic approach to the effects of hypertension on atherogenesis. 
5	Reconstruction of the severely atrophic edentulous mandible by means of autogenous bone grafts and simultaneous placement of osseointegrated implants. A method of reconstructing the severely atrophic mandible that simultaneously provides additional strength and the ability to house osseointegrated implants is presented. The performance of the procedure from an external approach minimizes the possibility of oral contamination and, therefore, infection. The procedure has been performed on 10 patients, with a longest follow-up of 3 years. A 93% success rate has been achieved, and bone resorption at the implant sites has thus far been negligible. Prosthetic rehabilitation has been done in 9 of the 10 cases; 3 have been tissue-supported prostheses, and 6 have been completely implant-supported prostheses. 
4	Intraoperative transesophageal color-coded Doppler echocardiography for evaluation of residual regurgitation after mitral valve repair. Because mitral valve competence after mitral valve reconstruction is awkward to assess during this procedure, we evaluated in this respect transesophageal color-coded Doppler echocardiography in 23 patients undergoing mitral valve reconstruction for severe mitral regurgitation. Transesophageal echocardiographic examinations were performed after induction of anesthesia but before sternotomy (baseline), after mitral valve repair before decannulation, and at sternal closure, all at similar mean aortic pressure and echocardiographic instrument settings. The degree of mitral regurgitation by transesophageal color Doppler flow mapping was visually quantified on a 5-point scale (0 to 4), pending the left atrial extent of the regurgitant jet. This was compared with the degree of mitral regurgitation by left ventricular cineangiography performed within several weeks after operation and also visually quantified on a 5-point scale (0 to 4), with use of the right anterior oblique projection. There was good correlation between the two methods (r = 0.83; p less than 0.001). We conclude that residual mitral regurgitation, as assessed by transesophageal color flow mapping in the operating room, highly correlates with the ultimate mitral regurgitation by cineangiography. Therefore transesophageal echocardiography can be helpful for evaluation of mitral valve competence during mitral valve reconstruction, and hence, in case of repair failure, allow valve replacement in the same surgical session, thus avoiding reoperation. 
2	Comparison of collagen propeptides as growth markers in children with inflammatory bowel disease. The serum concentrations of the carboxy-terminal propeptide of type I procollagen and the amino-terminal propeptide of type III procollagen as biochemical markers of growth activity were compared in 46 children and adolescents with inflammatory bowel disease. Significant correlations were noted between growth velocity and type I procollagen (r = 0.65; P less than 0.001) and type III procollagen concentrations (r = 0.64; P less than 0.001). Although the serum concentration of type I procollagen was generally about 15 times greater than that of type III, the respective serum concentrations were highly correlated (r = 0.66; P less than 0.001) at all growth velocities. The use of daily corticosteroid therapy was associated with significantly lower concentrations of both propeptides (P less than 0.01) than was alternate-day or no corticosteroid therapy, respectively. Children with growth arrest (0.0 cm/mo) had type I and type III procollagen concentrations similar to those found in adults. These observations indicate that the serum concentrations of both collagen propeptides reflect growth activity in children with inflammatory bowel disease and suggest that routine measurement of collagen propeptides may have clinical value in monitoring normal and abnormal growth. The data suggest that the measurement of one propeptide does not offer an advantage over the other. 
5	Role of phenytoin in healing of large abscess cavities. The promotion of healing of large abscess cavities attained with topical phenytoin was evaluated in controlled studies of clinical and experimental wounds. In the clinical abscess cavities, phenytoin application in 20 patients compared with conventional treatment in 20 patients resulted in earlier separation of slough, decrease in oedema, control of pain and overall enhanced healing. The mean(s.d.) rate of reduction of wound area was 2.02(0.48) cm2/day in the phenytoin group versus 1.58(0.51) cm2/day in controls (P less than 0.05) on day 10, and 1.8(0.32) cm2/day versus 1.19(0.21) cm2/day (P less than 0.01) on day 20. The mean volume reduction rates at both the 10th and 20th day were 0.48(0.01) cm3/day for phenytoin versus 0.32(0.04) cm3/day for controls; (P less than 0.005). By day 20, 17 of the patients treated with phenytoin were rated as having healed completely, compared with only one of the controls. In a standardized guinea-pig model of the clinical abscess cavity, which included inoculation of the wound with Bacillus proteus and Klebsiella pneumoniae, an enhanced healing rate was also observed (at 7 days 0.40(0.05) cm2/day with phenytoin versus 0.21(0.08) cm2/day in controls; P less than 0.005). All eight of the animals treated with phenytoin healed by day 21, compared with one of the eight controls. Biopsies of wounds treated with phenytoin showed less inflammation, no necrosis, and enhanced neovascularization, collagen deposition and fibroblast proliferation compared to controls. Bacterial colonies also decreased more rapidly with the use of phenytoin. 
1	Biopsy of the breast for mammographically detected lesions. We prospectively studied 718 women who underwent biopsy of the breast for suspicious, mammographically detected mammary lesions in an attempt to identify key clinical risk factors, as well as roentgenographic characteristics associated with the appearance of early carcinoma of the breast. Patients with a benign outcome had an average age of 55 years versus 63 years for patients with carcinoma of the breast. Seventy-six per cent of these patients had no previous history of mammary problems, 20 per cent had a positive family history for carcinoma of the breast, 58 per cent were premenopausal and 21 per cent had used birth control pills. Except for age (p less than 0.001), the distribution of clinical risk factors was equal among patients with benign or malignant outcomes. Suspicious mammographic findings included mass lesions (53 per cent), calcifications (36 per cent) and the association of both (11 per cent). The predominant Wolfe pattern on mammography was P1 (36 per cent). No relationship was observed between Wolfe pattern and malignant conditions. In this group of patients, mammography was poorly specific; however, the positive predictive value increased with age and is related to the age-specific prevalence of carcinoma of the breast. Eight hundred and twenty-five lesions were removed. Twenty-five per cent (n = 203) of the specimens taken at biopsy contained carcinoma. Stellate mass lesions were highly suggestive of a malignant growth (p less than 0.0001). No relationship between the size of the suspicious mammographic mass and the malignant lesion was observed. A marked correlation (chi-square test with Yate's correction) was observed between malignant tumor and lesions with a linear or branching pattern, more than 15 calcifications, or small sized calcifications. The presence of a mass with calcifications was associated with carcinoma in 34 per cent. The incidence of invasive carcinoma was much higher for mass lesions (81 per cent) than for suspicious calcifications (56 per cent) (p less than 0.0001). 
3	Intracranial aneurysms: interventional neurovascular treatment with detachable balloons--results in 215 cases Patients with complex or surgically difficult intracranial aneurysms are being treated with interventional neurovascular techniques. With neuroleptic anesthesia and a transfemoral femoral approach, a silicone micro-balloon can be flow directed through the intracranial circulation, guided directly into the aneurysm, and detached. The aneurysm is thus eliminated from the circulation, and the parent artery is preserved. For broad-based or ectatic aneurysms, test occlusion followed by permanent occlusion of the aneurysm and parent vessel can be performed. Since 1981, 211 patients with 215 aneurysms, including 177 cases involving the anterior and 38 cases involving the posterior circulation, have been treated with this technique. In 127 cases (59.1%), the parent vessel was occluded; in 88 cases (40.9%), primary occlusion of the aneurysm was achieved with preservation of the parent artery. Therapy-related complications included 21 deaths (9.8%) and 16 strokes (7.4%). Follow-up examinations were performed at 1, 3, and 12 months after treatment, and follow-up ranged from 5 months to 9 years. In patients in whom standard surgical therapy fails or for aneurysms in surgically inaccessible anatomic locations, interventional techniques that make use of detachable balloons may be a useful therapeutic alternative. 
2	Alpha 1-antitrypsin granules in the liver--always important? We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information. 
1	Generation of human monoclonal antibodies against colon cancer. Lymphocytes from regional lymph nodes of patients with colon cancer were fused with a human lymphoblastoid cell line with or without in vitro immunization. The efficacy of these two protocols for the generation of human monoclonal antibodies against colon cancer was investigated. The hyperplastic lymph nodes adjacent to the tumor were the best source of B lymphocytes. Fusion frequency and the number of tumor-reactive clones were markedly increased when the in vitro immunization protocol was applied prior to fusion. As a stimulant in in vitro immunization, the supernatant of pokeweed mitogen-stimulated T lymphocytes was superior to the supernatant of mixed lymphocytes culture. Carcinoembryonic antigen at 20 micrograms/L seemed to be the optimal dose for in vitro immunization. The reactivities of human monoclonal antibodies thus generated were measured by enzyme-linked immunosorbent assay and confirmed by immunoperoxidase staining. Combining in vitro immunization with lymphocytes of cancer patients may lead to the successful production of clinically useful human monoclonal antibodies. 
4	Left ventricular regional wall stress in dilated cardiomyopathy. Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janz's method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p less than 0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22 +/- 14% versus 54 +/- 9%, respectively, p less than 0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32 +/- 17% versus 15 +/- 4%, respectively, p less than 0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r = -0.60 to -0.86, p less than 0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM. 
4	Spontaneous changes in ventricular tachycardia cycle length. Understanding spontaneous fluctuations in ventricular tachycardia cycle length is required to develop algorithms for ventricular tachycardia detection and termination. Variations in cycle length, time to stable cycle length and the range of RR intervals during ventricular tachycardia were analyzed in 74 episodes of sustained monomorphic ventricular tachycardia induced in patients not taking antiarrhythmic medication. Linear regression demonstrated cycle length variability to decrease over time (41 +/- 24 to 17 +/- 19 ms, p less than 0.001). Slower ventricular tachycardia had more cycle length variability than faster ventricular tachycardia (p less than 0.001). Ventricular tachycardia that was initially more variable tended to remain more variable (p less than 0.001). Fifty-four percent of episodes stabilized within the first 15 beats, 75% by 30 beats and 93% by 50 beats. The number of beats to stable cycle length was independent of ventricular tachycardia rate. The average range in cycle length per episode was 127 +/- 72 ms; 12% of ventricular tachycardia episodes varied by less than 50 ms and 45% by less than 150 ms. The maximal range in RR intervals from a single episode of ventricular tachycardia was 290 ms. Therefore, ventricular tachycardia demonstrates a wide range of cycle lengths and has time-dependent changes in variability and stability. These cycle length changes should be considered in the algorithms for ventricular tachycardia detection and termination by automatic antitachycardia devices. 
4	Infrarenal abdominal aortic disease: a review of the retroperitoneal approach. Transabdominal exposure is the most widely used surgical approach to the infrarenal aorta. Over the last 30 years a number of surgeons have championed the retroperitoneal approach for repair of abdominal aortic aneurysms and aortoiliac occlusive disease using a variety of incisions. Several studies attest to the clinical superiority of this approach over the transabdominal route and recent evidence demonstrates reduced physiological disturbance with this technique. The retroperitoneal approach is suitable for all elective operations on the abdominal aorta, particularly in patients with high-risk aneurysms and in selected patients with symptomatic and ruptured aneurysms. 
4	Percutaneous angioscopy during coronary angioplasty using a steerable microangioscope. The feasibility of using a flexible, steerable angioscope to perform coronary angioscopy before and after percutaneous coronary angioplasty was tested. The microangioscope fits through an 8F coronary angioplasty guiding catheter and contains a multifiber viewing bundle incorporated into the body of a 4.3F balloon catheter with a central lumen for distal flushing and guide-wire passage. Angioscopy was performed without complications 45 times in 24 patients, including 6 patients with stable and 18 with unstable angina. Circumferential visualization of the target lesion was successful in 20 (83%) of the 24 patients and improved with operator experience. Excellent visualization of the target lesion was achieved in 16 (94%) of the last 17 patients. Plaque, thrombus and dissection were among the abnormal findings in the 20 patients (4 with stable, 16 with unstable angina) in whom circumferential viewing of the target lesion was achieved. In four patients with restenosis after angioplasty, the lesion morphology was distinctly different from that of lesions in arteries without prior angioplasty. In patients with stable angina, no thrombus or dissection was seen by angiography or angioscopy before angioplasty. In patients with unstable angina, thrombus was detected more frequently by angioscopy than by angiography before angioplasty (8 versus 2 of 16) and after (15 versus 2 of 16) angioplasty. Intimal dissection was also seen much more frequently by angioscopy than by angiography before angioplasty (7 versus 0 of 16) and after angioplasty (16 versus 7 of 16). It is concluded that high resolution percutaneous coronary angioscopy can be performed safely in conjunction with balloon angioplasty. Further investigation is needed before this diagnostic tool can be applied clinically. 
4	Fluosol: an oxygen-delivery fluid for use in percutaneous transluminal coronary angioplasty. Fluosol (20% intravascular perfluorochemical emulsion) is an oxygen-carrying emulsion used to deliver oxygen to ischemic myocardium during percutaneous transluminal coronary angioplasty (PTCA). Fluosol is composed of two perfluorochemicals, perfluorodecalin and perfluorotripropylamine. It has a high capacity for oxygen solubility, a low viscosity, and a small particle size. Following administration, the perfluorochemicals in fluosol are not metabolized. Rather, most are expired as gaseous particles through the lungs; the remainder are taken up by the organs of the reticuloendothelial system and later expired. When administered during balloon inflation in PTCA, fluosol preserves ventricular wall motion and global left ventricular ejection fraction. In addition, it minimizes ST segment changes and preserves cardiac output. Fluosol may be especially useful in patients who have poor contractile reserve, multivessel disease, or serious underlying illness. Other uses under investigation include limitation of myocardial infarct size and chemosensitization or radiosensitization of malignant tumors. Adverse effects secondary to the use of fluosol include ventricular arrhythmias, pruritus, bradycardia, chest pain, dyspnea, and increased respiratory rate. Fluosol must be thawed, admixed, warmed to body temperature, and oxygenated prior to intracoronary administration. The usual administration rate is 60 mL/min during each balloon inflation. 
5	The relationship of headache symptoms with severity and duration of attacks. Efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes. An alternative conceptual approach, the "severity model" of headache, considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms. A population-based telephone interview was carried out among 10,169 subjects aged 12-29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks. In an analysis of frequency of occurrence, pain and duration of recent (within 4 weeks prior to interview) headache attacks, the data revealed that common symptoms (such as forehead pain and pain in the back of the head, neck and shoulders) were reported frequently, but headaches with these symptoms were generally characterized by low levels of pain and short duration. Although not an original study objective, the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types. Symptoms of migraine were frequently experienced concomitant with tension-type symptoms; the resultant headaches were usually characterized as moderate in intensity. In contrast, symptoms usually associated with migraine in the absence of concomitant tension-type symptoms were infrequently experienced, but resulted in headaches causing the greatest disability. The data provide some support for the severity model of headache. 
3	Outpatient management of schizophrenia. As effective antipsychotic pharmacotherapy has become available, patients with schizophrenia are increasingly managed in an outpatient setting by primary care physicians. Pharmacotherapy is generally effective in treating "positive," or psychotic, symptoms and lessening the risks of relapse, but ineffective in improving "negative," or deficit, symptoms. Aggressive attempts to totally control positive symptoms and to ameliorate negative symptoms tend to increase side effects and may be detrimental to the patient. Intensive psychotherapeutic and rehabilitative approaches are generally unproductive. Attempting to obtain a cure is unrealistic. A moderate approach is recommended, taking into consideration the limitations of existing treatments, achieving control of extreme symptoms and minimizing social and occupational limitations. 
4	Transaortic endarterectomy of renal visceral artery lesions in association with infrarenal aortic surgery. The complexity of infrarenal aortic reconstruction increases when bypass grafts to revascularize associated renal and visceral arteries are needed. Lesions in these vessels, however, are usually limited to their aortic orifices and therefore are amenable to retroperitoneal transaortic endarterectomy. A combined infrarenal aortic reconstruction and transaortic endarterectomy of the renal/visceral vessels was used in 18 (16%) of 120 patients undergoing elective infrarenal aortic reconstruction over a 2-year-period. Transaortic endarterectomy was performed primarily for renal preservation in 11 patients with bilateral, high-grade renal artery stenoses and abnormal renal function (serum creatinine greater than or equal to 1.9 mg/dl). In seven patients transaortic endarterectomy was performed as a secondary procedure during the course of complex reconstruction of aneurysmal or occlusive aortic disease. Mean serum creatinine, which was elevated preoperatively in 14 (78%) patients (3.3 mg/dl), decreased significantly after the operation (2.0 mg/dl, p less than 0.01). A single death occurred in the 18 patients undergoing transaortic endarterectomy. Renal function preservation can be achieved by renal revascularization in patients with bilateral renal artery stenoses and decreased renal function. The retroperitoneal approach to aortic reconstruction and the use of transaortic endarterectomy allows correction of most renal/visceral vessel involvement in complex aortic revascularization procedures. 
1	Regional differences in the intranodal distribution of tumor cells. The intranodal distribution of tumor cells was examined in 103 mesenteric and 135 axillary nodes to determine the frequency of a circumferential type of distribution and its relationship, if any, to central necrosis. Eighteen percent of the mesenteric nodes removed at surgery from patients with colon cancer contained a circumferential rim of viable tumor cells in an area corresponding wholly or in part to the normal location of the marginal sinus. In each case this rim of tumor cells surrounded a large central area of necrosis. In contrast, only one of the 135 axillary nodes removed from patients with breast cancer demonstrated this pattern. These findings suggest that by interrupting blood and lymph vessels, the circumferential spread of tumor cells underlies development of central necrosis. Previously described structural dissimilarities between mesenteric and axillary nodes may explain the striking difference in incidence of this pattern in these nodes. 
4	The effects of epidural anesthesia on the Doppler velocimetry of umbilical and uterine arteries in normal and hypertensive patients during active term labor. To study the effects of epidural anesthesia on uterine and umbilical artery blood flow in preeclampsia, we observed 25 patients in active labor at 36 or more weeks' gestation. Seven had preeclampsia, eight had chronic hypertension, and ten had no complications. Doppler velocimetry of the uterine and umbilical arteries was performed before and after intravenous fluid loading and at 30 and 60 minutes after epidural blockade. Maternal vital signs and fetal heart rate were monitored continuously. After epidural block, mean maternal blood pressure fell significantly in all groups, but no maternal hypotension was observed. Mean maternal and fetal heart rates were unchanged. After epidural block, mean uterine artery systolic-diastolic (S-D) ratios did not change in the chronic-hypertension and normal groups, but fell significantly in the preeclamptic group to values similar to those of the normal group. Umbilical artery S-D ratios did not change in any group. In preeclamptic pregnancy, epidural anesthesia may help to reduce uterine artery vasospasm and may benefit intrapartum fetal well-being. 
5	Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts. We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells. 
4	Mechanisms of reoxygenation injury in cultured ventricular myocytes To investigate factors contributing to reperfusion and reoxygenation myocardial injury, we exposed layers of cultured chick ventricular myocytes to severe hypoxia for up to 3 hours in the presence of 20 mM 2-deoxyglucose, zero glucose, and 5 mM pyruvate, and then exposed the myocytes to reoxygenation. Lactate dehydrogenase (LDH) release was moderately increased during 3 hours of hypoxia but was increased markedly during reoxygenation. Coincident changes in intracellular calcium concentration ([Ca2+]i) and cell motion were also measured during hypoxia and reoxygenation. During hypoxia, [Ca2+]i increased to more than 1 microM, and with reoxygenation, [Ca2+]i abruptly decreased slightly but remained elevated more than 1 microM. Cells developed a stable rigor after 30 minutes of hypoxia. Reoxygenation caused a marked hypercontracture within 5 minutes. Pretreatment of myocytes with either 2,3-butanedione monoxime, which inhibits Ca2(+)-dependent force development, or cyanide inhibited reoxygenation hypercontracture. LDH release after reoxygenation was also significantly reduced in the presence of 2,3-butanedione monoxime. Treatment of myocytes with superoxide dismutase and catalase during hypoxia also resulted in a decrease in LDH release during reoxygenation. We conclude that an abrupt increase in [Ca2+]i during reoxygenation does not account for reoxygenation injury. However, in the presence of elevated [Ca2+]i, reoxygenation and the resulting probable resynthesis of ATP causes [Ca2+]i-dependent myofilament crossbridge cycling, and the resulting hypercontracture contributes to myocyte damage. The generation of oxygen free radicals after reoxygenation also appears to contribute to cell injury in this system. 
5	Bilateral vocal cord hematomas associated with shoulder harness use. A case of bilateral vocal cord hematomas caused by a shoulder harness injury is presented. The patient was restrained by a three-point belt system and was involved in a front-end collision. She presented with mild facial and chest injuries and a contusion of the neck. One hour after injury she began to complain of hoarseness without airway compromise. Fiberoptic laryngoscopy showed bilateral true vocal cord hematomas. The patient had an uneventful hospital course and a full recovery. The importance of the mechanism of injury and associated injuries is discussed. 
1	Spinal instability secondary to metastatic cancer. Fifty-five patients with severe pain from spinal instability secondary to metastatic cancer were referred to Hope Hospital, none being judged to be in a terminal condition. One patient had too extensive disease for surgery so 54 were treated by 55 spinal stabilisations; 49 obtained complete relief of pain and two had partial relief. There were three failures. Twenty-eight of the patients had clinical evidence of spinal cord or cauda equina compression and were decompressed at the time of stabilisation. Of these, 20 had major recovery of neurological function. Patients with pre-operative evidence of extradural tumour had 'prophylactic' decompression at the time of stabilisation; none of these patients later developed signs of cord or cauda equina compression. The results suggest that alleviation of pain and restoration of mobility are best achieved by segmental spinal stabilisation; a few patients require a combined anterior and posterior stabilisation. Postoperative radiotherapy should be given whenever possible, and the causative tumour should be treated by endocrine or chemotherapy, as indicated. 
2	Possible role of leukotrienes in gastritis associated with Campylobacter pylori. This study was done to evaluate the role of leukotrienes (LTs) in gastritis associated with Campylobacter pylori. Biopsy specimens of gastric mucosa were obtained endoscopically from 18 patients with nonulcer dyspepsia for bacteriological and histological examination and extraction of LTs. There was correlation between the LTB4 level in the mucosa and the degree of gastritis evaluated histologically. The level was higher when infiltration of neutrophils in the gastric mucosa was more extensive. The LTB4 level in mucosa infected with C. pylori was higher than that in noninfected mucosa. These findings suggest that endogenous LTs may be related to the pathogenesis of gastritis associated with C. pylori. 
1	Radiation therapy of early (stages I and II-A) seminoma of testis after initial orchiectomy. With initial orchiectomy and radiation therapy, the prognosis of the patients with early (Stages I and II-A) testicular seminoma is nearing almost 100 percent. Thirty-two patients with Stage I and 13 patients with Stage II-A seminoma of the testis were treated with initial orchiectomy. This was followed by estimation biochemical markers and radiologic investigations. All the patients with Stage I disease received radiotherapy to the ipsilateral pelvic and para-aortic nodes. The patients with Stage II-A disease also received radiation therapy to the supradiaphragmatic regions. The disease-free survival in both groups of patients was found to be 100 percent. 
3	Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia. 
3	Barrett's esophagus in children and young adults. Frequent association with mental retardation. Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication. 
1	High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials. 
1	Flow cytometric DNA index in the prognosis of colorectal cancer. The authors investigated the relationship between flow cytometric DNA index (DI, defined as the ratio of the DNA content of malignant cells to that of normal cells) and other prognostic factors (grade and stage, anatomical site, age and sex) with the survival of 115 patients with colorectal cancer. Multiple biopsy specimens from 62 patients were taken during colonoscopy before surgery. Additional samples from 53 patients were obtained from paraffin-embedded material. All patients were treated with surgery only. Fresh-frozen material gave higher incidence of DNA aneuploidy than paraffin-embedded material (79% versus 41%). The patients with DNA diploid tumors (DI = 1) had a better overall survival than those with DNA aneuploid tumors (DI = 1). Among DNA aneuploid tumors, those with DI greater than 1.2 (excluding DI = 2) were worse than those with DI = 1.2 (excluding DI = 1) and DI = 2. Cox's regression analysis showed that pathologic stage was more important for prognosis than DNA index, whereas age, sex, histologic grade, and anatomic site were removed from the analysis as not relevant for prognosis. Relative risk of death (RR), in reference to patients with DI = 1 and Stages A + B (RR = 1), were RR = 1.8 for patients with carcinomas with Stage C. RR = 2.7 for patients with carcinomas with DNA near-diploid and DNA tetraploid tumors. RR = 3.5 for those with DI greater than 1.2 (excluding DI = 2), and RR = 8.0 for those with Stage D. These data indicate that flow cytometrically evaluated DI values have a relevant independent power for predicting the clinical outcome of colorectal cancer patients. 
1	The expression of progesterone receptors coincides with an arrest of DNA synthesis in human breast cancer. Two main models to account for the heterogeneous expression of estrogen receptors (ER) and progesterone receptors (PR) in human breast cancer have been proposed: the clonal model and the stem cell model. The authors previously provided evidence supporting the stem cell model since it was found that most of the proliferating cells in ER-positive (ER+) human breast cancer lack ER and that the ER-negative (ER-) and ER+ subpopulations are interrelated. The authors have analyzed in eighteen ER+/PR+ primary breast tumors the simultaneous expression of ER or PR (by immunohistochemistry) and DNA synthesis (by autoradiography) after 30 minutes of 3H-thymidine incorporation. The authors demonstrated that: (1) the average numbers of ER+ and PR+ cells were similar (36.8 +/- 10.7% and 39.3 +/- 17.6%, respectively); (2) The thymidine-labeling indexes of the ER+, ER-, PR+, and PR- subpopulations were 0.53 +/- 0.69%, 0.74 +/- 0.49%, 0.21 +/- 0.21 and 0.94 +/- 0.54%, respectively; and (3) 75.2% of the DNA-synthesizing cells were ER-, and 88.8% of them were PR-. The authors conclude that the cellular subpopulations expressing ER and PR were not identical, and the expression of PR was associated with a lower rate of cellular proliferation than was ER expression. 
4	Coronary flow and mental stress. Experimental findings. The hemodynamic, electrocardiographic, and coronary flow responses to a psychological test were studied in 13 pigs both in the absence (group 1, n = 8) and the presence (group 2, n = 5) of a transient occlusion of the left anterior descending coronary artery. The psychological test consisted of presenting food to a fasting but restrained animal for 3 minutes. In group 1, stress increased the heart rate from 128 +/- 5 to 176 +/- 8 beats/min (mean +/- SEM) and arterial pressure from 93 +/- 4 to 112 mm Hg. Comparing the individual increase in rate-pressure product with the increase in coronary conductance during the test, a parallel response was found in only two animals, whereas a relatively lower coronary conductance was observed in the remainder, suggesting vasoconstriction. Clinical signs of ischemia or life-threatening arrhythmias were never observed in this group of animals. Each group 2 animal underwent two occlusions of the left anterior descending coronary artery, randomly performed on separate days both in the presence and the absence of the food deprivation stress. When the latter was applied in the presence of occlusion, all animals developed ventricular fibrillation in less than 2 minutes (mean, 81.4 seconds). Conversely, only one animal had ventricular fibrillation when a 3-minute occlusion was performed without exposure to stress. This occurred despite the fact that more severe ischemia (as detected by an increase in left ventricular end-diastolic pressure and decreases in dP/dt and systolic pressure) was recorded at 3 minutes of occlusion. 
3	Multiple noncontiguous spine fractures. The data from a prospective study of 508 spine injuries were reviewed to determine the incidence of multiple noncontiguous spine fractures. All patients were examined at admission and at 1 and 2 years postinjury. This series identified 77 (15.2%) multilevel fractures. Motor vehicle accidents were the primary cause of these fractures. The incidence of neurologic injury was not significantly different between multiple noncontiguous and single fractures. Failure to use seat belts and ejection from the vehicle were the main factors associated with multiple noncontiguous spine injuries. Seven major fracture patterns were identified, which accounted for 60% of these injuries. The prognosis for multilevel spine fractures was not significantly worse that that for single-level injuries. 
5	Laryngeal dystonia: a series with botulinum toxin therapy. Laryngeal dystonia is a syndrome characterized by action-induced, involuntary spasms of the laryngeal muscles. Most patients have involvement of the adductor laryngeal muscles producing uncontrolled spasms during phonation, and a "strain-strangle" speech pattern commonly termed "spastic dysphonia." Other patients have involvement of the abductor muscles producing "whispering dysphonia." Rare patients have paradoxical vocal cord motion during respiration with adductor spasms on inspiration. Over the past 5 years we have used botulinum toxin (BOTOX) to treat more than 200 patients with laryngeal dystonia. This group includes patients with adductor involvement (phonatory dystonia, recurrent laryngeal nerve section failure, respiratory dystonia) and those with abductor involvement (whispering dystonia). Patients received benefit within 24 to 72 hours, with sustained improvement for 2 to 9 months with an average of 4 months. Patients improved to an average of 90% of normal function. Clinically significant adverse effects included extended breathy dysphonia and mild choking on fluids. BOTOX has become our treatment of choice for dystonic conditions of the larynx. 
4	Surgical repair of Wolff-Parkinson-White syndrome complicated with myocardial bridging. Myocardial bridging causes myocardial ischemia during supraventricular tachycardia. We present a case of Wolff-Parkinson-White syndrome combined with myocardial bridging. The patient complained of angina pectoris during paroxysmal supraventricular tachycardia because of severe constriction of the left anterior descending coronary artery during systole. A myocardial scintigram revealed myocardial ischemia in the anteroseptal wall during paroxysmal supraventricular tachycardia. Myotomy to prevent myocardial bridging and interruption of the accessory conduction pathway was successfully accomplished in a one-stage operation. 
5	Long-term results of submandibular duct transposition for drooling. This study examines the long-term results and morbidity of submandibular duct transposition in drooling children. Twenty-two patients, aged 3 to 18 years, with neurological dysfunction and excessive drooling underwent submandibular duct transposition between 1984 and 1987. In January 1990, 20 patients were reviewed. Their degree of drooling pre-operatively, immediately post-operatively and currently was assessed. The rate of improvement and the occurrence of complications were noted. Drooling was 'much better' in the early post-operative period in 17 of the 20 patients, and this improvement was invariably noted within three weeks. In the three other patients drooling was 'better'. Deterioration occurred in only three patients over the entire follow-up period. Complications all occurred in the first 18 months following surgery; they consisted of salivary retention cysts in four and transient submandibular gland swelling in a fifth patient. 
5	Hepatocyte expression of HBcAg and serum HBeAg in hepatitis B: comparison of polyclonal and monoclonal antibodies during a trial of interferon. The distribution and quantitative expression of HBcAg in relation to serum HBeAg and liver histology before and after a trial of interferon in 50 patients with chronic type B hepatitis were evaluated using polyclonal and monoclonal antibodies. In general, both antisera showed a similar pattern in terms of the distribution of HBcAg, with predominant localisation of HBcAg in the cytoplasm in HBeAg positive patients with chronic active hepatitis. Semiquantitative analysis showed, however, that there was a higher degree of cytoplasmic expression of HBcAg with polyclonal than with monoclonal anti-HBc. Some of the HBeAg positive patients with only a focal expression of HBcAg in the cytoplasm by polyclonal anti-HBc showed no expression of HBcAg with monoclonal anti-HBc. The expression of HBcAg with polyclonal anti-HBc correlated better with the histological features of chronic active hepatitis or the persistence of serum HBeAg on follow up, suggesting that it did not result from non-specific or false positive staining. All of the HBeAg negative patients with minimal histological changes or inactive cirrhosis were HBcAg negative with both antisera. In conclusion, though both polyclonal and monoclonal antibodies produced a quite similar distribution of HBcAg in patients with chronic type B hepatitis, polyclonal antibody seemed to be more sensitive in detecting HBcAg in the cytoplasm than did monoclonal anti-HBc, and the expression of HBcAg with polyclonal anti-HBc correlated better with the clinical and histological outcome. 
1	Measurement techniques for melanoma: a statistical comparison Inter- and intra-observer variation in measuring the depth of invasion of malignant melanomas was assessed using three different techniques: eye-piece graticule, stage Vernier, and projection image analysis. Significant variation was found for all methods but was least pronounced with the stage Vernier. It is recommended that this should be the preferred technique for routine use. 
5	One hundred percent oxygen reverses muscle hypoxia in a rat hindlimb model of acute arterial occlusion. Significant morbidity results from extremity ischemia after acute arterial occlusion. Reestablishment of arterial flow is considered to be the ideal treatment, yet substantial tissue loss can occur before this is accomplished. Using a rat hindlimb model we investigated whether the administration of 100% oxygen would decrease tissue hypoxia from acute arterial occlusion. Adult male Sprague-Dawley rats were used, and Po2 recordings were taken from the gastrocnemius muscle by use of an oxygen electrode. Baseline muscle Po2 was recorded, and then the femoral artery was occluded. Repeat recordings were made after 20 minutes of ventilation with room air and after an additional 20 minutes of ventilation with 100% oxygen (N = 10). Control groups consisted of animals undergoing occlusion but continued on room air (N = 3) and animals undergoing sham occlusion but receiving the period of 100% oxygen ventilation (N = 3). Femoral artery occlusion produced a reduction in muscle Po2 from 28.0 +/- 1.4 to 6.1 +/- 2.0 (mean +/- SEM, p less than 0.001). Ventilation with 100% oxygen reversed the tissue hypoxia produced by occlusion (27.3 +/- 2.0, p less than 0.001). The administration of 100% oxygen without femoral artery occlusion resulted in a higher tissue Po2 than the occluded + oxygen group (94 +/- 12 vs 27.3 +/- 2.0, p less than 0.001). Mean arterial blood pressure increased in the experimental group concomitant with the administration of 100% oxygen, but there was no correlation between final blood pressure and final tissue oxygen tension. 
5	Influence of hepatitis delta virus replication in the presence of hepatitis B virus DNA in peripheral blood mononuclear cells. The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti-hepatitis delta positive), 16 anti-HBc-positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc-positive, HBsAg-negative patients. In anti-hepatitis delta-negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta-positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA-negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients. 
1	Altered expression of the retinoblastoma gene product in human sarcomas. BACKGROUND. The retinoblastoma-susceptibility (Rb) gene is a prototype tumor-suppressor gene originally isolated from patients with heritable retinoblastoma. This gene encodes a nuclear phosphoprotein whose expression is altered in several types of human tumors. METHODS. We studied the expression of the Rb protein in 44 primary and 12 metastatic high-grade human sarcomas by means of immunohistochemical methods and Western blotting. Computerized image analysis was used to quantify the level of Rb gene product in individual tumor cells. The expression of the Rb gene was then correlated with clinical outcome in the patients with primary tumors. RESULTS. Of the 44 patients with primary sarcomas, 13 (30 percent) had tumors with normal, homogeneous expression of the Rb protein in essentially all tumor cells. Thirty-one patients with primary tumors (70 percent) had altered Rb expression; in 18 (40 percent) the Rb protein was heterogeneously expressed, and in 13 (30 percent) it was detected in fewer than 20 percent of the tumor cells. All 12 of the patients with metastatic sarcomas had altered expression of the Rb protein. When the findings in the patients with primary tumors were correlated with clinical outcome, survival was found to be significantly increased in the patients whose tumors had homogeneous Rb expression, as compared with those with either heterogeneous expression (P = 0.026) or no expression (P = 0.012). CONCLUSIONS. Tumors in which the expression of Rb gene product was decreased were more aggressive than tumors in which this protein was expressed by nearly all cells. The Rb gene product may be an important prognostic variable in patients with these tumors. 
3	Functional outcome measures in stroke rehabilitation. I examine statistical considerations in the analysis of functional outcome following stroke and discuss the mathematical relation between improvement in function and discharge functional score. I demonstrate mathematically that the predictor variables of improvement and discharge functional score are the same and that the regression coefficients for improvement and discharge functional score will be equal, except for the admission functional score, for which a mathematically defined relation exists. I argue that the relation between admission functional score and discharge functional score must be positive and strong and that the relation between admission functional score and improvement must be negative for the stroke population. I believe that an ignorance of statistical concepts, especially confounding, and of the differences between raw correlations, partial correlations, and predictors have led to much confusion in functional outcome research. 
4	Hemodynamic determinants of subdiaphragmatic venous return during closed-chest CPR in a canine cardiac arrest model. OBJECTIVE: To assess the hemodynamic determinates of peripheral subdiaphragmatic venous-to-right-heart return during closed-chest CPR. MODEL: Seven anesthetized dogs subjected to electrically induced ventricular fibrillation for five minutes. INTERVENTIONS: Conventional closed-chest CPR and closed-chest CPR with continuous abdominal binding at a chest compression rate of 60 per minute, a compression-to-relaxation ratio of 50:50, and a ventilation-to-compression ratio of 1:5. METHODS: Solid-state catheters were positioned in the ascending aorta, right atrium (RA), and inferior vena cava (IVC). Cannulating electromagnetic flow probes were inserted into the IVC and a carotid artery. Analog-to-digital conversion was performed electronically. Five minutes after ventricular fibrillation was induced, interventions were performed in an alternating sequence. Systolic, diastolic, and mean pressures and flows were measured and compared. STATISTICAL METHODS: Two-tailed, unpaired t test applied to equal sample size, linear regression analysis, and multiple regression analysis. RESULTS: Abdominal binding during CPR significantly increased (P less than .05) all measured systolic and diastolic CPR intravascular pressures compared with CPR without abdominal binding but did not affect IVC-to-right-heart venous return. During conventional CPR without abdominal binding, venous return was dependent on the diastolic IVC pressure (r = .86, P = .014), mean IVC pressure (r = .80, P = .03), and carotid blood flow (r = .99, P = .001) but not on the IVC-to-RA pressure gradient. With abdominal binding, venous return was not correlated with any study hemodynamic variable, including the peripheral venous-to-RA pressure gradient. CONCLUSION: Venous return from the subdiaphragmatic venous bed during CPR is dependent on venous pressure, not on the peripheral venous-to-right-heart pressure gradient. Abdominal binding during CPR does not affect venous return. Venous return during CPR diastole is highly dependent on central venous capacitance (left heart outflow during CPR systole). 
1	Bilateral familial carotid body paragangliomas. Report of a case with DNA flow cytometric and cytogenetic analyses. A case study of bilateral familial carotid body paragangliomas with DNA flow cytometric and cytogenetic analyses is presented. Analysis of tumor cell nuclear DNA content by flow cytometry revealed aneuploid cell populations in both tumors. Standard cytogenetic analysis (Giemsa-banding technique used) of the right carotid body paraganglioma showed no evidence of numerical or structural abnormalities. We describe parameters currently used to "predict" biological behavior in these tumors. 
3	Visuospatial impairment in Parkinson's disease. We explored the nature of the visuospatial deficit in Parkinson's disease (PD) and its progression as a function of disease duration. We compared the performance of 183 patients with idiopathic PD and 90 control subjects matched for age and education on six visuospatial measures. We divided patients into three groups according to the disease duration: early (1 to 4 years), middle (5 to 10 years), and advanced (greater than 10 years). Performance deteriorated in five of the six visuospatial measures, as a function of disease duration. However, the pattern of visuospatial decline depended on whether dementia was present. The results were not influenced by age or anticholinergic medication. These findings support the presence of visuospatial deficits in PD patients, with a changing pattern of impairment related to dementia and progression of the disease. 
5	Recurrent urethral stricture disease managed by clean intermittent self-catheterization. We studied 41 patients with urethral stricture who had failed at least 1 operation, and were being maintained with filiform and follower dilation every 6 to 12 weeks. The patients were instructed in clean intermittent self-catheterization with a 16F red rubber catheter, which was performed every 1 to 30 days. Followup from 9 to 36 months revealed excellent compliance and average peak uroflow rates increased from 5.5 cc per second before dilation to 17.1 cc per second at the last followup visit. Clean intermittent self-catheterization is a simple method to maintain a patent urethra and obviates the need for further operations or painful dilations. 
3	Long-term follow-up review of 31 children with severe closed head trauma. Thirty-one children aged 3 to 15 years were followed for 5 to 11 years after suffering severe closed head trauma which caused coma for 1 week or more (median duration of coma 3 weeks). One patient remained in a persistent vegetative state until his death 9 years later. The other 30 recovered consciousness and were discharged. All suffered diminution of their abilities, and 24 of them had major permanent disability. The most common motor disabilities were pure spastic hemiparesis (seven cases), basal ganglia syndromes (four cases), ataxia (three cases), and a combination of hemiparesis and ataxia (five cases). Of the 30 patients, 26 regained independent ambulation, seven were epileptic, and 14 were dysarthric in various degrees. Only 10 had the cognitive ability to profit from the normal educational system, and none had attempted postsecondary education. Social problems were common. The worst outcomes were associated with intracranial bleeding and/or brain contusion seen on computerized tomography (CT) scans at the acute stage; the best were associated with normal CT scans. The degree of residual disability in these children seems no less than that of adults with trauma of similar severity. 
4	Plaque and structural characteristics of the descending thoracic aorta using transesophageal echocardiography. The in vivo acoustic and structural characteristics of atherosclerosis in the descending thoracic aorta have not been well delineated. We prospectively evaluated the descending thoracic aorta of 147 patients (35 women and 112 men; age, 61 +/- 14 years) who underwent clinically indicated transesophageal echocardiography. Patients with suspected disease of the aorta were excluded. Thirty-eight patients (26%) had protruding plaques (men, 25%; women, 29%). Six patients had mobile intimal densities with the mobile area ranging up to 1 cm2. As expected, aortic lumen area was decreased (plaque-free, 3.53 cm2; plaque, 3.19 cm2; p less than 0.05) and wall area was increased (plaque-free, 1.51 cm2; plaque, 1.92 cm2; p less than 0.05) in the regions of the plaque. However, total arterial area was not increased (plaque-free, 5.04 cm2; plaque, 5.09 cm2; difference not significant) in a compensatory manner as observed in other arterial beds. Plaque gray scale was less than the gray scale of plaque-free wall (plaque-free, 141.2; plaque, 122.7; p less than 0.05) when compared at the same level of the descending thoracic aorta or with a second aortic plaque-free level (plaque-free, 150.4; plaque, 122.7; p less than 0.05). Standard deviation of gray scale level was similar between plaque and normal regions. Unsuspected protruding plaques in the descending thoracic aorta occurred in one quarter of the patients referred for routine transesophageal examination. Plaques tended to have lower echogenicity and were differentiated from plaque-free walls within patients. Plaque formation did not result in increased total arterial area. These data suggest that the degree or character of compensatory atherosclerotic remodeling in the highly elastic descending thoracic aorta may differ from other arterial beds. 
1	The value of push-type jejunal endoscopy in familial adenomatosis coli/Gardner's syndrome. Push-type jejunal endoscopy using a long forward-viewing duodenofiberscope was performed in 10 patients with familial adenomatosis coli/Gardner's syndrome. Jejunal polypoid lesions were detected in nine of the 10 patients (90%). The lesions appeared sessile, whitish, and measured 3 mm or less in diameter. Histologic findings of the biopsy specimens from these polypoid lesions revealed tubular adenoma in all nine patients. In addition, this method led to the detection of duodenal adenomas in one patient, in whom duodenofiberscopy with the side-viewing instrument revealed no polypoid lesions in the bulb and second portion of the duodenum. In view of these results, we recommend that push-type jejunal endoscopy, as well as side-viewing duodenofiberscopy, should be added to the usual preoperative examinations done in patients with this disease. 
1	Autologous antibodies eluted from membrane fragments in human ovarian epithelial neoplastic effusions. III. Cytotoxic potential in vitro and characterization of antigen(s). Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain immunoglobulins with antitumor activity. Autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions react with cell-surface antigens on different human ovarian cell lines, surgical specimens of human ovarian adenocarcinoma, and human ovarian tumors grown in athymic Balb/c mice. The antibodies do not react with tissue preparations from normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that these antibodies are capable of complement-mediated lysis of human ovarian tumor cell lines in vitro. Preliminary characterization of the autologous ovarian tumor-associated antigen(s) indicates that it may be composed of three large-molecular-weight proteins of 182,000, 164,000, and 122,000 d. 
5	Postoperative ectopic craniopharyngioma. Case report. The case of an ectopic craniopharyngioma arising from a seed of tissue deposited along the operative track is reported. The uniqueness of this lesion is addressed. Ideal therapy and controversies regarding radiation therapy of craniopharyngiomas are discussed in light of this new variation in recurrence. 
1	Immunophenotyping in the management of gastric lymphoma. Primary gastric lymphoma is a rare tumor in which surgical resection plays a major role in improving the response rate and reducing the incidence of bleeding and perforation after chemotherapy. In 17 consecutive patients, the diagnosis of gastric lymphoma was made by immunophenotyping snap-frozen endoscopic biopsy specimens. All neoplasms were B-cell lymphomas. Pan B surface marker antigens were present in all patients. Levels of Ki-67, a nuclear marker of tumor proliferation, were greater than 45% in two of the four patients who died after progression of their lymphoma. All patients alive had Ki-67 levels of less than 30%. A lower proliferation index, as measured by Ki-67, appears to be associated with better prognosis. Ten of 11 patients treated by resection prior to chemotherapy had no complications. Immunophenotyping is the key in the differential diagnosis when considering malignant lymphoma with gastric carcinoma and benign conditions such as pseudolymphoma. 
4	Ultrasonographic diagnosis of a large placental intervillous thrombosis associated with elevated maternal serum alpha-fetoprotein level. A placental lesion associated with elevated maternal serum alpha-fetoprotein level and a positive Kleihauer-Betke test is reported. Serial ultrasonograms showed a progressive increase in the echogenicity of the lesion that corresponded to a large intervillous thrombosis after delivery. This case illustrates the importance of detailed ultrasonographic and pathologic placental investigations in pregnancies with unexplained elevated levels of alpha-fetoprotein. 
1	Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension. A series of 15 consecutive children with head and neck nonorbital rhabdomyosarcoma (RMSA) with meningeal extension were prospectively treated with chemotherapy consisting of Adriamycin (doxorubicin; Adria Laboratory, Columbus, OH) (ADM), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) followed by radiotherapy (60 Gy) to the primary tumor volume, along with intrathecal methotrexate (IT MTX). Thirteen of 15 responded to preradiation chemotherapy. Four of 13 relapsed. Relapse occurred at the level of the primary tumor in three of four. The 3-year progression-free survival (PFS) was 59%, similar to that achieved in a previous series treated with a comparable therapeutic approach that also included whole-brain radiotherapy as a prophylaxis of possible occult meningeal seeding. It is concluded that CNS prophylaxis with radiotherapy is questionable in the management of childhood RMSA with meningeal extension. 
1	Expression of beta 1 integrins in normal human keratinocytes. The majority of cell adhesive events to the extracellular matrix are mediated by cell surface receptors, beta 1 integrins. Keratinocytes express at least six different polypeptides of beta 1 integrin class, namely beta 1, alpha 2, alpha 3, alpha 5, and alpha 6 (alpha 6 is mainly associated with beta 4 polypeptide). These epithelial cells use alpha 2 beta 1 as a collagen receptor and alpha 3 beta 1 as a fibronectin receptor, while alpha 6 beta 4 is the major basement membrane receptor. Expression of alpha 5 beta 1 complex is low. Processing of beta 1 integrins is fast in keratinocytes; half-maximal maturation takes only 3 hours. In addition to their function in cell-matrix interactions, beta 1 integrins (alpha 2 beta 1 and alpha 3 beta 1) have also a role in maintaining keratinocyte cell-cell interactions. It is possible that resting basal keratinocytes use beta 1 integrins as cell-cell adhesion receptors, and during activation, like in wound healing, these receptors relocalize to mediate events involving cell-matrix interactions. 
3	Long-term efficacy of primary laser trabeculoplasty. Sixty glaucomatous eyes of 60 patients treated with laser trabeculoplasty as primary therapy were reviewed retrospectively. There were 42 eyes with capsular glaucoma and 18 with simple glaucoma. The mean prelaser intraocular pressure (IOP) was 35.2 (SD = 6.5) mmHg. Success was defined as IOP less than or equal to 22 mmHg without medication. The probability of success was 0.73 at 1 year, 0.66 at 2 years, 0.57 at 3 years, and 0.50 at 4 years. Three eyes experienced progressive visual field loss or disc damage in spite of an intraocular pressure below 22 mmHg without medication. High prelaser pressure and the severity of the visual field defects were significant predictors of treatment failure. 
5	Cluster of fulminant hepatitis B in crack users. Fulminant hepatitis occurs in only 1% of acute hepatitis B patients, requiring hospitalization, but coinfection with delta virus increases the incidence. Hepatitis B and D infection are commonly associated with intravenous drug abuse, but there have been no previous reports of an association with nonparenteral cocaine. Crack use, via sexual promiscuity, is associated with an increased risk for human immunodeficiency virus infection, but has never been associated with viral hepatitis. We report four fatal cases of fulminant hepatitis B including, one with delta virus coinfection and one with human immunodeficiency virus (HIV) infection, in young, sexually active, heterosexual crack users. These patients denied a history of intravenous drug abuse. Our patients probably contracted hepatitis B infection via heterosexual contact. Chronic cocaine exposure may or may not have contributed to the fulminant outcome. Crack users may be at increased risk of developing hepatitis B and D infection. Epidemiological studies are needed to evaluate their risk of viral hepatitis and the effect of cocaine on its outcome. 
5	Oxygen uptake and heart rate responses during hypoxic exercise in children and adults. Control of ventilation and heart rate during exercise appears to undergo maturation, while aerobic metabolism (VO2) may not. Since we had previously found that hypoxia during exercise produced different ventilatory responses in children (C) compared to adults (A), we hypothesized that VO2 and heart rate kinetics during exercise would show similar maturational responses to hypoxia. To test this hypothesis, we examined the responses during progressive (ramp) and constant work rate tests in children and adults breathing either room air or hypoxic gas (FiO2 = 0.15). When corrected for body weight, children and adults had similar values for lactic acidosis threshold (LAT) (C: 29.1 +/- 5.0 ml.min-1.kg-1; A: 27.9 +/- 4.3) and VO2max (C: 40.7 +/- 8.6 ml.min-1.kg-1; A: 45.2 +/- 6.7) during normoxia. Hypoxia significantly lowered LAT (C: 27.5 +/- 5.4 ml.min-1.kg-1; A: 23.2 +/- 3.8; both P less than 0.05) and VO2max (C: 37.7 +/- 8.3 ml.min-1.kg-1; A: 40.1 +/- 5.3; both P less than 0.05) in both children and adults. Metabolic efficiency (delta VO2/delta work rate) and the VO2-heart rate relationship (delta VO2/delta HR/kg) were similar in the two groups and unaffected by hypoxia. During the constant work rate exercise, VO2 kinetics (time constant during phase 2 of the response (pi 1) and the O2 deficit) were similar between children and adults and were significantly slowed by hypoxia, consistent with current understanding of the control of oxidative metabolism. Finally, heart rate was increased at rest and during exercise with hypoxia, while the time to reach 75% of the end-exercise response was delayed significantly, in both groups. 
1	Cutaneous horn of the penis: its association with squamous cell carcinoma and HPV-16 infection. Cutaneous horns of the penis are rare. Including this case, only 19 cases have been reported in the English-language literature. In 37% of the reported cases a malignant tumor was found beneath the cutaneous horn. Our case is remarkable because a stage I squamous cell carcinoma developed on the shaft of the penis of a neonatally circumcised man. Human genital carcinoma resulting from a multifactorial process in which "promoting" papillomavirus is an integral element is being increasingly reported. We review the relationship of circumcision to genital human papillomavirus infection and their synergism in the development of squamous cell carcinoma. 
4	Hypertension with concomitant conditions: the changing role of beta-adrenoceptor blockade. Hypertension often is associated with concomitant conditions such as chronic obstructive lung disease, diabetes mellitus, ischemic heart disease, and peripheral vascular disease. Moreover, other cardiovascular risk factors, including dyslipidemias and abnormalities of glucose and insulin metabolism, are common in patients with hypertension. Conventional beta-blockers used for antihypertensive therapy can have adverse effects in patients with airway disease, diabetes, and peripheral vascular disease, and can exaggerate the other risk factors. Newer beta-blockers such as celiprolol, which have selective partial agonist activity expressed at beta 2-receptors, appear to avoid these problems. Celiprolol exhibits antianginal and antihypertensive efficacy without adversely effecting left ventricular systolic function or exercise performance. It also may cause regression of left ventricular hypertrophy. The stimulatory action of celiprolol on vascular beta 2-receptors enhances regional flow and may increase walking distance in patients with claudication. The reduction in renal vascular resistance demonstrated by this drug is associated with preservation of renal blood flow and function. Spirometric measurements of airway function are unchanged during celiprolol treatment. Similarly, there are no adverse effects on lipid or glucose concentrations. These new developments in beta-blocker pharmacology indicate that this class of agents could be used in patients with hypertension with concomitant diseases or risk factors other than high blood pressure. 
2	Human T cell lymphotropic virus infection in Guaymi Indians from Panama. Preliminary studies found that 9% of Guaymi Indians from Bocas del Toro province have antibody to human T cell lymphotropic virus (HTLV-I/II). The present study enrolled 317 (21% of the population) Guaymi Indians from Changuinola, the capital of Bocas del Toro province and 333 (70% of the population) from Canquintu, an isolated rural village. Demographic information and family relationships were ascertained and subjects were screened for neurologic diseases. Serum specimens were screened by an enzyme-linked immunosorbent assay for HTLV-I/II antibody and positives were confirmed according to U.S. Public Health Service criteria. Twenty-five (8%) Guaymi residing in Changuinola and 7 (2.1%) from Canquintu were confirmed seropositive. In Changuinola, antibody was virtually limited to residents greater than or equal to 15 years of age (24 [16%] of 153) and rates were slightly higher in males than in females; in Canquintu, antibody rates did not increase significantly with age and appeared higher in females than in males. In Changuinola, there was no evidence for household clustering of infection. In contrast, HTLV antibody among Canquintu residents clustered significantly by household. HTLV-associated neurologic disease was not detected in either population. The atypical seroepidemiology observed in both locations might be explained if the virus endemic to the Guaymi differed from HTLV-I previously described in the Caribbean basin and Japan. 
2	Significance of anti-HBx antibodies in hepatitis B virus infection. Serological responses to hepatitis B virus-X determinants have been noted in human sera, but conflicting findings concerning the correlation of anti-HBx antibodies with different stages of hepatitis B virus infection or pathological sequelae have been reported. Using an adenovirus-based eukaryotic vector, the 17 kD X protein was efficiently expressed in 293 cells. Cellular extracts containing the eukaryotic X protein have been used to screen for anti-HBx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis B virus chronic hepatitis, hepatocellular carcinoma and acute viral hepatitis. Sera from 32 of 171 (19%) chronic hepatitis B virus patients were positive for anti-HBx antibodies. Only one of thirty-two (3%) HBsAg-negative, anti-HBs/anti-HBc-positive chronic hepatitis serum was anti-HBx positive. Very few sera from primary hepatocellular carcinoma patients showed positivity for anti-HBx (8 of 149 or 5%). Anti-HBx were also detected in 8 of 48 (17%) acute viral hepatitis patients. In the four cases that were followed up weekly, anti-HBx antibodies appeared 3 to 4 wk after the onset of the clinical signs. To compare the X protein expressed in eukaryotic and prokaryotic cells as a substrate for anti-HBx antibody detection, 171 sera were screened with HBx fusion proteins expressed in Escherichia coli. The prokaryotic cell extract test seems to be more sensitive. During the chronic phase of hepatitis B virus infection, the presence of anti-HBx antibodies detected with the eukaryotic cell extract correlates with the presence of well-established markers of ongoing viral replication: serum hepatitis B virus-DNA (p less than 0.001) and intrahepatic HBcAg expression (p less than 0.001). 
4	Pulmonary vascular steal in chronic thromboembolic pulmonary hypertension. After pulmonary thromboendarterectomy, performed for relief of chronic thromboembolic pulmonary hypertension, perfusion lung scans have frequently disclosed new perfusion defects in segments served by undissected pulmonary arteries. Our hypotheses were that these new postoperative defects occurred with great frequency and did not represent postoperative vessel occlusion. We retrospectively reviewed the preoperative and postoperative perfusion scans of 33 consecutive patients undergoing pulmonary thromboendarterectomy. New postoperative perfusion defects were noted in 23 of 33 patients. The incidence of new defects was increased tenfold in segments that had (1) normal preoperative angiographic findings, (2) normal preoperative radionuclide perfusion, and (3) not been entered at the time of surgery. Postoperative angiograms, available in 15 of 33 patients, documented the nonembolic, nonocclusive nature of the new perfusion scan defects. The most plausible alternate explanation for this previously undescribed finding is a redistribution of pulmonary arterial resistance induced by the thromboendarterectomy, namely, a pulmonary vascular "steal.". 
2	Two cases of adult T-cell leukemia associated with acute pancreatitis due to hypercalcemia. We report two cases of adult T-cell leukemia associated with acute pancreatitis and hypercalcemia. After sudden onset of epigastralgia, acute pancreatitis and hypercalcemia were found in both patients. There were no diseases that could explain the acute pancreatitis except for hypercalcemia probably due to adult T-cell leukemia. Thus we considered that hypercalcemia due to adult T-cell leukemia had led to acute pancreatitis. This is the first report of such a complication in adult T-cell leukemia. 
3	Evolution of energy expenditure and nitrogen excretion in severe head-injured patients. OBJECTIVE: The aim of the study was to estimate the influence of therapeutic changes on the level of energy expenditure (EE) and N excretion in a homogeneous group of patients usually considered hypermetabolic. DESIGN: EE and N excretion of head-injured patients were measured simultaneously at phases 1 and 2 (patients treated 4 +/- 3 and 18 +/- 8 days after injury, respectively). SETTING: Acute care hospital. PATIENTS: Eight severe head-injured patients, mean weight 63.1 +/- 6.1 (SD) kg, mean age 21 +/- 3.8 (SD) yr. INTERVENTIONS: At phase 1, all patients were sedated with fentanyl (6.7 +/- 1.9 micrograms/kg.hr) plus flunitrazepam (9.1 +/- 4.8 micrograms/kg.hr) and were mechanically ventilated. All patients received continuous total parenteral nutrition. The nonprotein caloric intake averaged 1092 +/- 200 kcal/day, including 77% glucose and 23% fat (Intralipid 20%). The total N intake averaged 7 +/- 5 g/day, consisting of crystalline amino acids. At phase 2, no patient received any sedative and all were breathing spontaneously via tracheostomy. All patients received parenteral and/or enteral nutrition. The nonprotein caloric intake averaged 1929 +/- 200 kcal/day consisting of 65% carbohydrates and 35% fat. The total N intake averaged 13 +/- 2 g/day. MEASUREMENTS AND MAIN RESULTS: The EE was significantly higher at phase 2 than at phase 1 (2121 vs. 1737 kcal), but the interindividual variability was low at both phases. N excretion was high at the two periods of the study and not correlated to the level of EE. The RQ was 0.75 at both periods, indicating predominant fat oxidation. CONCLUSIONS: We could not demonstrate any parallelism in the evolution of EE and protein catabolism in head-injured patients. The therapeutics (mechanical ventilation, sedation, and nutrition) have a major effect on EE but little on N excretion. 
5	Role of nerve-sparing radical prostatectomy for clinical stage B2 prostate cancer. To examine the role of nerve-sparing radical prostatectomy in patients with clinical stage B2 prostate cancer we reviewed the first 77 such patients in our series since we adopted the nerve-sparing technique. A total of 47 patients (61%) underwent bilateral and 26 (34%) underwent unilateral nerve-sparing prostatectomy, while in 4 (5%) both neurovascular bundles were resected. Among the patients followed for 12 months 27 of 41 (66%) treated with bilateral and 7 of 19 (37%) treated with unilateral nerve-sparing prostatectomy had potency preserved. With the strict clinicopathological criteria of organ-confined tumor, that is intracapsular tumor with negative surgical margins and undetectable postoperative prostate specific antigen levels, complete tumor excision was achieved in 17 patients (36%) treated with bilateral and 7 of 26 (27%) treated with unilateral nerve-sparing prostatectomy. All patients in whom both neurovascular bundles were resected had pathological stage C or D1 disease. Of the 24 patients who had complete tumor excision by the strict criteria only 15 (19.5% of the 77 preoperatively potent patients) had potency preserved. Of these patients 19 had microscopically positive margins without seminal vesicle invasion (pathological stage C1) with undetectable postoperative prostate specific antigen levels. In addition, 4 patients had seminal vesicle involvement with negative surgical margins and undetectable postoperative prostate specific antigen levels. If these patients also are considered as having complete tumor excision, there was an over-all complete tumor excision rate of 61% (47 of 77), of whom 25 (32% of the 77 patients) had preservation of potency. Ten patients with clinical stage B2 tumor whose potency was preserved had histological and serological evidence of incomplete tumor excision. Of 53 patients with pathological stage C1 disease 9 (17%) had margins positive only in the regions of the neurovascular bundles. Preoperative prostate specific antigen and acid phosphatase levels, and findings on transrectal ultrasonography failed to predict accurately which patients had extracapsular tumor extension. Patients with poorly differentiated tumors and/or bulky disease on rectal examination had a higher incidence of extracapsular extension and positive margins. We conclude that in the majority of potent patients with clinical stage B2 prostate cancer not all of the goals of nerve-sparing radical prostatectomy are realized.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Macrophages stimulate bone resorption when they phagocytose particles. We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene. 
4	Exercise echocardiography and technetium-99m MIBI single-photon emission computed tomography in the detection of coronary artery disease. To compare the relative diagnostic value of exercise echocardiography with perfusion technetium-99m metoxyisobutylisonitrile single-photon emission computed tomography (SPECT) in detecting coronary artery disease (CAD), 75 patients with suspected CAD but a normal electrocardiogram (ECG) at rest were included in a prospective correlative study. Both the exercise echocardiograms and SPECT studies were performed in conjunction with the same symptom-limited bicycle exercise test. The development of either a new wall motion abnormality or a reversible perfusion defect after exercise, or both, were regarded as a positive test for the exercise echocardiographic and SPECT studies, respectively. The results of these 2 diagnostic tests were compared with coronary arteriography. Exercise echocardiography identified 35 (71%) and SPECT 41 (84%, p = 0.13) of the 49 patients with significant CAD (defined as greater than 50% diameter stenosis). Twenty-five of the 26 patients (96%) without significant coronary stenosis had negative exercise echocardiographic results and 23 of 26 (88%) had negative SPECT results. Exercise-induced new wall motion abnormalities showed a good correlation with reversible perfusion defects, and the results of the 2 methods were concordant in 65 of 75 patients (agreement = 88%, kappa = 0.75 +/- 0.14). Both the diagnostic accuracy of exercise echocardiography and SPECT were significantly higher than the exercise ECG (81 vs 64%, p less than 0.02 and 88 vs 64%, p less than 0.005). The sensitivity and specificity for detecting individual diseased vessels were 60 and 95% for exercise echocardiography and 67 and 94% for SPECT. 
2	Transient mitral regurgitation due to mitral valve prolapse accompanied by systolic anterior motion of the mitral valve. A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure. 
5	Acute hypervolaemia increases gastroduodenal resistance to the flow of liquid in the rat. The effect of volume expansion of extracellular fluid on gastroduodenal resistance to the flow of isotonic saline was assessed in three groups of rats using intravenous infusions of isotonic, isotonic-isoncotic, and isotonic-isoncotic-isohaemic solutions. The gastroduodenal segment of 29 male Wistar rats was barostatically perfused at a constant pressure gradient of 4 cm H2O and changes in flow (ml/minute) were taken as a reflection of changes in gastroduodenal resistance. Isotonic expansion led to a 33% drop in gastroduodenal flow compared with the normovolaemic period in the same animals (p less than 0.01). Extracellular fluid expansion with isotonic-isoncotic and isotonic-isoncotic-isohaemic solutions was associated with reductions in gastroduodenal flow of 29% (p less than 0.05) and 31% (p less than 0.01) respectively. The increase in gastroduodenal resistance is due to hypervolaemia per se and not to haemodilution, decreases in plasma oncotic pressure, or electrolyte imbalance. The effect of hypervolaemia on gastroduodenal resistance, which was reversed by small haemorrhages (0.5-1.0 ml per 100 g body weight), may be due to changes in tonus or phasic motor activity, or both, and may be part of the homeostatic processes that help the organism minimise liquid volume excess. 
5	Final height in boys with untreated constitutional delay in growth and puberty. To determine the natural history and psychological impact of the growth pattern in boys with constitutional delay in growth and puberty (CDGP), 43 boys presenting with short stature due to CDGP were followed up to final height. At presentation mean (SD) chronological age was 14.0 (1.9) years, bone age delay 2.7 (1.0) years, standing height standard deviation score (SDS) -3.4 (0.6), and predicted adult height SDS -1.3 (0.7). Final adult height SDS was -1.6 (0.9), measured at 21.2 (2.6) years. There was no significant difference between final height and predicted adult height, but there was a significant difference between final height and measured mid-parental height. Psychological questionnaires showed no significant difference in self esteem, marital, or employment state between the CDGP group and a control group. There was no correlation between self esteem and final height, but 25 felt their growth delay had affected their success either at school, work, or socially and 20 would rather have had treatment to advance their growth spurt. This study supports the more frequent use of active medical treatment to advance growth in boys with CDGP, and shows that although boys with CDGP reach their predicted heights, this is short for their families. 
3	Paraesthesia with lumbar epidural catheters. A comparison of air and saline in a loss-of-resistance technique. The epidural space was located in 32 obstetric patients using loss of resistance to air, while in a further 35 saline was used. The incidence of paraesthesia was 56% in the air group and 57% in the saline group. There was no significant difference between the groups in terms of other complications or in the quality of analgesia provided. 
3	Effects of MK-801 on recovery from sensorimotor cortex lesions. Histologic evidence suggests that drugs acting as noncompetitive antagonists at the N-methyl-D-aspartate receptor can have beneficial or pathologic effects on central nervous system neurons. In the present experiments we examined the effects of MK-801 on recovery of behavioral function after unilateral lesions in the rat somatic sensorimotor cortex. In the first experiment, rats with unilateral sensorimotor cortex lesions were given either MK-801 (1 mg/kg) or saline 12-16 hours after surgery. Additional injections were given on postoperative days 2, 4, and 6. Behavioral tests measured somatosensory asymmetries (i.e., bilateral tactile stimulation tests) and forelimb placing. After creation of sensorimotor cortex lesions, rats showed an ipsilateral somatosensory bias and an impairment in placing the contralateral forelimb. Rats treated with MK-801 recovered slightly faster than saline-treated animals as measured by a bilateral tactile stimulation test (p less than 0.05). In contrast, there was no significant difference between the groups in the recovery of forelimb placing. In a second experiment, rats with sensorimotor cortex lesions were treated with a single injection of MK-801 after behavioral recovery. Twenty hours after the MK-801 injection, rats with sensorimotor cortex lesions showed a reinstatement of the placing deficits. The impairment endured for at least 7 days after injection. These behavioral data support the idea that MK-801 can have either beneficial or detrimental effects when administered after brain damage. 
4	Spinal extradural cavernous hemangioma. Three cases of isolated spinal extradural cavernous hemangiomas are reported, two in the thoracic and one in the lumbar region. One of them manifested as acute cord compression, the other two as chronic progressive myelopathy or radiculopathy. A total excision or subtotal excision with irradiation was performed. All of them had good functional recovery. The clinical picture, radiological diagnosis, and optimal method of treatment are discussed. The relevant literature is reviewed. 
5	Cerebral infarction: early detection by means of contrast-enhanced cerebral arteries at MR imaging. The authors describe a new magnetic resonance (MR) imaging sign of acute cerebral ischemia/infarction. Abnormally contrast material-enhanced curvilinear structures were demonstrated in eight patients in the evolving area of cerebral ischemia/infarction within 26 hours after the ictus on contrast-enhanced, high-field-strength (1.5-T), T1-weighted spin-echo images. The abnormal enhancement is considered to represent cortical arterial vessels of markedly slowed circulation in areas of underlying brain injury, which will eventually progress to frank brain infarction. This was demonstrated at computed tomographic (CT) and follow-up MR examinations. Characteristically, the degree of the contrast enhancement of vessels appeared most intense in the proximal portions, and the intensity of enhancement gradually diminished in the more distal portions of these vessels as they pass over the convexities and finally disappear. 
5	Characterization of a rat pancreatic secretory protein associated with pancreatitis. A new protein was purified from the pancreatic juice of rats with acute pancreatitis. That protein, not detectable in control animals, was called "pancreatitis-associated protein." It was first observed 6 hours after induction of experimental pancreatitis with taurocholate or cerulein, reached maximal levels of 45 micrograms/mg protein in zymogen granules and 1.8 micrograms/mg protein in pancreatic tissue during the acute phase (48 hours), and disappeared during recovery (day 5). It was never detected in spleen, liver, kidney, heart, or lung. The detection limit of the assay system was 12 ng/mg protein, so that pancreatitis-associated protein levels increased at least 100-fold in pancreatic tissue during the acute phase. The molecular weight (12,000) and isoelectric point (8.2) were determined by two-dimensional gel electrophoresis. Subcellular fractionation and immunoelectron microscopy showed that the protein was synthesized on the rough endoplasmic reticulum and stored in zymogen granules before being secreted, similar to other pancreatic secretory proteins. Immunoblotting and two-dimensional gel electrophoresis revealed that the same protein was synthesized upon induction of pancreatitis by cerulein infusion, by retrograde injection of bile acids, or pancreatitis induced by pancreatic surgery. The pancreatitis-associated protein is therefore an acute-phase protein that differs from other proteins of that family because of its exocrine nature. 
5	Outpatient management of burns in children. The majority of burn wound management can be performed on an outpatient basis by the primary care physician or emergency physician. The physician, however, needs to know when to refer the patient for surgical evaluation and must be reasonably certain that the family will be compliant with wound care and follow-up. Fire prevention counselling still remains one of the most important aspects of burn management. 
4	Admission and mid-stay MedisGroups scores as predictors of death within 30 days of hospital admission. We examined the ability of MedisGroups, a severity measure based on clinical data abstracted from the medical record, to predict mortality 30 days following admission. MedisGroups measures severity both on admission and approximately one week into the hospital stay. The data base was a random sample of 20,985 admissions of Medicare beneficiaries with one of six conditions from 833 hospitals in seven states between January 1985 and May 1986. In all six conditions, higher admission and mid-stay severity scores were generally associated with higher risk of death. Across the six conditions, the R-squared values for predicting death using admission scores ranged from 0.01 to 0.16; R-squared values using mid-stay scores ranged from 0.03 to 0.34; and R-squared values from combining admission and mid-stay scores ranged from 0.05 to 0.41. Admission MedisGroups score was thus only modestly predictive of 30-day mortality. While the mid-stay score was more powerful, it may not be an appropriate severity adjuster to screen for quality using hospital mortality rates because it could be influenced by substandard care. 
4	Comparison of SPECT using technetium-99m agents and thallium-201 and PET for the assessment of myocardial perfusion and viability. This report reviews the applications of tomographic imaging with current and new tracers in assessing myocardial perfusion and viability. Multiple studies with thallium-201 (TI-201) single photon emission computed tomography (SPECT) imaging for the detection of coronary artery disease (CAD) have demonstrated high sensitivity, high rates of normalcy and high reproducibility. In assessing viability, fixed defects are frequently detected in viable zones in 4-hour studies with TI-201 imaging. Redistribution imaging performed 18 to 72 hours after injection or reinjection of TI-201 before 4-hour redistribution imaging has been shown to improve accuracy of viability assessment. TI-201 SPECT studies are limited by the suboptimal physical properties of TI-201, which result in variable image quality. The 2 new technetium-99m (Tc-99m) - labeled myocardial perfusion tracers offer the ability to inject much higher amounts of radioactivity, making it possible to assess ventricular function as well as myocardial perfusion from the same injection of radiotracer. Tc-99m sestamibi has very slow myocardial clearance, which allows for prolonged imaging time and results in image quality superior to that obtained with TI-201 and Tc-99m teboroxime. The combination of minimal redistribution of Tc-99m sestamibi and high count rates makes gated SPECT imaging feasible, and also permits assessment of patients with acute ischemic syndromes by uncoupling the time of injection from the time of imaging. The combination of high image quality and first-pass exercise capabilities may lead to a choice of this agent over TI-201 for assessment of chronic CAD. 
5	Clinical and instrumental evaluation of sensory function before and after percutaneous anterolateral cordotomy at cervical level in man. Sensory perception thresholds were assessed by clinical testing and by quantitative instrumental testing before and after operation in 16 subjects for whom unilateral percutaneous cervical cordotomy was performed for the relief of pain due to malignant disease, and compared with clinical assessments of sensory function. We were able to confirm the association between deficit in pin-prick sensation and pain relief in the majority of instances, though the completeness or otherwise of pain relief does not correspond to absence of pin-prick sensation. There is no objective interference with low threshold mechanical sensation as measured instrumentally, although cordotomised subjects do not experience startle, tickle, or cutaneous erotic sensation when subjected to appropriate low intensity tactile sensation. Quantitative instrumental testing shows that the greatest deficits produced by cordotomy are in the sensations of skinfold pinch (? = tissue-damage pain) and skin cooling. The latter is transduced in the periphery by A delta fibres; sensations of warmth and hot pain, transduced by primary afferent C fibres, are much less significantly affected. Our findings thus fail to resolve the question as to whether chronic clinical pain is mainly an A delta- or a C fibre-mediated phenomenon. 
5	Splicing defect at the ornithine aminotransferase (OAT) locus in gyrate atrophy. Gyrate atrophy (GA), a recessive eye disease involving progressive vision loss due to chorioretinal degeneration, is associated with the deficiency of the mitochondrial enzyme ornithine aminotransferase (OAT), with consequent hyperornithinemia. We and others have reported a number of missense mutations at the OAT locus which result in GA. Here we report a GA patient of Danish/Swedish ancestry in whom one OAT allele produces an mRNA that is missing a single 96-bp exon relative to the normal mRNA. Polymerase-chain-reaction amplification and sequencing revealed a 9-bp deletion covering the splice acceptor region of exon 5, resulting in the absence of exon 5 sequences from the mRNA with no disruption to the reading frame. This mutation, which was not present in 15 other independent GA patients, adds to the array of allelic heterogeneity observed in GA and represents the first example of a splicing mutation associated with this disorder. 
3	Results of treatment of displaced patellar fractures by partial patellectomy. The results of partial patellectomy as a treatment for displaced patellar fractures were assessed retrospectively with use of clinical, radiographic, and isokinetic strength-testing criteria. Forty patients who had been followed for an average of 8.4 years were studied. In the extremity that had been operated on, the mean active range of motion was 94 per cent, the circumference of the thigh was 100 per cent, and the strength of the quadriceps was 85 per cent of these measurements in the contralateral extremity. The over-all result was rated as excellent in twenty patients, good in eleven, fair in six, and poor in three. There was a significant statistical correlation between the type of fracture and the outcome. The results of this study indicate that partial patellectomy can be an effective treatment for selected patellar fractures. 
4	Inability to demonstrate physiologic correlates of subjective improvement among patients taught the relaxation response. OBJECTIVE: To assess whether the regular elicitation of the relaxation response produces sustained physiologic changes coincident with symptomatic relief or improved psychological state. DESIGN: Prospective, cohort pilot study. SETTING: Clinical research center within a teaching hospital. PATIENTS: Thirteen athletic men, mean age 44.8 years, with borderline or labile hypertension, taking no medication. All 13 completed the study. INTERVENTIONS: Three baseline assessments of psychological state, symptom checklist, and assessment of autonomic response to infusion of beta agonist (isoproterenol). Daily relaxation response exercises for five consecutive weeks followed by repeat assessment of all parameters. Discontinuation of relaxation exercises for subsequent five weeks followed by repeat assessment of all parameters. Measurements and main results: After eliciting the relaxation response, subjects demonstrated significant decreases in anxiety (p less than 0.014) and somatic symptoms (p less than 0.02). Psychological and somatic variables returned toward baseline after the subsequent discontinuation of relaxation exercises. No significant concomitant change in urinary catecholamines, heart rate response to isoproterenol, blood pressure, pulse rate, or serum cholesterol was demonstrated. CONCLUSION: The regular elicitation of the relaxation response can improve psychological performance and reduce symptoms. However, the physiologic mechanism whereby these psychological and symptomatic improvements occur remains poorly understood and warrants further investigation. 
1	A palmar dermatosis linked to occult carcinoma of the upper thorax, head and neck: Bazex's syndrome and tripe palm. An unusual, persistent, corregated-to-honeycombed thickening of the palms accompanied by tenderness around the fingernails was found to be a cutaneous marker for internal malignancy. This combination of signs and symptoms has been reported under two clinical entities: Bazex's syndrome and tripe palm. This paraneoplastic syndrome is of interest to head and neck surgeons due to the location of the primary tumor, the site of metastatic disease, and the ability to cure the cutaneous disease by surgical removal of the primary tumor. In our patient, a squamous cell carcinoma of the lung not detectable on chest x-ray presented as a cervical mass accompanied by cutaneous changes on the palms and fingernails. Recognition of the relationship of the dermatologic changes to malignancy of a specific body region eventually led to the detection of the primary tumor. The characteristics of these paraneoplastic syndromes were reviewed in this report. 
1	Possible etiologic heterogeneity of vulvar intraepithelial neoplasia. A correlation of pathologic characteristics with human papillomavirus detection by in situ hybridization and polymerase chain reaction. A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the beta-globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a "condylomatous" appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus-16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV-positive women were younger than HPV-negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles. 
3	Fetal homotransplants (ventral mesencephalon and adrenal tissue) to the striatum of parkinsonian subjects. Fetal ventral mesencephalon and fetal adrenal tissue grafted to the caudate nucleus of four and three parkinsonian patients, respectively, have been shown to be an alternative treatment for the amelioration of the signs of the disease. The ventral mesencephalon patients had a significant amelioration of rigidity, bradykinesia, postural imbalance, gait disturbance, and facial expression. Three of these four patients have returned to work. The fatal adrenal group only showed amelioration of rigidity and bradykinesia. Though these patients are now able to perform their basic daily living activities, and one of them has renewed her household tasks, the other two have not yet been able to return to work. The differences observed between the ventral mesencephalon- and the fetal adrenal-transplanted patients may be related to the heterogeneity of their disease and/or the type of graft implanted. However encouraging our results may be, this experimental procedure obviously requires further studies, and should not be practiced outside of highly qualified clinical research centers. 
4	Infectious intracranial aneurysms: comparison of groups with and without endocarditis. A series of 12 patients with infectious intracranial aneurysms is presented, and a number of unusual features of the disorder are emphasized. A comparison of characteristics of the aneurysms and clinical course is made between patients with and without infective endocarditis. Most of the unusual characteristics of infectious aneurysms, including rare locations, causative organisms, and predisposing medical conditions, occurred in the group without endocarditis. The relationship of atypical features of infectious aneurysms to the etiology of aneurysm formation is discussed, and an approach to treatment is presented. 
5	Intrathoracic current flow during transthoracic defibrillation in dogs. Transcardiac current fraction. To achieve transcardiac threshold current during transthoracic defibrillation, a considerably larger current must be delivered to the thorax to compensate for the shunting effect of the lungs, the thoracic cage, and other elements of the torso. This shunting effect is thus an important determinant of transthoracic defibrillation threshold and can be quantified by the transcardiac current fraction (FC, the ratio of transcardiac to transthoracic threshold currents). Previous estimates of FC have ranged from as low as 3% to as high as 45%. The purpose of of this study was to quantify both FC and the major intrathoracic current pathways. Transthoracic and intrathoracic voltages and currents were simultaneously measured during high-voltage transthoracic shocks in 20 dogs. With correction factors determined from another set of 12 dogs, these raw data were corrected to compensate for field distortion caused by the presence of the intrathoracic electrodes, and the adjusted data were fit to a resistive network model. The results showed that 82% of the transthoracic current was shunted by the thoracic cage, while 14% was shunted by the lungs. The remaining 4% (FC) is the portion that passed through the heart. There was good agreement between the two independent methods used to calculate FC. Analysis based on the model indicated that FC was 3.7%, whereas FC determined by direct measurement with calibrated electrodes was 4.2%. Therefore, the results of this study, in contrast to earlier estimates of FC, show that defibrillation in dogs is achieved by only 4% of the total transthoracic current. 
4	Left ventricular end-systolic stress-volume index ratio in aortic and mitral regurgitation with normal ejection fraction. To evaluate the left ventricular contractile state in regurgitant valvular disease with normal ejection fraction, we analyzed the end-systolic stress-volume index relationship (ESSVR) by means of cineangiography in 15 normal subjects, 11 patients with aortic regurgitation (AR), and 10 patients with mitral regurgitation (MR) whose ejection fraction (EF) was 60% or more. The end-systolic stress-volume index ratio in normal subjects was 5.57 +/- 0.60 kdyne/cm5/m2 (mean +/- standard deviation), and we defined the range including +/- 2 standard deviations of the ratio as the normal ESSVR range. Six patients with AR and five patients with MR placed inside the normal ESSVR range, termed AR IN and MR IN, but the remaining five patients with AR and MR placed to the right of the normal range, termed AR OUT and MR OUT. EF did not differ between patients with AR IN and AR OUT (69.4 +/- 5.4 verus 70.7 +/- 6.1%) and between MR IN and MR OUT (71.6 +/- 3.6 versus 71.1 +/- 7.9%). The EF of the subdivided groups with AR and MR also did not differ from that of normal subjects (70.7 +/- 7.3%). This finding showed that the left ventricular contractile state was depressed in patients with AR OUT and MR OUT despite a normal EF. In AR and MR the end-systolic stress and end-systolic volume index of OUT did not differ from those of IN, but the end-diastolic volume index of OUT was larger than that of IN (AR OUT 156.8 +/- 27.9 versus AR IN 110.8 +/- 24.1 ml/m2, MR OUT 160.5 +/- 44.7 versus MR IN 101.0 +/ 16.6 ml/m2; both p less than 0.05), and the regurgitant fraction of OUT was higher than that of IN (AR OUT 52.6 +/- 13.6 versus AR IN 29.7 +/- 13.3%, MR OUT 52.9 +/- 10.2 versus MR IN 30.2 +/- 11.4%; both p less than 0.05). In addition, there was a linear inverse correlation between the end-systolic stress-volume index ratio and the end-diastolic volume index in all subjects (r = -0.82, n = 36). In normal subjects there was a linear inverse correlation between end-systolic stress and the EF (r = -0.91, n = 15), but this relationship failed to separate patients with OUT from those with IN. Results of the present study suggest that some patients with AR and MR whose EF was normal had a depressed contractile state, and these patients had a large end-diastolic volume index and a high regurgitant fraction.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Isovolumic hemodilution with dextran 40 in the rat: effect on the development of peripheral edema and various physiologic parameters. Low molecular weight dextran 40 (D40), 40,000 daltons, is a potential therapeutic agent for cerebral ischemia because it increases local cerebral blood flow. However, the evaluation of D40 in the rat has been difficult due to systemic effects. We evaluated the effects of isovolumic hemodilution with D40 on the development of peripheral edema, mean arterial pressure, hematocrit (Hct) and total blood volume in 18 rats, during 30 min or 4 hr i.v. infusions, in animals with and without previous challenge with D40. Reduction of Hct without peripheral edema to a mean of approximately 31% was only achieved in the animals challenged with i.p. D40 24 hr before hemodilution and who received D40 over a period of 4 hr. Infusion of D40 over a period of 30 min was associated with shorter survival time, compared to the 4-hr infusion group (P less than .005). In the pretreated, rapidly infused group, total blood volume per body weight decreased significantly over time (P less than .005) and the mean arterial blood pressure dropped, but not significantly (P less than .07), whereas no change in Hct was detected and there was a trend toward increased peripheral edema, relative to the slowly infused groups. We conclude that reduction of Hct can be achieved successfully with i.p. administration of D40 24 hr before the study combined with infusion of the agent during a 4-hr period, without significant peripheral edema and early hypotension. This procedure should be used to avoid allergic reactions when evaluating hemodilution with D40 in rats. 
5	Fibrosing mediastinitis with coronary artery involvement. This case report describes a patient with chronic fibrosing mediastinitis involving the entire intrapericardial aorta, innominate artery, and the base of the heart with involvement of the proximal segments of the coronary arteries. This finding was unsuspected before emergency coronary artery bypass grafting. Coronary stenosis due to fibrosing mediastinitis is a rare complication of fibrosing mediastinitis. Owing to the extensive fibrosis, the normal bypass, cardiac preservation, and revascularization techniques required alteration and are discussed. 
5	The Dutch experience in percutaneous transluminal angioplasty of narrowed saphenous veins used for aortocoronary arterial bypass. Of 19,994 percutaneous transluminal coronary angioplasty procedures performed in The Netherlands between April 1980 and January 1989, the long-term follow-up of 454 patients who underwent angioplasty of greater than or equal to 1 saphenous vein bypass graft was reviewed. In 46% of patients single graft angioplasty was attempted, and in 54% of patients sequential graft angioplasty was attempted. The clinical primary success rate was 90%. In-hospital mortality was 0.7%, 2.8% of patients sustained a procedural myocardial infarction, and 1.3% of patients underwent emergency bypass surgery. After a follow-up period of 5 years, 74% of patients were alive, and 26% were alive and event-free (no myocardial infarction, no repeat bypass surgery or repeat angioplasty). In patients in whom the initial angioplasty attempt was unsuccessful, only 3% were event-free at 5 years, versus 27% of successfully dilated patients. The time interval between the angioplasty attempt and previous surgery was a significant predictor for 5-year event-free survival. The event-free survival rates for patients who had bypass surgery 1 year before, between 1 and 5 years, and 5 years before angioplasty, were 45, 25 and 19%, respectively. Less than one-third of patients with previous bypass surgery who had angioplasty of the graft remained event-free after 5 years. In patients needing angioplasty within 1 year after bypass surgery, better long-term results were achieved. 
2	Effect of intraesophageal location and muscarinic blockade on balloon distension-induced chest pain. Intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain. In order to examine the effect of balloon location and muscarinic blockade on distension-induced pain, 10 asymptomatic male volunteers were studied on two separate days using a low-compliance perfused manometry system that incorporated a silicone rubber balloon. Five-second-duration balloon distensions using balloon volumes of 2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES) before and after administration of atropine (10 micrograms/kg intravenously) or placebo in a randomized double-blind fashion. A standardized scoring system was used to assess the balloon distension-induced pain. Pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site. This was not associated with any differences in intraballoon pressures between the two sites; however, contraction amplitude orad to the balloon was greater with balloon distension at the proximal site. Atropine significantly decreased pain sensation scores with the balloon located distally but not proximally. This attenuation was not associated with significant changes in intraballoon pressures; however, contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension. These studies indicate that balloon distension-induced pain varies depending on the location of distension. This difference is not explained by differences in esophageal wall tension at the site of distension. 
1	Inheritance of proliferative breast disease in breast cancer kindreds. Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer. 
5	The detubularized right colonic segment as urinary reservoir: evolution of technique for continent diversion. Continent diversion of urine via a cecal-right colonic reservoir has been performed at our university hospital since 1977. Several modifications of surgical technique have been devised to prevent problems of urinary leakage and difficulties in catheterization. The current technique, used during the last 3 years on 14 patients, involves use of a detubularized right colonic segment as a reservoir, ileal mesenteric exclusion, fashioning the intussuscepted ileal nipple valve with staples and anchoring of a fascia strip sling around the nipple base to the anterior rectus sheath. Complication from the reservoir outlet occurred in only 1 patient. 
5	The lovastatin-treated rodent: a new model of barrier disruption and epidermal hyperplasia. Recent studies have linked epidermal cholesterol synthesis with maintenance of the permeability barrier. To assess directly the importance of cholesterol synthesis, we applied lovastatin, a potent inhibitor of cholesterol synthesis, to hairless mouse skin. Transepidermal water loss (TEWL) began to increase after four to six daily applications. Co-application of cholesterol blocked the expected increase in TEWL, demonstrating the importance of cholesterol for development of the lesion. The histology of lovastatin-treated skin revealed epidermal hyperplasia, accompanied by accelerated DNA synthesis. Whereas cholesterol synthesis initially was reduced in lovastatin-treated epidermis, with further treatment cholesterol synthesis normalized, while fatty acid synthesis accelerated greatly. Although the total free sterol content of lovastatin-treated epidermis remained normal, the fatty acid content increased coincident with barrier disruption. Finally, morphologic abnormalities of both lamellar body structure and their deposited, intercellular contents occurred coincident with the emerging biochemical abnormalities. Thus, the abnormal barrier function in this model can be ascribed to an initial inhibition of epidermal sterol synthesis followed by an alteration in cholesterol and fatty acid synthesis, leading to an imbalance in stratum corneum lipid composition and abnormal membrane bilayer structure. 
1	Stimulation of tumor cell growth by vasoactive intestinal peptide. Vasoactive intestinal peptide (VIP) stimulated the growth of murine Lewis lung carcinoma cells in culture. The growth promoting effect was dependent on the concentration of VIP. Exposure to VIP for 12 hours followed by removal of the peptide resulted in sustained growth promotion for 4 to 5 days in culture. Synthetic fragments of VIP, i.e., VIP (1-16) and VIP (22-28), and the unrelated peptide neurotensin failed to stimulate the growth of the Lewis lung carcinoma cells. The growth-promoting effect of VIP was also observed in a murine mammary tumor cell line and a human lung adenocarcinoma cell line. 
4	Significance of the number of stimuli to initiate ouabain-induced arrhythmias in the intact heart. Ouabain-induced arrhythmias are a well-known model used to study triggered activity resulting from delayed afterdepolarizations. In the intact heart, initiation of these arrhythmias is promoted by pacing, especially at fast rates. However, the relevance of the number of stimuli is unknown. In conscious dogs with formalin-induced atrioventricular block, we investigated the effect of variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at progressive levels of ouabain intoxication, and 2) the induction of sustained ventricular tachycardia (VT). Twenty experiments were analyzed. Ouabain was administered as a bolus of 40 micrograms/kg followed by continuous infusion. Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until completion or induction of VT. When VT could not be initiated, the experiment was repeated at least 1 week later, adding 5-10 micrograms/kg ouabain to the bolus and increasing the infusion rate correspondingly. This was repeated until VT could be induced. Four interstimulus intervals (200, 400, 600, and 800 msec) and seven numbers of stimuli (5, 10, 20, 35, 50, 100, and 150) were given in two pacing protocols. The effect of these protocols on 1) the number of induced beats per stimulation train, 2) their first postpacing interval, and 3) induction of VT were studied. Initiation of VT occurred after 75 +/- 42 minutes. The bolus of ouabain needed to induce VT was inversely related to the body weight of the animals. Progression of ouabain intoxication resulted in 1) a significant increase in the number of induced beats per stimulation train and 2) a significant shortening of the first postpacing interval. Stimulation at a faster rate and/or more stimuli resulted in 1) a significantly pronounced increase in the number of induced beats at the higher levels and 2) a significantly shorter first postpacing interval at successive levels of ouabain intoxication. 
1	Antibodies to synthetic peptide (125-148) of the alpha-subunit of human nicotinic acetylcholine receptor in sera from patients with myasthenia gravis. We measured the amount of antibodies to a synthetic peptide that corresponds to the alpha-subunit residues Lys125-Thr148 of human acetylcholine receptor (AChR) in myasthenic sera. We detected anti-peptide antibodies in 52% (89/171) of the patients with myasthenia gravis (MG), but none in any of the healthy controls. Anti-peptide antibodies should provide a valuable immunologic parameter for the clinical evaluation of MG, but no apparent correlation was observed between the titers of anti-peptide and anti-AChR antibodies. 
3	Trichothiodystrophy with chronic neutropenia and mild mental retardation. Trichothiodystrophy is a feature of several diseases that consist of characteristic hair shaft abnormalities and a wide spectrum of other developmental defects. Detection of sulfur-deficient hairs identifies this disorder and separates it from other similar ectodermal dysplasias with normal sulfur content. Detection of low sulfur hair syndrome is also important for genetic counseling, because the disease appears to be an autosomal recessive trait. We report a patient with chronic neutropenia, mild mental retardation, and low sulfur content in hair. Our case expands the spectrum of disorders associated with trichothiodystrophy. 
4	Transcranial Doppler determination of cerebral perfusion in patients undergoing CPR: methodology and preliminary findings. STUDY OBJECTIVES: To correlate cerebral arterial blood velocity measurements as determined by transcranial Doppler ultrasound with various resuscitation maneuvers performed in an uncontrolled manner in a series of cardiac arrest patients undergoing standard resuscitation. TYPE OF PARTICIPANTS: Any patient undergoing resuscitation for a nontraumatic cardiac arrest was eligible for the study. INTERVENTIONS: Resuscitation was carried out while flow velocities were monitored in various intracranial arteries by transcranial Doppler ultrasound. Vessel identification was based on the angle and depth of insonation. MEASUREMENTS AND MAIN RESULTS: The internal carotid artery was located more consistently than either middle cerebral or ophthalmic arteries and provided superior waveforms for analysis. Alterations in flow velocity were noted and correlated to various therapeutic interventions. Flow velocities were 70% of normal during the early phase of resuscitation but deteriorated over time until there was no evidence of net forward flow. Even early in CPR, flow was demonstrated only during systole. CONCLUSION: Transcranial Doppler ultrasound appears to be a potentially promising means of determining cerebral flow in patients undergoing CPR. 
2	Successful treatment of pancreatic pseudocyst with a somatostatin analogue and catheter drainage. We report a patient with bile duct stone-induced pancreatitis who subsequently developed a large pseudocyst that became infected after endoscopic retrograde cholangiopancreatography (ERCP) was done for extraction of the stones. Percutaneous external drainage allowed control of the infection, but failed to seal the pseudocyst. We then treated the patient with a long-acting somatostatin analogue which shrunk the cyst within a week. Patients with pancreatic pseudocyst resistant to drainage should be offered a course of somatostatin before surgery is contemplated. 
1	The relationship of "high risk" mammographic patterns to histological risk factors for development of cancer in the human breast. In the UK Trial for the Early Detection of Breast Cancer in Nottingham, 119 women were identified as having fibrocystic change with epithelial hyperplasia or in situ carcinoma. Their mammograms were classified according to Wolfe's criteria and the corresponding histology for each patient was classified for degrees of epithelial hyperplasia, atypia and in situ neoplasia using Page's criteria. A control population of patients presenting for breast screening was used to represent the general population. No correlation was found between the four mammographic Wolfe patterns, N1, P1, P2 and DY and histological evidence of epithelial hyperplasia, atypia or in situ carcinoma. A further study was carried out to determine histological features of Wolfe pattern, using radiological examination of resected breast tissue. The variation in Wolfe pattern was related to the distribution of fibrous and adipose tissue in the breast interlobular stroma and appeared to have no relationship to epithelial parenchymal content. This information does not support the hypothesis that radiographic densities of P2 and DY patterns correspond to high risk epithelial proliferation. 
5	Urinary tract infection in women. Current role of single-dose therapy. Administration of a single dose of an antimicrobial agent is acceptable therapy for women with uncomplicated lower urinary tract infections. There is adequate information in the literature to support the clinical use of single-dose therapy, although there is still a need for further, well-designed, sufficiently large studies that compare single-dose therapy to abbreviated-course (3-day) and traditional (7- to 14-day) therapy. 
5	Results of vein graft reconstruction of the lower extremity in diabetic and nondiabetic patients. The results of 171 vein grafts of the lower extremity were evaluated. These were placed between January 1981 and December 1987 in 150 patients, 75 diabetic and 75 nondiabetic, to determine the influence of diabetes on the outcome of the procedure. One and four year patency rates were determined by a life table analysis. No statistical differences in primary patency were found between the patients with diabetes and those without diabetes for all indications of operations (one year, diabetic patients 95 +/- 3 per cent, nondiabetic patients 85 +/- 3 per cent; four years, diabetic patients 89 +/- 11 per cent and nondiabetic patients 80 +/- 12 per cent; p = n.s.). For those operated upon for salvage of the limb because of rest pain, ulceration or gangrene, patency in diabetic patients at one year approached a statistically significant advantage (diabetic patients 94 +/- 4 per cent versus nondiabetic patients 79 +/- 8 per cent; p = 0.056). We believe that arterial reconstruction of the lower extremity can be performed upon patients with diabetes with the same high degree of success for revascularization and salvage of the limb as can be accomplished in nondiabetic patients. This is true even though those with diabetes present with necrosis of the tissue and more often require bypass to distal tibial arteries. 
3	Effect of normal MSAFP screening on maternal age for genetic amniocentesis. Routine maternal serum alpha-fetoprotein (MSAFP) screening for neural tube defects is considered by many to be standard obstetrical care, and recently many have encouraged this test to screen for Trisomy-21 (Down's syndrome). We questioned whether, after a normal MSAFP screen, the risk of Trisomy-21 decreases enough to warrant modifying the recommended age for genetic amniocentesis for Down's syndrome. A logistic regression was developed which, using reported values for sensitivity and specificity for MSAFP detection of Trisomy-21 and assuming a constant threshold risk in opting for amniocentesis, indicates that genetic amniocentesis for Trisomy-21 may be deferred in some women who have a normal MSAFP screening. Sensitivity analysis of varying thresholds for a normal MSAFP demonstrates that a 37 year old woman with a median MSAFP level has the same risk for Trisomy-21 as an unscreened women who is 4.5 years younger. An abnormal MSAFP is useful in screening for neural tube defects and possibly for Trisomy-21. A normal MSAFP may allow for delaying the potentially risky amniocentesis in otherwise low-risk pregnancies. 
5	Use of a knee-brace for control of tibial translation and rotation. A comparison, in cadavera, of available models. We assessed the relative restraints that are provided by fourteen currently available functional knee-braces, using six limbs in cadavera. The tests were made at 30 and 60 degrees of flexion of the knee, and a mechanical loading system applied loads that caused anterior-posterior translation and internal-external rotation. The braces limited abnormal tibiofemoral displacements by 10 to 75 per cent in translation; there was more variation in rotation. This study demonstrated that functional knee-braces provide a restraining influence that may be beneficial in the control of abnormal displacements of the knee, but that the degree of restraint varies considerably. 
4	Comparison of early versus late experience with percutaneous mitral balloon valvuloplasty. The immediate outcome of the first 150 patients (Group 1) and the last 161 patients (Group 2) who underwent percutaneous mitral balloon valvuloplasty was compared. There was no difference between the two groups in age, gender, New York Heart Association functional class, presence of calcification, atrial fibrillation, degree of mitral regurgitation, mean pulmonary artery pressure, left atrial pressure, cardiac output, pulmonary vascular resistance, mitral valve gradient and mitral valve area. Fewer patients in Group 1 than Group 2 had an echocardiographic score less than or equal to 8 (62% versus 69%, respectively, p = 0.02). The atrial septum was dilated with an 8 mm balloon in 74% of patients in Group 1 and with a 5 mm balloon in all patients in Group 2. Ratio of effective balloon dilating area to body surface area was larger in Group 1 than in Group 2 (4.05 +/- 0.07 versus 3.7 +/- 0.03 cm2/m2, p = 0.0001). A good result (mitral valve area greater than or equal to 1.5 cm2) was obtained in 77% and 75% in Groups 1 and 2, respectively (p = NS). After percutaneous mitral valvuloplasty, a greater than or equal to 2 grade increase in mitral regurgitation was noted in 12% of Group 1 and 6% of Group 2 (p = 0.02) and a left to right shunt was detected in 22% of Group 1 and 11% of Group 2 (p = 0.0001). There were three procedure-related deaths in Group 1, but none in Group 2. 
3	Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system: I. Intraventricular and extracerebral lesions. The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project. 
4	Prevention of paraplegia during aortic operations. Ischemic spinal cord injury after aortic cross-clamping may be produced by a steal phenomenon. The present study investigates this possibility by directly measuring the oxygen tension on the spinal cord surface in pigs. After simple clamping of the aorta, oxygen tension decreased significantly distal to the clamping site both after occlusion of the thoracic aorta at T3-4 (group 1) and after occlusion of the abdominal aorta at L-1 (group 2). Exclusion of the thoracic aorta by a second clamp at T-13 restored oxygen tension almost to the original level, whereas segmentation of the abdominal aorta up to S-1 hardly affected oxygen tension in the area of the artery of Adamkiewicz in most of the animals. We conclude that after aortic cross-clamping, blood tends to drain away from the spinal cord rather than supplying it longitudinally. Without knowledge of the position of the Adamkiewicz artery in humans as well as of the competence of the collateral circulation in the excluded segment, it is necessary to develop a new strategy for repair of the aorta. We describe and discuss two surgical techniques for the prevention of paraplegia after aortic cross-clamping: the counterocclusion technique and the bypass fractionated technique. 
5	Expert testimony based on decision analysis: a malpractice case report. OBJECTIVE: Expert testimony in malpractice cases is often subjective and biased. Decision-analytic techniques might provide an objective basis for such testimony. DESIGN: Case report. This article reports the case of a patient with chest pain that resulted in a malpractice suit alleging a delay in diagnosis of coronary artery disease. SETTING: The case occurred in a private practice; the expert witnesses and the decision analysis originated from a university teaching hospital. METHODS: A decision tree and threshold analysis were used to define the thresholds of disease probability at which either testing or treatment should be implemented. The expert testimony of two witnesses that exercise stress testing was the standard of care was compared with the results of the decision analysis. MAIN RESULTS: Decision analysis supported the view that cardiac catheterization would have been the more appropriate test. CONCLUSIONS: Techniques of decision analysis provide a structured and quantitative basis for empirical judgment and may help to minimize current problems with expert testimony. 
4	Renal effects of angiotensin-converting enzyme inhibition in congestive heart failure. Some studies report that inhibition of angiotensin-converting enzyme (ACE) improves renal function in patients with congestive heart failure, whereas others report that renal deterioration is a frequent complication of treatment with ACE inhibitors. This article explores the mechanisms by which antagonism of the renin-angiotensin system improves kidney function in some patients while causing harm in others. ACE inhibition may alter renal blood flow, glomerular perfusion pressure, basement membrane activity and renal tubular function both directly and indirectly. In most patients, renal function is maintained as other neurohormonal mechanisms compensate for the negative effects and permit the positive effects (such as improved renal flow) to predominate. However, when physiologic characteristics or iatrogenic interventions (such as volume reduction or prostaglandin inhibition) limit the effectiveness of neurohormonal compensation to maintain renal autoregulation, clinically important deterioration in renal function may occur. An understanding of the renal effects of ACE inhibitors permits their safe and effective use in most patients with congestive heart failure. 
4	A 5.3-kb deletion including exon XIII of the protein S alpha gene occurs in two protein S-deficient families. Genomic DNA samples from 12 protein S-deficient families with hereditary thrombophilia were analyzed by Southern hybridization using protein S cDNA probes. Protein S-deficient members of families A and B possessed identical restriction fragment length polymorphisms, which suggest the absence of 5.3 kb from one of their protein S alpha alleles. The abnormal alleles from individuals A7 and B1 were amplified by the polymerase chain reaction using a forward primer in intron K and a reverse primer in exon XIV. The amplified DNA was cloned and sequenced. Sequence comparison with the normal protein S alpha gene showed that most of intron L (roughly 4.7 kb), the entire exon XIII (151 bp), and about a quarter of intron M (407 bp) were missing from both the A7 and B1 clones. Exon XIII contains all three potential N-glycosylation sites in human protein S. This deletion may result in RNA transcripts in which exon XII is spliced to exon XIV. Such an arrangement would generate a stop codon at position 463 and consequently produce a nonglycosylated protein S molecule truncated by 173 amino acids. 
2	Laparoscopic cholecystectomy using intracorporeal lithotripsy. Over a 13-month period (November 1988 to December 1989), we performed our first 104 laparoscopic cholecystectomies using an intracorporeal ultrasonic lithotripsy technique. The procedure in three of these patients was converted to an open operation because of hemorrhage with unexpected findings of cirrhosis in two patients and dense subhepatic adhesions in a third. Endoscopic retrograde cholangiopancreatography was successfully used in three other patients in whom common bile duct stones were identified. We encountered only three postoperative complications out of all the laparoscopic cholecystectomies performed. One complication was a biliary fistula that closed spontaneously 1 week after surgery. The remaining complications were attributable to abscesses, one subhepatic and one pelvic, which were aspirated and drained laparoscopically. There were no deaths. Advantages of the laparoscopic approach included decreased perioperative pain, shortened hospitalization, absence of scar, and more rapid return to prehospitalization activities. 
3	Normal proprioceptive trigeminal afferents in patients with Sjogren's syndrome and sensory neuronopathy. A pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described in patients with Sjogren's syndrome. Conventional electromyographic (EMG) studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion. Noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei, respectively, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigeminal reflexes in 5 patients with Sjogren's syndrome and pure sensory neuropathy, in 10 patients with sensory-motor neuropathies of other causes, and in 10 healthy subjects. Our results show that patients with Sjogren's syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal, cutaneous-induced masseter silent period had normal jaw jerks, whereas patients with sensory-motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks. These findings suggest that the lesion in pure sensory neuropathy involves damage to the neurons of the gasserian ganglia and not to the trigeminal axons, since an axonal lesion would be expected to involve the large axons from muscle spindle receptors. 
5	Combined modality therapy for locally advanced non-small cell lung carcinoma. Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting. 
1	High-risk factors in metastatic gestational trophoblastic neoplasia. The patient with gestational trophoblastic neoplasia faces a number of risks; the greatest is the failure of current treatment to bring about remission. Based on a review of past experience, a number of risk factors associated with failure of single-agent chemotherapy were identified, and the subsequent utilization of combination chemotherapy led to an improved outcome. An analysis of more recent experience has identified factors associated with the failure of standard combination chemotherapy, and it is hoped that the development of new treatments will again improve the outcome. This review provides a perspective on known high-risk factors in light of contemporary treatment. 
1	A prospective study of double diagnosis of nonpalpable lesions of the breast. Approximately three-fourths of open biopsies of the breast performed for mammographically detected suspicious lesions are shown histologically to be benign. Under the narrow conditions described herein, stereotaxic fine-needle aspiration (FNA) can identify these lesions with an accuracy of more than 90 per cent and a false-negative rate of 5 per cent. In an effort to reduce this failure rate, the mammographic appearance and stereotaxic FNA results of these lesions each were given scores on a scale of zero (benign) to five (malignant), to derive an over-all risk score prospectively applied to 264 suspicious occult lesions of the breast prior to open, biopsy. While all 264 lesions could be assigned a mammographic score, adequate tissue for assignment of a cytologic score could be obtained from 150 lesions. Of the 150 evaluable lesions, 53 were malignant and 97 were benign, historically. With a total score of two as the threshold for open biopsy, 21 of 150 (14 per cent) were proved to be benign, with no false-negative findings. If the total threshold score mandating an open biopsy was raised to four, the comparable figures were 61 of 150 (40 per cent) benign lesions and two false-negative instances of carcinoma in situ. Provided adequate tissue is aspirated for cytologic examination, we conclude that this algorithm has practical value in the management of nonpalpable lesions of the breast in that it can reliably identify a fraction of the benign lesions and spare these patients an operation. 
4	Acute myocardial infarction and chest pain syndromes after cocaine use. Seventy patients hospitalized with chest pain after cocaine use were retrospectively evaluated to define the risk and clinical course of acute myocardial infarction (AMI). AMI developed in 22 patients (31%) and transient myocardial ischemia was seen in an additional 9 patients (13%). Coronary risk factors did not distinguish those who developed AMI from those who did not. The presenting electrocardiogram was abnormal in 20 of 22 patients who evolved AMI and in 19 of 48 of those who did not. Creatine kinase levels were elevated in 75% of the patients, including 65% of those who did not develop AMI, but creatine kinase-MB elevations were only observed in the AMI group. The route of cocaine administration did not predict AMI and there was no predilection for a particular coronary vascular bed. The length of time between drug use and onset of AMI pain was often quite prolonged (median interval, 18 vs 1 hour in the non-AMI group). Eight of the patients with AMI underwent cardiac catheterization and 4 had significant coronary narrowing. 
2	Persistent hepatitis B virus following interferon alfa therapy and liver transplantation. A 44-year-old man with chronic hepatitis B virus infection and cirrhosis was treated with recombinant human interferon alfa for 67 days immediately before orthotopic liver transplantation and immunoprophylaxis with hyperimmune globulin to hepatitis B virus in the peritransplant period. Dot blots for hepatitis B virus DNA demonstrated marked reduction in viremia after 41 days of interferon alfa treatment. Southern analysis for hepatitis B virus in liver showed a pronounced decrement in actively replicating forms in the explant, although hepatic infection was still detectable. After liver transplantation, tests for serum hepatitis B virus DNA and hepatitis B surface antigen remained negative. The patient died 32 days after transplantation of causes unrelated to hepatitis B virus. DNA isolated from liver and other visceral organs at autopsy showed infection of the engrafted liver and the persistence of monomeric relaxed circular forms of hepatitis B virus DNA in pancreas, kidney, and spleen. Thus, graft reinfection occurred despite aggressive antiviral therapy and immunoprophylaxis combined with liver transplantation. Existing viral serological markers appear insufficiently sensitive to assess residual infectivity. 
5	Reduced atrial contribution to left ventricular filling in patients with severe tricuspid regurgitation after tricuspid valvulectomy: a Doppler echocardiographic study. Patients undergoing valvulectomy for isolated tricuspid valve endocarditis offer the unique opportunity to study the effects of acquired right ventricular volume overload on left ventricular filling in persons free of pulmonary hypertension and preexisting left heart disease. Eleven patients who had undergone total or partial removal of the tricuspid valve were compared with 11 age-matched control subjects; Doppler echocardiographic techniques were used to quantify changes in left ventricular filling and to relate them to changes in left ventricular and left atrial geometry caused by right ventricular and right atrial distension. The late diastolic fractional transmitral flow velocity integral, a measure of the left atrial contribution to left ventricular filling, was significantly decreased in patients undergoing tricuspid valvulectomy compared with control subjects (0.22 +/- 0.11 versus 0.32 +/- 0.09; p less than 0.04). Severe tricuspid regurgitation in these patients resulted in marked right atrial distension, reversal of the normal interatrial septal curvature and compression of the left atrium such that left atrial area was significantly smaller than in control subjects (5.9 +/- 2.2 versus 8.6 +/- 1.2 cm2/m2; p less than 0.005). Acting as a receiving chamber, the left ventricle was maximally compressed by the volume-overloaded right ventricle in late diastole, coincident with the timing of atrial systole, resulting in a significant increase in the left ventricular eccentricity index compared with that in control subjects (1.35 +/- 0.14 versus 1.03 +/- 0.1; p less than 0.001). Thus, right ventricular volume overload due to severe tricuspid regurgitation results in left heart geometric alterations that decrease left atrial preload, impair left ventricular receiving chamber characteristics and reduce the atrial contribution to total left ventricular filling. 
5	Cardiac arrhythmias from a malpositioned Greenfield filter in a traumatic quadriplegic. A case study is presented of premature Greenfield filter discharge with intracardiac migration and resulting life-threatening arrhythmias. These arrhythmias also interfered with the patient's transition from ventilatory support via orotracheal intubation to noninvasive positive airway pressure ventilatory support methods. The patient's arrhythmias were controlled by a demand cardiac pacemaker and cardiac glycoside therapy. No anticoagulants were used. She had no further filter migration nor significant complications for 16 months after hospital discharge. 
1	Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Optimum methods of harvesting circulating hematopoietic progenitors for autologous transplantation to support myeloablative cancer therapy are still uncertain, mostly because of the lack of an assay for marrow-repopulating stem cells. The CFU-GM assay, the commonly used indirect indicator of the quality of the graft, is poorly standardized and provides results evaluable only retrospectively. Based on the knowledge that hematopoietic progenitors express CD34 and CD33 differentiation antigens, we developed a dual-color direct immunofluorescence flow cytometry assay with the aim of replacing the CFU-GM assay advantageously. For this purpose, we applied both assays to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high-dose cyclophosphamide or etoposide cancer therapy with or without recombinant human GM colony-stimulating factor (rhGM-CSF). The appearance of CD34+ cells in the circulation indicated that hematopoietic progenitors had increased to more than 500 CFU-GM/mL, a level clinically adequate for large-scale harvest by leukapheresis. Total CD34+ cells correlated well with CFU-GM (r = .89), and data could be fitted by a linear regression line described by the equation y = 388.3 + 64.0x, where y = CFU-GM/mL and x = CD34+ cells per microliter. Moreover, in a series of six patients treated with myeloablative chemoradiotherapy, early hematopoietic recovery of marrow functions was predicted more accurately by the number of transplanted CD34+/CD33+ cells than by either total nucleated cells, CFU-GM, CD34+/CD33- cells, or CD34-/CD33+ cells. Data presented in this article favor clinical use of the CD34/CD33 flow cytometry assay to guide harvesting of circulating hematopoietic progenitors for autologous transplantation and contribute to better understanding of the role played by circulating hematopoietic progenitor cell subsets in marrow recovery after myeloablative cancer therapy. 
5	Profound digital collagen atrophy: a new cutaneous presentation of adrenal-dependent Cushing's syndrome. A 59-year-old Caucasian housewife presented with a 2-year history of marked loss of tissue substance from the finger and toe pulps and the heel pads. There was no clinical evidence or history of urticaria or other inflammatory change. Investigations demonstrated a raised plasma cortisol secondary to a left adrenal adenoma. Skin biopsies showed abnormalities of dermal collagen, but no evidence of elastin destruction. This case presents an unusual variant of the cutaneous atrophy associated with Cushing's syndrome. 
3	Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. In this study, the efficacy of Naproxen sodium (Nxs) in the prophylaxis of Menstrual Migraine (MM) was tested, versus Placebo (PL). Forty women suffering from MM were admitted to a double-blind treatment protocol with Nxs 550 mg twice each day by mouth or Placebo (PL), for 3 months; in the next 3 months all the women were treated with the active drug in an open study. The headache intensity and duration, as well as the number of days of headache and the analgesic consumption, were significantly reduced with Nxs compared to PL. The efficacy of Nxs, shown also in improving premenstrual pain, and its good tolerability, support the use of this drug in the prophylactic therapy of MM. 
3	Ulnar nerve decompression with medial epicondylectomy for neuropathy at the elbow. Ulnar nerve decompression with medial epicondylectomy was performed in 66 elbows between 1966 and 1986 for compressive ulnar neuropathy at the elbow. This study is an updated review that adds 36 cases to a previously published report on 30 cases. These elbows were graded preoperatively and postoperatively using McGowan's grading system. Eighty-three percent improved one or two grades, and 11% improved subjectively although they showed no objective improvement, 3% noted no change, and 3% were subjectively worse. One early case sustained damage to the ulnar collateral ligament with resultant instability. No other complications occurred. The best results were seen in the Grade I and II lesions, whereas those with Grade III lesions were the least predictable. The procedure is technically uncomplicated with minimal morbidity and reliable results. 
3	Circulatory and thermal adjustments to prolonged exercise in paraplegic women. The circulatory and thermal responses to 90 min of wheelchair ergometer exercise were examined in five wheelchair dependent (WD) women with low level spinal dysfunction and five able-bodied (AB) women who served as a comparison group. Metabolic rate during exercise was 221 W for WD and 255 W for AB (P greater than 0.05). Oral temperature (Tor), mean skin temperature (Tsk), oxygen uptake (VO2), heart rate (HR), and cardiac output (Qc) were assessed periodically throughout the exercise period. Ambient conditions were 24-25 degrees C and 38-52% relative humidity. A significant group X time interaction was found for Tor (P less than 0.001) and Tsk (P less than 0.001). Tor of the WD group steadily increased during the exercise, whereas the AB group showed a stable Tor. Tsk of WD increased rapidly during the first 5-10 min of exercise and continued to rise at a slower rate throughout the exercise. In contrast, Tsk of AB rose to a peak during the first 10 min and then showed a decreasing trend. VO2 and HR remained stable in both groups throughout the exercise period. Following an initial increase in Qc from minute 10 to minute 20 in both groups, values for WD continually decreased until Qc at 80 min was 14% lower than at 10 min. The findings suggest that the WD women had greater thermoregulatory strain than the AB women as indicated by a higher Tor and Tsk and by an inability to maintain Qc due to paralysis of the lower limbs and perhaps an increase in cutaneous blood volume. 
1	Complications associated with limb salvage for extremity sarcomas and their management. A retrospective clinical review of 100 consecutive patients with extremity sarcomas managed by limb salvage operations was performed to evaluate local tumor control and morbidity. The mean follow-up period was 45.1 months. Overall survival was 86%. There were local recurrences in 3% of patients, and 26 complications in 22 patients. Wound necrosis was the most frequent complication. Failure of allogeneic bone graft operations occurred in 25 patients. Most of the complications were salvageable without loss of limb. Limb salvage is an acceptable surgical treatment of extremity sarcomas based on adequate local control and minimal morbidity. 
4	Application of time series analysis to circadian rhythms: effect of beta-adrenergic blockade upon heart rate and transient myocardial ischemia. Circadian variations of transient myocardial ischemia and heart rate have been identified, but the rhythms and their response to beta blockade have not been fully characterized. Time-series analysis, a mathematical technique to describe oscillatory activity occurring within a continuous data set was used, to address these issues. Nine men with coronary artery disease underwent 72 hours of ambulatory electrocardiographic monitoring during therapy with placebo or metoprolol. During administration of placebo, ischemic time and heart rate showed a primary peak with a periodicity of approximately 24 hours with a tight coupling between the 2 variables and a secondary peak with a periodicity of 5 to 8 hours. During metoprolol therapy, heart rate and ischemic variation were reduced and the 24-hour periodicity for heart rate only remained. The 24-hour periodicity for ischemia was eliminated, but the data with 5- to 8-hour periodicity became the major component of the signal. 
5	Repair of cartilage lesions using biological implants. A comparative histological and biomechanical study in goats. We report the experimental use of three different biological implants to restore articular surface defects: glutaraldehyde-fixed bovine meniscal xenograft, glutaraldehyde-fixed bovine costal cartilage xenograft, and viable osteochondral allografts. The grafts were implanted in the knees of 19 goats who were allowed free-field activity and were studied for up to one year. The natural articular surfaces of meniscal fibrocartilage provided excellent articular surfaces at all times. Equally good articular surfaces were restored by host tissue growth covering costal cartilage grafts at six months, but by 12 months this surface had degenerated. The majority of the allografts survived and integrated with the host at six months, but many showed signs of failure at 12 months. Only three out of seven ungrafted defects healed completely at six months and the healed surfaces were degenerating at 12 months. 
4	Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial. The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers. 
5	Autoradiographic evaluation of monoclonal antibodies' access to melanoma-associated antigens in melanoma xenografts. Autoradiography of nude mice bearing human malignant melanoma xenografts was performed to characterize the distribution pattern of radioiodinated anti-melanoma monoclonal antibodies (MoAb) and fragments in macroscopic tumor nodules. Non-uniformity of radioactivity distribution was seen in all MoAb-xenograft combinations. The predominant patterns were marked deposition of radioactivity either in the periphery of nodules or in sharply delimited intra-tumoral foci. These patterns were generated by limitations in the accessibility of melanoma tissue rather than gross necrosis or heterogeneity of antigen expression. Computer-aided densitometry of autoradiograms was used to elaborate the difference of accumulation in intra-tumoral hot spots versus cold areas. It was found that increasing uniformity was achieved by increasing the dose of MoAb (i.e., intact IgG) injected, whereas a reduction in the size of MoAb (IgG greater than F(ab')2 greater than Fab) showed no such effect. 
4	Management of renovascular disease. A surgical perspective. The role of surgical revascularization in the management of patients with renal artery disease has changed in recent years. This has occurred due to the advent of percutaneous transluminal angioplasty as an effective method of treatment for certain patients, improved results of surgical revascularization in older patients with atherosclerosis, an enhanced appreciation of advanced atherosclerotic renal artery disease as a correctable cause of renal failure, and the development of more effective surgical techniques for patients with severe aortic atherosclerosis and branch renal artery disease. Surgical revascularization is currently the treatment of choice for patients with branch renal artery disease, ostial atherosclerotic renal artery disease, a renal artery aneurysm, and patients in whom renal percutaneous transluminal angioplasty has been unsuccessful. Excellent clinical results continue to be achieved with surgical revascularization in properly selected patients. 
3	Measurement of progressive cerebral ventriculomegaly in infants after grades III and IV intraventricular hemorrhages. To develop guidelines that might help predict prospectively which infants with severe intraventricular hemorrhage (IVH) would require intervention, we obtained serial cranial sonograms to measure the rate of growth of cerebral ventricular volumes in 48 preterm infants with and without IVH. The infants were divided into three groups: (1) those with no IVH (22 infants), (2) those with IVH with acute ventricular dilation (13 infants), and (3) those with IVH with progressive ventricular dilation requiring intervention (13 infants). The decision to intervene because of progressive ventricular dilation was based on clinical criteria and the subjective assessment of increasing ventricular size on weekly cranial sonograms. The rate of cerebral ventricular volume growth in infants with IVH who needed intervention was greater (4.2 +/- 3.3 ml/day) than that in infants without IVH (0.0 +/- 0.1 ml/day; p less than 0.001) and in infants with IVH and acute ventricular dilation (0.0 +/- 0.2 ml/day; p less than 0.001). Using these data, we generated guidelines for predicting prospectively which infants with IVH and ventricular dilation will need intervention for posthemorrhagic hydrocephalus. The guidelines were then confirmed prospectively in 10 infants. 
5	Nutrient modulation of inflammatory and immune function. The metabolic response to injury occurs after a diverse group of surgical injuries including major surgical intervention, shock, infection, and sources of inflammation such as pancreatitis. The response is mediated by the macroendocrine system, the autonomic nervous system, and the cell-cell communication system. The clinical manifestations include now well-described clinical, physiologic, and metabolic characteristics. The approach of aggressive source control, invasive circulatory resuscitation, and nutrition/metabolic support has been associated with an overall reduction in morbidity and mortality. In those patients who do not respond to this approach, the disease process progresses to multiple organ failure syndrome with its associated high mortality. Altering the route of feeding, preventing single nutrient and generalized nutrient deficiency, and reducing nosocomial infections with selective gut decontamination have not significantly altered the course or outcome of the disease process in this latter group of patients with persistent hypermetabolism. The available data support the position that this persistent hypermetabolism represents abnormal metabolic regulation resulting in persistence of the inflammatory response with associated suppression of the immune defenses. A number of research approaches are being taken to understand and modulate this abnormal state of regulation. Because of the role of specific nutrients in these regulatory processes, beyond their role in classic nutrition support, nutrients such as arginine n-3 polyunsaturated fatty acids, and RNA are being evaluated for their ability to modulate inflammation and to improve immune function. Preliminary results are encouraging. 
1	Corporate-sponsored breast cancer screening at the work site: results of a statewide program. Mobile screening mammography was offered to 3,627 employees of a large corporation in Pennsylvania and Delaware. The examination was available to women employees or employee spouses aged 35 years and older. Women were charged $30 for a standard two-view examination. They also received health education materials on mammography and breast self-examination. The remaining costs of the program were underwritten by the corporation. During this program, 3,627 mammographic studies were performed; 63 biopsies were recommended. Fifty-seven biopsies were performed, and nine cancers were diagnosed. Costs of this program are presented in detail. The authors conclude that mobile screening programs at the work site provide an inexpensive, convenient alternative to more traditional screening programs. The inherent advantages of this program are the low cost, the relative ease with which the examination can be performed, and the positive role that corporate medical personnel assume in encouraging individual and group participation. 
2	Biliary lithotripsy: in vitro analysis of gallstone fragmentation for equivalent stone volumes. The relationship between gallstone fragmentation during extracorporeal shock wave lithotripsy (ESWL) and gallstone volume is poorly understood. Clinical results of ESWL show that the highest stone-free rate at 6 months occurs with radiolucent single gallstones 20 mm or less in diameter. In an in vitro study, individual gallstones from cholecystectomy specimens were divided by size and composition into nine single- and nine multiple-stone groups; the stones were then paired on the basis of similar volume. ESWL was performed in a phantom and the size of the largest fragment was measured at 500, 1,000, and 1,500 shock waves. At 1,500 shock waves, sandlike particles were present in six of nine single stones versus two of nine multiple stone groups; the mean size of the largest fragment at 1,500 shock waves was 2.1 mm (single) and 4.4 mm (multiple) in diameter. When corrected for volume, the authors' data suggest that single stones are more easily broken into fragments smaller than 5 mm in diameter than multiple gallstones. The implication, especially when spark-gap technology is used, is that more shock wave energy (ie, an increased number of shock waves at a higher kilovoltage) will be necessary to achieve the same results when treating patients with multiple stones versus a single gallstone with a similar stone volume. 
1	Male breast cancer. Male breast cancer is uncommon but important. The diagnosis is easily made by breast biopsy, and patients are presenting earlier in the course of the disease than in the past. Despite this, patients are often first seen with tumors that have metastasized to the axillary nodes, which markedly decreases the survival rate. Therapy of localized disease includes simple excision, modified radical mastectomy, and radical mastectomy, but there is no consensus for which operation is appropriate. Radiation therapy should be strongly considered in patients with metastases to the axillary nodes, but the role of adjuvant hormonal therapy or chemotherapy is unclear. For treatment of disseminated disease, tamoxifen seems to be replacing orchiectomy. The favorable response rate, especially in patients with estrogen-receptor-positive tumors, the lack of side effects, and the high level of patient acceptability make it an attractive therapeutic choice. 
4	New developments in cardiopulmonary resuscitation. Since the last revision of the American Heart Association's guidelines in 1985, several new developments of clinical importance have occurred in the field of cardiopulmonary resuscitation. These include enhanced access to and earlier use of defibrillation, the use of high-dose epinephrine when standard doses fail, the assessment of resuscitative efforts with end-tidal CO2 monitoring and the addition of two new drugs, amiodarone (for refractory ventricular fibrillation) and adenosine (for paroxysmal supraventricular tachycardia). Time will determine the ultimate role of these advancements in the management of cardiac arrest. 
5	Genetics and biology of human ovarian teratomas. II. Molecular analysis of origin of nondisjunction and gene-centromere mapping of chromosome I markers. Chromosomal heteromorphisms and DNA polymorphisms have been utilized to identify the mechanisms that lead to formation of human ovarian teratomas and to construct a gene-centromere map of chromosome 1 by using those teratomas that arise by meiotic nondisjunction. Of 61 genetically informative ovarian teratomas, 21.3% arose by nondisjunction at meiosis I, and 39.3% arose by meiosis II nondisjunction. Eight polymorphic marker loci on chromosome 1p and one marker on 1q were used to estimate a gene-centromere map. The results show clear linkage of the most proximal 1p marker (NRAS) and the most proximal 1q marker (D1S61) to the centromere at a distance of 14 cM and 20 cM, respectively. Estimated gene-centromere distances suggest that, while recombination occurs normally in ovarian teratomas arising by meiosis II errors, ovarian teratomas arising by meiosis I nondisjunction have altered patterns of recombination. Furthermore, the estimated map demonstrates clear evidence of chiasma interference. Our results suggest that ovarian teratomas can provide a rapid method for mapping genes relative to the centromere. 
5	Silent ischemia after coronary angioplasty: evaluation of restenosis and extent of ischemia in asymptomatic patients by tomographic thallium-201 exercise imaging and comparison with symptomatic patients. One hundred sixteen patients were evaluated to determine the ability of single photon emission computed tomographic (SPECT) thallium-201 exercise and redistribution imaging to detect silent ischemia secondary to restenosis in asymptomatic patients after single and multiple vessel percutaneous transluminal coronary angioplasty and the findings were compared with SPECT imaging detection of restenosis in symptomatic patients. The value of exercise electrocardiography (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic patients were determined. Forty-one patients were asymptomatic after angioplasty; 77% of these had chest pain before angioplasty. Seventy-five patients had chest pain after angioplasty; 99% of these had chest pain before angioplasty. Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in 46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity, specificity and accuracy for detection of restenosis by SPECT in individual patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and accuracy for restenosis detection in individual vessels were 90%, 89% and 89% versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups (p = NS), with similar results for the three major arteries. Sensitivity and accuracy of exercise ECG were significantly less than those of SPECT imaging for the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p less than 0.001). Restenosis of vessels in the patients with silent and symptomatic ischemia was associated with an equal amount and degree of severity of ischemic myocardium in the two groups. 
1	The relationship of ABH(O) blood group antigen expression in intraepithelial dysplastic lesions to clinicopathologic properties of associated transitional cell carcinoma of the bladder. Paraffin-embedded, giant-step sections of 13 bladders with transitional cell carcinomas were stained with monoclonal anti-A or anti-B antibodies to investigate whether intraepithelial dysplastic lesions are related to obvious tumors. Normal and/or hyperplastic lesions were retained in only eight bladders; severe dysplasia and/or carcinoma in situ were found in all bladders except two. AB-antigen expression was retained in intraepithelial lesions of bladders with invasive carcinoma. Most intraepithelial lesions were AB-antigen negative in bladders with frequently recurrent tumors. In bladders with initially multiple tumors, AB-antigen expression was negative in almost one half of the intraepithelial lesions. Therefore, it appears likely that most multiple or recurrent bladder carcinomas arise from dysplastic cells in intraepithelial lesions which have acquired malignant potential; initially invasive tumors quickly develop from a limited lesion acquiring a high malignant potential without changes of cell phenotype in most intraepithelial lesions. 
4	Thrombolysis in acute myocardial infarction. The 1980s has been a critical decade for the management of acute myocardial infarction (MI) because of the concentration in a very short time span of innovative results produced by a new generation of trials, in which thrombolysis has been the preeminent topic. The message coming from the results in the more than 50,000 patients included in the five key trials is simple and clear: thrombolysis, of any type, is the cornerstone of acute treatment of MI, and it works well to produce a very favorable epidemiologic picture. In the GISSI-2 trial, the nationwide adoption of a package of recommended treatments centered on thrombolysis for the overall population of patients with an acute MI has produced a relevant modification of the natural history of the disease, reducing the in-hospital mortality by about 40% in few years (from 13% to 8.8%). In particular, in the great majority of cases (patients aged less than 70 years in Killip class I with a first acute MI), the mortality has gone down to 3%, making a further reduction very hard to obtain with new drugs or strategies. In this context, we will discuss the concept of the relevance for clinical practice of obtaining even greater patency rates with new thrombolytic agents (hopefully more efficient and safe) or with new combinations of traditional agents. 
3	Topographic comparative study of magnetic resonance imaging and electroencephalography in 34 children with tuberous sclerosis. A series of 34 children with confirmed tuberous sclerosis (TS) were studied prospectively by both EEG and magnetic resonance imaging (MRI) at ages ranging from 5 months to 18 years. Size and topography of the cortical tubers were analyzed on axial and coronal views, in T2 sequences, and the large tubers greater than 10 mm were studied. In addition, EEG follow-up data were reviewed retrospectively. Twenty-six patients (76%) had both MRI large cortical tubers and EEG foci, 3 had normal EEG, 2 had normal MRI, and the remaining 3 had only small tubers. The number of large tubers was significantly related to EEG foci. A topographic MRI/EEG correspondence was observed for at least one tuber in 25 of the 26 patients, and correspondence was complete in 10 patients. Large cortical tubers without corresponding EEG foci were observed in 11 patients; these tubers mainly involved the frontal regions and were found before the patients were 2 years old. EEG foci without corresponding tubers were observed in 4 patients. In addition, secondary bilateral synchrony was preferentially observed in patients with frontal lesions and after the age of 2 years. These data confirm that the cortical tubers are epileptogenic and that their expression may be influenced by regional cortical maturation. 
1	Gastric juice ascorbic acid: effects of disease and implications for gastric carcinogenesis. N-nitroso compounds (NOC) are strongly implicated in the causation of cancer of the stomach and it has been suggested that ascorbic acid might reduce the risk of gastric cancer by preventing their formation within gastric juice. However, until recently there have been no measurements of gastric juice ascorbic acid concentrations. We have measured both gastric juice ascorbic and total vitamin C (ascorbic acid and dehydroascorbic acid). Our findings suggest that ascorbic acid is secreted into the gastric lumen so that gastric juice concentrations are often greater than those in plasma. Gastric pathology affects this secretion, leading to values in gastric juice that are lower than plasma levels. Stimulation of gastric secretion does not raise vitamin C concentrations in individuals whose values are initially low. The role of ascorbic acid in preventing formation of NOC and protecting against gastric cancer is discussed in the light of these findings. 
4	Risk factors for carotid artery stenosis: an epidemiological study of men aged 69 years. Four hundred and seventy-eight men born in 1914 and residing in the city of Malmo, Sweden, underwent ultrasonic Doppler examination of the carotid arteries in 1982/83. The known risk factors for vascular disease--blood pressure, lipids, glucose, hematocrit, alcohol consumption and Body Mass Index were also measured. A moderate stenosis (diameter reduction 30-59%) of the internal carotid artery was found in 95 men (20%); 15 men (3%) had a greater than or equal to 60% stenosis of the internal carotid artery, while 7 (1.5%) had complete unilateral occlusion. Smoking was found to be significantly related to severe carotid artery disease. There was also a significant correlation between maximum flow velocity in the internal carotid artery and triglycerides. Those quitting smoking before the age of 50 had the same incidence of internal carotid artery disease as non-smokers, while those quitting later in life had a slightly higher incidence than life-long smokers. 
5	Follow-up results of balloon angioplasty of native coarctation in neonates and infants. The purpose of this study is to present intermediate-term results of balloon angioplasty of native aortic coarctation in neonates and infants less than 1 year of age. During a 60-month-period that ended in January 1990, 19 infants ages 3 days to 12 months (median, 2.5 months), underwent balloon angioplasty of native coarctation with resultant reduction in peak-to-peak systolic pressure gradient from 39 +/- 12 mm Hg (mean +/- SD) to 11 +/- 7 mm Hg (p less than 0.001) and increase in coarctation segment size from 2.2 +/- 0.8 mm to 4.7 +/- 1.0 mm. None required immediate surgical intervention. Thirteen of the 19 (68%) had severe associated cardiac defects. There was one death (5%) 2 days after balloon angioplasty, and it was related to associated cardiac defect. One infant was lost to follow-up. It is too soon to restudy one infant. The remaining 16 infants had clinical (36 +/- 18 months) and catheterization (12 +/- 4 months) follow-up data. The residual coarctation gradient (22 +/- 15 mm Hg) and coarcted segment size (4.4 +/- 1.6 mm) remain improved (p less than 0.01) when compared with pre-balloon angioplasty values. Five of the 16 (31%) infants (four were neonates at the time of balloon angioplasty) had evidence for recoarctation (defined as gradient greater than 20 mm Hg) and underwent surgical resection (two) or repeat balloon angioplasty (three), all with success. None developed aneurysms. 
5	Hyponatremia-induced inhibition of magnocellular neurons causes stressor-selective impairment of stimulated adrenocorticotropin secretion in rats. Chronically hyponatremic rats were subjected to various stressors in order to evaluate the possible contribution of magnocellular neurons to the regulation of ACTH secretion, since such rats have markedly inhibited secretion and synthesis of magnocellular arginine vasopressin (AVP) and oxytocin (OT). Stress caused by a novel environment or by insulin-induced hypoglycemia resulted in moderate increases in plasma ACTH, which were of similar magnitude in both hyponatremic and normonatremic rats, and these stressors caused no increase in plasma AVP and OT levels in either group of rats. However, when exposed to ether, hyponatremic rats exhibited a significantly blunted ACTH response compared to normonatremic controls (331 +/- 49 vs. 740 +/- 124 pg/ml; P less than 0.01, respectively), and plasma AVP levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. Intravenous infusion of 2 M NaCl also caused an ACTH release in hyponatremic rats that was significantly smaller than that in their normonatremic counterparts (228 +/- 52 vs. 479 +/- 85 pg/ml; P less than 0.05, respectively), and in this case both plasma AVP and OT levels were markedly increased in the normonatremic, but not in the hyponatremic, rats. However, hyponatremic rats exhibited greatly increased plasma ACTH levels 2 and 96 h after adrenalectomy (ADX), which were statistically equivalent to the increases in ACTH levels in normonatremic rats after ADX. Seven days after ADX parvocellular neurons of the paraventricular nucleus showed strongly increased CRF-41 and AVP-neurophysin, but not OT-neurophysin, immunoreactivities in both normonatremic and hyponatremic rats. These results show that parvocellular CRF-41/AVP-producing neurons in the paraventricular nucleus are not inhibited by chronic hyponatremia, in contrast to magnocellular neurons, and suggest that ACTH secretion induced by ether or hypertonic saline, but not by novel environment or insulin-induced hypoglycemia, is partially mediated by magnocellular AVP and/or OT. 
5	Referred pain of muscular origin resembling endodontic involvement. Case report. Referred pain is common in the orofacial region and can cause considerable difficulties in diagnosis. Referred pain is defined as pain that is referred to a part of the body other than the site of origin, and as a result, severe pain may arise without an associated causative lesion. A muscular trigger point that resembled a tooth with endodontic involvement is discussed. 
5	Decreased ventilation and hypoxic ventilatory responsiveness are not reversed by naloxone in Lhasa residents with chronic mountain sickness. Persons with chronic mountain sickness (CMS) hypoventilate and are more hypoxemic than normal individuals, but the cause of the hypoventilation is unclear. Studies of 14 patients with CMS and 11 healthy age-matched control subjects residing in Lhasa, Tibet, China (3,658 m) were conducted to test the hypothesis that hypoventilation, blunted hypoxic ventilatory responsiveness (HVR), and hypoxic ventilatory depression of CMS were due to increased endogenous opioid production. Patients with CMS compared with control subjects exhibited hypoventilation (end-tidal carbon dioxide pressure [PETCO2] = 36.6 +/- 1.0 versus 31.5 +/- 0.5 mm Hg, p less than 0.05), lower tidal volume (VT = 0.54 +/- 0.02 versus 0.61 +/- 0.02 ml BTPS, p less than 0.05), blunted HVR (shape parameter A = 17 +/- 8 versus 114 +/- 22 mm Hg/L BTPS/min, p less than 0.05), and a depressant effect of ambient hypoxia on ventilation (delta PETCO2 with acute hyperoxia = -3.5 +/- 0.5 versus -1.0 +/- 0.6 mm Hg, p less than 0.05). Reduced forced expiratory volume in 1 s to vital capacity ratios (FEV1/VC) and a higher proportion of cigarette smokers in the group of patients with CMS compared with control subjects suggested that at least some patients with CMS had mild airway obstructive lung disease. Naloxone infusion (0.14 mg/kg) to six patients with CMS did not change resting VT, PETCO2, HVR, or SaO2. 
1	Insulin-like growth factor binding protein secretion by breast carcinoma cell lines: correlation with estrogen receptor status. Breast tumor cell lines have been shown to secrete several distinct polypeptide growth factors, although conflicting results exist for the insulin-like growth factors (IGFs). In contrast a limited number of breast tumor cell lines have definitely been shown to secrete the high affinity IGF binding proteins (IGFBPs) that modify IGF actions. To characterize the types of IGFBPs that are secreted by breast tumor cell lines, conditioned medium was collected from seven separate tumor cell lines, three of which were estrogen receptor (ER) negative, and four of which were ER positive. All three of the ER negative cell lines, MDA-231, MDA-330, and HS578T, secreted binding proteins of 49,000 and 43,000 Mr (IGFBP-3) as well as 29,000 (IGFBP-1) and 24,000 Mr. In contrast, all four ER positive cell lines secreted 34,000 (IGFBP-2) or 24,000 Mr forms, and none secreted the 49,000 and 43,000 or 29,000 Mr forms. BT-20, a cell line that is positive for ER messenger RNA (mRNA) but negative for ER protein, secreted predominantly a 34,000 Mr protein. The amount of total IGFBP activity released in 24 h ranged between 0.4 and 5.6 nM equivalents of IGFBP-1, and there was no significant difference between the ER positive and negative cell lines. The MCF-7 cells that produced predominantly 34,000 and 24,000 Mr forms showed a 1.8-fold increase in IGFBP secretion after estrogen stimulation. Immunoblotting and a specific RIA for IGFBP-1 showed that only the ER negative lines MDA-330, MDA-231, and HS578T secreted this form. Northern blotting analysis for the mRNA encoding this protein showed that both MDA-330 and MDA-231 contained a single 1.6 kilobase mRNA species that hybridized with an IGFBP-1 complementary DNA (cDNA) probe. Immunoblotting analysis of the other cell lines showed that only the 34,000 Mr form secreted by the ER positive cell lines reacted with IGFBP-2 antisera. Exposure of the conditioned media from the three ER negative cell lines to N-glycanase revealed that the 49,000 and 43,000 Mr forms of IGFBP were glycosylated and therefore probably represent IGFBP-3. We conclude that ER negative cell lines secrete three forms of IGFBPs, IGFBP-1, IGFBP-3, and a 24,000 Mr form. In contrast, the ER positive cell lines secrete predominantly IGFBP-2 and the 24,000 Mr form but do not secrete IGFBP-3 or 1.(ABSTRACT TRUNCATED AT 400 WORDS). 
4	Biobehavioral factors in Cardiac Arrhythmia Pilot Study (CAPS). Review and examination. The behavioral studies component of the multicenter Cardiac Arrhythmia Pilot Study (CAPS) was designed to examine the relation of biobehavioral factors and frequency of ventricular premature complexes (VPCs), efficacy of antiarrhythmic therapy, and disease end points in a study population that had experienced recent myocardial infarction and significant ventricular ectopy. Biobehavioral factors included both psychosocial (depression, anxiety, social support, type A behavior, mood, defensiveness, and anger expressiveness) and psychophysiological (heart rate and blood pressure reactivity to a videogame stressor) variables. Data were collected at baseline and at 3-, 6-, 9-, and 12-month follow-ups. Of the 502 patients enrolled in CAPS, 353 participated in the behavioral studies component. At baseline, assessments of psychosocial variables revealed the CAPS study population to be generally similar to other heart disease populations, and no relation between these variables and psychophysiological reactivity or arrhythmias was found. At follow-up among patients assigned to the placebo condition, biobehavioral variables were not related to levels of VPCs or VPC suppression. Cox regression analyses revealed that type B behavior, depression, and reduced heart rate reactivity were associated with increased clinical events, even after controlling for baseline left ventricular ejection fraction, myocardial infarction before the qualifying event, use of beta-blockers, use of digitalis, Q wave of qualifying myocardial infarction, and presence of unsustained ventricular tachycardia on baseline electrocardiogram. It is hypothesized that the relation among reduced heart rate reactivity, depression, and clinical events is mediated by diminished cardiac vagal tone. 
4	Acute pulmonary oedema following administration of ornithine-8-vasopressin. We report the case of a patient who developed acute pulmonary oedema following a short and uneventful surgical procedure. Among the differential diagnoses, the role of ornithine-8-vasopressin is emphasized. 
5	Evaluation of current extrication orthoses in immobilization of the unstable cervical spine. An experiment was designed to evaluate the comparative stabilizing efficacy of several widely used semi-rigid orthoses applied to unstable fresh cadaver cervical spines subject to load. Cadaver specimens were surgically destabilized at the C4-5 segment. Lateral radiographs of the destabilized spine were obtained before and after collar placement and after the application of a 5-pound flexion force. Data analysis employing a one-way analysis of variance showed no statistically significant difference in the Necloc's, Philadelphia Collar's, or the Stifneck's ability to stabilize the cervical spine against a deforming flexion force (P greater than 0.05). They all provide translational stability while allowing angular changes to occur with application of the flexion force. The Philadelphia Collar Halo System is statistically superior to all three of the aforementioned collars in prevention of both translation and sagittal rotation (P less than 0.05). 
4	Primary repair for complete atrioventricular canal: recommendation for early primary repair. Forty patients with complete atrioventricular canal (CAVC) underwent primary repair at Fukuoka Children's Hospital in Fukuoka, Japan, between August 1, 1981 and July 31, 1989. The age at repair ranged from 2 months to 6 years (mean 19 months); weight ranged from 2.3 to 22 kg. The surgical mortality was 2.5%. Justification for early primary repair was examined. Eleven patients underwent repair before 6 months of age (Group 1), 12 patients, between 7 and 11 months of age (Group 2), and 17 patients, after 12 months of age (Group 3). Degenerative changes in the atrioventricular valve increased significantly as age at repair increased (p less than 0.05 Group 1 versus Group 3). The incidence of residual mitral regurgitation tended to increase in the order of Group 1, 2 and 3, though the degree ranged from trivial to mild. Study of the left atrium/aorta ratio by echocardiography revealed that stable values of around 1.1 in Groups 1 and 2 and around 1.3 in Group 3 continued during the follow-up period of 3 years. Assessment of the diameter of the repaired mitral valve in the mean interval of 26 months in groups 1 and 2 revealed normal growth of the mitral valve annulus. The angle between the repaired mitral valve and ventricular septum, which can be affected by the growth of the ventricular septum, converged to normal range in the mean interval of 26 months. Postoperative pulmonary vascular resistance in Groups 2 and 3 was higher at 4.4 +/- 2.3 and 6.3 +/- 2.2, respectively, than in Group 1 at 3.3 +/- 2.2 (p less than 0.01 versus Group 3). 
2	Selective intestinal decontamination prevents spontaneous bacterial peritonitis. In a prospective randomized study, selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels. The incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics. We found a significantly lower incidence of infections [1/32 (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs. 7/31 (22.5%); P = 0.052] in the treated group did not reach statistical significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P less than 0.05] in cirrhotic patients admitted because of ascites was also significantly lower in the treated group. The decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance. These data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels. 
5	Intestinal ischemia complicating abdominal aortic surgery. A 9-year experience with 2137 patients undergoing infrarenal abdominal aortic reconstruction was reviewed to determine both the incidence of intestinal ischemia and the clinical, anatomic, and technical factors associated with this complication of aortic surgery. A total of 24 (1.1%) patients had overt intestinal ischemia, documented by reoperation or endoscopic findings. Of these, colon ischemia occurred in 19 (0.9%) and small bowel ischemia developed in 5 (0.2%) patients. The incidence after elective operation for aneurysmal or occlusive disease did not differ, but patients with ruptured aneurysms and those undergoing reoperative procedures for total graft replacement were at higher risk. Preoperative angiography was most helpful in ascertaining risk. Ligation of a patent inferior mesenteric artery was the most common (74%) feature in patients with colon ischemia. With preexisting inferior mesenteric artery occlusion, impairment of collateral circulation was attributable to superior mesenteric artery disease, dissection or retractor injury, prior colon resection, or exclusion of hypogastric perfusion. Bloody diarrhea was the most frequent postoperative symptom and colonoscopy the most reliable means of diagnosis. One half of patients with colon ischemia required resection after late recognition of perforation. All cases of small bowel ischemia were related to superior mesenteric artery disease or injury or use of suprarenal clamping. The overall mortality rate was 25% but rose to 50% if bowel resection was required. Intestinal ischemia remains an infrequent but serious complication of aortic surgery. Despite a multifactorial cause, identification of patients at increased risk can lead to operative strategies to reduce its occurrence. 
1	Simultaneous presentation of adenocarcinoma of prostate and transitional cell carcinoma of bladder. Simultaneous presentation of transitional cell carcinoma of the bladder and adenocarcinoma of the prostate is not uncommon. Twenty-two patients were diagnosed as having simultaneous or concurrent presentation of prostate and bladder carcinomas between January 1970 and July 1986. The overall five-year survival was 40 percent, with patients presenting with prostate cancer doing better (50%) than those with bladder cancer (32%). Retrospective review of these cases suggests that primary therapy should be directed to the most advanced cancer. Incidental prostate cancer may be "cured" with a cystoprostatectomy and, when indicated, radiation therapy added postoperatively for the bladder cancer. Eleven patients presented with Stage A prostate cancer: 10 of the 11 were treated for their bladder cancer. Treatment was usually radical cystoprostatectomy with or without postoperative radiation. None died of prostate cancer. Patients presenting with advanced stage prostate cancer have had recurrence or have died of the cancer. 
5	Acute appendicitis in the pregnant patient. Acute appendicitis is the most common surgical problem in pregnancy requiring emergent intervention. To establish a contemporary patient profile and formulate an effective management strategy, a retrospective review was conducted of 84 pregnant patients who underwent laparotomy with a preoperative diagnosis of acute appendicitis. Gestational stage at presentation included the first trimester in 27 patients (32%), the second trimester in 37 patients (44%), the third trimester in 13 patients (16%), and the puerperium in 7 patients (8%). Fifty-four patients (64%) had pathologically proven acute appendicitis; the incidence did not vary by trimester. Other intra-abdominal conditions were detected in 15 patients (18%). There were no significant differences between patients with positive and negative laparotomies (or among trimesters) regarding frequency of presenting symptoms and signs or laboratory results. Operation occurred within 24 hours of symptom onset in 19 of 54 (35%) instances of proven acute appendicitis. Perforation occurred in 23 of 54 patients (43%), all of whom had symptoms exceeding 24 hours (p less than 0.0005). Five instances of perinatal death and one case of extreme perinatal morbidity were associated with negative laparotomies; only one of these was attributed to operation itself. No adverse long-term maternal morbidity or mortality occurred. Wound infection developed in seven cases of acute appendicitis (six perforated) and two negative explorations. We conclude that (1) gestational physiologic changes obscure the accurate diagnosis of acute appendicitis; (2) the natural history of acute appendicitis is not affected by trimester of presentation; and (3) adverse sequelae of acute appendicitis are obviated by prompt operative exploration and prevention of appendiceal perforation. 
2	Preoperative stabilisation in congenital diaphragmatic hernia. Between January 1983 and November 1986, 26 newborn infants with congenital diaphragmatic hernia were treated by early operation at a mean of 7 hours of age. A further 23 infants admitted between December 1986 and December 1989 were stabilised for a mean period of 40 hours before operation. There was no significant difference in survival between the two groups. Delayed operation is not detrimental to infants with congenital diaphragmatic hernia. 
1	Clinicopathological experience with pineocytomas: report of five surgically treated cases. The clinicopathological experience associated with five cases of pineocytoma is presented. All patients were treated by surgical removal without postoperative radiotherapy. In three individuals, 2000 cGy was administered to the tumor as a presurgical diagnostic test, with no evidence of response. All cases demonstrated histological features of pineocytoma, according to the criteria of Borit et al., and of the so-called "pineocytoma with neuronal differentiation," according to the criteria of Rubinstein. The experience obtained from the present series reveals that these tumors can occur in the initial decades of life, that a cystic appearance and the presence of calcifications are distinctive features of their radiological evaluation, and that they have a good prognosis after surgical removal, even when the histological data indicate local invasion. The convenience of reserving the term "pineocytoma" for these tumors, and of including the so-called "pineocytomas without further differentiation" within the group of pineoblastomas, is suggested in order to achieve a practical clinicopathological assessment of parenchymatous pineal tumors. 
5	A huge intracranial xanthogranuloma in the middle cranial fossa: case report. Xanthogranulomas of the dura presenting with clinical symptoms are rare. We report here a case of a huge dural xanthogranuloma in the middle cranial fossa, which caused hemiparesis through marked displacement and stenosis of the middle cerebral artery. Although such tumors usually arise in association with histiocytosis X or familial hyperlipoproteinemia, the present case was not associated with these diseases. 
5	Histology of the lens in the Weill-Marchesani syndrome. The Weill-Marchesani syndrome is a rare systemic connective tissue disease characterised by small stature, brachydactyly, ectopia lentis, and spherophakia. Three siblings with typical manifestations of this syndrome were reported. The ophthalmological findings in all these cases were spherophakia, severe myopia, a shallow anterior chamber, and narrow angle glaucoma. Two cases underwent laser iridotomy and drug treatment. In the third case the lens was removed from the eye because of injury, and this lens was examined by light and electron microscopy. 
5	Interphase cytogenetic analysis in the diagnosis and study of neoplastic disorders. Cytogenetic information usually is obtained through the direct analysis of chromosomes from cells arrested in metaphase. Recently, advances in molecular genetics have made it possible to acquire cytogenetic information through the study of interphase and terminally differentiated cells. By using chromosome-specific DNA probes or probes that are specific for certain chromosomal regions, and by employing techniques of in situ hybridization along with nonradioactive detection methods, it is now possible to detect numerical and structural chromosomal abnormalities from nonmetaphase cells. When used as an adjunct to conventional cytogenetic analysis or when used together with knowledge of established cytogenetic findings for a particular malignancy, this new technology can serve to broaden the scope and utility of cytogenetic analysis beyond the limits of the present metaphase-based technology. Interphase cytogenetic analysis has application to the diagnosis and study of neoplastic disorders and, thus, has particular importance in pathology. 
4	Comparison of lisinopril versus atenolol for mild to moderate essential hypertension. The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension. 
5	Dysgeusia, gustatory sweating, and crocodile tears syndrome induced by a cerebellopontine angle meningioma. Facial nerve involvement in cerebellopontine angle tumors, both during their development and after excision, may be expressed in irreversible dysfunction of the parasympathetic pathways. The exact location of the lesion along the efferent nerve fibers can be established through evaluation of the functional level of those organs supplied by the cholinergic motor secretory components. This report deals with a female patient in whom peripheral facial palsy developed shortly after removal of a right cerebellopontine angle meningioma. She had slight facial asymmetry and deafness in the right ear and complained of prandial flush and sweating of the right malar area. Occult ipsilateral hyposalivation and hypolacrimation were diagnosed. In patients with seventh and ninth cranial nerve pathoses, evaluation of the end organs that are supplied by their associated autonomous nerve fibers is mandatory to prevent late ocular and oral sequelae. 
4	Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28. X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria is clinically characterized by congenital dilated cardiomyopathy, skeletal myopathy, recurrent bacterial infections, and growth retardation. We analyzed linkage between the disease locus and X-chromosomal markers in a family with seven carriers, four patients, and eight unaffected sons of carriers. Highest lod scores obtained by two-point linkage analysis were 2.70 for St14.1 (DXS52, TaqI) at a recombination fraction of zero and 2.53 for cpX67 (DXS134) at a recombination fraction of zero. Multipoint linkage analysis resulted in a maximum lod score of 5.24 at the position of St35.691 (DXS305). The most distal recombination detected in this family was located between the markers II-10 (DXS466) and DX13 (DXS15). These data indicate the location of the mutated gene at Xq28. 
5	Multimodality evoked potential testing in acute mild closed head injury. Multimodality evoked potential (MEP) testing, including brainstem auditory, visual, and somatosensory evoked potentials, have been reported to be useful in predicting outcome in severe closed head injury. Brainstem auditory evoked potentials have been demonstrated to be abnormal in 10% to 40% of acute mild head injury. A prospective study of 18 patients with mild closed head injury was undertaken to determine the usefulness of MEP screening within two weeks of the acute event. Long latency event-related potentials (P300s), in response to auditory stimuli with an oddball paradigm, were included in the screening. The subjects had several symptoms consistent with the postconcussive syndrome at the time of the evoked potential testing. Only one patient had an abnormal evoked potential response (greater than three standard deviations from the mean) from all the testing done. The standard methods of MEP testing were insensitive to quantifying the possible physiologic changes that are associated with memory deficits, lethargy, and emotional irritability after mild closed head injury. 
4	Impact of nonoperative therapy on the clinical management of peripheral arterial disease. Nonoperative therapy includes conservative noninterventional modalities and the endovascular interventional modalities of percutaneous transluminal angioplasty and a variety of laser systems and atherectomy devices. The role and impact of all nonoperative treatments are considered in the perspectives of the natural history of lower-extremity arteriosclerosis and its present surgical (operative) treatment. Nonoperative treatments may replace and/or facilitate surgical treatment in operative candidates. Nonoperative methods may also justify treatment in patients who cannot or should not be subjected to surgery. Facts and opinions relating to these uses of nonoperative treatments are presented, and the qualifications and credentialing of individuals who should be treating patients with lower-extremity ischemia resulting from peripheral arteriosclerosis are discussed. 
1	Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression. 
4	Frequency and severity of mitral regurgitation one year after balloon mitral valvuloplasty. Mitral regurgitation (MR) was evaluated by Doppler echocardiography in 59 patients with mitral stenosis before, immediately after and 1 year after balloon mitral valvuloplasty (BMV). The severity of MR was graded on a scale from 1+ to 4+. Echocardiographic and hemodynamic variables were analyzed to study the potential factor(s) that might predict the long-term persistence of MR. Echocardiographic variables were mitral valve thickness and motion, subvalvular change, left atrial dimension, commissural calcification and effective balloon/mitral anular diameters. Hemodynamic variables were mitral pressure gradient, pulmonary arterial pressure, ejection fraction, mitral valve area index, age, gender and cardiac rhythm. Mitral valve area index increased from 0.9 +/- 0.5 to 1.5 +/- 0.8 cm2/m2 immediately after BMW, and to 1.4 +/- 0.3 cm2/m2 at 1 year follow-up (p less than 0.01). Immediately after BMV, MR grading did not change in 30 patients (51%), increased by 1+ in 23 patients (39%), by 2+ in 2 patients (3.3%) and by 3+ in 2 patients (3.3%), and decreased by 1+ in 2 others. At 1-year follow-up, only 1 patient with severe MR required valve replacement. Fifty-one patients (88%) had no change in the extent of MR (less than or equal to 1+) and 6 patients (10%) had a 1-grade decrease in their MR; only 1 patient had a 1-grade increase in MR. No clinical or hemodynamic variables or morphologic characteristics of the mitral valve could predict the development of significant MR after BMV. It is concluded that an increment in MR severity less than or equal to 2+ is frequently seen after BMV. 
1	A diagnostic expert system for colonic lesions. The diagnostic expert system for colonic lesions (DESCL) was designed to discriminate colonic adenoma and adenocarcinoma from normal colonic tissue. Although it was originally developed for use in conjunction with a machine vision analytic system, the DESCL has evolved into a teaching tool and a model for conceptual machine learning. The expert system is table driven and consists of a shell and a knowledge base. The latter comprises a series of architectural and cytologic observations and a quantitative estimate of diagnostic importance relating these observations to diagnostic outcome. In a validation study of 100 colonic lesions, the expert system achieved a success rate of 98%. It has the flexibility to allow individual pathologists to "customize" the knowledge base to suit their diagnostic criteria. 
3	Ocular manifestations of onchocerciasis in a rain forest area of west Africa. The epidemiology and natural history of onchocerciasis and its ocular complications in rain forest areas are poorly understood. The present study was conducted on a rubber plantation in a hyperendemic area in the rain forest of Liberia, West Africa, where 800 persons were examined. The prevalence of infection was 84% overall 29% had intraocular microfilariae, and 2.4% were blind in one or both eyes. Onchocerciasis was the cause of all binocular blindness and one-third of all visual impairment. Over half of the visual impairment caused by onchocerciasis was due to posterior segment diseases. Chorioretinal changes were present in 75% of people, and included intraretinal pigment clumping in 52% and retinal pigment epithelium atrophy in 32%. Atrophy of the retinal pigment epithelium was associated with increasing age and severity of infection. Intraretinal pigment was strongly associated with anterior uveitis. There was a strong correlation between uveitis and the inflammatory chorioretinal sequelae: retinitis, intraretinal pigment, subretinal fibrosis, and optic neuropathy. These findings indicate that considerable visual impairment associated with rain forest onchocerciasis is common and is due largely to chorioretinal disease. 
2	Hemodynamic effects of H2-receptor antagonists. Histamine H2-receptor antagonists (H2RAs) often are administered to intensive care unit patients in an attempt to reduce gastric acidity and to prevent stress-related mucosal damage. These agents have an extremely low overall incidence and severity of adverse reactions; however, hemodynamically significant hypotension has been noted. Clinical studies with rapidly administered intravenous cimetidine in critically ill patients have demonstrated a depression in blood pressure in up to 75 percent of patients. Ranitidine, also studied in this setting, does not appear to induce similar hemodynamic changes. The newer H2RAs, famotidine and nizatidine, have not been evaluated in critically ill patients. 
4	A composite driving system for LVAS and IABP: practical and effective driving and weaning. We have devised a new method, termed alternate synchronous driving (ASD), to wean patients from a left ventricular assist system (LVAS) to a pressure assist intraaortic balloon pump (IABP). We have built a new drive unit, VCT200, to apply ASD easily and automatically. After IABP insertion in the final weaning stage, this method drives the LVAS and IABP alternately, with electrocardiogram (ECG) synchronization. The pumping ratio of IABP increases while that of LVAS decreases according to recovery of natural heart function. In in vitro studies, ASD was effective when bypass flow (BF) was less than 50% of total flow (TF) (TF:BF + cardiac output [CO]), and its advantages increased under lower BF conditions. Mean aortic pressure (mAP) and CO increased 10 mmHg and 15%, respectively, with this method (IABP:LVAS = 1:1) when BF was 30% of TF. During in vivo studies, mAP increased 75.7 +/- 6.7 mmHg to 80.1 +/- 3.6 mmHg (p less than 0.001), and the CO increased from 3.1 +/- 0.5 L/min to 3.3 +/- 0.5 L/min (p less than 0.001), while the endocardial viability ratio (DPTI/TTI) increased 20-30%. This method was used in a 62-year-old man in which LVAS was applied after ventricular aneurysmectomy, BF was reduced from 2.2 L/min to 1.1 L/min by using ASD without any change in systemic perfusion. This reduction of BF could not be achieved with LVAS alone. From these data, this system could wean patients from LVAS and then switch to IABP smoothly, easily, and automatically, without hemodynamic instability. 
1	Pathological classification and follow-up of prostatic lesions initially diagnosed as "suspicious of malignancy". Sections from a series of prostatic specimens (n = 44) in which the initial diagnosis implied a suspicion of malignancy were reviewed and the patients followed up (group 1). The aim was to categorise the morphological appearances according to current criteria and to determine the natural history of any pre-malignant lesions within this group. A "control" series of patients (n = 40) in whom the primary diagnosis was benign were also reviewed and their course followed (group 2). The heterogeneity of the abnormalities in group 1 was striking. Of the 44 cases, pre-malignant lesions were seen in 8, microinvasive adenocarcinoma in 11 and lesions not now considered pre-malignant in the remaining 25. None of the 8 patients with pre-malignant lesions developed clinical evidence of carcinoma over a follow-up period of 8 to 12 years. In contrast, 3 of the 11 diagnosed on review as having microscopic invasive adenocarcinoma developed clinically evident tumour within 5 years of surgery. Of the 25 patients whose prostatic lesions were considered benign, 2 developed carcinoma 12 and 13 years after surgery. Only 1 of the 40 patients in group 2 had a pre-malignant lesion and he did not develop tumour within 10 years. However, adenocarcinoma was diagnosed incidentally in 1 patient 3 years after surgery. It was concluded that there is a need to standardise interpretation and reporting of pre-malignant lesions and microscopic foci of adenocarcinoma in the prostate. The limited results on the course of pre-malignant lesions diagnosed incidentally in patients over 60 years of age do not indicate that follow-up would have prompted the early diagnosis of invasive disease. 
4	Long-term function of persons with atherosclerotic bilateral below-knee amputation living in the inner city. Long-term function of 24 elderly persons with atherosclerotic bilateral below-knee amputation living in an inner city for at least six months after the second amputation, was determined. Twenty-one (87.6%) subjects were living at home; three were living in nursing homes. Fourteen (70%) of 20 subjects who received bilateral prostheses were ambulators. At interview, the mean age was 75.2 years; 4.87 years was the mean time since the second amputation. Ten (50%) subjects remained ambulatory. Among the other ten who received prosthesis, loss of ambulation occurred mostly due to medical factors, at an average of 3.47 years after the second amputation. Those no longer ambulatory were older and "sicker," and the interval between amputations was shorter. Fifteen (62.5%) subjects were independent in dressing, 14 (58.4%) in toileting, and only nine (33.3%) in bathing. All but one subject required housekeeping assistance. The anticipated effect on function of environmental and socioeconomic factors could not be demonstrated in this sample. Survival time and retention of ambulatory skills for an average of nine years after the second amputation in eight (33.3%) subjects who died before the end of the study was longer than previously described. The high rate of success in rehabilitation and in maintenance of ambulatory skills fully justifies intensive restorative efforts for this group of amputees. 
3	Comparative ophthalmologic studies on children and adults with craniopharyngiomas. The subjects of the study are 74 patients with craniopharyngiomas treated at the Clinic of Neurosurgery, Bulgarian Medical Academy, within the period 1960-1989. Fifty of the patients are children and 24 adults. The diagnosis of all patients is made on the base of clinical, X-ray and histological studies. The ophthalmologic state was studied in all patients, prior to operation, via routine methods. Reduced visual acuity was established in 69.6% of the children and 81.8% of the adults. The presence of congestive optic papilla was diagnosed in 22% of the children and 12.5% of the adults. Optic atrophy was established in 62.5% of the adults and 52% of the children. Various defects in the visual field were established in 67.7% of the children and 81.8% of the adults with the predomination of bitemporal defects. The use of highly informative conventional and modern X-ray methods is recommended in all patients suspected of compression of the visual pathways. 
1	Papillary endothelial hyperplasia in the thyroid following fine-needle aspiration. A 74-year-old woman was found to have exuberant papillary endothelial hyperplasia within her thyroid gland subsequent to multiple fine-needle aspiration biopsies of a Hurthle cell neoplasm. To our knowledge, this histologic alteration in the thyroid has not been previously reported. We describe this unusual complication following fine-needle aspiration, and we delineate the clinicopathologic and differential diagnostic features. 
4	False aneurysm formation of the great arteries after arterial switch operation. An infant with simple transposition of the great arteries underwent a two-staged arterial switch operation, after which mediastinal infection occurred. Continuous irrigation with povidone-iodine solution was performed for 10 days. After that, the patient experienced life-threatening hemorrhage three times. At the time of the second hemorrhage, greater omental transfer was performed. On postoperative day 109, false aneurysm was recognized, having developed from both great arteries. Successful repair was performed on postoperative day 110. 
5	Urinary tract infections. Urinary tract infections are a common infection for the primary care physician to see in the office. Epidemiology, pathogenesis, diagnosis, management, and prophylaxis are discussed. Information regarding special patient populations, such as pregnant women and children, is also provided. 
2	Cross-national changes in the effects of peptic ulcer disease. OBJECTIVE: To describe and to analyze the changing effects of peptic ulcer disease over time. DESIGN: Variables relating to peptic ulcer disease from 1970-1986 were compared. The variables included rates of mortality, hospitalizations, operations, physician visits, and endoscopies, and the amount of disability-related loss of work and early retirement in six countries (Belgium, England and Wales, the Federal Republic of Germany, The Netherlands, Sweden, and the United States). MEASUREMENTS: Nonparametric epidemiologic time-trend analysis. MAIN RESULTS: The historic, slow, declining trend in mortality and hospitalization rates continued. The rate of operations for peptic ulcer disease exhibited a large, one-time reduction, then returned to a parallel declining trend, but at a lower level. The rate of physician visits declined by 50%. The greatest changes were found in the rate of endoscopy use and in disability-related loss of work and early retirement, where increasing trends were quickly followed by decreasing trends. The elderly, especially women, generally did not share many of these benefits. CONCLUSIONS: The effects of new interventions can be understood more fully by examining several variables in many countries over a long time. Contrary to expectations, the effects of the widespread use of histamine H2 antagonists have been more indirect (affecting work loss and disability retirement more) than direct (affecting high-cost medical service use and mortality less). 
5	Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses BACKGROUND. Patients undergoing heart-valve replacement may receive a mechanical prosthesis, necessitating lifelong anticoagulant treatment, or a porcine bioprosthesis, which involves no absolute need for anticoagulants. METHODS. We carried out a randomized, prospective trial to compare the durability of the Bjork-Shiley mechanical prosthesis (spherical tilting-disk model) and the incidence of valve-related complications with those variables in the Hancock and the Carpentier-Edwards porcine prostheses. The mitral valve was replaced in 261 patients, the aortic valve in 211, and both in 61; the survivors have been followed up for a mean of 12 years. RESULTS. We found a trend toward improved actuarial survival after 12 years with the Bjork-Shiley prosthesis, but this trend was not statistically significant (group with Bjork-Shiley valve vs. group with porcine valve [mean +/- SE], 51.5 +/- 3.2 vs. 44.4 +/- 3.2 percent; P = 0.08). There was no significant difference in the actuarial incidence of reoperation after 5 years, but after 12 years significantly more patients with a porcine prosthesis had undergone reoperation (8.5 +/- 2.0 vs. 37.1 +/- 4.1 percent, P less than 0.001). An analysis combining death and reoperation as end points for an actuarial assessment of survival with the original prosthesis intact confirmed that the patients with Bjork-Shiley Shiley prostheses had improved survival (48.6 +/- 3.2 vs. 30.0 +/- 3.0 percent after 12 years, P less than 0.001). Bleeding requiring hospitalization or blood transfusion was significantly more frequent in the patients with Bjork-Shiley prostheses (18.6 +/- 3.2 vs. 7.1 +/- 2.3 percent after 12 years, P less than 0.01). There was no significant difference after 12 years in the actuarial occurrence of embolism (Bjork-Shiley vs. porcine, 21.1 +/- 3.1 vs. 26.4 +/- 3.5 percent) or endocarditis (3.7 +/- 1.4 vs 4.6 +/- 1.6 percent). CONCLUSIONS. Survival with an intact valve is better among patients with the Bjork-Shiley spherical tilting-disk prosthesis than among patients with porcine bioprostheses, but use of the Bjork-Shiley valve carries an attendant increased risk of bleeding associated with the need for anticoagulant treatment. 
3	Rett syndrome: findings suggesting axonopathy and mitochondrial abnormalities. We report the histopathologic findings of 3 sural nerve biopsies and 1 muscle biopsy from 3 patients with Rett syndrome. The 3 sural nerve biopsies demonstrated a few ultrastructural abnormalities, including the presence of many Pi-granules and mitochondrial changes in the cytoplasm of Schwann cells, occasional bands of Bungner and onion-bulb formations, and mitochondrial alterations in myelinated axons. Morphometric analysis disclosed reduction in the number of large myelinated fibers with normal densities in comparison to those of an age-matched normal control. Light microscopic examination of the biopsied muscle from a 6-year-old patient with Rett syndrome revealed the existence of many small, dark, angulated fibers with NADH-TR staining. Ultrastructural investigation of the muscle confirmed the presence of the dumbbell-shaped mitochondria. Peripheral nerve involvement and the possibility of mitochondrial abnormalities in Rett syndrome were suggested by the results. 
5	T-cell translocation gene 1 (Ttg-1) encodes a nuclear protein normally expressed in neural lineage cells. We previously identified and cloned T-cell translocation gene 1 (Ttg-1), a putative zinc finger protein, as a result of its deregulated expression in a T-cell acute lymphoblastic leukemia cell line (RPMI 8402) with a t(11;14)(p15;q11). We have now characterized its genomic organization and identified the major transcriptional start site to lie within an initiator-like motif. Ttg-1 is normally expressed in mouse brain and not in thymus. The mouse neuroblastoma cell line, N2a, also expresses Ttg-1. Antibodies raised against a TrpE-Ttg-1 fusion protein precipitate an 18-Kd nuclear protein from metabolically labeled 8402 cells. Immunofluorescence of N2a cells shows a nuclear pattern. The two potential zinc finger domains in Ttg-1 are highly homologous to similar regions in lin-11, mec-3, and lsl-1. This data suggests that Ttg-1 may be involved in gene regulation. 
1	Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. II. Relationship between receptor expression and response to epidermal growth factor. Previously we have shown that epidermal growth factor acts as a mitogen for some, but not all, ovarian cancer cells in culture. In this study we examined the effect of epidermal growth factor on proliferation of normal human ovarian epithelial cells in monolayer culture. We found that epidermal growth factor stimulated twofold to fourfold increases in proliferation in epithelial cells from each of five normal ovaries (p less than 0.01). In addition, Scatchard analysis of binding of epidermal growth factor tagged with iodine 125 indicated the presence of high-affinity receptors in all of the ovarian epithelial cells and ovarian cancer cell lines. The number and affinity of receptors was similar in the normal epithelium and cancer cell lines, and there was no relationship between epidermal growth factor receptor number and responsiveness to epidermal growth factor. We conclude that human ovarian epithelial cells normally express epidermal growth factor receptors and that epidermal growth factor acts as a mitogen for these cells. Although the mitogenic response to epidermal growth factor often is attenuated in ovarian cancer cell lines, loss of responsiveness to epidermal growth factor does not appear to be due to decreased receptor expression. 
5	Tissue expansion of the head and neck. Indications, technique, and complications. Tissue expansion is indicated in the reconstruction of various defects of the head and neck in instances where there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It may also be indicated in instances where repair of a defect by an alternative method such as a local, regional, or distant flap will result in an unacceptable donor or recipient site deformity. Although tissue expansion is simplistic in concept, it does require judgment and indepth preoperative planning to ensure optimal results. The complication rate is high for tissue expansion in the head and neck, particularly in the cheek and neck area. Despite the frequency of complications, in the vast majority of cases the intended reconstruction is successful. 
5	Bacteremia with otitis media. To investigate the occurrence and outcome of bacteremia associated with otitis media, charts were reviewed from patients who were 3 to 36 months of age, had temperatures greater than or equal to 39 degrees C, and were diagnosed with isolated clinical otitis media. A total of 2982 patients were identified. Blood cultures were obtained from 1666 (56%). Of the 1666 patients, who had blood drawn for cultures, 50 (3.0%) had bacteremia. These included 39 with Streptococcus pneumoniae, 4 with Haemophilus influenzae, 2 with Neisseria meningitidis, 3 with Salmonella species, and 2 with Staphylococcus aureus. The incidence of bacteremia increased at higher temperatures, being 1.9% at temperatures less than or equal to 40 degrees C and 5.0% at temperatures greater than 40 degrees C. Younger children were more likely to have bacteremia; 3.7% less than or equal to 12 months of age, 2.4% 13 to 24 months of age, and 1.9% 25 to 36 months of age had blood culture results that were positive (not significant). Reevaluation of the 50 bacteremic patients showed that 9 patients had continued fever, 3 patients had persistent bacteremia, pneumonia developed in 1 patient, and meningitis developed in 1 patient. It was concluded that (1) 3% of young febrile children with otitis media have bacteremia at the time of evaluation, a rate comparable to that previously reported in children with no focus of infection; (2) the incidence of bacteremia increases at higher temperatures; and (3) most febrile children with otitis media do well. The clinician must therefore weigh the potential benefit of drawing a blood culture to identify children at risk for complications against the inherent cost, inconvenience, and discomfort. 
5	Approach to the patient with genital ulcer disease. The three major diseases characterized by genital ulcers--genital herpes, syphilis, and chancroid--are common, with genital herpes being most common in industrialized countries and chancroid being most common in developing countries. One fourth to one half of patients with genital ulcers have no diagnosed cause for their illness despite diagnostic efforts. The bulk of these cases is probably constituted by one of the three diseases for which diagnostic tests are falsely negative. There is accumulating evidence that genital ulcers facilitate the transmission of human immunodeficiency virus (HIV), and they may also be markers of high-risk behavior for acquisition of HIV. Appropriate therapy of patients with genital ulcers (as well as their sexual partners) depends on accurate diagnosis. Patients with genital ulcers, particularly those with syphilis or chancroid, should be encouraged to undergo testing for HIV infection. 
5	Persistent ectopic pregnancy following laparoscopic linear salpingostomy. As the surgical approach for ectopic pregnancies evolves from radical to conservative procedures, the potential hazard of persistent ectopic pregnancy has become increasingly pertinent. From September 1, 1986 to August 31, 1989, 11 women with persistent ectopic pregnancy after laparoscopic salpingostomy were diagnosed and treated at Yale-New Haven Hospital. Persistent ectopic pregnancy was suspected in nine cases because of symptoms and in two because of plateauing beta-hCG titers. Ten of 11 patients underwent repeat surgery. Eight had partial or complete salpingectomy of the involved ipsilateral tube, two had repeat salpingostomies, and one was treated with methotrexate. When the 11 women with persistent ectopic pregnancies were compared with 70 patients treated successfully by laparoscopic salpingostomy using multivariate stepwise logistic regression, smaller size of the ectopic (P less than .01) and fewer days of amenorrhea (P less than .05) predicted persistent ectopic pregnancy after laparoscopic salpingostomy. Based upon our experience, we believe that earlier-treated ectopic pregnancies (ie, fewer than 42 days of amenorrhea) and/or smaller ectopics (ie, 2.0 cm or less in diameter) require treatment with particular caution and close postoperative surveillance. 
3	Anoxic injury of mammalian central white matter: decreased susceptibility in myelin-deficient optic nerve. The rat optic nerve, a typical central nervous system white matter tract, rapidly loses excitability when it is exposed to anoxia and is irreversibly damaged by prolonged anoxia. Neonatal optic nerve is extremely resistant to anoxia-induced dysfunction and injury; the adult pattern of response to anoxia appears between 10 and 20 days postnatal, that is, during the period of oligodendroglial proliferation and myelination. To test the hypothesis that myelination, or associated events, confer anoxic susceptibility on developing white matter, we analyzed the effects of anoxia on the myelin-deficient (md) strain of rat. Acutely isolated optic nerves from 19- to 21-day-old md rats and control optic nerves from unaffected male littermates were maintained in vitro at 37 degrees C, and exposed to a standard 60-minute period of anoxia. The supramaximal compound action potential was recorded and amplitude of the compound action potential, expressed as % of amplitude before anoxic exposure, was determined. The compound action potential was nearly abolished within 3 to 6 minutes after onset of anoxia in control optic nerves, while optic nerves from md rats displayed a slower decrease in compound action potential amplitude during anoxia, with a distinct action potential present even after 60 minutes of anoxia. Optic nerves from md rats showed significantly greater recovery of compound action potential (71 +/- 25%) than did control optic nerves (33 +/- 21%; p less than 0.02) after 60 minutes of anoxia. These findings support the hypothesis that myelination, or changes associated with it, may be important in the development of anoxic susceptibility in central white matter. 
5	Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study. A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities. 
5	Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness. Antibody-dependent enhancement of certain virus infections can occur in cells expressing Fc receptors. This mechanism plays an important pathogenetic role in the development of complications associated with dengue virus infection, including dengue hemorrhagic infection and dengue shock syndrome. The virulence of the virus, characterized by the ability to infect Fc receptor-bearing monocytes also influences the development of these severe illnesses. 
2	Primary and metastatic pulmonary meningioma. Patient 1 was a 53-year-old man who had a very rare primary pulmonary meningioma that developed in the left lingular segment. When this report was written, 7 years had passed since he underwent operation, and no recurrence of the meningioma had been detected. In Patient 2, a 61-year-old woman, multiple pulmonary metastases were confirmed 19 years after she had undergone operation for multiple cerebellar meningiomas, and the metastases were resected. After 2 years, multiple intraperitoneal metastases were found, and thus aggressive surgery was performed. Currently, 22 years after the operation for the primary cerebellar meningioma, the patient is alive without any subjective symptoms, although intraperitoneal metastases have recurred. To date, only four cases (all in women) of primary pulmonary meningioma have been reported. Case 1 reported in this article is thus the first case in a male patient to be reported, and, in addition, this patient also has the first reported case to have been evaluated for more than 5 years. In Case 2, however, each of the excised extracranial tumor lesions was histologically homogeneous and showed a hemangiopericytomatous pattern. The histologic picture of those tumor lesions was exactly the same as the picture of a small portion of the cerebellar meningiomas excised 19 years earlier. Thus, all those extracranial tumor lesions were diagnosed to be metastatic meningiomas. However, it is difficult to explain why there had been no symptoms for as long as 19 years until the pulmonary metastases were discovered. 
5	Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. One thousand and one men, aged 35-65 years, were identified from the age-sex register of one group general practice. Over four years 900 men were visited at home and asked questions about symptoms potentially related to sleep apnoea and snoring. Height, weight, neck circumference, resting arterial oxygen saturation (SaO2), and spirometric values were also determined. All night oximetry was then performed at home and the tracing analysed for the number of dips in SaO2 of more than 4%. Subjects with more than five dips of 4% SaO2 or more per hour were invited for sleep laboratory polysomnography. Seventeen per cent of the men admitted to snoring "often." Multiple linear regression techniques identified and ranked neck circumference (r2 = 7.2%), cigarette consumption (r2 = 3.4%), and nasal stuffiness (r2 = 2%) as the only significant independent predictors of snoring. Together these account for at least a sixfold variation in the likelihood of being an "often" snorer. Forty six subjects (5%) had greater than 4% SaO2 dip rates of over five an hour and 31 of these had full sleep studies. Three subjects had clinically obvious and severe symptomatic obstructive sleep apnoea, giving a prevalence of three per 1001 men (0.3%; 95% confidence interval 0.07-0.9%). Eighteen men had obstructive sleep apnoea only when supine and in 10 the cause of the SaO2 dipping on the original home tracing was not elucidated. The greater than 4% SaO2 dip rates correlated with the history of snoring. Multiple linear regression techniques identified and ranked neck circumference (r2 = 7.9%), alcohol consumption (r2 = 3.7%), age (r2 = 1%) and obesity (r2 = 1%) as the only significant independent predictors of the rate of overnight hypoxic dipping. This study shows that snoring in this randomly selected population correlates best with neck size, smoking, and nasal stuffiness. Obstructive sleep apnoea, defined by nocturnal hypoxaemia, correlates best with neck size and alcohol, and less so with age and general obesity. 
4	Differential light scattering cuvettes for the measurement of thromboemboli in high shear blood flow systems. Newly developed optical scattering cuvettes were constructed as a modification of our existing 1.0 mm and 3.0 mm internal diameter (ID) cuvettes to facilitate the measurement of platelet microemboli ranging from 20 microns to 1,000 microns diameter in whole blood in 0.9 mm ID flows ranging from 250 to 4,000 ml/min. A perturbation solution to the one-speed radiative transport equation was used in the design and calibration of these cuvettes. A series of tests were performed with these cuvettes in an extracorporeal left ventricular assist device bovine model, and in a recirculating closed-loop flow system containing anticoagulated whole baboon blood, to determine to what extent they affect platelet and erythrocyte function ex vivo and in vitro. Serial hemolysis tests, thromboxane radioimmunoassay measurements, platelet counts, and activated partial thromboplastin times were measured. All of these tests with cuvettes in the extracorporeal and in vitro circuits were statistically indistinguishable from baseline measurements, suggesting the usefulness of this system for the measurement of microemboli in blood-contacting materials of extracorporeal circuits and cardiac assist devices. 
5	A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions. 
5	Evaluation of the pre-S (pre-S(1)Ag/pre-S(2)Ab) system in hepatitis B virus infection. The diagnostic and prognostic value of pre-S(1)Ag and pre-S(2)Ab was investigated in 69 HBsAg surface antigen positive patients--14 with acute hepatitis B, 30 with chronic liver disease (six chronic persistent hepatitis, 14 chronic active hepatitis, 10 with cirrhosis) and in 25 asymptomatic carriers. Pre-S(1)Ag was found in all patients with chronic hepatitis B virus (HBV) infection regardless of viral replication. In contrast, pre-S(2)Ab was not detected in any patients. Acute hepatitis was studied sequentially with periodic controls at 20 day intervals. Pre-S(1)Ag cleared before HBsAg in six of 14 (43%) patients who progressed favourably, and the two antigens cleared simultaneously in eight of 14 (57%) cases. Patients with early clearance of pre-S(1)Ag progressed favourably, thus indicating the prognostic value of this test, which, however, is still of limited practical application given the small temporal difference between the moment of clearance of the two antigens. The first markers to clear, however, were HBeAg and DNA-HBV, which showed significant differences with respect to the clearance of HBsAg. Moreover, pre-S(2)Ab appeared before HBsAb in 57.1% of our patients and was found in some patients before pre-S(1)Ag and HBsAg had cleared (42.8%), thus allowing complete viral clearance and acute HBV infection to be predicted earlier. 
3	Elderly men with histories of heavy drinking: correlates and consequences. Recognition that the physical, psychological and social consequences of substance abuse may persist throughout the life span has led to increased study of the impact of lifetime drinking habits on the elderly. We examined the characteristics of elderly men with self-reported histories of having ever been heavy drinker (H+) in a population-based (N = 1,155, mean age = 73.7 years) longitudinal survey of community-dwelling elders; 10.4% of the men reported that they had been heavy drinkers at some time during their lives. H+ men were younger and less educated than non-heavy drinkers (H-) or never drinkers (N). Mortality was higher among H+ men who were current drinkers than among H- or N men. H+ men reported more major illnesses, poorer self-perceived health status, more physician visits, more depressive symptoms, lower levels of life satisfaction and smaller social networks than did H- or N men. Self-reported ability to perform activities of daily living and instrumental activities of daily living was poorest among H+ men, who also scored the lowest on a mental status examination. Thus, a history of having ever been a heavy drinker is predictive of widespread impairments in physical, psychological and social health and functioning among elderly men. 
5	Avulsion of the rectus femoris tendon: an unusual type of pelvic fracture. We present the case of a 15-year-old boy evaluated in the emergency department after sustaining an acute hip injury during track and field practice. Pelvic radiograph demonstrated an avulsion fracture of the anterior inferior iliac spine. Review of the literature reveals this to be a well recognized, yet unusual and interesting injury. 
4	Selective vasopressin inhibition in rats with heart failure decreases afterload and results in venodilatation. The hemodynamic effects of selective inhibition of arginine vasopressin (AVP) with a V1 antagonist, (CH2)5yreAVPa CL-1-4A, were studied in normal rats (n = 17) and in rats 4 weeks after coronary artery ligation with large myocardial infarctions and elevated left ventricular end-diastolic pressures (n = 22). In normal rats AVP inhibition with a 35-micrograms/kg bolus of AVP V1 antagonist did not change heart rate, right atrial, left ventricular systolic, left ventricular end-diastolic or aortic pressures. There were also no changes in mean circulatory filling pressure, unstressed vascular volume, blood volume or venous compliance. In rats with infarction and elevated left ventricular end-diastolic pressures, AVP inhibition did not change heart rate, right atrial pressure, mean circulatory filling pressure or blood volume, but mean aortic pressure decreased from 103 +/- 3 to 88 +/- 2 mm Hg (P less than .001), venous compliance increased (P less than .001) from 2.17 +/- 0.07 to 3.04 +/- 0.11 ml/mm Hg/kg and unstressed vascular volume decreased from 42.3 +/- 3.1 to 34.7 +/- 2.6 ml/kg (P less than .05). We conclude that inhibition of AVP with a specific V1 antagonist had no effect on the venous or arterial circulations in normal rats, but in rats with left ventricular dysfunction and heart failure after chronic myocardial infarction, AVP inhibition decreased arterial pressure and caused venodilatation. 
3	Idiopathic first seizure in adult life: who should be treated? OBJECTIVE--To assess the accuracy of the diagnosis, recurrence rate, and fate after the first recurrence in adult patients with an untreated idiopathic first seizure. DESIGN--Hospital based follow up study. SETTING--One university hospital and three general hospitals in The Netherlands. PATIENTS--165 patients aged 15 years or more with a clinically presumed idiopathic seizure; diagnosis was based on a description of the episode according to prespecified diagnostic criteria. MAIN OUTCOME MEASURES--Results of additional investigations and follow up regarding the accuracy of the diagnosis; first recurrence; and response to treatment after the first recurrence. RESULTS--Computed tomography showed major abnormalities in 5.5% of the patients and follow up led to doubts about the initial clinical diagnosis in another 6%. Cumulative risk of recurrence was 40% at two years. The cumulative risk of recurrence at two years was 81% (95% confidence interval 66% to 97%) in patients with epileptic discharges on a standard or partial sleep deprivation electroencephalogram, 39% (27% to 51%) in patients with other electroencephalographic abnormalities, and 12% (3% to 21%) in patients with normal electroencephalograms. Treatment was initiated in most patients who had one or more recurrences; 40 (70%) patients were completely controlled, eight (14%) had sporadic seizures, and nine (16%) did not become free of seizures within one year despite treatment. CONCLUSIONS--The decision to initiate or delay treatment should be based on electroencephalographic findings. 
4	The role of neutrophils and platelets in a rabbit model of thromboembolic stroke. Cerebral ischemia is accompanied by many of the cardinal features of acute inflammation such as neutrophil and platelet activation and accumulation. We sought to determine whether circulating neutrophils or platelets contribute to brain injury in a rabbit model of thromboembolic stroke that includes a fixed duration of superimposed systemic hypotension. We randomized 18 rabbits to receive either antineutrophil antiserum (n = 6), antiplatelet antiserum (n = 5), or nonimmune serum (n = 7). We assessed brain ischemia by measuring cerebral blood flow, intracranial pressure, and infarct size. Following the intracarotid administration of an autologous clot, cerebral blood flow in all groups fell to less than 5 ml/100 g/min during induced hypotension. After restoration of baseline blood pressure, mean cerebral blood flow in neutropenic animals recovered to 20-30 ml/100 g/min while that in control and thrombocytopenic rabbits remained at less than 10 ml/100 g/min. Intracranial pressure in control animals rose steadily to a final value of 241% of baseline, while a much smaller increase (148% of baseline) was noted in the thrombocytopenic group; no change from baseline was evident in the neutropenic group. Infarct size was significantly (p less than 0.05) reduced in the neutropenic group but not in the thrombocytopenic group. These results suggest that neutrophils may be important contributors to ischemia-induced brain injury whereas the role of platelets is more subtle. 
5	Nerve growth factor corrects developmental impairments of basal forebrain cholinergic neurons in the trisomy 16 mouse. The trisomy 16 (Ts16) mouse, which shares genetic and phenotypic homologies with Down syndrome, exhibits impaired development of the basal forebrain cholinergic system. Basal forebrains obtained from Ts16 and euploid littermate fetuses at 15 days of gestation were dissociated and cultured in completely defined medium, with cholinergic neurons identified by choline acetyltransferase (ChAT) immunoreactivity. The Ts16 cultures exhibited fewer ChAT-immunoreactive neurons, which were smaller and emitted shorter, smoother, and more simplified neurites than those from euploid littermates. Whereas the addition of beta-nerve growth factor (100 ng/ml) augmented the specific activity of ChAT and neuritic extension for both Ts16 and euploid cholinergic neurons, only Ts16 cultures exhibited an increase in the number and size of ChAT-immunoreactive neurons. Furthermore, Ts16 ChAT-immunoreactive neurites formed varicosities only in the presence of beta-nerve growth factor. 
1	Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at diagnosis. Three hundred seventeen patients with non-Hodgkin's lymphoma (NHL) (54 low grade, 180 intermediate grade, 76 high grade, and seven unclassified) treated with chemotherapy were evaluated for the presence of hematologic abnormalities at diagnostic staging. Anemia was present in 42%, leukopenia in 6%, thrombocytopenia in 13%, leukocytosis in 26%, and thrombocytosis in 14% at presentation. The presence of bone marrow involvement by lymphoma was more likely to be associated with leukopenia and thrombocytopenia than the absence of bone marrow involvement. Although anemia was slightly more common in patients with bone marrow lymphoma than in those without marrow lymphoma, the difference was not statistically significant. Hematologic parameters were similar for patients with B-cell or T-cell lymphoma. Evidence of bone marrow failure with multiple cytopenias was present in 26 patients (8%). Leukoerythroblastosis was present in 2%. Circulating lymphoma was present in 9.5%. Anemic patients had a shorter survival time than nonanemic patients, whether bone marrow was involved by lymphoma or not. Survival was not affected by the presence of leukopenia or mild leukocytosis, but, in patients without marrow lymphoma, leukocytosis with a leukocyte count greater than 20 x 10(9)/l was associated with short survival length. Thrombocytopenia was associated with short survival time only in patients with bone marrow involvement by lymphoma. Patients with multiple cytopenias or leukoerythroblastosis had short survival times, but the presence of circulating lymphoma did not alter survival when compared with other patients with bone marrow involvement by lymphoma. These data suggest that hematologic evaluation at the time of diagnostic staging of NHL provides useful prognostic information that may have therapeutic implications. 
5	Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Susceptible rat strains develop hepatobiliary injury following the surgical creation of self-filling blind loops that cause small bowel bacterial overgrowth. Luminal bacteria or their cell wall polymers were implicated in the pathogenesis of the lesions because sham-operated rats and rats with self-emptying blind loops, having only slightly increased bacterial counts, did not develop hepatic injury. In this study, antibiotics with different spectra of activities were continuously administered starting 1 day or 22 days after surgery to determine which intestinal flora may be responsible for the development of hepatic injury in rats with small bowel bacterial overgrowth. Four weeks following surgery, Lewis rats with self-filling blind loops receiving no antibiotics had elevated liver histology scores (8.2 +/- 1.3 vs. 0.7 +/- 0.4) and plasma aspartate aminotransferase levels (269 +/- 171 vs. 84 +/- 24) compared with sham-operated rats, P less than 0.001. Oral gentamicin as well as oral and intraperitoneal polymyxin B, which binds endotoxin, did not prevent hepatic injury in rats with self-filling blind loops. However, oral metronidazole and tetracycline therapy continuously administered beginning 1 day after surgery diminished hepatic injury (histology score 3.0 +/- 1.8, 2.9 +/- 1.1; aspartate aminotransferase 87 +/- 25, 98 +/- 34; respectively P less than 0.001 compared with self-filling blind loops receiving no antibiotics). Metronidazole also protected Wistar rats that require 12 weeks to develop hepatic injury following experimentally induced small bowel bacterial overgrowth compared with rats with self-filling blind loops that received no antibiotic treatment (histology score 10.4 +/- 1.3 vs. 0.7 +/- 1.1, and aspartate aminotransferase 273 +/- 239 vs. 76 +/- 20, P less than 0.001). When rats started metronidazole therapy 22 days after self-filling blind loop surgery, elevated aspartate aminotransferase values decreased to normal during the next 77 days and final histology scores were normal. All rats with self-filling blind loops had negative peritoneal, liver, spleen, and blood cultures but approximately 75% of mesenteric lymph node cultures were positive irrespective of antibiotic treatment. Because Bacteroides species have been implicated in causing vitamin B12 and disaccharidase deficiencies in rats with self-filling blind loops, we documented the presence or absence of these organisms from blind loops using selective culture techniques. Metronidazole and tetracycline eliminated Bacteroides sp. from blind loops, but polymyxin B and gentamicin did not.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	Histopathologic evidence of fibrovascular ingrowth four weeks after placement of the hydroxyapatite orbital implant. We studied the histopathologic findings after placement of an orbital hydroxyapatite implant in a patient. The implant was placed after enucleation for a choroidal melanoma and was removed four weeks later because histopathologic examination of the enucleated globe disclosed tumor invasion of the optic nerve that necessitated further orbital tissue removal. Our histopathologic findings confirm that there is significant ingrowth of fibrovascular tissue in these implants, even within weeks of implantation. 
3	Cavernous-carotid thrombosis and ocular motor paresis A 64-year-old man presented with the acute onset of unilateral blindness and ipsilateral ocular motor paresis. Occlusion of the central retinal artery associated with thrombosis of the internal carotid artery in the cavernous sinus was demonstrated by angiography and magnetic resonance imaging. Cases of carotid thrombosis associated with ipsilateral ocular motor paresis are rare. The pathophysiology of intracavernous carotid thrombosis is discussed in connection with blood supply of the cranial nerves in the cavernous sinus. 
4	Precertification for percutaneous transluminal coronary angioplasty in Medicare beneficiaries: a melting pot or a need for better national standards? The Health Care Financing Administration has contracted with state peer review organizations (PROs) in its effort to assure the quality of services and eliminate unreasonable and inappropriate care provided Medicare beneficiaries. By law, each state PRO must select 10 procedures for precertification. Coronary angioplasty has been chosen by 45 PROs for precertification and criteria in each state were developed with the advice of local physicians. This report describes the findings of a survey of these precertification criteria in an effort to determine their variability and to compare the PRO criteria to published national criteria created by expert panels. Current precertification criteria of Medicare beneficiaries show significant variability in the priorities and the clinical practice of cardiologists in performing coronary angioplasty, despite established and published guidelines for its safe and efficacious use. It is likely that the establishment of locally based criteria for coronary angioplasty will be geographically uneven and probably have a less than expected impact on the care provided to Medicare beneficiaries. 
4	Diabetic cardiomyopathy. The purpose of this article was to review the clinical and experimental features of diabetic cardiomyopathy, with particular relevance to the Black population. One hundred thirty-seven studies were identified, of which 57 were selected as references for this article. Diabetes is associated with the development of cardiomyopathy, independent of coronary atherosclerosis. Pathological studies show myocardial hypertrophy and fibrosis; microvascular pathology is also present, but all of these pathological findings have an uncertain relationship to myocardial failure. Hemodynamic findings of both congestive and restrictive cardiomyopathy have been described. Noninvasive studies revealed abnormal systolic and diastolic function in many diabetic subjects, particularly in the presence of diabetic complications and/or hypertension. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. One year of diabetes in dogs resulted in decreased left ventricular compliance and increased interstitial connective tissue. Studies in the diabetic rat showed a marked slowing of contraction and relaxation. Chronic insulin therapy reversed the changes in the rat model. Combining hypertension with diabetes in the rat resulted in increased myocardial and coronary microvascular pathology and greater changes in isolated muscle function, electrophysiology, and contractile protein biochemistry. Many hypertensive diabetic rats died spontaneously, showing signs of congestive heart failure. Diabetic cardiomyopathy is a significant cause of heart failure in diabetic subjects and occurs more frequently in those with microvascular complications and/or hypertension. Clinical studies are needed to clarify the natural history of this disorder, focusing on the benefits of tight control of hyperglycemia and treatment of associated hypertension. Experimental studies will clarify the pathophysiology and contribute to improved therapy. The high prevalence of diabetes and hypertension in Blacks makes these considerations especially relevant to this population. 
4	The relationship between sex hormones and high-density lipoprotein cholesterol levels in healthy adult men. The objective of this study was to clarify the complex and uncertain relationship between endogenous sex hormones and high-density lipoprotein (HDL) cholesterol levels in healthy men. Fifty-five healthy adult men were consecutively recruited from an ongoing cross-sectional study of cardiovascular disease risk factors from a lipid research clinic at the University of Washington, Seattle. Subjects receiving medication were excluded. Multiple linear regression analysis identified several factors that correlated highly significantly with HDL cholesterol levels, including alcohol intake; frequency of strenuous exercise; age; levels of total cholesterol, low-density lipoprotein cholesterol, and triglyceride; and carbohydrate intake. Nearly 80% of the heterogeneity in HDL cholesterol levels could be accounted for by these factors. Despite finding significant correlations with factors known to influence HDL cholesterol levels, no correlation with estradiol level, testosterone level, or the ratio of estradiol to testosterone levels was apparent. In conclusion, endogenous sex hormones do not appear to influence HDL cholesterol levels in healthy adult men. Alternatively, a large proportion of the heterogeneity in HDL levels in this group of men can be accounted for by environmental factors. The disparity between this conclusion and others may be partially due to differences in accounting for these confounding variables. 
4	Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension. 
1	Carcinoma of the extrahepatic bile ducts. Thirty-seven patients with carcinoma of the extrahepatic bile ducts (EHBD), diagnosed over 14 years from 1974 to 1987, were studied retrospectively. The most common presenting complaint was jaundice, followed by abdominal pain, nausea and vomiting, and weight loss. The majority of EHBD carcinomas were located at the middle third of the bile duct (43.2%), followed by upper third bile duct (37.8%), and lower third bile duct (18.9%). The resectability of the surgically managed group was 44.4%. The most common histologic type was adenocarcinoma. The 30-day postoperative mortality was 30.6%. The mean overall survival of the patients with EHBD carcinoma was 11.2 months. Patients with distal third tumors had the best prognosis with a mean overall survival of 16.0 months. The mean overall survival of patients with upper-third and middle-third tumors were 10.9 months and 9.4 months. A high index of suspicion of the disease as well as earlier, aggressive surgery may improve patient survival. 
1	Correlation between estrogen receptor status and histological malignancy in human breast cancer. Sixty-two breast carcinoma patients underwent mastectomy and were analyzed for correlations between estrogen receptor (ER) status of the tumor and the histological findings of tumor, age, nodal status, and tumor size. An immunocytochemical assay for the detection of ER in breast carcinomas was used to evaluate the staining intensity index (SII) of the ER level of the tumors, which was calculated from the staining intensity of cancer cells and the percentage of ER-positive cancer cells. The histological differentiation of carcinomas showed a strong correlation with the SII. A statistically significant (F = 10.580, P less than 0.0005) negative correlation was found between the grade of malignancy and the SII. Patients under 50 years of age tended to have a lower SII, whereas patients over 49 years of age tended to have a higher SII. The tumor size, and nodal status showed no correlations with the SII in any of the patients. The histological differentiation of the tumor cells showed a strong correlation with the heterogeneity of the distribution of ER-positive cells in breast cancers. 
2	Ileal pouch-anal anastomosis. The Emory University experience. The ileal pouch-anal anastomosis has become a practical alternative to proctocolectomy for the treatment of ulcerative colitis and polyposis coli. To evaluate its success, the Emory University Affiliated Hospital experience from February 1984 to March 1989 was retrospectively reviewed. There were a total of 50 patients identified; 84 per cent had ulcerative colitis, and 16 per cent had polyposis coli (familial polyposis and Gardner's syndrome). The majority of these patients underwent a two-stage operation, but one-third required a three-stage procedure due to difficulty in mucosal proctectomy or toxic megacolon. J-pouch construction was performed in 72 per cent of patients, S-pouch construction in 14 per cent, straight ileo-anal anastomosis in 8 per cent, and lateral isoperistaltic ileo-anal anastomosis in 6 per cent. Of the 50 patients, 36 (72%) have had closure of the temporary ileostomy. Fourteen patients have not had ileostomy closure due to change in diagnosis to Crohn's disease, operative complications, or ileostomy closure pending. The combined operative morbidity per patient for the ileal pouch-anal anastomosis and the closure of the ileostomy was 32 per cent. This included bowel obstruction, 16 per cent; pelvic abscess, 6 per cent; and ileo-anal separation, 4 per cent. Follow-up on patients with ileostomy closure ranged from 6 months to 4 years (mean, 1.3 years). Stool frequency was 5.9 stools per 24 hours at 6 months and improved with time. During the follow-up period, all patients were eventually completely continent of stool during the day, and most became completely continent of stool at night. 
5	Complications of laparoscopic cholecystectomy. The emergence of laparoscopic cholecystectomy as a viable alternative to traditional cholecystectomy has been greeted with enthusiasm by the surgical community. This new technique is not without complications, both potential and real. The complications associated with diagnostic laparoscopy are well documented, as are those associated with traditional cholecystectomy. All of these may also be seen with laparoscopic cholecystectomy. The incidence of their occurrence, however, may vary. It remains too early to evaluate the complication rates from this new procedure, as reports of large series are just beginning to emerge. Early reports are encouraging but caution that bile duct injury, hemorrhage, and even death may occur. Early enthusiasm for this new method must be tempered with care in its practice if complication rates are to be maintained at an acceptable level and the procedure is to earn a permanent place in the armamentarium of the surgeon. 
2	Nonpropulsive esophageal contractions and gastroesophageal reflux. Nonpropulsive esophageal contractions radiologically described as tertiary contractions or "corkscrew" esophagus suggest the presence of an underlying motility disorder and may lead to impaired acid clearance. The goals of this study were to determine the prevalence and role of gastroesophageal reflux (GER) in patients with tertiary contractions. Thirty-five consecutive patients with spontaneous, repetitive, nonpropulsive esophageal contractions noted on esophagography were studied with endoscopy, infusion esophageal manometry, and 24-h ambulatory pH monitoring. All patients had esophageal symptoms, mainly dysphagia, heartburn, and chest pain, but only three were found to have esophagitis by endoscopy and biopsy. Nineteen patients had repetitive, nonlumen-obliterating, nonperistaltic (tertiary) contractions, six had corkscrew esophagus, and 10 had forceful, lumen-obliterating simultaneous contractions (rosary bead esophagus). Twenty patients (58%) had GER by pH criteria with mean values: % time pH less than 4, 40.9; %upright pH less than 4, 41; %supine pH less than 4, 44.3%; number of episodes with greater than 5 min of pH less than 4, 12. Esophageal motility revealed "nutcracker" esophagus in eight, low LESP in two, and nonspecific esophageal motility disorder in 10. Symptoms or severity of nonperistaltic contractions did not correlate with GER. Radiologically demonstrable free reflux or the presence of heartburn did not predict GER. We conclude that 1) GER occurs in up to 58% of patients with nonpropulsive (tertiary) esophageal contractions on esophagography, and may play a role in the induction of abnormal peristaltic activity of the esophageal body; 2) GER is usually not associated with endoscopic evidence of esophagitis or characteristic symptoms, and is recognized by 24-h pH monitoring. We speculate that detection and treatment of GER may improve the symptomatic management of patients with nonpropulsive esophageal contractions. 
1	Hemicorporectomy: a collective review. Hemicorporectomy or translumbar amputation has been described as the most revolutionary of all operative procedures. Frederick E. Kredel, who first voiced the concept of the operation in 1950, referred to it as halfectomy. Demonstration of his cadaver studies established the feasibility of the operation. Amputation is effected through the lower lumbar area of the body. Necessary life functions are preserved in the upper torso. Kredel envisioned hemicorporectomy as a curative operation for locally advanced cancer, limited to the pelvis, not encompassable by standard operative intervention. Additional indications are intractable decubitus ulcers with malignant change, particularly in paraplegics; pelvic organs, and bone infection with nonhealing fistulae; and crushing trauma to the pelvis. The first hemicorporectomy operation was reported in 1960. Thirty-four operations have been recorded in the world literature. Two heretofore unreported cases are added, raising the total to 36. Review of these 36 cases confirms the conviction that hemicorporectomy is a humane and ethical alternative to the suffering encumbered by advancing, painful, malodorous malignant disease not treatable by conventional means. While cure rates are not substantial, the best results are reported in paraplegics with intractable decubitus ulcers with or without malignancy. Rehabilitation is prolonged and costly. Most survivors have been restored to preoperative occupations or other gainful employment. 
5	Ureteral obstruction and ureteral fistulas after aortofemoral or aortoiliac bypass surgery. Ureteral injury after aortofemoral or aortoiliac bypass surgery has seldom been described in the literature considering the large number of bypass operations performed. Some causative factors, such as the position of the bypass, are obvious while others are less clear. However, no attempt has been made to unify criteria to establish a management protocol. Of 154 cases of ureteral units with ectasia reviewed ureteral fistulas were present in 19. Radiological ureteral obstruction appears to precede fistula formation. Symptoms, time of diagnosis and treatment according to the predominant etiology have been discussed. Etiological (in varying degrees of importance), clinical and diagnostic criteria, together with a management and therapeutic protocol in which early and late lesions are clearly differentiated were established, while bearing in mind that not all radiological obstruction patterns correspond to true ureteral lesions. 
4	Downslope claudication in eosinophilic fasciitis: a fourth type of claudication--case presentations. Two patients who presented with discomfort in the calves while walking down a slope were diagnosed as suffering from eosinophilic fasciitis of the lower limbs. Following therapy of the underlying disease, this peculiar discomfort remitted concomitantly with the disappearance of the subcutaneous abnormalities. The authors posit that downslope claudication of the calves in eosinophilic fasciitis constitutes an additional variant of claudication of the lower limbs. 
5	Brain perfusion in acute encephalitis: relationship to prognosis studied using SPECT. Single photon emission computed tomography (SPECT) and cranial computed tomography were sequentially examined in 2 patients with acute encephalitis. Radiographic computed tomography revealed focal low-density areas within a few days of the onset of symptoms in both patients. In SPECT, 1 patient exhibited hyperperfusion in the corresponding area, while the other had a normal scan. The outcome of the former was poor, while the latter recovered fully. Abnormal brain perfusion, thus, coincided with a poor prognosis. SPECT may be used to promptly evaluate the focal change of acute encephalitis. 
4	Digitalis-like activity in human plasma: relation to blood pressure and sodium balance. PURPOSE: On the assumption that renal tubular cells are more important as the target cells for a natriuretic factor than blood cells, we used a well-characterized cultured renal tubular cell line, Madin-Darby canine kidney (MDCK), cells to monitor the circulating digitalis-like factor in human plasma and examine its role in the regulation of blood pressure and sodium balance. SUBJECTS AND METHODS: We investigated the effects of plasma on binding of radioactive ouabain to monolayered MDCK cells in order to determine the level of a circulating digitalis-like factor. First, we measured specific 3H-ouabain binding to MDCK cells in the presence of plasma from 71 outpatients (34 normotensive subjects and 37 hypertensive patients) after incubation for 4 hours. Second, we measured specific 3H-ouabain binding after incubation of cells with plasma from 16 hospitalized subjects (eight normotensive subjects and eight hypertensive patients) receiving low and high sodium diets. RESULTS: In Study 1, ouabain binding was lower by 30% with plasma from hypertensive patients than with plasma from normotensive subjects (p less than 0.01). There was a significant negative correlation between individual subject's systolic or mean blood pressure and ouabain binding (r = -0.34, p less than 0.01 or r = -0.29, p less than 0.01). In Study 2, ouabain binding was also significantly reduced by 25% in the presence of plasma from hypertensive subjects as compared with plasma from normotensive subjects irrespective of sodium intake (p less than 0.01). A significant negative correlation was also found for all subjects between either systolic, diastolic, or mean blood pressure and ouabain binding (r = -0.58, p less than 0.01, r = -0.51, p less than 0.01, or r = -0.55, p less than 0.01, respectively). With the changes from low to high sodium intake, there was a corresponding decrease in ouabain binding (p less than 0.01) and an increase in sodium excretion (p less than 0.01). A significant negative correlation was observed between these two parameters (r = -0.47, p less than 0.05). CONCLUSIONS: These findings suggest that a circulating digitalis-like factor, which may act on renal tubular cells as the ouabain-displacing compound, is increased in patients with essential hypertension and also demonstrate that plasma levels may be influenced by changes in dietary sodium intake. 
3	South American blastomycosis: ophthalmic and oculomotor nerve lesions. A case of South American blastomycosis began with an oropharyngeal lesion which was followed by a granulomatous uveitis. The patient was treated with Amphotericin B and showed a clinical regression. Four months later, he developed a right 3rd cranial nerve palsy, aggravating the clinical aspect with a severe generalized involvement of the central nervous system and death. Necropsy showed blastomycotic meningoencephalitis. 
4	Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction. The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering. 
4	Impact of echocardiography on the management of patients with mitral valve prolapse OBJECTIVE: To determine whether echocardiography affects the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients suspected of having mitral valve prolapse (MVP). DESIGN: Retrospective review of echocardiograms and clinical records. SETTING: Military tertiary care hospital. PATIENTS: 127 patients with clinically suspected MVP (105) or incidentally discovered MVP (22). MAIN RESULTS: Beta blockers were used more often in patients with suspected MVP and positive echocardiograms (45%) than in patients with normal echocardiograms (13%, p less than 0.001). Bacterial endocarditis prophylaxis was recommended more often in patients with suspected MVP and positive echocardiograms (65%) than in patients with normal echocardiograms (11%, p less than 0.001). Presence or absence of a murmur did not influence the decision to recommend bacterial endocarditis prophylaxis. Patients in whom MVP was incidentally discovered were unlikely to receive either beta blockers or the recommendation for bacterial endocarditis prophylaxis. CONCLUSIONS: The results of echocardiography affect the decisions to use beta blockers or to recommend bacterial endocarditis prophylaxis in patients with suspected MVP. 
5	Comparison of pump-driven and spontaneous continuous haemofiltration in postoperative acute renal failure. In a comparison of spontaneous continuous arteriovenous haemofiltration (CAVH) and pump-driven haemofiltration (PDHF) for acute renal failure after surgery, 116 patients admitted to a surgical intensive care unit were assigned CAVH (48) or PDHF (68). The method of assignment was that a patient was treated by PDHF if he or she was the only patient requiring treatment at that time (only one pump was available); any other patient coming to the unit would be treated by CAVH. The groups were slightly unbalanced because there were fewer simultaneous cases than expected. The main endpoints were survival rate, control of uraemia, and additional application of haemodialysis. There were no differences between the patient groups in age, duration of treatment, severity of illness, serum creatinine concentration at the start of treatment, or cause of acute renal failure. Both treatments adequately controlled uraemia and fluid overload. However, the survival rate was significantly higher with PDHF than with CAVH (6 [12.5%] vs 20 [29.4%]; p less than 0.05). The daily ultrafiltrate volume was significantly higher with PDHF than with CAVH (15.7 [95% confidence interval 13.6-17.8] vs 7.0 [6.6-7.4] l/day; p less than 0.05). The volume of ultrafiltrate in patients with ischaemic or sepsis-induced acute renal failure was correlated with the survival rate. This finding suggests that the better survival rate in the PDHF group was due to faster elimination of toxic mediators (of molecular weight 800-1000 daltons) through the filter membrane by high-volume haemofiltration. 
3	Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis. The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement. 
5	Prehospital prophylactic lidocaine does not favorably affect outcome in patients with chest pain. STUDY OBJECTIVES: The purpose of our study was to determine the morbidity and mortality in initially stable patients presenting to paramedics with chest pain; to examine possible beneficial effects of its use, including reduction of sudden death syndrome in the prehospital and emergency department setting; and to determine if prophylactic lidocaine is associated with adverse effects in this patient population. DESIGN AND SETTING: This was a randomized, prospective study using prophylactic lidocaine in patients complaining of chest pain who presented to our paramedic system between January 1984 and January 1988. TYPE OF PARTICIPANTS: All patients aged 18 years or older with chest pain of suspected cardiac origin who presented to paramedics during the study period were included. Excluded were patients presenting with warning arrhythmias, second- or third-degree heart block, bradycardias of less than 50, hypotension of less than 90 mm Hg systolic, or known allergy to lidocaine. INTERVENTIONS: Patients were randomized into two groups, the lidocaine-treated group and the control group. An initial bolus of 1 mg/kg IV lidocaine was administered to the lidocaine-treated group. A simultaneous 2 mg/min IV drip was established. Ten minutes after the first dose of lidocaine, a second bolus of 0.5 mg/kg was administered. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,427 patients were entered; 704 received lidocaine, and 723 did not. Discharge diagnoses included acute myocardial infarction (31%), unstable angina (33%), other cardiac problems (7%), and noncardiac problems (29%); overall mortality rate was 7.4%. There was an equal distribution of deaths between the lidocaine-treated group (57) and the control group (48). Six patients had a cardiac arrest in the prehospital setting, and 15 had a cardiac arrest in the ED. Malignant ventricular arrhythmias as the precipitating arrest rhythm in patients with acute myocardial infarctions were similar for the lidocaine-treated and control groups. The incidence of adverse effects, including hypotension, bradycardias, second- or third-degree heart blocks, tinnitus, and altered mental status, was similar in both groups. CONCLUSION: There are no benefits from the administration of prehospital prophylactic lidocaine in stable patients with chest pain; therefore, routine use in this setting appears unwarranted. 
3	The anatomical basis of the caecocentral scotoma. New observations and a review. It is shown that the 'papillomacular bundle' of optic nerve fibres, although a concept discussed frequently in the clinical literature, lacks a clear anatomical definition. It is suggested that the explanation for this is that the 'bundle' was originally described in autopsy studies of toxic amblyopia, not normal anatomy. The optic nerve fibre projection and vascular architecture of the caecocentral region of the retina is described. These anatomical features are discussed in relation to a number of possible anatomical explanations for the fact that a caecocentral scotoma is the characteristic field defect found in toxic amblyopia. We have been unable to identify a distinct anatomical feature which might explain this vulnerability but suggest that the problem has not as yet been clearly addressed by anatomists. 
4	Enalapril and renal injury in spontaneously hypertensive rats. Rats of the spontaneously hypertensive strain develop kidney damage that resembles the nephropathy seen in some cases of human essential hypertension. Previous studies with a triple drug antihypertensive regimen indicated that proteinuria and glomerular histopathology in spontaneously hypertensive rats might develop despite long-term effective control of systemic blood pressure. To investigate further the relation between hypertension and kidney disease, a group of spontaneously hypertensive rats were treated with enalapril at 15 weeks of age. Blood pressure, protein excretion, and kidney function were measured in those rats at regular intervals during the next year and a half and were compared with untreated spontaneously hypertensive rats and the normotensive Wistar-Kyoto parent strain. Kidney tissue samples from all three groups, collected at autopsy, were stained by immunohistochemical and conventional methods to assess the relative severity and nature of kidney damage. Although enalapril therapy was completely effective in controlling the blood pressure of spontaneously hypertensive rats, it only postponed the onset of kidney disease. Enalapril-treated spontaneously hypertensive rats eventually exhibited albuminuria as severe as that found in hypertensive rats. Kidney vessel pathology was completely prevented with enalapril, but the abnormal accumulation of mononuclear cells in tubulointerstitial and periglomerular sites was the same as in untreated spontaneously hypertensive rats. We have concluded that elevated protein excretion in rats of the spontaneously hypertensive rat strain is not a secondary consequence of systemic hypertension. Structural abnormalities of renal vessels also do not appear to contribute significantly to the pathogenesis of albuminuria in spontaneously hypertensive rats. Other explanations must be sought to account for the close link between spontaneous hypertension and kidney damage in this animal model. The clear dissociation of kidney disease from systemic hypertension exhibited by spontaneously hypertensive rats may also be relevant for human disease. 
2	The Exeter Dysphagia Assessment Technique. The Exeter Dysphagia Assessment Technique (EDAT) uses noninvasive equipment to record, simultaneously, "feeding respiratory patterns," the time drink entered the mouth, and associated swallow sounds during feeding. The easily portable equipment enabled patients' swallowing ability to be tested, at the bedside if necessary, using a small amount of fruit-flavored drink. The results appear in chart form. EDAT findings from groups of normal subjects aged 2-90 years were compared with those from patients with dysphagia of neurologic origin and normal subjects under experimental feeding conditions. The results revealed maturation of the feeding respiratory pattern in the teenage years and remarkable consistency thereafter. Differences in the recordings between the normal and abnormal subjects were sufficiently marked to allow the findings to be used in the diagnosis of other patients with dysphagia of doubtful neurologic cause. Interpretation of the charts and recorded timings of the oral and pharyngeal stages of swallowing permitted a more accurate identification of sensory nerve, motor nerve, and functional involvement causing dysphagia of neurologic origin and may be used as a guide to the origin of the sensory deficit. 
5	Transfection and stable transformation of adult mouse Schwann cells with SV-40 large T antigen gene. Cultured Schwann cells derived from adult mouse dorsal root ganglia and peripheral nerves were transfected with a plasmid containing SV-40 large T antigen gene, and 25 colonies of stable transformants were obtained, one of which was expanded and recloned. This transfected cell line, designated MS1, expressed SV-40 large T antigen and showed continuous cell growth with a doubling time of 27 hours. The MS1 cells had distinct Schwann cell phenotypes such as S-100 protein, laminin, 2',3'-cyclic nucleotide 3'-phosphodiesterase and P0 protein, as shown by immunofluorescence microscopy. When MS1 cells were exposed to dibutyryl cyclic adenosine-3',5'-monophosphate (dbc AMP), they extended long bipolar processes two- to ten-fold longer than those of untreated MS1 cells and frequently formed whorl-like alignments similar to palisade formations or organoid patterns observed in human Schwannomas and neurofibromas. These results suggest that transformed Schwann cells can be a useful model for analyzing regulatory mechanisms of Schwann cells, neuron-Schwann cell interactions and experimental Schwann cell neoplasms in vitro. 
5	Survival after hypertonic saline resuscitation from hemorrhage. There has been recent increased interest in hypertonic saline resuscitation from shock and hemorrhage. This study was performed to evaluate the survival effects of hypertonic saline resuscitation. Fifty male Sprague-Dawley rats of average weight of 325 grams were anesthetized with halothane. Animals were subjected to blood loss of 21 ml/kg over 5 minutes. Intravenous infusion was started 10 minutes after hemorrhage with either lactated Ringer's injection (42 ml/kg) or three per cent NaCl (10.64 ml/kg) chosen randomly. These doses provided equal amounts of sodium. At the end of fluid infusion, blood samples were obtained for electrolyte determination. Rats were observed 3 days for survival. Survival was significantly lower in the three per cent NaCl group compared with the lactated Ringer's group. It is probable that worsened outcome with three per cent NaCl was associated with intracellular dehydration. 
1	Dysgerminoma of the ovary: review of 27 cases. Twenty-seven patients with pure dysgerminoma were seen at the Tata Memorial Hospital, Bombay, between January 1980 and December 1984. Of the 10 patients in stage I, 2 patients underwent a unilateral salpingoophorectomy (USO) and were kept under observation without any adjuvant therapy, while the remaining patients received adjuvant treatment following surgery. All of the 6 patients in stage II and 4 of 7 in stage III had total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) followed by postoperative radiotherapy. One patient presented in stage IV and 3 patients presented with recurrence after previous definitive treatment undertaken at other institutions. The disease free, as well as the overall survival, at 108 months, for the 24 cases primarily treated at this institution, is 81% and 88% respectively, and, for patients in stages I and II, 100% (Kaplan-Meier estimation). The need for controlled clinical trials to devise optimal therapy in the early clinical stages and use of chemotherapy for advanced stages of this highly curable entity are stressed. 
5	Angiographic localization of spinal cord blood supply and its relationship to postoperative paraplegia. Forty-seven patients underwent selective catheterization of middle and lower thoracic intercostal and upper lumbar arteries to define the origin of the artery of Adamkiewicz. One patient had significant atheroembolism, and a second had transient lower extremity paresthesias. No other complications occurred. The origin was found in 26 (55%), and 21 patients underwent thoracoabdominal aneurysm repair with this knowledge. When the critical lumbar or intercostal artery could be included as part of a long proximal or distal anastomosis, all 12 patients could be included as part of a long proximal or distal anastomosis, all 12 patients survived, and one was paralyzed. However, if the aneurysm repair mandated a midgraft anastomosis to intercostal arteries critical to spinal cord perfusion, seven of nine patients either died or were paralyzed (p less than 0.05). In the group of 19 patients operated on in whom spinal cord blood supply was not identified three patients had a technically unsuccessful operation; two died, and one was paralyzed. Twelve of 16 patients who had an adequate, but unsuccessful attempt at localization were treated by intercostal "neglect" and survived. Late paresis developed in two patients, but they are walking now. One of the patients who died had multiple systems failure and awakened paraplegic. She had a patent, enlarged, thoracic radicular artery at T-5 which probably supplied to spinal cord and which was missed angiographically. Paralysis was associated with aneurysm extent (group 2 and III B, dissections vs group 1 & 3, p less than 0.05). Selective intercostal angiography requires further refinement, but it is safe and offers the promise of understanding the mechanisms and risks of spinal cord complications after repair of extensive thoracoabdominal aneurysms. 
1	Failure to detect human T-cell leukemia virus-related sequences in multiple sclerosis blood. We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis. 
5	AAEM case report #1: ulnar neuropathy at the elbow. A patient with bilateral cubital syndrome complicated by anomalous innervation is presented. The electrodiagnostic approach to patients with this neuropathy is reviewed emphasizing new developments. The interpretation of the findings in this patient centers around issues of pathophysiology and methodology. 
4	Right ventricular dysfunction in chronic obstructive pulmonary disease. Evaluation and management. Cor pulmonale is an important consequence of COPD. Although the incidence is not precisely known, it is seen more frequently in patients with hypoxemia, CO2 retention and severely reduced FEV1. When present, it limits peripheral oxygen delivery, increases shortness of breath, and reduces exercise endurance. It is also associated with higher mortality rates independent of other prognostic variables. Numerous factors may contribute to the development of cor pulmonale in patients with COPD, but its primary cause is chronic alveolar hypoxia resulting in pulmonary vasoconstriction, vascular remodeling and pulmonary hypertension. The physical exam, chest radiograph and ECG may be helpful in detecting the presence of cor pulmonale, but because of anatomic changes that occur in the chest, these tests are often insensitive in patients with COPD. Noninvasive diagnostic techniques utilizing Doppler echocardiography and radionuclide angiography allow for detection of RV dysfunction at an earlier stage and in most cases, preclude the need for right heart catheterization. LTO2 is the only therapy shown to improve survival in patients with COPD. However, statistical proof correlating improvements in pulmonary hemodynamics with increased survival is lacking. Bronchodilators, such as the beta 2 agonists and especially theophylline, may have beneficial effects on pulmonary hemodynamics in addition to their effect on respiratory function and are useful in COPD when RV dysfunction is present. Diuretics and phlebotomy are also useful in improving symptoms in appropriate patients. Vasodilators such as calcium channel blockers and ACE-inhibitors may improve pulmonary hemodynamics acutely, but may lower arterial PO2 by worsening ventilation-perfusion matching or blunt the improvement in pulmonary hemodynamics seen with supplemental oxygen. The long-term benefits of these agents have not been proven and their routine use in patients with cor pulmonale due to COPD cannot be recommended. 
5	Granulomatous sialadenitis. Granulomatous inflammation in salivary tissues is most often a response to liberated ductal contents, particularly mucin, in various degrees of obstructive sialadenopathy. Far less often is a granulomatous sialadenitis the result of specific infective granulomas or systemic granuloma-forming diseases. In these instances, the salivary parenchymal involvement is usually secondary to disease localization in regional lymph nodes. 
4	Use of arterial compliance for evaluation of hypertension. Arterial compliance describes a change in the volume of arteries following a change in blood pressure. The physical basis of the compliance concept and experimental procedures in animals both indicate that the relation between arterial compliance and blood pressure pattern is often unclear. Compliance is pressure-dependent because of the biphasic elastin and collagen composition of arteries and, hence, decreases when blood pressure increases. Compliance also determines the pulsatile amplitude of the pressure wave by regulating the buffering function of an artery's face to the cardiac pump and, accordingly, its reduction induces a selective increase in systolic level. The questions are whether these theoretical and experimental phenomena can be extrapolated to human hypertension and whether they can be assessed from indirect measurement of arterial compliance by means of a time-domain analysis of arterial pressure and flow waves via various models of the arterial tree. Whatever the method and site of measurement, arterial compliance was found to be decreased in different forms of hypertension. This low compliance can be considered to have a causal role in elderly patients with isolated systolic hypertension. In contrast, in patients with systolo-diastolic hypertension physiologic and pharmacologic arguments exist against the fact that low arterial compliance may be the pure consequence of mean blood pressure elevation. Moreover, it is suggested that aging acts in concurrence with pressure elevation to decrease arterial compliance, and that in certain hypertensive patients additional factors, perhaps atherosclerotic in nature, contribute to impair the elastic properties of arteries. 
3	Infantile CNS spongy degeneration--14 cases: clinical update. We studied 14 Arab infants with infantile spongy degeneration, 13 of whom were products of consanguineous marriages. They presented in infancy with macrocephaly, poor visual behavior or blindness, and axial hypotonia with appendicular spasticity. Brain CT and MRI showed diffuse symmetric leukoencephalopathy, even before neurologic symptoms. There were relatively normal EEGs. The visual evoked responses (P100) were either absent or delayed early in the course. The brainstem auditory evoked responses showed milder abnormalities, with loss of later components before the earlier ones. Deficient aspartoacylase activity in cultured fibroblasts or brain biopsy confirmed the diagnosis in all patients. 
5	Effect of sleep-induced increases in upper airway resistance on respiratory muscle activity. To investigate the response of inspiratory and expiratory muscles to naturally occurring inspiratory resistive loads in the absence of conscious control, five male "snorers" were studied during non-rapid-eye-movement (NREM) sleep with and without continuous positive airway pressure (CPAP). Diaphragm (EMGdi) and scalene (EMGsc) electromyographic activity were monitored with surface electrodes and abdominal EMG activity (EMGab) with wire electrodes. Subjects were studied in the following conditions: 1) awake, 2) stage 2 sleep, 3) stage 3/4 sleep, 4) CPAP during stage 3/4 sleep, 5) CPAP plus end-tidal CO2 pressure (PETCO2) isocapnic to stage 2 sleep, and 6) CPAP plus PETCO2 isocapnic to stage 3/4 sleep. Inspired pulmonary resistance (RL) at peak flow rate and PETCO2 increased in all stages of sleep. Activity of EMGdi, EMGsc, and EMGab increased significantly in stage 3/4 sleep. CPAP reduced RL at peak flow, increased tidal volume and expired ventilation, and reduced PETCO2. EMGdi and EMGsc were reduced, and EMGab was silenced. During CPAP, with CO2 added to make PETCO2 isocapnic to stage 3/4 sleep, EMGsc and EMGab increased, but EMGdi was augmented in only one-half of the trials. EMG activity in this condition, however, was only 75% (EMGsc) and 43% (EMGab) of the activity observed during eupneic breathing in stage 3/4 sleep when PETCO2 was equal but RL was much higher. We conclude that during NREM sleep 1) inspiratory and expiratory muscles respond to internal inspiratory resistive loads and the associated dynamic airway narrowing and turbulent flow developed throughout inspiration, 2) some of the augmentation of respiratory muscle activity is also due to the hypercapnia that accompanies loading, and 3) the abdominal muscles are the most sensitive to load and CO2 and the diaphragm is the least sensitive. 
1	Vaccination against tumor cells expressing breast cancer epithelial tumor antigen. Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts. 
4	Deprivation in infancy or in adult life: which is more important for mortality risk? Previous ecological studies have suggested that early life factors are important causes of adult cardiovascular and respiratory disease, by showing geographic correlations between past infant mortality rates and present adult mortality rates. However, these studies inadequately take account of the fact that areas which were severely deprived earlier this century remain the most deprived today. Thus the ecological relation between infant and adult mortality rates could simply reflect persistence in the geographic distribution of poor socioeconomic circumstances. To explore this hypothesis further infant mortality rates for 1895-1908 for 43 counties in England and Wales were correlated with cause-specific adult mortality for 1969-73 in people aged 65-74 years, with and without adjustment for present-day social deprivation and social class. The strong simple correlations found between infant mortality in 1895-1908 and adult mortality from various causes in 1969-73 were generally much attenuated or abolished by controlling for indices of present-day socioeconomic circumstances. Our results suggest that previous studies give no strong support for any direct influence of factors acting in early life on adult coronary heart disease mortality risk. Studies which gather data about infancy, childhood, and the full course of adult life are required to clarify this issue. 
5	Botulinum A toxin for the treatment of adult-onset spasmodic torticollis. Thirty-five patients with adult-onset idiopathic torticollis were treated by local injections of botulinum A toxin into dystonic cervical muscles. Substantial improvement with respect to reduction and elimination of pain was found in 81 percent, improvement in posture deformity and involuntary spasms in 70 percent, increased range of motion of the neck in 78 percent, reduction in visible sternocleidomastoid hypertrophy in 86 percent, and improvement in tremor in 65 percent. The syndrome was divided into four subtypes based on pattern of dystonic muscle groups involved in the dystonia, head and shoulder posture, and sternocleidomastoid muscle hypertrophy. Injection strategy based on this subdivision is described. 
1	Insulin secretion and action in patients with pancreatic cancer. The authors investigated insulin secretory capacity and insulin action in 11 preoperative patients with pancreatic carcinoma and 15 age-matched and weight-matched healthy subjects (C). Five patients were classified as diabetic (D), two as impaired glucose tolerant (IGT), and four as nondiabetic (ND). Postabsorptive serum insulin levels (mean +/- SE, in uU/ml) in D (12 +/- 2), IGT (17 +/- 7), and ND (10 +/- 2) were comparable. After administration of 100 g of oral glucose, peak insulin achieved in D (60 +/- 11) was lower than in IGT (101 +/- 26) and ND (83 +/- 20), whereas peak insulin levels in IGT and ND were significantly (P less than 0.05) higher than in C (45 +/- 6). Comparable insulin response to nonglucose stimuli was documented in all subjects using the slow arginine infusion test with mean serum insulin of 27 +/- 4 in D, 28 +/- 6 in IGT, 34 +/- 10 in ND, and 32 +/- 5 in C. In six patients (P) and six controls, insulin action was assessed by the euglycemic hyperinsulinemic clamp technique, with glucose turnover rates estimated by [3-3H]glucose infusion. Steady-state plasma glucose concentrations were maintained at 92 +/- 3 (P) and 91 +/- 1 mg/dl (C). After insulin infusion at the rate of 1.0 mU/kg/min, comparable high physiologic insulin levels were observed in P (73 to 104 uU/ml) and in C (81 to 103 uU/ml). Postabsorptive rates of endogenous glucose appearance (Ra) were higher in P (2.86 to 3.02 mg/kg/min) than in C (1.50 to 2.80 mg/kg/min). At high physiologic insulin concentrations, negative Ra values were documented in all subjects, and complete suppression of Ra was assumed. Total body glucose use (M) was consistently lower in P (3.90 to 6.40 mg/kg/min) than in C (6.98 to 10.40 mg/kg/min), consistent with a state of insulin resistance. Patients with pancreatic cancer manifest insulin resistance by virtue of a decrease in total body glucose use (M) and decreased insulin response to glucose due to either inherent beta cell dysfunction or decreased islet cell mass. The latter is not identifiable by histologic morphology. 
3	Isolated trigeminal sensory loss secondary to a distal anterior inferior cerebellar artery aneurysm: case report. A previously healthy 25-year-old woman suddenly developed right-sided facial numbness and a headache. The neurological examination was within normal limits with the exception of meningismus and right-sided facial sensory loss. A computed tomographic scan and a magnetic resonance imaging study demonstrated an acute hematoma in the right cerebellopontine angle. A 4-vessel cerebral angiogram revealed no abnormalities. Posterior fossa exploration disclosed a large, partially thrombosed, fusiform anterior inferior cerebellar artery aneurysm, which indented the pons at the trigeminal root entry zone. The aneurysm was excised, and the patient made an excellent recovery. She was left with a persistent trigeminal sensory deficit. Anterior inferior cerebellar artery aneurysms are rare lesions that generally present with a cerebellopontine angle syndrome; occasionally, facial sensory loss is also a feature. Isolated trigeminal sensory findings, as illustrated in this case, are extremely unusual in posterior fossa vascular lesions. 
1	Percutaneous aspiration of brain tumor cysts via the Ommaya reservoir system. We performed percutaneous aspiration of 21 brain tumor cysts in 20 patients using the Ommaya reservoir system. Ages ranged from 3 to 70 years, median 48. Sixteen were primary tumors (12 anaplastic glioma, 2 craniopharyngioma, 1 oligodendroglioma, 1 brainstem glioma) and 4 were metastatic. Fourteen had the CT appearance of a true cyst and 7 a pseudocyst. We placed 18 catheters through twist drill holes via CT stereotactic guidance and 3 through burr holes via CT guidance and effectively aspirated 3 to 50 ml cyst fluid from 1 to 18 times in each patient. Postaspiration CT showed complete or significant reduction in cyst size in all patients in whom it was performed (18 after initial aspiration and 9 after subsequent aspirations). Asymptomatic intracyst hemorrhage occurred in 2 patients after cyst wall biopsy and catheter placement. There have been no other complications at follow-up of 4 to 114 weeks. In our experience, tumor cyst aspiration by the Ommaya reservoir system is as effective as percutaneous needle aspiration, but after catheter placement aspiration can be performed with minimal technical skill, avoiding repeated CT guidance required for needle aspiration of recurrent deep-seated cysts. 
5	Flow cytometric determination of breast tumor heterogeneity. Flow cytometric analysis was done on the DNA content of nuclei obtained from different sites of small breast tumors. Although specimens for analysis were obtained within a few millimeters of each other, dramatic differences were occasionally observed in the DNA histograms. In a limited study involving 141 consecutive breast specimens submitted for flow cytometry, 52% (74) were found to have at least one DNA aneuploid population. In 18% of DNA aneuploid tumors, one or more specimens from areas grossly identified as tumor had no DNA aneuploid population. Because of the proposed correlation of aneuploidy with a poorer prognosis and possible responsiveness to chemotherapy, multiple sites should be assayed when flow cytometric DNA analysis is done. 
4	Results of the arterial switch operation in patients with transposition of the great arteries and abnormalities of the mitral valve or left ventricular outflow tract. Between January 1983 and October 1989, 290 patients underwent an arterial switch operation for transposition of the great arteries; 30 (10.3%) of the patients had abnormalities of the left ventricular outflow tract or mitral valve, or both. These abnormalities included isolated pulmonary valve stenosis (n = 9), septal (dynamic) subpulmonary stenosis (n = 5), anatomic (fixed) subpulmonary stenosis (n = 7), abnormal mitral chordae attachments (n = 2) or a combination of abnormalities (n = 7). There were two early deaths, one of which was due to previously unrecognized mitral stenosis and a subpulmonary (neo-aortic) membrane and one late death due to presumed coronary obstruction. Of the nine patients with pulmonary valve abnormalities due to either a bicommissural (n = 5) or a thickened tricommissural (n = 4) valve, only one underwent valvotomy. Peak systolic ejection gradients in these nine patients measured preoperatively ranged from 0 to 50 mm Hg. At follow-up study 5 to 30 months postoperatively, the neo-aortic valve gradient was less than or equal to 15 mm Hg in all patients; three patients had mild neo-aortic regurgitation. Preoperative gradients may overestimate the degree of obstruction because of the increased pulmonary blood flow present in transposition. No patient with "dynamic" subpulmonary obstruction before the arterial switch operation had a surgical procedure performed on the left ventricular outflow tract; none had evidence of subaortic obstruction after the arterial switch. 
5	Malignancy associated with chronic empyema: radiologic assessment. Radiologic findings of six cases of malignancy associated with chronic empyema 5-39 years in duration were reviewed. Pathologic examination confirmed three B-cell non-Hodgkin lymphomas, one round-cell sarcoma, one mesothelioma, and one adenocarcinoma. Retrospective findings on plain chest radiographs suggested the occurrence of malignancy: increased radiopacity in the thoracic cavity, soft-tissue bulgings and/or unsharpness of fat planes in the chest walls, destruction of bone near the empyema, and extensive medial deviation of the calcified pleurae. Computed tomography delineated masses with soft-tissue attenuation more clearly than radiography in all cases. Magnetic resonance images of three cases were informative because empyema cavities were surrounded by low-intensity rims, and two of them showed a signal intensity different from that of necrotic tumors. Scintigraphy revealed increased uptake of gallium in all cases. Ultrasonography was useful for biopsy guidance. Every radiologist should know this entity in observation of chest radiographs obtained in patients with chronic empyema, and further radiologic assessment and aggressive biopsy are recommended if malignancy is suspected. 
4	Influence of hypoxia on adrenergic modulation of triggered activity in isolated adult canine myocytes. Although findings from several reports suggest that nonreentrant or focal mechanisms contribute to the genesis of arrhythmias during early ischemia, the contribution of triggered activity arising from early or delayed afterdepolarizations has not been resolved. We have previously demonstrated that beta- but not alpha-adrenergic stimulation induces afterdepolarizations and triggered activity in isolated normoxic myocytes. In the present study, the influence of the extent of cellular derangements as well as increases in [K+]o on alpha- and beta-adrenergic-mediated afterdepolarizations and triggered activity was evaluated. Adult canine myocytes were exposed to one of the following experimental conditions with simultaneous intracellular transmembrane action potential recordings: 1) low PO2 (less than 10 mm Hg, obtained using a specially designed hypoxic chamber) and low (6.8) pH; 2) low PO2, low pH, and high extracellular potassium ([K+]o) (10 mM); or 3) severe metabolic inhibition with cyanide (10(-6) M). Cells from each group were superfused with either the alpha-agonist phenylephrine (10(-5) or 10(-7) M, with 10(-5) M nadolol) or the beta-agonist isoproterenol (10(-6) M). Moderate changes in the action potentials were observed under conditions 1 and 2 (moderate hypoxia), whereas marked but reversible changes were observed with cyanide (severe metabolic inhibition). During moderate hypoxia in normal [K+]o, delayed afterdepolarizations or triggered activity were elicited by both alpha- (12 of 13 cells) and beta-adrenergic (five of five cells) stimulation. Increasing [K+]o during moderate hypoxia completely abolished the afterdepolarizations induced by alpha-adrenergic stimulation and prevented the occurrence of triggered activity. In contrast, the influence of beta-adrenergic stimulation was only attenuated by an increase in [K+]o. Exposure to cyanide completely prevented the induction of afterdepolarizations and triggered activity by both alpha- and beta-adrenergic stimulation. Our findings indicate that moderate hypoxia in normal [K+]o is associated with the development of adrenergic-mediated afterdepolarizations and triggered activity. In contrast, accumulation of [K+]o or severe impairment of cellular metabolism is accompanied by inhibition of adrenergic-mediated afterdepolarizations and triggered activity. 
4	Conservative management of aortic lacerations due to blunt trauma. Three patients with angiographically documented thoracic aortic lacerations were managed conservatively over 8 years due to the nonthreatening appearance of the injuries in two and the presence of an associated major closed head injury in a third. The lesion(s) resolved in one, diminished in another, and remained unchanged in the third. At least ten other cases managed similarly are recorded in the literature. In certain selected circumstances this approach may represent a viable alternative to the current standard of immediate surgical correction of aortic injuries. 
2	Risk factors for transmission of hepatitis B virus to Gambian children [published erratum appears in Lancet 1990 Dec 22-29;336(8730):1596] Risk factors for hepatitis B virus transmission were examined in 973 Gambian children aged 6 months to 5 years. 33% had evidence of infection with hepatitis B virus and a third of these were carriers. A significant association was found between infection and tropical ulcer scars, and between e antigenaemia and the presence of bedbugs in each child's bed. There was no association between infection and traditional scarring, circumcision, or injections. Skin disease and arthropods are the two most likely modes of transmission of hepatitis B virus between children in West Africa. 
4	Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine. Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following ischemia/reperfusion. It has been suggested that leukotriene B4 may be released during ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a) leukotriene B4 is produced in the gut mucosa during ischemia and reperfusion, and (b) inhibition of leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline, ischemia at 3 hours and reperfusion at 1 hour. Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal leukotriene B4 was entirely prevented by pretreatment with either nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent lipoxygenase inhibitors. Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel. 
4	Tension pneumopericardium as a complication of single-lung transplantation. Tension pneumopericardium is distinctly uncommon in the adult population. We present a case of tension pneumopericardium as a complication of lung transplantation in a 54-year-old woman with thromboembolic pulmonary hypertension who underwent single-lung transplantation. 
3	Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin. Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period. 
2	Miliary tuberculosis presenting as hepatic and renal failure. A 67-year-old man developed hepatic and renal failure over a six-day period. Despite full supportive measures, he died on his 11th day of hospitalization with fulminant DIC and hepatic, renal, and respiratory failure. Postmortem examination revealed acid-fast bacilli in virtually all organ systems. Miliary tuberculosis should be considered as a potentially treatable cause of hepatic failure. 
1	Patient perceptions. The cancer patient's perceptions about treatment, prognosis, and long-term care have emerged in the context of interaction with the changing healthcare system. A brief overview of cancer patients' perceptions regarding their disease and subsequent care is provided. The economic, organizational, and technological environment in which this care is provided and the patient's perceptions of that environment are discussed. In addition to economic pressures, the ever-increasing number of cancer patients, prolonged survival, and patients' perceptions have created changes in the healthcare system. These changes are mediated by important socioeconomic, cultural, and demographic characteristics of the cancer patient. Recommendations to address these changes are discussed. 
5	Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography BACKGROUND. Echocardiography is recognized as the method of choice for the noninvasive detection of valvular vegetations in patients with infective endocarditis, with transesophageal echocardiography being more accurate than transthoracic echocardiography. The diagnosis of associated abscesses by transthoracic echocardiography is difficult or even impossible in many cases, however, and it is not known whether transesophageal echocardiography is any better. METHODS. To determine the value of transesophageal echocardiography in the detection of abscesses associated with endocarditis, we studied prospectively by two-dimensional transthoracic and transesophageal echocardiography 118 consecutive patients with infective endocarditis of 137 native or prosthetic valves that was documented during surgery or at autopsy. RESULTS. During surgery or at autopsy, 44 patients (37.3 percent) had a total of 46 definite regions of abscess. Abscesses were more frequent in aortic-valve endocarditis than in infections of other valves, and the infecting organism was more often staphylococcus (52.3 percent of cases) in patients with abscesses than in those without abscesses (16.2 percent). The hospital mortality rate was 22.7 percent in patients with abscesses, as compared with 13.5 percent in patients without abscesses. Whereas transthoracic echocardiography identified only 13 of the 46 areas of abscess, the transesophageal approach allowed the detection of 40 regions (P less than 0.001). Sensitivity and specificity for the detection of abscesses associated with endocarditis were 28.3 and 98.6 percent, respectively, for transthoracic echocardiography and 87.0 and 94.6 percent for transesophageal echocardiography; positive and negative predictive values were 92.9 and 68.9 percent, respectively, for the transthoracic approach and 90.9 and 92.1 percent for the transesophageal approach. Variation between observers was 3.4 percent for transthoracic and 4.2 percent for transesophageal echocardiography. CONCLUSIONS. The data indicate that transesophageal echocardiography leads to a significant improvement in the diagnosis of abscesses associated with endocarditis. The technique facilitates the identification of patients with endocarditis who have an increased risk of death and permits earlier treatment. 
5	Relationship of transfusion and infectious complications after gastric carcinoma operations. To determine the effect of transfusion on the incidence of postoperative infection, a retrospective cohort study of 196 patients who underwent surgery for gastric carcinoma in the period from 1985 through 1989 was carried out. Seventy-one patients (36.2%) developed postoperative septic complications; they had received an average of 4.2 blood units, as compared with 2.7 units received by patients not affected (p less than 0.0053). The hypothesis of dose-response relationship is supported by the Mantel-Haenszel test, as applied to the overall results (p less than 0.01) and the results grouped by duration of operation (p less than 0.02). Furthermore, logistic regression analysis shows transfusion to be an independent risk factor in the incidence of infection (p less than 0.01), as are antibiotic prophylaxis (p less than 0.015), urinary tract catheterization (p less than 0.002), and the duration of surgery (p less than 0.027). This significance is attained after adjustment for age, gender, period of evolution of symptoms; preoperative infection(s), number of white cells, hemoglobin level and total proteins on diagnosis, location of tumor, tumor, nodes, and metastasis staging, operative technique, drainage of the area of operation, enteral nutrition, and the histologic studies and macroscopic appearance of the tumor. This study is further evidence that transfusion may cause an increased incidence of postoperative infection. 
5	Successful treatment of an excimer laser-associated coronary artery perforation with the Stack perfusion catheter. A 64-year-old woman underwent excimer laser angioplasty of the right coronary artery. The procedure was complicated by perforation, which was successfully managed without complication with a Stack perfusion catheter. This report describes successful nonsurgical treatment of laser-induced coronary perforation and makes recommendations for avoiding this complication in other patients. 
1	Inflammatory atypia on cervical smears. A diagnostic dilemma for the gynecologist. In light of the current controversy on the significance, follow-up and management of women with cervical smears showing "inflammatory atypia" (IA), a study was conducted to correlate the initial cytologic diagnosis of IA with the follow-up findings in colposcopically directed cervical biopsies and smears. From March 1988 through June 1989, 70 women had two consecutive smears reported as IA; all underwent colposcopy and cervical biopsy. In 58 patients (83%) the biopsies and smears obtained during colposcopy were negative for condyloma and/or cervical intraepithelial neoplasia (CIN). Ten patients (14%) had condylomas, and two (3%) had condylomas with CIN (one CIN I and one II). The initial IA smears from those 12 patients were reviewed retrospectively: 2 showed condylomas (they had been undercalled), 5 were "suggestive of condyloma" (the atypical cells were too few or poorly preserved for a definitive diagnosis), and 5 showed IA. None showed cytologic evidence of CIN, most probably because of sampling error. Our results suggest that colposcopy is warranted after two consecutive diagnoses of IA on cervical smears, considering that 17% of the patients in our study showed underlying intraepithelial lesions of the cervix. 
1	Tumor necrosis factor regulates the expression of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors on human acute myeloid leukemia cells. Tumor necrosis factor (TNF) acts as a potent enhancer of granulocyte-macrophage colony-stimulating factor (GM-CSF)- and interleukin-3 (IL-3)-induced human acute myeloid leukemia (AML) growth in vitro. We have analyzed the effects of TNF alpha on the expression of GM-CSF and IL-3 receptors on AML cells. Incubation of blasts from seven patients with AML in serum-free medium with TNF (10(3) U/mL) and subsequent binding studies using 125I-GM-CSF and 125I-IL-3 show that TNF increases the specific binding of GM-CSF (30% to 280%) and IL-3 (40% to 600%) in all cases. From Scatchard plot analysis it appears that TNF upregulates (1) low-affinity GM-CSF binding sites, (2) common high-affinity IL-3/GM-CSF binding sites, and (3) unique (non-GM-CSF binding) IL-3 binding sites. The effect of TNF is dose dependent and is half maximal at a concentration of 100 U/mL, and becomes evident at 18 hours of incubation with TNF at 37 degrees C, but not at 0 degree C. The GM-CSF dose-response curve of AML-colony-forming units plateaus at a higher level in the presence of TNF, which indicates that additional numbers of cells become responsive to GM-CSF. Incubation of AML blasts with the phorbol ester 12-0-tetradecanoylphorbol-13-acetate or formyl-Met-Leu-Phe (protein kinase C activators) does not influence GM-CSF receptor expression, suggesting that receptor upregulation by TNF is not mediated through activation of protein kinase C. On the other hand, the protein synthesis inhibitor cycloheximide abrogates receptor upregulation induced by TNF. In contrast to these findings in AML, TNF does not upregulate GM-CSF receptor numbers on blood granulocytes or monocytes. We conclude that TNF exerts positive effects on growth factor receptor expression of hematopoietic cells. 
5	Intraoperative echocardiography of a dislodged Bjork-Shiley mitral valve disc. The successful management of a patient who suffered an outlet strut fracture of a Bjork-Shiley 60-degree convexo-concave mitral valve prosthesis is reported. Emergency operation was life-saving. Preoperative echocardiography assisted in making a prompt diagnosis, and intraoperative echocardiography allowed the detection and removal of the dislodged disc from the left ventricle at the time of the operation. The role of intraoperative echocardiography in the diagnosis of prosthetic strut fracture is emphasized. 
1	Pancreatic ascites presenting in infancy, with review of the literature. We report a 4-month-old boy with massive ascites in whom a diagnosis of pancreatitis was made on a raised ascitic amylase level after two inconclusive laparotomies. He developed a pseudocyst which was managed with repeated percutaneous needle aspirations, nutrition being maintained intravenously. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a congenital intra-pancreatic cyst. He thrived after operation drainage for recurrent pseudocyst, but repeat ERCP shows that the cyst in the head of the pancreas remains. Pancreatic ascites is rare in children and diagnosis is frequently delayed. A third of reported cases in childhood present in the first year of life. A search for the underlying cause should include an ERCP to demonstrate abnormalities of the pancreaticobiliary ducts. 
3	Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects. Conductance of cerebrospinal fluid (CSF) outflow (Cout) is an important parameter to be considered in patients with CSF circulation abnormalities. In patients with normal-pressure hydrocephalus it is the single most important parameter in determining if the patient needs CSF shunting. The lower normal limit for Cout has been estimated from the effect of shunting in patients with normal-pressure hydrocephalus, from patients retrospectively reevaluated after recovering from illness, and from patients with known abnormalities in the brain or the CSF system. The true value of Cout in normal individuals, however, has hitherto not been reported. In the present study, Cout has been measured by a lumbar infusion test in eight young volunteers with no suspicion of disease. The mean intracranial pressure (ICP) was 11 mm Hg and a linear relationship was found between CSF absorption and ICP. The mean Cout was 0.11 ml/min/mm Hg and the lower 95% confidence level was 0.10 ml/min/mm Hg. These values are in accordance with those obtained from previous studies. 
1	Palliation of malignant esophageal obstruction. Progressive dysphagia is common in patients with advanced esophageal carcinoma. Multiple nonsurgical techniques are available to provide palliation and improved nutrition. Simple dilatation is the oldest technique and newer methods may offer greater efficacy. Laser therapy now provides an excellent opportunity to treat obstructing tumors. Placement of an esophageal prosthesis may become particularly useful when dilatation must be performed too frequently or has become ineffective or in the patient with an esophageal-pulmonary fistula. Newer techniques including BICAP tumor probe, intracavitary radiotherapy, or absolute alcohol injection offer promise. This review discusses the advantages and disadvantages of these different palliative techniques for patients with the extremely poor prognosis associated with esophageal cancer. 
2	Operative choledochoscopy: common bile duct exploration is incomplete without it. This paper reviews the reported experience of operative choledochoscopy. Development of choledochoscopes to the currently available rigid and flexible instruments is described. The collected results of both rigid and flexible choledochoscopy are reported. Retained stones occurred in 97 of 2712 stone-positive explorations with the rigid choledochoscope (3.6 per cent) and in 35 of 1726 stone-positive explorations with the flexible choledochoscope (2.0 per cent). Choledochoscopy should now be a mandatory part of common bile duct exploration. 
5	Characterization of the in vitro maturation of monocytes and the susceptibility to HIV infection. The in vitro maturation of peripheral blood monocytes to macrophages can be followed morphologically, and by measurement of cell surface antigens (CD4, HLA-DR, and FcR III) and lysozyme production. We used these markers to correlate monocyte maturation with susceptibility to human immunodeficiency virus (HIV) infection. Maturation of peripheral blood monocytes is associated with a decrease in membrane CD4, while HLA-DR and FcR III expression increase along with lysozyme secretion. Cells at all stages of maturation were susceptible to HIV infection, even mature macrophages without CD4 detectably by immunofluorescent staining. Maximal replication was observed in 7-day-old cells. 
5	Therapy of persistent human papillomavirus disease with two different interferon species. Consensus interferon and interferon alfa-2a were used to treat patients with persistent human papillomavirus disease. Thirty-one patients were treated with either consensus interferon or a placebo (25 received active drug and 6 received placebo), and 24 patients were treated with interferon alfa-2a. Of the 25 patients who received consensus interferon, 19 (76%) showed either complete or partial clearing of condyloma 10 and 16 weeks after initiation of therapy; in 22 of the 24 patients (91%) who received interferon alfa-2a, clearing was demonstrated after a similar time period. Thirty of 34 patients who had no response or a partial response requested additional therapy, and 20 of these patients treated with adjunctive therapy had a complete response. The results of this study support the efficacy of both interferons in the treatment of overt condyloma acuminatum and suggest that interferon enhances subsequent adjunctive therapy. 
1	Flow cytometric DNA-ploidy analysis of synchronously occurring multiple malignant tumors of the female genital tract. In this study the authors applied flow cytometric DNA-ploidy analysis to multiple female genital tract malignant tumors in 43 patients, most of whom (n = 37) had bilateral ovarian cancer. An algorithm was developed for calculation of the likelihood ratio of the probabilities that measured DNA index differences between multiple tumor localizations within the same patient could be attributed to measurement variation or to true biologic DNA content differences. The results of this statistical analysis show that in 72% of the cases (31 of 43) this probability ratio exceeded 1. Because the probability that two independent tumors will have a near-identical aneuploid DNA content is very low, this finding supports a metastatic process rather than the occurrence of multiple primary tumors in these patients. Thus, flow cytometric DNA-ploidy analysis can be helpful in the identification of metastatic disease in patients with multiple female genital tract malignant tumors. 
1	Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion. The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed. 
5	Diffuse hemangiomatosis of the spleen: splenic hemangiomatosis presenting with giant splenomegaly, anemia, and thrombocytopenia. In an elderly patient with oligosymptomatic giant splenomegaly, clinical and laboratory data were nondiagnostic, while nonhomogeneous splenic enlargement was the only finding detected by imaging procedures. Splenectomy was performed and diffuse hemangiomatosis of predominantly capillary-type found. The failure of imaging techniques to even hint at the nature of the underlying disorder is comprehensible in view of the organ being essentially replaced in toto by the abnormal vascular channels. Diffuse splenic hemangiomatosis, a rare condition, may cause hypersplenism, and its diagnosis may be elusive because of misleading patterns on imaging. 
5	Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor. Normal dogs were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 10 micrograms/kg/day for 30 d, which caused an initial neutrophilia, followed by a prolonged period of chronic neutropenia. A control dog treated with recombinant canine G-CSF (rcG-CSF) showed persistent neutrophilia over 3 mo. Serum from dogs during neutropenia contained an antibody to rhG-CSF, which neutralized the stimulatory effects of both rhG-CSF and rcG-CSF on dog marrow neutrophilic progenitor cell growth and on NFS-60 cell proliferation. 4 mo after discontinuation of rhG-CSF, the dogs' neutrophil counts returned to the normal range. Rechallenge with the rhG-CSF re-induced severe neutropenia in 1 wk. Neutropenia was transferred by plasma infusion from a neutropenic dog to a previously normal dog. These data suggest that human rhG-CSF immunizes normal dogs and thereby induces neutralization of endogenous canine G-CSF and neutropenia. This model system should allow more precise definition of the in vivo role of G-CSF. 
4	Listerial myocarditis in cardiac transplantation. Clinical signs of heart failure developed in two cardiac transplant recipients and were interpreted initially as graft rejection. Morphologic examination of explanted hearts revealed myocarditis with abscess formation and necrosis consistent with a bacterial process; Listeria monocytogenes was isolated from myocardial tissue in the first case and from blood in both. The first patient also developed signs of meningoencephalitis, but the second had no signs of infection outside the heart. Antimicrobial therapy and retransplantation were successful in eradicating listeriosis. The differential diagnosis of heart failure in cardiac transplant recipients includes infectious myocarditis due to L. monocytogenes. 
5	Post-cannulation radial artery aneurysm--a rare complication. The following case report describes an expanding aneurysmal dilatation of the radial artery which developed 17 days following cannulation. Possible causes of this complication are: abnormal state of the vessel wall, multiple attempts at cannulation, and haematoma or infection at cannulation site. Other major and minor sequelae following arterial cannulation are reviewed. 
5	Sudden cardiac death during exercise in a weight lifter using anabolic androgenic steroids: pathological and toxicological findings. A 21-year-old, previously healthy weight lifter collapsed during a bench press workout. He had taken anabolic androgenic steroids parenterally for the previous several months. Pertinent autopsy findings included marked cardiac and renal hypertrophy and hepatosplenomegaly, with regional myocardial fibrosis and focal myocardial necrosis. Nandrolone (19-nor-testosterone) metabolites were identified in postmortem urine. The possible etiologies of the cardiac findings are discussed. 
1	Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I. 
4	Effect of captopril injection in patients with moderate to severe hypertension. The effect of intravenous captopril was studied in 24 white patients who had moderate to severe hypertension. Patients received incremental doses of 1 to 10 mg delivered at 10 min intervals over 50 to 80 min. Blood pressure (BP) was lowered within 5 to 10 min after the initial dose was administered and continued to decline, reaching a maximum response after 20 min (2 to 4 mg). At this time group mean BP fell from 175 +/- 3/111 +/- 1 to 166 +/- 3/97 +/- 2 mm Hg (P less than 0.01). Additional dose increments to an average cumulative dose of 40 mg did not increase the initial effect. No adverse side effects or symptomatic hypotension occurred in any subject. There was a significant correlation between diastolic BP decreases observed in response to intravenous captopril and subsequent long-term oral captopril therapy. The addition of hydrochlorothiazide increased the proportion of patients reaching normotension. We conclude that small intravenous bolus injections of captopril appear to be effective rapidly and are well tolerated in moderate to severe essential hypertension. Short-term intravenous administration seems to predict the response to chronic oral captopril therapy. 
4	Restenosis after directional coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection. Rates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions. After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01). Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histologically identical to restenotic tissue developing after balloon angioplasty (n = 37). These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions. 
1	Bone marrow findings after treatment with recombinant human interleukin-3. In a phase I/II study, bone marrow biopsy specimens and aspirates of 20 patients with malignant tumors but normal bone marrow (n = 6), bone marrow failure resulting from chemotherapy (n = 4), myelodysplastic syndrome (n = 5), and aplastic anemia (n = 5) were evaluated before and after patients were treated with recombinant human interleukin-3 (rhIL-3). This cytokine proved to be an effective hematopoietic growth factor with only mild side effects. The rhIL-3 treatment led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells, except in most patients with aplastic anemia. In all patients, significant eosinophilia and, in some instances, bone marrow fibrosis developed. In addition to the increase in the number of circulating neutrophilic granulocytes, platelets, and reticulocytes, an increase of peripheral blood monocytes and lymphocytes was observed. The histologic and cytologic findings support the concept that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells. It appears to be a safe and efficient therapeutic modality in patients with bone marrow failure. Additional clinical studies are needed to determine which patients will profit most from rhIL-3 treatment. 
2	Antibiotic use among children in an urban Brazilian slum: a risk factor for diarrhea? [published erratum appears in Am J Public Health 1991 Apr;81(4):417] Among a cohort of children in a poor urban setting in Brazil, the relative risk for the occurrence of a new episode of diarrhea in the two weeks following antibiotic use vs all other weeks was 1.44 (95% confidence interval (CI) = 1.33, 2.45). Among children ever [corrected] exposed to antibiotics, the odds ratio was 1.34 (95% CI = 0.84, 2.16) after stratifying by individual child and controlling for previous diarrhea. Further research is needed to confirm whether antibiotics are a risk factor for diarrhea in such settings. 
4	Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor. The hetrazepine WEB 2170 (international nonproprietary name: bepafant), a thieno-triazolodiazepine that is structurally related to the recently described platelet activating factor (PAF) antagonist WEB 2086, is a potent and selective PAF antagonist both in vitro and in vivo. WEB 2170 inhibited PAF-induced human platelet and neutrophil aggregation in vitro (IC50 values: 0.3 and 0.83 microM, respectively) but had little or no inhibitory action against aggregation induced by other agonists. The potency in vitro was comparable to that described recently for WEB 2086 (Casals-Stenzel, J., Muacevic, G. and Weber, K.H.: J. Pharmacol. Exp. Ther. 241: 974-981, 1987). When guinea pigs were given i.v. infusions of PAF at 30 ng x kg-1 x min-1, oral (0.005-0.5 mg/kg) as well as intravenous (0.005-0.05 mg/kg) treatment with WEB 2170 abrogated the intrathoracic accumulation of 111In-labeled platelets, the bronchoconstriction and the hypotension as well as the finally occurring death in a dose-dependent fashion. Oral (0.01-1 mg/kg) and intravenous (0.005-0.1 mg/kg) WEB 2170 shared with the beta 2 agonist fenoterol and the steroid dexamethasone the property of protecting elderly NMRI mice from the lethal effect of PAF. In anesthetized rats, intravenous (0.001-0.1 mg/kg) and oral (0.05-1 mg/kg) WEB 2170 inhibited PAF-induced hypotension in a dose-related manner. Coadministration of WEB 2170 inhibited PAF-induced increase of vascular permeability in rat skin very effectively. The half-time of duration of action in the rat was estimated to be about 5 to 6 h after oral administration and about 1.1 to 2.3 h after intravenous application. In conclusion, the hetrazepine WEB 2170 is a strong and selective PAF antagonist, which is in vitro more or less equipotent to WEB 2086. In contrast, in vivo oral WEB 2170 is--depending on the species and considered parameter--about 5 to 40 times more potent against exogenous PAF-induced alterations than the recently described hetrazepine WEB 2086. Particularly in mice and rats, oral WEB 2170 is by far superior to WEB 2086. 
1	Clonal origin of pituitary adenomas. As the pathogenesis of pituitary adenomas remains unclear, the tumor clonal composition of these common neoplasms was studied. Clonality was determined in female patients by analysis of restriction fragment length polymorphisms of the X-chromosome genes hypoxanthine phosphoribosyl transferase and phosphoglycerate kinase in conjunction with their respective methylation patterns. Peripheral lymphocyte DNA was screened from 62 female patients undergoing transsphenoidal surgery for pituitary adenoma. Eleven patients were heterozygous for the BglI site on PGK, 4 for the BamHI site on HPRT, and 1 patient for both sites. Of these 16 patients, 3 had acromegaly, 4 had Cushing's disease, 7 had hyperprolactinemia, and 2 were clinically nonfunctional. After surgery, morphological study, including immunohistochemistry and electron microscopy of the pathological specimens, allowed a direct comparison between clonality and tumor cell type. Control fresh normal pituitary tissue was found to be polyclonal. The following tumors were monoclonal: all 3 somatotroph adenomas, 4 of 4 lactotroph tumors, 3 of 4 corticotroph cell adenomas, a gonadotroph adenoma, and a nonsecretory adenoma. A mixed plurihormonal adenoma was polyclonal, as were 2 tumors consisting of adenomatous lactotrophs interspersed with nontumorous adenohypophyseal pituitary tissue and one corticotroph adenoma mixed with normal pituitary tissue. Functional pituitary adenomas derived from somatotrophs, corticotrophs, or lactotrophs and nonsecretory tumors are monoclonal in nature, suggesting that somatic cell mutations precede clonal expansion of these cells and play a major role in pituitary tumorigenesis. 
3	In vivo leukocyte migration in arthritis. We quantitated in vivo migration of neutrophils into the knees of patients with rheumatoid arthritis (RA) and osteoarthritis, using 99mtechnetium-hexamethyl-propylene-amineoxime-labeled leukocytes and gamma scintigraphy. Significant neutrophil migration occurred in patients with RA irrespective of disease duration, and it was reduced by 60% following intraarticular steroid injection. The reduction in neutrophil migration correlated with reduction in pain. Leukocyte migration into osteoarthritic joints was also demonstrated, although it was much less than that seen in rheumatoid joints. No significant leukocyte migration into the joints of patients without arthritis was demonstrated. This technique appears to provide a sensitive method for quantitatively assessing the neutrophil component of inflammation in individual joints of patients with arthritis. 
5	Thrombotic thrombocytopenic purpura treated with high-dose intravenous gamma globulin. Plasma infusion and/or plasma exchange has become standard therapy in the treatment of thrombotic thrombocytopenic purpura (TTP). The management of patients in whom such primary therapy fails is difficult and uncertain. We have described a patient who obtained a sustained remission with the use of high-dose IV gamma globulin after an initial response to aggressive plasma exchange was followed by prompt relapse. Our case and others suggest that high-dose IV IgG may induce remission in patients with TTP who do not respond to standard plasma infusion and/or exchange. 
3	Childhood stroke after minor neck trauma: case report. Cerebral infarction after minor trauma to the neck has rarely been reported. A case is presented of a child with trauma to the vertebrobasilar artery resulting in stroke. Computerized tomography scan and angiography results are presented. Despite two subsequent, separate transient episodes of vertigo, the child had good functional recovery with complete restoration of language and cognitive function. After 28 months, residual impairments identified were a mild right-sided ataxia and hemiparesis. 
3	Profound papilledema due to cryptococcal meningitis in acquired immunodeficiency syndrome: successful treatment with fluconazole. Although cryptococcal meningitis is a frequent infection in patients with AIDS, papilledema is rarely reported. We have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with AIDS. After treatment failure with amphotericin B, the patient was successfully treated with fluconazole, and the papilledema resolved. 
3	Efficacy and complications of radiotherapy of anterior visual pathway tumors. A progressive disturbance in visual acuity or visual field, along with an unexplained optic nerve atrophy, suggests the possibility of a tumor. Tumors that frequently affect the anterior visual pathway include primary optic nerve sheath meningiomas, intracranial meningiomas, optic gliomas, pituitary tumors, and craniopharyngiomas. The location of these tumors sometimes prohibits a complete surgical excision that might jeopardize the visual system. Radiation therapy, however, can be beneficial in these cases. This article reviews the indications for radiotherapy of tumors that involve the anterior visual pathway, along with the possible complications. Cases that present the effect of radiation therapy and radiation damage are presented. 
4	Efficacy of transesophageal echocardiography as a perioperative monitor in patients undergoing cardiovascular surgery. Analysis of 149 consecutive studies. To evaluate the usefulness of transesophageal echocardiography as a perioperative monitor in patients undergoing cardiovascular surgery, 149 consecutive patients were studied since 1985. Left ventricular function was assessed by measurement of left ventricular dimension and ejection fraction in patients with valvular disease. This monitoring was useful in detecting the changes in left ventricular performance in patients with volume overload and in managing patients in the early postoperative period. Cardiac tamponade was clearly demonstrated before changes in electrocardiogram and hemodynamic data. In 27 patients, transesophageal color Doppler echocardiography was used to confirm that there was no residual regurgitation immediately after valvular reconstructive surgery. Transesophageal color Doppler echocardiography was also useful in detecting the entry of false lumen before surgery in 7 patients with dissecting aortic aneurysm. There were no unsuccessful introductions, no traumatic or thermal injuries, 18 patients (12.1%) with hoarseness and 5 patients (3.4%) with transient arrhythmia. In conclusion, transesophageal echocardiography provides a good imaging window to the heart and great vessels perioperatively. This expedient, safe informative imaging method can be used more routinely in patients during surgery. 
1	Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial OBJECTIVES--To assess outside a clinical trial the psychological outcome of different treatment policies in women with early breast cancer who underwent either mastectomy or breast conservation surgery depending on the surgeon's opinion or the patient's choice. To determine whether the extent of psychiatric morbidity reported in women who underwent breast conservation surgery was associated with their participation in a randomised clinical trial. DESIGN--Prospective, multicentre study capitalising on individual and motivational differences among patients and the different management policies among surgeons for treating patients with early breast cancer. SETTING--12 District general hospitals, three London teaching hospitals, and four private hospitals. PATIENTS--269 Women under 75 with a probable diagnosis of stage I or II breast cancer who were referred to 22 different surgeons. INTERVENTIONS--Surgery and radiotherapy or adjuvant chemotherapy, or both, depending on the individual surgeon's stated preferences for managing early breast cancer. MAIN OUTCOME MEASURES--Anxiety and depression as assessed by standard methods two weeks, three months, and 12 months after surgery. RESULTS--Of the 269 women, 31 were treated by surgeons who favoured mastectomy, 120 by surgeons who favoured breast conservation, and 118 by surgeons who offered a choice of treatment. Sixty two of the women treated by surgeons who offered a choice were eligible to choose their surgery, and 43 of these chose breast conserving surgery. The incidences of anxiety, depression, and sexual dysfunction were high in all treatment groups. There were no significant differences in the incidences of anxiety and depression between women who underwent mastectomy and those who underwent lumpectomy. A significant effect of surgeon type on the incidence of depression was observed, with patients treated by surgeons who offered a choice showing less depression than those treated by other surgeons (p = 0.06). There was no significant difference in psychiatric morbidity between women treated by surgeons who offered a choice who were eligible to choose their treatment and those in the same group who were not able to choose. Most of the women (159/244) gave fear of cancer as their primary fear rather than fear of losing a breast. The overall incidences of psychiatric morbidity in women who underwent mastectomy and those who underwent lumpectomy were similar to those found in the Cancer Research Campaign breast conservation study. At 12 months 28% of women who underwent mastectomy in the present study were anxious compared with 26% in the earlier study, and 27% of women in the present study who underwent lumpectomy were anxious compared with 31% in the earlier study. In both the present and earlier study 21% of women who underwent mastectomy were depressed, and 19% of women who underwent lumpectomy in the present study were depressed compared with 27% in the earlier study.) CONCLUSIONS--There is still no evidence that women with early breast cancer who undergo breast conservation surgery have less psychiatric morbidity after treatment than those who undergo mastectomy. Women who surrender autonomy for decision making by agreeing to participate in randomised clinical trials do not experience any different psychological, sexual, or social problems from those women who are treated for breast cancer outside a clinical trial. 
5	Toxic carbamazepine concentrations following cardiothoracic surgery and myocardial infarction. Carbamazepine is being used more frequently in the U.S. as an initial agent of choice to treat generalized tonic-clonic, mixed, and partial seizures with complex symptomatology. Carbamazepine is extensively metabolized in the liver; however, there is little information available on its pharmacokinetics in patients following surgery or myocardial infarction, or in those with liver disease. We report a case of a patient who attained toxic carbamazepine serum concentrations (ranging from 18.2 to 21.5 micrograms/mL) two days after cardiothoracic surgery and an intraoperative myocardial infarction, and experienced lethargy, diplopia, dysarthria, diaphoresis, and horizontal and downgaze nystagmus. These alterations in serum carbamazepine concentration normalized ten days after surgery. They may have been due to a combination of changes in protein binding and decreased elimination due to altered intrinsic hepatic clearance. With carbamazepine achieving a more prominent place in anticonvulsant therapy, the influence of various procedures and disease processes on the pharmacokinetics and pharmacodynamics of carbamazepine, as well as the clinical consequences of such changes, need further investigation. 
4	The natural history of peripheral vascular disease. Implications for its management. The durability and the eventual complication rate of endovascular therapy (percutaneous transluminal angioplasty, laser-assisted angioplasty, and atherectomy) are not yet entirely clear, especially with respect to the treatment of atherosclerotic lesions in the femoropopliteal or distal arterial segments. Therefore, the indications for its use have not been firmly established and must take into consideration the natural history of the occlusive disease itself. Although some type of procedural intervention clearly is warranted in the presence of ischemic rest pain or tissue necrosis, intermittent claudication is the only complaint in approximately 70% of patients who present with either aortoiliac or femoropopliteal involvement. Most nondiabetic patients experience substantial symptomatic improvement with a daily exercise program, and their long-term risks for either abrupt deterioration (20-25%) or amputation (less than 10%) are relatively low. In comparison, the 5-year mortality rate ranges from 20-40% even in claudicants, and as many as 40% of those with clinical indications of associated coronary artery disease have been shown angiographically to be candidates for myocardial revascularization. These observations suggest that traditional indications for surgical treatment (truly disabling claudication and/or limb salvage) also should be applied to endovascular therapy until its success is confirmed beyond speculation, and that incidental coronary disease deserves particular attention in patients with lower extremity ischemia. 
1	Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy. We report the cases of four patients who were taking the anticonvulsant drugs phenytoin or carbamazepine and in whom skin lesions developed that showed histologic features suggestive of mycosis fungoides. Two patients had a solitary lesion on the trunk, whereas the other two patients had multiple plaques. In all four patients systemic signs were absent. 
5	Endolymphatic hydrops precipitated by haemodialysis. We report a case of endolymphatic hydrops preceded by haemodialysis in the contralateral ear of a patient with known Meniere's disease, and discuss the possible mechanism. It is suggested that the sudden decrease of plasma osmolality during haemodialysis acts as a reverse glycerol test. The audiometric and electrophysiological recordings pre- and post-dialysis and the induction of the Meniere's triad of symptoms during dialysis, were strongly indicative of the presence of endolymphatic hydrops. 
5	Effect of chemodenervation on the cerebral vascular and microvascular response to hypoxia. This study evaluated the effect of bilateral carotid chemodenervation on the cerebrovascular response to hypoxia in conscious rats. Cerebral blood flow was measured using 4-iodo[N-methyl-14C]antipyrine, and the total and perfused microvasculature was studied by injection of fluorescein isothiocyanate dextran and alkaline phosphatase staining. To maintain constant PCO2, hypoxia was achieved in chemoreceptor-intact rats by the use of 4% CO2-8% O2-88% N2 and in chemodenervated rats by the administration of 8% O2-92% N2. Blood gas and hemodynamic parameters were similar in the two groups of rats. Chemodenervation had no significant effect on either resting blood flow or the perfused microvasculature during normoxia. A significant increase in cerebral blood flow (from 71 +/- 3 to 138 +/- 9 ml/min/100 g in control and from 91 +/- 5 to 127 +/- 7 ml/min/100 g in chemodenervated rats) and in the percent of cerebral arterioles and capillaries perfused occurred in both hypoxic control and chemodenervated rats. In chemoreceptor-intact rats, the greatest increase in blood flow and in perfused microvasculature occurred in caudal structures (medulla and pons) in comparison with rostral structures (cortex, thalamus, and hypothalamus). In chemodenervated rats, a similar increase in blood flow and perfused microvasculature occurred in all brain regions, with no regional differences. Thus, chemodenervation did not affect the overall cerebral blood flow or the microvascular response to hypoxia; however, rostral-to-caudal regional differences in the hypoxic response were lost after chemodenervation. 
1	Drug-induced DNA damage and tumor chemosensitivity. Cytotoxic drugs act principally by damaging tumor-cell DNA. Quantitative analysis of this interaction provides a basis for understanding the biology of therapeutic cell kill as well as a rational strategy for optimizing and predicting tumor response. Recent advances have made it possible to correlate assayed DNA lesions with cytotoxicity in tumor cell lines, in animal models, and in patients with malignant disease. In addition, many of the complex interrelationships between DNA damage, DNA repair, and alterations of gene expression in response to DNA damage have been defined. Techniques for modulating DNA damage and cytotoxicity using schedule-specific cytotoxic combinations, DNA repair inhibitors, cell-cycle manipulations, and adjunctive noncytotoxic drug therapy are being developed, and critical therapeutic targets have been identified within tumor-cell subpopulations and genomic DNA alike. Most importantly, methods for predicting clinical response to cytotoxic therapy using both in vitro markers of tumor-cell sensitivity and in vivo measurements of drug-induced DNA damage are now becoming a reality. These advances can be expected to provide a strong foundation for the development of innovative cytotoxic drug strategies over the next decade. 
1	Specific binding sites for insulin-like growth factor I in the ovarian stroma of women with polycystic ovarian disease and stromal hyperthecosis. Women with polycystic ovarian disease and hyperthecosis have hyperinsulinemia and insulin resistance. It is possible that insulin in supraphysiologic concentration exerts its steroidogenic action on ovarian stromal cells through insulin-like growth factor I receptors. We undertook this study to investigate whether the ovarian stroma of women with hyperthecosis has specific binding sites for insulin or insulin-like growth factor I. Ovarian stromal tissue was obtained from seven women with normal ovulatory cycles and from five women with hyperthecosis of the ovaries. Binding studies with insulin tagged with iodine 125 and insulin-like growth factor I tagged with iodine 125 revealed specific binding sites both for insulin and insulin-like growth factor I in the ovarian stroma. The binding of insulin tagged with iodine 125 in the ovarian stroma of women with hyperthecosis (3.4% +/- 1.1% (+/- SE) per 100 micrograms protein) was significantly (p less than 0.04) lower than that observed in normal premenopausal women (8.3% +/- 1.6% per 100 micrograms protein). By contrast, the specific binding of insulin-like growth factor I tagged with iodine 125 in the ovarian stroma of women with hyperthecosis (7.1% +/- 1.7% per 100 micrograms protein) was higher than that observed in the ovarian stroma from normal women (4.5% +/- 1.7% per 100 micrograms protein), although the difference was not statistically significant. The affinity constants for these high-affinity receptors were similar (1.2 to 3.6 x 10(9) L/mol) in the two groups of women. These results indicate that (1) the ovarian stroma has specific binding sites both for insulin and for insulin-like growth factor I; (2) in women with hyperthecosis, the ovarian stroma has decreased binding sites for insulin but has normal concentrations of insulin-like growth factor I receptors; and (3) in women with hyperthecosis, stimulation of ovarian androgen synthesis by insulin may be mediated through the insulin-like growth factor I receptors. 
5	Some osseous and soft tissue causes of human intervertebral canal (foramen) stenosis. Much attention has been paid to the causes of vertebral canal stenosis in humans but relatively little has been documented with regard to intervertebral canal (intervertebral "foramen," lateral spinal canal, nerve root canal) stenosis. As the dural sleeve ends at the outer opening of the intervertebral canal, a false "normal" myelogram is possible when a space occupying lesion occurs beyond the subarachnoid space. Also, if stenosis affects only vascular structures, compression of these structures cannot be noted during myelography, so venous stasis may be overlooked. Our cadaveric study investigates some causes of intervertebral canal stenosis due to encroachment by bony and soft tissue structures, and low magnification photomicrographs are used to illustrate some causes of stenosis. 
5	The growing teratoma syndrome. Thirteen patients with metastatic non-seminomatous germ cell tumours and enlarging metastases consisting of teratoma differentiated only were identified. Patients were managed with surgical resection soon after the growing lesions were documented. Surgical morbidity was minimal and 12 patients are alive (10 are disease-free) at a median follow-up of 28 months. 
3	Diagnostic and prognostic value of electrophysiologic tests in meralgia paresthetica. Electrophysiologic diagnosis of unilateral meralgia paresthetica is usually assessed by side-to-side comparison of SNAP amplitudes, SNCVs, and SEP latencies following stimulation of lateral femoral cutaneous nerves. To determine the relevance for diagnosis of these tests and side-to-side comparison, the results were compared in patients with unilateral meralgia paresthetica and normal subjects. The long-term outcome was also considered, in order to determine whether electrophysiologic findings contribute to the prognosis. In our study, SNAP amplitude comparison was found to be more useful for diagnosis than SNCV and SEP latency comparisons. However the value of the SNAP amplitude on the affected side, just as the results of the other tests, was not found to be predictive of the outcome. Also the results of the tests depend on the methods used and on the nerve's route. 
5	Does use of gastroepiploic artery graft increase surgical risk? Seventy patients in whom the gastroepiploic artery was used for coronary artery bypass grafting were compared with 70 patients in whom the gastroepiploic artery was not used. Mean age was 56.8 years in the group in which this artery was used and 61.8 years in the group in which it was not (p less than 0.001). All other preoperative characteristics including number of women, extent of coronary artery disease, previous myocardial infarction, unstable angina, and preoperative left ventricular function were not significantly different between the two groups. An internal mammary artery graft was concomitantly used in 68 patients (97%) of the group with a gastroepiploic artery graft and in 61 patients (87%) without such a graft. The mean number of distal anastomoses was 3.3 and 3.4, aortic crossclamp time was 65.3 +/- 19.9 minutes and 54.0 +/- 20.1 minutes, and cardiopulmonary bypass time was 114.8 +/- 23.6 minutes and 112.9 +/- 25.0 minutes, respectively, in the groups with and without a gastroepiploic artery graft. Only aortic crossclamp time was significantly (p less than 0.05) longer in the group with a gastroepiploic artery graft. There were two (2.9%) early deaths and two (2.9%) new Q-wave infarctions in both groups. Intraaortic balloon pumping was required in five patients (7.1%) in the group with a gastroepiploic artery graft and in three patients (4.3%) without this graft. Postoperative complications were similar and rare in both groups. Intraoperative endoscopic laser Doppler study demonstrated no significant change of gastric mucosal blood flow before and after division of the gastroepiploic artery. We concluded that there is no additional risk in the use of the gastroepiploic artery for coronary bypass grafting, and a favorable outcome can be expected. 
4	Spinal cord injury after subclavian flap aortoplasty. An experimental study in piglets. Paraplegia is a rare but much feared complication of corrective surgery for coarctation of the aorta. The problem was studied in 31 newborn pigs submitted to subclavian flap aortoplasty. The aortic cross-clamping time ranged from 9-25 min. Twenty-three piglets with clamping times 9-18 min were neurologically intact, whereas eight with aortic clamping for 18-25 min became paraplegic. The clinical implications for newborn children with symptomatic aortic coarctation are discussed with regard to these experimental findings. 
1	Nonseminomatous germ cell tumor with very high serum human chorionic gonadotropin. Most patients with disseminated nonseminomatous germ cell tumor (NSGCT) have an excellent prognosis with modern chemotherapy, although certain subgroups with a worse prognosis have been described. One such subgroup includes patients with high serum levels of the tumor marker, human chorionic gonadotropin (HCG). Sixteen patients of 104 treated for NSGCT at the CRC Wessex Medical Oncology Unit (Southampton, UK) presented with serum HCG greater than 25,000. Most of these patients exhibited features of the "choriocarcinoma syndrome" with bulky, rapidly progressive disease; frequent pulmonary, hepatic, and central nervous system complications; and a generally poorer response to standard NSGCT chemotherapy. Histologic identification of trophoblastic tumor was not made in all patients and is not essential for the diagnosis of the syndrome; indeed, closed biopsy may be contradicted in some circumstances because of the risk of hemorrhage. The NSGCT patients with poor prognosis, including patients with the choriocarcinoma syndrome, must be clearly identified in order to improve management and, eventually, cure rates. 
4	Immunohistochemical study of vascular lesions in severe hypertension induced by DOCA and salt administration to spontaneously hypertensive rats. In order to evaluate whether immunoglobulin deposition in vessels plays some role in the development of vascular lesions in severe hypertension, an immunohistochemical study was performed in spontaneously hypertensive rats (SHRs), to which deoxycorticosterone acetate (DOCA) and salt were administered. DOCA and salt rapidly induced severe hypertensive vascular lesions, including necrotizing arteriolitis and productive endarteritis. In these rats, considerable deposits of IgG and IgM were found in the small arteries and arterioles of the kidneys. These deposits were accompanied by complement (C3), and could be eluted by acid incubation. They were localized in periodic acid-Schiff-positive insudative lesions, which were thought to be an early phase of the hypertensive vascular lesions. These results suggest that the immunoglobulins might be bound to an unknown antigen in the vascular lesions and that some immunological mechanism mediated by the immunoglobulins is involved in the development of vascular lesions in severe hypertension. 
1	Function after amputation, arthrodesis, or arthroplasty for tumors about the knee. We studied the function of twenty-two patients who had had a malignant skeletal tumor adjacent to the knee. An above-the-knee amputation was done in seven; a resection arthrodesis, in nine; and a replacement arthroplasty, in six. The patients all walked at a similar speed (sixty-one to sixty-six meters per minute), which is slower than normal (eighty meters per minute). They all walked with comparable efficiency at three velocities: the mean consumption of oxygen was 0.210 milliliter per kilogram of body weight per meter at free velocity, 0.215 milliliter per kilogram of body weight per meter when they walked 25 per cent faster, and 0.211 to 0.240 milliliter per kilogram of body weight per meter when they walked 50 per cent faster. The three groups of patients and a normal control group consumed oxygen at similar rates. The patients who had had an amputation were very active, and they were the least worried about damaging the affected limb, but they had difficulty walking on steep, rough, or slippery surfaces. The patients who had had an arthrodesis had a more stable limb and performed the most demanding physical work and recreational activities, but they had difficulty sitting. The patients who had had an arthroplasty led sedentary lives and were the most protective of the limb, but they were the least self-conscious about the limb. 
1	Extramedullary blast crisis in a patient with Philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic remission. Treatment of Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) with recombinant interferon-alpha (IFN-A) results in complete disappearance of the Ph chromosome in about 10% to 15% of patients in early chronic phase. This group has a long survival and very low incidence of blast crisis. The first known case is reported of extramedullary blastic transformation in a patient with medullary complete cytogenetic response (0% Ph-positive metaphases) to IFN-A. Four episodes of extramedullary blast crisis have occurred in this patient. The first three episodes were lymphoid by morphology and cytochemical stains. Molecular analysis confirmed breakpoint cluster region rearrangement. The most recent transformation was myeloid in nature and involved bone and pulmonary parenchyma. The patient is currently undergoing a second autologous transplantation with stored bone marrow that is Ph negative. The patient has survived more than 18 months since the first episode of blast crisis, and the bone marrow is normal. 
2	Ischemic colitis in a crack abuser. We report a case of acute colitis temporally associated with smoking crack. Colonoscopy revealed a patchy left-sided hemorrhagic inflammation from the rectosigmoid colon to the splenic flexure. Biopsy specimens were consistent with resolving ischemic colitis. This entity should be considered in the differential diagnosis of acute bloody diarrhea in recreational drug users. 
5	Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria. Seventeen adult patients with acute Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases, were studied. Serial measurements of the serum concentration of C-reactive protein, serum amyloid A protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. Initial C-reactive protein and serum amyloid A concentrations were increased (C-reactive protein mean 49.0 mg/l serum amyloid A 28 mg/l) falling towards the normal range by the seventh day of treatment. There was a significant correlation between the pretreatment parasite count and clinical and laboratory markers of inflammation. C-reactive protein and serum amyloid A concentrations correlated inversely with the serum sodium. These results indicate that measurement of acute phase reactants such as C-reactive protein and serum amyloid A may prove valuable in assessing the severity of P falciparum malaria, and in following the response to antimalarial treatment. 
2	Carbohydrate malabsorption. Its measurement and its contribution to diarrhea. The major purpose of this research was to gain insight into the effect of carbohydrate malabsorption on fecal water output. To do this we measured daily fecal output of total carbohydrate, reducing sugars, and organic acids (a product of bacterial fermentation). Normal subjects were studied in their native state and when diarrhea was induced by mechanisms that did and did not involve carbohydrate malabsorption. Patients with malabsorption syndrome were also studied. We concluded that: (a) Excretion of carbohydrate and its breakdown products can be expressed as a single number by converting organic acids to their monosaccharide equivalents. (b) Diarrhea per se causes only a trivial increase in fecal carbohydrate excretion. (c) The molar output of osmotic moieties in feces due to unabsorbed carbohydrate can be determined by adding fecal reducing sugars to organic acids and their obligated cations. This expression parallels almost exactly the effect of increasing doses of lactulose (a nonabsorbable sugar) on fecal water output; one excreted millimole obligates 3.5 g of stool water. This relationship can be used to predict the effect of carbohydrate malabsorption on stool water output in patients with diarrhea. (d) 12 of 19 patients with malabsorption syndrome due to various diseases had excessive fecal excretion of carbohydrate and its breakdown products; of the diseases that cause malabsorption syndrome, combined small and large bowel resection is most likely to result in excessive fecal excretion of carbohydrate and monosaccharide equivalents. In 6 of these 19 patients carbohydrate malabsorption appeared to be the major cause of diarrhea. 
4	Focal scleroderma and severe cardiomyopathy. Patient report and brief review. A 21-month-old infant presented with simultaneous localized scleroderma and severe cardiomyopathy with heart failure. Cardiac abnormalities and serological changes (positive rheumatoid factor assay, elevated IgM and IgG levels, and elevated erythrocyte sedimentation rate) reverted to normal with prednisone therapy, and there was substantial, though incomplete, resolution of her skin changes during the same period. To our knowledge, this is the first patient with definite, clinically significant cardiac involvement associated with focal scleroderma. The possibility of internal organ involvement, including cardiac involvement, must be considered with focal scleroderma as well as with progressive systemic sclerosis. 
4	Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy. Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we measured the maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR: 51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria, and in 18 sex-, age-, and body mass index-matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Diabetes per se seems to enhance Na+/Li+ countertransport activity. 
1	Extramedullary hematopoiesis in a bronchial carcinoid tumor. An unusual complication of agnogenic myeloid metaplasia. A case of bronchial carcinoid tumor with foci of extramedullary hematopoiesis is presented. The patient had a 6-year history of agnogenic myeloid metaplasia and hepatosplenomegaly. All three hematopoietic cell lines were represented in different areas of the bronchial tumor. To our knowledge, this is the first case of extramedullary hematopoiesis described in a bronchial carcinoid and only the fourth report of hematopoietic cells in a neoplasm of otherwise unrelated origin. The pathogenesis of this uncommon finding is discussed and the literature is reviewed. 
4	Production of thrombi on intact endothelium by use of antiheparin agents in vivo. It had been suggested that antithrombin activity on the surface of intact endothelial cells may play a role in inhibiting platelet adhesion and thrombus formation. The antithrombin activity may be due to thrombomodulin or to activation of antithrombin III by glycosaminoglycans or thrombomodulin, or possibly a combination of these. This inhibitory activity has been shown to be affected by such antiheparin agents as protamine, hexadimethrine bromide (Polybrene; Aldrich Chemical Co., Milwaukee, Wis.) and platelet factor 4, as well as by such enzymes as heparinase and heparitinase. We have used a hamster cheek pouch preparation to observe thrombus formation in vivo in a normal vascular flow, to determine whether the production of thrombi by thrombin can be enhanced by antiheparin agents. After intra-arterial injection or topical application of protamine or hexadimethrine bromide, platelet adhesion and thrombus formation on intact arteriolar endothelium was produced by a dose of thrombin, which when injected alone had no effect. No thrombi were found in venules or capillaries. Injection of heparin before or after the antiheparin agents necessitated a larger dose to enhance the action of thrombin. On electron microscopy the thrombi were found to consist primarily of platelets adherent to an intact endothelium. The possible clinical implications of these observations are discussed. 
5	Concordance for dyslipidemic hypertension in male twins. Sixty cases of dyslipidemic hypertension were identified in the 1028 middle-aged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome. 
1	Pharmacodynamics in cancer therapy. Our understanding of anticancer pharmacodynamics, and the relationships between pharmacologic measurements and clinical effects, has grown markedly in recent years due to advances in analytical and computational technology. Although methotrexate plasma levels have been empirically used to guide leucovorin dosing during high-dose methotrexate therapy, there has been no other standard use of therapeutic drug monitoring in oncology. More recently, investigators have attempted to titrate precisely the dose of antineoplastic agents based on previously derived models and real-time analysis of plasma drug or tissue concentrations. Studies have been completed or are in progress using hexamethylene bisacetamide, etoposide, teniposide, fluorouracil (FUra), and cytarabine (ara-C). Future studies will focus on optimal sampling strategies, analysis of intermediate biochemical end points, combination chemotherapy, modulation by colony-stimulating factors, and more sophisticated pharmacodynamic models. 
1	Cholangiocarcinoma. The diagnosis of cholangiocarcinoma can now be made with greater rapidity and accuracy. In the clinical setting of obstructive jaundice, a CT scan or sonogram may suggest cholangiocarcinoma if dilated intrahepatic ducts are seen with a nondilated extrahepatic biliary tree. The diagnosis is confirmed by cholangiography, and the tumor is staged by the combination of cholangiography and angiography. If the tumor extensively involves both lobes of the liver or involves the main portal vein or hepatic artery, the lesion is considered unresectable. These patients are best palliated nonoperatively, but they should still have an attempt at a tissue diagnosis, as various other lesions can masquerade as cholangiocarcinoma. In comparison, if the tumor is confined to or is distal to the hepatic duct bifurcation, extends into only one lobe of the liver, or involves only the right or the left portal vein or hepatic artery, the lesion may be resectable, and exploration is indicated. As many as half of all patients explored with curative intent will have a successful resection. Various surgical options are appropriate for patients undergoing tumor resection, depending on the site and extent of the lesion. Similarly, several surgical options are possible for palliation in patients with unresectable cholangiocarcinoma. The role of radiotherapy in the management of cholangiocarcinoma is uncertain. Our results, like those of many other retrospective analyses, suggest that radiotherapy prolongs survival after curative resection as well as after palliative stenting. However, further data from randomized studies are necessary to support or refute this impression. Further studies of adjuvant chemotherapy or hormonal therapy will also be necessary to improve patient survival. 
5	Vasopressin response in collecting ducts of rats resistant to mineralocorticoid hypertension. In previous studies we found that vasopressin stimulation of both cyclic AMP (cAMP) formation in cortical collecting tubules (CCT) and sodium reabsorption in isolated perfused kidneys was markedly exaggerated in rats with mineralocorticoid hypertension. In the present study, we tested the response (cAMP accumulation) of cortical and outer medullary collecting tubules (OMCT) to vasopressin in two rat models that are resistant to deoxycorticosterone acetate (DOCA)-induced hypertension, the Wistar-Furth strain and NaCl-deficient rats. The blood pressure of normal outbred Wistar rats rose to hypertensive levels (systolic pressure more than 165 mm Hg) during a 5-week treatment with DOCA (10 mg/week) and 1% saline to drink. Significant hypertrophy of the heart and kidneys was also observed. Vasopressin (10(-8) M)-induced cAMP formation was enhanced 3.4-fold in the CCT (OMCT unchanged) of hypertensive rats compared with normotensive controls. Significant hypertrophy (as indexed by tubule diameter) of the CCT but not the OMCT was also observed in DOCA-salt hypertensive rats. Restriction of dietary NaCl (0.13% in chow, tap water to drink) completely prevented DOCA-induced hypertension, organ and CCT hypertrophy, and enhancement of vasopressin-stimulated cAMP formation in the CCT. In Wistar-Furth rats, DOCA-salt treatment did not alter blood pressure or cause significant organ hypertrophy. However, DOCA-salt treatment enhanced vasopressin-stimulated cAMP formation by 4.1-fold in CCT of Wistar-Furth rats, with significant tubular hypertrophy in the CCT but not the OMCT. We conclude that DOCA-induced hypertension and changes in CCT function are dependent on excess dietary NaCl. 
1	Management of patients with thyroid carcinoma: application of thallium-201 scintigraphy and magnetic resonance imaging Thyroid carcinoma has the ability to concentrate radioiodine, an attribute that can be used both for detection of thyroid cells and for treatment. Unfortunately, however, radioiodine uptake is not observed in all patients and a radioiodine scan requires that the patient be rendered hypothyroid for 4-6 wk. In the present study, we analyzed the utility of thallium-201 scanning and the usefulness of magnetic resonance imaging (MRI) in the detection of thyroid cancer. Nineteen patients with thyroid cancer had a total of 24 radioiodine scans, 33 thallium scans, and 10 MRI examinations. Of the 19 patients in the study, 17 had differentiated thyroid carcinoma. In these 17 cases, all paired studies were concordant for the presence (n = 7) or absence (n = 10) of disease. However, in one case (Patient 10), the 201Tl studies showed far more extensive disease than was observed on the 131I scan. Thyroid cancer was also detected on seven MRI studies. In summary, thallium and MRI scans are adjunctive techniques to radioiodine scanning that can either confirm the presence of neck bed activity, residual disease or metastatic cancer and may delineate tumor deposits not detected by radioiodine scanning. Thallium may be capable of detecting tumor deposits even while a patient remains euthyroid. 
4	Early diagnosis and surgical intervention of acute aortic dissection by transesophageal color flow mapping. To determine whether transesophageal color Doppler echocardiography (TEE) is useful for the early diagnosis and surgical intervention in acute aortic dissection, 57 serial patients with acute aortic dissection were examined. These patients were evaluated by TEE with either the single-plane probe (39 patients) or the biplanar probe (18 patients) just after admission. The intimal flap was detected in all patients, and there were 18 patients with type A dissection and 39 patients with type B dissection. The entry was visualized in 83% of type A dissection cases and in 90% of type B dissection cases. In two of 18 patients examined with the biplanar probe technique, the entry was detected in the longitudinal view only. Emergency operations were performed in 18 patients with type A dissection and in 10 patients with ruptured type B dissection. Twenty-nine of 39 patients with type B dissection were treated conservatively. The operative mortality rate of patients with type A dissection was 22%, and that of patients with ruptured type B dissection was 60%. The major advantage of TEE is its ease of application at the bedside or in the operating room, which allows immediate and accurate diagnosis of acute aortic dissection for emergency surgical intervention. Biplanar TEE provides additional acoustic windows, ease of spatial orientation, and more accurate visualization of entry. TEE is a useful and powerful diagnostic tool for acute aortic dissection, and by using this method, one may achieve a more rapid and aggressive surgical approach for patients with acute aortic dissection. 
5	Outcome of pregnancies experienced during residency. To investigate potential adverse effects of residency training on pregnancy outcome, a cohort study was conducted among 45 university-affiliated residency programs. Outcomes of the first pregnancy experienced during residency were compared between 92 female residents and 144 spouses of male residents. Despite long hours, sleep deprivation, and an increase in perceived stress, the female residents were as likely to give birth to a live, full-term newborn as the spouses of male residents. For white cohort members, an increased risk of premature labor without delivery was identified (RR = 12.3, 95% confidence interval 2.4-61.6). No significant differences were found in prematurity, spontaneous and therapeutic abortions, or presence of congenital abnormalities in the infants. Method of delivery and use of anesthetics and of other medications were similar in both groups. Pregnancy outcomes between the two groups were similar; however, the increased risk for premature labor among female residents is a cause for concern and should be further investigated. 
5	The infant with a reddish diaper. The infant with a reddish diaper presents a diagnostic challenge to the primary care physician. As described by Dr Baumgardner, the cause may be benign, but more ominous disorders must be ruled out. 
4	Management of hypertension by reduction in sympathetic activity. The sympathetic nervous system may initiate or maintain hypertension, and a range of approaches that reduce sympathetic activity is often of value in management. These may include nonpharmacological methods, such as the various forms of behavioral therapy (e.g., meditation, relaxation, and biofeedback techniques); weight reduction and avoidance of particular foods and agents that stimulate sympathetic activity (including caffeine and alcohol), and regular physical exercise. Pharmacological therapy includes centrally acting drugs such as alpha-methyldopa, clonidine, and reserpine; ganglionic blockers such as hexamethonium; agents acting on sympathetic nerve terminals such as guanethidine and debrisoquine; and drugs that may act at multiple sites, such as the beta-adrenergic blockers. The role of reducing sympathetic activity in the current management of hypertension and its complications is considered in this overview. 
5	Venous hemodynamics in a chronic venous valvular insufficiency model. To develop a large-animal model of chronic venous valve incompetence, 13 greyhound dogs underwent unilateral hindlimb venous valve lysis with a valve cutter apparatus pulled retrograde through the iliac, femoral, and lateral saphenous veins. Bilateral venous pressures in the lateral saphenous vein were recorded before valve lysis, immediately after valve lysis, and at intervals from 1 to 14 weeks after valve lysis, with the dogs in the supine position and elevated 80 degrees semierect, as well as after stimulated hindlimb muscle contraction to empty the hindlimb veins. Passive venous filling time with elevation and 90% venous refilling time after muscle contraction were calculated. From immediately after through 14 weeks after valve lysis, a shortened venous filling time and 90% venous refilling time as well as an elevated poststimulation venous pressure were noted. This valve lysis method successfully produced a hemodynamically verified model of venous valvular insufficiency. 
5	Eosinophilia-myalgia syndrome (L-tryptophan-associated neuromyopathy). Histopathologic study of skeletal muscle biopsy in a patient with eosinophilia-myalgia syndrome following L-tryptophan use showed prominent lymphocytic perineuritis, neuritis, and perimysial fasciitis. The presence of perineuritis and neuritis provides a histopathologic basis for clinical features of neuropathy in eosinophilia-myalgia syndrome and occurred in conjunction with a fasciitis or interstitial myositis that was predominantly perimysial and focally endomysial. 
4	An analysis of outcome following percutaneous transluminal coronary artery angioplasty. An autopsy series. We analyzed autopsy findings on 26 patients who died following percutaneous transluminal coronary angioplasty (PTCA). Twenty-one patients died within 3 weeks of undergoing PTCA; demonstrable cardiac complications were found in 19 patients: platelet-fibrin thrombi (10 patients [48%]), coronary artery dissections (17 patients [81%]), thromboemboli (13 patients [62%]), atheroemboli (seven patients [33%]), and myocardial infarcts (17 patients [81%]). An increased incidence of coronary platelet-fibrin thrombi was noted when compared with a non-PTCA cardiac autopsy population (five of 53 patients). Apparently there was an increased incidence of coronary atheroemboli and thromboemboli in the patients with coronary platelet-fibrin thrombi (eight patients) when compared with patients who did not have platelet-fibrin thrombi (five patients), although this was not statistically significant. There was no evidence of a systemic hypercoagulable state or of disseminated intravascular coagulation. The pathogenesis of this is unclear; however, vasospasm and a disruption of the endothelial surface induced by PTCA with subsequent platelet activation are possible causes. Although not statistically significant, there was a proponderance of female subjects (seven patients) and an increased incidence of diabetes mellitus (six patients) and hypertension (13 patients) when compared with a control population of all patients undergoing PTCA at The Cleveland (Ohio) Clinic Foundation in 1987, suggesting that diabetes mellitus, hypertension, and female sex may be clinical risk factors for fatal complications following PTCA. 
2	What affects continence after anterior resection of the rectum? Functional results after anterior rectal resections are commonly considered satisfactory but variable percentages of postoperative incontinence are often reported. Continence was evaluated after 20 low anterior resections (LAR) and 13 high anterior resections (HAR) by means of clinical assessment, anorectal manometry, and evacuation proctography. Whereas all HAR patients had perfect continence, 10 patients (50 percent of the LAR group had occasional episodes of soiling from liquid feces, 5 patients (25 percent had frequent soiling or occasional incontinence for solid feces, and 1 patient (5 percent had frequent solid stool loss requiring surgical treatment. Anal canal resting pressure at 3 and 4 cm from the anal verge was significantly lower in the LAR group (P less than 0.02 and P less than 0.05, respectively) than in the HAR group. However, the maximum voluntary contraction did not differ between the two groups. Rectoanal inhibitory reflex was found to be present in 17 of the 20 patients with LAR and in all patients with HAR. The volume at which the anal sphincter is continuously inhibited was significantly reduced in the LAR group (P less than 0.001). Also, the conscious rectal sensibility volumes were found to be significantly reduced for threshold, constant, and maximum tolerated volume. Threshold volume for internal sphincter relaxation was lower than the threshold volume for rectal sensation in some patients with LAR. This could allow postoperative fecal soiling. Rectal compliance was decreased (P less than 0.001) in the LAR group. Evacuation proctography, performed in six LAR patients affected by major soiling or solid stool loss, revealed an abnormal obtuse anorectal angle and pathologic lowering of the perineum at rest and during defecation. The concomitance of internal and sphincter impairment, reduction in rectal compliance, and previous pelvis floor muscle damage are postulated as cause affecting continence in patients who underwent LAR. 
3	Intestinal permeability in patients with chronic urticaria-angioedema with and without arthralgia. We evaluated the clinical response to oligoallergenic dietary treatment and the intestinal absorption of a protein antigen, cow milk beta-lactoglobulin (BLG) in 24 patients with chronic urticaria/angioedema syndrome 13 of whom also suffered from joint symptoms. Sixteen patients (77% of those with arthralgia) responded to diet (RD) with marked reduction of symptoms; the others did not respond (NR). Ten (all but one RD with arthralgia) had increased permeability to BLG after oral administration of cow milk. Four with high titers of IgG to BLG showed the highest absorption of BLG and the groups with arthralgia showed higher BLG levels than those without arthralgia. In all cases, specific IgE to cow milk was absent. These data suggest that the symptoms of a subgroup of patients with chronic urticaria, and especially patients with joint complaints that subside with diet, are related to excess intestinal permeability. The measurement of gut permeability to food proteins may be useful to define those who may benefit from dietary restriction. 
5	Candidal infection in oral lichen planus. The prevalence of candidal infection in lichen planus (LP) and its possible association with ulceration were independently examined in two archived series of 108 and 77 cases derived from two separate populations. To ensure that similar material was being compared, each case was histopathologically reassessed and confirmed as LP or reclassified as nonspecific lichenoid stomatitis (NSLS), lichenoid dysplasia (LD), or other (O). Three further sections, cut at 25 microns intervals, were stained with periodic acid-Schiff reagent for the identification of intraepithelial candidal pseudohyphae. As control specimens, 61 normal and 59 hyperkeratotic mucosal samples were similarly processed and examined. Candidal infection was found in 17.4% and 16.4% of ulcerated and nonulcerated LP cases, respectively, and in 40.0% and 16.7% of ulcerated and nonulcerated NSLS cases, respectively. One case of LD was infected. Each control series contained one infected case. The results indicate that candidal infection occurs more readily in LP and NSLS, with no apparent association with ulceration in LP. The comparatively marked increase in the infection prevalence of ulcerated NSLS cannot be statistically confirmed, and its significance remains uncertain. 
5	Role of cephamycins in obstetrics and gynecology. Infections of the female upper genital tract are usually polymicrobic, often involving mixed aerobic (facultative) and anaerobic bacteria. Optimal therapy provides coverage against aerobes (both gram positive and gram negative and especially the Enterobacteriaceae) and anaerobes (especially the beta-lactamase-producing gram-negative species, such as Bacteroides). A variety of antibiotics provide the broad spectrum of activity needed for these infections, including clindamycin plus an aminoglycoside, cephalosporins and cephamycins, imipenem, extended-spectrum penicillins and the beta-lactam agents combined with a beta-lactamase inhibitor. The cephamycins--cefoxitin, cefotetan and cefmetazole--have been shown to have a high rate of clinical efficacy and bacteriologic response. The cephalosporins are usually used for prophylaxis at the time of obstetric and gynecologic surgery. The cephamycins have recently undergone extensive evaluation for prophylaxis and have demonstrated comparable microbiologic and clinical efficacy. A pharmacokinetic comparison of cefoxitin, cefotetan and cefmetazole points to cefmetazole as a cost-effective alternative to cefoxitin and cefotetan for both prophylaxis and treatment of pelvic infections. 
5	Role of xanthine oxidase and neutrophils in ischemia-reperfusion injury in rabbit lung. This study evaluated the effect of ischemia-reperfusion (I-R) on pulmonary capillary permeability in isolated rabbit lungs and the roles of xanthine oxidase (XO), aldehyde oxidase (AO), and neutrophils (PMN) in producing this lung injury. Effects of XO and AO were studied by inactivation with a tungsten-enriched diet (0.7 g/kg) and inhibition of XO by allopurinol (100 microM) or AO by menadione (3.5 microM). PMN effects were studied by preventing endothelial adhesion with the monoclonal antibody IB4 (10 microM). Vascular permeability was evaluated by determining the capillary filtration coefficient (Kf,c) measured before and after I-R in all experimental conditions. Reperfusion after 2 h of ischemia significantly increased pulmonary capillary permeability (Kf,c changed from 0.096 +/- 0.014 to 0.213 +/- 0.025 ml.min-1. cmH2O-1.100 g-1), and this increase was blocked by the addition of catalase (50,000 U) at reperfusion (baseline Kf,c was 0.125 +/- 0.023 and 0.116 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). XO inactivation with the tungsten-supplemented diet and XO inhibition with allopurinol prevented the Kf,c increase observed after I-R (0.183 +/- 0.030 to 0.185 +/- 0.033 and 0.126 +/- 0.018 to 0.103 +/- 0.005 ml.min-1.cmH2O-1.100 g-1). Inhibition of AO had no effect on I-R injury (Kf,c 0.108 +/- 0.011 to 0.167 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). Preventing PMN adhesion resulted in significant attenuation of the change in Kf,c associated with I-R (0.112 +/- 0.032 to 0.090 +/- 0.065 ml.min-1.cmH2O-1.100 g-1). We conclude that XO and PMN adherence, but not AO, are involved in the increased capillary permeability associated with I-R. 
4	Effect of stress on diagnosis of hypertension. Blood pressure assessment by a physician elicits an alerting reaction and a pressor response in the patient. The magnitude and time course of this response are described for a large number of hypertensive subjects in whom the assessments were performed during ambulatory intra-arterial blood pressure monitoring. In nearly all of the subjects, the physician's visit was accompanied by blood pressure and heart rate increases that peaked within 4 minutes and then declined. The response was characterized by a relatively high average value; a large between-subject variability; no relation with patient age, baseline hemodynamic values, and responses to laboratory stressors; and no attenuation with multiple repetition of the physician's visit. On the other hand, the increase in blood pressure was considerably less when blood pressure assessment was made by a nurse than when it was made by a physician; in both instances, a 10-minute wait was associated with marked reduction of the initial response. Thus, the stress inherent in usual blood pressure-measuring procedures is responsible for considerable overestimations of patients' blood pressures. There are means by which this can be minimized, although a residual error is likely to remain in most subjects. Whether the stress-devoid blood pressure is a better prognostic index than the stress-related one remains unknown. 
2	Disseminated, nonmeningeal gastrointestinal cryptococcal infection in an HIV-negative patient. Gastrointestinal cryptococcosis is extremely rare, especially in patients with no involvement of the central nervous system. We describe a 63-yr-old man undergoing prednisone therapy for chronic hepatitis and cirrhosis who presented with peritonitis, colitis, and skin lesions. Pathological studies revealed necrosis and numerous cryptococcal organisms in the colon, omentum, and skin, and cultures yielded Cryptococcus neoformans. The patient died of multisystem organ failure following emergency exploratory surgery performed when he had onset of symptoms of a bowel perforation after an endoscopic biopsy. Clinicians should be aware that gastrointestinal cryptococcosis can occur in the absence of infection of the central nervous system or lungs, and that it may affect relatively healthy patients who are immunocompromised because of splenectomy, chronic liver disease, or steroid therapy. 
1	Community lifestyle characteristics and risk of acute lymphoblastic leukaemia in children. High rates of leukaemia in children and young people have been associated with features of community isolation and population growth. Incidence data collected by two specialist registries were used to compare incidence rates at ward level with relevant ward characteristics derived from routine census and Ordnance Survey data for England and Wales. An excess risk of childhood acute lymphoblastic leukaemia (ALL) was found for wards which are farthest from large urban centres. The excess was greatest for wards of higher socioeconomic status and for children aged 1-7 years (the childhood peak), for which a two-fold excess was seen. These findings in general support the hypothesis that childhood leukaemia has an infectious aetiology. 
1	A phase II trial of carboplatin and vinblastine in the treatment of advanced squamous cell carcinoma of the esophagus. Cisplatin-containing regimens are active in the treatment of esophageal cancer, with response rates of 25% to 35% in advanced disease. Carboplatin is less toxic than cisplatin; as a single agent, several responses were seen against esophageal tumors. To better define the role of carboplatin in esophageal cancer, the authors treated 19 chemotherapy-naive patients with advanced squamous cell carcinoma of the esophagus with carboplatin and vinblastine. Carboplatin (450 mg/m2 intravenously [IV] on days 1, 29, 57, and every 6 weeks thereafter) was given with vinblastine (5 mg/m2 IV on day 1 and then every 2 weeks). No major responses were seen. No significant renal toxicity and only mild gastrointestinal toxicity (emesis, diarrhea) were observed. Hematologic toxicity was more severe in patients with prior radiation therapy (RT), with three of six patients with prior RT exhibiting Grade 4 hematologic toxicity. Although generally less toxic than cisplatin-containing regimens, carboplatin and vinblastine is also less active in the treatment of squamous cell carcinoma of the esophagus. Hematologic toxicity with this regimen was severe in patients who had received prior RT. 
2	Antenatal spontaneous perforation of the extrahepatic biliary tree. Spontaneous perforation of the biliary system is an unusual neonatal phenomenon that is rarely recognized at birth. To date, it has not been reported antenatally. A 16-year-old pregnant adolescent had an ultrasonogram at 25 weeks of pregnancy that revealed ascites in the fetus. After the infant was delivered at 32 weeks, a hepato-iminodiacetic acid scan showed a spontaneous rupture of the common bile duct. The infant was treated with external drainage of the biliary tree and recovered well. This case demonstrates that spontaneous perforations of the bile ducts can occur much earlier than the usually described 2 to 12 weeks after birth, can be diagnosed antenatally, and should be added to the list of causes of fetal ascites. 
4	Treatment of abdominal aortic aneurysm by exclusion and bypass: an analysis of outcome. Abdominal aortic aneurysm is conventionally treated by aneurysmorrhaphy with inlying graft. Alternatively, division of the aorta, with suture closure of the distal aorta and outflow vessels (exclusion of the aneurysm), and end-to-end proximal to distal bypass may be performed. However, the long-term fate of this operation has not been determined. Specifically, concern exists that the excluded blood filled aneurysm may not thrombose or may be the source of late sepsis. During an 8-year period we have treated 280 abdominal aortic aneurysms (urgent and elective) by exclusion of the abdominal aortic aneurysm sac and bypass via the posterolateral retroperitoneal approach. Mean age was 70 years (range, 44 to 88), with 217 men and 63 women. Preoperative CT scanning and aortography were performed to assess arterial anatomy. Seventy tube grafts and 260 bifurcation grafts were used. Thirty-day mortality rate was 4%. Estimated blood loss was 731 +/- 52 ml; mean transfusion requirements were 456 +/- 82 ml. The minor complication rate was 6%, and it is of great interest that there were no cases of ischemic colitis requiring colectomy. Aneurysm sacs thrombosed except in two anticoagulated patients who required further treatment. No late infections occurred. Five-year bypass patency rate was 98%. These data demonstrate that this method of treatment effectively minimized operative dissection and blood loss and therefore is a viable alternative for the management of abdominal aortic aneurysms. 
1	Endoscopic ultrasonography in staging rectal cancer. Endoscopic ultrasonography (EUS) was used to stage rectal cancer by assessing depth of invasion through bowel wall layers and/or involvement of lymph nodes. EUS findings were correlated with histopathologic findings to discern the usefulness of this modality in predicting which patients could be candidates for sphinctersaving procedures and the avoidance of abdominoperineal resection. The Olympus EU-M3 endoscopic ultrasound system was used to assess depth of penetration through rectal wall layers and to identify lymph nodes. Comparison of EUS findings to histopathologic findings was possible in 13 patients. EUS agreed with histopathology in 9 of 13 cases (69.3%) ( p = 0.07, kappa statistic). EUS agreed with histopathology as the presence or absence of lymph nodes in 9 of 13 cases (69.3%) (p = 0.07). However, the presence of lymph nodes could not necessarily predict metastatic involvement of these nodes. In one patient, invasion of vaginal cuff was correctly predicted. In nine cases, computed tomographic analysis (CT) was available for comparison to EUS in detection of penetration beyond the bowel wall. CT agreed with histopathology in 3 of 9 (33%), whereas EUS agreed with histopathology in 7 of 9 (78%). 
5	Organic dust toxic syndrome: an acute febrile reaction to organic dust exposure distinct from hypersensitivity pneumonitis. Organic dust toxic syndrome is a term recently coined to describe a noninfectious, febrile illness associated with chills, malaise, myalgia, a dry cough, dyspnea, headache and nausea which occurs after heavy organic dust exposure. Organic dust toxic syndrome shares many clinical features with acute farmer's lung and other forms of hypersensitivity pneumonitis, including the presence of increased numbers of neutrophils in bronchoalveolar lavage. However, organic dust toxic syndrome differs from acute hypersensitivity pneumonitis in several respects: the chest X-ray does not show infiltrates, severe hypoxemia does not occur, prior sensitization to antigens in the organic dust is not required and there are no known sequelae of physiological significance, such as the recurrent attacks and the pulmonary fibrosis which may be seen with chronic hypersensitivity pneumonitis. Organic dust toxic syndrome is thought to be much more common than farmer's lung. It is important for clinical and investigational purposes that organic dust toxic syndrome be distinguished from acute farmer's lung. 
5	The use of L-dopa and carbidopa in metastatic malignant melanoma. A combination of L-dopa and carbidopa was given orally to 17 patients with metastatic melanoma. Maximum tolerated oral doses were given, up to 4 grams daily. No response was seen in 15 patients evaluable for response. Toxicity was considerable, with seven of 17 patients (41%) stopping treatment because of unacceptable gastrointestinal toxicity or postural hypotension. Contrary to previous anecdotal reports, there was no evidence that L-dopa/carbidopa treatment resulted in accelerated progression of metastatic melanoma. Orally administered L-dopa/carbidopa is ineffective as therapy for advanced melanoma when maximum tolerated doses are used. 
2	Colonoscopic fine needle aspiration cytology in the diagnosis of ileocecal tuberculosis. Two cases of ileocecal tuberculosis are presented. The diagnosis was achieved by endoscopic fine needle aspiration cytology (FNAC), while endoscopic biopsies and brush cytology were negative. The usefulness of endoscopic FNAC in the diagnosis of gastrointestinal tract tuberculosis is highlighted. 
1	Glossopharyngeal schwannoma: review of five cases and the literature. Glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8%-10% of intracranial tumors. There have been 23 reported cases in the literature. This report of five cases is the largest series of these tumors. The presentation, radiological workup, operation, and long-term postoperative results will be presented, along with a review of the literature. 
2	Anatomy of anal sphincters and related structures in continent women studied with magnetic resonance imaging. Five anally continent nulliparas of reproductive age were studied with magnetic resonance imaging. The internal and external anal sphincters could be easily delineated, as could the intervening longitudinal musculature, puborectalis muscle, anococcygeal raphe, anorectal lumen, vagina, uterus, bladder, urethra, coccyx, and pubis. The shape of the sphincters was nearly cylindrical, with an anterior component averaging 18.3 mm thick and 28.0 mm long. Fifty-four percent of this anterior thickness was attributable to the internal sphincter. The anorectal angle varied considerably, with a mean of 86.8 +/- 19.1 degrees (range 60-112). The angle between the portion of the rectal lumen supported by the anococcygeal raphe, or levator plate, and the plane of the puborectalis muscle was consistent at 149.0 +/- 6.3 degrees (138-154). The finding of anterior anal sphincters with substantial thickness and length contrasts markedly with a view often pictured in the literature of a female anal sphincter that narrows anteriorly to half its posterior length and forms a small bundle of muscle rather than a broad band. Knowledge of these relationships is important in primary repair of obstetric sphincter lacerations as well as in surgical correction of anal incontinence. 
4	Raynaud's syndrome. Using a range of therapies to help patients. Raynaud's syndrome is a common medical problem. Approach to diagnosis must involve a search for underlying causes. Treatment includes avoidance of precipitating factors, biofeedback, and possibly pharmacologic therapy, after careful consideration of risks. 
1	Detection, prevalence, and prognosis of asymptomatic carcinoma of the cervix. Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis. Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease. Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA. In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years. To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department. Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening. In the age category 35-55 years, 54 of 160 (34%) were asymptomatic. Patients aged 35-55 years had undergone population screening or incidental screening. In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients. Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence. Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence. Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status. 
5	Infantile systemic hyalinosis: newly recognized disorder of collagen? Four infants with stiff skin and painful joint contractures in the first few months of life are described. Other features included small papules, particularly on the face and trunk, perianal nodules, hyperpigmentation over the metacarpophalangeal joints and over the malleoli, gingival hyperplasia, persistent diarrhea, and failure to thrive. Two of these infants died before the age of 18 months. In each case hyaline material was found in the papillary dermis. Ultrastructurally, there was a distinctive fibrillogranular appearance in which a banding pattern could be observed. This material was also found within membrane-bound vacuoles in macrophages and fibroblasts. It had an appearance and localization identical with that of collagen type VI. These features are similar to those reported in juvenile hyaline fibromatosis. It is believed that these infants have a closely related, but nonetheless distinctive, inherited disorder of collagen. 
5	Erythema infectiosum and pregnancy-related complications Erythema infectiosum, an acute, communicable viral disease with a highly distinctive exanthem, follows the usual course of a self-limiting benign disease. In pregnant women, however, it may be associated with fetal death and nonimmune hydrops fetalis. Because of the association of human parvovirus (HPV) B19 infection with fetal damage we reviewed the current knowledge of the clinical aspects of erythema infectiosum, focusing on pregnancy and fetal outcome, to determine the magnitude of fetal risk and offer recommendations for management. Among 180 infected pregnant women 44 fetal deaths (24%) occurred, 1 to 12 weeks after the infection was noted. Pregnant women should be advised that (a) because of the high prevalence (up to 65%) of anti-HPV B19 IgG antibody among adults most of them are not at risk and (b) if maternal infection does occur therapeutic abortion is not indicated since intrauterine infection causes fetal death more often than abnormal development. Infection should be suspected in pregnant women who exhibit the symptoms of erythema infectiosum with or without arthropathy. They should be monitored for an elevated serum alpha-fetoprotein level (indicating fetal aplastic crisis) and undergo serial ultrasonography for the detection of hydrops fetalis. Although the incidence of congenital malformation is no higher than the expected rate in the general population (3% to 5%), the precise incidence of fetal adverse outcomes remains unknown and requires investigation in larger, prospective studies. 
4	Hemodynamic influence of LVAD on right ventricular failure. Left ventricular assist device (LVAD) pumping has hemodynamic and anatomic influences on right ventricular performance. A total artificial heart (TAH) model was employed to better understand the hemodynamic influence of an LVAD on the failing right ventricle. Biventricular failure was simulated by reducing both ventricular drive pressures of the TAH. After getting hemodynamic data, LVAD pumping in the case of right ventricular failure was simulated by increasing just the left ventricular drive pressure. In the LVAD-simulating condition, cardiac output increased and right atrial pressure decreased significantly (p less than 0.05) compared with the biventricular failure condition, whereas right ventricular function and minute work were the same in these two conditions. Even though changes were accompanied by adaptive increases in pulmonary resistance, substantially lower pulmonary artery and left atrial pressures resulted in the LVAD-simulating condition. From a hemodynamic perspective, these results indicate that an LVAD can increase right ventricular volume work by decreasing right ventricular pressure work, whereas right ventricular net pressure-volume work is unchanged and right ventricular failure is not worsened. 
2	Enhanced expression of CD2 antigen on lung T cells. CD2 molecules not only function in the adhesion of T cells to other cell types but also in the activation of T cells via an alternative pathway. To investigate the possible roles of CD2 molecules in the activation and accumulation of lung T cells, using monoclonal antibodies and a flow cytometer we evaluated CD2 antigen expression on lung and blood lymphocytes in 10 normal subjects, 30 patients with pulmonary sarcoidosis, 7 patients with interstitial pneumonia associated with collagen vascular disease, 5 patients with farmer's lung disease, and 8 patients with Crohn's disease. The mean fluorescence intensity (MFI) of CD2 on lung T cells obtained by bronchoalveolar lavage (BAL) was significantly higher than that on blood T cells in all study groups except the control group. In patients with pulmonary sarcoidosis this enhancement of the expression of CD2 antigen was observed only on CD4+ T cells. Since ligands for CD2 are present on immunocompetent cells of other types in the local pulmonary milieu, these results suggest that increased expression of CD2 molecules could facilitate the communication and interaction of lung T cells with their environment in the lung and thereby possibly contribute to the local accumulation of T cells. 
5	Six year follow up of a consecutive series of patients presenting to the coronary care unit with acute chest pain: prognostic importance of the electrocardiogram In a retrospective 6 year follow up data were obtained for 536 of 566 (95%) consecutive patients admitted to a coronary care unit with acute chest pain. Their diagnoses were acute myocardial infarction in 290 (54%), myocardial ischaemia in 164 (31%), pericarditis in 16 (3%), and non-cardiac in 66 (12%). Six year mortality was 36%, 24%, 0%, and 16% respectively. In patients with acute myocardial infarction a higher mortality rate during follow up was associated with a higher than average age, a higher than average creatine kinase, previous myocardial infarction, Q wave infarction, and the presence of reciprocal changes. The presence of reciprocal changes was associated with higher than average concentration of serum creatine kinase, indicating more extensive infarction. Infarction complicated by ventricular fibrillation or left bundle branch block was associated with a higher death rate. The electrocardiogram recorded at the time of acute myocardial infarction contains much useful prognostic information. 
4	Postural hypotension: pressor effect of octreotide not mediated by norepinephrine. Orthostatic hypotension of the Shy-Drager syndrome is a chronic incapacitating condition characterized by lack of an appropriate increase in the plasma norepinephrine level in response to standing. Recently, the somatostatin analogue octreotide has been reported to induce a pressor response in patients having this syndrome. We have reported a case of Shy-Drager syndrome in which octreotide was effective, but the rise in blood pressure was not accompanied by an increase in the plasma norepinephrine level. Hence, the pressor effect of octreotide is not mediated by stimulation of the sympathetic nervous system, but probably through splanchnic vasoconstriction. 
5	Correlation of the structure of the transmembrane domain of the neu oncogene-encoded p185 protein with its function. The human homologue of the neu oncogene is frequently found in human tumors. Certain amino acid substitutions at position 664 in the transmembrane domain of the neu oncogene-encoded p185 protein product are known to cause malignant transformation of cells. Using conformational energy analysis based on ECEPP (empirical conformational energies for polypeptides program), we have previously determined the preferred three-dimensional structures for the transmembrane domain of the p185 protein with a transforming (glutamic acid) and a nontransforming (valine) substitution at the critical position 664 and found that the global minimum-energy conformation of this region in the nontransforming protein contains a sharp bend, whereas the global minimum-energy conformation for this region from the transforming protein is entirely alpha-helical. We now demonstrate that this result holds for other known nontransforming (glycine, histidine, tyrosine, and lysine) and transforming (glutamine) substitutions at position 664. Furthermore, a simple statistical thermodynamic analysis of the results indicates that approximately 85% of each of the nontransforming sequences exist with the bend at positions 664 and 665, while approximately 90% of each of the transforming sequences exist as an alpha-helix. About 9% of the nontransforming sequences exist as the alpha-helix. These results suggest that if the intracellular concentration of the normal protein is increased at least 10-fold, thereby increasing the alpha-helical form by this factor, cell transformation should result. This conclusion is directly supported by genetic experiments in which this level of overexpression of the normal protein was achieved with attendant cell transformation. 
2	Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist. Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial. 
4	Practicalities of lipids: ICU patient, autoimmune disease, and vascular disease. Although the use of lipids should be individualized, certain generalizations are appropriate. 1. Lipid infusion should be limited in the fulminately septic patient to 10% of total calories in an effort to reduce immunosuppression. 2. The stressed, nonseptic patient with difficulties in ventilator weaning or TPN-induced hepatic dysfunction may reap benefit from a reduction in dextrose calories and the provision of daily lipids. 3. Patients with severe autoimmune disease have had mild amelioration of symptoms with PUFA supplementation. The relative benefits of omega-6 vs omega-3 continue to be examined. 4. Dietary immunomodulation in transplant and burns remains an area of active investigation. 5. Patients with fat-free TPN show transient declines in serum lipids. The development of a "fat-solubilizer" remains in the experimental realm. 6. The provision of fish oil, high in W-3 EPA, has shown promise in atherosclerosis and immunomodulation. The changes in the relative amounts of each prostaglandin class depend on precursor prevalence. 
1	Surgical management of carcinoid heart disease Metastatic carcinoid tumor is often seen with flushing, diarrhea, and cardiac symptoms--the carcinoid syndrome. Cardiac failure is often associated with major morbidity and mortality in carcinoid disease. In this report, a case of successful cardiac valvar surgical intervention has resulted in prolonged alleviation of cardiac symptoms and survival. 
4	Contractility and stiffness of noninfarcted myocardium after coronary ligation in rats. Effects of chronic angiotensin converting enzyme inhibition. BACKGROUND. Previous studies have shown that global left ventricular function is depressed after myocardial infarction. However, little is known about the effects of myocardial infarction on contractility and the passive-elastic properties of residual myocardium. METHODS AND RESULTS. We evaluated isometric function and passive myocardial stiffness in isolated, noninfarcted left ventricular papillary muscle from rats 6 weeks after sham operation or myocardial infarction. Maximal developed tension and peak rate of tension rise (+dT/dt) were significantly decreased in untreated rats with large myocardial infarction compared with controls (3.3 +/- 1.1 versus 4.3 +/- 0.6 g/mm2 and 49.5 +/- 17.5 versus 72.5 +/- 10.5 g/mm2/sec, respectively). Time to peak tension was prolonged (120 +/- 8 versus 102 +/- 4 msec) and myocardial stiffness was increased in untreated myocardial infarction rats compared with controls (35.2 +/- 4.9 versus 24.2 +/- 3.7). Rats with smaller myocardial infarctions differed from controls only with respect to a prolongation of time to peak tension. Papillary muscle myocyte cross-sectional area was increased by 44% (p less than 0.05), and myocardial hydroxyproline content was increased by 160% (p less than 0.05) in rats with large myocardial infarctions compared with controls. To determine whether treatment that improves left ventricular function after myocardial infarction also improves myocardial function, rats were treated with captopril beginning 3 weeks after myocardial infarction and continuing for 3 weeks. Treatment with captopril attenuated the prolongation in time to peak tension in the myocardial infarction rats; however, developed tension, +dT/dt, and muscle stiffness remained abnormal. Compared with untreated myocardial infarction rats, captopril-treated myocardial infarction rats had a 9% decrease in myocyte cross-sectional area (p = 0.1) but a persistent increase in myocardial collagen content. In summary, large myocardial infarction in rats causes contractile dysfunction, increased stiffness, myocyte hypertrophy, and increased collagen content in the residual noninfarcted myocardium. Treatment with captopril alters the process of cardiac remodeling and hypertrophy and improves one parameter of contractility in noninfarcted myocardium; however, myocardial collagen content and myocardial stiffness remain abnormal. CONCLUSIONS. These findings suggest that angiotensin converting enzyme inhibition in the rat infarct model of heart failure improves global cardiac performance via combined effects on myocardial function and the peripheral circulation. 
4	Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials. In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment. 
4	Intravenous enalaprilat therapy for hypertension. The angiotensin-converting enzyme inhibitor enalapril is available for intravenous administration in the form of enalaprilat. Intravenous enalaprilat is indicated for the management of hypertension when oral therapy is not feasible. However, there are no reports of intravenous enalaprilat therapy exceeding one week in duration. We report the case of a critically ill, 39-year-old woman who received intravenous enalaprilat for the management of hypertension for a period of 21 days. The patient's blood pressure and heart rate were controlled adequately on a regimen of enalaprilat 1.25 mg iv piggyback q6h without any apparent adverse effects. 
1	Treatment of the acquired immune deficiency syndrome-related Kaposi's sarcoma with bleomycin as a single agent. A nonrandomized trial was conducted to assess the efficiency and toxicity of bleomycin as a single agent in treatment of non-life-threatening AIDS-related Kaposi's sarcoma (KS). Sixty patients were enrolled in this study. They all had a disseminated and progressive non-life-threatening AIDS-related KS associated with systemic symptoms and/or CD4 lymphocyte count less than 400/mm3. Thirty patients were treated with intramuscular bleomycin (5 mg/d for 3 days every 2 or 3 weeks) and 30 others with a slow continuous intravenous infusion of bleomycin (6 mg/m3/d for 4 days every 4 weeks). The mean duration of therapy was 5 months (range, 2 to 24 months). A partial response was observed in 29 patients (48.3%) and the disease was stabilized in 18 additional patients (30%). Bleomycin failed in 21.6% of patients. Therapy had to be discontinued in two patients because of side effects. Thus bleomycin as a single agent is a good alternative therapy for AIDS-related KS. 
5	The hypotympanum and infralabyrinthine cells in chronic otitis media. Despite the localization implied by the term "chronic otitis media," little attention has been paid to the role of the hypotympanum in chronic active otitis media. Most authors have emphasized the role of recurrent cholesteatoma or unexenterated cells in the mastoid cell system as causes of recurrent disease. Seven cases are reported in which clinical evidence indicated that recurrent chronic otitis media was limited to the hypotympanum and infralabyrinthine cell system. In the five cases in which revision surgery was done, exenteration of this area resulted in an asymptomatic ear. The anatomy, radiographic evaluation, and surgical approach to the hypotympanum are reviewed. Careful inspection of the hypotympanum in primary surgery for chronic ear disease and exenteration of the hypotympanic and proximal infralabyrinthine cell tract are advocated when these regions contain cholesteatoma or extensive granulomatous disease. 
3	Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL.kg-1.min-1 and pressure at greater than 50 mm Hg. Flows and pressures less than target occurred in 21.6% and 97.1% of patients, respectively. Fifteen patients (3.0%) suffered new renal and 13 (2.6%) new central nervous system dysfunction. Low pressure or flow during cardiopulmonary bypass, expressed in absolute values or in intensity-duration units, were not predictors of either adverse outcome. Multivariate analysis identified use of postoperative intraaortic balloon counterpulsation (p less than 10(-6], excessive blood loss in the ICU (p less than 10(-4], need for vasopressors before cardiopulmonary bypass (p less than 10(-4], postoperative myocardial infarction (p less than 10(-3], emergency reoperation (p less than 0.002), excessive postoperative transfusion (p less than 0.02), and chronic renal disease (p less than 0.03) as independent predictors of postoperative renal dysfunction. Independent predictors of postoperative central nervous system dysfunction were cardiopulmonary resuscitation in the intensive care unit (p less than 10(-6], intracardiac thrombus or valve calcification (p less than 0.02), and chronic renal disease (p less than 0.03). Age greater than 65 years (40.7% of patients) did not predict either outcome. We conclude that failure of the native circulation during periods other than cardiopulmonary bypass rather than the flows and pressures considered here is the major cause of renal and clinically apparent central nervous system dysfunction after cardiac operations. 
1	The role of etoposide in the treatment of poorly differentiated carcinoma of unknown primary site. Patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA) of unknown primary site comprise 25% to 35% of the patients with carcinoma of unknown primary site. Some of these patients have neoplasms that are highly responsive to combination chemotherapy, and a minority have potentially curable tumors. Between 1978 and 1982, 68 patients were treated with combination chemotherapy (most received cisplatin, vinblastine, and bleomycin [PVB] with or without doxorubicin). Thirty-eight patients (56%) responded to treatment, with 15 (22%) complete responder (CR) and 9 (13%) long-term, disease-free survivors. Since that time, we have incorporated etoposide into the treatment of these patients because of its synergism with cisplatin and its great activity against several other neoplasms, including germ cell tumors. Seventeen patients with PDC of unknown primary site received salvage therapy with etoposide and cisplatin after failing PVB. Ten of these patients had partial responses (PR), with a median response duration of 5 months (range, 2 to 12 months). Thirty-two previously untreated patients with PDC received etoposide and cisplatin combinations as initial treatment. Eighteen of 30 evaluable patients (60%) responded to therapy, and 11 patients (37%) had CR. Seven patients remain disease-free 39 to 63 months after the completion of therapy. Etoposide is an active drug in the treatment of PDC of unknown primary site. Preliminary results indicate that initial treatment with etoposide and cisplatin combinations produces results equivalent to or superior to those achieved with PVB. 
4	Differential histopathology of primary atherosclerotic and restenotic lesions in coronary arteries and saphenous vein bypass grafts: analysis of tissue obtained from 73 patients by directional atherectomy. Vascular tissue obtained using a directional percutaneous atherectomy device was examined microscopically. Tissue was obtained from coronary arteries without prior instrumentation (primary lesions, n = 31), aortocoronary saphenous vein bypass grafts with primary lesions (n = 8), coronary arteries with lesions developing after prior balloon angioplasty or mechanical atherectomy (restenotic lesions, n = 30) and vein bypass grafts with restenotic lesions (n = 4). Primary lesions were characterized by dense intimal fibrosis with necrotic debris (83% of intimal tissue) and foam cells typical of atherosclerosis. These lesions frequently contained cholesterol crystals (45% of coronary arteries, 50% of vein grafts) and calcium deposits (65% of coronary arteries, 38% of vein grafts). Restenotic lesions were characterized by an increased proportion of loose fibroproliferative tissue (45% of coronary artery intima, 35% of vein graft intima). Immunohistochemical stains confirmed this proliferative tissue to be primarily smooth muscle cells. Thrombus was rarely observed. Comparison of resected tissues indicated that dense fibrosis and necrosis are significantly more common in primary than in restenotic lesions (83% versus 56% of intimal tissue, p = 0.0005), whereas smooth muscle cell hyperplasia is more common in restenotic than in primary lesions (44% versus 17% of intimal tissue, p less than 0.0005). Partial-thickness resection of medial tissue or full-thickness resection of media with associated adventitial tissue occurred in 27 (56%) of 39 primary atheromatous lesions and 16 (47%) of 34 restenotic lesions; subintimal tissue obtained from primary lesions appeared identical to that obtained from restenotic lesions. These data indicate that the histopathologic characteristics of the neointimal layer of restenotic lesions differ from those of the intimal layer of primary atherosclerotic lesions. 
1	Survival and quality of life among patients receiving unproven as compared with conventional cancer therapy. BACKGROUND. Cancer treatments without proved efficacy have achieved new levels of popularity, particularly among well-educated patients. The value of these therapies is vigorously debated. METHODS. We compared the length of survival and quality of life in patients who received treatment at a prominent unorthodox cancer clinic in addition to conventional treatment and in matched control patients from an academic cancer center who received only conventional treatment. All the patients had documented extensive malignant disease associated with a predicted median survival time of less than one year. The study sample consisted of 78 pairs of patients matched according to sex, race, age, diagnosis, and time from the diagnosis of metastatic or recurrent disease, who were enrolled over a period of 3 1/2 years. Periodic follow-up (approximately every two months) continued until death. RESULTS. There was no difference between the two patient groups in length of survival. Median survival for both groups was 15 months (P = 0.22; relative risk, 1.23; 95 percent confidence interval, 0.88 to 1.72). Quality-of-life scores were consistently better among conventionally treated patients from enrollment on. CONCLUSIONS. For this sample of patients with extensive disease and for this particular unorthodox treatment regimen, conventional and unorthodox treatments produced similar results. 
5	Limitations of electroencephalographic monitoring in the detection of cerebral ischemia accompanying carotid endarterectomy. An analysis was undertaken of 458 consecutive carotid endarterectomies performed over 6 years with the patient under general anesthesia and with electroencephalographic monitoring. Seventy patients (15%) had electroencephalographic changes suggestive of ischemia with carotid clamping and had shunts placed. Ischemic encephalographic changes occurred in 26% of patients with an occluded contralateral carotid artery, 21% of patients with a prior stroke history, and 12% of patients with no stroke history and a patent contralateral carotid artery. Nineteen strokes (4.1%), nine transient deficits (2.0%), and one death (0.2%) occurred in the 458 endarterectomies in this experience. Ten of the 19 strokes and five of nine transient deficits were immediately apparent when patients awoke from anesthesia. Five of 10 patients with immediate strokes and all five patients with immediate transient deficits had no ischemic electroencephalographic changes during the procedure. Two other patients with immediate strokes initially had ischemic electroencephalographic changes after carotid clamping that reversed with increased blood pressure or shunting. Therefore 7 of 10 patients with immediate strokes and all 5 patients with immediate transient deficits had electroencephalographs unchanged from baseline at completion of the procedure, and thus deficits not manifest by operative electroencephalographic changes developed. Our data do not support the tenet that electroencephalographic monitoring will always predict neurologic deficits accompanying carotid endarterectomy. 
4	Relation of serum lipoprotein cholesterol levels to presence and severity of angiographic coronary artery disease. To assess the relation of lipid levels to angiographic coronary artery disease (CAD), lipid profiles were obtained on 125 men and 72 women undergoing diagnostic coronary angiography. CAD, defined as greater than or equal to 25% diameter narrowing in a major coronary artery, was present in 106 men (85%) and 54 women (75%). Multiple regression analyses revealed that only high-density lipoprotein (HDL) cholesterol level in men, and age and total/HDL cholesterol ratio in women, were independently associated with the presence of CAD after adjustment for other risk factors. HDL cholesterol level and age were significantly correlated with both extent (number of diseased vessels) and severity (percent maximum stenosis) of CAD in men. In women, age was the only independent variable related to severity, whereas age and total/HDL cholesterol ratio were related to extent. Of 71 patients with total cholesterol less than 200 mg/dl, 79% had CAD. With multiple regression analyses, HDL cholesterol was the only variable independently related to the presence and severity of CAD in these patients after adjustment for age and gender; extent was significantly associated with age and male gender, and was unrelated to any of the lipid parameters. With use of multiple logistic and linear regression analyses of the group of 197 patients, HDL cholesterol was the most powerful independent variable associated with the presence and severity of CAD after adjustment for age and gender. HDL cholesterol was also an independent predictor of extent. Age was independently associated with each of the end points examined, and was the variable most significantly related to extent. These data add to the growing body of information demonstrating an important association between HDL and CAD. 
1	Evidence of heterogeneous mechanisms in lipoprotein lipid alterations in hyperandrogenic women. Fifty-one hyperandrogenic women had their lipoprotein lipid profiles determined. Free and albumin-bound testosterone was associated with triglycerides and with high-density lipoprotein cholesterol independent of fasting insulin levels, percent ideal body weight, and waist/hip ratio. To gain insight into mechanisms of these lipid alterations, the women were subgrouped according to apparent source of androgen excess. Whereas all groups had low levels of high-density lipoprotein-2 cholesterol and high triglyceride concentrations, only in those with high luteinizing hormone-to-follicle-stimulating hormone ratios was free and albumin-bound testosterone associated with triglycerides and high-density lipoprotein cholesterol independent of fasting insulin levels. Relationships between percent ideal body weight and waist/hip ratios, free and albumin-bound testosterone, sex hormone binding globulin, fasting insulin and 2-hour insulin levels and blood pressure are not significant in all subgroups, suggesting differing endocrinological influences and differing mechanisms for lipoprotein lipid alterations. 
4	Calcium channel blockers versus angiotensin-converting enzyme inhibitors: renal effects. Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are two classes of antihypertensive agents with novel effects on renal function. In both experimental and clinical studies, calcium channel blockers tend to increase renal blood flow, glomerular filtration rate, and urinary sodium excretion in essential hypertension. ACE inhibitors have similar effects on renal blood flow and glomerular filtration rate in essential hypertension, but they tend to cause sodium retention. ACE inhibitors can cause marked reductions in glomerular filtration rate in renovascular hypertension, making them a problematic choice for the treatment of this form of hypertension. In chronic, progressive renal diseases, ACE inhibitors have been shown to decrease protein excretion and morphologic evidence of glomerulosclerosis. The relationship of the decrease in protein excretion to the progression of renal disease has not yet been established. 
1	Platelet norepinephrine and epinephrine concentration in patients with pheochromocytoma. Platelet and plasma catecholamine concentrations were determined in 17 patients with surgically proven pheochromocytoma (mean age 42.3 years); in 31 patients with borderline hypertension (mean age 35.3 years) and in 9 healthy controls (mean age 39.3 years). Both platelet norepinephrine and epinephrine were significantly increased in patients with pheochromocytoma when compared with hypertensive and control groups (P less than .001). No correlation between platelet and plasma catecholamines was detected in all studied groups. The diagnostic accuracy of platelet catecholamine in pheochromocytoma is limited since increased platelet norepinephrine was found in 35.5% and increased platelet epinephrine was found in 19.4% of patients with essential hypertension. 
3	Quantitation of skin vasomotor control in normal subjects and in diabetic patients with autonomic neuropathy. Peripheral autonomic neuropathy in diabetes has been difficult to evaluate. We have developed a test to quantitate sympathetic skin vasomotor function in the extremities. Skin vasomotor reflexes were investigated after warming and cooling the left arm and recording changes in skin temperature as a measure of skin blood flow in the right hand and both feet. Twenty-three diabetic patients with cardiac autonomic neuropathy and 28 healthy control subjects were examined. In contrast to the healthy subjects, the diabetic patients showed reduced or even absent responses in skin temperature to both warming and cooling. The rate of skin temperature decrease for the hand and feet during cooling, which was used as the actual parameter to quantitate skin vasomotor control, was significantly reduced in the diabetic group as compared with the healthy control subjects. We conclude that this technique provides a simple non-invasive method for quantitating skin vasomotor function in the extremities of diabetic patients. 
4	Magnitude and time course of beta-adrenergic antagonism during oral amiodarone therapy. To examine the presence and time course of beta-adrenergic antagonism produced by amiodarone, the heart rate, QT interval and arrhythmia frequency in response to graded doses of isoproterenol were evaluated in eight patients treated with oral amiodarone for sustained ventricular tachycardia. Measurements were made before and every 2 days after beginning oral amiodarone therapy (600 mg twice daily). Isoproterenol was given in doses of 12.5, 25 and 50 ng/kg body weight per min. The mean heart rate at rest decreased from 73.1 +/- 17.8 beats/min on day 0 to 57.8 +/- 15.0 beats/min after 12 days of amiodarone therapy. A significant linear decline in heart rate at rest was observed until day 6 (p less than 0.05 for all comparisons). On all days isoproterenol produced a progressive increase in heart rate that reached 115.5 +/- 20.2 beats/min on day 0 and 94.2 +/- 18.5 beats/min on day 12. Amiodarone blunted the heart rate increase produced by isoproterenol on days 2 to 12 (p less than 0.05 versus day 0). This effect was present by day 2 and did not change significantly thereafter. The mean corrected QT (QTc) interval increased from 430 +/- 30 ms on day 0 to 449 +/- 63 ms on day 12. A significant linear increase in QTc interval was observed until day 6 (p less than 0.05 for all comparisons). There was no systematic effect of isoproterenol on the QTc interval. Five of eight patients had a significant number of isoproterenol-induced premature ventricular complexes. Ventricular ectopic activity in response to isoproterenol was abolished after 4 days of amiodarone therapy. 
4	Treatment of postoperative infection of ascending aorta and transverse aortic arch, including use of viable omentum and muscle flaps. Postoperative infection of the ascending aorta and aortic arch in 40 patients was treated by antibiotic therapy alone (4 patients) or by operation and lifelong suppressive antibiotic therapy (36 patients). Complications of infection included antibiotic-resistant infection, infected false aneurysm, rupture of suture line, aortocutaneous fistulas, aortic-right ventricular fistulas, arterial embolus, aortic valve insufficiency, aortobronchial fistula, mediastinal abscess, and chest wall problems. These were treated by a variety of operations including composite valve-graft replacement, graft replacement, patch-graft closure of false aneurysm, simple suture of disrupted suture lines and false aneurysm, and debridement of mediastinum and chest wall. The area of reconstruction was covered, and mediastinal dead space was reduced by mobilization of viable tissue, including local tissue and distant structures such as flaps of muscle and omentum. Thirty-three patients (83%) were early survivors, and 28 patients (70%) were alive and well at last follow-up 4 months to 6.5 years after operation. 
1	Flow cytometric analysis of DNA content in partial hydatidiform moles with persistent gestational trophoblastic tumor. Hydatidiform moles may be classified as partial or complete based on genetic and pathologic criteria. Between January 1979 and January 1990, 17 (5.5%) of 310 patients followed for partial mole developed persistent gestational trophoblastic tumor. Tissues from 14 partial moles were available for flow cytometric analysis of DNA content. Eleven partial moles (85%) were triploid, two (15%) were diploid, and one DNA histogram was uninterpretable. All patients with triploid partial moles achieved complete remission with one course of single-agent chemotherapy. The two with diploid partial mole required multiple courses of chemotherapy to achieve gonadotropin remission. Although the DNA content of most partial moles with persistent gestational trophoblastic tumor was triploid, diploid partial moles with persistent tumor were less sensitive to single-agent chemotherapy. 
1	Diet and female sex hormone concentrations: an intervention study for the type of fat consumed. A possible mechanism by which dietary fat may influence the development of breast cancer is by influencing the concentration of female sex hormones. This study investigated the effect of alteration in the type of fat consumed on concentrations of female sex hormones in serum. Female volunteers were randomly assigned to continue on their usual meat-eating diet, change to a vegetarian diet, or change to a diet that was predominantly vegetarian but where fish was consumed at least three times per week. Change to the vegetarian or fish diet had little effect on diet total hormone concentrations; however, the amount of estradiol was significantly decreased in the vegetarian group. When nutrient consumption was correlated with hormone concentrations, prolactin was directly associate with fat consumption, sex-hormone-binding globulin was inversely associated with fat consumption (particularly cholesterol consumption), and the proportion of nonprotein-bound estradiol was directly associated with complex carbohydrate consumption. 
2	Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method. The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has so far been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure. The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy. 
5	Sexual changes in hemiparetic patients. Eighty-six patients, each with hemiparesis caused by a single stroke, were studied to assess the changes in sexual life experienced after the onset of the illness. Clinical data were collected, and a questionnaire concerning both sexual behavior and feelings about sexuality was administered to the patients and their spouses. Twenty-four couples were eliminated from further analysis because of a discrepancy between husband and wife in the answers concerning sexual behavior after stroke. A marked decline in sexual activity after stroke was found in both genders; other aspects of sexual behavior underwent fewer changes. The feeling of an overall change in sexual life was reported more frequently by male patients. Most patients' spouses reported the feeling of an overall psychological change in their partners and the feeling of an overall change in sexual life after the onset of the illness. No significant associations were found between clinical features and changes in sexual life. This study confirms that cerebrovascular accidents are generally followed by some important alterations in sexual life. Clinical factors do not seem to play a crucial role in determining these changes, which may be better explained in terms of maladjustment attributable to psychologic and interpersonal factors. 
5	Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma. We measured the rate of change of visual field threshold values over time (mean follow-up, 44.9 +/- 17.4 months) by trend analysis in 40 eyes of 40 patients with chronic open-angle glaucoma. Twenty-eight eyes had stable visual fields, and two eyes had significant visual field improvement. Ten eyes had significant visual field deterioration and showed a correlation between indices of intraocular pressure (standard error of the mean, P = .02; standard deviation, P = .04; and range, P = .05) and the rate of visual field loss in the superonasal region of the visual field, such that the greater the variation of intraocular pressure the greater the rate of loss. The group losing visual fields had a higher mean visual field threshold value and significantly less optic disk pallor and cupping at the start of the study than the stable visual field group. Thus, a significant rate of visual field loss occurred at an earlier stage of the disease and showed a correlation with intraocular pressure in this stage. 
5	Effect of V1-vasopressin receptor blockade on arterial pressure in conscious rats with cirrhosis and ascites. Angiotensin II blockade with saralasin in human cirrhosis with ascites is associated with a significant reduction in arterial pressure, indicating that endogenous angiotensin II plays an important role in the maintenance of systemic hemodynamics in this condition. The aim of the current study was to investigate whether vasopressin also contributes to the maintenance of arterial pressure in cirrhosis with ascites. The study was performed using three groups of cirrhotic rats with ascites and three groups of control animals. The administration of d(CH2)5Tyr(Me)AVP, a selective antagonist of the vascular effect of vasopressin, to 10 cirrhotic rats induced a significant reduction in mean arterial pressure (from 94 +/- 4 to 85 +/- 4 mm Hg; P less than 0.001) and a significant increase in plasma renin activity (from 24.3 +/- 4.9 to 34.3 +/- 5.9 ng/mL.h; P less than 0.02) and plasma norepinephrine concentration (from 1474 +/- 133 to 2433 +/- 253 pg/mL; P less than 0.01). Similar results were observed following saralasin administration in a second group of 5 cirrhotic rats [mean arterial pressure decreased from 97 +/- 4 to 85 +/- 5 mm Hg (P less than 0.0001); and plasma renin activity and norepinephrine concentration increased from 18.4 +/- 5.8 to 40.3 +/- 5.7 ng/mL.h (P less than 0.02) and from 1383 +/- 70 to 2312 +/- 334 pg/mL (P less than 0.05), respectively]. The simultaneous blockade of angiotensin II and vasopressin in a third group of cirrhotic rats resulted in a significantly greater reduction of mean arterial pressure (from 97 +/- 6 to 74 +/- 6 mm Hg; P less than 0.05). No changes in arterial pressure were observed in the three groups of control rats. These findings indicate that endogenous vasopressin is as important as angiotensin II in the maintenance of arterial pressure in cirrhotic rats with ascites and support the contention that arterial hypotension is the initial event leading to the stimulation of the renin-angiotensin system and vasopressin in this animal model of cirrhosis. 
4	Renal vein renins: inability to predict response to revascularization in patients with hypertension. To determine whether the captopril-stimulated renal vein renin ratio (CSRVRR) could enable identification of patients with hemodynamically significant renovascular lesions who would respond to revascularization, the authors measured CSRVRRs in 143 consecutive patients with hypertension who had been selected because of clinical features suggestive of renovascular hypertension. All patients underwent conventional renal arteriography. Renovascular hypertension was the final diagnosis if revascularization resulted in cure or improvement in blood pressure. Complete data were available for 133 patients. Twenty patients had renovascular hypertension; CSRVRR was greater than 1.5 in 13 of these 20 patients (sensitivity, 65%). However, it was also greater than 1.5 in 54 of the 113 patients without renovascular hypertension (false-positive rate, 47.8%). The positive predictive value of CSRVRR was 18.6%; the negative predictive value, 89.3%. It is concluded that CSRVRR is not sufficiently sensitive to enable prediction of which patients will respond to revascularization and is not specific enough to exclude patients who do not have renovascular hypertension. 
2	Intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy. An unusual but favorable association? During the 26th week of a first pregnancy, a 25-year-old woman presented with pruritus suggesting an intrahepatic cholestasis of pregnancy. The pruritus, however, persisted despite the premature delivery of a normal newborn at the 35th week. Moreover, aspartate aminotransferase activity increased, reaching a maximum of 38 times normal level on the 17th day after the delivery. Thus, an acute fatty liver of pregnancy was suspected and confirmed by liver biopsy. This patient appeared to have both intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy, an association not previously reported. It is suggested that intrahepatic cholestasis of pregnancy caused premature delivery, which in turn may have prevented the onset of severe maternal and fetal complications caused by acute fatty liver of pregnancy. 
5	A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia BACKGROUND. We identified a motile, curved, gram-negative bacillus as the cause of persistent fever and bacteremia in two patients with symptomatic human immunodeficiency virus infection. The same organism was subsequently recovered from a bone marrow-transplant recipient with septicemia and from two immunocompetent persons with week-long febrile illnesses. All the patients recovered after antimicrobial therapy. METHODS AND RESULTS. Primary cultures of blood processed by centrifugation after blood-cell lysis yielded adherent, white, iridescent, morphologically heterogeneous colonies in 5 to 15 days. Subcultures grew in four days on chocolate, charcoal-yeast extract, or blood agar. The organisms stained weakly with safranin and were not acid-fast. Fluorescent-antibody tests for legionella and francisella were negative. Biochemical reactivity was minimal and difficult to ascertain. Agar-dilution testing revealed in vitro susceptibility to most antimicrobial agents tested. The cellular fatty acid composition of the isolates was similar, resembling that of Rochalimaea quintana or brucella species, but not Helicobacter pylori or species of campylobacter or legionella. As resolved by gel electrophoresis, cell-membrane preparations of all isolates contained similar proteins, with patterns that differed from that of R. quintana. Patterns of digestion of DNA from all isolates by EcoRV restriction endonuclease were virtually identical and also differed from that of R. quintana. On immunodiffusion, serum from one convalescent patient produced a line of identity with sonicates of all five isolates. CONCLUSIONS. This pathogen may have been unidentified until now because of its slow growth, broad susceptibility to antimicrobial agents, and possible requirement of blood-cell lysis for recovery in culture. It should be sought as a cause of unexplained fever, especially in persons with defective cell-mediated immunity. 
1	Paraneoplastic limbic encephalitis: clinico-pathological correlations. Three new cases of limbic encephalitis in association with malignancy are reported. The literature on this condition is reviewed and the clinical, laboratory and histopathological features of cases proven at necropsy are correlated. The possible pathogenic mechanism of this disorder is discussed. 
4	Hemodynamics in internal carotid artery occlusion examined by positron emission tomography. Using positron emission tomography in nine patients with minor strokes, unilateral internal carotid artery occlusion, and good collateral circulation through the anterior portion of the circle of Willis, we analyzed regional cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume. These studies allowed quantification of the regional hemodynamic status, especially in relation to watershed areas. Compared with eight normal controls, the patients had significantly (p less than 0.01) decreased regional cerebral blood flow in the middle cerebral artery territory and the surrounding watershed areas of the occluded hemisphere. The oxygen extraction fraction rose with the distance from the anterior portion of the circle of Willis, attaining the highest value in the superior parietal and posterior temporo-occipital watershed area. A concomitant decrease in the cerebral blood flow/cerebral blood volume ratio suggested reduction in the mean blood flow velocity, whereby elevated blood viscosity would be more liable to reduce cerebral blood flow. These findings suggest hemodynamic vulnerability of the watershed areas after internal carotid artery occlusion in persons with good collateral circulation through the anterior portion of the circle of Willis. Our results also emphasize the importance of systemic hemodynamic factors such as blood pressure and circulating blood volume in the genesis of watershed infarction. 
1	The immunoperoxidase localization of tumour markers in ovarian cancer: the value of CEA, EMA, cytokeratin and DD9. Primary tumours from 40 patients with epithelial ovarian cancer, treated at St Thomas's Hospital over a 10-year period, were studied for the immunocytochemical expression of the following tumour markers in formalin-fixed paraffin embedded material: carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CAM 5.2), and DD9. An indirect immunoperoxidase staining technique was used. All of the tumours were positive for EMA and CAM 5.2, and 30% of them were positive for both CEA and DD9. The absence of CEA and DD9 may be of value in differentiating between metastatic abdominal adenocarcinomas of ovarian origin and those of gastrointestinal origin, but no indication of prognosis was obtained using these epithelial markers. The strong and widespread staining of all the tumours for EMA suggests that this may be a useful marker for detecting metastatic or recurrent disease by immunoscintigraphy. 
5	Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs. We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299). 
2	Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Bismuth subsalicylate (BSS) and placebo were evaluated in a double-blind, placebo-controlled study as adjunct to rehydration therapy in 123 children, aged 4 to 28 months, hospitalized with acute diarrhea. The dosing regimen was 20 mg/kg five times daily for 5 days. Significant benefits were noted in the BSS group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency, significant improvement in clinical well-being, and shortening of the disease duration. Patients treated with BSS had a significant reduction in duration of hospital stay (6.9 days) compared with placebo-treated patients (8.5 days). Also, intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the BSS-treated group. Bismuth subsalicylate was associated with clearance of pathogenic Escherichia coli from the stools in 100% of cases but was not different from placebo in rotavirus elimination. Bismuth subsalicylate was well tolerated with no reported adverse effects. Blood bismuth and serum salicylate levels were well below levels considered toxic. In this study, BSS provided effective adjunctive therapy for acute diarrhea, allowing children to get well sooner with less demand on the nursing and hospital staff. 
2	Irritable bowel syndrome in office-based practice in the United States. United States estimates of the frequency of visits to physicians and patterns of medical care for the diagnosis of the irritable bowel syndrome were derived from the 1975, 1980-1981, and 1985 National Ambulatory Medical Care Surveys. These surveys of office-based physicians allow national estimates of various aspects of ambulatory care. The overall rate of visits with the diagnosis of irritable bowel syndrome in 1980-1981 and 1985 were 10.6 per thousand U.S. population. Women had 2.4 times the rate of visits by men and rates rose in both sexes until middle-age. Irritable bowel syndrome was the leading digestive disease diagnosis among gastroenterologists but only the seventh leading diagnosis among all physicians. Gastrointestinal symptoms, association with mental disorders, prescriptions, and disposition were also examined in patients with visits for irritable bowel syndrome. Among records with digestive tract symptoms and a first listed diagnosis of irritable bowel syndrome, stomach or abdominal pain was listed on only about one half of records and disorders of bowel function were listed on fewer than 40%. In 1975 and 1985, irritable bowel syndrome was noted approximately twice as often as other digestive diseases at visits with mental disorder symptoms and diagnosis, although mental disorder symptoms and diagnoses were noted at fewer than 15% of visits with irritable bowel syndrome. Medications were prescribed at approximately 75% of visits for irritable bowel syndrome; the most common were gastrointestinal medications followed by combination gastrointestinal-psychoactive medications. Subsequent appointments were scheduled following at least 50% of the visits of patients with irritable bowel syndrome. 
4	Optimum results of the surgical treatment of carotid territory ischemia. Continuing controversy over the role of carotid endarterectomy in stroke prevention is based largely on reports in which high perioperative morbidity and mortality rates obviate possible long-term benefit from the procedure. The purpose of this review is to examine optimal results of carotid surgery in order to describe the potential for the procedure in stroke prevention. Optimal surgical results are compared with optimal medical results in the therapy of symptomatic patients and with optimal nonsurgical results in the therapy of asymptomatic patients. Factors common to series with excellent results, such as patient selection and operative technique, are examined, and problems such as recurrent carotid stenosis and coexisting coronary disease, which continue to plague even the best surgical series, are discussed. 
4	Perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for poor risk transitional cell carcinoma of the bladder: an Eastern Cooperative Oncology Group pilot study. A total of 18 patients with locally advanced transitional cell carcinoma of the bladder underwent 2 preoperative cycles of chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin followed by radical cystectomy and 2 postoperative cycles of chemotherapy. Radical cystectomy was performed in 17 of 18 patients (94%) with a pathological partial response in 3 (17%) and a pathological complete response in 2 (11%), for an over-all response rate of 28% (95% confidence limits 10 to 53%). At 23-month median followup 9 patients (50%) remained without evidence of recurrent disease, while 9 (50%) died of metastatic bladder cancer. Average relative dose intensity of all therapy given was 78%. Hematological toxicity was moderate, with no septic deaths or bleeding complications. However, 4 thromboembolic events occurred. While downstaging of the primary bladder tumor can occur with this perioperative schedule our results were not as impressive as some previously reported findings. The incidence of thromboembolic events is worrisome. 
5	Replacement of the aortic valve or root with a pulmonary autograft in children. Between January 1967 and December 1988, 34 patients ranging in age from 3 to 18 years (mean, 14 +/- 3.6 years) underwent replacement of the aortic valve or root with their own pulmonary valve. The indication for operation was left ventricular outflow obstruction in 16 patients (47%), aortic regurgitation in 14 (41%), mixed aortic valve disease in 3 (9%), and failure of a previously implanted aortic homograft in 1 (3%). There were four early deaths, all before 1971, giving a hospital mortality of 11.8% (70% confidence interval, 6% to 20%). Surviving patients have been followed up a cumulative total of 214 patient-years, the longest period of observation being 16 years 8 months. Late mortality was 13.3% (70% confidence interval, 7% to 23%), and 4 other patients required removal of the pulmonary autograft for endocarditis. Actuarial rates at 16 years were 74% +/- 11% for freedom from reoperation on the left ventricular outflow tract, 80% +/- 10% for freedom from reoperation on the right ventricular outflow tract, and 77% +/- 10% for late survival. There was no instance of primary structural degeneration in the pulmonary autograft, and all surviving patients were in New York Heart Association functional class I without medication. This experience demonstrates that the pulmonary autograft can achieve good early and medium-term results in young patients. Should growth potential be realized, it might constitute the ideal biological valve for the left ventricular outflow in children. 
4	Direct monitoring of capillary perfusion following normovolemic hemodilution in an experimental skin-flap model. The effects of normovolemic hemodilution on skin flap survival are studied in a recently developed skin-flap model (homozygous hairless mouse ear) in which nutritional capillary flow is monitored directly by means of intravital microscopy from the time of flap creation throughout the establishment of necrosis. Two diluting agents (dextran 60 and hydroxyethyl starch 200) are utilized. Our quantitative findings demonstrate that the amount of nonperfused tissue following flap creation in both the dextran (n = 23) and starch (n = 13) groups was significantly decreased as compared with controls (n = 19). Our qualitative observations suggest that improved hemorrheologic properties at the microcirculatory level are responsible for the observed decreased necrosis. Various mechanisms by which hemodilution may act to prevent necrosis are discussed. 
4	Effect of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics in essential hypertension. The effects of a calcium-entry blocker, nicardipine, on intrarenal hemodynamics were studied in essential hypertension. A 4-week study was performed in eight patients with essential hypertension who were given a regular sodium diet in the first and third weeks, and a sodium-restricted diet in the second and fourth weeks. Nicardipine, 60 mg/d, was administered in the third and fourth weeks. The urinary sodium excretion rate (UNaV) was plotted on the y-axis against the mean arterial pressure (MAP) on the x-axis before and after the administration of nicardipine. Assuming the difference between MAP and the x-intercept of this renal function curve represents the effective filtration pressure across the glomerular capillaries, the intrarenal hemodynamics such as afferent arteriolar resistance (RA) and efferent arteriolar resistances (RE), glomerular pressure (PG), and gross filtration coefficient (KFG) were calculated. Although the MAP on regular salt diet was lowered from 125 +/- 3 to 109 +/- 2 mm Hg by nicardipine, neither the renal blood flow rate (RBF) (670 +/- 40 mL/min) nor the glomerular filtration rate (GFR) (79 +/- 2 mL/min) was altered. The RA was estimated to be reduced from 9,300 +/- 900 to 7,400 +/- 700 dyne.s.cm-5 (P less than 0.01), while no changes were noted in RE (4,900 +/- 400 dyne.s.cm-5), PG (50 +/- 1 mm Hg), or KFG (0.180 +/- 0.041 [mL/s]/mm Hg). Essential hypertension has been characterized by a prominent increase in RA, resulting in maintenance of normal PG. This Ca-entry blocker worked to normalize intrarenal hemodynamics in essential hypertension by dilating afferent arterioles alone. 
3	Management of arginine monohydrochloride extravasation in the forearm. We initially observed our patient, who had subcutaneous arginine monohydrochloride extravasation in the volar forearm, until his wound demarcation was complete. After wound demarcation, we proceeded with debridement and partial-thickness skin grafting. Upper extremity function was totally normal 3 months after this therapy. This is the first case report in the literature that describes a child with an arginine monohydrochloride-induced extravasation necrosis. 
5	Acute pulmonary oedema on the Ruwenzori mountain range. A 40 year old man had an episode of severe pulmonary oedema at 4000-5000 m during the ascent of the Margherita peak (5109 m) of Mount Stanley on the Ruwenzori. He had taken acetazolamide and high dose dexamethasone to treat symptoms of acute mountain sickness. Six years before he had been studied by right heart catheterisation as a healthy volunteer during hypoxic breathing at sea level. His pulmonary vascular reactivity had been within the normal range for 32 healthy subjects. This man had high altitude pulmonary oedema despite currently recommended treatments for acute mountain sickness and normal pulmonary vascular reactivity to hypoxia at sea level. 
1	Single photon emission computed tomography and positron emission tomography in cancer imaging. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are now being used to improve the information available from radioisotopic imaging of patients with cancer. These nuclear medicine techniques offer the potential for studying regional function and biochemistry by using radiolabeled substrates. The chemical changes of malignancy precede anatomic changes, and PET and/or SPECT may detect these changes before anatomic changes have occurred. The superiority of SPECT compared with planar imaging has been demonstrated for cardiac and brain imaging. Radiopharmaceuticals containing technetium 99 m (99mTc) are best suited for SPECT imaging because large amounts of radioactivity are administered and the collimator-camera systems are optimized for the 140 keV photons of 99mTc. The current interest in imaging cancer with SPECT relates to the use of gallium 67 citrate and monoclonal antibodies labeled with iodine 123 or indium 111. SPECT can image these radioisotopes, but the advantages compared with planar imaging have not been clearly defined. Furthermore, the ability to quantitate the distribution of single photon emitters other than 99mTc has not been demonstrated. New SPECT systems with three heads or rings of detectors offer promise for improved, quantitative imaging. PET has the capability of imaging tracers with the biologically important elements C-11, N-13, O-15, and F-18 used for positron labeling. These radioisotopes have short half-lives and require a cyclotron close to the PET facility. The most prominently used radiopharmaceutical for PET is F-18 fluorodeoxyglucose (FDG). PET studies with FDG in patients with primary brain tumors have demonstrated the ability to determine the degree of malignancy, to differentiate necrosis from recurrent tumor after radiation therapy or chemotherapy, and to predict prognosis. Other metabolic functions of cancer have been studied, including amino acid accumulation, thymidine uptake, oxygen utilization, intermediary metabolism, and receptor status. PET has the potential to make a major impact on the characterization of a malignancy and the effect of therapy. 
2	Infantile form of carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to carnitine palmitoyltransferase II deficiencies. Reported cases of carnitine palmitoyltransferase II (CPT II) deficiency are characterized only by a muscular symptomatology in young adults although the defect is expressed in extra-muscular tissues as well as in skeletal muscle. We describe here a CPT II deficiency associating hypoketotic hypoglycemia, high plasma creatine kinase level, heart beat disorders, and sudden death in a 3-mo-old boy. CPT II defect (-90%) diagnosed in fibroblasts is qualitatively similar to that (-75%) of two "classical" CPT II-deficient patients previously studied: It resulted from a decreased amount of CPT II probably arising from its reduced biosynthesis. Consequences of CPT II deficiency studied in fibroblasts differed in both sets of patients. An impaired oxidation of long-chain fatty acids was found in the proband but not in patients with the "classical" form of the deficiency. The metabolic and clinical consequences of CPT II deficiency might depend, in part, on the magnitude of residual CPT II activity. With 25% residual activity CPT II would become rate limiting in skeletal muscle but not in liver, heart, and fibroblasts. As observed in the patient described herein, CPT II activity ought to be more reduced to induce an impaired oxidation of long-chain fatty acids in these tissues. 
1	Posttranslational gastrin processing depends on tumor morphology. Extracellular matrices have recently been demonstrated to alter cell morphology in culture. Altered cell morphology has been associated with changes in gene transcription and translation, but it is not known whether it also affects posttranslational processing. Using tyrosine-O-sulfation as a marker of processing, we studied the effects of various substrates on biologically active gastrin (IRG) production and sulfation in gastrin-containing tumor cells (GT cells). Dispersed GT cells were plated onto different substrates and then incubated. Culture media from days 4, 7, and 28 were assayed with specific antibodies that recognize total IRG and nonsulfated IRG. Cells cultured on plastic and dried films of laminin, collagen, and Matrigel (Collaborative Research Inc., Lexington, Mass.) flattened and formed monolayers of GT cells. Cells cultured on a porous membrane and hydrated gels of collagen and Matrigel did not flatten but formed spheroids of GT cells. The monolayer cultures showed an increase in sulfation with time but a decrease in IRG production. The spheroid cultures maintained a constant level of sulfation over time and, with the exception of Matrigel (gel), also showed a decrease in IRG production. These results indicate that the level of sulfation was unchanged from that of the original tumor when cells were grown in spheroids but increased when cultured as monolayers. It appears that alteration of the cellular milieu alters colony morphology, which in turn alters gastrin processing. 
4	Unusual opening of coronary sinus in atrioventricular septal defects. The coronary sinus is an important landmark for the position of the atrial component of the atrioventricular conduction axis and, thus, assumes special relevance to the surgeon in the operating room. We describe here 2 patients with atrioventricular septal defect characterized by an unusual termination of the coronary sinus within the left atrium. We discuss the potential importance of this finding to the disposition and surgical avoidance of the conduction tissues. 
3	Assessment of the components of observed chronic pain behavior: the Checklist for Interpersonal Pain Behavior (CHIP). This article describes the development of the Checklist for Interpersonal Pain Behavior (CHIP), an observation scale which assesses overt pain behavior. The study is an extension of an earlier study in which the dimensions and components of observed chronic pain behavior were examined. A broad definition of pain behavior is chosen (interpersonal pain behavior), namely the interaction between the pain patient and his/her direct environment. The list of pain behaviors, taken from the earlier study, has been transformed into a 78-item global rating scale to be used by nurses to quantify observed pain behavior in a clinical setting. Six studies examine the factor structure and the psychometric properties of this behavioral observation method. In the first study, 6 internally reliable factors are derived using factor analytic techniques from a sample of 152 chronic pain patients. They are labeled as: 'distorted mobility,' 'verbal complaints,' 'non-verbal complaints,' 'nervousness,' 'depression' and 'day sleeping.' Internal consistency of all factors, except 'day sleeping' was excellent. The following studies show that the CHIP is sufficiently reliable and valid. After a discussion on the advantages of this observation scale, the conclusion seems justified that the CHIP is a useful tool in pain assessment that can easily be used by nurses. 
5	The TURP syndrome. This article discusses the presentation, aetiology, treatment and prevention of central nervous system disturbances after transurethral resection of the prostate. Nausea and vomiting, visual symptoms, and altered states of consciousness have been reported as complications due to intravascular absorption of irrigating fluid. Hypotonicity after absorption of the irrigating fluid causes cerebral oedema. Hyperglycinaemia may cause visual disturbances and hyperammonaemia may cause delayed coma. 
3	Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage. Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe. 
4	Comparison of clinical and electrophysiologic features of preexcitation syndromes in patients presenting initially after age 50 years with those presenting at younger ages. Although patients may develop arrhythmias due to preexcitation syndromes at any time from the prenatal period to late adulthood, presentation in late adulthood is considered uncommon and has not been well studied. From June 1981 to June 1989, 73 patients were documented to have preexcitation syndromes on the basis of electrophysiologic studies. Those whose initial arrhythmias appeared at an age greater than 50 years (group 1, n = 13) were compared with the remaining 60 patients (group 2). All group 1 patients presented in the setting of acute medical or surgical diseases (n = 7), or chronic cardiac disease (n = 6) commonly associated with middle age and often with atrial arrhythmias; only 13 group 2 patients had underlying illnesses (p = 0.0001). Almost two-thirds of group 2 patients were evaluated because of narrow complex orthodromic tachycardia or palpitations and electrocardiographic evidence of preexcitation. Wide complex tachycardia was more often a reason for referral of older patients (7 of 13 vs 11 of 60, p less than 0.05), among whom atrial fibrillation/flutter also tended to be more frequent (4 of 13 vs 11 of 60, difference not significant). The PR and QRS intervals of group 1 patients were within the normal range and differed significantly from those of group 2 patients (PR, 0.15 +/- 0.04 vs 0.11 +/- 0.03 second, p less than 0.001; QRS, 0.09 +/- 0.01 vs 0.12 +/- 0.03 second, p less than 0.001), making electrocardiographic identification of preexcitation more difficult in group 1. Several factors likely contributed. 
3	Etiologic importance of the intimal flap of the external carotid artery in the development of postcarotid endarterectomy stroke. A technically unsatisfactory end point (transition from the removed diseased plaque to normal distal intima) leading to an intimal flap of the external carotid artery has been identified as a source of perioperative stroke. The mechanism involves thrombus formation with retrograde propagation of the thrombus and subsequent embolization of the internal carotid artery. This report describes three cases illustrating this mechanism and methods of identification and correction. This mechanism of postoperative stroke adds further justification for the routine use of intraoperative surveillance studies to document the technical result of endarterectomy involving the internal and external carotid arteries. When an unsatisfactory end point is identified in the external carotid artery, it should be corrected with the same sense of concern as a similar finding in the internal carotid artery. 
2	NSAID-induced gastrointestinal damage. A critical review of prophylaxis and therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute diffuse injury to the gastroduodenal mucosa, and also cause chronic focal ulcers that may bleed or perforate without warning symptoms. Acute and chronic lesions are distinct, are pathogenetically different, respond differently to drugs, and require different management strategies. The principal rationale for antiulcer therapy in NSAID users is to prevent or reduce potentially fatal outcomes; to date no evaluated drug meets this criterion for efficacy. Antacids and H2-receptor antagonists, based on open uncontrolled studies, appear to heal both gastric and duodenal ulcers, and maintain them healed during continued NSAID use; larger gastric ulcers show delayed healing with conventional doses of H2-receptor antagonists during NSAID therapy. No such delay occurs with omeprazole therapy. The suggests that if NSAID-associated gastric ulcers are treated with H2-receptor antagonists, larger doses should be given for longer periods. In patients with no pre-existing ulcer disease, H2-receptor antagonists given prophylactically prevent duodenal but not gastric ulcers; sucralfate does the same. In individuals without peptic ulcer disease taking NSAIDs, misoprostol, given as prophylaxis, reduces the development of gastric ulcers; its beneficial effects on ulcer healing or symptoms during continued NSAID therapy, or its ability to prevent duodenal ulcers or ulcer complications, are not established. Because of diarrhea, the 400 micrograms/day dosage is recommended, especially in the elderly. 
2	Gastric duplication cyst communicating with the pancreatic duct: a rare cause of recurrent abdominal pain. A 41-year-old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct. Celiotomy demonstrated a noncontiguous gastric duplication cyst. Internal drainage was curative. 
3	Presentation and management of an acute caffeine overdose. A one-year-old white female ingested approximately two to three grams of caffeine (200-300 mg/kg). The patient survived the ingestion with a maximum caffeine concentration of 385 micrograms/ml four hours postingestion. The child developed ventricular arrhythmias, seizures, metabolic disturbances, and severe pulmonary edema. She survived without apparent long-term sequelae despite having reached a serum caffeine concentration that is the second highest reported level in a survivor. 
5	Laparoscopic cholecystectomy: report of 82 cases. In our initial experience with 82 patients, laparoscopic cholecystectomy has shown numerous advantages over open cholecystectomy. Both intraoperative blood loss and postoperative need for pain medication have been minimal. Most patients were discharged within 24 to 36 hours and resumed normal activities within 3 to 5 days. The aesthetic aspect is also an obvious advantage, since the laparoscopic procedure avoids disfiguring abdominal scars. Previous abdominal surgery is not a contraindication to attempting this procedure. Based on our experience, laparoscopic cholecystectomy can be done safely on most patients who are candidates for open cholecystectomy, including the elderly, the obese, and those with acute gangrenous cholecystitis. 
1	The value of nucleolar organizer regions in uveal melanoma. The Collaborative Ocular Melanoma Study Group. Silver staining of nucleolar organizer regions is an objective method for evaluating the malignancy of a variety of tumors. We studied 126 ciliochoroidal melanomas, three coincidental nevi that occurred in eyes with melanomas, and one magnocellular nevus collected from the Collaborative Ocular Melanoma Study to determine the effectiveness of the silver-stained nucleolar organizer region technique in assessing the malignant potential of these tumors. Malignant lesions demonstrated higher mean silver-stained nucleolar organizer region counts (4.347) than benign nevi (1.855) (P less than or equal to .0001). Among malignant melanomas, mixed-cell melanomas had slightly higher counts than spindle-cell melanomas (P less than or equal to .0001), but this difference was not important clinically. Results were also compared to other histopathologic variables, which disclosed correlation of silver-stained nucleolar organizer regions with mitoses and tumor size. Comparison with computerized cytomorphometric analyses of prognosis also disclosed significant correlation. This technique may prove to be a useful adjunct in the assessment of malignancy and treatment response of uveal melanomas. 
1	The changing face of dermatology out-patient referrals in the south-east of Scotland. A study of out-patient dermatological services (NHS and private) in the south-east of Scotland was carried out by medical staff in the Department of Dermatology in Edinburgh during the month of November 1988. The aim was to assess changes in referral patterns and workload compared with the findings of an identical investigation undertaken in November 1981. Of particular interest were the possible effects of recent publicity campaigns aimed at increasing public awareness about skin cancer. The medical complement of the dermatology department had changed minimally since 1981 and the population increase in the south-east of Scotland over the same period was 1.5%. During November 1988 1592 new patients and 2037 review patients were seen. This represented an increase of 29.2% and 28.3%, respectively, since 1981. The most striking changes in diagnostic groups were a 173% rise in new cases presenting with benign tumours (excluding viral warts) and a 106% increase in new patients with malignant tumours. Viral warts and eczema were, as in 1981, the second and third most common diagnostic categories amongst new patients. There was a 98% increase in the number of surgical procedures performed on new patients compared with 1981. We conclude that the substantial increase in numbers of both benign and malignant tumours and the consequent doubling in surgical treatments was due to increased public awareness and concern about skin cancer. 
1	Caseating hepatic granulomas in Hodgkin's lymphoma. A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver. 
5	Reliability of the clinical and electromyographic examination of tendon reflexes. The reliability of clinical examination of the tendon reflexes was examined by studying inter-observer agreement. Twenty patients were examined by three neurologists. The briskness of the tendon reflexes in arms and legs was scored on a nine-point scale. In 28% of the 160 examined reflexes the observations disagreed 2 scale units or more. Disagreement on the presence of asymmetry occurred in 45% of the 80 reflex pairs. In 15% one observer judged a reflex pair to be symmetrical while another observer found asymmetry of at least 2 scale units. In a second experiment clinical observation of apparently asymmetrical quadriceps reflexes was compared with measurement by surface electromyography. A significant, semi-logarithmic relationship was found between clinical scores and measured reflex amplitudes. Measured reflex asymmetry always agreed with clinical asymmetry, and the magnitudes of right-left amplitude differences were correlated with the magnitude of clinically observed asymmetry. The bedside examination of tendon reflexes is subject to considerable inter-observer disagreement. 
4	Stress and sudden death. The case of the long QT syndrome. The idiopathic long QT syndrome (LQTS) represents a unique clinical example of stress-related sudden cardiac death. LQTS is characterized by the association of several distinctive electrocardiographic features, among which prolongation of the QT interval is the best known, with life-threatening arrhythmias that usually occur under conditions of physical or psychological stress. Effective therapies exist and are represented by antiadrenergic interventions; beta-adrenergic-blocking agents are the treatment of choice. When they fail, left cardiac sympathetic denervation has also proven to be very effective. The latter result suggests a role for alpha-adrenergic mechanisms in the arrhythmias of LQTS. The stressors more frequently associated with syncopal events in LQTS patients include fear, exercise fraught with emotions, swimming, and awakening because of a loud noise. Experimentally, life threatening arrhythmias have been induced during a highly emotional situation in conscious cats with normal hearts in which right stellate ganglia have been ablated, resulting in QT interval prolongation. This selective denervation creates a sympathetic imbalance of the type proposed by one of the pathogenetic hypotheses for LQTS. 
4	Are ioxaglate and iopamidol equally safe and well tolerated in cardiac angiography? A randomized, double-blind clinical study. A randomized, double-blind, parallel-group study was performed in 50 patients undergoing left ventriculography and coronary arteriography to evaluate ECG changes and the effects on left ventricular function of a low-osmolar ionic contrast agent, ioxaglate, as compared with a low-osmolar nonionic contrast medium, iopamidol. Twenty-five patients received ioxaglate (group 1) and 25 patients received iopamidol (group 2). All patients underwent 48 hours of continuous ECG recording beginning 24 hours before the cardiac catheterization. Left ventricular systolic and end-diastolic pressure, peak positive dp/dt, and dp/dt/P ratio were measured immediately before and after left ventriculography and 3 minutes later. Left ventricular systolic pressure did not change after injection of either contrast medium. Left ventricular end-diastolic pressure increased by 30% in group 1 (p less than 0.01) and by 22% in group 2 (p less than 0.01) immediately after left ventriculography. A further increase by 45% in group 1 (p less than 0.01) and by 24% in group 2 (p less than 0.01) was observed 3 minutes later. No differences were observed between values obtained in the two groups. Peak positive dp/dt did not change immediately after injection of either contrast medium but decreased by 5% (not significant) in group 1 and by 7% (p less than 0.02) in group 2 three minutes after left ventriculography. There were no significant differences between the two groups. Analysis of continuous 48-hour ECGs showed that both ioxaglate and iopamidol induced a slight increase (by 8% and 7%, respectively; p less than 0.05) in heart rate during injection with early and complete recovery. 
1	Ovarian metastases are rare in stage I adenocarcinoma of the cervix. Over a 32-year period at the University of California, Los Angeles Medical Center, all cases of adenocarcinoma and adenosquamous carcinoma of the uterine cervix were reviewed to determine the incidence of ovarian metastases in stage I disease. One of 25 patients (4.0%) who underwent an exploratory laparotomy and radical hysterectomy had a microscopic ovarian metastasis. A literature review identified nine additional patients who had ovarian metastases and stage I adenocarcinoma of the cervix. Including our series, the overall reported rate of ovarian metastases is 1.8%. All ten patients had at least one of the following additional characteristics: They were postmenopausal, they had adnexal pathology, or they had positive pelvic lymph nodes. Thus, ovarian preservation is warranted in premenopausal patients who do not have ovarian pathology or evidence of other metastatic disease at surgery. Bilateral oophorectomy may be performed if frozen-section examination of enlarged or suspicious nodes documents metastases. If the ovaries are left in the pelvis at the completion of the surgical procedure and microscopic spread to other pelvic tissues is documented, pelvic irradiation can be administered. 
3	Ventilatory function as a predictor of fatal stroke. OBJECTIVE--To investigate the relation between ventilatory function and subsequent mortality due to cerebrovascular disease. DESIGN--Prospective longitudinal study. SUBJECTS--A total of 18,403 male civil servants aged 40-64 years at entry examination for the Whitehall study. MAIN OUTCOME MEASURE--Mortality from cerebrovascular disease (ICD8 430-438) after 18 years of follow up. RESULTS--In all, 262 men with sinus rhythm at entry died due to stroke during the 18 years of follow up. Compared with men with a forced expiratory volume in one second of greater than or equal to 3.5 litres those with a value of less than 3.0 litres were almost twice as likely to die of cerebrovascular disease (rate ratio adjusted for age and systolic blood pressure = 1.88, 95% confidence interval 1.32 to 2.69). This increased risk occurred within each tertile of systolic blood pressure. Nested case-control analyses were used to control precisely for confounding effects of age, height, and smoking (by matching) and employment grade and physiological risk factors (by modelling). The effect of forced expiratory volume in one second was independent of age, height, smoking habits, employment grade, blood pressure, weight, cholesterol concentration, glucose tolerance, electrocardiographic abnormalities, history of chest pain, and history of intermittent claudication. CONCLUSIONS--Measurements of ventilatory function may assist clinical decisions about whether to treat mild hypertension. Impaired ventilatory function and stroke may share common causes. 
5	Percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections. Operative drainage is the cornerstone of therapy for pancreatic abscess. Recently it has been suggested that successful percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections may serve as definitive therapy. We undertook therapeutic, computed tomography-directed percutaneous drainage in a selected group of 29 patients with infected pancreatic and peripancreatic fluid collections. Twenty-three patients (79%) were successfully treated with percutaneous drainage. Of six patients (21%) representing failures of percutaneous drainage, four died and two recovered after operative drainage. The four patients who died had a mean APACHE (acute physiology and chronic health evaluation) II score of 23 and five of Ranson's prognostic signs. Ranson's signs and APACHE II scores were predictive of success and mortality. We conclude that in selected patients, infected pancreatic and peripancreatic fluid collections can be treated definitively with therapeutic percutaneous catheter drainage. Based on this experience, recommendations regarding patient selection are included. 
3	Temporal lobectomy and independent bitemporal interictal activity: what degree of lateralization is sufficient? We attempted to determine whether the degree of lateralization of independent bitemporal interictal spikes and sharp waves (ISSW) is correlated with good results after temporal lobectomy. Three observers independently counted ISSW in the scalp EEGs of 59 candidates for temporal lobectomy to determine the degree of lateralization of ISSW. Interobserver correlation in percentage of lateralization was excellent (r = 0.92). Thirty-one candidates were also evaluated with depth EEG (DEEG). Operative success was graded by the number of seizures reported in the second postoperative year. There was a significant progressive decrease in the number of good operative results as the degree of lateralization of ISSW lessened (p = 0.0142). Ninety-two percent of patients with greater than 90% lateralization had a good surgical outcome, whereas only 50% with less than 90% lateralization had a good outcome. Even when all DEEG-recorded seizures emerged from the side of the lobectomy, patients with greater than 90% lateralization appeared to have better outcomes than patients with less than 90% lateralization. We conclude that greater than 90% lateralization of temporal ISSW is associated with good surgical outcome, and DEEG may not be necessary in these patients. Less than 90% lateralization is associated with poor surgical outcome and the additional information provided by DEEG may be especially useful in such patients. 
5	Reduction in bleeding after heart-lung transplantation. The importance of posterior mediastinal hemostasis. To reduce perioperative hemorrhage following heart-lung transplantation, several technical modifications were introduced in June 1988 to secure better posterior mediastinal hemostasis. The intraoperative and postoperative use of blood and blood products, as well as the chest tube drainage in the first 24 hours postoperatively, were compared in the seven patients operated on since June 1988 with the nine patients operated on before that date. Significant (p less than 0.05) reductions were demonstrated in the intraoperative and postoperative transfusion of packed cells, in the postoperative administration of fresh frozen plasma, and in the chest tube drainage within the first 24 hours postoperatively. The one-month and total hospital mortality rates were 6 percent and 12.5 percent, respectively. It is concluded that newer techniques to obtain optimal posterior mediastinal hemostasis have significantly reduced blood loss following heart-lung transplantation in our experience and have contributed to our excellent early postoperative results. 
4	US-assisted aspiration thrombectomy: in vitro investigations. The authors describe the use of a new ultrasound (US)-aspiration thrombectomy technique. An oscillating US probe was inserted into a thin-walled, large-bore aspiration catheter. Experiments tested the ability of the new device and other catheter combinations to remove clot material from a Petri dish, as well as from small and large vessel models made of silicone and glass tubes, respectively. Results of the experiments demonstrated that an oscillating 1.0-mm US probe inserted into an aspiration catheter (7-9 F in diameter) promoted clot fragmentation and allowed continuous aspiration of thrombi of any size. When compared with simple large-bore catheter aspiration and with mechanical fragmentation by means of a US probe within a catheter that was flushed to cool the probe, US-assisted aspiration thrombectomy demonstrated significantly better results for percutaneous transcatheter removal of fresh thrombi. 
1	Manometric evaluation of jejunal limb after total gastrectomy and Roux-Orr anastomosis for gastric cancer. Total gastrectomy with Roux-Orr anastomosis is frequently performed for gastric cancer. Since intestinal motility of the Roux limb has never been evaluated after this operation, pressure activity was investigated in the Roux limb of ten patients (aged 51-77 years) who had undergone total gastrectomy and Roux-Orr reconstruction. Investigations were carried out during a 6-h fast and 3 h after a 605 kcal mixed meal. During fasting only two patients had activity fronts and these were abnormal. All ten patients displayed non-propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions. The fed state was characterized by a severely reduced motor activity pattern and other abnormalities. Total gastrectomy with Roux-Orr anastomoses provokes a relatively severe disturbance in intestinal activity. 
5	Gastrointestinal side-effects of octreotide during long-term treatment of acromegaly. Gastrointestinal side-effects of prolonged therapy (greater than 2 yr) with the long-acting somatostatin analog octreotide were studied in 10 acromegalic patients. After 2 yr of therapy, 6 of 10 patients had newly developed gallstones, complicated by cholangitis and jaundice in 1. Serum vitamin B-12 concentrations declined in all 10 patients [from 380 +/- 32 to 172 +/- 21 pmol/L (mean +/- SE); P = 0.023] and became abnormally low in 4. Gastric biopsy specimens, obtained during gastroscopy (9 patients), showed moderate to severe active gastritis, with damage to the superficial and deeper layers of the mucosa in 9 of 9 and focal atrophy in 7 of 9 patients. Campylobacter pylori was found in the antral mucosa in 8 of 9 patients. Although information is lacking on similar studies in untreated acromegalic patients, we suggest that patients receiving chronic octreotide therapy be closely monitored for these and possible other side-effects related to gastrointestinal actions of octreotide. 
4	Concealed entrainment as a guide for catheter ablation of ventricular tachycardia in patients with prior myocardial infarction. Fifteen consecutive patients with drug-refractory, recurrent, sustained, monomorphic ventricular tachycardia and a history of remote myocardial infarction underwent catheter ablation of ventricular tachycardia. Shocks of 100 to 300 J were delivered to sites at which pacing during ventricular tachycardia resulted in concealed entrainment, in which the ventricular tachycardia accelerated to the pacing rate, there was a long stimulus to QRS interval and there was no change in the configuration of the QRS complex during pacing at several rates compared with the configuration during ventricular tachycardia, thus identifying a zone of slow conduction in the reentrant circuit. Concealed entrainment was demonstrated in nine (60%) of 15 patients, and the stimulus to QRS intervals were 90 to 400 ms. At sites of concealed entrainment, the endocardial activation time relative to the QRS complex during ventricular tachycardia ranged from -125 to +50 ms, the timing of the local electrogram relative to the QRS complex was the same during entrainment as during ventricular tachycardia and the pace map during sinus rhythm was discordant with that of the ventricular tachycardia in seven patients. In the six patients in whom a site of concealed entrainment could not be identified, the target site for ablation was selected on the basis of identification of an isolated mid-diastolic potential, activation mapping and pace mapping. The mean (+/- SD) cumulative number of joules delivered to the target site was 306 +/- 140. A successful long-term clinical outcome was achieved in 9 of the 15 patients (mean follow-up 20 +/- 7 months). The clinical success rate was the same whether the target site was selected on the basis of concealed entrainment (five of nine, 56%) or on the basis of the other mapping techniques (four of six, 67%). In conclusion, the responses to pacing suggest that sites at which there is concealed entrainment may be located within a zone of slow conduction in the ventricular tachycardia reentry circuit, although not necessarily in an area critical for the maintenance of reentry. The long-term clinical efficacy of catheter ablation targeted to sites of concealed entrainment is about 60%, similar to the results achieved when conventional mapping techniques are used. 
4	Surgical treatment of renal artery stenosis after failed percutaneous transluminal angioplasty. From 1980 to 1989, 53 patients with renovascular hypertension underwent surgical treatment after initial unsuccessful management with percutaneous transluminal angioplasty. Renal artery stenosis was due to fibrous dysplasia in 17 patients and atherosclerosis in 36. The reasons for failure of percutaneous transluminal angioplasty were inability to dilate the stenotic lesion (32 patients), acute renal arterial occlusion (2) or dissection (8) from attempted percutaneous transluminal angioplasty, and the development of recurrent renal artery stenosis after initially successful percutaneous transluminal angioplasty (11). Three patients underwent nephrectomy due to the finding of a nonviable kidney at operation. Successful surgical revascularization was achieved in 50 patients. There was no significant fibrosis or inflammation around the previously dilated renal artery. Percutaneous transluminal angioplasty necessitated performance of a more complicated revascularization operation in only 1 patient. If the kidney is viable at operation in patients treated by percutaneous transluminal angioplasty renovascular reconstruction is not more technically difficult than when done primarily and the same excellent results can be achieved. 
5	Relationship of drusen and abnormalities of the retinal pigment epithelium to the prognosis of neovascular macular degeneration. The Macular Photocoagulation Study Group. We graded macular features of 127 fellow eyes of participants in the Macular Photocoagulation Study who had an extrafoveal choroidal neovascular membrane secondary to age-related macular degeneration in the first eye and no initial evidence of the neovascular form of age-related macular degeneration in the fellow eye. Our aims were to determine the relationship of drusen characteristics and retinal pigment epithelial abnormalities to the risk of subsequent development of neovascularization in the fellow eye and the risk of subsequent development of recurrent neovascular membranes after photocoagulation in the first eye. Regression analysis demonstrated that the presence of large drusen and focal hyperpigmentation of the retinal pigment epithelium were independent risk factors for the subsequent development of neovascularization in the fellow eye (relative risk, 2.4 and 2.5, respectively). Only 10% of eyes with no large drusen or any retinal pigment epithelial hyperpigmentation compared with 58% of eyes with both large drusen and retinal pigment epithelial hyperpigmentation developed neovascularization in the fellow eye within 5 years. Using multivariate Cox regression analysis, we noted that the risk of developing recurrent neovascular membranes in the first eye was significantly increased when large drusen (relative risk, 2.8) were noted in the fellow eye at the time of laser treatment in the first eye. Fundus features in the fellow eye appear to help identify patients at high risk of developing visual loss from recurrent neovascular membranes following laser treatment in the first eye and from development of a neovascular membrane in the fellow eye. 
4	Putative mechanism of blood pressure reduction induced by increases in dietary calcium intake. An increase in dietary calcium intake lowers blood pressure in spontaneously hypertensive rats and in some patients with arterial hypertension. The mechanisms by which this decrease come about are not clear. A membrane-stabilizing effect wrought by an increase in extracellular calcium would appear unlikely, since the increases in extracellular calcium concentration with increased dietary intake are minimal. Calcium regulatory hormones may be the mediators, and a cybernetic framework has been suggested. Striking defects have been reported in the calcium handling and hormonal household of the spontaneously hypertensive rat. However, a clear cut relationship in terms of a hormonal "template" has not yet been identified in prospective experiments. Data have been presented to show that increased calcium intake has a direct effect on regulatory areas in the brain. However, the mechanisms by which such a response would be mediated are entirely unknown. Increased calcium intake may induce natriuresis. It has been suggested that increased calcium intake helps the "salt sensitive"; however, prospective studies to this effect have not been presented. Increased calcium intake may induce phosphaturia. However, the evidence that blood pressure lowering effects are mediated by phosphate depletion are unconvincing. Some evidence suggests that increased calcium intake may influence local regulatory processes which in turn influences cell integrity and growth. At this point, a unifying hypothesis is not available. However, the clues to various possibilities are intriguing. 
4	Adjunctive use of beta-adrenergic blockers, calcium antagonists and other therapies in coronary thrombolysis. The availability of thrombolytic agents for use in the treatment of acute myocardial infarction is an important step in the management of a common, often debilitating, and potentially lethal disorder. However, despite the proven benefits of coronary thrombolysis, the importance of adjunctive treatment modalities is being increasingly recognized. Beta-adrenergic blockers, calcium antagonists, nitrates, magnesium, and angiotensin-converting enzyme inhibitors each exert favorable cardiovascular properties that may offer additional benefits. Clinical trials combining thrombolytic and adjunctive pharmacologic agents offer hope for further advances in the treatment of acute myocardial infarction. 
3	Right parietal stroke with Gerstmann's syndrome. Appearance on computed tomography, magnetic resonance imaging, and single-photon emission computed tomography. We examined a patient who exhibited Gerstmann's syndrome (left-right disorientation, finger agnosia, dyscalculia, and dysgraphia) in association with a perioperative stroke in the right parietal lobe. This is the first description of the Gerstmann tetrad occurring in the setting of discrete right hemisphere pathologic findings. A well-localized vascular lesion was demonstrated by computed tomography, magnetic resonance imaging, and single-photon emission computed tomographic studies. The patient had clinical evidence of reversed functional cerebral dominance and radiologic evidence of reversed anatomic cerebral asymmetries. 
3	Rett syndrome and the autistic disorders. Rett syndrome is a disorder noted to date only in females and characterized by a pervasive developmental disability following apparently normal early infancy. In addition to gait difficulties, stereotypic hand movements, and loss of communication and purposeful hand skills, autistic-like behavior is an early sign that often results in misdiagnosis. Despite these significant clinical abnormalities, neuropathologic features are modest, and no consistent laboratory abnormality or diagnostic marker has been identified. The current status of research in RS is considered within the context of autism and other disorders in which autistic features may occur, such as the fragile X syndrome. The concept of autism as neurobiologically based behavior is developed. As such, autism is regarded as an umbrella category containing an ever-expanding list of specific disorders. 
5	Altered pattern of calcium kinetics in hemodialysis patients after parathyroidectomy. Six HD patients with severe secondary hyperparathyroidism (sHPT) underwent studies of calcium kinetics prior to and after parathyroidectomy (PTX) with autotransplantation. Postoperatively, patients received vitamin D and calcium supplementation. Before PTX, a markedly elevated bone turnover was found, with increased fluxes of calcium from plasma into the exchangeable calcium pool. This pool was three times larger than normal, indicating a high risk of extraosseous calcifications. Despite a marked fall in parathyroid hormone (iPTH) levels after PTX, bone cell activity was maintained, as indicated by elevated values for Ca retention. Although Ca efflux from plasma into other compartments of the exchangeable pools remained above normal, the size of the total exchangeable calcium pool markedly decreased after PTX, indicating that PTX with autotransplantation, followed by vitamin D therapy, can normalize bone turnover and shift the balance of calcium flux towards mineralized bone. Reduction in the exchangeable calcium pool may explain the clinical finding that extraosseous calcifications regress in some patients after PTX. 
4	Silent ischemia after coronary angioplasty: evaluation of restenosis and extent of ischemia in asymptomatic patients by tomographic thallium-201 exercise imaging and comparison with symptomatic patients. One hundred sixteen patients were evaluated to determine the ability of single photon emission computed tomographic (SPECT) thallium-201 exercise and redistribution imaging to detect silent ischemia secondary to restenosis in asymptomatic patients after single and multiple vessel percutaneous transluminal coronary angioplasty and the findings were compared with SPECT imaging detection of restenosis in symptomatic patients. The value of exercise electrocardiography (ECG) and the amount of ischemic myocardium in symptomatic and asymptomatic patients were determined. Forty-one patients were asymptomatic after angioplasty; 77% of these had chest pain before angioplasty. Seventy-five patients had chest pain after angioplasty; 99% of these had chest pain before angioplasty. Restenosis occurred in 61% of asymptomatic and 59% of symptomatic patients and in 46% of the vessels in both asymptomatic and symptomatic patients. Sensitivity, specificity and accuracy for detection of restenosis by SPECT in individual patients were 96%, 75% and 88% versus 91%, 77% and 85%, respectively, in the asymptomatic versus symptomatic groups (p = NS). Sensitivity, specificity and accuracy for restenosis detection in individual vessels were 90%, 89% and 89% versus 84%, 77% and 84%, respectively, in the asymptomatic and symptomatic groups (p = NS), with similar results for the three major arteries. Sensitivity and accuracy of exercise ECG were significantly less than those of SPECT imaging for the patients with silent (40% and 44%) and symptomatic (59% and 64%) ischemia (p less than 0.001). Restenosis of vessels in the patients with silent and symptomatic ischemia was associated with an equal amount and degree of severity of ischemic myocardium in the two groups. 
1	Intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor causes a cutaneous eruption The intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor to three patients with leukemia who were receiving marrow aplasia-inducing chemotherapy resulted in the development of wide-spread erythematous macules and papules. The course of the eruption paralleled the time of infusion of the granulocyte-macrophage colony-stimulating factor. Skin biopsy specimens taken from two of the eruptions displayed characteristic changes consisting of a variable mixture of granulocytes and lymphocytes, increased number and size of dermal macrophages, mild to moderate epidermal exocytosis, intercellular edema, and rare dyskeratotic keratinocytes. Immunophenotypic analysis of one specimen was notable for keratinocyte intercellular adhesion molecule-1 expression. Administration of the recombinant human cytokine in pharmacologic doses is postulated to induce changes in the immunologic status of the skin, resulting in the expression of a cutaneous eruption. 
3	Stiff-man syndrome: a GABAergic autoimmune disorder with autoantigenic heterogeneity. Autoantibodies that reacted with cell bodies and axon terminals of gamma-aminobutyric acid (GABA)ergic neurons were present in the serum and cerebrospinal fluid in a patient with stiff-man syndrome with type I diabetes. Immunoblot experiments using this patient's serum and cerebrospinal fluid did not corroborate an earlier observation that these autoantibodies are directed against the GABAergic cytosolic enzyme, L-glutamic acid decarboxylase. While L-glutamic acid decarboxylase autoantibodies may be associated with this syndrome, they do not appear to be easily demonstrated. 
4	Experience with in situ saphenous vein bypasses during 1981 to 1989: determinant factors of long-term patency. From 1981 to 1989, 361 consecutive in situ saphenous vein bypasses were performed. Indications for revascularization were critical limb ischemia (n = 335, 93%), popliteal aneurysm (n = 15, 4%), and claudication (n = 11, 3%). Outflow tract was the popliteal artery in 116 (32%) and tibial artery in 245 (68%) of bypasses. At 6 years primary patency was 63% and secondary patency was 81%. During the performance of the in situ bypass procedure, 86 (24%) venous conduits were modified because of a technical failure (n = 49, 13%) or an inadequate vein segment (n = 37, 10%). Secondary patency at 4 years for bypasses requiring modification was 72% compared to 84% for bypasses not modified (p less than 0.05). Atherosclerotic disease of the inflow artery necessitating endarterectomy, patch angioplasty, or replacement lowered primary patency at 3 years (69%) compared to the inflow artery not requiring reconstruction (46%, p less than 0.02). In the follow-up period, 95 (26%) bypasses were revised because of thrombosis or hemodynamic failure. Bypasses requiring revision had a 4-year secondary patency of 68% compared to 88% for bypasses not revised (p less than 0.02). The first 179 cases (1981 to 1985) were compared to the subsequent 182 cases (1986 to 1989). The secondary patency at 3 years for the latter half (92%) compared to the first half (80%) of the experience was significantly improved (p less than 0.02). The secondary patency for bypasses not requiring revision was significantly improved (p less than 0.02) for the latter half (n = 142, 97%) compared to the first half (n = 124, 83%) of the series. Long-term patency with the in situ saphenous vein bypass is dependent on surgical experience, quality of the venous conduit, and atherosclerotic disease of the inflow artery that necessitates reconstruction. Meticulous surgical technique and compulsive bypass surveillance results in superior long-term patency. 
2	Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis. The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach. 
5	Assessment of dilation methods in achalasia: large diameter mercury bougienage followed by pneumatic dilation as needed. In a retrospective study, 33 achalasia patients were treated with dilation therapy using large diameter mercury bougienage (mean, 56 French) and/or pneumatic balloon dilation. Mean follow-up time was 35 months. Mercury bougienage, performed in 20 patients, was successful in 10 (50%) with no complications. Pneumatic dilation was performed as initial therapy or in those having failed previous pharmacologic therapy and/or bougienage. A successful response was achieved in 19 of 23 patients (83%), with a 3.2% complication rate. In addition, in four patients with eventual recurrence of symptoms after initial pneumatic dilation, bougienage was used as a successful alternative to repeat pneumatic treatment. The combined efficacy of both forms of dilation was 88% with a complication rate of 1.4%. These data indicate that mercury bougienage should be considered initial therapy for achalasia in view of its simplicity, safety, and acceptable efficacy, followed by pneumatic dilation if bougienage is unsuccessful. Bougienage also may be considered if eventual recurrent symptoms develop after initially successful pneumatic dilation. Surgery should be utilized only if dilation therapy fails to achieve a satisfactory response. 
1	An unusual epidural, vascular spinal lipoma in a 3-year-old child: a case report and review of the literature. Epidural lipomas are usually benign tumors affecting the spinal cord. We report the unusual presentation of a cervicothoracic spinal lipoma associated with a cervical dysraphism in a young boy. Diagnostic options using magnetic resonance imaging and gadolinium-diethylenetriaminepentaacetic acid are discussed as a pathway to early diagnosis of these and other occult spinal lesions. 
4	Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy The purpose of this study was to investigate the relation between acoustic properties of the myocardium and magnitude of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. An on-line radio frequency analysis system was used to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior free wall in 25 patients with hypertrophic cardiomyopathy and 25 normal age-matched control subjects. The integrated values of the radio frequency signal were normalized for the pericardial interface and expressed in percent. Tissue reflectivity was significantly increased in the hypertrophied ventricular septum, as well as in the nonhypertrophied posterior free wall, in patients with hypertrophic cardiomyopathy (58 +/- 15% and 37 +/- 12%, respectively) compared with values in normal subjects (33 +/- 10% and 18 +/- 5%, respectively; p less than 0.001). Furthermore, measurements of reflectivity of the septum or posterior free wall, or both, were beyond 2 SD of normal values in greater than 90% of the patients and were also abnormal in each of the five study patients who had only mild and localized left ventricular hypertrophy. No correlation was identified between myocardial tissue reflectivity and left ventricular wall thickness in the patients with hypertrophic cardiomyopathy (correlation coefficient r = 0.4; p = NS). These findings demonstrate that myocardial reflectivity is abnormal in most patients with hypertrophic cardiomyopathy and is largely independent of the magnitude of left ventricular hypertrophy. Moreover, quantitative analysis of ultrasonic reflectivity can differentiate patients with hypertrophic cardiomyopathy from normal subjects independently of clinical features and conventional echocardiographic measurements. 
4	Significance of discordant ST alternans in ventricular fibrillation. With the use of epicardial mapping, we investigated the electrical alternans of the ST segment during acute myocardial ischemia and studied the difference in ST alternans between dogs with resultant ventricular fibrillation and those without it. During the 7-minute occlusion of the left anterior descending coronary artery below its first diagonal branch, 60 epicardial unipolar electrograms were recorded simultaneously at 1-minute intervals by a computerized mapping system. ST alternans was found in the eight dogs we observed. The amplitude of ST alternans (difference in the ST segment elevation of two consecutive electrograms) was greater in dogs with ventricular fibrillation (n = 4) than in those without it (n = 4) (3.92 +/- 1.24 versus 0.58 +/- 0.49 mV, p less than 0.05). Three of the four dogs with ventricular fibrillation demonstrated discordant ST alternans (i.e., adjacent leads were out of phase). Results from the present study indicate that an increased amplitude and discordance of ST alternans during acute myocardial ischemia are related to ventricular fibrillation and act as indicators of time and spatial unevenness of ventricular repolarization. 
5	Future needs for ERCP: incidence of conditions leading to bile duct obstruction and requirements for diagnostic and therapeutic biliary procedures. Although the development of endoscopic methods of treatment for biliary obstruction has proceeded rapidly in recent years, endoscopic retrograde cholangiopancreatographic (ERCP) services are patchily distributed. A recent survey by the British Society of Gastroenterology has shown that almost half the district general hospitals questioned did not have a sphincterotomy service available locally. To assess the level of provision required, two investigations have been undertaken. Firstly, an epidemiological study of bile duct obstruction has been carried out in the South Western Region. Secondly, the actual surgical and endoscopic workload in treating obstructive jaundice has been analysed in two health districts. Using present incidence and treatment rates at least 50 ERCPs per 100,000 of the population per year are estimated to be required in the future. Surgical treatment rates can be expected to fall as the number of therapeutic ERCPs increases. The implications of this estimate in equipment and staffing terms are discussed. 
1	Selective catheterization of the inferior petrosal sinuses: new catheter design. Catheters for selective catheterization of the right and left inferior petrosal sinuses have been developed to replace the complex tip-deflector catheter-guide-wire system currently used. The new catheters are easily formed from commonly available straight catheters with the use of steam. They have been successfully tested in 22 patients; the only complications were minor groin hematomas. 
1	Diagnosis of nasopharyngeal carcinoma by means of recombinant Epstein-Barr virus proteins. The immune response of patients with nasopharyngeal carcinoma to Epstein-Barr virus (EBV) antigens is diagnostic of the tumour. Existing tests use EBV antigens produced in EBV-infected lymphoblastoid cells, but the virus replicates poorly in these cells. Serum samples from 18 patients diagnosed as having nasopharyngeal carcinoma were screened by western blot analysis, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence tests for antibodies to the EBV-coded alkaline deoxyribonuclease (DNase), thymidine kinase, and membrane antigen (gp340/220) produced in recombinant baculovirus or bovine papillomavirus systems. Each protein was a useful diagnostic marker for nasopharyngeal carcinoma, although in the gp340/220 ELISAs there was substantial overlap for both IgG and IgA antibodies between serum samples from nasopharyngeal carcinoma patients and those from healthy donors seropositive for EBV. The EBV thymidine kinase was the most sensitive predictor of nasopharyngeal carcinoma; all such samples showed both IgG and IgA antibody responses to this protein and all gave clearly distinct titres from those of the EBV-seropositive donors in the IgA test. Each of the recombinant systems described is suitable for use in large-scale screening programmes for the early diagnosis of nasopharyngeal carcinoma. 
1	Family cancer syndrome: a study of the kindred of a man with osteogenic sarcoma of the mandible. Several familial cancer syndromes have been identified. The syndrome of sarcomas, breast cancer and other neoplasms, known as Li-Fraumeni syndrome, is characterized by several different neoplasms presenting at young ages with autosomal dominant transmission and a high incidence of second primaries. In this paper, we studied six generations (51 people) of the family of a 24-year-old man with osteogenic sarcoma of the mandible. Twelve malignancies in 11 people, including several rare tumors, were revealed. Mean age of presentation was 24 years old. Nine of the 11 patients died of disease. One developed a second primary. Two tumors presented in the head and neck. Transmission was autosomal dominant. The karyotypes of two family members were normal. Identification of Li-Fraumeni syndrome in a family is important in determining appropriate follow-up for the patient and family. Such families are models for studying carcinogenesis. 
1	Colon carcinoma associated with ureterosigmoidostomy. A patient developing a colonic adenoma 38 years following ureterosigmoidostomy is presented. The mechanisms of neoplastic transformation associated with ureterosigmoidostomy is now better understood. This knowledge is being applied to develop modifications both of the surgical technique and the management of patients with this form of urinary diversion, and is a subject of discussion. 
5	Ultrasonography in patients with suspected acute appendicitis: a prospective study. The diagnostic accuracy of high-resolution real-time ultrasonography was prospectively studied in 240 patients admitted to the hospital with suspected acute appendicitis. The criteria for ultrasound diagnosis of appendicitis included a sausage-shaped, aperistaltic, hypoechoic structure when imaged along its longitudinal axis, with a target-like appearance on transverse section. The ultrasonographic findings were correlated with surgical-pathological outcome in 82 cases with proven appendicitis, with laparotomy findings in another 21 patients and with clinical follow-up in the remainder. The overall sensitivity, specificity and accuracy of ultrasonography in the diagnosis of acute appendicitis were 78%, 92% and 87%, respectively. The positive predictive value was 84% and the negative predictive value was 88%. Ultrasonography may significantly improve the diagnostic accuracy in patients with suspected acute appendicitis and should be performed in all patients in whom the clinical diagnosis is equivocal. The ultrasonographic findings must be interpreted in light of the clinical findings. 
1	Adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung. Two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma. No other known precipitants were evident. The adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors. Tumour related blood borne factors may have contributed to lung injury in these cases. 
1	Detection of colorectal liver metastases using intraoperative ultrasonography. Intraoperative ultrasonography of the liver has been carried out in 99 patients undergoing surgery for colorectal cancer. Palpation of the liver, preoperative abdominal ultrasonography and computed tomography scanning were also performed in all patients. Metastases were identified in 26 of the 99 patients (26 per cent). Intraoperative ultrasonography diagnosed more metastases than palpation, abdominal ultrasonography or CT scanning, identifying metastases in 24 of the 26 patients, including six patients in whom the metastases were not detected by any other technique. Identification and localization of impalpable liver metastases is therefore possible using intraoperative ultrasonography. 
4	Proximal posterior cerebral artery occlusion simulating middle cerebral artery occlusion. We describe 12 cases of acute stroke in which clinical features of proximal posterior cerebral artery occlusion simulated the clinical syndrome of middle cerebral artery occlusion. The majority of patients developed contralateral hemiparesis, homonymous hemianopia, hemispatial neglect, and sensory loss or sensory inattention. All 8 patients with dominant hemisphere lesions were aphasic. Accurate diagnosis in each case was achieved only after a head CT, showing occipital lobe, thalamic, and inferomesial temporal lobe infarction. "Cortical" signs are probably explained by thalamic involvement. Recognition of this syndrome has implications for management and prognosis. 
5	Expression of the human papillomavirus E7 oncogene during cell transformation is sufficient to induce susceptibility to lysis by activated macrophages. Human papillomaviruses (HPV), and in particular HPV type 16, are etiologic agents in the development of cervical cancer, which is the second most common form of cancer in women worldwide. Mammalian cells are susceptible to transformation in vitro by the E6 and E7 oncogenes derived from the HPV-16 genome. NIH-3T3 cells transfected with the HPV-16 E7 oncogene were found to exhibit cytolytic susceptibility to murine-activated macrophages. In comparison, E6 oncogene-expressing cells were not susceptible to lysis by activated macrophages. The E7 oncoprotein is multifunctional, being capable of complexing with the retinoblastoma tumor suppressor gene (anti-oncogene) product, stimulating DNA synthesis, and causing cell transformation in vitro. Macrophage killing assays performed on cell lines expressing E7 mutants revealed that the ability to complex the retinoblastoma tumor suppressor gene product and stimulate DNA synthesis did not induce susceptibility to activated macrophages, whereas the ability of E7 to cause transformation was required to induce susceptibility to activated macrophages. These data suggest that cell transformation is a more important prerequisite for inducing susceptibility to activated macrophages than is the loss of tumor suppressor gene function. This study also provides an initial link between HPV-16 oncogene expression and the ability of activated macrophages to selectively recognize and destroy HPV-16-associated neoplastic cells. 
5	A comparison between single and double dose intravenous Timentin for the prophylaxis of wound infection in elective colorectal surgery. A prospective, randomized, single-blind, controlled clinical trial was undertaken to determine whether two doses of systemic Timentin provided superior prophylaxis against postoperative sepsis in elective colorectal surgery compared with a single dose of the same antibiotic. Timentin, a combination of ticarcillin and clavulanic acid was administered intravenously (3.1 g) at the commencement of operation to all patients, and this was repeated after 2 hours in those patients randomized to receive a second dose. The wound infection rate was 11 percent in the 143 patients completing follow-up and receiving a single dose, and 13 percent in the 128 patients receiving two doses of Timentin (P greater than 0.05). The rates of postoperative septicemia 3 vs. 4 percent and intra-abdominal abscess 5 vs. 8 percent were similar. Multivariate analysis of the factors likely to affect postoperative would infection rate demonstrated an association with the type of hospital, public or private, wound infection rate 16 and 6 percent, respectively (P less than 0.01), and the surgeon group defined by the number of patients contributed greater than 25 or less than 25, wound infection rate 6 and 18 percent, respectively (P less than 0.05). We concluded that a single dose of intravenous Timentin was as effective as two doses for prophylaxis against surgical infection and that the surgeon group and the hospital in which the operation took place were statistically significant predictors of postoperative wound infection. 
5	Balloon angioplasty of stenosed Blalock-Taussig anastomosis: role of balloon-on-a-wire in dilating occluded shunts. Six children with cyanotic congenital heart defects, aged 6 to 60 months, underwent percutaneous balloon angioplasty of a narrowed Blalock-Taussig (BT) shunt to improve arterial oxygen saturation. The indication for angioplasty was a cyanotic heart defect not amenable to total surgical correction, either because of the age and size at presentation or because of anatomic complexity, but at the same time requiring palliation of pulmonary oligemia. Following balloon angioplasty, there was an increase in arterial oxygen saturation from 71 +/- 8% to 81 +/- 6% (p less than 0.05). In one child with long segment narrowing, there was no significant improvement in oxygen saturation, and this child underwent an additional BT shunt on the contralateral side. On follow-up 3 to 12 months after balloon angioplasty, the oxygen saturations remained improved (78 +/- 10%) in the remaining five patients. In two children with either complete or almost complete blockage of the BT shunt, we were unable to advance any catheter across the shunt but we were able to advance a 2 or 3 mm balloon on a wire and dilate the shunt, followed by introduction of a catheter carrying a larger balloon for angioplasty. This has permitted us to obtain the pulmonary artery pressure directly (this information was of obvious value in patient management) and resulted in an improvement in the arterial oxygen saturation. It is concluded that (1) balloon angioplasty of narrowed BT shunts is feasible, effective, and safe and (2) even completely occluded shunts can be cannulated and the balloon dilated with the newly available balloon-on-wire devices. 
5	Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Glutamate uptake into nerve and glial cells usually functions to keep the extracellular glutamate concentration low in the central nervous system. But one component of glutamate release from neurons is calcium-independent, suggesting a non-vesicular release that may be due to a reversal of glutamate uptake. The activity of the electrogenic glutamate uptake carrier can be monitored by measuring the membrane current it produces, and uptake is activated by intracellular potassium ions. Here we report that raising the potassium concentration around glial cells evokes an outward current component produced by reversed glutamate uptake. This current is activated by intracellular glutamate and sodium, inhibited by extracellular glutamate and sodium, and increased by membrane depolarization. These results demonstrate a non-vesicular mechanism for the release of glutamate from glial cells and neurons. This mechanism may contribute to the neurotoxic rise in extracellular glutamate concentration during brain anoxia. 
2	Schatzki's ring: long-term results following dilation The purpose of this study is to report long-term results of 61 patients with Schatzki's ring who were dilated for relief of dysphagia. The severity of Schatzki's ring was mild in 28 patients (46%), moderate in 26 (43%), severe in 5 (8%), and indeterminate in 2 (3%). Follow-up information was available in 56 of 61 patients (mean, 75 months). During follow-up, 35 patients (63%) developed recurrent dysphagia and required repeated dilations: 19 patients (34%) had one to two dilations, 9 patients (16%) had three to seven dilations, 6 patients (11%) had more than seven dilations; 1 patient underwent surgery for resection of the Schatzki's ring (2%). The mean (range) dilation-free interval was 50.1 months (11.8 to 100 months) in mild cases, 44.5 months (8.9 to 82 months) in moderate cases, and 28.6 months (9 to 76 months) in severe cases. There was no significant correlation between the severity of Schatzki's ring on initial presentation and the subsequent dilation-free interval. Our data indicate that recurrent dysphagia is common among patients with Schatzki's ring after a successful dilation, and that the severity of Schatzki's ring is not a good prognostic indicator of the need for subsequent dilation. 
5	Isometric features of orthostatic tremor: an electromyographic analysis. A patient is described with "orthostatic" tremor. Electromyography revealed tremor bursts of 15 Hz in the lower extremities while standing and with isometric activation of the muscles, but the bursts disappeared with isotonic activation of muscles. Similar tremor was recorded in the arms with isometric, but not isotonic activation. Review of previously reported cases confirms these findings. The clinical and electrophysiologic features of this tremor distinguish it from other recognized forms of tremor. 
2	Pancreatic function in Crohn's disease. We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease. 
1	Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. BACKGROUND. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS. The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy. 
5	Sarcosaprophagous fly activity in Maryland. Eighty-six successful rearings of sarcosaprophagous flies characteristic of the first successional insect wave of infestation of a corpse were conducted under field conditions in Maryland. Different species were observed to be active during spring and summer. The development times for the immature stages of each species, with the related temperatures at which the development occurred are reported for both seasons studied. 
1	Central nervous system haemangioblastoma: a clinical and genetic study of 52 cases. Fifty two cases of haemangioblastoma were reviewed for their clinical, genetic and prognostic features. Of 34 patients with apparently isolated cerebellar lesions, postoperative outcome was good in 79%. Six isolated spinal lesions presented more insidiously and morbidity was related to incomplete resection. Twelve (23%) of the patients definitely had von Hippel-Lindau disease (VHLD). The true proportion may be higher as this diagnosis was not definitely excluded in many of the remainder; only ten patients with seemingly isolated cerebellar tumours were appropriately investigated and two had evidence of VHLD. Four out of 26 cases (15%) with apparently completely resected, isolated, cerebellar lesions later developed recurrent tumours. Brainstem and supratentorial haemangioblastomas were rare and were always associated with VHLD. The cerebellar or spinal haemangioblastomas due to VHLD had no distinctive clinical features compared with isolated tumours and there was considerable overlap in age of onset between the two groups of cases. All patients with an apparently isolated CNS haemangioblastoma should be investigated for evidence of von Hippel-Lindau disease. 
5	Tracheal and main bronchial disruptions after blunt chest trauma: presentation and management Tracheobronchial disruption is one of the less common injuries associated with blunt thoracic trauma. This injury can be life threatening, however, and failure to diagnose it early can lead to disastrous acute or delayed complications. Nine cases of tracheobronchial disruption in the setting of nonpenetrating thoracic trauma were seen at four Los Angeles trauma centers between 1980 and 1987. Mechanism of injury, presentation, diagnosis, and management of these patients were reviewed. Disruptions involved the trachea in 3 patients, the right bronchus in 5 patients, and the left bronchus in 2 patients. Tracheobronchial disruptions occurred in settings of high-energy impact-type injuries and were more likely to have associated injuries than they were to occur alone. Common presenting signs included subcutaneous emphysema, dyspnea, sternal tenderness, and hemoptysis. Radiographic findings were most commonly pneumothorax, pneumomediastinum, and clavicle or rib fractures. Rigid bronchoscopy and fiberoptic bronchoscopy were both highly accurate methods for diagnosis but only in the hands of trained cardiothoracic surgeons. Delay in diagnosis increased the likelihood of postoperative complications. 
5	Sudden death caused by coronary artery aneurysms: a late complication of Kawasaki disease. The authors describe three cases (two blacks and one Latin American) of sudden death caused by late complications of Kawasaki disease (mucocutaneous lymph node syndrome). At autopsy each heart contained multiple coronary artery aneurysms with luminal stenosis caused by intimal hyperplasia and thrombi. Although virtually all fatal cases of Kawasaki disease occur within six months of the onset of symptoms, there have been other reported deaths up to 14 years after the acute illness. The coronary artery aneurysms of Kawasaki disease may persist and cause death years after the acute illness. 
4	Electrocardiographic J waves after resuscitation from cardiac arrest. A patient was monitored prior to, during, and after cardiac arrest with a Holter monitor and an electrocardiograph. The arrest occurred without any premonitory signs on the ECG. At the onset of the arrest, torsades de pointes ventricular tachycardia occurred, which quickly degenerated into ventricular fibrillation. After a successful second defibrillation, the patient developed Osborn waves, which subsided within a few minutes. 
4	Lobular pattern of choriocapillaris in pre-eclampsia with aldosteronism. We report a case of geographic or mosaic pattern yellowish opaque foci in the left eye of a 36-year-old woman who suffered from severe pre-eclampsia. Though the geographic lesions resulted in chorioretinal atrophy, the mosaic lesion led to no significant atrophy. These two findings were both diagnosed as manifestations of choroidal ischaemia, the former due to choroidal artery occlusion, the latter to transient insufficiency of choroidal circulation, which reflects the lobular pattern of the choriocapillaris. 
4	Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase. A brother and sister with long-standing symptoms of postural hypotension are described. They were considerably worse in the morning, after exercise and in warm weather. In the male, erection was unaffected but ejaculation was prolonged or absent. Both had nocturia, but there were no urinary bladder, bowel or sweating abnormalities. Autonomic function tests confirmed sympathetic adrenergic failure with spared sympathetic cholinergic and intact parasympathetic function. There were no other neurological abnormalities. Noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was elevated. Urinary levels of noradrenaline and adrenaline metabolites were below detection limits, but dopamine metabolites were normal or elevated. Dopamine beta-hydroxylase activity was undetectable in the plasma. Immunohistochemical studies of perivascular cutaneous tissue confirmed normal peptidergic and tyrosine hydroxylase immunoreactivity, with absent dopamine beta-hydroxylase immunoreactivity. The findings were consistent with an enzymatic deficit in the conversion of dopamine to noradrenaline. The parents were clinically and biochemically normal. Treatment of both patients with the synthetic amino acid, d-l-threo-dihydroxyphenylserine, which contains a hydroxyl group and is converted to noradrenaline by dopa-decarboxylase, reduced symptoms and signs of postural hypotension and increased levels of plasma noradrenaline and its urinary metabolites. In the male, ejaculation became possible. Behavioural changes included a feeling of confidence and optimism, with a tendency to be argumentative. The laevo isomer also raised blood pressure and plasma noradrenaline levels. The drug had no direct pressor effects, as its actions were prevented by the dopa-decarboxylase inhibitor, carbidopa. 
5	A 5.3-kb deletion including exon XIII of the protein S alpha gene occurs in two protein S-deficient families. Genomic DNA samples from 12 protein S-deficient families with hereditary thrombophilia were analyzed by Southern hybridization using protein S cDNA probes. Protein S-deficient members of families A and B possessed identical restriction fragment length polymorphisms, which suggest the absence of 5.3 kb from one of their protein S alpha alleles. The abnormal alleles from individuals A7 and B1 were amplified by the polymerase chain reaction using a forward primer in intron K and a reverse primer in exon XIV. The amplified DNA was cloned and sequenced. Sequence comparison with the normal protein S alpha gene showed that most of intron L (roughly 4.7 kb), the entire exon XIII (151 bp), and about a quarter of intron M (407 bp) were missing from both the A7 and B1 clones. Exon XIII contains all three potential N-glycosylation sites in human protein S. This deletion may result in RNA transcripts in which exon XII is spliced to exon XIV. Such an arrangement would generate a stop codon at position 463 and consequently produce a nonglycosylated protein S molecule truncated by 173 amino acids. 
1	Use of a probe to repeat sequence of the Y chromosome for detection of host cells in peripheral blood of bone marrow transplant recipients. In situ hybridization for the Y chromosome (Y-ISH) was used to identify residual host cells in the peripheral blood of 51 recipients of sex-mismatched allogeneic marrow not depleted of T cells following conditioning with high-dose cyclophosphamide and total body irradiation (TBI). One patient who rejected the graft showed rapid reappearance of host cells after transient donor marrow engraftment. Host cells were detected at low levels in 49 of the remaining 50 patients. Host peripheral blood mononuclear cells (PBMC) decreased with time and reached a plateau at 1.0 +/- 0.2% within four weeks after transplantation, while the percentage of host granulocytes (GRAN) reached a plateau at background level. The mean absolute numbers of host PBMC or GRAN were less than 0.015 x 10(9)/L and did not vary significantly over the period studied. Neither the percentages nor the absolute numbers of host PBMC or GRAN were significantly affected by HLA-matching, TBI dose-intensity, pretransplant remission status, subsequent development of acute or chronic graft-versus-host disease or relapse after transplantation. The authors conclude that it is common to find a few residual host cells in the peripheral blood of allogeneic marrow transplant recipients, and the presence of these cells has no clinical significance. 
3	Landau-Kleffner syndrome: a clinical and EEG study of five cases. In five children with normal initial psychomotor development, a Landau-Kleffner syndrome appeared at age 3-7 years. No neuroanatomic lesions were noted. Aphasia and hyperkinesia were isolated in three patients and associated with global regression of higher cortical functions in one patient. Massive intellectual deterioration and psychotic behavior were associated with transient aphasia in one patient. The epilepsy (focal motor and generalized tonic-clonic seizures, subclinical EEG focal seizures during sleep, and atypical absences) always regressed spontaneously or with antiepileptic drug (AED) treatment. The EEG in waking patients showed focal and generalized spike-wave discharges on a normal background rhythm. Discharge topography and pattern changed frequently. During sleep, discharges always increased. At some time during syndrome development, all patients had bilateral spike-waves for greater than 85% of the sleep period, while at other times the discharges were discontinuous or continuous but focal or unilaterally hemispheric. Discharge topography and abundance changed from night to night. The abnormal EEG and the impaired higher functions developed and regressed together, but not with strict temporal correlation. Our own experience suggests that the Landau-Kleffner syndrome and epilepsy with continuous spike-wave activity in slow-wave sleep cannot be clearly differentiated. They may be different points on the spectrum of a single syndrome. 
5	Cardiovascular effects of nicardipine. Nicardipine, a new 1-4 dihydropyridine calcium antagonist, has chemical properties that allow oral and stable intravenous preparations. It is the first intravenous dihydropyridine calcium antagonist available in the United States. Among its drug class it has a unique chemical structure that affords properties useful in the treatment of acute cardiovascular conditions, such as myocardial ischemia, congestive heart failure, hypertension, cerebrovascular disease, and other related disorders. In patients with coronary artery disease, intravenous nicardipine has been found to reduce myocardial oxygen demand by reducing afterload and increasing myocardial oxygen supply through coronary vasodilatation. It enhances left ventricular performance and augments coronary blood flow beyond that required by increased myocardial oxygen consumption. Nicardipine may also offer protection from ischemic injury to the heart and central nervous system. Alone and in combination with other antihypertensive agents, nicardipine has been shown to be effective in the treatment of mild to moderate hypertension. It is safe for use in patients with certain types of conduction disturbances because it does not greatly affect sinoatrial and atrioventricular conduction. Additional advantages for nicardipine's use in the management of acute cardiovascular disorders are its rapid onset and short duration of action. 
3	Synaptic transmission in human neocortex removed for treatment of intractable epilepsy in children. Synaptic transmission to pyramidal cells was studied in slices of neocortex resected from infants and children (n = 10, age 8 months to 13 years) undergoing surgical treatment for intractable epilepsy. Most specimens were from the least abnormal area of the resection. Stable intracellular recordings could be obtained for up to 8 hours. Most of the recorded neurons had electrophysiological characteristics similar to those of regular-firing pyramidal cells and were in layers III to V, which was confirmed by intracellular staining with Lucifer yellow. Local extracellular stimulation evoked a sequence of excitatory and inhibitory postsynaptic potentials. After application of the gamma-aminobutyric acid antagonist, bicuculline (10-30 microM), extracellular stimulation induced large excitatory postsynaptic potentials and epileptiform bursts. Spontaneous bursts occasionally occurred in bicuculline. This effect of bicuculline was observed in all the tissue samples, even those from infant patients (n = 4, age 8-16 months). Kynurenic acid depressed or abolished both spontaneous and stimulation-induced bursts. The competitive antagonist for N-methyl-D-aspartate receptors, DL-2-amino-5-phosphonopentanoic acid decreased the duration of bicuculline-induced bursts. These data provide evidence that, similar to rat and cat neocortex, excitatory and inhibitory amino acids are important transmitters to pyramidal cells in immature human neocortex. 
1	Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia. Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention. 
4	Deep venous thrombosis. Implications after open heart surgery. We reviewed the cases of 10,638 cardiac surgical patients to determine the incidence of deep vein thrombosis (DVT) after open heart surgery (OHS). Seventy-seven patients (0.7 percent) had DVT. Group 1 included 36 patients who had DVT without pulmonary embolism (PE). Occurrence was equal in either leg. Anticoagulation with heparin and warfarin sodium (Coumadin) was employed as treatment. Extension of hospital stay was 10.8 days. Group 2 consisted of 41 patients who experienced PE 9.9 days after OHS. Sixteen patients had known DVT and were receiving heparin. In 25 patients, PE was the first event. Risk factors for PE included perioperative myocardial infarction (16 percent), atrial fibrillation (41 percent); blood type A (70 percent) (p less than 0.05), and coronary artery bypass graft (CABG) (98 percent). Twenty-four patients were treated with anti-coagulation alone. Six died of recurrent PE; mortality was 25 percent. Seventeen patients received anticoagulation plus inferior vena cava (IVC) interruption using a Hunter balloon. There were no recurrent PEs and there was one death from myocardial infarction (6 percent). Deep vein thrombosis and PE are rare complications of OHS. Routine prophylaxis with either heparin or warfarin is unnecessary. Patients with DVT, atrial fibrillation (AF), and perioperative myocardial infarction are at high risk of PE. Aggressive diagnosis to identify major venous thrombi along with anticoagulation and early consideration of IVC interruption are recommended for these patients. Patients who have undergone OHS and who have PE are at an unusually high risk for recurrent PE with death and are more safely treated with IVC interruption and anticoagulation than anticoagulation alone. 
1	Scientific inquiry in childhood cancer psychosocial research. Theoretical, conceptual, and methodologic issues in the investigation and behavioral treatment of procedure-related distress. This paper discusses the current status of scientific inquiry in childhood cancer psychosocial research. The investigation and behavioral treatment of procedure-related distress serves as a model for illustrating and outlining some of the theoretical, conceptual, and methodologic issues and problems that exist in the area of childhood cancer psychosocial research. Specifically, issues related to the process of scientific inquiry, theoretical/conceptual modeling, measurement and assessment, and behavioral treatment strategies are discussed. Examples of how these issues have been addressed in our investigations of procedure-related distress are presented and recommendations for facilitating growth and development in the field of childhood cancer psychosocial research are offered. 
3	Burden: a review of measures used among caregivers of individuals with dementia This paper critiques and discusses 10 measures of burden that have been used with caregivers of individuals with dementia. Current measures target diverse caregiver and care recipient populations, and vary in conceptualization and measurement of burden. Although many measures contain reliability data, relatively few report content validity, convergent/divergent validity, criterion validity, or sensitivity to change. Implications of these limitations for research and clinical practice are discussed. 
5	Spontaneous regression of giant arteriovenous fistulae during the perinatal period. Case report. A unique case of spontaneous regression of giant arteriovenous fistulae during infancy is described in this report. A female infant, the product of normal labor and delivery, demonstrated severe ventriculomegaly and an intracranial hemorrhage at birth. Cerebral angiography at 5 days of age revealed several large fistulae fed by the anterior and middle cerebral arteries draining into the deep venous system through a dilated internal cerebral vein and ectatic vein of Galen. Two days following the angiogram, a second intracranial hemorrhage occurred. Active hydrocephalus developed over the next 6 months and was treated with ventriculoperitoneal shunting. When the child was 8 months of age, angiography failed to demonstrate the fistulae. It was postulated that pressure effects from the intracranial hematoma and long-standing intracranial hypertension as well as stenosis in the anomalous venous outflow resulted in vascular stasis, venous thrombosis, and selective arterial occlusion. Hydrocephalus was a result of the compression of the intraventricular foramina by dilated embryonic vessels. This anomaly, predominantly involving the anterior circulation, may be homologous to the vein of Galen aneurysm in the posterior circulation. 
5	Proliferation and substrate effects on endothelial cell thrombogenicity. The effects of the cellular differentiation status and the adhesive-substrate on endothelial cell function in cell culture were measured with an enzyme based assay of surface thrombogenicity. A solid plastic, microporous polymeric, and fibronectin (FN) treated microporous polymeric were used as substrates for growth of endothelial cells. The microporous and FN treated synthetic substrates have been shown to aid in the induction of cellular differentiation mechanisms. Cells were studied under proliferative and nonproliferative growth conditions. The thrombogenicity of the surface created by the endothelial cell monolayers under various experimental conditions was determined using an enzyme based assay of fibrin deposition. Actively proliferating cells on the solid plastic substrate produced the most thrombogenic surface, while confluent endothelial cell monolayers grown on FN treated microporous substrate were the least thrombogenic surfaces. These data suggest that endothelial cell surface thrombogenicity is under substrate control, and also related to the cellular differentiation status. These findings are being used to design a novel approach to the small diameter synthetic vascular graft problem. 
1	Removal of radiation-induced cataracts in patients treated for retinoblastoma. Experience with removal of radiation-induced cataract in patients treated for retinoblastoma is limited. We retrospectively reviewed the records of 38 patients with retinoblastoma (42 eyes) who underwent removal of radiation-induced cataract from 1973 to 1989. Nineteen eyes (45%) without macular tumors or severe radiation complications had final visual acuities in the range of 20/20 to 20/50. One eye (2.4%) developed a rhegmatogenous retinal detachment and four eyes (9.5%) were noted to have amblyopia after cataract removal. Three eyes (7%) developed retinoblastoma recurrence, one with extension of retinoblastoma into the subconjunctival space through the previous sclerotomy. Exenteration was performed and the patient was alive after 8 years. Cataract removal can be visually beneficial in selected patients with radiation-induced cataracts. 
4	Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin. 
2	Gastrointestinal complications after cardiac transplantation: a spectrum of diseases. Cardiac transplantation has become an accepted treatment modality for end-stage cardiac failure. The gastrointestinal (GI) tract represents a potential source of posttransplant morbidity and mortality. To define the scope of this problem, records of all patients undergoing cardiac transplantation at UCLA between January 1984 and July 1989 were reviewed. In all, there were 120 patients (90 males and 30 females) with a mean age of 45.4 yr. Among them, there were 61 patients (51%) who developed a total of 112 posttransplant GI complications. Of the entire 120 patients, 41 (34%) developed minor complications and 20 (17%) sustained major GI morbidity. Eighteen patients (15%) underwent either endoscopy or surgical intervention. These data suggest that most cardiac transplant recipients will experience some form of GI complication, although most are minor and can be managed conservatively. However, when major, life-threatening complications occur, evaluation and intervention should proceed expeditiously. The gastroenterologist and GI surgeon should play complimentary roles in the care of these complicated patients. 
5	Sex reversal syndrome (XX male). Men who appear normal and live a normal life, may have a 46,XX karyotype and present with the typical features of infertility and end organ (testicular) failure. They are azoospermic and their small testicles show specific patterns on light and electron microscopy. Recent advances in genetics (1) favor the "X-Y interchange" theory to explain this phenomenon; (2) hypothesize about the roles of the H-Y antigen and testis determining factor (TDF) in determining "maleness"; and (3) allow mapping of the relative positions of H-Y and TDF loci on the Y chromosome. 
5	Mechanism of intermittent preexcitation in the Wolff-Parkinson-White syndrome. The concept of electronically mediated conduction across an inexcitable gap. A man with intermittent preexcitation in the Wolff-Parkinson-White syndrome is reported. Once a sinus impulse was blocked in the accessory pathway, the block (ie, loss of preexcitation) was continued for a while until a PP interval reached or exceeded a critical period inducing sudden reappearance of preexcitation. This critical period was considerably longer than the effective refractory period of the accessory pathway. These findings are explained by the use of the concept of electronically mediated conduction across an inexcitable gap in the accessory pathway. It seems that when loss of protection was maintained, the sinus impulse was blocked at the site proximal to the gap, but the impulse passing through the atrioventricular node always reached retrogradely the site distal to the gap, and therefore, the next sinus impulse was blocked again. 
1	Adult T-cell leukemia-derived factor/thioredoxin, produced by both human T-lymphotropic virus type I- and Epstein-Barr virus-transformed lymphocytes, acts as an autocrine growth factor and synergizes with interleukin 1 and interleukin 2. Interleukin 1 (IL-1) has been obtained from the Epstein-Barr virus-infected B-lymphoblastoid cell line 3B6 and shown to be involved in autocrine growth of 3B6 B cells. Independently, adult T-cell leukemia-derived factor (ADF) was purified from human T-lymphotropic virus I-infected leukemic T-cell line (ATL-2) and reported as an interleukin 2 (IL-2) receptor-inducing factor. We have previously reported the same molecular mass, pI, and NH2-terminal amino acid sequence for both 3B6-derived IL-1 and ADF. cDNA cloning of ADF demonstrated high homology with the prokaryotic disulfide reducing enzyme thioredoxin. We show here that ADF and 3B6-derived IL-1 are identical. By RNA blot, 3B6 and ATL-2 cells were shown to contain high levels of 0.6-kilobase mRNA corresponding to ADF. Such message was not detected in resting peripheral blood lymphocytes but could be weakly induced by lymphocyte activation. Antibodies have been raised against synthetic peptides corresponding to the NH2 terminus and the COOH terminus of ADF. Immunoblotting and sequential immunoprecipitation with these antibodies revealed the same 13-kDa protein in 3B6 and ATL-2 cells. Recombinant ADF could sustain growth of 3B6 and ATL-2 cells at low cellular concentration without fetal calf serum; ADF, thus, appears involved in their autocrine growth. Similarly, recombinant ADF could enhance growth of other B-cell lines, including the Epstein-Barr virus-negative Burkitt lymphoma line BL41 and the lymphoblastoid cell lines CRAG8, CRB95, and 1G8. Finally, recombinant ADF exhibits marked synergism with other cytokines, such as IL-1 and IL-2, allowing virally infected lymphocytes to respond to suboptimal amounts of a variety of growth factors. 
1	Scanning acoustic microscopy of neoplastic and inflammatory cutaneous tissue specimens. Acoustic microscopy utilizes high frequency ultrasound to generate microscopic images. The current study was designed to examine representative disorders of the skin by use of a reflective scanning acoustic microscope (R-SAM), and to determine whether the obtainable resolution was sufficient to render a microscopic diagnosis. An Olympus UH3 Scanning Acoustic Microscope was utilized with lenses producing burst wave frequencies at 600 and 800 MHz (600 and 800 million cylces/sec). Cutaneous tissue specimens representing 12 different neoplastic and inflammatory disorders were examined. Acoustic images of unstained sections were compared with conventional light microscopic study of sections stained with hematoxylin-eosin. In most neoplasms examined, it was possible to make a specific diagnosis primarily from low magnification pattern analysis. Although individual cells could be visualized, cytologic atypia was poorly defined. In the inflammatory disorders, a specific diagnosis was possible in all but bullous pemphigoid and lichen planus, because the composition of the inflammatory infiltrate was difficult to determine. The advantages of the R-SAM include the capability of producing an acoustic profile of the tissue and the future possibility of in situ diagnosis. 
1	A rhesus monkey model for sexual transmission of a papillomavirus isolated from a squamous cell carcinoma. Recently we molecularly cloned and characterized a papillomavirus from a lymph node metastasis of a primary penile carcinoma found in a rhesus monkey; this virus species, rhesus papillomavirus type 1 (RhPV-1), is similar to oncogenic human papillomaviruses (HPVs), such as HPV-16 or HPV-18, in that the RhPV-1 DNA was found to be integrated in the tumor cell DNA. To compare the sexual transmission and oncogenic nature of RhPV-1 with these HPVs, we undertook an extensive retrospective study of a group of rhesus monkeys whose sexual mating and offspring histories were known. These animals had mated directly with the index male mentioned above or were secondarily exposed to this virus through intermediate sexual partners. This study combines cytological, histopathological, and several complementary hybridization and DNA amplification techniques on multiple tissue samples to demonstrate the sexually transmitted nature of RhPV-1. The oncogenic potential of RhPV-1 is suggested in several of the infected animals by the presence of various degrees of neoplasia including squamous cell cancer of the cervix. 
2	Omeprazole in the management of intractable esophageal ulceration following injection sclerotherapy. Transient esophageal ulceration is a common finding after sclerotherapy of varices. A small proportion of these ulcers become chronic and resistant to conventional therapy. Such chronic ulcers have been associated with pain, stricture formation, and recurrent hemorrhage. The use of omeprazole, a proton pump inhibitor, was examined in the current study in the treatment of 10 patients (6 women, 4 men; age range, 27-86 years) with cirrhosis (PBC, 4; sclerosing cholangitis, 2; chronic active liver disease, 2; alcohol, 1; and cryptogenic, 1) who developed an esophageal ulcer after a mean of 13 (range, 8-21) sessions of sclerotherapy. The ulcers had been present for 3-54 months despite prolonged treatment with high-dose H2-receptor antagonists and sucralfate. In each case one or more complications had occurred: severe pain in 3, stricture formation in 4, and recurrent hemorrhage in 7 cases. After an 8-week course of omeprazole, 40 mg daily, endoscopy confirmed complete healing of the ulceration in all 10 cases with symptom resolution. In 2 cases the ulcer recurred, with associated bleeding within 6 weeks of discontinuing the treatment in 1 patient. Both cases responded to repeat therapy. These results confirm the efficacy of omeprazole for postsclerotherapy ulceration and imply that acid-pepsin has a role in perpetuating such ulcers. 
5	Concealed entrainment as a guide for catheter ablation of ventricular tachycardia in patients with prior myocardial infarction. Fifteen consecutive patients with drug-refractory, recurrent, sustained, monomorphic ventricular tachycardia and a history of remote myocardial infarction underwent catheter ablation of ventricular tachycardia. Shocks of 100 to 300 J were delivered to sites at which pacing during ventricular tachycardia resulted in concealed entrainment, in which the ventricular tachycardia accelerated to the pacing rate, there was a long stimulus to QRS interval and there was no change in the configuration of the QRS complex during pacing at several rates compared with the configuration during ventricular tachycardia, thus identifying a zone of slow conduction in the reentrant circuit. Concealed entrainment was demonstrated in nine (60%) of 15 patients, and the stimulus to QRS intervals were 90 to 400 ms. At sites of concealed entrainment, the endocardial activation time relative to the QRS complex during ventricular tachycardia ranged from -125 to +50 ms, the timing of the local electrogram relative to the QRS complex was the same during entrainment as during ventricular tachycardia and the pace map during sinus rhythm was discordant with that of the ventricular tachycardia in seven patients. In the six patients in whom a site of concealed entrainment could not be identified, the target site for ablation was selected on the basis of identification of an isolated mid-diastolic potential, activation mapping and pace mapping. The mean (+/- SD) cumulative number of joules delivered to the target site was 306 +/- 140. A successful long-term clinical outcome was achieved in 9 of the 15 patients (mean follow-up 20 +/- 7 months). The clinical success rate was the same whether the target site was selected on the basis of concealed entrainment (five of nine, 56%) or on the basis of the other mapping techniques (four of six, 67%). In conclusion, the responses to pacing suggest that sites at which there is concealed entrainment may be located within a zone of slow conduction in the ventricular tachycardia reentry circuit, although not necessarily in an area critical for the maintenance of reentry. The long-term clinical efficacy of catheter ablation targeted to sites of concealed entrainment is about 60%, similar to the results achieved when conventional mapping techniques are used. 
4	Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens. BACKGROUND. Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas. METHODS AND RESULTS. A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media. CONCLUSIONS. Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty. 
1	Characteristics of erythroleukemia cells selected for vincristine resistance that have accelerated inducer-mediated differentiation. The induction of murine erythroleukemia cells (MELC; DS19/Sc9) to terminal differentiation by hexamethylenebisacetamide (HMBA) is characterized by a latent period of 10-12 hr before onset of commitment to terminal-cell division and increased transcription of globin genes. MELC variants, derived from this parental cell line, selected for resistance to vincristine (VC), can be induced to differentiate with little or no latent period. This study shows that accelerated HMBA-induced commitment is characteristic of MELC with a low level (2- to 5-fold) of VC resistance in four independently derived cell lines. Both resistance to VC and accelerated differentiation are stable phenotypes for at least 50 passages (approximately 5 months) in the absence of VC. Low-level VC-resistant MELC do not display increased levels of P-glycoprotein or mdr1, mdr2, and mdr3 mRNAs, nor do they exhibit cross-resistance to colchicine or doxorubicin. These cells do show (i) increased level of protein kinase C activity, (ii) reduced accumulation of [3H]VC, and (iii) restoration of VC sensitivity in the presence of verapamil. MELC selected for higher levels of VC resistance (approximately 500-fold) do express high levels of P-glycoprotein and the mdr3 gene. During HMBA-induced differentiation, DS19/Sc9 decrease [3H]VC accumulation, but P-glycoprotein content does not change. A VC-transport-associated protein, also critical for the process of induced differentiation, may be constitutively present in VC-resistant MELC, accounting for their enhanced sensitivity to inducer. This protein accumulates by exposure of VC-sensitive cells to HMBA, contributing to their differentiation and decreased level of VC accumulation. 
5	Cortical blindness after coronary angiography: a rare but reversible complication. Transient cortical blindness is a recognized complication after vertebral and cerebral angiography but is a rare event after cardiac angiography. The development of cortical blindness appears to be an adverse reaction to the contrast agent which results in an osmotic disruption of the blood-brain barrier which appears to be selective for the occipital cortex. Patient outcome appears to be generally favorable with return of vision within 24-48 hr. This study describes three patients who had transient cortical blindness after cardiac catheterization and reviews what is known about this unusual problem. 
3	Effects of age on seizure susceptibility in genetically epilepsy-prone rats (GEPR-9s). To study the effect of age on seizure latency, intensity, reproducibility, and mortality in genetically epilepsy-prone rats of the severe colony (GEPR-9s), 472 seizure-naive rats, ranging in age from 14 to 65 days, received a series of three audiogenic stimulations. Both the percentage of rats having one or more seizures and the percentage of seizures that were stage 9 generally increased with advancing age of the animal at the time of the first stimulation. Mean latency to seizure onset decreased while seizure intensity increased with increasing age of the animal. Reproducibility of seizure stage also increased with advancing age of the animal. The effects of senescence on seizure susceptibility were also investigated in an additional 18 prepubescent rats (25-35 days) who received three audiogenic stimulations and were tested again between the ages of 480 and 540 days with identical testing procedures. No significant changes occurred with either latency to seizure onset or seizure intensity in rats tested during prepubescence and again at senescence. Although GEPR-9s provide an excellent model of inherited seizures, latency to seizure onset, seizure intensity, and seizure reproducibility is dependent on age of the animal. Once established, however, audiogenic-induced seizures persist throughout life. 
3	The modified Schollner costoplasty. The modified Schollner costoplasty is a cosmetic procedure for the correction of rib prominence deformity in scoliosis. We present the results of the procedure in 21 patients who had previously undergone spinal fusion for scoliosis. We found the procedure to be well tolerated without major complications. Objective cosmetic improvement was achieved in all but one case. All but one patient considered the procedure to have been of cosmetic benefit. 
4	Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies BACKGROUND. Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. METHODS AND RESULTS. The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. CONCLUSION. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD. 
1	Thymic carcinoma. A clinicopathologic study of 60 cases. The clinicopathologic features of 60 patients with thymic carcinoma were studied. Patients ranged in age from 10 to 76 years (mean, 46), of whom 24 were females and 36 were males. Overall survival at 1, 3, and 5 years was 56.6%, 40%, and 33.3%, respectively. The following morphologic features were correlated with survival: type of tumor margins; presence or absence of a lobular growth pattern; nuclear atypia; necrosis; mitotic activity; and histologic tumor type and grade. Eighty eight percent of patients with poorly circumscribed/infiltrating neoplasms died of their tumors as compared with 16.6% of patients with well-circumscribed neoplasms (P less than 0.0000). Of patients whose tumors had mitotic counts exceeding 10/10 high-power fields (HPF), 84.3% died, as compared with 21.4% of patients with lower mitotic counts (P less than 0.0000). Of patients whose tumors showed lack of lobular growth pattern, 91.6% died, as compared with 29% of those whose tumors had a lobular growth pattern (P less than 0.0000). Finally, 84.6% of patients whose tumors displayed a high-grade histology (lymphoepithelioma-like carcinoma, small cell/neuroendocrine carcinoma, clear cell carcinoma, sarcomatid carcinoma, and anaplastic/undifferentiated carcinoma) died of tumor, as compared with 0% of patients whose tumors were of low-grade histology (well-differentiated squamous carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma) (P less than 0.0000). Evaluation of the various treatment modalities used to treat these patients did not yield any statistically significant correlations with survival. Two clinically distinct groups of patients were identified: one after a relatively favorable clinical course with long survival, and one after a rapidly fatal outcome. The morphologic features of the tumors in these patients correlated well with their clinical behavior; histologic type (and the grade to which it was assigned) constituted the most reliable and important predictor of prognosis. 
5	The role of indium-labelled leukocyte imaging in pyrexia of unknown origin. Indium-111-labeled white blood cell scanning is often used in the investigation of pyrexia of unknown origin (PUO) to locate an otherwise occult source of sepsis. From a series of 166 white blood cell studies performed for sepsis, 28 cases of true PUO were identified and reviewed. The sensitivity was 60% and specificity 70%, with a positive predictive value of 38% and negative predictive value of 90%. Only 11% of studies revealed a pyogenic cause for PUO. These results are discussed and the potential role of gallium scanning in PUO is raised. 
4	Secondary prevention of acute myocardial infarction with beta-blocking agents and calcium antagonists. The discovery that beta blockers possess clinically useful hypotensive, antianginal and antiarrhythmic properties has attracted the interest of clinicians, researchers and the pharmaceutical community alike. In addition, minor differences in a variety of ancillary properties have led to speculation that specific classes of drugs might have advantages over other classes. The enthusiasm that greeted reports from the first small trials, which showed that beta blockers reduced the postmyocardial infarction mortality rate, attracted the commercial support necessary to evaluate different beta blockers in this clinical setting. The plethora of beta blockers that subsequently became available for study led to considerable improvement in both the design and implementation of large clinical trials. Despite apparent discrepancies in the results of various trials, meta-analysis indicates that most, if not all, beta blockers reduce postinfarction mortality. However, because meta-analysis cannot recommend a particular drug or specific dose for use in an individual patient, clinical practice must be based on the results of individual trials, not on the conclusions of meta-analysis. The clinical utility of beta blockers in the secondary prevention of myocardial infarction, coupled with experimental evidence that calcium antagonists reduce infarct size, led to a series of large studies designed to establish whether calcium antagonists have any effect on reducing mortality in patients with myocardial infarction. Lessons learned from the beta-blocker trials permitted a more rapid evaluation of the efficacy of calcium antagonists in this setting. It is clear that, unlike beta blockers, calcium antagonists are not effective in the secondary prevention of myocardial infarction. 
1	How American oncologists treat breast cancer: an assessment of the influence of clinical trials. The present study was designed to assess the preferred methods of treatment of breast cancer by American oncologists, and the impact of clinical trials on their practice. We mailed 465 questionnaires to surgical, radiation, or medical oncologists. The questionnaire described five hypothetic patients with breast cancer, and respondents were asked to select their preferred treatment for each patient. For primary breast cancer, most physicians would offer the choice of local excision followed by radiation therapy or modified radical mastectomy. About 80% of physicians would prescribe adjuvant chemotherapy for a premenopausal woman with estrogen receptor-negative, axillary node negative breast cancer, and for a postmenopausal woman with estrogen receptor-negative, node-positive disease. This policy was favored by male and female physicians of each specialty. Almost all respondents would treat a young woman with inflammatory breast cancer with initial chemotherapy followed by radiation and/or surgery, and about 60% would recommend chemotherapy to a postmenopausal patient with estrogen receptor-negative disease and minimally symptomatic bone metastases. Clinical trials have compared treatment strategies that could be applied to patients described in our questionnaire. Preferred treatments for primary breast cancer, and for inflammatory breast cancer are supported by the results of clinical trials. Recommendation of adjuvant chemotherapy for node-negative breast cancer is not based on a consistent demonstration of improvement in survival, although randomized trials with short follow-up have shown delay to recurrence. Recommendation of adjuvant chemotherapy for a postmenopausal woman with node-positive breast cancer is contrary to the results of large randomized controlled trials (and to a meta-analysis), which have shown that this policy does not lead to improved survival. Our report suggests that even large randomized clinical trials may have a minimal impact on practice if their results run counter to belief in the value of the treatment. 
5	Decreased osmotic stability of dystrophin-less muscle cells from the mdx mouse Human X-linked Duchenne and Becker muscular dystrophies are due to defects in dystrophin, the product of an exceptionally large gene. Although dystrophin has been characterized as a spectrin-like submembranous cytoskeletal protein, there is no experimental evidence for its function in the structural maintenance of muscle. Current hypotheses attribute necrosis of dystrophin-less fibres in situ to mechanical weakening of the outer membrane, to an excessive influx of Ca2+ ions, or to a combination of these two mechanism, possibly mediated by stretch-sensitive ion channels. Using hypo-osmotic shock to determine stress resistance and a mouse model (mdx) for the human disease, we show that functional dystrophin contributes to the stability of both cultured myotubes and isolated mature muscle fibres. 
5	Anaesthetic hazards of aortocaval fistula. A 66-yr-old man was anaesthetized for repair of a suspected ruptured aortic aneurysm. He became deeply cyanosed and suffered two episodes of asystole as the surgeons entered the abdomen. After the aorta was cross-clamped his condition improved markedly and no further problems ensued. Surgical exploration demonstrated intact aneurysms of the aorta and left iliac artery, the former containing a 3-4 cm long aortocaval fistula. The aneurysms and fistula were repaired and his further course was uncomplicated. Potential causes for the cyanosis and cardiac arrest in this patient are discussed. 
1	Idiopathic hypereosinophilic syndrome terminating as disseminated T-cell lymphoma. The authors describe a case of idiopathic hypereosinophilic syndrome (HES) terminated as a T-cell lymphoma in a 3-year-old girl. The clinical course was chronic and characterized by chronic eczema, persistent peripheral blood eosinophilia, organomegaly, interstitial lung change, and pericarditis. Postmortem examination demonstrated a disseminated T-cell lymphoma involving the inguinal lymph node, liver, lung, and kidney. The findings of the current case suggest a possibility that certain abnormalities in this case of idiopathic HES per se may have triggered the development of malignant lymphoma, and it may represent a transition of idiopathic HES into a T-cell lymphoma. Other possible sequences are discussed. The development of T-cell malignancy in idiopathic HES in a girl is quite an unusual presentation. 
3	Brain potentials associated with movement in traumatic brain injury. Brain potentials may be used to assess the functional abnormalities that underlie impairments of movement. The purpose of this article is to illustrate the usefulness of examining these potentials. In addition to an overview of the topic, the article includes a report of a study demonstrating that there were differences between the brain potentials of five patients with traumatic brain injury and those of four healthy control subjects. All five patients were in the postacute phase of hemiplegia. Slow cortical potentials associated with simple goal-directed forearm and finger movements were recorded from frontal and parietal electrodes. Two seconds of movement-related electroencephalographic activity (movement-related potential) were recorded. The patients showed reduced brain potentials for movements associated with their paretic limb and, to a lesser extent, reduced brain potentials for movements associated with their nonparetic limb. The waveforms obtained from the patients were unusual, with uncharacteristic cross-cortical movement-related potential correlations associated with specific electrode configurations, as well as with specific movement conditions. Brain potentials associated with the fore-period interval of a simple reaction time paradigm were later recorded in two of the patients with traumatic brain injury and in a control subject to help determine the functional significance of the relative positivity apparent in their movement-related potential data. This preliminary study indicates that electroencephalographic potentials obtained during the preparation for and execution of movement can provide information regarding the basis for motor dysfunction. 
4	Simultaneous occurrence of mitral valve prolapse and systolic anterior motion in hypertrophic cardiomyopathy. This report describes the simultaneous occurrence of mitral valve prolapse (MVP) and systolic anterior motion (SAM) in hypertrophic cardiomyopathy (HC). In 25 patients (aged 7 to 62 years, mean 29), 15 (60%) of whom were male, distal portions of the anterior or posterior mitral leaflets approached or made midsystolic contact with the ventricular septum, whereas the proximal portion of the mitral leaflets showed marked cephalad excursion into the left atrium, 5 to 15 mm beyond the mitral annular plane. Three mitral valves that were available for gross visual inspection were not morphologically typical of patients with primary MVP. Clinical features and natural history (1 to 14 years [mean 6] of follow-up), cardiac dimensions, and distribution of left ventricular hypertrophy defined in the study patients did not appear to differ distinctly from those in the overall referral population of patients with HC evaluated at our institution. Hence, patients with HC may show a striking pattern of mitral valvular motion involving SAM into the left ventricular outflow tract, as well as MVP; this prolapse motion is probably due to anatomic disproportion between the mitral valve and the small left ventricular cavity rather than to the coexistence of 2 separate disease entities. Such patients further define the great diversity evident within the broad clinical spectrum of HC. 
1	Dissection of the cardinal ligament in radical hysterectomy for cervical cancer with emphasis on the lateral ligament. Surgical experience with carcinomas of the uterus and rectum has provided new insights into the surgical anatomy of a lamina, which separates the paravesical space from the pararectal space. It has been proved that each of the lamina consists of the cardinal and lateral ligaments and pelvic splanchnic nerves, descending in the following order. The cardinal and lateral ligaments, as a connective stalk, insert into the lateral walls of the uterus and rectum extending from the inner aspect of the pelvic wall. Clarification of this structural relationship led to the development of a new procedure for the dissection of the cardinal ligament in radical hysterectomy, while still preserving the lateral ligament. This facilitated systematic dissection of the cardinal and uterosacral ligaments with posterior manipulation, leading to a reduction in blood loss and to prevention of brisk bleeding from the venous plexuses. 
5	Comparative yield of Salmonella typhi from blood and bone marrow cultures in patients with fever of unknown origin. Over three years, a comparative study on 100 selected patients with fever of unknown origin was undertaken to determine the yield of Salmonella typhi from their blood and bone marrow cultures. The results indicate that in patients who had an infection with S typhi the organism was isolated from the bone marrow in all of them and from the blood in only 66%. This suggests that bone marrow cultures may be attempted when blood cultures are negative for bacterial growth after three to four days of incubation. 
5	Radial shortening for Kienbock disease. The cases of twenty-nine consecutive patients (thirty wrists) who had radial shortening for the treatment of stages I through IIIB Kienbock disease were reviewed to assess the results of this procedure. Thirteen patients (45 per cent) had a history of trauma, and all thirty wrists had a negative ulnar variance (average, 2.8 millimeters) on radiographs. All wrists were re-examined after an average follow-up of 3.8 years (minimum, two years). At that time, the pain had decreased in 87 per cent of the wrists. Extension of the wrist had improved an average of 32 per cent; flexion, 27 per cent; radial deviation, 30 per cent; ulnar deviation, 41 per cent; and grip strength on the affected side, 49 per cent. Analysis of the radiographs by computer digitization showed no significant changes in the amount of collapse of the lunate at the latest follow-up. In two wrists, there were complications at follow-up (excessive shortening of the radius and non-union of the radial osteotomy). Radial shortening is an effective treatment for Kienbock disease in wrists that do not have degenerative changes in adjacent carpal joints. Pain, range of motion, and strength can be expected to improve, but the radiographic appearance of the lunate changes little, if any. 
1	Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies [published erratum appears in J Clin Invest 1991 Feb;87(2):757] In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti-mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW-MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma. 
5	Fibrin glue inhibits intra-abdominal adhesion formation. To determine the effect of fibrin glue on intra-abdominal adhesion formation, 45 rats were randomized to three groups. Each animal received two adhesion models. Group 1 received no further treatment. Groups 2 and 3 had the adhesion models covered with fibrinogen from fresh frozen plasma (1.77 g/L) and cryoprecipitate (23.6 g/L), respectively. In group 1, 13 of 15 rats had high-grade adhesions in both models. In group 2, high-grade adhesions were noted in nine of 15 rats in model 1 and in 12 of 15 rats in model 2. In group 3, however, high-grade adhesions were seen in only three of 15 rats in model 1, with 11 rats having no adhesions, and in only two of 15 rats in model 2. Histologic analysis suggested accelerated healing in group 3. We conclude that (1) fibrin glue inhibits intra-abdominal adhesion formation in rats, (2) the inhibitory action is dependent on the fibrinogen concentration of the fibrin glue, and (3) adhesions are reduced by fibrin glue regardless of whether the peritoneal defect is closed. 
5	Deep vein obstruction and leg swelling caused by femoral ganglion. We present a case of a rare ganglion cyst originating from the hip joint and compressing the common femoral vein producing signs and symptoms that mimicked a deep vein thrombosis. Excision of the mass promptly restored normal venous return. This condition has not been previously reported in the English-language medical literature. 
3	Acute pulmonary embolism triggered by the act of defecation. Pulmonary embolism associated with the act of defecation has not been previously well described. Recently, we reported our experience with four patients who presented to us over a 12-month period with syncope, near syncope, or sudden death following the act of defecation. In all four cases, acute pulmonary embolism was shown to be the etiology of the defecation-associated events. A retrospective chart review of all patients with the diagnosis of pulmonary embolism at our institution over a three-year period yielded five additional patients with the diagnosis of defecation-associated pulmonary embolism. These nine patients accounted for 6.8 percent of all patients with a discharge diagnosis of pulmonary embolism seen at our institution during the three-year study period. Six of the nine patients died from their defecation-associated pulmonary embolism. These six deaths accounted for 25 percent of all deaths from pulmonary embolism seen at our institution during the study period. Based on our experience, we suggest that the act of defecation may trigger the development of acute pulmonary embolism in some patients with deep vein thrombosis. 
5	Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria. Two mutations of the porphobilinogen (PBG) deaminase gene resulting in cross-reacting immunological material (CRIM) positive forms of acute intermittent porphyria (AIP) have been identified by in vitro amplification of cDNA and cloning of the amplified products in a bacterial expression vector. Both mutations resulted from G to A transitions in exon 10 of the gene and produced arginine to glutamine substitutions in the abnormal protein. Expression of mutant cDNA in Escherichia coli reveals that one but not the other of these amino acid changes results in a striking decrease of the optimal pH of the mutated enzyme. One or the other of these two mutations accounted for the defect causing AIP in six unrelated patients among the eight patients evaluated with the CRIM positive subtype of this disorder. 
5	Epidural morphine for analgesia after caesarean section: a report of 4880 patients This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated. 
1	Immunohistologic localization of alpha, mu, and pi class glutathione S-transferases in human tissues. Human alpha, pi, and mu class glutathione S-transferases (GSH S-T) have been localized immunohistologically in a variety of organs. Alpha GSH S-T are found principally in hepatocytes, proximal convoluted tubules of kidney, the deep reticular layer of the adrenal gland, interstitial cells of the testis, and oxyntic cells of the stomach. The pi GSH S-T are present in relative abundance in ductular, as opposed to parenchymal cells in the liver, pancreas, salivary glands, and kidney. The presence of mu GSH S-T in the tissues of certain patients and its absence in the same tissues from other patients has been demonstrated. The pi GSH S-T seems to be most persistently and strongly expressed in tumors but alpha GSH S-T are also found in some neoplasms whereas the mu GSH S-T are occasionally present when the other two transferases are weak or absent. 
1	Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells. Human erythroblastic precursor cells adhere to fibronectin (Fn) but the exact nature of the receptors mediating this interaction has not been characterized. In this study, we report data showing that immature human erythroblasts express the integrins VLA-4 and VLA-5 and that both these molecules act as fibronectin receptors on these cells. We have recently demonstrated that adhesion to Fn of purified human CFU-E and their immediate progeny preproerythroblasts was inhibited by antibodies directed against the human fibronectin receptor (VLA-5). Here we have extended those results and characterized by immunoprecipitation with specific antibodies the integrins expressed on surface-labeled normal human immature erythroblasts. A polyclonal antibody recognizing the common VLA beta 1 subunit yielded two polypeptides of 120 and 160 kD. Our data further demonstrate that the polypeptide of 160 kD contains alpha subunits corresponding to both alpha 4 and alpha 5. Thus, erythroblast lysates prepared in 0.3% CHAPS and immunoprecipitated with antibodies which specifically recognize the alpha 4 subunit showed a heterodimer with peptides of 120 (beta 1) and 160 kD (alpha 4) and the additional peptides of 70 and 80 kD which usually coprecipitate with the alpha 4 chain. On the other hand, specific anti-alpha 5 antibodies immunoprecipitated an alpha 5/beta 1 complex with peptides of 120 and 160 kD which under reducing conditions migrated as a single band of 130 kD. Similar experiments performed with an erythroleukemic cell line (KU 812) showed that these cells also coexpress both the VLA-4 and VLA-5 members of the integrin family. Furthermore, monoclonal antibodies recognizing the VLA alpha 4 chain blocked the adhesion of immature erythroblasts to Fn-coated surfaces, thus demonstrating that, as VLA-5, VLA-4 is also a functional Fn receptor on these cells. 
4	Preoperative evaluation and surgical treatment for tricuspid regurgitation associated with acquired valvular heart disease. The Kay-Boyd method vs the Carpentier-Edwards ring method. This study compared the results of annuloplastic repair of tricuspid regurgitation (TR) using Doppler echocardiography. Sixty-three patients who underwent tricuspid annuloplasty were studied. Thirty-four patients received Kay-Boyd annuloplasty and 29 Carpentier-Edwards ring annuloplasty. A new classification of TR based on the direction and area of regurgitation flow on Doppler echocardiogram was applied preoperatively. In the Kay-Boyd group, 10 cases showed massive TR and 24 cases showed localized TR preoperatively. Localized TR was well controlled in all cases, but 8 of 9 cases of massive TR showed grade III residual TR. In the C-E group, 21 cases showed massive TR and 8 cases showed localized TR. All cases were well controlled postoperatively. We conclude that (1) although the Kay-Boyd method is acceptable for localized TR, the C-E method should be employed for massive TR; (2) analyzing the regurgitant pattern of TR by Doppler echocardiogram is useful in selecting an appropriate surgical technique. 
5	Effect of desmopressin acetate on hemorrhage without identifiable cause in coronary bypass patients. After early hopeful reports, the ability of desmopressin acetate (DDAVP) to substantially reduce post surgical hemorrhage has been questioned. A total of 74 elective coronary bypass patients (Group A) receiving DDAVP (0.3 micrograms/kg) who, in the opinion of the operating surgeon, did not achieve adequate hemostasis after protamine neutralization of heparin were studied. They were compared with 91 age- and sex-matched controls (Group B). Before surgery there was no difference in hematocrit (40.8% vs. 40.3%); bleeding time (5.3 vs. 4.9 sec); platelet count (267 +/- 8 vs. 309 +/- 13 X 10(3)/mm3); fibrinogen (363 vs. 361 mg/dl); or activated clotting time (ACT) (168 +/- 4 vs. 163 +/- 3 sec). Both groups had the same number of grafts (3.3/pt), use of the mammary artery (72%), and average bypass time (124 min). There were also no differences in postbypass ACT (142 +/- 3 vs. 135 +/- 2 sec); platelet count (97 +/- 10 vs. 120 +/- 24 X 10(3)/mm3); and fibrinogen (157 +/- 35 vs. 207 +/- 40 mg/dl). However, postoperative hemorrhage was strikingly different: 1306 +/- 89 vs. 896 +/- 33 ml (P less than .0001). Fifteen patients in Group A bled more than 1.5 liters compared with 4 in Group B. Red cell transfusion rates were 1.23 +/- 0.26 for Group A and 0.35 +/- 0.8 for Group B (P less than 0.005). Sixteen Group A patients received additional blood products (plasma and platelets). The hemorrhage difference remained significant even when these patients were excluded (1098 +/- 57 vs. 896 +/- 34, P less than 0.003). Three Group A patients were re-explored without a bleeding source located. 
2	Further study of mucosal repair by sofalcone in experimental gastritis. The effect of sofalcone on the glandular structure and cell proliferation in the gastric mucosa of rats with gastritis induced by the administration of sodium taurocholate (TCA) for 6 months was examined by histoquantitative analysis and [3H]thymidine autoradiography. Morphometric observation revealed that, with TCA treatment, mucosal thickness, parietal cell mass, and the ratios of the length of the glandular portion/total length of the gastric gland were decreased in both the fundic and pyloric glands. Inflammatory cell infiltration and collagenous fiber proliferation were present in the gastric mucosa following TCA and indicated the presence of atrophic gastritis. These atrophic changes and inflammatory cell infiltration were reversed by a 3 week administration of sofalcone. Cellular proliferative activity assessed by the labeling indices of the gastric mucosa increased in TCA-induced gastritis in rats. The administration of sofalcone to rats with TCA-induced gastritis significantly increased labeling indices, particularly in the pyloric glands. From these results, it appears that sofalcone stimulates the compensatory increase in proliferative activity of generative cells, which then may become available to heal the gastritis. 
4	Evaluation of preload reserve during isometric exercise testing in patients with old myocardial infarction: Doppler echocardiographic study. To estimate the preload reserve in response to an increase in afterload in patients with old myocardial infarction, the relation between the Doppler echocardiographic inflow velocity pattern and left ventricular end-diastolic pressure was investigated during isometric handgrip exercise testing. The study population consisted of 16 normal subjects and 40 patients with old myocardial infarction. The 40 patients were subdivided into two groups according to left ventricular end-diastolic pressure at rest: group I (22 patients), less than 18 mm Hg; group II (18 patients), 18 mm Hg or more. At rest, the ratio of peak velocity in atrial contraction phase to peak velocity in early diastolic filling phase (A/E) was significantly higher in the patients with old myocardial infarction than in normal subjects; values in the two subgroups of myocardial infarction did not differ significantly. The A/E ratio and left ventricular end-diastolic pressure increased significantly during exercise in group I. Conversely, the change in left ventricular end-diastolic pressure during exercise in group II was significantly greater than that in group I, and was associated with a decrease in the A/E ratio. Thus, an atrial compensatory mechanism operated effectively in response to the increase in afterload in patients with a normal left ventricular filling pressure, whereas this compensatory mechanism deteriorated in patients with elevated left ventricular filling pressure due to a limited preload reserve. 
1	Rationalisation of follow-up in patients with non-invasive bladder tumours. A preliminary report. The risk of recurrence and progression in 170 patients presenting with pTa urothelial tumours of the bladder has been estimated so that follow-up can be rationalised. Patients were followed up for between 1 and 15 years, the original pathology reviewed and those with carcinoma in situ (CIS) or dysplasia of the background urothelium excluded. Only 5 patients progressed over the whole follow-up period, giving an overall progression rate of 3%. Solitary tumours had an annual initial recurrence risk (AIR) of 0.23 in the first year; after the first year the AIR fell to approximately 0.1 but did not fall significantly in subsequent years up to 8 years. Of the 45 patients with multiple tumours, 32 suffered recurrences within the first year (AIR 0.71). Tumour grade did not influence either recurrence or progression. The results indicate that for solitary pTa tumours, less frequent endoscopic follow-up is justified but some continued surveillance after 5 disease-free years is necessary. The estimated risk of recurrence is a useful factor to consider when planning follow-up. 
4	Sudden death from acute cocaine intoxication in Virginia in 1988. A review of medical examiners' autopsy records revealed that in 1988, 33 residents of Virginia died of acute cocaine intoxication. The subjects were 19 to 45 years old; most were men, used cocaine intravenously, and used other toxic substances with the lethal dose of cocaine. 
1	Expression of the human nephron differentiation molecules in renal cell carcinomas. The authors tested frozen sections from 28 renal cell carcinomas (RCC)--21 clear, 1 eosinophilic, 4 basophilic, and 2 spindle-shaped cell type--with monoclonal antibodies (MAb) reacting against cytokeratin, vimentin, CD24, CALLA/CD10, villin, CD26, and HLA class I and class II molecules. These molecules are markers of specific segments of the mature kidney, and their loss or acquisition reflects the different steps of human nephrogenesis. KI67 MAb was used to evaluate cell-proliferating activity. All RCC cases expressed cytokeratin. Coexpression of vimentin was observed in 21 of 28 cases. Whether of clear or chromophilic type, all tumoral cells strongly expressed CD24 molecule, present on primitive blastema cells. All clear-type RCCs expressed CALLA/CD10 and 60% were also villin positive; some were faintly positive for CD26. CALLA, villin, and CD26 were not detected in basophilic cell type. HLA class I molecules were variably expressed in almost all cases, but HLA class II were never detected on tumoral cells. Except for the spindle-shaped population, cell-proliferating activity was low. These results favor the hypothesis that RCCs derive from cells that have 'recovered' the different options of metanephric differentiation. Clear cells show evidence of maturation toward proximal type, while basophilic cells do not. It would be of interest to evaluate the usefulness of serum measurements of villin and/or CALLA as markers in clear cell-type RCC. 
1	Insulinoma after streptozotocin therapy for metastatic gastrinoma: natural history or iatrogenic complication? Islet cell carcinoma frequently produces more than one chemical product, although its clinical expression is usually restricted to a single hormone. We describe an unusual patient who presented with full-blown metastasizing gastrinoma. He was treated with cimetidine for five years and then streptozotocin therapy, which resulted in a regression in hepatomegaly and a fall in serum gastrin levels. Following one year's therapy with streptozotocin, he was admitted in hyperinsulinemic hypoglycemic stupor. This appears to be the first reported case of a "shift" from clinical gastrinoma to insulinoma possibly related to prolonged streptozotocin therapy. 
1	Locally recurrent endometrioid adenocarcinoma of the prostate after radical prostatectomy. Endometrioid carcinoma of the prostate is considered a variant of classical prostatic ductal carcinoma. Endometrioid carcinoma variant often has the unique clinical presentation of gross hematuria. The propensity of this tumor to spread within the urothelium makes local failure of curative therapy commonplace. We present 2 representative cases with a review of followup surveillance procedures and treatment options for the local recurrence once identified. 
4	Combined aortic and visceral arterial reconstruction: risks and results. The indications, morbidity, and efficacy of combined reconstruction of the abdominal aorta and visceral arteries (renal and superior mesenteric; excluding suprarenal aortic aneurysms) were analyzed retrospectively in 29 consecutive patients who underwent surgery from June 1984 through February 1990. Seventeen men and 12 women ages 32 to 76 years (mean, 66 years) were studied. Follow-up was complete in all patients to either death or calendar year 1989 to 1990 (mean, 31.9 months; range, 2 to 66 months). All patients underwent bypass of angiographically proven severe lesions of one renal artery (19 patients), both renal arteries (8 patients), or the superior mesenteric artery and renal arteries (2 patients), in concert with synthetic distal aortic replacement for occlusive disease (10 patients) or aneurysm (19 patients). Indications for renal artery repair included severe hypertension in 13 patients, ischemic renal insufficiency in 8 patients, and lesion morphology alone in 8 patients. Operative mortality rate was 3 of 29 (10.3%), and each death was the result of multisystem organ failure. Nonfatal complications occurred in 11 of the 26 survivors (42%), and this group differed significantly from the uncomplicated 15 patients only in having a higher mean preoperative serum creatinine (2.5 +/- 1.1 mg/dl vs 1.6 +/- 0.9 mg/dl, p = 0.04, t test). The mortality rate of patients with preoperative serum creatinine greater than or equal to 2.0 mg/dl, was 15.4% (2/13 patients), compared to 6.2% (1/16) in patients with creatinine less than 2.0 mg/dl. Three late deaths occurred (2 stroke, 1 cancer). Hypertension control improved in 64% of patients overall, and in 7 of 9 patients whose major operative indication was renovascular hypertension. Renal function remained stable or improved in 12 of 15 patients (80%) with renal insufficiency, but 3 patients progressed to require dialysis. Long-term graft patency was demonstrated by angiography or on duplex scan in all studied survivors (21 patients). Although operative risks are clearly increased compared to less complex vascular procedures, careful patient selection and management will yield a favorable outcome in most patients with such combined lesions. 
3	Neurologic status of spina bifida patients and the orthopedic surgeon. The purpose of this paper is to review recent developments in the neurologic assessment of spina bifida patients. Determination of the neurosegmental level of the lesion, recognition of spasticity and progressive paralysis, the potential for deformity, and functional expectations are described. The status of the neurologic deficit remains the most important factor in determining the myelomeningocele patient's ultimate functional abilities. Accurate neurologic assessment will assist in meeting the aims of orthopedic management, which include preventing joint contracture, correcting deformity, preventing skin sores, and obtaining the best possible locomotor function. 
4	Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion. We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon. Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium. The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion. Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control). After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control). At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion. By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS). There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium. Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium. Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS). After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively). Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS). 
4	Dissection of the aorta and dissecting aortic aneurysms. Improving early and long-term surgical results. We report the improving surgical results in a consecutive series of 690 patients referred to one of us (E.S.C.) for aortic dissection between December 1956 and September 1989, a substantial portion of whom had dissection as a complication of either previous aortic (n = 113, 16) or previous cardiac (n = 54, 8%) operation. Our initial operation of choice in patients requiring multiple operations in this group of 690 patients was based on the most life-threatening or symptomatic aortic segment involved, which was ascending aorta and/or aortic arch (Asc/Arch) in 301 (44%) patients, descending thoracic aorta (Desc) in 195 (28%) patients, and thoracoabdominal aorta (TaA) in 194 (28%) patients. As detailed below, considerable improvement occurred in the 30-day survival rates over time, particularly for acute dissection: [table; see text] The independent determinants of both early and long-term mortality were identified. Independent determinants of late fatal rupture, reoperation, and neuromuscular dysfunction for distal dissectors were also identified. In our experience, continued aggressive surgical intervention for aortic dissection with modern operative techniques has resulted in markedly improved 30-day operative survival (approaching 95% including those patients with acute dissection) and significant improvement in late results. 
4	Intra-arterial urokinase as the initial therapy for acutely ischemic lower limbs Acute ischemia of the lower limb remains a significant risk to both life and limb. Mortality rates of approximately 10-30% and amputation rates of the same magnitude in the survivors are repeatedly reported despite advances in medical and surgical techniques. Our experience, which utilized percutaneous intra-arterial thrombolysis as the initial treatment in 72 instances (63 patients), has resulted in a markedly lower mortality rate of 1.6% and a lower amputation rate of 8.5% in the survivors. Careful categorization by clinical degree of ischemia indicates that 82% of the cases were either threatened or irreversible limb ischemia. The initial treatment with thrombolysis did not preclude subsequent prompt surgical treatment when necessary; in these cases, thrombolysis promoted improved surgical results (100%) when it was successful. It markedly reduced the need for urgent surgery, usually simplified the subsequent surgical approach, diminished the overall need for surgery, and often accomplished a successful outcome alone (31%). Significant bleeding was not noted during subsequent surgical procedures and was noted in only 2.8% of the cases. Confirmation of these results and further improvements in technique might justify the use of an initially high-dose urokinase transcatheter infusion regimen as the initial treatment of choice for acute lower-limb ischemia. 
5	A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway Major histocompatibility complex (MHC) class I molecules export peptides to the cell surface for surveillance by cytotoxic T lymphocytes. Intracellular peptide binding is critical for the proper assembly and transport of class I molecules. This mechanism is impaired as a result of a non-functional peptide supply factor gene (PSF) in several human mutant cell lines with genomic lesions in the MHC. We have now identified PSF in the MHC class II region by deletion mapping in mutants and chromosome-walking. PSF is homologous to mammalian and bacterial ATP-dependent transport proteins, suggesting that it operates in the intracellular transport of peptides. 
5	Evaluation of ventilating tubes and myringotomy in the treatment of recurrent or persistent otitis media In a prospective controlled study of the efficacy and sequelae of ventilating tubes, 44 children with bilateral recurrent acute otitis media (greater than 6 episodes/year) and 13 children with bilateral persistent middle ear effusion (greater than 3 months) received unilateral ventilating tube insertion in a randomly selected ear. The contralateral ears were randomized to receive either myringotomy alone or no surgery. Clinical, otoscopic, tympanometric and audiologic examinations were performed before the study and 2 to 4 weeks later, then at 3-month intervals for up to 2 years and at 36 months after surgical randomization. Medical therapy and antibiotic prophylaxis were used whenever indicated. While the ventilating tubes remained functional (mean duration, 10 months) the ears with a tube had significantly fewer episodes of otitis media than their contralateral ear (P less than 0.001; 95% confidence intervals -0.7, -1.7) and had more hearing improvement (P = 0.005; 95% confidence intervals, -5.9, -1.2). After tube extrusion there was a tendency for surgically treated ears to have more otitis and worse hearing, but not at a significant level. Tympanosclerosis, retraction and atrophy were more common in ears that received tubes. The majority of ears treated medically also improved. There is need for a more cautious and selective use of ventilating tubes. 
1	Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autografts treatment of childhood acute leukemia/lymphoma with high-risk features. Clinical and pharmacokinetic studies were performed regarding the toxicity of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) with other drugs, in conjunction with a peripheral blood stem cell autograft (PBSCT), for treating 26 children with acute leukemia or lymphoma associated with high-risk features. In the early phase of the study, MCNU (300 to 500 mg/m2) was administered with cytosine arabinoside (Ara-C) (1.6 to 16 g/m2), etoposide (VP-16) (0.8 to 1.6 g/m2), cyclophosphamide (CY) (100 to 200 mg/kg), or busulfan (16 mg/kg). No acute toxicity was noticed after this high-dose therapy. The dose-limiting factor of the regimens was significant but reversible interstitial pneumonitis (IP). In a subsequent trial with an MCNU/VP-16/Ara-C/CY (MCVAC) regimen in which the dose of MCNU was reduced, the risk of IP diminished. This study is still in progress, but the clinical response has so far been encouraging. Fifteen of 26 children are alive and well in unmaintained complete remission (CR) with a median follow-up period of 11 months (range, 3 to 34 months) after transplantation. This MCNU-based regimen without total body irradiation (TBI) is especially important in children to avoid the serious sequelae of irradiation. Our results justify a broader clinical trial to evaluate the effects of the MCVAC regimen followed by PBSCT. 
1	Differentiated thyroid carcinomas in children and adolescents. An analysis of differentiated thyroid carcinomas in children and adolescents revealed that the incidence was 3.05% of total number of patients with differentiated thyroid cancers in all age groups. There was a female preponderance. The incidence of papillary, follicular and papillary with follicular elements was equal. There were no papillary carcinomas observed in children younger than 10 years. The predominant mode of presentation was a solitary nodule of thyroid and some of them had associated cervical adenopathy. A considerable number presented with only cervical adenopathy. The incidence of nodal metastases was 50% at time of presentation and lung involvement was present in 15% of children at the time of diagnosis. Radioiodine treatment was given in 70% of children. Ablation was achieved in 86% of patients given two doses of radioiodine (200 millicuries). The more resistant cases were those with lung and nodal metastases. There was complete ablation in 100% with only residual thyroid tissue, 83% in those with associated nodal metastases, and 57% in those with lung involvement. Average duration of follow-up was 10.3 years (range, 2 to 19 years). Recurrence rate or relapse was observed in 8.5% and was in the regional nodes. There was no recorded mortality due to the disease. 
3	Ocular motor abnormalities from head trauma. Head injuries cause the hospitalization of 200-300 persons per 100,000 population per year. Ophthalmologists provide diagnostic and therapeutic care to those trauma victims with damage to the globe, optic nerve, orbit, and ocular motor system. Eye movements can be affected by damage at any level of the central nervous system or peripheral motor unit. Comprehensive ocular motor assessment of the trauma patient can substantially contribute to the understanding of the patient's injury, recovery, and rehabilitation. This review examines all aspects of head and face trauma that can lead to ocular motility disturbances. 
5	Muscle involvement in the scleroderma syndromes. Muscle involvement was identified in 14 patients with scleroderma or a connective tissue disease overlap syndrome with predominant features of scleroderma. Patients presented with symmetrical proximal weakness indistinguishable from other inflammatory myopathies. Creatine kinase and electromyography were useful to demonstrate muscle involvement. Muscle histopathology demonstrated primarily the vasculopathy of scleroderma or polymyositis in similar numbers of patients. Scleroderma vasculopathy and polymyositis generally occur without specificity to diffuse scleroderma, the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia syndrome, or an overlap syndrome with arthritis. Polymyositis also occurs when the vasculopathy of scleroderma involves other organ systems. 
1	Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group. A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life-threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further. 
5	Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PET data correction for atrophy. Part II. Aging and Alzheimer dementia A new, computerized segmentation technique, in which magnetic resonance (MR) imaging produces accurate volumetric measurements of brain and cerebrospinal fluid (CSF) without the limitations of computed tomography, was used in a retrospective analysis of digitized T2-weighted MR images of 16 healthy elderly control subjects and 16 patients with Alzheimer dementia. Ventricular and extraventricular CSF was quantified, and the effects of aging were studied; in both groups, the atrophy measurement was used to correct metabolic values obtained with positron emission tomography. Patients with Alzheimer dementia had higher total CSF; extraventricular, total ventricular, and third ventricular CSF volumes (49%, 37%, 99%, and 74%, respectively); and 7% lower brain volumes than the control group. The patients also showed a more marked decline in brain volumes and a greater increase in CSF volumes with advancing age than the control group. They had a 25.0% increase in corrected whole-brain metabolic rates; the control group had only a 15.8% increase. The use of this technique may provide a basis for further studies of aging and dementia, including regional volume analysis. 
1	Effect of prostaglandin E in multiple experimental models: V. Effect on tumor/host interaction. Prostaglandin E (PGE) has long been incriminated as a cause of the immunosuppression seen in cancer patients and for the increased rates of tumor growth due to the impairment of the immunologic response to the tumor. We have investigated the effect of PGE on tumor-host interaction by utilizing a parenterally administered long-acting PGE derivative, 16,16-dimethyl-prostaglandin E (dPGE). Administration of dPGE was found to decrease the rate of tumor growth but at a cost of decreasing tumor-free body mass. The dPGE did not alter resting metabolic rates but did alter some parts of brain dopamine metabolism and significantly decreased the serum level of multiple amino acids. In conclusion, elevated PGE levels may significantly alter metabolism in tumor patients. 
3	Auditory brain stem implant: effect of tumor size and preoperative hearing level on function. The auditory brain stem implant is an investigational device designed to provide hearing sensations to patients without functioning auditory nerves. We analyzed results from 17 implants in 15 patients to determine if tumor size or preoperative hearing level might be related to proper device function. We found no significant correlation between preoperative hearing level or tumor size and device function. We also found no significant correlation between preoperative hearing level and tumor size in these 15 patients. 
4	Prosthetic above-knee femoropopliteal bypass for intermittent claudication. There is no consensus about the most appropriate management of the patient with intermittent claudication due to a superficial femoral artery occlusion. To evaluate the natural history of prosthetic above-knee femoropopliteal (AKFP) bypass, 200 operations for intermittent claudication were reviewed. One hundred AKFP bypasses were done with PTFE and 100 with dacron. In the 30 day postoperative period, four PTFE and three dacron grafts occluded without consequence and only one patient died. Analysis of results by the life-table method demonstrated statistically similar primary graft patency rates at five years (PTFE 65% SE +/- 6.5, dacron 57% +/- 6.2) and ten years (PTFE 31% +/- 18/9, dacron 32% +/- 13.2) (p greater than 0.10). Redo procedures (e.g., thrombectomy, angioplasty) were necessary on 21 grafts (12 PTFE, 9 dacron) and "secondary" patency rates at five years were 76% PTFE and 62% dacron; no grafts which required a redo procedure were patent at ten year follow-up. Major amputations during ten year follow-up were necessary in 16 (8%) patients; all amputations were in diabetic patients. Survival rates were 79% at five and 42% at ten years. An anticipated, the leading cause of death was cardiac related (25 patients); 28 (14%) patients underwent aortocoronary bypass during follow-up. A prosthetic AKFP bypass graft is a safe and durable operation which provides relief from the symptoms of intermittent claudication while allowing for the preservation of the saphenous vein for use later in the coronary or infrapopliteal circulations, should the need arise. These results indicate that the risk of amputation after AKFP is no greater than the natural history of untreated claudication; however, AKFP offers a significant improvement in life-style. 
2	Alcoholic liver disease. Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease. 
1	Intravesical condyloma acuminatum with progression to verrucous carcinoma. Condyloma acuminatum is a common form of venereal disease. Most patients with condylomata acuminata suffer from only the local cosmetic and irritative effects of the lesions. Few patients have progression to aggressive, regionally distributed lesions that can be life-threatening. We describe a forty-three-year-old white woman who had a seventeen-year history of scleroderma with extravesical and intravesical condylomata acuminata. During two years of conservative management with transurethral excision, electrocoagulation, and intravesical chemotherapy, the disease progressed to involve the entire bladder and resulted in obstructive renal insufficiency that required anterior exenteration and urinary diversion. The natural history of the disease is described, and the relevant literature is reviewed. 
4	Malignant thymoma presenting as intracardiac tumor and superior vena caval obstruction. A case of malignant thymoma with intracardiac infiltration and intrinsic superior vena caval obstruction due to the tumor is reported. Intracardiac invasion by a thymoma is rare and for this reason is believed worthy of a report. 
5	Tracheoplasty for congenital long-segment intrathoracic tracheal stenosis. Congenital long-segment intrathoracic tracheal stenosis (CTS) is a rare life-threatening obstruction in infancy and childhood. From July 1983 to March 1988 six infants aged 14 days to 14 months with CTS were identified. Symptoms ranged from recurrent stridor and wheezing to severe respiratory compromise and hypercarbia. Routine chest x-rays were not diagnostic. Definitive diagnosis was made by bronchoscopy, which showed complete tracheal rings in all patients with severely compromised tracheobronchial lumens. In three patients, pericardium was successfully used for anterior tracheoplasty with one early death due to fulminant sepsis in an infant with undiagnosed sickle cell disease. The other two died late, at 3 and 9 months from problems unrelated to the repair. In three patients a rib graft was used for repair; in one, tracheoplasty was required after earlier repair of tetralogy of Fallot. All are late survivors with no postoperative symptoms. After recognition of CTS, prompt surgery is warranted to avoid the late complications of tracheostomy for long-term ventilatory support. Rigid repair with rib cartilage is preferable to use of pericardium. Proper rib harvesting with intact perichondrium, intraoperative bronchoscopy, oxygenation by cardiopulmonary bypass, and meticulous graft alignment are necessary for successful postoperative outcome. 
5	Hydrocephalus: overdrainage by ventricular shunts. A review and recommendations. Selected literature review of the clinical course of patients with ventricular shunts for hydrocephalus shows that the effects of cerebrospinal fluid overdrainage are subdural hematoma, craniosynostosis, slit ventricle syndrome, and low intracranial pressure syndrome. These occur sequentially at different age groups, but approximate averages of incidence and time of occurrence after first shunt reveal an overall incidence of 10%-12% for at least one of these appearing at 6.5 years after shunting. The basic etiology, diagnosis, and variety of treatment modalities available are reviewed, including the need for shunt closing intracranial pressure control. Included is a hydrocephalus program designed to minimize the need for long-term extracranial shunts and to maximize therapeutic intracranial procedures for hydrocephalus. 
5	Malnutrition and carbohydrate malabsorption in children with vertically transmitted human immunodeficiency virus 1 infection. The nutritional needs of children with human immunodeficiency virus infection are poorly understood. Twenty-eight children with vertically transmitted human immunodeficiency virus infection were evaluated for carbohydrate malabsorption using lactose hydrogen breath tests and d-xylose absorption studies. Lactose malabsorption was a common finding in human immunodeficiency virus-infected children and occurred in 8 of 20 patients who had no identifiable enteric pathogen. Lactose malabsorption occurred at an earlier age in human immunodeficiency virus-infected children than in an age-matched group of 45 symptomatic control children (P = 0.02). However, lactose malabsorption was not associated with higher rates of diarrhea or growth failure. Abnormalities in d-xylose absorption were not significantly associated with either diarrhea or growth failure. However, 39% of d-xylose studies (9 of 23) showed abnormal results and were significantly associated with enteric infections (P = 0.004). Abnormalities in small-bowel morphology were found in 4 of 9 children with growth failure, 3 of whom had an enteric infection and low d-xylose absorption. Lactose hydrogen breath testing and d-xylose testing showed carbohydrate malabsorption in 61% of children (17 of 28). This study demonstrates that human immunodeficiency virus-infected children are at risk for malabsorptive disorders, which are not always related to clinical symptoms. We speculate that human immunodeficiency virus may be directly involved in the development of lactose malabsorption. Carbohydrate malabsorption in human immunodeficiency virus-infected children may not be the only factor responsible for growth failure. 
5	Renal carcinoma in a solitary kidney. We studied the clinical and pathological features of 26 patients with renal carcinoma of a solitary kidney, including 6 treated at this hospital. Four patients had a contracted kidney and 22 had previously undergone nephrectomy. Partial nephrectomy was performed in 16 patients, enucleation of the tumour in 5 and radical nephrectomy in 5 because of the size of the tumour. Ex vivo surgery was carried out in 4 patients. The duration of ischaemia ranged from 15 to 365 min but was longer in those who underwent ex vivo surgery (149 to 365 min). Of the 21 patients who underwent partial nephrectomy or enucleation, the serum creatinine level increased (greater than or equal to 2.0 mg/dl) post-operatively in 16 patients, of whom 9 required temporary haemodialysis. No recurrence has been noted in those who underwent partial nephrectomy, but 1 patient who underwent enucleation of the tumour developed a solitary pancreatic metastasis 2 years 6 months after surgery and was treated by a partial pancreatectomy. Kidney-preserving surgical procedures are considered to improve the quality of life, but careful follow-up is necessary. 
5	A strategy to reduce infant mortality. Using maternal mortality reviews as an historic model, fetal and infant mortality reviews are proposed to reduce infant mortality in the United States. The national program has three elements: 1) guidelines and direction from a national multidisciplinary steering panel and staff, 2) a technical advisory capacity to translate guidelines and to work with local and regional review committees, and 3) local review committees. A special emphasis, lacking in the limited efforts of previous infant mortality reviews, would be given to fetal mortality. The plan proposes a broad classification of potential contributing causes of mortality, from those related strictly to medical care, to the health system, and to individual patient factors. This will allow different and more effective targeted responses to factors identified locally. Critical impetus will be gained with The American College of Obstetricians and Gynecologists leading the effort from the private medical sector in partnership with national, state, and local public health agencies and other national medical societies. 
1	Terminal cancer care and patients' preference for place of death: a prospective study. OBJECTIVE--To assess the preference of terminally ill patients with cancer for their place of final care. DESIGN--Prospective study of randomly selected patients with cancer from hospital and the community who were expected to die within a year. Patients expected to live less than two months were interviewed at two week intervals; otherwise patients were interviewed monthly. Their main carer was interviewed three months after the patient's death. SETTING--District general hospital, hospices, and patients' homes. MAIN OUTCOME MEASURE--Stated preferred place of final care; actual place of death; reason for final hospital admission for those in hospital; community care provision required for home care. RESULTS--Of 98 patients approached, 84 (86%) agreed to be interviewed, of whom 70 (83%) died during the study and 59 (84%) stated a preferred place of final care: 34 (58%) wished to die at home given existing circumstances, 12 (20%) in hospital, 12 (20%) in a hospice, and one (2%) elsewhere. Their own home was the preferred place of care for 17 (94%) of the patients who died there, whereas of the 32 patients who died in hospital 22 (69%) had stated a preference to die elsewhere. Had circumstances been more favourable 67% (41) of patients would have preferred to die at home, 16% (10) in hospital, and 15% (9) in hospice. CONCLUSION--With a limited increase in community care 50% more patients with cancer could be supported to die at home, as they and their carers would prefer. 
5	Surgical indication and significance of portal vein resection in biliary and pancreatic cancer. Tumor and vascular resection was carried out in 27 patients with biliary and pancreatic cancer. Vascular resection included resection and reconstruction of the both the portal vein and hepatic artery in two of the patients. Portal vein resection only was carried out in 23 patients, and resection of the side wall and plasty of the portal vein was carried out in the other two patients. The technical limit of portal vein resection without graft was 4 cm in the hepatic hilus and 7 cm after total pancreatectomy or pancreatoduodenectomy without grafts. On temporary occlusion of the portal vein between resection and reconstruction, simple occlusion was sufficient if it occurred within 30 minutes. In occlusion of more than 30 minutes, simultaneous occlusion of the superior mesenteric artery is better to prevent congestion of the intestine. If occlusion of more than 60 minutes is anticipated, a bypass between the superior mesenteric vein and the femoral vein with Anthron tube is recommended. The postoperative course was uneventful in 20 of the 27 patients. Two patients died within 1 month after surgery. The mortality rate for this aggressive surgery was 8.4%. Minor complications such as hydrothorax, small bile leakage, and localized abscess were observed but soon subsided in five patients. Fourteen of 27 patients survived or are alive after more than 1 year, and 9 of 14 patients survived or are alive after 2 years. Forty-seven percent of the patients who had no lymph node metastasis or peritumor lymph node metastasis without cancerous invasion of the portal vein intima survived more than 2 years. The longest length of survival of a patient with nonfunctioning islet cell carcinoma of the pancreatic head was 5 years 9 months. The longest surviving patient with ductal cell carcinoma of the pancreas is still living after 4 years. This approach is recommended in certain patients with vascular involvement but without lymph node metastasis or those patients with only peritumor lymph node involvement. Frozen section of mesenteric and paraaortic nodes should be standard practice before this aggressive resection. 
5	Wound infection following early repeat sternotomy for postoperative bleeding. An experience utilizing intraoperative irrigation with povidone iodine. A prospective observational study of median sternotomy wound infection was carried out in two consecutive groups of unselected patients undergoing early repeat sternotomy for postoperative haemorrhage. In Group A the pericardial cavity and sternotomy wound layers were irrigated with aqueous povidone iodine prior to repeat closure, while Group B did not receive povidone iodine. No median sternotomy infections were recorded in Group A compared to 5 cases in Group B (0 out of 22 vs 5 out of 21 patients, p less than 0.05). Amongst the patients with wound infection, three developed sternal dehiscence and mediastinitis with one death. The data suggests that povidone iodine irrigation may be effective in reducing wound infection in patients undergoing early repeat sternotomy after cardiac surgery. 
1	Early diagnosis of breast cancer. Universal screening is essential. Breast cancer strikes 1 in 10 women in the United States. Early diagnosis of breast cancer improves chances of survival. With universal screening and expert evaluation of early clinical signs and symptoms of breast cancer, mortality rates can be reduced by 30% to 40%. Physicians can help achieve this goal by taking an active role in patient education and promoting the availability of affordable screening mammography. 
5	Long-term effect of dopaminergic drugs in restless legs. A 2-year follow-up. Thirty patients with restless legs syndrome, who initially had all responded well to treatment with levodopa and benserazide, were studied as to the long-term effect of the drugs (at least 2 years). During the 2-year period, two patients were switched from levodopa to bromocriptine. Two patients no longer needed levodopa; one of them had developed paraplegia and in the other the symptoms of restless legs syndrome had disappeared completely. The remaining 26 patients continued to use levodopa. Eight patients maintained the original dose, nine had to use an increased dose, and nine found a decreased dose to be sufficient. The only side effect was transient nausea reported by two of the 30 patients. The study showed that the relief of symptoms of restless legs syndrome by dopaminergic drugs does not wear off with the passage of time, that side effects are minimal even with long-term use, and that the dose needed to obtain relief may increase as well as decrease. 
1	New primary basal cell carcinomas arising in skin flaps following Mohs micrographic surgery for primary and recurrent basal cell carcinoma. Two patients developed new primary basal cell carcinomas (BCCs) in skin flaps used to reconstruct wounds that followed an earlier primary BCC and a recurrent BCC treated by Mohs micrographic surgery. Criteria for distinguishing a new primary BCC arising in a skin flap or full-thickness skin graft at a previous treatment site for BCC from a truly recurrent BCC are presented. The distinction between a new primary BCC and true tumor recurrence is important for accurate clinical assessment and may have a dramatic impact on the type of subsequent treatment. In addition, there may be less medicolegal liability in the case of a new primary BCC arising at the site of a previously treated BCC than for a BCC that is determined to be recurrent. 
1	Collagen metabolism in gynecologic patients: changes in the concentration of the aminoterminal propeptide of type III procollagen in serum. We have previously found the serum concentration of the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, to be increased in advanced ovarian cancer. In this study we measured the serum aminoterminal propeptide of type III procollagen concentration in healthy women during the menstrual cycle and in patients with salpingo-oophoritis, leiomyomas, endometriosis, and benign ovarian tumors. The concentration was higher in the luteal phase than that in the follicular phase, suggesting an association of collagen metabolism with ovarian steroid hormones. Severe salpingo-oophoritis increased the serum level of the aminoterminal propeptide of type III procollagen with a decrease to normal during recovery. Elevated values were occasionally seen in endometriosis and leiomyomas. These findings indicate that the aminoterminal propeptide of type III procollagen is a relatively unspecific indicator of ovarian carcinoma. 
1	Pharyngeal adenocarcinoma with intestinal features. A high grade adenocarcinoma arising primarily in the pharynx of a 67-year-old man is presented. A CT-scan revealed a tumour mass growing in the pharynx, largely affecting parapharyngeal soft tissues. Lymph node metastases were found at clinical presentation. Both morphological and immunohistochemical studies displayed similar features to those of intestinal origin. To our knowledge, no previous examples of such neoplasm have been reported at this site. Its possible histogenetical origin is discussed. 
5	The evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. Digoxin intoxication has been reported to be a common adverse drug reaction with an in-hospital incidence of 6% to 23% and an associated mortality rate as high as 41%. A retrospective review was conducted to assess the accuracy of diagnosis, the morbidity and mortality of digoxin intoxication, and its incidence in hospitalized patients with heart failure. We reviewed the medical records of 219 patients discharged with the diagnosis of digoxin intoxication between 1980 and 1988. Patients were classified as follows: (1) Definite intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication that resolved after discontinuation of digoxin; (2) possible intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication in the absence of documented resolution after discontinuation of digoxin, or the presence of other clinical illnesses that could possibly account for those findings; (3) no intoxication--patients whose symptoms or ECG abnormalities were clearly explained by other associated clinical illnesses and persisted after withdrawal of digoxin. We identified only 43 patients (20%) with definite intoxication. The majority of patients discharged with the diagnosis of digoxin intoxication (133 or 60%) were classified as possibly digoxin intoxicated, and 43 patients (20%) had no clinical evidence to support this diagnosis. To estimate the incidence of digoxin intoxication, we also reviewed the medical records of 994 patients admitted in 1987 with heart failure. Of these, 563 were receiving digoxin and in 27 the diagnosis of digoxin intoxication was made by their clinicians. Our review showed that only four were definitely intoxicated (0.8%), and the diagnosis could not be excluded in another 16 (4%). 
1	Normal and abnormal pituitary glands: gadopentetate dimeglumine-enhanced MR imaging. Dynamic magnetic resonance (MR) imaging with a 1.5-T superconductive unit was used in the evaluation of nine normal pituitary glands and 10 pituitary adenomas, including four microadenomas and six macroadenomas. Seven to 10 images were obtained every 20-30 seconds with use of the spin-echo technique after rapid injection of gadopentetate dimeglumine. The earliest contrast material enhancement of normal structures was seen in the infundibulum and posterior lobe of the pituitary gland at 20 seconds, followed by gradual contrast material enhancement of the anterior lobe of the pituitary gland from the junction of the infundibulum to the peripheral portion of the anterior lobe of the pituitary gland within 80 seconds after gadopentetate dimeglumine injection. The peak enhancement of pituitary adenomas occurred at 60-200 seconds, usually after the most marked enhancement of the normal pituitary gland. Microadenomas are best visualized at earlier phases of gadopentetate dimeglumine-enhanced dynamic imaging, with signal intensity lower than that seen on images of normal pituitary glands. 
5	Laryngomalacia in children. Two hundred three (68 percent) of 297 children with laryngomalacia had associated respiratory disorders by flexible fiberoptic bronchoscopy (FFB). Associated disorders included congenital respiratory anomalies, a variety of anatomic obstructions of the upper and lower airways, and aspiration disorders. Mean age for isolated laryngomalacia (type 1) was 11.5 weeks (range, 5 weeks to 4 months) while children with laryngomalacia and associated respiratory disorders (type 2) had a mean age of 9.06 years (range, 6 weeks to 18 years). We conclude the following: (1) complete evaluation of the pediatric airways (bronchoscopy) is recommended in every symptomatic child with diagnosis of laryngomalacia confirmed by laryngoscopy; (2) type 1 laryngomalacia was more common in early infancy while type 2 laryngomalacia was associated with older age; (3) although type 2 laryngomalacia is the most common endoscopic diagnosis in our experience, the majority of cases were associated with lower airway dysfunction. 
4	Isolated systolic hypertension in the elderly: an epidemiologic review. Isolated systolic hypertension (ISH) is usually defined as a systolic blood pressure greater than or equal to 160 mm Hg and diastolic blood pressure less than 90 or 95 mm Hg. Systolic blood pressure has been found to increase with age in most populations studied and thus the prevalence of ISH can be expected to increase with age. ISH is more prevalent in elderly women than in elderly men. Estimates of the prevalence of ISH vary according to its definition and the number of blood pressure measurements. There is evidence that the prevalence of ISH is decreasing. Results of a survey of the prevalence of ISH in 11 countries are presented; the estimates among men aged 60 to 69 years ranged from 1% in Israel to 24% in Norway. Only a prospective standardized survey conducted in several countries will reveal the true prevalence of ISH. 
4	Rapid and correct diagnosis of myocardial infarction: standardized case history and clinical examination provide important information for correct referral to monitored beds. The value of thorough examination of the case history as a diagnostic tool on hospitalization of patients with suspected myocardial infarction was investigated in three independent prospective studies. Use of a limited number of pain-related elements (= 'criteria'), that had already been obtained in the emergency room, could improve the decision on whether or not to admit patients to the coronary-care unit. As an example, in one of the studies, use of such criteria would have reduced the number of 'unnecessary' coronary-care-unit admissions from 298 to 162, a 46% reduction (P less than 0.001). In the same patient sample, use of the criteria could have reduced the number of patients with definite acute myocardial infarction, admitted to the general wards, from 47 to 22, a 53% reduction (P less than 0.01). These favourable results were confirmed in the two independent, smaller-scale studies. 
1	Occupational exposure and head and neck carcinoma. An epidemiological case-control study was conducted to investigate occupational risk factors in cancers of the upper respiratory and digestive tract. Cases were men with squamous cell carcinoma of the oropharynx (667), hypopharynx (348), glottis (246), supraglottis (219), epilarynx (204), and 4 subsites of the oral cavity (787). Controls were healthy patients or patients with cancer of another site or another histological type (147 men). Past occupational exposures of cases and controls were compared. The analysis was performed independently for each site of cancer, controlling for age, amount and type of alcohol and tobacco consumption, and state of dentition. Results showed that cancer of the supraglottis was associated with exposure to oil and grease (odds ratio = 2.4; 95% confidence interval 1.0-5.8), and with exposure to cement (odds ratio = 4.2; 95% confidence interval = 1.1-16.4). Cancer of the glottis was also associated with exposure to dye (odds ratio = 6.4; 95% confidence interval = 0.7-56.6). Exposure to flour occurred more frequently among controls than among patients with pharyngeal or oral cancer. This might reflect an association between this occupational exposure and some particular types of cancer included in the control group. 
3	Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain. To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned. 
4	Should family doctors screen asymptomatic children for high blood pressure? Whereas the United States Task Forces on Blood Pressure Control in Children have recommended annual blood pressure screening in all children, a working party of the British Hypertension Society has formed the opposite opinion. Relevant literature is reviewed here, and the conclusion reached that on epidemiological and ethical grounds, screening children for hypertension cannot at present be justified. 
5	A comparative trial of three agents in the treatment of acute migraine headache. STUDY OBJECTIVES: A study was conducted to evaluate the relative efficacy of three non-narcotic agents, chloropromazine, lidocaine, and dihydroergotamine, in the treatment of migraine headache in an emergency department setting. DESIGN: The trial was randomized and single blinded. SETTING: The study was conducted in two university-affiliated EDs. TYPE OF PARTICIPANTS: All patients had an isolated diagnosis of common or classic migraine. INTERVENTIONS: Patients were pretreated with 500 mL (IV) normal saline before randomization. Study drugs as administered were dihydroergotamine 1 mg IV repeated after 30 minutes if the initial response was inadequate; lidocaine 50 mg IV at 20-minute intervals to a maximum total dose of 150 mg as required; or chloropromazine 12.5 mg IV repeated at 20-minute intervals to a total maximum dose of 37.5 mg as required. Patients were asked to grade headache severity on a ten-point scale before and one hour after the initiation of therapy. Follow-up by phone was sought the following day. MEASUREMENTS AND MAIN RESULTS: Of 76 patients completing the trial, 24 were randomized to receive chloropromazine, 26 to receive dihydroergotamine, and 26 to receive lidocaine. Reduction in mean headache intensity was significantly better among those treated with chloropromazine (P less than .005). Persistent headache relief was experienced by 16 of the chloropromazine-treated patients (88.9%) contacted at 12 to 24 hours follow-up compared with ten of the dihydroergotamine-treated patients (52.6%) and five of the lidocaine-treated group (29.4%). CONCLUSION: The relative effectiveness of these three antimigraine therapies appears to favor chloropromazine in measures of headache relief, incidence of headache rebound, and patient satisfaction with therapy. 
5	Life table analysis of fecundity in intravenously gonadotropin-releasing hormone-treated patients with normogonadotropic and hypogonadotropic amenorrhea. The success of pulsatile intravenous (IV) gonadotropin-releasing hormone (GnRH) treatment in patients with normogonadotropic and hypogonadotropic amenorrhea was studied retrospectively using life table analysis. Two hundred forty-four ovulatory cycles in 48 normogonadotropic and hypogonadotropic patients were evaluated. The cumulative conception rate after 12 cycles was 93%, with a mean conception rate of 22.5% per cycle. Comparing cycles 1 to 6 with cycles 7 to 12, no significant difference in conception rate was observed. Subdivisions were made relative to the presence of additional infertility factors, history of weight loss, actual weight, estrogenic status, and primary versus secondary amenorrhea. The life table curves of patients either with or without other infertility factors were significantly different. No statistically significant differences were found in the other subdivisions. It is concluded that IV GnRH therapy is highly successful in patients with normogonadotropic and hypogonadotropic amenorrhea, especially if no other infertility factors are present. 
5	Cerebrovascular complications of inflammatory bowel disease. There is an increased incidence of central nervous system thromboembolic events in young patients with inflammatory bowel disease. A 33-yr-old woman previously diagnosed with pseudotumor cerebri suffered superior sagittal and transverse sinus thromboses during a severe flare of ulcerative colitis. These were documented on contrast computed tomographic (CT) and magnetic resonance imaging (MRI) scans. Stroke may be more common in patients with ulcerative colitis than in patients with Crohn's disease; arterial disease is more prevalent than venous and dural sinus disease, and is correlated with an active phase of inflammatory bowel disease. It is difficult to assess whether there is a relationship to concurrent steroid use, and a consistent relationship to duration of inflammatory bowel disease or to other extraintestinal manifestations is not apparent. 
2	Choledocholithiasis in Chinese immigrants with cholelithiasis. During the period from January 1987 to December 1989, admissions for biliary tract disease at the New York Infirmary--Beekman Downtown Hospital were split almost evenly between Chinese immigrants from southeast Asia and all other ethnic groups (Caucasian, Hispanic, black, et cetera). However, the incidence of choledocholithiasis in patients undergoing cholecystectomy for cholelithiasis was much higher in the Chinese immigrant population, 37.2 versus 11.8 per cent, a highly significant difference (p = 0.001). In addition, we often found the disease to be of greater severity in Chinese patients. They were more likely to have large numbers of stones in the duct and more likely to have significant ductal enlargement. This increased risk was essentially constant regardless of age. Because of this threefold risk of choledocholithiasis when operating on a Chinese immigrant from southeast Asia for cholelithiasis, intraoperative cholangiography is mandatory, even in those without other indications for common bile duct exploration. 
4	"White coat" versus "sustained" borderline hypertension in Tecumseh, Michigan During a survey of young subjects not receiving treatment for hypertension in Tecumseh, Michigan, clinic and self-monitored blood pressures taken at home (14 readings in 7 days) were obtained in 737 subjects (387 men, 350 women, average age 31.5 years). Hypertension in the clinic was diagnosed if the clinic blood pressure exceeded 140 mm Hg systolic or 90 mm Hg diastolic. In the absence of firm criteria for what constitutes hypertension at home, subjects whose average home blood pressure was in the upper decile of the whole population were considered to have hypertension at home. By these criteria, 7.1% of the whole population had "white coat" hypertension (i.e., high clinic but not elevated home readings). The prevalence of "sustained" hypertension (i.e., high readings in the clinic and at home) was 5.1%. Subjects with white coat and sustained borderline hypertension in Tecumseh were very similar. Both groups showed, at previous examinations (at ages 5, 8, 21, and 23 years), significantly higher blood pressure readings than the normotensive subjects. As young adults (average age 33.3 years), the parents of both hypertensive groups had significantly higher blood pressure readings than the parents of normotensive subjects. Both hypertensive groups had faster heart rates, higher systemic vascular resistance, and higher minimal forearm vascular resistance. Both hypertensive groups were more overweight, had higher plasma triglycerides, insulin, and insulin/glucose ratios than normotensive subjects. The white coat hypertensive group also had lower values of high density lipoprotein than the normotensive group. White coat hypertension is a frequent condition. 
5	Experimental intracerebral hemorrhage: early removal of a spontaneous mass lesion improves late outcome. The purpose of the present study was to determine whether early removal of an experimental intracerebral mass altered cerebral blood flow, brain water content, neuropathological findings, or neurological function 24 hours later. In three experimental series, a 50-microliter balloon was inflated within the right caudate nucleus in rats. At 24 hours after inflation, we studied cerebral blood flow by quantitative autoradiography, brain specific gravity, and qualitative histopathology by light microscopy. The animals were also assessed using a simple neurological deficit scale. In each series, half of the animals had the balloon inflated for 10 minutes (Group 1), and half had the balloon inflated permanently (Group 2). After transient inflation, there were surprisingly small differences in the blood flow between the two cerebral hemispheres at 24 hours. By contrast, in animals with permanent inflation, several indices of blood flow were significantly worse in the hemisphere ipsilateral to the balloon: the mean and median blood flow levels in the caudate nucleus; the mean blood flow in the cerebral cortex; and the area of cortex with ischemic levels of blood flow. The specific gravity was reduced in areas surrounding the site of balloon insertion after either transient or permanent inflation, and there was evidence of ischemic cell damage in all animals studied. These changes were more severe after permanent inflation, but the differences were not significant. Neurological outcome was significantly better after transient as compared with permanent inflation. The present findings contradict previous results and suggest that early removal of an intracerebral mass may have subsequent benefits. 
4	A new method for quantification of regurgitant flow rate using color Doppler flow imaging of the flow convergence region proximal to a discrete orifice. An in vitro study. While color Doppler flow mapping has yielded a quick and relatively sensitive method for visualizing the turbulent jets generated in valvular insufficiency, quantification of the degree of valvular insufficiency has been limited by the dependence of visualization of turbulent jets on hemodynamic as well as instrument-related factors. Color Doppler flow imaging, however, does have the capability of reliably showing the spatial relations of laminar flows. An area where flow accelerates proximal to a regurgitant orifice is commonly visualized on the left ventricular side of a mitral regurgitant orifice, especially when imaging is performed with high gain and a low pulse repetition frequency. This area of flow convergence, where the flow stream narrows symmetrically, can be quantified because velocity and the flow cross-sectional area change in inverse proportion along streamlines centered at the orifice. In this study, a gravity-driven constant-flow system with five sharp-edged diaphragm orifices (ranging from 2.9 to 12 mm in diameter) was imaged both parallel and perpendicular to the direction of flow through the orifice. Color Doppler flow images were produced by zero shifting so that the abrupt change in display color occurred at different velocities. This "aliasing boundary" with a known velocity and a measurable radial distance from the center of the orifice was used to determine an isovelocity hemisphere such that flow rate through the orifice was calculated as 2 pi r2 x Vr, where r is the radial distance from the center of the orifice to the color change and Vr is the velocity at which the color change was noted. Using Vr values from 54 to 14 cm/sec obtained with a 3.75-MHz transducer and from 75 to 18 cm/sec obtained with a 2.5-MHz transducer, we calculated flow rates and found them to correlate with measured flow rates (r = 0.94-0.99). The slope of the regression line was closest to unity when the lowest Vr and the correspondingly largest r were used in the calculation. The flow rates estimated from color Doppler flow imaging could also be used in conjunction with continuous-wave Doppler measurements of the maximal velocity of flow through the orifice to calculate orifice areas (r = 0.75-0.96 correlation with measured areas). 
5	Patient compliance--a factor in facial trauma repair. The clinical records of 25 consecutive patients who were treated for facial trauma were reviewed and analyzed to ascertain what effect patient cooperation had on the outcome of facial fracture repair. The study was designed to establish the incidence of complications and to discover what factors contributed to untoward sequela in such patients. Overall, 15 patients (60%) were noncompliant in one or more aspects of their care. Six patients (24%) had significant postoperative complications associated with their facial injuries. Four of these patients were not fully cooperative. 
1	Spinal cord decompression via a modified costotransversectomy approach combined with posterior instrumentation for management of metastatic neoplasms of the thoracic spine. Fifteen patients with thoracic spinal cord compression from metastatic neoplastic processes were managed by spinal canal decompression via a modified costotransversectomy approach. Ten of the patients also underwent sequential posterior stabilization with Luque or Harrington instrumentation based upon proximity of the lesion to the thoracolumbar junction, prognosis for regaining or maintaining ambulatory ability, and additional spinal stability considerations. A modified lateral decubitus position with the scapula falling away from the side of exposure was used for T1-5 segment lesions, and a prone position was used for the (T-6)-(T-12) segment. Adequate decompression of the spinal canal was achieved in all cases. All patients who were ambulating preoperatively maintained ambulatory ability, and pain and/or further neurological improvement as well occurred in 75%. 
5	The sequelae of Haemophilus influenzae meningitis in school-age children. BACKGROUND. Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS. Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the children's hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS. Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute-phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS. We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b. 
1	Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA. In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine-administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis. 
4	Blood pressure level, trend, and variability in Dunedin children. An 8-year study of a single birth cohort In a birth cohort of children in the Dunedin Multidisciplinary Health and Development Study in New Zealand, resting blood pressures were recorded biennially five times from age 7 to 15 years. Using previously described methods, we examined the level, trend, and variability of blood pressures in those children with at least three readings. The level, trend, and variability of height, weight, and body mass index were compared among six separate groups of children. Two groups were categorized on the basis of high systolic pressure levels, one with low variability and the other with high variability, which was thought to resemble adult labile hypertension. Two additional groups were categorized on the basis of increasing and decreasing blood pressure trends; the fifth group had consistently low blood pressures, and the sixth group consisted of the remaining children. There were significant differences among the groups for the level of all the physical measurements and for the trend of body mass index. No significant differences were found among the groups for gender or socioeconomic status. A parental history of high blood pressure, stroke, or heart attack was significantly more common in the first two groups. 
5	Supported employment: an alternative model for vocational rehabilitation of persons with severe neurologic, psychiatric, or physical disability. Participation in paid work in competitive industry through placement in supported employment is compared and analyzed for 278 severely disabled persons. Differential outcomes are described for persons with chronic mental illness, cerebral palsy, traumatic brain injury, and dual diagnosis of chronic mental illness and mental retardation. Results indicated that supported employment appears to be an effective means of assisting these historically unemployable individuals to acquire and retain work. Cross-disability group differences were found in areas such as hourly wages, type of employment, services provided by employment specialists, and job retention. The results represent a baseline from which to evaluate future efforts at competitive work placement for persons with severe disabilities, using the supported-employment model. 
5	Sequential magnetic resonance imaging following stereotactic radiofrequency ventralis lateralis thalamotomy. Serial postoperative magnetic resonance (MR) studies were obtained in 21 patients who underwent somatotopically placed stereotactic radiofrequency (rf) ventralis lateralis thalamotomy for the control of movement disorders. The MR studies were reviewed to determine the MR characteristics of early-phase (less than or equal to 7 days) and late-phase (8 days to 5 months) lesions. Surgery was performed for the control of parkinsonian tremor (14 cases), intention tremor (six cases), and essential tremor (one case). Single rf lesions were made with an electrode (1.6 mm in diameter, 3 mm in tip length) heated to 78 degrees C for 60 seconds. On MR images of the lesions, three distinct concentric zones were identified, described as follows (from the center outward). Zone 1 gives increased signal on long-relaxation time (TR) (T2-weighted) MR images in early- and late-phase lesions and decreased signal on short-TR (T1-weighted) MR images in early-phase lesions only. Zone 2 gives decreased signal on long-TR (T2-weighted) images in early- and late-phase lesions; it gives isointense signal on short-TR (T1-weighted) images in early-phase lesions only. Zone 3 gives increased signal on long-TR (T2-weighted) images in early-phase lesions only and decreased signal on short-TR (T1-weighted) MR images in early-phase lesions only. It is considered that in early-phase lesions, Zone 2, with a mean diameter of 7.3 mm on axial long-TR (T2-weighted) imaging, represents an area of hemorrhagic coagulation necrosis. In late-phase lesions, Zone 2, with a mean diameter of 5.0 mm on axial long-TR (T2-weighted) imaging, represents hemosiderin deposition. Zone 3 likely represents edema, and this zone disappears between the early and late periods. From regression analysis, lesion size began to stabilize at approximately 7 months with a mature lesion diameter of 3.3 mm. Long-term follow-up monitoring (median 16 months) showed good tremor control. Based on clinical and radiological findings, the authors conclude that forms of hemoglobin are suitable markers to assess the size of rf lesions. Serial MR imaging provides a noninvasive means of studying the evolution of rf thalamotomy lesions. 
5	Lymphocytic hypophysitis with involvement of the cavernous sinus and hypothalamus. Two cases of lymphocytic hypophysitis are reported, in which hypothalamic involvement causing diabetes insipidus was a prominent clinical feature. In one case, a man had clinical and radiological evidence of the involvement of the cavernous sinus. This represents the second reported case of a man with lymphocytic hypophysitis. A transsphenoidal biopsy established the diagnosis in both cases. Neither the involvement of the cavernous sinus nor permanent diabetes insipidus has been reported previously. A review of the literature is provided. 
1	The reliability of frozen sections in the evaluation of surgical margins for melanoma. As the width of surgical margins declines, histologic evaluation of the margins is needed to assess the completeness of excision of a malignant melanoma. We studied 221 specimens in 59 patients and compared the interpretations of frozen and paraffin sections from the same block. Frozen sections had a sensitivity of 100% in detecting melanoma when present and a specificity of 90%. 
1	Performing cytogenetic studies on ascitic, amniotic and hygroma fluid. The importance of obtaining cytogenetic studies on antenatally diagnosed structural malformations is well recognized. In two cases, three fetal compartments were sampled, each resulting in successful cytogenetic studies. Fluid was obtained under ultrasound guidance from amniotic fluid, fetal ascites and cystic hygroma fluid. Fluid from the hygroma itself may be the easiest compartment to analyze. 
5	Partial duplication of the face: case report and review. Complete or partial facial duplication is a rare congenital malformation. A spectrum of structural abnormalities varying in degrees of severity has been described in affected individuals. We present discordance for facial duplication between monozygotic twins in which maxillary and mandibular duplication was present in one. The involved twin showed the following findings: ocular hypertelorism, bifidity of the nose, duplication of the maxilla, macrostomia, cleft of the lower lip, hamartoma of the vomer, supernumerary teeth, duplication of the mandibular teeth, bifidity of the tongue, and hamartoma of the floor of the mouth. Surgical management of the facial anomalies is discussed. A review of the literature and discussion of this rare malformation are presented. 
5	Acute abdominal pain in the elderly. STUDY OBJECTIVES: To determine the incidences of both specific diagnosis and surgical diseases in patients more than 65 years old who present to the emergency department with nontraumatic abdominal pain of less than one week's duration, and to determine the ED staff's ability to diagnose and triage elderly patients with acute abdominal pain. DESIGN: A 12-month retrospective review of all elderly patients who presented to the ED with acute, nontraumatic abdominal pain. SETTING: A regional trauma center serving a predominately rural population in the Midwest. The ED has 55,000 patient visits yearly. MEASUREMENTS AND MAIN RESULTS: Of the 127 patients enrolled, 30 (24%) had no specific diagnosis made in the ED. Biliary tract disease (12%) and small bowel obstruction (12%) were the two most common specific diagnoses. Overall, 53 patients (42%) required surgery, usually during the initial hospitalization. In four cases, the postoperative diagnosis differed significantly from the ED diagnosis. Of the 74 patients (58%) who did not undergo surgery, 51 had follow-up information available. In 14 patients, the follow-up diagnosis differed from the original diagnosis, but most of these changes did not appreciably alter the treatment and outcome. CONCLUSIONS: The incidence of surgical disease is high in elderly patients with acute abdominal pain, and ED staff are able to diagnose and triage these patients accurately. 
5	The influence of neutralizing heparin after carotid endarterectomy on postoperative stroke and wound hematoma. The influence of neutralizing or not neutralizing heparin after carotid endarterectomy on postoperative stroke and wound hematoma is unknown. During the past 6 years some of the authors frequently gave protamine sulfate to neutralize heparin, whereas others did not unless a patch was used or wound hemostasis was not readily obtained. To determine the influence of protamine sulfate on stroke and wound hematoma the records of 697 patients having a carotid endarterectomy from January 1984 to September 1989 were reviewed. Protamine sulfate was given to 328 patients, and 369 did not receive protamine sulfate. The incidence of stroke in the two groups was 1.8% (n = 6) and 2.7% (n = 10), respectively, and the difference was not significant (p = 0.6019). Excluding three strokes that could not be related to neutralizing or not neutralizing heparin, the difference remained insignificant (1.5% vs 2.2%, p = 0.7290). The incidence of wound hematoma was 1.8% (n = 6) in patients given protamine sulfate and 6.5% (n = 24) in patients not given protamine sulfate, and this difference was significant (p = 0.0044). The difference remained significant when three hematomas not related to protamine sulfate were excluded (1.2% vs 6.2%, p = 0.0013). In patients not given protamine sulfate draining the wound lessened the incidence of wound hematoma (4.4% vs 8.6%), but this difference was not statistically significant (p = 0.1475). In patients given protamine sulfate the dose of protamine sulfate (15 to 45 mg vs 50 to 75 mg) had no statistically significant effect on the incidence of stroke (0.8% vs 2.0%, p = 0.6530) or wound hematoma (1.6% vs 1.0%, p = 1.000). 
5	Clinical experience implanting an inflatable penile prosthesis with controlled-expansion cylinder. Ninety-four patients with erectile dysfunction underwent implantation of controlled-expansion inflatable penile prosthetic cylinders. Most of these patients had aneurysmal dilatation of the corpora cavernosa after prior implantation of inflatable devices. Follow-up of forty-six months has shown their efficacy to be excellent for management of primary impotence, penile straightening procedures, and revision after cylinder leaks. None of the patients has had recurrence of the primary condition that required revision. 
4	Femoral artery cannulation for monitoring in critically ill children: prospective study. Seventy-seven attempted percutaneous femoral artery cannulations were prospectively evaluated in 74 children. Artery cannulation was successfully accomplished in 73 (95%) cases and lasted for a mean of 6 days. Sixty percent of the catheters were inserted on the first attempt. Fifty-two (71%) patients weighed less than 10 kg and 55 (75%) patients were less than 12 months old. Fifty-one (70%) patients received inotropic support at the time of cannulation, and 27 (37%) eventually died from causes unrelated to catheter insertion. There was one episode each of line-associated infection and transient distal ischemia not resulting in tissue loss, and two episodes of catheter malfunction. In eight (11%) patients, signs of distal vascular insufficiency developed shortly catheter placement and resolved after catheter removal. The development of this complication correlated significantly (p less than .05) with younger age (5.5 vs. 22.3 months). We conclude that femoral artery cannulation has a high degree of success in very small, critically ill children. It should be considered an acceptable alternative to small-vessel cannulation when the latter is not technically achievable, or in the unstable patient where rapid establishment of reliable arterial access is necessary. 
4	Duchenne's cardiomyopathy in a canine model: electrocardiographic and echocardiographic studies. Thirteen dogs affected with X-linked Duchenne's muscular dystrophy and 11 female carrier dogs were studied by electrocardiography (ECG) and echocardiography. Twelve of the affected dogs were studied as immature animals and followed at 1 to 6 month intervals until they were 7 to 46 months of age. Compared with control dogs, affected dogs had significantly increased (p less than 0.02) Q/R ratios in ECG leads II, III, aVF, CV6LL (V2) and CV6LU (V4). Carrier dogs had significantly increased (p less than 0.02) Q/R ratios in leads V2 and V4. The Q/R ratio increased in three of six dogs followed up from age 6 months to greater than 2 years. The PR intervals were significantly shorter (p less than 0.02) in affected dogs. Ventricular arrhythmias were identified in four of six mature affected dogs. Two-dimensional echocardiography revealed distinctive hyperechoic lesions in 12 of the 13 affected dogs and in 6 of the 11 carrier dogs. Hyperechoic lesions corresponded to calcified myocardium and surrounding dense connective tissue. This study establishes the dog affected with Duchenne's muscular dystrophy as an animal model of Duchenne's cardiomyopathy and demonstrates that the heart in carrier dogs is affected by the dystrophic process. 
1	Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen. Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation. 
5	Calmodulins with deletions in the central helix functionally replace the native protein in yeast cells. Deletion of Glu-84, Glu-83 and Glu-84, or Ser-Glu-Glu-Glu (residues 81-84) from the central helix of mammalian calmodulin is known to result in a 5-7 times decrease in its apparent in vitro affinities for three calmodulin-dependent enzymes. However, based on in vitro experiments, it is difficult to estimate how these deletions might affect in vivo cellular function. The yeast Saccharomyces cerevisiae, which requires calmodulin for growth, provides an excellent system to evaluate these deletion proteins in vivo. Based on its ability to restore normal growth characteristics to yeast cells, mammalian calmodulin is functionally identical to the yeast protein; herein we evaluate the effect of deleting residues 84, 83 and 84, or 81-84 from the central helix. Sequences encoding the deletion proteins and an unaltered control sequence were introduced by means of a yeast shuttle vector and were expressed under control of the yeast calmodulin promoter. The deletion and control calmodulins are produced at levels similar to that observed for the yeast protein, and they completely restore normal growth characteristics. This result suggests that the regions deleted from the central helix are not critical for activation of any yeast calmodulin target normally required for cell growth or division. It is likely that there are twisting and shortening motions associated with the deletions from the central helix that alter significantly the spatial relationship between the two lobes of calmodulin. The abilities of the deletion calmodulins to restore completely normal growth characteristics to yeast cells suggest that the lobes of all the deletion proteins can still be appropriately positioned in calmodulin-target complexes. This is consistent with the hypothesis that the central helix of calmodulin is analogous to a flexible tether rather than to a rigid connector between the two lobes of the molecule. 
4	An evolutionary perspective on salt, hypertension, and human genetic variability. Natural selection for electrolyte conservation has likely been the norm throughout human evolutionary history. However, the current patterns of excessive dietary salt intake create the potential for salt overload. Under these conditions, hypertension may be considered an expected pathological response to an evolutionarily new constraint. The transatlantic Middle Passage may have created a genetic bottleneck for salt conservation in African-Americans. Although the initial consequences of this important historical event probably constricted genetic variability and further magnified the potential for salt-sensitive hypertension, the Middle Passage undoubtedly also served as a more generalized major source of environmental stress and may have stimulated subsequent hereditary diversity in the survivors of this holocaust and their descendants. Accelerated rates of mutation, genetic recombination, and transposable genetic elements in conjunction with enhanced opportunities for gene flow, new selective pressures, and drift have all contributed to the tremendous heterogeneity of contemporary African-Americans. It is unlikely that a single genetic event, even of the severity of the Middle Passage, can account comprehensively for the apparent susceptibility of this macroethnic group to high blood pressure and hypertension. 
3	Ectopic retinoblastoma within the 3rd ventricle: case report. Ectopic intracranial retinoblastomas are rare. These tumors usually occur in the pineal, parasellar, or suprasellar regions several years after the successful treatment of ocular retinoblastomas with no evidence of direct extension or distant metastasis. We report here a case of ectopic retinoblastoma occurring within the third ventricle. The tumor was surgically excised by the transventricular approach. Ectopic retinoblastomas exhibit greater differentiation than one would expect to observe in a metastatic lesion of this tumor. The distinction of ectopic retinoblastomas and metastasis from ocular retinoblastomas is important, since ectopic retinoblastomas, unlike metastasis, can be successfully managed by intensive therapy including radical excision. 
2	Anterior lesser curve seromyotomy and posterior truncal vagotomy versus truncal vagotomy and pyloroplasty in the treatment of chronic duodenal ulcer. In a prospective randomized controlled clinical trial, anterior lesser curve seromyotomy with posterior truncal vagotomy (AMPT, n = 77) has been compared with truncal vagotomy and pyloroplasty (TVP, n = 69) in 146 patients with chronic duodenal ulcer with a mean duration of symptoms of 7 years. The mean follow-up time was 4.5 years with a range of 2-7 years. One elderly patient died from a myocardial infarction in the TVP group. Acid secretory inhibition in response to insulin and pentagastrin stimuli was equal in both groups, indicating a similar degree of vagal denervation. Recurrent ulcers were more common after AMPT (five) than TVP (two) (P = 0.29, n.s.). Dumping and diarrhoea were significantly commoner (P less than 0.001) after TVP, with 31 instances as opposed to eight with AMPT. The mean operating time was increased by 6 min when AMPT was performed rather than TVP. The results of this study have shown that AMPT is associated with a lower incidence of dumping and diarrhoea and achieves better overall Visick grading. However, continued monitoring is required to assess the long-term incidence of recurrent ulceration after this procedure. 
1	Fetal ovarian cysts: prenatal ultrasonographic detection and postnatal evaluation and treatment. Ovarian cysts were diagnosed by antenatal ultrasonographic examination in 15 fetuses between 19 and 37 weeks' gestation. In six cases there was ultrasonographic evidence of torsion. Intracystic flocculation, which typically was deposited on the sloping part of the cyst, gave a characteristic liquid interface that was regarded as ultrasonographic evidence of torsion. All cases with evidence of torsion were managed surgically post partum, and in all patients this complication was confirmed. The remaining nine cases were followed up by repeated ultrasonograms, and in all patients disappearance of the cyst was documented within the first 6 months of life. The mean size of cysts with evidence of torsion was 5.41 +/- 0.25 cm, and the mean size of those without torsion was 4.33 +/- 0.3 cm (p less than 0.01). Histologic examination of the surgical specimen in the cases with evidence of torsion revealed follicular cysts in three cases and necrotic ovarian cysts with no specific epithelial findings in the remaining three. We recommend continuous ultrasonographic assessment of antenatally diagnosed cysts and believe that the choice of treatment depends on the appearance of the cyst and its evolution throughout pregnancy. 
4	Protamine-heparin-induced pulmonary hypertension in pigs: effects of treatment with a thromboxane receptor antagonist on hemodynamics and coagulation. Adverse hemodynamic reactions after protamine neutralization of heparin are an infrequent but important clinical problem. Pre-treatment of swine with a thromboxane A2 receptor antagonist has been reported to prevent the pulmonary hypertensive response occasionally seen after protamine reversal of heparin anticoagulation. In the current study, a control group of pigs (n = 9) received intravenous heparin (300 IU/kg), followed after 10 min by a neutralizing dose of protamine (3 mg/kg). A treatment group of pigs (n = 11) was treated identically, except that the thromboxane A2 receptor antagonist L-670596 (2 mg/kg) was infused intravenously 2 min after the protamine infusion. Hemodynamic and coagulation profiles were monitored during these procedures. Pulmonary hypertension developed and reached a peak within 2 min of protamine administration, often at the same time that L-670596 was administered in the treatment group. There was no statistical difference between control and treatment groups' peak pulmonary arterial pressure and peak pulmonary vascular resistance. However, the interval for return of mean pulmonary artery pressure from peak to baseline values was 11.6 +/- 3.1 versus 5.5 +/- 1.9 min (mean +/- SD) for control and treatment groups, respectively (P less than 0.01). Thromboxane B2 plasma concentrations increased in both groups and were correlated with the pulmonary hypertensive response (r = 0.86, P less than 0.01). Platelet aggregation to collagen was inhibited by the thromboxane A2 receptor antagonist (P less than 0.05). Bleeding time was prolonged beyond normal range in 50% of L-670596-treated pigs. All other coagulation tests in both groups returned to baseline after reversal of heparin with protamine and were unaffected by L-670596. 
2	Helicobacter pylori in dyspeptic patients in Kuwait. Two hundred and four patients, mainly Arabs, attending for upper gastrointestinal endoscopy at the gastroenterology clinic in Mubarak Al-Kabeer Hospital, Kuwait, were examined for evidence of infection with Helicobacter pylori and associated inflammation. Biopsy specimens of antrum, body, and duodenum; gastric juice; and antral mucosal brushings were investigated by microbiological, cytological, and histopathological methods. Clinical conditions diagnosed at endoscopy included gastritis, gastric ulcer, duodenitis and duodenal ulcer, but half the patients had endoscopically normal gastric and duodenal mucosae. H pylori was detected by one or more of the procedures in at least one specimen from 197 (96.6%) of the patients. Histological and cytological analysis showed equal sensitivity, but bacteriological culture was less reliable. The proportion of positive cases was high, compared with other reported series, which may have been accounted for by the variety of diagnostic techniques used in this study, the selected population (all with gastrointestinal symptoms) or genetic or environmental predisposing factors peculiar to the sample population. 
2	The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract. The cause of the disease is unknown, and no effective medical treatment exists. In this study, 12 patients received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg bid). Their course was compared with that of a group of concurrent historical controls. At 6 and 12 months, there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls. At 24 months, however, no significant differences in biochemical tests were appreciated between treated and untreated patients. Analysis of serial liver biopsies showed no differences in histologic change in the two groups. During the 2 yr of follow-up, there were two deaths in the control group but none in the treated group. Four untreated patients developed ascites; gastrointestinal bleeding developed in three untreated patients, one of whom developed ascites. In contrast, in the treated group, ascites and bleeding developed in only one patient. We conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy. There is a trend toward less clinical deterioration and improved survival after 2 yr of treatment. On the basis of these findings, we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis, but suggest that, if they are to be used at all in PSC, they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease. 
4	Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch, utilizing circulatory arrest and retrograde cerebral perfusion. Recently we replaced the ascending aorta and aortic arch in 8 patients with aneurysm or dissection, using profound hypothermic circulatory arrest with retrograde cerebral perfusion. There were no operative deaths. Open aortic anastomosis facilitated repair of the aortic arch without clamping the arch tributaries, and embolism due to particulate debris from clamping of the arch vessels was eliminated. Retrograde cerebral perfusion during profound hypothermic circulatory arrest is a simplified technique that may protect the brain. This method offers advantages over previously described methods, particularly in obviating dissection of the arch tributaries and the clamping thereof, and in protecting the central nervous system. 
4	Seven-pathogen tricuspid endocarditis in an intravenous drug abuser. Pitfalls in laboratory diagnosis. Polymicrobial endocarditis is being reported with increasing frequency in drug abusers. However, the full extent of infection may be unrecognized with routine blood culture techniques because of the overgrowth of more fastidious organisms by other pathogens. This report documents an intravenous drug abuser with the first reported case of tricuspid valve endocarditis involving seven pathogens, discusses pitfalls of routine blood cultures and examines the role of the laboratory in microbiologic diagnosis. 
1	Hemorrhagic pituitary adenomas: clinicopathological features and surgical treatment. Forty-five (9.9%) of 453 pituitary adenomas operated on between January 1973 and November 1988 demonstrated hemorrhagic changes at surgery: 24 had a blood collection, 12 had a blood collection associated with hemorrhagic necrosis, and 9 had hemorrhagic necrosis. Thirteen patients (28.9%) experienced the acute symptoms of pituitary apoplexy, whereas another 32 had an "asymptomatic" hemorrhage, that is, the clinical course was comparable to an uncomplicated adenoma. Nineteen tumors (42.2%) showed marked suprasellar extension, 8 (17.8%) showed moderate extension, and 11 (24.5%) showed slight extension; another 2 (4.4%) were laterosellar and 5 (11.1%) were intrasellar. Invasive behavior was present in 32 cases (71.1%) and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage. The incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive; therefore, we do not suggest preoperative bromocriptine treatment in this type of tumor. Two of 14 patients operated on by the transcranial route died after surgery, whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route. It proved advantageous to operate as early as possible, even during the acute phase of pituitary apoplexy. The transsphenoidal approach gave the best results, but to achieve satisfactory late results multidisciplinary treatment was necessary, namely, postoperative radiotherapy in 23 patients, bromocriptine in 12, and endocrine replacement therapy in almost all. In an average follow-up period of 6.2 years, 5 (11.1%) symptomatic recurrences were observed. 
4	Changes in cerebral blood flow velocity after release of intraoperative tourniquets in humans: a transcranial Doppler study. The effect of release of intraoperative thigh tourniquets on velocity of blood flow in the middle cerebral artery was examined in five patients given general anesthesia with controlled ventilation for lower extremity orthopedic procedures using transcranial Doppler sonography. Middle cerebral artery blood flow velocity increased significantly from 52 +/- 6 (SEM) to 82 +/- 24 cm/s (an increase of 58% +/- 13%) within 4 +/- 1 min after tourniquet release and remained significantly elevated for 7 min. A positive linear correlation was found between middle cerebral artery blood flow velocity and PETCO2 on each occasion (0.97 greater than or equal to r greater than or equal to 0.84, 0.001 greater than P greater than 0.0001) after tourniquet deflation. Assuming a linear relationship between flow velocity and flow, these findings suggest that significant increase in cerebral blood flow can occur after intraoperative tourniquet release and that this increase appears to be mostly CO2-dependent. 
3	Can clinical judgment detect children with speech-language problems? Pediatricians often rely on clinical judgment derived from observation or parental concern to identify children with developmental problems. The less popular but recommended alternative is to repeatedly administer standardized screening tests. Such tests are time consuming but, unlike clinical judgment, have known detection rates. Preliminary research concerning clinical judgment showed that clusters of parental concerns related to their childrens' performances on screening tests. In the present study, previous research was refined by assessment of the meaning of parents' concerns about their childrens' speech-language development. In this study of 157 families seeking pediatric care, 72% of children whose speech-language screening yielded positive results had parents who were concerned about their speech-language development. Of children with negative screening results, 83% had parents with no concerns about their speech-language development. Although standardized screening tests should be used occasionally in the developmental surveillance process, the findings show that the problems of most children with developmental problems were detected through clinical judgment based on parental concern. 
2	Surgical aspects of sclerosing encapsulating peritonitis. Sclerosing encapsulating peritonitis (SEP) is associated with the administration of beta-blocking agents as well as continuous ambulatory peritoneal dialysis. The predisposing factors in the latter group are recurrent peritonitis, presence of acetate in the dialysate, and antiseptics used during bag exchanges. We report a case of SEP following chronic ambulatory peritoneal dialysis and review the literature on this benign yet potentially lethal condition. Sclerosing encapsulating peritonitis frequently leads to intestinal obstruction, small-bowel necrosis, enterocutaneous fistulas, and malnutrition. There is a high incidence of anastomotic failure when a resection and primary intestinal anastomosis is performed in patients with SEP. Although SEP is not commonly reported in the surgical literature, its importance to surgeons is indicated by the fact that the overall mortality rate is close to 60% in patients with SEP who develop surgical complications. 
5	Analysis of base station morphine orders: assessment of supervising physician consistency. Paramedic contact with a base station should gemerate consistent recommendations reflecting a consensus of base station physician care. In our urban EMS system, paramedics must contact a single base station to provide morphine sulfate (MS) for a patient with chest pain. We performed a retrospective cohort analysis of all prehospital MS requests for chest pain to determine the consistency of the circumstances for which the paramedic team was refused MS. These MS requests represented 123 of the 1,715 (7%) on-line physician consultations during the 6-month study. Only 15 of the 123 (12%) MS requests were refused. Neither the mean patient age, sex distribution, or presenting vital signs correlated with MS refusal. A maximum estimate of transport time to the hospital of less than or equal to 5 minutes was noted for 7 of 15 (47%) medication refusals compared to only 11 of 96 (11%) approvals with documented estimated transport times (P less than or equal to 0.005). A simultaneous request for nitroglycerin (NTG) was noted for 6 of the 15 (40%) medication refusals and 15 of the 108 (14%) approvals (P less than 0.05). We found refusal of MS administration to be uncommon. Supervising physicians tended to refuse MS when the transport time was short and when NTG was requested for concomitant administration. We also noted physician inconsistencies in refusal scenarios. These findings can guide physician consensus development to avoid sending mixed messages to paramedics. 
3	The role of diencephalic pathology in human memory disorder. Evidence from a penetrating paranasal brain injury. A patient (B.J.) is reported who developed severe memory impairment following a penetrating brain injury caused by a snooker cue which entered through his left nostril into the basal regions of the brain. Initially, his memory disorder had the clinical features of a dense amnesic syndrome, with both anterograde and retrograde amnesia, but B.J. subsequently showed significant recovery of memory function. Formal memory testing was carried out 21 months after injury. This demonstrated marked verbal memory impairment, as severe as that seen in patients with the amnesic syndrome. On nonverbal memory tests, his impairment was relatively mild and patchy. His retrograde amnesia had regressed mainly to affect a 6 month period before the injury. On other cognitive tasks, he performed at an average or above average level, and there was no neuropsychological evidence of frontal lobe dysfunction. Neuroradiological investigations at various stages after his injury failed to demonstrate a lesion in any of the thalamic nuclei. Magnetic resonance imaging showed a lesion in the hypothalamus in the region of the mamillary bodies. Our study demonstrates that marked, relatively focal, memory disorder after diencephalic injury can occur without direct pathology to the body of the thalamus. It also indicates that structures in or adjacent to the hypothalamus, such as the mamillary bodies, may play a more important role in human memory functioning than has hitherto been considered. 
2	Asialoglycoprotein receptor function in benign liver disease: evaluation with MR imaging. An arabinogalactan-coated ultrasmall superparamagnetic iron oxide (AG-USPIO) preparation specific for asialoglycoprotein (ASG) receptors on hepatocytes was used as a magnetic resonance (MR) imaging contrast agent in the evaluation of a spectrum of benign liver diseases in animal models. The activity of hepatocyte ASG receptors, which directly reflects liver function, was directly assessed by measuring liver relaxation times in vitro and MR signal intensity in vivo. The following measurements allowed three-dimensional assessment of liver function: (a) liver relaxation time, (b) native MR signal intensities of liver, (c) response of liver to the AG-USPIO probe (percentage decrease of liver signal intensity after intravenous administration of 10 mumol/kg of AG-USPIO: normal liver 55%, fatty liver 57%, acute hepatitis 36%, chronic hepatitis 29%, and cirrhosis 46%), and (d) redistribution of hepatocyte-specific AG-USPIO to the spleen (present in hepatitis and cirrhosis but not in normal liver and fatty liver). The results of this study indicate that cellular hepatic abnormalities can be detected and quantitated with MR receptor imaging. 
4	Myocardial metabolic and hemodynamic effects of a sustained intravenous infusion of nifedipine with and without metoprolol in patients with unstable angina. We tested the usefulness of a sustained intravenous infusion of nifedipine and a combination of nifedipine and metoprolol in the early management of 14 patients with unstable angina pectoris. After a 24-hour run-in period, nifedipine was titrated in a stepwise fashion (mean dose 27 +/- 7 micrograms/min). After nifedipine treatment coronary blood flow increased from 150 +/- 66 to 183 +/- 74 ml/min (p less than 0.05), whereas double product, myocardial oxygen consumption, and both arterial and coronary sinus (nor)epinephrine levels were unchanged. Myocardial lactate uptake increased from 3.4 +/- 26.1 to 31.3 +/- 26.6 mumol/min (p less than 0.005) and free fatty acid uptake from 7.2 +/- 22.1 to 34.5 +/- 33.7 mumol/min (p less than 0.05). A small nonsignificant improvement in amino acid metabolism was observed. Metoprolol was added in seven patients and led to a decrease in double product (-2.2 +/- 1.6 x 10(3); p less than 0.01) and myocardial oxygen consumption (-3.2 +/- 3.8 ml/min; p less than 0.05). The lactate uptake/oxygen uptake ratio increased by 18% after metoprolol (p = NS). The number of episodes of chest pain decreased from 2.4 +/- 1.1/24 hours to 0.1 +/- 0.2 in the nifedipine group and from 2.9 +/- 1.1/24 hours to 0.3 +/- 0.5 in the nifedipine plus metoprolol group (both p less than 0.01). We conclude that in the acute phase of unstable angina, intravenous nifedipine can be carefully titrated to improve coronary blood flow and oxidative metabolism. The addition of metoprolol is also associated with a reduction in myocardial oxygen demand. This treatment results in significant hemodynamic stability. 
1	Effect of 17 beta-estradiol on the growth of an estrogen receptor-positive human esophageal carcinoma cell line. Receptors for estrogen and for androgen in the nucleus and cytosol (ERn, ERc, ARn, and ARc, respectively) were studied on two newly established human esophageal carcinoma cell lines, ES-25C and ES-8C. ES-25C was ERn+ (the binding content 4.0 fmol/mg protein, Kd 0.09 nM), ERc-, ARn-, and ARc-. No receptors were found in ES-8C. Various doses of 17 beta-estradiol (E2) were added in vitro to investigate its effect on the growth of these cell lines. No effect of E2 was observed on ER--ES-8C cell line. The growth of ES-25C cell was significantly inhibited at the doses of 10(-10) and 10(-12) mol/l E2 compared with the control. The doubling time of 10(-12) mol/l E2-treated cells was 32 hours whereas that of control was 20 hours. This slower growth was reflected in the deduction of cells in S-phase utilizing 5-bromo 2'-deoxyuridine (BrdU) labeling. The current results strongly suggest that the growth inhibition of ER+ esophageal cancer cell by E2 is mediated by signal transduction induced by the estrogen-estrogen receptor system. 
3	"Moustache" appearance in craniopharyngiomas: unique magnetic resonance imaging and computed tomographic findings of perifocal edema. This report describes two cases of craniopharyngioma with perifocal edema. In both patients, computed tomography and magnetic resonance imaging (MRI) revealed that the tumors occupied the suprasellar cistern, invaginated the floor of the 3rd ventricle and were tightly adherent to the ventricular walls. The intraventricular portions of the tumors were cystic, containing protein-rich fluid as suggested by MRI and confirmed by operative findings. There was perifocal edema in the hypothalamus adjacent to the intraventricular tumor, the optic tracts, and the posterior limbs of the internal capsules, resembling the shape of a moustache on axial computed tomographic and MRI scans. The perifocal edema subsided after treatment of the intraventricular tumor by surgical resection or radiation therapy. The "moustache" appearance seems a unique, characteristic feature of perifocal edema, which is observed infrequently with certain craniopharyngiomas. 
5	Treatment with desmopressin acetate in routine coronary artery bypass surgery to improve postoperative hemostasis. Desmopressin acetate (DDAVP) has been shown to decrease blood loss and transfusions in complex cardiac operations with long extracorporeal times. Its use in routine cardiac valve operations has been shown not to be beneficial, but its role in routine coronary artery bypass grafting operations has not been defined. We examined the effect of DDAVP in a prospective study of 60 patients undergoing uncomplicated primary coronary artery bypass grafting operations. Thirty consecutive patients received DDAVP (0.3 micrograms/kg) after cardiopulmonary bypass and were compared with 30 consecutive patients who did not receive DDAVP. No significant differences were seen in 12-hour mediastinal blood loss (465 +/- 207 ml with DDAVP versus 511 +/- 221 ml without DDAVP) or 12-24-hour mediastinal blood loss (236 +/- 127 ml with DDAVP versus 260 +/- 112 ml without DDAVP). Transfusion of blood products were similar for both groups. Platelet aggregometry at intraoperative and postoperative time points using ADP, collagen, and ristocetin was not significantly different from baseline values in either group. In a subgroup of patients with poor initial ristocetin-induced platelet aggregometry, a significant increase (p less than 0.05) in ristocetin-induced platelet aggregometry was seen postoperatively only in those patients who had received DDAVP. A decrease in blood loss and transfusions, however, was not demonstrable. In those patients who had been on aspirin or nonsteroidal anti-inflammatory drugs preoperatively, DDAVP did not improve mediastinal blood loss or transfusion needs. 
5	Balloon expandable stent implantation in stenotic right heart valved conduits. Although valved conduits have been used successfully in severe forms of right ventricular-pulmonary artery discontinuity, progressive valved conduit stenosis is an important clinical problem. To determine the feasibility of reducing right heart valved conduit stenosis with a balloon expandable stent, a baboon model was used, in which the pulmonary artery was ligated and a right ventricular to pulmonary artery 14 mm bioprosthetic Dacron valved conduit implanted. In five baboons, at an average of 40 months after valved conduit implantation, fibrointimal stenosis at the valve site resulted in narrowing and a mean transconduit pressure gradient of 49 mm Hg (range 33 to 65). A tubular slotted steel stent (1.2 cm long) was deployed within the valved conduit after inflation of an 8 to 15 mm diameter balloon catheter that was introduced through the femoral vein. A stent was delivered to all valved conduits; however, in two baboons, balloon undersizing resulted in stent dislodgment. In the remaining three baboons, the transconduit gradient was reduced by 59% (49 to 20 mm Hg) and right ventricular systolic pressure decreased acutely by 35% (77 to 50 mm Hg). It is concluded that stent deployment is feasible in right ventricular to pulmonary artery stenotic valved conduits and may result in significant hemodynamic improvement. However, successful stent delivery is critically dependent on the proper selection of stent length and balloon diameter. 
2	The VER as a diagnostic marker for childhood abdominal migraine. Abdominal migraine is a common childhood migraine equivalent, for which diagnostic criteria have not been defined. As in other children with migraine equivalents this leads to difficulties in diagnosis and determination of prevalence. By recording the fast wave activity (beta rhythmn) in the visual evoked response (VER) to red and white flash, the pattern stimulation, 27 out of 28 children with clinically diagnosed abdominal migraine revealed significant differences compared with normal controls, outside the attack phase. Comparisons with children diagnosed as migraine with or without aura revealed, from the VER findings of higher amplitude fast wave activity and the presence of paroxysmal sharp wave activity, that abdominal migraine appears to be a specific form of childhood migraine. We found that both clinically and electrophysiologically, abdominal migraine changes with age; older children exhibiting a shorter duration of abdominal pain during attacks, and less evidence of sharp wave activity in the VER. 
5	Demonstration of two distinct subsets of gastric varices. Observations during a seven-year study of endoscopic sclerotherapy. Over a seven-year period, assessment of gastric varices was made on 225 patients receiving endoscopic sclerotherapy for variceal hemorrhage. Of 170 patients with complete data, gastric varices were observed in 26 (15.3%). Importantly, two distinct subsets of gastric varices were identified: varices distal to the gastroesophageal junction without extension into the fundus, termed "junctional varices," occurred in 11.2%, and varices that were confined only to the fundus, termed "fundal varices," occurred less frequently in 4.1%. Although rebleeding was increased in both subsets of gastric varices, junctional varices were more amenable to sclerotherapy. Patients with fundal varices (N = 7) had a significantly higher rebleeding rate, increased complications with sclerotherapy, and significantly decreased survival (P less than 0.005) when compared to patients with esophageal varices alone (N = 87) who were followed for more than three months. Cumulative survival was not significantly different (P less than 0.08) in patients with junctional varices (N = 19) when compared with patients with esophageal varices alone. We conclude that not all patients with gastric varices have a poor result with sclerotherapy. Recognition of these subsets may improve treatment strategies in patients with gastric varices. 
4	An increase in plasma cholesterol independent of thyroid function during long-term amiodarone therapy. A dose-dependent relationship. OBJECTIVE: To determine whether long-term amiodarone treatment is associated with a rise in plasma cholesterol, and, if so, to analyze its relation with thyroid function. DESIGN: Consecutive entry trial, including cardiac patients who initiated amiodarone medication but excluding those with abnormal thyroid function (defined as peak thyroid-stimulating hormone [TSH] response to thyrotropin-releasing hormone [TRH] less than 2.8 or greater than 22.0 mU/L) either before or during amiodarone treatment. PATIENTS: Twenty-three patients who remained euthyroid were studied. INTERVENTION: Oral administration of amiodarone (mean duration of treatment, 17 months; range, 6 to 30 months). MEASUREMENTS: Fasting plasma lipids, thyroid hormones, and peak TSH to TRH values were recorded before and every 6 months during amiodarone treatment. RESULTS: Plasma cholesterol gradually increased from 5.1 +/- 0.2 mmol/L before treatment to 6.9 +/- 0.8 mmol/L after 30 months of amiodarone medication (P less than 0.001); the peak TSH response to TRH did not change. When age- and sex-specific reference values were applied, 30% of the patients had cholesterol values above the 75th percentile before treatment; this number rose to 69% after 2 years of treatment. The rise in plasma cholesterol was associated with an equal increase in apoprotein B. Plasma cholesterol was not related to the daily dose of amiodarone or to plasma concentrations of amiodarone, desethylamiodarone, thyroxine (T4), triiodothyronine (T3), or reverse triiodothyronine (rT3). Linear regression analysis indicated a positive relation between plasma cholesterol and the cumulative dose of amiodarone (r = 0.25, P less than 0.05). CONCLUSION: Long-term amiodarone treatment is associated with a dose-dependent increase in plasma cholesterol that is independent of thyroid function. 
3	Quantitative evaluation of hypnotically suggested hyperaesthesia and analgesia by painful laser stimulation. The ability to reduce both clinically and experimentally induced pain by hypnotic suggestion of analgesia is well known. However, the nature of hypnotic analgesia still remains uncertain. Attempts to demonstrate and identify specific psychophysiological mechanisms have, so far, been unsatisfactory. Methodological problems in inducing pain and monitoring physiological responses may be the reason for this lack of success. In the present study, we have attempted to eliminate some of these methodological problems. The sensory and pain thresholds to laser stimulation were determined, and the laser-evoked brain potentials were measured for 8 highly hypnotically susceptible subjects in 3 conditions: (1) waking state, (2) suggestion of hyperaesthesia, (3) suggestion of analgesia. The thresholds were reduced during induced hyperaesthesia and increased during analgesia. During hyperaesthesia sensations could be evoked by laser intensities which were below intensities that could be perceived in the awake state. The amplitude of the evoked brain potentials increased during hyperaesthesia and decreased during analgesia. The latency of the potential remained constant. The perception of pain during hypnosis can change very fast, indicating that slow endogenous mechanisms may play only a minor role in suggested hyperaesthesia/analgesia. 
2	Transcatheter treatment of splenic artery aneurysms (SAA). Report of two cases. Splenic artery embolization with steel coils was performed in two patients who both had large splenic artery aneurysms and hepatic cirrhosis complicated by hypersplenism. A good clinical effect was noticed after the procedure. It was concluded that this treatment is safe and effective and decreases the risk of splenic artery rupture. It also corrects hypersplenism. Transcatheter embolization appears to be a preferable alternative to surgery in such cases. 
5	Reoperation for persistent outflow obstruction in hypertrophic cardiomyopathy. This study compares results of a second left ventricular myotomy and myectomy (M + M) with those of mitral valve replacement (MVR) as reoperative procedures for persistent left ventricular outflow obstruction after M + M in hypertrophic cardiomyopathy. Comparison of the second M + M group (n = 12) with the MVR group (n = 11) disclosed significant difference (p less than 0.05) in mean age at the initial operation (29 +/- 11 years versus 40 +/- 8 years), interval between operations (46 +/- 57 months versus 18 +/- 13 months), and age at reoperation (33 +/- 10 years versus 42 +/- 8 years); and insignificant differences in mean preoperative functional class, cardiac index, left ventricular outflow gradients at rest or with provocation, and hospital mortality at reoperation (2/12 versus 1/11). At 6 months after reoperation, comparison of results of a second M + M with MVR showed that mean functional class, cardiac index, and left ventricular outflow gradient at rest were similarly improved, but the outflow gradient with provocation was significantly higher in the second M + M group (57 +/- 44 mm Hg versus 14 +/- 9 mm Hg, p less than 0.05). Total follow-up was 108 patient-years (100% complete) with an average of 5.9 years per patient in the second M + M group and 3.4 years per patient in the MVR group. Actuarial survival, including hospital mortality, at 3 and 5 years was 83% and 76%, respectively, after the second M + M, which was similar to 92% and 77% after MVR. 
5	Kinematic analysis of lower-limb movement during ergometer pedaling in hemiplegic and nonhemiplegic subjects. The purpose of this descriptive study was to examine bicycle pedaling as a model for studying motor control dysfunction in persons with hemiplegia. Results of a kinematic analysis of the involved lower extremity of 10 hemiplegic patients were compared with the lower-extremity kinematic data of 10 "normal" (nonhemiplegic) subjects. Subjects pedaled at a constant work load at two pedaling rates. Hip, knee, and ankle angular-displacement variables were studied. Statistical comparisons for variables at the hip and knee were not significantly different between groups or between pedaling speeds. Ankle dorsiflexion and total ankle excursion were significantly different across pedaling speeds, but not between groups. Phase-plane analyses of angular-displacement and angular-velocity variables revealed that the most striking difference between the hemiplegic and the normal subjects was the control of ankle displacement and velocity of the lower extremity during pedaling. 
3	Return to work for persons with traumatic brain injury: a supported employment approach. Supported employment was used to place 41 persons into competitive employment during 30 months. All individuals had experienced severe head injuries; almost 70% of injuries were due to motor vehicle accidents. A mean of seven years had passed since injury for all referred clients, who had been unconscious a mean of 53 days. Only 36% of referred clients had achieved any competitive postinjury employment, compared with 91% of the same group who were competitively employed before injury. A job retention rate of 71% was reported, with most jobs in warehouse, clerical, and service-related occupations. A mean of 291 hours of job coaching was required to place and maintain all clients in supported employment. 
4	Comparison of exercise performance in left main and three-vessel coronary artery disease. From a consecutive series of patients who underwent rest and exercise radionuclide angiography over several years, we retrospectively identified 34 patients with left main coronary artery disease and 103 patients with three-vessel coronary artery disease who did not have significant left main disease. The results of gated equilibrium radionuclide angiography were compared in these 2 groups. Multiple exercise hemodynamic, exercise electrocardiographic, and exercise radionuclide angiographic parameters were considered in an attempt to separate the 2 groups. The only parameter that was significantly different between the 2 groups was exercise heart rate. However, no value of the exercise heart rate could meaningfully separate the 2 groups. Despite their known difference in prognosis, patients with left main and three-vessel disease had very similar exercise performance and could not be distinguished from one another by exercise electrocardiography or exercise radionuclide angiography. The inability to distinguish these two groups is a clear limitation of noninvasive exercise modalities. 
1	Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high-grade glioma in adults: a phase II study. We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma. 
2	Differences in expression of cystic fibrosis in blacks and whites. The recent identification of the cystic fibrosis (CF) gene confirms that genetic heterogeneity occurs in CF. A three-base-pair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product, termed the CF conductance regulator protein, accounts for 70% of cases of CF in white subjects. However, this gene defect occurs in only 37% of affected blacks. Analysis of CF genes from American blacks has revealed a number of mutations, most of which are unique to that population. We therefore searched for potential differences in expression of CF between 24 black and 48 white patients with CF matched for birth date and gender. Black patients more frequently presented with only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77% vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than white patients. Complication rates were similar except for a higher incidence of hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in blacks. Survival time appeared to be longer in blacks, but the difference was not statistically significant. We conclude that phenotypic differences exist between black and white patients with CF, which may be due to the genetic heterogeneity between these two populations. 
4	Relation between leisure-time physical activity and blood pressure in older women. Although there is some evidence that physical activity may decrease blood pressure in young and middle-aged women, the physical activity-blood pressure association in older women has rarely been studied. As part of an ongoing community-based study of chronic disease, 641 Caucasian women between the ages of 50 and 89 years had blood pressure measured following the Hypertension Detection and Follow-up Program protocol. They also answered selected Health Interview Survey questions about their leisure-time activity and were classified into categories of light (58%), moderate (24%), heavy (6%), or no physical activity (12%) by the estimated metabolic rate required for each activity. Women who engaged in any physical activity were significantly younger and thinner than sedentary women and had lower fasting and 2-hour postchallenge insulin levels. They did not differ in alcohol consumption, cigarette use, or prevalence of coronary heart disease or diabetes. Rates of systolic and diastolic hypertension were significantly lower in women participating in light, moderate, or heavy physical activity compared with sedentary women. Blood pressure levels decreased with each increase in reported activity intensity (p less than 0.005 for trend), with systolic blood pressure approximately 20 mm Hg lower in the heaviest activity group compared with systolic blood pressure in sedentary women. Intergroup differences remained statistically significant after adjustment for age and body mass index. Although physical activity was associated with lower fasting and 2-hour postchallenge insulin levels (p less than 0.01 for trend), adjustment for insulin levels did not alter blood pressure differences among activity groups. 
2	Role of upper gastrointestinal investigations in a screening study for colorectal neoplasia. Should patients with positive faecal occult blood screening tests who are free of colorectal neoplasia undergo upper gastrointestinal investigation? Altogether 16,985 faecal occult blood tests were completed in a group of 18,818 asymptomatic patients (45-75 years) offered screening at two yearly intervals. A total of 447 (2.6%) were positive and underwent large bowel investigations. No neoplastic disease was identified in 283 (63%) of them. Fourteen (5%) also underwent gastroscopy for upper gastrointestinal symptoms, benign conditions were identified in five and a gastric carcinoma in one. No further investigations were instituted in the remaining 269 subjects who have now been followed up for a median period of 5 years (2-8 years). Five have been referred for benign upper gastrointestinal conditions, but none for upper gastrointestinal malignancy. Thirty one subjects have died - one from gastric cancer (a patient who had undergone a previous partial gastrectomy for a duodenal ulcer and who had persistent upper gastrointestinal symptoms). The remaining deaths were unrelated to the upper gastrointestinal tract. Nineteen people who have left the trial area have been monitored for the development of malignant disease; none have presented with upper gastrointestinal malignancy. These data support the view that upper gastrointestinal investigations need not be performed routinely in this group of subjects, but may be reserved for those with relevant symptoms. 
1	The prophylactic use of octreotide in a patient with ovarian carcinoid and valvular heart disease. This case report describes the use of octreotide, a long-acting somatostatin analogue, in the management of a patient with an ovarian carcinoid tumour and severe cardiac valvular disease. This patient underwent laparotomy and tumour resection without complication. Anaesthesia was induced with midazolam, fentanyl, and vecuronium, and maintained with isoflurane as well as additional fentanyl and vecuronium. However, we feel that it was the use of octreotide that prevented a life-threatening crisis intraoperatively, and recommend its use in patients with carcinoid syndrome undergoing anaesthesia and surgery. 
3	Cognitive function testing in comprehensive geriatric assessment. A comparison of cognitive test performance in residential and clinic settings. Tests of cognitive function are frequently used in geriatric assessment, but the effect of test setting has rarely been explored. To determine the effect of testing site on the performance of elderly patients undergoing a comprehensive geriatric assessment, we administered the Mini-Mental State Exam to 116 geriatric patients in the clinic and at their residence. Their cognitive abilities varied from normal to severely impaired. The patients' scores were 1.5 +/- 3.6 (mean +/- SD) higher at their residence. The clinical importance of a difference in score of 1.5 is not clear. For this reason a second analysis was performed in which a difference in scores of five points or greater between settings was considered clinically meaningful. Twenty-five percent (29 of 116) differed by five points or more. Of these 29 patients, 22 (76%) tested better in the residential setting. These differences were statistically significant (P = .001). We conclude that the testing site may affect test performance and that in-home assessment may reveal the optimal cognitive function of geriatric patients. 
5	Chronic dehydration stone disease. A study was made of 819 patients attending a metabolic stone clinic. A firm diagnosis was made in 708 (86%) and in 132 of these (19%) the diagnosis was thought to be chronic dehydration. The records were available for study for 87 males and 11 females in the chronic dehydration group. The mean age at presentation was 43 years. The causes of chronic dehydration were hot climate (62%), with hot occupation and low water intake almost equal in second place. In patients with a single cause of chronic dehydration, 57% also had a dietary risk factor for urolithiasis and this was most commonly high oxalate intake. Following dietary advice, the mean urinary volume increased from 1720 to 2475 ml/24 h. This was accompanied by a rise in mean urinary calcium from 6.02 to 6.96 mmol/24 h, presumably due to the calcium in the additional water drunk. Urinary oxalate did not change significantly. The mean follow-up time was 4.85 years and the stone recurrence rate was low. It was concluded that chronic dehydration is a common cause of urolithiasis; this can be treated satisfactorily by increasing water intake plus dietary advice in certain cases. 
3	Physical features of Prader-Willi syndrome in neonates. A retrospective study of 16 patients was undertaken to identify physical features that may typify neonates with Prader-Willi syndrome. Several features known to be typical of Prader-Willi syndrome in early infancy were confirmed, including hypotonia and genital hypoplasia. A number of features that have not previously been emphasized as characterizing Prader-Willi syndrome were also identified, most notably abnormal cry and, in males, signs of genital hypoplasia but with an apparently normal phallus. Other features included disproportionately large head circumference, disproportionately large anterior fontanelle, mild micrognathia, mild anomalies of the gingivae or alveolar ridges, and changes in the appearance of the skin. Appreciation of these features may assist the pediatrician in recognizing the child with Prader-Willi syndrome during the neonatal period, before the appearance of better-known findings of later onset, such as obesity and acromicria. 
5	One-stage laryngotracheoplasty. This article documents the evolution of our approach to the repair of subglottic stenosis in infants. With increasing experience in the management of subglottic stenosis using the anterior cricoid split procedure, we extended our procedure to include older children. This then led to the use of the one-stage procedure for repair of severe and mature subglottic stenosis. We present the results of surgical repair in 13 patients. Extubation was accomplished in 12 of 13 patients using one-stage laryngotracheoplasty. 
4	Interleukin-2-induced lung permeability is mediated by leukotriene B4. Interleukin (IL)-2 therapy leads to respiratory dysfunction due to increased vascular permeability. This study examines the role of the chemoattractant, immunomodulator, and permeability-promoting agent leukotriene (LT) B4 in this setting. Sheep with chronic lung lymph fistulae were given IL-2, 10(5) U/kg as an IV bolus (n = 6). Within 2 hours this led to a significant increase in LTB4 levels in both plasma and lung lymph. The mean pulmonary artery pressure (MPAP) rose while the pulmonary artery wedge pressure was unchanged. Arterial oxygen tension (PaO2) fell. Lung lymph flow (QL) was tripled (P less than 0.05) at 3 hours, coinciding with an increase in the lymph/plasma (L/P) protein ratio (P less than 0.05) resulting in an increase in the lymph protein clearance (P less than 0.05), data documenting increased microvascular permeability to protein. Mild leukopenia and thrombocytopenia (P less than 0.05) occurred. Body temperature rose and shaking chills were common. Pretreatment with the lipoxygenase inhibitor diethylcarbamazine (DEC; n = 6) reduced baseline plasma LTB4 levels and prevented the IL-2-induced increases in LTB4 in plasma and lung lymph (P less than 0.05). In contrast to IL-2 treatment alone, DEC blunted the increase in MPAP and prevented the rises in QL (P less than 0.05), L/P protein ratio (P less than 0.05), and lymph protein clearance (P less than 0.05). DEC also prevented the IL-2-induced leukopenia, the fall in platelet count, and the rise in body temperature (P less than 0.05, respectively). Infusion of IL-2 excipient control (n = 5) did not affect plasma or lymph LTB4 levels but there were mild increases in MPAP (P less than 0.05). The QL also rose but this occurred while the L/P protein ratio fell (P less than 0.05). Body temperature rose moderately. The PaO2, leukocyte, and platelet counts were unaffected. These data indicate that IL-2 administration leads to pulmonary dysfunction manifest by pulmonary hypertension and increased vascular permeability, events associated with LTB4 synthesis and prevented by DEC. Leukotriene B4 appears therefore to mediate the IL-2-induced lung injury. 
5	Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer. To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer. 
5	Emergent saphenous vein graft stenting for acute occlusion during percutaneous transluminal coronary angioplasty. This report describes the initial use in the United States of emergency intravascular stenting for the treatment of acute coronary occlusion complicating elective saphenous vein graft angioplasty. This case adds further support to the role of the balloon expandable stent as an effective "bail out" device for failed angioplasty. 
5	Radical intracapsular removal of acoustic neurinomas. Long-term follow-up review of 11 patients. Historically, the neurosurgical treatment of large acoustic neurinomas has developed with two principal goals: complete tumor removal and preservation of facial nerve function. A recent goal for small tumors is the preservation of hearing. Out of a personal series of 124 acoustic neurinomas treated over the past 35 years, the senior author has undertaken a radical intracapsular approach in 12 patients with large tumors (greater than 3 cm in diameter). Surgical indications for intracapsular removal included advanced age (five cases), the patient's wish to avoid any risk of facial paralysis (six cases), contralateral facial palsy (one case), and contralateral deafness (one case). Eleven of these 12 patients were available for follow-up review. Tumor recurrence developed in two patients (18%) at 2 and 3 years postoperatively; there were no late recurrences. Four patients died of unrelated causes, 10 to 19 years after surgery. The remaining five patients have survived a mean of 12 years since surgery without recurrence (range 3 to 22 years). Facial function was preserved in nine patients (82%). The results suggest that radical intracapsular removal may be the procedure of choice under certain circumstances and may offer an alternative to focused high-energy radiation. 
1	Quality-of-life-adjusted survival for comparing cancer treatments. A commentary on TWiST and Q-TWiST. In chronic disease situations where treatment comparisons favor no particular therapy, or where definitive outcome requires a considerable follow-up period, it is useful to have additional and perhaps intermediate endpoints of relevant clinical significance to compare treatments. One such endpoint is Time Without Symptoms and Toxicity (TWiST) which, together with Q-TWiST, attempts to address the quality of life of patients receiving the competing regimens. This paper provides a commentary on these techniques with an emphasis on the problems inherent in implementing Q-TWiST, a measure that attempts to incorporate patient value preferences into TWiST. It is argued that while Q-TWiST is intuitively appealing in the clinical setting, there are formidable design and psychometric hurdles that must be overcome to fully operationalize the concept. 
3	Shy-Drager syndrome. Effect of fludrocortisone and L-threo-3,4-dihydroxyphenylserine on the blood pressure and regional cerebral blood flow. In nine cases of Shy-Drager syndrome, the changes in blood pressure and cerebral blood flow on sitting up from a supine position were studied. The influence of fludrocortisone, a synthetic mineralocorticoid, and L-threo-3,4-dihydroxyphenylserine (DOPS), a precursor of norepinephrine, on these changes was examined. On sitting up, the regional cerebral blood flow (rCBF) measured by Xe133 inhalation showed a tendency to decrease. Fludrocortisone reduced the fall of the mean blood pressure significantly. DOPS reduced the fall of both the diastolic blood pressure and rCBF significantly. 
5	Tick-borne borreliosis in west Africa. Reported cases of tick-borne relapsing fever due to the spirochaete Borrelia crocidurae are rare in West Africa, and few epidemiological data are available. To see how common relapsing fever is in Senegal thick blood smears from cases of fever of unknown origin and from randomly selected clinic outpatients from a rural dispensary were examined for Borrelia. The prevalence of Borrelia infections in small mammals was also assessed. Borrelia was seen in smears of 12 (0.9%) of 1340 children. All children who tested positive had complained of acute fever. Prevalence was 0% (0/496), 0.5% (2/417), 1.6% (5/308), and 4.2% (5/119) at ages 0-1, 2-4, 5-9, and 10-14, respectively. 26 other instances of borreliosis were seen in patients from different regions of Senegal. Blood samples from 7 of these patients were inoculated intraperitoneally into white mice; serious infection developed in all mice. Borrelia was seen in thick smears from 65 of 461 wild rodents or insectivores. Six rodents species were infected. From a sample of 93 rodents, 33.3% were infected, as judged by intraperitoneal inoculation of white mice, compared with 14.1% by direct smear examination. The findings suggest that borreliosis has a wide distribution and a high incidence in Senegal. This disease may be a major cause of morbidity in rural areas throughout much of West Africa. 
1	Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein kinase. The molecular structure of a rat hepatoma 70-kDa insulin/mitogen-stimulated S6 protein kinase, obtained by molecular cloning, is compared to that of a rat homolog of the 85-kDa Xenopus S6 protein kinase alpha; both kinases were cloned from H4 hepatoma cDNA libraries. The 70-kDa S6 kinase (calculated molecular mass of 59,186 Da) exhibits a single catalytic domain that is most closely related in amino acid sequence (56% identity) to the amino-terminal, kinase C-like domain of the rat p85 S6 kinase (calculated molecular mass of 82,695 Da); strong similarity extends through a further 67 residues carboxyl-terminal to the catalytic domain (40% identity), corresponding to a region also conserved among the kinase C family. Outside of this segment of approximately 330 amino acids, the structures of the p70 and p85 S6 kinases diverge substantially. The p70 S6 kinase is known to be activated through serine/threonine phosphorylation by unidentified insulin/mitogen-activated protein kinases. A model for the regulation of p70 S6 protein kinase activity is proposed wherein the low activity of the unphosphorylated enzyme results from the binding of a basic, inhibitory pseudosubstrate site (located carboxyl-terminal to the extended catalytic domain) to an acidic substrate binding region (located amino-terminal to the catalytic domain); substrate binding is thereby prevented. S6 kinase activation requires displacement of this inhibitory segment, which is proposed to occur consequent to its multiple phosphorylation. The putative autoinhibitory segment contains several serine and threonine residues, each followed directly by a proline residue. This motif may prevent autophosphorylation but permit transphosphorylation; two of these serine residues reside in a maturation promoting factor (MPF)/cdc-2 consensus motif. Thus, hormonal regulation of S6 kinase may involve the action of MPF/cdc-2 or protein kinases with related substrate specificity. 
5	Properties of strains of Escherichia coli O26:H11 in relation to their enteropathogenic or enterohemorrhagic classification. Thirty-seven strains of Escherichia coli O26:H11 from infants and calves with diarrhea were examined for properties associated with enteropathogenic (EPEC) or enterohemorrhagic E. coli (EHEC). Strains were heterogeneous with respect to Vero cytotoxin (VT) production and hybridization with the EHEC plasmid-specific (CVD419) probe; 26 strains produced VT1; 1 produced VT2. Twenty-four of 27 VT+ strains and 5 of 10 VT- strains hybridized with the CVD419 probe and produced enterohemolysin; these properties are characteristic of EHEC. The strains did not hybridize with the EPEC adherence factor probe, a property characteristic of some EPEC. Nevertheless, 36 strains adhered to HEp-2 cells in a localized manner and were positive by the fluorescence actin staining (FAS) test that is considered to correlate with the ability to cause attaching and effacing lesions in vivo. EPEC and EHEC cause these lesions. Although the FAS test appeared to be the most general pathogenicity test for the O26:H11 strains, it could not be used to assign strains specifically to EPEC or EHEC groups. 
5	Unusual complication of an ingested foreign body. Migration of a foreign body from the mouth and throat to the subcutaneous tissue of the neck is very rare. We present a case of a migrating foreign body (a piece of straw) from the floor of the mouth to the neck. To our knowledge, this is the second case reported in the English literature. 
3	Practice effects on the preprogramming of discrete movements in Parkinson's disease. The effects of practice on the simple and choice reaction times (RTs) of Parkinson's disease (PD) and control subjects in a discrete aiming task were analysed. For controls, practice led to a selective decrease in choice RTs, as has been reported previously. An opposite effect was seen in the PD group, with little change in choice RTs and substantial reduction in simple RTs. The results suggest that PD subjects can use advance information to initiate discrete movements more rapidly, but that this ability to "preprogramme" movements requires practice. Reconciliation of these results with studies reporting an inability to preprogramme in PD are made in a discussion of task characteristics which may allow or preclude preprogramming. 
1	Clustering of cancer in families of patients with primary lung cancer. We have previously shown that patients with a positive family history of lung cancer did not exhibit characteristics expected if the familial association was a surrogate for a genetic mechanism which was absent in those without such a history. In this study, we examine the incidence of cancer (all sites) in two groups of families: (a) those ascertained through a patient with primary lung cancer (n = 359 families) and (b) through a community control subject (n = 234). The index subjects were excluded from all incidence data analyses. Most families (62 vs 57%) reported at least one member with a history of neoplastic disease. Patients' families were more likely to have 2 or more affected members (p less than 0.05), to exhibit a multigenerational pattern (33 vs 24%) and to have a higher risk of multiple tumours (OR = 1.5) in the same individual. However, most of the sites with the highest odds ratios (males, vocal cord/esophagus 8.3; colon/rectum 2.3; lung 1.96; females, pancreas 4.8; vocal/cord esophagus 4.1; lung 1.8) are smoking associated although these were not necessarily the most frequently affected sites. In conclusion, these data support an ecogenetic etiology of cancer within families. 
5	Ritual and dying: a cultural analysis of social support for caregivers. This study examines the role of social support in the process of caring for someone dying at home. Based on data from in-depth ethnographic interviews with 16 caregivers, it employs a cultural analysis to draw parallels with rituals of transition. Ritual provides a broad context of meanings and routines for securing the doubts and unknowns of individual experience. The way social support is provided plays a key role in the caregiver's transition to bereavement. 
1	Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. In a 3-year prospective study of 643 consecutive laparoscopies for infertility, pelvic pain, or infertility and pain, the pelvic area, the depth of infiltration, and the volume of endometriotic lesions were evaluated. The incidence, area, and volume of subtle lesions decreased with age, whereas for typical lesions these parameters and the depth of infiltration increased with age. Deeply infiltrating endometriosis was strongly associated with pelvic pain, women with pain having larger and deeper lesions. Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class, considerations for a simplifying revision with inclusion of deep lesions are suggested. In conclusion, suggestive evidence is presented to support the concept that endometriosis is a progressive disorder, and it is demonstrated that deep endometriosis is strongly associated with pelvic pain. 
4	Coronary angiographic patterns in hypertensive compared with normotensive patients. Patients in this study were assessed by coronary angiography because of classic effort angina and a positive exercise test. Of these patients, 320 had untreated primary hypertension and 320, similar in age and gender distribution, were normotensive. In all patients coronary angiography documented that at least one major epicardial branch was restricted by 50% or more. Prevalence of single- and double-vessel disease in the fourth and fifth decades of life was similar in the two populations and in both tended to decline with age. Prevalence of triple-vessel disease was also similar in the two populations in the fourth and fifth decades; in either population it rose with age and reached a peak at the seventh decade of life. The percentages of hypertensive patients in the sixth and seventh decades with triple-vessel disease was significantly (p less than 0.01) greater (40% and 50%, respectively) than the corresponding values in normotensive individuals (25% and 31%, respectively). The left main coronary artery was not significantly more involved in the high blood pressure group. Pressure was moderately and similarly raised at any age in hypertension; serum cholesterol and triglyceride levels, blood glucose, and smoking habits were comparable in the two populations. These results suggest that hypertension does not accelerate the appearance of significant coronary narrowing or multiple vessel involvement. Starting from the sixth decade, the natural age-related evolution of coronary disease seems to be aggravated in hypertensive subjects, as reflected by an augmented number of diseased vessels. This process is probably related to high blood pressure in itself; whether the severity of hypertension might also exert an influence is not deducible from this study. 
3	Potentially fatal asthma and syncope. A new variant of Munchausen's syndrome in sports medicine. We report a case of Munchausen's syndrome in a 19-year-old female college athlete who presented with potentially fatal asthma and recurrent syncopal episodes. Failure to control her asthma with the appropriate medications and the lack of objective findings on both physical examination and diagnostic testing raised the possibility of factitious disease. Munchausen's syndrome, although not described with any frequency in asthmatic patients, should be considered in the differential diagnosis of those patients refractory to aggressive medical management. 
3	Ultrastructural study of Norrie's disease. We studied the clinicopathologic and ultrastructural features of a full-term infant with Norrie's disease. The infant had bilateral retrolental fibrous vascular masses and retinal detachment with no other apparent physical abnormalities and no family history of ocular defects. A vitrectomy and a membrane peeling were attempted, and specimens of the retina, the retrolental membrane, and a vascularized epiretinal peripheral mass were examined by light and electron microscopy. The retrolental membrane was composed of layered collagenous tissue and contained structures resembling blood vessels. Inner and outer neuroblastic layers were identified in the retinal tissue, but no vessels were present. In the epiretinal mass, portions of retina and cortical vitreous were seen along with primitive vascular structures. The histologic appearance of these specimens suggests that the major pathologic event of Norrie's disease occurs in the retina in the third to fourth gestational month. We believe the subsequent ocular abnormalities found in this patient were secondary to this early retinal malformation and did not represent a progressive ocular disorder. 
1	Primary renal lymphoma. Lymphoma arising in the kidney is rare. Although 31 cases have been reported in the literature, it is likely that most of these neoplasms do not arise in the kidney. This report describes two cases of primary renal lymphoma and compares their clinical presentation, diagnostic modalities, treatment, and survival with the previously reported patients who satisfied our criteria for the diagnosis of primary renal lymphoma. 
1	Recurrent renal cell carcinoma arising in Wilms' tumor. A 19-month-old black girl had a radical nephrectomy for a Wilms' tumor that contained areas of epithelium indistinguishable from renal cell carcinoma. She was treated with chemotherapy but subsequently had pulmonary metastases develop and massive abdominal recurrence. The recurrent tumor was histologically renal cell carcinoma with no identifiable Wilms' tumor elements. The child died with recurrent and metastatic tumor 13 months after nephrectomy. Pathologic, immunoperoxidase, and flow cytometric studies of this unusual case are presented. 
4	Large arteries involvement in scleroderma--a case report. The authors describe a thirty-nine-year-old woman patient presenting with progressive systemic sclerosis and an unusual angiographic picture of an impairment of large arteries, which in their opinion is due to the primary disease. The review literature reports about similar arterial involvement in scleroderma. 
4	Vasopressin response in collecting ducts of rats resistant to mineralocorticoid hypertension. In previous studies we found that vasopressin stimulation of both cyclic AMP (cAMP) formation in cortical collecting tubules (CCT) and sodium reabsorption in isolated perfused kidneys was markedly exaggerated in rats with mineralocorticoid hypertension. In the present study, we tested the response (cAMP accumulation) of cortical and outer medullary collecting tubules (OMCT) to vasopressin in two rat models that are resistant to deoxycorticosterone acetate (DOCA)-induced hypertension, the Wistar-Furth strain and NaCl-deficient rats. The blood pressure of normal outbred Wistar rats rose to hypertensive levels (systolic pressure more than 165 mm Hg) during a 5-week treatment with DOCA (10 mg/week) and 1% saline to drink. Significant hypertrophy of the heart and kidneys was also observed. Vasopressin (10(-8) M)-induced cAMP formation was enhanced 3.4-fold in the CCT (OMCT unchanged) of hypertensive rats compared with normotensive controls. Significant hypertrophy (as indexed by tubule diameter) of the CCT but not the OMCT was also observed in DOCA-salt hypertensive rats. Restriction of dietary NaCl (0.13% in chow, tap water to drink) completely prevented DOCA-induced hypertension, organ and CCT hypertrophy, and enhancement of vasopressin-stimulated cAMP formation in the CCT. In Wistar-Furth rats, DOCA-salt treatment did not alter blood pressure or cause significant organ hypertrophy. However, DOCA-salt treatment enhanced vasopressin-stimulated cAMP formation by 4.1-fold in CCT of Wistar-Furth rats, with significant tubular hypertrophy in the CCT but not the OMCT. We conclude that DOCA-induced hypertension and changes in CCT function are dependent on excess dietary NaCl. 
5	Recurrent seizures in children with Shigella-associated convulsions. Fifty-five children with Shigella-associated convulsions were followed prospectively to investigate their risk of subsequent febrile or nonfebrile seizures. The duration of the follow-up period was between 6.9 and 14.1 years (9.7 +/- 3.1 years). No case of nonfebrile seizures and only 2 cases (3%) of subsequent febrile seizures were observed during this period. We conclude that although febrile and Shigella-associated convulsions share many clinical features, the natural history of these two conditions seems to be distinctly different. Shigella-related convulsions are not associated with an increased incidence of subsequent febrile or nonfebrile convulsions. 
5	Evidence for platelet-activating factor as a late-phase mediator of chronic pancreatitis in the rat. The role of platelet-activating factor (PAF) as a mediator of pancreatic inflammation was examined in the rat pancreatic duct ligation model of obstructive pancreatitis. Pancreatic generation of PAF, as measured by bioassay (ie, platelet [3H]serotonin secretion), was determined at various times after induction of inflammation. Tissue levels of PAF in the normal pancreas averaged 600 +/- 49 pg/g, but PAF was not detectable during the initial 24 hours of pancreatitis, a time when the inflammatory reaction would be considered acute, that is, during the period of maximal serum amylase release and the development of interstitial edema. However a substantial increase in pancreatic PAF levels (12 times control levels) was observed 7 to 14 days after duct ligation during the late-phase response interval similar to the situation characteristic of chronic pancreatitis in which parenchymal atrophy, fibrosis, and pancreatic insufficiency evolve. One week after duct ligation when PAF levels peaked, an evaluation was made of the effects of PAF antagonists (BN52021 and WEB2170) on pancreatic lesions using Evan's blue extravasation, pancreatic myeloperoxidase (MPO) activity, and acid phosphatase activity in peritoneal lavage fluid. BN52021 or WEB2170 treatment was shown to reduce pancreatic damage and inflammation significantly. Long-term in vivo administration of exogenous PAF (20 micrograms/kg/hr for 7 days) exhibited a reduction of [3H]thymidine uptake into and amylase release from pancreatic acini in vitro. Our observations 1) that pancreatic PAF levels increased significantly during the chronic phase of obstructive pancreatitis induced by duct ligation; 2) that inhibition of the action of PAF, through specific receptor antagonism, caused an attenuation of pancreatic lesions; and 3) that chronic administration of PAF resulted in decreased pancreatic regeneration and exocrine function are consistent with a pivotal role for PAF as a late-phase inflammatory mediator in chronic pancreatitis in rats. 
5	Axial myoclonus of propriospinal origin. Three patients are described with nonrhythmic repetitive axial myoclonic jerks causing symmetric flexion of the neck, trunk, hips and knees. No electrophysiological evidence of a cortical or brainstem reticular origin for the myoclonus was found. In the first patient the axial jerks only occurred spontaneously. The latencies of recruitment of spinal segments during a jerk indicated that the discharge arose in the mid thoracic cord and then slowly spread at about 5 ms-1 up and down the cord to involve rostral and caudal segments. No structural lesion was identified in this patient. In the second patient spontaneous and reflex axial jerks developed following the excision of a cervical haemangioblastoma. In the stimulus-induced jerks the relative latencies of muscles innervated by rostral and caudal spinal segments suggested that the myoclonus originated between the upper cervical and midthoracic cord. In the final patient, EMG activity during spontaneous and stimulus-induced jerks commenced in the rectus abdominis, and was followed by later activity in muscles innervated by rostral spinal segments, suggesting that the myoclonus originated in the midthoracic cord. No structural lesion was identified in this patient. Electrophysiological evidence is used to argue a spinal origin for these axial jerks in all 3 cases. There are striking features common both to this form of human myoclonus and to long propriospinal pathways identified in animals. The new concept of propriospinal myoclonus is suggested. 
5	Gallium-67 imaging in retroperitoneal fibrosis: significance of a negative result. A patient with retroperitoneal fibrosis and right peritracheal and hilar lymphadenopathy was studied using gallium-67-citrate. No abnormal uptake was seen in the regions of retroperitoneal fibrosis, while there was avid uptake in chest lesions later shown to represent small cell lung carcinoma. Retroperitoneal fibrosis which does not show gallium uptake is most likely mature, with few inflammatory elements. In patients with multiple retroperitoneal and/or mediastinal masses, gallium imaging may be useful in identifying the most active sites of disease for possible biopsy and for subsequent monitoring of response to therapy. 
4	Angioplasty of coronary bifurcation stenoses: immediate and long-term results of the protecting branch technique. Percutaneous transluminal angioplasty (PTCA) of coronary stenoses involving major bifurcations carries a small but significant risk of side branch occlusion which can be avoided by simultaneously using multiple dilatation systems. Among 1,275 PTCA procedures performed between 1984 and 1988 in 1,035 consecutive patients, 42 double wire procedures were applied (4%) to protect and/or dilate major coronary side branches. A total of 80 coronary stenoses were attempted of which 76 were located on a bifurcation and 4 on other segments. In the first 11 patients (group A), 2 guiding catheters were used and PTCA of each vessel was successfully performed by means of separate double lumen over-the-wire balloon catheters. In the next 31 patients (group B), 2 guidewires were advanced through a single guiding catheter and PTCA was attempted using "Monorail" balloon catheters sequentially advanced over the wires. In group B, a successful PTCA was obtained in 29 patients (93%) but twisting of the wires hampered balloon progression in 5 cases, such that dilatation could only be performed by stepping back to a single wire technique. The procedure time in group B was significantly shorter than in group A: 144 +/- 30 versus 230 +/- 52 minutes (p = .01). Repeat angiography was performed in 35 out of 40 patients (87%) after a mean of 180 +/- 46 days following successful PTCA. Angiographic restenosis was present in 37% (24/65) of bifurcation segments which, in our experience, is not significantly different from the angiographic restenosis rate in less complex lesions (248/740; 34%; NS). 
4	Results of primary angioplasty for acute myocardial infarction in patients with multivessel coronary artery disease. The influence of multivessel coronary artery disease on the outcome of reperfusion therapy for myocardial infarction has not been fully characterized. Direct coronary angioplasty without antecedent thrombolytic therapy was performed during evolving myocardial infarction in 285 patients with multivessel coronary artery disease at 5.2 +/- 4.2 h after the onset of chest pain. Two vessel disease was present in 163 patients (57%) and three vessel disease in 122 (43%). An anterior infarct was present in 123 patients (43%), cardiogenic shock in 33 (12%) and age greater than or equal to 70 years in 59 (21%). Angioplasty of the infarct-related vessel was successful in 256 patients (90%), including 92% with two vessel and 88% with three vessel disease (p = NS). Emergency bypass surgery was needed in six patients (2%). In-hospital death occurred in 33 patients (12%), including 13 with two vessel and 20 with three vessel disease (p less than 0.05). The mortality rate was only 4% in the subgroup of 101 patients who met entry criteria for thrombolytic trials. The in-hospital mortality rate was 45% in patients in shock and 7% in patients not in shock (p less than 0.01). Logistic regression analysis identified shock and age greater than or equal to 70 years as independently associated with in-hospital death. In 135 patients who underwent predischarge left ventriculography, global ejection fraction increased from 50% to 57% (p less than 0.001) and regional wall motion in the infarct zone improved in 59% of patients. Follow-up data were available in 251 patients (99%) at a mean of 35 +/- 19 months. 
1	Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa Hepatocellular carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia. Hepatitis B virus and aflatoxins are risk factors for HCC, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines, and allelic losses from chromosome 17p have been found in HCCs from China and Japan. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G----T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa, which is both a mutagen that induces G to T substitution and a liver-specific carcinogen. 
5	Pachyonychia congenita complicated by hidradenitis suppurativa: a family study. A family is described in which five of the six members with the Jackson-Lawler type of pachyonychia congenita also had varying degrees of hidradenitis suppurativa. We suggest an association between this type of pachyonychia congenita and hidradenitis suppurativa. 
3	Thrombolytic therapy for noncoronary diseases. Thrombolytic therapy has been used fairly extensively in the management of acute proximal deep-vein thrombophlebitis of the extremities, acute pulmonary embolism, and acute peripheral arterial thrombosis and embolism in addition to acute thrombotic coronary events. In the presence of acceptable indications and a favorable benefit to risk ratio, this form of therapy, when successful, has served as a useful adjunct in the management of these disorders. In deep-vein thrombophlebitis, lysis of the thrombus before permanent pathological changes (eg, organization, scarring) have occurred can prevent venous valvular dysfunction and postural venous hypertension and its complications, especially the postphlebitic syndrome. In the more severe forms of acute pulmonary embolism, thrombolytic therapy, when applied early after symptom onset, decreases morbidity and is likely to prevent a chronic increase in pulmonary vascular resistance and persistent pulmonary hypertension. In peripheral arterial thrombo-occlusive events, early restoration of flow through thrombolysis has been shown to limit ischemic damage and serve as a useful supplement to angioplasty or surgery. Thrombolytic therapy has been used less extensively in acute strokes. Here the danger of reperfusion causing bleeding into a softened area of brain undergoing infarction has slowed its evaluation for this disorder; its application to stroke remains experimental. 
3	Patterns of neuropsychological impairment after severe blunt head injury. A consecutive series of 100 subjects with severe blunt head injuries was followed up 6 years after trauma. Neuropsychological test performances of 82 subjects and of a noninjured control group were analyzed by two principal components analyses (PCAs). Each PCA extracted 15 factors relating to a range of cognitive impairments, as well as neuropsychological features consistent with posttraumatic personality changes. Measures identified by the PCAs were applied to 85 head-injured subjects in the series to examine the incidence of impairment in four neuropsychological areas: disorders of learning and memory, neuropsychological features consistent with posttraumatic personality change, slowness in rate of information processing, and a range of basic neuropsychological skills. Overall, impairments occurred in 70% of the series. Disorders of learning and memory were the most common type of deficit (56.5%), with disturbances in basic neuropsychological skills the least frequent (16.5%). Variability among subjects with respect to the types and combinations of neuropsychological impairments was a characteristic feature of this clinical group, but the largest proportion (one-third) demonstrated isolated impairments. The implications of the incidence and selectivity of neuropsychological impairments are discussed. 
4	Mechanism of early ischemic contractile failure. Inexcitability, metabolite accumulation, or vascular collapse? The basis of early ischemic contractile failure was investigated in perfused ferret hearts at 27 degrees C. Isovolumic left ventricular developed pressure fell by more than 50% within 30 seconds of the onset of total global ischemia and reached zero by 5 minutes. Monophasic action potential recordings revealed no decrease in excitability during this period. Phosphorus nuclear magnetic resonance spectra obtained at 30-second resolution showed no significant changes in inorganic phosphate or phosphocreatine during the first 30 seconds of ischemia. Intracellular pH (pHi) and ATP changed even more slowly; therefore, none of these metabolites could account for the rapid fall in force. To gauge the contribution of intravascular pressure, we compared ordinary aortic flow occlusion with tissue-level ischemia induced by massive coronary microembolization at the level of the precapillary arterioles. Functional depression developed significantly more slowly in the microembolized hearts, despite accumulation of inorganic phosphate and protons comparable with that in ordinary ischemia. After microembolization, the time course of functional depression reflected much more closely the concomitant inorganic phosphate and pHi changes. Thus, our results provide novel evidence supporting the importance of vascular collapse in the mechanism of early ischemic contractile failure. 
5	Total hip arthroplasties in patients younger than 45 years. A nine- to ten-year follow-up study. Eighty-one cemented total hip arthroplasties in patients younger than 45 years were reviewed with an average 9.2-year follow-up interval. The results were compared with the same group previously reported at an average follow-up time of 4.5 years. Clinically satisfactory results were 58% compared with 78% at 4.5 years. The revision rate almost tripled to 33%. Impending failure was present in 56% of those hips not yet revised. In the first study, technique was a primary determinant of success. In this report there was no influence of technique on the incidence of revision. Age did not influence revision rates either, with 35% in patients younger than 30 years and 32% in patients aged 30-45 years. Patients younger than 30 years had fewer satisfactory clinical results and a higher rate of impending failure. As in the first study, the best results were obtained in patients with inflammatory collagen disease aged from 30 to 45 years. 
2	Comparison of gall bladder bile and endoscopically obtained duodenal bile. In 10 patients with gall stone disease (eight women, two men; mean (SD) age 47.4 (13) years), bile was obtained by endoscopic aspiration after stimulation of the gall bladder with ceruletid and also by fine needle puncture of the gall bladder under local anaesthetic. The total lipid concentration of the puncture bile samples was mean (SD) 11.9 (4.7) g/dl, significantly higher than the endoscopic bile samples (3.9 (3.3) g/dl, p less than 0.001). Total bile acids, phospholipids, and biliary cholesterol (expressed in mol%) and cholesterol saturation index showed no significant differences between the two types of samples. The glycocholic acid concentration in the endoscopically obtained bile (27.7 (6.6) mol% v 23.3 (5.4) mol%; p less than 0.01) was significantly higher than the puncture bile samples. Puncture bile exhibited a significantly shorter nucleation time (3.5 (3.3) days v 19.6 (11.9) days; p less than 0.001). For determination of the nucleation time, endoscopic bile aspiration after gall bladder stimulation with ceruletid led to adequately concentrated samples in 50% of the study subjects. Cholesterol monohydrate crystal formation in native bile was observed in six samples of puncture bile and in three samples of the endoscopically obtained bile. The presence of cholesterol crystals and the determination of nucleation time in the puncture bile were the best discriminants between cholesterol and pigment gall stones and correlated well with computed tomogram analysis. 
2	Transient and distant infections alter later intraperitoneal abscess formation. Transient nosocomial infections, such as line sepsis and pneumonia, are common in today's critical care patient population. Although generally well treated, the effect of these transient antigen exposures on the immune system is unclear. We have previously shown that prior intraperitoneal inoculation with live bacteria leads to increased numbers of intraperitoneal abscesses. Data presented here demonstrate in a murine model that two immunizations with live Escherichia coli, Bacteroides fragilis, or both, administered systemically via intracardiac injection or at a focal distant site in subcutaneous tissue, significantly increased the number of mixed E coli/B fragilis intraperitoneal abscesses when induced 1 week later. Further, immunization with E coli, either alone or in combination with B fragilis, increased the total number of anaerobes recovered per mouse. Transient or focal sublethal infections can significantly alter an animal's immune response to later infectious insults, particularly the formation of intraperitoneal abscesses. 
5	Latent sensitisation to respiratory syncytial virus during acute bronchiolitis and lung function after recovery. To determine whether latent sensitivity to respiratory syncytial virus antigen(s) occurs after infection, 27 infants with acute bronchiolitis were studied and compared with 15 hospital controls. Blood was collected for whole blood challenge, and histamine release was measured by a high performance liquid chromatography technique with fluorometric detection. There was a significantly greater histamine release to respiratory syncytial virus antigen(s) in those with bronchiolitis than in controls, expressed either in amount (median 154 nmol/l compared with 104 nmol/l) or percentage release (median 20% compared with 3%). There was a significant difference between index and control groups in terms of individual histamine responses. These findings strongly suggest that infants develop latent sensitivity to respiratory syncytial virus antigen(s) during the course of acute bronchiolitis. Serial lung function tests were performed in 15 infants. All infants had abnormalities of lung function at some stage, but the small numbers of subjects precluded comparison between 'sensitised' and 'non-sensitised' infants. Further study is indicated to define the relation of latent sensitisation and subsequent bronchial hyper-responsiveness after respiratory syncytial virus infection in infants. 
1	Protective role of vitamin E in biological systems. Vitamin E is well accepted as nature's most effective lipid-soluble, chain-breaking antioxidant, protecting cell membranes from peroxidative damage. Free-radical-mediated pathology has been implicated in the development over time of degenerative diseases and conditions. This paper reviews the current research on the protective role and requirements for vitamin E and the other antioxidants in preventing or minimizing free-radical damage associated with specific diseases and lifestyle patterns and processes, including cancer, aging, circulatory conditions, arthritis, cataract, pollution, and strenuous exercise. While awaiting results of further human studies, research evidence suggests that an adequate intake of vitamin E and the other antioxidants can provide protection from the increasingly high free-radical concentrations caused by air pollutants and current lifestyle patterns. 
3	Alkalinisation of prilocaine for intravenous regional anaesthesia. Suitability for clinical use. Eighty unpremedicated patients undergoing day-case hand surgery under intravenous regional anaesthesia were randomly allocated to receive, in a double-blind study, either 40 ml 0.75% prilocaine hydrochloride, with 5 ml 8.4% sodium bicarbonate or 5 ml 0.9% saline. The alkalinised group had significantly less pain on injection (p = 0.0045), during surgery (p = 0.0074) and 5 minutes after the tourniquet was deflated (p = 0.0027). The time elapsed between insertion of the block and commencement of surgery was not affected. 
5	Alexia without agraphia associated with spleniogeniculate infarction. Pure alexia, following an infarction in the distribution of the left posterior cerebral artery, is attributed to damage of the left occipital lobe and the splenium of the corpus callosum. We describe a case of pure alexia in a 57-year-old woman with infarction of the left lateral geniculate body and the splenium of the corpus callosum, a variation on this classic disconnection syndrome. 
1	Giant enterocystoma within an infant's tongue. A rare developmental cyst within the tongue and submandibular triangle of a male infant containing heterotopic gastric and intestinal epithelium (enterocystoma) is described and its derivation discussed. This cyst was of such a size as to cause feeding difficulties and partial airway obstruction during sleep. Following C.T. scanning, total obstruction necessitated an emergency tracheostomy. Successful enucleation via a median labiomandibulotomy was performed without further complication and two years later there is no sign of recurrence. 
1	Neonatal subependymal giant cell astrocytoma associated with tuberous sclerosis: MRI, CT, and ultrasound correlation. We describe a term newborn with tuberous sclerosis who presented with a neonatal brain tumor, diagnosed as a subependymal giant cell astrocytoma. We compare the various imaging modalities used in the diagnosis of this tumor. 
1	Campylobacter pylori interactions with gastric cell tissue culture. Many investigators have reported that gastric mucosal biopsies of patients with chronic gastritis and peptic ulcer disease show the presence of Campylobacter pylori in a large majority of cases. Histologic examinations of such tissues indicate a close approximation of C. pylori with gastric surface epithelial cells. A recent report has described both adherence and cell invasion of gastric cells by C. pylori. Using a transmission electron microscope, we have examined the interaction between C. pylori, C. jejuni, and E. coli in vitro with a gastric cancer cell line, Kato III. Our results indicate marked toxicity of E. coli and moderate toxicity of C. jejuni for Kato III cells. C. pylori had only a minor effect on tissue culture viability. C. pylori was found to have a strong association with the Kato III cell membranes and evidence of occasional cell invasion. Both C. jejuni and E. coli showed no attachment or association with the Kato III cells. We interpret these findings as indicating that C. pylori may have a specific adhesion for gastric cells. 
3	Iatrogenic saphenous neuralgia: successful therapy with neuroma resection. We report the case of a patient with saphenous neuralgia secondary to iatrogenic trauma resulting from bypass surgery in the femoral-popliteal region. Early symptoms of this condition were medial calf and ankle pain, with no findings of motor and reflex abnormalities. Exploration of the thigh 2 years later revealed a neuroma of the nerve in the distal dissection site, medial to the knee. Resection of the neuroma alleviated this condition. It is noted that saphenous neuropathy is seen as a spontaneous entrapment syndrome as well as a complication of orthopedic and vascular procedures performed on the medial area of the knee. Saphenous neuralgia is often not recognized by neurosurgeons. If the condition is intractable, it does respond to surgical therapy. 
2	Kaposi's sarcoma of the colon in a young HIV-negative woman with Crohn's disease. We report a case of isolated colonic Kaposi's sarcoma in a 36-year-old HIV-negative woman with refractory Crohn's disease of the colon and perineum following 11 months' treatment with azathioprine. The clinical features of this case are quite different from those classically described in Kaposi's sarcoma. Among the known risk factors, iatrogenic immunosuppression would appear to be the most probable. 
1	Protection from chemotherapy-induced alopecia in a rat model. Alopecia (hair loss) is among the most distressing side effects of cancer chemotherapy. Little progress has been made, however, in its prevention or treatment, partly because of the lack of suitable experimental model. In recent work on the treatment of myelogenous leukemia in the rat, the following observations were made: (i) treatment of 8-day-old rats with cytosine arabinoside consistently produced alopecia, and (ii) ImuVert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against the alopecia. In subsequent experiments, both cyclophosphamide and doxorubicin also produced alopecia in this model, and the doxorubicin-induced alopecia was prevented by treatment with ImuVert. The potential relevance of these observations to chemotherapy-induced alopecia in the clinical setting should be examined. 
2	Collagenous colitis as a cause of chronic diarrhea. When the usual workup for chronic diarrhea fails to provide a diagnosis and the endoscopic findings are normal, alternative etiologies must be considered. This case of collagenous colitis represents such an alternative diagnosis. The patient is a 65-year-old woman who complained of abdominal cramps and watery diarrhea for an 8-month span. The key element to her diagnosis was subepithelial collagen deposits of the mucosa of the colon. Her symptoms were resolved with supportive care, diet, and diphenoxylate. Essential features and treatment of collagenous colitis are reviewed. 
1	Rhabdomyosarcoma. From the laboratory to the clinic. The prospect of identifying and developing new agents for treatment of rhabdomyosarcomas is discussed in the light of current prognosis for children with advanced stage disease. Preliminary attempts to identify tumor-specific agents using in vitro cell culture show potential promise, but as yet remain unproven. The more complex system of identifying therapeutically active agents using human tumor xenografts has demonstrated usefulness. The potential problems associated with this system are discussed. 
4	Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA. The perfluorochemical Fluosol-DA has been shown to reduce infarct size. However, the dose-response relationship of the agent is unknown. Because perfluorochemicals (PFC) can potentially saturate the reticuloendothelial system and decrease carbon clearance as well as cause a transient elevation in liver enzymes, the present study was conducted to determine the lowest effective dose. New Zealand White rabbits (n = 73) were randomly selected prior to infarction to receive 10, 15, 20, 25, or 30 ml/kg PFC or an equivalent volume of 5% dextran (control) intravenously. Animals underwent 30 minutes of coronary artery occlusion with PFC or dextran infused over a 30-minute period starting at 20 minutes into the occlusion. Animals were put to death at 24 hours and infarct size was determined histologically and quantitated by computerized planimetry. Neutrophil infiltration into the ischemic myocardium was evaluated semiquantitatively. No hemodynamic differences were noted within groups. Infarct size was similar to that of controls in animals treated with 10 or 15 ml/kg PFC. Significant infarct size reduction, however, was noted in animals treated with 20, 25, and 30 ml/kg PFC versus controls; (p = 0.05, 0.04, and 0.02, respectively). Maximal infarct size reduction was seen with 30 ml/kg PFC (35%). Neutrophil infiltration was significantly decreased in all groups treated with PFC. These results show that intravenous Fluosol-DA significantly reduces infarct size at a minimal dose of 20 ml/kg. 
1	Posterior nuchal cystic hygroma [published erratum appears in Clin Perinatol 1990 Dec;17(4):viii] When cystic hygroma is detected antenatally, the prognosis is usually poor, and intrauterine or neonatal death are common. This seems especially true for Turner syndrome (the largest etiologic group associated with cystic hygroma) and the lethal multiple pterygium syndromes. However, some fetuses with Turner syndrome, and also with certain other diagnoses, had a good outcome, and further study of these conditions is required before more definite prognostic indicators and risk figures will be available. Increasing numbers of syndromes are being reported in association with fetal cystic hygroma, and lymphedema may be a common element in their pathogenesis. Mild, short-lived, or otherwise uncomplicated jugular lymphatic obstruction may be a cause of the neck webbing seen in the Noonan, familial pterygium colli, and distichiasis-lymphedema syndromes. With earlier and more widespread fetal ultrasonography, and more sensitive techniques, a greater number of resolving fetal cases may be reported. This may clarify the natural history and provide prospective criteria for the conditions that have better prognoses. The associated conditions include autosomal dominant and recessive genetic traits. Careful ultrasound study for other malformations, polyhydramnios and fetal growth parameters, a fetal karyotype, and, if appropriate, pathologic examination are required to determine the etiology and recurrence risk. The parents should be asked about exposure to alcohol or other agents and should be examined for signs of pterygium colli or Noonan syndrome. If the decision is made to continue the pregnancy, and there is doubt about the natural history and prognosis, multi-disciplinary supervision should include social services, neonatology, pediatric surgery, cardiology, and genetics specialties when indicated. 
5	Magnetic resonance imaging and computer tomography of acute spinal cord trauma. Spinal cord lesions are not detectable on roentgenograms and computed tomography (CT) scans. Magnetic resonance images (MRIs) are able to make soft-tissue lesions visible. Interpretations of MRIs, CT scans, and roentgenograms were compared in 25 patients and three postmortem specimens with spinal cord injuries. In 14 patients and one specimen with normal roentgenograms and CT scans, the MRI demonstrated ten soft-tissue injuries as minimal displacement of the vertebral bodies or as a high signal intensity in the disc space, indicating a hematoma. Seven of the ten patients demonstrating soft-tissue injuries also had an intramedullary lesion, while in five of the 15 patients with normal CT scans, only a medullary lesion was present on MRI. In 11 patients and two postmortem specimens, fractures were seen on roentgenograms and CT scans. In these patients, the CT was superior to the MRI in detecting small bony fragments, but the medullary lesions were visible only on the MRIs. An intramedullary low signal intensity corresponded to macroscopically visible hemorrhages in the three postmortem specimens. The MRI provided important information in patients with neurologic deficits. No obvious pathologic changes were evident on the roentgenograms and CT scans. The MRI also demonstrated intramedullary and extramedullary soft-tissue lesions and was useful in establishing a diagnosis and in choosing appropriate therapy. CT, on the other hand, was superior in detecting small bony fragments and fracture lines. 
4	The effect of abdominal surgery on the serum concentration of the tumour-associated antigen CA 125. The CA 125 assay is used to monitor the course of disease in women with adenocarcinoma of the genital tract. We measured serum CA 125 levels longitudinally in three different groups of patients who had normal serum CA 125 levels (less than or equal to 16 U/ml) before extensive intraperitoneal abdominal surgery (group 1, second-look laparotomy in 28 women with ovarian cancer; group 2, radical hysterectomy in 42 patients with cervical cancer; group 3, 13 men and one woman who had aortic surgery for atherosclerotic occlusive disease or aneurysm formation). Following surgery, rising serum CA 125 levels were observed in 69 out of the 84 patients (82%), irrespective of the primary diagnosis, type of operation or sex. The highest levels were found during the second week after the operation (range 3-336 U/ml) and decreased gradually thereafter, to become normal at 8 weeks after surgery. It was concluded that abdominal surgery interferes with the specificity of CA 125 as a tumour marker during the early postoperative period. 
4	Influences of angiotensin on renal function in renal vascular hypertension. The scope and the magnitude of the roles which angiotensin plays in the generation and maintenance of elevated blood pressure in models of renal vascular hypertension are continuing to expand. It is now clear that specific angiotensin dependent mechanisms contribute importantly to the pathophysiology of hypertension and altered renal function in models of two-kidney, one clip hypertension in rats. The generation of angiotensin in the local intrarenal environment of the kidney is a new and potentially important mechanism contributing to altered renal function in these models. Application of antagonists of the renin-angiotensin system to rat models of renal vascular hypertension indicate that the effects of angiotensin attenuate renal hemodynamic and excretory behavior, particularly in the nonclipped kidney. Further, angiotensin may attenuate the efficiency of autoregulation of renal hemodynamics in the nonclipped kidney. Evidence that inhibition of angiotensin reverses or improves these altered hemodynamic and excretory functions indicate that angiotensin may contribute importantly to the pathophysiology of hypertension in these models by altering or impairing the ability of the nonclipped or normal kidney to excrete sodium and volume. 
4	Apical aortic cannulation: application of an old method with new paraphernalia. An instrument assembly consisting of a special aortic cross-clamp and double-lumen perfusion cannula is presented. The application of these instruments allows occlusion of the ascending aorta traversed by the perfusion cannula inserted directly or through the apex of the heart as well as simultaneous left ventricular venting. 
4	Grinspan's syndrome: a drug-induced phenomenon? Three cases of apparently drug-induced Grinspan's syndrome involving the triad of oral lichen planus, diabetes mellitus, and hypertension are reported. Because drug therapy for diabetes mellitus and hypertension is capable of producing lichenoid reactions of the oral mucosa, the question arises as to whether Grinspan's syndrome is an iatrogenically induced syndrome. 
4	Timing and triggers of transient myocardial ischemia. Use of exercise tolerance testing and new techniques of ambulatory electrocardiographic monitoring to more objectively measure myocardial ischemia have enabled clinicians to better recognize the magnitude, timing and variable characteristics of transient ischemic events. These commonly occurring events in patients with coronary artery disease have a diurnal pattern strikingly similar to that reported for catastrophic cardiovascular events such as myocardial infarction, sudden cardiac death and stroke. Whether those factors that contribute to reversible ischemic events are similar to those causing infarction and sudden death has not been resolved. However, the parallel increase in morning activity for these related phenomena suggests that a better understanding of the triggers of reversible myocardial ischemia may help improve understanding of the causes of myocardial infarction and sudden cardiac death. 
3	Early cerebral infarction: gadopentetate dimeglumine enhancement Gadopentetate dimeglumine was administered prospectively to 50 patients who presented for magnetic resonance (MR) imaging within 2 weeks after a cortical cerebral infarction. Twenty-two patients (44%) were imaged within 3 days after clinical ictus. Abnormalities detected with gadopentetate dimeglumine enhancement were observed in 46 (92%) of 50 patients. Classic parenchymal enhancement was a late finding, observed in all patients (17 of 17) imaged at 7-14 days after infarction. Before this time, three additional phases of contrast material-related abnormalities were observed. Enhancement of vessels supplying the infarct ("intravascular enhancement sign") was the earliest finding, seen in 17 (77%) of 22 infarcts aged 1-3 days. From day 2 to day 6, abnormal enhancement of meninges adjacent to the infarct was frequently noted ("meningeal enhancement sign"). Finally, a transition phase that combined intravascular or meningeal enhancement with early parenchymal enhancement was seen from day 3 to day 6. Gadopentetate dimeglumine-enhanced MR imaging in early stroke reveals evidence of vascular engorgement and sluggish flow, which precede the development of classic parenchymal enhancement. 
5	Perinatal mortality rates in isolated general practitioner maternity units OBJECTIVE--To determine the perinatal mortality rate among normally formed, singleton babies with birth weights greater than or equal to 2500 g in Bath health district based on the intended place of delivery at the time of onset of labour or at the time of diagnosis of intrauterine death. DESIGN--The numbers of live births and stillbirths were collected monthly returns from the maternity units concerned. Deaths of infants aged less than or equal to 1 week were collected in the same returns. The intended place of delivery was confirmed at the monthly perinatal mortality meeting, during which maternal and fetal factors were discussed. SETTING--A rural health district of 400,000 population where one third of all deliveries occurred in seven isolated general practitioner maternity units, 8% in the integrated general practitioner unit, and the remainder in the consultant unit. SUBJECTS--All babies of women whose deliveries were booked in the district before the onset of labour or the diagnosis of intrauterine death, excluding twins, babies with lethal congenital malformations, and those less than 2500 g. MAIN OUTCOME MEASURES--Outcome of all deliveries and parity of mothers. RESULTS--14,415 Deliveries were analysed. The perinatal mortality rate was 2.8/1000 births in the consultant unit (7950 deliveries), 4.8 in the isolated general practitioner units (5237 deliveries), and zero in the integrated general practitioner unit (1228 deliveries). Perinatal deaths attributable to asphyxia were more common in the isolated general practitioner units (1.5 per 1000) than the consultant unit (0.6 per 1000). The perinatal mortality rate among babies born to nulliparous women was 3.2/1000 births in the consultant unit and 5.7 in the isolated general practitioner units; for those born to multigravid women it was 2.4 and 4.2 respectively. CONCLUSIONS--The outcome of delivery was not influenced by parity. Both antenatal and intrapartum care were responsible for the higher perinatal mortality rate in the isolated general practitioner units. The integrated unit, which shared midwifery staff with the consultant unit, seemed to work well. Analysis by intended place of delivery at the time of onset of labour or diagnosis of intrauterine death suggested that the care given in isolated units needs to be improved, perhaps by better training of general practitioners and consultant supervision of antenatal care. 
2	Anal ulcerations due to cytomegalovirus in patients with AIDS. Report of six cases. Lesions due to cytomegalovirus (CMV) are frequent in the immunocompromised patient. This is particularly the case in patients with AIDS, where the colon and rectum are the regions most often involved. The authors report six cases of anal ulcerations due to CMV in patients with AIDS. These lesions, confirmed histologically, were either isolated or associated with other localizations. Treatment is based on specific antiviral agents but resistance and recurrence can occur. The current report underlines the importance of histologic examination of anal lesions in HIV-infected subjects. 
4	Occlusion of an "accessory" distal anterior cerebral artery during treatment of anterior communicating artery aneurysms. Report of two cases. Two cases are presented in which clip occlusion of a third distal anterior cerebral artery segment occurred during treatment of anterior communicating artery aneurysms. Case histories, angiograms, operative descriptions, and postmortem findings are presented. The incidence of this anomalous vessel is reviewed. Preoperative and intraoperative vigilance in determining the presence of this anomaly prior to clip placement is emphasized. 
1	Rural-urban differences in stage at diagnosis. Possible relationship to cancer screening. Stage at diagnosis was examined for various malignancies identifiable through screening to determine whether rural-urban differences exist in Georgia. Data were obtained from a population-based cancer registry which registers all incident cancers among residents of metropolitan Atlanta and ten neighboring rural counties. Black and white patients with a first primary invasive malignancy newly diagnosed between 1978 and 1985 were included in this study. Residents of the rural area were twice as likely to have unstaged cancers (18.3%) as were urban residents (9.6%). Among patients with known stage at diagnosis, rural patients tended to have more advanced disease than urban patients. The relative excess of nonlocalized malignancies in rural Georgia was 21% for whites and 37% for blacks. The rural excess of nonlocalized prostate cancer among blacks was especially pronounced. Differences in access to or utilization of early detection methods may contribute to the rural-urban differential in the extent of disease at diagnosis. 
1	Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. BACKGROUND. Malignant soft-tissue tumors often present substantial diagnostic challenges. Chromosome aberrations that might be diagnostic have been identified in some types of soft-tissue tumors, but the overall frequency and diagnostic relevance of these aberrations have not been established. METHODS. We attempted to determine the karyotypes of a series of 62 consecutive, unselected malignant spindle-cell or small round-cell soft-tissue tumors (from 46 adults and 16 children) after direct harvesting of cells or short-term culture. All tumors were examined independently by immunohistochemical staining in addition to routine light-microscopical evaluation, and all but two tumors were examined by electron microscopy. RESULTS. Metaphases were obtained from 61 of the 62 tumors, and clonal chromosome aberrations were identified in 55 (89 percent). In the six tumors that yielded metaphases but lacked apparent clonal aberrations, the normal metaphases were found to originate from non-neoplastic stromal elements within the tumor specimens. Thus, all tumors in which karyotyping was successful contained clonal chromosome aberrations. Forty of 62 tumors (65 percent) contained clonal chromosome aberrations that either suggested or confirmed a specific diagnosis; in 15 of these tumors (24 percent of all tumors), the aberrations were important in establishing the final diagnosis. Cytogenetic analyses were particularly informative about small round-cell tumors from children: 8 of 14 round-cell tumors contained diagnostically important chromosome aberrations. Using the combined approaches of light and electron microscopy, immunohistochemistry, and cytogenetics, we established an unambiguous diagnosis for 60 of 62 tumors. CONCLUSIONS. Cytogenetic analyses reveal clonal chromosome aberrations in virtually all malignant soft-tissue tumors. These clonal chromosome aberrations, particularly in small round-cell tumors in children, often have diagnostic relevance. 
1	Ethanol causes accelerated G1 arrest in differentiating HL-60 cells. The effects of clinically relevant ethanol concentrations on myeloid differentiation in the HL-60 cell promyelocytic leukemia line have been studied. The exposure of noninduced stem cells to 60 mM ethanol results in an increase in G1 cells, but there is no increase in superoxide production or expression of the Mo1 antigen. When HL-60 cells are induced to differentiate along the myeloid line with dimethylsulfoxide (DMSO) or retinoic acid (RA), there is a shift to smaller cell size, an increase in G1 cells and acquisition of the ability to produce superoxide as reported previously by several authors. When ethanol is present during differentiation, there are further increases in G1 cells, and increases in the percentage of cells which produce superoxide and express Mo1, and decreases in mean cell size and total growth during the incubation period. Regrowth experiments after periods of differentiation indicate that the increased G1 arrest seen in the presence of ethanol represents terminal commitment if inducer is present, but in the absence of inducer the increased G1 percentage is readily reversible. Examination of RNA content by flow cytometry reveals a decrease in both the peak and mean G1 RNA content during DMSO or RA induced differentiation. These decreases are accentuated by the presence of ethanol, resulting in a higher G1A/G1B ratio than in nonexposed cells. These findings indicate that ethanol enhances G1 growth arrest in HL-60 cells exposed to myeloid inducers. Partial differentiation occurs during this process, resulting in terminally arrested cells, some of which have undergone fewer postinduction cell divisions than normal and may not be fully competent. 
4	Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina. Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression. 
2	Esophageal motility in an adult with a congenital H-type tracheoesophageal fistula. Congenital H-type tracheoesophageal fistulas (TEF) are rare. Long-standing respiratory symptoms are the most common presenting complaints. Patients with these fistulas have a congenital esophageal motor abnormality characterized by uncoordinated, low-amplitude peristalsis of the esophageal body; both low and normal lower esophageal sphincter pressures have been described. These findings persist despite fistula repair. A case history of an adult patient with congenital TEF is presented and the literature is reviewed. This patient is unusual in that esophageal symptoms (dysphagia) were more prominent than the usual respiratory symptoms. 
2	Diurnal fluctuations of arterial ketone body ratio in normal subjects and patients with liver dysfunction. To explore the metabolic aspects of chronic liver disease, diurnal changes of arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were investigated in normal subjects, patients with chronic liver disease (Child's class A or B), and patients with hepatic failure (Child's class C). Ketone body ratio in normal subjects increased after breakfast from 0.96 to 2.00, after lunch from 2.17 to 2.38, and after dinner from 1.23 to 2.55 with blood glucose level ranging from 103 to 141 mg/dL (5.7 to 7.8 mmol/L). By contrast, the ketone body ratio in the Child A or B group changed little and remained within a range of 0.70-1.35 despite a large change in blood glucose level from 102 to 176 mg/dL (5.7 to 9.8 mmol/L). Ketone body ratio in Child's class C remained near or below 0.4 with no response to glucose administration, despite a marked elevation in blood glucose level. These results indicate that hepatic mitochondrial redox potential undergoes diurnal changes in sharp response to meals in normal liver function but that these fluctuations are absent in patients with liver damage (Child's class A, B, and C). Furthermore, it remains at low levels in severe liver failure (Child's class C). It is also suggested that hepatic mitochondrial redox potential plays an important role in the regulation of blood glucose levels. 
3	Blood pressure reactivity predicts myocardial infarction among treated hypertensive patients. High blood pressure (BP) defines a prognostically heterogeneous group. Because BP varies according to time, setting and means of observation, it has been postulated that BP reactivity might better predict cardiovascular disease (CVD) than does unidimensional measurements. To assess BP reactivity, the difference between pretreatment nurse (RN) and physician (MD) diastolic BP (DBP)--systematically recorded in that order--or MD-RN DBP, was obtained in 1737 previously untreated patients with sustained, RN BP greater than or equal to 160 and/or 95 mmHg. Patients stratified by tertiles of MD-RN DBP [(I) less than or equal to - 3, (II) -2 to 3 and (III) greater than or equal to 4 mmHg] were similar by sex, race, age, body mass index, cholesterol, electrocardiography, prior CVD, smoking and pretreatment or attained in-treatment BPs. During 14 years of followup, myocardial infarction (MI) incidence per 1000/year were, tertile I (3.2), II (3.7), III (7.6) (relative risk = 2.4, III vs I + II, p less than 0.05), whereas stroke incidence and non-CVD mortality were evenly distributed. By Cox survival analysis, controlling for other entry characteristics only age, sex and DBP reactivity remained predictive (p less than or equal to 0.03) of MI or total CVD. Thus, BP reactivity, probably a centrally-mediated phenomenon, identifies a subgroup of hypertensives with an increased propensity for MI despite successful BP control. 
5	Infection with Chlamydia pneumoniae in Brooklyn. Of 91 children and adults with lower respiratory tract infection, 17 (18.7%) had evidence of infection with Chlamydia pneumoniae. Infection was more common in older adolescents and adults than in children. Only 3 of 8 culture-positive patients with paired sera had serologic evidence of acute infection. Two patients were culture positive over a 12-month period. Two other culture-positive patients had evidence of coinfection with other bacterial respiratory tract pathogens, which in these cases appeared to be responsible for the acute episode of pneumonia. Patterns of infection ranged from acute pneumonia to apparent chronic asymptomatic carriage, and there was no characteristic clinical presentation. Studies using cultures in other populations, including asymptomatic individuals, are needed for a better understanding of the epidemiology and clinical relevance of this organism. 
4	Molecular biology in cardiology: recent developments and opportunities for clinical applications. The revolution in molecular biology that has taken place in the last decade has provided powerful research methods that are changing our understanding of cardiovascular physiology and disease. This editorial commentary will highlight several areas of current research activity within the broad and expanding field of molecular cardiology, with a special emphasis on prospects for clinical applications in cardiovascular medicine. 
5	Takayasu's disease with axillary, right coronary artery, and right internal mammary stenosis treated with angioplasty. A 47-year-old woman presented with progressive angina and failed medical therapy. After an unsuccessful attempt at angioplasty of a totally occluded right coronary artery, coronary artery bypass using the right internal mammary artery was performed. She presented 2 years later with stenosis in the mammary graft, right coronary artery, and axillary artery. These lesions were all treated with angioplasty. 
3	Failed acromioplasty for impingement syndrome. We evaluated 67 shoulders in 65 patients who had pain and dysfunction for more than two years after an initial acromioplasty for impingement syndrome without a rotator cuff tear. In addition to a thorough history, physical examination, local anaesthesia injection and any other necessary investigations all patients had arthroscopic evaluation of the shoulder. In 27 shoulders there had been diagnostic errors, and in 28 operative errors; only in 12 had the diagnosis and the operative procedure both been correct. Subsequent operative intervention in patients not receiving worker's compensation benefit had a 75% success rate, whereas in those receiving such benefits the success rate was only 46%. 
1	Management of subglottic stenosis in the adult. Twenty-one adult patients were surgically treated for severe subglottic stenosis refractory to endoscopic treatment. Patients were treated by anterior or anterior and posterior cricoid division with costal cartilage grafting. Seventy-six percent of the patients were successfully decannulated. Success of treatment was not dependent on cause of the stenosis or age or sex of the patient. There was a significantly better outcome (p less than .05) in patients with isolated subglottic stenosis versus those with combined glottic and subglottic stenosis. 
5	Ischaemic heart disease among men in Norway during the period 1966-1985: two counties with different mortality time trends. We have examined regional differences in mortality from ischaemic heart disease, including sudden, unexpected death (IHD/SUD), among Norwegian men aged 30-69 years, during the period 1966-1985. Mortality time trends were considered. The two counties with the most widely differing IHD/SUD mortality time trends were Rogaland and Oppland. Rogaland, located in south-western Norway, experienced a 24.1% IHD/SUD mortality rate decrease between 1966-1970 and 1981-1985, while Oppland, in central south-eastern Norway, experienced a mortality rate increase of 12.4%. Marked regional differences within these counties were found. The highest IHD/SUD mortality rate increase occurred in rural areas of Oppland. Urban areas of Rogaland had sharply decreasing rates. Knowledge of such regional mortality differences could provide useful information regarding aetiological factors and serve as a basis for preventive measures and health-care planning. 
4	Survey of the use of thrombolysis for acute limb ischaemia in the UK and Ireland. A total of 156 vascular surgeons from the UK and Ireland responded to a postal questionnaire on the use of thrombolysis in acute limb ischaemia. Almost half had used thrombolysis in the previous 12 months. Low dose intra-arterial streptokinase (89 per cent) was the regimen most frequently used, but 33 per cent had used intravenous streptokinase. Detailed results for 103 patients (limb salvage rate 60 per cent, amputation rate 35 per cent, mortality rate 5 per cent) were similar to those of previously published reports. Complications in most series were infrequent, but in the entire survey there were six bleeding-related deaths and one death from anaphylaxis. A total of 67 per cent of surgeons with working experience indicated that selected patients with acute arterial thromboses were most suitable for thrombolysis, particularly if there was no neurological deficit and no run-off for surgical bypass. Distal or late emboli and graft occlusions were regarded as appropriate by some surgeons. This study demonstrated that many vascular surgeons currently use thrombolysis, although sparingly and in selected cases. Patients with acute limb ischaemia should be managed by experienced vascular surgeons who are aware of the new therapeutic alternatives, an ideal supported by almost three-quarters of respondents to this survey. 
5	Hemopump support for the failing heart. Under fluoroscopy, the hemopump is passed through the aortic valve into the left ventricle through a Gortex (WF Gore, Denver, CO) chimney sewn to a surgically exposed femoral artery. The system aspirates the left ventricular blood and actively pumps it into the aorta. Five patients (four men, one woman), aged 47-71 years (mean, 62 years), were candidates for hemopump support because of refractory cardiogenic shock. Three were recovering from repeated coronary artery bypass graft (CABG) surgery, and two required postoperative emergency CABG for failed percutaneous transluminal coronary angioplasty (PTCA). One patient died during insertion, and four had the hemo-pump successfully placed. All patients had low cardiac out-put and had intraaortic balloons in place. Average insertion time took 20 min, with maintenance on the hemopump for an average of 13 hr. One patient was maintained on the hemopump for 12 hr, but because of continued deterioration, was placed on a total artificial heart (Harvik 7-70). Patients 3 (hemopump inserted transthoracically) and 4 had the hemopump discontinued because of brain death, and the fifth survived. This patient is alive and working 1 yr later. The hemopump is an effective left ventricular support system that is less invasive than conventional transthoracic systems. 
1	Value of retesting subjects with a positive Hemoccult in screening for colorectal cancer. Within a prospective randomized screening study for early detection of colorectal cancer with rehydrated Hemoccult II test, the possibility of increasing the specificity of the test by retesting patients with an initially positive Hemoccult II test was investigated. Of those offered the test 3561 (62.6 per cent) returned it and it was positive in 210 cases (5.9 per cent). The repeat test was performed by 184 patients and was positive in 68 (1.9 per cent). All those with a positive initial test had rectosigmoidoscopy to 60 cm and a double contrast enema. A carcinoma was found in one in seven patients with a positive retest but in only one in 100 patients with a negative retest (P less than 0.001). The specificity of the test was, therefore, increased from 95 per cent to 98 per cent and the sensitivity was unchanged. Rescreening was offered at a later date and increased numbers were available: 7147 patients returned the test and 369 (5.2 per cent) were positive. The test was repeated in 360 patients and 118 (1.7 per cent) were positive. A colorectal neoplasm was found in one in three of those with a positive repeat test, compared with one in seven of those with a negative repeat test. In conclusion, screening for early detection of colorectal cancer with a rehydrated Hemoccult II test may be followed by investigation of only those patients with a positive retest. Such a procedure will reduce the work-load by 60 per cent without reducing sensitivity. 
3	Myelopathy presenting decades after surgery for congenital cervical cutaneous lesions. We report on two patients in whom cervical myelopathy developed decades after they had undergone surgery for congenital cervical cutaneous lesions. Preoperative magnetic resonance imaging demonstrated dorsal tethering and cavitation of the cervical cord in the area of the previous surgery and was helpful in decision making regarding surgical exploration and in planning for it. We stress the importance of long-term follow-up by both clinical examination and magnetic resonance imaging in children who have been operated on for cervical cutaneous masses that may have central connections. 
1	Benign lymphangioendothelioma. We have studied eight cases of an acquired lymphatic endothelial lesion for which we propose the name "benign lymphangioendothelioma." The lesions developed as solitary, slowly extending, erythematous macules and plaques, usually occurring on the extremities or the shoulders in adolescents or adults. The characteristic histopathologic feature is permeation of the dermal collagen by flattened, endothelium-lined channels and spaces. Hemorrhage, iron deposition, and inflammation were not part of the lesion. Ulex europaeus agglutinin I labeled the lesional endothelial cells consistently, but factor VIII-related antigen labeling was negative. This histologic pattern and the special studies suggested a lymphatic lesion. Surgical excision, performed in six patients, was not followed by recurrence. 
5	Splenic septic emboli in endocarditis. The significance of septic emboli to the spleen is inferred by the frequency of septic emboli in general seen in patients with left-sided infective endocarditis who are referred for valve replacement. To determine the proper management of splenic infarcts and abscess due to septic emboli, we retrospectively reviewed the records of 108 patients with left-sided endocarditis who underwent valvular surgery at the University of Illinois Hospital from 1980 through 1988. Intravenous drug abuse was the etiology in 68% (n = 73). The incidence of splenic infarcts and abscess was 19% (n = 20), but an incidental finding of splenic infarcts was found in 38% (n = 11) of 29 asymptomatic patients who had computed tomograms. Streptococci and staphylococci were the causative organisms in 85% (n = 17). Localized findings were absent in 90% of splenic infarcts and abscesses. Abdominal computed tomograms were diagnostic of the sequelae of splenic septic emboli in 100%. No patient had intra-abdominal bleeding complications associated with cardiopulmonary bypass. Splenectomy was performed in 50% (n = 10) of patients 3-24 days (mean, 11.2 days) after valve replacement. Indications for splenectomy included persistent sepsis in 60% (n = 6), large (greater than 2 cm) and peripheral lesions in 30% (n = 3), and splenic rupture in 10% (n = 1). Perioperative mortality of patients who underwent splenectomy was 30% (n = 3). The following conclusions can be drawn: 1) Splenic septic embolus is common in endocarditis. 2) Abdominal computed tomography should be performed for all patients. 
2	Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial. In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse. 
3	The child with recurrent syncope: autonomic function testing and beta-adrenergic hypersensitivity. Recurrent syncope in the child with a normal heart poses both diagnostic and therapeutic problems. To assess autonomic contributions to syncope, formal autonomic function testing was performed in 22 children (aged 7 to 18 years) with recurrent syncope and a normal heart. Autonomic testing consisted of eight to nine separate tests; 14 of the 22 patients had reproduction of syncope or symptoms during testing. Patients with a positive test had a lower norepinephrine level while supine (334 +/- 86 versus 547 +/- 169 pg/ml, p less than 0.01) and lower norepinephrine level in the upright position (628 +/- 219 versus 891 +/- 270 pg/ml, p less than 0.05) than did patients with a negative test. The slope of heart rate response versus log isoproterenol dose was greater in patients with a positive test than in those with a negative test (1.70 +/- 0.70 versus 0.89 +/- 0.19, p less than 0.01). All five patients with a positive test who were given intravenous propranolol had elimination of syncope with repeat testing. Eight of 10 patients with a positive test were successfully treated with atenolol, including 2 patients without prior resolution of symptoms after pacemaker implantation for symptoms attributed to bradycardia. Beta-adrenergic hypersensitivity may cause recurrent syncope in young patients. Inappropriate heart rate response to standing may elicit the Bezold-Jarisch reflex, resulting in bradycardia or hypotension, or both, in some patients. Beta-adrenergic blockade is of benefit in many of these patients. 
1	Clostridial bacteremia in cancer patients. A 12-year experience. Over 12 years, 136 episodes of bacteremia caused by clostridial species were documented. Eighty-three were monomicrobial, and 53 were polymicrobial. Gastrointestinal, genitourinary carcinomas, and acute leukemia were the most common underlying malignancies. Septic shock occurred in 29% of monomicrobial bacteremias and 45% of polymicrobial bacteremias and was associated with a high mortality rate. Acute hemolysis, gas gangrene, and diffuse spreading cellulitis occurred infrequently but were associated with a 100% fatality rate. Many infections caused by Clostridium perfringens and C. septicum were associated with abdominal disease. The most commonly isolated organism was C. perfringens, followed by C. septicum and C. sporogenes. Overall survival was 58%, but it was 66% for monomicrobial episodes and 45% for polymicrobial infections. All of the patients with bacteremia due to an aerobic gram-negative bacillus in addition to the clostridial species died of their infection. The most effective antibiotics were clindamycin, penicillin, metronidazole, and moxalactam. Surgical drainage of abscesses was an important component of therapy. 
4	The effect of local temperature versus sympathetic tone on digital perfusion in Raynaud's phenomenon. Matched groups of 7 to 8 patients with primary Raynaud's phenomenon, systemic sclerosis, and undifferentiated connective tissue disease and cold-tolerant normal control subjects were studied by simultaneous digital strain gauge plethysmography and laser Doppler capillary velocimetry during two controlled cycles of hand warming and cooling with and without addition of central cooling and during clinical maneuvers to evoke sympathetic tone. Transient vasoconstrictor responses of comparable degree could be evoked in all patient groups and in both the arterial and microvascular beds. While the addition of central cooling had little influence on arterial flow, patients with systemic sclerosis manifested a failure to maintain nutritive perfusion at finger temperatures associated with Raynaud's phenomenon. Linear regression and multivariate analysis suggested that finger temperature was the principal determinant of arterial flow in systemic sclerosis and that arterial flow was the principal determinant of microvascular perfusion. The inability of patients with systemic sclerosis to maintain nutritive flow in the face of either reflex or cold-induced proximal arterial constriction is consistent with their clinical propensity to ischemic tissue injury and separates these patients physiologically from other forms of Raynaud's phenomenon. 
1	A seromuscular stripping method to create a nipple valve without metal stapling for continent urinary reservoir. Urinary continence with a Kock or Mainz pouch is achieved by a nipple valve of the invaginated ileum which is usually fixed with metal staples. However, metal staples can cause various complications as a foreign body. The seromuscular stripping method, a new technique to create a nipple valve, was applied to 17 patients with bladder cancer in the construction of a continent urinary reservoir by the ileocolonic pouch (Mainz pouch). Metal staples were not used. The results were satisfactory except for 2 patients who became incontinent because of prolapse of the nipple in one and insufficient valve function due to ischemic change of the nipple valve in the other. Histology of the nipple valve from an autopsy case showed a good double layer nipple valve that functioned well to preserve continence. 
2	Resting and total energy expenditure in patients with inflammatory bowel disease. Patients with inflammatory bowel disease often present with weight loss. Among possible causes, an elevated energy expenditure has frequently been suggested but is the least documented. In this study resting metabolic rate (RMR) and total daily energy expenditure (TDEE) were measured in 15 outpatients with inflammatory bowel diseases and in eight healthy control subjects. Measured RMR as a percentage of that predicted from fat-free mass was not significantly different for control subjects (102 +/- 9.8%, mean +/- SD) and patients (100 +/- 13.3%). TDEE, expressed as a multiple of RMR, was 1.70 +/- 0.31 for control subjects and 1.78 +/- 0.24 for patients. When patients were subgrouped as greater than or equal to 90% or less than 90% desirable body weight, a mean increase over RMR predicted from fat-free mass was seen in the underweight patients (106 +/- 9.3%) but not in normal-weight patients (99.0 +/- 15.6%). Mean TDEE/RMR values for the patient subgroups were 1.70 +/- 0.30 and 1.88 +/- 0.08, respectively. We conclude that stable outpatients with inflammatory bowel disease have only a minimal increase in energy needs. 
3	Dementia, depression, or grief? The differential diagnosis. Depression, grief, and dementia are conditions frequently encountered among the community-living elderly. This review offers a primary care perspective of the distinguishing features for each and discusses the special issues of managing the elderly. Major depression in the elderly usually responds to antidepressant medication, whether the depression occurs alone (endogenous) or as a response to another condition (reactive). 
5	Irritant and sensitizing potential of copper, mercury and tin salts in experimental contact stomatitis of rat oral mucosa. HgCl2, CuSO4, SnCl2, SnCl4 or sodium lauryl sulphate (SLS) were openly applied to rat oral mucosa for 1 min, followed 6 h later by histologic examination of the tissue response. Granulocytes were the predominant inflammatory cells and no lymphocytic infiltration could be seen with any of the substances tested. Irritant threshold levels were defined histologically for each of the substances. CuSO4 was found to be non-irritant at all concentrations. The addition of non-irritant concentrations of SLS lowered the threshold levels for HgCl2 and SnCl2, but CuSO4/SLS was non-irritant at all concentrations tested. Preapplication to the mucosa of SLS at non-irritant concentrations gave results with HgCl2, SnCl2 and CuSO4 similar to those with SLS added to the metal salt solutions. Lesions of allergic contact type could not be induced in the oral mucosa to any of the metal salt preparations. 
5	Graft stenosis: justification for 1-year surveillance. In all, 412 femorodistal grafts (femoropopliteal and femorocrural), performed between 1984 and 1988, have been prospectively studied at 6 weeks and 3, 6, 9 and 12 months after operation and at intervals of 6 months thereafter by duplex scanning and intravenous digital subtraction angiography. The overall incidence of stenoses was 16 per cent (femorocrural 20 per cent, femoropopliteal 15 per cent). All stenoses were detected in the first year after operation and none occurred after this. Twenty-four non-haemodynamically significant stenoses were not treated but were followed at intervals of 3 months. Forty-two haemodynamically significant stenoses were detected and secondary procedures were performed in 30 grafts at a mean of 8 months after surgery. Thirteen had percutaneous balloon dilatation and six (46 per cent) remain patent at a mean follow-up of 22 months. Two grafts which occluded within 30 days and three which restenosed at a mean of 8 months had tertiary procedures. Seventeen grafts were surgically revised, nine with patch grafts and eight with bypass grafts. Eleven of these remain patent at a mean follow-up of 30 months. One occluded immediately and three occluded late. Two grafts which restenosed at a mean of 19 months had successful tertiary procedures. In total, seven grafts had tertiary procedures (two had balloon dilatation and five had surgery) and six of these remain patent at a mean follow-up of 13.5 months. In conclusion, 37 procedures have been performed on 30 grafts, of which 23 (77 per cent) remain patent at a mean follow-up of 12 months. Approximately one-quarter of femorodistal grafts will develop graft-related stenoses and graft surveillance is worthwhile, but only for the first year after operation. 
5	Dexamethasone in the prevention of postextubation stridor in children. To assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children, we conducted a prospective, randomized, double-blind trial of dexamethasone versus saline solution. The patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor: age, duration of intubation, upper airway trauma, circulatory compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting. There was no statistical difference in incidence of postextubation stridor in the two groups; 23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy (p = 0.21). We conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted. 
1	Diagnosis of abdominal masses with percutaneous biopsy guided by ultrasound OBJECTIVE--To assess the accuracy and safety of percutaneous biopsy of abdominal masses guided by ultrasound. DESIGN--Prospective study. SETTING--Combined gastroenterology service, Scarborough Hospital. PATIENTS--108 Consecutive patients identified as having a discrete mass on diagnostic ultrasound examination of the abdomen. INTERVENTION--A sample of tissue was obtained with an aseptic technique under local anaesthesia: an 18 steel wire gauge needle (Tru-Cut) was mounted in a spring loaded firing device (Biopty gun) that was advanced under simultaneous ultrasound scanning, permitting precise localisation of the target organ. MAIN OUTCOME MEASURE--Results of histological examination of tissue specimens. RESULTS--Biopsy failed in four patients. Adequate histological specimens were obtained in 104 patients with masses in the liver (31), pancreas (37), kidney (10), and adrenal glands (six) and in 20 undiagnosed abdominal and retroperitoneal masses. Follow up was until death or confirmation of the diagnosis. Three complications but no deaths occurred. Malignancy was suspected in 84 patients before biopsy. This was confirmed in 70 patients, in 26 of whom confirmation of dissemination obviated the need for further investigation. In 10 patients biopsy indicated a previously unsuspected primary tumour, and in 12 it showed only a benign lesion. Among 24 patients considered to have benign disease biopsy showed an unsuspected neoplasm in seven. Use of biopsy thus had a major effect on clinical management in 55 patients. Four false negative but no false positive diagnoses resulted from the procedure. CONCLUSION--Percutaneous biopsy of abdominal and retroperitoneal masses under ultrasound guidance is a safe and accurate method of obtaining a histological diagnosis. The results obtained have a considerable effect on clinical management. 
4	Reduction in incidence of inducible ventricular tachycardia after myocardial infarction by treatment with streptokinase during infarct evolution. The aim of this study was to determine whether intravenous streptokinase administered with or without oral aspirin to patients with evolving myocardial infarction reduces the inducibility of ventricular tachycardia at electrophysiologic study and thus the risk of sudden death in infarct survivors. Of 159 patients randomized at Westmead Hospital to the multicenter Second International Study of Infarct Survival (ISIS-2) after streptokinase and aspirin in acute myocardial infarction, 87 underwent electrophysiologic testing 6 to 28 days after infarction to determine their risk of subsequent ventricular arrhythmias (streptokinase 20 patients; aspirin 25 patients; streptokinase and aspirin 21 patients; both placebos 21 patients). Patients who underwent electrophysiologic testing had similar clinical characteristics to those of patients who did not. The stimulation protocol comprised up to and including four extrastimuli applied to the right ventricular apex at twice diastolic threshold. An abnormal result was defined as ventricular tachycardia with a cycle length greater than or equal to 230 ms lasting greater than or equal to 10 s. Ventricular tachycardia was inducible at electrophysiologic study in 8 patients who received placebo streptokinase, but in no patient who received active streptokinase (8 of 46 versus 0 of 41; p = 0.005, Fischer's exact test). Ventricular tachycardia was inducible in 4 patients who received aspirin therapy and 4 who did not (4 of 41 versus 4 of 46; p = NS). During a mean follow-up period of 39 +/- 9 months, there were no spontaneous episodes of ventricular tachycardia, ventricular fibrillation or witnessed sudden death in the streptokinase-treated group compared with three such events in the placebo-treated group (p = 0.13). When compared with placebo therapy, intravenous streptokinase substantially reduced the incidence of inducible ventricular tachycardia in infarct survivors. No similar benefit was attributable to aspirin therapy. 
2	Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance. 
3	rCBF-SPECT in brain infarction: when does it predict outcome? We prospectively studied 26 patients with ischemic stroke within 24 hr, after 2 wk, and after 6 mo with thallium-201-diethyldithiocarbamate single-photon emission computed tomography (SPECT) and neurologic and functional assessments. The admission flow deficits correlated with outcome. The admission and 6-mo scores correlated with clinical conditions at each time. At 2 wk, the flow deficits were smaller and did not correlate with clinical parameters. Nor did the presence or absence of hyperfixation of the radiopharmaceutical. Six months after the infarct, the flow defect had decreased in 9 of 15 patients in whom three serial scans were available, with better clinical improvement than in the remaining six whose flow deficits increased. More patients in the first group had been treated randomly with the calcium-entry blocker flunarizine. SPECT imaging of rCBF within 24 hr after stroke correlates with clinical outcome and condition, whereas rCBF imaging at 2 wk after the stroke shows no clinical correlation. 
5	A community-based study of acute respiratory tract infection in Thai children. A 2-year longitudinal study was conducted among the population of a socioeconomically depressed urban community in Bangkok, Thailand, from January 1986 through December 1987 to determine the incidence, etiologic agents, and risk factors associated with acute respiratory tract infection (ARI) in children less than 5 years of age. Data were obtained for a total of 674 children, who were visited twice weekly for detection of signs and symptoms of ARI. During the first year of the study, throat-swab specimens were obtained for bacterial culture from both ill and healthy children and a nasal wash was performed on mildly ill children for detection of virus. During both years of the study, nasopharyngeal aspiration for identification of virus was performed for children with more severe infection. The overall incidence of ARI was 11.2 episodes per child-year. The highest (14.9) and lowest (8.8) rates per child-year occurred in age groups 6-11 months and 48-59 months, respectively. Respiratory syncytial virus, parainfluenza virus, adenovirus, Streptococcus pneumoniae, and Haemophilus influenzae were the prevalent pathogenic agents identified. Factors associated with higher risk of ARI were low family income, working mothers, mothers with allergies, chronic malnutrition, and crowding in the home. 
1	Spitz nevi in black children. Four black children with Spitz nevi are presented. The initial clinical diagnosis was pyogenic granuloma for three patients. One child had two Spitz nevi. Histologic examination revealed melanocytic dendritic hyperplasia in all cases. 
1	Cancer in the families of children with soft tissue sarcoma. The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis. 
1	Lateral temporal bone resections. Eighteen consecutive patients underwent a lateral temporal bone resection for the treatment of tumors originating in the auricle, the external auditory canal, the periauricular skin, or the parotid and were retrospectively analyzed. The different lateral temporal bone resections performed have been categorized into four types. The type I resection consists of the removal of the tympanic bone and the external auditory canal lateral to the tympanic membrane. The type II resection consists of the removal of the entire tympanic bone, the tympanic membrane, the incus, and the malleus, preserving the facial nerve and the inner ear. Type III resections remove, in addition to the those structures removed in type II resections, the distal facial nerve and fallopian canal, the mastoid tip, the styloid process, and the stylomastoid foramen. The type IV resection consists of the removal of only the mastoid tip and the inferior portion of the tympanic bone. When the techniques of lateral temporal bone resection are used appropriately, adequate surgical treatment of patients with selected advanced and recurrent malignant tumors of the external ear, the periauricular skin, and the parotid is possible with low morbidity and a high probability of local regional control. 
4	Studies of myocardial protection in the immature heart. III. Models of ischemic and hypoxic/ischemic injury in the immature puppy heart. This study compares the metabolic and functional effects of three different models of ischemia in the immature heart. The intent was (1) to develop a model of energy-depleted and functionally depressed heart to be used in subsequent studies of myocardial protection and (2) to characterize the biochemical changes following different interventions. Forty-five minutes of normothermic global ischemia produced severe depletion of adenosine triphosphate and creatine phosphate (greater than 70%) but was associated with 85% +/- 10% recovery of left ventricular function. Postischemic functional depression (less than 30% recovery) could be produced by either (1) extending the ischemic duration to 60 minutes or (2) preceding 45 minutes of ischemia by 60 minutes of hypoxic stress (oxygen tension 25 to 30 mm Hg). Neither of these more severe interventions caused more profound depletion of adenosine triphosphate or creatine phosphate, but hypoxic stress produced marked tissue depletion of glutamate (52%) and aspartate (48%) before aortic clamping. Longer ischemia or preceding hypoxia led to greater myocardial accumulation of lactate (greater than 250 versus 104 mumol/gm dry weight) and succinate (18 versus 11 mumol/gm dry weight) during aortic clamping, p less than 0.05 versus 45 minutes of ischemia) and greater postischemic depression and amino acid (greater than 65% aspartate depletion) and carbohydrate (greater than 50% glycogen depletion) metabolism, p less than 0.05 versus simple ischemia. These findings suggest that more severe ischemic/hypoxic models are needed in immature hearts to produce functional depression, and the biochemical analyses suggest the characteristics of metabolic defects that must be corrected to resuscitate these hearts during surgical correction of congenital defects. 
4	Hemodynamic and electrophysiologic evaluation of patients with hypertrophic cardiomyopathy surviving cardiac arrest. Hemodynamic and electrophysiologic studies were performed in 30 survivors of sudden cardiac arrest with hypertrophic cardiomyopathy (HC) to determine responsible factors. Electrophysiologic abnormalities alone were present in 27 patients (90%): sinus node dysfunction in 14 (47%), delayed atrio-ventricular nodal conduction in 1 (3%), abnormal His-Purkinje conduction in 7 (23%), an inducible atrial tachycardia in 7 (23%), and inducible sustained ventricular arrhythmia in 21 (70%). Sustained ventricular arrhythmia was polymorphic ventricular tachycardia (VT) in 18 patients (86%), monomorphic VT in 2 patients (7%) and ventricular fibrillation in 1 patient (3%). In 1 patient the arrhythmia recorded during an episode of cardiac arrest and induced at electrophysiologic study was polymorphic VT. VT was induced with less than or equal to 2 extra-stimuli in only 1 patient (3%) but with less than or equal to 3 extra-stimuli in 20 patients (97%). Potential causes of sudden cardiac arrest were found in all patients and were multiple in 13 patients (43%). These were (1) ventricular electrical instability in 21 patients (70%), (2) severe left ventricular outflow tract obstruction in 8 patients (27%), (3) bradycardia in 5 patients (17%), (4) myocardial ischemia associated with hypotension in 5 patients (17%), and (5) atrial tachycardia resulting in hypotension in 4 patients (13%). Of the 21 patients with inducible sustained ventricular arrhythmia, 17 received an implantable defibrillator device and 4 were treated with antiarrhythmic drugs. Seven patients underwent left ventricular septal myectomy. 
5	Itraconazole in the management of chronic dermatophytosis. Fifty-five patients with griseofulvin-unresponsive dermatophytosis caused by Trichophyton rubrum were treated with itraconazole. They had either tinea corporis or "dry type" infections of the palms, soles, or nails. The following sites were affected: trunk (12 infections), soles (47), toe webs (52), palms (26), fingernails (29), and toenails (42). Patients were treated with oral itraconazole until clinical and mycologic remission were achieved. Response rates and mean times to recovery were as follows: trunk, 100%, 1.5 months; soles, 83%, 6.7 months; toe webs, 90%, 7.2 months; palms, 96%, 4.6 months; fingernails, 90%, 5.4 months; and toenails, 76%, 10.3 months). In a 6-month follow-up period 7 of 30 patients with toenail infections who had responded to treatment had a clinical and mycologic relapse, usually of one nail. Side effects were minimal but included abdominal discomfort (three patients), headache (one), and weight gain (two). No persistent abnormalities in blood biochemistry were seen, even in patients who received itraconazole for more than 9 months. 
4	Quantitative relationships between left ventricular ejection and wall thickening and geometry. The quantitative relationships that exist between left ventricular (LV) wall shortening, wall thickening, and geometry during LV ejection are not well defined. We used a mathematical model to measure these parameters in 40 patients with various LV geometries studied by echocardiography. As opposed to wall shortening, the percent contribution of wall thickening to LV ejection (% delta Vh) was 25 +/- 2% in normal subjects; in all the patients, it varied from 18 to 45% and was inversely correlated (r = 0.94) to the midwall radius-to-wall thickness ratio (R/h) of the ventricle at end diastole. On the other hand, the ratio of the quantity of blood ejected per unit of LV wall volume magnitude of delta V/V omega magnitude of varied from 0.20 to 1.20 (normal subjects 0.83 +/- 0.11) and was directly correlated (r = 0.94) to R/h; using independent data in the literature, we also found a similar relationship (r = 0.80) between the ratio of quantity of blood ejected per unit of LV mass (magnitude of delta V/M omega magnitude of) and R/h. Patients with presumably abnormal myocardial function did not satisfy the relationship between magnitude of delta V/V omega magnitude of or magnitude of delta V/M omega magnitude of and R/h. 
5	Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm. 
2	A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains. 
5	Parietal cell vagotomy and dilatation for peptic duodenal stricture. Gastric outlet obstruction due to peptic duodenal stricture (pyloric stenosis) was treated with parietal cell vagotomy and dilatation of the stricture in 32 patients. Follow-up is in the range of 5 years in 37.4% of the patients, while 6 to 10 years follow-up is available in 62.4% of the patients. At their last follow-up, 74.9% of the patients were in either Visick 1 or 2 clinical status. Recurrence rates have been 3.1% at 1 year, 9.3% at 5 years, and 21.8% after 6 to 10 years follow-up. There has been only one instance (3.1%) of restenosis. Two patients required reoperation because of recurrence and one of them died. 
1	Greenfield filter as primary therapy for deep venous thrombosis and/or pulmonary embolism in patients with cancer. In 1985, as a result of the high complication rate associated with anticoagulants in patients who have cancer and deep venous thrombosis (DVT) and/or pulmonary embolism (PE), we established a policy of placing Greenfield filters (GFs) as primary therapy instead of anticoagulation. Since 1985 we have been asked to consult in the treatment of 18 patients with cancer and with DVT and/or PE, and we have placed a GF in each of these patients. This represented 34% (18/53) of the filters placed during that same period. Over the same 4-year period, 11 patients with cancer and DVT and/or PE underwent anticoagulation therapy. The purpose of this study was to compare the results of anticoagulation versus GF insertion in these two groups of patients. A significantly higher number of major complications (n = 4) occurred in the anticoagulation group (p less than 0.05, Fisher's exact test) than in the GF group (n = 0). The four complications that occurred in the anticoagulation group included three bleeding episodes (tumor bleeding, gastrointestinal bleeding, and hip hematoma) and one PE, despite adequate anticoagulation. Two patients died as a direct result of these complications (PE and gastrointestinal bleeding). The three patients with bleeding complications each required a transfusion of more than 3 units of blood. All four of the patients with complications had metastatic disease (pancreatic carcinoma, chronic lymphocytic leukemia, prostate carcinoma, and uterine carcinoma). Although this is a small, nonrandomized, nonprospective study, the data seem to indicate that GF placement is safer than anticoagulation for DVT or PE in patients with cancer and particularly in patients with metastatic disease. We conclude that GF insertions may be a better primary treatment than anticoagulation. 
4	Autosomal dominant polycystic kidney disease--more than a renal disease. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease, affecting a half million Americans. The clinical phenotype can result from at least two different gene defects. One gene that can cause ADPKD has been located on the short arm of chromosome 16. This discovery has made possible new methods for diagnosing the disorder in gene carriers prior to the development of renal cysts. Although renal cysts are clearly an important manifestation of the gene defect, other systemic manifestations are both common and clinically important. Cardiac valvular lesions, intracranial aneurysms, hepatic cysts, and diverticula are included in the array of systemic manifestations. Moreover, renal cysts are only one of a myriad of renal manifestations. Although ADPKD was long considered an adult cystic disease, it is also a common cause of childhood cystic disease and must be considered in the differential diagnosis in that setting. 
5	High or low hepaticojejunostomy for bile duct strictures? The 19 patients who underwent 22 postoperative repairs of bile duct stricture in our institution between 1973 and 1984 were evaluated to assess whether the recognition of the tenuous blood supply of the supraduodenal bile duct in 1979 had improved the results thereafter. Thirteen of these 22 operations followed a previous biliary tract repair; in 10 of the operations a low anastomosis had been performed without taking blood supply into account. Follow-up was complete and ranged from 5 to 15 years. There were no operative deaths and minimal morbidity. There were three deaths at a later time. Five of the 11 patients treated by surgery to 1979 had a clinically unsatisfactory result: recurrent strictures developed in all five patients. All but one of the eight patients receiving a high hepaticojejunostomy from 1980 had a clinically satisfactory result with no recurrent strictures. The one exception was the patient who had a second repair with separate high right and left hepatic duct anastomoses and who has ongoing symptoms from preexisting secondary sclerosing cholangitis. The results in the five high repairs performed for low strictures were particularly striking: All five were asymptomatic. This study lends support to the hypothesis of an ischemic basis for biliary strictures and to the recommendation that strictures be repaired with a high hepaticojejunostomy. 
4	Sodium-potassium interaction in hypertension and hypertensive cardiovascular disease. Epidemiological evidence suggests that low potassium intake is associated with the probability of occurrence of hypertension and stroke. The short-term response to increased potassium intake is increased sodium excretion as well as increased potassium excretion; the short-term response to increased sodium intake is increased potassium excretion as well as increased sodium excretion. In some experimental studies, increased amounts of potassium have been able to block the noxious influences of sodium. Sodium and potassium must be concomitantly considered in the investigation of the association of either of these cations with hypertension and cardiovascular disease. The chloride ion is also important for sodium's effects; its importance in potassium's effects has not been extensively explored. 
4	Training increases muscle blood flow in rats with peripheral arterial insufficiency. This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running. Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF. Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk). Hindlimb BF was determined with 85Sr- and 141Ce-labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability). Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group. Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb. Two factors contributed to a higher BF to the distal limb muscle of the trained animals. A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue. In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025). The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals. 
5	Hazards of internal fixation in the treatment of slipped capital femoral epiphysis. We reviewed the records of 202 patients (308 hips) in whom a slipped capital femoral epiphysis had been fixed with pins or screws. A serious complication that was directly related to the use of internal fixation developed in eighty hips (26 per cent). The rate of complications in the 202 patients was 40 per cent. In thirty-six (18 per cent) of the 202 patients, an additional procedure was done to correct a pin-related complication. Forty-one hip joints had been penetrated by a pin. Other complications included avascular necrosis (fourteen hips), chondrolysis (nine), fracture (one), infection (one), further slippage (one), sciatic-nerve injury (one), and breakage of a screw (eight). Ways of decreasing the incidence of complications of fixation were explored. 
2	Hormonal and enzymatic parameters of hepatic regeneration in patients undergoing major liver resections. Thirteen patients who underwent 40% to 80% removal of their livers had blood samples drawn initially and daily on postoperative days 1 to 7. The enzyme marker of heightened polyamine metabolism, ornithine decarboxylase, and the indicator of DNA synthesis, thymidine kinase, were measured. In addition, the hormones (insulin, glucagon, estradiol and androgen), which in animals are known to reflect and possibly modulate regeneration, were measured. Changes in all these indices followed the same pattern as in rats, dogs and swine but at a slower rate. Ornithine decarboxylase and estradiol increased within 24 hr, but thymidine kinase and insulin rises did not become statistically significant until 3 to 5 days. Using these plasma or serum indices as surrogate measures of biochemical events in the liver itself, regeneration reached a maximum after 4 or 5 days. By computed tomography scan analysis, restoration of hepatic cell mass was not complete until 3 wk. 
4	Cigarette smoking, adiposity, non-insulin-dependent diabetes, and coronary heart disease in Japanese-American men. PURPOSE: Coronary heart disease has been described to be increased with both glucose intolerance and cigarette smoking. All three of these have also been reported to be associated with central adiposity (disproportionate deposition of fat on the trunk compared to the extremities). The purpose of this analysis was to determine the relationship of cigarette smoking to glucose intolerance and coronary heart disease, the relationship of cigarette smoking to risk factors such as adiposity, body fat distribution, and plasma lipoprotein and insulin levels, the relationship of cigarette smoking to these risk factors independent of disease status, and whether these risk factors could account for any of the relationship between cigarette smoking and disease status. PATIENTS AND METHODS: The study design was cross-sectional. The study sample contained 219 middle-aged and elderly Japanese-American men: 77 with normal and 74 with impaired glucose tolerance and 68 with type II diabetes. There were 54 men with coronary heart disease. A detailed smoking history was obtained. Glucose tolerance status was established by medical history and a 75-g oral glucose tolerance test. Coronary heart disease was determined by medical history and a resting electrocardiogram. Adiposity and fat distribution measurements were body mass index (kg/m2), skinfold thicknesses, body circumferences, and cross-sectional fat areas by computed tomography. Levels of insulin, C-peptide, cholesterol (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], HDL2, HDL3, very-low-density lipoprotein [VLDL]), and triglyceride (total, VLDL) were measured in fasting blood specimens. RESULTS: A central pattern of body fat was associated with both non-insulin-dependent diabetes mellitus and coronary heart disease. Smoking history was related to both adiposity and body fat distribution, and was strongly related to coronary heart disease but not to diabetes. Past smokers who had smoked up to a month ago were the heaviest while present smokers who were currently smoking or had smoked within the past month were the leanest. However, although present smokers had reduced amounts of fat, this was attributable to those present smokers without heart disease. Present smokers with heart disease were not as lean and had increased amounts of intra-abdominal fat. Past smokers had the greatest amount of central fat and this was attributable to those with heart disease. By two-way (smoking history and coronary heart disease status) analysis of covariance, smoking history was significantly related only to subcutaneous fat disposition on the chest and abdomen independent of coronary heart disease, while coronary heart disease status was strongly related to plasma levels of insulin C-peptide, VLDL, HDL, HDL2, and HDL3 cholesterol, and total and VLDL triglyceride, independent of smoking history. Further analysis showed that none of the body fat variables could account for the risk of coronary heart disease associated with smoking history. Higher fasting plasma C-peptide levels in past smokers accounted statistically for part of the risk of coronary heart disease associated with cigarette smoking. However, this effect was not mediated by any of the body fat measurements. CONCLUSIONS: Disproportionately increased intra-abdominal fat is related to coronary heart disease but not to smoking history. Smoking history is related to coronary heart disease but not to diabetes. Weight gain is associated with smoking cessation and appears to be concentrated in the central subcutaneous regions, especially for those who have coronary heart disease. Weight gain associated with cessation of smoking appears to be unrelated to atherogenic changes in lipids, lipoproteins, or insulin. Other pathogenic processes must be considered in the association between smoking and coronary heart disease. 
5	Reperfusion and readmission of oxygen. Pathophysiological relevance of oxygen-derived free radicals to arrhythmogenesis. We have examined the pathophysiological role of readmission of oxygen (and hence production of oxygen-derived free radicals) in the initiation of reperfusion-induced arrhythmias by separating, on a temporal basis, readmission flow from readmission of oxygen. Isolated rat hearts (n = 12/group) were subjected to 10 minutes of regional ischemia and 10 minutes of reperfusion. In controls reperfused with oxygenated solution (Po2 greater than 600 mm Hg), 92% of hearts developed ventricular fibrillation (VF) during the first 20 seconds of reperfusion, whereas in hearts reperfused with hypoxic solution (Po2 9.3-12.2 mm Hg), the incidence of VF was only 17% (p less than 0.05). Subsequent readmission of control solution (Po2 greater than 600 mm Hg) to the latter group led, within 20 seconds, to the appearance of VF in seven of the 10 hearts (70%) that had not previously fibrillated. To examine whether hypoxic reperfusion had prevented VF or merely delayed its onset, the studies were repeated in separate groups of hearts with the duration of hypoxic reperfusion extended to 5 minutes. In addition, to examine the partial pressure dependence of the relation, the Po2 in the reperfusion solution was set at one of five different levels: greater than 600, 150-192.7, 69-85.6, 9.2-14.8, or 0.0 mm Hg. It was found that hypoxia merely delayed VF onset by 20-40 seconds and did not significantly reduce the incidence of VF, which was 83%, 92%, 67%, 58%, and 58%, respectively. This indicated that readmission of oxygen is unnecessary for the initiation of VF during reperfusion. The hearts that reverted to sinus rhythm during the ensuing 5 minutes (n = 8, 4, 5, 9, and 8, respectively) were used to assess the arrhythmogenic consequences of readmission of oxygen. When control solution (Po2 greater than 600 mm Hg) was readmitted, new episodes of VF were elicited within 20 seconds in a manner that was inversely proportional to the preceding Po2 (p less than 0.05), the incidence of new episodes of VF being 0%, 0%, 40%, 67%, and 86%, respectively. The arrhythmogenic effect of readmission of oxygen was not the result of a sudden increase in heart rate, because a similar arrhythmogenic effect of readmission of oxygen was seen in separate groups of hearts that were paced (350 beats/min) throughout hypoxia and readmission of oxygen. In conclusion, readmission of flow and readmission of oxygen are independent determinants of reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS). 
2	Variceal rebleeding after portosystemic shunting. Strategies and solutions to a vexing problem. The purpose of this review was to discuss an approach to the treatment of recurrent bleeding from esophageal or gastric varices after portosystemic shunt. From our own clinical experience, as well as that of others, it appears that re-establishment of portal decompression should offer the best chance at long-term survival. Luckily, innovations in angiographic technique have allowed attainment of this goal without the inordinate risk of an operative procedure. However, not all patients' situations will be amenable to such treatment. For some of them, operative decompression of the portal venous system can be carried out in an anatomic area previously untouched. For those patients in whom no decompression is possible, direct endoscopic treatment of the varices will offer an alternative, albeit temporizing, approach. 
5	Intramyocardial shotgun pellets diagnosed on initial emergency room chest X-ray: case report. The diagnosis of retained intracardiac missile is usually made at thoracotomy or fluoroscopy. Close inspection of plain chest X-rays may reveal blurring of radiopaque objects that are moving with the beating heart. In a gunshot wound victim who is initially stable, observation of this phenomenon should prompt a very high index of suspicion for cardiac injury. Invasive hemodynamic monitoring is indicated, and thoracotomy should be performed if penetrating cardiac injury is confirmed. 
3	Risk monitoring of randomized trials in emergency medicine: experience of the Brain Resuscitation Clinical Trial II. Risk monitoring for the Brain Resuscitation Clinical Trial II, a multicenter, placebo-controlled trial to evaluate the efficacy of the calcium-entry blocker lidoflazine in the amelioration of brain damage in comatose cardiac-arrest survivors, posed unexpected challenges. Concern arose when monitoring of adverse reactions showed an excess of dangerous cardiac arrhythmias, including rearrest, in the lidoflazine group. To ascertain the cause of this problem and determine whether it was ethical for the trial to continue, an in-depth review of data was conducted, outside experts were consulted, and additional data were collected. These efforts suggested possible causes for the problem. Existing drug administration protocols for blood pressure control were reinforced, resulting in lower subsequent arrhythmia rates. Thus, through an efficient monitoring system, an important problem was uncovered and resolved, allowing the trial to be completed without major changes. 
4	Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat. Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary occlusion in the rat. There is little data available on whether ischemic preconditioning (PC) of hearts can reduce the incidence of such arrhythmias. The effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on development of arrhythmias after a subsequent 5-minute coronary artery occlusion and reperfusion was studied. Rats (n = 16 each group) underwent 5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion, and biopsies were taken for creatine phosphate and adenosine triphosphate in ischemic and nonischemic zones of the left ventricle. PC reduced the incidence of ventricular tachycardia (VT) during occlusion (81% control versus 13% PC, p less than 0.001). On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC animals versus 13 (81%) of controls (p less than 0.001), and irreversible VF in zero of PC versus seven (44%) of controls (p = 0.007). VT occurred in four (25%) of PC versus all (100%) of controls (p less than 0.001). PC reduced mean duration of VT plus VF from 320 +/- 54 to 5 +/- 1 seconds (p less than 0.001) and delayed arrhythmia onset from 8 +/- 2 to 85 +/- 35 seconds after reperfusion. There was no difference in creatine phosphate levels in the ischemic zone at the end of reperfusion in PC animals compared with controls without irreversible VF (16.2 +/- 4.1 versus 15.5 +/- 3.9 nmol/mg protein, p = NS). 
4	Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation. To test the practicality of Doppler echocardiography to measure serial change, biventricular outputs were measured in 15 patients with aortic regurgitation during control periods and during interventions of bicycle exercise, cold pressor stimulation, and vasodilation. Biventricular stroke volumes were measured in 10 normal subjects for validation of methods and differed by 2.8%. Reading errors were 3.7%. Signal quality improved between the first and last observation (p less than 0.05). Velocity signals were corrected for intercept angles, which averaged 12 and 19 degrees for right heart flows and 31 and 32 degrees for the left side of the heart in all subjects. Negative correlations occurred between intercept angles and the chronologic order in which the patients were studied for left (p = 0.02) and right (p = 0.05) flows. Mean flow areas varied 9% in the left ventricle and 20% in the right ventricle. Total variability for measuring flow determined from control values was 11% to 13%. When twice the variability was used as the detectable level of change, only exercise provoked real increases in biventricular flows in the majority of patients. We conclude that serial measurements of flow by Doppler echocardiographic methods had to exceed 20% to 25% to achieve significant change. Measuring intercept angle, resolving flow area, and learning are variables that need greater emphasis. 
1	The significance of gastrinomas found in peripancreatic lymph nodes. A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma. 
2	Antropyloric muscle thickness at US in infants: what is normal? The authors reviewed the ultrasonographic (US) images and medical records of 145 consecutive infants who were seen for evaluation of the upper gastrointestinal tract because of chronic vomiting and/or regurgitation. At US, the antropyloric muscle of each patient was measured in the midlongitudinal plane. On the basis of this measurement, the patients were divided into the following categories: group 1 (1-2 mm; 99 patients), group 2 (greater than or equal to 3 mm; 40 patients), and group 3 (2- less than 3 mm; six patients). Patients in group 1 were considered to have normal antropyloric muscle thickness, those in group 2 had abnormal thickness, and those in group 3 had muscle thickness that was not definitely normal or abnormal. The final clinical diagnoses for all of the infants in the three groups confirmed the authors' initial impressions that antropyloric muscle thickness of less than 2 mm was anatomically normal, muscle measuring 3 mm or greater was abnormal and diagnostic for pyloric stenosis, and muscle from 2 to less than 3 mm was abnormal but not specifically diagnostic for pyloric stenosis. Two of the six patients in group 3 eventually were diagnosed as having pyloric stenosis; thus, the authors believe that only those patients with antropyloric muscle less than 2 mm thick should be considered unequivocably normal. 
3	National General Practice Study of Epilepsy: recurrence after a first seizure In the National General Practice Study of Epilepsy 564 patients classified as having definite seizures have been followed up for 2-4 years. 67% (95% confidence interval 63-71%) had a recurrence within 12 months of the first seizure, and 78% (74-81%) had a recurrence within 36 months. Seizures associated with a neurological deficit presumed present at birth had a high rate of recurrence (100% by 12 months), whereas seizures that occurred within 3 months of an acute insult to the brain, such as head injury or stroke, or in the context of an acute precipitant such as alcohol, carried a much lower risk of recurrence (40% [29-51%] by 12 months). Other factors affecting the risk of recurrence were age-the highest risk being for patients under the age of 16 (83% [77-89%] by 36 months) or over the age of 59 (83% [76-90%] by 36 months-and type of first seizure-the risk of recurrence being much higher for patients with simple partial or complex partial seizures (94% [90-99%] by 36 months) than for those with generalised tonic clonic seizures (72% [67-77%] by 36 months). 
5	Gaucher's disease complicated by bleeding esophageal varices and colonic infiltration by Gaucher cells. We report a 10-yr-old child with Gaucher's disease who developed upper gastrointestinal bleeding from esophageal varices, as well as hemorrhage from a colonic polyp infiltrated with Gaucher cells. Both the varices and polyp were treated endoscopically, and the outcome was successful. Although gastrointestinal hemorrhage due to portal hypertension is considered a rare complication of Gaucher's disease, colonic infiltration with Gaucher cells has not been recognized previously. 
5	Quality of life in elderly, chronically ill outpatients. Quality of life (QL) in elderly outpatients is poorly characterized. We interviewed 258 elderly outpatients from three health care settings to identify the attributes and events that affect self-assessment of QL. These outpatients rated their QL as acceptable, citing medical care, health, interpersonal relationships, financial status, and functional status as affecting their QL. Overall QL ratings were not strongly associated with objective indicators such as demographic characteristics and use of health care services. Subjective indicators, including patient perceptions of health, memory, and financial concerns, were correlated independently with global QL (sigma R2 = .35). We conclude that older, chronically ill patients generally consider their QL to be acceptable and affected by a variety of factors, including their perceptions of their emotional, socioeconomic, intellectual, and physical functioning. Furthermore, QL is poorly associated with objective indicators. Thus, in assessing the QL of elderly, chronically ill outpatients, physicians should elicit information regarding these perceptions. 
4	Stunned myocardium and myocardial collagen damage: differential effects of single and repeated occlusions. It has been suggested that collagen loss and damage is responsible for the dysfunction seen in stunned myocardium. To test this hypothesis we compared collagen in canine hearts stunned by repeated occlusion with collagen in hearts stunned by a single occlusion. Regional contractile function was equally depressed in both groups: segment shortening at 1 hour after reperfusion averaged 37% +/- 9% versus 32% +/- 9% of preocclusion values in repeated and single occlusion models, respectively. Midmyocardial collagen content was not different in either single occlusion (10.5% +/- 0.4%) or repeated occlusion models (9.5% +/- 0.7%) when compared with nonischemic hearts (8.5 +/- 0.8%). Collagen damage, which was revealed with polarized light microscopy, was seen in 5 of 6 dogs after repeated occlusion but was not apparent after a single occlusion. Thus although both models of stunned myocardium produce similar dysfunction, there was no apparent collagen loss. Furthermore, collagen damage was only seen after repeated occlusion. Therefore it appears unlikely that collagen damage is a primary mechanism of stunned myocardium. 
1	Is urethral sparing at cystectomy a safe procedure? Urethrectomy is performed with cystectomy when the neoplasm is multifocal, at the bladder neck, or associated with carcinoma in situ (CIS). The records of the most recent 20 patients treated by radical cystectomy at our institution were reviewed. In 50 percent of the cases, the extent of disease within the bladder was found to have been underestimated to the point that a urethral sparing operation (i.e., to maintain urinary continence with an intestinal segment and an intact urethra) might have been dangerous. 
3	Strategies underlying the control of disordered movement. The purpose of this article is fourfold. First, a theory of motor control--the dual-strategy hypothesis--is outlined. Second, the methodologies and theoretical framework that are used to develop this theory are examined. Third, motor dysfunction is discussed in the context of this theory. In particular, Down syndrome, Parkinson's disease, cardiovascular accidents, and spasticity are discussed. Finally, potential applications of the theory to physical therapy are considered. 
5	The electrocardiogram in chronic obstructive pulmonary disease. The electrocardiogram is often abnormal in patients who have chronic obstructive pulmonary disease. The most frequent abnormalities are a rightward P-wave axis (greater than or equal to 70 degrees) and a rightward QRS axis (greater than or equal to 90 degrees). In addition, low voltage in the limb leads, an S1S2S3 pattern, poor R-wave progression, a posterior-superior terminal QRS vector or other changes may be present. Transient atrial and ventricular dysrhythmias are common. Knowledge of the usual electrocardiographic manifestations of chronic obstructive pulmonary disease enables the clinician to recognize uncharacteristic abnormalities, which often represent the effects of superimposed illnesses or drug toxicity. 
2	Granulomatous vasculitis in Crohn's disease [published erratum appears in Gastroenterology 1991 Aug;101(2):595] This study investigated a possible vascular origin for granulomas in Crohn's disease. Twenty-four consecutive resected specimens of small and large intestinal Crohn's disease were preserved by arterial perfusion-fixation with 10% formol saline, at mean arterial pressure (100 mm Hg). Fifteen specimens contained granulomas on routine examination of H&E-stained sections. These 15 specimens were examined in detail using a range of immunohistochemical staining techniques to identify vascular structures and granulomas. A total of 485 granulomas were found, 85% of which were identified as being directly involved in vascular injury. The majority (77%) of granulomas were deep to the mucosa; they were found most frequently in the submucosa (42%). The techniques used in this study enhanced the recognition of granulomatous vasculitis. The results suggest that the majority of granulomas in Crohn's disease form within walls of blood vessels. Vascular localization of granulomatous inflammation suggests that the intestinal microvasculature contains an early element in the pathogenesis of Crohn's disease. 
3	The contribution of median nerve SEPs in the functional assessment of the cervical spinal cord in syringomyelia. A study of 24 patients. Since the early study of Halliday and Wakefield (1963) it has generally been agreed that scalp somatosensory evoked potentials (SEPs) are normal in patients with dissociated loss of pain and temperature sensation. Up to now a few patients with abnormal spinal N13 and preserved scalp P14 and N20 have been reported in the literature, but there is no firm evidence, based on group data, that this dissociation can be related to any form of dissociated sensory loss. We studied median nerve SEPs in 24 patients with syringomyelia documented by CT scan or MRI. For the recording of the cervical N13 we used a Cv6 anterior cervical montage, which cancels the potentials generated above the foramen magnum and enhances the amplitude of N13. Scalp far-field and early cortical SEPs were recorded using a noncephalic reference electrode. Since N13 pathological changes are mainly changes in amplitude we measured the N13/P9 amplitude ratio in normal subjects and patients and found that it was a reliable index to quantify the amplitude decrease of N13. Absent or reduced N13 was observed in 40 median nerve SEPs (83%) in conjunction with normal P14 and N20 in 30 SEPs. Thus the dissociated loss of the cervical N13 was identified as the most conspicuous SEP feature in syringomyelia. A significant correlation was found between abnormal N13 and loss of pain and temperature sensations, whereas P14 abnormalities correlated well only with loss of joint and touch sensations. In the median nerve territory, sensation was either normal (6 cases) or lost only for pain and temperature (24 cases) when SEPs showed abnormal N13 and normal P14. Although it does not directly reflect the postsynaptic activity of spinal cells receiving their inputs from A delta and C fibres the N13 potential proved to be a reliable index of spinal cord grey matter dysfunction in syringomyelia. 
2	Persistent mullerian duct syndrome. Persistent mullerian syndrome is rare. A case of phenotypically normal male with persistent mullerian structures that consisted of a bicornuate uterus, fallopian tubes, and upper third of the vagina is reported. These unusual structures were found in association with bilateral cryptorchidism and a right inguinal hernia, and were diagnosed while repairing the hernia in the neonatal period. The uterus and fallopian tubes were removed via laparotomy when the child was eighteen months old; at the same time a bilateral orchiopexy was performed. To avoid damage to the vas deferens, which lay in closely to the mullerian structures and could not be separated from the vaginal wall, a small segment of the upper third of the vagina was retained. The testicles, although normal on pathologic examination, have shown poor response to hormonal stimulation with human chorionic gonadotropin. Long-term follow-up for these patients is necessary because they have an increased risk of testicular tumors developing. 
3	Myasthenia gravis. Myasthenia Gravis is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors. The disease is characterized clinically by variable weakness accentuated by repetitive muscular activity and usually responding to the administration of acetylcholinesterase inhibitors. Myasthenia Gravis is a complex disease and requires understanding of the many facets of its natural history and immunological basis to ensure optimal individual patient management. The long-term goal is control of the immunological imbalance; treatment regimens include thymectomy, corticosteroids, azathioprine, and plasmapheresis. The common use of acetylcholinesterase inhibitors provides symptomatic relief during variable daily muscular activity. Disability due to myasthenia gravis is to a large extent reversible and death is preventable. Early recognition of myasthenia gravis and appropriate treatment are often rewarded by remission that may be permanent. 
1	Muscle fibre type and habitual snoring. Although anatomical abnormalities of the upper airway have been recorded in some patients with obstructive sleep apnoea (OSA), a muscle tone dysregulation also seems to have an important role in this disorder. Since habitual snoring is the initial stage of OSA, the structural characteristics of upper airway muscles (medium pharyngeal constrictor muscle [MPCM]) from 13 men (9 non-snorers and 4 habitual snorers) were studied. MPCM fibre structure in non-snorers was broadly similar to that in normal limb muscles, with the exception that fibre diameters were smaller for all fibre types. Compared with limb muscles, MPCM had a smaller proportion of type IIb fibres and a higher proportion of types I and IIa fibres. MPCM in habitual snorers had an abnormal distribution of fibre types (low percentage of type I and type IIb fibres and high percentage of type IIa fibres) compared with non-snorers (p less than 0.001) and the type IIa fibres were hypertrophic. No myopathic or neurogenic changes were seen. Two possible hypotheses explain the abnormal distribution of fibre types in snorers. First, a constitutionally determined reduction of slow alpha-motor neurons induces an adaptive transformation of type IIb to type IIa fibres and a hypertrophy of type IIa fibres; or, second, motor neurons change their patterns of discharge and, hence, of activation, and modify fibre-type distribution of MPCM as an adaptation to the anatomical characteristic of upper airway and habitual snoring. 
1	Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction. In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid ([99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of [99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl). 
5	1990 Volvo Award in clinical sciences. Lumbar spinal pathology in cadaveric material in relation to history of back pain, occupation, and physical loading. The occurrence of symmetric disc degeneration, anular ruptures, end-plate defects, vertebral body osteophytosis, and facet joint osteoarthrosis was examined radiographically and osteologically in 86 male cadavers for whom occupational, physical loading, and back pain histories were obtained from the men's families. History of back pain and the parameters of spinal pathology were related to the highest and lowest degrees of physical loading. In multivariate analyses, history of back injury was related to the occurrence of symmetric disc degeneration, anular ruptures, and vertebral osteophytosis. Symmetric disc degeneration was associated with sedentary work, and vertebral osteophytosis was related to heavy work. History of back pain was related to occupational physical loading after control for the effects of the other covariates. The results indicate that the least pathology stemmed from moderate or mixed physical loading, but the least back pain was associated with sedentary work. 
4	A forme fruste of Marfan's syndrome: case history. A thirty nine year old woman presented with multiple aneurysms and dissections of the arterial system secondary to cystic medial necrosis is presented. After assessment of the family history a diagnosis of a forme fruste of Marfan's syndrome was made. Preoperative consideration of this rare diagnosis is important for treatment and surgical management. 
4	Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy. A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication. 
4	Protecting the vasculature: an eye toward the future. Although calcium antagonists were originally developed for use in the management of patients with angina pectoris, they are now used in the management of other cardiovascular disorders, including hypertension. More recently, the calcium antagonists have been under investigation for their potential protective role in atherosclerosis. Coupled with these new possibilities for therapeutic use are the development of new, long-acting, tissue-specific calcium antagonists. Amlodipine belongs to this group, and although it is a dihydropyridine-based calcium antagonist, its pharmacologic profile differs from that of other dihydropyridine-based calcium antagonists. Differences include: different pH optimum for receptor binding, different rates of association and dissociation, and differences in allosteric interaction with the diltiazem and verapamil binding sites. Amlodipine, when given orally to rabbits receiving a high-cholesterol diet, reduces atheroma formation. Evidence of its ability to protect the vasculature is provided by its ability to significantly increase (p less than 0.001) survival in stroke-prone hypertensive rats. 
4	Hypertension and acculturation in elderly Mexican Americans: results from 1982-84 Hispanic HANES. The purpose of our study was to describe the relationship between acculturation and hypertension in elderly Mexican Americans. Two age groups, 55-64 and 65-74, were examined from data provided in the Hispanic Health and Nutrition Examination Survey (HHANES). The prevalence of hypertension among subgroups of different acculturation was ascertained based on the modified Cuellar Acculturation Scale. Each age group was also stratified using the HHANES poverty index, with those above the index compared to those below. A stepwise logistic regression was performed among the variables of poverty, gender, age, and acculturation in relation to hypertension. The results indicate that acculturation and age are stronger predictors of hypertension than poverty in elderly Mexican Americans, with acculturation being a stronger predictor among those age 55-64. Factors related to acculturation may have a stronger influence on the prevalence of hypertension in older Mexican Americans than differences related to socioeconomic status. 
1	Endoscopic palliative intubation of the esophagus invaded by lung cancer. Thirty-two patients with esophageal involvement by lung cancer were managed by endoscopic intubation. In 22 patients with extrinsic esophageal strictures, the success rate of intubation was 91%, and 82% were discharged with their dysphagia relieved and esophageal patency restored. The mean survival rate was 4.4 months. In 10 patients with esophago-bronchial fistulas, 3 had the fistulous tract obliterated and lived a mean of 5 months. This low success rate of closing fistulas is due to failure to seal off the space between the stent and the fistula because of absence of tumor-associated stenosis. The overall morbidity rate was 28.1% (18.8% perforation, 6.3% hemorrhage, and 3.1% tracheal obstruction). The overall mortality rate was 18.8%. Although complications were more frequent than in primary esophageal tumors, endoscopic intubation was the only way to palliate this desperate condition and provided 66.6% of patients with relief of symptoms, nutritional improvement, and a mean survival time of 4.5 months. 
4	Reactivity of eccentric and concentric coronary stenoses in patients with chronic stable angina. Dynamic coronary stenoses may be the cause of a variable angina threshold and rest angina in patients with chronic stable angina. It has been suggested that eccentric but not concentric coronary artery stenoses have the potential for dynamic changes of caliber in response to vasoactive stimuli. The vasomotor response of eccentric (asymmetric narrowing) and concentric (symmetric narrowing) coronary stenoses to ergonovine (20 micrograms intracoronary or 300 micrograms intravenous) and isosorbide dinitrate (1 mg intracoronary) was studied in 51 patients with chronic stable angina. Diameter of reference segments (angiographically normal segments proximal to the stenoses) and that of eccentric (n = 30) and concentric (n = 35) coronary stenoses that ranged from 50% to 90% luminal diameter reduction were measured by computerized quantitative angiography before and after ergonovine and isosorbide dinitrate. Ergonovine reduced stenosis diameter (by greater than or equal to 10%) in 80% of eccentric stenoses and 42% of concentric stenoses (p less than 0.05). Mean (+/- SEM) diameter reduction with ergonovine was 19 +/- 3% and 9.5 +/- 2% for eccentric and concentric stenoses, respectively (p less than 0.05). Isosorbide dinitrate increased coronary diameter (by greater than or equal to 10%) in 70% of eccentric and 43% of concentric stenoses (p less than 0.05). Mean diameter of eccentric stenoses increased from 1.15 +/- 0.05 to 1.35 +/- 0.06 mm after nitrate (18.6 +/- 2.5%), whereas diameter of concentric stenoses increased from 1.05 +/- 0.05 to 1.14 +/- 0.05 mm (10 +/- 2.5%) (p less than 0.05). Average dilation of reference segments with administration of isosorbide dinitrate and constriction with ergonovine were not significantly different in patients with concentric and eccentric stenoses. 
1	Tissue distribution of 2-3 and 2-6 sialyl Lewis A antigens and significance of the ratio of two antigens for the differential diagnosis of malignant and benign disorders of the digestive tract. The authors investigated the tissue distribution of two kinds of sialylated derivatives of Lewis A (Le(a)) antigen in patients with cancers of the digestive system using specific monoclonal antibodies, and evaluated the significance of determining the 2-3 and 2-6 sialylated Le(a) antigen levels for the diagnosis of cancer. In most specimens from patients with cancers of the pancreas, biliary tract, stomach, and colon, the 2-3 sialylated Le(a) antigen was strongly expressed in cancer cells. However, 2-6 sialylated Le(a) antigen was less frequently expressed in cancer cells. The former is therefore more specific to cancer than the latter. Also, the serum level of the 2-3 sialylated Le(a) antigen was significantly higher than that of the 2-6 counterpart in patients with cancers of pancreas, biliary tract, stomach, and colon. The resulting ratio of serum 2-3/2-6 sialylated Le(a) antigens was frequently high in patients with malignancy and was low in patients with benign disorders of these digestive organs. Therefore, the 2-3/2-6 sialylated Le(a) antigen ratio is a useful for the differential diagnosis of malignant disorders in these organs. However, liver disorders were found to be exceptional in that both antigens were mostly absent in hepatocellular carcinoma (HCC) cells in immunohistologic examination, as well as in nonmalignant parenchymal liver cells. Only the epithelial cells of the intrahepatic bile ducts expressed the 2-6 sialylated Le(a) antigen strongly, and expressed the 2-3 sialylated Le(a) antigen moderately. The levels of both antigens were sometimes high in patients with liver disorders, but the ratio always remained low in patients with HCC as well as benign liver disorders such as cirrhosis or chronic hepatitis. The sialylated Le(a) antigens, which sometimes accumulate in the sera of patients with HCC, were concluded to originate from the epithelial cells of the proliferating small bile ducts, and those serum antigens cannot be considered as evidence for the presence of liver cancer cells. 
4	Electrocardiographic signs of atrial overload in hypertensive patients: indexes of abnormality of atrial morphology or function? Left atrial electrocardiographic (ECG) abnormalities have been reported as common findings in hypertension; however, their relationships with atrial anatomy are still uncertain. In addition, in arterial hypertension several studies demonstrated an abnormal left ventricular filling. The aim of this study was to investigate the relationships of the ECG signs of left atrial abnormality to atrial anatomy and left ventricular filling as evaluated by pulsed-wave (PW) Doppler in a group of patients with uncomplicated essential hypertension. To this end, 53 untreated essential hypertensive patients (age 44 +/- 8 years; blood pressure 160.5 +/- 21.5/104.7 +/- 13.5 mm Hg) underwent a complete 12-lead ECG and a PW Doppler study of the transmitral flow velocities. The ECG criteria of left atrial abnormality were: P wave wider than 0.12 (or 0.10) second or higher than 0.25 mV in lead II; P wave/PR segment ratio (Macruz index) greater than 1.6 in lead II; and P wave terminal forces in lead V1 equal to or more negative than 0.04. Echocardiographic measurements were made according to American Society of Echocardiography (ASE) convention. Doppler parameters of left ventricular filling were measured as E and A peak velocity, A/E ratio, and the ratio between the velocity-time integral under the E peak and that of the whole diastolic flow, which represents the rapid filling fraction (RFF). At least one ECG sign of atrial abnormality was present in 34 patients (64%); the Macruz index gave the most common ECG index of atrial abnormality (31 patients). 
1	Rhinosporidiosis associated with squamous cell carcinoma in the tongue. The peritumoural region of a squamous cell carcinoma of the tongue when examined with light and electron microscope showed nodular bodies in the submucosa with all the distinctive features of 'sporangium and 'spores' of rhinosporidiosis. The occurrence of rhinosporidiosis in the tongue along with malignancy has not been reported hitherto. Some interesting observations and causal relationships are discussed. 
3	Effect of age on the efficacy of blood pressure treatment strategies. To study whether the proportion of excess cardiovascular events attributable to various levels of systolic blood pressure varies with age, we calculated the population-attributable risk of all-cause mortality, fatal and nonfatal cardiovascular events (stroke, coronary heart disease, angina, congestive heart failure, and peripheral vascular disease), and stroke incidence due to systolic blood pressure in men and women 45 years of age or older in the United States during 1980. Our estimates are based on US census counts, blood pressure prevalence distributions from the second National Health and Nutrition Examination Survey, and the annual risk of cardiovascular complications during 18 years of follow-up in the Framingham cohort. We then determined the impact of age on the relative efficacy of mass treatment and case-finding strategies in preventing systolic blood pressure-related events. At 45-54 years of age, only 30-40% of systolic blood pressure-related excess events occur in hypertensive individuals (systolic blood pressure greater than or equal to 160 mm Hg). With increasing age, however, the percentage of systolic blood pressure-related events that occur in hypertensive individuals rose substantially; in the older age group (greater than or equal to 75 years), 65-70% of fatal and nonfatal cardiovascular disease events occur in hypertensive persons. The pattern is similar for men and women. The potential impact of a mass treatment strategy designed to shift the distribution of blood pressure downward by a small amount is greater in younger than in older groups, whereas an opposite trend is seen for a high-risk, hypertensive case-finding and treatment approach. 
1	Lip paresthesia associated with a jaw mass. A case is reported in which mandibular swelling and lower lip numbness were the first signs of a metastatic adenocarcinoma of the lung. The development of paresthesia, with or without other oral symptoms, requires that a diagnosis of malignancy be considered until confirmed or ruled out by tissue biopsy. A thorough head and neck examination in all patients, especially in those whose history or habits may indicate increased risk of malignancy is necessary. 
5	Diagnosis and treatment of pneumonia in the surgical intensive care unit [published erratum appears in Surg Gynecol Obstet 1991 Apr;172(4):324] It is often difficult to detect the onset of parenchymal pulmonary infection (pneumonia) in a surgical intensive care unit (SICU) setting. Clinical and laboratory parameters that usually indicate the presence of pneumonia, such as fever, elevated white blood cell count and abnormal sputum culture, may also be present in patients with nonpneumonic infection. Prompt diagnosis is particularly important for patients in SICU because the mortality rate associated with pneumonia in these patients may be as high as 50 per cent. In the SICU setting, pneumonia is best diagnosed using well-defined roentgenologic criteria. Treatment should consist of a broad-spectrum antibiotic regimen to which all sputum pathogens are sensitive. Such a regimen significantly reduces the mortality rate for patients with pneumonia in an SICU setting. Aztreonam has been found to be as effective against susceptible gram-negative bacilli as traditional agents, such as the aminoglycosides, and to have a significantly milder side effect profile. 
2	Management of childhood diarrhoea by pharmacists and parents: is Britain lagging behind the Third World? OBJECTIVE--To investigate the role of community pharmacists in providing advice and treatment for children with diarrhoea; to investigate mothers' responses to diarrhoea in their children. DESIGN--Cross sectional questionnaire study of a random selection of community pharmacists and of mothers attending child health clinics. Pharmacists were interviewed and given a questionnaire and a separate group was visited by a researcher posing as a parent; mothers were interviewed at the clinic. SETTING--Newcastle upon Tyne. SUBJECTS--20 pharmacists were interviewed and visits by a researcher posing as a parent were carried out to 10 different pharmacists; 58 mothers were interviewed. MAIN OUTCOME MEASURES--Advice given by pharmacists was contrasted with standard advice on management of diarrhoea in children. RESULTS--Half of the pharmacists interviewed and 70% of pharmacists visited by a researcher posing as a parent recommended inappropriate treatment of childhood diarrhoea (such as antidiarrhoeal drugs and withholding breast milk), and only 30% at interview stated that they would ask for the age of the child. Mothers' knowledge of home treatment was inadequate. All pharmacists in the posed visits recommended a purchased treatment. CONCLUSION--Pharmacists are widely used by parents for consultation for children's ailments but their advice is not always appropriate; hence they should be given more consistent training in recognising and managing clinical problems. Medical advice on management of diarrhoea is also inconsistent and should be modified to conform to the guidelines of the World Health Organisation. 
1	Continuous muscle fiber activity, peripheral neuropathy, and thymoma. Two patients, one of them with myasthenia gravis, presented symptoms of continuous muscle fiber activity syndrome before discovery of a thymoma. Peripheral neuropathy was present in both patients, with axonal and demyelinating lesions in sural nerve biopsy. The syndrome remained unchanged or worse after thymectomy. Both patients died of associated complications. 
5	Exacerbation of bacterial toxicity to infant ferrets by influenza virus: possible role in sudden infant death syndrome [published erratum appears in J Infect Dis 1991 Jul;164(1):232] Of several toxins examined, only staphylococcal alpha and gamma toxin, endotoxin, and diphtheria toxins were lethal for 5-day-old ferrets. Their toxicities were enhanced in animals infected at 1 day old with influenza virus, from 3-fold with staphylococcal gamma toxin through 14-fold for staphylococcal alpha toxin, 84-fold for endotoxin, and 219-fold for diphtheria toxin. No increased viral replication occurred in any tissue; thus the effects of the toxins were exacerbated by the infection, not vice versa. Neonates died suddenly without clinical symptoms as in human babies dying from the sudden infant death syndrome (SIDS). Pathologic examination showed inflammation in the upper respiratory tract, lung edema and collapse, and early bronchopneumonia in the toxin- and influenza virus-treated animals but not in those treated with toxin or virus alone. Thus, bacterial toxins could play a role in SIDS, this being more likely with a concomitant influenza virus infection. 
1	Lymphocyte subset distribution after radiation therapy for cancer of the uterine cervix. Possible prognostic implications and correlation with disease course. An analysis of lymphocyte subpopulations was done in patients with cancer of the uterine cervix before and at different intervals after the commencement of radiation therapy. A common feature was a duration of T-cell and B-cell lymphopenia after therapy. The findings relating to the T-cell subsets were interesting. Although the CD4/CD8 ratio remained unchanged in Stages I/IIA for 24 months after treatment, patients with Stages IIB and III showed a lowering of the ratio immediately after treatment. Distinctive patterns of lymphocyte subset distribution were seen in a comparison between patients who were disease-free and those with recurrent disease. The CD4+ cell counts and CD4/CD8 ratio differed between the two groups, with consistent lowered values during the follow-up associated with recurrent disease. This study demonstrates the effects of radiation therapy in altering lymphocyte subset distribution, resulting in characteristic patterns which could be used as clinical and prognostic indicators. 
1	Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause. 
4	Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus. In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from greater than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a greater than or equal to 90% successful amoxicillin treatment of experimental endocarditis due to penicillinase-negative MRSA compared with cloxacillin, which was totally ineffective (P less than .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections. 
2	Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding. Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy. 
5	Nicardipine reduces the cardio-respiratory toxicity of intravenously administered bupivacaine in rats. The purpose of our study was to examine the effect of intravenous (IV) nicardipine pretreatment (30 micrograms.kg-1), given three minutes before an IV bolus of bupivacaine to determine its effect on the incidence of fatal bupivacaine cardio-respiratory toxicity in adult male Sprague Dawley rats anaesthetized with intraperitoneal pentobarbital. Fifty rats were divided into four groups. Groups I and II (n = 10 each) received 3.5 mg.kg-1 0.5 per cent bupivacaine and Groups III and IV (n = 15 each) received 5.0 mg.kg-1, 0.5 per cent bupivacaine. Groups I and III received pretreatment with normal saline before bupivacaine, whereas Groups II and IV were given pretreatment with nicardipine, 30 mg.kg-1. There was no difference in the incidence of survival between the nicardipine pretreatment group and the saline placebo pretreatment group given 3.5 mg.kg-1, 0.5 per cent bupivacaine (no fatalities in either group). However, there was significant protection by nicardipine pretreatment in the group given 5 mg.kg-1, 0.5 per cent bupivacaine (13 of 15 survived, compared with only 4 of 15 in the saline pretreatment group, P less than 0.001). In conclusion, our data demonstrate that in rats given 0.5 per cent bupivacaine, 5 mg.kg-1, nicardipine pretreatment protected against fatal cardio-respiratory toxicity. 
4	Impairment of cerebral autoregulation during the development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates. We studied the impairment of autoregulation of cerebral blood flow (CBF) and its effect on the electrical activity of the brain during the development of chronic cerebral vasospasm after subarachnoid hemorrhage, using a vasospasm model in primates. Fourteen animals were divided into two groups: a clot group (8) and a sham-operated group (6). To induce subarachnoid hemorrhage, all the animals underwent craniectomy, and in the clot group, the autologous blood clot was located around the arteries dissected free from the arachnoid membrane. Cerebral angiography was performed before subarachnoid hemorrhage and 7 days after (Day 7). On Day 7, regional CBF in the parietal lobe--measured by the hydrogen clearance method--and central conduction time were studied during either graded hypertension or hypotension. In the clot group, the mean vessel caliber of the cerebral arteries on the right side (clot side) of the circle of Willis showed significant (P less than 0.01) reduction (more than 40%) as compared with the values on the contralateral, non-clot side. The values for the bilateral parietal CBF in the sham-operated group and the left parietal CBF in the clot group were fairly constant when the mean arterial blood pressure (MABP) was in the range of 60 to 160 mm Hg. In the clot group, right parietal CBF was significantly (P less than 0.05) smaller than that on the left side at an MABP level of 40 to 100 mm Hg, and increased at an MABP level of 180 mm Hg. The right parietal CBF increased as the arterial blood pressure increased, showing impairment of autoregulation. 
1	Pancreatic carcinoma in an elderly woman with an organic affective disorder and AIDS delusion. An elderly woman with symptoms of depression and an AIDS delusion was found also to have pancreatic carcinoma. I have discussed her case in conjunction with organic affective disorder, the evaluation of depression in the elderly, and suicide in the elderly. 
5	Fistulas between the aorta and tracheobronchial tree. Aortobronchial fistula is a rare condition that is invariably fatal if not diagnosed and surgically treated. With appropriate surgical intervention, survival rates greater than 70% can be achieved. A review of the literature and an illustrative case report are presented. A total of 63 fistulas in 62 patients have been described. The case we present is unusual in the use of serratus anterior muscle for repair of the fistula. Eighty-seven percent of the cases documented in the literature were associated with an aneurysm of the thoracic aorta. Eighty-six percent of the fistulas were between the descending aorta and left bronchopulmonary tree. More than 95% of patients experienced at least a single episode of hemoptysis, and massive hemoptysis occurred in more than half of the reported cases. A correct preoperative diagnosis was made in only 54% of cases. Plain chest radiographs definitively demonstrated an aneurysm in only 16%. The computed tomographic scan was the most rewarding test, identifying an aneurysm in 11 of 12 patients and the fistula in 50% of them. Surgical repair resulted in a 76% survival rate. 
5	Control of immediate postoperative pain with topical bupivacaine hydrochloride for laparoscopic Falope ring tubal ligation. Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical (band or clip) tubal ligation. Sixty-four patients were studied prospectively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale. Patients randomly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes, the right tube only, or the left tube only, or received none (controls). A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment. Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment (P less than .05). There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment. The value of topical bupivacaine was demonstrated by both subjective patient response (McGill Pain Scale) and reduced need for pain medication before outpatient discharge. Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical (band or clip) tubal ligation. 
1	Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer. To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer. 
5	Ileal pouch-anal anastomosis. Reoperation for pouch-related complications. The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients. 
1	Evaluation of a simple line width test involving magnetic resonance spectroscopy of plasma in carcinoma of the ovary. Magnetic resonance spectroscopic (MRS) measurement of human plasma has been reported as a generally applicable marker for malignancy: patients with malignancy had a MRS line width significantly different from patients with benign diseases or healthy controls. The authors investigated the value of this test in 213 women with ovarian carcinoma, benign pelvic masses, benign nongynecologic diseases, and healthy controls. The MRS measurements were performed on plasma samples at 21 degrees C or 27 degrees C. The line width parameters were obtained by averaging the width at half the height of the methyl and methylene peaks on the resonance spectra. At 27 degrees C using 33 Hz as the threshold for an abnormal result, there was a significant correlation between the result of the test and the presence or absence of malignancy. However, the study demonstrates that the specificity (0.44) and positive predictive value (0.42) are too low for the test to be useful in the management of patients with carcinoma of the ovary. At 21 degrees C no correlation between the results of the test and the clinical status of women with carcinoma of the ovary were observed. In 47 patients the test did not predict preoperatively the benign or malignant nature of a pelvic mass. 
5	Long-term course of patients with persistent hypercalcitoninemia after apparent curative primary surgery for medullary thyroid carcinoma. Thirty-one patients with persistent hypercalcitoninemia after seemingly adequate primary operation for medullary thyroid carcinoma (MTC) were followed for a mean period of 11.9 years after operation. Ten patients had sporadic MTC and the remaining patients were members of families with multiple endocrine neoplasia (MEN)--either MEN 2A (15 patients) or MEN 2B (six patients). Overall 5- and 10-year survival rates were 90% and 86%, respectively. Only four patients died at the completion of the study: two of MTC and two of unrelated causes. Eleven patients (35.5%) underwent surgical re-exploration after demonstration of recurrent disease clinically or radiologically. In no patient did the calcitonin level return to normal after re-exploration. The presence of more than three metastatic nodes at the time of initial operation was a statistically significant (p = 0.003) predictor for disease recurrence. Factors approaching statistical significance were patients younger than age 35 (p = 0.06) and the percentage of cells in the S phase of cell division (0.07). This data supports a conservative surgical philosophy in the management of the patient with persistent hypercalcitoninemia after resection of MTC. 
5	Anti-Kveim monoclonal antibody. New monoclonal antibody reacting to epithelioid cells in sarcoid granulomas. A monoclonal antibody to the sarcoid granulomagenic agent contained in Kveim suspension was prepared by immunizing mice with Kveim suspension. One monoclonal antibody (IHY-1) that reacted with the epithelioid cells in sarcoid granulomas on immunoperoxidase technique was selected. The immunoperoxidase technique was used to compare this monoclonal antibody's binding to sarcoidosis- or tuberculosis-affected lymph nodes. IHY-1 is a monoclonal antibody of IgM class. This antibody did not react to erythrocytes, lymphocytes, monocytes, alveolar macrophages, or the macrophage-derived cell lines such as U-973 and KG-1. It reacted to granuloma epithelioid cells of sarcoidosis-affected lymph nodes. The monoclonal antibody also reacted positively to epithelioid cells in tuberculous granulomas although the reaction was not as strong. Since IHY-1 was found to bind to both types of granulomas, this suggests that the epithelioid cells in sarcoidosis have antigenicity common to the epithelioid cells in tuberculosis. 
4	Endocardial resection in the treatment of ventricular tachycardia secondary to cardiac trauma. Sustained ventricular tachycardia with left ventricular aneurysm formation is a rare complication following penetrating cardiac trauma. We present an unusual case of serious ventricular tachycardia which developed 35 years after a World War II injury and was successfully treated with aneurysmectomy, map-guided subendocardial resection, and cryoablation. 
1	Extradural implantation of sacral anterior root stimulators. A technique for extradural deafferentation of the S2 to S5 segments and extradural implantation of stimulating electrodes is described, and its application to twelve patients with spinal cord lesions is reported. Nine patients use their implants for micturition, and seven are fully continent. The advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed. 
4	Regression of atherosclerosis: what does it mean? Angiographic evidence of coronary artery atherosclerosis regression has been demonstrated in controlled clinical trials. The significance of this regression appears to depend in a complex way on the degree of atherosclerosis present when a regression regimen is initiated. Angiographic trials indicate that lesion change is a continuum, with a gradual transition from progression to stability and regression. Divergent lesion change can be seen in the same patient with a progression of some lesions and a regression of others. This makes it necessary to perform a comprehensive survey of all visible coronary segments when evaluating angiograms to determine the outcome of a clinical trial. An important finding in clinical trials is that new lesion formation can be reduced. This indicates that effective control of atherosclerosis may be possible with procedures now available, but noninvasive coronary artery imaging methods need to be refined. 
1	A predominantly adrenaline-secreting phaeochromocytoma. A 61-year-old woman who presented with diabetes, nausea, weight loss and sweating was found to have a phaeochromocytoma secreting adrenaline, with a small amount of N-methyladrenaline. There was no significant increase in noradrenaline secretion. She was normotensive, and developed profound hypotension in response to the alpha-adrenergic antagonist phenoxybenzamine. These features are unusual in phaeochromocytoma, but similar features occurred in the very few previous reported cases of pure adrenaline-secreting phaeochromocytoma. We conclude that it is important to identify such patients, so that they should not be given alpha-adrenergic antagonist drugs. 
5	Atherosclerotic carotid disease and the eye. The evaluation and management of retinal ischemia from atherosclerotic carotid disease is in a state of flux reflected by the change from emphasizing surgical management in the '70s toward skepticism about the benefit of surgery in the '80s. In addition, reliable noninvasive diagnostic testing of the carotid artery has reduced the risk. The decision to consider surgical versus medical management must be made on an individual basis based on the patient's health, age, and the risk of angiography and surgery at each institution. In children and young adults, amaurosis fugax is a benign condition. In the older population amaurosis fugax is often the sentinel event of diffuse atherosclerotic disease and possible early death from myocardial infarction. A team including the neurologist, internist, ophthalmologist, and surgeon optimizes care of the whole disease and not just the symptom. It is hoped that information in the next decade will supply additional guidance in the care of this multifaceted malady. 
1	A,B blood group antigens in tissues of AB heterozygotes. Emphasis on normal and neoplastic urothelium. The tissue distribution of the A and B blood group antigens was studied in 41 individuals with the heterozygous AB red blood cell (RBC) phenotype. A total of 134 biopsies from a variety of normal tissues (94 from urothelium and 40 from other tissues) were examined. In addition, changes in the expression of these antigens associated with neoplastic transformation were evaluated in 70 biopsies from transitional cell carcinomas of 19 AB heterozygous patients. There was heterogeneity in the distribution of tissue A and B antigens, depending on the cell type, as well as among cells of the same type. Ninety-one percent of AB heterozygotes expressed both A and B antigens in normal epithelial cells, with a mosaic distribution clearly apparent in 50% of these individuals. In 21% of these subjects, the A antigen was undetectable in the vascular endothelial cells in all biopsies from several organs. In most (79%) transitional cell neoplasms, only one of the two antigens was consistently expressed. The results of this study may have implications for the clonal or specific gene deletion theories of neoplasia. They also demonstrate the existence of a subgroup of AB individuals in whom the A antigen is absent specifically from the vascular endothelium. 
5	Morbidity associated with childhood systemic lupus erythematosus. A complete analysis of the outcome of childhood onset systemic lupus erythematosus (SLE) requires determination of survival statistics and consideration of disease and treatment morbidity. The course of 32 patients with SLE diagnosed at or prior to age 16 and followed from 1979-1988 was analyzed with emphasis on the morbidity of pediatric SLE. Clinical characteristics were similar to those in previous studies. Five year survival, calculated by life-table analysis, was 85.3%, comparable to recent studies. Treatment consisted of corticosteroids (32 patients), antimalarials (14), cyclophosphamide (9) or azathioprine (2). Eighty-four percent of patients experienced a noninfectious drug related complication. A major infection contributed in all 5 patients who died. Higher total corticosteroid dose was associated with more severe infections. Eighty-eight percent of patients were left with chronic organ dysfunction. Survival in childhood onset SLE has improved, but morbidity remains a significant problem from organ dysfunction and complications of therapy. Our study is the first to address the issue of morbidity in childhood SLE. 
5	Filler DNA is associated with spontaneous deletions in maize. We have determined the structure of five spontaneous deletions within the maize waxy (Wx) gene. Of these, four were found in spontaneous wx mutants (wx-B, wx-B1, wx-B6, wx-C4) and include exon sequences; the fifth is restricted to an intron and represents a restriction fragment length polymorphism of a nonmutant allele (Wx-W23). The deletions, which range in size from 60 to 980 base pairs (bp), cluster in a G+C-rich region of approximately 1000 bp that is capable of forming stable secondary structures. Most striking is our finding that all of the alleles have DNA insertions (filler DNA) of 1-131 bp between the deletion endpoints. For three of the five deletions, the filler DNA and sequences at the deletion termini appear to be derived from sequences near one deletion endpoint. A previously reported spontaneous deletion of the maize bronze gene (bz-R) also contains filler DNA. The association of filler DNA with maize deletion endpoints contrasts dramatically with the rarity of similar events in animal germ-line and bacterial mutations. 
5	Renal function in obstructive jaundice in man: cholangiocarcinoma model. Renal function with respect to water clearance and renal hemodynamics was studied in 15 patients with obstructive jaundice due to cholangiocarcinoma. The results were compared with those of the control normal subjects. There was no change in renal function in the patients with mild to moderate jaundice, with total serum bilirubin from 8.0 to 15.1 mg/dl. Increased urinary sodium excretion and decreased free water and negative water clearances were observed in the patients with severe jaundice with total serum bilirubin from 27.0 to 40.4 mg/dl and normal serum albumin. Renal blood flow was normal, but creatinine clearance was decreased. In severely jaundiced patients with serum bilirubin from 30.5 to 40.1 mg/dl and hypoalbuminemia urinary sodium excretion, free water clearance, negative water clearance, renal blood flow and creatinine clearance were decreased. There was salt and water retention in this group. The findings suggest that in severe jaundice there is inhibition of sodium chloride reabsorption in the thick ascending limb of Henle's loop. ADH and increased hydraulic conductivity of the collecting tubules possibly contribute to decreased free water clearance. In severely jaundiced patients with hypoalbuminemia this salt losing effect is converted to salt retention by increased proximal tubular reabsorption of sodium. 
2	Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy. 
2	Antiemetic prophylaxis with promethazine or droperidol in paediatric outpatient strabismus surgery. This randomized, double-blind study evaluated the antiemetic efficacy and the side-effects of promethazine pretreatment (0.5 mg.kg-1 IV + 0.5 mg.kg-1 IM) versus droperidol + placebo pretreatment (droperidol, 0.075 mg.kg-1 IV + physiological saline, 0.02 ml.kg-1 IM). One hundred unpremedicated ASA physical status I children ranging from two to ten years, and undergoing outpatient strabismus surgery were studied. All children received inhalational anaesthesia with halothane, nitrous oxide and oxygen. Neither opioids nor muscle relaxants were used. The incidence of vomiting and/or retching and the incidence of side-effects were determined in the post-anaesthesia recovery room (PARR), in the short-stay surgical unit (SSSU), and after discharge from the hospital (including the journey and the stay at home during the first postoperative day). Promethazine and droperidol were equally effective in reducing the incidence of vomiting before discharge to two and eight per cent respectively. On the contrary, the incidence of vomiting after discharge and overall were significantly less with promethazine (ten and ten per cent) than with droperidol pretreatment (54 and 56 per cent) (P less than 0.0001). Promethazine permitted the time to discharge from the hospital to be reduced to an average of three hours, without increasing the incidence of vomiting postdischarge. Promethazine pretreatment is much less expensive than droperidol pretreatment. The incidence of restlessness was significantly less with droperidol (eight per cent) than with promethazine (36 per cent) (P less than 0.001). Promethazine pretreatment demands the use of an analgesic like acetaminophen in order to reduce the incidence of postoperative pain and restlessness. 
3	Assessing clinical significance of apnea exceeding fifteen seconds with event recording. Using event recording, we determined how often apnea exceeding 15 seconds in duration was associated with bradycardia and how often patients with apnea resumed breathing spontaneously. Of 1306 documented apnea events exceeding 15 seconds (54 patients), 926 lasted 16 to 20 seconds, 262 lasted 21 to 25 seconds, and 118 exceeded 25 seconds. Of these episodes, 75.3% were isolated and 14.9% were associated with pulse deceleration, 4.4% with irregular transthoracic impedance, and 5.4% with bradycardia. Event recording provided data supporting discontinuation of monitoring in 50 of 54 patients: 36 spontaneously resumed breathing before the auditory alarm and 14 had a decreased incidence of apnea with maturation. Follow-up of 51 patients (three not located) showed that none had subsequent apparent life-threatening events or sudden infant death syndrome. Our results in these older infants and children (median age 6.7 months) provide substantiation that such patients with apnea of less than 20 seconds without bradycardia do not require continued monitoring. Further, these data suggest that in selected older infants, longer isolated apnea may be well tolerated; however, hemoglobin saturation during sleep and the ability to resume breathing after the apnea alarm delay is prolonged should be verified. Our patient population had a wide age range and heterogeneity of diagnoses, and was typically free of symptoms, so these results should not be extrapolated uncritically to premature infants, infants with chronic lung disease, and patients with symptomatic apnea. 
4	Influence of desflurane on regional distribution of coronary blood flow in a chronically instrumented canine model of multivessel coronary artery obstruction. The influence of desflurane on myocardial perfusion measured by a microsphere technique during a total occlusion of the left anterior descending coronary artery and concomitant moderate or severe stenosis of the left circumflex coronary artery was evaluated in chronically instrumented dogs. Hemodynamics, regional contractile function, and myocardial blood flow were measured during the conscious state and after anesthesia with desflurane (8.2%-9.2% and 12.5%-12.7%) with and without control of arterial pressure. Total left anterior descending occlusion produced in combination with a left circumflex coronary artery stenosis significantly (P less than 0.05) increased heart rate and left ventricular end diastolic pressure in the absence of desflurane anesthesia. Desflurane, administered only in the presence of left anterior descending occlusion and left circumflex stenosis, significantly (P less than 0.05) decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular positive dP/dt50 without change in heart rate. Blood flow to the subendocardium of normal myocardium was reduced during the high concentration of desflurane (P less than 0.05), but perfusion of the subepicardium and midmyocardium was maintained at conscious levels. When the left circumflex stenosis was of moderate severity, only blood flow to the subendocardium distal to the stenosis was reduced by desflurane (P less than 0.05). In the presence of a severe stenosis, perfusion was decreased in the subepicardium, midmyocardium, and subendocardium of the stenotic zone (P less than 0.05). During the reduction in arterial pressure produced by desflurane, collateral blood flow in the left anterior descending region was reduced in dogs with either a moderate or severe left circumflex stenosis (P less than 0.05). When arterial pressure and heart rate conditions observed in the postocclusion conscious state were restored during the high concentration of desflurane, myocardial blood flow in all regions returned to those levels present in the conscious state (P less than 0.05). Ratios of flow between occluded and normal zones were decreased when hypotension produced by desflurane was uncontrolled, but when arterial pressure and heart rate were adjusted to conscious postocclusion levels using partial thoracic aorta occlusion and atrial pacing, the ratio remained at conscious control levels regardless of the degree of left circumflex stenosis severity (P less than 0.05). Results of this investigation indicate that desflurane does not redistribute blood flow away from collateral-dependent myocardium to other regions via a "coronary steal" mechanism in a chronically instrumented canine model of multivessel coronary artery disease. 
4	Clinicopathologic studies of children who die of acute lower respiratory tract infections: mechanisms of death. Clinicopathologic correlations for 71 cases of fatal pneumonia in children were determined. The mechanism of death for these patients was multifactorial. Severe pneumonia alone accounted for 11 deaths (15.5%). Pneumonia associated with sepsis occurred in 42 children (59.2%). Heart failure (8.5%), hypovolemia (4.2%), and nosocomial infection (12.6%) were also seen in children with fatal acute lower respiratory tract infection. Extensive consolidation, squamous metaplasia, and hyaline membranes were present in the lungs of these children. Patients with severe disease must receive, in addition to antibiotics for acute episodes, individualized intensive respiratory and supportive care. Since these types of care are not available in poor communities, vaccination against measles and vitamin A supplementation for malnourished children may ameliorate the conditions that appear to predispose these children to severe or fatal disease. 
2	The isolation and characterization of a Norwalk virus-specific cDNA. Norwalk virus, an important cause of epidemic, acute, nonbacterial gastroenteritis in adults and children, has eluded adaptation to tissue culture, the development of an animal model, and molecular cloning. In this study, a portion of the Norwalk viral genome encoding an immunoreactive region was cloned from very small quantities of infected stool using sequence-independent single primer amplification. Six overlapping complementary DNA (cDNA) clones were isolated by immunologic screening. The expressed recombinant protein from a representative clone reacted with six of seven high titer. Norwalk-specific, postinfection sera but not with corresponding preinfection sera. Nucleic acid sequence for all clones defined a single open reading frame contiguous with the lambda gt11-expressed beta-galactosidase protein. Only oligonucleotide probes specific for the positive strand (defined by the open reading frame) hybridized to an RNaseA-sensitive, DNaseI-resistant nucleic acid sequence extracted from Norwalk-infected stool. Furthermore, RNA extracted from serial postinfection, but not preinfection, stools from three of five volunteers hybridized to a Norwalk virus cDNA probe. Clone-specific oligonucleotide probes hybridized with cesium chloride gradient fractions containing purified Norwalk virion. In conclusion, an antigenic, protein-coding region of the Norwalk virus genome has been identified. This epitope has potential utility in future sero- and molecular epidemiologic studies of Norwalk viral gastroenteritis. 
2	Omeprazole. Overview and opinion. Omeprazole, a substituted benzimidazole, is a specific inhibitor of the enzyme H+/K(+)-ATPase, which is found on the secretory surface of the parietal cell. This enzyme, the "proton pump," catalyzes the final step in acid secretion. Omeprazole is a powerful inhibitor of gastric acid secretion. At the time of writing, omeprazole has been licensed in the United States for the treatment of severe grades of gastroesophageal reflux disease (GERD) as well as GERD unresponsive to treatment with currently available agents, and for the treatment of Zollinger-Ellison syndrome and other gastric hypersecretory states. Most recently, it has been recommended by the FDA advisory committee for approval as first-line therapy in duodenal ulcer disease. 
5	Cause of thrombosis in human atherosclerotic arteries. Although it has been known for a long time that thrombosis nearly always develops in atherosclerotic arteries--and almost never in normal vessels--the mechanism through which atherosclerosis promotes thrombosis was unknown until this problem was explored through histologic examination of complete serial section sets of thrombosed atherosclerotic arteries. These studies, repeatedly confirmed, revealed that the thrombi are triggered by microscopic cracks in the collagen cap of advanced plaques. Blood most often seeps from the arterial lumen through the cracks into the underlying lipid gruel before the breaks or cracks are plugged by the thrombi (which function as hemostatic seals of the breaks). These results are parallel to results of experimental studies in which the synergism of endotheliotoxic and pressor agents produced thrombi over cap breaks and sub-break hemorrhages only in arteries with advanced collagen-rich plaques, not in arteries with early atherosclerosis or in normal vessels. This finding indicates that advanced atherosclerosis makes the arterial wall much more fragile and that, once broken, this wall exposes the blood to powerful thrombogenic materials that do not exist in normal arterial tissue. At present, human and experimental evidence suggest that the thrombogenic fissures of advanced plaque caps can be promoted by several factors, such as a surge in intraarterial pressure or insults that damage the caps structurally and increase their vulnerability to any type of stress such as certain metabolic, exogenous chemical and immune insults, spontaneous molecular changes of collagen with time and hemorrhages of capillaries that invade advanced plaques from the adventitia or the arterial lumen. 
5	Endourological treatment of ureteroenteric anastomotic strictures: long-term followup. In 1987 we reported our initial experience with an endosurgical incisional approach to ureteroenteric anastomotic strictures (that is endoureterotomy). We have extended that initial report to encompass 15 patients with 19 ureteroenteric strictures followed for an average of 2.5 years. In all cases an endosurgical approach was well tolerated, blood loss was less than 50 cc and hospital stay averaged 3.5 days. A 16 to 22F external stent was left in place for 4 to 6 weeks postoperatively in 14 strictures. A permanent external 12F catheter was left in 5 strictures due to the presence of metastatic disease (4) and a complete dense stricture (1). The only major complication was a ureteroenteric fistula that healed over a ureteral stent without any open surgical intervention. Among 14 ureteroenteric strictures in which the stent was removed, the ureteroenteric area has remained patent in 8 (57%) with an average followup of 28.6 months (range 9 to 57 months). Failures were associated with metastatic disease in 2 cases, generalized debility in 2 and unexplained in 2. In this series an endosurgical approach to ureteroenteric strictures provided long-term satisfactory management of the problem in the majority of patients with benign and malignant disease. By current standards, only 1 patient (7%) would have been considered a candidate for open surgical repair. 
5	Pulmonary vascular steal in chronic thromboembolic pulmonary hypertension. After pulmonary thromboendarterectomy, performed for relief of chronic thromboembolic pulmonary hypertension, perfusion lung scans have frequently disclosed new perfusion defects in segments served by undissected pulmonary arteries. Our hypotheses were that these new postoperative defects occurred with great frequency and did not represent postoperative vessel occlusion. We retrospectively reviewed the preoperative and postoperative perfusion scans of 33 consecutive patients undergoing pulmonary thromboendarterectomy. New postoperative perfusion defects were noted in 23 of 33 patients. The incidence of new defects was increased tenfold in segments that had (1) normal preoperative angiographic findings, (2) normal preoperative radionuclide perfusion, and (3) not been entered at the time of surgery. Postoperative angiograms, available in 15 of 33 patients, documented the nonembolic, nonocclusive nature of the new perfusion scan defects. The most plausible alternate explanation for this previously undescribed finding is a redistribution of pulmonary arterial resistance induced by the thromboendarterectomy, namely, a pulmonary vascular "steal.". 
3	An eosinophilia-myalgia syndrome associated with an L-tryptophan containing product. A syndrome of eosinophilia and myalgias associated with the usage of L-tryptophan containing products has been recently described by the Centers for Disease Control. We report a case of this new clinical entity, highlighted by severe myositis, and compare this illness with similar reported syndromes. 
1	Molteno implants and operating microscope-induced retinal phototoxicity. A clinicopathologic report. The right eye of a 75-year-old man with a history of cataract extraction, three penetrating keratoplasties, laser trabeculoplasty, two Molteno implants, and an operating microscope-induced retinal phototoxic lesion was studied post mortem. Histopathologic examination of the anterior segment showed evidence of penetrating keratoplasty, cataract surgery, and two Molteno implants with minimal associated tissue response. Ultrastructural examination showed a loose collagenous matrix surrounding the Molteno reservoirs, suggesting aqueous percolation from the reservoirs into the conjunctiva. Posteriorly, in the area of the phototoxic operating microscope-induced lesion, a nodule of retinal pigment epithelial hyperplasia with overlying atrophy of the photoreceptor cell layer of the neurosensory retina was noted. The retina also contained cystoid macular edema and an extensive preretinal membrane that was clinically unexpected. 
1	SPECT quantitation of iodine-131 concentration in phantoms and human tumors. The validity of SPECT measurement of iodine-131 (131I) concentration was tested in vitro in phantoms and in vivo by measuring bladder urine concentrations. Phantom studies comparing known and SPECT measured concentrations showed a good correlation for 131I (r = 0.98, s.e.e. = 20.94 counts/voxel) for phantoms of 25 to 127 cc and concentrations of 0.13 to 9.5 microCi/cc. The in vivo, in vitro correlation of 131I concentrations in the urine was also good (r = 0.98, s.e.e. = 0.677 microCi/cc). Quantitative SPECT was used to calculate the effective half-life and dosimetry of radioiodine in 12 sites of thyroid carcinoma in seven patients. SPECT was also used to determine the dosimetry of [131I]MIBG (metaiodobenzylguanidine) in two patients with carcinoid, two with neuroblastoma, and one with pheochromocytoma. The radiation dose for thyroid carcinoma metastases varied between 6.3 and 276.9 rad/mCi. The dose from MIBG varied between 13.4 and 57.8 rad/mCi. These results indicate the validity of quantitative SPECT for in vivo measurement of 131I and the need to measure the concentration of 131I in individual human tumor sites. 
5	Color Doppler imaging. A new noninvasive technique to diagnose and monitor carotid cavernous sinus fistulas. Color Doppler imaging is a recent development in ultrasonography that allows for simultaneous two-dimensional structural imaging and Doppler evaluation of blood flow. With this technique, one patient with a traumatic carotid cavernous sinus fistula and two patients with spontaneous dural cavernous arteriovenous malformations were evaluated. Color Doppler imaging demonstrated a dilated superior ophthalmic vein with arterialized blood flow in all three patients. In two cases the diagnosis was confirmed by angiography, and in one of these cases the fistula was occluded with a detachable balloon catheter. Postembolization color Doppler imaging revealed return of normal venous flow in the superior ophthalmic vein. This technique offers a noninvasive means to confirm the clinical diagnosis and to track the hemodynamics of these arteriovenous fistulas. In certain cases, color Doppler imaging may eliminate the need for computed tomography and magnetic resonance imaging in the evaluation of suspected arteriovenous malformations of the orbit. 
1	Bladder perforation resulting from the use of the neodymium:YAG laser. Complications resulting from the use of the neodymium:YAG (Nd:YAG) laser to treat superficial bladder cancer are uncommon and are usually associated with abnormally high laser power outputs. We report a case of bladder perforation in a human attributed to the Nd:YAG laser used at a low power setting and comment on those factors that contributed to this complication. 
3	Screening for biotinidase deficiency in children with unexplained neurologic or developmental abnormalities. To test the hypothesis that the frequency of biotinidase deficiency is greater in children with unexplained developmental delay or neurologic abnormalities than in the general population, we studied children seen at a large outpatient clinic over a four-year period who had one or more of these neurologic abnormalities and for whom no specific cause for their abnormalities could be found. The group totaled 274 children (163 boys; 111 girls) whose ages ranged from 2 weeks to 17 years. Characteristics were IQ/DQ, 30 to 70 in the 115 for whom scores were available; 41% had seizures; 15% had sensorineural hearing loss; 54% showed gross motor delay or ataxia; and 27% had decreased muscle tone. One patient with a classical clinical picture of biotinidase deficiency was diagnosed during the study period and was not included in the study. None of the patients with nonclassic findings had a deficiency of biotinidase activity. Our results suggest that biotinidase deficiency does not account for a large proportion of children with unexplained neurologic abnormalities or developmental delay. This does not negate the importance of biotinidase testing in children with clinical patterns specifically suggestive of the deficiency. 
1	Visual disturbance in patients with melanocytoma of the optic disk. Visual disturbance in 11 patients with melanocytoma of the optic disk was analyzed. Goldmann visual field examination showed enlargement of Mariotte's blind spot in 7 of 10 patients (70%) and visual field defect or depression in 7 patients (70%). In 6 of the 7 patients with visual field defect of depression (86%), the portion of visual field damage corresponded with the location of the tumor and retinal nerve fiber bundle defect. In 1 patient, sudden loss of visual acuity occurred, presumably due to anterior ischemic optic neuropathy induced by melanocytoma. 
1	Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly. To determine the prevalence of carcinoma in situ of the testis and other testicular histopathological abnormalities in the general male population, we examined gonads from 399 men 18 to 50 years old who died suddenly and unexpectedly. No sign of malignancy was found in any of these gonads. However, 3 of the 399 men had been previously treated for testicular tumor or carcinoma in situ. Thus, the over-all prevalence of testicular neoplasia in the population studied was 0.8% (95% confidence limits 0.2 to 2.2%). This frequency is of the same magnitude as the lifetime risk of testicular cancer in the Danish male population. The median weights of the left and right testes were 19.3 and 19.7 gm., respectively. This difference was statistically significant (p = 0.00003). Thus, our study confirmed that on average the left testis is smaller than the right testis. The median weight of the gonads collected in our study was 0.9 gm. lower than the weight of testes examined 40 years earlier at the same department of forensic medicine. However, this difference was not statistically significant (p = 0.17). Microscopic examination of the gonadal specimens revealed that 83% of the men exhibited complete spermatogenesis, including late spermatids in all tubules. In the age group studied we found no age-related changes in testicular weight or in the proportion of tubules with degenerative changes, such as spermatogenic arrest, the Sertoli-cell-only syndrome or hyalinization. 
5	Clinical choices for circulatory assist devices. Approximately 1.0% of open heart surgery patients become unweanable from cardiac bypass during the surgical procedure. In addition, nearly 20% of patients accepted for cardiac transplantation die while waiting for a donor heart. Pulsatile pneumatic ventricular assist devices (VADs) provide a realistic solution to these dilemmas. Currently, there are five manufacturers who are competing for the major market share in the clinical use of these devices. Novacor, Thermetics, Thoratec, Symbion, and Abiomed all have competitive VAD systems. Because no one system is optimal for all patients, the limitations, similarities, and strengths of each system should be known to enhance the patient's outcome when using these devices. Successful use of VAD systems, either as a bridge to transplantation or to ventricular recovery, is best approached by adherence to strict patient selection. Once instituted, VAD management centers on detailed attention to anticoagulation and prompt diagnosis and treatment of various complications. 
2	Effect of motilin on gastric emptying in patients with diabetic gastroparesis. OBJECTIVES: Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND METHODS: The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects. RESULTS: During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values. CONCLUSIONS: These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects. 
4	Doppler assessment of pulmonary hypertension induced by hypoxic breathing in subjects susceptible to high altitude pulmonary edema. To verify the abnormal pulmonary vascular response implicated in the pathogenesis of high altitude pulmonary edema (HAPE), we examined the hemodynamic responses to hypoxia in HAPE-susceptible subjects (HAPE-S) by means of both right heart catheterization and pulsed Doppler echocardiography. The HAPE-S were seven men and one woman with a history of HAPE. Six healthy volunteers who had repeated experiences of mountain climbing without any history of altitude-related problems served as control subjects. The HAPE-S showed much greater increase in pulmonary vascular resistance (PVR) than did the control subjects, resulting in a much higher level of pulmonary arterial pressure (Ppa) under acute hypoxia both of 15% O2 and 10% O2. We then evaluated the usefulness of pulsed Doppler echocardiography in the prediction of pulmonary hypertension. Acceleration time (AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern in the right ventricular outflow tract. The ratio of AcT to RVET was correlated to invasively determined mean Ppa (Ppa) and PVR. The results were as follows: (1) AcT/RVET = 0.52 to 0.0047 (Ppa), r = -0.93, SEE = 0.017, p less than 0.001 (HAPE-S); (2) AcT/RVET = 0.55 to 0.0055 (Ppa), r = -0.70, SEE = 0.030, p less than 0.001 (HAPE-S); (4) AcT/RVET = 0.52 to 0.00077 (PVR), r = -0.91, SEE = 0.016, p less than 0.001 (control subjects). We conclude that HAPE-S have a constitutional abnormality in the pulmonary vascular response to hypoxia, which is a possible causative factor of HAPE, and that pulsed Doppler echocardiography may be supportive to assess the pulmonary vascular pressor response in the HAPE-S. 
4	Paradoxical embolism: an underestimated entity. A plea for comprehensive work-up. Forty-one cases of arterial embolism were reviewed. The work-up included M + 2D echocardiography in 29 patients (71%), arteriography in 22 (54%), both echocardiography and arteriography in 19 (46%), and abdominal aortic ultrasound in 18 (43%). The sources of emboli were probable cardiac (8 = 20%)--mural cardiac thrombus detected by echocardiogram; possible cardiac (12 = 29%)--arrhythmias or other cardiac pathology detected without mural thrombus; probable arterio-arterial (7 = 17%)--proximal arterial thrombus detected; probable paradoxical embolism (2 = 5%)--fulfills the Johnson criteria with cardiac defect and right-to-left shunt detected by contrast echo in one patient and cardiac catheterization in the other; possible paradoxical embolism (3 = 7%)--meets two of three Johnson criteria without evidence of other source; and unknown source (9 = 22%)--conventional work-up negative or incomplete. Five of nine patients (56%) less than 50 years old had probable or possible paradoxical embolism, while in two patients (22%), the origin was unknown. Conclusion: (1) A significant proportion of patients with an arterial embolus are discharged with the source of emboli unknown, (2) paradoxical embolism must be considered and contrast saline or transesophageal echocardiogram should be done in patients under 50 years old. 
4	Dynamic changes in left ventricular outflow tract flow velocities after amyl nitrite inhalation in hypertrophic cardiomyopathy. Doppler echocardiography was performed in 21 patients with hypertrophic cardiomyopathy (HC), in nine patients with no evidence of left ventricular (LV) hypertrophy by two-dimensional echocardiography, and in five patients with systemic hypertension and concentric LV hypertrophy. The LV outflow tract (LVOT) peak velocity was recorded by continuous wave Doppler technique at rest and after amyl nitrite inhalation. The LVOT pressure gradient was calculated by the modified Bernoulli equation. A significant increase in heart rate and a drop in systolic blood pressure were observed in all patients after amyl nitrite inhalation; no adverse effects were encountered. The peak LVOT velocity and pressure gradient increased significantly after provocation in all patients, but the increase was much more pronounced in patients with HC (peak LVOT velocity increased from 2.2 +/- 0.8 to 4.3 +/- 1.0 m/sec and peak gradient increased from 22 +/- 17 to 78 +/- 36 mm Hg). The Doppler spectral signal in patients with HC demonstrated a characteristic contour, with peak velocity occurring in late systole. However, the observed increase in LVOT peak velocity was not statistically different between treated (with beta-blockers and calcium blockers) and untreated patients with HC. We conclude that LVOT peak velocity and pressure gradients in patients with HC can be readily assessed by Doppler echocardiography both at rest and after amyl nitrite inhalation. The dynamic changes in LVOT velocity induced by this provocation have certain characteristic features in obstructive HC but appear to be independent of the medical regimen used, at least in the dosages tested in our study. 
4	Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. A 65 year old patient who was exposed to topical bovine thrombin during cardiac surgery developed markedly prolonged clotting times and a severe bleeding diathesis. Mixing studies with normal plasma failed to correct the clotting times. Platelet transfusions, immunosuppressive and immunomodulatory therapies were ineffective, but plasmapheresis was effective in decreasing clotting times and in the resolution of clinical bleeding events. The patient's purified IgG reacted with bovine thrombin by immunoblotting and enzyme-linked immunosorbent assay (ELISA). However, the IgG reacted minimally with human thrombin. In view of the severe bleeding, a coexisting inhibitor was sought. The patient's factor V activity was 1% of normal and was not corrected by mixing with normal plasma, demonstrating the presence of an inhibitor against factor V. The patient's IgG reacted with both bovine and human factor V. Immunoblotting localized the site of antibody binding to the light chain of activated bovine factor V. Detectable amounts of bovine factor V were found in commercial bovine thrombin preparations by ELISA. The data suggest that patients exposed to topical bovine thrombin may develop antibodies to thrombin and factor V. Anti-thrombin antibodies may mask coexisting factor V inhibitors responsible for clinical bleeding. 
5	The sulphated glycosaminoglycan levels in synovial fluid aspirates in patients with acute and chronic joint disease. Proteoglycan levels were measured in a series of synovial fluid samples from patients with acute and chronic joint diseases using a modified chemical dye binding method. Levels found in 50 miscellaneous inflammatory arthritis fluids (mean = 173.2 +/- 90.9 micrograms/ml) were higher than found in either 50 with rheumatoid arthritis (96.3 +/- 31.3 micrograms/ml) or 50 with osteoarthritis (83.8 +/- 27.3 micrograms/ml). For comparison, proteoglycan levels were measured in 15 cadaver synovial fluids (98.9 +/- 44.2 micrograms/ml) and 12 synovial fluids from patients with sports injury (163.7 +/- 79.4 micrograms/ml). Patients were recruited into a trial where synovial fluid was aspirated as often as possible over a 6-month period during which the patients were followed using a number of well proven clinical parameters. No correlation was found between the degree of joint destruction as measured by X-ray damage and the concentration or total amount of proteoglycan in the synovial fluid. In addition, there was no correlation between the level or total amount of proteoglycan and any clinical parameter of disease activity. 
4	Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts BACKGROUND. Iron may play a central role in oxygen radical generation during myocardial ischemia and after reperfusion. Because conditions during ischemia may also liberate iron, we hypothesized that administration of the iron chelator deferoxamine during ischemia would result in improved functional and metabolic recovery after postischemic reperfusion. METHODS AND RESULTS. Isolated, perfused rabbit hearts were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. The hearts received one of three treatments: deferoxamine at the onset of 30 minutes of global ischemia (n = 9), deferoxamine as a bolus followed by a continuous 15-minute infusion begun at reflow (n = 9), or standard perfusate (n = 7). Hearts treated with deferoxamine during ischemia showed better recovery of developed pressure than did control hearts (63.2 +/- 7.5% versus 41.2 +/- 2.9% of baseline) (p = 0.02) and better recovery of myocardial phosphocreatine content (92.4 +/- 10.3% versus 68.2 +/- 4.5% of baseline, p less than 0.05). These functional and metabolic benefits were comparable to those obtained with deferoxamine treatment during early reperfusion. In 15 additional hearts, intraischemic treatment with deferoxamine resulted in no reduction in oxygen radical concentrations as measured on frozen tissue by electron paramagnetic resonance spectroscopy at end ischemia, but the treatment eliminated the reperfusion-induced increase of free radical generation observed in control hearts (2.9 +/- 0.01 versus 7.0 +/- 0.07 microM, p less than 0.001). The magnitude of reduction was similar to that when deferoxamine was given at the onset of reflow (2.4 +/- 0.02 microM, p less than 0.001 versus control). CONCLUSIONS. These results demonstrate improved functional and metabolic recovery of myocardium treated with deferoxamine during ischemia, accompanied by a reduction in reperfusion-induced oxygen free-radical generation to the same degree as reflow treatment, confirming the importance of iron in the pathogenesis of myocardial reperfusion injury. 
5	Persistent carcinoma in situ of the testis after chemotherapy for advanced testicular germ cell tumours. The chemosensitivity of testicular carcinoma in situ (CIS) was analysed in 25 testes excised 10 weeks to 4.5 years following platinum-based chemotherapy. CIS was present in 8 of the 23 evaluable cases (35%), in 5 of which the lesion coexisted with invasive germ cell tumour. It is concluded that CIS may persist or recur after chemotherapy. This has implications for occult presentation of metastatic germ cell tumours and also for the management of the contralateral testis in patients with testicular germ cell tumours. 
1	Nerve growth factor stimulates protein tyrosine phosphorylation in PC-12 pheochromocytoma cells. The cellular actions of nerve growth factor (NGF) and epidermal growth factor (EGF) may be mediated by changes in protein phosphorylation. The tyrosine phosphorylation of two predominant proteins of molecular mass 40 and 42 kDa is seen in PC-12 cells treated with NGF or EGF, correlating with activation of a previously identified serine/threonine protein kinase that phosphorylates microtubule-associated protein (MAP). Stimulation of phosphoprotein (pp) 40 and 42 phosphorylation and MAP kinase activity by NGF but not EGF is selectively attenuated by staurosporine and K-252A. Moreover, the time courses of pp40/42 phosphorylation and MAP kinase activation produced by NGF or EGF are identical. Chromatography of lysates from growth factor-treated cells on ion-exchange or hydrophobic-interaction HPLC resolves MAP kinase into two peaks, neither of which precisely coelutes with pp40 or pp42. One of these peaks (II) exhibits no detectable phosphotyrosine. The other peak (I) has some overlap with pp40. However, the activity residing in both peaks is almost completely inhibited after treatment with alkaline phosphatase, suggesting that, at least, serine/threonine phosphorylation is required for the activity of these enzymes. These data indicate that while tyrosine phosphorylation appears to be a critical early event in NGF action, the role of this modification in activation of MAP kinases remains unclear. 
1	Multiple intracranial mucoceles associated with phaeohyphomycosis of the paranasal sinuses. The purpose of this article is to alert clinicians to a new pathogenic fungus of the paranasal sinuses called Exserohilum rostratum. Exserohilum species are one of the etiologic agents of phaeohyphomycosis, a constellation of entities caused by dematiaceous fungi. This class of fungal sinus infection has emerged only in the past decade; it occurs primarily in immunocompetent individuals and produces a tenacious, progressive pansinusitis. To our knowledge, this study describes the first case of multiple intracranial mucoceles secondary to E rostratum. The diagnostic workup includes computed tomography and magnetic resonance imaging followed by direct microscopic examination of tissue biopsy specimens. A craniotomy followed by a bilateral external ethmoidectomy was necessary for complete extirpation of the infected mucoceles. Aggressive surgical management of this mycotic infection is described. 
5	A cost-minimization study of cancer patients requiring a narcotic infusion in hospital and at home. We conducted a retrospective, non-randomized, cost-minimization study, from the perspective of the Ministry of Health, to compare the cost of managing cancer patients who required narcotic infusions, in hospital and at home. Our medical costs averaged $369.72 per inpatient day and $150.24 per outpatient day (saving $219.48 per diem, 1988 Canadian dollars), while narcotic costs were the same for any given patient in both settings. Sensitivity analysis showed that no reasonable changes in the quantity and cost of services reduced our savings by more than 50%. During incremental analysis, savings increased as more outpatient days were managed by our centre, from $0.00 for 318 days, to more than $500,000 for over 2000 days per annum. As this program has been extremely cost effective and preferred by our patients, other hospitals and central funding agencies might consider establishing a regional outpatient narcotic infusion program to reduce their costs. 
2	Treatment of hepatitis B virus-associated membranous nephropathy with adenine arabinoside and thymic extract. Previously we found that corticosteroid treatment in the hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) was not associated with a favorable outcome. To distinguish the differences of the HBV DNA in macrophage, T and B cells among HBVMN patients with or without corticosteroid treatment, serial studies at different time points were investigated. HBV DNA appeared as an "episomal" molecule as with 3.2 kb in macrophage, T and B cells. This molecule disappeared after 12 months among HBVMN patients without corticosteroid treatment. HBV DNA, by contrast, appeared as episomal form even three years later in T cells, with frequent proteinuria among HBVMN patients with corticosteroid treatment. This finding indicates that the use of corticosteroids leads to a potential risk of enhancing HBV viral replication in T cells. We studied 24 HBVMN patients who had previously received corticosteroid treatment and had persistent proteinuria, who were administered combination therapy with adenine arabinoside for two weeks and thymic extract (Thymostimulin) for six months to decrease urine protein loss and obtain seroconversion. These 24 patients had heavy (22 of 24, 91.6%) or mild (2 of 24, 8.4%) proteinuria prior to adenine arabinoside and thymostimulin treatment. All 24 patients demonstrated HBV DNA in mononuclear cells and simultaneously exhibited sera positive with HBsAg and HBeAg. In contrast, after treatment only one case (4.2%) had heavy and two cases (8.4%) mild proteinuria; HBV DNA was demonstrated in macrophage (4 of 24, 16.7%), T cells (9 of 24, 37.5%), and B cells (6 of 24, 25%) as well as serum (24 of 24, 100%) prior to treatment. 
5	The effect of spine fusion on respiratory function in Duchenne muscular dystrophy. Serial measures of respiratory function were made in 17 patients with Duchenne muscular dystrophy who underwent segmental spine fusion and in 22 patients who did not. No significant differences were observed between the 2 groups (operated vs. nonoperated) in terms of declining respiratory function. Nonetheless, all operated patients reported either improved sitting comfort, appearance, or both. Thus, our results suggest that there are distinct benefits from segmental spine fusion; however, there was no salutary effect upon respiratory function either in the short term or after up to 5 years follow-up. 
4	Prospective randomized multicenter comparison of in situ and reversed vein infrapopliteal bypasses. We have performed a prospective, randomized, multicenter study to compare in situ and reversed vein grafts for long limb salvage bypasses from the proximal thigh to an infrapopliteal artery. Three hundred eighty-four patients required an infrapopliteal bypass for critical lower extremity ischemia. Of these, 259 were excluded because a short vein bypass was performed or because the vein was considered inadequate. The remaining 125 patients had a randomized vein bypass, 63 reversed, 62 in situ. The two groups were similar with regard to risk factors, indications, graft dimensions, and outflow. Secondary patency at 30 months was similar for both techniques: reversed 67% +/- 9% (+/- SE); in situ 69% +/- 8%. For veins less than or equal to 3.0 mm in minimum distended diameter 24-month patency rates were 61% +/- 22% for 12 in situ veins and 37% +/- 29% for 10 reversed veins (p greater than 0.05). Angiographic evaluation of failing grafts revealed lesions similar in type and frequency in both types of grafts. These included focal (in situ, n = 4; reversed, n = 7) and diffuse vein hyperplasia (in situ, n = 2; reversed, n = 1), and inflow and outflow stenoses (in situ, n = 4; reversed, n = 3). The incidence of wound complications and the mortality rate were similar for the two groups. These data show no significant difference in overall patency rates for the two types of vein grafts at 2 1/2 years. 
3	Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease. Von Hippel Lindau disease (VHL) is a hereditary syndrome, associated with tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The availability of a genetic test for the early and reliable detection of individuals carrying the defective gene would be beneficial for VHL patients and their relatives, since many of the manifestations of VHL can be successfully treated if detected in their early stages, while the complications of undetected disease can be devastating. We have previously shown that the VHL gene maps to chromosome 3p. To provide genetic markers for the development of a reliable diagnostic test, and to further narrow and eventually clone the VHL defect, we have generated DNA markers for chromosome 3p. With these markers, we have performed a multipoint genetic linkage analysis in 28 VHL pedigrees, comprising 470 individuals, 164 of whom were affected with VHL. Here we report the identification of tightly linked markers, including flanking markers that bracket the VHL gene to a small region on chromosome 3p25-p26. This finding has several major implications. While visceral cysts of the kidney, pancreas, and epididymis are commonly found in VHL and are considered diagnostic criteria for this disorder, they also occur in the general population. The presence of cysts, unaccompanied by other more typical lesions such as retinal and cerebellar hemangioblastoma, may therefore represent a major diagnostic problem, leading to errors in the assessment of disease status. The application of flanking markers for the VHL gene for presymptomatic diagnostic testing confirms that epididymal cysts are indeed not suitable as a diagnostic criterion in this disorder. Pheochromocytomas occur nonuniformly in VHL families and may also be associated with other hereditary tumor syndromes; our genetic studies imply that the phenotype in VHL families with and without pheochromocytomas is caused by defects within the same gene. The absence or presence of this tumor type is therefore due to the pleiotropic expression of a single gene rather than to the existence of several different genes for VHL. The region on chromosome 3p13-p14 known to contain several chromosomal translocation breakpoints in families with "pure familial renal cell carcinoma" is quite proximal to the VHL locus in 3p25-p26 we have identified. Chromosome 3p may therefore contain two loci for renal cell carcinoma: one gene (or genes) in 3p13-p14 and the VHL gene in 3p25-p26, whose aberration is also associated with other typical manifestations of VHL.(ABSTRACT TRUNCATED AT 400 WORDS). 
2	Cholangiocarcinoma complicating primary sclerosing cholangitis. Cholangiocarcinoma is more likely to develop in patients with primary sclerosing cholangitis. Our aims were to describe the clinical presentation, course, and management of patients afflicted with both cholangiocarcinoma and primary sclerosing cholangitis and to estimate the prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis. A retrospective analysis was conducted of 30 patients with both primary sclerosing cholangitis and cholangiocarcinoma managed at our institution during an 8-year period. Development of cholangiocarcinoma was heralded by rapid clinical deterioration with jaundice, weight loss, and abdominal discomfort. Cholangiocarcinoma complicating primary sclerosing cholangitis often was detected at an advanced tumor stage, which precluded effective therapy, and overall median survival was 5 months. Earlier recognition and treatment of cholangiocarcinoma in such patients will be necessary to increase survival rates. Seventy patients with primary sclerosing cholangitis were followed prospectively in a clinical trial of medical therapy for an average of 30 months. Twelve patients died and five were found at autopsy to have cholangiocarcinoma. The potential for cholangiocarcinoma to develop in patients with primary sclerosing cholangitis may indicate that liver transplantation should be considered earlier in the course of the disease. 
4	Fatal pulmonary venoocclusive disease secondary to a generalized venulopathy: a new syndrome presenting with facial swelling and pericardial tamponade. We describe a patient who developed fatal pulmonary artery hypertension secondary to diffuse venulitis. This otherwise healthy young woman first presented with generalized venulopathy, with chemosis, facial swelling, pleural effusions, and pericardial tamponade. The symptoms partially responded to steroid therapy, but over a 2-year course, a rapidly progressive and fatal venoocclusive disease developed. No other primary condition was diagnosed, and at autopsy, the patient had striking venulitis throughout, including the pulmonary bed. We believe that this is a unique case of pulmonary hypertension resulting from a generalized venulopathy. 
3	The effect of epilepsy or diabetes mellitus on the risk of automobile accidents BACKGROUND. Previous studies of possible associations between chronic medical conditions and traffic safety have been inconsistent and subject to bias because of the incomplete identification of affected persons. Recent advances in the diagnosis and management of epilepsy and diabetes mellitus have improved the control of these disorders and suggest a need to reexamine the risk of traffic mishaps among patients with these conditions. METHODS. We conducted a population-based retrospective cohort study of 30,420 subjects 16 to 90 years of age, with and without epilepsy or diabetes mellitus. Subjects included all the licensed drivers in seven contiguous ZIP Code areas in which the Marshfield Clinic and St. Joseph's Hospital, Marshfield, Wisconsin, are the primary sources of medical care. Standardized rates of moving violations and accidents over a four-year period (1985 through 1988) were compared in affected and unaffected cohorts. RESULTS. Standardized mishap ratios for subjects with diabetes were 1.14 for all moving violations (P = 0.23) and 1.32 for accidents (P = 0.01); for subjects with epilepsy the ratios were 1.13 for moving violations (P = 0.26) and 1.33 for accidents (P = 0.04). CONCLUSIONS. We conclude that drivers with epilepsy or diabetes mellitus have slightly increased risks of traffic accidents as compared with unaffected persons. The increases in risk observed in our study were generally smaller than those in previous studies, and we believe they are not great enough to warrant further restrictions on driving privileges. 
1	Prospective study of alcohol intake and large bowel cancer. The alcohol intake of a cohort of Japanese men in Hawaii is directly and significantly related to the risk of developing rectal cancer, whether assessed on the basis of amount consumed or as a percent of total calories. Wine and whiskey are directly related to rectal cancer, but beer is the only alcoholic beverage that displays a statistically significant dose-response (P = 0.008). Colon cancer risk also is related directly to alcohol intake, but the association is statistically significant only when measured as a percent of energy intake. This suggests that alcohol might displace cancer inhibitors from the diet. Calcium, vitamin C, and dietary fiber are inversely related to colon cancer risk in this cohort, and each of these micronutrients displays statistically significant negative correlation with alcohol intake. A possible positive association between alcohol and lung cancer was ruled out after adjusting for cigarette smoking. Cancers of the prostate and stomach were unrelated to alcohol intake, but the risk of acquiring cancer at all other sites combined was strongly related to alcohol intake. 
5	Methodology of head-up tilt testing in patients with unexplained syncope Prolonged 60 degree head-up tilt has been shown to be valuable in the investigation of unexplained syncope, diagnosing neurally mediated bradycardia/hypotension or malignant vasovagal syndrome. To evaluate the methodology of tilt testing, the following were examined: reproducibility of results, tilt duration, angle of tilt, method of tilt support and effect of age in patients and control subjects. Seventy-one patients with recurrent unexplained syncope underwent 60 min of 60 degree tilt; 53 (75%) had an abnormal test with vasovagal syncope at 24 +/- 10 min (mean +/- SD). Tilting to 60 degrees resulted in an abnormal test in only 2 (7%) of 27 control subjects without cardiovascular symptoms (p less than 0.001); and 5 (15%) of 34 patients with syncope and documented conduction tissue disease (p less than 0.001). Of 15 youthful fainters, 3 (20%) had vasovagal reactions as did 1 (8%) of 12 asymptomatic youthful control subjects. These 12 control subjects also underwent tilting with a saddle support and 7 (67%) had vasovagal reactions. It is concluded that the duration of tilting at 60 degrees should be 45 min (mean time to syncope +2 x SD in the 53 patients with abnormal results). Twenty percent of patients with an abnormal tilt test may not demonstrate syncope with repeat tilting. Saddle tilt testing in unexplained syncope may result in a loss of specificity. Tilting at less than 60 degrees results in a loss of sensitivity. Head-up tilt may be less useful in youthful subjects with vasovagal syncope than in other subjects. 
1	Shear stress induces not only platelet aggregation but also platelet-tumor cell interaction. To investigate the interaction between platelets and tumor cells under well-defined flow conditions, the effect of tumor cells on platelet aggregation induced by shear stress was studied using a cone and plate viscometer adapted for measuring transmitted light intensity. Aggregation was markedly enhanced by HMV-1 cells in a cell number-dependent fashion under shear stress of 12 dyne/cm2. Enhancement was not observed at a high shear stress of 108 dyne/cm2. A monoclonal antibody against GPIIb/IIIa, 7E3 completely abolished enhancement of aggregation by HMV-1. Apyrase had similar inhibitory effects. Scanning electronmicroscopy showed that direct contacts of platelets with HMV-1 cells could be demonstrated when platelet-platelet interaction was inhibited by 7E3 or apyrase. These results may indicate that, at a shear stress of 12 dyne/cm2, direct contacts of platelets and HMV-1 cells may trigger enhancement of platelet aggregation. 
3	Sensitivity for detecting fibrillation potentials: a comparison between concentric and monopolar needle electrodes. The sensitivity of monopolar and concentric electrodes for detecting fibrillation potentials (FP) has never been formally compared. We studied 35 muscles with FP, sampling 20 sites each with concentric and monopolar needles. The concentric needle identified 0.88 +/- 3.44 (mean +/- standard deviation) more sites with spontaneous activity. Although statistically significant (Wilcoxon signed rank test P less than .03), this difference in sensitivity did not appreciably affect diagnostic interpretation. Subjects described the concentric needles as more painful. Needle insertions in 25 other muscles demonstrated that needle movement generated the majority of FP. We suggest that the increased tissue injury caused by concentric needles may account for both their increased sensitivity and discomfort. 
1	Ampullary carcinoma in patients under 50 years of age with a poor prognosis. Clinicopathologic features of 145 Japanese patients with ampullary carcinoma were compared among three age groups. The 145 patients were divided into three groups by the patient's age at the time of operation; there were 24 patients in group I (younger) aged less than or equal to 50 years, 99 in group II (ordinary) aged 51-69, and 22 in group III (elderly) aged greater than or equal to 70. The three groups showed no significant difference in sex, icterus, duration of icterus, size of the tumor, year of operation, macroscopic type, histopathologic type, tumor margin, lymphatic permeation, venous invasion, or pancreatic invasion. The survival curve of group I was worse than those of groups II and III. Multivariate regression analysis using 11 prognostic variables failed to reveal that the age of the patient at the time of operation was an independent factor. The younger patients aged less than or equal to 50 fared worse than the elderly patients aged greater than or equal to 70, because the group I tumors included a significantly greater number of advanced ampullary carcinoma with more frequent perineural invasion than did the group III tumors. 
2	Diltiazem therapy for symptoms associated with nutcracker esophagus. A randomized double-blind, cross-over prospective trial in 22 patients was designed to evaluate possible effect of an oral calcium channel blocker, diltiazem, on symptoms of chest pain and/or dysphagia in patients with nutcracker esophagus. We studied 22 consecutive patients referred to an esophageal diagnostic center for evaluation of noncardiac chest pain or dysphagia having high amplitude esophageal contractions, 14 of whom completed the study. Diltiazem (60-90 mg qid) was compared with placebo, each being administered for 8 wk. Patients were evaluated with esophageal motility pre- and posttreatment periods and with regular symptom assessment throughout each 8-wk treatment. Active diltiazem therapy resulted in significantly lower (p less than 0.05) mean distal esophageal peristaltic pressure (128 +/- 20 mm Hg; +/- SE) than placebo (158 +/- 16 mm Hg). Mean chest pains scores were significantly (p less than 0.05) lower with diltiazem therapy than with placebo. Only nine of the 14 patients fulfilled presently acceptable criteria for diagnosing nutcracker esophagus, and the diltiazem effect was similar, although not significant, because of the smaller sample. Conclusions: In this preliminary study involving 14 patients, the oral calcium channel blocker, diltiazem, appeared to improve noncardiac chest pain associated with strong esophageal contraction, the nutcracker esophagus. These improved symptoms were associated with significant decreases in contraction pressure. 
4	Quantitative assessment of cerebral blood volume by single-photon emission computed tomography. We implemented a technique for measuring regional cerebral blood volume using single-photon emission computed tomography and in vivo technetium-99m-labeled red blood cells and then evaluated it in nine normal human volunteers (controls) and seven patients with bilateral occlusion or severe stenosis of the internal carotid artery. We also measured regional cerebral blood flow using single-photon emission computed tomography and intravenous xenon-133 in the same subjects. We studied regional cerebral blood flow, regional cerebral blood volume, and their ratio before and after the intravenous injection of 1 g acetazolamide. Mean +/- SD baseline regional cerebral blood volume was higher in the patients than in the controls (4.1 +/- 0.6 versus 3.2 +/- 0.3 ml/100 g, p less than 0.01), and mean +/- SD baseline regional cerebral blood flow was lower in the patients than in the controls (40.5 +/- 11 versus 55.6 +/- 11 ml/100 g/min, p less than 0.05). Acetazolamide induced similar mean +/- SD increases in regional cerebral blood volume in both the controls and the patients (0.3 +/- 0.1 and 0.3 +/- 0.2 ml/100 g), while the mean +/- SD regional cerebral blood flow reactivity was significantly less in the patients than in the controls (12.6 +/- 7.6 versus 24.5 +/- 9.6 ml/100 g/min, p less than 0.05). Our study shows that single-photon emission computed tomography can provide quantitative estimates of both regional cerebral blood volume and regional cerebral blood flow in humans. 
5	Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter. Two types of high-signal intensity abnormalities are frequently found bilaterally in the cerebral white matter of brains of elderly patients on T2-weighted magnetic resonance imaging (MRI) scans. One is located in the immediate periventricular region; the other, in the deep subcortical white matter (centrum semiovale). The diagnostic implications of this second type continue to be uncertain. To determine the neuropathologic correlates of these lesions, the brains from seven elderly patients were fixed in buffered formaldehyde solution, subjected to MRI scanning, and examined neuropathologically. Variable degrees of bilateral periventricular (subependymal) sharply defined areas of high-signal intensity were found in all the brains, and the larger of these showed corresponding areas of myelin pallor with gliosis and dilated perivascular spaces. Discrete bilateral patches of high-signal intensity were found in the centrum semiovale in five patients. Myelin and axon stains showed varying degrees of diffuse white matter pallor in many areas examined, both with and without these areas of high-signal intensity on MRI scans. Neither the myelin nor the axon stains showed discrete white matter abnormalities that corresponded to the MRI findings. We believe that these changes, so commonly found on MRI scans in the elderly, reflect actual changes in the white matter but that their nature and clinical significance need to be elucidated. 
3	Orthostatic hypotension after spinal cord injury: treatment with fludrocortisone and ergotamine. We report a case of a 28-year-old woman with C5 quadriplegia, unresponsive to conservative treatment for orthostatic hypotension. Ergotamine, daily combined with fludrocortisone, successfully prevented symptomatic hypotension. In this report, neural, renal, and hormonal blood pressure regulatory mechanisms are described. Experiences obtained from this case and the existing literature suggest that (1) in persons with quadriplegia, plasma catecholamine levels show little increase with sitting, indicating an inability to activate baroreceptor and chemoreceptor reflexes, (2) elevated plasma aldosterone and renin levels indicate a renal compensatory response to decreased renal perfusion secondary to low plasma volume and/or chronic hypotension, and (3) the net effect of ergotamine and fludrocortisone is probably a combination of plasma volume expansion and direct peripheral vasoconstriction. 
5	Nosocomial infections due to Xanthomonas maltophilia (Pseudomonas maltophilia) in patients with cancer. From December 1985 to May 1986, Xanthomonas maltophilia (formerly known as Pseudomonas maltophilia) was isolated at an increased rate at our institution; 52 isolates of X. maltophilia were obtained in cultures of clinical specimens from 38 patients during that time. The records of 35 of these patients form the basis of this study. Twelve (71%) of the 17 infected and nine (50%) of the 18 colonized patients had received or were receiving antimicrobial therapy. Eleven of 17 patients (three of seven with septicemia, three of five with pneumonia, three with urinary tract infection, and two with wound infection) responded to antimicrobial therapy. Microbiologic studies of the potential environmental sources revealed growth of X. maltophilia in two water faucets and in one water sample from the medical intensive care unit. X. maltophilia is emerging as an important nosocomial pathogen in immunocompromised patients, especially those receiving broad-spectrum antimicrobial therapy. 
5	Vascular hypertrophy, renin and blood pressure in the young spontaneously hypertensive rat. 1. Cardiovascular reactivity, blood vessel morphology, blood pressure and the activity of the renin-angiotensin system were determined in the 3-week-old spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and outbred Wistar (WIS) rat. 2. In an isolated perfused mesenteric artery preparation the SHR had a significantly increased maximum response to KCl and noradrenaline (P less than 0.02) compared with the WKY. Using a myograph, vascular structure was measured over a range of resistance arteries and showed a significant correlation between lumen diameter and both media cross-sectional area and thickness, with the regression line for the SHR shifted upwards indicating both increased media area and thickness. This was associated with a slight, but significant, narrowing of the lumen (P less than 0.01) and an increased media/lumen ratio (0.049 +/- 0.01, 0.034 +/- 0.007, 0.036 +/- 0.008 for SHR, WKY and WIS, respectively, means +/- SD P less than 0.001). The SHR had a greater heart/body weight ratio than either the WKY or the WIS (P less than 0.001). 3. Both mesenteric artery and membrane protein content were higher in the SHR, indicating an increase in cell size or number. 4. Plasma renin activity (means +/- SD) was lower in the SHR (1.0 +/- 0.7 pmol of angiotensin I h-1 ml-1) than in the WKY (2.2 +/- 1.2 pmol of angiotensin I h-1 ml-1, P less than 0.001) but not different from that in the WIS (1.2 +/- 0.8 pmol of angiotensin I h-1 ml-1). Mesenteric artery vascular renin concentration was also lower in the SHR (P = 0.06). 
5	The mechanism of spastic muscle hypertonus. Variation in reflex gain over the time course of spasticity. The electromyographic (EMG) response of the initially passive biceps brachii muscle to imposed extension applied at the elbow was studied in 19 hemiparetic and 12 normal subjects. In relaxed normal subjects, the biceps muscle was found to respond only at displacement velocities above 175 deg/s, with a single early burst of activity in the biceps EMG. In contrast, the hemiparetic subjects, in addition to the early EMG activity, also showed considerable late activity, which persisted even with stretch velocities as low as 35 deg/s. This late activity is a stretch reflex, present in fully plegic arms. It was seen in all spastic subjects in whom the tone of the biceps had been clinically assessed to be raised, but was never observed in subjects with normal muscle tone. The mean level of this EMG response was highly correlated with displacement velocity and its duration to the duration of the applied displacement. It is suggested that this reflex EMG activity is the major factor in the genesis of spastic hypertonus in the arm and that it arises not from a reduction in the threshold of the stretch reflexes of the muscle, but from a pathological increase in stretch reflex gain. It is further shown that this activity is at a high level between the first and third months after the onset of spasticity and that the reflex gain is significantly reduced when spasticity is established for a year or more. It is concluded that, while changes in passive mechanical properties may play a role when spasticity has been established for more than a year, the major cause of spastic muscle hypertonus is a pathological increase in stretch reflex activity. 
4	The cardiovascular effects of cocaine. Cocaine use and abuse continue to overwhelm urban economic, social, and health care systems. Patients frequently present to the emergency department with life-threatening manifestations of cocaine use, including trauma, acquired immune deficiency syndrome, psychomotor agitation, and cardiovascular collapse. Adequate treatment of the cocaine-intoxicated patient requires a critical understanding of the risk-to-benefit ratios for pharmacologic, toxicologic, and surgical or obstetric interventions. The pharmacologic and physiologic bases for the vascular manifestations of cocaine toxicity and experimental evidence for treatment strategies are reviewed. 
2	Breakdown of gastric mucus in presence of Helicobacter pylori. The potential of Helicobacter pylori to degrade gastric mucus was examined. Colonies of H pylori cultured from antral mucosal biopsy specimens of patients with non-autoimmune gastritis were washed with sterile saline, passed through a sterilisation filter, and the filtrate examined for urease, protease, and mucolytic activity. The filtrate failed to hydrolyse bovine serum albumin, or to degrade stable mucus glycoprotein structures of high particle weight that had been separated from human gastric mucus on Sepharose 2B. The high particle weight mucus glycoprotein was, however, extensively degraded when incubated with H pylori filtrate (which possessed urease activity) in the presence of 2 M urea, to release fragments of Mr approximately 2 X 10(6). The high particle weight mucus glycoprotein was also broken down to a comparable extent when incubated with Jack bean urease in the presence of 2 M urea, or 1 M ammonium carbonate, or 40 mM carbonate-bicarbonate buffer (pH 8.7), but not when treated with 4 M urea alone, or Jack bean urease alone. These results indicate that the loss of high particle weight mucus glycoprotein in gastric mucus from patients with gastritis and gastric ulcers is unlikely to be due to the mucolytic action of an extra-cellular protease produced by H pylori, but it may result from the destabilising effects of a carbonate-bicarbonate buffer, generated at the mucosal surface when H pylori urease hydrolyses transuded plasma urea. 
4	Factors related to treatment resistance in hypertension. Hypertension which is resistant to treatment carries a relatively bad prognosis. Factors associated with treatment resistance were examined in a case-control study in a hospital hypertension clinic. Patients with resistant hypertension had more severe hypertension and more frequently had evidence of end-organ damage on presentation to the clinic. The prevalence of accelerated phase hypertension, renovascular disease and impaired renal function was also higher in these patients. Cigarette smoking, and the combination of cigarette smoking and heavy caffeine use, were greater in patients with resistant hypertension. Resistant hypertension did not appear to be associated with older age, obesity, regular alcohol use, various psychological factors or non-compliance. These findings support an aggressive investigation policy in resistant hypertension, and underline the harmful effects of cigarette smoking to hypertensive subjects. 
4	Hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis model. We induced severe pulmonary hypertension and acute lung injury in 6 pigs by Pseudomonas aeruginosa infusion. We studied the effect of pulmonary artery catheter inflation of a pulmonary artery catheter balloon in the left lower lobar pulmonary artery was accompanied by a significant (p less than 0.05, paired t test) increase in pulmonary artery pressure, a decrease in left atrial pressure, a decrease in cardiac output, and a decrease in mean arterial pressure. No significant changes occurred when the catheter was advanced into the wedged position without balloon inflation. Balloon inflation had no significant effect on these variables before bacterial infusion. We conclude that with sufficiently severe pulmonary hypertension in association with diffuse lung injury, lobar pulmonary artery occlusion may cause alterations in cardiac output and left atrial pressure. This may confuse interpretation of pulmonary artery catheter measurements. 
2	Acute abdominal pain in the elderly. STUDY OBJECTIVES: To determine the incidences of both specific diagnosis and surgical diseases in patients more than 65 years old who present to the emergency department with nontraumatic abdominal pain of less than one week's duration, and to determine the ED staff's ability to diagnose and triage elderly patients with acute abdominal pain. DESIGN: A 12-month retrospective review of all elderly patients who presented to the ED with acute, nontraumatic abdominal pain. SETTING: A regional trauma center serving a predominately rural population in the Midwest. The ED has 55,000 patient visits yearly. MEASUREMENTS AND MAIN RESULTS: Of the 127 patients enrolled, 30 (24%) had no specific diagnosis made in the ED. Biliary tract disease (12%) and small bowel obstruction (12%) were the two most common specific diagnoses. Overall, 53 patients (42%) required surgery, usually during the initial hospitalization. In four cases, the postoperative diagnosis differed significantly from the ED diagnosis. Of the 74 patients (58%) who did not undergo surgery, 51 had follow-up information available. In 14 patients, the follow-up diagnosis differed from the original diagnosis, but most of these changes did not appreciably alter the treatment and outcome. CONCLUSIONS: The incidence of surgical disease is high in elderly patients with acute abdominal pain, and ED staff are able to diagnose and triage these patients accurately. 
1	Renal carcinoma in a solitary kidney. We studied the clinical and pathological features of 26 patients with renal carcinoma of a solitary kidney, including 6 treated at this hospital. Four patients had a contracted kidney and 22 had previously undergone nephrectomy. Partial nephrectomy was performed in 16 patients, enucleation of the tumour in 5 and radical nephrectomy in 5 because of the size of the tumour. Ex vivo surgery was carried out in 4 patients. The duration of ischaemia ranged from 15 to 365 min but was longer in those who underwent ex vivo surgery (149 to 365 min). Of the 21 patients who underwent partial nephrectomy or enucleation, the serum creatinine level increased (greater than or equal to 2.0 mg/dl) post-operatively in 16 patients, of whom 9 required temporary haemodialysis. No recurrence has been noted in those who underwent partial nephrectomy, but 1 patient who underwent enucleation of the tumour developed a solitary pancreatic metastasis 2 years 6 months after surgery and was treated by a partial pancreatectomy. Kidney-preserving surgical procedures are considered to improve the quality of life, but careful follow-up is necessary. 
5	Pancreaticobiliary ductal union. The main pancreatic duct and the common bile duct open into the second part of the duodenum alone or after joining as a common channel. A common channel of greater than 15 mm (an anomalous pancreaticobiliary duct) is associated with congenital cystic dilatation of the common bile duct and carcinoma of the gall bladder. Even a long common channel (greater than or equal to 8 mm) is associated with a higher frequency of carcinoma of the gall bladder. Gall stones smaller than the common channel and a long common channel predispose to gall stone induced acute pancreatitis. Separate openings for the two ductal systems predisposes to development of gall stones and alcohol induced chronic pancreatitis. The role of ductal union has also been investigated in primary sclerosing cholangitis and biliary atresia. 
4	Clinical efficacy of PTCA and identification of restenosis: evaluation by serial body surface potential mapping. We used serial body surface potential mapping (BSPM) with the departure map technique to evaluate the clinical efficacy of percutaneous transluminal coronary angioplasty (PTCA) in various pathophysiologic stages of coronary artery disease, and to detect restenosis. The BSPM was performed prior to, 1 week after, and 1 month after PTCA. A follow-up coronary angiography was performed 3 to 6 months after PTCA, and BSPM was also performed at the same time. The results of BSPM were compared with those of thallium-201 single-photon emission computed tomography (Tl-201 SPECT) and radionuclide ventriculography. After PTCA, BSPM showed a significant reduction in the departure area, the Tl-201 SPECT also showed a significant reduction in the extent and severity scores, and the left ventricular ejection fraction improved significantly. In the cases with restenosis, the departure area, which had decreased in size after PTCA, showed an increase in size. After successful re-PTCA, the size of the departure area again became smaller. We concluded that BSPM, which is a simple, noninvasive, and inexpensive method, is useful in the evaluation of the clinical efficacy of PTCA and in the detection of restenosis after successful PTCA. 
5	Flow-volume characteristics in the pulmonary circulation. Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation. With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range. Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight. At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion. Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013). The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions. The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08). In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05). 
1	Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial. Between 1976 and 1985, 391 patients (202 premenopausal, 189 postmenopausal) with operable breast cancer and positive axillary lymph nodes were randomized after total mastectomy and axillary clearance to receive cyclophosphamide, methotrexate, and fluorouracil (CMF) (n = 193) or no adjuvant therapy (n = 198). After a median follow-up of 8 years, both relapse-free survival (RFS) and survival (S) were significantly prolonged in premenopausal patients receiving CMF (RFS, P less than .001; S, P = .003). Treatment with CMF resulted in a significant improvement in RFS in premenopausal patients both with steroid receptor-positive and steroid receptor-negative tumors and also in subgroups of premenopausal patients defined by the number of axillary nodes involved. Premenopausal patients who developed permanent amenorrhea following CMF had a significantly better RFS than those who continued to menstruate. Induction of amenorrhea following CMF was related to age, with almost all patients over 40 years becoming amenorrheic. For patients less than or equal to 40 years, development of amenorrhea following CMF did not influence outcome. No difference was detected between control and CMF groups (RFS, P = .9; S, P = .9) in postmenopausal patients nor in any subgroup of these patients. The results of this trial of the efficacy of CMF for improving RFS and S have strengthened with longer follow-up. 
4	Pericardial effusion in primary hypothyroidism. Pericardial effusion is reported to occur in 30% to 80% of subjects with hypothyroidism. However, these earlier studies were conducted when the diagnosis of hypothyroidism was only suspected and was confirmed only in the presence of classic clinical features. In contrast, the diagnosis has recently been established in the early mild stage or more often in an asymptomatic stage because of more frequent or routine determinations of thyroid function tests, especially in the elderly. Thus the subjects in the older studies were severely hypothyroid at the time of diagnosis and may not be representative of the present hypothyroid population. For this reason, 30 subjects with hypothyroidism were evaluated with echocardiography to reassess the evidence of pericardial effusion in this disorder. Only two subjects demonstrated pericardial effusion, and in only one of them with severe disease could the pericardial effusion be attributed to hypothyroidism, since it resolved on the patient's attaining the euthyroid state. Thus the incidence of pericardial effusion was only 3% to 6%, depending on the inclusion of one or both subjects, an extremely infrequent occurrence when compared with that of previous studies. Moreover, the occurrence of pericardial effusion in hypothyroidism appears to be dependent on the severity of the disease. Thus pericardial effusion may be a frequent manifestation in myxedema, an advanced severe stage, as previously found, but a rare association of hypothyroidism, an early mild stage, because of the timeliness with which the latter condition is nowadays detected. 
1	Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity. 
1	Hemiparesis and ischemic changes of the white matter after intrathecal therapy for children with acute lymphocytic leukemia. Three children with acute lymphocytic leukemia (ALL) developed delayed-onset transient hemiparesis and facial palsy after intrathecal (IT) administration of methotrexate (MTX) alone or as part of triple intrathecal chemotherapy for central nervous system (CNS) prophylaxis. The hemiparesis developed 10 to 14 days after IT therapy. Two of three children also experienced transient, profound expressive dysarthria. These episodes occurred during maintenance treatment after multiple IT administrations and without previous CNS toxicity. Two of three children received intermediate-dose MTX, 1 g/m2, not less than 5 weeks before events. These patients had not received cranial irradiation and had no evidence of CNS leukemia before or after these episodes. Ischemic changes on computerized tomographic scan or magnetic resonance imaging studies were documented in all three cases. Such changes are unusual manifestations of neurotoxicity in children after intrathecal therapy. 
5	Coronary pathology predicts conduction disturbances after coronary artery bypass grafting. Conduction disturbances after coronary artery bypass grafting may result from compromised septal blood flow. To examine this hypothesis we reviewed the preoperative coronary angiography of 55 consecutive patients undergoing coronary artery bypass grafting. Thirty-five patients had either no lesion or a discrete lesion in the left anterior descending coronary artery that did not include the septal perforator (type I anatomy). Twenty patients had a lesion of the left anterior descending coronary artery at the origin of the first septal branch, a lesion of the first septal artery, or a pair of lesions in the left anterior descending coronary artery that straddled the origin of the first septal artery; all lesions were proximal to the graft site (type II anatomy). None of the patients with type I anatomy had a major conduction disturbance after coronary artery bypass grafting. Eleven of the patients with type II anatomy had major conduction disturbances after coronary artery bypass grafting; right bundle-branch block in 1, right bundle-branch block and left anterior hemiblock in 2, left bundle-branch block in 5, and complete atrioventricular block that required pacemaker implantation in 3 (p less than 0.001). In the 20 patients with type II anatomy, the appearance of conduction disturbances correlated well with the absence of retrograde flow to the septal branches from the right coronary artery (p less than 0.01). Pathological lesions in the left anterior descending coronary artery that compromise flow in the first perforator and that do not provide an adequate circulation produce localized damage and conduction disturbances after coronary artery bypass grafting. This can be predicted from the preoperative angiographic anatomy. 
1	The effect of age on treatment choice and survival in elderly breast cancer patients. To investigate the effect of age on treatment choice and survival in patients with breast cancer, data from the cancer registry of the Netherlands Cancer Institute (NKI, Amsterdam, The Netherlands) on 611 women have been analyzed. All patients 55 years and older admitted to the NKI for primary treatment of breast cancer between 1981 and 1986 were selected. For women 75 years and older, physicians were less likely to use treatment of adjuvant radiation therapy after a mastectomy and more often employed primary hormonal therapy only for local stage disease than for younger patients. Life-table analysis showed that disease-specific survival at 7 years for patients 65 through 74 years of age was significantly better (65%) than that of the youngest (55%) and the oldest age group (50%). In multivariate regression analysis (Cox), age older than 74 years was significantly and independently associated with a shorter disease-specific survival as compared with patients younger than 75 years. This difference in survival, however, does not seem to be the result of the difference in treatment between the age groups, but suggests an influence of age-related factors such as comorbid diseases and weak physical condition, which manifest themselves most strongly in the oldest age category and make the older woman more vulnerable to the course of malignant disease. 
4	Detection of myocardial infarction in the presence of Wolff-Parkinson-White syndrome by QRST isoarea map in dogs. The possibility of detecting myocardial infarction (MI) in the presence of Wolff-Parkinson-White (WPW) syndrome by means of body surface QRST isoarea maps was studied in eight dogs. Eighty-seven body surface ECGs were recorded simultaneously. Recordings were taken during right atrial (RA) and right atrial and right ventricular (RA + RV) sequential pacing, which simulated WPW syndrome, during control periods and at 1-hour intervals for up to 5 hours after occlusion of the left anterior descending coronary artery. In ECGs during the RA drive, diagnostic findings of MI such as abnormal Q waves were observed but became obscure during the RA + RV drive. On the contrary, the QRST values over the anterior chest during both drives were positive soon after coronary occlusion, decreased gradually as time passed, and became abnormally negative after 5 hours. The QRST isoarea maps during RA and RA + RV pacing showed quite similar patterns and were highly correlated with each other throughout this study (r greater than 0.95). These findings demonstrate that localized abnormalities resulting from MI are evident in QRST isoarea maps even in the presence of preexcitation and fusion. 
1	Extramedullary plasmacytoma of the urethra: a case report. Extramedullary plasmacytomas are uncommon manifestations of plasma cell neoplasms, which occur rarely in the urinary tract. We report to our knowledge the third case of primary IgA plasmacytoma of the urethra. Diagnosis, therapy and followup with magnetic resonance imaging are presented. 
1	Primary lymphoma of the central nervous system in two children with acquired immune deficiency syndrome. Postmortem examination disclosed central nervous system non-Hodgkin's lymphoma in two children who died of acquired immune deficiency syndrome (AIDS) at 6 and 14 months of age, respectively. Systemic signs of lymphoma were not present. The B-cell origin and clonality of the neoplastic cells were established by immunohistochemistry in one case and by molecular analysis of immunoglobulin gene rearrangement in the other. Moreover, in the latter case the neoplastic cells were characterized by the presence of a single episomal EBV genome. According to these data, the monoclonal B-cell proliferation occurred after EBV infection, thus suggesting a possible pathogenetic role of EBV in the early stages of lymphomagenesis. 
5	Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas. 
1	Aneuploidy in pancreatic insulinomas does not predict malignancy. Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow-up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. Of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas. 
1	Marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas. To investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies, a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as granulosa cell tumor. Using monoclonal antibodies against different keratin subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4 and 13 were not found in mesothelial cells, but positive groups of cells were identified in several cystomas, adenomas, and carcinomas. While mesothelial cells did not react with the pan-epithelial marker BW495/36, invaginating metaplastic mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an increasing reactivity with BW495/36, with an increasing degree of malignancy. The reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC 125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50% of the ovarian cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or disappeared in granulosa cells of mature follicles (Graafian follicles), whereas granulosa cell tumors did not react with anti-keratin antibodies. The reactivity of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian carcinoma-associated antigens were not expressed in granulosa cells or granulosa cell tumors. The data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production of ovarian carcinoma associated antigens, in addition to focal production of keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200-kd glycoprotein and the ovarian carcinoma-associated antigens. 
5	Nontuberculous mycobacterial infections of the skin. Report of fourteen cases and review of the literature. This study comprised 14 patients from whose skin nontuberculous mycobacteria were recovered. Most clinical manifestations were relatively nonspecific. Various histopathologic patterns were observed in 22 biopsy specimens. Recurrences were common and prolonged treatment was often necessary. Culture of tissue remains the definitive diagnostic procedure. Cutaneous lesions can be the first or only site of nontuberculous mycobacteriosis. 
5	Influence of the menstrual cycle on systemic diseases. Physiological changes associated with the menstrual cycle influence the clinical course of some diseases such as bronchial asthma, allergies, anaphylaxis, epilepsy, migraine, dermatoses, and porphyria. Hormonal manipulation can be beneficial in some patients. 
3	The timed "Up & Go": a test of basic functional mobility for frail elderly persons. This study evaluated a modified, timed version of the "Get-Up and Go" Test (Mathias et al, 1986) in 60 patients referred to a Geriatric Day Hospital (mean age 79.5 years). The patient is observed and timed while he rises from an arm chair, walks 3 meters, turns, walks back, and sits down again. The results indicate that the time score is (1) reliable (inter-rater and intra-rater); (2) correlates well with log-transformed scores on the Berg Balance Scale (r = -0.81), gait speed (r = -0.61) and Barthel Index of ADL (r = -0.78); and (3) appears to predict the patient's ability to go outside alone safely. These data suggest that the timed "Up & Go" test is a reliable and valid test for quantifying functional mobility that may also be useful in following clinical change over time. The test is quick, requires no special equipment or training, and is easily included as part of the routine medical examination. 
1	Ganglioglioma: a clinical study with long-term follow-up. Gangliogliomas are uncommon tumors of mixed neoplastic glial and neuronal elements. Because of their low incidence, few large series exist that fully describe the clinical characteristics of patients afflicted with this tumor. We have reviewed the medical records of 20 patients at Duke University Medical Center with histologically proven gangliogliomas. These patients typically presented within the first three decades of life and their most common presenting symptom was seizures. Therapies included surgical resection, either partial or total, radiation therapy, and/or chemotherapy. Long-term follow-up was achieved by chart review and by telephone interview. Patients who underwent gross total resection alone seemed to fare the best when comparing all treatment groups, and we therefore recommend this as the main form of treatment. 
4	Beta-blocker duration of action and implications for therapy. Two studies were conducted to measure the effect of serum half-life on beta-blocker-related heart rate reduction throughout the 24-hour period. In the first study, nadolol, atenolol and pindolol were associated with significant (p less than 0.01) heart rate reduction even at 24 hours after dose. Nadolol, with a plasma half-life of 15.5 hours, had the most pronounced heart rate-lowering effect 24 hours after the daily dose compared to pindolol, which had a half-life of 5.5 hours. In a randomized, double-blind, crossover study, nadolol and atenolol had similar effects 3 to 4 hours after the daily dose. Nadolol, however, produced greater suppression of heart rate and double product (blood pressure x heart rate) than atenolol (compared to placebo) 24 hours after ingestion of the daily dose. On ambulatory electrocardiography 24 hours after medication administration, 80 to 100% of the heart rate-attenuating effect of nadolol was maintained versus only 20 to 45% of atenolol's effect. Statistically significant (p less than 0.05) reductions in heart rate were produced by nadolol, but not by atenolol, between 4 and 5 A.M., 6 and 7 A.M., 8 and 9 A.M. and 9 and 10 A.M. Furthermore, nadolol remained at 52% of peak blood level at 24 hours, whereas atenolol was at 20%. The data from these 2 studies indicate that significant differences in duration of action exist between beta blockers. 
4	Prostaglandin modulation of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium chloride combined with efferent cardiac sympathetic stimulation in dogs. Prostaglandins inhibit efferent cardiac sympathetic nerve effects by acting at presynaptic sites and may act to suppress some arrhythmias. In the present study, the effects of intravenous administration of prostacyclin (PGI2) and prostaglandin E2 (PGE2) on early afterdepolarizations and ventricular tachycardia induced by cesium chloride (0.5 mmol/liter per kg body weight intravenously) combined with stimulation of bilateral ansae subclaviae in anesthetized dogs were examined. The right atrium was paced at a constant cycle length of 600 ms. A left ventricular endocardial monophasic action potential catheter was used to detect early afterdepolarizations. Prostacyclin (0.2 microgram/kg per min) reduced the amplitude of the early afterdepolarizations (39.2 +/- 8.4% of the monophasic action potential amplitude during control study to 28.7 +/- 5.5%, n = 10; p less than 0.001) as well as the prevalence of ventricular tachycardia (11 of 14 dogs during control study to 5 of 14 dogs; p = 0.031). Prostaglandin E2 (0.2 to 0.6 microgram/kg per min) did not significantly reduce the early afterdepolarization amplitude (34.7 +/- 8.9% to 25.1 +/- 10.7%, n = 8; p = 0.085) or the prevalence of ventricular tachycardia (8 of 10 versus 6 of 10 dogs; p = 0.50). Alpha- and beta-adrenoceptor blockade with combined intravenous administration of propranolol (0.5 mg/kg) and phentolamine (0.3 mg/kg) decreased the amplitude of the early afterdepolarizations induced by cesium chloride and bilateral ansae subclaviae stimulation from 38.6 +/- 11.2% to 18.8 +/- 3.3% (n = 6; p = 0.005). Additional administration of PGI2 further reduced the early afterdepolarization amplitude from 18.8 +/- 3.3% to 9.8 +/- 4.8% (n = 6; p = 0.001). 
5	Intraocular lens complications. The authors implanted intraocular lenses (IOL) in 780 eyes and considered complications of this surgery, dividing the complications into intraoperative and postoperative, the latter early and late. The most frequent intraoperative complications were: hyphema, vitreous injury, pupil deformation with an IOL in the anterior chamber (AC), and hyphema and corneal lesions with an IOL in the posterior chamber (PC). Among the early postoperative complications of an IOL in the AC the authors noticed striate keratopathy and uveal flare and postoperative transitory ocular hypertension and striate keratitis with an IOL in the PC. Moreover, in late postoperative complications in AC implantation they observed: cystoid macular edema, bullous keratitis, retinal detachment, late uveitis, opacification of posterior capsule, eccentric displacement of the IOL, and less frequently, cystoid macular edema in PC implantations. The authors prefer IOL implantation in the PC after extracapsular cataract extraction, since this surgery causes less problems in the cornea, vitreous, and retina. 
2	Traumatic diaphragmatic hernia and intestinal obstruction due to penetrating trunk wounds. We have reported two cases of intestinal obstruction due to traumatic diaphragmatic hernia, both resulting from apparently trivial knife wounds. When TDH is due to a penetrating injury, it tends to produce symptoms of intestinal obstruction. A high index of suspicion, a chest x-ray film, and barium studies of the gastrointestinal tract are usually needed to make the diagnosis, though CT scans, ultrasonography, laparoscopy, and radionuclide scanning may also be useful. Surgeons and emergency physicians should be aware of the potential for TDH when there is a history of a penetrating wound of the chest or abdomen. 
3	Large cystic optic glioma. A 5 1/2-year-old boy developed a huge cyst in his chiasmal glioma 4 years after radiation therapy. The cyst produced obtundation but was successfully treated. 
4	Emergent aneurysm surgery without cerebral angiography for the comatose patient Neurologically based clinical grading scales offer excellent prognostic information for the patient suffering diffuse subarachnoid hemorrhage (SAH). These grading scales are less applicable to patients with life-threatening intraparenchymal hematomas after aneurysmal rupture. During the last 3 years, four patients in a comatose state with brain stem compression syndromes documented by computed tomographic scans have undergone emergent operation in our neurosurgical service. Each patient was so critically ill that we believed it unwise to delay craniotomy for diagnostic angiography. The average delay from the onset of coma to skin incision was 3.02 hours (range, 1.67-6.5 hours), and the average delay from arrival in our unit until skin incision was 1.8 hours (range, 0.75-2.5 hours). The condition of two arousable patients deteriorated while they were in the emergency room, presumably from new bleeding. Each patient underwent craniotomy for hematoma evacuation, definitive aneurysm clipping, and lobectomy for decompression. Temporary clipping was employed in one patient, and intraoperative rupture occurred in two others. Three patients survived but retain significant disability. Emergent craniotomy with empiric exploration of appropriate subarachnoid cisterns after hematoma decompression may be life-saving in some cases. The delay imposed for diagnostic angiography may be avoided in attempts to save vital minutes of severe brain stem compression. 
1	Dexamethasone-nonsuppressible cortisol in two cases with aldosterone-producing adenoma. Forty-one patients with aldosterone-producing adenoma (APA) were subjected to a dexamethasone suppression test (DST) before surgery. Serum cortisol and urinary excretion of 17-hydroxycorticosteroids were suppressed by dexamethasone in 39 patients [DST(+)]. In two patients (cases A and B), they were not suppressed [DST(-)]. Clinical manifestations of the two DST(-) patients were similar to those of DST(+) patients. Hypertension, hypokalemia, high serum aldosterone levels, and suppressed PRA were found in all of the patients. The cut surfaces of the adenomas from all of the patients, including cases A and B, were golden yellow, which is typical of APA. However, atrophies of the adjacent normal tissues were evident exclusively in the two DST(-) patients. After removal of the affected adrenals, the serum cortisol level was suppressed by dexamethasone in one of the DST(-) patients (case B). These findings suggested autonomous cortisol production by APA. To evaluate whether cortisol could be produced from the adenoma tissue, the presence of several steroidogenic enzymes was studied by immunohistochemistry and mRNA analysis in the adenomas and the adjacent nonneoplastic adrenals from the 2 DST(-) and 5 DST(+) patients. Immunohistochemical analysis demonstrated that steroidogenic enzymes were expressed in APA tumor tissues from both DST(-) and DST(+) patients. In both groups, mRNAs coding steroidogenic enzymes were present not only in the nonneoplastic but also in the tumor tissues. Quantitative analysis of the mRNA levels revealed that in the adrenals from DST(+) patients, the mRNAs were more abundant in nonneoplastic tissue than in tumor tissue. However, in those from DST(-) cases, the mRNAs were much more abundant in the tumor tissues than in the nonneoplastic tissues. These results indicate that tumor cells of the two DST(-) patients autonomously synthesized not only aldosterone but also cortisol. The diameters of the tumors from the two DST(-) patients exceeded 3 cm, while those from other DST(+) patients were smaller. In patients with large APA, adrenal insufficiency should be anticipated upon removal of the tumor. 
5	Intradural chordoma of the tentorium cerebelli. Case report. A rare case of intradural chordoma is described. The literature contains seven examples of intradural extraosseous chordoma, all reported in a ventral location. This is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra- and infratentorial compartments. 
4	The effect of alcohol in isolated blunt splenic trauma. The effect of alcohol on trauma patients is controversial, with numerous authors citing no difference in mortality in acutely intoxicated patients. The purpose of our study was to retrospectively investigate the effect of alcohol in adult patients with isolated blunt splenic injury. From 1980 through 1989, 47 adult patients with splenic trauma as the only major injury were admitted to the Trauma Service. There were 37 males and ten females with a mean age of 29 years (range, 15 to 61). Motor vehicle accidents were responsible for 44 (94%) of the injuries. Group 1 consisted of 24 patients with a mean blood alcohol level of 185 mg/dl (range, 15 to 380). In Group 2 there were 23 patients without detectable blood alcohol. There were no statistically significant differences between the two groups in age, Abbreviated Injury Severity Score, initial hematocrit, and grade of splenic injury. Hypotension was present in 13 patients (55%) in Group 1 versus six patients (26%) in Group 2 (p less than 0.05). Significant abnormalities in clotting studies were present on admission in six patients (25%) in the alcohol-detected group versus one in the other group (p less than 0.05). Blood transfusion requirements in the first 24 hours were significantly greater in Group 1 (mean, 3.9 units) versus Group 2 (mean, 0.5 units) (p less than 0.001). If alcohol was present, there was much less chance for splenic conservation, as 18 patients (75%) underwent splenectomy versus seven patients (30%) in the nonalcohol group (p less than 0.05). There was one death and this occurred in a patient acutely intoxicated who suffered a cerebral infarct. 
1	Histopathologic study of otitis media in individuals with head and neck tumors. Five temporal bones, each including the eustachian tube, were obtained from five adults with advanced malignant tumors of the head and neck. The specimens were from the side on which the tumor had occurred. Otitis media had been detected clinically in two cases, and was detected histopathologically in the other three. We discuss the possibility that otitis media might have been caused by tumor invasion of the paratubal area, by postoperative inflammation in the nasopharynx, or by an inflammatory reaction of tubal structures to radiotherapy, or that these conditions may have coexisted. 
5	Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome. The recent recognition of the eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan prompted an analysis of the peripheral blood eosinophil phenotypes and of the serum eosinophil hematopoietins in this disorder. Five patients with an illness characterized by the abrupt onset of aching skeletal muscles, edema, thickening and induration of the skin, and marked blood eosinophilia associated with L-tryptophan ingestion provided eosinophils, serum, or both, for evaluation. Gradient sedimentation density analysis of the peripheral blood eosinophils from four of these patients revealed that 43 +/- 13% (mean +/- SEM) of the cells had converted to the abnormal (hypodense) sedimenting phenotype. When normodense eosinophils from the reference donors were cultured for 3 days in medium supplemented with increasing concentrations of serum from the patients with EMS, their viability increased in a dose-dependent manner to 45%, which was significantly augmented over the effect of normal serum. This eosinophil viability-sustaining activity was inhibited by 76 +/- 7% (mean +/- SEM; n = 3) by the addition of anti-interleukin 5 (IL-5) but not by neutralizing antibodies monospecific for either granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3. IL-5, an eosinophilopoietic factor, converts normodense peripheral blood eosinophils in vitro to a hypodense sedimenting form with extended viability and augmented biologic responses to activating stimuli. Thus, the presence of IL-5 in the sera of patients with EMS may contribute to the development and maintenance of the eosinophilia and may regulate the conversion of the peripheral blood eosinophils to the hypodense phenotype with augmented pathobiologic potential. 
4	Histologic abnormalities of large and small coronary arteries, neural structures, and the conduction system of the heart found in postmortem studies of individuals dying from the toxic oil syndrome. Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, in this study we examined the small and large coronary arteries, neural structures, and conduction system from eight victims dying with the toxic oil syndrome. Dense fibrosis of the sinus node in two hearts resembled changes found in scleroderma. Atrionodal junctional hemorrhages and cystic degeneration of the sinus node present in the other six hearts resembled changes found in lupus erythematosus. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Both the arterial and neural abnormalities prominently involved the conduction system. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, we suggest that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reconsider the widely recommended use of any rapeseed oil product as a suitable food for man or other animals. 
5	External ear resonance in children with otitis media with effusion. A middle ear effusion has been shown, in KEMAR, to increase the height of the resonant peak of the external auditory canal by 6 dB SPL. It has also been shown that the hearing impairment due to otitis media with effusion is related to the volume of middle ear fluid. Therefore, it was hypothesized that measurement of the height of the resonant peak of the external auditory canal could be used as a method of assessing the magnitude of any hearing impairment due to otitis media with effusion. 182 ears from 182 children aged 3-12 (mean 6.3) years were studied. Pure-tone audiometry and impedance tympanometry were performed, and the acoustics of the external auditory canal were measured using the Rastronics CC1-10 frequency response analyser. The mean height of the resonant peak (17.9 dB SPL) of children with a type A tympanogram was significantly different from the mean value (23.6 dB SPL) of those with a type B tympanogram. There was a significant correlation between the height of the resonant peak and the speech frequency average of the pure-tone thresholds. The sensitivity and specificity of using the height of the resonant peak to detect hearing impairments in different age groups were calculated and compared with the sensitivity and specificity of tympanometry. The test did not provide the same degree of sensitivity as tympanometry but was more specific. The additional advantages of the test are that it is quick, taking less than 1 min per ear, and is well tolerated by children in whom there was a 99% compliance. 
1	Doxorubicin for unresectable hepatocellular carcinoma. A prospective study on the addition of verapamil. A prospective study was conducted to assess the safety and efficacy of the addition of oral verapamil to intravenous Adriamycin (doxorubicin) for the management of patients with unresectable hepatocellular carcinoma (HCC). All 28 patients studied had histologically verified disease, and cirrhosis was present in 20 of the 21 patients with adequate tissue sampling. The overall median survival was 57 days. Chemotherapy was terminated in seven patients after one course of treatment. Partial response and complete response were noted in four patients (19%) and one patient (4.8%), respectively, among the 21 patients evaluated. Side effects related to the chemotherapy were present in all patients studied. Death from fulminating sepsis occurred in three of the 13 patients with leukopenia. Symptomatic myocardial dysfunction developed in one patient. The addition of verapamil apparently did not potentiate the tumoricidal effect of systemic Adriamycin on HCC but probably did increase its complications. 
5	In vivo nonthrombogenicity of heparin immobilized polymer surfaces. The authors developed two different methods to immobilize heparin on polymer surfaces. One method involves in situ heparin immobilization on a segmented polyurethane urea (Biomer) surface via hydrophilic poly(ethylene oxide) (PEO, Mn = 4,000) spacers. The other method uses PEO/poly(dimethylsiloxane) (PDMS) block co-polymer and heparin covalently linked in a block co-polymer system (PEO-PDMS-Hep). These surfaces have demonstrated high heparin bioactivity in vitro and excellent blood compatibility in in vitro-ex vivo experiments. This report evaluates the long-term in vivo blood compatibility of these heparin immobilized surfaces. Vascular grafts (6 mm ID, 7 cm in length) were fabricated with Biomer, and heparin was immobilized in situ with PEO spacers (B-PEO4K) and coated on their luminal surfaces with PEO-PDMS-Hep. Biomer and PEO (Mn = 4,000) grafted Biomer (B-PEO4K) were used as controls. The grafts were implanted in the abdominal aorta of dogs and retrieved at 3 months or when graft occlusion was suspected. Retrieved grafts were evaluated with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). TEM measured the thickness of the adsorbed protein layer on the surface and the protein distribution (albumin, fibrinogen, and IgG) visualized by an immunogold method. All heparin immobilized grafts were patent at 3 months, whereas Biomer and B-PEO4K grafts occluded within 1 month. SEM pictures of heparin immobilized surfaces after 3 months demonstrated minimal platelet adhesion and activation without detectable fibrin formation. Heparin immobilized surfaces showed a thin protein layer (300-600 A) even after 3 months, with high concentrations of albumin and IgG and less fibrinogen. 
1	Overexpression of normal and mutated forms of HRAS induces orthotopic bladder invasion in a human transitional cell carcinoma. Recent studies have shown that orthotopic (transurethral) transplantation of human bladder cancer cell lines into nude mice permits tumor growth that accurately reflects their clinical malignant status in the original host. Thus, such a system allows a unique opportunity to analyze the genetic events involved in the conversion of low-grade bladder cancer, the vast majority of which are curable, to the high-grade life-threatening form of the disease. Since 5-10% of transitional cell carcinomas (TCCs) have been shown to contain a mutated HRAS gene, and protein expression levels of all forms of HRAS have been correlated with TCC progression, we chose to study the contribution of the HRAS oncogene in bladder tumor progression. We evaluated the effects of transfection of normal or mutated HRAS genes into a human TCC, called RT-4, that behaves as a superficial noninvasive papillary tumor after transurethral orthotopic inoculation into athymic nude mice. We found that overexpression of either transfected normal or mutated HRAS genes converted RT-4 cells to express an invasive phenotype remarkably similar in nature to the clinical behavior of high-grade bladder carcinomas. These results suggest a role for overexpressed normal or mutated RAS genes in human bladder carcinoma progression, and highlight the importance of using orthotopic inoculation systems for evaluation of the contribution of oncogenes to malignant tumor progression. 
4	Calcium, parathyroid hormone, and vitamin D in the "prehypertensive" Dahl salt-sensitive rat. The purpose of this study was to determine if alterations of calcium and calcium regulating hormones precede the onset of NaCl-induced hypertension in the Dahl salt-sensitive (S) rat. After a 5-day balance study, serum ionized calcium, parathyroid hormone (PTH), and 1,25-dihydroxy vitamin D concentrations were measured in Dahl-S and salt-resistant (R) rats that had been maintained on a "normal" (1%) or high (7%) NaCl intake. Blood pressure was higher in Dahl-S than Dahl-R (P less than .01), but was not affected by 5 days of high NaCl. On both NaCl intakes, urine calcium excretion was increased, serum calcium was decreased, and serum PTH and 1,25 dihydroxy vitamin D were increased in Dahl-S compared to Dahl-R (P less than .01). On the high NaCl intake, fecal calcium was greater in Dahl-S than in Dahl-R, and net 5-day calcium balance was less positive in Dahl-S (P less than .05). Thus, alterations of calcium, PTH, and vitamin D precede NaCl-induced hypertension in Dahl-S. These alterations may contribute to the development of hypertension in this animal model. 
5	Strategy for breakpoint cluster region analysis in chronic myelocytic leukemia in a routine clinical laboratory. Despite the increasing reliance on breakpoint cluster region (bcr) determinations in diagnosis of chronic myelocytic leukemia (CML), few reports have dealt with the practical aspects of specimen analysis. In the setting of a routine molecular diagnostics laboratory, samples from 68 patients with active CML were evaluated for bcr rearrangements, with the use of a variety of enzymes and two probes. The data have been used to develop an efficient strategy for bcr screening and breakpoint determination. Screening with the universal bcr (UBCR) probe on Xba I and BgI II digests yielded bcr rearrangements in 100% of the Ph1-positive patients and three of the seven Ph1-negative patients, giving bcr analysis a sensitivity of 100%. A single-enzyme screen using the UBCR probe would have resulted in a false negative rate of 10%. The false negative rate was determined during the breakpoint site analysis from additional digests hybridized to both the 3' and UBCR probes. The false negative rate for the 3' probe was 26.5%, because of deletions or 5' rearrangements. The method of breakpoint site determination was dependent on screening results. In 78% of cases, one additional hybridization with two enzyme digests was required. During breakpoint site analysis, a rare false negative result was also demonstrated with Bam HI and Eco RI. This screening strategy has made bcr analysis competitive with cytogenetic analysis at the authors' institution; although turnaround time may be slightly longer, bcr analysis can yield information (such as detecting bcr-positive/Ph1-negative patients and determining breakpoint site) that cannot be obtained by cytogenetics. 
4	ST segment alternans during percutaneous transluminal coronary angioplasty--a case report. The occurrence of electrical alternans of the ST segment has been reported in patients with variant angina. The authors encountered a patient with typical electrical alternans of the ST segment in leads V4 through V6, which developed during percutaneous transluminal coronary angioplasty (PTCA) of the proximal left anterior descending artery. Hemodynamic pulsus alternans of the aortic pressure tracing was not observed during electrical alternans, and a Ca2+ blocker could not prevent this phenomenon during PTCA. 
4	Transplant coronary artery disease: histopathologic correlations with angiographic morphology. Accelerated coronary artery disease is a major cause of morbidity and mortality among cardiac transplant recipients. Ten patients who died or underwent retransplantation within 2 months of coronary angiography had direct correlation of angiographic (normal discrete lesions, diffuse concentric narrowing) with histologic appearance of coronary arteries. Of the 26 angiographically normal segments, 73% showed mild to moderate fibrous intimal thickening by light microscopy. The remainder had intermediate lesions or atheromatous plaques. Discrete stenoses usually corresponded to lipid-rich intermediate or atheromatous disease. In contrast, angiographically diffuse, concentrically narrowed lesions usually were areas of severe fibrous intimal thickening. Fresh or organizing thrombus was most often associated with discrete lesions and accounted for all complete occlusions. Histologic and angiographic comparisons of the degree of luminal narrowing showed generally good correlation for high grade stenoses. Lesions graded as having less than 25% diameter narrowing were often underestimated angiographically as compared with histologic determinations. Transplant coronary artery disease has a heterogeneous histologic and angiographic appearance, with angiographic underestimation of disease in some patients. 
2	Risk factors for gallstones among Chinese in Taiwan. A community sonographic survey. A health survey of adults aged 30 years or more was carried out in southwest Taiwan to determine the prevalence of gallstones and to study risk factors associated with gallstones. Blood samples were collected and abdominal sonographic examination and anthropometric measurements were performed on a total of 923 people. The 40 gallstone cases detected resulted in a prevalence of 4.3%. The risk factors explored included age, sex, hepatitis, obesity, hyperlipidemia, and diabetes mellitus (DM). Age and DM were the only significant factors associated with gallstones in our study. With a reference group of 30-39-year-olds as a comparison, multiple logistic regression analysis showed a trend effect with odds ratios of 1.73, 3.74, and 6.32 for age groups of 40-49, 50-59, and 60 or above, respectively. The odds ratio for DM was as high as 2.59. However, sex, body weight index, chronic hepatitis B, and hyperlipidemia were not significantly associated with gallstones. 
1	Lung cancer in patients younger than 40 years of age. The records of 52 patients younger than 40 years of age who had bronchogenic carcinoma diagnosed between 1965 and 1985 were reviewed. The preponderance of adenocarcinoma (54%), the lower male-female ratio in this age group compared with patients age 40 or older (2:1), the importance of cigarette smoking as a causative factor (80% of patients), the long mean duration of symptoms (5 months), and the high incidence of advanced stage at diagnosis (77% Stages III and IV) in these patients are findings similar to those reported in other published series. There was no significant difference in resectability (23% versus 19%), median survival length (5.3 months versus 6.9 months), median survival length of patients who had surgical resection (10.5 months versus 10.8 months), and 5-year survival rate (11.5% versus 6.3%) in these patients compared with a randomly selected group of 260 patients with lung cancer who were age 40 or older. 
3	Protective and curative effects of rifampicin in Acanthamoeba meningitis of the mouse. BALB/c mice inoculated nasally with Acanthamoeba culbertsoni, resulting in amebic encephalitis and death 3-7 days, were treated with rifampicin prophylactically (daily for 2 days with 75 and 100 mg/kg) and after infection (daily for 5 days with doses of 10-100 mg/kg). Prophylactic treatment resulted in full protection against infection, as assessed by absence of symptoms of central nervous system malfunction and negative brain culture 10 days after inoculation. Curative treatment was effective at the same doses; however, at doses of 10, 25, and 50 mg/kg, only two of six animals were free of symptoms and infection. 
5	Changes in cardiovascular homeostasis after injury are mediated by tissue damage and not haemorrhage. During treatment of the injured patient it is assumed that the cardiovascular responses follow recognized physiological principles. Studies in humans have shown that injury causes a profound suppression of arterial baroreflex function which alters the normal relationship between heart rate and blood pressure and casts doubt on this assumption. To investigate the mechanism of baroreflex suppression, we have studied the effects of the two major components of injury, blood loss and tissue damage, on baroreflex function in healthy volunteers. Baroreflex function was assessed using suction stimulation of the carotid sinus. The loss of 500 ml blood had no effect on baroreflex sensitivity. A human laboratory model of tissue injury reduced the ability of the baroreflex to compensate for a rise in blood pressure (P less than 0.05, Wilcoxon signed rank test). We conclude that tissue damage, rather than hypovolaemia, appears to mediate the effect of injury on baroreflex function in the injured. Blockade of neural signals from damaged tissue may have a role in the treatment of injury. 
4	Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. The records of 2,673 patients randomized according to seven consecutive Eastern Cooperative Oncology Group (ECOG) studies of adjuvant therapy for breast cancer were reviewed for the occurrence of vascular complications. All protocols opened and closed between June 1977 and July 1987. The objectives of the present study were (1) to compare the frequency of vascular complications among patients who received adjuvant therapy for breast cancer with patients on observation, and (2) to estimate the contribution of chemotherapy and hormonal therapy to the occurrence of venous and arterial thrombi. The frequency of thrombosis, both venous and arterial combined, was 5.4% among patients who received adjuvant therapy and was 1.6% among patients on observation (P = .0002). Premenopausal patients who received chemotherapy and tamoxifen had significantly more venous complications than those who received chemotherapy without tamoxifen (2.8% v 0.8%, P = .03). Postmenopausal patients who received tamoxifen and chemotherapy had significantly more venous thrombi than those who received tamoxifen alone (8.0% v 2.3%, P = .03) or those who were observed (8.0% v 0.4%, P less than .0001). Premenopausal patients who received tamoxifen and chemotherapy had a 1.6% frequency of arterial thrombosis, significantly more than patients who received chemotherapy alone (1.6% v 0.0%, P = .004). The frequency of arterial thrombosis among postmenopausal patients was not significantly correlated with adjuvant therapy. In conclusion, patients who received adjuvant therapy for breast cancer had a 5.4% frequency of thromboembolic complications, significantly more than those who were observed. The combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with more venous thrombi than tamoxifen alone among postmenopausal patients. 
2	Diagnosis and treatment of cytomegalovirus disease in transplant patients based on gastrointestinal tract manifestations. Infection due to cytomegalovirus is a substantial cause of morbidity and mortality in immunocompromised patients. In particular, cytomegalovirus infection has been associated with a significant detrimental effect on patient and allograft survival after solid-organ transplantation. We are evaluating a new antiviral agent, ganciclovir 9-[1,3-dihydroxy-2-2 propoxymethyl] guanine (DHPG), used in solid-organ transplant recipients who developed life-threatening cytomegalovirus infections. Between March 1, 1987, and June 30, 1989, we treated 93 solid-organ transplant patients who developed tissue-invasive cytomegalovirus disease. From this group of patients we have identified 14 patients with primary gastrointestinal cytomegalovirus disease who received treatment with DHPG. Tissue diagnosis was made by endoscopy of the upper gastrointestinal tract (11 patients) or colonoscopy (three patients). Invasive cytomegalovirus disease was identified prior to severe complications of the gastrointestinal tract in all but one patient, who suffered colonic perforation prior to treatment with DHPG and subsequently died of bacterial sepsis. While 13 of the 14 patients improved after treatment with DHPG, four patients required additional treatments for recurrent cytomegalovirus disease and recovered. No DHPG toxicity was observed. We believe treatment with DHPG is indicated in this patient population, but that further studies are indicated to fully define the impact of this recommendation on both patient and allograft survival after solid-organ transplantation. 
5	Loop ileostomy after ileal pouch-anal anastomosis--is it necessary? Construction of a loop ileostomy is usually advised in patients having an ileal pouch-anal anastomosis to minimize the complication of chronic pelvic sepsis. Formation and closure of a loop ileostomy was associated with a 41 percent and 30 percent complication rate, respectively, in a prospective series of 34 patients. This morbidity must now be assessed in relation to the benefits of avoiding temporary fecal diversion in restorative proctocolectomy. 
5	Interaction of the v-rel protein with an NF-kappa B DNA binding site. The avian reticuloendotheliosis virus T contains within its genome the oncogene rel. The expression of this gene is responsible for the induction of lymphoid tumors in birds. Recently, the rel gene was shown to be related to the p50 DNA binding subunit of the transcription factor complex NF-kappa B. Binding sites for the NF-kappa B complex are found in the enhancer regions of a number of genes, including the immunoglobulin kappa gene and the human immunodeficiency virus long terminal repeat. In this communication we identify an activity from avian reticuloendotheliosis virus T-transformed avian lymphoid cells that binds in an electrophoretic-mobility-shift assay to an NF-kappa B binding site from the kappa enhancer. This activity contains proteins immunologically related to rel, as detected by polyclonal and monoclonal antibodies directed against v-rel. In a DNA affinity precipitation assay using the NF-kappa B site from the human immunodeficiency virus long terminal repeat, v-rel and several other proteins were identified. These data suggest that oncogenic transformation by v-rel is the result of an altered pattern of gene expression. 
1	Endoprosthetic reconstruction after bone tumor resections of the proximal tibia. The advent of successful adjuvant chemotherapy and radiation therapy protocols for primary malignant tumors and the development of custom-designed metallic endoprostheses has now made possible a successful limb salvage procedure for malignancies of the proximal tibia. Use of the transposed medial gastrocnemius flap, as proposed by Dr. Jean Duboussett of Paris, has been critical to the soft-tissue reconstruction that routinely permits an excellent active and passive range of motion for these patients. This article describes the operative techniques and technical considerations necessary for a successful proximal tibial endoprosthesis reconstruction. 
4	A possible role for antiphospholipid antibodies in acquired cardiac valve deformity. We studied the frequency of antiphospholipid antibodies (aPL) in patients undergoing cardiac valve replacement, and present the results in the context of the pathology of the valve lesions. Forty-eight consecutive patients undergoing valve replacement were studied. Of the whole group, 15 (31%) had antibody levels greater than 2 SD above the mean for a control group of healthy persons and 11 (23%) had a level of greater than 3 SD. There was an increased frequency of elevated antibody levels in patients with valves showing fibrocalcific change and a significant association between aPL and valve thrombus. The possible role of these antibodies in the pathogenesis of the valve lesions is discussed. 
5	The distribution of enkephalins in human carotid bodies showing cellular proliferation and chronic glomitis. Human carotid bodies obtained at necropsy that showed prominence of either the sustentacular cell or the dark variant of chief cell or chronic carotid glomitis were studied by an immunogold labeling technique. The peptides methionine and leucine enkephalin had a similar distribution to that found in the normal human carotid body. They were localized prominently and predominantly in the dark and progenitor variants of chief (type I) cells. The sustentacular (type II) cells showed no immunoreactivity for the enkephalins. Cell counts on immunolabeled chief cells in cases of sustentacular cell hyperplasia and chronic carotid glomitis were found to be at the lower end of the normal range, whereas those in dark cell prominence occurred nearer the upper limit. 
4	Heart transplantation in patients with severe pulmonary hypertension and increased pulmonary vascular resistance. Irreversibly increased pulmonary vascular resistance is a contraindication for cardiac transplantation. At our hospital patients referred for recipient evaluation with systolic pulmonary artery pressure greater than 50 mmHg and pulmonary vascular resistance greater than 2 Wood units (Wu) are tested with intravenous sodium nitroprusside for reversibility. In 23 patients whose increased systolic pulmonary artery pressure (67.4 +/- 10.4 mmHg) and resistance (4.8 +/- 2.4 Wu) were reduced by nitroprusside, orthotopic heart transplantation was performed without early mortality. Right heart catheterization after transplantation revealed a significant and persistent fall of the elevated pulmonary artery pressure and pulmonary vascular resistance. We conclude that if severe pulmonary hypertension and elevated pulmonary vascular resistance are reversible with nitroprusside, the patient can safely undergo heart transplantation. 
4	Risks factors for cerebral infarction in good-grade patients after aneurysmal subarachnoid hemorrhage and surgery: a prospective study. A prospective series of 265 patients with aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) upon admission were evaluated as to neurological outcome and computerized tomography (CT) findings 1 to 3 years (mean 1.4 years) after the SAH and surgery. A total of 73 patients underwent acute surgery (within 72 hours after the bleed: Days 0 to 3), 86 were operated on subacutely (between Days 4 and 7), and 91 had late surgery (on Day 8 or later). Fifteen patients died before surgery was undertaken and another 20 patients died during the follow-up period. A total of 104 patients received nimodipine and the rest of the patients received either placebo (109 patients) or no medication (52 patients). A logistical regression analysis revealed the following prognostic factors for cerebral infarction, in order of importance: the amount of blood on the primary CT scan; postoperative angiographic vasospasm; the timing of the operation; and a history of hypertension. The use of nimodipine was associated with a significant reduction of cerebral infarcts visualized by CT scanning in patients who received intermediate or late surgery. In patients who underwent acute surgery no significant difference between the incidence of cerebral infarcts was observed. 
5	Metaplastic change in mesenchymal stem cells induced by activated ras oncogene. 3T3 T murine mesenchymal stem cells have the potential to differentiate into a variety of different cell types even though they show a predilection to undergo adipocyte differentiation in vitro. The possibility that the activated c-Ha-ras (EJras) oncogene might influence the pathway of differentiation of these stem cells is investigated in the current study. Activated ras oncogene was transfected and stably expressed in 3T3 T cells; assays then were performed to determine its effect on differentiation. The results show that all EJras-transfected cell lines lose their ability to differentiate to adipocytes and instead differentiate into cells that express many characteristics of macrophages. Such cells contain numerous cytoplasmic granules, extensive nonspecific esterase activity, and anchorage-independent growth. The modulation of differentiation pathway from an adipocyte lineage to a macrophagelike cell lineage does not result from the transforming effect of EJras, because a nontransformed cell clone that expresses p21EJras protein also exhibits this modified differentiation pathway. These data suggest that the EJras oncogene specifically modulates the differentiation pathway of 3T3 T mesenchymal stem cells. This experimental system should therefore provide an excellent model to evaluate the mechanistic role of EJras in the process of metaplasia. 
4	Femoral noninfected anastomotic aneurysms. A report of 56 cases. Fifty-six femoral non infected anastomotic false aneurysms (FAAs) were observed in 49 patients admitted to the Institute of Vascular Surgery, University of Milan, from 1975 to 1988; in 6 patients they were bilateral. These aneurysms developed after primary revascularization procedures at a mean interval of 66 months (range 12 to 156 months); one recurred after reparative surgery. Forty-four FAAs (78.6%) were asymptomatic, whereas 3 (5.3%) were complicated by acute expansion and 9 (16.1%) by thrombosis. Host vessel degeneration was the cause of aneurysm formation in most cases. A history of hypertension was present in 30% of the patients. All anastomotic aneurysms were operated upon except for one small aneurysm that was asymptomatic. In 5 patients aneurysm resection was carried out on both sides. The surgical technique was endoaneurysmectomy in all the cases with insertion of an interposition graft in 48 cases, a fabric patch in 2 cases and prosthesis re-anastomosis in 5 cases. One case of peripheral embolization occurring in the early postoperative period was successfully treated and there was no operative mortality. In our opinion elective repair of these aneurysms should be recommended whenever possible because of their propensity to develop serious complications and the operative morbidity is low. 
1	Participation of serotonergic mechanisms in the pathophysiology of experimental neoplastic spinal cord compression. We evaluated the role of serotonin (5-HT) in neoplastic cord compression in paraplegic rats harboring a thoracolumbar epidural tumor. We measured serotonin and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in the C-1 to C-7, T-1 to T-6, T-7 to T-12, and T-13 to L-3 spinal segments of tumor-free and tumor-bearing rats. In normal controls, a consistent rostral-to-caudal gradient for 5-HT and 5-HIAA was evident, but the 5-HIAA/5-HT ratio remained constant. In paralyzed rats, 5-HT levels were unchanged, but the 5-HIAA/5-HT ratio was elevated, especially in the compressed segments. Treatment with either dexamethasone or indomethacin delayed onset of paraplegia but had no effect on 5-HT metabolism. Blocking 5-HT receptors by cyproheptadine, evaluated 30 hours after onset of paralysis and treatment, resulted in a reduction in the high water content, vascular permeability, and prostaglandin E2 synthesis in the compressed cord. Early administration of cyproheptadine effectively delayed the onset of paraplegia. These data indicate that receptor-activated serotonergic mechanisms participate in the disruption of the blood-spinal cord barrier and that these effects can be manipulated pharmacologically. 
4	Propranolol and the morning increase in sudden cardiac death: (the beta-blocker heart attack trial experience). To provide insight into the protective effect of propranolol on mortality after myocardial infarction observed in the beta-Blocker Heart Attack Trial, the time of occurrence of sudden cardiac death was examined in this population. Between 5 A.M. and 11 A.M., 25 of the 56 total deaths (38%) occurred in the placebo patients compared with 11 of 45 (24%) in the propranolol patients. Excluding this period, there were nearly equal numbers of sudden cardiac deaths in the propranolol and placebo groups. This retrospective analysis suggests that beta blockade is protective during the morning hours when a surge of sympathetic activity may increase the risk of sudden cardiac death. 
3	Feasibility of reversing benzodiazepine tolerance with flumazenil To examine whether the benzodiazepine antagonist flumazenil can reverse tolerance to benzodiazepines but without precipitating withdrawal seizures, the antiepileptic effect of flumazenil itself and its ability to reverse tolerance at a dose that would leave sufficient receptors free for the binding of benzodiazepines were investigated. Electroencephalographic studies in 6 patients with partial and 6 with generalised seizures showed that flumazenil had a short (20 min) non-dose-dependent suppressant effect on epileptic discharges in those with partial seizures. Receptor occupancy studies in 12 patients showed that 1.5 mg flumazenil given intravenously occupied 55% receptors, whereas 15 mg occupied nearly all receptors. When 3 patients with partial seizures who had become tolerant to clonazepam were given 1.5 mg flumazenil, they were seizure-free for 6-21 days after the injection. The value of intermittent therapy with a benzodiazepine antagonist for preventing or reversing tolerance to benzodiazepine agonists ought to be investigated further. 
5	The hazards of surgical glove dusting powders. Surgical contaminants of many kinds, including glove powder, constitute a source of formation of granulomas. This is particularly well-documented in the peritoneal cavity ("starch peritonitis"), but has been documented in most anatomic sites. The production of starch-free gloves should remove this hazard, but the surgeon should remain aware that most particulate substances introduced into the body inevitably set up an inflammatory response. 
4	Severity of coronary atherosclerosis correlates with the respiratory component of heart rate variability. Decreased vagal activity is frequently observed in coronary artery disease, but the mechanism of this association is unknown. We investigated cardiac autonomic function by relating heart rate spectral components to clinical and angiographic findings in 80 patients who were undergoing coronary angiography. The age- and sex-adjusted magnitude of the respiratory spectral component, which is an index of cardiac vagal tone, showed a significant negative correlation with the extent of coronary atheromatosis (r = -0.43, p less than 0.0001) and a less significant negative correlation with the severity of coronary stenosis (r = -0.30, p = 0.0070). These relationships were independent of previous myocardial infarction and of left ventricular function. Stepwise regression analysis showed that the respiratory spectral component contributed to atheromatosis independently of established coronary risk factors (partial R2 = 9.4%, p = 0.002), but not to stenosis. Our results support the hypothesis that decreased cardiac vagal activity is associated with an increased risk of coronary atherosclerosis. 
4	Rib compression of the coronary arteries. This report describes the finding of coronary artery narrowing caused by compression by an overlying rib in two patients with cardiomegaly. There is probably no clinical significance to this finding. The primary differential diagnostic entity is myocardial bridging. 
5	Facial muscle reanimation using the trigeminal motor nerve: an experimental study in the rabbit. Surgical repair of facial nerve deficits may be marred by lack of muscle control and donor region paresis. Using New Zealand white rabbits, a study was undertaken to evaluate facial muscle reanimation with a donor source not previously used: the motor division of the trigeminal nerve. The results were compared with the severed facial nerve and hypoglossal-facial coaptation. An atrophy scale was calibrated for facial muscles of the rabbit. Clinical, electromyographic, and histomorphometric findings confirmed that the trigeminal nerve was a suitable donor source. The neurorrhaphy produced an exponential rate of repair. 
1	The World Health Organization's histologic classification of gastrointestinal tumors. A commentary on the second edition. The World Health Organization's (WHO) histologic classification of gastrointestinal tumors has been revised. Although the general basis of classification and the overall outline remain similar to the first edition, advances in the last decade justified changes in classifying certain entities; among them were malignant lymphomas, endocrine tumors, and dysplasias. Several newly recognized entities have also been added. 
5	Conduction system injury after aortic valve dilation in the dog single- versus double-balloon catheters. The range of morbidity induced by valvuloplasty is not fully known, but transient conduction disturbances are common. The authors performed aortic valve balloon dilatation on 10 closed-chest dogs with normal aortic valves, using a femoral cutdown approach and fluoroscopic guidance. Four were done with a single 15 mm balloon catheter, and in the other 6 two 12 mm balloon catheters were used. Balloons were inflated to 5 to 12 atms pressure with contrast solution. After several inflations the dogs were sacrificed, the hearts removed and examined. Gross examinations revealed subendocardial hemorrhage in the outflow tract in 5 of the 6 in which double balloons had been used. Microscopically, all aortic valve areas showed hemorrhage, mostly in loose connective tissues of the valve leaflets. The severity of injury appeared greater when two balloons had been used. Histologic examination showed definite injury to the myocytes of the left bundle branch in all 6 of the double-ballooned dogs, but in none of those subjected to the single-balloon procedure. During aortic valve dilation the only manifestation of conduction system injury was prolongation of the QRS complex in 3 of the 6 dogs in which a double-balloon catheter had been used. The results suggest that electrocardiographic conduction disturbances observed in patients undergoing aortic valvuloplasty may be the result of direct injury of conduction tissue and may be more likely to occur when larger balloons are used. 
5	Sudden death behind the wheel from natural disease in drivers of four-wheeled motorized vehicles. The heart was studied in 30 persons who died suddenly from natural causes in the driver's seat of an automobile, truck or bus. Twenty had cardiac arrest while driving and the other 10 while sitting in the driver's seat of a parked vehicle. Of the 20 drivers, 16 died from atherosclerotic coronary artery disease (CAD): 12 (75%) had minor collisions and 4 did not. Of the 16 with fatal CAD, an average of 2.3 +/- 0.8 of the 4 major coronary arteries were narrowed greater than 75% in cross-sectional area (CSA) by plaque; of 668 five-mm segments of the 4 major (right, left main, left anterior descending, left circumflex) coronary arteries in 13 of these 16 cases, 27 (4%) were narrowed 96 to 100% and 127 (19%) were narrowed 76 to 95% in CSA by plaque. The remaining 4 drivers died from noncoronary conditions: aortic rupture associated with the Marfan syndrome in 1; cardiac sarcoidosis in 1; thoracic aortic dissection in 1; and severe mitral regurgitation from infective endocarditis, which had healed in 1. The other 10 persons were found dead in the driver's seat of a parked vehicle and 8 of them had fatal CAD. Of the 8 CAD victims, an average of 2.5 +/- 1.2 of the 4 major coronary arteries was narrowed greater than 75% by plaque; of the 283 five-mm segments of coronary arteries in 7 of the 8 cases, 44 (16%) were narrowed 96 to 100% and 69 (24%) were narrowed 76 to 95% in CSA by plaque. 
2	Comparison of anterior sphincteroplasty and postanal repair in the treatment of idiopathic fecal incontinence. Both postanal repair and anterior sphincteroplasty with levatorplasty have been advocated in the treatment of idiopathic fecal incontinence. To assess the functional results of these procedures, physiologic and radiologic measurements were carried out prospectively in 33 patients with idiopathic incontinence undergoing operative treatment, and 12 age- and sex-matched controls. Sixteen patients had anterior sphincteroplasty and levatorplasty and 17 had postanal repair. A satisfactory postoperative outcome was defined as perfect continence or incontinence of flatus only. Ten patients in the anterior sphincteroplasty group had satisfactory results (64 percent) and 10 in the postanal repair group (59 percent). Preoperatively, both groups had decreased resting and squeeze pressures, impaired and mucosal electrosensitivity, and marked pelvic descent vs. controls. Postoperatively, significant improvement in sphincter pressures and mucosal electrosensitivity was seen in both groups. No significant change in anorectal angle was demonstrated in the postanal repair group, whereas it was made significantly more obtuse in the anterior sphincteroplasty group. It is likely that the improved continence resulting from either of these two procedures is secondary to better anal sphincter muscle function and improved and sensation. It would appear that the anorectal angle is not crucial in maintaining continence. 
5	Intraoperative air testing of colorectal anastomoses: a prospective, randomized trial. A total of 145 consecutive patients receiving a colorectal anastomosis were randomized to 'test' or 'no test' once the anastomosis had been completed. Anastomotic testing was performed with the pelvis filled with saline and the rectum distended by sigmoidoscopic insufflation of air. Any leaks demonstrated were oversewn. A water-soluble contrast enema was performed on the tenth postoperative day. Seventy-four patients were randomized to 'test' and 71 to 'no test' but one patient was withdrawn from each group leaving a total of 143 for analysis. The two groups were well matched for age, sex, diagnosis and operative details. Eighteen (25 per cent) air leaks were detected and repaired in the 'test' group. After operation there were three (4 per cent) clinical leaks in the 'test' group and ten (14 per cent) in the 'no test' group (Fisher's exact test, P = 0.043). There were eight (11 per cent) radiological leaks in the 'test' group and 20 (29 per cent) in the 'no test' group (P = 0.006). Intraoperative air testing and repair of colorectal anastomoses significantly reduces the risk of postoperative clinical and radiological leaks. 
1	Chondrosarcoma of bone in children. Chondrosarcoma of bone rarely occurs in children. This report analyzes the clinicopathologic features in a series of 47 patients with conventional chondrosarcoma who were less than 17 years of age. Of the 47 cases, 14 were from the Mayo Clinic files, and 33 were from our consultation files. Most of the lesions occurred in the trunk and upper ends of the long bones, with the humerus being the most frequent skeletal site. Twelve of the 47 tumors were secondary. The radiographic findings were the same as those seen in adult chondrosarcoma. Pathologically, the tumors were low grade. En bloc resection is the treatment of choice because of the high incidence of local recurrence with lesser surgical margins. Prognosis in childhood chondrosarcoma is no different from that in adult chondrosarcoma. None of the patients with follow-up data had metastasis. 
1	Magnetic resonance imaging of radiation optic neuropathy. Three patients with delayed radiation optic neuropathy after radiation therapy for parasellar neoplasms underwent magnetic resonance imaging. The affected optic nerves and chiasms showed enlargement and focal gadopentetate dimeglumine enhancement. The magnetic resonance imaging technique effectively detected and defined anterior visual pathway changes of radionecrosis and excluded the clinical possibility of visual loss because of tumor recurrence. 
5	Mechanical cardiopulmonary support for refractory cardiogenic shock. From February 1982 to February 1990, 38 patients (30 male patients and 8 female patients) ranging in age from 10 to 78 years (mean 49.4 years) have been supported with arteriovenous extracorporeal membrane oxygenation (ECMO) at St. Louis University Medical Center as a resuscitative system for cardiac arrest or cardiogenic shock. All patients were unresponsive to conventional resuscitative measures including an intraaortic balloon pump in 25 patients. Patients were resuscitated in the intensive care unit, cardiac catheterization laboratory, or the emergency department. Diagnosis varied from acute myocardial infarctions (12 patients), ischemic disease (15 patients), end-stage cardiomyopathy (7 patients), congenital heart disease (3 patients), or postoperative cardiac transplant graft rejection (1 patient). Three patients could not be resuscitated with ECMO because of low flow, but the remaining 35 (92%) achieved hemodynamic stability with ECMO flows greater than 2 L/min/m2. Duration of support ranged from 0.5 to 130 hours (mean 28 hours). Twenty-four patients were successfully weaned from ECMO support after coronary artery bypass (five patients), cardiac transplantation (two patients), or ventricular assist device insertion (eight patients), or with inotropic support (nine patients). Of the 14 patients not weaned, three were inadequately resuscitated, two had percutaneous transluminal coronary angioplasty while receiving ECMO, and nine were not candidates for further intervention. Nine (24%) patients were discharged and are long-term survivors. Our results indicate that resuscitative ECMO is useful for intervals of 12 to 24 hours and can best be applied with (1) patients younger than 60 years of age; (2) patients having acute events (failed percutaneous transluminal coronary angioplasty) amenable to surgical intervention; and (3) candidates for cardiac transplantation who could be switched to more sophisticated devices within 12 to 24 hours of ECMO insertion. With these criteria, ECMO, when used as a resuscitative system, can result in increased survival in selected patients with refractory cardiogenic shock or cardiac arrest. 
1	Glucocorticoids locally disrupt an array of positioned nucleosomes on the rat tyrosine aminotransferase promoter in hepatoma cells. Transcriptional activation by steroid hormones is often associated with the appearance of a DNase I hypersensitive site resulting from a local alteration of the nucleoprotein structure of the promoter. For the mouse mammary tumor virus long terminal repeat, a viral promoter under glucocorticoid control, a model has been proposed: the appearance of the hormonodependent DNase I hypersensitive site reflects the displacement of a single precisely positioned nucleosome associated with the glucocorticoid responsive elements. To determine if such a mechanism is of general relevance in transcriptional activation by steroid hormones, we have investigated the nucleosomal organization of the rat tyrosine aminotransferase promoter over a 1-kilobase region that contains the glucocorticoid regulatory target. This region displays a hormonodependent DNase I hypersensitive site. In the absence of hormone, micrococcal nuclease digestion of nuclei demonstrates the presence of positioned nucleosomes, with cutting sites centered around positions -3080, -2900, -2700, -2800, -2255, and -2040. Treatment of the cells with dexamethasone induces a disruption of the chromatin structure over a relatively short stretch of DNA (approximately positions -2400 to -2650) that overlaps two nucleosomes. These observations suggest a strong similarity in the role of chromatin structure in glucocorticoid-dependent transcriptional activation of mouse mammary tumor virus and tyrosine aminotransferase promoters. 
3	A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the Log IgG-Index. A comparison and diagnostic applications. Cerebrospinal fluid and serum immunoglobulin G from 1007 patients with suspected neurological disease were analysed by 2 methods: isoelectric focusing for the detection of oligoclonal banding, and quantitative measurement of IgG and albumin for the formulation of a Log IgG-Index. A comparison of the 2 methods in the detection of local synthesis of IgG showed that isoelectric focusing not only gave a much higher yield overall, with 282 patients showing local synthesis versus 225 for the Log IgG-Index, but also a higher specificity, with a false positive rate of 0% versus 3.5%. In addition, of the 282 patients positive by isoelectric focusing only 163 (58%) were positive by the Log IgG-Index. Of the 1007 patients studied, 206 had multiple sclerosis (MS), and isoelectric focusing showed local synthesis in 95% of clinically definite cases, with a 90% detection rate overall. The Log IgG-Index was positive in only 67% of clinically definite cases, with an overall 59% detection rate. Thus with the exceptions noted above, local synthesis of IgG as defined by isoelectric focusing is confined to demyelinating, inflammatory, infectious and postinfectious disorders. Our results compare very favourably with the published sensitivities of magnetic resonance imaging in the detection of abnormalities in multiple sclerosis, and better than those for evoked potentials. Where both these investigations are readily available isoelectric focusing provides a useful adjunct. For the majority of physicians and neurologists who do not have ready access to magnetic resonance imaging, isoelectric focusing is an excellent alternative. We would also recommend that it become the standard for the measurement of IgG abnormalities in the cerebrospinal fluid and that the use of quantitative data be abandoned for routine purposes. 
4	The incidence of myocarditis in endomyocardial biopsy samples from patients with congestive heart failure. We present the combined experience of three Yugoslavian cardiovascular centers in the application of endomyocardial biopsy for the diagnosis of myocarditis in patients who present clinically with congestive heart failure. The study group comprised 107 patients (mean age, 40.8 years; range, 19 to 61 years). On the basis of patient history and diagnostic tests, the following clinical diagnoses were established: dilated cardiomyopathy (85), myocarditis (16), and alcohol-induced heart disease (6). EMB samples were taken from the left ventricle (95) or both ventricles (12) by use of a King's College bioptome, with a mean of 3.2 samples per patient. Histologic evidence of myocarditis was noted in 10 of 85 patients (12%) with a clinical diagnosis of dilated cardiomyopathy, in 2 of 6 patients (33%) with alcohol-induced heart disease, and in 12 of 16 patients (75%) with a clinical diagnosis of myocarditis. There was confirmation of the clinically suspected diagnosis in 63% of cases, a change of diagnosis based on histology in 15% of cases, and nonspecific findings in 22%. However, useful information was obtained in 78% of the cases, and there was a 22% incidence of histologically proven myocarditis for the entire group. Our results indicate that endomyocardial biopsy is beneficial in determining the true incidence of myocarditis in patients with a clinical presentation of dilated cardiomyopathy. 
1	Peritumoral blood flow in intracranial meningiomas. Blood flow was measured in intratumoral tissue, the cerebral hemispheres and particularly in the peritumoral area of 12 patients with intracranial meningiomas using the stable xenon-enhanced computed tomographic scan. Tumor blood flow frequently showed a heterogeneous pattern of enhancement with high flow at the tumor periphery and a central area of hypoperfusion. Blood flow values were on average 28% lower in the peritumoral area than in the ipsilateral cerebral hemisphere. In individual cases, blood flow values in the peritumoral edematous area were very low. These findings suggest that the hypodense area surrounding meningiomas does not solely represent vasogenic edema, but may actually represent tumor pressure ischemia. 
4	The legal implications of dietary fats: risks of cardiovascular disease and the duty of food manufacturers. The arguments for a warning on foodstuffs open new ground in product liability. Some of the dangers of fat-laden foods have been apparent for many years and are widely known to the public. Other aspects of fat consumption, specifically hidden fats, such as saturated fats, have only recently been explored, and are known to a limited segment of the population at risk. Negligence and warranty theories are too narrow to encompass this situation, wherein the benefits and risks of a product are not well defined and not easily separable. Some warning about the dangers resulting from fat ingestion is necessary, but may be adequately dispensed by ingredient labeling. If consumers are aware of the potential for harm, then they are assuming a substantial portion of the risk. How risk-free can we, or should we, make our society? The marketplace is the appropriate venue for determining the acceptance of saturated-fat-containing products by our society. Clear and open labeling policies will allow consumers to weigh the relative advantages and disadvantages of lower fat intake. Warnings of fat content need not be extreme, but should disclose the possible physiological outcome of the heavy ingestion of saturated fat. 
5	Might free arterial grafts fail due to spasm? The rat femoral artery was used as a free graft and was studied after 2, 7, 14, 30, and 60 days. The patency of the grafts was 100% (2 days, n = 6), 78% (7 days, n = 9), 63% (14 days, n = 8), 33% (30 days, n = 12), and 18% (60 days, n = 11). Histology showed an intimal thickening after 14 days and the media, which in the controls consisted of eight to ten layers of myocytes, was reduced to six to eight cell layers. During the first 2 weeks the graft segments had an impaired contraction when exposed to Krebs solution with 124 mmol/L K+, whereas after 1 month and later the graft segments approached the controls or had even higher contractile force. The thromboxane mimic U-46619 elicited full contractile force at all times whereas the potency was significantly lower during the first 14 days. Noradrenaline was unable to induce contraction in the graft segments during the first 14 days, but at 30 and 60 days it had regained full contractile force and was significantly more potent (approximately 60 times) in the graft segments compared with the controls. This study suggests that intimal thickening and hypercontractility might be a problem in free muscular arterial grafts. 
1	Anti-tumor X anti-lymphocyte heteroconjugates augment colon tumor cell lysis in vitro and prevent tumor growth in vivo. Cross-linking an anti-tumor antibody, specific for tumor cell surface antigens, and an anti-lymphocyte antibody, specific for the T lymphocyte receptor complex (TCR/CD3), produces a heteroconjugate that can direct T cells to lyse tumor cells. We tested the ability of anti-tumor X anti-lymphocyte (CD3) heteroconjugates to redirect human peripheral blood lymphocytes (PBLs) to lyse human colon cancer cells in cytotoxicity assays and in a murine colon tumor model. We demonstrated in vitro, that cultured human PBLs alone produced low levels of tumor lysis, but PBLs treated with anti-tumor X anti-CD3 heteroconjugates produced significantly greater tumor cell lysis (P less than 0.0025). Similarly, nude mice injected with LS174T human colon cancer cells and treated with cultured human PBLs and anti-tumor X anti-CD3 heteroconjugates survived significantly longer than saline control mice (P less than 0.01), or mice treated with PBLs alone (P less than 0.01), or heteroconjugates alone (P less than 0.05). F(ab')2 heteroconjugates were equally as effective in prolonging animal survival, but irrelevant heteroconjugates and monoclonal anti-tumor antibodies showed no therapeutic benefit. Anti-tumor X anti-CD3 heteroconjugates may represent an effective approach to tumor-specific cellular immunotherapy. 
4	The syndrome of bilateral hemispheric border zone ischemia. Symptoms compatible with vertebrobasilar ischemia have been reported in patients with unilateral or bilateral carotid occlusive disease. Intracranial steal phenomena have been proposed to explain the symptoms. In a review of 54 patients with angiographically documented severe bilateral carotid stenosis (less than or equal to 2 mm residual lumen) or occlusion, eight had symptoms suggesting vertebrobasilar insufficiency. Five patients were identified retrospectively, and the other three were evaluated prospectively. Symptoms included various combinations of hemodynamically mediated, transient bilateral motor, sensory, or visual impairment. Dysarthria, dysphagia, and diplopia were generally absent. Each patient also described additional symptoms compatible with transient hemispheric or retinal ischemia. The anatomic regions subserving the bilateral vertebrobasilar-like symptoms could be correlated with angiographically estimated arterial border zones in both hemispheres and may thus represent bilateral hemispheric border zone ischemia rather than brain stem ischemia. An intracranial steal need not be invoked. 
5	Traumatic asphyxia. Traumatic asphyxia is a distinctive clinical syndrome characterized by cervicofacial cyanosis and edema, multiple petechiae, and subconjunctival hemorrhage after a severe crush injury of the thorax or of the upper part of the abdomen. A case of traumatic asphyxia is reported, and its clinical and pathophysiologic features are discussed. 
1	Combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap for the repair of wide defects of the lower leg. The tensor fasciae latae musculocutaneous flap has great advantages for reconstruction of the abdominal wall, but the medial border of its territory is limited to the thigh. In order to expand the territory, a combined tensor fasciae latae musculocutaneous flap and sartorius musculocutaneous flap was devised. This flap was successfully used to resurface a large defect in the lower leg as a distally based musculocutaneous flap. The advantages of this flap are its extremely large territory, the fact that total necrosis of the flap cannot occur, and that as a proximally or distally pedicled flap it is suitable for large defects in the abdominal wall, lower leg, and gluteal region. 
5	Pelvic resections: the Rizzoli Institute experience. Materials, methods, and techniques of pelvic resections are discussed. Results, including the complications of nerve damage, infection, and vascular, visceral, and reconstructive complications are tabulated. 
5	The use of internalised ureteric stents in renal transplant recipients. Since 1982, we have used internal indwelling ureteric stents for the management and prevention of ureteric reconstruction complications in 28 renal allograft recipients. A total of 30 stents were placed in 18 patients either diagnostically or therapeutically in the management of allograft ureteric obstruction. In 16 patients internal stents were placed at the time of reconstruction for primary ureteropyelostomy (3), secondary ureteropyelostomy (8), repeat reimplant (3) and repair of ureteric or pelviureteric junction injury (2). Complications included 3 episodes of transplant pyelonephritis, proximal stent migration (1), persistent bacteriuria (1) and prolonged healing of a ureteropyelostomy (1). Internalised ureteric stenting is a safe and effective means of managing or preventing ureteric reconstruction complications in renal transplant recipients. 
4	Usefulness of the automatic implantable cardioverter defibrillator in improving survival of patients with severely depressed left ventricular function associated with coronary artery disease. Clinical outcome was analyzed among a group of 39 consecutive patients with coronary artery disease, left ventricular (LV) ejection fractions less than 30% and arrhythmias that required an automatic implantable cardioverter defibrillator (AICD) in an attempt to better define the role of the device in patients with severely depressed LV function. Twenty-nine (74%) were survivors of out-of-hospital cardiac arrest and 10 (26%) had ventricular tachycardia that was refractory to electrophysiologically guided antiarrhythmic therapy. The study group had the following demographic characteristics: 90% were men, mean age was 64 years (range 41 to 79) and mean LV ejection fraction was 21 +/- 4%. Concomitant pharmacotherapy included antiarrhythmic drugs 31 (79%), vasodilators in 22 (56%) and digoxin in 20 (51%). There was no statistical difference in baseline characteristics between survivors and nonsurvivors. Patients were followed for a mean of 24 months (range 2 to 72) from implantation. The difference between actuarial survival--77% at 1 year and 72% at 2 years--and projected survival without the AICD (patients who survive without appropriate device discharge)--30% at 1 year and 21% at 2 years--was significant (p less than 0.01 and less than 0.05 at 1 and 2 years, respectively). This study suggests that the AICD improves survival in patients with coronary artery disease despite severely depressed LV function. 
3	Bacterial meningitis in adults. Bacterial meningitis continues to be an important cause of morbidity and mortality despite the availability of effective bactericidal antibiotics. Penicillin or ampicillin remains the drug of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third generation cephalosporins have revolutionized the treatment of gram-negative meningitis. Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease. 
1	Presence of identical mitochondrial proteins in unstimulated constitutive steroid-producing R2C rat Leydig tumor and stimulated nonconstitutive steroid-producing MA-10 mouse Leydig tumor cells. The acute regulation of steroidogenesis in steroidogenic tissues requires de novo protein synthesis. It is believed that these newly synthesized proteins are instrumental in the delivery of the substrate, cholesterol, to the inner mitochondrial membrane where the cholesterol side-chain cleavage complex converts cholesterol to pregnenolone. A number of studies have attempted to characterize the protein(s) synthesized in response to hormone stimulation and, hence, function in the delivery of cholesterol to the cholesterol side-chain cleavage complex. While a number of potential protein candidates have been described, there is at present no unequivocal evidence which indicates that they are involved in steroidogenic regulation. We and others have described proteins that are induced in a variety of steroidogenic tissues in response to hormone stimulation and are localized in the mitochondria of these tissues. In an attempt to determine whether these induced proteins may be involved in steroidogenesis, we compared mitochondrial protein profiles in two separate Leydig tumor cell line. One cell line, the MA-10 mouse Leydig tumor cell line, has a very low basal steroid production, but synthesizes large amounts of progesterone in response to both tropic hormone and cAMP analog. The other cell line, the R2C rat Leydig tumor cell line, produces constitutively large amounts of progesterone, which cannot be increased further with hormone stimulation. Two-dimensional polyacrylamide gel electrophoresis profiles of newly synthesized mitochondrial proteins demonstrated that four 30-kDa proteins are induced in response to hormonal stimulation in MA-10 cells. Further, it was shown that proteins identical to these induced proteins are present constitutively in the mitochondria of R2C cells and cannot be further increased with hormone stimulation. These results strongly suggest that the 30-kDa mitochondrial proteins shown to be induced in several steroidogenic tissues are involved in the acute regulation of steroid production. 
3	Randomised, double-blind, placebo-controlled trial of nimodipine in acute stroke. Trust Study Group. The value of oral nimodipine 120 mg per day for acute stroke was assessed in a randomised, double-blind, placebo-controlled multicentre study of 1215 patients. The primary end-point was independence after 6 months, defined as a score of 60 or more on an activities of daily living (ADL) scale, the Barthel index. Patients were entered into the trial if they were aged over 40, became hemiparetic in the previous 48 h, were conscious, were able to swallow, and had been living independently before the stroke. At 6 months, 55% of the nimodipine group and 58% of the placebo group were independent, the odds ratio for independence on nimodipine being 0.88 (95% confidence limits 0.70-1.10). For mortality the odds ratio with nimodipine was 1.22 (95% confidence limits 0.95-1.57). ADL and neurological scores also suggested delayed recovery in the nimodipine group at 3 weeks. The results do not support the case for oral nimodipine therapy 120 mg per day starting within 48 h of the stroke, for patients with acute stroke. 
5	U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. rev-regulated expression of HIV-1 envelope proteins from a simian virus 40 late replacement vector was found to be dependent on the presence of a 5' splice site in the env mRNA in spite of the fact that this mRNA remains unspliced. When the 5' splice site upstream of the env open reading frame was deleted or mutated, expression of envelope protein was lost. RNA analysis of cells transfected with 5' splice-site mutants showed a dramatic reduction in the steady-state levels of env mRNA whether or not rev was present. Envelope expression could be restored in one of the 5' splice-site mutants by cotransfection with a plasmid expressing a suppressor U1 small nuclear RNA containing a compensatory mutation. These experiments show that U1 small nuclear RNA plays a direct and essential role in the formation of an unspliced RNA that is subject to regulation by rev. 
1	Renal cell carcinoma vs. renal oncocytoma. Report of a case with overlap features and review of the literature Although the salient features of renal oncocytomas and renal cell carcinomas have been discussed in the recent literature, renal masses with features of both entities will present diagnostic difficulty, especially when the cells are diffusely eosinophilic on microscopic examination. A case of a firm, tan, rounded mass replacing the lower pole of the kidney is discussed. The final diagnosis of renal cell carcinoma, granular cell type, was made after multiple sections of the tumor were examined, and after electron microscopy was performed. A thorough search by light microscopy should be made for clear cell foci, necrosis, mitotic activity, and vascular or capsular invasion, features generally accepted as pathognomonic for renal cell carcinoma. Cellular and especially nuclear pleomorphism is typically focal or mild in renal oncocytomas. True oncocytic tumors will be packed with mitochondria on electron microscopy; however, granular renal cell carcinomas will contain mitochondria as well as other cellular organelles, lipid, and glycogen. Electron microscopy should be performed on tumors suspected of being oncocytomas because eosinophilia on hematoxylin and eosin stain, as demonstrated by this case, is not a predictable measure of mitochondria content. Immunoperoxidase staining for vimentin in oncocytomas has recently been shown to be negative, and may offer a method of ruling out oncocytoma in vimentin-positive tumors, pending further studies. 
4	Delayed rupture of a pseudoaneurysm of the costocervical trunk: treatment with therapeutic embolization. Fourteen days after removal of an internal jugular catheter inserted prior to renal transplantation, a patient presented with brisk arterial hemorrhage from the insertion site. The hemorrhage, caused by a ruptured pseudoaneurysm of the costocervical trunk, was controlled by transcatheter embolization with gelatin particles. One year later the patient reported no problems related to the pseudoaneurysm or its management. 
1	Simple technique for long term central venous access in the patient with thrombocytopenic carcinoma. A technique for the insertion of a central venous access device in the patient with thrombocytopenia is described. Using the Seldinger technique, a wire is placed into the internal jugular vein. A catheter tunneled from the anterior part of the chest is inserted through a peel-away sheath into the central venous system. The incision is then closed. 
4	Hypertensive heart disease in African-Americans. Hypertensive heart disease is a frequent complication in hypertensive African-Americans because of inadequate high blood pressure control. Moreover, African-Americans may be predisposed to develop LVH earlier in life and more readily than Caucasians, and it may be more malignant. The appearance of both LVH and congestive heart failure are ominous developments in individual patients, and early detection of LVH is mandatory for adequate management and reversal of this complication, if possible. Additional research is needed, and new, sensitive tools for detecting LVH will accelerate such studies. Further investigations are also needed on the reversibility of LVH, preferred antihypertensive agents for accomplishing reversal, and whether expected benefits result. 
3	Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank. The outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank (TCDB). Of 300 eligible survivors, the quality of recovery 1 year after injury was assessed by at least the Glasgow Outcome Scale (GOS) in 263 patients (87%), whereas complete neuropsychological assessment was performed in 127 (42%) of the eligible survivors. The capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the GOS score at the time of hospital discharge. The neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing. In contrast, language and visuospatial ability recovered to within the normal range. The lowest postresuscitation Glasgow Coma Scale (GCS) score and pupillary reactivity were predictive of the 1-year GOS score and neuropsychological performance. The lowest GCS score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation. Notwithstanding limitations related to the scope of the TCDB and attrition in follow-up material, the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head-injured patients. 
2	Ichthyosis, exocrine pancreatic insufficiency, impaired neutrophil chemotaxis, growth retardation, and metaphyseal dysplasia (Shwachman syndrome). Report of a case with extensive skin lesions (clinical, histological, and ultrastructural findings). The Shwachman syndrome comprises exocrine pancreatic insufficiency, growth retardation, and bone marrow hypoplasia resulting in neutropenia. Clinical, morphological, and ultrastructural studies, as well as hair analysis, were performed in a patient with Shwachman's syndrome and severe ichthyosis. Clinical findings were lamellar ichthyosiform desquamation on the extremities. The hair was scanty and short on the scalp, in the eyelashes, and in the eyebrows. The nails were hyperkeratotic. Morphologic findings were slight, regular acanthosis and severe diffuse hyperkeratosis with variable parakeratosis. The granular layer was thickened. The papillary dermis showed very slight perivascular lymphocyte infiltration. The most prominent ultrastructural finding was the presence of solitary or multiple droplets of varying size in the cytoplasm of the keratinocytes. Hair analysis revealed no abnormalities; the cystine concentration in hair specimens was normal. 
5	Partial cytochrome b deficiency and generalized dystonia. An 18-year-old female had clinical features of idiopathic torsion dystonia with bilateral hypodense putaminal lesions on computed tomography. Mitochondrial encephalomyopathy was suspected because of persistent lactic acidemia and myopathy. Studies of oxidative metabolism on isolated skeletal muscle mitochondria revealed partial cytochrome b deficiency indicating a defect in the cytochrome b- c1 complex. This finding represents a unique, multisystem syndrome of progressive dystonia, putaminal degeneration, myopathy, and mitochondrial cytochrome b deficiency. Mitochondrial metabolic disorders may be a cause of torsion dystonia when other known associated factors are absent. 
1	Mortality among workers at Oak Ridge National Laboratory. Evidence of radiation effects in follow-up through 1984 [published erratum appears in JAMA 1991 Aug 7;266(5):657] White men hired at the Oak Ridge (Tenn) National Laboratory between 1943 and 1972 were followed up for vital status through 1984 (N = 8318, 1524 deaths). Relatively low mortality compared with that in US white men was observed for most causes of death, but leukemia mortality was elevated in the total cohort (63% higher, 28 deaths) and in workers who had at some time been monitored for internal radionuclide contamination (123% higher, 16 deaths). Median cumulative dose of external penetrating radiation was 1.4 mSv; 638 workers had cumulative doses above 50 mSv (5 rem). After accounting for age, birth cohort, a measure of socioeconomic status, and active worker status, external radiation with a 20-year exposure lag was related to all causes of death (2.68% increase per 10 mSv) primarily due to an association with cancer mortality (4.94% per 10 mSv). Studies of this population through 1977 did not find radiation-cancer mortality associations, and identical analyses using the shorter follow-up showed that associations with radiation did not appear until after 1977. The radiation-cancer dose response is 10 times higher than estimates from the follow-up of survivors of the bombings of Hiroshima and Nagasaki, Japan, but similar to one previous occupational study. Dose-response estimates are subject to uncertainties due to potential problems, including measurement of radiation doses and cancer outcomes. Longer-term follow-up of this and other populations with good measurement of protracted low-level exposures will be critical to evaluating the generalizability of the results reported herein. 
2	Blunt trauma of the abdomen in children. Abdominal trauma in children is usually due to motor vehicle accidents or falls, but child abuse is also a common cause. Injuries to the small intestine are particularly worrisome because symptoms may not appear for hours, days, or even weeks. This can cause significant difficulty for the investigator trying to determine when an injury occurred, or who may have caused it. 
4	Advantages of beta blockers versus antiarrhythmic agents and calcium antagonists in secondary prevention after myocardial infarction. Patients who have sustained greater than or equal to 1 myocardial infarcts are at high risk for sudden death or reinfarction; the risk is highest for those with lowest ventricular ejection fraction, continuing myocardial ischemia and asymptomatic high-density and complex premature ventricular contractions. At present, beta blockers when given prophylactically are the only agents that reduce the incidence of sudden death and reinfarction in survivors of myocardial infarction (MI) in the first 2 years. The beneficial effect was shown to correlate with a reduction in heart rate, the effect being absent or deleterious with beta blockers with marked sympathomimetic activity. The effects of beta blockers on ventricular fibrillation appeared to be dissociated from those on premature ventricular contractions. Trials with calcium antagonists indicate that these drugs had no effect or increased the mortality rate. The divergent effect of beta blockers and calcium antagonists is unexplained but may be due in part to a lack of bradycardiac effect of calcium antagonists; there were no differences in effect among different calcium antagonists. Data from trials involving class I antiarrhythmic agents indicate that agents acting by depression of cardiac conduction are either devoid of effect or produce a modest increase in mortality. Results of the Cardiac Arrhythmia Suppression Trial, employing the newer class I agents flecainide and encainide, were used to determine whether the suppression of premature ventricular contractions in the survivors of acute MI reduces mortality. Flecainide and encainide suppressed premature ventricular contractions greater than 80%, but resulted in an increased mortality rate undoubtedly due to a marked proarrhythmic effect. Whether these data can be extrapolated to all class I agents is uncertain. Preliminary data with class III antiarrhythmic agents suggest that these agents, especially amiodarone, similarly to beta blockers, have the potential to reduce mortality in survivors of MI. Evolving data suggest that in the secondary prevention of morbid events in the survivors of acute MI, the focus must shift away from antiarrhythmic agents that delay conduction and toward beta blockers and antifibrillatory actions resulting from a prolongation of refractoriness. 
1	Management of perineal wounds following abdominoperineal resection with inferior gluteal flaps. Our experience treating perineal wounds secondary to abdominoperineal resection, either for inflammatory bowel disease or cancer, is presented. A total of 16 patients were treated either on a delayed basis or at the same time as the abdominoperineal resection. All wounds were closed using the inferior gluteal myocutaneous flap. Fifteen of 16 patients have achieved healing, eight of whom had no complications. Only minor revisions or local wound care were required in the remaining patients, with only one patient failing to heal. Our results compare favorably with previous reports of treatment of this difficult problem. 
3	Assessment of Proplast-Teflon disc replacements [published erratum appears in J Oral Maxillofac Surg 1991 Feb;49(2):220] This retrospective study reports the findings in the follow-up of 31 temporomandibular joints in which Proplast-Teflon (Vitek Inc, Houston, TX) replacements were used. Among the problems noted were pain, malocclusion, restricted opening, and degenerative changes in the condyle and fossa. 
5	Adult hepatic fibropolycystic disease presenting as obstructive jaundice. Obstructive jaundice caused by compression of the common hepatic duct by a simple hepatic cyst in a 31 year old Europid man is reported. The jaundice and duct compression resolved after percutaneous aspiration of the cyst under ultrasound direction and the patient has been well for 12 months. 
3	Meningeal involvement in Bence Jones multiple myeloma. A case of Bence Jones kappa multiple myeloma with meningeal involvement in a 64-year-old woman is presented. Three years after the diagnosis of multiple myeloma, gait disturbances developed followed by visual disorders and impaired consciousness. A lumbar puncture revealed numerous atypical plasma cells in the cerebrospinal fluid. Craniospinal irradiation and intrathecal injections of methotrexate, cytarabine, and prednisolone were effective for a short period. At autopsy, the leptomeninges were infiltrated diffusely with atypical plasma cells. A review of the literature showed that multiple myeloma with meningeal involvement is accompanied frequently by circulating atypical plasma cells or plasma cell leukemia. Meningeal involvement is a rare complication and shows poor prognosis in cases of multiple myeloma. 
5	Reliability of six pulse oximeters in chronic obstructive pulmonary disease. Six pulse oximeters with finger probes were studied in three groups of 17 hypoxemic patients with COPD aged 50 to 75 years. Transcutaneous arterial oxygen saturation (SpO2) was measured with the Nellcor N101 (oximeter 1a), the Ohmeda Biox III (oximeter lb), the Nellcor N200 (oximeter 2a), the Critikon Oxyshuttle (oximeter 2b), the Radiometer Oxi100 (oximeter 3a), and the Ohmeda Biox 3700 (oximeter 3b). The SpO2 was compared with SaO2 measured in simultaneously withdrawn samples of arterial blood (Radiometer OSM2) at three 20-minute steady-state levels of FIO2 ranging from 0.21 to 0.40 (SaO2, 62 to 100 percent). The bias (mean SpO2-SaO2 difference) and the error in precision (SD of the differences) were both below 4 percent for instruments 1a and 1b and remained below 1.2 and 3 percent, respectively, for the others. A good agreement between SpO2 and SaO2, as reflected by the Bartko intraclass correlation coefficient, was observed in instruments 2a, 3a, and 3b. The individual relationships between SpO2-SaO2 differences and SaO2 appeared to be linear and parallel. With four instruments (1a, 1b, 2a, and 2b), the mean slope of this relationship was negative, showing a systematic instrumental error: the lower the SaO2, the larger the overestimation of SaO2. The scattering of the data (precision) principally reflects a subject source of error. In most instruments a technical adjustment could greatly improve instrumental errors and accuracy. The correction of the errors due to between-subject variation would require a system of calibration adjustable by the users to each individual. 
5	Nipple discharge in women. Is it cause for concern? Nipple discharge is one of the most common breast complaints in women. Galactorrhea (milky discharge) may occur during pregnancy or breast-feeding or as a result of drug therapy, hypothyroidism, or hyperthyroidism. Nonbloody discharge is most common and is usually benign. Bloody discharge should be considered a sign of cancer until proved otherwise. Persistent galactorrhea and nonbloody discharge can be treated by transecting the mammary ducts. Simple mastectomy may be appropriate in patients with persistent bloody discharge who have a strong family history of breast cancer. 
5	Flexion-extension views in the evaluation of cervical-spine injuries. STUDY OBJECTIVE: To determine the efficacy of flexion-extension (F/E) cervical-spine radiographs in detecting acute cervical-spine instability in emergency patients. DESIGN: We retrospectively reviewed the charts of 141 consecutive trauma patients who had F/E views performed after a routine cervical-spine series (three views) was obtained in the emergency department. Interpretations of the routine series were compared with those of the F/E views to determine if additional useful information was provided by the latter. The charts also were reviewed to determine if any variables were associated with an increased use of F/E views, an increased likelihood of these views demonstrating instability, or any neurologic sequelae resulted from these studies. SETTING: An urban Level I adult trauma center. MEASUREMENTS: The interpretations of the routine series were noted to be either normal, abnormal but without demonstrable fracture/dislocation, or demonstrating a fracture/dislocation. The F/E views were categorized as stable, unstable, or uninterpretable. RESULTS: Cervical-spine instability was demonstrated by F/E views in 11 of the 141 patients (8%), four of whom had normal routine cervical-spine films. Three of these four patients required surgical stabilization. Prolonged neck pain (more than 24 hours), an initially abnormal spine series, and a neurosurgical consult were all associated with an increased use of F/E views. Ten of 11 patients with radiographic instability had significant neck pain by history; the remaining patient was intoxicated. No neurologic sequelae resulted from performing F/E studies. There was one false-negative F/E study, which raises concern about the reliability of this procedure in the ED. CONCLUSION: We believe that a large prospective study is required to determine which patients warrant F/E views. 
1	Acinic cell carcinoma. Clinicopathologic review. The authors reviewed 90 cases of acinic cell carcinoma treated at the Mayo Clinic to assess long-term follow-up and to study features predictive of disease progression. Sixty-three patients (55 females and 35 males) were seen for primary treatment; 27 had recurrent disease when first evaluated. Histologically, these tumors were composed of serous acinar cells and intercalated duct-type cells. Morphologic patterns included solid, microcystic, follicular, and papillary-cystic. All patients were followed for at least 10 years or until death. Of the primary treatment group, 44% had local recurrence, 19% had metastasis, and 25% died of disease. Disease first recurred locally up to 30 years after presentation and resulted in death after as many as 38 years. Poor prognostic features include pain or fixation; gross invasion; microscopic features of desmoplasia, atypia, or increased mitotic activity; and excision as initial treatment. Neither morphologic pattern nor cell composition was a predictive feature. 
1	Fibrosarcoma of the head and neck. The UCLA experience. Between 1955 and 1987, twenty-nine patients with the diagnosis of fibrosarcoma of the head and neck were seen at the UCLA Medical Center. Follow-up ranged from 15 to 192 months, with a median of 66 months. Absolute 5-year survival was 62% (13/21). Five of 17 patients treated initially with surgery alone achieved local control and long-term survival. All five had low-grade lesions. Five patients received postoperative radiation therapy because of positive surgical margins. Three were rendered disease free, and all had low-grade lesions. Radiation therapy was used as primary treatment in six patients, four of whom received additional chemotherapy. Of these six, two are disease free with longer than 5-year follow-up. Surgery with and without adjuvant therapy successfully salvaged 42% (5/12) of the patients with local recurrence. Eighty percent (12/15) of the patients with low-grade lesions were ultimately rendered disease free vs only 8% (1/12) of the patients with high-grade histologic features. Seventy-two percent (13/18) of the patients with local recurrence were known to have positive surgical margins. Sixty-eight percent (13/19) of the patients with recurrent disease had high-grade lesions and/or tumor size larger than 5 cm. Tumor grade is the most important prognostic factor followed by tumor size and surgical margin status. Patients with low-grade lesions and adequate surgical margins are treated well with surgery alone. Patients with high-grade lesions or positive surgical margins should receive adjuvant treatment. 
1	Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. Recently purified and molecularly cloned monocyte chemotactic and activating factor (MCAF) may play a major role in recruiting and activating monocytes in the inflammatory process. We examined the effects of a potent anti-inflammatory agent, dexamethasone (DXS), on the production of this factor. Over a wide range of concentrations (10(-5) to 10(-8) M), DXS inhibited the production of MCAF at the mRNA and protein level in a human fibrosarcoma cell line, which was stimulated with either IL-1 or TNF-alpha. We examined the turn-over of synthesized MCAF mRNA that showed DXS decreased the stability of MCAF mRNA. Furthermore, the addition of actinomycin D and cycloheximide abolished this effect of DXS, indicating that de novo mRNA and protein synthesis were required for this process. In addition, a nuclear run-off analysis revealed that DXS also inhibited the transcription of IL-1- or TNF-activated MCAF genes. Therefore, both the destabilization of MCAF mRNA and the inhibition of transcription of the gene contribute to the decrease in the MCAF mRNA steady state level by DXS. 
3	Approach to diagnosis of meningitis. Cerebrospinal fluid evaluation. CSF evaluation is the single most important aspect of the laboratory diagnosis of meningitis. Analysis of the CSF abnormalities produced by bacterial, mycobacterial, and fungal infections may greatly facilitate diagnosis and direct initial therapy. Basic studies of CSF that should be performed in all patients with meningitis include measurement of pressure, cell count and white cell differential; determination of glucose and protein levels; Gram's stain; and culture. In bacterial meningitis, Limulus lysate assay and tests to identify bacterial antigens may allow rapid diagnosis. Where there is strong suspicion of tuberculous or fungal meningitis, CSF should also be submitted for acid-fast stain, India ink preparation, and cryptococcal antigen; unless contraindicated by increased intracranial pressure, large volumes (up to 40-50 mL) should be obtained for culture. If a history of residence in the Southwest is elicited, complement-fixing antibodies to Coccidioides immitis should also be ordered. Newer tests based on immunologic methods or gene amplification techniques hold great promise for diagnosis of infections caused by organisms that are difficult to culture or present in small numbers. Despite the great value of lumbar puncture in the diagnosis of meningitis, injudicious use of the procedure may result in death from brain herniation. Lumbar puncture should be avoided if focal neurologic findings suggest concomitant mass lesion, as in brain abscess, and lumbar puncture should be approached with great caution if meningitis is accompanied by evidence of significant intracranial hypertension. Institution of antibiotic therapy for suspected meningitis should not be delayed while neuroradiologic studies are obtained to exclude abscess or while measures are instituted to reduce intracranial pressure. 
1	E1a-dependent expression of adenovirus genes in OTF963 embryonal carcinoma cells: role of E1a-induced differentiation. Some undifferentiated F9 embryonal carcinoma cells allow adenovirus genes to be expressed independently of the E1a oncogene normally required for their activation; this has been attributed to a cellular equivalent of E1a in F9 cells. However, transcription of all early genes was low in undifferentiated OTF963 embryonic carcinoma cells during the first 48 hr after infection with adenovirus type 5 (Ad5). Transcription then increased to about the level seen 16 hr after infection of cells induced to differentiate by retinoic acid (RA) (referred to as RA-dF9 cells), but this increase did not occur in cells infected by the E1a deletion mutant dl312. Addition of E1a in trans, or of RA, had no immediate effect on viral transcription in OTF963 cells, but viral transcription increased about 48 hr after these additions. Ad5 induced transcription of several differentiation-specific genes in OTF963 cells with about the same kinetics as their induction by RA. These genes were superinduced in RA-dF9 cells by cAMP or infection by adenovirus. We suggest the small amount of E1a produced early in infection of OTF963 cells activates cellular genes, some of which are differentiation specific and required for efficient transcription of viral genes, so that E1a both induces and is induced by differentiation. The simple hypothesis of a cellular equivalent to E1a does not adequately explain the complex interactions between viral and cellular genes in OTF963 embryonic carcinoma cells. 
2	Multifocal colitis associated with an epidemic of chronic diarrhea. An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea. 
4	The role of lasers in hemorrhoidectomy. Eighty-eight patients who received treatment for hemorrhoids were randomized into two groups. Group A received the Nd-YAG laser phototherapy for internal hemorrhoid combined with the CO2 laser for external hemorrhoid. Group B was treated with closed Ferguson hemorrhoidectomy. The need of narcotic injections for pain relief was 11 percent in group A vs. 56 percent in group B (P less than 0.001). The incidence of postoperative urinary retention was 7 percent in group A, vs. 39 percent in group B (P less than 0.05). No enema was required postoperatively in group A, vs. 9 percent in group B; 84 percent of the patients in group A were discharged on the second postoperative day, vs. 83 percent of the patients in group B discharged on the fifth postoperative day. The cost was 20 percent less in the former group. The overall complications in both groups were insignificant in difference, except prolonged wound healing in group A was noted. One year follow-up showed satisfactory results. Laser treatment is considered one of the alternatives to conventional treatment, but the surgeon needs to be aware of laser hazards. 
4	Dietary calcium, vascular reactivity, and genetic hypertension in the Lyon rat strain. In order to examine the relationship existing between dietary calcium and the development of hypertension, we developed a long-term study in the Lyon hypertensive rat strain (LH) and two control strains, the Lyon normotensive (LN) and low blood pressure rats (LL) given enriched (HCa, 2.5%), deprived (LCa, 0.03%) and normal (NCa, 0.6%) calcium diets. Evolution of body weight, systolic blood pressure (BP), plasma calcium and magnesium was monitored from 4 to 23 weeks of age. Total cardiovascular reactivity and contractile response of isolated aorta to norepinephrine were measured at 23 weeks of age. LH rats on HCa diet failed to develop hypertension (BP less than 150 mm Hg) whereas LH rats on LCa diet exhibited higher blood pressure levels than their controls fed the NCa diet. Moreover, in LN rats HCa diet slightly decreased BP whereas LCa had no effect. In the LL rats, on the contrary, only LCa diet slightly increased BP. In vivo responsiveness to NE was significantly higher in LH compared to LL and LN rats fed a NCa diet. HCa and LCa diets both induced a significant decrease in this response in LH rats. HCa diet increased the response in LN rats but decreased it in LL. In contrast, at the same age, the in vitro contractile response of isolated aorta to NE was significantly decreased in LH compared to LN and LL rats receiving NCa diet. Moreover in LH and LN rats on HCa diet the contractile response was markedly increased but no significant difference was observed with LCa diet. 
2	Adenovirus colitis in the acquired immunodeficiency syndrome. Adenovirus was identified in colonic tissue by transmission electron microscopy or culture in 5 of 67 (7.4%) homosexual men seropositive for human immunodeficiency virus (51 with the acquired immunodeficiency syndrome) with diarrhea. Colonoscopy showed the mucosa to be normal in 3 cases and mildly inflamed in 2. Light microscopy showed foci of mucosal necrosis that contained chronic inflammatory cells and degenerating and necrotic epithelial cells with amphophilic nuclear inclusions. By transmission electron microscopy, hexagonal viral particles characteristic of adenovirus were identified within the inclusions. Only 1 patient was concomitantly infected by a second potential enteric pathogen. It was concluded that adenovirus, an uncommon enteric pathogen in immunocompetent adults, causes intestinal pathology and may be associated with diarrheal illness in persons with the acquired immunodeficiency syndrome. 
1	Prognosticators of second-look laparotomy findings in patients with epithelial ovarian cancer. Prognosticators of outcome at second-look laparotomy (SLL) were evaluated in 49 patients with epithelial ovarian carcinoma undergoing SLL. Residual tumor volume was found to be the most significant prognosticator of outcome, with initial tumor stage being of secondary importance. Grade of tumor played no role in outcome at SLL. The results of the study led us to the conclusion that the second-look procedure may be safely omitted in stage I patients. The importance of optimal cytoreduction during primary surgery was stressed. 
1	Renal cell metastases versus liver hemangioma. We present the case of a man with presumed metastatic renal cell carcinoma based on radiologic examination and weight loss, who refused treatment of any kind for one year. A surgical exploration to control hematuria revealed a Stage I tumor. 
1	Localization and peptide content of endocrine pancreatic tumors. Endocrine pancreatic tumors contain and frequently secret neurohormonal peptides. This phenomenon can be used as a diagnostic and classifying tool. This study analyzes 31 patients operated on because of an endocrine pancreatic tumor, including the diagnostic procedures and the localization methods. In 15 insulinoma cases only 6 patients had a positive arteriography, while all 11 selective pancreatic vein samplings were positive. The immunoreactivity showed that, besides insulin, most tumors also contained other peptides. Of four gastrinoma cases the arteriography was positive in three, but the selective vein sampling localized the tumor in all. The tumor's content of peptides showed mixed patterns. In the four glucagonomas, the arteriography was positive in all and the venous sampling performed in three of the cases also was positive. In five pancreatic polypeptide-containing tumors (PP-omas) the arteriography was positive in four and sampling performed in two was positive in both. In the PP-omas the peptide pattern showed that these tumors frequently contain several peptides. We used selective pancreatic vein sampling in 21 cases with positive result in all. In the cases in which arteriography was negative, the sampling results helped the surgeon to find the tumor. The peptide pattern in the tumors varied greatly and most tumors were multihormonal. 
5	Rectovulvar fistula in a child secondary to an unusual foreign body. Foreign bodies in the female genital tract are well recognized as a cause of pain, discharge, secretions, and infection. In the small child, the presence of a vaginal discharge is usually associated with either a common object which has been inserted or sexual abuse complicated by a sexually transmitted disease. A 3-year-old child presented with a recurrent labial secretion and drainage due to an unusual foreign body. It was only during a second operation that the possibility of a foreign body was entertained, and diagnostic testing was begun. A third operation permitted removal of the foreign body, a large bone probably of animal origin. The fistula tract was closed after a colostomy was performed. This represents the first reported case of a rectovulvar fistula not of a congenital nature. 
4	Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis. Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis. 
1	A three-dimensional system for long-term culture of human colorectal adenomas. Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression. Progress recently was reported in the development of monolayer culture systems. The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth. We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines. Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets. The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2. Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days. Cell viability was confirmed histologically by light and electron microscopy. The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes. Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma. Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%. A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo. This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma. 
5	Patients at risk for cardiac death late after aortic valve replacement. A total of 100 patients aged 24 to 78 years were screened prospectively a mean of 71 months after aortic valve replacement for the presence of left ventricular hypertrophy (LVH) on the ECG (Estes scores greater than or equal to 5.0) and for repetitive ventricular premature beats VPBs greater than or equal to 2 couplets/24 hr) during 24-hour Holter monitoring. During the subsequent 41-month follow-up (range 10 to 50 months), the yearly cardiac mortality rate was 1.3% in patients with LVH, 2.9% in patients with VPBs, and 8.0% in patients with LVH plus VPBs but only 0.6% when none of these factors was present (p less than 0.05 chi 2 test). The patient groups did not differ with regard to age, time elapsed since operation, underlying valve lesion, and coronary artery disease. Both LVH and VPBs occurred more frequently in patients with left ventricular dysfunction. We conclude that after aortic valve replacement cardiac mortality is markedly increased in patients with LVH and repetitive VPBs, since they are noninvasive markers of left ventricular dysfunction. 
5	Extrageniculate vision in hemianopic humans: saccade inhibition by signals in the blind field. The functional competence of extrageniculate visual pathways in hemianopic humans was demonstrated by showing that distractor signals in the blind half of the visual field could inhibit saccades toward targets in the intact visual field. This inhibitory effect of unseen distractors in patients occurred only when distractors were presented in the temporal half of the visual field, was specific to oculomotor responses, and did not occur in normal subjects. These results show that a peripheral visual signal activates retinotectal pathways to prime the oculomotor system and that these pathways can mediate orienting behavior in hemianopic humans. 
5	Disseminated Pneumocystis carinii infection with hepatic involvement in a patient with the acquired immune deficiency syndrome. Extrapulmonary infection with Pneumocystis carinii (P. carinii) in AIDS patients is uncommon, and is often described only at postmortem examination. Although most antemortem cases involve spread to the bone marrow or spleen, P. carinii involvement of other organs has only recently been described. Despite the frequency of liver enzyme abnormalities in AIDS patients with a history of P. carinii pneumonia, P. carinii has been observed only rarely in the liver. We present a well-documented case of P. carinii involving the liver in an AIDS patient with P. carinii pneumonia and progressive liver enzyme abnormalities. We suggest that P. carinii infection should be considered in the differential diagnosis of AIDS-related liver disease. 
5	Comparison of i.m. ketorolac trometamol and morphine sulphate for pain relief after cholecystectomy. I.m. ketorolac trometamol 30 mg was compared with morphine sulphate 10 mg after cholecystectomy in a double-blind, multiple dose, randomized study of 100 patients. Assessments of pain were made immediately after operation (day 1), and the next morning (day 2). Pain intensity (verbal response score and visual analogue scale) was recorded before injection and then over a 6-h period. Pain relief was assessed also. The effect of ketorolac on operative blood loss and platelet function was examined. Time to commencing oral intake and the duration of administration of i.v. fluids were recorded. Adverse events were noted. Ketorolac produced significantly less analgesia than morphine on day 1, but on day 2 the two drugs produced a similar effect. Blood loss was not increased by ketorolac, although platelet function was impaired. Repeated i.m. administration of ketorolac did not produce any serious adverse effects. 
1	Clinicopathologic and flow cytometric DNA study of medullary thyroid carcinoma. Sixty-one patients with medullary thyroid carcinoma were investigated to establish relationships between the neoplasm's DNA content, other clinicopathologic factors, and patient survival (at least 5 years' follow-up). There were 26 (42.6%) familial and 35 (57.4%) sporadic carcinomas. Forty-two neoplasms (68.8%) were diploid and 19 (31.2%) were aneuploid by flow cytometric assessment. In univariate analysis, age, hereditary background, DNA content, calcitonin immunoreactivity, and type of surgery were strong predictors of clinical outcomes. In multivariate regression analysis, none of these factors was an independent prognosticator. Patients' gender, clinical stage, histologic subtype, and amyloid content of the tumor did not influence survival. 
5	Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen. We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality. 
4	Recognition and embolic potential of intraaortic atherosclerotic debris. Atherosclerotic disease of the thoracic aorta is common in the elderly and patients with clinical coronary artery disease. Although embolization can occur from atherosclerotic debris within the thoracic aorta, it is not commonly considered in the differential diagnosis of the source of a systemic embolism. In the current study, the prevalence, clinical significance and embolic potential of intraaortic atherosclerotic debris as detected by transesophageal echocardiography was determined. Intraaortic atherosclerotic debris was identified in 38 (7%) of 556 patients undergoing transesophageal echocardiography. An embolic event occurred among 11 (31%) of the 36 study patients with intraaortic atherosclerotic debris. The incidence of an embolic event was higher when the debris was pedunculated and highly mobile (8 [73%] of 11 patients) than when it was layered and immobile (3 [12%] of 25 patients) (p less than 0.002). Among 15 patients undergoing an invasive procedure of the aorta, the incidence of embolism was 27%. In conclusion, in a patient with an embolic event, the thoracic aorta should be considered as a potential source. Transesophageal echocardiography can reliably detect intraaortic atherosclerotic debris, and when it is identified, an invasive aortic procedure should be avoided if possible. 
1	Mixed glioblastoma multiforme and sarcoma. A clinicopathologic study of 26 radiation therapy oncology group cases. Twenty-six cases are reported of gliosarcoma (GS) retrieved from a series of 1479 glioblastomas (GBM) that were part of five consecutive, randomized Phase II or III malignant glioma protocols initiated by the Radiation Therapy Oncology Group between 1974 and 1983. The clinicopathologic features of these 26 cases, including actuarial survival times, were compared with the remaining 1453 GBM. The minimal qualitative and quantitative histologic criteria required to diagnose GS are presented. In most cases the sarcomatous component was a malignant fibrous histiocytoma; a minority were fibrosarcoma. No significant differences between GS and GBM were found with regard to age, sex, pretreatment Karnofsky performance status, tumor location, size, median survival (8.3 and 9.6 months, respectively), and actuarial survival. None of the treatment regimens, which included various combinations of radiation therapy and chemotherapy, improved the survival of GS over GBM. Selective involvement of the temporal lobe by GS was not found, and the frequency of GS was determined to be only 1.8% of all GBM. 
5	Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus. Susceptibility to systemic lupus erythematosus is associated with major histocompatibility complex (MHC)--encoded genes. We have used nucleotide sequence analysis to better define the disease-associated MHC alleles. HLA-DR2, DQw1, and especially the rare allele DQ beta 1. AZH confer high relative risk (RR = 14) for lupus nephritis in a Caucasian population of patients. Pilot studies using historical controls suggest that these genes also confer a high risk in non-Caucasian ethnic groups (RR = 24-78). We have found that DR4 is significantly decreased in patients with lupus nephritis. Fifty percent of the patients with lupus nephritis had either the DQ beta 1.1, the DQ beta 1.AZH, or the DQ beta 1.9 alleles. These alleles share amino acid residues that have been predicted to be the contact points for antigen and the T cell receptor. These HLA alleles appear to have a direct role in the predisposition to lupus nephritis, whereas DR4 may have a "protective" effect. 
5	Helium-oxygen mixture in the treatment of postextubation stridor in pediatric trauma patients. OBJECTIVE: To assess the effectiveness of a helium-oxygen mixture in reducing post-extubation stridor in children hospitalized for burns or trauma. DESIGN: Randomized, controlled crossover trial. SETTING: Harborview Medical Center's Burn and Trauma ICUs from March to September 1989. PATIENTS: Children less than 15 yr old who were electively extubated and had symptoms of postextubation stridor, but required less than or equal to 35% oxygen. INTERVENTION: Each treatment (helium-oxygen and oxygen-supplemented room air) was given in random order for 15 min after extubation. MEASUREMENTS: Respiratory distress was assessed by a physician blinded to treatment order using a standard stridor score and clinical judgment. RESULTS: There were 13 children with 15 extubations; seven (47%) of 15 patients required subsequent treatment with racemic epinephrine or reintubation. Stridor scores were lower with helium-oxygen than with oxygen-supplemented room air (2.8 vs. 3.7, p less than .005), and helium-oxygen was preferred in eight of nine trials in which one treatment was clearly favored by the physician. CONCLUSION: Because helium-oxygen therapy can reduce stridor scores and is clinically preferred by physicians caring for stridorous children, it may be a useful adjunctive therapy in pediatric trauma patients with postextubation stridor. 
5	Seizure outcome from anterior and complete corpus callosotomy. Eighty patients underwent anterior corpus callosotomy for treatment of generalized seizures. The patients' mean age was 18.3 years (range 4 to 53 years); the mean age at seizure onset was 5.27 years (range 0.1 to 27 years). The mean intelligence quotient (IQ) of 41 testable patients was 71.12 (range less than 30 to 114). The seizure outcome was as follows: 13% were seizure-free, 65% were significantly improved, and 22% were unchanged. Ten patients subsequently underwent a second operation to complete the callosal sectioning which resulted in additional seizure improvement in only five of them. Five complications resulted from 90 operations: two epidural hematomas, one delayed subdural hematoma, one bone-flap infection, and one postcallosotomy disconnection syndrome; two patients died. A younger age at onset of seizures, a higher IQ, and generalized tonic-clonic, atonic, complex-partial, and mixed seizure types were associated with improved seizure outcome. 
3	Long-term follow-up of cemented total hip arthroplasty in rheumatoid arthritis. Seventy-five primary cemented total hip arthroplasties (THAs) were performed in 53 patients with rheumatoid arthritis and juvenile rheumatoid arthritis. All patients were followed for an average of 7.4 years, unless their prosthetic hips failed before that time. Clinical evaluation was based on a 10-point maximum rating scale, and ratings for pain, walking, function, and activity improved from preoperative values to the most recent follow-up examination. Revision THA was performed for aseptic acetabular loosening in four hips, and femoral loosening in one hip. Sepsis occurred in another four hips. Complications of wound healing occurred in 14 hips. Roentgenographic evidence of loosening was seen in six acetabular components, in three femoral components, and in the femoral and acetabular component of one hip; none of these hips have as yet required revision THA. The Kaplan-Meier survivorship analysis revealed a 93% survival probability at seven years, which fell to 77% at 12 years in these patients. A trend was that younger, larger patients had increased failure and component loosening rates. Cemented primary THA has been a satisfactory operation in the rheumatoid patient. The relatively high rate of wound healing problems and sepsis may be due to the systemic immune nature of rheumatoid arthritis; however, 25% of these prosthetic hips either failed or are at risk for future failure. Thus, improved techniques are still necessary to increase the long-term success of THA in the rheumatoid patient. 
3	Pain in children. The assessment and management of children's pain is a topic that has received a great deal of attention since the late 1970s. Nurse researchers have played a dominant role in all areas of pediatric pain relief and likely will continue to do so. There are currently a number of pediatric pain assessment instruments developed that are used in selected practice settings, but their use should be extended to document the existence of pediatric pain and its relief. Pharmacologic interventions for pediatric pain relief have been hampered by incorrect beliefs about analgesic risks, prescribing and administrating habits, and a virtual explosion of information in the area of analgesics. Although nurses have traditionally used nonpharmacologic interventions for pain relief, these methods have not been well researched. Continued research efforts in this important area will result in improved diagnosis and management of pediatric pain. 
5	Tamm-Horsfall autoantibodies in interstitial cystitis. Interstitial cystitis presents a diagnostic and therapeutic challenge. Although many etiologies, including autoimmunity, have been proposed its pathogenesis remains obscure. Tamm-Horsfall protein has been identified in the superficial urothelium of patients with interstitial cystitis demonstrating abnormal urothelial permeability. Eight patients with a clinical diagnosis of interstitial cystitis underwent cystoscopy and bladder biopsy. Characteristic cystoscopic findings were present, and each patient had chronic inflammation and mast cells by histopathological analysis. Preoperative anti-Tamm-Horsfall protein serum antibody (IgG) titers were determined by enzyme-linked immunosorbent assay (range 500 to 8,000, mean 2,750). A control group of 8 patients with a negative urological history also had titers of 0 to 500 (p = 0.02). The humoral response to Tamm-Horsfall protein in these patients suggests a role for Tamm-Horsfall protein in interstitial cystitis. Measurement of serum Tamm-Horsfall protein antibody may prove to be useful as a noninvasive diagnostic test in patients with this disease. 
5	Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now. 
5	Use of magnetic resonance imaging in the diagnosis of cortical blindness in pregnancy. Magnetic resonance imaging (MRI) may be helpful in the assessment of eclampsia and preeclampsia with central nervous system symptomatology such as cortical blindness. We describe a rare case of complete binocular blindness postpartum with no other neurologic deficits, in which MRI abnormalities were undetected on computed tomography. The better soft-tissue discrimination of MRI may visualize important but subtle lesions which ultimately may help to explain the underlying pathophysiologic mechanism in such cases. 
5	Plasma tumour necrosis factor alpha in cystic fibrosis. Plasma tumour necrosis factor alpha (alpha) concentration is increased in acute Gram negative sepsis, but the effect of chronic infection on plasma concentrations is unknown. A study was carried out in patients with cystic fibrosis to determine the effect of chronic lung infection with Pseudomonas aeruginosa on the plasma concentration of tumour necrosis factor and two other indicators of the inflammatory response, circulating C reactive protein and neutrophil elastase-alpha 1 antiproteinase complex (elastase complex). The concentration of immunoreactive tumour necrosis factor in plasma was greater than the upper 95% confidence interval for healthy subjects (2.6 U/ml) on 129 out of 189 occasions in 14 patients observed for about a year. The increase in tumour necrosis factor was associated with increased circulating C reactive protein and elastase complex. Twelve patients with an exacerbation of respiratory symptoms were studied before and after two weeks' treatment with anti-pseudomonal antibiotics. All three indicators of the inflammatory response fell after treatment, though median tumour necrosis factor (4.8 U/ml) and elastase complex (0.41 microgram/ml) concentrations remained above the upper limits for healthy subjects. During a period of clinical stability plasma tumour necrosis factor was increased in 10 of the 12 patients, elastase complex was increased in 10 of the 12, and C reactive protein was increased in seven. Increased plasma immunoreactive tumour necrosis factor was a feature of the near continuous inflammatory response to chronic P aeruginosa infection in cystic fibrosis and may be a factor contributing to the progressive lung destruction seen in this disease. 
3	Heritability of symptoms in an experimental model of neuropathic pain. Male and female rats underwent transection and ligation of the sciatic and saphenous nerves, and the development of autonomy was monitored. The deafferented animals were then interbred, always selecting males and females that expressed relatively high and, alternatively, relatively low levels of autotomy. Offspring were similarly operated and interbred. By the sixth generation of selective breeding, lines were achieved in which autotomy was consistently high (HA) or consistently low (LA). There was no indication of sex linkage. Thermal and mechanical nocifensive responsiveness co-selected with propensity to express autotomy following nerve injury: response thresholds were lower in HA than in LA rats. F1 hybrids formed by crossing homozygous HA and LA animals showed low levels of autotomy, similar to LA stock. This indicates recessive inheritance of the autotomy trait. Backcrossing F1 hybrids onto the LA line yielded a low autotomy phenotype in almost all cases; backcrossing F1 hybrids onto HA stock yielded about 50% high autotomy and 50% low autotomy. These ratios are consistent with simple mendelian inheritance of a single gene. Taken together, the data suggest that autotomy is inherited as a single-gene autosomal recessive trait. 
5	The validity of canine platelet aggregometry in predicting vascular graft patency. Several laboratories have found canine platelet aggregometry predictive of thrombotic potential in vascular grafts. Adenosine diphosphate (ADP) is a frequently used agonist, often at unspecified or differing concentrations. This study was designed to evaluate the predictive value of ADP-induced platelet aggregometry and the validity of the methodology. Platelet aggregometry in response to 2 x 10(-5) M ADP was assayed in 70 dogs. Twenty-six percent were aggregators, 51% were non-aggregators, and 20% were indeterminant. All dogs were then treated with aspirin and dipyridamole. Vascular prostheses were implanted bilaterally (aorto-iliac) and anti-platelet therapy continued for two weeks. Dose-response to ADP was studied at three concentrations in 20 dogs. At 2 x 10(-5) 1/20 aggregated, at 4 x 10(-5) 3/19 aggregated and at 2 x 10(-4) 15/20 aggregated. Time between samples and study was evaluated in 11 dogs, with 2/11 changing from non-aggregator to aggregator at two or three hours. Daily reproducibility was studied in 70 dogs, 14 of which changed aggregation status between days. Patency was 58/68 (85%) for non-aggregators, 23/34 (68%) for aggregators (p = 0.038). Platelet aggregometry has significant predictive value for graft patency but methodology must be specified and standardized. 
1	Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. The t(4;11)(q21;q23) chromosomal abnormality was identified in 40 (2%) of 1,986 children with newly diagnosed acute lymphoblastic leukemia (ALL). This translocation was associated with female sex (63%), age less than 1 year (60%), hyperleukocytosis (median leukocyte count, 156.5 x 10(9)/L), CD10-/CD19+ B-precursor cell immunophenotype, and myeloid-associated antigen (CD15) expression (63%). Nearly all cases had at least some CD24- blast cells. The CD10-/CD15%/CD19+/CD24/+ phenotype was found in 20 of the 32 t(4;11) cases tested. None of the 40 cases had the cytogenetic finding of hyperdiploidy greater than 50, which is a favorable prognostic feature. For clinical comparison, the t(4;11) cases were divided into three groups according to age at diagnosis: less than 1 year (n = 24), 1 to 9 years (n = 8), and greater than or equal to 10 years (n = 8). Compared with older patients, infants were more likely to have initial central nervous system leukemia (P = .05) and less likely to have pre-B-cell ALL (P = .05). Complete continuous remission has been maintained in only 7 of 24 infants and 2 of 8 patients aged greater than or equal to 10 years, in contrast to 7 of 8 children in the intermediate age group (P = .048). These findings suggest that the t(4;11) is an adverse prognostic feature in these two age groups. 
1	Effects of radiation therapy on skeletal growth in childhood. Ionizing radiation was used to treat childhood cancer long before the advent of chemotherapy, and it took little time for physicians to appreciate the deleterious effects it had on skeletal growth. The cause of this complication results predominantly from alteration of chondroblastic activity. This may stem directly from irradiation at the epiphyseal plate or indirectly from irradiation of glands that secrete growth-mediating hormones. The complication can go far beyond the obvious physical afflictions and extend into the psychologic domain, rendering deeper, more permanent scars. Presently, many of these effects are predictable, reducible, and treatable without compromising the cure that so often depends on the use of irradiation. Because of the complexities of childhood cancer therapy, strategies aimed at diminishing these effects are challenging. It is imperative that these effects be understood so that they can be reduced in current patients and prevented in future patients. 
5	Paralysis of saccades and pursuit: clinicopathologic study. We report a 73-year-old patient with an eye movement disorder characterized by paralysis of saccades and pursuit. At autopsy, there were small cortical lesions in the middle frontal gyrus immediately anterior to the precentral gyrus and in the inferior parietal lobule on both sides. 
2	Loss of duodenal folds allows diagnosis of unsuspected coeliac disease. We report three patients with coeliac disease who presented without the classic features of malabsorption and who underwent biopsy and were diagnosed only because of the endoscopic finding of the disappearance of Kerckring's folds in the descending duodenum. This sign constitutes a new and valid aid for the identification of patients with otherwise unsuspected coeliac disease. 
5	Outcome of renal transplantation after urinary diversion and enterocystoplasty: a retrospective, controlled study. A total of 17 patients with intestinal urinary diversion of enterocystoplasty underwent renal transplantation between 1970 and 1988. Patient age ranged from 4 to 35 years (mean age 20 years). The patients were divided into 2 groups. In group 1 (10 patients, 2 of whom required retransplantation) the ureter of the transplanted kidney was implanted into an ileal (7) or colonic (1) conduit or enterocystoplasty (2). In group 2 (7 patients, 1 of whom required a second transplant) the diversion was taken down and the transplanted ureter was implanted into the defunctionalized bladder. There were 14 living related and 6 cadaveric kidneys transplanted. Graft survival rates were 58 and 87% in groups 1 and 2, respectively, with an over-all rate of 70% (14 of 20 kidneys). There was no statistical difference in the graft survival rate between the 2 groups. The complications in group 1 included ureteroileal anastomotic leak (3 patients), ureteroileal stenosis (1), calculus formation (1), urosepsis (1), hyperchloremic metabolic acidosis (1), and wound infection and dehiscence (1). There were no complications in group 2. Renal transplantation into a pre-existing urinary intestinal conduit or augmented bladder does not statistically adversely affect patient or graft survival. However, the complication rate is much higher when the ureter is implanted into an intestinal segment. Therefore, it is preferable whenever possible to implant the ureter into the native bladder. 
5	Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. A patient is described who has features of Pearson syndrome and who presented in the neonatal period with a hypoplastic anemia. He later developed hepatic, renal, and exocrine pancreatic dysfunction. At the age of 5 years he developed visual impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia, and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 4.9 kb. The deleted region was bridged by a 13-nucleotide sequence occurring as a direct repeat in normal mtDNA. Both Pearson syndrome and Kearns-Sayre syndrome have been noted to be associated with deletions of mtDNA; they have not previously been described in the same patient. These observations indicate that the two disorders have the same molecular basis; the different phenotypes are probably determined by the initial proportion of deleted mtDNAs and modified by selection against them in different tissues. 
1	Continent ileocolonic urinary reservoirs for filling and lining the post-exenteration pelvis. Pelvic exenteration has a high complication rate due, in large part, to the extensive raw surfaces and dead space it creates. Numerous techniques have been used to control this space and line these surfaces, but none, to date, has proven to be a reliable solution. We investigated the use of continent ileocolonic urinary reservoirs as a new "flap" to fill and line the pelvis in 17 patients, and found that our historical complication rate of 44% for pelvic exenteration was reduced to 18%. These reservoirs appear to be an improved method of managing the post-exenteration pelvis. 
5	Emergency intraosseous infusion in severely burned children. Severely burned patients require rapid administration of large volumes of isotonic fluids. Obtaining adequate intravenous (IV) access in children with greater than 70% total body surface area burns may be difficult, time-consuming, and sometimes impossible. This report describes the use of intraosseous infusion technique as a life-saving means of establishing IV access in two severely burned children. 
2	Evaluation of women with possible appendicitis using technetium-99m leukocyte scan. The authors evaluated the use of technetium-99m albumin colloid white blood cell (TAC-WBC) scan in women with possible appendicitis. One hundred and nine women underwent 110 TAC-WBC scans. One woman had a second scan on a separate admission and was considered two individual patients in the analysis. Twenty-six women had appendicitis, 10 of whom had a perforated appendix at surgery. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in 52 women (47%), nine of whom had appendicitis. Fifty-eight scans were read as positive or negative for appendiceal pathology. There were 16 true positives, 5 false positives, 36 true negatives, and 1 false negative. The predictive value of a positive scan was 76%, and the predictive value of a negative scan was 97%. The TAC-WBC scan was positive in 62% of patients with appendicitis and negative in 43% of the patients without appendicitis resulting in an overall accuracy of 47% in the 109 women. The main value of TAC-WBC scan in women with possible appendicitis is its high negative predictive value and the main problem with the TAC-WBC scan is its high indeterminate rate. 
1	Small cell lung cancer: staging with MR imaging. Small cell lung cancer is an aggressive neoplasm; metastases are detected in two-thirds of patients at diagnosis with use of conventional staging, which includes bilateral bone marrow biopsy, bone scintigraphy, and computed tomography (CT) of the head and abdomen. In 25 patients, small cell lung cancer was staged prospectively with both conventional staging and a magnetic resonance (MR) imaging protocol that included 1.5-T MR imaging of the pelvis, abdomen, spine, and brain. According to conventional staging, 14 patients had extensive disease and 11 patients had limited disease; according to staging with MR, 19 patients had extensive disease and six had limited disease. All metastatic disease sites seen with conventional staging were identified on MR images. MR images showed additional metastatic involvement in bone (four patients) and liver (three patients) not detected at conventional staging. A low-attenuation hepatic lesion on a CT scan was identified as a hemangioma on MR images. These preliminary data suggest that small cell lung cancer may be accurately staged with use of a single MR imaging study. 
1	The use of cytochemical procedures in the diagnosis and management of acute and chronic myeloid leukemia. The use of Wright-Giemsa-stained smears alone for the classification of acute leukemias often proves unsatisfactory. Some cases of M1, M5a, M7, and L2 are morphologically similar. In such cases, cytochemical stains can provide an inexpensive and available diagnostic tool. M1 is positive for SBB and MPO. M5a is usually NSE positive, whereas SBB and MPO are negative. M7 usually is ANA esterase, PAS, and AP reactive, and do not stain with SBB, MPO, and ANB esterases. The megakaryocytic lineage usually is confirmed by ultrastructural cytochemistry for PPO or immunocytochemistry for platelet glycoproteins and von Willebrand factor. PAS block positivity and AP dotlike reactivity are suggestive of lymphoid lineage. NSE stains are useful in differentiating M2 from M4. Morphologic and cytochemical techniques also can suggest the presence of certain chromosomal abnormalities such as t(8;21) and inv(16), which may have an influence on prognosis. Because not all cases of acute leukemia are easily subtyped by morphology and cytochemistry, immunophenotyping, karyotyping, and molecular analysis of DNA and RNA of leukemia cells also may be required to define cell lineage. 
5	The Caspar microsurgical discectomy and comparison with a conventional standard lumbar disc procedure. The outcome in 119 patients who were operated on with a conventional standard lumbar discectomy procedure was retrospectively compared with that in 299 patients who were operated on with a microsurgical discectomy technique developed in Homburg/Saar, Federal Republic of Germany by the senior author (W.C.). All patients in this consecutive series had "virgin" lumbar radiculopathy evaluated and operated upon by two experienced surgeons at one institution. Determination of the final outcome was made objectively by an impartial third party using identical criteria for both groups, and with a patient self-evaluation form. The study looked at various pertinent aspects of the treatment course and at final outcome. The results in the microsurgical group were significantly favorable: fewer levels were explored: there was less operative blood loss and a decreased incidence of deep venous thrombosis, urinary tract infections, pulmonary emboli, and bladder catheterization; the time to full ambulation, discharge, and return to work was faster: and there was a decrease in change of occupation and a greater percentage of satisfactory final outcomes, as measured both objectively and subjectively. A description of the microsurgical technique used in this study, which differs significantly from existing microdisectomy techniques, is presented. The authors conclude that the microsurgical disectomy technique presented in this study is a safe and effective approach to the treatment of lumbar radiculopathy. 
4	Fibrosing mediastinitis with coronary artery involvement. This case report describes a patient with chronic fibrosing mediastinitis involving the entire intrapericardial aorta, innominate artery, and the base of the heart with involvement of the proximal segments of the coronary arteries. This finding was unsuspected before emergency coronary artery bypass grafting. Coronary stenosis due to fibrosing mediastinitis is a rare complication of fibrosing mediastinitis. Owing to the extensive fibrosis, the normal bypass, cardiac preservation, and revascularization techniques required alteration and are discussed. 
5	Managing geriatric arrhythmias, II: Drug selection and use [published erratum appears in Geriatrics 1991 Jun;46(6):100] Age-related impairments in antiarrhythmic drug distribution, metabolism, and excretion may result in accumulation of these potent drugs, increasing the risk of adverse drug reactions and drug interactions in the elderly. These risks are minimized by using modest initial dosage with slow dosage titration. Therapeutic drug monitoring is a method which employs antiarrhythmic concentration data and a determination of drug clearance in order to develop an optimal dosing regimen. The pharmacology, indications for use, and adverse effects of currently available antiarrhythmics are reviewed. Dosing guidelines for the geriatric population are provided. 
4	(A)typical symptoms during single needle dialysis. In 5 elderly patients, an abnormally high occurrence of some symptoms was noted during dialysis. All patients were dialyzed with biocompatible membranes, bicarbonate dialysate, and a blood flow of 250 to 300 ml/min by a single needle system, on a fistula 14 Gauge catheter-needle. These symptoms were: 1) "angina," resistant to O2 and nitrates, with biochemical stigmata of infarction, but without electrocardiogram (ECG) localization; 2) intractable persistent hypotension, not hypovolemic, lasting 1 or 2 days; 3) esophagal spasms, with inability to swallow solid food. Because we knew that these symptoms were compatible with hemolysis (biochemically proven by the increase in serum LDH during dialysis and by a fall in haptoglobin) due to red cell fragmentation (RCF), we switched these patients from fistula dialysis (A) to central catheter dialysis (B), with the same apperture, blood flow, etc. The total number of sessions of A versus B were 512 and 891; the mean LDH ratios (serum LDH postdialysis divided by predialysis) were 1.8 and 1.0 (= no RCF); angina events were 132 (26%) for A, and 25 (3%) for B; persistent hypotension was seen 37 (7%) times in A and 5 (0.6%) times in B; esophagal spasms were noted 65 (13%) times for A, and 0 times for B. This clinical improvement was so overwhelming that 3 patients refused to be dialyzed again using their well functioning fistulae. This study also proved the need for a better designed and manufactured peripheral dialysis catheter-needle. 
4	Correlation of isomeric fatty acids in human adipose tissue with clinical risk factors for cardiovascular disease. The relationships between the adipose tissue concentrations of 19 geometric and positional fatty acid isomers and 10 cardiovascular disease risk factors were determined in 76 free-living adult males. The percentages for trans isomers (total mean +/- SD 4.14 +/- 0.97%) and cis isomers (total mean +/- SD 2.91 +/- 0.34%) in adipose tissue generally agreed with dietary estimates based on the consumption of hydrogenated oils. A major exception was the percentage of 11c-18:1, which was twofold higher in adipose tissue. The total level of fatty acid isomers in adipose tissue or a factor (derived by factor analysis) that was representative of isomers of dietary origin was not significantly correlated with the cardiovascular risk factors. Only three trans isomers (11t-18:1, 12t-18:1, and 5t-14:1) and three cis isomers (11c-18:1, 13c-18:1, and 7c-16:1) were weakly correlated either positively or negatively with age, body mass index, plasma and lipoprotein cholesterol, and/or blood pressure (P less than 0.05, r greater than 0.231). 
5	Recurrent herpetic keratitis: failure to detect herpes simplex virus infection using the Syva MicroTrak HSV1/HSV2 direct specimen identification/typing test. A 35-year-old man had developed recurrent herpetic keratitis characterized by dendritic keratitis at intervals of a year. We were able to culture cytopathic agents repeatedly from his lesions by inoculating Vero cells. The cultures yielded definitive evidence of a virus that caused a cytopathic effect within 3 days. However, these virus strains could not be identified as herpes simplex virus (HSV) in immunofluorescence assays using the Syva MicroTrak HSV1/HSV2 direct specimen identification/typing test. Rather they were identified as strains of HSV type 1 (HSV-1) on the basis of plaque morphology, neutralization tests, electron-microscopic examination and DNA restriction endonuclease analysis. Our results allow us to assume the existence of HSV-1 strains isolated clinically that are negative to analysis using the Syva Micro-Trak HSV1/HSV2 direct specimen identification/typing test. 
3	Buffered versus plain lidocaine as a local anesthetic for simple laceration repair. STUDY OBJECTIVE: Buffered lidocaine was compared with plain lidocaine as a local anesthetic for simple lacerations. DESIGN: Randomized, double-blind, prospective clinical trial. SETTING: Urban emergency department. TYPE OF PARTICIPANTS: Ninety-one adult patients with simple linear lacerations were enrolled. Patients with allergy to lidocaine and patients with an abnormal mental status were excluded. INTERVENTIONS: Each wound edge was anesthetized with either plain or buffered lidocaine using a randomized, double-blind protocol. The pain of infiltration was measured with a previously validated visual analog pain scale. MEASUREMENTS AND MAIN RESULTS: Analysis of pooled data and paired data (using patients as their own controls) revealed that infiltrating buffered lidocaine was significantly less painful than plain lidocaine (P = .03 and P = .02, respectively). There was no significant difference in the anesthetic effectiveness of the two agents during suturing. CONCLUSION: Buffered lidocaine is preferable to plain lidocaine as a local anesthetic agent for the repair of simple lacerations. 
1	Familial occurrence of gastric cancer in the 2-year experience of a population-based registry. The authors studied the familial occurrence of tumors in 154 individuals with gastric cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1986 through 1987 in the Local Health Care District of Modena, Italy, for cancer of the stomach. Crude and age-adjusted (world population) incidence rates of gastric cancer were 34.0 and 21.4 new cases/100,000/year, respectively, in men, and 24.5 and 10.9 in women, respectively. Among first-degree relatives of the registered patients there were 30 cases of gastric carcinoma versus 15 cases in a control group matched for age and sex (Mantel-Haenszel odds ratio [M-H OR] 3.14, P less than 0.01). This excess of gastric neoplasms was observed in siblings (17 versus 7, M-H OR 4.33, P less than 0.02) but not in parents (13 versus 8, not significant). Besides gastric cancer, there was no significant excess of other type of tumors in case families. The familial occurrence of gastric cancer tended to be more frequent in patients with "diffuse" carcinoma (52%) than in subjects with "intestinal" cancer (33%), although the difference was not statistically significant. In conclusion, the current investigation suggests that a "family history" for gastric neoplasms is usually observed in approximately 10% to 15% of the registered cases. As already described for other common malignancies, therefore, the familial occurrence of gastric carcinoma suggests the existence of a genetic susceptibility to cancer of the stomach, at least in a fraction of these patients. 
3	Internuclear ophthalmoplegia in the Chiari type II malformation. We describe 3 cases of Chiari type II malformation presenting with bilateral internuclear ophthalmoplegia (INO). Although prominent, the INO was not an isolated sign in any of the patients; superimposed abduction paresis was present in 2, and deficits in smooth pursuit, optokinetic nystagmus, and vestibulo-ocular responses were present in 3. Two had hydrocephalus: 1 was clinically unchanged without therapy after 5 years; the other did not improve with shunting. Findings in our 3 patients, along with the 4 previously reported, confirm that INO is 1 manifestation of widespread brainstem or cerebellar dysfunction. Its origin is probably multifactorial, related to hydrocephalus, vascular compromise, direct neuronal distortion, or congenital neural malformation. 
5	Topical silicone gel for the prevention and treatment of hypertrophic scar. We studied the effects of a silicone gel bandage that was worn for at least 12 hours daily on the resolution of hypertrophic burn scar. In a second cohort, the prevention of hypertrophic scar formation in fresh surgical incisions by this bandage was also evaluated. In 19 patients with hypertrophic burn scars, elasticity of the scars was quantitated serially with the use of an elastometer. An adjacent or mirror-image hypertrophic burn scar served as a control. Scar elasticity was increased after both 1 and 2 months compared with that in controls. There was corresponding improvement clinically that persisted for at least 6 months. In the other cohort, scar volume changes in 21 surgical incisions were measured before and after 1 and 2 months. Gel-treated incisions gained less volume than control incisions after both intervals. Clinical assessment corroborated this quantitative demonstration of a decrement in scar volume. We concluded that topical silicone gel is efficacious, both in the prevention and in the treatment of hypertrophic scar. 
4	Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn. Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension. 
1	Extrathoracic metastatic malignant thymoma. Diagnosis by aspiration cytology. A fine-needle aspirate from a hepatic mass in a 65-year-old white man was examined. The patient had a history of histologically confirmed thymoma with metastases in multiple thoracic sites. The smears showed a dimorphic population of epithelial cells and lymphocytes, characteristic of thymoma. The resemblance of the cytologic pattern to the primary neoplasm and positive reactivity with various immunohistochemical agents peculiar to thymomas confirmed the diagnosis. Aspiration cytology has been described in the diagnosis of primary thymoma. To our knowledge, this is the second reported case of a cytologic diagnosis of metastatic thymoma and the first one with immunohistochemical studies. 
5	MyoD induces growth arrest independent of differentiation in normal and transformed cells. MyoD is a gene involved in the control of muscle differentiation. We show that MyoD causes growth arrest when expressed in cell lines derived from tumors or transformed by different oncogenes. MyoD-induced growth inhibition was demonstrated by reduction in the efficiency of colony formation and at the single-cell level. We further show that MyoD growth inhibition can occur in cells that are not induced to activate muscle differentiation markers. The inhibitory activity of MyoD was mapped to the same 68-amino acid segment necessary and sufficient for induction of muscle differentiation, the basic-helix-loop-helix motif. Mutants with alterations in the basic region of MyoD that fail to bind or do not activate a muscle-specific enhancer inhibited growth; mutants with deletions in the helix-loop-helix region failed to inhibit growth. Thus, inhibition of cell growth by MyoD seems to occur by means of a parallel pathway to the one that leads to myogenesis. We conclude that MyoD is a prototypic gene capable of functionally activating intracellular growth inhibitory pathways. 
2	Achieving pH control in the critically ill patient: the role of continuous infusion of H2-receptor antagonists. Stress-related gastric mucosal damage is a common occurrence in intensive care unit (ICU) patients. Because of the significant morbidity and mortality associated with this mucosal damage, many ICU patients routinely receive prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs). Gastric acid secretion occurs in a circadian pattern, with late afternoon and evening surges. H2RAs by continuous infusion may control this uneven pattern of secretion more effectively than H2RAs given by bolus injection. More studies are needed to identify the target ICU population for prophylactic treatment. 
3	Familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex. A 55-year-old man with cerebellar ataxia and steatocystoma multiplex was found to have reduced serum concentrations of total cholesterol, betalipoprotein and apolipoprotein B. Computed tomography revealed atrophy of the cerebellum and brain stem. Of the six family members examined, four had hypobetalipoproteinaemia, and one had mild ataxia. Similar skin lesions were noted in five male relatives. This case represents a rare combination of familial hypobetalipoproteinaemia, cerebellar ataxia and steatocystoma multiplex. 
1	Invasive lobular carcinoma: mammographic findings in a 10-year experience From January 1, 1976 to December 30, 1985, 1,966 cases of breast carcinoma were diagnosed and treated at Malmo General Hospital, Malmo, Sweden. Of these cases, 185 (9.4%) involved invasive lobular carcinoma (ILC). Mammography in 137 cases demonstrated the following findings: spiculated opacity (53%), architectural distortion (16%), poorly defined opacity (7%), normal or benign findings (16%), and parenchymal asymmetry (4%). Radiographic definition of the ILC lesion varied greatly with projection: The craniocaudal view demonstrated significant findings more frequently than either the oblique or lateral views. Secondary radiographic findings were present in 31%, microcalcifications were rare, and physical findings were present in 89%. Because of its diffuse growth pattern and tendency to form lesions with opacity equal to or less than that of the parenchyma, ILC can be extremely difficult to detect mammographically. Therefore, the radiologist must be alert for subtle mammographic signs of malignancy and highly suspicious of any abnormal physical findings regardless of the mammographic appearance. 
3	An unusual complication of silastic dural substitute: case report. A case is presented in which a patient developed an unusual complication after the use of Silastic dural substitute. In 1983, the patient underwent removal of a meningioma with the involved dura. Five years later, he developed around the graft material a very thick connective tissue capsule, which simulated a recurrent meningioma clinically and radiologically. 
1	Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. There is no consistently reliable treatment for endocarditis resulting from chronic Coxiella burnetii infection, the causative agent of Q fever. Although certain antibiotics are recommended on the basis of their in vitro bactericidal activities, results of therapy with these antibiotics are often disappointing. To evaluate whether the currently recommended antibiotic susceptibility tests for C. burnetii give misleading results because of continued division of uninfected cells, thereby resulting in the dilution of infected cells and, hence, a false picture of antibiotic efficacy, we blocked cell division during antibiotic susceptibility testing with cycloheximide. Using this new method, we found that the currently recommended antibiotics for the treatment of Q fever, doxycycline, pefloxacin, and rifampin, did not reduce the ratio of infected to noninfected cells (either L929 or P388D1) by 9 days postinfection. To test the hypothesis that this lack of antibacterial activity is due to antibiotic inactivation by the low pH of the phagolysosomes in which C. burnetii is found, we used alkalinizing lysosomotropic agents (chloroquine or amantadine) concurrently with doxycycline. This resulted in the sterilization of C. burnetii infection in P388D1 cells. This finding seems to confirm our suspicion that the acidic conditions of the phagolysosomes in which C. burnetii is located inhibit antibiotic activity. This inhibition can be reversed in vitro when lysosomotropic alkalinizing agents are used. 
4	Bacterial endocarditis presenting as acute myocardial infarction: a cautionary note for the era of reperfusion. Coronary embolism is a known complication of bacterial endocarditis that sometimes causes acute myocardial infarction. The necessity for rapidly restoring coronary artery perfusion and the time constraints governing clinical decisions may prevent endocarditis from being diagnosed before pharmacologic or mechanical thrombolysis. This report describes the first documented cases of coronary angioplasty in two patients with acute myocardial infarction caused by bacterial endocarditis, and reviews the literature on coronary artery complications of bacterial endocarditis. The first patient developed a coronary artery mycotic aneurysm at the dilatation site; the second experienced a small intracerebral hemorrhage following reperfusion. It is, of course, unwise to generalize from two cases, but we believe that in patients who are most likely to have endocarditis as the cause of acute myocardial infarction, the impulse to follow conventional strategies for coronary reperfusion should be tempered by thoughts of possible consequences. 
5	Idiopathic intracranial hypertension. Although the cause of IIH remains obscure, loss of visual function is common, and patients may progress to blindness. Diagnosis should adhere to the modified Dandy criteria. Recent case-control studies cast doubt on the validity of many frequently cited conditions associated with IIH. Valid associations include obesity, recent weight gain, female sex, vitamin A intoxication, and steroid withdrawal. Management should include serial perimetry using a sensitive disease-specific strategy so the proper therapy can be selected and visual loss prevented or reversed. 
4	Alcohol consumption--a risk factor for hemorrhagic and non-hemorrhagic stroke. PURPOSE: The risks of alcohol consumption and its association with stroke were studied in 621 patients with stroke and 573 control subjects using case-control methods. PATIENTS AND METHODS: Patients with stroke were subdivided into 193 with subarachnoid hemorrhage, 91 with intracerebral hemorrhage, and 337 with cerebral infarction. Data on recent alcohol consumption were obtained by questionnaire in patients with stroke and compared with data from an occupational screening survey in control subjects. RESULTS: Relative risks, adjusted for confounding variables, exhibited J-shaped associations with increasing levels of alcohol consumption classified into four categories--abstainer, 1 to 90 g, 100 to 390 g, and greater than or equal to 400 g weekly). The individual risks were 1, 0.7, 0.5, and 1.3 for subarachnoid hemorrhage; 1.0, 0.6, 0.5., and 2.5 for intracerebral hemorrhage, and 1.0, 0.6, 0.7, and 2.4 for cerebral infarction for men and women combined. CONCLUSIONS: The results suggest that low levels of alcohol consumption may have some protective effect upon the cerebral vasculature, whereas heavy consumption predisposes to both hemorrhagic and non-hemorrhagic stroke. 
4	Depression after acute myocardial infarction. The role of primary care physicians in rehabilitation. Depression is a common problem after myocardial infarction. Diagnosis is facilitated by use of the criteria for depression in the Diagnostic and Statistical Manual of Mental Disorders and self-rating questionnaires. Treatment may involve both psychological and pharmacologic interventions. The patient's medical status must be carefully assessed before administration of antidepressant medication. All antidepressants are contraindicated immediately after myocardial infarction. When signs and symptoms of depression are exhibited early in the recovery phase, alprazolam (Xanax) may offer advantages over more traditional antidepressants. Further research is necessary to determine the safety of newer antidepressants. 
5	Dysplasia and DNA aneuploidy in a pelvic pouch. Report of a case. A patient with an 18-year history of ulcerative colitis was operated on with colectomy, mucosal proctectomy, ileoanal anastomosis, and an S-type pelvic pouch due to intractable chronic continuous disease. The patient was followed by endoscopic controls and biopsy sampling from the pouch at regular intervals. A gradual development of severe atrophy in the ileal mucosa was followed by the development of low grade dysplasia. At the most recent endoscopic control, 4 years after the construction of the pouch, biopsies were sampled also for flow cytometric DNA analyses. DNA aneuploidy was detected in a biopsy from the center of the pouch, and a biopsy taken immediately adjacent showed low grade dysplasia. These findings underline the importance of endoscopic follow-up after construction of a pelvic pouch and focus attention to the potential of malignant transformation of the mucosa. 
5	Perirenal candidial abscess. Perirenal candidial abscesses are rare, with few well-documented cases in the literature. We describe a case of a perinephric abscess treated with amphotericin B and nephrectomy. 
5	Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. The putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas. The bcl-2 gene product is not altered by the translocation, but its expression is deregulated, presumably by the Igh enhancer E mu. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress and thereby confer a growth advantage. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro but do not show a propensity for spontaneous tumorigenesis. In contrast, an analogous myc transgene, designed to mimic the myc-Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. E mu-bcl-2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than E mu-myc mice. Suprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell. 
4	Time delays in the diagnosis and treatment of acute myocardial infarction: a tale of eight cities. Report from the Pre-hospital Study Group and the Cincinnati Heart Project. To establish the magnitude of prehospital and hospital delays in initiating thrombolytic therapy for acute myocardial infarction, the time from telephone 911 emergency medical system (EMS) activation to treatment and its components were analyzed from eight separate ongoing trials. This included estimates of ambulance response time, prehospital evaluation and treatment time, and time from admission to the hospital to initiation of thrombolytic therapy. The average time from EMS activation to patient arrival at the hospital was prospectively determined to be 46.1 +/- 8.2 minutes in 3715 patients from eight centers. The time from admission to the hospital to initiation of thrombolytic therapy was retrospectively determined to be 83.8 +/- 55.0 minutes in a separate group of 730 patients from six centers. Both the prehospital and hospital time delays were much longer than those perceived by paramedics and emergency department directors. Shorter hospital time delays were observed in patients in whom a prehospital ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and a diagnosis of acute infarction made before arrival at the hospital (36.3 +/- 11.3 minutes in 13 patients). These results show that the magnitude of time required to evaluate, transport, and initiate thrombolytic therapy will preclude initiation of treatment to most patients within the first hour of symptoms. Implementation of a protocol-driven prehospital diagnostic strategy may be associated with a reduction in time to thrombolytic therapy. 
4	Deferoxamine fails to improve postischemic cardiac function in hypertrophied hearts. Myocardial hypertrophy is a well-recognized risk factor in congenital cardiac surgery. Hypertrophied hearts have been demonstrated to have an increased vulnerability to ischemia/reperfusion injury. We studied the effects of the iron chelator and hydroxyl radical scavenger deferoxamine given during early reperfusion in a model of isolated retroperfused rabbit hearts made hypertrophic by aortic banding early in life (1 week of age). The rabbits were studied at 6-8 weeks of age, and the hearts were subjected to 30 minutes of 37 degrees C ischemia followed by 30 minutes of reperfusion. Postischemic recovery of isovolumic developed pressure was measured by using an intracavitary balloon in both the untreated (n = 6) and the deferoxamine-treated (n = 6) groups and compared with normal age-matched controls. Deferoxamine (50 mumol/kg) was given to one group with the hypertrophied hearts during the first 10 minutes of reperfusion. The left ventricular weight/body weight ratio in the hypertrophied hearts was 2.9 +/- 0.4 x 10(-3) (n = 14) versus 2.0 +/- 0.1 x 10(-3) in the age-matched controls (p less than 0.05). Postischemic peak developed pressure recovered to 102 +/- 6% of the preischemic value in the normal hearts after 30 minutes of reperfusion compared with 75 +/- 5% for the untreated and 71 +/- 4% for the deferoxamine-treated hearts (p less than 0.05 vs. control). We conclude that chronic hypertrophy from early in life leads to increased susceptibility to ischemia and that the iron chelator deferoxamine is not effective in preventing the injury of reperfusion in hypertrophied hearts. 
2	The recalcitrant perineal wound after rectal extirpation. Applications of muscle flap closure. Perineal wounds developing after abdominoperineal resection result in chronic purulent drainage and intermittent episodes of sepsis and are generally unresponsive to conservative medical and surgical treatment. Thirteen consecutive patients (aged 27 to 74 years; mean, 48 years) who underwent debridement and immediate muscle flap closure of these wounds were analyzed to identify risk factors for delayed healing and to evaluate the effectiveness of muscle flap coverage. Three risk factors were identified: preoperative or postoperative radiation therapy, resection for recurrent carcinoma, and inflammatory bowel disease. A total of 19 muscle flaps (11 gracilis, five gluteal thigh, two gluteus maximus, and one rectus abdominis) were used to close these wounds. During an average 3.5-year follow-up, four (31%) minor complications and one (8%) recurrence were noted to occur. Muscle flaps provide safe, effective, single-stage procedures for the closure of chronic perineal wounds. 
5	Multi-Hospital Eastern Atlantic Restenosis Trial: design, recruitment, and feasibility. M-HEART Investigators. A randomized control trial was set up to examine factors that influence restenosis and determine the effects of corticosteroids on restenosis following successful PTCA. The rationale for the study agent chosen, design, recruitment, and feasibility, as well as initial patient demographic data and initial results are presented. 
3	Seizure-associated speech arrest in elderly patients Recurrent, brief episodes of speech arrest associated with bifrontal electroencephalographic seizure activity developed in three ill elderly patients. The seizures ceased after the initiation of antiepileptic drug therapy and the correction of metabolic abnormalities. The cause of the seizure activity remains unknown, but a possible mechanism may be a transient epileptogenic cortical dysfunction that predominantly affects the frontal lobes as a result of concomitant metabolic alterations. 
4	Protective effect of a novel calcium blocker, S-312-d, on ischemic acute renal failure in rat. The effect of the calcium blocker S-(+)-methyl 4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitro-phenyl)thieno[2,3-b]pyridine- 5-carboxylate (S-312-d) on ischemic acute renal failure (ARF) was studied in rats. Ischemic ARF was induced by temporary (30-60 min) clamping of the left kidney 2 weeks after contralateral right nephrectomy. Plasma creatinine, creatinine clearance, urinary osmolality and fractional excretion of sodium were used to test the effectiveness of the drug. S-312-d (0.01-0.1 mg/kg b.wt. i.v.) administration before ischemia offered dose-dependent protection against the functional impairment induced by ischemia. This effect was accompanied by an increase in the survival rate of ischemic rats. S-312-d given after ischemia was not effective. The renal cortical edema induced by ischemia was significantly reduced by pretreatment with S-312-d. The increase in renal tissue calcium content observed after ischemia was also suppressed by S-312-d. Comparison with other established calcium blockers indicated S-312-d to be a good candidate for protection against ischemic ARF. These findings indicate that S-312-d may be clinically useful against renal ischemia. 
2	Anomalies of intestinal rotation in childhood: analysis of 447 cases. This report concerns 447 infants and children with anomalies of rotation and fixation. Patients were placed in four groups based on initial symptoms. Group A involved 18 patients with acute midgut volvulus. At laparotomy, midgut volvulus was noted and reduction of midgut volvulus and a Ladd procedure were performed in 10 cases and resection was required in 8. There were five deaths (28%). Group B included 54 children with chronic symptoms of intermittent volvulus or duodenal obstruction. Group C involved 44 cases of malrotation observed during exploration for other disorders. Patients in groups B and C underwent a Ladd procedure and appendectomy. There were five unrelated deaths. Group D included 331 neonates with malrotation caused by either diaphragmatic hernia (n = 111) or abdominal wall defects (n = 220). A Ladd procedure was performed on 48 patients with abdominal wall defects and 29 surviving children with diaphragmatic hernia. Only 2 of 172 (1.2%) patients with abdominal wall defects and 1 of 34 (2.9%) patients with diaphragmatic hernia not treated for malrotation had midgut volvulus. Midgut volvulus is more common in infants and is associated with a high mortality rate (28%). Patients with malrotation and chronic obstructive symptoms or those observed during other elective procedures should undergo a Ladd procedure because of the risk of midgut volvulus. The risk of midgut volvulus is low in patients with abdominal wall defects and, probably as a result of adhesions from previous neonatal operations. 
5	Benign biliary strictures: treatment with percutaneous cholangioplasty. Results of percutaneous balloon cholangioplasty of 17 patients with 28 benign biliary strictures were compared with those of published radiologic and surgical series to determine whether stricture location was related to therapeutic success and whether a patient should undergo percutaneous or surgical therapy. Treatment was considered successful if there was no anatomic evidence of recurrent stricture or need for surgery (mean follow-up, 32 months). Treatment was successful in all nine (100%) intrahepatic (zone 1) strictures, 11 of 12 (92%) extrahepatic-extrapancreatic (zone 2) strictures, one of three (33%) intrapancreatic (zone 3) strictures, and three of four (75%) bilienteric anastomotic (zone 4) strictures. Restenosis occurred in five patients; cholangioplasty was ultimately successful in two of those patients after redilation and stent placement. On the basis of these results and those of published radiologic and surgical series, the authors believe that cholangioplasty is the treatment of choice for zone 1 strictures and is as effective as surgery for zone 2 and 4 strictures. Patients with zone 2 and 4 strictures with concomitant portal hypertension or a history of multiple previous biliary surgical procedures should be considered good candidates for cholangioplasty. Zone 3 strictures may be better treated surgically than percutaneously. 
3	Is caffeine withdrawal the mechanism of postoperative headache? This study examined the hypothesis that headache after general anesthesia is related to a caffeine withdrawal state. Two hundred eighty-seven patients undergoing minor elective procedures under general anesthesia were studied. Four to six hours after anesthesia each patient completed a questionnaire assessing his or her own alcohol, tobacco, and caffeine consumption, and the occurrence of postoperative side effects. A highly significant difference was found between the caffeine consumption of patients with and without preoperative (P = 0.0035) and postoperative (P less than 0.0001) headache. Logistic regression analysis of trend between headache and caffeine consumption suggested that with each 100-mg increase in caffeine consumption, there was a 12% increase in the odds of headache developing in the immediate preoperative period (P less than 0.0066) and a 16% increase in the odds of postoperative headache developing (P less than 0.0001). No relationship was found between headache and the patients' age, sex, usual frequency of headache, consumption of alcohol or nicotine, or the anesthetic agents or adjuvants used. It is concluded that postoperative headache is related to caffeine intake and that this relationship is explained, at least in part, by a perioperative caffeine withdrawal syndrome. 
3	Coffee, caffeine, and cardiovascular disease in men BACKGROUND. For many years, an association between coffee consumption and the risk of coronary heart disease has been suspected. Although based on small numbers of end points, a prospective study has suggested a particularly strong association between recent coffee drinking and the incidence of cardiovascular disease. METHODS. We examined prospectively the relation of coffee consumption with the risk of myocardial infarction, need for coronary-artery bypass grafting or angioplasty, and risk of stroke in a cohort of 45,589 U.S. men who were 40 to 75 years old in 1986 and who had no history of cardiovascular disease. RESULTS. During two years of follow-up observation, 221 participants had a nonfatal myocardial infarction or died of coronary heart disease, 136 underwent coronary-artery surgery or angioplasty, and 54 had a stroke. Total coffee consumption was not associated with an increased risk of coronary heart disease or stroke. The age-adjusted relative risk for all cardiovascular disease among participants who drank four or more cups of coffee per day was 1.04 (95 percent confidence intervals, 0.74 to 1.46). Increasing levels of consumption of caffeinated coffee were not associated with higher risks of cardiovascular disease. Higher consumption of decaffeinated coffee, however, was associated with a marginally significant increase in the risk of coronary heart disease (relative risk, 1.63; 95 percent confidence interval, 1.02 to 2.60). Finally, we observed no pattern of increased risk across the subgroups of participants with increasing intakes of caffeine from all sources. Adjustment for major cardiovascular-risk indicators, dietary intake of fats, and cholesterol intake did not materially alter these associations. CONCLUSIONS. These findings do not support the hypothesis that coffee or caffeine consumption increases the risk of coronary heart disease or stroke. 
1	The pathology of heart allograft rejection. The pathologist plays an important role in the care of cardiac transplant recipients. Day-to-day management of immunosuppression is largely dependent on the diagnosis and grading of acute rejection. While noninvasive methods have been tried experimentally, the endomyocardial biopsy remains the gold standard in monitoring the rejection status of the heart allograft. The diagnosis of rejection, however, is complicated by a variety of other histologic findings, which may be procedural or processing related, due to sampling, or specifically related to transplantation. Failed allografts, whether from autopsy or explantation, provide the opportunity to study short- and long-term changes in the transplanted heart. Allograft arteriopathy, or graft atherosclerosis, is the major limiting factor in long-term recipient survival. While the morphological features of graft arteriopathy have been well described, the mechanism and factors contributing to its development remain unclear. 
5	A prospective randomized study of cerebrospinal fluid drainage to prevent paraplegia after high-risk surgery on the thoracoabdominal aorta. This article is concerned with the study of the effect of several variables, principally that of cerebrospinal fluid drainage, on the incidence of neurologic deficit in a prospective randomized series of patients with extensive aneurysms of the descending thoracic and abdominal aorta (thoracoabdominal type I and II). Forty-six patients had cerebrospinal fluid drainage, and 52 were controls, with a total of 98 available for study. Cerebrospinal fluid pressure was continuously monitored in the former group and pressure maintained less than or equal to 10 mm Hg in 20, less than or equal to 15 mm Hg in 20, and greater than 15 mm Hg in 6 patients during period of aortic clamping. The method of treatment including reattachment of intercostal and lumbar arteries (p = 0.2), temporary atriofemoral bypass during aortic occlusion (p = 0.3), and spinal fluid drainage (p = 0.8) were not statistically significant in reducing the incidence of neurologic deficits. Thus cerebrospinal fluid drainage as we used it, was not beneficial in preventing paraplegia. On appropriate statistical analysis we found that the only significant predictor of delayed deficits was postoperative hypotension (p = 0.006). 
1	Inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia. A patient with inflammatory pseudotumor of the liver associated with acute myelomonocytic leukemia (M4) is reported. He had spiking fever, epigastralgia, and elevated levels of serum C-reactive protein (CRP) and alkaline phosphatase (ALP). Ultrasonography showed a hypoechoic mass in the liver, and ultrasonically guided fine needle aspiration biopsy of the mass revealed that it was composed of fibrous connective tissue infiltrated with plasma cells, eosinophils, and neutrophils. Accordingly, a diagnosis of inflammatory pseudotumor of the liver was made. Marked reduction in the size of the lesion and a decrease of the levels of the CRP and ALP occurred without specific treatment. We emphasize the importance of ultrasonically guided aspiration biopsy in diagnosis of inflammatory pseudotumor of the liver without the need for surgery. 
5	Neuropsychological profile linked to low dopamine: in Alzheimer's disease, major depression, and Parkinson's disease. A distinct pattern of neuropsychological deficits was associated with low homovanillic acid (HVA) in the cerebrospinal fluid of 21 patients with: Alzheimer's disease (9), Parkinson's disease (8) and major depressive disorders (4). Regardless of clinical diagnosis, patients with low HVA were slower on a test of efficiency of processing timed information, and showed greater benefit from semantic structure on a verbal fluency task than patients with high HVA. However, low HVA subjects were not significantly impaired on confrontation naming (Boston Naming Test). Across three diagnostic groups, patients with lower HVA also tended to have more extrapyramidal motor signs and were significantly more depressed. These results demonstrate a significant relationship between specific neuro-behavioural deficits and dopaminergic activity which cuts across traditional diagnostic categories. 
2	High-fat semielemental diet in the treatment of protracted diarrhea of infancy. The capacity for greater fat absorption relative to carbohydrate absorption in protracted diarrhea of infancy was studied in a developed and a developing country (Buffalo, NY, and Bangkok, Thailand). Fifty patients with protracted diarrhea in the first year of life (defined as liquid stools of more than 20 mL/kg per day with more than a 14-day duration) were randomly assigned to receive either a standard semielemental diet (Pregestimil) or a high-fat semielemental diet that contained 40% more fat. The increased fat was largely in the form of medium-chain triglycerides, with the new diet providing 60% of the fat as medium-chain triglycerides compared with 40% in the standard diet. Tolerance to both diets was good in both studies. Both groups showed adequate weight gain and an improvement in anthropometric and biochemical parameters. The patients receiving the high-fat diet showed no initial weight loss, however, and their weight gain was initiated earlier. Cumulative weight gain was also higher in the group receiving the high-fat semielemental diet. Fecal fat analyses were performed after 1 week of therapy. There was no difference observed in the coefficient of fat absorption between the groups receiving the two formulas, indicating that infants with protracted diarrhea may be able to tolerate a higher fat intake than is normally provided. As carbohydrate intolerance is known to be a complicating factor when using semielemental enteral feeds for infants with protracted diarrhea, a higher-fat semielemental diet may be the most appropriate way to provide adequate caloric intake. 
5	Esophageal contribution to chest pain in patients with coronary artery disease. We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients. 
1	Mohs micrographic surgery fixed-tissue technique for melanoma of the nose. Mohs micrographic surgery, fixed-tissue technique, for excision of nasal melanoma provides three important benefits: 1) assurance of eradication of the main mass along with its "silent" contiguous outgrowths, 2) safe management of non-contiguous satellites too small to be visible initially, and 3) safe sparing of maximal amounts of surrounding normal tissues. These benefits are achieved because all incisions are through chemically fixed (killed) tissue, eliminating the danger of disseminating the highly transplantable melanoma cells and permitting the excision of successive layers for microscopic scanning of their undersurfaces by the systematic use of frozen sections. The process is continued to the termination of each ramification. There is no need to remove a wide margin of normal tissue as is customary with conventional surgery. Clinically invisible satellites are not moved or disturbed and can be removed safely by the same method if they appear. The reliability of the method is manifested by the 62.5% 5-year cure in a series of 10 consecutive patients, all of whom had no local recurrence after micrographic surgery. 
5	Lumbar spinal nerves in the neural foramen: MR appearance. The appearance of the proximal lumbar spinal nerves at magnetic resonance (MR) imaging has not, to the authors' knowledge, been described. MR images and exactly corresponding sections obtained from four cadavers by means of a freezing microtome were correlated to characterize the MR appearance of the proximal spinal nerves. The junction of the dorsal and ventral rami with the dorsal and ventral roots consists of a group of six to 15 fascicles measuring 2-6 mm in length. These fascicles appear in MR images obtained with short repetition times as small foci of lower signal intensity than that of surrounding fat. The proximal spinal nerve and its relationship to the intervertebral disk and osseous margins of the neural foramen can be demonstrated effectively with MR imaging. 
3	Hypoxemia alone does not explain blood pressure elevations after obstructive apneas. In patients with obstructive sleep apnea (OSA), substantial elevations of systemic blood pressure (BP) and depressions of oxyhemoglobin saturation (SaO2) accompany apnea termination. The causes of the BP elevations, which contribute significantly to nocturnal hypertension in OSA, have not been defined precisely. To assess the relative contribution of arterial hypoxemia, we observed mean arterial pressure (MAP) changes following obstructive apneas in 11 OSA patients during non-rapid-eye-movement (NREM) sleep and then under three experimental conditions: 1) apnea with O2 supplementation; 2) hypoxemia (SaO2 80%) without apnea; and 3) arousal from sleep with neither hypoxemia nor apnea. We found that apneas recorded during O2 supplementation (SaO2 nadir 93.6% +/- 2.4; mean +/- SD) in six subjects were associated with equivalent postapneic MAP elevations compared with unsupplemented apneas (SaO2 nadir 79-82%): 18.8 +/- 7.1 vs. 21.3 +/- 9.2 mmHg (mean change MAP +/- SD); in the absence of respiratory and sleep disruption in eight subjects, hypoxemia was not associated with the BP elevations observed following apneas: -5.4 +/- 19 vs. 19.1 +/- 7.8 mmHg (P less than 0.01); and in five subjects, auditory arousal alone was associated with MAP elevation similar to that observed following apneas: 24.0 +/- 8.1 vs. 22.0 +/- 6.9 mmHg. We conclude that in NREM sleep postapneic BP elevations are not primarily attributable to arterial hypoxemia. Other factors associated with apnea termination, including arousal from sleep, reinflation of the lungs, and changes of intrathoracic pressure, may be responsible for these elevations. 
5	Splinter hemorrhages as a possible clinical manifestation of cholesterol crystal embolization. We describe a patient with cholesterol crystal embolization who demonstrated splinter hemorrhages of multiple fingernails and toenails as part of her clinical presentations. Our patient's clinical presentation, and review of the medical literature, raise the possibility that cholesterol crystal embolization may be associated with splinter hemorrhages. 
5	Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat. Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models. To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria. Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin. Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy. 
2	Bile sampling, processing and analysis in clinical studies. Obtaining a proper bile sample for investigative purposes is of utmost importance to obtain valid results. Bile can be collected by direct aspiration of the gallbladder, by duodenal intubation or by T-tube drainage. The optimal method of collection depends on the investigative question, as well as on the resources available to the investigator. The procedures for obtaining, processing and analyzing human bile (gallbladder and hepatic) are summarized, pointing out the disadvantages and pitfalls that may occur. 
1	Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long-term results. A total of 441 stage T1-2N0M0 and 11 stage T1-2N0M0 cancer patients with an elevated acid phosphatase level only, and 18 stage T1-2N+M0 cancer patients underwent radical prostatectomy. Analysis of the 441 stage T1-2N0M0 cancer patients demonstrated that failure and survival were a function of the disease being organ-confined, specimen-confined or margin-positive, with 10-year failure rates of 12, 30 and 60%, respectively. Of the patients with positive margins 44 were and 79 were not irradiated postoperatively. Postoperative radiation produced no survival advantage. No difference in interval to failure or of survival could be identified between 105 patients whose disease was diagnosed by transurethral resection and 328 who had a palpable abnormality. Eleven patients had negative bone and node findings but they had an elevated acid phosphatase level. All 8 patients not treated with immediate androgen deprivation failed within 36 months. 
5	Effects of halothane on hypoxic pulmonary vasoconstriction in canine atelectasis. We studied the interactions of atelectasis and halothane on hypoxic pulmonary vasoconstriction using an isolated canine lobe. We divided pulmonary vascular resistance into arterial, venous, and middle segmental resistances by a vascular occlusion technique. We found that middle segmental resistance significantly increased (P less than 0.05) from 0.016 +/- 0.007 cm H2O.mL-1.min-1 during normoxic ventilation to 0.06 +/- 0.007 cm H2O.mL-1.min-1 during hypoxic ventilation. We then produced sublobar atelectasis by introducing 4.5-mm steel ball bearings into the lobar bronchus, which resulted in a significant increase (P less than 0.05) of middle segmental resistance to 0.046 +/- 0.014 cm H2O.mL-1.min-1 during normoxic ventilation and a further significant increase (P less than 0.05) to 0.084 +/- 0.02 cm H2O.mL-1.min-1 during hypoxic ventilation. Ventilation with 2.0% halothane but not 0.5% halothane prevented the increases in middle segmental resistance observed with either atelectasis or hypoxic ventilation. Values of arterial and venous segmental resistances were not similarly affected. We conclude that sublobar atelectasis increases pulmonary vascular resistance by stimulating hypoxic pulmonary vasoconstriction. Both halothane and hypoxia primarily act upon the middle vascular segment, but their effects are in opposite directions and, in the former instance, are concentration-dependent. 
3	Vesicular changes in the myopathies of AIDS. Ultrastructural observations and their relationship to zidovudine treatment. Six patients with AIDS and AIDS related complex (ARC) who developed neuromuscular symptoms associated with vesicular changes in muscle fibres are reported. Two patients in the advanced stages of AIDS, who did not receive zidovudine, developed proximal limb weakness and wasting: both had a necrotising myopathy with an unusual segmental vesicular change of myofibres. There were numerous vesicles 0.1 to 2 microns in diameter produced by dilatations of the sarcoplasmic reticulum in fibres depleted of myofibrils. Four patients developed a myopathy while receiving zidovudine for AIDS. One of these had an inflammatory myopathy which showed the development of vesicular change due to enlargement and electron lucency of mitochondria. The three other patients with ARC developed muscle pains or weakness and elevated serum CK while on zidovudine. These patients also showed vesicular changes due to enlargement and electron lucency of mitochondria associated with disruption of sarcomeres and the presence of cytoplasmic bodies. The muscular symptoms resolved when ziduvodine was stopped and repeat biopsy in one case revealed no abnormalities. 
3	Long-term potentiation of electrotonic coupling at mixed synapses. Long-term potentiation of chemical synapses is closely related to memory and learning. Studies of this process have concentrated on chemically mediated excitatory synapses. By contrast, activity-dependent modification of gap junctions, which also widely exist in higher structures such as hippocampus and neocortex, has not been described. Here we report that at mixed synapses between sensory afferents and an identified reticulospinal neuron, the electrotonic coupling potential can be potentiated, as well as the chemically mediated excitatory postsynaptic potential, for a prolonged time period using a stimulation paradigm like that which produces long-term potentiation in hippocampus. The effect on coupling is due to an increase in gap-junctional conductance. Our data indicate that the potentiation of both synaptic components requires an increase in intracellular calcium, involves activation of NMDA (N-methyl-D-aspartate) receptors, and is specific to the tetanized pathway. 
1	Treatment of leptomeningeal carcinomatosis with continuous intraventricular infusion of recombinant interleukin-2. A 42-year-old man developed leptomeningeal carcinomatosis 6 years after treatment of a malignant melanoma. He was treated with two courses of recombinant interleukin-2, administered as a continuous intraventricular infusion (6 X 10E5 U/24 h) during 5 days. During the first day of the first course he also received 5 X 10E9 lymphokine-activated killer cells intraventricularly. This gave rise to a severe elevation of intracranial pressure, with headaches and meningismus. During the second course no LAK cells were administered. This course was tolerated much better. The neurological status did not change during the treatment. Recombinant interleukin-2 levels were maintained at about 300 U/mL during both courses. 
4	Prevention of hypertension and vascular changes by captopril treatment. Treatment of female spontaneously hypertensive rats (SHR) and control Wistar-Kyoto (WKY) rats with captopril was carried out by the addition of the drug in the drinking water throughout pregnancy and lactation and after weaning. At 28 weeks of age, average systolic blood pressure of treated SHR was 113 +/- 3 mm Hg, which was below that of control SHR (188 +/- 3 mm Hg) and WKY rats (124 +/- 3 mm Hg). Body weight and heart rate of the SHR were not affected by the treatment. Tissue level of catecholamines was increased by captopril treatment in the superior cervical ganglia but remained unchanged in the plasma, heart, mesenteric arteries, and the adrenal glands of both SHR and WKY rats. Left ventricular weight, wall thickness, and internal diameter of the left ventricle in the SHR were reduced by the treatment. Morphometric measurements of the mesenteric arteries showed that vascular alterations present in the control SHR were prevented by the treatment. In the superior mesenteric artery and large mesenteric artery, smaller lumen size at maximal relaxation found in the control SHR was normalized to the level of the WKY rats. Hypertrophy of the medial wall in the superior mesenteric, large and small mesenteric arteries, and an increase in the number of smooth muscle cell layers in the large mesenteric artery of the SHR were prevented by the treatment. Perfusion study of the mesenteric vascular bed showed that reactivity of these vessels to norepinephrine was reduced, and sensitivity to norepinephrine (as determined by the effective dose that causes 50% of maximal response) was increased in the SHR by captopril treatment. Sensitivity of the tail artery in response to norepinephrine was not altered by the treatment. We conclude that long-term treatment with captopril of SHR before and after birth prevented the development of hypertension, structural and functional alterations of the mesenteric arteries, and cardiac hypertrophy. 
5	An evaluation of cocaine-induced chest pain STUDY OBJECTIVE: To determine if enzymatic evidence of acute myocardial injury is present in patients complaining of chest pain after cocaine use when the ECG is normal or nondiagnostic. DESIGN: Serial ECG and creatinine kinase (CK) and CK isoenzymes (CK-ISO) determinations were performed at time of emergency department presentation and every six hours over 12 hours on individuals complaining of chest pain within six hours of last cocaine use. SETTING: ED of an urban tertiary care center. TYPE OF PARTICIPANTS: Forty-two individuals with a mean age of 28.5 years. INTERVENTIONS: Patients with positive CK-ISOs were admitted immediately to formally rule out myocardial infarction. Patients developing ECG changes during observation period also were admitted even if CK-ISOs were normal. Patients with unchanged ECGs and normal CK-ISOs were discharged after 12 hours of observation. RESULTS: Eight patients (19%) had elevated CK and CK-ISO values at presentation. Two of these patients had elevated values on three sequential determinations and were believed to have sustained acute myocardial infarction. Six patients had elevated CK and CK-ISOs at presentation only. ECGs remained normal or nondiagnostic in all patients. CONCLUSIONS: Enzymatic evidence of acute myocardial injury may occur in patients who develop chest pain after cocaine use and have normal or nondiagnostic ECGs. This injury may reflect acute infarction or transient ischemia. Single or serial normal or nondiagnostic ECGs do not rule out ischemia or injury in this group of patients. 
1	Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene-1-bisphosphonate. Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed. 
4	Conjunctival involvement in pemphigus vulgaris: a clinical, histopathological and immunofluorescence study. Eleven patients with pemphigus vulgaris and with eye complaints had histopathological and direct immunofluorescence (DIF) studies on biopsies of their conjunctivae. In eight of the patients the ocular symptoms preceded the other manifestations of pemphigus. None of the 11 patients had any detectable conjunctival blisters or erosions. The conjunctivitis in three of the patients proved on histopathology and DIF to be a manifestation of pemphigus vulgaris. In the remaining patients, conjunctival hyperaemia with or without a mucoid discharge was observed, but there were no specific histopathological features, although one of them had a positive DIF. 
3	Young-onset Parkinson's disease: a clinical review. Young-onset Parkinson's disease (YOPD) is arbitrarily defined as that which produces initial symptoms between the ages of 21 and 39, inclusive. The special problems and concerns of the patient with YOPD present as much of a challenge and opportunity for the clinician as the disease itself does for the researcher. In contrast to juvenile parkinsonism, which is a heterogeneous group of clinicopathologic entities presenting (also arbitrarily) before age 21, YOPD appears to be the same nosologic entity as older-onset PD. It comprises approximately 5% of referral populations in Western countries and about 10% in Japan. Its annual incidence relative to the population at risk is about 1/10 that of PD at age sixty. YOPD tends to have more gradual progression of parkinsonian signs and symptoms, earlier appearance of levodopa-related dyskinesias and levodopa-dose-related motor fluctuations, and frequent presence of dystonia as an early or presenting sign. Studies conflict with regard to the suspected greater familial frequency and lesser frequency of dementia than in older-onset PD. 
5	Urological complications in 350 consecutive renal transplants. Ten urological complications (2.9%) were found in 350 kidney transplants performed in this centre. These included obstructive uropathy (20%), urinary leaks (40%), distal uretic fistulas (necrosis) (30%) and renal calculi (10%). Two grafts were lost due to chronic rejection 9 and 30 months post-operatively. The remaining 8 patients have stable renal function (mean creatinine 1.5 mg%). It was concluded that meticulous surgical technique may reduce the number of urological complications and early diagnosis and prompt surgical treatment may help to save the grafts. 
3	Celiac disease, brain atrophy, and dementia. We report 5 patients who developed dementia before age 60 and were subsequently found to have celiac disease (CD). Intellectual deterioration ranged from moderate to severe, and diffuse cerebral or cerebellar atrophy was found on brain CT. Diagnosis of CD was confirmed by findings of subtotal villous atrophy in jejunal biopsy specimens and positive serum reticulin and gliadin antibodies. Conspicuously, gastrointestinal symptoms were mild. The gluten-free diet failed to improve the neurologic disability except in 1 patient. CD is a multisystem disorder and may play a role in some cases of presenile dementia. Although the pathogenetic mechanisms are obscure, immunologic mechanisms are implicated. 
1	Intramedullary spinal ependymal cyst: case report. A cervical intramedullary spinal ependymal cyst in a 39-year-old man is reported. Diagnosis was made through magnetic resonance imaging. Total enucleation was possible. This is the sixth such reported case. 
4	Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension. Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization. 
5	Results of surgical treatment for hyperparathyroidism associated with renal disease. Recently, the role and timing of surgery for treating secondary and tertiary hyperparathyroidism (HPT) have been questioned. In order to delineate the indications for surgery in these patients, a retrospective analysis of 53 consecutive patients treated with parathyroidectomy was conducted. Subtotal thyroidectomy was done in 37 of 45 patients undergoing their initial operations for HPT. Eight additional patients were referred after failed operations. Of 33 patients with preoperative bone pain, 70% improved. Joint pain improved in 87% of 30 patients, pruritus improved in 81% of 27 patients, and preoperative malaise improved in 73% of 33 patients after parathyroidectomy. Abdominal pain and irritated eyes were unlikely to improve. The best predictors of a successful outcome were a markedly elevated preoperative immunoreactive parathyroid hormone (mid-region) level and an elevated alkaline phosphatase level. There were no perioperative deaths. One patient (1.6%) had a recurrent laryngeal nerve injury, and one patient required reoperation for a neck hematoma. No patient had permanent hypoparathyroidism, but transient hypocalcemia (less than 7 mg/dL) occurred in 22%. Postoperative hypocalcemia correlated with elevated preoperative alkaline phosphatase levels (r2 = 0.247). 
3	A case-control study of Alzheimer's disease in Australia. We conducted a case-control study of clinically diagnosed Alzheimer's disease (AD) on 170 cases aged 52 to 96 years, and 170 controls matched for age, sex and, where possible, the general practice of origin. Trained lay interviewers naive to the hypotheses and to the clinical status of the elderly person carried out risk-factor interviews with informants. Significant odds ratios were found for 4 variables: a history of either dementia, probable AD, or Down's syndrome in a 1st-degree relative, and underactivity as a behavioral trait in both the recent and more distant past. Previously reported or suggested associations not confirmed by this study include head injury, starvation, thyroid disease, analgesic abuse, antacid use (aluminum exposure), alcohol abuse, smoking, and being left-handed. 
4	In vivo rheologic effects of lipid apheresis techniques: comparison of dextran sulfate LDL adsorption and heparin induced LDL precipitation. The effects of two different LDL apheresis techniques, heparin-induced LDL precipitation (HELP) and dextran sulfate LDL adsorption (DSA), were compared in six patients with familial hypercholesterolemia. Total and LDL cholesterol were effectively lowered with both techniques. The reduction of serum triglycerides was more pronounced with DSA, whereas the reduction of HDL cholesterol was more pronounced with HELP. Single sessions using both techniques immediately reduced whole blood and plasma viscosity, as well as erythrocyte aggregation. Serum fibrinogen decreased by 62% (HELP) and 11% (DSA). Maintenance lipid apheresis administered 1 time per week resulted in a sustained reduction of total and LDL cholesterol and was associated with a sustained improvement in blood flow properties. Data suggest that besides serum fibrinogen, serum lipoproteins may adversely effect the rheologic characteristics of blood. 
3	A discriminant validity study of negative symptoms with a special focus on depression and antipsychotic medication. If the construct validity of the negative symptom syndrome is to be established, the conceptual and operational overlap between negative symptoms and other syndromes such as depression and the effects of medication must be explained. The author assessed 26 patients with schizophrenia and 21 patients without schizophrenia, most of whom had depression, at the end of an average 2-week drug washout period and after approximately 2 months of psychotropic medication administration. Negative symptoms were remarkably consistent in patients with schizophrenia despite pharmacological intervention. In contrast, the patients without schizophrenia manifested significant decreases in negative symptoms. 
5	Thrombus in a natural left ventricle during left ventricular assist: another thromboembolic risk factor. Systemic thromboembolism is one of the serious complications during use of a left ventricular assist system (LVAS). The authors' original LVAS has excellent antithrombogenicity to reduce this risk, but thrombus formation in a natural left ventricle (LV) is another risk factor for systemic embolization. We used our LVAS in 22 patients. Of these, LV wall motion was studied in 15, and a smoke-like echo disclosed thrombus in the LV in eight. When LVAS sufficiently supported the systemic circulation, LV wall motion was irregular upon closure of the aortic valve. Upon recovery of LV function and decrease of LVAS flow, the smoke-like echo diminished and LV thrombus decreased in one, but LV thrombus remained unchanged or increased in seven. Systemic administration of antithrombotic agents had an unclear effect. Seven of eight patients with LV thrombus on echo died during or after LVAS. In these seven, a high incidence of LV thrombus (71%), and systemic embolism to the brain (29%) or kidney (86%), were revealed at necropsy. We subsequently used local heparinization to prevent LV thrombus formation. One patient with a smoke-like echo had no evidence of LV thrombus or systemic embolism. During LV assist, careful management of the LVAS, and intra-LV heparinization should be considered to reduce the risk of thrombus formation in the natural LV. 
3	Computerized neuropsychological assessment of cognitive functioning in children with epilepsy. The value of a range of computer-aided tests in the neuropsychological assessment was investigated in 94-177 children with epilepsy, aged 8-18 years, compared with 68-161 controls in the same age group. Children from the age of 8 years could cope with rather complex tests in a wide range of functions: reaction time measurements, motor speed, information processing, and memory. The speed of performance tended to increase with age in both groups, with differences in information processing becoming apparent from the age of 12 years. The precise control of stimulus and response required to define the mainly minor differences between the epilepsy and control groups can only be fulfilled by computerized testing, which should undergo further refinement including voice and language recognition, followed by artificial intelligence. 
4	Balloon dilatation of the mitral valve by a single bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter. The efficacy of balloon dilatation of the mitral valve by a bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter (single catheter technique) was assessed in 53 patients (mean age 28) with mitral stenosis, most of whom were women. The procedure was unsuccessful in three patients. After balloon dilatation the left atrial pressure decreased from 22 mm Hg to 13 mm Hg and the mitral valve gradient from 12 mm Hg to 4 mm Hg. The mitral valve area increased from 0.7 cm2 to 2.1 cm2. Exercise time on the standard Bruce protocol increased from 3.9 minutes to 7.2 minutes. In 22 (44%) patients mitral regurgitation developed or the grade of regurgitation increased. Left to right shunts with pulmonary to systemic flow ratios greater than 1:5 were detected in four patients. Transient cerebrovascular episodes developed in two patients. One patient died after emergency valve replacement for severe mitral regurgitation. Balloon dilatation of the mitral valve by the single catheter technique with the bifoil or trefoil catheters is an effective treatment for patients with mitral stenosis. Mild mitral regurgitation is a frequent complication of the procedure. 
3	Motor dysfunction in HIV-infected patients without clinically detectable central-nervous deficit. Motor tests were performed in 50 HIV-infected patients in all stages according to the current CDC classification, but without any clinically evident central nervous system deficit, and the results compared with an age-matched control group. Patients were excluded from the study if there was alcohol or drug abuse, fever and/or opportunistic cerebral infection. The parameters tested were postural tremor of the outstretched hands, most rapid voluntary alternating index finger movements (MRAM) and rise time of most rapid index finger extensions (MRC). Whereas tremor peak frequencies did not differ significantly in the patients and controls, MRAM and rise times of MRCs showed significant slowing in the patient group. Morphologically, the motor test performance of the HIV-infected patients was similar to that of patients with manifest basal ganglia disease (Parkinson's, Huntington's and Wilson's diseases). MRI scans of all patients were normal. It is concluded that in HIV-infected patients there is a very early subclinical central nervous system affection, especially of the basal ganglia, which is detectable with appropriate, quantitative motor function tests. These functional abnormalities precede the structural alterations in the MRI scans. 
5	Infrainguinal revascularization for limb salvage in patients with end-stage renal disease. We studied the efficacy of infrainguinal bypass for limb salvage in patients with end-stage renal disease. The patency of 42 femoropopliteal and femorodistal bypasses, performed for limb salvage in 37 patients with end-stage renal disease, was assessed with Doppler ultrasonography and dye tests. Patency rates and limb salvage were determined by life-table analysis. Average age was 45 years (range, 28 to 61 years); 23 of the 37 were men. Twenty-three patients had diabetes mellitus, and 16 were smokers. Bypass procedures were done in 32 instances while the patients were maintained with chronic hemodialysis and in five instances with peritoneal dialysis; in five instances the patients had had successful renal transplantation. Indications for revascularization included pain at rest, nonhealing ulcer, or distal gangrene. Femoropopliteal bypass was done in 32 limbs; 10 were more distal procedures. Reversed saphenous vein was the conduit in 30 cases; prosthetic material was used in the remainder. Autogenous material was used in all distal bypasses. Four patients required graft revision during the initial hospitalization, but none thereafter. Two patients died within the operative period, nine within 18 months of operation. Nine major operations were required. Three-month cumulative graft patency was achieved in 41 cases and corresponding limb salvage in 33 cases; 18-month patency was achieved in 34 cases and overall limb salvage in 33 cases. Success of limb salvage most closely correlated with preoperative ankle-brachial ratio and level of bypass required. 
4	Pheochromocytoma with electrocardiographic change mimicking angina pectoris, and cyclic change in direct arterial pressure--a case report. A forty-two-year-old man was admitted because of chest pain. Electrocardiograms at admission showed horizontal ST depression in leads, II, III, aVF, V4, V5, and V6. Direct blood pressure monitoring revealed cyclic change between 160/100 mmHg and 70/50 mmHg and heart rate between 80/sec and 120/sec at fifteen minute intervals. The plasma norepinephrine and epinephrine concentrations were elevated during the episodes of hypertension. Pheochromocytoma was found in the right adrenal gland. These cyclic changes in blood pressure and heart rate are an aid for diagnosis. 
3	Vasospasm contributes to monosodium glutamate-induced headache. Consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients. In this study the direct effects of glutamate and its metabolite, glutamine, on arterial contractility were examined using rings of rabbit aorta. In a high concentration glutamate caused significant concentration-dependent contractions (EC50, 10(-1)M; maximum tension, 188.4 +/- 33.3 mg wt tension/mg tissue). Agonists and antagonists for alpha-adrenergic, histaminergic, serotonergic, cholinergic, and GABA-nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions. At high concentrations (10(-5)M) the calcium channel blocker, verapamil, inhibited the glutamate response. Glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine (NE), phenylephrine (PE), histamine, serotonin (5-HT), and prostaglandin F2 alpha (PGF2 alpha)-induced contractions. Kainic acid (10(-4)M), an agonist of one subpopulation of central glutamate receptor, potentiated glutamate-induced vasoconstriction; a higher concentration (10(-3)M) produced an irreversible inhibition of glutamate contractility. Only the central glutamate receptor antagonist, ketamine (10(-4)-10(-2)M), induced a reversible, concentration dependent inhibition of glutamate-induced contractions. Glutamate contractility was not dependent on extracellular calcium, an intact endothelium or neuronal function. These results demonstrate a direct effect of glutamate on peripheral arterial tone. Dietary consumption of large quantities of MSG may represent a serious health hazard to certain individuals with pre-existing vascular disease. 
1	Carcinoma of the cervix: value of MR imaging in detecting parametrial involvement. In patients with cervical carcinoma, precise knowledge of parametrial tumor extension affects the therapeutic decision between surgery and radiation therapy. The purpose of this prospective study was to determine the efficacy of MR imaging in detecting the presence or absence of parametrial invasion in patients with cervical cancer thought clinically to be confined to the cervix. Twenty-five consecutive patients were included in the study. All patients underwent radical hysterectomy or total abdominal hysterectomy and had detailed histologic evaluation of the parametrium. Ten had pathologic evidence of parametrial invasion; in the remaining 15, no parametrial invasion was identified pathologically. MR findings were compared with pathologic findings in all cases. For determining parametrial involvement, MR imaging had an accuracy of 88%, a sensitivity of 100%, and a specificity of 80%. Our results suggest that MR imaging is a reliable means of assessing parametrial invasion by cervical cancer. 
1	Extracranial repair of cerebrospinal fluid fistulas: technique and results in 37 patients. Although neurosurgeons have traditionally preferred intracranial repair for the management of cerebrospinal fluid (CSF) fistulas, this approach is associated with the complications of a craniotomy, anosmia, and a high incidence of recurrent fistulas. Extracranial repair, on the other hand, produces no central nervous system morbidity, preserves olfaction, and is associated with a low incidence of recurrence. Although there have been several reports of extracranial repair of CSF fistulas by otorhinolaryngologists, this approach has received scant mention in the neurosurgical literature. We report here our experience with 37 patients with CSF rhinorrhea or otorrhea who underwent extracranial repair. The etiology of the fistula was postoperative in 22, traumatic in 6, and spontaneous in 9. The fistulas were repaired using one of four techniques: external ethmoid-sphenoid in 18 patients, transmastoid in 9, transseptosphenoid in 7, and osteoplastic frontal sinusotomy in 3. In 32 of the 37 patients (86%) the fistulas were successfully repaired with the initial procedure. Of the 5 patients requiring a second operation, the fistula was successfully closed in 4 for an overall success rate of 97%. Complications were few and consisted of a transient facial paresis in a patient undergoing transmastoid repair and one death from meningitis. The authors conclude that because of low morbidity and mortality and a high success rate in closing fistulas, extracranial repair is the preferred technique for the operative management of CSF rhinorrhea and otorrhea. 
5	An evaluation of the Level 1 blood warmer series The Level 1 blood warmer series comprises three infusion sets and two blood warmers of different power outputs. All systems were found to be extremely efficient, with the larger 500 series capable of warming the equivalent of 80 units of blood an hour almost to body temperature. 
5	Human atherosclerotic coronary artery xenografts: a model for investigation of transluminal recanalization. A model for testing transluminal recanalization techniques was developed. Fragments of human atherosclerotic coronary arteries were transplanted into carotid arteries of dogs and evaluated by angiographic, angioscopic, and histologic study within a three-month period. An inflammatory response was most intense within the first week. By two weeks no inflammation was noted. Total occlusion (n = 13) and stenosis (n = 11) of the carotid arteries were achieved without complications. The model is easy to produce within a short period and the arterial occlusion resembles human vascular disease. This model has been used to evaluate laser recanalization of vascular obstructions. 
5	The current spectrum of peptic ulcer disease in the older age groups. Not only has there been a relative increase in the prevalence of peptic ulcer disease (PUD) among America's older age groups, but the characteristics of PUD in these patients differ significantly from those of the general population. Seventy-two consecutive patients 60 years of age or older who underwent operation for PUD between 1984 and 1989 were studied. The unusual features in these patients were 1) 92 per cent required emergency operation, 2) 57 per cent with perforated PUD were female, 3) 85 per cent had duodenal pathology, 4) 28 per cent were currently taking nonsteroidal anti-inflammatory agents, and 5) over one half of all patients had serious postoperative complications. The increasing incidence and associated serious complications of PUD in the elderly population present new challenges to physicians in the diagnosis and treatment of this disease. 
5	Changing arteriosclerotic disease patterns and management strategies in lower-limb-threatening ischemia. From January 1, 1974 to December 31, 1989, we treated 2829 patients with critical lower-extremity ischemia. In the last 5 years, 13% of patients had therapeutically significant stenoses or occlusions above and below the groin, while 35% had them at two or three levels below the inguinal ligament. Unobstructed arterial flow to the distal half of the thigh was present in 26% of patients, and 16% had unobstructed flow to the upper third of the leg with occlusions of all three leg arteries distal to this point and reconstitution of some patent named artery in the lower leg or foot. In the last 2 years, 99% of all patients with a threatened limb and without severe organic mental syndrome or midfoot gangrene were amenable to revascularization by percutaneous transluminal angioplasty (PTA), arterial bypass, or a combination of the two, although some distal arteries used for bypass insertion were heavily diseased or isolated segments without an intact plantar arch. Limb salvage was achieved and maintained in more than 90% of recent patient cohorts, with a mean procedural mortality rate of 3.3%. Recent strategies that contributed to these results include (1) distal origin short vein grafts from the below-knee popliteal or tibial arteries to an ankle or foot artery (291 cases); (2) combined PTA and bypass (245 cases); (3) more distal PTA of popliteal and tibial artery stenoses (233 cases); (4) use of in situ or ectopic reversed autogenous vein for infrapopliteal bypasses, even when vein diameter was 3 to 4 mm; (5) composite-sequential femoropopliteal-distal (PTFE/vein) bypasses; (6) reintervention when a procedure thrombosed (637 cases) or was threatened by a hemodynamically significant inflow, outflow, or graft lesion (failing graft, 252 cases); (7) frequent follow-up to detect threatening lesions before graft thrombosis occurred and to permit correction of lesions by PTA (58%) or simple reoperation; and (8) unusual approaches to all infrainguinal arteries to facilitate secondary operations, despite scarring and infection. Primary major amputation rates decreased from 41% to 5% and total amputation rates decreased from 49% to 14%. Aggressive policies to save threatened limbs thus are supported. 
3	Response to treatment with antihistamines in a family with myotonia congenita. In a family in which myotonia congenita was found in five generations, both great-grandparents of the index case were affected. In subsequent generations mild and severely affected cases were clearly segregated down parallel lines of this family. The grandmother of the index case had noted improvement with an antihistamine. When the index case was prescribed trimeprazine, she showed a striking reduction in severity of symptoms. Antihistamines seem to deserve further evaluation as a safe and effective treatment for myotonia congenita. 
5	Thoracoscopic carbon dioxide laser treatment of bullous emphysema. A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation. 
4	Effects of enalapril and neuroendocrine activation on prognosis in severe congestive heart failure (follow-up of the CONSENSUS trial). CONSENSUS Trial Study Group. This study enrolled 253 patients with severe heart failure (New York Heart Association functional class IV) from 35 centers in Scandinavia, randomly assigned to treatment with placebo or enalapril, in addition to their usual treatment for heart failure. After an initial titration period, the daily doses of enalapril ranged from 2.5 to 40 mg. At the end of the trial, 46% of the placebo-treated patients and 61% of the enalapril-treated patients were alive (p = 0.003); the survival figures at 8 months after completion of the trial were 32 and 48%, respectively (p = 0.001); and 21 and 30%, respectively (p = 0.006) at the 2-year follow-up. In the placebo group, there was a significant positive association between mortality and baseline levels of norepinephrine, epinephrine, angiotensin II, aldosterone and atrial natriuretic peptide; no such association was found in the enalapril-treated patients. The results suggest that the effects of enalapril on mortality are related to a counteraction of the neuroendocrine activation in general and to the renin-angiotensin system in particular. 
4	Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group. We compared 211 consecutive patients who had acute ischemic hemispheric stroke and atrial fibrillation with 837 consecutive patients who had stroke without atrial fibrillation. The atrial fibrillation group included a higher frequency of women, older subjects, and those with a severe neurologic deficit, abnormal computed tomogram, and elevated heart rate. The 1-month case-fatality rate in the atrial fibrillation group was 27% while that in the group without atrial fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40% and 20%, respectively. The risk of death attributable to atrial fibrillation, adjusted for the effect of other prognostic factors, was significant at 1 month (relative risk = 1.55) and at 6 months (relative risk = 1.74). The causes of death were equally distributed in the two groups during both the acute and subacute phases. We conclude that atrial fibrillation is a negative prognostic factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism alone does not completely explain the increase in mortality for stroke patients with atrial fibrillation. Other associated pathogenetic mechanisms must also be taken into account. 
1	Novel antigens characteristic of neuroendocrine malignancies. The authors describe the immunochemical detection, biochemical characterization, and tissue distribution of neuroendocrine antigens recognized by three newly developed monoclonal antibodies (MoAb) obtained after immunization of mice with the variant small cell lung cancer (SCLC) cell line NCI-H82. RNL-1 was reactive with neuroendocrine tissues similar to the SCLC cluster-1 MoAb, known to recognize N-CAM. Antibodies RNL-2 and RNL-3 are directed against different epitopes on the same proteinaceous complex. Both MoAb recognize an intracellularly located, water-soluble antigen which has a subunit composition with a protein triplet ranging in molecular weight between 44 and 45 kilodaltons (kD) next to a component of approximately 30 kD. The antibodies RNL-2 and RNL-3 reacted with a subset of neuroendocrine tissues and neuroendocrine neoplasms. In lung cancer both antibodies reacted only with some SCLC and carcinoids and not with nonneuroendocrine lung carcinomas. The potential diagnostic applicability of antibodies RNL-1, RNL-2, and RNL-3 is discussed. 
5	Pancreatogastrostomy: a safe drainage procedure after pancreatoduodenectomy. The purpose of this study was to evaluate the role of pancreaticogastrostomy as an alternative method of restoring pancreaticointestinal continuity after pancreaticoduodenectomy. Since 1975, 45 patients have undergone pancreaticogastrostomy after pancreaticoduodenectomy at our institution. Pancreaticoduodenectomy was performed for pancreatic carcinoma (24 patients), ampullary carcinoma (8 patients), duodenal carcinoma (4 patients), common bile duct carcinoma (4 patients), pancreatic islet cell carcinoma (1 patient), trauma (1 patient), extensive colon carcinoma (1 patient), chronic pancreatitis (1 patient), and gastroduodenal artery aneurysm (1 patient). There was one operative death, for an overall operative mortality rate of 2%, and seven patients had major postoperative complications, for an overall morbidity rate of 15%. No pancreatic anastomotic leaks or other complications related to the pancreaticogastrostomy occurred. Twenty-four patients have died of recurrent carcinoma, with a mean survival of 25 months (range, 5 to 66 months), and 20 patients are alive and well, with a mean follow-up of 27 months (range, 2 to 106 months). Eight of these patients are alive 2 or more years after operation and four do not have exocrine pancreatic insufficiency. This experience confirms that pancreaticogastrostomy is a safe method of pancreatic drainage after pancreaticoduodenectomy and suggests that it may have technical advantages and therefore merits more widespread application. 
3	Accessory arm--dysraphism or disparity? Case report. The case of a 3-month-old infant with an accessory third arm is reported. The extra appendage was attached at the midcervical region and was associated with posterior cervical dysraphism and a cervical cord lipoma. Possible theories of origin are examined. 
3	Surgical correction of the snapping iliopsoas tendon. Eighteen patients with 20 symptomatic hips underwent lengthening of the iliopsoas tendon for persistent painful snapping of this "internal" variety of snapping hip. We referred to the pathologic, painful snapping of the iliopsoas in the deep anterior groin as the "internal" snapping hip. This is in contrast to the more common and better-known "external" snapping that involves the greater trochanter and its overlying soft tissues. The results of our iliopsoas lengthening procedure are presented here. Lengthening of the iliopsoas tendon was accomplished by step cutting of the tendinous portion of the iliopsoas. The pathoanatomy of this poorly understood symptom complex was described in 1984 paper from this institution and is reviewed here. Iliopsoas bursography demonstrated a sudden jerking movement of the iliopsoas tendon between the anterior inferior iliac spine and iliopectineal eminence, synchronous with the patient's pain and often accompanied by an audible snap. The average preoperative duration of symptoms was 2.9 years, and the average length of postoperative followup was 25 months. All patients, except one, had a marked reduction in the frequency of snapping after tendon lengthening, and 14 of 20 hips had no snapping postoperatively. Of the six patients who had recurrence of snapping, all but one stated that this occurred much less frequently and was much less painful compared to the preoperative state. Two hips required reoperation. Postoperatively, only three patients complained of subjective weakness, and most patients were unlimited in physical activity with return to activities such as competitive football, pole vaulting, and long-distance running. 
5	Chylothorax as presenting manifestation of adenocarcinoma with probable gastric primary. Chylothorax is an unusual complication of various malignant neoplasms, generally lymphomas. The few reported cases of chylothorax with gastric and other abdominal malignancies have involved large abdominal masses with prominent adenopathy and chylous ascites. We describe a patient in whom chylothorax was the presenting manifestation of an adenocarcinoma with probable gastric primary, developing prior to any clinical or radiologic evidence of tumor. 
5	Aortic occlusion and vascular isolation allowing avascular hepatic resection. Occlusion of the supraceliac abdominal aorta and hepatic vascular isolation were employed in a series of 15 patients as a definitive method to allow avascular hepatic resection. The series was compared with an earlier group of patients treated conventionally. In the avascular hepatic resection group there was no mortality; hypotension did not occur at the time of hepatic vascular isolation; rapid, accurate excision of the hepatic lesions could be achieved in a bloodless field; resection of midline lesions and those involving the great veins was possible; and "segmentectomies," or resections crossing segmental boundaries, could be performed where previously formal hepatic lobectomies were required. Concomitantly, the greatest amount of uninvolved hepatic parenchyma remained in situ. There was increased ease of operative management, reduced blood loss, and reduced operating time (mean, 2.8 hours). 
5	Jejunal-rectal fistula as a complication of postoperative radiotherapy. We present the case of a patient with an unusual, complex enteric fistula with multiple tracts and associated abscesses. The fistula was a late complication of radiotherapy, administered three years earlier, after resection for carcinoma of the sigmoid colon. Most of the small bowel was involved in the radiation-induced disease. A wide resection was performed successfully. This report reviews current literature on intra-abdominal postradiotherapy injuries, particularly intestinal fistulae. 
5	Surgical management of nonparasitic cystic liver disease. We report clinical features, surgical management, recurrences, and follow-up study of 12 patients with simple hepatic cyst, 11 patients with polycystic liver disease, and 19 patients with cystadenoma who were surgically treated over a 25-year period. The median age of patients was 48 years, and 37 women and 5 men were in the series. The most common presenting symptom and physical finding were chronic abdominal pain and tenderness in the right upper quadrant. The most commonly associated disease was polycystic kidney disease, which was an associated finding in 5 of the 11 patients with polycystic liver disease (45%). The most valuable diagnostic studies in all groups were computed tomography and ultrasonography. The location of the disease was bilobar in patients with polycystic liver disease, with a right lobe predominance in 18% of patients. The right lobe was also predominant in 83% of patients with simple hepatic cyst and 58% of patients with cystadenoma. Of all solitary cystic lesions in the left lobe, 75% of them were cystadenomas. Of the 66 surgical procedures performed, aspiration was associated with a failure rate of 100%; partial excision, a failure rate of 61%; and total excision and liver resection, a failure rate of 0%. Orthotopic liver transplantation was performed in three patients and was associated with two early deaths. Partial excision relieved symptoms in three patients (43%) with polycystic liver disease. Total excision, enucleation, or liver resection with cyst(s) is the treatment of choice for non-parasitic cystic lesions of the liver. 
1	Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. Ninety-eight patients with differentiated thyroid carcinoma were studied. Actuarial methods were used to investigate the 10-yr probability of survival (pS) and disease-free survival (pDFS). Our results show that the pDFS is a function of: (1) clinicopathologic stage: Stages I-II, pDFS = 90.9% +/- 5.0% versus Stages III-IV, pDFS = 55.9% +/- 17.8% (p less than 0.005); (2) age: Age less than 45 yr, pDFS = 87.2% +/- 10.0% versus age greater than or equal to 45 yr, pDFS = 66.6% +/- 12.0% (p less than 0.002); and (3) plasma thyroglobulin (Tg) levels: Tg less than or equal to 23 ng/ml, pDFS = 100% versus Tg greater than 23 ng/ml, pDFS = 68.3% +/- 10.6% (p less than 0.005). Using the multivariate analysis of proportional risk, the regression coefficients obtained (Stage: beta = 0.7615; Age: beta = 1.6398, and Tg: beta = 1.7607) allowed us to establish two different groups of risk of relapse on the basis of a prognostic index. 
1	Potential value of hormone receptor assay in carcinoma in situ of breast. The estrogen receptor (ER) expression of invasive breast cancer has been extensively studied both biochemically and with specific monoclonal antibodies against ER. Relatively few studies have attempted to characterize ER pattern in breast carcinoma in situ (CIS) and in other premalignant lesions. In the current study, the authors investigated the pattern of ER expression in 62 cases of breast CIS, 30 of which had a component of invasive cancer, and 36 cases of atypical hyperplasia. Paraffin sections of formalin-fixed breast tissue underwent enzyme pretreatment to expose nuclear antigenic sites as previously described. Breast tissues then underwent estrogen immunocytochemical assay using specific monoclonal antibodies (Abbott Laboratory, Chicago, IL). The cases were evaluated for heterogeneity, intensity of staining, and percentage of ER-positive cells. An attempt was made to study the relation between the pattern of ER expression, nuclear pleomorphism, and type of CIS. The results of ER immunocytochemical assay showed positive nuclear staining for ER in 75% of the CIS, 73% of CIS with invasive cancer, and 100% of atypical hyperplasias. ER expression in CIS agreed with that in the invasive carcinoma in 29 of 30 cases. This study also suggests that comedocarcinoma has a higher incidence of negative ER expression than the other types of CIS, particularly when it is associated with significant nuclear pleomorphism. There was no significant difference in ER tumor heterogeneity between premalignant and malignant lesions. 
4	Doppler color-flow images from a stenosed arterial model: interpretation of flow patterns. The capability of the recently introduced Doppler color-flow mapping devices to accurately detect flow patterns in the region of an arterial stenosis was evaluated by use of an in vitro flow model. Pulsatile flow simulating that in a low-resistance vessel was induced through a straight acrylic tube, which alternatively contained axisymmetric stenoses of 0%, 20%, 40%, 60%, and 80% diameter reduction. Doppler color-flow mapper images were taken in realtime along the tube midplane from 0 to 8 diameters downstream of each stenosis. Comparison of the Doppler color-flow mapping results with similarly recorded flow visualization (hydrogen bubble) images showed a close correspondence of key features of the flow, including detection of a high-velocity, centerline jet and near-wall separated flow zones. Distinctive flow patterns exist with each stenotic case, and these should be of considerable value in diagnosing clinical disease conditions. 
3	Pharmacokinetics of tiaprofenic acid after oral administration in fasting patients during and between migraine attacks. This study examined the pharmacokinetics of 300 mg of tiaprofenic acid, a NSAID belonging to the 2-arylpropionic class, as a single oral dose, in 10 migraine patients during and out of migraine attacks. Plasma concentration of tiaprofenic acid was determined by HPLC analysis. Drug absorption appeared to be the same during and out of migraine attacks (absorption half life: during attack, 0.249 +/- 0.122 hr; out of attack, 0.249 +/- 0.105 hr; maximum plasma concentration: during attack, 37.8 +/- 9.8 ug/ml; out of attack, 40.1 +/- 13.2 ug/ml). The other pharmacokinetic parameters evaluated were not affected by headache attacks as well. We conclude that tiaprofenic acid absorption and metabolism are not affected by migraine attacks. Also, our data suggest that tiaprofenic acid might be useful in the treatment of migraine. 
5	Spontaneous rupture of liver during pregnancy: current therapy. Spontaneous hepatic rupture secondary to severe pregnancy-induced hypertension is associated with a high rate of maternal and fetal mortality. Numerous types of surgical management have been described, but a uniform surgical approach has not been accepted. The purpose of this review was to examine modes of surgical therapy reported in the literature since 1976, as well as the 11-year experience at our institution. Twenty-eight cases were extracted from the literature and seven more were identified at our institution. The incidence in our population was one per 45,145 live births. Among 27 cases managed by packing and drainage, an 82% overall survival was achieved, whereas only 25% of eight patients undergoing hepatic lobectomy survived (P = .006). Hepatic hemorrhage with persistent hypotension unresponsive to blood products should be managed by evacuating the hematoma, packing the damaged liver, and draining the operative site. More aggressive surgical techniques, such as hepatic artery ligation or hepatic lobectomy, should be reserved for refractory cases. 
4	Spontaneous alterations in coronary blood flow velocity before and after coronary angioplasty in patients with severe angina. Cyclic coronary artery flow variations with a spontaneous decline in coronary blood flow to very low levels have been documented in stenosed canine coronary arteries with endothelial injury. These flow variations are associated with transient platelet aggregation and dislodgment and the release of selected mediators, including thromboxane A2 and serotonin. However, cyclic or spontaneous flow variations have not been demonstrated in stenosed coronary arteries in humans. In this study, the hypothesis was tested that spontaneous coronary blood flow velocity variations occur in some patients with stenosed coronary arteries before or after coronary artery angioplasty. Thus, 13 patients with severe and limiting angina underwent intracoronary pulsed Doppler velocimetry of their dilated artery immediately before and after percutaneous transluminal coronary angioplasty, whereas 9 control patients underwent velocimetry of an angiographically normal coronary artery. A 3F catheter with a 20 MHz Doppler crystal was positioned to achieve a maximal stable signal, and the flow velocity signal was recorded continuously for 20 min. Spontaneous flow velocity variations (greater than or equal to 38% change in Doppler frequency shift with wide morphologic changes) were present in 3 of the 13 patients tested. Spontaneous flow velocity variations occurred before angioplasty in one patient, after angioplasty in another and both before and after angioplasty in a third. In addition, 2 of the 13 patients, 1 with spontaneous coronary artery flow velocity variations before angioplasty, had frank vasospasm in an adjacent area just distal to the area of coronary dilation immediately after balloon inflation. These data establish that spontaneous coronary artery flow velocity variations occur in some patients with severe and limiting angina before and after coronary angioplasty. These variations may be related to platelet aggregation or coronary vasoconstriction, or both, at sites of endothelial injury resulting from plaque fissuring or ulceration and endothelial and medial injury occurring during coronary angioplasty. 
3	A case of cerebrotendinous xanthomatosis. II: The sterol content of a cataractous lens. The cholestanol content of a cataractous lens nucleus from a patient with cerebrotendinous xanthomatosis (CTX) was quantified by gas chromatography-mass spectrometry and found to be 0.27 micrograms per mg freeze-dried lens tissue. The cholestanol-cholesterol ratio of 1.7% in the lens nucleus was similar to that in the serum of the CTX patient. The cholestanol content and cholestanol-cholesterol ratio in the CTX lens were approximately four-fold and six-fold greater respectively than the mean levels found in three senile cataractous lens nuclei analysed simultaneously for comparative purposes. 
5	Lower leg subcutaneous blood flow during walking and passive dependency in chronic venous insufficiency. The blood flow in the subcutaneous adipose tissue of the lower leg of eight normal subjects and 19 patients with chronic venous insufficiency was measured. The 133Xe-washout technique was used with portable CdT1(C1) detectors and a data storage unit. Only those patients with ulcers and a systolic blood pressure at the toe of greater than or equal to 60 mm were investigated. In the controls the relative blood flow during sitting was 0.61 (range 0.35-0.80). In the patients it was 0.46 (range 0.22-0.87). This difference was not significant. During walking the blood flow increased in controls as well as in the patients compared to the value determined in the sitting position (P = 0.0078 and P = 0.0028, respectively, Wilcoxon matched-pairs test). The relative blood-flow rate during walking was 0.96 (range 0.60-1.58) in the controls, and 1.04 (range 0.49-1.46) in the patients. The difference between the normal subjects and the patients was not significant (P = 0.79). We conclude from our studies that patients with venous insufficiency are able to increase their blood flow during walking to the same extent as normal controls. 
5	Aerosol pentamidine prophylaxis following Pneumocystis carinii pneumonia in AIDS patients: results of a blinded dose-comparison study using an ultrasonic nebulizer PURPOSE: To compare the efficacy and safety of three different doses of prophylactic aerosol pentamidine in patients with one prior episode of Pneumocystis carinii pneumonia (PCP) and the acquired immunodeficiency syndrome. PATIENTS AND METHODS: The design of the study was a double-blind, randomized, dose-comparison clinical trial conducted at 13 medical centers within the United States. In stage I of the trial, patients were randomized to receive either 5 mg, 60 mg, or 120 mg of aerosol pentamidine delivered biweekly with the Fisoneb (Fisons, Inc., Rochester, New York) ultrasonic nebulizer. After 24 weeks of therapy, patients entered stage II of the trial, where the 5-mg group was re-randomized to either the 60-mg or 120-mg group. RESULTS: One hundred seventy-five patients entered stage I of the trial and received prophylaxis for a mean of 123.6 days. Seven assigned to the 5-mg biweekly dosing schedule had a confirmed recurrence of PCP, compared with none in the 60-mg group (p = 0.007) and three in the 120-mg group (p = 0.304). During stage II of the trial, eight patients in the 60-mg group and one additional patient in the 120-mg group had recurrent PCP. After 52 weeks of observation, the likelihood of being PCP-free was 88.0% in the 60-mg group and 93% in the 120-mg group (p = 0.712). Minor adverse events related to aerosol pentamidine administration included cough, taste perversion, chest pain, bronchospasm, and dyspnea. These side effects were more common in the 60-mg and 120-mg treatment groups and resulted in withdrawal from the study by one patient. Serious events were more common after 24 weeks of therapy and included asymptomatic hypoglycemia (five), pancreatitis (two), pneumothorax (one), and extrapulmonary pneumocystosis (one). CONCLUSIONS: These results demonstrate that biweekly administration of 60 mg or 120 mg of aerosol pentamidine significantly decreases PCP recurrence when compared with a 5-mg regimen or findings in historic controls and is generally well tolerated. There is no significant difference in effect or safety between these two dosing regimens in patients followed for at least 52 weeks of therapy. 
4	Peripheral arterial occlusive disease: prospective comparison of MR angiography and color duplex US with conventional angiography. Conventional angiography, two-dimensional inflow magnetic resonance (MR) angiography, and color duplex ultrasound (US) were performed on 12 patients in a blinded, prospective study. The ability to grade arterial lesions and plan revascularization interventions were compared. Arterial lesions were categorized as nonsignificant (0%-49% diameter reduction) or significant (50%-100% diameter reduction). Determination of nonsignificant and significant lesions with MR angiography was in agreement with that at conventional angiography in 100 of 140 lesions (71%). Agreement between results of conventional angiography and color duplex US occurred with 114 of 123 infrainguinal lesions (93%). Twenty-one vascular interventions were planned by using conventional angiography; there was agreement with color duplex US in 11 cases and MR angiography in five. Color duplex US performed well in the assessment of infrainguinal disease but was limited in the evaluation of iliac segments because of nonvisualization. The iliac region was visualized in more patients with MR angiography than with color duplex US, but image quality with MR angiography was inconsistent. Strategies to improve MR angiography of the peripheral vasculature merit further study. 
5	Relevance of focal cerebral ischemia models. Experience with fibrinolytic agents. Despite the limitations of individual ischemia models, experience with fibrinolytic agents suggests that 1) early intervention with rt-PA may result in rapid thrombolysis, functional recovery, and decreased mortality in small animal stroke thromboembolism models, 2) rt-PA has no general effect on clinical recovery following MCA occlusion and reperfusion in the nonhuman primate at dose rates capable of producing very high circulating rt-PA levels, while u-PA has an apparently salutary effect, and 3) intravenous infusion of rt-PA or u-PA early after ischemia/infarction in several model systems is not associated with significant intracerebral hemorrhage. The true clinical relevance of these general impressions must await the completion of human studies and studies in well-conceived models designed to define the vascular consequences to be expected from reperfusion achievable with thrombolytic agents. 
5	Acute splenic sequestration crisis in two adults with sickle cell disease: US, CT, and MR imaging findings. Acute splenic sequestration crisis (ASSC) is a rare complication in adults with sickle cell disease that is diagnosed clinically by means of sudden splenic enlargement and a rapid fall in hematocrit. Two cases of ASSC in adults with heterozygous sickle cell disease (sickle cell-thalassemia and sickle cell-hemoglobin C disease) were studied with use of duplex Doppler ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging. In both cases, US showed patency of the splenic vein and multiple hypoechoic lesions on the periphery of an enlarged spleen that were of low attenuation on CT scans and hyperintense on both T1- and T2-weighted MR images. These findings were believed to be suggestive of subacute hemorrhage. This was confirmed pathologically in one case and suggested in the other by the presence of a low-signal-intensity ring, probably hemosiderin, surrounding one of the lesions. Also, the remainder of the spleen in both patients was of normal signal intensity, unlike the diminished signal intensity seen in patients with homozygous sickle cell disease. Further study is needed to determine the role of imaging in the diagnosis and treatment of ASSC. 
4	ECMO assisted angioplasty for cardiomyopathy patients with unstable angina. Patients who are otherwise unsuitable candidates for coronary bypass surgery or standard coronary angioplasty (PTCA) may be successfully treated with PTCA during ECMO. Five patients (3 men, 2 women), with a mean age of 57 years, are reported on here. They were not considered good candidates for standard therapy because of poor left ventricular function (mean EF, 24; range, 16 to 28%). Patients were supported by percutaneous femoral bypass using a BARD CPS machine, and underwent successful PTCA of either two vessels (three patients) or three vessels (two patients); in addition, one patient had dilatation of a stenotic aortic valve. Patients were supported with ECMO for 26 to 140 (mean 104) minutes, and required transfusion with 0 to 4 (mean 2) units of blood during or after the procedure. Complications included groin hematoma in two patients. All were discharged within 4 days of the procedure. Follow-up of the patients has been completed (4-7 mo) with no further hospitalizations for unstable angina. All patients remain in NYHA Class II or III. These data suggest that ECMO-assisted angioplasty is a safe and effective method of palliation of unstable angina associated with cardiomyopathy. 
4	Chronic therapy for congestive heart failure with benazepril HCl, a new angiotensin converting enzyme inhibitor. Benazepril HCl is an orally effective angiotensin converting enzyme (ACE) inhibitor previously shown to have significant acute hemodynamic benefits in patients with congestive heart failure. In this study, 21 patients with New York Heart Association Class III or IV congestive heart failure were treated with 2 to 15 mg of benazepril HCl as a single daily oral dose for 28 days to determine the clinical and hemodynamic value of chronic therapy. Each patient underwent clinical evaluation during the 28-day period, as well as invasive hemodynamic studies on the first two and last two days of the trial. Plasma ACE activity and aldosterone levels fell significantly and renin levels rose after therapy. Benazepril HCl produced significant (p less than 0.01) reductions in arterial pressure and systemic vascular resistance, with corresponding increases in cardiac output and decreases in pulmonary artery wedge pressure. Responses after 28 days of therapy were equivalent to those after the initial doses. Clinical effects included reduced rest, exertional and paroxysmal nocturnal dyspnea, as well as reduced peripheral edema. Only one patient developed symptomatic orthostatic hypotension. Thus, benazepril HCl, given once daily, is an effective and well tolerated oral agent for the chronic treatment of advanced congestive heart failure. 
4	Bilateral infrapatellar tendon rupture in a patient with jumper's knee. This is the fourth case report of bilateral infrapatellar tendon rupture as a result of indirect trauma in a patient without systemic disease. This is the only report we have found of jumper's knee leading to simultaneous infrapatellar tendon ruptures. 
3	Meningiomas mimicking cerebral schwannoma. A brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis, which confirmed the neoplasm as a meningioma. This prompted reexamination of a similar tumor, described in a previous publication as a cerebral schwannoma, with identical immunohistochemical techniques. The results obtained favored alteration of this diagnosis to that of meningioma. This experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms. 
5	Prospective comparison of a conventional and an accelerated protocol for programmed ventricular stimulation in patients with coronary artery disease. BACKGROUND. This study compared the sensitivity, specificity, and efficiency of a "conventional" and "accelerated" programmed stimulation protocol in 293 patients with coronary artery disease who had a history of sustained or nonsustained monomorphic ventricular tachycardia (VT). METHODS AND RESULTS. In the conventional protocol, one and two extrastimuli were introduced during sinus rhythm and during basic drive trains at cycle lengths of 600 and 400 msec at the right ventricular apex and then at the outflow tract or septum. In the accelerated protocol, one, two, and then three extrastimuli were introduced at each of three basic drive train cycle lengths (350, 400, and 600 msec) at the right ventricular apex; the procedure was repeated at a second right ventricular site. Six hundred thirty-four electrophysiological tests were performed using one of these two protocols either in the baseline state (293 tests) or during drug testing (341 tests). The yield of sustained, monomorphic VT was 89% with the conventional protocol and 92% with the accelerated protocol during baseline tests in patients who had a history of sustained VT (p = 0.05); 20% and 34%, respectively, during baseline tests in patients with a history of nonsustained VT (p = 0.06); and 70% and 77%, respectively, during drug testing (p = 0.2). To induce sustained, monomorphic VT, 10.1 +/- 5.0 (mean +/- SD) protocol steps and 14.4 +/- 8.7 minutes were required with the conventional protocol, compared with 4.0 +/- 3.7 steps and 5.6 +/- 6.1 minutes with the accelerated protocol (p less than 0.001 for each comparison). Among the tests in which sustained, monomorphic VT was induced, sustained polymorphic VT or ventricular fibrillation was induced more often with the conventional protocol (3.6%) than with the accelerated protocol (0.9%, p = 0.05). CONCLUSIONS. The efficiency of programmed stimulation can be improved by the early use of a basic drive train cycle length of 350 msec and three extrastimuli. Compared with a conventional stimulation protocol, the accelerated protocol used in this study reduces the number of protocol steps and duration of time required to induce monomorphic VT by an average of more than 50% and improves the specificity of programmed stimulation without impairing the yield of monomorphic VT. 
5	The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in preterm premature rupture of the membranes. The relationships among umbilical artery velocimetry, fetal biophysical profile, and placental inflammation in 44 consecutive patients with preterm premature rupture of the membranes were determined. All patients were followed up with daily fetal biophysical profiles and systolic/diastolic ratios. After delivery, placental pathologic examination for histologic evidence of infection (umbilical vasculitis) was performed in all cases according to a standard protocol. The longitudinal trends of fetal biophysical profile scores and systolic/diastolic ratios were analyzed for patients with and without umbilical vasculitis. Analysis of the longitudinal trend during the period of 2 to 7 days before delivery showed that there were no differences of biophysical scores of systolic/diastolic ratios in either group. However, in the last examination, within 24 hours of delivery, patients with umbilical vasculitis had higher systolic/diastolic ratios and lower biophysical profile scores as compared with previous examinations. In addition, the biophysical profile score of the last examination 24 hours before delivery in patients with umbilical vasculitis was found to be significantly lower as compared with patients without umbilical vasculitis (mean +/- SD, 6.6 +/- 2.3 versus 8.2 +/- 2.4, respectively). These data suggest that subclinical stages of infection are associated with biophysical alterations of the fetoplacental unit (i.e., simultaneous decrease in fetal biophysical activities and increase in systolic/diastolic ratios). Daily umbilical artery systolic/diastolic ratios, in conjunction with biophysical profiles, may be useful to follow up patients with preterm premature rupture of the membranes. 
1	A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02). 
4	When is echocardiography unreliable in patients undergoing catheterization for pediatric cardiovascular disease? Technologic advances in echocardiography (e.g., better spatial resolution, Doppler, and color flow mapping) have improved our ability to demonstrate anatomy and physiology in previously problematic conditions, precluding catheterization and angiography in some instances. However, diagnostic catheterization remains necessary in other instances. The aims of this study were to determine whether echocardiography alone was sufficient to delineate the anatomic and flow abnormalities in patients subsequently selected to undergo catheterization and, if not, under what circumstances was echocardiography unable to establish the definitive diagnosis. Echocardiograms of 252 infants and children who underwent catheterization during a 14-month interval were analyzed retrospectively to determine whether the echographic assessment was nondiscrepant (group 1) or discrepant (group 2) with the catheterization assessment. Any deviation in the complete accurate assessment constituted a discrepancy; identification of more than one discrepancy in a single patient was possible. Independent variables included patient's age, weight, operative status, use of color flow mapping, echocardiograph operator, and interval between echocardiogram and catheterization. To determine whether the discrepancies were clinically significant, data from patients in group 2 were reviewed independently by three cardiologists to determine whether patient management would have changed given the added data provided by catheterization. Echocardiographic evaluations were discrepant in 155 instances. In 54 of 155 instances (35%), discrepancies were judged to be clinically significant (group 3). Twenty-three of 54 cases (43%) involved extracardiac lesions (i.e., aortic arch, pulmonary arterial, bronchial collateral, and pulmonary venous anomalies), 20 of 54 (37%) involved pressure gradients, 7 of 54 (13%) involved intracardiac lesions, and 4 of 54 (7%) involved coronary arterial lesions. 
5	Causes of failure after repeat vitreoretinal surgery for recurrent proliferative vitreoretinopathy. During the last two years, we performed vitreoretinal surgery on 37 eyes with retinal detachments and recurrent severe proliferative vitreoretinopathy in 37 patients who had had previous failed scleral buckling and vitreous surgery for proliferative vitreoretinopathy. Anterior proliferative vitreoretinopathy was present in 32 of 37 eyes (86%); posterior proliferative vitreoretinopathy of fixed retinal folds in four quadrants of narrow or closed funnel shape occurred in 23 of 37 eyes (62%); and subretinal proliferation was noted in 16 of 37 eyes (43%). The retinas in 12 eyes (32%) redetached from new or recurrent anterior proliferative vitreoretinopathy in nine eyes, reopening of pre-existing retinal breaks in two eyes, or recurrent posterior periretinal proliferation in one eye. With additional vitreoretinal procedures in six eyes and after a mean follow-up period of 11 months, 27 of 37 retinas (73%) were totally reattached, and an additional five eyes (13%) had retinal reattachment posterior to the scleral buckle. Of the 32 patients with posterior retinal reattachment, final visual acuity of 5/200 or better was attained in 19 eyes (59%). 
3	Long-term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula Serous detachment of the macula is a well-known complication in patients with an optic nerve pit. Despite the many descriptions of this condition and possible treatment options, the long-term natural history is not well known. The authors identified 15 eyes of 15 consecutive patients seen over 21 years who were diagnosed with a serous detachment of the macula arising from an optic nerve pit. Average length of follow-up was 9 years. Twelve eyes lost three or more lines of vision, two eyes remained unchanged, and only one eye improved. All of the 12 eyes losing three or more lines of vision experienced this decrease within the first 6 months of follow-up. Although only two patients had a visual acuity of 20/200 or less initially, 12 of 15 patients had a visual acuity of 20/200 or less at the time of their last examination. The appearance of the macula at last examination included cystic changes of the neurosensory retina, full-thickness hole formation, retinal pigment epithelial mottling, and lamellar hole formation in the outer retinal layer. The long-term visual prognosis in patients with optic nerve pit and untreated serous retinal detachment of the macula is poor, and visual loss occurs within 6 months of the serous detachment. 
5	Assessment of fibrin(ogen) degradation products in preeclampsia using immunoblot, enzyme-linked immunosorbent assay, and latex-based agglutination. Plasma and serum from pregnant women with preeclampsia (N = 35) and normotensive pregnant (N = 71) and nonpregnant (N = 10) controls were screened for fibrin(ogen) degradation products (fibrinogen and cross-linked fibrin degradation products, and fibrin polymers) using three different assay systems (immunoblot, enzyme-linked immunosorbent assay [ELISA], and latex-bead agglutination assay). All tests showed statistically significant differences (P less than .05) between the preeclamptic patients and the other two groups (pregnant and nonpregnant women). The ELISA assay for total fibrin(ogen) degradation products was the most sensitive test, but was less specific than D-dimer latex. Eleven of the 35 preeclamptic women developed HELLP syndrome (hemolysis, elevated liver enzyme, and low platelet counts). Positive tests were as common in the 11 preeclamptic women who developed the syndrome as in the 24 who did not. These results suggest that fibrinolytic disorders are secondary pathophysiologic events in the course of preeclampsia, but further studies with a larger number of patients are needed. 
5	Chromosome studies in 104 patients with polycythemia vera. Chromosome studies were done in 104 patients with various stages of polycythemia vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome studies were successful in 86 patients, 37 (43%) of whom had a chromosome abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among the 63 patients with successful chromosome studies during the first 10 years of disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the disease for more than 10 years, 87% had an abnormal clone. Chromosome abnormalities were found in 11 of the 60 patients who either were untreated or underwent only phlebotomy and in 26 of the 44 patients who were treated with myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients early during the course of their disease and also among untreated patients. These chromosome abnormalities seem to be related to the natural course of PV rather than to therapy. Patients with a chromosomally abnormal clone at the time of diagnosis of PV had a poorer survival than did those with only normal metaphases. Cytogenetic results did not predict evolution of the disease, but they did provide clues to hematologic phenotype, duration of the disease, and consequences of myelosuppressive therapy. 
4	Pseudoaneurysm of the abdominal aorta: a case report and review of the literature. Pseudoaneurysm of the abdominal aorta is a rare finding, accounting for only 1% of all abdominal aneurysms. Abdominal pseudoaneurysms have been reported only in males, and two-thirds of the cases are the result of penetrating trauma. Pain, abdominal mass, and vascular occlusion are the most common presenting signs and symptoms. The interval between injury and rupture may range from hours to years, and accordingly, a high index of suspicion is needed to make the diagnosis. 
3	Cardiopulmonary perfusion and cerebral blood flow in bilateral carotid artery disease The fear of cerebral complications after cardiopulmonary bypass in patients with heart disease and severe carotid artery disease has led many authors to suggest combined approaches in these patients. The pathogenetic mechanism for stroke is based partly on the stenotic narrowing of the carotid artery. A diameter reduction of 75% is frequently considered hemodynamically significant and indicative of an increased risk for neurological morbidity. We studied the cerebral blood flow in 7 patients undergoing coronary artery bypass grafting who also had severe bilateral carotid disease. The results were compared with the results in 17 patients without carotid disease who had bypass grafting. The cerebral blood flow was measured by xenon 133 washout technique before, during, and after cardiopulmonary bypass with moderate hypothermia. Acid-base regulation was according to the alpha-stat theory, and blood pressure was kept greater than 50 mm Hg. The cerebral blood flow levels (mL.100g-1.min-1) before, during, and after cardiopulmonary bypass in the study group (30 +/- 11, 31 +/- 8, 47 +/- 20) (mean +/- standard deviation) were almost identical to those in the control group (30 +/- 11, 28 +/- 8, 47 +/- 12). The cerebral blood flow levels for the left and right hemispheres in the group with carotid disease were comparable and within normal ranges. In 2 patients, slight differences were noted between hemispheres, and this finding may indicate an increased risk for ischemia. These patients, however, did not show any signs of postoperative deficit. The flow limitations of critical carotid stenoses do not seem to imply a risk for cerebral hypoperfusion if cardiopulmonary perfusion is performed in a controlled manner. 
4	Rupture of a giant carotid aneurysm after extracranial-to-intracranial bypass surgery. We report a case of a fatal rupture of a previously unruptured giant aneurysm of the bifurcation of the internal carotid artery (ICA), which occurred after an extracranial-intracranial (EC-IC) bypass and the partial occlusion of the ICA. Interim angiography showed retrograde filling of the proximal middle cerebral artery to the aneurysm. There have been four previously reported cases of giant aneurysms rupturing after treatment with an EC-IC bypass and carotid ligation, and it appears likely that a change in pressure/flow dynamics produced by the bypass may have been the cause. The technique of carotid ligation with an EC-IC bypass is used frequently to treat unclippable intracranial aneurysms, and the resulting hemodynamic changes need to be considered carefully to prevent this type of complication. To minimize hemodynamic stress on the aneurysm, we suggest that 1) the bypass caliber should be as small as possible consistent with sufficient cerebral blood flow after ICA occlusion, and 2) complete ICA occlusion should be performed as soon as possible after the bypass. 
3	Oculo-bulbar myasthenic symptoms as the sole sign of tumour involving or compressing the brain stem. Four patients with tumours involving or compressing the brain stem are described whose initial clinical symptoms of fluctuating paresis of the external ocular muscles and/or the pharyngeal muscles without other neurological deficits led to the primary diagnosis of focal myasthenia. The combination of an unusual clinical pattern, involvement of muscles of only one ocular nerve or severe dysphagia/dysarthria without extension of the myasthenic symptoms, should lead to further investigation to exclude other reasons of a focal myasthenic syndrome such as a brain-stem tumour. 
4	Role of new anticoagulants as adjunctive therapy during thrombolysis. Procoagulant activity may persist during coronary thrombolysis and result in either delay in the time to recanalization or recurrent thrombosis. Although heparin and aspirin form the mainstay of current therapy, recurrent thrombosis occurs despite adjunctive heparin therapy during thrombolysis. Newer agents that inhibit thrombin by antithrombin III-independent mechanisms, or that inhibit earlier steps in the coagulation cascade, have been shown to be effective in the experimental preparation of coronary thrombolysis. Because heparin-antithrombin III is a relatively inefficient inhibitor of thrombin bound to fibrin, agents such as hirudin or small peptide inhibitors of the thrombin-active site appear to be more effective inhibitors of clot-associated thrombin activity. Inhibition of early steps in the coagulation cascade with the inhibitor of tissue factor-factor VIIa complex, or with activated protein C, also appears to be an effective anticoagulant strategy. In experimental preparations all of these agents have shown superiority in preventing recurrent thrombosis compared with heparin, and in some cases they appear to accelerate the rate of clot lysis. 
5	Immunologic defects in patients with refractory sinusitis. Sixty-one patients with chronic sinusitis who were referred for an allergy evaluation were evaluated for immunologic competence including assessment of quantitative serum immunoglobulin levels, IgG subclass levels, and response to pneumococcal and Haemophilus influenzae vaccines. In addition to chronic sinus disease, recurrent otitis media and asthma exacerbation were common problems in this group. Five patients had an elevated age-adjusted IgE level and 22 patients had positive prick tests to one or more environmental inhalants; these findings suggest an allergic component in this subgroup. Twelve additional patients had highly reactive intradermal tests to common environmental allergens, which also may be clinically significant for underlying atopy. Eleven patients had low immunoglobulin levels, 6 had low immunoglobulin levels and vaccine hyporesponsiveness, and 17 had poor vaccine response only. Thus, 34 of 61 patients with refractory sinusitis had abnormal results on immune studies, with depressed IgG3 levels and poor response to pneumococcal antigen 7 being most common. In addition to allergy, immunologic incompetence may be an important etiologic factor in patients with chronic, refractory sinusitis. 
1	Bone metastases: pathophysiology and management policy. The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response. 
5	Feasibility and cost savings of outpatient electrophysiologic testing. The feasibility of outpatient electrophysiologic testing was examined by reviewing 100 consecutive outpatient tests performed in 95 patients. Seventy-one of the patients (75%) had no underlying heart disease. The electrophysiologic tests were performed to evaluate supraventricular tachycardias (n = 47), nonsustained ventricular tachycardia (n = 20), unexplained syncope (n = 21), palpitation (n = 9) or intermittent heart block (n = 2). A mean of 2.8 +/- 0.5 6F electrode catheters were inserted through a femoral vein. An electrode catheter was inserted into a subclavian or internal jugular vein in 28 tests and a 5F cannula was inserted into a femoral artery to monitor the blood pressure in 20 tests. The results of 61 tests (61%) were abnormal. Patients were monitored for a mean of 3.8 +/- 1.2 h after the procedure and then discharged. No complications occurred. For cost analysis a subgroup of 60 of these patients was matched for age, gender, heart disease and indication for electrophysiologic testing with a group of 60 patients who underwent electrophysiologic testing as inpatients. Physicians' fees for the two groups were similar; however, the mean hospital charge was $5,845 +/- 3,763 for the inpatient group compared with only $2,120 +/- 1,244 for the outpatient group (p less than 0.001). Thus, outpatient electrophysiologic testing is feasible and safe and results in substantial cost savings in patients without life-threatening arrhythmias. 
3	Flexion-extension views in the evaluation of cervical-spine injuries. STUDY OBJECTIVE: To determine the efficacy of flexion-extension (F/E) cervical-spine radiographs in detecting acute cervical-spine instability in emergency patients. DESIGN: We retrospectively reviewed the charts of 141 consecutive trauma patients who had F/E views performed after a routine cervical-spine series (three views) was obtained in the emergency department. Interpretations of the routine series were compared with those of the F/E views to determine if additional useful information was provided by the latter. The charts also were reviewed to determine if any variables were associated with an increased use of F/E views, an increased likelihood of these views demonstrating instability, or any neurologic sequelae resulted from these studies. SETTING: An urban Level I adult trauma center. MEASUREMENTS: The interpretations of the routine series were noted to be either normal, abnormal but without demonstrable fracture/dislocation, or demonstrating a fracture/dislocation. The F/E views were categorized as stable, unstable, or uninterpretable. RESULTS: Cervical-spine instability was demonstrated by F/E views in 11 of the 141 patients (8%), four of whom had normal routine cervical-spine films. Three of these four patients required surgical stabilization. Prolonged neck pain (more than 24 hours), an initially abnormal spine series, and a neurosurgical consult were all associated with an increased use of F/E views. Ten of 11 patients with radiographic instability had significant neck pain by history; the remaining patient was intoxicated. No neurologic sequelae resulted from performing F/E studies. There was one false-negative F/E study, which raises concern about the reliability of this procedure in the ED. CONCLUSION: We believe that a large prospective study is required to determine which patients warrant F/E views. 
5	Bialaphos poisoning with apnea and metabolic acidosis. A 64-year-old man with ethanol intoxication, ingested a bottle of Herbiace (100 ml, 32 w/v% of bialaphos, CAS #35597-43-4, Meiji Seika Kaisha, Tokyo, Japan). He had severe metabolic acidosis and was treated with infusions of sodium bicarbonate and furosemide, plus gastric lavage and enema. The metabolic acidosis improved 15 hours after treatment but nystagmus, apnea and convulsions were progressive. Although his sensorium was clear, spontaneous respirations were not observed for 64 hours. The electroencephalographic findings of atypical triphasic waves and slow waves suggest a unique response to bialaphos poisoning. His clinical course indicates that the management of apnea is critically important to recovery from bialaphos poisoning. 
5	Traumatic aneurysm of the superior cerebellar artery: case report and review of the literature. Less than 10% of the 250 reported cases of traumatic intracranial aneurysms have involved the posterior circulation. Traumatic aneurysms of the superior cerebellar artery are extremely rare, with only three cases previously reported. This is the first report of a traumatic superior cerebellar artery aneurysm in which the diagnosis was suggested by computed tomographic scan. The potential for a good outcome suggests the value of early angiography when the history and diagnostic imaging studies suggest the possibility of a traumatic aneurysm. 
5	Prophylaxis of deep venous thrombosis after acute abdominal operation. Two hundred and forty-five patients who underwent acute extensive abdominal operations were randomized into three regimens to achieve optimal prophylaxis of postoperative thromboembolic complications. All of the patients were screened by the 125I-fibrinogen uptake test for seven days and if the phlebographic findings were positive. Of 81 patients receiving low dose heparin, 12 had thromboembolism. Of 79 receiving a combination of low dose heparin and graded compression stockings, two had thromboembolism, and of 85 receiving a combination of dextran and graded compression stockings, 13 had this complication. This difference is significant in favor of the second treatment (p = 0.013). It is concluded that the combination of low dose heparin and graded compression stockings is an effective way to prevent thromboembolism after acute abdominal operations. 
3	Are myotonias and periodic paralyses associated with susceptibility to malignant hyperthermia? Excised muscles from patients with myotonia or periodic paralysis were subjected to the in vitro contracture test for susceptibility to malignant hyperthermia (MH). In a group of 44 patients, this standard test gave four positive, 10 equivocal and 30 negative results. The results for 27 control muscles from normal subjects were negative. When the test was performed with less than normal concentrations of contracture-triggering substances (caffeine less than or equal to 2 mmol litre-1, less than or equal to 2% halothane), 70% of the muscles from the patients and only 15% of the controls responded with small contractures (less than 0.2 g). These results should not be taken to indicate that the patients have the genetic trait for MH. The positive and equivocal test results, in addition to the slight contractures, may be accounted for by the electrical after-activity in the cases of pure myotonia, and by increased resting myoplasmic [Ca2+] in myotonic dystrophy. This shows that the in vitro contracture test lacks specificity. 
5	Memory retraining to support educational reintegration. A memory retraining package specifically designed to facilitate reintegration of head injured patients into an educational environment is described. Two adolescent patients who had severe head injuries were administered the memory retraining package approximately three months postinjury. A single case study and multiple baseline design was used to evaluate the efficacy of the memory retraining program. The results suggested that this is a promising avenue for improving memory functioning and facilitating educational reintegration, but only where moderate rather than severe memory deficits are involved. Studies involving groups of patients and the collection of data on generalization are required to confirm usefulness. 
5	HBV-DNA detection by gene amplification in acute hepatitis B. Serum samples from 62 women, inadvertently infected with hepatitis B virus in an in vitro fertilization program, were tested for the presence of hepatitis B virus-DNA using the polymerase chain reaction. Under conditions of a strict spatial separation of DNA extraction, amplification and product analysis, we succeeded in detection of as few as 360 hepatitis B virus particles per milliliter. Hepatitis B virus-DNA was detected with a high frequency during HBsAg and HBeAg antigenemia (98.5%) but also in the convalescent phase after appearance of antibody to HBsAg (18.2%). However, all patients with hepatitis B virus-DNA in convalescent sera were hepatitis B virus-DNA negative 3 to 6 mo later. All patients with HBeAg-positive samples showed hepatitis B virus-DNA positivity by polymerase chain reaction. For acute hepatitis, gene amplification restores the relationship between HBeAg and hepatitis B virus-DNA observed in serum from chronic hepatitis B patients and calls attention to the prolonged presence of hepatitis B virus-DNA in serum after generally accepted criteria for resolution of the infection have been reached. 
5	Control of total peripheral resistance during hyperthermia in rats. To elucidate the effect of blood volume on the circulatory adjustment to heat stress, we studied alpha-chloralose-anesthetized rats at three levels of blood volume: normovolemia (NBV), hypervolemia (HBV; +32% plasma volume by isotonic albumin solution infusion), and hypovolemia (LBV; -16% plasma volume by furosemide administration). Body surface heating was performed with an infrared lamp to raise arterial blood temperature (Tb) at the rate of approximately 0.1 degree C/min. Before heating, central venous pressure (CVP) was significantly higher in HBV (0.41 +/- 0.25 mmHg) and lower in LBV (-1.44 +/- 0.22 mmHg) than in NBV (-0.41 +/- 0.10 mmHg). The Tb at which CVP started to decrease was approximately 40 degrees C in HBV, approximately 41 degrees C in NBV, and approximately 42 degrees C in LBV, and it decreased by 1.53 +/- 0.14, 1.92 +/- 0.24, and 0.62 +/- 0.14 mmHg from 37 to 43 degrees C of Tb in HBV, NBV, and LBV, respectively. Stroke volume was closely correlated with CVP, and this relationship was not affected by Tb. Heart rate responses to the raised Tb were similar among the three groups. Mean arterial pressure (MAP) was not affected by blood volume modification or CVP and was maintained at preheating (Tb 37 degrees C) level until Tb rose to 40 degrees C. Above this Tb, MAP increased until Tb reached 43 degrees C (+30-40 mmHg) for all three groups. Total peripheral resistance (TPR) was inversely correlated with CVP, and the slope of the linear relationship between TPR and CVP in LBV was three- to fourfold steeper than in NBV or HBV. 
5	Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model. Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly following stimulation by nicotine. This most likely results from the stimulated release of opioid peptides and catecholamines from the transplanted chromaffin cells. However, chronic pain models may more closely resemble human clinical pain, and the arthritic rat model has been used for screening potential therapeutic strategies. The purpose of the present study was to assess the potential for adrenal medullary tissue implanted into the spinal subarachnoid space to alleviate chronic pain. Adrenal medullary tissue was implanted into adjuvant-induced arthritic rats, and changes in body weight and vocalization responses were monitored over the 10 week course of the disease. Results indicate that the severe weight reduction normally associated with this inflammatory arthritis was attenuated by adrenal medullary, but not control, implants. In addition, vocalizations were reduced in animals implanted with adrenal medullary, but not control tissue following nicotine stimulation. This reduction was blocked by the opiate antagonist, naloxone, and partially attenuated by the alpha-adrenergic antagonist, phentolamine. Together, these results suggest that the transplantation of adrenal medullary tissue into the subarachnoid space of the spinal cord may provide a local source of opioid peptides and catecholamines for the reduction of chronic pain. 
3	Mesencephalic cholinergic nuclei in progressive supranuclear palsy. Using an antibody against choline acetyltransferase (ChAT), mesencephalic cholinergic cell nuclei were studied in autopsy material from 3 cases of progressive supranuclear palsy (PSP) and 4 controls. ChAT-immunoreactive neurons were quantified in sections that spanned the rostrocaudal extent of each nucleus. In PSP, there was a significant decrease in the number of neurons with detectable immunoreactivity for ChAT in and adjacent to the central gray substance in the following nuclei: the nucleus of Edinger-Westphal (69%); the rostral interstitial nucleus of the medial longitudinal fasciculus (97%); the interstitial nucleus of Cajal (78%). A cell loss was also evident in a group of neurons found in the deep layers of the superior colliculus (93%). In contrast, the estimated number of ChAT-immunoreactive cell bodies in cranial nerves III and IV, in the mesencephalic reticular formation, and in the parabigeminal nucleus was not different from that of controls. The results are compatible with the notion that, in PSP, there is a regionally selective destruction of cholinergic neurons. 
5	Palliative operations for colorectal cancer. A review of 96 consecutive patients who underwent palliative surgery for primary colorectal cancer was undertaken to clarify the value of palliation achieved with surgical treatment. The overall rate of postoperative mortality was 8 percent (8 of 96) and the overall rate of postoperative morbidity was 24 percent (23 of 96). The mortality rate was 5 percent (3 of 66) after resective surgery and 17 percent (5 of 30) after nonresective surgery. Three deaths were related to the malignant disease, three were related to the intra-abdominal infection, and two were related to formation of intestinocutaneous fistulas. Of the 8 patients who died, 1 had a tumor with local visceral involvement only and 7 had a tumor with more distant spread. Median survival was 10 months for all patients, 15 months for patients treated with resective surgery, and 7 months for nonresected patients. Five patients (5 percent) have survived for longer than 5 years. The median relief of preoperative cancer symptoms was 4 months (4 months after resective surgery and 1 month after nonresective surgery). Twenty-five patients have undergone second surgery. It is concluded that palliative resective surgery for colorectal cancer can improve patient comfort with an acceptable postoperative mortality rate when cancer growth is localized and in favorable cases with more distant spread, whereas nonresective surgery fails to achieve symptom relief. 
1	Chondrolipoangioma. A cartilage-containing benign mesenchymoma of soft tissue. The clinical and pathologic features of four cases of benign mesenchymoma in which mature cartilage represented the predominant component are reported. The distinctive histologic feature in all four cases was a lobular proliferation of cartilaginous tissue exhibiting a spectrum of hyaline cartilage, fibrocartilage, myxoid cartilage, and cartilage with ossification and even bone marrow formation, intimately associated with mature adipose tissue and vascular elements. The localization of these tumors was in the proximity of a bone, but not attached to the periosteum or in continuity with a joint. Because these lesions may be mistaken for other cartilaginous neoplasms of soft tissue, recognition of this entity has potentially important diagnostic and therapeutic implications in that mutilating surgery may be avoided. 
5	Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension. 
2	Radiographic techniques and efficacy in evaluating esophageal dysphagia. The radiographic examination of the esophagus to determine structural and/or functional causes of dysphagia is best performed with multiple techniques. These include full-column studies to produce distended films with or without the use of a solid bolus, mucosal relief films to identify mucosal defects such as esophagitis or the presence of varices, double-contrast films, and motion recording (fluoroscopy). The efficacy of each technique depends on the quality of the study and the specific disorder to be detected. Esophageal lesions producing dysphagia are classified into extrinsic structural lesions, intrinsic structural lesions, and esophageal motility disorders. Radiographic studies are the preferred screening techniques for patients with dysphagia. Although not as sensitive for the evaluation of mucosal lesions, radiographic studies are superior to endoscopy for the detection of abnormal motility, esophageal rings, and strictures. 
4	Delayed onset of cardiac arrhythmias from sustained-release verapamil. Sustained-release products in overdose are known to produce prolonged effects as well as delayed onset. The availability of sustained-release calcium channel blockers may produce an initial misleading picture for patients who are at risk for serious toxicity. We report the cases of two adults who had delayed onset of arrhythmias after ingestion of sustained-release verapamil. In both cases, a single dose of activated charcoal was administered, but the patients still developed toxicity. Some of the unique problems encountered with sustained-release formulations are discussed, and 24-hour cardiac monitoring for sustained-release calcium channel blocker overdoses, despite a possible early asymptomatic period, is suggested. 
5	The relationship between hypochondriasis and medical illness. Forty-one Diagnostic and Statistical Manual of Mental Disorders-III-Revised hypochondriacs were accrued from a primary care practice. Seventy-five control subjects were selected at random from among the remainder of the patients in the same clinic. All subjects completed a structured diagnostic interview and standardized self-report questionnaires. Medical morbidity was assessed with a medical record audit and with primary physicians' ratings. The hypochondriacal and comparison samples did not differ in aggregate medical morbidity, although the hypochondriacal sample had more undiagnosed complaints and nonspecific findings in their medical records. Within the comparison sample, higher levels of medical morbidity were associated with higher levels of hypochondriacal symptoms. This occurred primarily because the most serious medical disorders were associated with more bodily preoccupation, disease conviction, and somatization. Within the hypochondriacal sample, no correlation was found between the degree of hypochondriasis and the extent of medical morbidity. 
5	Possible role of leukotrienes in gastritis associated with Campylobacter pylori. This study was done to evaluate the role of leukotrienes (LTs) in gastritis associated with Campylobacter pylori. Biopsy specimens of gastric mucosa were obtained endoscopically from 18 patients with nonulcer dyspepsia for bacteriological and histological examination and extraction of LTs. There was correlation between the LTB4 level in the mucosa and the degree of gastritis evaluated histologically. The level was higher when infiltration of neutrophils in the gastric mucosa was more extensive. The LTB4 level in mucosa infected with C. pylori was higher than that in noninfected mucosa. These findings suggest that endogenous LTs may be related to the pathogenesis of gastritis associated with C. pylori. 
1	Hepatocellular carcinoma as second malignant neoplasms in successfully treated Wilms' tumor patients. A National Wilms' Tumor Study report. Although rare, second malignant neoplasms (SMN) after treatment for Wilms' tumor are deadly. A recent National Wilms' Tumor Study (NWTS) report identified 15 patients with second malignancies discovered over 14,381 person-years of observation. This report described four patients with secondary hepatocellular carcinoma in greater detail. These patients were strikingly similar in that all had right-sided tumors and each one had received right upper-quadrant irradiation. All patients died shortly after diagnosis of the SMN. 
2	Familial occurrence of inflammatory bowel disease. BACKGROUND AND METHODS. We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohn's disease) provided adequate information. RESULTS. As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohn's disease was not significant in the relatives of patients with ulcerative colitis. The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative. The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives. The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohn's disease) among second-degree relatives was increased; the prevalence of the other disease was not increased. CONCLUSIONS. The 10-fold increase in the familial risk of ulcerative colitis and Crohn's disease strongly suggests that these disorders have a genetic cause. 
1	Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype. We have studied the phenotypic characteristics and growth properties of murine T lymphoma cell lines derived from primary x-ray-induced thymic lymphomas at the earliest stage at which they can be detected, and well before spreading to other organs has occurred. These cell lines serve as model systems for the earliest events in T cell lymphoma induction, before tumor cell progression and spreading to other organs. We find that primary x-ray-induced T cell lymphoma lines have phenotypic characteristics of thymic pre-T cells and show no proliferative response to any of the IL tested nor to other hematopoietic growth factors. However, they do proliferate in response to insulin-like growth factor I (IGF-I) and to a small autocrine peptide distinct from IGF-I, which we term lymphoma growth factor. One of the earliest lesions in T cell lymphoma induction may therefore be an inhibition of differentiation at one of several specific points. In its early stages, T lymphoma cell growth may be restricted to an environment where local concentrations of specific growth factors such as IGF-I or lymphoma growth factor are sufficiently high. 
3	Fourth ventricular schwannoma. Case report. A schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described. A ventricular schwannoma has not previously been reported in the literature. The presenting clinical and radiographic features and the pathology of this tumor are summarized, and an explanation is sought for its unusual location. 
3	West syndrome associated with hyperlexia. Two patients are reported with West syndrome associated with hyperlexia. They had peculiar linguistic and psychosocial development and autistic behavior, yet began to read Japanese and Chinese characters, numbers, Roman alphabet letters, and trademark letters at 3 years of age. Neuropsychologic, electroencephalographic, and radiologic studies were performed at 11 years of age in Patient 1 and at 10 years of age in Patient 2. Although they were able to read fluently with correct intonation, their comprehension was significantly impaired. The neuropsychologic evaluation of both patients demonstrated selective, excellent ability in auditory memory in contrast to impairment of associational abilities, visual retention, and visual constructional abilities. These findings suggest that the functions in the nondominant hemisphere were also impaired. Although children with West syndrome frequently have associated mental retardation, patients with West syndrome associated with hyperlexia have never been reported. A neuropsychologic investigation of epileptic children with mental retardation is necessary for the detection of hyperlexia. 
5	Overnight admission of outpatient strabismus patients. The trend to outpatient strabismus surgery prompted us to determine the frequency of, and the reasons for, postoperative overnight hospital admission following such surgery. In one year, 303 outpatient strabotomies were performed at the Jules Stein Eye Institute on patients over 15 months old. Twenty-four (7.9%) were admitted overnight postoperatively. Compared with controls, those admitted were older (37 vs 20.5 years), and had a longer duration of anesthesia (145 vs 116 minutes) and surgery (104 vs 75 minutes) (P less than .01 for each). The time that surgery commenced and the use of perioperative medications were not significant factors. The most frequent reasons for overnight admission were nausea (38%) despite prophylaxis and the use of bilateral patches (16%). To minimize postoperative admissions, better strategies should be developed to decrease the frequency of significant postoperative nausea, the duration of surgery and anesthesia, and, if possible, the use of bilateral patches. 
5	Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts. The first superior vena cava-pulmonary artery shunt (Glenn shunt) in our series was performed in February 1958. From then through September 1988, 91 patients have undergone this procedure for a wide variety of congenital defects. We here report follow-up data available on all patients. Ages ranged from 2 days to 46 years (mean 6.8). Diagnoses were as follows: tricuspid atresia, 27; single ventricle, 22; tetralogy of Fallot, 14; D-transposition of the great arteries, ventricular septal defect, and pulmonary stenosis, 9; D-transposition, 5; Ebstein's anomaly, 4; pulmonary atresia + intact septum, 4; and others, 6. The hospital mortality rate was 7.7% (one death in the last 53 patients, 1.9%). Five deaths occurred in patients less than 6 months old. There were 20 late deaths (22%) with actuarial survival rates of 84% and 66% at 10 and 20 years, respectively. Pulmonary arteriovenous fistula formation was seen in 18 patients (19.7%), six of whom have undergone therapeutic embolization with improvement in saturation. The prevalence of pulmonary arteriovenous fistula increases with time after shunt. No long-term shunt thrombosis or stricture formation was seen. Fifty percent of shunts were still functioning at 20 years. Palliation was limited because of decrease in blood flow to the contralateral pulmonary artery, collaterals between the inferior and superior venae cavae, and pulmonary arteriovenous fistula formation. Improvement in saturation was obtained in eight otherwise inoperable patients by creation of a right axillary arteriovenous fistula up to 19 years after the Glenn shunt. Three patients had conversion of a Blalock-Taussig shunt to a Glenn shunt with improvement in congestive heart failure. Twenty-six patients have undergone a Fontan procedure with two deaths. Compared with the group having a Fontan procedure without a prior Glenn operation, there was no difference in early or late mortality. Thirty years after a Glenn shunt, the first patient in this series is working full time after having undergone a modified Fontan procedure in 1981. We conclude that the Glenn connection, usually with supplemental procedures to enhance oxygenation, has provided excellent physiologic palliation with low mortality up to 30 years with no late thrombosis or stricture formation. The incidence of pulmonary arteriovenous fistula increases with time and can be effectively treated with embolization. Physiologic repair after the Glenn shunt carries a low mortality. Although currently used infrequently, superior vena cava-pulmonary artery shunting remains a useful method of palliation in selected patients.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Interruption of critical aortoiliac collateral circulation during nonvascular operations: a cause of acute limb-threatening ischemia. In patients with aortoiliac occlusive disease interruption of critical collaterals during another nonvascular or cardiac operation may threaten limb viability. This occurred in four patients whose limb-threatening ischemia was precipitated by radical cystectomy with bilateral hypogastric artery ligation, left colon resection, or coronary artery revascularizations by means of the internal mammary artery. Important collateral pathways, the interruption of which may account for this phenomenon, are detailed, and approaches are outlined for prevention and management of acute ischemia in this setting. 
1	Subdural hematoma associated with metastatic neoplasms. Two cases of subdural hematoma, one acute and the other chronic, associated with cancer metastatic to the dura are reported. Various mechanisms of the association of hematomas with cancer are reviewed. 
2	Cystic mesothelioma of peritoneum: occurrence in a man. We report a case of cystic mesothelioma of the peritoneum in a 54-year-old man in whom cystic masses were removed twice by surgery at an interval of 2 years. The patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer. The pathogenesis of the disease is uncertain, but we consider it neoplastic of low grade malignancy. 
1	Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT) with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction angiography, computed tomography, and immunohistochemistry. A 27-year-old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography, computed tomography, and digital subtraction angiography before the operation. Because a malignancy was suspected, the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography. The radioantibody accumulated strongly into the neoplasm. Tumor to background ratio was 2.2. Samples of the excised tumor were stained immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA (carcinoembryonic antigen), and factor VIII. They showed that the antibody uptake was of unspecific nature and not due to CEA expression in the tumor. 
1	Merkel cell carcinoma metastatic to the testis. Tumor metastases to the testes are rare and are usually found incidentally at autopsy or after orchiectomy for prostatic carcinoma. It is even more unusual for testicular metastases to be clinically detected or symptomatic. The authors report two cases of clinically detected testicular metastases from Merkel cell carcinoma of the skin. Merkel cell carcinoma metastatic to the testes has not been reported previously. The two tumors, to some degree, resembled testicular lymphomas and the interstitial type of seminoma. 
5	Translocation (9;22) is associated with extremely poor prognosis in intensively treated children with acute lymphoblastic leukemia. The prognostic implications of t(9;22)(q34;q11) were assessed at a median follow-up of 3.5 years in 434 children receiving intensive treatment for acute lymphoblastic leukemia (ALL). Four-year event-free and overall survivals were 81% and 88%, respectively, in 419 children lacking t(9;22), but were 0% and 20%, respectively, in 15 children with t(9;22) (P less than .001). Poor outcome for children with t(9;22)-positive ALL was particularly notable because we have reported improved survival in other historically poor prognosis ALL cytogenetic categories when treated with similarly intensive therapy. We recommend that very intensive treatment approaches, including bone marrow transplantation in first remission, be considered for all children with t(9;22)-positive ALL. 
4	Strokes in African-Americans. Hypertension is the most important risk factor for stroke, especially in African-Americans. Improved control of high blood pressure nationwide is a key factor in the recent dramatic decline in stroke frequency, most notably in African-American women. Hypertension control programs must be adequately funded and expanded. African-Americans have a disproportionately high incidence of risk factors for stroke, including hypertension. There is evidence that the cerebral vessels involved in ischemic stroke in African-Americans may differ from those of Caucasians. There is an urgent need for more research on stroke in general, risk factor relations in particular, and mechanisms in the pathogenesis of stroke in African-Americans. 
4	Percutaneous transluminal coronary angioplasty in hypothyroidism. PURPOSE: To determine the risks of percutaneous transluminal coronary angioplasty (PTCA) in hypothyroid individuals. PATIENTS AND METHODS: In a retrospective cohort study, 13 patients with primary hypothyroidism were identified among 382 consecutive PTCA cases in 1987. Twenty-two euthyroid PTCA control subjects and 13 hypothyroid patients who underwent coronary artery bypass surgery (CAB) were identified for comparison. RESULTS: Hypothyroid and euthyroid PTCA patients had similar mean ages, numbers of prior and recent acute myocardial infarctions, diseased coronary arteries, coronary arteries dilated, and serum cholesterol levels. There were no significant differences in procedure-related mortality (0% versus 0%); coronary artery dissection (23% versus 23%); reocclusion (8% versus 5%); bradycardia (0% versus 0%); heart failure (0% versus 5%); hypotension (31% versus 27%); myocardial infarction (8% versus 0%); gastrointestinal dysfunction (0% versus 0%); neuropsychiatric disturbance (15% versus 9%); hyponatremia (23% versus 23%); hypothermia (0% versus 0%); or fever (15% versus 5%). Hematoma formation tended to be more frequent in the hypothyroid group (38% versus 18%, p = 0.18). Similar results were obtained when the subgroup of more severely hypothyroid patients (thyrotropin level more than 20 mU/L, n = 7) was examined. Compared to hypothyroid CAB patients, hypothyroid PTCA patients had less incidence of heart failure (0% versus 31%, p less than 0.025); neuropsychiatric disturbance (15% versus 54%, p less than 0.025); hyponatremia (23% versus 62%, p less than 0.05); gastrointestinal dysfunction (0% versus 23%, p less than 0.025); and fever (15% versus 62%, p less than 0.001). CONCLUSION: PTCA can be performed in hypothyroid patients without increased mortality or major morbidity, and when appropriate, may be preferred to bypass surgery for coronary revascularization in patients intolerant of full thyroid hormone replacement. 
3	Spinal cord stimulation: a contemporary series Forty-three patients with chronic pain disorders of different causes were selected for spinal cord stimulation. All underwent implantation of a ribbon electrode through a small laminotomy, under general anesthesia. Thirteen patients (30%) failed to obtain significant pain relief during a period of trial stimulation, and their electrodes were removed. The remainder underwent a definitive implant and were followed for a mean of 13 months (range, 3-33 months). Nineteen of them (63%) continued to experience pain relief. A detailed analysis of this series, as well as a literature review, is presented. 
1	Flow cytometric DNA analysis of hepatocellular carcinoma: preliminary report. Flow cytometric DNA analysis was performed in 50 paraffin-embedded specimens of clinical hepatocellular carcinoma (HCC) after hepatic resections. The DNA distribution pattern was classified in two types, diploid and aneuploid, according to the degree of dispersion on the DNA histogram. The major DNA pattern of HCC in this report proved to be aneuploid (78%), although 22% of tumors revealed a diploid pattern. The serum alpha-fetoprotein level exceeded 40 ng/ml in 86.1% of the aneuploid tumors and in 13.9% of the diploid tumors (p less than 0.05). We found no correlation between DNA distribution and hepatitis B surface antigen positivity, the presence of liver cirrhosis or tumor size. Additionally we noted no significant correlation between the DNA pattern and survival rates in patients with HCC who underwent hepatic resection. 
1	Elective diagnostic laparoscopy. Laparoscopy developed as a science at the turn of the century, and many scientists assisted in the evolution of this technique. However, it was many years before the multiple trocar system was developed that allowed internal organs to be moved and biopsies to be obtained. This has led to the development of numerous indications for elective diagnostic laparoscopy. Adequate preparation and attention to instrumentation ensure the safety of this operation. Elective diagnostic laparoscopy is a useful adjunct to many other diagnostic modalities such as, for instance, the assessment of abdominal pain, abdominal masses, fever of unknown origin, and gastrointestinal bleeding. In many other circumstances, such as the assessment of oncology cases, this modality is superior to conventional radiology because biopsy specimens may be obtained. If the procedure is correctly performed, the diagnostic yield is extremely high and the morbidity and mortality are low. The role of this important technique should not be underestimated by today's practicing surgeon. 
1	Inflammatory pseudotumor of intra-abdominal lymph nodes manifesting as recurrent fever of unknown origin: a case report. A 27-year-old man presented with a 7-month history of debilitating recurrent fever and weight loss. Extensive clinical evaluation led to the discovery of splenomegaly and retroperitoneal lymphadenopathy. The patient underwent splenectomy as well as liver and lymph node biopsy. Histologic examination of the lymph nodes, but not the liver and spleen, revealed inflammatory pseudotumor of lymph nodes. The patient has remained asymptomatic for more than 3 years following the surgical procedure despite the absence of further intervention. Inflammatory pseudotumor of lymph nodes should be considered in the differential evaluation of prolonged or relapsing fever of unknown etiology. 
4	Onset of induced atrial flutter in the canine pericarditis model To test the hypothesis that induced atrial flutter evolves from a transitional rhythm, the onset of 99 episodes of induced atrial flutter (mean cycle length 135 +/- 18 ms) lasting greater than 5 min in 40 dogs with sterile pericarditis was first characterized. In 85 (86%) of the 99 episodes, atrial flutter was preceded by a brief period (mean 1.4 +/- 0.9 s, range 0.4 to 42) of atrial fibrillation. Then, in 11 open chest studies, atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the onset of 18 episodes of induced atrial flutter (mean cycle length 136 +/- 16 ms). Atrial flutter was induced by a train of eight paced atrial beats, followed by one or two premature atrial beats (7 episodes) or rapid atrial pacing (11 episodes). A short period of atrial fibrillation (mean cycle length 110 +/- 7 ms) induced by atrial pacing activated the right atrium through wave fronts, which produced a localized area of slow conduction. Then unidirectional conduction block of the wave front occurred for one beat in all or a portion of the area of slow conduction. This permitted the unblocked wave front to turn around an area of functional block and return through the area of slow conduction that had developed the unidirectional conduction block, thereby initiating the reentrant circuit. The location of the unidirectional block relative to the direction of the circulating wave fronts determined whether the circus movement was clockwise or counterclockwise. The area of slow conduction and unidirectional conduction block occurred where the wave front crossed perpendicular to the orientation of the atrial muscle fibers, suggesting a role for anisotropic conduction. These areas included the high right atrial portion of the sulcus terminalis (10 episodes), the low right atrial portion of the sulcus terminalis (4 episodes) and the pectinate muscle region (4 episodes). It is concluded that the development of a localized area of slow conduction in the right atrium followed by unidirectional conduction block in this area produced during a short period of atrial fibrillation or rapid atrial pacing is necessary for atrial flutter to occur in this model. 
1	Characterization of a newly established malignant meningioma cell line of the human brain: IOMM-Lee. A permanent malignant meningioma (MM) cell line of the human brain designated "IOMM-Lee" is reported. This cell line was successfully established from the tumor of a 61-year-old Chinese man with repeated recurrent primary intraosseous malignant meningioma of the skull. It has been subcultured for more than 60 passages during the past 30 months. The doubling time of cultured cells is approximately 62 hours. Tumorigenicity in athymic nude mice (Balb/c-nu/nu) who develop multiple pulmonary metastases was observed; the doubling time of tumor volume in vivo is approximately 5 days. Karyotypic analysis revealed this cell line to be of human origin and near-diploid, with a modal chromosome number of 49. The mesenchymal tumor marker vimentin and intracytoplasmic microfilaments were identified in the cytoplasm of tumor cells by indirect immunohistochemical peroxidase-anti-peroxidase assays and immunogold ultrastructural localization by transmission electron microscopy, respectively. Scanning electron microscopy of cultured cells and xenografted tumors revealed ellipsoidal or carrot-shaped tumor cells presenting a wrinkled surface with short sparse microvilli. Potential proliferating activity was determined by Ki-67 monoclonal antibody; the Ki-67 labeling index of cultured cells and xenografted tumors was approximately 36% and 30%, respectively. This newly established malignant meningioma cell line of the human brain may prove useful as a research model. 
3	Cerebellar and frontal hypometabolism in alcoholic cerebellar degeneration studied with positron emission tomography. Local cerebral metabolic rate for glucose was studied utilizing 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 14 chronically alcohol-dependent patients and 8 normal control subjects of similar age and sex. Nine of the 14 patients (Group A) had clinical signs of alcoholic cerebellar degeneration, and the remaining 5 (Group B) did not have signs of alcoholic cerebellar degeneration. PET studies of Group A revealed significantly decreased local cerebral metabolic rates for glucose in the superior cerebellar vermis in comparison with the normal control subjects. Group B did not show decreased rates in the cerebellum. Both Groups A and B showed decreased local cerebral metabolic rates for glucose bilaterally in the medial frontal area of the cerebral cortex in comparison with the normal control subjects. The severity of the clinical neurological impairment was significantly correlated with the degree of hypometabolism in both the superior cerebellar vermis and the medial frontal region of the cerebral cortex. The degree of atrophy detected in computed tomography scans was significantly correlated with local cerebral metabolic rates in the medial frontal area of the cerebral cortex, but not in the cerebellum. The data indicate that hypometabolism in the superior cerebellar vermis closely follows clinical symptomatology in patients with alcoholic cerebellar degeneration, and does not occur in alcohol-dependent patients without clinical evidence of cerebellar dysfunction. Hypometabolism in the medial frontal region of the cerebral cortex is a prominent finding in alcohol-dependent patients with or without alcoholic cerebellar degeneration. 
3	The effect of pH buffering on reducing the pain associated with subcutaneous infiltration of bupivicaine [published erratum appears in Am J Emerg Med 1991 Jul;9(4):410] The authors propose that pH buffering of bupivicaine with sodium bicarbonate reduces the pain associated with its local subcutaneous infiltration. In a double-blind, prospective study, 62 healthy adult volunteers received a 0.5 mL subcutaneous infiltration of 0.5% buffered bupivicaine into the dorsum of a randomly chosen hand. The pH was adjusted to 7.0 by adding 0.05 mL of sodium bicarbonate (1 mEq/L [corrected]) to 10 mL vials of commercially available bupivicaine (1:200 dilution). The control hand was injected with the same amount of unbuffered agent. Pain was scored after each infiltration using a nonsegmented visual analogue scale. Student's t-test for paired measurements was used to analyze intergroup pain score differences. Forty-three subjects (69%) reported less pain with buffered bupivicaine and only 17 (27%) noted a modest increase: two subjects (3%) reported no difference. The mean pain score for the buffered agent was 22 mm compared with 30 mm for the control. The mean difference (control-experimental) was 8 mm (t = 4.64, df = 61, P less than .001). The authors conclude that the addition of sodium bicarbonate to bupivicaine reduces the pain associated with its local infiltration. 
4	Role of angiotensin in the renal vasoconstriction observed during the development of genetic hypertension. Studies have examined renal function to determine the role of the kidney in the pathogenesis and maintenance phases of hypertension in the Okamoto-Aoki strain of spontaneously hypertensive rat (SHR). As compared to age-matched Wistar-Kyoto rats (WKY), 4- to 6-week old SHR are moderately hypertensive and have a reduced glomerular filtration rate (GFR) and renal blood flow (RBF), and an increased renal vascular resistance. Cross-breeding studies indicate the reduction in RBF and GFR in young SHR is genetically linked to the hypertension and thus may be of primary pathogenetic importance. The combination of an elevated vascular resistance and reduced RBF and GFR in young SHR implicates increased activity of a vasoconstrictor system(s), decreased activity of a vasodilator system(s), or both. Observations from several laboratories support the notion that endogenous angiotensin II contributes to the renal vasoconstriction in young SHR during the developmental phase of hypertension. Acute and chronic inhibition of angiotensin converting enzyme reduce arterial pressure, reduce renal vascular resistance and increase renal blood flow in young and adult SHR. Renal vascular tone in SHR is more dependent on angiotensin converting enzyme activity than that in WKY. The ability of angiotensin converting enzyme inhibitors to produce renal vasodilation may be responsible, at least in part, for its antihypertensive effects. Other studies indicate that renal vascular reactivity to angiotensin II is exaggerated in young SHR. The strain differences in renal reactivity to angiotensin II can be abolished by cyclooxygenase inhibition with indomethacin, indicating that endogenous prostanoids counteract some of the constrictor action of angiotensin II, with more pronounced buffering activity in WKY. 
2	Edrophonium provocative test in noncardiac chest pain. Evaluation of testing techniques. Edrophonium chloride is used frequently as a provocative agent in the assessment of noncardiac chest pain (NCCP). However, the optimum dose and most appropriate method of interpreting test results is controversial. We studied 150 consecutive NCCP patients and 50 age-matched controls who alternately received either 80 micrograms/kg or 10 mg intravenous bolus doses of edrophonium preceded by saline placebo injections. Distal esophageal pressures were measured before and after drug injection in response to ten 5-cc wet swallows. Following 10 mg of edrophonium, 33% of patients and 4% of controls reported chest pain, while 29% of patients and no controls receiving the 80 micrograms/kg dose complained of chest pain. Amplitude changes after either dose were not significantly different for all comparisons, but the duration of response did distinguish the two doses in patients with chest pain. A significantly greater (P = 0.01) increase in distal contraction duration occurred after 10 mg (74 +/- 12%; +/- SE) compared to 80 micrograms/kg dose (43 +/- 6%). However, individual responses to the two doses overlapped considerably. If a positive test is redefined to include both chest pain and manometric changes that are significantly different from controls, the positivity rate changes drastically; 33% to 9% in the 10-mg group and 30% to 3% in the 80-micrograms/kg group. Side effects were similar between doses, but there was a significant (P = 0.02) linear relationship between intensity of side effects and the edrophonium dose per kilogram of body weight. 
4	Transmural myocardial deformation in the ischemic canine left ventricle. The myocardium is a complex three-dimensional structure consisting of myocytes interconnected by a dense collagen weave that courses in different directions. Regional ischemia can be expected to produce complex changes in ventricular deformation. In the present study, we examined the effects of ischemia on two- and three-dimensional finite strains during acute transmural myocardial ischemia in 13 open-chest anesthetized dogs. In contrast to systolic deformation observed during the control period in which circumferential shortening exceeded longitudinal shortening, our results indicate that after 5 minutes of acute ischemia, end-systolic in-plane lengthening across the left ventricular wall occurs in approximately equal amounts in the circumferential and longitudinal directions. Along with these changes in extensional strains, there were significant negative transverse shearing deformations during ischemia. Myocardial ischemia also resulted in a loss of the normal end-systolic transmural gradients of shortening and thickening. Three-dimensional end-diastolic strains indicate that the left ventricular wall undergoes a significant passive reconfiguration that varies transmurally with lengthening in the epicardial tangent plane and wall thinning increasing from the epicardium toward the endocardium. The large systolic changes in shearing deformations with ischemia could potentially influence collateral blood flow and certainly indicate that uniaxial measurements of deformation in the ischemic myocardium, which do not account for shearing deformation, are incomplete and must be interpreted with caution. Moreover, normal transmural systolic gradients in deformation, which would be anticipated on geometric grounds, are lost during ischemia, implying that the material properties of ischemic tissue or the loading conditions imposed on the ischemic region by partially impaired adjacent myocardium vary transmurally. 
1	Surgical treatment of extramammary Paget's disease. A report of six cases and a reexamination of Mohs micrographic surgery compared with conventional surgical excision. Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, usually on the genitalia, that almost always extends beyond clinically apparent margins. Recurrences after standard methods of surgical excision are notoriously frequent; effective treatment with Mohs micrographic surgery was first reported in 1979. It has since been suggested this malignancy may be multifocal, and reports of recurrences after resection with micrographic surgery have appeared. The authors report six cases treated with Mohs surgery, two of which recurred. They also present data on 42 additional cases obtained from a written survey of members of the American College of Mohs Micrographic Surgery and comparison cases selected from the literature. The recurrence rate after micrographic surgery appears to be at least as low as that after conventional surgical excision with vertical frozen section or paraffin section margin control. Mohs micrographic surgery allows for maximal tissue sparing of critical anatomic structures and is performed under local anesthesia as an outpatient; because of this, it may be superior to conventional surgical excision. A scheme for management of this malignancy is presented. Surgeons should be aware radical excision is not needed for most cases of extramammary Paget's disease and very long-term patient follow-up is required. 
2	Umbilical cord ulceration and intestinal atresia: a new association? In three fetuses, congenital intestinal atresia was associated with linear ulcerations of the umbilical cord. In two cases, hemorrhage was seen from the cord ulcer. Both fetuses required emergency cesarean section for fetal distress and were born anemic. The third fetus was mildly hydropic, attributed to hemorrhage, and was stillborn. The mechanism of the association could not be determined. These cases suggest a risk of prenatal umbilical cord hemorrhage in infants with intestinal atresia. 
3	Cerebellar degeneration and Meige's syndrome. We have reported a case of Meige's syndrome in a middle-aged man who eventually had a cerebellar degeneration syndrome. The extrapyramidal symptoms preceded cerebellar signs and symptoms by 5 years. Most patients with idiopathic Meige's syndrome show some improvement with high-dose anticholinergic therapy. Our patient's lack of response to such agents and his subsequent cerebellar symptoms are reminiscent of the situation seen with parkinsonian patients who do not respond to medications, indicating a more widespread degenerative disease. The association of extrapyramidal symptoms with some spinocerebellar disorders, and the pathologic changes seen in the one reported autopsy case, should place the group of spinocerebellar disorders high on the differential list. 
3	Alpha 1-antichymotrypsin as a possible biochemical marker for Alzheimer-type dementia. We measured serum alpha 1-antichymotrypsin levels in 38 patients with Alzheimer-type dementia, 89 control subjects, 2 subjects with Down's syndrome, 20 with vascular dementia, 18 with Parkinson's disease, 14 with spinocerebellar degeneration, 15 with cerebrovascular disease without dementia, and 14 with Duchenne muscular dystrophy. Cerebrospinal fluid (CSF) levels of alpha 1-antichymotrypsin were also measured in 15 patients with Alzheimer-type dementia, 26 control subjects, 6 with vascular dementia, 7 with cerebrovascular disorder, and 11 with degenerative disorders. In control subjects, there were no age-related changes or sex differences. Serum and CSF levels were significantly and specifically higher in patients with Alzheimer-type dementia than in other subjects (serum, p less than 0.001; CSF, p less than 0.05). Serum levels of alpha 1-antichymotrypsin were significantly elevated in the early stage of Alzheimer-type dementia, whereas there was no definite correlation between serum levels and the degree of dementia. CSF levels of alpha 1-antichymotrypsin tended to parallel the severity of dementia. Serum levels were not correlated with CSF levels. These data indicate that serum and CSF levels of alpha 1-antichymotrypsin might be independently upregulated in Alzheimer-type dementia. We concluded that the measurement of serum levels of alpha 1-antichymotrypsin could be useful as a screening marker for Alzheimer-type dementia. In addition, CSF levels also could be a useful marker for Alzheimer-type dementia, because they might reflect the state of dementia. 
5	Vagal modulation of the rate-dependent properties of the atrioventricular node. Vagal effects on atrioventricular (AV) nodal conduction are accentuated by increases in heart rate. To establish the mechanism of these rate-dependent negative dromotropic actions, we studied the properties governing AV nodal adaptation to changes in heart rate in chloralose-anesthetized dogs in the absence and presence of bilateral cervical vagal nerve stimulation (20 Hz, 0.2 msec). Stimulation protocols were applied to evaluate the contributions of changes in AV nodal recovery, facilitation, and fatigue independently of each other. Vagal stimulation slowed AV nodal recovery in a voltage-dependent way, increasing the time constant of recovery (tau r) from 80 +/- 7 to 194 +/- 16 msec (mean +/- SEM, p less than 0.01) at the highest voltage studied. The facilitating effect of a premature (A2) beat was manifested by a leftward shift of the recovery curve (A3H3 versus H2A3) of a subsequent A3 beat. The magnitude of shift depended on the A1A2 coupling interval and was reduced by vagal stimulation at all A1A2 intervals (maximum shift: control, 63 +/- 12 msec; vagus, 24 +/- 11 msec; p less than 0.01). When recovery and facilitation were kept constant, abrupt increases in AV nodal activation rate caused a slow (tau = 75 beats) increase in AH interval (fatigue). Vagal stimulation increased the magnitude of this process (maximum: control, 11 +/- 2 msec; vagus, 27 +/- 3 msec; p less than 0.001), without altering its time course. At activation rates comparable to sinus rhythm in humans, vagal stimulation at an intermediate voltage increased the AH interval by 25 msec. As heart rate increased, vagally induced changes in dynamic processes amplified AH prolongation up to fivefold at maximum rate. The role of vagal changes in individual functional properties depended on heart rate, but slowing of recovery was the single most important factor, constituting over 50% of overall vagal action at rapid rates. We conclude that vagal stimulation alters the ways in which the AV node responds to changes in activation rate and that at rapid rates most of the negative dromotropic action of the vagus is due to changes in the AV nodal response to tachycardia. Alterations in rate-dependent AV nodal properties are a novel and potentially important mechanism through which interventions may affect AV nodal conduction. 
2	Normal small bowel biopsy followed by coeliac disease. We report four patients (two children, one adolescent, and one adult) having normal small bowel mucosa shown on a biopsy specimen taken before the initial diagnosis of coeliac disease was made. The first biopsy was undertaken in two cases because of suspected malabsorption, in the third because of suspected dermatitis herpetiformis, and in the fourth as part of a coeliac disease family study. After a further 2.6 to 9 years on a diet containing gluten, small bowel villous atrophy with crypt hyperplasia compatible with coeliac disease was found on a second biopsy specimen. The HLA type of the patients was that typical for coeliac disease; all were DR3 positive. Within the families three other patients with coeliac disease have been diagnosed, two earlier and one at the time the first biopsy was undertaken. Four other HLA-DR3 positive haploidentical first degree relatives were found and had biopsies. All four had normal small bowel villous architecture, one had an increased intraepithelial cell count, and another was positive for reticulin and endomysium antibodies. Coeliac disease may exist latent in patients having normal mucosa when eating a normal diet containing gluten. 
5	Hemorrhagic pituitary adenomas: clinicopathological features and surgical treatment. Forty-five (9.9%) of 453 pituitary adenomas operated on between January 1973 and November 1988 demonstrated hemorrhagic changes at surgery: 24 had a blood collection, 12 had a blood collection associated with hemorrhagic necrosis, and 9 had hemorrhagic necrosis. Thirteen patients (28.9%) experienced the acute symptoms of pituitary apoplexy, whereas another 32 had an "asymptomatic" hemorrhage, that is, the clinical course was comparable to an uncomplicated adenoma. Nineteen tumors (42.2%) showed marked suprasellar extension, 8 (17.8%) showed moderate extension, and 11 (24.5%) showed slight extension; another 2 (4.4%) were laterosellar and 5 (11.1%) were intrasellar. Invasive behavior was present in 32 cases (71.1%) and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage. The incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive; therefore, we do not suggest preoperative bromocriptine treatment in this type of tumor. Two of 14 patients operated on by the transcranial route died after surgery, whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route. It proved advantageous to operate as early as possible, even during the acute phase of pituitary apoplexy. The transsphenoidal approach gave the best results, but to achieve satisfactory late results multidisciplinary treatment was necessary, namely, postoperative radiotherapy in 23 patients, bromocriptine in 12, and endocrine replacement therapy in almost all. In an average follow-up period of 6.2 years, 5 (11.1%) symptomatic recurrences were observed. 
3	Pathogenesis and pathophysiology of meningitis. Advances in the understanding of the pathogenesis and pathophysiology of meningitis have occurred primarily through the use of experimental animal models. These models have proven to be particularly valuable in experimental bacterial meningitis, focusing on the bacterial virulence factors responsible for the initiation of infections, CNS invasion, and induction of SAS inflammation. Recent studies have examined the formation of host inflammatory cytokines in response to these virulence factors. These cytokines may be responsible for many of the pathophysiologic consequences of bacterial meningitis (eg. increased BBB permeability, cerebral edema, and increased intracranial pressure). Meningitis due to C. neoformans occurs most commonly in patients with defects in cell-mediated immunity (eg, AIDS), and the depletion of T helper cells in AIDS patients may allow unrestricted cryptococcal growth. Viral meningitis is an illness of low prevalence when compared with the overall occurrence of viral infections at other sites. CNS infection usually occurs by means of traversal across barriers that normally exclude viral invasion of the CNS, primarily through hematogenous dissemination from initial sites of infection. These advances in the pathogenesis and pathophysiology of bacterial, fungal, and viral meningitis may lead to the development of innovative treatment strategies for these disorders. 
4	Prognosis of patients with ventricular tachycardia or fibrillation and a normal electrophysiologic study. The outcome of 26 patients with sustained ventricular tachycardia (n = 16) or ventricular fibrillation (n = 10) and no inducible ventricular tachycardia (less than or equal to 10 beats) by baseline programmed stimulation was studied. Coronary artery disease was present in 14 patients, dilated cardiomyopathy was seen in seven, valvular heart disease was present in two, and no apparent cardiac abnormalities were found in three. The mean left ventricular ejection fraction was 53 +/- 14%. During the follow-up period of 24 +/- 16 months, actuarial survival rates at 1 and 2 years were 95% and 89% for sudden death and 95% and 83% for total cardiac death, respectively. No patients with a known ejection fraction greater than 30% died suddenly during the follow-up. Noninducibility by programmed stimulation in patients with sustained ventricular tachycardia or fibrillation is associated with a relatively preserved ventricular function. It may predict a low risk of sudden death in patients with preserved ventricular function. 
4	Effect of activity on supraventricular tachyarrhythmias after coronary artery bypass surgery. The purpose of this study was to evaluate patient activities, professional staff activities, backrest position, and diurnal variations as factors that may contribute to the onset of supraventricular tachyarrhythmias (SVT) after coronary artery bypass surgery (CABG). The activities surrounding the recognition of first-onset SVT, as well as preoperative and postoperative data and patient characteristics were examined in 249 patients having CABG. One hundred seventy-three patients qualified for the study; 28% of these patients (n = 49) had SVT. No statistical difference was found between the subjects with SVT and those without SVT when sex, cross-clamp time, creatine kinase peak, hemoglobin and hematocrit levels, and number of bypasses were examined. Patients who had SVT were older than those who did not: 64.8 years for the SVT group versus 60.7 years for the non-SVT group (p less than 0.01). SVT was rare in the first 24 hours after surgery, whereas 60% of the cases occurred during the next 48 hours, without significant diurnal variation: mean time of onset was 11:50 AM. No particular activity of the patient or nurse influenced the onset of SVT during the postoperative period in this group. 
1	Alcohol consumption in patients with colorectal adenomatous polyps. The risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors. We found an association with current alcohol and cigarette consumption. The risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink, with those who both drank and smoked having 12 times the risk of total abstainers. Since colonic adenomatous polyps are generally regarded as premalignant lesions, these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal carcinogenesis. The role of smoking, however, is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies. 
1	Strabismus caused by melanoma metastatic to an extraocular muscle. Nonocular melanoma rarely metastasizes to the orbit. We report the case of a melanoma presumably arising from an axillary lymph node sinus that metastasized to the left medial rectus muscle causing proptosis, diplopia, and reduced saccadic velocity measurements. Clinical, radiographic, and histopathologic data are presented and discussed. 
2	Estimates of morbidity and mortality rates for diarrheal diseases in American children. Although the importance of diarrhea as a prime cause of morbidity and death in developing countries is well recognized, the disease burden in the United States has never been thoroughly examined. We have prepared national estimates of the annual number of cases of diarrhea in children less than 5 years of age and of the outcome, measured in terms of visits to a physician, hospitalizations, and deaths. The annual number of diarrheal episodes was estimated by reviewing longitudinal studies of childhood diarrhea conducted in the United States and extrapolating these data to the nation. Estimates of physician visits, hospitalizations, and deaths were prepared from a variety of national data sources. We estimate that 16.5 million children less than 5 years of age have between 21 and 37 million episodes of diarrhea annually. Of these, 2.1 to 3.7 million episodes lead to a physician visit, a total of 220,000 patients are hospitalized, and 325 to 425 children die. The major cost of diarrhea lies in the high numbers and cost of hospitalizations, because approximately 10.6% of hospitalizations in this age group are for diarrhea. Diarrheal deaths occur in relatively small numbers, are more common in the South and among black persons, are potentially avoidable, and could represent as much as 10% of the preventable postneonatal infant death in the United States. These estimates underscore the extensive burden of diarrheal illness in children in the United States and suggest that interventions to prevent disease or decrease its severity could be cost-effective. 
3	Implications of a dynamical systems approach to understanding infant kicking behavior. Implications of the dynamical systems approach to understanding movement dysfunction in infants are discussed. Traditional theories of motor development attribute changes in movement to the hierarchical maturation of the central nervous system. The dynamical systems approach emphasizes that movement self-organizes as the result of the interaction of the participating subsystems in developmental and real time. In this article, I discuss, from the theoretical perspective of the dynamical systems approach, the organization of leg movements in low- and high-risk preterm and full-term infants, developmental changes in movement in low-risk preterm infants from 34 weeks' gestational age to 40 weeks' postgestational age, and differences in movement between low-risk preterm infants at 40 weeks' postgestational age and full-term infants. Preliminary data on high-risk preterm infants are presented. Based on these data, the necessity to review and reinterpret traditional concepts of motor development is explored. Suggestions are offered and questions posed on how the dynamical systems perspective may influence the practice of physical therapy in the evaluation, and treatment of infants at risk for movement dysfunction. 
4	Estimation of myocardial infarct size with ultrasonic tissue characterization. BACKGROUND. Ultrasonic tissue characterization (UTC) can distinguish normal from infarcted myocardium. Infarcted myocardium shows an increase in integrated backscatter and loss of cardiac cycle-dependent variation in backscatter. The cyclic variation of backscatter is closely related to regional myocardial contractile function; the latter is a marker of myocardial ischemia. The present study was designed to test the hypothesis that intramural cyclic variation of backscatter can map and estimate infarct size. METHODS AND RESULTS. Transmural myocardial infarction was produced in 12 anesthetized, open-chest dogs by total occlusion of the left anterior descending coronary artery for 4 hours. A real-time ultrasonic tissue characterization instrument, which graphically displays integrated backscatter Rayleigh 5, cardiac cycle-dependent variation, and patterns of cyclic variation in backscatter, was used to map infarct size and area at risk of infarction. Staining with 2,3,4-triphenyltetrazolium chloride (TTC) and Patent Blue Dye was used to estimate infarct size and the area at risk, respectively. The ratio of infarct size to area at risk of infarction determined with UTC correlated well with that determined with TCC (r = 0.862, y = 23.7 +/- 0.792x). Correlation coefficients for infarct size and area at risk were also good (r = 0.736, y = 12.3 +/- 737x for infarct size and r = 0.714, y = 5.80 +/- 1.012x for area at risk). However, UTC underestimated both infarct size and area at risk. CONCLUSIONS. Ultrasonic tissue characterization may provide a reliable, noninvasive method to estimate myocardial infarct size. 
5	Hepatic lesions in the rabbit induced by acoustic cavitation. Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma. 
5	Complications of the pectoralis major myocutaneous flap in head and neck reconstruction. A retrospective review of the complications in 211 patients undergoing pectoralis major myocutaneous flap reconstruction is presented. The flap was used for mucosal lining of the oral cavity or oropharynx in 109 patients, for pharyngoesophageal reconstruction in 44, for skin coverage in 47, and for other locations in 14 patients. Flap-related complications developed in 63% of the patients. These included flap necrosis, suture line dehiscence, fistula formation, infection, and hematoma. Analysis of risk factors for the development of flap complications showed the following factors to be significant: age over 70; female gender; nomographic overweight; albumin less than 4 g/dL; use of the flap in reconstruction of the oral cavity after major glossectomy; and presence of other systemic diseases. The median length of hospitalization for those developing complications was 33 days compared with 16 days for those who did not develop any complications. Thirty-five (26%) of the 135 patients developing complications required reoperation and only 2 among these required a second flap. Similarly, only 13 of the 61 patients who developed fistulas required surgical closure. 
5	Pathophysiology, monitoring, and management of the ventilator-dependent patient: considerations for drug therapy, emphasis on stress ulcer prophylaxis. Adult respiratory distress syndrome (ARDS), or noncardiac pulmonary edema, is a form of acute hypoxemic respiratory failure. The goals of treatment for patients with ARDS are to provide supportive therapy, to reverse the underlying etiology or pathology, and to prevent subsequent complications. Supportive therapy consists of supplemental oxygen, positive end-expiratory pressure, and, often, mechanical ventilation. The reversal of the underlying pathology varies according to the etiologic origin of ARDS. Complications from ARDS include stress ulcers, which occur when gastric aggressive and defensive functions become unbalanced. Antacids and cytoprotective agents are used for stress ulcer prophylaxis, but histamine H2-receptor antagonists are now regarded as the standard of care. Because all the marketed H2-receptor antagonists are efficacious, choice of the agent is based on the adverse effect profile and drug interactions. No definitive data currently exist linking stress ulcer prophylaxis regimens that raise intragastric pH to a significant risk for nosocomial pneumonia. 
4	Plasma concentrations of epinephrine during CPR in the dog. STUDY OBJECTIVE: The purpose of this study was to evaluate whether the marked increase in the plasma concentrations of epinephrine during cardiopulmonary arrest and basic life support (BLS) could be due in part to decreased distribution and/or elimination. DESIGN AND INTERVENTIONS: Dogs were randomly assigned to undergo adrenalectomy or sham-operation. Some adrenalectomized animals received an epinephrine infusion. MEASUREMENTS AND MAIN RESULTS: In the seven sham-operated dogs, the plasma epinephrine concentrations increased markedly during BLS as expected. In the seven adrenalectomized dogs receiving a constant infusion of epinephrine, cardiopulmonary arrest and BLS induced a three to sixfold increase in plasma epinephrine concentrations, with an increase in the mean plasma epinephrine concentrations (calculated from the area under the curve) of 1.21 +/- 0.12 ng/mL (P less than .05). In the seven adrenalectomized dogs receiving a constant epinephrine infusion but not subjected to cardiopulmonary arrest, the plasma epinephrine concentrations remained stable. Finally, in the seven adrenalectomized dogs not receiving an epinephrine infusion, the mean plasma epinephrine concentrations during BLS (calculated from the area under the curve) increased only by 0.05 +/- 0.04 ng/mL, significantly less than in adrenalectomized dogs receiving an epinephrine infusion (P less than .01). CONCLUSION: The increase in plasma epinephrine concentrations during cardiopulmonary arrest and BLS is due in part to an altered disposition of epinephrine. 
5	Cultured human atherosclerotic plaque smooth muscle cells retain transforming potential and display enhanced expression of the myc protooncogene. The proliferation of vascular smooth muscle cells (SMC) is critical to atherosclerotic plaque formation. The monoclonal hypothesis proposes that the stimulus for this SMC proliferation is a mutational event. Here we describe a procedure for growing human plaque smooth muscle cells (p-SMC) in culture. We show that p-SMCs derived from two patients differ from SMC cultured from normal vascular tissue in expression of the protooncogene myc. One p-SMC strain was extensively characterized; these diploid, karyotypically normal cells have a finite life span in culture. Ultrastructural examination revealed two populations, one with classic contractile SMC appearance, the other, modulated to a synthetic state. Northern blotting showed a 2- to 6-fold and a 6- to 11-fold enhanced expression of myc by p-SMC, compared to SMC derived from healthy human aorta (HA-SMC) and saphenous vein (HV-SMC), respectively. In contrast, the p-SMC and HV-SMC expressed similar levels of message for the genes N-myc, L-myc, Ha-ras, fos, sis, myb, LDL receptor, EGF receptor, IGF I receptor, IGF II, and HMG CoA reductase. Finally, although p-SMCs are not tumorigenic, DNA isolated from these cells is positive in the transfection-nude mouse tumor assay. Myc, however, does not appear to be the transforming gene because no newly introduced human myc gene was detected in the p-SMC-associated nude mouse tumor. Thus human atherosclerotic p-SMCs possess both an activated myc gene and a transforming gene that is retained throughout many cell passages. 
4	Dose-response evaluation of oral labetalol in patients presenting to the emergency department with accelerated hypertension. STUDY OBJECTIVE: Dose-response evaluation of oral labetalol (100, 200, or 300 mg) on heart rate and systemic blood pressure in emergency department patients with hypertensive urgency (diastolic blood pressure, 110 to 140 mm Hg, and no end-organ evidence of hypertensive emergency). METHODS: This acute-treatment, dose-ranging study used a randomized, double-blind, parallel design. Patients with supine diastolic blood pressure of 110 to 140 mm Hg after 30 minutes of bedrest received an oral dose of labetalol. Supine blood pressure and heart rate were measured manually and recorded hourly for four hours after dose. Diastolic blood pressure of 100 mm Hg or less or a 30-mm Hg reduction in diastolic blood pressure was considered a treatment success. RESULTS: Two hundred fifty-five patients were evaluated for inclusion, and 36 patients (19 women and 17 men; mean age, 44 years; age range, 23 to 67 years) were studied. The most frequent reason for exclusion was a spontaneous decrease in diastolic blood pressure to less than 110 mm Hg (31%) with bedrest. There were 12 patients in each treatment group. Compared with baseline, the 100-mg dose significantly (P less than .05) reduced heart rate at three and four hours after dose, and the 300-mg dose significantly (P less than .05) reduced heart rate at one, two, and three hours after dose; the 200-mg dose did not significantly affect heart rate. All doses produced a significant decrease in systolic and diastolic blood pressures at one, two, three, and four hours after dose compared with baseline. There were no statistically significant differences between treatment groups with regard to systolic or diastolic blood pressure or heart rate at baseline or one, two, three, or four hours after dose. At two hours after dose, diastolic blood pressure control was observed in 75%, 58%, and 67% of patients receiving 100, 200, and 300 mg, respectively (P = .903). At four hours after dose, diastolic blood pressure control was observed in 50%, 64%, and 67% of patients receiving 100, 200, and 300 mg, respectively (P = .755). A comparison of treatment success rates between the two time periods showed a waning of response with the 100-mg dose of labetalol at hour 4 compared with hour 2 (P less than .05). No adverse effects were observed. CONCLUSION: Labetalol provides safe and effective treatment for hypertensive urgencies when administered orally in doses of 100 to 300 mg. 
3	Heterogeneity in spasmodic dysphonia. Neurologic and voice findings. Spasmodic dysphonia is a disturbance of phonation with laryngeal spasms. We report voice and neurologic examination findings in 45 subjects. Neurologic abnormalities were found in 32 subjects (71.1%). Rapid alternating movement abnormalities, weakness, and tremor were common. Incoordination and spasticity were rare. Lower extremity findings were frequent. Abnormalities were bilateral. Spasmodic dysphonia severity was related to age. Type, severity, and duration of vocal symptoms were not different for subjects with or without neurologic abnormalities. Vocal tremor was more frequent in neurologically abnormal subjects. Involvement of a pallidothalamic-supplementary motor area system could account for neurologic findings, brain imaging findings, and clinical heterogeneity. The view emerging is that spasmodic dysphonia is a manifestation of disordered motor control involving systems of neurons rather than single anatomical sites. 
2	Pathogenesis of biliary sludge. The increasing application of ultrasonography in biliary tract disease had led to more frequent recognition of an old disorder--"biliary sludge." Sludge is detected on ultrasound as low-amplitude echoes without acoustic shadowing. It layers in the most dependent part of the gallbladder and shifts with positioning. Particulate matter in bile, such as cholesterol monohydrate crystals, has been shown to be echogenic. Agglomeration of these crystals in biles with high mucus content accounts for the layering and the characteristic appearance of the movement of sludge with alteration in patient position. Within the gallbladder, the stability of the vesicular form of cholesterol and protein-lipid interactions are important determinants of cholesterol precipitation. In mixed and pigment gallstones, the equilibrium between ionized and unionized calcium and the hydrolysis of conjugated bilirubin are also important factors. Although the risk factors contributing to the formation of gallbladder sludge have not been critically examined, it is now known that in some instances sludge can produce biliary pain and can be associated with acalculous cholecystitis, recurrent pancreatitis and, ultimately, the formation of gallstones. A better appreciation of the pathogenesis of sludge formation can help in the understanding of the genesis of gallstones and also perhaps in understanding other documented but poorly understood biliary and pancreatic disorders. 
1	Effective surgical adjuvant therapy for high-risk rectal carcinoma BACKGROUND. Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. In a previous study, combined radiation and chemotherapy improved survival significantly as compared with surgery alone, but not as compared with adjuvant radiation, which many regard as standard therapy. We designed a combination regimen to optimize the contribution of chemotherapy, decrease recurrence, and improve survival as compared with adjuvant radiation alone. METHODS. Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were randomly assigned to postoperative radiation alone (4500 to 5040 cGy) or to radiation plus fluorouracil, which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine (methyl-CCNU). RESULTS. After a median follow-up of more than seven years, the combined therapy had reduced the recurrence of rectal cancer by 34 percent (P = 0.0016; 95 percent confidence interval, 12 to 50 percent). Initial local recurrence was reduced by 46 percent (P = 0.036; 95 percent confidence interval, 2 to 70 percent), and distant metastasis by 37 percent (P = 0.011; 95 percent confidence interval, 9 to 57 percent). In addition, combined therapy reduced the rate of cancer-related deaths by 36 percent (P = 0.0071; 95 percent confidence interval, 14 to 53 percent) and the overall death rate by 29 percent (P = 0.025; 95 percent confidence interval, 7 to 45 percent). Its acute toxic effects included nausea, vomiting, diarrhea, leukopenia, and thrombocytopenia. These effects were seldom severe. Severe, delayed treatment-related reactions, usually small-bowel obstruction requiring surgery, occurred in 6.7 percent of all patients receiving radiation, and the frequencies of these complications were comparable in both treatment groups. CONCLUSIONS. The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis, as compared with postoperative radiation alone. 
5	Hybridization protection assay: a rapid, sensitive, and specific method for detection of Philadelphia chromosome-positive leukemias. The Philadelphia (Ph1) chromosome is present in greater than 90% of patients with chronic myelogenous leukemia (CML) and in 2% to 20% of those with acute leukemias, for which it is an important prognostic marker too. The chimeric BCR-ABL mRNAs resulting from the translocation encode either a 210-Kd or a 190-Kd protein. The techniques used to detect Ph1 chromosome include karyotyping, Southern analysis to demonstrate bcr rearrangement, and polymerase chain reaction to amplify the BCR-ABL transcripts. However, the routine performance of these methods by clinical laboratories is cumbersome, time consuming, and exposes laboratory personnel to radioisotopes. We describe here the clinical application of a new method, the hybridization protection assay (HPA), which uses chemiluminescent acridinium-ester-labeled probes in conjunction with PCR for detection of the amplified BCR-ABL sequences. The method is sensitive, specific, and can reliably distinguish between the transcripts for P190BCR-ABL and P210BCR-ABL. In contrast to the 2 days or longer required for conventional hybridization, HPA analysis can be completed in less than 30 minutes. We have successfully used this method to analyze 60 leukemia samples (34 from Ph1-negative acute leukemias; 6 from Ph1-positive acute leukemias; and 20 from CML) with complete correlation (of BCR-ABL positivity or negativity) with the results of karyotype or Southern Blot analysis of genomic DNA for bcr rearrangement. Therefore, the HPA, in conjunction with PCR, appears to provide a rapid and reliable test for the diagnosis of Ph1-positivity. 
5	Relation between flow grade after thrombolytic therapy and the effect of angioplasty on left ventricular function: a prospective randomized trial. Recent intervention trials during myocardial infarction demonstrated no benefit from emergency angioplasty after thrombolytic therapy when compared with either delayed percutaneous transluminal coronary angioplasty (PTCA) or a conservative strategy. However, it is possible that subgroups of patients may benefit from early intervention with angioplasty. We performed a prospective randomized trial in patients with a patent infarct-related artery after thrombolytic therapy to determine whether initial flow grade is related to infarct-zone function and whether patients with ineffective reperfusion (greater than 90% stenosis or Thrombolysis in Myocardial Infarction [TIMI] flow less than or equal to 2) might benefit from immediate PTCA. Thrombolytic therapy was administered to 170 patients at a mean of 2.1 +/- 0.5 hours after onset of myocardial infarction. A patent infarct-related artery that was suitable for angioplasty was present in 89 patients who comprised the study group; after randomization, 47 of 50 patients with a patent infarct-related artery had successful emergency PTCA 3.8 +/- 1.5 hours after onset of symptoms, and 39 were scheduled for delayed (18 to 48-hour) PTCA. Reocclusion occurred before the scheduled (delayed) procedure in eight patients (20.5%), and was symptomatic in six. Infarct-region function (by the centerline method) measured initially, before discharge, and at 4 months was similar in both groups; improvement was significant (p less than 0.001) at discharge when compared with initial values with no further change at 4 months. However, patients with ineffective reperfusion had greater hypokinesia initially (p less than 0.05) compared with those with effective reperfusion (less than or equal to 90% stenosis plus TIMI flow 3). Moreover, independent of the timing of PTCA, improvement was greater before discharge in patients with ineffective reperfusion (p less than 0.05) with a trend also evident at 4 months. Importantly, 42 of 51 patients (82%) with a residual lumen less than 0.4 mm after thrombolysis had some improvement in function at discharge; this compared with a previous study in which patients with a similar degree of stenosis (without PTCA) had no improvement. Moreover, reocclusion occurred before scheduled (delayed) PTCA in 37% of patients with greater than 90% stenosis compared with only 5% in those with less than or equal to 90% stenosis (p = 0.02). Thus flow grade is an important determinant of myocardial function in patients with a patent artery after thrombolytic therapy and is predictive both of improvement in wall motion after PTCA and early reocclusion.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	Giant hemangioma of the liver with pain, fever, and abnormal liver tests. Report of two cases. In conclusion, we report the cases of two patients with large hemangiomas of the liver, abdominal pain, increased ESR and fibrinogen, increased serum alkaline phosphatase and gamma-glutamyltransferase activity, and normal white blood cell counts. Clinical and biochemical abnormalities disappeared after surgical resection. Increased ESR and fibrinogen are probably related to thrombosis within the tumor. This mode of presentation may suggest a diagnosis of hepatocellular carcinoma. 
3	Intraoperative ultrasonic imaging of the ascending aorta in ischemic heart disease. In an attempt to locate any atherosclerotic lesion in the ascending aorta and to prevent embolization, intraoperative B-mode ultrasonography was performed in 100 patients with ischemic heart disease (31 women and 69 men). Ultrasonography was carried out with a 10-MHz probe placed directly on the ascending aorta. Ultrasonic imaging demonstrated an atherosclerotic lesion in the lower half of the aorta in 76 patients (76%), a lesion in the upper half of the aorta in 89 patients (89%), and a lesion at the orifice of the innominate artery in 99 patients (99%). Prospective palpation identified an atherosclerotic lesion in 12 (25%) of 48 patients. Thoracic computed tomography in 79 patients showed calcification in the lower half of the aorta in 6 patients (7.6%) and in the upper half of the aorta in 11 (13.9%). Palpation and thoracic computed tomography underestimated the frequency of atherosclerotic lesions. Intraoperative ultrasonography accurately identified atherosclerotic disease. This technique allows the surgeon to modify cannulation, aortic clamping, and operative technique to reduce the risk of perioperative stroke due to embolization of atherosclerotic debris from the ascending aorta. 
1	Ability of circular extrachromosomal DNA molecules to carry amplified MYCN proto-oncogenes in human neuroblastomas in vivo. Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification. 
5	Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group BACKGROUND. Adverse cardiac events are a major cause of morbidity and mortality after noncardiac surgery. It is necessary to determine the predictors of these outcomes in order to focus efforts on prevention and treatment. Patients undergoing noncardiac surgery sometimes have postoperative cardiac events. It would be helpful to know which patients are at highest risk. METHODS. We prospectively studied 474 men with coronary artery disease (243) or at high risk for it (231) who were undergoing elective noncardiac surgery. We gathered historical, clinical, laboratory, and physiologic data during hospitalization and for 6 to 24 months after surgery. Myocardial ischemia was assessed by continuous electrocardiographic monitoring, beginning two days before surgery and continuing for two days after. RESULTS. Eighty-three patients (18 percent) had postoperative cardiac events in the hospital that were classified as ischemic events (cardiac death, myocardial infarction, or unstable angina) (15 patients), congestive heart failure (30), or ventricular tachycardia (38). Postoperative myocardial ischemia occurred in 41 percent of the monitored patients and was associated with a 2.8-fold increase in the odds of all adverse cardiac outcomes (95 percent confidence interval, 1.6 to 4.9; P less than 0.0002) and a 9.2-fold increase in the odds of an ischemic event (95 percent confidence interval, 2.0 to 42.0; P less than 0.004). Multivariate analysis showed no other clinical, historical, or perioperative variable to be independently associated with ischemic events, including cardiac-risk index, a history of previous myocardial infarction or congestive heart failure, or the occurrence of ischemia before or during surgery. CONCLUSIONS. In high-risk patients undergoing noncardiac surgery, early postoperative myocardial ischemia is an important correlate of adverse cardiac outcomes. 
5	Tissue-expanded radial forearm free flap in neck burn contracture. Neck contracture after burn injury can result in severe functional as well as aesthetic deformities. Contracture can recur even after wide and complete release and full-thickness skin grafting. Recurrence is partly due to the inherent difficulties in both early postoperative immobilization and the required long-term splinting. When adjacent tissues are also burned, adequate local tissue for reconstruction may not be available; therefore, free-tissue transfer may be necessary. The large surface area that is required after adequate release may be provided by tissue expansion before free-tissue transfer. In the case presented the use of tissue-expanded radial forearm free flap for the reconstruction of a recurrent neck contracture is described. 
4	Atheroemboli to the lower urinary tract: a marker of atherosclerotic vascular disease--a case report. Atheroemboli to the lower genitourinary tract may serve as a marker for disseminated atheroembolic disease, a highly lethal condition. A case presentation and review of our institional experience is presented. 
5	HLA-DQ beta sequence polymorphism and genetic susceptibility to IDDM. The analysis of HLA-DQ beta nucleotide sequence polymorphism in insulin-dependent diabetes mellitus (IDDM) patients and control subjects suggests a role for the DQ beta-chain in genetic susceptibility. Sequence determination and oligonucleotide hybridization was carried out on enzymatically amplified DNA from various HLA-DR-typed individuals, including the rare class of DR2+ patients. In the analysis of DQ beta variation in DR4, DRw6, and DR2 haplotypes, a correlation was observed between the presence of the negatively charged residue Asp at position 57 and low susceptibility and the presence of an Ala (DR4), Val (DRw6), or Ser (DR2) and higher susceptibility. However, important exceptions to this pattern have been identified in the analysis of heterozygous DR1/4 IDDM patients. In these individuals, susceptibility appears to correlate with specific DR beta l alleles (Dw4) on the DR4 haplotype, rather than with the DQ beta allele (DQB3.2) that contains Ala at position 57. The DQ beta alleles found in some Chinese IDDM patients also proved discordant with the position-57 correlations. Thus, although there is a general correlation between the residue at position 57 of the DQ beta-chain and IDDM susceptibility, these data do not support the notion that Asp 57 confers complete resistance or protection to IDDM. In general, these results suggest that IDDM susceptibility is conferred by specific combinations of DQ beta and DR beta sequences. 
5	Hair transplantation (a new method for recipient site suturing): the upper dermal running stitch. Recipient hair transplant plugs may heal into place with palpable, and unfortunately, visible borders. This appearance, called "cobblestoning," is reminiscent of the bumps in a cobblestone street. The author presents a new, rapid method of suturing transplanted plugs that greatly reduces cobblestoning, virtually eliminates traumatic plug loss, and facilitates row-by-row hair transplantation. Additionally, postoperative bandaging is not necessary, shower cleansing may commence within hours, and postoperative activity may be unlimited. 
5	Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance. The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade. 
4	Cardiac arrest after hypertonic citrate anticoagulation for chronic hemodialysis. The use of regional citrate anticoagulation as an alternative to standard therapy in hemodialysis patients at risk for bleeding complications has been well described. Recently, a method using hypertonic citrate has been reported as being safe and efficacious, and having several advantages over the usual techniques. Two patients who suffered cardiac arrests after dialysis using hypertonic citrate are discussed. Both received anticoagulation as described in the literature, although the citrate infusion rate was lower than recommended. Electrocardiograms obtained during the first such session showed no change in the Q-Tc interval with initiation of the infusion in either patient. Both were noted to have cardiac arrest within 5 minutes of discontinuation of dialysis, without warning symptoms, following the second and fifteenth treatments, respectively. The initial rhythm of ventricular fibrillation did not respond to standard advanced cardiac life support therapy, and the patients were not successfully resuscitated until they received intravenous calcium. The authors postulate that the loss of positive calcium flux from the dialysate, in conjunction with circulating unmetabolized citrate, caused an electrolyte imbalance leading to the potentially fatal arrhythmia. Caution is recommended in using this method of regional anticoagulation. 
4	Blood pressure measurements during dental checkups representative of 26-hour registration. The effect of dental checkups on blood pressure was investigated. In 27 normotensive patients (13 men and 14 women) aged 22 to 64 years (mean 39.75 +/- 10.5 years), a 26-hour continuous, noninvasive blood pressure registration was carried out. Of each patient at least 175 blood pressure measurements were registered during these 26 hours, giving a total amount of 4725 blood pressure measurements. A dental checkup appointment with the family dentist was included. Blood pressure values displayed the well-known diurnal variation, but the visit to the dental surgeon was not accompanied by a rise in blood pressure. There was no significant difference between the blood pressure values during the 26-hour period and those during the checkup period. During a rest period after the dental checkup, neither the systolic nor the diastolic pressure fell to any degree in relation to the 26-hour values or the visit to the surgeon. 
2	Miscellaneous adverse effects of low-versus high-osmolality contrast media: a study revised The authors analyzed data from two recent articles in Radiology in which the quality and results of randomized control trials (RCTs) comparing the efficacy or safety of the low-osmolality contrast media (LOM) iopamidol, iohexol, and ioxaglate with that of the high-osmolarity contrast media (HOM) diatrizoate, iodamide, iopamide, iothalamate, and metrizoate were assessed. One conclusion in the source articles was that no differences were seen between the two groups of contrast media in frequency of nausea, vomiting, and urticaria. However, the LOM group included both nonionic LOM (NIM) and the ionic contrast medium ioxaglate. The authors found that various complications associated with the use of contrast media were much less common with NIM than with HOM; statistically this lower frequency is highly significant. This difference was obscured in the previous studies by the pooling of RCTs in which the less toxic NIM were used and RCTs in which the more toxic ionic contrast medium ioxaglate was used. 
1	Primary malignant lymphoma of the bladder. We treated 11 patients with primary malignant lymphoma of the bladder. The typical patient is a woman more than 50 years old who presents with urgency and frequency of micturition, and occasionally gross hematuria. Hydronephrosis is present in half of the patients and cystoscopy usually reveals a solid tumor. Partial cystectomy, when feasible, with or without radiotherapy and chemotherapy is the usual treatment modality. When localized to the bladder, malignant lymphoma has an over-all favorable prognosis. 
4	Diagnosis of tracheal injury in mechanically ventilated premature infants by flexible bronchoscopy. A pilot study. Flexible bronchoscopy (FB) is uniquely suited for the study of large airway lesions in the ventilated premature infant. However, no standardized clinical scoring system of distal tracheal injury exists and the adverse consequences of FB in ventilated premature infants are not well described. Using a prototype Olympus fiberoptic ultrathin bronchoscope with a directable tip and an outer diameter of 2.2 mm, we serially scored distal tracheal injury in conventionally ventilated premature infants on the basis of mucosal and obstructive changes observed at bronchoscopy. In addition, we prospectively evaluated the incidence of adverse cardiovascular and pulmonary effects during, immediately after, and within 1 h of FB. We performed 21 FBs in eight conventionally ventilated premature infants with birth weight of 1,239 +/- 438 g and gestational age of 30 +/- 3 weeks. The carina and mainstem bronchi were easily visualized in all infants using the prototype bronchoscope. During the first several days of life, moderate-to-severe distal tracheal mucosal injury occurred frequently, while moderate-to-severe obstructive injury occurred infrequently. Distal mucosal injury appeared to improve during the fourth week of life. Mild distal obstructive injury began to appear during the second week of life. Adverse consequences of FB observed in our patient population included transient hypoxemia and bradycardia during FB, changes in systolic blood pressure immediately and within 1 h after FB, and emesis immediately after FB. Serious adverse cardiovascular or pulmonary effects were not observed. We conclude that FB can be performed safely with appropriate monitoring and is a useful tool in the clinical assessment and serial evaluation of distal tracheal injury in ventilated premature infants. We speculate that moderate-to-severe distal tracheal mucosal injury may be associated with the development of later obstructive injury. On the basis of this preliminary study, further prospective investigations of tracheal injury in ventilated premature infants appear to be warranted. 
4	Diabetic retinopathy in blacks. Diabetic eye disease, particularly diabetic retinopathy, is the leading cause of new cases of legal blindness in people 20-74 yr of age in the United States. The prevalence and rate of diabetes in this age-group are higher in Blacks than in Whites. The rate of blindness from diabetic eye disease is also higher in Blacks than in Whites. Severe macular edema, the most frequent cause of decreased vision in diabetic retinopathy, appears to be more common in Blacks. Risk factors for developing macular edema include poorly controlled hypertension, hyperglycemia, and duration of disease. The higher prevalence of hypertension in Blacks may contribute to the increased severity of diabetic retinopathy. Further evaluation is necessary to determine the influence of race on the severity of diabetic retinopathy. 
4	The management of aneurysms and arterio-venous fistulae of the popliteal artery arising from war trauma. Emphasis on sigmoid operative approach. Between 1986-1988, 600 vascular cases arising from the Iran-Iraq conflict were dealt with within an 18 month period and 60 cases of popliteal artery and/or venous disruption were encountered presenting at variable times after injury. A policy of management between the forward and base hospital surgical teams was introduced, observing the following broad categorizations: (a) assessment/referral, (b) assessment/fasciotomy/referral, (c) immediate operation/referral for further operation/review/management. Two types of incision were used to enter the popliteal fossa: (a) a medial incision and (b) a sigmoid posterior incision (which we now favor). The results of this strategy of management and operative technique (when compared with our previous experience within the same time frame) suggested an improved outcome. Fifty-four out of 60 cases had a satisfactory operative result with below-knee amputation being required in only four cases and higher amputations in two others. No operative or postoperative deaths occurred. The implementation of this "vetting policy" at the front line appeared to reduce the number of amputations and assisted the clarification of management criteria in assessing limb viability at the forward hospital when a large number of casualties were being received. Operative access using the sigmoid posterior incision was not associated with any complications, offered better exposure than the medial incision and was technically easier for the surgeon to perform. 
1	Prostate cancer: transrectal ultrasound and pathology comparison. A preliminary study of outer gland (peripheral and central zones) and inner gland (transition zone) cancer. A study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A cancer; one patient had cancer detected by palpation and not detected by ultrasound. Cancers in the outer gland (peripheral and central zones) were compared with cancers in the inner gland (transition zone) by both ultrasound and pathology. Forty-eight percent (52 of 108) of cancers originating in the outer gland showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the outer gland were the prostatic capsule (38%), anterior fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of cancers originating in the inner gland (transition zone) showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled. Gleason scores were significantly different for inner and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9, respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic extension for outer gland cancer. Outer gland cancers showed increased aggressive behavior of both histologic and biologic nature. The difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options. Use of other diagnostic parameters, such as DNA ploidy, may help to determine which cancers to treat and when to treat them; this may have more relevance for cancers originating in the inner gland. Strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known. Thus, transrectal ultrasound may be our "window of observation" through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers. 
5	Two urokinase dose regimens in native arterial and graft occlusions: initial results of a prospective, randomized clinical trial. The effects of two urokinase (UK) dose regimens on lysis time, lytic success, primary clinical success, and frequency of complications of peripheral thrombolysis were compared. Seventy-two intraarterial UK infusions were performed by means of standard catheter-directed infusion techniques in 63 patients with symptomatic peripheral arterial or bypass graft occlusions. Patients were prospectively randomized to high-dose (250,000 U/h for 4 hours and then 125,000 U/h) or low-dose (50,000 U/h) regimens. The mean time to complete lysis was 20.8, 26.0, 16.5, and 18.2 hours for the high-dose artery, low-dose artery, high-dose graft, and low-dose graft groups, respectively (P was not significant). Respective mean infusion durations were 27.1, 35.4, 22.2, and 25.3 hours. Clinical success was achieved in 65%-85% of cases. The frequency of complications was equivalent between groups, except for a higher frequency of minor bleeding complications in the high-dose group. The two urokinase dose regimens studied were equally effective in enabling peripheral thrombolysis. 
5	Use of N2O/O2/enflurane anesthesia for dental treatment of the handicapped. To develop an anesthesia maintenance method that could be expected to maintain a reasonably stable state during dental treatment of the handicapped, three methods (N2O/O2 [0% enflurane (E), n = 12], N2O/O2/0.6% E [n = 8], N2O/O2/1.5% E [n = 7]) were evaluated in terms of changes in plasma levels of cortisol, epinephrine (EP), and norepinephrine (NE). During a treatment period of 60 minutes, cortisol levels increased in the 0% E group (from 9.5 +/- 1.8 micrograms/dL to 19.4 +/- 2.4 micrograms/dL, P less than .01), did not change in 0.6% E group, and decreased in 1.5% E group (from 9.3 +/- 1.7 micrograms/dL to 5.8 +/- 1.0 micrograms/dL, P less than .01). Epinephrine and NE levels increased in the 0% E group, but were suppressed in the 0.6% E and 1.5% E groups. It is suggested that N2O/O2 inhalation anesthesia supplemented with low-dose enflurane produces a stable state during dental treatment with respect to cortisol, EP, and NE responses. 
1	Hemodialysis for acute renal failure in patients with hematologic malignancies. OBJECTIVE: To assess the prognosis of patients with hematologic malignancies in acute renal failure who require hemodialysis. DESIGN: Retrospective study. SETTING: ICU. PATIENTS: Forty-three consecutive patients. METHODS: Prognostic analysis using both univariate and multivariate (stepwise regression) methods. RESULTS: Fifteen (35%) patients recovered from acute renal failure and 12 (28%) were discharged from the ICU. The prognosis of patients with acute renal failure linked to sepsis is poorer than the prognosis of the patients with acute renal failure from other etiologies. Only one patient survived in the former group (n = 26) and 11 in the latter group (n = 17); p less than .0001 in multivariate analysis. When accompanied by associated respiratory failure, mortality rate was higher (93% vs. 33%; p less than .0001). The Simplified Acute Physiology Score (SAPS) calculated within the first 24 hr of admission was significantly (p less than .001) related to mortality when the SAPS was greater than or equal to 13. The presence of neutropenia and the type of hematologic malignancy were not related to a worse prognosis. Tolerance to hemodialysis appeared good, and complications were rare. 
4	Carotid-subclavian bypass--a decade of experience. From August 1979 to August 1989, carotid-subclavian bypass or transposition procedures were performed on 18 women and 13 men ranging in age from 19 to 75 (mean, 58.2) years. Indications for surgery included symptoms of vertebrobasilar insufficiency in 16 (52%), upper extremity ischemia in six (19%), both vertebrobasilar insufficiency and extremity ischemia in four (13%), and stroke and/or hemispheric transient ischemic attacks in four (13%) patients. One patient (3%) had angina pectoris caused by "coronary-subclavian steal." Formal bypass grafts were performed in 28 (90%) cases by means of polyterafluoroethylene (24), Dacron (2), or saphenous vein (2), and carotid-subclavian transposition was performed in three (10%) cases. Synchronous procedures included carotid endarterectomy (4), carotid-carotid bypass (1), and axillobrachial bypass (1). There was no operative mortality. Thirty-day primary patency was 97%. Follow-up has ranged from 1 to 121 (mean, 42) months. Three grafts (polytetrafluoroethylene) have occluded during follow-up yielding long-term primary patency of 92% at 5 years and 83% at 8 years. Relief of symptoms was initially achieved in 30 (97%) patients. Recurrent symptoms have developed in six (20%) patients from 2 to 55 (mean, 26) months after surgery, including two with occluded and four with patent grafts. Symptom-free survival is 89% at 1 year, 84% at 2 years, and 71% at 7 years of follow-up. Six patients have died during follow-up yielding overall survival of 88% at 5 years, and 48% at 10 years. 
3	Percutaneous aspiration of brain tumor cysts via the Ommaya reservoir system. We performed percutaneous aspiration of 21 brain tumor cysts in 20 patients using the Ommaya reservoir system. Ages ranged from 3 to 70 years, median 48. Sixteen were primary tumors (12 anaplastic glioma, 2 craniopharyngioma, 1 oligodendroglioma, 1 brainstem glioma) and 4 were metastatic. Fourteen had the CT appearance of a true cyst and 7 a pseudocyst. We placed 18 catheters through twist drill holes via CT stereotactic guidance and 3 through burr holes via CT guidance and effectively aspirated 3 to 50 ml cyst fluid from 1 to 18 times in each patient. Postaspiration CT showed complete or significant reduction in cyst size in all patients in whom it was performed (18 after initial aspiration and 9 after subsequent aspirations). Asymptomatic intracyst hemorrhage occurred in 2 patients after cyst wall biopsy and catheter placement. There have been no other complications at follow-up of 4 to 114 weeks. In our experience, tumor cyst aspiration by the Ommaya reservoir system is as effective as percutaneous needle aspiration, but after catheter placement aspiration can be performed with minimal technical skill, avoiding repeated CT guidance required for needle aspiration of recurrent deep-seated cysts. 
5	(A)typical symptoms during single needle dialysis. In 5 elderly patients, an abnormally high occurrence of some symptoms was noted during dialysis. All patients were dialyzed with biocompatible membranes, bicarbonate dialysate, and a blood flow of 250 to 300 ml/min by a single needle system, on a fistula 14 Gauge catheter-needle. These symptoms were: 1) "angina," resistant to O2 and nitrates, with biochemical stigmata of infarction, but without electrocardiogram (ECG) localization; 2) intractable persistent hypotension, not hypovolemic, lasting 1 or 2 days; 3) esophagal spasms, with inability to swallow solid food. Because we knew that these symptoms were compatible with hemolysis (biochemically proven by the increase in serum LDH during dialysis and by a fall in haptoglobin) due to red cell fragmentation (RCF), we switched these patients from fistula dialysis (A) to central catheter dialysis (B), with the same apperture, blood flow, etc. The total number of sessions of A versus B were 512 and 891; the mean LDH ratios (serum LDH postdialysis divided by predialysis) were 1.8 and 1.0 (= no RCF); angina events were 132 (26%) for A, and 25 (3%) for B; persistent hypotension was seen 37 (7%) times in A and 5 (0.6%) times in B; esophagal spasms were noted 65 (13%) times for A, and 0 times for B. This clinical improvement was so overwhelming that 3 patients refused to be dialyzed again using their well functioning fistulae. This study also proved the need for a better designed and manufactured peripheral dialysis catheter-needle. 
2	Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid. 
4	Comparison of two levels of anticoagulant therapy in patients with substitute heart valves After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves. 
1	Breast cancer during pregnancy and lactation. Breast cancer is the most frequently seen cancer in pregnancy and lactation, but the incidence is low, the disease being seen in approximately 0.03% of pregnancies. Only 1% to 2% of breast cancer overall is diagnosed during pregnancy or lactation. There is no evidence to implicate pregnancy or lactation in either the etiology or the progression of breast cancer. Careful breast examination early in the pregnancy is very important to find solid masses that require biopsy before breast engorgement hides them. Therapeutic options vary, depending on the stage of disease and the stage of the pregnancy. Operable disease in the first 6 to 7 months of the pregnancy should be treated by mastectomy, as irradiation is contraindicated. Late in the pregnancy, a lumpectomy and axillary dissection can be done, with irradiation being delayed until after delivery. General anesthesia is safe if the usual precautions are taken to compensate for the physiologic changes induced by pregnancy. Unfortunately, delay in diagnosis is common, and 70% to 89% of patients with operable primary lesions have positive axillary lymph nodes. Late stage appears to be the only reason for the generally worse prognosis in these patients, as stage for stage, they have a course similar to that of nonpregnant patients. Adjuvant chemotherapy can be considered late in the pregnancy but should usually be delayed until after delivery. In patients with locally advanced or metastatic cancer diagnosed early in the pregnancy, for whom both chemotherapy and radiation therapy would normally be recommended, consideration must be given to termination of the pregnancy. There is no evidence that termination of pregnancy improves the outlook for the patients, but it does permit standard aggressive therapy in advanced disease. 
1	Intraoperative ultrasonography and the detection of liver metastases in patients with colorectal cancer. A total of 213 patients with carcinoma of the colon and rectum were examined to detect liver metastases. The study compared preoperative ultrasonography and inspection and palpation of the liver during surgery with intraoperative ultrasonography. Preoperative ultrasonography, inspection and palpation identified 238 metastases in 42 patients. Intraoperative ultrasonography detected 116 previously unrecognized metastatic tumours during 40 surgical procedures (P less than 0.01). High resolution intraoperative ultrasonography is safe and more accurate than preoperative imaging and surgical exploratory methods. The examination is simple to perform and success appears to be related to careful attention to detail. 
5	Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity. A total of 121 infants who required indomethacin for persistent ductus arteriosus in Liverpool and Cambridge over a four year period were randomised to receive either 0.1 mg/kg daily for six days or 0.2 mg/kg every 12 hours for three doses. The groups were of similar birth weight and gestational and postnatal age, though those treated with a low dose were by chance receiving a higher percentage of oxygen at the start of treatment and there were more deaths from bronchopulmonary dysplasia in this group. Of 59 infants treated with the prolonged course 53 (90%) responded initially to indomethacin compared with 48 of 62 (77%) treated conventionally--a difference of 13% (95% confidence interval for the difference 0 to 26%). Of the 53 responders 11 (21%) relapsed after low dose indomethacin, whereas after the shorter course 19 of 48 (40%) relapsed. This difference was significant (95% confidence intervals 3 to 37%). Side effects, mainly gastrointestinal haemorrhage, were similar in both groups. Significantly fewer infants experienced a rise in serum creatinine or urea concentration after treatment with low dose indomethacin. A prolonged low dose course of indomethacin offers advantages over conventional treatment. 
4	Preoperative selection for curable renovascular hypertension. Clinical research has defined the criteria for identifying "curable" renovascular hypertension. The prediction is based on the measurement of plasma renin activity in peripheral veins, renal veins, and the aorta. Renin profiles can be examined with the method of Laragh and coworkers (the so-called incremental method), in which values for plasma renin activity are incorporated into formulas to compute indexed parameters. A score is attributed to each index and the prediction is based on the final score. Because the identification of curable renovascular hypertension is made according to numerical rules, the method is easily transformed into a computer-assisted process. The program is written in BASIC, and it is short enough to run on a personal computer. 
3	Snoring and sleep architecture. The purpose of this study was to examine whether snoring adversely affects sleep architecture and sleep efficiency, and thus may account for the frequent complaints of daytime tiredness and fatigue expressed by heavy snorers. We recruited eight self-confessed heavy snorers and six self-confessed nonsnorers. All subjects had full nocturnal polysomnography, including continuous monitoring of snoring, which was quantified by counting the number of snores per hour of sleep (snoring index), the number of snores per minute of snoring time (snoring frequency), maximal and mean nocturnal sound intensity (dBmax and dBmean, respectively). We found that even the self-confessed nonsnorers snored lightly, with significantly smaller frequency and index than the heavy snorers. Sleep architecture was similar in both groups. Distribution of snoring among the sleep stages differed for light and heavy snorers: light snorers snored uniformly throughout all sleep stages, whereas heavy snorers tended to snore more during slow-wave and REM sleep. Snoring frequency and snoring index were similar during all sleep stages in light snorers, but they were higher during slow-wave sleep in heavy snorers. Wakefulness time after sleep onset and sleep efficiency correlated significantly with the snoring index. We conclude that although snoring does not affect sleep architecture in general, it influences sleep efficiency and wakefulness time after sleep onset; this may have an adverse effect on daytime function of heavy snorers. 
1	Deficient counterregulatory hormone responses during hypoglycemia in a patient with insulinoma. Counterregulatory hormone responses were evaluated in a 37-yr-old woman before and after removal of a benign insulin-producing islet cell tumor. Counterregulatory hormone concentrations were measured during a glucose clamp with graded reductions of plasma glucose from 5.2 to 2.6 mmol/L. In the study before surgery, the increase in plasma epinephrine concentration was markedly blunted (by greater than 90%) compared to that in the study after surgery. The peak plasma norepinephrine concentration was similarly reduced by 71%, and plasma cortisol by 63%. In addition, the glycemic thresholds for secretion of the counterregulatory hormones were lower before removal of the tumor. Peak plasma GH responses were equivalent before and after surgery, but the threshold for GH secretion was 21% lower in the first hypoglycemia study. We conclude 1) that there is evidence for abnormal glucose counterregulatory hormone secretion in this patient, which may contribute to the pathogenesis of hypoglycemia seen in patients with insulinoma; 2) the reversal of reduced counterregulatory hormone secretion after tumor resection suggests that these defective hormonal responses may be related to recurrent hypoglycemia, persistent hyperinsulinemia, or both; and 3) that abnormal glucose counterregulation may exist in the absence of type 1 diabetes. 
5	Serial magnetic resonance imaging of hamstring anterior cruciate ligament autografts during the first year of implantation. A preliminary study. A prospective, observational study was performed to document the serial changes in the magnetic resonance signal of devascularized, hamstring ACL autografts during the 1st year of implantation. Twenty-one ACL deficient knees (14 chronic, 7 acute) were reconstructed. Instability developed in five knees within the first 6 months of graft implantation (24%). Magnetic resonance examinations were performed at 1, 6, 12, 24, 36, and greater than 48 weeks postoperatively (repetition time 1500, echo delay time = 50). A total of 104 scans were reviewed (average, five per knee). The ACL graft was divided into four unequal size zones for analysis. The proximal, middle, and distal thirds of the intraarticular portion of the graft and the portion of the graft within the tibial tunnel were independently analyzed. The magnetic resonance signal in each portion of the graft was graded on a scale with (I) being a normal signal, (II) greater than 50% of the total volume of the graft having a normal signal, (III) less than 50% of the graft having a normal signal, and (IV) 100% of the graft having an increased signal. The increased magnetic resonance signal of the ACL graft was observed to be regionalized and confined to the distal two-thirds of the intraarticular portion of the graft. The portion of the graft exiting the femoral tunnel and within the tibial tunnel retained a normal magnetic resonance signal. The increases in magnetic resonance graft signal were time-dependent, became well established by 3 months, and remained unchanged at 1 year. The clinical outcome could not be predicted based on the magnetic resonance signal of the graft. 
5	Focal nodular hyperplasia of the liver. Twenty-four patients underwent biopsy or resection of the liver for focal nodular hyperplasia (FNH) at Memorial Sloan-Kettering Cancer Center from 1978 to 1988. Twenty-two of the patients were women. The mean age was 35 years. A history of antecedent oral contraceptive or conjugated estrogen (Premarin) use was obtained in 18 of 21 women. There were two men, aged 26 and 37 years; neither gave a history of hormone use. Most of the tumors were solitary (22 of 24) and located in the left lobe of the liver (17 of 22). Fifteen of the patients had a prior or simultaneous malignant lesion and six had other benign tumors. Most of the tumors were resected with a wedge or subsegment of liver (13 of 24). Four patients underwent segmentectomy and five required lobectomy for removal of the tumors. Two patients had an intraoperative biopsy only. The patients in whom the tumor was diagnosed preoperatively underwent computed tomography and arteriography routinely. Scintigraphy of the liver with sulfur colloid was obtained in only three patients, despite its distinct potential for nonoperative diagnosis of FNH. 
2	A topographical relationship between Helicobacter pylori and gastritis: quantitative assessment of Helicobacter pylori in the gastric mucosa. A topographical relationship between the number of Helicobacter pylori in the gastric mucosa and the histological severity of gastritis was studied in 902 pairs of biopsy specimens taken from 314 patients. A pair of biopsies were taken from the antrum, the lesser curvature of the middle body, and the greater curvature of the upper body of the stomach. The quantitative assessment of H. pylori was made based on smear, culture, and tissue section. The histological severity of gastritis was assessed as to the degrees of mononuclear cell and polymorphonuclear leukocyte infiltration. A positive correlation was confirmed between the number of H. pylori and the severity of polymorphonuclear leukocyte infiltration. The degrees of inflammatory cells infiltration in the specimens with H. pylori colonization were significantly lower in the upper body than in the antrum. 
1	Primary sarcomas of the major salivary glands. Sarcomas arising in the major salivary glands are rare. This article presents the clinicopathologic features of 11 patients with primary sarcomas of the parotid gland (eight men and three women aged 7 to 75 years; mean age, 42 years). The 11 sarcomas were histologically typified as follows: three malignant fibrous histiocytomas and two each of neurosarcomas, rhabdomyosarcomas, fibrosarcomas, and osteosarcomas. Four patients experienced disease recurrences, and seven patients developed metastases. Seven patients died of their sarcomas, with a mean survival time of 30 months. Four patients were alive from 5 to 12 years (one each with angiomatoid malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, fibrosarcoma, and neurosarcoma). Prognosis correlated with size of the neoplasm, type of sarcoma, and histologic grade. In this respect, salivary gland sarcomas behaved in identical fashion to their soft-tissue counterparts. 
3	Posthypoxic glucose supplement reduces hypoxic-ischemic brain damage in the neonatal rat. We evaluated the effect of posthypoxic glucose supplement in a neonatal hypoxic-ischemic animal model. Seven-day-old rats underwent bilateral ligation of the carotid arteries, followed by exposure to an 8% oxygen atmosphere for 1 hour. The extent of hypoxic-ischemic brain damage was assessed histologically 72 hours later. Glucose load immediately after the end of the hypoxic exposure reduced the volume of neocortical infarction to 37% of the unsupplemented value, and attenuated ischemic damage in the striatum and the dentate gyrus. At the end of the hypoxic exposure, the brain level of glucose was 0.3 mmol/kg and the level of lactate 9 mmol/kg. Glucose supplement produced a rapid rise in brain glucose level to 3 to 5 mmol/kg over the next 2 hours. Lactate in both brain and plasma gradually fell toward the baseline level during the first hour of recovery. Posthypoxic glucose supplement slightly retarded lactate restitution. At any period of this neonatal model, brain lactate levels did not exceed the toxic level, which is postulated to be responsible for cerebral infarction in adult ischemic models. These results illustrate the important role of glucose in the development of neonatal hypoxic-ischemic encephalopathy and the fact that full cortical infarction can develop even if brain lactate levels are low. 
1	Malignant thymoma presenting as intracardiac tumor and superior vena caval obstruction. A case of malignant thymoma with intracardiac infiltration and intrinsic superior vena caval obstruction due to the tumor is reported. Intracardiac invasion by a thymoma is rare and for this reason is believed worthy of a report. 
5	Thrombolytic therapy for noncoronary diseases. Thrombolytic therapy has been used fairly extensively in the management of acute proximal deep-vein thrombophlebitis of the extremities, acute pulmonary embolism, and acute peripheral arterial thrombosis and embolism in addition to acute thrombotic coronary events. In the presence of acceptable indications and a favorable benefit to risk ratio, this form of therapy, when successful, has served as a useful adjunct in the management of these disorders. In deep-vein thrombophlebitis, lysis of the thrombus before permanent pathological changes (eg, organization, scarring) have occurred can prevent venous valvular dysfunction and postural venous hypertension and its complications, especially the postphlebitic syndrome. In the more severe forms of acute pulmonary embolism, thrombolytic therapy, when applied early after symptom onset, decreases morbidity and is likely to prevent a chronic increase in pulmonary vascular resistance and persistent pulmonary hypertension. In peripheral arterial thrombo-occlusive events, early restoration of flow through thrombolysis has been shown to limit ischemic damage and serve as a useful supplement to angioplasty or surgery. Thrombolytic therapy has been used less extensively in acute strokes. Here the danger of reperfusion causing bleeding into a softened area of brain undergoing infarction has slowed its evaluation for this disorder; its application to stroke remains experimental. 
4	Nonpeptide angiotensin II receptor antagonists. Although the most direct way to interfere with the renin-angiotensin system (RAS) is at the level of the angiotensin II (AII) receptor, the currently available AII receptor antagonists are peptides still retaining significant agonistic properties with the obvious drawbacks of limited stability and lack of oral activity. We have characterized simple N-benzylimidazoles as weak, but selective AII receptor antagonists with a competitive mode of action. Chemical modification of these early leads led to EXP6155 and EXP6803, which show approximately 10- and 100-fold higher affinity. Oral activity was obtained for EXP7711, and in particular for EXP9654. This class of compounds displaces 3H-AII from its specific binding sites in various tissues. They competitively antagonize AII-induced responses in various in vitro and in vivo preparations, but do not influence AII-induced responses to KCl, norepinephrine, and vasopressin, nor do they affect converting enzyme or renin. In high renin models of elevated blood pressure, such as the renal hypertensive rat and sodium-depleted dog, these substances produce a sustained decrease in arterial pressure without changing heart rate after intravenous and oral (EXP7711 and EXP9654) administration. None of these compounds showed agonistic activity in any of the above test systems. In conclusion, the nonpeptide structures described herein are selective and competitive AII receptor antagonists and add another dimension to the arsenal of drugs manipulating the RAS. 
3	Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats. The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195 +/- 8 to 125 +/- 5 and 148 +/- 3 mm Hg, respectively [mean +/- SEM]; p less than 0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911 +/- 155 to 1,244 +/- 101 and 1,388 +/- 59 microns 2, respectively, compared with 1,405 +/- 95 microns 2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 +/- 6 to 62 +/- 2 mm Hg with cilazapril versus 79 +/- 5 mm Hg for hydralazine compared with 60 +/- 4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 +/- 4 to 100 +/- 4 microns for cilazapril versus 91 +/- 3 microns for hydralazine compared with 107 +/- 3 microns for untreated WKY rats). 
3	Tuberothalamic infarct after division of a hypoplastic posterior communicating artery for clipping of a basilar tip aneurysm: case report. The authors present a case of a tuberothalamic infarct subsequent to division of the posterior communicating artery for clipping of a high-lying aneurysm of the basilar bifurcation using the pterional approach. In view of this clinical observation and some particular aspects of the microsurgical anatomy of the perforating vessels of the posterior communicating artery, we conclude that interrupting this parent vessel carries a significant risk of infarction. 
1	Intradural epithelial cyst at the craniovertebral junction. Case report. A case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37-year-old man. The classification of these rare lesions is discussed. 
5	Regional differences in the intranodal distribution of tumor cells. The intranodal distribution of tumor cells was examined in 103 mesenteric and 135 axillary nodes to determine the frequency of a circumferential type of distribution and its relationship, if any, to central necrosis. Eighteen percent of the mesenteric nodes removed at surgery from patients with colon cancer contained a circumferential rim of viable tumor cells in an area corresponding wholly or in part to the normal location of the marginal sinus. In each case this rim of tumor cells surrounded a large central area of necrosis. In contrast, only one of the 135 axillary nodes removed from patients with breast cancer demonstrated this pattern. These findings suggest that by interrupting blood and lymph vessels, the circumferential spread of tumor cells underlies development of central necrosis. Previously described structural dissimilarities between mesenteric and axillary nodes may explain the striking difference in incidence of this pattern in these nodes. 
4	Intracoronary urokinase for intracoronary thrombus accumulation complicating percutaneous transluminal coronary angioplasty in acute ischemic syndromes. Intracoronary urokinase was used to treat flow-limiting intracoronary thrombus accumulation that complicated successful percutaneous transluminal coronary angioplasty (PTCA) during acute ischemic syndromes in 48 patients who were followed up through the acute phase of their illness. The study group comprised 10 patients with unstable angina pectoris, 18 patients with an evolving acute myocardial infarction, and 20 patients with postinfarction angina. The initial mean percent coronary diameter stenosis for the entire population was 95 +/- 7% and decreased with initial PTCA to 41 +/- 20% (p less than 0.001), with improved corresponding coronary flow by Thrombolysis in Myocardial Infarction trial (TIMI) grade. However, thrombus accumulation then resulted in a significant increase in percent diameter stenosis to 83 +/- 17% (p less than 0.001); a corresponding significant reduction in coronary flow also occurred by TIMI grade. After administration of intracoronary urokinase (mean dose, 141,000 units; range, 100,000-250,000 units during an average period of 34 minutes), with additional PTCA, mean percent diameter stenosis significantly decreased to 34 +/- 17% (p less than 0.001); a correspondingly significant improvement in mean coronary flow by TIMI grade occurred to 2.9 +/- 0.2. Overall, the angiographic success rate was 90%. There were no ischemic events requiring repeat PTCA and no procedure-related myocardial infarctions or deaths before hospital discharge. One patient was referred for urgent coronary artery bypass graft surgery after a successful PTCA. Plasma fibrinogen levels were obtained in 15 patients, and in no patient was the level below normal for our laboratory. 
1	Tumefactive fibroinflammatory lesions of the head and neck. The term 'tumefactive fibroinflammatory lesion' has been used to describe a fibrosclerosing disorder which has a locally destructive nature but is characterized by a benign histological appearance. We report five patients, over a five year period, with such a lesion. The clinical behaviour and surgical findings suggest the lesion to be an invasive malignancy. However, the histological appearance of an admixture of chronic inflammatory cells and fibrosis is consistent with a benign condition. We recommend surgical excision of the lesion as the mainstay of treatment; other studies report the use of steroids and radiotherapy. 
5	Emphysematous gastritis: case report and review. Emphysematous gastritis is a condition involving gastric wall inflammation, radiologic or intraoperative evidence of intramural gas, and systemic toxicity. A recent case of emphysematous gastritis in a 57-year-old diabetic man is reported, and 27 cases published since 1889 are reviewed. Predisposing factors include ingestion of corrosive substances (37%) and alcohol abuse (22%). Diagnosis of emphysematous gastritis is based on the clinical presentation of an acute abdomen with systemic toxicity and on radiographs demonstrating gas bubbles within the stomach wall. For the case reported herein, computed tomography was useful both in establishing the diagnosis and in following the resolution of emphysematous gastritis. Organisms most commonly involved were Escherichia coli (six cases), Streptococcus species (six cases), Enterobacter species (five cases), and Pseudomonas aeruginosa (three cases). The mortality was 61% (17 of 28 patients), and morbidity with gastric contractures occurred in 21% of cases (6 of 28). Optimal therapy has not been defined; however, antimicrobial chemotherapy and surgery, when appropriate, may improve survival rates. 
1	Total gastrectomy for gastric cancer in the elderly. Of 1070 patients with gastric cancers, 292 patients underwent total gastrectomy during 13 years. Sixty patients were more than 70 years of age and 232 were under 69 years. The incidence of well-differentiated carcinomas and poorly differentiated carcinomas was the same in the elderly patients, whereas the latter was dominant in the young patients. However, there was no significant difference between the two groups regarding location, size, macroscopic patterns, extent of lymph metastases, or stage classification. The rates of preoperative surgical risk factors were significantly different between the two groups (p less than 0.01): 90.0% for the elderly and 34.9% for the young patients. However, the rates of postoperative morbidity and mortality were 31.7% and 3.3% for the elderly and 24.1% and 1.3% for the young patients, respectively, with no significant difference. The 5- and 10-year survival rates after curative total gastrectomy were 48.6% and 23.2% for the elderly compared with 49.4% and 33.6% for the young patients, respectively, with no significant difference. A 5-year survival rate after noncurative operation was 0% for the elderly and 6.4% for the young patients. These results indicate that, when performed for cure, total gastrectomy with systematic lymphadenectomy can provide good long-term results for elderly, as well as young, patients. 
4	Surgery for thoracoabdominal aortic aneurysms. From July 1985 to July 1989, Loma Linda University Medical Center evaluated 46 thoracoabdominal aortic aneurysms (TAAAs). Forty patients were taken to surgery--18 (45%) were operated on an emergency basis for reasons including rupture (12 patients, 30%), dissection (5 patients, 12.5%), and severe pain (1 patient). The overall mortality for all operated patients was five (12.5%-17% for emergency surgery versus 9% for elective surgery). Nonfatal complications occurred in 40 per cent of patients (16). The overall incidence of paraplegia was 10 per cent (4/40), emergency patients 17 per cent (3/18) versus elective patients 4.5 per cent (1/22). Careful preoperative evaluation, standardization of operative technique, and good postoperative management have improved the outlook for these patients who otherwise would progress to eventual rupture and death. Because mortality and morbidity are substantially reduced in elective patients, we recommend that all patients with TAAAs be evaluated for surgery as soon as diagnosis is made. 
1	Carcinosarcoma and spindle cell carcinoma of the lung. Clinicopathologic and immunohistochemical studies. We examined pulmonary carcinomas with prominent sarcoma-like lesions both clinicopathologically and immunohistochemically. Grossly, two tumors had predominantly endobronchial growths, four bulky parenchymal growths, and two endobronchial, parenchymally mixed growths. In these eight patients, six tumors were completely resected, one patient was given irradiation only, and one patient died in the early postoperative period. On the basis of specific differentiation of the sarcoma-like lesions, the tumors were separated into three groups: two with "true" sarcoma differentiated into soft tissues such as striated muscle or osteoid tissue; three with a fibromatous sarcoma resembling atypical pseudosarcomatous stroma; and three with spindle cell carcinoma with evidence of epithelial differentiation. The prognosis was poor, and tumors with specific differentiation into rhabdomyosarcoma, chondrosarcoma, or spindle cell carcinoma progressed more rapidly than did those with a fibromatous sarcoma. Because the fibromatous sarcoma-like lesions were found to relate to a longer survival time for the patients, we wish to emphasize that a distinction of sarcomatous components should be made with regard to assessing the prognosis of pulmonary carcinoma with sarcoma-like lesions. 
4	Abnormal cardiovascular reactivity in borderline and mild essential hypertension. Cardiovascular and hemodynamic reactivity was evaluated with M-mode echocardiography, phonocardiography, and carotidography in correlation with circulating catecholamine levels in 25 normotensive subjects, 15 borderline hypertensive patients, and 42 mildly hypertensive patients during isometric exercise at 30% of the maximum force for 3 minutes. At rest, norepinephrine and epinephrine levels were significantly higher, and the cardiac index was similarly increased in both groups of hypertensive patients, but the cardiac mass index was significantly increased only in the mildly hypertensive group. During isometric exercise, the sympathoadrenal reactivity as well as the pressor and chronotropic responses were similar in normotensive subjects and both groups of hypertensive patients. However, the variations in blood pressure were achieved through totally different hemodynamic mechanisms in normotensive subjects and hypertensive patients. In normotensive subjects, the increase in blood pressure could be linked mainly to an increase in cardiac contractility and performance, whereas in either group of hypertensive patients, the increase in blood pressure was mainly associated with an increase in peripheral resistance. These observations are consistent with the hypothesis of a blunted beta-adrenergic reactivity and a predominance of alpha-adrenergic vascular reactivity in borderline and mildly hypertensive patients. This phenomenon, which appears to be unrelated to age or severity of hypertension, could be an important mechanism underlying the development of hypertension in humans. 
5	Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion. 
3	Cerebral glucose utilization during sleep in Landau-Kleffner syndrome: a PET study. Three right-handed male children (aged 5, 6, and 11 years) with signs, symptoms and/or history of the syndrome of acquired aphasia-epilepsy (Landau-Kleffner syndrome) were studied during drug-induced, electroencephalographically (EEG)-monitored sleep by positron-emission tomography (PET) and the [18F]fluorodeoxyglucose (FDG) method. Our data demonstrate that in Landau-Kleffner syndrome, cerebral glucose utilization is not normal during sleep. The metabolic pattern varied between the children but the metabolic disturbances always predominated over the temporal lobes. They were right-sided, left-sided, or bilateral. In the two first patients, EEG recordings showed continuous spike-and-wave discharges during sleep and a right-greater-than-left asymmetry was observed in temporal areas. In patient 1, the asymmetry was associated with a relative increase of glucose utilization of the right posterior temporal region. In patient 2, the glucose utilization was relatively decreased in the left anterotemporal and left perisylvian regions. In patient 3, the sleep EEG showed no discharge and no significant asymmetry was observed; however, glucose utilization of both temporal lobes was decreased. Lower metabolic rates in subcortical structures than in cortex were also noted in the three children. This metabolic pattern may be related to the maturation of the central nervous system (CNS). 
5	Repeated intestinal ulcerations in a patient with systemic lupus erythematosus and high serum antiphospholipid antibody levels. We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered. 
3	Rheumatoid arthritis and comorbidity. Data collected from 288 patients with rheumatoid arthritis (RA) indicated that 54% of respondents also reported other chronic conditions, and that 20% rated at least one of these other conditions as severe. Both the frequency and severity of these comorbidities affected scores on measures of depressive symptoms, social connectedness and on the Arthritis Impact Measurement Scales. These findings suggest that the absence of controls for comorbidity may bias measures of functional status among patients with RA. 
1	Frequency and clinical implications of monoclonal antibody detection of tumor-associated antigens in serum of patients with lung cancer. We previously showed that a panel of monoclonal antibodies (MAb) (5E8, 5C7, and 1F10) that detect serum tumor-associated antigens (TAA) could distinguish patients with lung cancer from those without to a highly significant degree. However, among patients with lung cancer, the frequency and clinical importance of serum TAA expression were not established. Therefore, we analyzed the serum and initial clinical characteristics of 52 Philadelphia VA patients with newly diagnosed lung cancer seen over a 13-month period. A modified semiquantitative ELISA was employed to determine MAb reactivity. Our cohort was characterized by a mean age of 65 +/- 9 year (SD) and mean Karnovsky score of 74 +/- 10; marked weight loss was present in 28 subjects, and 39 presented with either Stage III or IV disease. The panel detected TAAs in 38 of 52 cases (sensitivity 73%; 95% Cl, 60-83%), including 13 of 22 squamous cell, 9 of 12 adenocarcinoma, 10 of 11 undifferentiated, and 6 of 7 small cell carcinomas. No significant differences were found between the reactive and nonreactive patients in terms of age, stage at presentation, histologic subtype, performance status, or weight loss. However, 1F10 and 5C7 were each associated with a greater risk of early death by Cox proportional hazard analysis (p = 0.017 and 0.006, respectively) even when other prognostic variables are accounted for. We conclude that specific serum TAA can be detected in the majority of lung cancer patients with all major histologic subtypes in a cohort with advanced tumors and poor prognostic indices. 
4	Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography. To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients). Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%. Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease. The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%. An index incorporating both number and severity of defects derived from circumferential profile analysis was significantly lower in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/- 0.8 versus 2.7 +/- 2.4; p less than 0.005). Thus, noninvasive positron emission tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy, and a semiquantitative index such as circumferential profile analysis is superior to that of visual analysis alone. 
4	Penetrating trauma involving the innominate artery. Penetrating trauma involving the innominate artery is uncommon. Few surgeons have experience with this injury. A successfully managed case of penetrating innominate artery trauma is summarized and the literature reviewed. 
3	Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides. The concentration of keratan sulfate (KS) epitope was measured in the serum of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay and compared with that in the serum of patients with primary fibromyalgia syndrome (PFS) and of controls who had no joint disease. By Student's tau-test, the mean serum KS concentrations in OA and RA patients measured with monoclonal antibodies (MAb) 5-D-4 and 2-D-3 were significantly increased over those in the PFS and normal groups; similar findings were observed using a nonparametric test, except that levels in RA patients showed no difference from those in PFS patients and normal subjects. There was no significant correlation between joint scores or disease duration and KS levels in OA or RA patients. Gel filtration of sera revealed mainly large, polydisperse KS-bearing fragments which eluted in a broad profile. KS purified from sera by immunoaffinity chromatography consisted mainly of high-density proteoglycans. Electrophoresis of pooled high-density KS fractions in polyacrylamide-agarose gels followed by Western blotting with MAb 5-D-4 showed diffuse bands with relative mobilities corresponding to large proteoglycans. These findings are consistent with attachment of KS to protein core fragments of various sizes; KS in patient sera is comparable in size with that in normal sera. Elevations of serum KS levels occur in the presence of cartilage degradation, but do not quantitatively define the extent or duration of articular involvement. 
5	Cocaine babies: the scourge of the '90s. Six cases of cocaine-related deaths of infants have covered the spectrum of potentially devastating effects. They include an intrauterine death of a 35-week-old fetus following acute maternal cocaine abuse; anoxic encephalopathy at birth with 3 months' vegetative survival from a similar episode; traumatic compression asphyxia in a 4-month-old; infectious cardiomyopathy with heart failure in a twin at age 21 months following maternal cocaine abuse at birth; malnutrition and dehydration in a 7-week-old during continuing cocaine abuse by the parents; and a teenage sibling's cocaine lacing of a baby milk bottle ingested by his 6-week-old brother. All the cases had positive toxicological screening for cocaine or metabolites or both in the mother at delivery or in the infant at birth, or both. There were no instances of sudden infant death syndrome (SIDS, or "crib death"). Pathologic and toxicologic, as well as birth, developmental, and social data are presented. An integrated medical, public health, law enforcement, and educational policy to prevent or at least ameliorate these tragic cases, now approaching epidemic proportions, has yet to be developed. A careful obstetrical history and examination of the mother, indication on the birth certificate of maternal drug abuse, and notification of health authorities (by birth certificate checking, among other ways) may send an early warning message to providers for intercession. Active ingestion/injection and passive inhalation by older children and teenagers require more intensive monitoring and aggressive interaction by pediatricians, social workers, school authorities, and employers. 
1	Endoscopic ventricular fenestration using a "saline torch". The fiberoptic endoscope has never gained popularity among neurosurgeons although it is ideally suited for navigating within the cerebral ventricles. Recent advances in optics and miniaturization make the application of endoscopy in neurosurgery more practical. The authors report eight children who underwent ventriculoscopic fenestration of symptomatic loculated cerebrospinal fluid (CSF) collections. These CSF collections were either isolated ventricular cysts or trapped lateral ventricles secondary to obstruction at the foramen of Monro. Cyst wall dissection was carried out with a "saline torch" dissector which was introduced through a working channel in the ventriculoscope. The torch was used to coagulate vessels and to sculpt large windows in cyst walls or in the septum pellucidum. Ventriculoscope-guided cyst fenestration can be performed safely and easily under direct vision. The technique may permit simplification of shunt systems in some patients and elimination of shunts in others. 
4	An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987) BACKGROUND. Phenacetin abuse is known to produce kidney disease; salicylate use is supposed to prevent cardiovascular disease. We conducted a prospective, longitudinal epidemiologic study to examine the effects of these drugs on cause-specific mortality and on cardiovascular morbidity. METHODS. In 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin, as measured by urinary excretion of its metabolites, and a matched control group of 621 women. Salicylate excretion was also measured. All subjects were examined over a period of 20 years. RESULTS. Life-table analyses of mortality during the 20 years, with adjustment for the year of birth, cigarette smoking, and length of follow-up, revealed significant differences between the groups in overall mortality (study group vs. control group, 74 vs. 27 deaths; relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.3), deaths due to urologic or renal disease (relative risk, 16.1; 95 percent confidence interval, 3.9 to 66.1), deaths due to cancer (relative risk, 1.9; 95 percent confidence interval, 1.1 to 3.3), and deaths due to cardiovascular disease (relative risk, 2.9; 95 percent confidence interval, 1.5 to 5.5). The relative risk of cardiovascular disease (fatal or nonfatal myocardial infarction, heart failure, or stroke) was 1.8, and the 95 percent confidence interval 1.3 to 2.6. The odds ratio for the incidence of hypertension was 1.6, and the 95 percent confidence interval 1.2 to 2.1. The effects of phenacetin on morbidity and mortality, with adjustment for base-line salicylate excretion, were similar. In contrast, salicylate use had no effect on either mortality or morbidity. CONCLUSIONS. Regular use of analgesic drugs containing phenacetin is associated with an increased risk of hypertension and mortality and morbidity due to cardiovascular disease, as well as an increased risk of mortality due to cancer and urologic or renal disease. The use of salicylates carries no such risk. 
4	Retinal vasculitis--a primer. Retinal vasculitis is a diagnosis that is generally suggested by an ophthalmologist. Frequently patients with the disorder are referred to nonophthalmologists for further diagnostic evaluation or treatment. The criteria for defining vasculitis differ greatly between ophthalmologists and other physicians. To facilitate collaboration between ophthalmologists and their colleagues, we have sought to clarify the term "retinal vasculitis" by discussing its subcategories, the potential role of antiphospholipid antibodies, and the etiology of retinal vasculitis. We offer guidelines for evaluating the disorder and treating patients. 
4	Large diameter expanded polytetrafluoroethylene grafts for infrarenal aortic aneurysm surgery. The performance of an expanded polytetrafluoroethylene (ePTFE) graft used for aortic aneurysm replacement was evaluated. ePTFE grafts were implanted in 241 patients undergoing infrarenal abdominal aortic aneurysm (AAA) repair. Sixty patients were operated as emergencies for aneurysm rupture and 181 electively. One hundred and fourteen bifurcated and 127 tube grafts were inserted. The transperitoneal approach was used in 64 cases and the remainder were placed using a retroperitoneal approach. There was a one-month mortality of 2.8% in elective and 20% in emergency cases. Median follow-up was 26 months. Specific graft complications included one infected graft resulting in a graft-enteric fistula. No graft rupture, degeneration, dilatation, pseudoaneurysm or late graft limb thromboses were observed in up to 7 years of follow-up. The aortic ePTFE prosthesis demonstrated satisfactory performance over the period studied. 
3	Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature. We describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin. No evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease. We have chosen to call this entity "primary leptomeningeal lymphoma" (PLML). This unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis. 
3	The influence of age vs peak serum concentration on life-threatening events after chronic theophylline intoxication. To identify risk factors for the development of seizures and cardiac arrhythmias after chronic, unintentional theophylline intoxication we monitored the clinical course of 72 consecutive patients referred to a regional poison center with chronic theophylline intoxication (serum theophylline concentration, greater than or equal to 167 mumol/L after protracted use). The median age of the sample was 47.5 years (range, 4 days to 91 years). Median peak theophylline concentration was 239 mumol/L, with a range of 167 to 722 mumol/L. A life-threatening event (LTE) occurred in 28 patients (39%) that included seizures in eight and a major cardiac arrhythmia in 22. The median peak (theophylline) of patients who had an LTE vs those who did not was 235.8 vs 238.7 mumol/L. However, the median age of patients with an LTE compared with those without an LTE was significantly greater (70.5 vs 18.0 years). Stratification of data by chronologic age revealed a stepwise increase in the frequency of LTE with advancing years: patients more than 75 years old had a 16.7-fold greater risk of LTE than patients less than 25 years old (95% confidence interval, 3.56, 77.5) despite comparable intergroup median serum (theophylline). These data suggest the primary determinant of LTEs after chronic theophylline intoxication is chronologic age. Elderly patients have an inordinately greater risk of LTE than younger patients. Peak serum theophylline concentration cannot predict which patients with chronic theophylline intoxication will have an LTE. Finally, these data indicate that theophylline should be used cautiously and with frequent monitoring of serum theophylline concentrations in elderly patients. 
5	Comparison of a 3- and 6-mm incision in combined phacoemulsification and trabeculectomy. We studied 216 eyes of 160 patients who underwent combined phacoemulsification and posterior chamber intraocular lens implantation with trabeculectomy. The mean follow-up was 18.7 months, with a minimum follow-up of six months. To assess the safety and efficacy of a recently developed 3-mm incision procedure with foldable intraocular lens implantation (phacotrabeculectomy), we compared 104 eyes subjected to this procedure with 112 eyes subjected to a 6-mm procedure at different follow-up periods. Intraocular pressure control (less than 21 mm Hg) was attained in 44 of 46 eyes (96%) in the 3-mm group and 71 of 76 eyes (93%) in the 6-mm group at one year postoperatively. Visual acuity of 20/40 or better was attained in 40 of 46 eyes (87%) in the 3-mm group and 66 of 76 eyes (87%) in the 6-mm group. The incidence of postoperative complication was significantly lower (P less than .001) and visual acuity in the early postoperative period was significantly better (P less than .01) in the 3-mm incision group than in the comparison group. 
5	Neurogenic control of the cerebral circulation during global ischemia. The influence of the trigeminal nerve on the cerebral circulation was investigated in chronically denervated cats during and after reversible four-vessel occlusion for 10 minutes combined with controlled hypotension (50 mm Hg). Postocclusive hyperemia 30 minutes after reperfusion was attenuated by up to 48% in cortical gray matter of the anterior, middle, and posterior cerebral artery territories on the side of trigeminal ganglionectomy. Similar results were observed for denervation accomplished by direct surgical ablation and by the topical application of capsaicin to a cortical branch of the middle cerebral artery. Denervation did not alter basal cerebral blood flow or the duration of hyperemia, nor did it impair the cerebrovascular response to hypercapnia. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion and suggest that strategies directed at blocking axon reflex-like mechanisms may be beneficial in reducing the morbidity that follows severe cortical hyperemia. 
4	Lower extremity revascularization via the lateral plantar artery. Lower extremity bypass grafts to the tibial and crural arteries are commonly employed to treat patients with atherosclerotic limb-threatening ischemia. Although occasional series have mentioned bypasses to a plantar artery, few of these specifically examine the results of arterial reconstructions using these vessels. Six patients underwent femoral to lateral plantar artery (LPA) bypass within a 19-month period for gangrene of the forefoot. There was one early graft failure and in the five completely autogenous reconstructions, graft patency and limb salvage had been achieved during a follow-up ranging from three to 22 months. The LPA is an acceptable site for anastomosis of lower extremity bypass grafts and the early results presented herein support its more liberal use when proximal sites are unavailable. 
4	A histopathologic study of spinal cord ischemia using an isohistogenic rat upper-half-body transplantation model. To study the histopathologic changes of spinal cords exposed to long-duration complete ischemia, the authors developed an upper-half-body transplantation model of inbred rat. In this model, an infant Lewis rat is transplanted to the inguinal region of another adult Lewis rat using microsurgical vascular anastomosis. Even when 2-week-old donor rats were exposed to complete ischemia for 90 minutes, functions of the spinal cord were comparatively preserved. In histopathologic observations, degeneration proportional to complete ischemia duration was noted. In the 60-minute ischemia group of 2-week-old donor rats, however, no substantial differences from normal spinal cord were observed. Under conditions of equal ischemia duration, it appeared the younger animal had the greater ischemic tolerance. 
5	Effect of abrupt mitral regurgitation after balloon valvuloplasty on myocardial load and performance. The concept that mitral regurgitation masks myocardial dysfunction by reducing afterload and augmenting ejection performance has not been well established in humans. The effect of abruptly produced mitral regurgitation on left ventricular loading and performance was therefore evaluated in five patients who developed this complication after an otherwise successful percutaneous balloon mitral valvuloplasty. Mitral valve area by Gorlin formula calculated with forward flow increased from 0.92 +/- 0.14 to 2.75 +/- 0.82 cm2. Mean left atrial pressure did not decrease (19 +/- 4 to 19 +/- 6 mm Hg). The size of the left atrial V wave relative to mean left atrial pressure (peak V - mean left atrial pressure) increased from 7 +/- 4 to 19 +/- 6 mm Hg. Angiographic mitral regurgitation increased from 0+ or 1+ to greater than 3+ in each patient and regurgitant fraction increased from 0.23 +/- 0.11 to 0.55 +/- 0.09 (p less than 0.01). End-diastolic volume increased modestly from 148 +/- 15 to 159 +/- 15 ml (p = NS). Heart rate increased from 54 +/- 5 to 71 +/- 8 beats/min (p less than 0.05), which may have prevented further increases in preload by shortening the filling period. End-systolic stress decreased by 32% from 277 +/- 34 to 188 +/- 52 kdyn/cm2 (p less than 0.01) as a result of a 25% decrease in end-systolic pressure from 121 +/- 8 to 91 +/- 7 mm Hg and a 16% decrease in end-systolic volume from 67 +/- 13 to 56 +/- 8 ml (p = NS). 
2	Gallbladder carcinoma producing human chorionic gonadotropin. A primary carcinoma of the gallbladder producing human chorionic gonadotropin (HCG) was encountered in an 83-yr-old Japanese woman, with elevation of HCG/beta-HCG in urine and serum. Remarkable elevation of serum estradiol was an associated finding, with increased HCG. At autopsy, we found that the primary carcinoma of the gallbladder extensively involved the liver. Histologically, the tumor revealed adenosquamous cell carcinoma in the primary site, and moderately to poorly differentiated adenocarcinoma in metastatic foci. Immunohistochemical staining for beta-HCG showed a positive reaction in adenocarcinoma components. This is an extremely rare case of an HCG-producing gallbladder carcinoma, which leads us to speculate that HCG-positive tumor cells may occur due to dedifferentiation. 
4	A randomized trial comparing direct current therapy and bipolar diathermy in the outpatient treatment of third-degree hemorrhoids. Fifty patients with third-degree hemorrhoids were randomized to receive outpatient treatment with either bipolar diathermy or direct current therapy. Direct current therapy was used to treat 26 patients and bipolar diathermy was used to treat 24 patients. Twenty patients in each group were successfully treated as judged by resolution of symptoms and shrinkage of hemorrhoidal tissue. Both treatments are effective in the outpatient management of large, prolapsing hemorrhoids. Bipolar diathermy is less time consuming and better tolerated. 
5	Interventional radiology of the biliary tract. Metallic stents. Biliary metallic stents were placed in 18 patients with bile duct obstruction. Six patients received Gianturco stents and 14 Wall-stents. Results of these tests are discussed. 
3	Treating systemic fungal infections in AIDS patients. Prolonging life against the odds. Fungal infections have become one of the major causes of death among immunocompromised patients, particularly patients with AIDS. Accurate and quick diagnosis is difficult; therefore, empirical therapy is often necessary. This scenario is complicated by the fact that most antifungal agents are toxic at the doses used or relatively ineffective against deep-seated mycoses. Because the population of AIDS patients is increasing, physicians will be faced more often with the management of systemic fungal infections. Despite the current bleak prognosis for these patients, several new antigen detection tests are being developed and triazole agents are proving to be effective and less toxic than their predecessors. Many cases of systemic mycoses do result in mortality, but appropriate treatment can both prolong life and improve its quality. 
2	Adenocarcinoma of the colon occurring with intussusception in an adolescent. Hydrostatic reduction of intussusception is definitive therapy in most infants with this abnormality. In the older child, adolescent, and adult, a polyp or tumor is often present. Operative intervention should be considered earlier in the clinical course both to relieve the intussusception and to define the nature of the lead point. 
5	Rhegmatogenous retinal detachments in patients with AIDS and necrotizing retinal infections. Rhegmatogenous retinal detachments can occur in patients with acquired immune deficiency syndrome (AIDS) and necrotizing retinal infections. Of 68 patients with AIDS and necrotizing retinal infections seen between 1983 and 1987, rhegmatogenous retinal detachments developed in 16 patients (27 eyes). In this group, cytomegalovirus retinopathy was present in 75% (12 of 16) of patients, 18.8% (3 of 16) had probable herpes simplex virus retinopathy, and 6.2% (1 of 16) had toxoplasmic retinochoroiditis. Retinal detachment was bilateral in 68.8% (11 of 16) of patients. The retina was reattached successfully in 91% (10 of 11) of operated eyes. Proliferative vitreoretinopathy was present preoperatively in 95% of these eyes. Seven of 11 operated eyes had initial improvement in visual acuity. However, 5 of 11 continued to lose vision despite successful reattachment. Techniques included pneumatic reattachment, scleral buckle, vitrectomy, and silicone oil injection. Complicated retinal detachments in AIDS patients with rhegmatogenous retinal detachments and necrotizing retinal infections are common and can be repaired, but the prognosis is guarded in many patients. 
5	Determination of hepatitis B virus DNA in serum using the polymerase chain reaction: clinical significance and correlation with serological and biochemical markers. Sera from 98 patients with various stages of chronic hepatitis B virus infection were studied to determine the clinical significance of hepatitis B virus DNA in serum detected by the polymerase chain reaction. Patients were divided into three groups according to their HBsAg and HBeAg status. Group I (n = 31) had detectable HBsAg and HBeAg, group II (n = 46) had HBsAg but not HBeAg and group III (n = 21) consisted of patients who were once chronic hepatitis B virus carriers but had lost HBsAg during follow-up. Group I patients usually had significant liver disease (raised serum aminotransferases), had higher titers of HBsAg and had been infected with hepatitis B virus for a shorter period than patients in the other two groups. All patients in group I had hepatitis B virus DNA detectable by polymerase chain reaction and 94% had sufficient hepatitis B virus DNA present for detection by dot-blot hybridization. Group II patients had lower mean serum aminotransferase activities and titers of HBsAg than those in group I. Serum hepatitis B virus DNA was detectable by polymerase chain reaction in 78% but in only 30% of group II patients by dot-blot hybridization. Group II patients who did not have hepatitis B virus DNA detectable by polymerase chain reaction had mean serum aminotransferase levels within the normal range and had a younger mean age than those with hepatitis B virus DNA. Group III patients generally had no evidence of active liver disease. 
4	Reducing unnecessary coronary care unit admissions: a comparison of three decision aids OBJECTIVE: To determine whether published decision rules for ischemic heart disease have practical value in reducing unnecessary admissions to coronary care units. DESIGN: Prospective cohort study. SETTING: A community hospital emergency room. PATIENTS: 235 consecutive patients presenting to an emergency room with a chief complaint of chest pain. MEASUREMENTS: Clinical information, including observations needed to use previously published decision aids, was collected on special forms at the time of the emergency room visit. Follow-up information was obtained from the medical records of patients who were admitted and by telephone interviews with patients who were discharged. The authors compared the residents' actual decisions with the predictions of the decision aids regarding their ability to predict complications (that is, to identify patients who needed admission or intensive care). MAIN RESULTS AND CONCLUSIONS: None of the decision aids could reduce unnecessary admissions without seriously increasing the rate of inappropriate discharges. However, within the clinically relevant subgroup of patients for whom the decision to admit or discharge was not obvious on clinical grounds (those without complications on presentation whom the residents chose not to discharge), the decision aids examined, used in combination to verify the need for admission, might have safely averted some unnecessary admissions. 
2	Late arterial hemorrhage secondary to a Greenfield filter requiring operative intervention. Retroperitoneal hematomas associated with Greenfield filters have been described and are generally characterized as clinically insignificant. We report a retroperitoneal hematoma that was associated with a Greenfield filter and that required operative intervention because of hemodynamic instability. At operation a lumbar arterial laceration apparently caused by a protruding filter prong was identified and ligated. The implications of this occurrence for filter placement indications are discussed. The potential life-threatening severity of filter-associated hematomas is emphasized. 
4	Non-drug related asystole associated with anaesthetic induction. A patient is presented where routine venepuncture associated with anaesthetic induction resulted in bradycardia and asystole. The case highlights the need for special caution with, and ECG monitoring throughout induction for, patients with a history of syncope. It also demonstrates the need for caution when attributing cardiovascular events during induction to the effect of the induction agents used. 
1	Colonic lipoma as a source of massive hemorrhage. Report of a case. Colonic lipomas are a rare source of massive lower gastrointestinal bleeding requiring operative intervention. A case of massive hemorrhage from cecal lipomatosis is presented. The methods of preoperative diagnosis and treatment are discussed. 
1	Cardiopulmonary resuscitation and the patient with cancer. The records of 114 cancer patients suffering cardiopulmonary arrests (CPA) during a 3-year period at Memorial Sloan-Kettering Cancer Center (MSKCC) were retrospectively reviewed to identify variables predicting final outcome in these patients. Although 65.7% of the patients were successfully resuscitated, only 12 (10.5%) were discharged alive from the hospital. Median survival after discharge was 150 days. By univariate and multivariate analysis, the only variable predicting the likelihood of a patient's being discharged alive after a CPA was the performance status of the patient at the time of admission to the hospital. Thus, a patient spending more than 50% of the time in bed at the time of admission had only a 2.3% chance of being discharged alive after CPA. A thorough discussion of these findings between physicians and patients and their families is strongly recommended at the time of admission to spare cancer patients unnecessary invasive resuscitative procedures. 
4	Serological arguments for classifying Raynaud's phenomenon as idiopathic. Twenty-five patients with idiopathic Raynaud's phenomenon were followed prospectively for a mean period of 48 months. Clinical and laboratory assessments were performed on admission and on followup. The sera were analyzed for the presence of autoantibodies (antinuclear, antiskeleton and antiorganelle antibodies). Sixteen patients were antinuclear antibody positive and 2 anticentromere antibody positive. Eight patients produced antivimentin, 5 antimitochondrial, 4 anti-Golgi complex, and 3 anticentriol antibodies. Eleven patients produced antidesmosome antibodies. Only one patient (anti-RNP and antidesmosome antibody positive) developed a systemic disease (mixed connective tissue disease) during followup. The initial screening of sera may help to classify Raynaud's phenomenon as idiopathic more accurately. 
1	Jejunal-rectal fistula as a complication of postoperative radiotherapy. We present the case of a patient with an unusual, complex enteric fistula with multiple tracts and associated abscesses. The fistula was a late complication of radiotherapy, administered three years earlier, after resection for carcinoma of the sigmoid colon. Most of the small bowel was involved in the radiation-induced disease. A wide resection was performed successfully. This report reviews current literature on intra-abdominal postradiotherapy injuries, particularly intestinal fistulae. 
5	Recurrent prolonged erections and priapism as a sequela of priapism: pathophysiology and management. Veno-occlusive priapism may be associated with prolonged corporeal ischemia, subsequent fibrosis of the corpora and impotence. We report on 6 patients who presented with an unusual sequela of veno-occlusive priapism, recurrent episodes of prolonged erections or priapism. In all cases the subsequent episodes were idiopathic and veno-occlusive, occurred with a frequency ranging from several times per day to once per month and were symptomatically disabling. Pharmacocavernosometry ruled out mechanical occlusion of corporeal venous drainage by demonstrating elevated flows to maintain intracavernosal pressures following smooth muscle contraction and markedly decreased flow rates following smooth muscle relaxation. Treatment of the recurrent episodes with intracavernous self-injection of phenylephrine resulted in successful detumescence. The use of oral phenylpropanolamine reduced the frequency and duration of the recurrences, and markedly reduced the need for adrenergic self-injection. It is proposed that this syndrome may develop secondary to the initial ischemic episode, resulting in a functional alteration of the adrenergic and/or endothelial-mediated mechanisms that control penile tumescence and maintain penile flaccidity. 
5	Clinical and pathological findings in prostates following intravesical bacillus Calmette-Guerin instillations. The prostates of 36 patients who were treated with intravesical bacillus Calmette-Guerin were evaluated by digital rectal examination and transrectal ultrasonography. When abnormal palpatory and/or ultrasonographic findings were detected, core needle biopsies from the suspicious areas were performed. Of the 36 patients 20 underwent biopsies of the prostate. Pathological findings revealed typical granulomas in 8 patients (3 caseating and 5 noncaseating multifocal granulomas). Nonspecific chronic prostatitis was noted in 4 patients and benign prostatic hyperplasia was noted in 8. The number of bacillus Calmette-Guerin instillations ranged from 6 to 19. The interval from initiation of therapy to biopsy ranged from 1.5 to 14.5 months. Caseating granulomas were found during the early course of bacillus Calmette-Guerin instillations (1.5 to 3.0 months), whereas noncaseating granulomas were detected at later stages (4 to 14.5 months). These findings present a high incidence of granuloma formation in patients treated with intravesical bacillus Calmette-Guerin. The duration of therapy is a determinant factor in the induction of granuloma type. 
5	Reflux nephropathy and primary vesicoureteric reflux in adults We have studied the clinical features and course of adults with reflex nephropathy and/or primary vesicoureteric reflux, paying particular attention to the differences between males and females, and the presenting features that influence prognosis. In our series of 293 patients, females outnumbered males in the ratio 5:1 and most presented with urinary infection, whereas males most commonly presented with features of renal damage such as proteinuria, hypertension or renal failure. Males more commonly had bilateral scarring and persistent reflux. One hundred and forty-seven patients were followed for two years or more (range 2-19 years); deterioration in renal function occurred in 55 (37 per cent). Risk factors for a rise in plasma creatinine were, in descending order, the presence of proteinuria, an elevated plasma creatinine concentration, bilateral scarring, male sex and the presence of hypertension. Stepwise multiple regression analysis showed that the independent risk factors were proteinuria, elevated plasma creatinine concentration and hypertension; gender and the presence of persistent reflux had no independent influence on the course of renal failure. 
4	Novacor left ventricular assist filling and ejection in the presence of device complications. In order to better understand the relationship among certain device related complications and Novacor left ventricular assist system (LVAS) pumping parameters, a Mock Circulatory Loop was utilized to simulate the following clinically realistic conditions: 1) inflow valve regurgitation, 2) inflow cannula obstruction, 3) outflow valve regurgitation, and 4) outflow cannula obstruction. Various pumping parameters (e.g., pump rate, stroke volume, pump output) were recorded at baseline (control) and during each simulation. Additionally, pump volumes were continuously recorded and differentiated for calculation of rates of pump filling (FR) and ejection (ER). The results indicate that perfusion pressures and rates of filling and ejection change significantly in the presence of device complications. The implications of these findings, as relates to assessment of pump operation in LVAS patients, are discussed. 
3	Scalp pilomatrix carcinoma as an extra-axial mass. We report the CT, MRI, and angiographic findings in a case of pilomatrix carcinoma that had invaded the temporal bone and presented itself as an extra-axial mass. Even though bone destruction was better shown with CT, the tumor mass with its meningeal and tentorial extension was seen more clearly with MRI. The arteriogram demonstrated a unique vascular supply from the external carotid artery. 
5	Gallbladder wall thickening (congestive cholecystopathy) in chronic liver disease: a sign of portal hypertension. A thickened gallbladder wall is often seen with ultrasound in alcoholic cirrhosis. Hypoalbuminaemia is thought to be the cause since there is a strong association between bowel wall thickening and low serum albumin. To determine the role of portal hypertension in producing gallbladder wall thickening we studied 40 consecutive stable patients-37 with cirrhosis and three with portal hypertension due to primary biliary cirrhosis. Ultrasound assessment of the gallbladder wall was made after an overnight fast using a Technicare autosector. Wall thickness 4 mm or greater was considered abnormal. Twenty-seven patients had a thickened gallbladder wall and all had evidence of portal hypertension. Hypoalbuminaemia was not an important factor since it was only present in six cases with thickened walls. In two cases reduction in portal pressure with oral propranolol was associated with a decrease in gallbladder wall thickness. These results suggest that portal hypertension, not hypoalbuminaemia, is the dominant factor causing gallbladder wall thickening in cirrhosis. Ultrasound demonstration of gallbladder wall thickening in chronic liver disease should suggest the presence of portal hypertension. 
5	Posttraumatic cortical blindness: are we missing the diagnosis in children? A potential etiology of anxiety and agitation in the posthead trauma patient is cortical blindness. Cortical blindness can be seen after both mild and severe head trauma. Early recognition and understanding of this syndrome can lead to a decreased anxiety level, not only for the patient, but for the parents as well. Two cases of posttraumatic cortical blindness are presented. The signs and symptoms of cortical blindness, its presentation, diagnosis, and outcome are discussed. The available literature is reviewed and discussed. 
1	Renal function after tumor enucleation in a solitary kidney. Whether extensive ablation of renal mass in humans leads to progressive glomerulosclerosis, proteinuria, and hypertension, as it does in animal models, is a matter of controversy. We have studied kidney function in six patients who underwent enucleation of a renal cell carcinoma in a solitary kidney. Four patients had previously had a nephrectomy. The two others each had one atrophic, nonfunctioning kidney. Serum creatinine levels before surgery were within the normal range (mean, 99.9 mumol/L [1.13 mg/dL]). Two weeks after tumor enucleation, creatinine levels were significantly higher than the preoperative values (mean, 124.6 mumol/L [1.41 mg/dL]). The follow-up period varied from 10 to 23 months. In all patients, kidney function improved during the following months. Serum creatinine levels nearly reached preoperative values in all patients (mean, 105.2 mumol/L [1.19 mg/dL]). None of the patients showed a progressive deterioration in renal function or proteinuria. We found a modest increase in blood pressure in two patients who had been normotensive before surgery. In conclusion, tumor enucleation in a solitary kidney did not cause significant renal injury to the remnant kidneys in our patients, at least in the short term. 
5	Undetected fatal acute pancreatitis: why is the disease so frequently overlooked? An analysis of postmortem investigations between 1980 and 1985 revealed 43 patients with acute pancreatitis. In 13 (30.2%) of them, the diagnosis was first established at autopsy. In eight of the latter patients, the diagnosis could have been present on admission. The etiology was alcoholism in three patients, hypothermia in one, biliary tract disease in one, and unknown in three patients. In five patients, acute pancreatitis developed after gastric, pancreatic, or biliary tract surgery. Abdominal pain was present in only one patient. Amylase levels had been estimated in 11 patients, but the level was in the diagnostic range (greater than or equal to 3 times of upper normal level) in only four. Consequently, ultrasound examination was performed in only two of the latter four patients, but failed to show the pancreas because of intestinal gas. To diagnose acute pancreatitis at an earlier stage and to improve therapy and prognosis, we recommend that serum amylase levels be measured and ultrasound examination be performed. If the results are inconclusive, this should be followed by computed tomography for all abdominal emergency cases and for patients who have undergone cardiopulmonary or upper abdominal surgery, especially when the patients deteriorate or fail to improve postoperatively. 
5	Is gastric acid responsible for the pain in patients with essential dyspepsia? The pathogenesis of symptoms in patients with essential dyspepsia is not known. Since treatment with H2-receptor antagonists has provided symptomatic relief in some reports, we carried out the present study to investigate whether gastric acid is responsible for symptoms in these patients. Fifty patients with essential dyspepsia and 25 healthy control subjects were studied. After an overnight fast, a nasogastric tube was passed and its tip positioned in the antrum under fluoroscopic control. Normal saline or 0.1 M hydrochloric acid was infused in a randomized, double-blind fashion. Eleven (22%) patients developed pain with acid infusion, but none with normal saline (p less than 0.005). In 10 of these 11 patients, pain recurred on rechallenge with acid infusion but was promptly relieved with infusion of 1 M sodium bicarbonate. None of the healthy controls developed pain on infusion of acid or saline. These observations suggest that acid has a definite role in the pathogenesis of symptoms in some patients with essential dyspepsia, although other factors may also be important. 
3	Epidermoid cysts of the brain stem. Report of three cases. The authors report the cases of three patients with epidermoid cysts which insinuated themselves into the brain stem. In all three patients, the tumor occupied the pons, although in one it was predominantly located in the medulla. The cyst contents and nonadherent tumor capsule were removed in all three patients, but no attempt was made to remove tumor densely adherent to the brain stem. One patient's cyst was removed in one operation, but maximal resection in the other two required two operations. After surgery, sixth nerve function completely returned in one patient; another patient had a stable pontine gaze palsy but developed new facial weakness; and the third patient had stable cranial nerve deficits with a diminished hemiparesis. The last patient developed a pseudomeningocele and communicating hydrocephalus, and required a lumboperitoneal shunt. In all three patients, computerized tomography scans demonstrated hypodense tumors not enhanced by contrast material. Magnetic resonance imaging was performed on two patients; in both, the tumors showed increased signal intensity relative to brain on T1-weighted images and decreased signal intensity relative to brain on T2-weighted studies. Magnetic resonance imaging, the most accurate modality for localizing these lesions and determining their extent, was also invaluable for postoperative monitoring and follow-up evaluation. Safe and adequate resection includes decompression of cyst contents and removal of nonadherent portions of the cyst capsule. Cyst wall adherent to the brain stem, however, should not be removed. 
3	Developments in 5-hydroxytryptamine receptor pharmacology in migraine. Because a satisfactory animal model for migraine does not exist, attempts to determine a common mechanism of action for effective antimigraine agents may be of benefit in elucidating the pathogenesis of this neurologic syndrome. The present review demonstrates that the clinical data that has developed over the past 30 years may allow for the elucidation of the role of specific 5-HT receptor subtypes in the pathophysiology of migraine. A large number of both acute and prophylactic antimigraine agents share an ability to interact with 5-HT receptor subtypes in human brain. As summarized in Table 3, acute antimigraine drugs (e.g., ergots, sumatriptan) share high affinity for 5-HTID receptors and somewhat lower affinity for 5-HT1A receptors. These receptors are present in certain intracranial blood vessels. 5-HT1D receptors are also located on nerve terminals where they act to inhibit the release of 5-HT and other neurotransmitters. Theoretically, 5-HTID receptor agonists may acutely inhibit the release of vasoactive or pain-inducing substances in the perivascular space. Conceivably, drugs acting at this receptor would stop the progression of this perivascular process. In addition, a number of prophylactic antimigraine drugs display a relatively high affinity for both 5-HT2 and 5-HT1C receptors in human brain. Although these receptors are also found in certain blood vessels, they are present throughout the nervous system. The receptors appear to mediate neuronal depolarizations at the cellular level. Moreover, the 5-HT2 receptor appears to play a key role in the development of inflammation in certain smooth muscle systems. Theoretically, the ability of 5-HT2 antagonists to protect perivascular inflammation may account for their efficacy in the prophylactic treatment of migraine. These data offer a novel approach to the analysis of antimigraine agents. Drugs could be selected for use in clinical migraine studies based on their selectivity for a specific 5-HT receptor subtype. For example, an agent that displays both high affinity and selectivity for 5-HT1D receptors could be clinically evaluated. Its effectiveness, or lack thereof, would indicate the importance of this specific 5-HT receptor site in the pathogenesis of migraine. Future attempts to determine a common mechanism of action for effective antimigraine agents should facilitate the elucidation of the pathogenesis of this neurologic syndrome. 
2	Germfree animals and technics in surgical research. Germfree animals have been reared to a size, weight, and age permitting the performance of major surgical procedures and the pursuit of a variety of surgical research problems. Germfree dogs have been maintained in the isolator system through three generations, indicating that life, reproduction, and growth are all possible in the absence of microbial contamination. The value of the germfree approach to surgical problems has been utilized in studies of a variety of gastrointestinal problems, shock, cancer, immunology, burns, wound healing, and in direct patient application. Patients have been maintained in isolator environments for prevention of infection, for operative procedures, for treatment of extensive burns, and for management of immune-suppressed individuals. We conclude that germfree animals and germfree technics provide a valuable addition to the armamentarium of the surgeon in both research and clinical applications. 
4	Frequency of low-grade residual coronary stenosis after thrombolysis during acute myocardial infarction. The clinical, angiographic and demographic characteristics of 42 patients with low-grade (less than 50%) residual stenosis at the infarct lesion after thrombolysis for acute myocardial infarction (MI) were assessed. The study group (group I) represented 21% of 198 consecutive patients receiving thrombolytic therapy over a 59-month period. Data on the 156 remaining patients were pooled for comparison (group II). Group I patients were predominantly men (86%) who were cigarette smokers (81%). Group II patients were predominantly men (75%, p greater than 0.10) but were significantly older (52 +/- 12 vs 56 +/- 10 years, p = 0.02). Prior acute MI or angina was unusual in group I. Sixty percent had no significant (greater than 50%) residual coronary artery disease while 25% had residual single artery disease. Average significant (greater than 50% diameter stenosis) residual vessel disease was 0.6 +/- 1.0 for group I and 1.9 +/- 0.9 for group II (p less than 0.001). In group I, average residual infarct lesion diameter stenosis was 36 +/- 7% in the right anterior oblique and 34 +/- 8% in the left anterior oblique views. Thirty-nine group I patients were discharged with medical therapy and 100% follow-up was obtained over a mean interval of 18 +/- 17 months. Fifteen patients experienced chest pain after acute MI accounting for 17 discrete events. Fifty-nine percent of group I had a benign course on follow-up. Eight events were classified as unstable angina, 4 as acute MI and 5 as atypical angina. Documented coronary vasospasm occurred in 3. 
1	Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole. In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates. 
4	Dietary taurine deficiency and dilated cardiomyopathy in the fox. Taurine deficiency has been implicated as a potential cause of dilated cardiomyopathy. However, the relationship between taurine and myocardial function is presently unclear. The purpose of this study was to determine whether dilated cardiomyopathy in the fox is associated with dietary taurine deficiency. A total of 68 foxes from farms with a history of death caused by dilated cardiomyopathy and 14 foxes from a farm with no history of dilated cardiomyopathy were studied. Dilated cardiomyopathy was diagnosed by echocardiography in 48% of the foxes from one farm with a positive history and in none of the foxes from the control farm. Foxes less than 9 months of age were more commonly affected than older foxes (p = 0.03). Plasma taurine concentrations were significantly less (p less than 0.01) in foxes that had dilated cardiomyopathy (26.8 +/- 16.4 nmol/ml) than in the control foxes (99.3 +/- 60.2 nmol/ml). A significantly higher (p less than 0.01) incidence of dilated cardiomyopathy was present in foxes with a history of a sibling or offspring that died of dilated cardiomyopathy than in foxes without a family history of cardiac death. In one fox with dilated cardiomyopathy that was tested, the myocardial taurine concentration was lower (1.7 mumol/gm wet weight) than that of control foxes (7.3 +/- 1.6 mumol/gm wet weight). Hepatic cysteinesulfinic acid decarboxylase activity was significantly less (p less than 0.001) in foxes with dilated cardiomyopathy (0.97 +/- 0.2 nmol/mm.mg protein) than in control foxes (2.11 +/- 0.07 nmol CO2/mm.mg protein). 
3	Some endorphin derivatives and hydrocortisone prevent EEG limbic seizures induced by corticotropin-releasing factor in rabbits. Corticotropin-releasing factor (CRF) injected into the cerebral ventricles of small mammals induces EEG limbic seizures, behavioral excitability, stereotyped behavior, and tardive enhancement of hippocampal theta voltage and frequency. Because we addressed this phenomenon when we explained the pathogenesis of infantile spasms in children, we wished to study the interference exerted by some gamma-endorphin fragments on EEG epileptiform and behavioral symptoms induced by CRF in the rabbit. Animals were implanted intracerebroventricularly (i.c.v.) with semichronic cortical and hippocampal electrodes, together with a cannula into the left lateral ventricle. When some gamma-endorphin derivatives (DT gamma E, DE gamma E) were injected intravenously (i.v.) for 4 days (or hydrocortisone once), they prevented the EEG ictal seizures induced in the hippocampus of rabbits by CRF injected i.c.v. Hydrocortisone and DE gamma E also prevented the appearance of scattered spiking and partially prevented tardive enhancement of theta voltage in the hippocampal EEG. Finally, DE gamma E also prevented stereotyped behavior and excitability induced by CRF. These results confirm the regulatory role exerted by CRF in limbic structure excitability and suggest that the above peptides may be involved in a regulatory feedback mechanism of CRF metabolism or activity. The possibility that these peptides may also have interesting antiepileptogenic properties should be considered. 
1	Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease. 
5	Job's syndrome: a rare cause of recurrent lung abscess in childhood. A clinical syndrome characterized by recurrent staphylococcal infection of the skin and respiratory tract from birth was described in 1966 and referred to as Job's syndrome. Marked hyperimmunoglobulinemia E was later found to be associated with this syndrome. This article describes a case of Job's syndrome as a cause of recurrent lung abscess during childhood necessitating lung resection. 
2	Clinical features of misdiagnosed appendicitis in children. STUDY OBJECTIVE: To compare clinical features of children with misdiagnosed appendicitis with those of children with appendicitis initially diagnosed correctly. DESIGN: Retrospective review of hospital, emergency department, and clinic records. SETTING: University medical center with annual ED census of 40,000 patients. PARTICIPANTS: Children less than 13 years old admitted between May 1, 1979, and April 30, 1989, with a discharge diagnosis of appendicitis. MEASUREMENTS: Records were reviewed for historical, physical examination, laboratory, and pathologic features for all patients on their initial presentation to a physician and on final presentation during which the correct diagnosis was made. Using chi 2 analysis and Student's test, clinical features of misdiagnosed patients and patients diagnosed correctly were compared. RESULTS: One hundred eighty-one cases were identified with 50 initially misdiagnosed. On initial presentation, misdiagnosed patients were younger and more likely to have vomiting before pain onset, constipation, diarrhea, dysuria, and signs and symptoms of upper respiratory infections. Misdiagnosed cases were less likely to have right lower quadrant tenderness and documentation of bowel sounds, peritoneal signs, and rectal examinations. On final presentation, misdiagnosed patients were more likely to have pain duration of more than two days, temperature of more than 38.3 C, and to appear lethargic and irritable (P less than .05 for all measurements). CONCLUSION: Clinical features of children with misdiagnosed appendicitis differ from those of children with appendicitis initially diagnosed correctly. 
5	Diaphragmatic force and substrate response to resistive loaded breathing in the piglet. Inspiratory resistive loaded (IRL) breathing results in hypoventilation and diaphragmatic fatigue in the piglet. We studied the effects of 6 h of IRL on ten 1-mo-old piglets. The load was adjusted to increase spontaneously generated transdiaphragmatic pressure five to six times baseline. Six 1-mo-old piglets acted as controls and were identically instrumented but were not subjected to IRL. Measurements of ventilation, blood gases and pH, diaphragmatic electromyogram, force-frequency curve, blood flow, and end-expiratory lung volume were obtained hourly. Diaphragmatic muscle samples were obtained after 6 h for determination of ATP, phosphocreatine, lactate, and glycogen levels. No changes occurred in the control animals. IRL resulted in a significant decrease in ventilation, an increase in diaphragmatic EMG, onset of abdominal expiratory muscle activity, and a fall in end-expiratory lung volume by 1 h. The force-frequency curve adjusted for lung volume change fell by 20% at all frequencies of stimulation at 1 h and by 40% at 6 h. Blood flow to the costal and crural diaphragm increased by 51 and 141%, respectively. No differences were noted in ATP, phosphocreatine, lactate, or glycogen between control and IRL animals. It is concluded that submaximal spontaneous contractions of the piglet diaphragm over a 6-h period cause a substantial decrease in its maximal force-generating capacity that is not related to substrate depletion. 
5	Application of microwave tissue coagulation in partial nephrectomy. Microwave tissue coagulation was used during partial nephrectomy in 10 mongrel dogs, without clamping the renal artery. There were no major complications, such as retroperitoneal hematoma, abscess formation, or macroscopic infarction of the kidney tissue related to this new procedure. The advantages of microwave coagulation are reduced blood loss, shorter operative time, and minimal risk of vascular injury. 
2	Small cell carcinoma of the pancreas and biliary tract. Four cases of anaplastic carcinoma of the pancreas or biliary tract were studied clinicopathologically and immunohistochemically. All four cases were intermediate cell type and contained a minimum amount of microscopic foci of differentiated glandular adenocarcinoma. Argyrophilic tumor cells were not seen in any of the four tumors. Immunohistochemically, no tumor was positive for hormonal products, but all tumors were positive for epithelial markers. These findings suggest that the anaplastic carcinoma are not derived from argyrophilic cells, but rather from adenocarcinomas which have the potential for anaplastic metaplasia. The long-term survival of one patient emphasized the importance of chemotherapy in the treatment of small cell carcinoma of the pancreas and biliary tract. 
1	Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients. Multiple gastric and duodenal biopsy specimens from 102 asymptomatic patients with familial adenomatous polyposis, taken during a prospective endoscopic screening programme were examined. One hundred patients had microscopic gastroduodenal pathology, often in the absence of macroscopic lesions. Adenomas were found in 94 patients in the duodenum, in the second and third parts. Hyperplasia of villous and crypt epithelium was also seen, sometimes in the absence of adenomas: this may be a precursor of neoplastic change. In the stomach fundic gland polyps were the commonest abnormality, seen microscopically in 44 patients. Chronic antral gastritis was common in patients without fundic polyps. Gastric adenomas were present in six patients, all of whom also had duodenal adenomas. If duodenal adenomas in familial adenomatous polyposis have a similar malignant potential to those in the colorectum sequential endoscopy and biopsy are necessary to detect cancer in these patients. 
4	Fibrinopeptide A is released into the coronary circulation after coronary spasm. To examine whether acute myocardial ischemia activates the coagulation system and platelet activation in the coronary circulation, we measured plasma levels of fibrinopeptide A and beta-thromboglobulin in the coronary sinus and the aortic root simultaneously in 15 patients with coronary spastic angina before and after the left coronary spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Fifteen patients with chest pain but normal coronary arteries and no coronary spasm served as controls. The coronary sinus-arterial difference of fibrinopeptide A increased markedly (p less than 0.001) from 0.1 +/- 0.2 to 4.3 +/- 0.7 ng/ml after the anginal attacks in the coronary spastic angina group. However, fibrinopeptide A levels remained unchanged after the attacks in the stable exertional angina group and after intracoronary injection of acetylcholine in the control group. Plasma beta-thromboglobulin levels remained unchanged after the attacks in both patient groups and after acetylcholine in the control group. Our data indicate that coronary spasm induces thrombin generation and may lead to thrombus formation in the coronary artery involved, but pacing-induced ischemia does not activate the coagulation system. 
4	Arterial blood oxygen desaturation in infants and children during upper gastrointestinal endoscopy. Arterial blood oxygen desaturation and abnormal electrocardiographic changes have been reported in adults undergoing upper gastrointestinal endoscopy. We studied 32 infants and children less than 12 years of age using pulse oximetry and continuous electrocardiography before, during, and after upper gastrointestinal endoscopy performed under intravenous sedation. Sinus tachycardia was the most common electrocardiographic change, and no clinically significant electrocardiographic abnormalities were induced by the procedure. Desaturation to less than or equal to 90% was found in 37.5% of the patients and was most commonly noted during the endoscopy procedure and in patients with cardiopulmonary disease. The desaturation was unpredictable because there was no correlation between desaturation and medication, tolerance to the procedure, weight, or age of the child. Some patients who subjectively appeared to tolerate the procedure well had significant desaturation. The use of pulse oximetry should be considered for all children undergoing upper gastrointestinal endoscopy. 
4	The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects. We compared the changes in serum creatinine levels over time after a mean follow-up of 9.8 years in essential hypertensive (EH, n = 56) and control (n = 59) male veteran subjects. All subjects had normal serum creatinine levels (62 to 124 mumol/L) and "normal" urinalysis results on entry into the study. Subjects with comorbid renal diagnoses and diabetes mellitus were eliminated from the analysis. Although not statistically significant, the rate of change in the serum creatinine concentration over time was greater in the EH cohort compared with the control cohort (1.08 +/- 4.8 vs 0.027 +/- 3.5 mumol/L per year). The difference was especially marked in black EH subjects vs black control subjects (1.60 +/- 6.2 mumol/L per year vs -0.21 +/- 3.3 mumol/L per year). When age, race, body mass index, and a diagnosis of EH were entered into a logistic regression analysis, EH subjects had a statistically significantly greater rate of decline in renal function than did control subjects (1.5 +/- 8.3 mumol/L per year). When mean time-averaged systolic blood pressure for each subject was also included in the logistic regression analysis, only systolic time-averaged blood pressure was statistically significant (0.063 +/- 0.029 mumol/L per year). We conclude that in the absence of clinically detected parenchymal renal disease, EH subjects have a greater rate of decline in renal function than do nonhypertensive subjects. Time-averaged blood pressure is predictive of the change in serum creatinine concentration not only in EH subjects but also in nonhypertensive subjects. Thus, preservation of renal function may require a blood pressure lower than the currently accepted normotensive range. 
5	Awareness during caesarean section. Between 1982 and 1989 over 3000 patients were questioned about recall and dreaming after general anaesthesia for Caesarean section. Some 28 (0.9%) patients were able to recall something of their operation and 189 (6.1%) reported dreams. There was uniform adherence to a rigid anaesthetic protocol up to and including 1985, but a much publicized incident reported from the courtroom stimulated a relaxation of this regimen. Consequently the incidence of awareness decreased from 1.3% to 0.4%, and the incidence of dreaming was also reduced. Recollections of surgery were confined to manipulations, noises and voices. None of our patients complained of pain at the time of interview, although one since has. The inadequacies of the initial protocol and an approach to informed consent are discussed. 
5	Quantification of vascular stenosis with color Doppler flow imaging: in vitro investigations. The accuracy of quantifying the degree of vascular stenosis with color Doppler flow imaging (7.5-MHz, linear array system) was determined in an experimental study carried out on six concentric and five eccentric model stenoses (cross-sectional area reduction, 13.4%-93.8%). The measurements were made with use of pulsatile flow at four different flow rates (70.8-339.0 mL/min). The degree of stenosis was calculated from the ratio of prestenotic to intrastenotic flow velocity. The most exact measurement of the degree of stenosis could be achieved with Doppler spectral analysis by determining the maximum peak systolic velocity (r = .994, y = 0.98x - 3.2). With the velocity values derived only from the color-coded image, it was also possible to find the most exact degree of stenosis (r = .995, y = 0.99x - 2.9). For quantification of stenosis, pre- and intrastenotic Doppler spectral analysis is no longer necessary if the stenosis can be imaged sufficiently with color Doppler. 
5	Clinical and electrographic effects of acute anticonvulsant withdrawal in epileptic patients. We retrospectively investigated the effects of acute antiepileptic drug (AED) withdrawal on seizure symptomatology--including frequency, clinical features, and electrical onset--by studying 35 patients during evaluation for epilepsy surgery. The highest risk for both partial and secondary generalized seizures occurred during absent or subtherapeutic, and not during rapidly falling, AED levels. AED withdrawal had minimal effect on clinical symptomatology or electrographic onset. 
3	Cognitive function and time-of-day variation in serum carbamazepine concentration in epileptic patients treated with monotherapy. Different parameters of antiepileptic drug (AED) treatment have been shown to affect cognitive function. The drug, dose, and duration of treatment have been studied. The present study assessed cognitive function in relation to time-of-day variation in serum carbamazepine (CBZ) concentration in epileptic patients treated with monotherapy. We studied 10 males and 12 females with a mean age of 36 years and a mean duration of CBZ-therapy of 4.4 years. Patients had been seizure-free for at least 1 month and took two daily CBZ doses. The test battery included tests of motor speed, reaction time, attention, and memory. In the experimental design, the subjects were tested twice at times close to expected daily maximum and minimum serum CBZ concentration. They were studied in two balanced blocks (block 1 tested at 8 a.m. and noon, block 2 tested at noon and 8 p.m.). Blood samples were collected every 2 hr from 8 a.m. to 8 p.m. The subjects showed significant differences in serum CBZ concentration between testing times, with suggested maximum concentration between 10 a.m. and noon. The test battery showed no consistent differences between performance at times of high versus low serum concentration. A supplementary analysis of correlations between mean performance level on cognitive tests and variables related to CBZ treatment did not show consistent trends. 
4	Marfanoid children. Etiologic heterogeneity and cardiac findings. The clinical, cardiac, and echocardiographic test results of 20 children with marfanoid features are reviewed. Fifteen were diagnosed as having Marfan syndrome, two had "possible" Marfan syndrome, and three had other diagnoses. On first evaluation, eight patients with Marfan syndrome (53%) had mitral regurgitation and none had aortic regurgitation. Echocardiography showed aortic root enlargement in 12 (80%) of 15 patients and mitral valve prolapse in 12 (80%) of 15. None had a normal echocardiogram. At follow-up examination, one patient had developed aortic root enlargement, and one patient, mitral valve prolapse. Thus, although aortic root enlargement is usually present in early childhood in patients with Marfan syndrome, it is not considered specific because in this study it also occurred in one child with Alport's syndrome and in one with marfanoid features. Four patients with aortic root enlargement were treated with propranolol and their echocardiograms showed no further increase in the aortic root diameter for several years. We recommend echocardiography in the diagnosis and routine management of children in whom Marfan syndrome is suspected. 
1	Carcinoma of the head of the pancreas. Optimal treatment for unresectable carcinoma of the pancreas remains controversial. This study was done to examine the relationship between perioperative jaundice and postoperative morbidity, and type of palliative biliary bypass and postoperative morbidity and jaundice clearance. Seventy-six patients with obstructive jaundice secondary to carcinoma of the head of the pancreas were studied. Forty-nine patients underwent one of four different types of palliative bypass: 1, cholecystojejunostomy (n = 22); 2, choledochojejunostomy (n = 11); 3, choledochoduodenostomy (n = 9), and 4, cholecystoduodenostomy (n = 7). Age, sex and preoperative health status were similar for all operative groups, as well as for those with and without postoperative morbidity. The postoperative complication rate was 33 per cent and there was one postoperative death. Length of preoperative jaundice and peak preoperative bilirubin levels were independent of morbidity. Postoperative morbidity was similar for each type of bypass used and no significant difference was found when cholecystoenteric (1 and 4) and choledochoenteric (2 and 3) bypass were compared. The results of this study support the view that postoperative morbidity is not directly related to the presence of jaundice preoperatively. Furthermore, the rate of jaundice clearance and the occurrence of postoperative complications are not dependent on the type of bypass used. 
2	Palliative treatment of bile duct tumoral compression by an endoprosthesis: clinical results. The palliative therapy of stenoses of the biliary tract is a difficult choice. Because percutaneous or endoscopic drainage methods are fraught with complications, an endoprosthesis for surgical intubation of the biliary tract has been developed. Thirty patients were treated by this method. After choledochotomy, the endoprosthesis is positioned surgically above the sphincter of Oddi, thereby avoiding ascending cholangitis. Twenty-nine patients (13 with gallbladder cancer, 11 with cholangiocarcinomas, 5 with metastases) presented with neoplastic compression, and one patient had an early postoperative stricture with loss of substance after right hepatectomy for hepatic metastases. The operative mortality was 3.3% (one pulmonary complication). Resolution of jaundice was obtained in all but two patients, and pruritus always resolved. The mean survival time for the patients with cholangiocarcinoma was 12.2 months and 6.33 months for those with gallbladder cancer. Indices of satisfaction (Bismuth's method) were 71% (gallbladder cancer), 93.5% (hilar cholangiocarcinoma), and 92% (metastatic compressions). This new type of surgical endoprosthesis is an alternative in the palliative treatment of neoplastic hilar compression because it is well tolerated, has a low rate of operative mortality or morbidity, and affords an acceptable quality of life for the patients. 
5	Perforated duodenal ulcer: an unusual complication of gastroenteritis. A 7 year old boy was admitted to hospital with gastroenteritis, which was complicated by an acute perforated duodenal ulcer. After oversewing of the perforation he made an uncomplicated recovery. Peptic ulceration is under-diagnosed in childhood and this leads to delay in diagnosis and appropriate management. Ulceration is associated with severe illness and viral infections, but perforation is rare. 
4	Vertebrobasilar occlusion following minor trauma in an 8-year-old boy. An 8-year-old boy developed seizures and coma 2 days after a trivial bicycle accident. Computed tomography failed to show pathology. Magnetic resonance imaging of the head showed infarction of the pons and right cerebellum. Angiography showed occlusion of the right vertebral and basilar arteries. Minor traumatic injuries to the cervical spine may result in vertebrobasilar occlusion. The neurologic manifestations of this disorder and emergency department diagnosis and management are discussed. 
3	Slow release carbamazepine in treatment of poorly controlled seizures. Thirty three children with poorly controlled epilepsy, and six new patients, were treated with slow release carbamazepine. Twelve of the former had a reduction in the number of seizures of more than half, and 10 had fewer side effects. Three of the new patients stopped having seizures. Variations in plasma concentrations between doses was significantly less when patients took the slow release preparation (22%) compared with the standard preparation (41%). Slow release carbamazepine may improve the conditions of children whose seizures are poorly controlled. 
4	Circadian rhythms in blood pressure in school-age children of normotensive and hypertensive parents. The purpose of this study was to describe the characteristics of blood pressure rhythms in school-age children and to compare the circadian mesors and amplitudes between children of normotensive parents and children of hypertensive parents. The sample consisted of 40 healthy children between 8 and 10 years old; 20 children had a parental history of hypertension and 20 did not. Blood pressure was measured every 2 hours during the day and every 90 minutes during the night for one 24-hour cycle using a Dinamap monitor equipped with an automatic printer. Cosinor analyses revealed statistically significant circadian rhythms for systolic and diastolic blood pressures in 12 of the 40 subjects. The acrophases for systolic and diastolic pressures occurred between 1200-1800 hours. The mean systolic mesor was 108.50 while the mean diastolic mesor was 61.41. The mean amplitudes were 8.85 for systolic pressure and 7.44 for diastolic pressure. No statistically significant differences in circadian mesors and amplitudes between children of normotensive parents and children of hypertensive parents were found. 
2	Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy. PURPOSE: To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease. PATIENTS AND METHODS: Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis. RESULTS: H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%. CONCLUSIONS: H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism. 
1	Race, nutritional status, and survival from breast cancer. The effects of nutritional status on differences in the survival of black and white women with breast cancer were studied in a cohort of 1,960 Georgia women diagnosed during 1975-1979. After data were adjusted for stage of disease, socioeconomic status, and other prognostic factors, poorer survival rates were shown in black women. Within each stage classification, lower levels of serum albumin and hemoglobin and higher relative body weight were more common among blacks and were independently associated with poorer survival. Among women with stage 3 disease, adjustment for these variables substantially reduced the excess mortality rate among blacks, suggesting that racial differences in survival may be partly explained by differences in nutritional status or extent of disease within stage. 
2	Role of free radicals and platelet-activating factor in the genesis of intestinal motor disturbances induced by Escherichia coli endotoxins in rats. The effects of IV administration of Escherichia coli endotoxin on intestinal myoelectric activity was investigated in conscious fasted rats chronically implanted with nichrome electrodes in the duodenojejunum. These effects were compared with those of platelet-activating factor and were evaluated in animals pretreated with a specific platelet-activating factor antagonist, BN 52021, indomethacin, a selective prostaglandin E2 antagonist, SC 19220, and several free radical scavengers. Intravenous administration of endotoxin (E. coli S.O111:B4) at a dose of 50 micrograms/kg suppressed the migrating myoelectric complexes, which were replaced by continuous rhythmic clusters of rapidly propagated spike bursts for 114.7 +/- 19.9 minutes. Intraperitoneal platelet-activating factor (25 micrograms/kg) also inhibited the migrating myoelectric complex pattern for 146.1 +/- 24.1 minutes. Previous IV administration of BN 52021 (50 mg/kg-1) abolished the motor alterations induced by platelet-activating factor and significantly reduced to 43.1 +/- 12.2 minutes those induced by endotoxin (P less than 0.01). Indomethacin (10 mg/kg IP), injected before endotoxin or platelet-activating factor, also significantly reduced the duration of migrating myoelectric complex inhibition to 45.6 +/- 7.8 and 47.7 +/- 8.3 minutes, respectively (P less than 0.01). SC 19220 significantly reduced the effects of platelet-activating factor from 151.8 +/- 26.4 to 67.4 +/- 14.7 min (P less than 0.01). Superoxide dismutase (15,000 U/kg IV) injected before either endotoxin or platelet-activating factor shortened the migrating myoelectric complex inhibition to 45.7 +/- 9.9 and 72.9 +/- 10.4 minutes, respectively (P less than 0.01). Allopurinol and dimethylsulfoxide administered orally at 50 mg/kg 1 hour before endotoxin reduced the migrating myoelectric complex inhibition to 42.5 +/- 6.5 and 38.2 +/- 6.4 minutes, respectively (P less than 0.01). They also reduced platelet-activating factor-induced intestinal myoelectric alterations to 68.5 +/- 10.6 and 31.7 +/- 6.1 minutes, respectively (P less than 0.01). It is concluded that endogenous release of platelet-activating factor is partly responsible for the intestinal motor alterations induced by endotoxin, these effects being also mediated through the release of prostaglandins and free radicals. However, prostaglandins, as well as free radicals, appear to be partly involved in the platelet-activating factor-induced action of E. coli endotoxin on intestinal motility. 
5	Tracheal extubation in children: halothane versus isoflurane, anesthetized versus awake. The authors compared the incidence of respiratory complications and arterial hemoglobin desaturation during emergence from anesthesia in children whose tracheas were extubated while they were anesthetized or after they were awake and to whom halothane or isoflurane had been administered. One hundred children 1-4 yr of age undergoing minor urologic surgery were studied. After a standard induction technique, patients were randomized to receive either isoflurane or halothane. In 50 patients tracheal extubation was performed while they were breathing 2 MAC of either halothane or isoflurane in 100% oxygen. The remaining 50 patients received 2 MAC (volatile agent plus nitrous oxide) during the operation, but tracheal extubation was delayed until they were awake. A blinded observer recorded the incidence of respiratory complications and continuously measured hemoglobin saturation for 15 min after extubation. When tracheal extubation occurred in deeply anesthetized patients, no differences were found between the two volatile agents. When tracheal extubation of awake patients was performed, the use of isoflurane was associated with more episodes of coughing and airway obstruction than was halothane (P less than 0.05). Awake tracheal extubation following either agent was associated with significantly more episodes of hemoglobin desaturation than was tracheal extubation while anesthetized. 
3	Goal attainment scaling and outcome measurement in postacute brain injury rehabilitation. Relationships among two-month and final goal attainment scaling (GAS) scores, preadmission and final Portland Adaptability Inventory (PAI) scores, and work outcome for 16 graduates of a comprehensive, postacute brain injury rehabilitation program were examined. Final GAS scores were higher for program graduates who obtained the most desirable work outcomes, and preadmission and final PAI scores were lower for the successful program graduates. Final GAS scores were significantly correlated with other outcome measures. Preadmission PAI scores predicted work outcome, and two-month GAS scores predicted final GAS scores. Initial PAI scores distinguished between program successes and failures, but not between program successes and dropouts. A brief look at one case illustrates the modified application of GAS in postacute brain injury rehabilitation. Results of this study and case analyses support GAS as a quantifiable, individualized measure that is useful for (1) monitoring patient progress, (2) structuring team conferences, (3) ongoing rehabilitation planning and decision-making, (4) concise, relevant communication to family, referral sources, and funding sources, and (5) overall program evaluation when used in the context of other objective outcome measures. Although our results support the clinical utility of GAS, further study is recommended to assess the psychometric characteristics of GAS in this application. 
5	Intraoperative bronchial aspiration of ruptured pulmonary hydatid cysts. Ruptured pulmonary hydatid cysts are seen clinically and radiologically as persistent cavitary lesions of the lung. Bronchi opening into the pericyst cavity allow for discharge of fluid matter but not the escape of solid remnants of the collapsed parasite. Operative manipulation of the involved lung in the course of surgical management of chronic ruptured pulmonary hydatids can force fragments of the laminated membrane or small daughter cysts into the bronchial tree. Such extruded solid fragments lodge in bronchi of the same or opposite lung with resulting acute obstruction of airways. Intraoperative bronchial aspiration of hydatid material was seen in 7 patients with ruptured hydatid cysts of the lung, either primary or secondary to transdiaphragmatic extension of liver hydatids. The first clinical sign can be unexplained difficulty in ventilation. Effective management consists of prompt exposure of the stem bronchus on the operative side, with bronchotomy for suction retrieval of escaped solid fragments of the parasite. 
5	Leiomyosarcoma of the larynx: emergency laryngectomy. Leiomyosarcoma of the larynx is extremely rare. A patient with respiratory obstruction due to such a tumour is presented. This was originally misdiagnosed as hysteria. The treatment of choice was an emergency laryngectomy. 
5	Resolution of inferior vena cava syndrome after embolization of a hepatic adenoma. A 77-year-old man presented with severe pruritus and massive lower body edema. Computerized axial tomography of the abdomen showed a large hepatic mass compressing the inferior vena cava, and a liver biopsy specimen showed hepatic adenoma. Embolization of vessels feeding the hepatic tumor resulted in complete resolution of pruritus and ascites, and clinical remission has persisted for 1 year following partial obliteration of tumor vasculature. Angiographic ablation of tumor blood supply represents a nonoperative means for inducing clinical remission in patients with symptomatic hepatic adenoma who are at high surgical risk. 
5	Acute respiratory failure caused by pulmonary vasculitis after L-tryptophan ingestion. This report describes two women who presented with severe respiratory failure and diffuse pulmonary infiltrates in the fall of 1989. Both required prolonged assisted ventilation because of severe shunt physiology. Open lung biopsies on admission revealed a small vessel vasculitis as the sole morphologic abnormality in both patients. Both responded to high dose corticosteroids. Neither patient exhibited evidence of systemic vasculitis, and neither had serologic evidence of an immune disorder. Common to both patients was ingestion of L-tryptophan. One patient exhibited several features of the eosinophilia-myalgia syndrome. The other patient did not appear to have the syndrome, but the temporal relationship between the onset of symptoms and initiation of L-tryptophan treatment was striking. The presentation of these patients alters our notions concerning the spectrum of clinical manifestations caused by this agent, and the response to methylprednisolone supports its efficacy in the treatment of this disorder. 
1	Oncogenes and suppressor genes: their involvement in colon cancer [editorial] Abnormalities in oncogenes, which are broadly classified into viral and cellular oncogenes, and suppressor genes appear critical for the development of colon cancer. Cellular oncogenes contribute to malignant transformation when they become activated by point mutation, translocation, amplification, or loss of regulator sequences. The properties of the oncoproteins, the proteins encoded by oncogenes which are essential for carcinogenesis, are unclear. Suppressor genes normally suppress the tumorigenic phenotype by keeping the growth of cells in check; it is their inactivation that contributes to malignant transformation. Development of colon cancer appears to take place by stepwise accumulation of multiple genetic alterations during the progression from normal colon to adenoma and carcinoma. Activation of ras, an early event in this sequence, is found in 50% of colon cancers; overexpression of c-myc is found in approximately 80%. Inactivation of suppressor genes, which occurs during later stages, is noted in greater than 70% of tumors. A current model of colonic tumorigenesis is presented. 
5	Urinary tract dilatation in pregnancy. Right-sided ureteral and renal pelvis dilatation was observed during routine uterine ultrasonographic examination at 30 weeks' gestation. This continued to progress with the renal pelvis measuring 8.9 cm in diameter at 35 weeks, leading to early delivery. Renal function remained normal and these changes resolved completely after delivery. 
5	Independence of pressure reactivity from pressure levels in Tecumseh, Michigan. The relation between blood pressure level and reactivity to mental arithmetic and isometric exercise was investigated in 169 men and 120 women (average age, 32.3 years) from the village of Tecumseh, Mich. In the entire population, the correlation between baseline blood pressure and blood pressure response to both stressors was not significant. Blood pressure reactivity to both stressors was not increased in participants with borderline hypertension (one clinic reading of more than 140 mm Hg systolic and/or 90 mm Hg diastolic). When subjects were classified according to blood pressure response (below and above the 80th percentile), the hyperreactors to mental and physical stress had normal baseline blood pressure values. The hyperreactors also had clinic-to-home blood pressure differences similar to those of the rest of the population. Participants who had borderline hypertension at age 32 years had significantly elevated blood pressures at ages 5, 8, 12, 21, and 22 years. Those who were hyperreactors at age 32 years had normal blood pressures as children and young adults. Results of the present study lend no support to an association between higher blood pressures and blood pressure hyperreactivity. Study participants in Tecumseh will be recalled for future examinations. The independence of blood pressure levels from blood pressure reactivity offers a unique opportunity to prospectively evaluate their separate effects on cardiovascular morbidity. 
2	p53 expression in colorectal tumors. The expression of the nuclear phosphoprotein p53 was studied immunohistochemically in a series of 150 benign and malignant colorectal tumors. Using monoclonal antibody PAb1801, tumors divided unequivocally into two groups on the basis of immunohistochemistry. Forty of the carcinomas (46.5%) showed positive staining but only 4 of the adenomas (8.7%) were positive (P less than 0.001). The few positive adenomas always showed moderate or severe dysplasia. Metaplastic polyps (n = 9) and small familial adenomatous polyposis-related adenomas (n = 9) were uniformly negative. Carcinomas with p53 expression did not differ from those without in terms of site, differentiation or the prognostic indicators of Dukes' stage, DNA ploidy, or tumor histology. The improved morphologic resolution available in periodate lysine paraformaldehyde dichromate (PLPD)-fixed, paraffin-embedded tissue permitted several conclusions to be made: p53 is confined to neoplastic nuclei; staining in positive tumors is heterogeneous and often more marked at the infiltrative margins; and staining intensity is dramatically reduced in mitotic cells. It is concluded that expression of immunohistochemically detectable p53 (probably representing mutated forms of the protein) occurs in some adenomas around the time of transition to carcinoma. Therefore there is an association with the appearance of infiltrative behavior but not with degree of tumor progression (including metastasis) at the time of resection. 
1	Intraoperative pancreatic fine needle aspiration biopsy. Results in 166 patients. Intraoperative fine needle aspiration biopsy (NAB) of undiagnosed pancreatic masses was studied in 166 patients over a 17-year period. The cytologic diagnoses were correlated with histologic specimens, autopsy results, or clinical follow-up (benign disease was documented if the patient was alive without malignancy at least 2 years after laparotomy). Aspirates were interpreted as benign, suspicious, malignant, or unsatisfactory. Malignant disease was the final diagnosis in 109 patients; the cytology was concordant in 101 and was interpreted as suspicious in four. Four patients with benign cytology later proved to have malignant disease--a false-negative rate of 2.5 per cent. A total of 57 patients had benign disease; 51 of these had benign cytology. The remaining patients had "unsatisfactory" cytology reports. A 93 per cent sensitivity, 100 per cent specificity, and 0 per cent complication rate are reported. There were no false-positive cytology reports. Complications are rare and represent case reports, thus, additional sampling is at minimal risk. Intraoperative pancreatic NAB is a safe, easy, more accurate biopsy technique than historical wedge or core needle biopsies. It is the biopsy method of choice for pancreatic masses found at laparotomy. 
1	Effect of interleukin-1-beta on metastasis formation in different tumor systems. Experiments were done to determine the effect of interleukin-1-beta (IL-1 beta) on metastasis formation in different tumor systems. Intravenous administration of 1 microgram of human recombinant IL-1 beta given 1 hour before tumor cell injection augmented lung colony formation (experimental metastases) by the human A375 melanoma variants, the human HT-29M colon carcinoma, the SN12-K1 renal carcinoma in nude mice, the murine B16 melanoma variants, and the murine UV-2237M fibrosarcoma in syngeneic recipients. The same treatment did not induce lung colony formation by a human rectal carcinoma (HCC-P2988) or by a murine reticulum cell sarcoma (M5076), both of which are not metastatic to the lung. Spontaneous metastases were studied in C57BL/6 mice bearing the B16-BL6 melanoma (metastatic to the lung) in their footpad and the M5076 reticulum cell sarcoma (metastatic to the liver) subcutaneously. Daily intraperitoneal treatment with 1 microgram of IL-1 beta increased lung and liver metastases. These findings indicate that treatment of mice with IL-1 beta can increase the number of artificial or spontaneous metastases and that this effect is not limited to a single tumor type or to a specific organ. 
2	The value of the rectus abdominis myocutaneous flap in the treatment of complex perineal fistula. Complex perineal fistula and persistent perineal sinus are difficult to treat. We describe our experience with wide excision of the diseased perineum using a combined abdominoperineal approach. Ten patients were reconstructed by a rectus abdominis myocutaneous flap (n = 7), rectus abdominis muscle flap (n = 2), and omental graft (n = 1). Primary healing was achieved in all cases. A median follow-up of 18 months (range 6-54 months) has shown no recurrence of perineal disease or associated abdominal incisional hernia. There were no perioperative deaths. We propose that the rectus abdominis myocutaneous flap is indicated if large amounts of perineal skin has to be sacrificed. When less skin is removed a repair with greater omentum or rectus muscle alone is adequate. The abdominoperineal approach together with filling the residual pelvic cavity with well-vascularized tissue allows definitive treatment to be carried out in one stage. 
5	Mayer-Rokitansky-Kuster-Hauser syndrome with splenosis. A case report. This is the first reported case of simultaneously occurring pelvic splenosis and Mayer-Rokitansky-Kuster-Hauser syndrome. No other congenital or anatomic abnormalities were observed in the patient, and she had no history of abdominal trauma or surgery. Endometriosis was suspected initially during laparoscopy for pelvic pain. After tissue removal at laparotomy, the histologic evaluation established the diagnosis of splenosis. Biopsy at laparoscopy should be considered to confirm the diagnosis in the presence of a congenital anomaly and lesions suspected of being endometriotic. 
4	Hypertension prevalence and the status of awareness, treatment, and control in the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-84 The prevalence rates of hypertension among adult (ages 18-74) Mexican Americans, Cuban Americans, and Puerto Ricans were estimated using data from the 1982-84 Hispanic Health and Nutrition Examination Survey (HHANES). Hypertension is defined as diastolic greater than or equal to 90 mm Hg, or systolic greater than or equal to 140 mm Hg, or currently taking antihypertensive medication. Among Mexican Americans in the Southwestern United States, 16.8 percent of the males and 14.1 percent of the females were found to be hypertensive. Among Cuban Americans in Dade County, Florida 22.8 percent of the males and 15.5 percent of the females were hypertensive. Among Puerto Ricans in the New York City area 15.6 percent of the males and 11.5 percent of the females were hypertensive. The age-adjusted rates are significantly lower than comparable rates for Whites and Blacks as measured in the second National Health and Nutrition Examination Survey (NHANES II), 1976-80. Control of hypertension in the HHANES populations fall short of the 1990 Objectives for the Nation established by the US Public Health Service 60 percent (34 percent controlled Mexican American hypertensives, 27.8 percent controlled Cuban American hypertensives, and 29 percent controlled Puerto Rican hypertensives. 
1	Differential effects of sodium butyrate and hexamethylene bisacetamide on growth and secretion of cultured human endocrine tumor cells. Advanced gastrointestinal endocrine tumors respond poorly to conventional chemotherapy. In this study we examined the effects of two agents that promote cellular differentiation, sodium butyrate and hexamethylene bisacetamide, on the in vitro growth and secretory responses of a human pancreatic carcinoid (BON) and human gastrinoma (PT-2 and PT-SM) cell lines that have been established in our laboratory. We found that both sodium butyrate and hexamethylene bisacetamide strongly inhibited growth of BON, PT-2, and PT-SM cells. With continuous exposure of BON cells to sodium butyrate (2 mmol/L), the doubling time was prolonged, from 60 hours in controls to 156 hours, and saturation density was reduced to 28% that of controls. Hexamethylene bisacetamide (4 mmol/L) reduced saturation density to 37% that of controls in BON cells and prolonged the doubling time, from 60 hours to 103 hours. Antiproliferative effects of similar magnitudes were observed in the gastrinoma cell lines. In contrast, differential effects were produced on amine biosynthesis in BON cells; sodium butyrate stimulated levels of 5-hydroxytryptamine in the cells, whereas hexamethylene bisacetamide caused a profound dose-dependent inhibition of amine biosynthesis. The significant antiproliferative activity of sodium butyrate and hexamethylene bisacetamide and the inhibitory effects of hexamethylene bisacetamide on amine biosynthesis warrant evaluation of these agents or analogues for treatment of metastatic carcinoid and gastrinoma. 
5	Sudden infant death syndrome and small airway occlusion: facts and a hypothesis. Respiratory failure is almost certainly the cause of death in the majority of cases of sudden infant death syndrome (SIDS), but the mechanisms leading to it have not been elucidated. SIDS shares many environmental and socioeconomic risk factors with severe forms of bronchiolitis, and the age distribution of incident cases is similar. Present knowledge of lung and airway development during infancy, determinants of peripheral airway patency, changes in lung surface activity in infants with SIDS, and fluid film dynamics in small airways are reviewed. It is hypothesized that many cases of SIDS may be due to a final episode of progressive peripheral bronchial occlusion in infants with preceding critically diminished conductance of the smaller airways. 
4	Total knee arthroplasty in diabetes mellitus. A retrospective study was done of 59 total knee arthroplasties (TKAs) in 40 patients diagnosed with diabetes mellitus. The overall infection rate was 7%, with an overall revision rate of 10% and an average follow-up period of 4.3 years. Wound complications were present in 12% of the TKAs. The rate of deep joint infections in diabetic patients was statistically higher than the reported incidence of sepsis in nondiabetic patients. Therefore, maximum precautions should be taken for diabetic patients having TKA to minimize both wound complications and joint sepsis. 
5	Antibiotic pharmacokinetics in surgery Pharmacokinetics is the study of variables that affect drug concentrations at the effector site. The descriptive terms peak concentration, elimination half-life, volume of distribution, and bioavailability are commonly used to express pharmacokinetic variability among drugs used in patient care. The pharmacokinetic characteristics of drugs are important for surgeons to understand because they represent differences that may assume clinical significance when selecting antibiotics for preoperative preventive indications. In addition, the changing hemodynamic pattern of the stressed and septic patient may result in changing pharmacokinetic patterns for an antibiotic, which, in turn, may require changes in the dosing regimen during the course of treatment. 
5	Perinatal mortality in Victoria, Australia: role of group B Streptococcus. Group B beta-hemolytic streptococcus is the most common infective cause of neonatal morbidity and mortality. It is therefore surprising that no agreement exists for an approach to its prevention. There is also increasing evidence that occult infection may play an etiologic role in premature rupture of the membranes and preterm labor. In this report we review the role of group B beta-hemolytic streptococcal sepsis as a cause of perinatal wastage in the state of Victoria, Australia during the period 1982 to 1987. Group B beta-hemolytic streptococcus accounted for 1.7% of overall perinatal deaths, and for 30.3% (77 of 254) perinatal deaths directly attributable to infection. By comparison, over the same 6-year period, erythroblastosis accounted for 0.5% of perinatal wastage and there were only two deaths as a result of congenital syphilis. The true incidence of lethal group B beta-hemolytic streptococcal infection is probably greater because of the absence of histologic and bacteriologic studies in many perinatal deaths. We believe that intrapartum chemoprophylaxis with penicillin of all group B beta-hemolytic streptococcus-positive carrier mothers would significantly reduce neonatal morbidity and mortality from this cause. 
5	High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. The purpose of this study was to estimate the incidence and to establish which factors were associated with an increased risk of hemorrhagic complications in an historic cohort of 117 consecutive and unselected patients with chronic idiopathic thrombocytopenic purpura (ITP). Sixty-eight patients (58%) underwent medical treatment and/or splenectomy and 33 (48% of treated) achieved a complete stable remission. At equivalent platelet count the incidence of major hemorrhagic complications was significantly higher in aged (greater than 60 years) than in younger (less than 40 years) patients (10.4% v 0.4%/pt-y, relative risk = 28.9, P less than .01). A previous hemorrhagic event was identified as another major risk factor for hemorrhage (relative risk = 27.5, P less than .0005), while hypertension and underlying disorders had no influence. We conclude that age more than 60 years and a previous history of bleeding are major risk factors for severe hemorrhages in adults with ITP. 
3	Leukocyte alkaline phosphatase score in patients with cerebrovascular disease and in patients with primary and metastatic brain tumors. Leukocyte alkaline phosphatase (LAP) activity in peripheral blood was determined in 54 patients with cerebrovascular disease (CVD), 11 patients with primary brain tumor, and 23 patients with metastatic brain tumor. The LAP score of the primary brain tumor patients (155 +/- 40) was significantly higher (P less than 0.03) than the LAP score for cerebrovascular disease patients (96 +/- 87). The LAP score levels of the metastatic brain tumor patients (251 +/- 55) was significantly higher as compared with both the cerebrovascular disease (P less than 0.001) and primary brain tumor groups (P less than 0.001). The LAP score could serve as an additional, although non-specific, marker to assist in the differentiation between cerebrovascular disease and brain tumors. 
5	Natural history of congestive gastropathy in cirrhosis. The Liver Study Group of V. Cervello Hospital. In a prospective study of the natural history of congestive gastropathy, 212 consecutive cirrhotic patients (75 treated with sclerotherapy) were included. Mean follow-up was 46 months. Mild gastropathy (mosaiclike pattern) was found in 110 patients and severe gastropathy (granular mucosa with cherry spots) was found in 20. Prevalence of Helicobacter pylori, formerly Campylobacter pylori, was 50% in patients without, 43% in those with mild, and 28% in those with severe gastropathy. Congestive gastropathy was significantly more frequent in patients treated with sclerotherapy (83% vs. 50%, P less than 10(-5)). Sixty-month actuarial proportions of patients free of anemia (in the absence of hematemesis or melena), were 17% with severe, 62% with mild, and 93% without gastropathy (P less than 10(-8]. Corresponding figures for overt bleeding were 25%, 73%, and 87% (P less than 10(-7], whereas those for survival were 46%, 72%, and 85% (P = 0.0005), respectively. A multivariate regression analysis supported the following conclusions: (a) sclerotherapy and the presence of large esophageal varices significantly increase the risk of congestive gastropathy, which (b) is a significant risk indicator of both chronic and overt bleeding but does not independently affect survival. 
5	The "numb cheek-limp lower lid" syndrome. A patient developed isolated numbness, 1st confined to the lateral nose and upper lip, but later involving the cheek, lower lip, upper gingiva, and the palate. This numbness was later associated with paresis of the muscles of the upper lip and angle of the mouth and with ipsilateral lower lid droop (the "numb cheek-limp lower lid" syndrome). Squamous cell carcinoma was discovered infiltrating the infraorbital nerve and distal branches of the facial nerve. Cheek numbness associated with lower eyelid or upper lip weakness may herald a neoplasm affecting the infraorbital nerve and distal facial nerve branches. 
3	Restricted dose and duration of corticosteroid treatment in patients with polymyalgia rheumatica and temporal arteritis. To analyze whether corticosteroids in low doses during limited time periods could be safely used in the treatment of patients with polymyalgia rheumatica (PMR) or temporal arteritis (TA) the records of 91 patients diagnosed between 1980 and 1987 were reviewed. The mean initial prednisolone dose was in patients with PMR 18 mg/day and the mean duration of treatment was 17 months. In patients with TA the mean initial dose was 31 mg/day and the mean duration of treatment 16 months, and in all the corticosteroid treatment was terminated within 24 months. Patients with coexisting TA and PMR demanded longer treatment compared to patients with either TA or PMR and thus 18/91 patients were treated for more than 2 years. No visual or neurological complications occurred after treatment with corticosteroids had been initiated. Our study indicates that most patients with PMR or TA can be treated safely with an initial prednisolone dose of 10 mg given twice daily. With few exceptions corticosteroid treatment can be terminated within 24 months. 
5	Routes and incidence of communication of lumbar discs with surrounding neural structures. Several authors have previously reported the complications resulting from contact between a diagnostic or therapeutic agent injected into an intervertebral disc and neural tissue. This study was undertaken to demonstrate the common routes by which, and frequency with which this contact occurs. Of 105 cadaveric intervertebral discs studies, 15 (14%) leaked. Of the discs that leaked, 27% demonstrated contact of injected dye with the adjacent spinal nerve. The high rate of leakage may be related to the age of the cadavers. Nonetheless, the contact between substances injected into an intervertebral disc and adjacent neural tissue during discography offers an alternate mechanism of pain reproduction in an incompetent disc. It also suggests that nontoxic agents should be used for discography and that intervertebral discs should be proved competent before chemonucleolysis. 
5	Comparison of rectal, axillary, and tympanic membrane temperatures in infants and young children. STUDY OBJECTIVE: To evaluate the reliability of a tympanic membrane thermometer in detecting fever in young children presenting to the emergency department. SETTING: Pediatric emergency department in an urban teaching hospital, DESIGN/MEASUREMENT/PARTICIPANTS: Temperature measurements were obtained sequentially at three body sites in children less than 3 years old presenting to the pediatric ED. Axillary and rectal temperatures were obtained with an electronic thermistor probe (Diatek 500), and tympanic membrane temperatures were obtained with a noncontact, infrared sensing device (First TEMP). Patients were stratified by age, ear canal patency, presence of otitis media, and rectal temperature. RESULTS: Of 224 patients enrolled, 87 (39%) were febrile. Overall correlation of axillary and tympanic membrane measurements to rectal for all strata was .75 (P = .001) and .81 (P = .001), respectively. Sensitivity in detecting fever for axillary and tympanic membrane sites was .48 and .55, respectively. Otitis media and ear patency did not influence correlation of tympanic membrane measurements. Low tympanic membrane temperature sensitivity may be a result of probe configuration. CONCLUSION: Tympanic membrane and axillary temperatures should be viewed with caution in children less than 3 years old as neither can detect fever reliably. 
5	Factors predictive of results of direct ablative operations for drug-refractory ventricular tachycardia. Analysis of 80 patients. During a 9-year period 80 patients with drug-resistant sustained ventricular tachycardia underwent direct surgical ablation of arrhythmogenic myocardium. Sixty-nine were male (86%) and 11 female (14%), with 1.9 +/- 1.1 (standard deviation) ventricular tachycardia morphologies per patient. The mean number of drugs failed was 3.7 +/- 1.6 per patient. The preoperative left ventricular ejection fraction was 36.4% +/- 14.4%. Complete preoperative endocardial mapping data (greater than 4 endocardial sites in each ventricular tachycardia) were available for 60 of the 80 patients (75%) and intraoperative endocardial data in the clinical ventricular tachycardia was obtained in 37 (46.3%) of the patients. In 17 patients mapped intraoperatively by computer-assisted techniques, complete epicardial and endocardial data in the clinical ventricular tachycardia were obtained in 14 patients (82.4%). Overall, 73 of 80 (91.3%) had some mapping data available. Hospital mortality occurred in 10 patients (12.5%) at a mean interval of 13.5 days, range 0 to 62 days. Postoperatively the clinical ventricular tachycardia has not recurred in 65 of 70 surviving patients (92.9%). Nonclinical ventricular tachycardia occurred in another four patients. All nine patients with postoperative ventricular tachycardia responded to drugs. The major factors predictive of hospital mortality were prolonged cardiopulmonary bypass (greater than 150 minutes), preoperative ejection fraction less than 31%, and incomplete preoperative mapping. Hospital mortality in patients with an ejection fraction below 31% was significantly associated with a history of amiodarone usage. At 3 years of follow-up, freedom from sudden cardiac death was 95.7%, and 86.7% of patients were free of ventricular tachycardia on no antiarrhythmic drugs. These results suggest that direct ventricular tachycardia operations are an effective form of therapy for patients with sustained monomorphic ventricular tachycardia. 
5	All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Twenty-two patients with acute promyelocytic leukemia were treated with all-trans retinoic acid (RA, 45 mg/m2 per day) for 90 days. Of the 22, four patients were previously untreated, two were resistant after conventional chemotherapy, and 16 were in first (n = 11), second (n = 4), or third (n = 1) relapse. We observed 14 complete response, four transient responses, one failure, and three early deaths. Length of hospitalization and number of transfusions were notably reduced in complete responders. Correction of coagulation disorders and an increase of WBCs were the first signs of all-trans RA efficacy. Morphologic analysis performed at days 0, 15, 30, 45, 60, and 90 showed that complete remissions were obtained without bone marrow (BM) hypoplasia. Presence of Auer rods in the maturing cells confirmed the differentiation effect of the treatment. At remission, the t(15;17) initially present in 20 patients was not found. The in vitro studies showed a differentiation in the presence of all-trans RA in 16 of the 18 tested cases. The single nonresponder to all trans RA in vitro did not respond in vivo. Adverse effects of RA therapy--skin and mucosa dryness, hypertriglyceridemia, and increase of hepatic transaminases--were frequently noted. We also observed bone pain in 11 patients and hyperleukocytosis in four patients. Whether maintenance treatment consisted of low-dose chemotherapy or all-trans RA, early relapses were observed. Five patients are still in complete remission (CR) at 4 to 13 months. Our study confirms the major efficacy of all-trans RA in M3, even in relapsing patients. Remissions are obtained by a differentiation process. 
1	Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer. 
1	Retroperitoneal lymph node dissection in malignant mesothelioma of tunica vaginalis testis. A case of metastatic mesothelioma of the tunica vaginalis testis in a 57-year-old man is reported. Clinicopathological findings and treatment options are reviewed. 
5	Circadian variation in onset of acute ischemic stroke. A circadian pattern for the onset of myocardial and cerebral infarction has been identified. To evaluate this phenomenon further, we analyzed prospectively collected data from 151 patients with acute ischemic stroke. The number of strokes per 6-hour period were the following: midnight to 6 AM, 20 (13%); 6 AM to noon, 86 (57%); noon to 6 PM, 21 (14%); and 6 PM to midnight, 24 (16%). This pattern was not affected by previous use of aspirin. The most frequent time of onset was 6 AM to noon for all subgroups of ischemic stroke: small artery, 71%; cardioembolic, 62%; large artery atherothrombotic, 57%; large artery atheroembolic, 46%; and "other" or unknown cause, 40%. We also investigated the time between awakening and stroke onset in 145 patients and found that 24% of ischemic strokes occurred within the first hour after awakening. Our data demonstrate that an early morning peak exists for all subtypes of stroke. Our data also suggest that the most critical period is the first hour after awakening. 
5	Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation. In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells. 
2	The site of recurrent duodenal ulcer. The aim of this retrospective study was to determine the site of recurrent duodenal ulcer in relation to the site of the index ulcer. One hundred and thirty-five patients who had recurrent duodenal ulcer after documented healing of an index ulcer were studied. The recurrent ulcer was more likely to occur in the anterior bulb if the index ulcer was anterior (35 of 58 = 60%) than if the index ulcer was not anterior (29 of 77 = 38%, p less than 0.01). However, the likelihood of a recurrent ulcer on the posterior wall of the bulb was not significantly different whether the index ulcer was posterior (11 of 36 = 31%) or not (22 of 99 = 22%, p less than 0.24). Three of 20 patients (15%) who initially presented with bleeding bled again with their recurrent ulcers, compared with eight of 115 patients (7%) who first presented with dyspepsia only (p = 0.39). Thirteen patients were assessed independently by two endoscopists to determine ulcer site. Their assessments concurred for 12 (92%). 
2	A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. The role of leukocyte adherence in the mechanism of gastropathy induced by nonsteroidal antiinflammatory drugs was investigated using a rabbit model. Gastric damage was induced by intragastric instillation of indomethacin [5 mg/mL] for a period of 30 minutes. Histologically, this treatment resulted in extensive vascular congestion and leukocyte margination within the mucosa. Pretreatment with a monoclonal antibody [IB-4] directed against the common beta subunit of the CD11/CD18 adhesion glycoprotein complex significantly (P less than 0.05) reduced both the vasocongestion and the prevalence of leukocyte margination. Macroscopically, indomethacin treatment resulted in the formation of numerous hemorrhagic lesions in the corpus region of the stomach. Pretreatment with IB-4 reduced the extent of gastric hemorrhagic damage by approximately 85% (P less than 0.001). Damage in the group pretreated with IB-4 did not differ significantly from that in rabbits that did not receive indomethacin. In separate experiments, the dose of IB-4 used was shown to completely suppress the recruitment of granulocytes in response to two different agonists. These results support the hypothesis that leukocyte adherence to the vascular endothelium is an important event in the pathogenesis of ulceration induced by nonsteroidal antiinflammatory drugs. Leukocytes might contribute to ulceration by occluding microvessels, thereby reducing mucosal blood flow, and by releasing various mediators, proteases, and free radicals that can produce tissue necrosis. 
5	New surgical approach to complicated gastroesophageal reflux disease: transthoracic parietal cell vagotomy. Surgical treatment of peptic stricture of the esophagus associated with columnar (Barrett) metaplasia can be a difficult problem. Collis-Nissen fundoplication restores an intraabdominal antireflux barrier for most cases of peptic stricture; however, 20% of patients may have persistence of pathological acid reflux. By reducing acidity of postoperative reflux, parietal cell vagotomy may complement nonresectional surgical results for Barrett stricture. 
1	Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Acute promyelocytic leukemia (APL; FAB M3) is characterized by a predominance of malignant promyelocytes that carry a reciprocal translocation between the long arms of chromosomes 15 and 17, t(15;17) (q22;q11.2-q12). This translocation has become diagnostic for APL, as it is present in almost 100 percent of cases. A Not I linking clone was used to detect this translocation initially on pulsed-field gel electrophoresis and subsequently with conventional Southern (DNA) analysis. The breakpoints in ten APL cases examined were shown to cluster in a 12-kb region of chromosome 17, containing two CpG-rich islands. The region is the first intron of the retinoic acid receptor alpha gene (RARA). 
1	Chondrosarcoma of the larynx. Diagnosis with magnetic resonance imaging and computed tomography. Chondrosarcomas are the most common sarcomas of the larynx. They are generally slow-growing lesions with insidious onset of symptoms. We are presenting a case of chondrosarcoma that recurred 10 years after excision of a presumed chondroma. Computed tomographic and magnetic resonance imaging (MRI) scans were performed. Both studies delineated the lesion nicely. To the best of our knowledge, this is the first report on MRI characteristics of chondrosarcoma of the larynx. A review of the literature regarding the use of computed tomography in the management of chondrosarcoma is presented. The MRI characteristics are discussed and the two scanning modalities are compared. Computed tomography is an excellent study in its ability to demonstrate the extent of the lesion within the laryngeal skeleton. Furthermore, it is more highly sensitive than plain roentgenograms in the detection of calcifications that are highly suggestive of chondrosarcoma. Alternatively, MRI can also demonstrate the lesion within the larynx but it has the added advantage of superior contrast resolution of the tumor and paralaryngeal tissues. When the three-dimensional imaging capacity of MRI is considered as well, MRI seems to be the superior study. 
5	Chemotherapy-related hemolytic-uremic syndrome after the treatment of head and neck cancer. A case report. A 62-year-old woman who was being treated for squamous cell carcinoma of the head and neck developed a chemotherapy-related hemolytic-uremic syndrome during the second cycle of neoadjuvant chemotherapy consisting of cisplatin, bleomycin, and methotrexate. Though the syndrome was suspected early, attempts at reversing the hematologic and renal abnormalities were unsuccessful. At postmortem examination, the characteristic microvascular lesions of the hemolytic-uremic syndrome were found in the kidneys. 
4	Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease. Treatment of normal platelet-rich plasma with a physiological amount of insulin (100 microunits/ml, optimum concentration) for 3 hours at 23 degrees C stimulated the binding of prostaglandin E1 by more than twofold (3,940 +/- 250 sites/10(8) platelets) compared with the nontreated, control platelet-rich plasma (1,590 +/- 265 sites/10(8) platelets). After platelet-rich plasma from patients with acute ischemic heart disease (n = 43), whose platelets showed impaired prostaglandin E1/I2 receptor activity (850 +/- 100 sites/10(8) platelets), was incubated with insulin (optimum amounts varied from 100 to 200 microunits/ml), the binding of the prostanoid was restored to normal levels (1,790 +/- 140 sites/10(8) platelets) in 75% of the cases. Twenty-five percent of the patients did not respond to the stimulatory effect of insulin. The increased binding of the prostanoid to the insulin-treated platelets also resulted in increased cyclic AMP levels both in normal subjects (44.14 +/- 3.1 pmol/10(8) [insulin-treated] platelets versus 16.35 +/- 2.91 pmol/10(8) [control] platelets) and in patients with acute ischemic heart disease (23.87 +/- 4.1 pmol/10(8) [insulin-treated] platelets versus 7.70 +/- 2.0 pmol/10(8) [control] platelets) by the prostanoid (1.0 microM). The treatment of platelet-rich plasma with the hormone decreased the minimum inhibitory concentration of the prostanoid from 34 +/- 14 to 15 +/- 9 nM (p less than 0.001) in the case of normal volunteers and from 49 +/- 15 to 32 +/- 11 nM (p = 0.002) in the case of "responder" patients. Insulin did not produce any effect on the inhibition of platelet aggregation by the prostaglandin in "nonresponder" patients. In the follow-up study, although the stimulatory effects of insulin on platelets from responder patients were improved to normal levels, the platelets from the nonresponder patients remained persistently unresponsive to the effect of the hormone. 
5	Underlying illness associated with failure to thrive in breastfed infants. Over a four-year period in a suburban pediatric practice, 38 infants aged six months or less were identified with failure to thrive (FTT) while breast-feeding. In seven cases (18.4%), an associated organic illness was diagnosed. Only 2 of 28 breast-fed neonates (8%) were found to have FTT associated with another illness, as compared to 5 of 10 older infants (50%). Breast-fed infants with FTT, particularly those presenting after the first month of life, should be considered high risk for having other disease. Their clinical evaluation should include an appropriate search for organic illnesses. 
5	Remote effect of deep-seated vascular brain lesions on cerebral blood flow. We measured regional cerebral blood flow using the xenon-133 inhalation method, at approximately 1 month after onset, in 60 stroke patients who had no evidence of major carotid artery stenosis or occlusion. Their single lesions (43 infarcts and 17 hematomas) were located in the capsulothalamolenticular region, sparing the cortex. Hemispheric mean cerebral blood flow was reduced on the side of the lesion in 25 patients and on both sides in 20. Regional hypoperfusion was observed in 46 patients (ipsilaterally in 34, bilaterally in 10, and contralaterally in two). Regional hypoperfusion was observed most frequently in the frontal lobe, particularly in the motor and premotor cortices of the prerolandic area. The 46 patients with regional hypoperfusion were compared with the 14 patients without regional hypoperfusion, considering the size and location of the lesion as well as the functional and analytic motor performances. As a rule, the lesion was slightly smaller and more posterior and the functional (p less than 0.001) and analytic (p less than 0.05) motor performances were significantly better in the 14 patients without regional hypoperfusion. Since the xenon-133 inhalation method examines cortical blood flow, we can attribute blood flow reductions resulting from deep-seated lesions to a functional depression akin to diaschisis. Interpretation of the clinical consequences and pathogenesis of this phenomenon requires further sequential and pathologic studies. 
4	Early diastolic clicks after the Fontan procedure for double inlet left ventricle: anatomical and physiological correlates. M mode echocardiograms and simultaneous phonocardiograms were recorded in four patients with early diastolic clicks on auscultation. All had double inlet left ventricle and had undergone the Fontan procedure with closure of the right atrioventricular valve orifice by an artificial patch. The phonocardiogram confirmed a high frequency sound occurring 60-90 ms after aortic valve closure and coinciding with the time of maximal excursion of the atrioventricular valve patch towards the ventricular mass. One patient had coexisting congenital complete heart block. The M mode echocardiogram showed "reversed" motion of the patch towards the right atrium during atrial contraction. Doppler flow studies showed that coincident with this motion there was forward flow in the pulmonary artery with augmentation when atrial contraction coincided with ventricular systole. The early diastolic click in these patients was explained by abrupt cessation of the motion of the atrioventricular valve patch towards the ventricular mass in early diastole. In one patient atrial contraction led to a reversal of this motion and was associated with forward flow in the pulmonary artery. 
1	In situ hybridization for the detection of Epstein-Barr virus in central nervous system lymphomas. Epstein-Barr virus (EBV) has been implicated in the development of lymphomas in immunocompromised patients. To test this hypothesis, 26 lymphomas involving the central nervous system (CNS) (11 primary, 15 systemic) were studied for the presence of EBV. In situ hybridization (ISH) was performed on formalin-fixed, paraffin-embedded tissue using a sulfur 35 (35S)-labeled EBV probe (EBV BAMH1-W). The results were interpreted without knowledge of the patients' immunologic status. The EBV sequences were detected in 11 lymphomas, nine of which were mixed or large cell subtypes. Review of the clinical information revealed that nine of the 26 lymphomas occurred in immunocompromised patients secondary to renal transplantation, human immunodeficiency virus infection, leukemia, and Wiskott-Aldrich syndrome. The EBV sequences were detected in all nine lymphomas occurring in immunocompromised patients, whereas two of the 17 lymphomas occurring in immunocompetent patients expressed EBV sequences. The authors conclude that the presence of EBV sequences in CNS lymphomas is highly correlated with a history of compromised immune status supporting a pathogenetic role of EBV in the development of CNS lymphomas in immunocompromised patients. 
2	Recovery from disturbed colonic transit time after alcohol withdrawal. The effects of alcohol withdrawal on total and segmental transit time were evaluated in 20 chronic alcoholic subjects. After withdrawal, colorectal transit time significantly increased from 24.9 +/- 3.6 to 33.3 +/- 4.5 hours mean +/- SE (P less than 0.01). This was the result of an exclusive increase in rectosigmoid transit time from 2.8 +/- 0.7 to 9.8 +/- 2.1 hours (P less than 0.001). No variations were found in right or left colon transit time. Distal colonic motility is thus a crucial factor in the genesis of diarrhea in chronic alcoholic subjects. 
4	Studies of controlled reperfusion after ischemia. XVIII. Reperfusion conditions: attenuation of the regional ischemic effect by temporary total vented bypass before controlled reperfusion. This study tests the hypothesis that total vented bypass can attenuate the regional ischemic effect during a defined time interval before controlled blood cardioplegic reperfusion. Thirty-three dogs underwent 2 or 4 hours of occlusion of the left anterior descending coronary artery and then received a regional blood cardioplegic reperfusate on total vented bypass. Cardiopulmonary bypass and reperfusion were started after 2 hours of ischemia in eight dogs, and after 4 hours of ischemia in 25 others. Among the 25 dogs, seven had total vented bypass started after the first 2 hours of the 4 hours of regional ischemia. Segmental shortening (ultrasonic crystals), tissue water content (wet/dry weight), and histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours after reperfusion. Dogs reperfused after 2 hours of ischemia recovered 73% +/- 8% of control systolic shortening and sustained only 11% triphenyltetrazolium chloride nonstaining. Dogs undergoing 4 hours of regional ischemia, but with total vented bypass 2 hours before reperfusion had improved recovery of systolic shortening (49% versus 31%, p less than 0.05), limited epicardial edema (79.6% versus 81.1% water content, p less than 0.05), and reduced histochemical damage (24% versus 39% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings imply that institution of total vented bypass during ischemia attenuates the infarct process, increases regional recovery of contractility, limits edema and restricts histochemical damage, and may be a useful adjunct to myocardial salvage when controlled reperfusion can be provided. 
2	Excipients in valproic acid syrup may cause diarrhea: a case report. A 5-year-old child receiving valproic acid syrup for seizure control developed diarrhea probably from the excipient ingredients. Each 5 mL of valproic acid syrup contains sucrose 3 g, glycerin 0.75 g, and sorbitol 0.75 g, providing daily amounts of 36, 9, and 9 g of sucrose, glycerin, and sorbitol, respectively. The diarrhea resolved when the child was switched to another valproic acid product. Clinicians should be aware of potential problems that may occur from excipient ingredients in pharmaceutical products when evaluating adverse effects of medications. 
2	A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Pancreatic necrosis is now recognized as a principal determinant of survival in acute pancreatitis. However, it is currently unknown how frequently pancreatic necrosis develops in acute pancreatitis, how often pancreatic necrosis becomes secondarily infected, and whether sterile pancreatic necrosis represents an indication for surgery or can be treated by conservative means. In 194 patients with unequivocal acute pancreatitis, pancreatic necrosis developed in 38 (20%), as documented by dynamic pancreatography, and was confirmed by histologic diagnosis at surgery in 28. All patients were prospectively treated by medical means. Patients with pancreatic necrosis who remained persistently febrile underwent fine needle aspiration for bacterial culture. Infected pancreatic necrosis was demonstrated in 27 of the 38 patients (71%) with pancreatic necrosis and was treated by open drainage, yielding a mortality rate of 15%. All 11 patients with demonstrated sterile pancreatic necrosis, including 6 with pulmonary and renal insufficiency, were successfully treated without surgery. Pancreatic necrosis occurs in approximately 20% of patients with acute pancreatitis and is necessary for the development of secondary pancreatic infection. However, pancreatic necrosis by itself, even when accompanied by organ failure, is not an absolute indication for surgery. A trial of medical treatment for all patients with sterile pancreatic necrosis is in order. 
1	Comparison of a new immunoassay for determining serum pancreatic isoamylase with two standard techniques. A method has recently been developed for measuring serum pancreatic (P) isoamylase, using two monoclonal antibodies specific for salivary isoamylase. We performed this test on 67 healthy controls and 133 patients: 15 with acute pancreatitis, 53 with chronic pancreatitis (20 during painful relapse and 33 in clinical remission), 18 with pancreatic cancer, 41 with nonpancreatic disease with abdominal pain, five with macroamylasemia, and one with total pancreatectomy. Results were compared with those of a wheat germ inhibition method and with electrophoresis on cellulose acetate. A close correlation was found between the results of immunoinhibition assay and those of the other two tests. All patients with acute pancreatitis had abnormally high values in all three tests. In the group with chronic pancreatitis studied during painful relapse, 16 had an increase in P-isoamylase, as determined with the immunoinhibition assay, 13 with the wheat germ inhibition test, and 15 with electrophoresis. In the group with chronic pancreatitis in clinical remission, we found low values in one patient, by immunoinhibition assay, but found low values in 17 and 19 patients by wheat germ inhibition and electrophoresis, respectively. Low P-isoamylase values corresponded to a severe exocrine pancreatic insufficiency. In the group with pancreatic cancer, the three tests showed similar results, and the majority of the patients had normal values. In the patients with nonpancreatic diseases, abnormally high levels were found in five, by immunoassay, in four by electrophoresis, and in three by the wheat germ inhibition method. In the five cases with macroamylasemia, both inhibition assays erroneously demonstrated an abnormal P-isoamylase elevation. The results show that the three tests are equally useful for the diagnosis of acute pancreatitis, or chronic pancreatitis during an acute relapse. In these diseases, the immunoinhibition test would be the preferred assay because it is simple and rapidly performed. 
4	Platelet thromboxane release and delayed cerebral ischemia in patients with subarachnoid hemorrhage. Adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release were studied in 52 patients with subarachnoid hemorrhage (SAH) in order to detect a possible association between altered platelet function and development of cerebral ischemic complications after SAH. Compared to the values on admission, the patients showed significantly increased platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001) 1 to 2 weeks after SAH. The highest values of thromboxane release were seen in patients who deteriorated due to delayed cerebral ischemia with a permanent neurological deficit. Thromboxane release was significantly higher (p less than 0.05) before the onset of severe delayed ischemia in six patients with preoperative ischemia compared to the patients without delayed ischemia. In five others, both ischemic deterioration and elevated thromboxane release occurred after operation. These patients had preoperative values similar to the values in those without ischemic symptoms. The observations suggest that increased platelet aggregability and thromboxane release are associated with delayed cerebral ischemia both before and after surgery. 
3	Diagnostic significance of flow separation within the carotid bifurcation demonstrated by digital subtraction angiography. The presence of an area of reversed blood flow due to flow separation in the interval carotid artery is a normal finding in Doppler ultrasound studies in vivo as well as in model carotid bifurcations. This flow separation phenomenon is caused by the geometry of the carotid bifurcation and the fluid dynamics of blood. We demonstrated the flow separation phenomenon on lateral-projection intra-arterial digital subtraction angiograms in 99 of 100 carotid bifurcations. The mean duration of flow separation was 5.8 seconds, with values up to 14 seconds in normal carotid bifurcations. The presence of this flow separation phenomenon is almost independent of atherosclerotic lesions and is not correlated with cerebral ischemia. Therefore, the angiographic finding of a flow separation has no diagnostic value. However, our results refer to a factor that may be important in the genesis of atherosclerosis at the carotid bifurcation, namely the duration of the stay of blood and its components within the area of flow separation. 
3	Mini-Mental State exam scores vary with education in blacks and whites. Previous studies have suggested that education and race may affect performance on standardized mental status tests. In order to more clearly define these relationships, a prospective longitudinal study was devised to answer two questions: (1) whether race or level of education affects scores on the Mini-Mental State (MMS) exam in non-demented people and (2) what numerical cutpoints maximize the sensitivity and specificity of utilizing the MMS to help diagnose dementia in blacks of varying educational attainment. A total of 100 white and 258 black individuals, recruited from two city hospital primary care geriatric clinics, were evaluated and subsequently followed longitudinally over a 2 1/2 year period in order to assess accurately the presence or absence of dementia. In the non-demented, total MMS scores and performance on each item of the MMS were analyzed, revealing that people with an 8th grade or less education consistently had significantly (P less than .01) worse results than the better educated (9th grade or better) on borough, attention items, recall of table and dog, copying, sentence writing, phrase repeating, and total score. Furthermore, a total of 25% of the lower education group had an MMS score in the 18-23 range, traditionally thought to suggest dementia. There were no consistently significant differences between blacks and whites of equal education. In the better educated groups, using a score of 23 or less to define dementia maximizes the sensitivity and specificity of using the MMS in this diagnosis at 93% and 100%, respectively. In the lower education group, using 17 or less to define dementia maximizes sensitivity and specificity at 81% and 100%, respectively. 
1	Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy. The epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems. From among over 60 patients with ENS presenting with neurologic manifestations, we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies. Associated brain and neurologic abnormalities included gyral malformations in 12 of 12, mental retardation in 13 of 14, seizures in 16 of 17 (including 9 with infantile spasms), and contralateral hemiparesis in 7 of 12. All had ipsilateral epidermal nevi of the head, and several had ipsilateral facial hemihypertrophy. We concluded that these abnormalities comprise a recognizable neurologic variant of ENS that we believe represents the full expression of primary brain involvement. Several patients also had evidence of acquired brain lesions such as infarcts, atrophy, porencephaly, and calcifications, which are best explained by prior ischemia or hemorrhage. Given repeated observations of blood vessel anomalies in ENS patients, we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions. The same cause may be invoked to explain the wide variety of neurologic symptoms reported in ENS patients without hemimegalencephaly. While the cause of ENS remains unknown, several observations suggest a somatic mutation. 
5	Interleukin-8 production in red blood cell incompatibility. Hemolytic transfusion reactions (HTR) are characterized by fever, shock, organ system failure, intravascular coagulation, and possibly death. The same findings may be associated with sepsis. Neutrophils have been implicated in the pathogenesis of HTR, although a mechanism for neutrophil activation has not been shown. In addition, the possible role that cytokines may play in HTR has not been investigated. We show that interleukin-8 (IL-8), a cytokine with chemotactic and neutrophil-activation properties, is produced in whole blood following addition of ABO-incompatible red blood cells, in a dose- and time-dependent manner related to the degree of hemolysis, and is inhibited by inactivation of complement. IL-8 production is accompanied by increased gene expression in the buffy coat. This observation has implications for the understanding of the pathogenesis of and for the treatment of HTR. 
5	T cell subsets (Tc, Th, Ts, Tsi) and IL2 receptor-bearing cells in peripheral blood of patients in the acute phase of alcoholic hepatitis. The present study was designed to evaluate the proportion of T cell subsets and IL2 receptor positive cells in the peripheral blood of patients with acute alcoholic hepatitis (AAH) using monoclonal antibodies to T cell antigens and Tac in a double immunofluorescent technique. The results indicate that the percentage of the total T cells and the intensity of all the T cell antigens are significantly reduced and the percentage of T helper cells and the ratio between Th/Ts cells are significantly increased in AAH when compared to healthy controls. But, significant differences in values observed in this study were not found for the absolute number of these cells. These altered values returned to normal levels during convalescence. 
5	Dysphagia as a manifestation of occult hypoxemia. The role of oximetry during meal times. A 25-year-old woman with severe kyphoscoliosis reported a six-month history of increasing dysphagia to both liquids and solids. A barium swallow and esophageal motility studies showed no significant gastrointestinal abnormalities. Trials of antispasmodic agents were unsuccessful in relieving her symptoms. Pulmonary function tests showed a severe restrictive ventilatory defect (vital capacity = 0.67 L) with adequate oxygenation and alveolar ventilation as reflected by arterial blood gas testing during quiet wakefulness. However, continuous noninvasive oximetry demonstrated desaturation to 85 percent while eating. These transient episodes of desaturation were abolished by the administration of supplemental oxygen delivered by nasal prongs. Following the prescription of supplemental oxygen, dysphagia resolved immediately, with weight gain following over several weeks. We conclude that dysphagia may be a presenting feature of hypoxemia. This case report draws attention to the usefulness of continuous noninvasive monitoring of oxygenation and the clinical importance of at least some transient hypoxemic events. 
2	Giardia lamblia infestation reveals underlying Whipple's disease in a patient with longstanding constipation. Whipple's disease is an uncommon disorder, generally associated with gastrointestinal symptoms; of these, diarrhea is a common feature. We report a case of Whipple's disease associated with chronic constipation which was not diagnosed until after Giardia lamblia infestation had caused diarrhea. To the best of our knowledge this association has not previously been reported. The clinical, laboratory, endoscopic, and manometric aspects are described and discussed. 
1	The use of in situ hybridization to show human papillomavirus deoxyribonucleic acid in metastatic cancer cells within lymph nodes. Southern blot hybridization has been used to identify human papillomavirus types in both primary tumors and lymph node metastases. However, this technique requires fresh-frozen tissue and is incapable of localizing deoxyribonucleic acid sequences to specific cell types in the tumor sample. In contrast, in situ hybridization precisely locates viral sequences within tumor cells while preserving cellular architecture. Further, in situ hybridization requires only small samples of formalin-fixed, paraffin-embedded tissues. Five lymph nodes (from four patients) containing metastatic cervical squamous tumor cells (identified with hematoxylin and eosinophil staining) were analyzed with in situ hybridization techniques with human papillomavirus type 16 deoxyribonucleic acid probes labeled with sulfur 35. The primary cervical cancer from all four patients had been shown to contain human papillomavirus type 16 sequences by Southern blot. Three specimens from two patients clearly showed the presence of human papillomavirus type 16 sequences within the nuclei of metastatic tumor cells, whereas two specimens were nondiagnostic most likely as a result of the small volume of cancer relative to the size of the lymph node. This information indicates that it is the tumor cells themselves that contain viral deoxyribonucleic acid and provides additional evidence linking human papillomavirus with cervical carcinogenesis. 
2	Chylous ascites should suggest constrictive pericarditis even in a patient with cirrhosis. Chylous ascites, a milky, high triglyceride fluid is usually found in patients with lymphatic obstruction from malignancy. We describe a patient with cirrhosis who developed constrictive pericarditis and chylous ascites. Long-standing portal hypertension compounded by elevated central venous pressure provided several pathophysiologic contributions to the formation of the chylous ascites. Chylous ascites even in a cirrhotic requires prompt assessment for conditions leading to elevated central venous pressure. 
5	Effect of severe pulmonary hypertension on the calculation of mitral valve area in patients with mitral stenosis. We studied 50 consecutive patients with mitral valve stenosis (MS) by cardiac catheterization and Doppler echocardiography to assess whether the presence of severe pulmonary hypertension affected the calculation of valve area by Doppler pressure half-time method and by the Gorlin formula using pulmonary capillary wedge pressure as an index of left atrial pressure. Patients with severe mitral regurgitation were excluded. In patients with pulmonary artery systolic pressure (PAS) less than 70 mm Hg (n = 33), there was good correlation between the mitral valve area derived from Doppler echocardiography and from cardiac catheterization (r = 0.85). However, in patients with PAS greater than or equal to 70 mm Hg (n = 17), this correlation was not as good (r = 0.57). In these 17 patients, the Gorlin formula tended to underestimate the valve orifice area (mean valve area 0.85 +/- 0.49 and 1.06 +/- 0.46 cm2 by catheterization and by Doppler respectively, p = NS). Direct measurement of the valve area by two-dimensional echocardiography was possible in 12 of the 17 patients and correlated well with Doppler values (r = 0.91). Hence in the presence of severe pulmonary hypertension, Doppler pressure half-time estimation of mitral valve area is more accurate than is catheterization-derived valve area, using the wedge pressure and the Gorlin formula. 
1	Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer. In ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with head and neck cancer. The incidences of intra-esophageal multiple occurrence of esophageal cancer are 27.3% and 26.3% in those with associated head and neck cancer and gastric cancer, respectively, and higher than 7.1% in those without such a concurrent cancer. There was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers, except for the higher incidence of metachronous occurrence in the former. These findings suggest that, in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer, intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis. 
5	Recovery of CD3+ and CD5- lymphocyte subpopulation after autologous bone marrow transplantation and chemotherapy. Although most circulating T cells in normal subjects express both CD3 and CD5 antigens on the cell surface, a small number lack the CD5 antigen. Recipients of allogeneic bone marrow transplants develop increased numbers of CD3+ CD5- cells, particularly those who develop graft versus host disease (GVHD). This CD3+ CD5- population may rise transiently in patients who have received an autologous bone marrow transplant (BMT) and in patients following completion of intensive chemotherapy for acute myeloid leukaemia (AML). These findings suggest that these CD3+ CD5- cells are a normal component of the regenerating lymphoid system after BMT or chemotherapy. 
5	Long-term results of operation for non-small cell lung cancer in the elderly. We surgically treated 185 patients with non-small cell lung cancer who were 70 years old or older. The operative mortality rate was 3%, and the 5-year survival rate was 48%. The mortality and prognosis were similar to those in younger patients. The number of elderly patients who smoked heavily or who had ventilatory defects was high, but the incidence of pneumonectomy was low. There were no differences based on age in regard to histological type, TNM classification, and curability. Pulmonary complications occurred in 21% of the elderly patients and were correlated with preoperative pulmonary function and smoking habits. When the elderly are to undergo elective pulmonary resection for lung cancer, the preoperative evaluation of pulmonary function should be thorough, and both preoperative and postoperative physical therapy should be given. If postoperative pulmonary function is predicted to be less than 0.8 L/m2 of vital capacity and 0.6 L/m2 of forced expiratory volume in 1 second, a limited resection or nonsurgical therapy should be considered. 
5	Subacute necrotizing sialadenitis. Twelve cases of a heretofore unreported minor salivary gland disease have been reported. Although an infectious cause is suspected for this self-limiting inflammatory process, the actual cause remains unknown. It typically presents as a unilateral, erythematous, nonuclerated but painful, solitary firm swelling of the posterior hard palate. Patients are most often young white men who have spent several weeks in a new environment with a group of people living in close quarters such as military barracks. 
5	Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats. The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195 +/- 8 to 125 +/- 5 and 148 +/- 3 mm Hg, respectively [mean +/- SEM]; p less than 0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911 +/- 155 to 1,244 +/- 101 and 1,388 +/- 59 microns 2, respectively, compared with 1,405 +/- 95 microns 2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 +/- 6 to 62 +/- 2 mm Hg with cilazapril versus 79 +/- 5 mm Hg for hydralazine compared with 60 +/- 4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 +/- 4 to 100 +/- 4 microns for cilazapril versus 91 +/- 3 microns for hydralazine compared with 107 +/- 3 microns for untreated WKY rats). 
5	A giant renal artery aneurysm diagnosed post partum. We report a case of a 5.8 cm. right renal artery aneurysm diagnosed intact 8 weeks post partum. Rupture of a renal arterial aneurysm during pregnancy is a rare but well described catastrophic event. There are no previous reports of an intact renal artery aneurysm diagnosed either ante partum or post partum. To our knowledge, this also represents the largest reported renal artery aneurysm. The aneurysm was repaired successfully with kidney salvage and closure of the fistulous connection to the renal vein. 
1	In vivo phosphorus 31 magnetic resonance spectroscopy of human uveal melanomas and other intraocular tumors. We studied the feasibility of using the surface coil probe technique for the noninvasive in vivo study of ocular tumors by phosphorus 31 magnetic resonance spectroscopy. The characteristic organophosphate metabolites of suspected uveal melanomas before proton beam irradiation were determined qualitatively by phosphorus 31 magnetic resonance spectroscopy in vivo using a three-turn surface coil. Spectra of choroidal hemangioma, osteoma, and metastasis were also obtained in vivo and compared with those of uveal melanomas. Analysis of spectra performed at 1.5 T showed significant peaks of phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and adenosine 5'-triphosphates. The unusually high concentration of phosphodiesters may be considered as a marker for uveal melanomas and other choroidal tumors. By analyzing the ratio of phosphocreatine to phosphodiesters spectral area values, we interpreted qualitatively spectra of intraocular tumors to differentiate malignant tumors from benign lesions. Nevertheless, the main limitation of interpreting the spectra was their contamination by signals from surrounding tissues. 
5	The molecular biology of acute myeloid leukemia. Proto-oncogene expression and function in normal and neoplastic myeloid cells. Proto-oncogenes and suppressor genes fall into four functional groups: growth factors, growth factor and hormone receptors, signal transducers, and transcriptional regulatory factors. Many of these genes are selectively expressed in myeloid cells and may play a role in normal development of the myeloid lineages. Furthermore, chromosomal rearrangements, deletions, and mutations may disrupt the normal expression or function of these genes, promoting MPD and leukemogenesis. Many of the genes altered by karyotypic abnormalities in myeloid disorders are only beginning to be identified. Future studies undoubtedly will determine the molecular mechanisms whereby these genes, residing at karyotypic breakpoints in myeloid disorders, promote neoplastic transformation of myeloid cells. 
1	DNA image cytometry. A prognostic tool in squamous cell carcinoma of the esophagus? In 45 patients who underwent an esophagus resection due to a squamous cell carcinoma, in addition to the TNM classification and usual morphologic criteria, the paraffin-embedded material underwent deparaffinization, was rehydrated, and was mechanically and enzymatically processed into a single-cell solution. For evaluating the DNA histogram this was analyzed with the help of automatic single-cell cytophotometric study. The method, contrary to that of flow cytometric study, allows for the selective analysis of tumor cells due to the electronically, previously given selection criteria, whereas artifacts, stroma, and infection cells remain excluded from analysis. The multivariate analysis shows that the prognosis is only correlated with DNA content of the tumor cells. Patients with diploid tumors had a median survival time of 32 months as compared with the 22 months of patients with hypotriploid tumors, and 6.5 months with hypertriploid tumors. DNA cytometric analysis should be included when diagnosing patients with esophagus carcinoma. 
1	A modified rhombic transposition flap and its application in dermatology. A modified rhombic transposition flap based around a circular primary defect is described. We have found it to be a versatile design that produces good cosmetic results with a low incidence of postoperative complications. It has become the most frequently used transposition flap in our dermatologic practice. 
1	Histopathologic grading of salivary gland neoplasms: II. Acinic cell carcinomas. Acinic cell carcinomas display varied cytoarchitectural patterns of growth that should allow for formulation of histopathologic grading. Grading of these carcinomas may serve to identify subsets whose biologic behavior is more aggressive than the usually accepted low-grade behavior of acinic cell carcinomas as a group. To that end, a three-level histopathologic grading scheme is presented. 
5	The role of the chest roentgenogram in febrile neutropenic patients. In a retrospective review of patients with neutropenia and fever, we sought to determine how often roentgenograms detected pulmonary disease, especially pneumonia, not suggested by signs and symptoms. Further, we sought to determine how often therapy was changed as a result of roentgenographic findings. Overall, 41 (22%) of 187 chest roentgenograms obtained during initial febrile episodes, recurrent fevers, or persistent fevers were abnormal. While most patients had signs and symptoms suggesting the presence of pulmonary disease, 17% had roentgenographic abnormalities detected in the absence of such findings. During initial febrile episodes, therapy was not changed in response to findings on the chest roentgenogram. However, during episodes of persistent or recurrent fever, findings on chest roentgenograms led to changes in therapy in eight (61%) of 13 episodes of which six (40%) resulted in clinical improvement. Chest roentgenograms were therefore found to be an important diagnostic tool in evaluating recurrent or persistent fever in the neutropenic patient but of little use during initial febrile episodes. 
5	Chronic musculoskeletal pain and depressive symptoms in the general population. An analysis of the 1st National Health and Nutrition Examination Survey data. Chronic pain and depression frequently occur together. A selection bias afflicts all hospital clinic and family practice populations in which this relationship has been examined. We report here some of the results from civilian populations outside institutions, examined in the United States in national surveys. The findings are based upon the recollection of individuals with respect to the period of 12 months prior to interview and upon the occurrence of depression in the previous week as indicated by the answers to the Depression Scale of the Centre for Epidemiologic Studies (CES-D). They indicate that 14.4% of the United States population between the ages of 25-74 suffer from definite chronic pain related to the joints and musculoskeletal system. Another 7.4% have some pain of uncertain duration. Eighty-three percent of the definite pain group received treatment. Chronic pain subjects scored significantly higher than normals on the CES-D (10.68 +/- S.E.M. 0.76 vs. 8.05 +/- 0.23, P less than 0.01) with subjects with pain of uncertain duration scoring similar to the definite chronic pain population (11.13 +/- 0.76). Using a high cut-off score for depression. 18% of the population with chronic pain were found to have depression. This is in contrast to 8% of the population who did not have chronic pain. 
5	Rice-based oral electrolyte solutions for the management of infantile diarrhea BACKGROUND. In infants the treatment of acute diarrhea with glucose-based solutions results in rehydration but does not reduce the severity of diarrhea. Oral rehydration with solutions based on rice powder may reduce stool output as well as restore fluid volume. METHODS. We designed a prospective, randomized, double-blind study to evaluate the efficacy of two rice-based rehydration solutions and a conventional glucose-based solution. Solution A contained only rice-syrup solids, solution B contained rice-syrup solids and casein hydrolysate, and solution C, the glucose-based solution, served as control. The study subjects were 86 mildly to moderately dehydrated infant boys, 3 to 18 months old, who were admitted to a children's hospital with acute diarrhea. We measured fluid intake, fecal and urine output, and absorption and retention of fluid, sodium, and potassium at intervals for 48 hours in all 86 infants. RESULTS. The mean (+/- SE) fecal output was significantly lower in the infants given solution A (group A infants) than in the infants given solution C (group C) (29 +/- 4 vs. 46 +/- 7 ml per kilogram of body weight, P less than 0.05) during the first six hours of therapy. The infants in group A also had greater fluid absorption (221 +/- 16 vs. 167 +/- 9 ml per kilogram, P less than 0.05) over the entire 48 hours of therapy and greater potassium absorption (1.6 +/- 0.2 vs. 0.6 +/- 0.1 mmol per kilogram, P less than 0.05) during the first six hours than the infants in group C. Solution B offered no advantages over solution A. CONCLUSIONS. Solutions containing rice-syrup solids were effective in the rehydration of infants with acute diarrhea. They decreased stool output and promoted greater absorption and retention of fluid and electrolytes than did a glucose-based solution. 
5	Significance of blasts in low-cell-count cerebrospinal fluid specimens from children with acute lymphoblastic leukemia. The purpose of this study was to determine whether the presence of more than 5% blasts in a differential count of cytocentrifuged cerebrospinal fluid (CSF) with less than 6 leukocytes/microliter was predictive of central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL). A double concentrate method of cytocentrifuge preparation was used to analyze 4543 consecutive CSF specimens from 349 children with ALL between January 1, 1982, and September 30, 1988. One hundred nine CSF specimens from 58 evaluable children had less than 6 leukocytes/microliter and more than 5% blasts on cytocentrifuge differential count (low-cell-count specimen with blasts [LCB]). During the study period, 25 of 332 evaluable children (7.5%) had CNS leukemic recurrence. In 22 of 25 (88%), the CNS relapse was preceded by at least one abnormal low-cell-count CSF specimen. One of 34 patients with a single LCB at diagnosis (3%) had subsequent CNS relapse compared with five of eight patients (62.5%) with a single LCB during remission (P = 0.0002). Of 16 children with two or more LCB during remission, nine (56%) had CNS relapse defined by standard criteria, whereas six additional patients in this group were declared to be in CNS relapse on the basis of their repetitive LCB. Whether diagnosing CNS recurrence earlier in its course based on a modification of the definition of CNS leukemia will change the frequency of subsequent adverse events or make possible decreased intensity of CNS retreatment remains to be determined. 
2	Unique features of Helicobacter pylori disease in children. In a six-year period, 41 children had endoscopically documented duodenal ulcer disease or primary H. pylori antral gastritis without duodenal ulcer. Of 37 children with H. pylori gastritis, group 1 comprised 23 patients with duodenal ulcer disease and group 2 had 14 patients without ulcers (primary H. pylori gastritis). Group 3 comprised four children with duodenal ulcer disease and H. pylori-negative antral biopsies. During the study period, all primary chronic ulcer disease was duodenal; no primary chronic gastric ulcer was present. Two distinct types of duodenal ulcer disease were identified; the majority (85%) was always associated with significant active H. pylori antral gastritis (group 1). The minority (15%) had virtually absent gastritis and no H. pylori (group 3). Native Indian children were represented in group 1 quite out of proportion to the referral population and had the most severe disease. While it is established that a higher prevalence of asymptomatic H. pylori infection exists in non-Caucasians, this appears to be the first demonstration of a higher prevalence of symptomatic ulcer disease in non-Caucasian children or adults. Caucasian children tended to have primary H. pylori gastritis (group 2) or duodenal ulcer without H. pylori (group 3). Antral nodularity was found to be an important specific endoscopic sign, unique to those children with H. pylori disease. It has not been described in adult H. pylori disease. Non-Caucasian children, especially Native Indians, in British Columbia have more prevalent and more severe H. pylori disease than Caucasians. Endoscopy with gastric antral biopsies is necessary to distinguish different types of duodenal ulcer disease and to diagnose primary H. pylori gastritis. 
1	A human CD5+ B cell clone that secretes an idiotype-specific high affinity IgM monoclonal antibody. We previously demonstrated the occurrence of a naturally arisen human anti-idiotypic B cell clone, that we transformed with EBV (EBV383). We show evidence that EBV383 not only expresses the CD5 surface Ag, but also contains the 2.7-kb mRNA transcript encoding this protein. In addition, we show the presence of the 3.6-kb mRNA precursor. Most Ig produced by CD5+ B cells are polyreactive natural IgM antibodies encoded by unmutated copies of germline VH genes. However, in this study we present data demonstrating the monoreactive high affinity character of the anti-idiotypic antibody (mAb383) produced by EBV383. These data are in agreement with our previous observations, showing that the VH chain of mAb383 is encoded by an extensive somatically mutated VHV gene in a way that is consistent with an Ag-driven immune response. A possible role for this remarkable anti-idiotypic antibody in the maintenance of B cell memory is discussed. 
5	Asymptomatic periapical radiolucent lesion found in an area of previous trauma [published erratum appears in J Am Dent Assoc 1991 Feb;122(2):18] The case of an anterior mandibular radiolucent area, which unexpectedly yielded salivary gland tissue, is described. Salivary gland depressions in the posterior mandible are readily recognized because of their almost pathognomonic radiographic appearance. A salivary gland inclusion in the anterior mandible in the proximity of teeth may create a diagnostic dilemma where superimposed periapical pathosis is present. The clinical importance lies in the recognition and appropriate treatment of the lesion. For the anterior salivary gland inclusion, a biopsy and a microscopic examination provide the most reliable diagnosis. 
1	How district health authorities organise cervical screening [published erratum appears in BMJ 1990 Nov 24;301(6762):1209] OBJECTIVES--To examine how district health authorities organised cervical screening with respect to Department of Health guidelines and to determine their assessment of the problems encountered. DESIGN--Postal questionnaire sent to all 190 district health authorities in England in 1989. PARTICIPANTS--190 District health authorities in England. MAIN OUTCOME MEASURES--Population coverage of screening, quality of smear testing, and follow up of abdominal test results in comparison with national guidelines for district cervical screening services, and problems encountered by districts. RESULTS--Replies were received from 178 (94%) of districts, in 143 of which the person named as responsible for cervical screening contributed. All districts implemented a computer managed scheme, 150 by the target date of 31 March 1988, but not all of these conformed with the guidelines. At the time of the survey only just over half called women in the target age group of 20-64 and only 70% expected to meet the target date of 13 March 1993 for completing the call. Considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage, quality of testing, and follow up of abnormal results. The problems most commonly identified by the districts (n = 174) were laboratory workload (107, 61%), computer software (104, 60%), availability of resources (78, 45%), non-attendance (77, 44%), rate of opportunistic screening (62, 36%), and investigation and treatment (60, 34%). CONCLUSIONS--Current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer. 
3	Hydrocephalus: overdrainage by ventricular shunts. A review and recommendations. Selected literature review of the clinical course of patients with ventricular shunts for hydrocephalus shows that the effects of cerebrospinal fluid overdrainage are subdural hematoma, craniosynostosis, slit ventricle syndrome, and low intracranial pressure syndrome. These occur sequentially at different age groups, but approximate averages of incidence and time of occurrence after first shunt reveal an overall incidence of 10%-12% for at least one of these appearing at 6.5 years after shunting. The basic etiology, diagnosis, and variety of treatment modalities available are reviewed, including the need for shunt closing intracranial pressure control. Included is a hydrocephalus program designed to minimize the need for long-term extracranial shunts and to maximize therapeutic intracranial procedures for hydrocephalus. 
2	Seronegative juvenile rheumatoid arthritis and mast cell-associated gastritis. We describe 4 children with seronegative inflammatory arthritis who had persistent, severe nausea and abdominal pain over several months, in spite of vigorous medical therapy, including antacids and histamine H2 receptor antagonists. Endoscopy and biopsy of gastric and duodenal mucosa showed antral gastritis and an increased number of mast cells in 3 of the 4 patients. In the fourth patient, urinary histamine levels were elevated. These findings suggest an association between inflammatory arthritis and localized mast cell disease in some individuals. Further studies are needed to determine whether this association represents an independent syndrome or whether mast cell-related disease is secondary to long-term treatment with nonsteroidal antiinflammatory drugs in children with mild arthritis. 
1	Epithelial cells immortalized by human papillomaviruses have premalignant characteristics in organotypic culture. Three HPV-16--and four HPV-18--immortalized human foreskin keratinocyte cell lines were analyzed on organotypic epidermal raft cultures at various passage levels. This culture system allowed normal cultured keratinocytes to stratify and differentiate in a manner similar to normal epidermis. All seven HPV-immortalized cell lines displayed epidermal morphologies on organotypic cultures, which were clearly abnormal and resembled premalignant lesions in vivo. Features of premalignant lesions that were shared by all of the HPV-immortalized cell lines included disorganized tissue architecture, mitotic cells present throughout the living layers of the epidermal sheet, abnormal mitoses, enlarged nuclei, and variable cell size and shape. Most HPV-immortalized cell lines were stable in terms of epidermal morphology with long-term passage in culture. Two of the HPV-18--immortalized cell lines, however, lost all morphologically apparent terminal squamous differentiation potential after long-term passage in monolayer culture. These results strongly support the idea that immortalization of squamous epithelial cells in culture by HPV-transforming genes generates a morphologically premalignant cell. 
1	Dioxin-inducible, Ah receptor-dependent transcription in vitro. We have developed a homologous in vitro transcription system that requires (i) 2,3,7,8-tetrachlorodibenzo-p-dioxin (called TCDD or dioxin), (ii) the Ah receptor, and (iii) a dioxin-responsive enhancer for activity. Unfractionated nuclear extracts from mouse hepatoma cells contain an inhibitor and fail to direct transcription in vitro. However, following phosphocellulose chromatography and reconstitution, the fractionated nuclear extract directs accurate transcription in vitro, using as a template the promoter/enhancer region from the mouse cytochrome P1-450 gene (Cyp1a1) linked to a "G-free cassette" (which generates a transcript with no guanosine residues). Extracts from TCDD-treated cells exhibit higher activity than extracts from untreated cells when transcribing a template containing both the promoter and enhancer but not when transcribing a template containing the promoter alone. Extracts from Ah receptor-defective cells fail to direct in vitro transcription in a TCDD-inducible fashion. A regulatory element that contains two binding sites for the liganded Ah receptor plus a truncated Cyp1a1 promoter suffices to direct TCDD-inducible, Ah receptor-dependent transcription in vitro. The inducible, receptor-dependent, enhancer-dependent properties of this system make it appropriate for analyzing in vitro the mechanism of dioxin action and the function of the Ah receptor. 
3	Emergence of recreational drug abuse as a major risk factor for stroke in young adults OBJECTIVE: To investigate the clinical and epidemiologic relations between recreational drug abuse and stroke in young persons. DESIGN: A case-control study based on medical records. SETTING: San Francisco General Hospital, a 400-bed municipal hospital. PATIENTS: Consecutive sample of 214 patients aged 15 to 44 years, admitted between 1979 and 1988 with a diagnosis of ischemic or hemorrhagic stroke. An equal number of control patients admitted with diagnoses of status asthmaticus, acute appendicitis, or acute cholecystitis were matched to stroke patients by age, sex, and year of hospitalization. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients with stroke (34%) were drug abusers compared with 18 (8%) of the controls. In 47 patients with stroke, temporal proximity of drug administration (n = 34) or infectious endocarditis (n = 13) suggested a direct association between drug abuse and stroke. After controlling for other identifiable stroke risk factors, the estimated relative risk for stroke among drug abusers compared with that among non-drug abusers was 6.5 (95% CI, 3.1 to 13.6), and this increased to 49.4 (CI, 6.4 to 379.0) for those patients whose symptoms began within 6 hours of drug administration. Among patients less than 35 years of age, drug abuse was the most commonly identified potential predisposing condition (47%), and it was the only condition with a significantly elevated relative risk for stroke (11.7; CI, 3.2 to 42.5). Further, a substantial rise in the proportion of drug-related strokes was observed in the last 3 years of the study (31% in 1986 to 1988, compared with 15% in 1979 to 1985, P = 0.008). Cocaine, especially recently, was the drug used most frequently in drug-related strokes. CONCLUSION: In an urban population such as ours, recreational drug abuse appears to be a prominent and growing risk factor for strokes in young adults. 
3	Perivascular innervation of the cerebral arteries in spontaneously hypertensive rats--an immunohistochemical study. Perivascular innervation in cerebral arteries of spontaneously hypertensive rats and of normotensive Wistar-Kyoto rats was studied. Adrenergic nerve fibers and neuropeptide Y-containing nerve fibers, indicative of vasoconstrictor nerves, were denser in all cerebral arteries of spontaneously hypertensive rats than those of Wistar-Kyoto rats. In contrast, cholinergic nerve fibers and vasoactive intestinal polypeptide, substance P-containing nerve fibers, indicative of vasodilator nerves, remained unchanged in all cerebral arteries of spontaneously hypertensive rats, as compared with findings in the Wistar-Kyoto rats. Thus, not only adrenergic nerve fibers but also neuropeptide Y-containing nerve fibers may play an important role in preventing the disruption of the blood-brain barrier and the development of hypertensive encephalopathy in spontaneously hypertensive rats. 
2	A case of lisinopril-induced lithium toxicity We describe a patient who developed lithium toxicity when lisinopril was substituted for clonidine. Possible mechanisms of angiotensin-converting enzyme (ACE) inhibitor-induced lithium toxicity are discussed. Aggressive serum lithium concentration monitoring and a reduction in the dose of lithium is advised when using ACE inhibitors because of disturbances and shifts in fluid and electrolyte balance. 
4	Prognostic value of electrophysiology testing in asymptomatic patients with Wolff-Parkinson-White pattern [published erratum appears in Circulation 1991 Mar;83(3):1124] The prognostic value of electrophysiology testing was studied in 75 asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. All patients underwent electrophysiology testing at entry to the study and were followed up annually for a total of 348 patient-years (median, 4.3 years). There were 44 male and 31 female patients, and age at enrollment ranged from 7 to 77 years (mean, 34 +/- 14 years). The median effective refractory period of the accessory pathway was 293 msec (interquartile range, 280-310 msec), and the median shortest RR interval between preexcited beats during atrial fibrillation (SRR) [corrected] was 274 msec (240-320 msec). Twenty-three patients had an SRR of 250 msec or less and eight patients had a median shortest SRR interval of 200 msec or less. Twelve patients had inducible sustained reciprocating tachycardia, 10 patients had inducible nonsustained reciprocating tachycardia, and 23 patients had inducible sustained atrial fibrillation. Twenty patients (27%) lacked retrograde conduction over the accessory pathway. No patient died suddenly during a median follow-up of 4.3 years. Six patients (8%) became symptomatic with documented supraventricular tachycardia, of whom two underwent operative ablation of their accessory pathways. No patient with absent retrograde accessory pathway conduction during the electrophysiology study became symptomatic. Inducible sustained or nonsustained reciprocating tachycardia at electrophysiology study did not predict the development of subsequent symptomatic supraventricular tachycardia. Nine patients lost preexcitation during follow-up. Age at enrollment (relative risk/decade, 1.4; 95% confidence interval, 1.0-1.8) and anterograde accessory pathway refractory period (relative risk, 1.06/10 msec; 95% confidence interval, 1.0-1.12) were independent predictors of loss of preexcitation. 
5	Pseudohypoglycemia in adult victims of adolescent incest. Two patients with complaints of hypoglycemia came for evaluation, and both complained of intermittent episodes of mental dullness, disorientation, confusion, and palpitations relieved by eating. Plasma glucose levels at the time of symptoms were always above 70 mg/dL. Initial onset of symptoms was within 1 to 2 years after cessation of repeated incest, and on recognition of this, both patients associated the onset of episodes of similar feelings with the acts of incest. Recognition of this connection did not decrease the frequency of episodes. Both persistently refer to the episodes as "hypoglycemia" despite recognition that no glucose level below 70 mg/dL has been recorded during an episode. Recurrent episodes of derealization and depersonalization in both patients appear to be sequelae of adolescent incest experiences, but these patients cling to the label "hypoglycemia," perhaps in part because they are unwilling to accept a psychiatric diagnosis for their episodes. 
1	Mapping the site of interaction between murine IgE and its high affinity receptor with chimeric Ig. We have investigated the interaction of mouse (m) IgE with its Fc epsilon RI on rat basophilic leukemia cells using a set of chimeric Ig that were constructed by exchanging homologous H chain C domains between human (hu) IgG1 and mIgE. Binding affinities were examined with equilibrium and kinetic measurements, and we found that epsilon/C gamma 3 (mIgE with C epsilon 4 replaced by C gamma 3) was indistinguishable from mIgE. The huIgG1 and the other chimeric Ig, which did not contain both C epsilon 2 and C epsilon 3, did not bind detectably to rat basophilic leukemia cells (Ka less than 10(6) M-1). The ability of these chimeric Ig to stimulate a cellular response (degranulation) in the presence of multivalent Ag was also tested. The epsilon/C gamma 3 was indistinguishable from mIgE in eliciting a high level of degranulation, whereas the other chimeric Ig stimulated no response even when they were preaggregated to enhance their binding avidity. These results demonstrate that C epsilon 4 may be replaced by C gamma 3 without affecting the binding and cell activating properties of mIgE. The lack of binding by the other chimeric Ig indicates that both C epsilon 2 and C epsilon 3 are necessary for the binding interaction. 
5	Acute hemorrhagic edema of infancy (AHEI)--a variant of Henoch-Schonlein purpura or a distinct clinical entity? Acute hemorrhagic edema of infancy (AHEI) is an acute cutaneous leukocytoclastic vasculitis (LCV) of infants. The clinical picture has a violent onset with a short benign course followed by spontaneous complete recovery. We report 12 infants with AHEI who were studied clinically, serologically, and immunohistologically. Edema and palpable purpuric skin lesions were present in all infants who were in good general condition. Serologic studies were unremarkable. Light microscopic examination of the skin biopsy specimens revealed LCV as in Henoch-Schonlein purpura (HSP). Direct immunofluorescent study revealed depositions of various immunoreactants, including fibrinogen, C3, IgG, IgM, IgA, and IgE (100%, 100%, 22%, 78%, 33%, and 33%, respectively) in the wall and around the small vessels. Similar deposition of Clq was also present in three infants in whom Clq could be studied (100%). The clinical similarities and differences between AHEI and HSP have been discussed in the literature. AHEI is observed before 2 years of age and is confined to the skin. The skin lesions of HSP are more polymorphic. Although histopathologic findings are similar, the immunohistologic pattern found in our series of AHEI is rather different from the pattern of HSP. Taking all of these findings into account, we suggest that AHEI should be considered as a separate, clinicopathologic entity or a possible variant of HSP. The more descriptive term "acute benign cutaneous LCV of infancy" is offered for this clinicopathologic entity. 
3	Overt hepatic encephalopathy precipitated by zinc deficiency. Encephalopathy in liver disease may be unresponsive to protein restriction, lactulose, and neomycin. Zinc supplements have been reported to improve psychometric performance in liver cirrhosis, but the importance of zinc deficiency in overt hepatic encephalopathy has not yet been clearly established. A patient with severe recurrent hepatic encephalopathy was studied to determine the relation between her signs of encephalopathy and zinc deficiency. The study included a period in which zinc deficiency was artificially induced by oral histidine. An episode of overt encephalopathy occurred that was identical to earlier episodes and responded to oral zinc. The study showed an association between encephalopathy and zinc deficiency by successive zinc depletion and supplementation regimens. Long-term zinc supplementation improved severe recurrent hepatic encephalopathy and therefore the quality of life. 
1	Clinical significance of colonic fermentation. Recent evidence of the potential benefits of short chain fatty acids has prompted renewed interest in the area of human colonic fermentation. This paper reviews the clinical and metabolic consequences of colonic fermentation. 
2	Gastric infarction. We have described a patient with an acute condition of the abdomen who had infarction of the stomach and the small intestine due to atheromatous thrombus of celiac and superior mesenteric arteries. We believe this unusual simultaneous occurrence of gastric and small intestinal infarction is coincidental. The outcome of gastric infarction is frequently fatal. 
1	Vulvar condylomas and squamous vestibular micropapilloma. Differences in appearance and response to treatment. A study of 37 women with typical condylomas and so-called squamous micropapilloma was undertaken to determine their response to systemic interferon and/or podophyllin treatment. Thirty lesions were classified as condylomas and 9 as squamous micropapillomas; two women had both lesions. Twenty-six (87%) of 30 condylomas responded, whereas only 1 (11%) of the 9 cases of micropapillomatosis showed a partial response (P less than .001) to podophyllin and/or interferon. Twenty-six biopsies from condylomas in which sufficient DNA was available for analysis contained human papillomavirus (HPV) DNA sequences that hybridized to an HPV 6 + 16 probe mix under nonstringent conditions. In contrast, HPV DNA sequences could not be detected in any of the nine cases of micropapillomatosis. Immunoperoxidase studies performed on these lesions failed to demonstrate viral capsid antigen. Thus, despite certain similarities in the clinical presentation and microscopic features of condylomas and squamous micropapillomas, it is not clear at present whether micropapillomas are HPV-related lesions. 
1	Surgical treatment of brain metastases in malignant melanoma. The authors report the results of a retrospective review of 13 patients who underwent 19 craniotomies for resection of metastatic malignant melanoma at the University of Colorado (Denver, CO) between 1983 and 1989. There was preoperative evidence of extracranial disease in 11 patients. Eight patients had more than one intracranial metastasis at operation. Intraoperative ultrasound was used in 18 of the 19 craniotomies to minimize surgical trauma to the brain. The 30-day mortality was zero. The 30-day morbidity was minimal. No patient acquired a new neurologic deficit as a result of surgery. All patients regained at least their preoperative level of functioning. Six of the patients who were living at the time of review have been followed for 4 to 25 months (median, 7.5 months). The seven patients who were dead at the time of review survived 4 to 18 months (median, 10 months). These results compare favorably with the survival of untreated patients with metastatic melanoma to the brain (median, 1 month), patients treated with radiation therapy alone (median, 2-4 months), and those treated with chemotherapy alone (median, 2-4 months). The excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this problem with little morbidity and mortality even in the presence of other metastases. 
2	Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation defect in the offspring. A case of a 29-year-old woman who has had two episodes both clinically and biochemically consistent with acute fatty liver of pregnancy is described. These episodes occurred in two successive pregnancies, and liver biopsy confirmed the diagnosis in the second pregnancy. Both pregnancies were managed by prompt fetal delivery; on both occasions this led to a complete biochemical resolution of the liver function abnormalities. Two healthy babies were delivered by ceasarian sections. This case is of particular importance because a rapidly progressive and devastating illness developed in both infants, leading to death at 6 1/2 and 6 months, respectively. The illness in both babies was characterized by wide-spread fatty infiltration of several vital organs and a failure of any treatment to influence the outcome of that illness. Studies suggested that the illness in the children was caused by a still ill-defined disorder of fatty acid oxidation. The biochemical disorder evidenced in this family is discussed, in an attempt to shed light on the etiology of acute fatty liver of pregnancy. 
1	Demonstration of Lipiodol in paraffin sections using a modified silver impregnation technique. To demonstrate postangiographic Lipiodol (LIP) in hepatocellular carcinoma (HCC) in paraffin sections, direct impregnation of formalin-fixed tissue blocks with silver nitrate (AgNO3) was followed by routine processing. LIP appeared as black globules in the sinusoids. Ninety-four tissue blocks from 13 postangiographic LIP HCCs and 69 from 8 non-LIP HCCs and 4 fatty livers were studied. Seventy-two of 73 negative controls and all positive blocks as seen on soft tissue radiographs (STRs) were correctly coded (specificity 98.6%, sensitivity 100%). Twenty-six of the 44 LIP-negative areas on STRs from LIP cases contained scanty globules of less than 10 microns in diameter. Fatty change gave no positive readings. Thus, modified AgNO3 impregnation is a simple, accurate means of detecting LIP in high-quality paraffin sections suitable for tumor diagnosis and, if applied to postangiographic LIP, ultrasonographically guided liver biopsy, can verify that a biopsy has reached a suspected tumor focus. 
4	How long can a coronary reperfusion catheter be placed in acute coronary occlusion following failed transluminal coronary angioplasty? A case report. A coronary reperfusion catheter (CRC) is designed to preserve antegrade coronary flow when abrupt coronary closure occurs during percutaneous transluminal coronary angioplasty (PTCA). Insertion of the catheter to an occluded coronary artery for a few hours has been reported to be effective for myocardial salvage: however, it is unknown how long the catheter can be kept in place without causing extension of myocardial ischemia. The authors experienced a case in which the CRC was kept in place for twenty-four hours for anticoagulant therapy of an occluded coronary artery following failure of PTCA. This case suggests that adequate anticoagulant therapy can prolong the period during which a CRC can be kept in place if emergency coronary bypass surgery cannot be performed immediately after failure of coronary angioplasty. 
3	A prognostic system for transient ischemia or minor stroke. OBJECTIVE: To build a prognostic system for patients with carotid transient ischemic attack or minor stroke. DESIGN: Inception cohort study with 2-year follow-up. SETTING: Urban community teaching hospital. PATIENTS: Eligible patients (n = 142), identified on a carotid ultrasound roster, had been hospitalized between 1984 and 1987 within 30 days of a first carotid transient ischemic attack or minor stroke. MEASUREMENTS: Stroke or death within 2 years. MAIN RESULTS: Three factors were associated with stroke or death: age of more than 65 years, diabetes, and hypertension. Based on regression coefficients, age of more than 65 years was assigned 3 points; diabetes, 3 points; and hypertension, 2 points. An initial prognostic system comprised risk groups 1 (0 points), 2 (1 to 5 points), and 3 (6 to 8 points). Outcome rates in the three groups were 2%, 31%, and 54% (P less than 0.0001), respectively. In an independent test sample, the corresponding outcome rates for the initial system were 12%, 21%, and 31% (P = 0.04). A final prognostic system, including two additional predictors (coronary heart disease [1 point] and the distinction between stroke and transient ischemic attack for the baseline event [2 points]), comprised risk groups 1 (0 to 2 points), 2 (3 to 6 points), and 3 (7 to 11 points). Corresponding outcome rates were 3%, 27%, and 48% (P less than 0.001) in the original cohort and 10%, 21%, and 59% (P less than 0.001) in the test cohort. CONCLUSION: For selected patients with carotid transient ischemia or minor stroke, five clinical features can be combined to stratify effectively the risk for a subsequent stroke or death. 
5	Deletion of the human retinoblastoma gene in primary leukemias. As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study. 
4	Role of dipyridamole-echocardiography test in the evaluation of coronary reserve after coronary artery bypass grafting. The object of this study was to assess the usefulness of the dipyridamole-echocardiography test in the early evaluation of coronary artery bypass grafting, when the use of an exercise stress test is precluded. We studied 39 consecutive patients (37 men and two women, mean age 57.3 years) referred to our institute for elective coronary artery bypass. Five patients had single, 12 patients double, 20 patients triple vessel disease, and two had left main stem disease. Nineteen left internal mammary artery grafts, 20 sequential grafts, and 39 single vein grafts were performed. All the patients were subjected to the test before (time range 1 to 3 days) and after (time range 6 to 10 days) the operation in the absence of therapy. Dipyridamole was administered intravenously 0.56 mg/kg over 4 minutes (low dose); if no effect was apparent, an additional 0.28 mg/kg over 2 minutes (high dose) was given. During the test, blood pressure and a twelve-lead electrocardiogram were monitored. An arbitrary wall motion score was derived by dividing the left ventricle into six regions and grading from 0 to 3-normokinetic, hypokinetic, akinetic, and dyskinetic zones. Preoperatively the test was positive in 38 patients as evidenced by wall motion abnormalities (36 patients had electrocardiographic changes) and in one patient by electrocardiographic changes and chest pain; 22 tests were positive after the low dose and 17 after the high dose. Angina was present in 33 patients. Mean wall motion score was 1.64 per patient in the basal condition and 4.03 per patient after the test (p less than 0.001). After coronary bypass in three patients the test was positive at the same dosage that was used preoperatively, as shown by wall motion abnormalities (in two patients by electrocardiographic changes, as well). Four patients had symptoms. Furthermore, at 6 months' follow-up, a treadmill stress test performed in these three patients was positive for ischemia and angina. The wall motion score was 1.25 per patient in the basal condition and 1.53 per patient after the test (no significant difference). When the preoperative wall motion score obtained after dipyridamole echocardiography was compared with the postoperative score, a statistically significant difference was seen: 4.03 per patient versus 1.53 per patient (p less than 001). In eight patients we observed an improvement of basal myocardial contractility after the operation, which indicates the reversibility of wall motion abnormalities observed before coronary bypass. In conclusion our data show that the dipyridamole-echocardiography test is a suitable method for the early assessment of bypass grafting when other methods, exercise dependent, are not indicated.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	An effective and adaptable transvenous defibrillation system using the coronary sinus in humans. With use of a coronary sinus catheter electrode, a right ventricular catheter electrode and a chest wall patch electrode system, defibrillation threshold voltage, current and energy were measured with four distinct transvenous defibrillation techniques delivered in random sequence in each of 12 survivors of cardiac arrest immediately before implantation of a standard epicardial patch defibrillation system. The four transvenous defibrillation techniques were 1) single pathway monophasic pulsing, 2) single pathway biphasic pulsing, 3) dual pathway sequential pulsing, and 4) dual pathway simultaneous pulsing. A transvenous defibrillation method was considered to be potentially useful only if the defibrillation threshold was less than or equal to 500 V (less than or equal to 15 J delivered energy). The 500 V value would allow a 2:1 defibrillation safety margin for a device with a maximal output of 30 J. No single transvenous pulsing technique was uniformly superior in efficacy. However, by choosing the best pulsing technique for each patient, it was possible to obtain an average defibrillation threshold of 410 +/- 135 V leading edge voltage, 7.2 +/- 2.5 A leading edge current and 11.3 +/- 7.4 J delivered energy for the group of 12 patients. With the ability to vary defibrillation technique, transvenous antiarrhythmic device implantation would have been possible in 10 (83%) of the 12 patients at or below a 15 J defibrillation threshold cutoff point. In contrast, if only one transvenous defibrillation method had been used, as few as 5 and at most 8 of the 12 patients would have been candidates for a transvenous defibrillation system given a 15 J defibrillation threshold cutoff point for insertion. 
4	Conservative therapy for adnexal torsion. A case report. Adnexal torsion has traditionally been treated with oophorectomy because of the fear that untwisting the ovarian pedicle may result in a thrombotic embolus. Such a patient had bilateral adnexal torsion secondary to dermoid cysts. Since standard therapy, oophorectomy, was performed, the patient was surgically castrated. A review of the literature revealed no reported cases of a thrombotic embolus arising from the untwisting of twisted adnexa and supported conservation of the adnexa rather than routine extirpation, except when necrotic. 
1	Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. We compared T-cell proliferative responses to acetylcholine receptor (AChR) and to purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, and blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus cells gave significantly higher and more consistent responses to AChR than parallel cultures of autologous blood cells, whereas responses to PPD showed an opposite trend. Thus there was a preferential localization of AChR-reactive T cells in the hyperplastic MG thymus. Furthermore, there was a strong correlation between blood and thymus cell responses to PPD (but not to AChR), arguing that the hyperplastic MG thymus contains a sample of sensitized peripheral T cells. By contrast, both AChR- and PPD-responsive T cells were almost undetectable in thymus from nonmyasthenic patients, which is evidently much less receptive to circulating T cells. Cells from MG thymomas showed the highest stimulations by AChR but did not consistently react to PPD. However, the uninvolved thymus adjacent to these thymomas behaved almost identically to the hyperplastic samples described above. Our interpretation is that AChR-specific T cells are initially sensitized in the MG thymoma but are selectively trapped in the hyperplastic thymus after being primed elsewhere. 
3	Sumatriptan in acute migraine: pharmacology and review of world experience. The introduction of sumatriptan, a novel abortive antimigraine agent, has generated a significant amount of preclinical and clinical interest during the past few years. At the scientific level, sumatriptan is unique in terms of its selective pharmacological properties. The effects of sumatriptan in various experimental paradigms have led to new insights into the pathophysiology of migraine. At the clinical level, sumatriptan appears to be an effective abortive anti-migraine agent with minimal side effects. Its ability to decrease, rather than exacerbate, the nausea and vomiting of migraine appears to be an important advance in the treatment of migraine. 
4	Options for surgical repair in hearts with univentricular atrioventricular connection and subaortic stenosis. Thirteen patients have undergone surgical treatment because of subaortic obstruction in hearts with a univentricular atrioventricular connection. Nine patients underwent surgical enlargement of the ventricular septal defect and four patients had construction of an aortopulmonary anastomosis and closure of the pulmonary trunk (the Damus-Kaye-Stansel procedure). Two patients undergoing enlargement of the septal defect and two having the Damus-Kaye-Stansel procedure also had a modified Fontan procedure. One patient had complete atrioventricular dissociation after direct enlargement of the ventricular septal defect, which necessitated insertion of an epicardial pacemaker. One patient died within 30 days of the operation after enlargement of the defect and two patients after the Damus-Kaye-Stansel procedure. There was one late death, occurring in a patient who underwent enlargement of the ventricular septal defect. Ten patients have subsequently undergone conventional cardiac catheterization and angiography or transcutaneous Doppler flow studies to assess the relief of the subaortic obstruction. The result has been satisfactory in all. Because of this experience, we now recommend direct surgical enlargement of the restrictive ventricular septal defect for direct relief of subaortic stenosis occurring with a univentricular atrioventricular connection to a dominant left ventricle, inasmuch as it appears to be hemodynamically effective with a low operative mortality and morbidity. The Damus-Kaye-Stansel procedure can also have a role in relieving subaortic stenosis when the atria are connected to a dominant right ventricle. 
2	Perianal appearances associated with constipation. The perianal appearances were studied prospectively of 136 constipated children (mean age 3.9 years, 67 boys, 69 girls). Anal dilatation, fissures, tags, warts, perianal oedema, redness, blueness, and veins were recorded. It was noted whether dilatation occurred immediately or at 30 and 60 seconds with the buttocks minimally separated, and on subsequent firm lateral traction of the buttocks. The degree of faecal loading was assessed in all children. Anal dilatation was found in 24 (18%) and first appeared on lateral traction in eight (6%). In three quarters of the children with dilatation faecal loading or perianal signs were present. Fissures were found in 35 (26%) children and tags in seven (5%). Perianal redness was more likely to be associated with fissures, and blueness with dilatation. We conclude that there are no pathognomonic perianal signs in childhood constipation and that the technique of anal examination should be standardised. 
1	Coexisting thymic carcinoid tumor and thymoma. Thymic carcinoid tumors are unusual neoplasms that are different from thymomas. We report a case of coexisting thymic carcinoid tumor and thymoma associated with myasthenia gravis. The clinicopathological findings are discussed with a review of the literature. 
1	Extraoral application of osseointegrated implants. The use of osseointegrated implants to provide support for craniofacial prostheses has provided the clinician with another approach to the treatment of complex craniofacial reconstructive problems. The surgical technique is reviewed and the Mayo Clinic experience is presented. 
2	Effect of portasystemic shunts on subsequent transplantation of the liver. Portasystemic (PS) shunts have been regarded as a relative contraindication to hepatic transplantation (HT) because of the potential for increased technical difficulties during the transplant operation. We compared operative blood loss, morbidity and mortality in 27 patients with PS shunts and 147 patients with no shunts (NS) who underwent HT. The PS shunt group included 12 portocaval (PC), eight mesocaval, four central splenorenal and four distal splenorenal shunts. The PS shunt and NS groups were similar with respect to age, preoperative medical status and ABO blood group matching between donors and recipients. There were no significant differences in the mean (plus or minus S.D.) intraoperative blood transfusion (9.1 +/- 7.6 versus 9.2 +/- 11.0 units), mean (plus or minus S.D.) duration of anesthesia (8.1 +/- 1.4 versus 7.8 +/- 1.5 hours) and operative mortality (7 versus 11 per cent) between the PS shunt and NS groups, respectively. Complications of the biliary tract were significantly higher in the PS shunt group (22.0 versus 5.4 per cent, p less than 0.01) but they did not increase the mortality rate. We conclude that a prior PS shunt should not influence the decision to accept patients for HT. PS shunts remain a reasonable surgical option for patients with cirrhosis and variceal hemorrhage (refractory to sclerotherapy) who, by virtue of good hepatic function, do not merit immediate HT. 
3	Denervation in hemiplegic muscles. This study examined the frequency of denervation activity in hemiplegic muscles in relation to the size and location of the central lesion. We studied 20 patients, 14 with major unilateral cerebral infarctions in the middle cerebral or internal carotid territories; four with a single lacune in the pons, internal capsule, or thalamus; and two with precentral infarcts. Using somatosensory evoked potentials, motor conduction studies, and assessments of conduction across the plexus and roots, we detected no conduction abnormalities on the affected side. Fibrillation was common in both groups, especially in distal and intermediate muscles. The distribution of the fibrillation and the normal conduction studies suggested that trauma of peripheral nerves was not a factor. Although the normal conduction studies and pattern of fibrillation activity do not exclude peripheral nerve trauma as the cause of the fibrillation, we suggest that transsynaptic degeneration is a reasonable alternative explanation. 
2	Prognostic significance of proteinuria one year after onset of diarrhea-associated hemolytic-uremic syndrome. We examined the prognostic value of changes in the amount of proteinuria, measured as protein/creatinine ratios in early-morning urine samples, in 40 children who had had diarrhea-associated hemolytic-uremic syndrome. One year after diagnosis, 87% of those who seemed to have fully recovered had normal urinary protein/creatinine ratios, compared with none of those with poor outcomes (p less than 0.001). None of those with poor outcomes achieved normal protein/creatinine ratios during follow-up to a maximum of 5 1/2 years, but 93% of those who made a full clinical recovery no longer had proteinuria. Measurement of the protein/creatinine ratio in an early-morning sample of urine is a simple, cost-effective, and noninvasive means of monitoring the progress of patients with diarrhea-associated hemolytic-uremic syndrome, provided that a technique sensitive at low protein concentrations is employed. 
5	Aggravation of myasthenia gravis by erythromycin. Erythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction. 
5	Acute lower respiratory tract infection due to virus among hospitalized children in Dhaka, Bangladesh. The nature of acute lower respiratory tract infection (ALRI) in hospitalized children and of the associated viral agents was assessed in a study of 601 children less than 5 years old over a 24-month period. Of these children, 80% were less than 24 months of age and the ratio of boys to girls was 1.7:1. Pneumonia (86.5% of cases) was the most frequently observed clinical manifestation. Shedding of virus was detected in 21.1% of the children; the highest rate occurred in infants 0-5 months old (27%) as compared with a rate of only 12.5% in children 25-60 months old. Virus was detected in 33.3%, 32.8%, 21.2%, and 20% of the cases of tracheobronchitis, bronchiolitis, pneumonia, and croup, respectively. Among the viruses detected, 78% were respiratory syncytial virus (RSV) (91% of infections with this virus occurred in children less than 2 years old) and 14.4% were influenza virus types A and B. Of the RSV infections, 61% occurred in infants less than 1 year old. The case-fatality rate was 6.8% overall and was 4.8% in virus-associated cases. No consistent pattern of seasonal occurrence of viral infections was discerned. RSV was detected throughout the year, with increased prevalence from January to April. 
1	Antigen-presenting activity of draining lymph node cells from mice painted with a contact allergen during ultraviolet carcinogenesis. The induction of skin cancers in mice by chronic UV irradiation is accompanied by a decrease in the numbers of Ia+ and Thy-1+ dendritic cells in the epidermis early in the course of UV irradiation. Subsequently, the number of Ia+ cells, but not Thy-1+ cells, increases until the time of tumor development. To assess the functional significance of these changes in cutaneous immune cells, and to help define the role these cells may play in immune surveillance against skin cancers, we tested the afferent immunologic capability of the skin during the development of UV-B radiation-induced skin cancers. Afferent immune function was measured by testing the Ag-presenting capacity of draining lymph node (DLN) cells from mice sensitized epicutaneously with dinitrofluorobenzene. A reduced contact hypersensitivity response was induced in mice immunized with DLN cells from UV-irradiated mice that had been sensitized with hapten on UV-irradiated skin. This decreased reactivity was present during the entire latent period of tumor development. However, in tumor-bearing mice, the DLN cells from UV-irradiated, sensitized animals exhibited normal Ag-presenting activity. DLN cells from UV-irradiated mice sensitized on ventral, unirradiated skin exhibited normal Ag-presenting activity. The lowest amount of Ag-presenting activity in the draining lymph nodes of UV-irradiated mice correlated temporally with the lowest number of Ia+, adenosine triphosphatase+ dendritic epidermal cells in the UV-irradiated skin. At least during the early part of the tumor latent period, an increase in the number of these cells was paralleled by an increase in the Ag-presenting activity of the DLN cells. In contrast, the number of Thy-1+ dendritic epidermal cells in UV-irradiated skin did not correlate with the Ag-presenting activity. Thus, the decrease in the number of identifiable epidermal Langerhans cells early in the course of chronic UV irradiation correlated with a decrease in Ag-presenting activity after sensitization through the UV-irradiated skin. These studies demonstrate that the afferent arm of the cutaneous immune response is impaired in the site of tumor development throughout the latent period of UV carcinogenesis. 
1	Screening colonoscopy in asymptomatic average-risk persons with negative fecal occult blood tests. Colonoscopy was performed on 210 asymptomatic average-risk persons, aged 50-75 years, who had negative fecal occult blood test results. Colonoscopy was complete to the cecum in 209 subjects. Fifty-three subjects (25%) had adenomas and two had cancer. All of the adenomas greater than or equal to 1 cm in size and both cancers occurred in subjects aged greater than or equal to 60 years. Fifty-one percent of subjects with adenomas and one with cancer had no neoplasms distal to the sigmoid-descending colon junction. One subject had a major postpolypectomy hemorrhage that stopped spontaneously. Screening colonoscopy, therefore, has a high yield for detection of neoplasms in asymptomatic average-risk persons aged greater than or equal to 60 years with negative fecal occult blood test results. The yield is low in persons aged 50-54 years and intermediate in persons aged 55-59 years. 
4	Improving compliance and increasing control of hypertension: needs of special hypertensive populations. Approximately 60 million people in the United States have hypertension. More than half are either untreated or treated without blood pressure control, despite the well-known risks of hypertension and the established benefits of treatment. The major reason for inadequate control of hypertension is poor adherence to treatment. Approximately 50% of patients with hypertension fail to keep follow-up appointments, and only 60% take their medications as prescribed. Barriers to effective therapeutic adherence include poor doctor-patient communication, cost of antihypertensive therapy, and side effects of the drugs. To increase control of hypertension, compliance with therapy must be improved. Physicians and patients must be mutually committed to achieving control of blood pressure. Physicians should communicate instructions clearly and prescribe therapies that are effective, affordable, and have minimal or no adverse effects on patient quality of life or overall cardiac risk profile. The needs of special hypertensive populations (i.e., elderly, black, and young patients) must also be recognized and addressed. Patients must follow recommendations and alert their physicians to any problems with their medications--particularly those relating to side effects and cost. When selecting drug therapy it should be noted that older patients are sensitive to volume depletion and sympathetic inhibition. In this group of patients, initial drug doses should be low and increments smaller and more gradual than in younger patients. Black patients with hypertension show an accentuated response to diuretics and blunted responses to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors as monotherapy. However, when used with a diuretic, there are no racial differences in the blood pressure lowering effects of beta-blockers and ACE inhibitors. 
4	Cavernous malformations and capillary telangiectasia: a spectrum within a single pathological entity. Cerebral vascular malformations have traditionally been divided into four categories: arteriovenous, venous, cavernous, and capillary telangiectases. A controversy exists about separating the latter two lesions into separate entities. Critics claim the distinction is arbitrary but have been unable to present convincing evidence linking the two types of lesions. We have reviewed the histories of 20 patients with cavernous malformations and have analyzed the clinical, radiographic, and surgical-autopsy data associated with these lesions. In some patients, multiple lesions, including cavernous malformations, capillary telangiectases, and transitional forms between the two, were identified. Based on this analysis, we conclude that capillary telangiectasia and cavernous malformations represent two pathological extremes within the same vascular malformation category and propose grouping them as a single cerebral entity called cerebral capillary malformations. 
2	Late cholangitis after successful surgical repair of biliary atresia. Bacterial cholangitis is a frequent complication of successful surgical repair of biliary atresia, occurring in 93% of patients before the age of 1 year, but thought to be rare after 2 years of age. Among 76 children free of jaundice more than 5 years after operation, four presented with late cholangitis (7 to 13.5 years old), consisting of fever, jaundice, and abdominal pain with biochemical features of an inflammatory process and cholestasis. Liver biopsy specimens consistently demonstrated histological features of cholangitis, growth of microorganism, or both. Cholangitis subsided spontaneously in one patient or in response to intravenous administration of antibiotics. Cholangiography consistently demonstrated biliary abnormalities but no definite obstruction to the bilioenteric anastomosis. All the children had good hepatic function 3 weeks to 4 years after the episode of cholangitis. These results suggest that cholangitis may occur several years after surgery but does not seem to alter prognosis. 
4	Beat-to-beat detection of ventricular late potentials with high-resolution electrocardiography. To detect dynamic changes of VLPs we developed a low-noise, HR-ECG with a gain of 10(5)-10(6)X. This system allows the beat-to-beat detection of low-amplitude signals at the bedside in a nonshielded room without any averaging process. Analysis was performed in 39 normal subjects (group A: 27 men, 12 women, mean age, 28 +/- 8 years), in 98 patients with coronary artery disease without documented sustained ventricular tachycardia (group B: 86 men, 12 women, mean age, 59 +/- 10 years) and in 41 patients coronary artery disease with sustained monomorphic ventricular tachycardia (group C: 36 men, 5 women; mean age 63 +/- 9 years). Comparison was made with time-domain signal-averaging (SA-ECG) in all cases at the same electrode position and with identical band-pass filtering. In group A no VLPs were detected; the total filtered QRS duration was 84 +/- 8 msec (mean +/- SD), and the time interval during which the terminal QRS did not exceed 40 microV (I-40) was less than 30 msec in all cases (mean, 17 +/- 6 msec). In group B, VLPs were detected by HR-ECG in 34 of 98 patients (35%); the total QRS duration was 102 +/- 16 msec (mean +/- SD, p less than 0.01 vs group A), and the I-40 was 29 +/- 13 msec (mean +/- SD, p less than 0.01 vs (group A). In group C, VLPs were detected by HR-ECG in 38 of 41 patients (93%); the total QRS duration was 123 +/- 22 msec (mean +/- SD, p less than 0.01 vs group A and group B), and the I-40 was 40 +/- 14 msec (mean +/- SD, p less than 0.01 vs group A and group B). Concordant results between HR-ECG and SA-ECG were observed in 91% of the cases (59 positive and 103 negative results). Late potentials that exhibited dynamic variations were detected by HR-ECG alone in 13 cases, and very low amplitude VLPs were detected by SA-ECG alone in three cases. In conclusion, the present study demonstrates the feasibility of body-surface recording of VLPs on a beat-to-beat basis, without any averaging process, at the bedside in a nonshielded room. This new approach may allow the study of dynamic changes of VLPs during spontaneous ventricular arrhythmias or ischemia. 
2	Refractory parastomal ulcers: a multidisciplinary approach. Chronic parastomal ulcers in patients with ileostomy or colostomy stomas are unusual. Previous reports have implicated infections, fistulas, recurrent inflammatory bowel disease (IBD), pyoderma gangrenosum, and trauma. Over the past 8 years we have evaluated 10 cases of such refractory parastomal ulcers that occurred at a mean of 11 years after stomal surgery. Eight patients had had an ileostomy for IBD while two had undergone colostomy for colon cancer. Five patients with IBD were diagnosed as having pyoderma gangrenosum ulcerations. They required systemic treatment for a mean of 25 weeks to effect ulcer healing. The other five patients had either parastomal ulcers on the basis of dermatoses (contact dermatitis, eczema, or bullous pemphigoid) or contact ulcers due to face-plate pressure and parastomal dermatitis. These patients received topical treatment with healing of ulcers in a mean of 4 weeks. We conclude that parastomal ulcers occurring in patients without IBD or IBD patients without classic pyoderma gangrenosum require early dermatologic evaluation as they respond relatively quickly to appropriate local therapy. 
1	Pneumocystis carinii pneumonia associated with profound lymphopenia and abnormal T-lymphocyte subset ratios during treatment for early-stage breast carcinoma. Two women with Stage II breast carcinoma treated with lumpectomy followed by breast irradiation and adjuvant chemotherapy developed Pneumocystis carinii pneumonia while receiving cytotoxic chemotherapy. Neither woman had evidence of immunosuppression before therapy. They both had profound lymphopenia, reversed CD4/CD8 ratios, and normal peripheral blood total leukocyte counts at the time of their infections. Both women were seronegative for human immunodeficiency virus type 1 and had no risk factors for such an infection. The patients' CD4 lymphocyte counts increased after chemotherapy for breast carcinoma was discontinued. Thus, it appears that the therapy they received may have caused severe T-lymphocyte mediated immunosuppression. 
5	Natural history and prognostic factors for chronic hepatitis type B. One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n = 46) or chronic active hepatitis without cirrhosis (n = 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3.7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p less than 0.0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p less than 0.0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis. 
4	Effect of alpha-adrenergic blockade on blood pressure, glucose, and lipid metabolism in hypertensive patients with non-insulin-dependent diabetes mellitus. To clarify the long-term effects of alpha-adrenergic blockade on blood pressure, glucose, and lipid metabolism, a selective alpha 1-adrenergic inhibitor (prazosin, 1.0 to 2.0 mg/day in divided doses) was administered as a single antihypertensive agent to 10 (four men and six women, aged 52 to 76 years) hypertensive patients (systolic blood pressure [SBP] greater than or equal to 150 mm Hg or diastolic blood pressure [DBP] greater than or equal to 90 mm Hg) with non-insulin-dependent diabetes mellitus (NIDDM) for up to 20 weeks. Blood pressure, glucose tolerance and immunoreactive insulin (IRI) response to 75 gm oral glucose load, hemoglobin A1 (Hb A1), serum lipid profile, and serum apolipoprotein were examined before and after treatment. SBP and DBP were significantly reduced at 20 weeks after treatment with the selective alpha 1-adrenergic inhibitor (SBP 167 +/- 6 mm Hg versus 152 +/- 7 mm Hg; DBP 81 +/- 3 mm Hg versus 76 +/- 3 mm Hg, (p less than 0.05 and p less than 0.01, respectively). Glucose tolerance and IRI response to glucose load were not significantly changed at 4 and 12 to 20 weeks after selective alpha 1-inhibitor treatment compared with the baseline data before treatment; the level of Hb A1 was not significantly changed at 4 and 20 weeks after treatment. 
4	Omeprazole in the management of intractable esophageal ulceration following injection sclerotherapy. Transient esophageal ulceration is a common finding after sclerotherapy of varices. A small proportion of these ulcers become chronic and resistant to conventional therapy. Such chronic ulcers have been associated with pain, stricture formation, and recurrent hemorrhage. The use of omeprazole, a proton pump inhibitor, was examined in the current study in the treatment of 10 patients (6 women, 4 men; age range, 27-86 years) with cirrhosis (PBC, 4; sclerosing cholangitis, 2; chronic active liver disease, 2; alcohol, 1; and cryptogenic, 1) who developed an esophageal ulcer after a mean of 13 (range, 8-21) sessions of sclerotherapy. The ulcers had been present for 3-54 months despite prolonged treatment with high-dose H2-receptor antagonists and sucralfate. In each case one or more complications had occurred: severe pain in 3, stricture formation in 4, and recurrent hemorrhage in 7 cases. After an 8-week course of omeprazole, 40 mg daily, endoscopy confirmed complete healing of the ulceration in all 10 cases with symptom resolution. In 2 cases the ulcer recurred, with associated bleeding within 6 weeks of discontinuing the treatment in 1 patient. Both cases responded to repeat therapy. These results confirm the efficacy of omeprazole for postsclerotherapy ulceration and imply that acid-pepsin has a role in perpetuating such ulcers. 
1	Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers. The poor prognosis for esophageal cancer could be improved if lesions were detected at an early stage. To detect early esophageal cancer, endoscopic screening of the esophagus with the Lugol dye method was performed in patients with head and neck cancers who were asymptomatic but regarded as being at high risk for synchronous or metachronous esophageal cancer. Of 178 patients screened, 9 had esophageal cancer (5.1%). Eight of these patients (89%) were at early stages with no lymph node metastasis. Most of the lesions (9 of 13 lesions) were not detectable by barium studies or ordinary endoscopic study. The epidemiologic statistical analysis of the patients confirmed that they had a significantly high observed and expected number (O/E) ratio (39.7; P less than 0.001). These results demonstrate the value of endoscopic screening of the esophagus with the Lugol dye method in patients with head and neck cancers and imply that endoscopic screening with the Lugol dye method may be useful for detecting early esophageal cancer in individuals at risk for other causes. 
1	Unilateral hydrocephalus in adults. The authors report 14 cases of unilateral hydrocephalus in adults. Headache was the most common presenting symptom. Unilateral hydrocephalus was documented in each patient with computed tomography scans; magnetic resonance imaging was also used in seven patients in the latter part of the series. Unilateral hydrocephalus was caused by tumor (seven patients), venous angioma (one patient), ependymal cyst (one patient), postinflammatory gliosis (one patient), and was idiopathic in four patients. The primary surgical treatment was craniotomy with fenestration of the septum pellucidum, which relieved symptoms in eight of nine patients for whom long-term follow-up data were available. 
5	Pleural anesthetics given through an epidural catheter secured inside a chest tube. Pain management after thoracic surgical procedures is a difficult clinical problem. A variety of pain management methods are used with variable efficacy. This paper presents an effective method of pleural anesthetic administration using a pleural catheter inserted through a chest tube. 
3	Right-left disorientation in dementia of the Alzheimer type. We demonstrated that right-left orientation (R/L-O) on a confronting subject is more impaired in patients with dementia of the Alzheimer type than in patients with multi-infarct dementia of comparable degree of dementia. The impairment in R/L-O is independent of aphasia and spatial disorientation. 
4	Amiodarone versus bretylium for suppression of reperfusion arrhythmias in dogs. Reperfusion arrhythmias are an important complication of interventions to limit infarct size. Recently, amiodarone has been shown to be rapidly effective in suppressing sustained, incessant ventricular tachycardia and ventricular fibrillation in this setting. This study evaluated the time course of arrhythmia suppression and comparative efficacy of amiodarone versus bretylium in a canine model of reperfusion arrhythmias. Of 23 dogs subjected to a Harris two-stage coronary artery ligation followed by release, 18 demonstrated clinically significant ventricular arrhythmias and received either intravenous amiodarone, 5 mg/kg (9 dogs), or intravenous bretylium, 5 mg/kg (9 dogs). Direct-current shocks for sustained ventricular tachycardia or ventricular fibrillation were administered as necessary. Amiodarone rapidly suppressed sustained ventricular tachycardia and ventricular fibrillation in this model with no dog in the amiodarone-treated group requiring cardioversion after completion of the 15-minute infusion versus 4 of 9 dogs in the bretylium-treated group (p less than 0.05). Amiodarone was more effective than bretylium in suppressing episodes of sustained ventricular tachycardia/ventricular fibrillation, episodes of nonsustained ventricular tachycardia, and premature ventricular complexes. The blood pressure and heart rate decreased more after amiodarone administration than after bretylium administration. We conclude that, in the canine reperfusion arrhythmia model, amiodarone is rapidly effective in suppressing ventricular arrhythmias and is more effective than bretylium. 
5	Ampullary hamartoma: endoscopic diagnosis and treatment. This study shows a patient who presented with intermittent biliary tract obstruction caused by ampullary hamartoma. Endoscopic retrograde cholangiopancreatography showed a large ulcerated papilla and dilated biliary ducts. Tissue diagnosis was established by a large particle biopsy obtained with a snare. The patient underwent a successful endoscopic sphincterotomy and has remained symptom free for 4 years. 
1	Absence of acetylcholine-induced current in epithelial cells from thymus glands and thymomas of myasthenia gravis patients. We investigated the activity of ion channels in epithelial cells from human thymus glands and thymomas kept in short-term cell culture by clamping the membrane potential of the cells at -85 mV and determining the membrane current flowing on application of acetylcholine, glycine, or gamma-aminobutyric acid. In concentrations of up to 10(-3) M, none of the neurotransmitters induced any detectable current. This suggests (1) that there are no acetylcholine receptors (AChRs) or other products of the AChR gene family having ion-channel properties in the membranes of these epithelial cells, and (2) that the alpha-bungarotoxin-binding protein of thymus and thymoma has no AChR-like ion-channel property. These results support the hypothesis that the cross-reacting structures that elicit the anti-AChR autoimmune response in thymoma-associated myasthenia gravis are antigens having only limited homology with the AChR. Myasthenia gravis not associated with thymoma might have a different pathogenesis. 
3	Percutaneous balloon pulmonary valvuloplasty in sickle cell anemia: a case report. Percutaneous balloon pulmonary valvuloplasty was performed on a 19-year-old female who had moderate pulmonary valve stenosis with sickle cell anemia. The patient developed sickle cell crisis resulting in occipital infarction, but she made a good recovery. We describe this case and the methods of reducing the risk of sickle cell crisis. 
1	Thallium-201 scintigraphy in differentiated thyroid cancer: comparison with radioiodine scintigraphy and serum thyroglobulin determinations. The role of thallium-201 (201TI) scintigraphy in the follow-up evaluation of differentiated thyroid carcinoma (DTC) is controversial. Desirable characteristics of 201TI scintigraphy including the potential for no thyroid hormone withdrawal, immediate imaging postinjection, and low radiation burden relative to iodine-131 (131I) suggests it is logistically superior to 131I scintigraphy. Fifty-two patients with DTC were evaluated with 201TI and 131I neck and chest images, and serum thyroglobulin measurements. In post-thyroidectomy and pre-131I ablation therapy patients, very little 201TI accumulation was noted within the thyroid bed, with discordantly increased 131I activity and normal serum thyroglobulin measurements. Twenty-nine percent of patients evaluated after 131I ablative therapy had elevated serum thyroglobulin levels and localized neck and chest abnormalities on 201TI scan that were not seen on 131I studies. Our data suggest that 201TI is more sensitive than 131I diagnostic (5 mCi) studies for detection of DTC, while 131I is more sensitive in detecting normal residual thyroid tissue postoperatively. 
4	Cardioplegia-induced damage to ischemic immature myocardium is independent of oxygen availability. The known benefits of hypothermic pharmacological cardioplegia in protecting the ischemic adult heart may not extend to children. Protection of the ischemic immature rabbit heart with hypothermic Krebs-Henseleit bicarbonate buffer is better than with hypothermic St. Thomas' II cardioplegic solution. We investigated whether the availability of oxygen in the preischemic perfusate is responsible for the increased tolerance to ischemia of immature (7- to 10-day-old) hearts perfused with Krebs buffer in comparison with St. Thomas' II solution immediately before ischemia. After obtaining preischemic control data in the "working" mode, we perfused hearts (n = 8 per group) for 3 minutes with hypothermic (14 degrees C) Krebs buffer or hypothermic St. Thomas' II solution saturated with 0%, 25%, or 95% oxygen. This was followed by 2 hours of global ischemia at 14 degrees C. Hearts were reperfused for 15 minutes in the Langendorff mode and 35 minutes in the working mode, and recovery of function was measured. For preischemic oxygen concentrations of 0%, 25%, and 95%, recovery of aortic flow in hearts protected by hypothermia alone during ischemia was 74% +/- 9%, 82% +/- 4%, and 99% +/- 2% of preischemic values, respectively. In hearts protected by hypothermia plus cardioplegia, the values were 69% +/- 6%, 72% +/- 3%, and 86% +/- 5%, respectively. Thus, at equal oxygen concentrations, recovery of postischemic function was better in hearts protected by hypothermia alone compared with hypothermia plus cardioplegia. We conclude that factors other than oxygen availability are responsible for the damaging effect of St. Thomas' II solution on the ischemic immature rabbit heart. 
2	Esophageal perforation during pneumatic dilatation for achalasia: a possible association with malnutrition. Pneumatic balloon dilatation of the lower esophageal sphincter is commonly utilized as primary therapy for achalasia. Perforation related to pneumatic dilatation is uncommon (2-6%) but may result in severe morbidity. Factors associated with risk of perforation are not well defined. We noted perforation in three patients undergoing forceful balloon dilatation. All these patients had clinical evidence of significant malnutrition (recent marked weight loss and severe hypoalbuminemia). Malnutrition may be a causal factor for perforation in patients with achalasia undergoing dilatation. 
3	Comparative pharmacodynamics and brain distribution of E-delta 2-valproate and valproate in rats. The E-isomer of 2-unsaturated valproate (E-delta 2-VPA) is a pharmacologically active metabolite of VPA that is less teratogenic and hepatotoxic than its saturated precursor. To assess potential use of E-delta 2-VPA as an alternate to VPA, a dose-response study comparing the anticonvulsant activity and neurotoxicity of E-delta 2-VPA and VPA was conducted in rats using the intravenous (i.v.) pentylenetetrazol (PTZ)-infusion threshold seizure model. Assay of drug in whole brain and plasma allowed comparison of the drug concentration-effect relationships and the brain distribution characteristics of the two compounds. E-delta 2-VPA was two to three times more potent than VPA in elevating the clonic seizure threshold of PTZ, in reference to either plasma or whole-brain drug concentrations. Furthermore, much steeper response curves were observed with E-delta 2-VPA as compared with VPA. Within the pharmacologic concentration range (defined as EC25 to EC75), E-delta 2-VPA was less neurotoxic than VPA as assessed by behavioral tests. Therefore, E-delta 2-VPA has a much more favorable protective index than VPA. At low doses, the concentration ratios of brain to plasma for both E-delta 2-VPA and VPA increased markedly with increasing plasma drug concentration. E-delta 2-VPA and VPA were previously shown to exhibit saturable binding to rat plasma proteins. If we assume that uptake of drug into the CNS is limited to the equilibrium plasma free fraction in the brain microvasculature, much of the nonlinear brain distribution features of VPA could be accounted for by saturable drug plasma protein binding. On the other hand, more complex kinetics involving simultaneous saturation of plasma protein binding and blood-to-brain transport are proposed to explain the brain distribution of the unsaturated compound. In addition, the brain-to-free drug concentration ratios for both E-delta 2-VPA and VPA were below unity at high drug-concentration range, consistent with the presence of an efficient efflux mechanism of these compounds from brain. 
5	The long-distance effects of brain lesions: visualization of myelinated pathways in the human brain using polarizing and fluorescence microscopy. We describe several new possibilities for the study of degenerated myelinated tracts in the human central nervous system (CNS). The methods are based on the visualization of myelin breakdown products that show birefringence in polarized light and, when stained with Nile blue and benzpyrene-3,4, exhibit fluorescence. Even after lengthy formalin fixation, the methods permit the localization of anterogradely degenerated tracts in a variety of fiber systems in the brains of patients who died between five and 20 months after the onset of neurological symptoms. Particularly the polarizing technique, because of its simplicity, can be added to the usual neuropathological methods for demonstrating the long-distance effects of a brain lesion. As research tools, these methods would also aid in the study of the anatomical substrate of human neurological symptomatology. 
4	Sustained calcium channel blockade in the treatment of severe hypertension. A two year experience. Thirty-nine patients with severe hypertension (diastolic blood pressure greater than 120 mm Hg) predominantly drawn from an inner-city population were placed on nifedipine gastrointestinal therapeutic system (GITS) for long-term treatment to achieve a sustained diastolic blood pressure less than 95 mm Hg. Fourteen patients failed to complete 6 months of therapy. For the 25 who remained in treatment for 6 months or more, systolic/diastolic blood pressure reductions were 62 +/- 5/40 +/- 2 mm Hg at 6 months; for those followed more than 12 months (n = 18), 58 +/- 7/37 +/- 3 mm Hg at 12 months; and for those followed more than 18 months (n = 11), 54 +/- 6/37 +/- 3 mm Hg at 18 months. Overall, 75% of these severely hypertensive patients were controlled with nifedipine GITS alone; 80% required 90 mg/day or more. During the two years of observation, no patient had a severe medical event, and 44% of those who entered remain in treatment. Left ventricular hypertrophy, as determined by echocardiography, diminished significantly during the course of treatment. These results indicate nifedipine GITS is well-tolerated and effective as monotherapy in the treatment of severe hypertension. 
3	X-linked spinal muscular atrophy (Kennedy's syndrome). A kindred with hypobetalipoproteinemia. Kennedy's syndrome, X-linked adult-onset bulbospinal muscular atrophy, has been described in over 30 families. The characteristic distribution of weakness creates a recognizable syndrome, augmented by frequent findings of testicular atrophy and gynecomastia. Type IV or type II hyperlipoproteinemia has been found in some families. We have studied another family with Kennedy's syndrome, this one with hypobetalipoproteinemia. The diversity of serum patterns suggests that lipoprotein abnormalities are not causally related to either the endocrinopathy or the spinal muscular atrophy. However, gene linkage studies indicate proximity of the gene for Kennedy's syndrome and the gene encoding the androgen receptor, which could explain the combination of a motor neuron disorder and the endocrine abnormalities. 
4	Acute myocardial infarction resulting from the migration of a Greenfield filter. A paraplegic patient who underwent the placement of Greenfield filters to prevent pulmonary emboli had one of the filters migrate proximally to the junction of the inferior vena cava and right atrium, then into the right atrium a few months later. This resulted in an acute myocardial infarction by apparently causing an intimal dissection of the posterior descending artery. Treatment, follow-up and causes of filter migration are discussed. 
5	Coronary angioplasty after coronary bypass surgery: initial results and late outcome in 422 patients. From 1978 to 1988, coronary angioplasty was performed in 422 patients with prior coronary artery bypass surgery (264 patients with native coronary artery angioplasty and 158 patients with graft angioplasty). Angioplasty was successful in 84%, unsuccessful but uncomplicated in 11% and complicated by one or more major cardiac events in 5% (myocardial infarction 5%, emergency bypass surgery 2% and death 0.2%). Follow-up data were obtained in 99% of 356 patients with successful angioplasty. At a mean of 33 +/- 26 months, 92% were alive, 73% had improvement in angina and 61% were free of angina. One or more of the following late events occurred in 67 patients (19%): myocardial infarction (6%), elective reoperation (13%) and cardiac death (6%). Repeat angioplasty was performed in 27%, with a success rate of 89% and no deaths. Initial success rates were equal in native vessel versus graft angioplasty, but late outcome was less favorable with the latter because of a higher rate of infarction (11% versus 4%, p less than 0.05) and need for reoperation (19% versus 10%, p less than 0.05). The initial success rate was higher in vein grafts less than 1 year old compared with grafts 1 to 4 years or greater than 4 years after operation (92% versus 85% versus 83%, respectively) and adverse late events were less frequent after angioplasty in recent vein grafts (less than 1 year 13%, 1 to 4 years 35%, greater than 4 years 29%; less than 1 versus greater than 1 year, p less than 0.05). 
4	Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study. The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than thiazide diuretics (n = 1,625). A substantial part of this study was the metoprolol arm of the Heart Attack Primary Prevention in Hypertension (HAPPHY) study. The HAPPHY study was a pooling of the effect of different beta-blockers, mainly metoprolol and atenolol, in which no favorable effect in relative risk was observed for atenolol as compared with diuretics. In the present study, 255 patients suffered definite coronary events during follow-up; 25% of these events were fatal, 39% were acute myocardial infarctions, and 36% were silent myocardial infarctions. The risk for coronary events was significantly lower in patients on metoprolol than in patients on diuretics (111 versus 144 cases, p = 0.001, corresponding to 14.3 versus 18.8 cases/1,000 patient years and a relative risk of 0.76 at the end of the trial; 95% confidence interval 0.58-0.98). This difference in risk has potentially important implications for clinical practice because of the large number of hypertensive patients who are at increased risk for coronary events. Because a placebo group, for ethical reasons, could not be included, relative risk can only be expressed in relation to diuretics. There was no difference between the two treatment groups in baseline characteristics, blood pressure during follow-up, or stroke rates. Thus, the difference in risk for coronary events is probably mediated via mechanisms other than blood pressure control. However, present data might suggest that different beta-blockers may have different efficacy in preventing coronary events. The reasons for this possibility are as yet unknown. 
2	Gastroduodenal mucosa in uraemia: endoscopic and histological correlation and prevalence of helicobacter-like organisms. This study aimed to determine the prevalence of endoscopic and histological gastroduodenitis as well as helicobacter-like organisms in patients with end stage renal failure undergoing maintenance dialysis treatment. A total of 322 out of 422 patients in our dialysis programme underwent endoscopy and gastroduodenal biopsy specimens were taken from 260. Endoscopic gastroduodenitis occurred in 158 (49%). Histological gastritis occurred in the gastric body or antrum in 134 patients (52%) and duodenitis in 52 (21%). There was no correlation between endoscopic and histological gastritis in contrast to a significant correlation for duodenitis. Helicobacter-like organisms occurred in the body or antrum in 81 (31%). Their presence was associated with gastritis--in particular acute and acute on chronic gastritis rather than chronic gastritis. Patients with gastritis were significantly older than those without (p less than 0.001) and had lower basal and peak acid outputs. 
3	Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy OBJECTIVE--To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN--Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING--One routine diabetic unit in a university teaching hospital. PATIENTS--23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES--Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS--There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS--Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy. 
4	Conjugal temporal arteritis. We report the simultaneous occurrence of biopsy-proven temporal arteritis in husband and wife. Serologic and viral studies were negative, including viral culture of the wife's temporal artery. The concurrent incidence of giant cell arteritis in a married couple would suggest a common exogenous exposure. 
5	Risk for colon adenomas in patients with rectosigmoid hyperplastic polyps OBJECTIVE: To determine whether hyperplastic polyps found in the rectosigmoid area of the colon are associated with proximal adenomas, and to judge whether patients with distal hyperplastic polyps found during sigmoidoscopy might benefit from full colonoscopy. DESIGN: Data on patients having colonoscopy collected prospectively according to a set protocol. The size and location of all polyps were noted, and all polyps were biopsied. SETTING: Two university hospitals. PATIENTS: One thousand eight hundred and thirty-six consecutive patients referred for colonoscopy between 31 December 1987 and 31 August 1989. RESULTS: Of the 970 patients who met eligibility requirements, 274 (28.3%) had adenomas and 108 (11.1%) had hyperplastic polyps. The proportion of patients with distal hyperplastic polyps and proximal adenomas (31.9%) was similar to the proportion of those without distal hyperplastic polyps (23.0%) (crude odds ratio, 1.57; 95% CI, 0.77 to 3.06). After adjusting for age and sex, the results were unchanged (adjusted odds ratio, 1.53; CI, 0.82 to 2.88). Patients with distal adenomas, on the other hand, were three times more likely to have proximal adenomas than those without distal adenomas (adjusted odds ratio, 3.42; CI, 1.99 to 5.88). CONCLUSIONS: Distal hyperplastic polyps are not strong predictors of risk for proximal adenomas. Based on the magnitude of the risk difference, we do not believe that finding a hyperplastic polyp during sigmoidoscopy justifies doing a full colonoscopy to search for proximal adenomas. Because rectosigmoid adenomas are associated with proximal adenomas, however, small polyps seen during sigmoidoscopy should be biopsied to determine their type. Colonoscopy should be reserved for patients who are proved to have adenomas. 
4	Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. Forty-seven patients with metastatic malignant melanoma were treated with two 5-day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2. 
3	A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia. Pergolide is a synthetic ergoline derivative with highly potent long-acting PRL-lowering activity, allowing therapy of hyperprolactinemia with a once daily administration of the drug. The results of two open-label, randomized controlled multicenter clinical trials are reported. Pergolide (taken once a day), was compared with bromocriptine (taken two to four times daily) regarding efficacy and safety in the reduction of PRL levels, the cessation of galactorrhea and amenorrhea, the improvement in sexual function, and tumor shrinkage in hyperprolactinemia without (trial I; 61 patients) and with radiologically evident pituitary tumors (trial II; 96 patients). Both drugs were equally effective in lowering PRL levels in both trials. A median optimal dose of 50 micrograms pergolide and 5 mg bromocriptine/day suppressed PRL levels in the 61 patients of trial I by more than 80%. During the 24-week investigational period galactorrhea disappeared in 96% and 87% of patients, whereas menstruation returned in 90% and 96% of patients, respectively. An equally high efficacy (optimal median dose: 75-100 micrograms pergolide, 7.5-10 mg bromocriptine daily) was observed in trial II, although the resumption of menses was less frequent than in the patients of trial I (50% and 58% of patients, respectively). Sexual dysfunction improved similarly on both drugs in about half the patients. In addition, tumor shrinkage occurred to a similar extent with both drugs. A high incidence of adverse events was noted especially at the initiation of therapy with both compounds: nausea, dizziness, vomiting, asthenia, headache, and decrease in blood pressure occurred at a similar incidence and extent during the use of pergolide and bromocriptine. Patients in trial I treated with pergolide reported a slightly higher incidence of fever, vasodilatation, and flu syndrome. Conclusions: in these 24-week studies comprising a total of 157 hyperprolactinemic patients, a once daily administration of pergolide was shown to be as safe and effective as the two to four times daily ingestion of bromocriptine. Longer-acting dopamine agonists like pergolide that can be taken once daily, are likely to increase the ease to adherence to the therapeutic regimen. This might result in a higher compliance to medical treatment of hyperprolactinemia. 
1	Fine-needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus-positive patients. A multiparameter approach. Forty-six fine-needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus (HIV)-positive patients were reviewed using cytomorphologic, immunocytochemical, flow cytometric (FCM), cytogenetic, and molecular studies. There were 29 lymphomas (15 small non-cleaved cell [SNCL], 11 large cell [LCL], one small lymphocytic, and two Hodgkin's), 14 reactive hyperplasias, and three "atypical lymphoid proliferations." The reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations; six of seven were diploid on FCM, the seventh was hypodiploid. Higher proliferative indices (mean, 11.6%) and higher RNA indices (mean, 1.2) characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without HIV positivity. Aspirates of SNCL showed monotonous populations of intermediate-sized cells except in one patient where a giant cell syncytial variant occurred. Nine of 13 SNCL aspirates showed light chain restriction. JH rearrangement revealed B-cell lineage in one aspirate in which immunocytochemical study was negative for Kappa, lambda, B1, and Leu-4. Nine of 12 SNCL were diploid; the mean proliferative index was 25.6% and the mean RNA index 2.3. Chromosomal translocations involving the c-myc locus were demonstrated in five of seven SNCL aspirates karyotyped. Five of eight LCL showed light chain restriction the remaining three showed null cell phenotype. Large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22.0% and mean RNA index of 2.2. One of two LCL aspirates karyotyped demonstrated c-myc translocation. Despite the multiparameter approach, a definitive diagnosis could not be reached in three aspirates. 
4	The diagnosis and prognosis of autosomal dominant polycystic kidney disease. BACKGROUND. Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS. We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS. In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS. At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life. 
5	Total left main coronary artery occlusion after aortic aneurysm repair and valve replacement. A 38-year-old woman with complete occlusion of the left main coronary artery secondary to cannulation during aortic valve replacement is presented. The clinical course was characterized by progressive left ventricular dysfunction and congestive heart failure. Recognition of this potential problem when it occurs is important as to institute therapeutic measures which may interrupt a patient's progressive clinical deterioration. 
4	Inotropic response to norepinephrine is augmented early and maintained late in conscious dogs with perinephritic hypertension. We studied the inotropic responses to intravenous infusions of norepinephrine in nine conscious chronically instrumented dogs before and early (2-4 weeks) in the development of perinephritic hypertension; seven conscious dogs were studied later (approximately 14 weeks), during a more stable phase of hypertension. perinephritic hypertension was associated with a 24% increase in left ventricular (LV) mass during developing hypertension; no further increase was seen during the stable hypertension phase. LV end-systolic stress was increased early (p less than 0.01) but was normalized later. The LV end-systolic stress-volume relation demonstrated an enhanced contractile response to norepinephrine during developing hypertension, which returned toward control later in the course of stable hypertension. The LV dP/dt responses to norepinephrine (0.4 microgram/kg/min) were significantly greater during developing hypertension (7,509 +/- 337 mm Hg/sec, p less than 0.05) compared with the control period (4,737 +/- 286 mm Hg/sec) and returned toward the control value during stable hypertension (5,168 +/- 465 mm Hg/sec). The enhanced inotropic responses to norepinephrine in developing hypertension were preserved in the presence of ganglionic blockade, suggesting that the augmentation was not mediated via reflex mechanisms. These physiological responses were associated with an increase in beta-adrenergic receptor density, but no significant change in basal or maximal adenylate cyclase stimulation occurred during developing hypertension. Thus, in contrast to prior studies in anesthetized animals, the inotropic response to beta-adrenergic stimulation is not depressed in conscious dogs but is enhanced selectively during the development of hypertension and maintained during stable hypertension. 
5	The classification of childhood seizures and epilepsy syndromes. The classification of seizures and the epileptic syndromes is particularly relevant to those who treat children, as most syndromes are age related, with onset between the neonatal and adolescent periods. Whereas seizures are characterized by ictal behavior and EEG findings, epilepsy syndromes are defined by seizure type, etiology, age of onset, natural history, possible genetic factors, and prognosis. Limitations exist, but attempts to use these classifications typically lead to a better understanding of the patient and allow for more precise evaluation and treatment. 
5	Biomechanics of a double prosthetic ligament in the anterior cruciate deficient knee. We have assessed the biomechanical properties of a 'double-bundle' prosthetic ligament replacing the anterior cruciate in cadaver knees. We compared the results with those of single bundle 'over-the-top' and 'through-the-condyle' techniques, performing anterior drawer tests at 20 degrees and 90 degrees knee flexion. The over-the-top reconstruction gave better anteroposterior stability at 20 degrees, while the through-the-condyle repair was more stable at 90 degrees. The double-bundle reconstruction gave practically normal anterior stability at both 20 degrees and 90 degrees. 
1	Evaluation of the serum level of immunosuppressive substance in oral cancer patients. The serum level of immunosuppressive substance (IS) was studied in 40 patients with primary oral cancer and in 79 patients without cancer. Its usefulness was evaluated as a parameter for monitoring therapy as well as recurrence of the tumors. Mean values for serum IS in patients with cancer and patients without were 687 +/- 284 micrograms/mL and 464 +/- 153 micrograms/mL, respectively. Normal healthy controls had a mean value of 431 +/- 105 micrograms/mL, with the cutoff value set at 641 micrograms/mL (mean +2 SD). Patients without cancer who had a severe infectious disease showed conspicuously high serum IS levels, and these values were closely correlated with their C-reactive protein values. The positive rate of IS increased in all patients with oral cancer was 58%. The mean level of serum IS in cancer patients was significantly higher than that of the controls (P less than .01), and the level was found to be more elevated as the stage of the disease advanced (stage I to III, 48%; stage IV, 68%). Histologic analysis of the tumor cells in patients with squamous cell carcinoma (SCC) showed that the mean serum IS level of those who had poorly differentiated SCC was much higher (937 +/- 181 micrograms/mL) than that of patients with well-differentiated SCC (616 +/- 159 micrograms/mL). Patients who had recurrent or metastatic cancer, or those who died from the cancer exhibited marked elevation of the serum IS levels, whereas patients who remained free of cancer in the follow-up period showed significantly lower serum IS levels. The rise and fall of the serum IS level was closely correlated with the disease progression and/or remission. These data strongly suggest that serum IS is a useful parameter for monitoring the disease stage as well as the effect of therapy on patients with oral cancer. 
4	Indications, timing, and optimal technique for diagnostic angiography and angioplasty in acute myocardial infarction. Emergency cardiac catheterization and coronary angioplasty for acute myocardial infarction (MI) have a continuing role in the thrombolytic era. Although thrombolytic therapy has revolutionized the treatment of MI, it has significant shortcomings: about 75% of patients with acute MI cannot be treated with thrombolytic agents, 25% of treated patients will have persistent occlusion of the infarct-related artery, 70% will have a residual stenosis greater than or equal to 70%, and 20% of treated patients will experience reocclusion. Cardiac catheterization identifies the coronary anatomy for mechanical revascularization and allows the unstable patient to receive special therapy, such as intra-aortic balloon pumping. Many large clinical studies have evaluated approaches to coronary angioplasty for acute MI. Deferred angioplasty has indisputable advantages over immediate routine angioplasty. Direct angioplasty without concomitant thrombolytic therapy has acceptable success and complication rates, so that it can be considered the treatment of choice for acute MI in centers with an angioplasty program if thrombolytic therapy is contraindicated. Patients at very low risk may not require cardiac catheterization routinely before discharge, since their good prognosis cannot be improved by invasive evaluation and intervention. Emergency surgical revascularization is indicated in a very small percentage of cases. 
4	Alfentanil pharmacokinetics in patients undergoing abdominal aortic surgery. The pharmacokinetics of alfentanil, 300 micrograms.kg-1 IV, were determined in patients undergoing elective abdominal aortic reconstruction. The mean age (+/- SD) of the patients was 64.3 +/- 7.4 yr; their mean weight was 74.7 +/- 13.8 kg. Five patients underwent aneurysm repair and six had aortobifemoral grafting. Serum alfentanil concentrations were measured by gas-liquid chromatography in samples drawn at increasing intervals over a 24-hr period. A three-compartment model was fitted to the concentration versus time data. The volume of the central compartment and the volume of distribution at steady state (Vdss) were 0.44 +/- 0.022 and 0.63 +/- 0.32 L.kg-1, respectively. Total drug clearance was 6.4 = 1.9 ml.min-1.kg-1. The elimination half-time was 3.7 +/- 2.6 hr. Patient age was positively correlated with both Vdss and elimination half-time. There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of IV fluids infused intraoperatively. In general surgical patients, the elimination half-time of alfentanil has been reported to be 1.2-2.0 hr. Although the elimination half-time of alfentanil was longer in patients undergoing abdominal aortic surgery, alfentanil was eliminated much faster than either fentanyl or sufentanil in this patient population. 
4	Superiority of retrograde cardioplegia after acute coronary occlusion. Because antegrade cardioplegia may limit the distribution of cardioplegia beyond a coronary occlusion, this study was undertaken to determine whether retrograde coronary sinus cardioplegia provides superior myocardial protection during revascularization of an acute coronary occlusion. In 20 adult pigs, the second and third diagonal branches were occluded with a snare for 1 1/2 hours. Animals were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic arrest with multidose, potassium, crystalloid cardioplegia. In 10 animals, the cardioplegia was given antegrade through the aortic root, whereas in 10 others, it was given retrograde through the coronary sinus. After the arrest period, the coronary snares were released and all hearts were reperfused for 3 hours. Postischemic damage in the myocardium beyond the occlusions was assessed by wall motion scores using two-dimensional echocardiography (4 = normal to -1 = dyskinesia), the change in myocardial pH from preischemia, and the area of necrosis/area of risk (histochemical staining). Hearts protected with retrograde coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/- 0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/- 0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/- 3.6% versus 73.3% +/- 3.5%; p less than 0.0001). We conclude that retrograde coronary sinus cardioplegia provides more optimal myocardial protection than is possible with antegrade cardioplegia after revascularization of an acute coronary occlusion. 
2	Intestinal vascular sensitivity to vasopressin in portal hypertensive rats. The intestinal vascular responsiveness to arginine vasopressin was evaluated in rats with chronic portal hypertension. Male Sprague-Dawley rats were made portal hypertensive by stenosis of the portal vein. Ten to twelve days after the induction of chronic portal hypertension, the responsiveness of the small intestinal circulation to cumulative doses of vasopressin was evaluated using an isolated pump-perfused small intestinal preparation. The ED50 for maximal vasoconstriction was increased twofold in portal hypertensive rats compared with control rats. To determine if the impaired responsiveness to arginine vasopressin was related to the hyperglucagonemia of chronic portal hypertension, plasma glucagon levels were elevated in normal rats to levels previously measured in portal hypertensive rats (i.e. approximately 450 pg/mL), and the dose response studies were repeated. Glucagon significantly attenuated the responsiveness of the intestinal vasculature to vasopressin. Equipotent doses of nitroprusside also attenuated intestinal vascular responsiveness to vasopressin. The results indicate that there is a reduced vascular sensitivity to vasopressin in the intestine of portal hypertensive animals and suggest that elevations in circulating vasodilators in portal hypertensive conditions may partially explain this altered vascular responsiveness. 
4	Axillosubclavian vein thrombosis produced by retrosternal thyroid. Several causes of axillosubclavian vein thrombosis have been described. Trauma to the subclavian vein by pacemaker wires or central venous lines as well as the so-called effort thrombosis have been recognized as frequently diagnosed precipitating factors. A patient is herein presented with thrombosis of the subclavian vein caused by a giant substernal thyroid compressing the innominate vein. 
5	Abdominal trauma in pregnancy. When is fetal monitoring necessary? The type and duration of observation and monitoring of mother and fetus after abdominal trauma are dependent on gestational age and severity of trauma. Fetal monitoring is usually not required when the fetus is not viable; the primary consideration is the safety of the mother. When the fetus is viable, 24-hour inpatient fetal monitoring is indicated in cases of major trauma, even when no symptoms of injury are obvious. 
3	Symptomatic carotid endarterectomy trials. The possible benefit of carotid endarterectomy in stroke prevention is being evaluated in three major clinical trials. To date, the European Carotid Surgery Trial has randomized 2,200 patients, 30% of whom have a carotid stenosis of greater than 70% appropriate to their symptoms. The North American Symptomatic Carotid Endarterectomy Trial has randomized 1,000 patients, of whom more than half have this severity of appropriate stenosis. Quality control and the evaluation of outcome events in this trial is achieved by a three-tier review, including review by medical and surgical adjudicators who are blinded to the treatment arm of each patient. Baseline characteristics of the patients eligible but not randomized are similar to those of patients who have been randomized. Two percent of the patients randomized to the surgical arm have declined surgery and crossed over to the medical arm, and 3% have elected surgery after randomization to the medical arm. Both of these studies, as well as a Veterans Administration trial, are continuing to randomize patients. 
1	Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma. Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lymphomas was tested for reactivity with both B-cell leukemias and lymphomas. Ten of 40 (25%) cases of chronic lymphocytic leukemia (CLL) reacted with at least one of the 29 anti-SId MoAbs. Three cases reacted with more than one anti-SId MoAb, but there was no repetitive pattern of a single anti-SId MoAb reacting with a large proportion of CLL cases. In contrast, for B-cell lymphoma, in which 11 of 31 (36%) cases reacted, one anti-SId (B4-1) reacted with five of the positive cases; all were diffuse histology. Restricted anti-SId reactivity may lead to important insights into the etiology of certain B-cell lymphomas. In addition, these anti-SIds may obviate the need to develop "tailor-made" antibodies for individual patients. 
4	Cardiomyopathy associated with the smoking of crystal methamphetamine. The smoking of crystal methamphetamine, or "ice," is a growing drug abuse problem in the United States. The toxic effects of methamphetamine smoking have not been well described. We describe two patients with cardiovascular toxic effects associated with the smoking of crystal methamphetamine. In our first patient, the use of smokeable methamphetamine was associated with the subsequent development of pulmonary edema and a dilated cardiomyopathy. In our second patient, the smoking of crystal methamphetamine likely produced diffuse vasospasm that resulted in acute myocardial infarction, cardiogenic shock, and death. The recognition of potentially lethal cardiac complications associated with the smoking of crystal methamphetamine is of extreme significance and should be emphasized to potential abusers of this drug. 
4	A hematologist's view of contrast media, clotting in angiography syringes and thrombosis during coronary angiography. While ionic contrast media (CM) are stronger anticoagulants and antiplatelet agents, both nonionic and ionic CM retard clotting, fibrinopeptide A generation and platelet aggregation (at least by Born-O'Brien aggregometry). Thus, nonionic CM do not cause clots and thrombi. Rather, the driving force for clot or thrombus formation, when it occurs, is blood contact with and activation by the foreign surface of a syringe or catheter itself. A marked enhancement of clotting by glass syringes in comparison to plastic ones supports this view. Blood in any syringe or catheter, therefore, will clot more slowly in the presence of nonionic or ionic CM, the inhibitory effects of the latter being more profound. With respect to models of thrombosis at sites of vascular injury or stenosis, the antithrombotic effects of CM may either be transient owing to the dynamic nature of blood flow (local endothelial cell denudation model), or as in the case of ionic CM, actually to enhance local platelet aggregation (stenosis model). In these situations, preservation of the antithrombotic functions of endothelium with nonionic CM may be quite critical. 
4	Total knee arthroplasty in obese patients. We examined 182 patients (257 knees) who had had a total knee arthroplasty two to five six years earlier. The patients were grouped into five weight classes. Eighteen patients (twenty-seven knees) were considered moderately obese and twelve patients (twenty-seven knees), severely obese. The results in all but four knees were rated excellent or good. One patient needed a revision procedure for late infection, and the result was rated poor. Three results were rated fair. There was no discernible difference in the over-all scores among the five weight groups. However, 30 per cent of the knees of the moderately and severely obese patients had patellofemoral symptoms, whereas the incidence was 14 per cent in the other groups (p less than 0.03). No clear-cut association was found between obesity and either thrombophlebitis or complications related to the wound. 
3	Neurinoma in the cavernous sinus: report of two cases. Two cases of trigeminal neurinoma located solely in the cavernous sinus are reported. Preoperatively, magnetic resonance imaging provided the accurate localization of the lesions, allowing precise planning of the surgical approach, that is, a subtemporal lateral approach and a pterional superior approach, respectively. The neurinomas inside the cavernous sinus were removed successfully, and the patients developed no new neurological deficits except for anesthesia in the 1st division of the trigeminal nerve. The characteristic magnetic resonance imaging findings of trigeminal neurinoma in the cavernous sinus are presented, and the different surgical approaches are discussed. 
5	Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas' cardiopathy. A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiania, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P less than 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease. 
1	A hepatoblastoma originating in the caudate lobe radically resected with the inferior vena cava. Complete resection of a rare hepatoblastoma in the caudate lobe, involving the inferior vena cava (IVC), is reported. After systemic chemotherapy, a 5-year-old child underwent exploratory laparotomy at another hospital, but resection was not attempted because the tumor in the caudate lobe had extensively invaded the retrohepatic IVC. However, because not only the lack of distant metastases but also the establishment of extrahepatic collaterals were confirmed by imaging, we thought it was possible to radically resect the tumor. We successfully performed an extended left hepatic lobectomy including total excision of the caudate lobe and the involved portion of the IVC. Although we did not reconstruct the IVC, no clinical manifestations arising from caval congestion were seen. The serum alpha-fetoprotein value declined below the normal limit. Our experience with this case has introduced a radical resectability for hepatic malignancy in the caudate lobe, even if it has extended into the IVC. 
4	Experimental pericardial effusion: relation of abnormal respiratory variation in mitral flow velocity to hemodynamics and diastolic right heart collapse Pericardial effusion is associated with an abnormal increase in respiratory variation in mitral flow velocity. However, the relation of the changes in flow velocity to pericardial pressure, hemodynamics and two-dimensional echocardiographic findings is not established. Therefore, 11 sedated dogs with extensive hemodynamic instrumentation were studied with two-dimensional and Doppler echocardiography during four stages of progressively larger pericardial effusion. During all stages of effusion, respiratory variation in peak mitral flow velocity in early diastole and left ventricular isovolumetric relaxation time was increased compared with baseline (p less than 0.05). This increase was seen at the earliest stage of effusion (mean pericardial pressure 4.2 +/- 1.4 versus -0.8 +/- 0.9 mm Hg at baseline, p less than 0.05), and preceded the appearance of unequivocal diastolic right heart collapse in every dog. Maximal respiratory variation coincided with the appearance of right atrial collapse (mean pericardial pressure 7.1 +/- 2.4 mm Hg; mean inspiratory decrease in aortic pressure 9.5 +/- 2.6 mm Hg; mean aortic pressure 88.2 +/- 15.2 versus 102.2 +/- 11.2 mm Hg at baseline, p less than 0.05; and cardiac output 3.8 +/- 1.2 versus 5.5 +/- 1.3 liters/min at baseline, p less than 0.05), but did not increase at stages associated with more severe hemodynamic compromise. In addition, the respiratory changes in peak mitral flow velocity in early diastole were associated with simultaneous changes in the diastolic transmitral pressure gradient. It is concluded that in this model of acute pericardial effusion 1) increased respiratory variation in early diastolic mitral flow velocity, peak mitral flow velocity in early diastole and left ventricular isovolumetric relaxation time occurs almost immediately as pericardial pressure increases and persists at all stages of increasing pericardial effusion; 2) the abnormal respiratory variation occurs before equalization of intracardiac pressures and before the onset of unequivocal right heart collapse; 3) the respiratory variation occurs as a result of changes in the diastolic transmitral pressure gradient; and 4) the magnitude of the respiratory change is not necessarily predictive of pericardial pressure or severity of hemodynamic compromise, especially at the more severe stages of pericardial effusion. 
5	DNA analysis of multiple synchronous renal cell carcinomas. The authors used retrospective quantitative DNA analysis to study interrelationships between multiple synchronous renal cell carcinomas in seven patients. DNA content was determined by image analysis on Feulgen-stained nuclear smears prepared from multiple paraffin blocks from each tumor. Tumors were unilateral in four cases and bilateral in three. Ten tumors had homogeneous, and four heterogeneous DNA stemlines. Intertumoral heterogeneity in four cases suggested multifocal origin. Identical DNA aneuploid indices in bilateral tumors in one case suggested metastasis from a solitary origin. Abnormal DNA content and heterogeneous populations began to appear in the size range 2.0 to 5.0 cm. All tumors over 5.0 cm contained nondiploid populations. Although the interrelationships between these multiple synchronous neoplasms are not entirely clear, the DNA analysis suggests that the occurrence of nondiploid stemlines and heterogeneous DNA content may parallel both tumor growth and more aggressive behavior. 
5	Clinical presentation of suspected malignant hyperthermia during anaesthesia in 402 probands. As anaesthetists have become more aware of malignant hyperthermia the mortality rate has fallen, but concommitantly the number of dubious and aborted cases has increased. All probands who developed a suspected malignant hyperthermia reaction during anaesthesia and subsequently underwent muscle biopsy were classified according to the clinical presentation. A probability for malignant hyperthermia can be calculated, using the classification, for each type of clinical presentation; this varied from 0.96 to 0.07. Certain clinical features were found to be of more value as predictors than others; these included a high creative kinase and myoglobinuria. The accuracy of prediction depends on a clear contemporaneous description of the clinical events. 
5	Correlation between essential tremor and migraine headache. The relationship between essential tremor (ET) and migraine was investigated in a prospective study. In a group of 74 ET patients 36.5% had migraine compared with 17.7% of 102 control subjects without tremor. In a group of 58 patients with migraine 17.2% had ET compared with 1.2% of 85 controls without migraine. The prevalence of ET in migraine controls was greater than controls without migraine (22% compared with 1%; p = 0.002). It is concluded that there is an association between essential tremor and migraine. 
4	A case of lisinopril-induced lithium toxicity We describe a patient who developed lithium toxicity when lisinopril was substituted for clonidine. Possible mechanisms of angiotensin-converting enzyme (ACE) inhibitor-induced lithium toxicity are discussed. Aggressive serum lithium concentration monitoring and a reduction in the dose of lithium is advised when using ACE inhibitors because of disturbances and shifts in fluid and electrolyte balance. 
4	Dissociation of changes in cardiovascular mass and performance with angiotensin-converting enzyme inhibitors in Wistar-Kyoto and spontaneously hypertensive rats. The effects of angiotensin-converting enzyme inhibitors on cardiovascular mass and function were measured in three groups of 22 week old male Wistar-Kyoto normotensive and spontaneously hypertensive rats treated with CGS-16617, cilazapril or quinapril. Left ventricular performance was assessed by electromagnetic flow meter during rapid whole blood infusion before and after arterial pressure and increased abruptly with aortic snare; aortic distensibility also was assessed in vitro. The systemic hemodynamic effects of these three agents were similar, yet their structural effects varied. Although left ventricular and aortic masses diminished and right ventricular mass remained unchanged (with all three agents) in the spontaneously hypertensive rats, CGS-11617 and cilazapril also reduced left ventricular mass in the normotensive Wistar-Kyoto rats without changing aortic mass. All three agents improved aortic distensibility whether or not mass was decreased. Left ventricular structural changes were associated with variable changes in pumping ability. These data show that reduced mass associated with angiotensin-converting enzyme inhibitor treatment was not consistent in ventricles and aorta, that a dissociation exists between structural and functional changes and that reduction of cardiac mass alone does not relate to changes in chamber mass or in function. Thus, biologic and pharmacodynamic differences exist among angiotensin-converting enzyme inhibitors as well as between classes of antihypertensive agents. 
5	Features of "near-death experience" in relation to whether or not patients were near death The medical records of 58 patients, most of whom believed they were near death during an illness or after an injury and all of whom later remembered unusual experiences occurring at the time, were examined. 28 patients were judged to have been so close to death that they would have died without medical intervention; the other 30 patients were not in danger of dying although most of them thought they were. Patients of both groups reported closely similar experiences but patients who really were close to death were more likely than those who were not to report an enhanced perception of light and enhanced cognitive powers. The claim of enhancement of cognitive functions despite the likelihood that brain function had probably become disturbed and possibly diminished, deserves further investigation. 
3	Silent myocardial ischemia during rehabilitation for cerebrovascular disease. In asymptomatic patients the importance of silent ischemic ST-T wave changes on Holter monitoring is known to be a significant predictive variable for one-year mortality of postmyocardial infarction patients. This case report represents the uses of ambulatory ECG to detect ischemic ST changes in patients who have had recent strokes. The cases reported here of silent myocardiac ischemia in stroke patients reflect previous reports in which 70% of the ischemic episodes in patients with symptomatic coronary artery disease are not associated with angina and in which approximately 10% to 15% of acute myocardial infarctions are silent. We now believe that the incidence of "silent" ischemia may be precipitated in poststroke patients during their rehabilitation program. This belief is supported by two main factors. First, a high level of personally relevant mental stress exists which activates the sympathoadrenal system, which may lead to myocardial ischemia. Second, some stroke patients become aphasic and are unable to communicate adequately even if they experience angina symptoms. We have found that poststroke, most patients could not undergo exercise treadmill testing secondary to a variety of factors: inability to coordinate limbs, poor endurance, inability to follow directions, and/or lack of attention. We now propose that 24-hour monitoring for ST-T wave changes poststroke should be considered as part of a vigorous investigation for myocardial ischemia during the rehabilitation of these patients because they have an increased risk of cardiac morbidity. 
5	Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas. Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation. 
5	Next-day memory impairment with triazolam use The prevalence, rate, and degree of memory impairment for next-day activities during a short, intermittent course of bedtime doses of triazolam, temazepam, and placebo were assessed in a double-blind parallel-group study. 5 of the 6 subjects in the triazolam group reported at least one episode of next-day memory impairment/amnesia, with a total of 12 episodes being reported for the 30 subject-drug nights (a rate of 40%). In the temazepam group there were no such episodes of memory impairment. Immediate and delayed recall were also tested and related to whether active drug or placebo had been taken the night before. Impairment of delayed recall was significantly and several times greater than that in the temazepam or placebo groups. Next-day memory impairment/amnesia after a bedtime dose of triazolam tended to increase with continued or intermittent drug use. Cognitive impairments associated with triazolam probably represent a spectrum of organic brain dysfunction, with memory impairment/amnesia and confusion being the commonest, and milder manifestations and hallucinations and delusions the more severe and less common, features. 
4	Effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter, regional cerebral blood flow, and brain structure in cats. Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 +/- 7.5% (SE) and infarction was 34.5 +/- 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 +/- 8.1% (SE), and infarction was 8.1 +/- 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary. 
1	Cutaneous vasculitis associated with pheochromocytoma. We describe a patient who presented with constitutional symptoms, severe hypertension, and purpuric lesions over the knees, thighs, and penis. The patient was eventually diagnosed as having multiple endocrine neoplasia type II, with cutaneous leukocytoclastic vasculitis. The cutaneous vasculitis persisted despite treatment with high-dose systemic corticosteroids, but rapidly resolved after the removal of bilateral pheochromocytomas. This case demonstrates cutaneous leukocytoclastic vasculitis in association with pheochromocytoma. 
1	Extended neck dissection. From the time Crile described radical neck dissection in 1906, this surgical procedure became popular in the management of metastatic cancer in the neck. Over the past two decades, the modified neck dissection has been effectively utilized for conservation of function and cosmesis while achieving the same oncologic goals. However, there are several instances where the above standard procedures are not adequate for resection of malignant tumors. Although there is a definite trend toward conservation procedures, extended neck dissection is often necessary especially in patients with N2 and N3 disease. Apart from the standard structures removed in radical neck dissection, the other structures removed in extended neck dissection include skin, the digastric muscle, hypoglossal nerve, vagus nerve, sympathetic chain, ramus mandibularis, carotid artery, tracheo-esophageal nodes, etc. Over the past seven years, we have performed 40 extended neck dissections. All the patients had N2 or N3 disease in the neck. Nine patients had unknown primaries. Thirteen patients had their primary tumors in the oral cavity and 11 in the laryngopharynx. Five patients had primary tumor in the salivary glands and two patients had metastatic melanoma. Patients who underwent extensive skin excision had pectoralis myocutaneous flap reconstruction. All patients received postoperative radiation therapy. One patient died of cardiac problems 4 weeks after operation. Local control was achieved in 70%. The most difficult region for local control was the disease behind the mastoid process, and the most difficult problems were patients with involvement of the subdermal lymphatics. Our data suggests that there are definite situations where extended neck dissection is indicated with satisfactory local control of the nodal disease. 
1	Coexpression of galanin and adrenocorticotropic hormone in human pituitary and pituitary adenomas. Galanin is a neuropeptide that regulates the secretion of several pituitary hormones, including prolactin (PRL) and growth hormone (GH). Galaninlike immunoreactivity (Gal-IR) and galanin mRNA in the rat anterior pituitary is cell lineage specific, with predominant expression in lactotrophs and somatotrophs. The authors examined the cellular distribution of human Gal-IR in seven normal postmortem pituitaries and 62 pituitary tumors by immunoperoxidase staining. In contrast to the rat, Gal-IR in human anterior pituitaries was present in corticotrophs scattered throughout the gland, but not in lactotrophs, somatotrophs, thyrotrophs, or gonadotrophs. Distinct Gal-IR also was present in hyperplastic and neoplastic corticotrophs in 19 of 22 patients with Cushing's disease. In noncorticotroph cell tumors, unequivocal Gal-IR was present in 5 of 11 GH-secreting tumors associated with clinical acromegaly, 9 of 18 nonfunctioning pituitary adenomas, and 2 of 14 prolactinomas. Of these galanin-positive tumors, four of the five GH-secreting adenomas, six of the nine nonfunctioning adenomas, and both of the prolactinomas also contained adrenocorticotropic hormone immunoreactivity (ACTH-IR). Immunostaining and in situ hybridization on adjacent sections using an 35S-labeled probe complementary to human galanin mRNA demonstrated predominant galanin expression in normal corticotrophs. Immunoelectron microscopy confirmed the presence of Gal-IR in pituitary cells characteristic of corticotrophs in both normal and neoplastic pituitaries. Thus, as in the rat, galanin gene expression in the human pituitary is cell-type specific. Unlike the rat, however, human galanin gene expression is restricted to the corticotroph lineage. Studies of tumors confirmed the observed coexpression of galanin and adrenocorticotropic hormone. The divergent cell type specificity of galanin production in human and rat pituitaries reflects different patterns of gene activation in these two species. In addition, these results suggest that galanin in the human pituitary may participate locally in the regulation of the hypothalamic-pituitary-adrenal axis. 
2	Pelvic pain: lessons from anatomy and physiology. Pelvic pain is often a difficult differential diagnosis in the emergency department. For physiologic reasons, pain in the pelvis is difficult to localize to a specific organ, and pelvic peritonitis is hard to recognize. On the other hand, differences in types of pain can be very useful in arriving at a correct diagnosis. The clinician must learn to recognize superficial and deep somatic pain, and differentiate between various types of visceral pain which originate from inflammation, ischemia, or colic. A review of the anatomy and physiology of pelvic pain helps identify some of the problems as well as potential aids in approaching the patient with pelvic pain. 
1	Lewis system alterations in gastric carcinogenesis. Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma. The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings. An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients. The prevalence of this anomaly increased with the evolution of the premalignant process, in agreement with the commonly accepted model of gastric carcinogenesis. Thus, anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases, in 64.6% of intestinal metaplasia, in 15.4% of atrophic gastritis, and in 7.4% of superficial gastritis. No alterations were found in subjects with normal gastric mucosa. Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11). In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation. The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors. These findings suggest that, during gastric carcinogenesis, antigenic alterations may precede neoplastic transformation. An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals. 
1	Pigmented spindle cell naevus. We report 22 cases of pigmented spindle cell naevus (PSCN). The usual appearance of these naevi is that of a heavily pigmented papule found mostly on the legs of young patients. Histologically, PSCN was characterized by symmetrical proliferation of spindle-shaped pigmented melanocytes grouped in large junctional nests. Pagetoid spread of single cells in the overlying epidermis was frequently found. In our opinion, PSCN is a distinctive benign acquired melanocytic naevus that in the past has been frequently misdiagnosed as atypical Spitz naevi or malignant melanoma. 
5	Ureteral triplication and ureterocele: report of 3 cases and review of the literature. We report 3 cases of ureterocele associated with ureteral triplication and review the literature. Ureteral triplication was type I in 2 patients and type II in 1. Diagnosis was established preoperatively in 2 cases and intraoperatively in 1. All patients were initially treated by upper pole partial nephrectomy and aspiration of the ureterocele, leaving the ureteral stump open in the retroperitoneum. Subsequent excision of the ureterocele and ureteral reimplantation for persistent ipsilateral vesicoureteral reflux and recurrent urinary tract infections were required in 2 cases. 
5	Visualization of acute pulmonary emboli by transesophageal echocardiography. This report describes a patient who became hypoxic and hypotensive while awaiting cardiac surgery. An urgent transesophageal echocardiogram in the operating room showed a mass at the junction of the main and right pulmonary arteries consistent with thrombus. The thrombus was removed surgically, and the patient then had a successful aortic valve replacement. Transesophageal echocardiography is therefore useful in the evaluation of the critically ill patient. 
2	Treatment of anorectal abscess with or without primary fistulectomy. Results of a prospective randomized trial. To determine whether primary fistulectomy should be performed or not at the time of incision and drainage, a prospective, randomized study in 70 patients with anorectal abscess was conducted. Thirty-six patients underwent incision, drainage and fistulectomy with primary partial internal spincterectomy (group I), whereas in 34 patients anorectal abscess was treated by incision and drainage alone (group II). After a median follow-up of 42.5 months, the combined recurrence or persistence rate was 2.9 percent in group I and 40.6 percent in group II (P less than 0.0003, log-rank test). Recurrent abscesses or persistent fistulas were treated by secondary partial internal sphincterectomy. Comparing anal continence before and 1 year after definite treatment, we found increased anal function disturbances in 39.4 percent of the patients in group I and in 21.4 percent of the patients in group II (P less than 0.106, Fisher-exact test). The combined recurrence or persistence rate of 40.6 percent indicates that more than half of the patients with anorectal abscess will have no further problems after simple incision and drainage. This finding, as well as the increased anal function disturbances after partial internal sphincterectomy (either primary or secondary) are the main reasons to reserve fistulectomy as a second stage procedure if necessary. 
5	Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease. Treatment of normal platelet-rich plasma with a physiological amount of insulin (100 microunits/ml, optimum concentration) for 3 hours at 23 degrees C stimulated the binding of prostaglandin E1 by more than twofold (3,940 +/- 250 sites/10(8) platelets) compared with the nontreated, control platelet-rich plasma (1,590 +/- 265 sites/10(8) platelets). After platelet-rich plasma from patients with acute ischemic heart disease (n = 43), whose platelets showed impaired prostaglandin E1/I2 receptor activity (850 +/- 100 sites/10(8) platelets), was incubated with insulin (optimum amounts varied from 100 to 200 microunits/ml), the binding of the prostanoid was restored to normal levels (1,790 +/- 140 sites/10(8) platelets) in 75% of the cases. Twenty-five percent of the patients did not respond to the stimulatory effect of insulin. The increased binding of the prostanoid to the insulin-treated platelets also resulted in increased cyclic AMP levels both in normal subjects (44.14 +/- 3.1 pmol/10(8) [insulin-treated] platelets versus 16.35 +/- 2.91 pmol/10(8) [control] platelets) and in patients with acute ischemic heart disease (23.87 +/- 4.1 pmol/10(8) [insulin-treated] platelets versus 7.70 +/- 2.0 pmol/10(8) [control] platelets) by the prostanoid (1.0 microM). The treatment of platelet-rich plasma with the hormone decreased the minimum inhibitory concentration of the prostanoid from 34 +/- 14 to 15 +/- 9 nM (p less than 0.001) in the case of normal volunteers and from 49 +/- 15 to 32 +/- 11 nM (p = 0.002) in the case of "responder" patients. Insulin did not produce any effect on the inhibition of platelet aggregation by the prostaglandin in "nonresponder" patients. In the follow-up study, although the stimulatory effects of insulin on platelets from responder patients were improved to normal levels, the platelets from the nonresponder patients remained persistently unresponsive to the effect of the hormone. 
1	A case of cecocolic intussusception with complete invagination and intussusception of the appendix with villous adenoma. Villous adenoma of the appendix is a rare neoplasm and intussusception of the appendix is a rare pathologic condition. A very rare case seen in a 35-year-old male with pain in the right lateral abdomen is reported. In this patient, the appendix along with the villous adenoma intussuscepted and invaginated into the cecal lumen, and presented as cecocolic intussusception. A polypoid lesion was diagnosed in the cecum by fiberoptic colonoscopy. Unlike polypoid lesions at other sites in the large intestine, polypoid lesions of the cecum may accompany intussusception and invagination of the appendix. Consequently, caution is required in performing endoscopic polypectomy in cases of polypoid lesions of the cecum. 
5	Mucosal characteristics of pelvic ileal pouches. This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all eight with pouchitis) had subtotal or total villous atrophy and crypt hyperplasia. In this group, nine had colorectal type sulphomucin and the 40kD colonic protein was detected in two. These changes were not observed in patients with less severe villous abnormalities. Sucrase-isomaltase activity was, however, present in all 25 pouch specimens. We conclude that although some ileal pouches acquire certain colonic characteristics, complete colonic metaplasia does not occur. 
4	Clinical characteristics and coronary angiographic findings of patients with unstable angina, acute myocardial infarction, and survivors of sudden ischemic death occurring during and after sport. The clinical characteristics and coronary angiographic findings of 42 well-conditioned subjects with an acute ischemic event related to sport are reported. Five patients had unstable angina, 25 had acute myocardial infarction (AMI), and 12 were resuscitated victims of sudden ischemic death. Twenty-two events occurred during sport (group A) and 20 after sport (group B). There were two women and 40 men. The mean age was 46 years (range 25 to 65). Twelve out of 30 patients who smoked cigarettes had an adjunctive risk factor for coronary artery disease. Twelve others (28%) had no identifiable risk factor. Prodromal cardiac symptoms were detected in three patients (group A). Two patients had previous myocardial infarction (group B). Coronary angiography was performed acutely in 39 patients. The distribution of the ischemia-related coronary artery was comparable in both groups. The lesion morphology of 35 culprit coronary arteries was described as concentric in six patients and eccentric with regular borders (type I lesion) in 11 and irregular borders (type II lesion) in 18. Eccentric lesions consistent with ruptured plaques prevailed in both groups. Associated coronary artery disease was present in 10 patients. There was no relationship between the number of risk factors and the extent of diseased coronary arteries. Clinical characteristics and coronary angiographic findings of patients with unstable angina, AMI, and sudden death either during or after sport are similar and indicate a common pathogenesis. The probable mechanism of a coronary event related to sport is exercise-induced plaque rupture. In most instances such an event is unexpected and unpredictable. Identification of some subjects at risk is possible. 
2	Clinical evaluation of an algorithm for the interpretation of hyperamylasemia. Total amylase concentration in serum continues to be widely determined in the diagnosis of acute pancreatic disease. Accumulated experience has made clear, however, that this determination has distinct limitations. Consequently, the knowledge of the origin of hyperamylasemia may have an important influence on treatment, hospitalization, and extent of clinical investigations. We undertook a logical and systematic approach to the interpretation of hyperamylasemia through the use of an algorithm that can be applied in clinical situations without the need for the integration of radiologic procedures or clinical data. The proposed algorithm was tested for effectiveness in 97 consecutive hospitalized patients with hyperamylasemia (amylase level greater than twice the upper reference limit) for a 2-year period. The majority (52.5%) of these patients had acute pancreatitis. The algorithm assigned the correct diagnostic categories in 95.8% of cases, with a disagreement between patient diagnosis and algorithm-generated diagnosis in only four cases. These four patients (two with acute biliary disease, one with bacterial peritonitis, and one with chronic renal failure) had pancreatic lipase values greater than five times the upper reference limit, so that the algorithm classified their condition as acute pancreatitis. The clinical trial indicated that the proposed decision tree, which requires only knowledge of biochemical data that are readily available, is useful in the evaluation of elevated amylase activity and facilitates arrival at a definitive diagnosis. 
2	Cerebrovascular complications of inflammatory bowel disease. There is an increased incidence of central nervous system thromboembolic events in young patients with inflammatory bowel disease. A 33-yr-old woman previously diagnosed with pseudotumor cerebri suffered superior sagittal and transverse sinus thromboses during a severe flare of ulcerative colitis. These were documented on contrast computed tomographic (CT) and magnetic resonance imaging (MRI) scans. Stroke may be more common in patients with ulcerative colitis than in patients with Crohn's disease; arterial disease is more prevalent than venous and dural sinus disease, and is correlated with an active phase of inflammatory bowel disease. It is difficult to assess whether there is a relationship to concurrent steroid use, and a consistent relationship to duration of inflammatory bowel disease or to other extraintestinal manifestations is not apparent. 
4	Two urokinase dose regimens in native arterial and graft occlusions: initial results of a prospective, randomized clinical trial. The effects of two urokinase (UK) dose regimens on lysis time, lytic success, primary clinical success, and frequency of complications of peripheral thrombolysis were compared. Seventy-two intraarterial UK infusions were performed by means of standard catheter-directed infusion techniques in 63 patients with symptomatic peripheral arterial or bypass graft occlusions. Patients were prospectively randomized to high-dose (250,000 U/h for 4 hours and then 125,000 U/h) or low-dose (50,000 U/h) regimens. The mean time to complete lysis was 20.8, 26.0, 16.5, and 18.2 hours for the high-dose artery, low-dose artery, high-dose graft, and low-dose graft groups, respectively (P was not significant). Respective mean infusion durations were 27.1, 35.4, 22.2, and 25.3 hours. Clinical success was achieved in 65%-85% of cases. The frequency of complications was equivalent between groups, except for a higher frequency of minor bleeding complications in the high-dose group. The two urokinase dose regimens studied were equally effective in enabling peripheral thrombolysis. 
4	Clinical controversies surrounding thrombolytic therapy in acute myocardial infarction. The treatment of acute myocardial infarction has changed tremendously in the past decade because thrombolytic therapy has become the treatment of choice for the patient with acute myocardial infarction. Although many issues have been resolved, several controversial issues remain unresolved. This article addresses thrombolytic agents in terms of their superiority in achieving infarct vessel patency and mortality reduction as well as the role of thrombolysis in patients who present with chest pain of greater than 6 hours' duration, who are elderly, and who have an inferior infarction. 
1	A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells. Malignant spreading of cancer cells requires cell surface proteases that cleave the crosslinked collagenous matrix of connective tissues. From correlating the morphologically defined invasiveness of tumor cells with the presence of specific membrane-associated proteases, we have identified a malignant human melanoma cell line, LOX, that invades crosslinked gelatin films in vitro and contains uniquely a neutral 170-kDa gelatinase in the cell membrane. A similar gelatinase was found in membranes recovered from culture media conditioned with LOX. The 170-kDa gelatinase is a wheat germ agglutinin-binding protein. The proteolytic activity is maximal at neutral pH, enhanced by EDTA and dithiothreitol, inhibited by the cysteine protease inhibitors N-ethylmaleimide, HgCl2, and phenylmethylsulfonyl fluoride, and can bind to an organomercurial adsorbent, suggesting that it is a neutral sulfhydryl-sensitive protease. This 170-kDa gelatinase of LOX cells was not found in a control melanoma cell line, SK-MEL28, or in 32 other tumor cell lines that did not show extracellular gelatin degradation. Thus, we have identified a large membrane-bound protease that may be a specific marker molecule for melanoma cell invasiveness. 
1	Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain. To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned. 
5	Pharmacokinetics of paracetamol after cardiac surgery. Plasma concentration was measured after rectal and nasogastric administration of paracetamol 15 mg/kg to 28 febrile children aged between 9 days to 7 years who had undergone cardiac surgery. After equivalent doses, rectal administration in neonates and children on the first postoperative day was found to produce plasma concentrations below the therapeutic range with higher concentrations after nasogastric paracetamol on the second postoperative day. There was less variance in plasma paracetamol concentrations in neonates. Both plasma elimination half life and area under the plasma concentration time curve were significantly increased in neonates after suppository dosing compared with older children. There was no difference in antipyretic effect between the two routes of administration, but this was much lower than that previously reported in febrile children. 
5	Prevalence of human immunodeficiency virus seropositivity in pediatric emergency room patients undergoing phlebotomy. Information on the prevalence of human immunodeficiency virus (HIV) infection among children and adolescents requiring medical care is sparse. A small but significant risk of seroconversion occurs in health care workers who handle blood and body fluids of patients infected with HIV. The prevalence of HIV seropositivity in children who had phlebotomy as part of emergency care was measured. Of 749 blood samples, 21 (2.8%) tested positive for HIV antibody by enzyme-linked immunosorbent assay and Western Blot analysis: 14 samples from 6 patients with hemophilia, 6 from 3 patients with acquired immunodeficiency syndrome/acquired immunodeficiency syndrome-related complex, and 1 from a patient with asthma. Of these 21 blood samples, 10 were from 4 children previously known to be HIV positive, 4 were from patients with a known parental risk factor, and 16 were from patients with known history of blood transfusion. One sample was from a children with unknown HIV status and no documented risk factors. Procedures included 9 venipunctures, 17 intravenous line placements, 1 lumbar puncture, and 1 pelvic examination. Most patients with HIV seropositivity had been known to be HIV seropositive or at significant risk for HIV seropositivity. Although the potential risk to health care workers from children without known risk factors for HIV seropositivity was small in this population, the currently recommended infection-control precautions should always be observed. 
4	Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization. To compare left ventricular filling variables as derived by transmitral pulsed Doppler echocardiography (tpDE) and hemodynamic variables as assessed at right heart catheterization (RHC), 104 ICU patients (64 male, 40 female) aged 26 to 73 yr (mean 54.6 +/- 10.3) without valvular heart disease were examined. Simultaneously with RHC, transmitral flow velocity profiles were obtained by tpDE, and the ratio of the velocity-time integrals of late diastolic active (A wave) and early diastolic passive inflow into the left ventricle (E wave) was calculated (A/E ratio). Invasively determined pulmonary capillary wedge pressure (WP) ranged from 3 to 36 mm Hg (median 13.35, 5%/95% 6/31 mm Hg). Linear regression analysis showed a highly significant correlation between the A/E ratio and WP (r = .98, p less than .001, standard error of the estimate [SEE] = 0.10). The A/E ratio also correlated with other hemodynamic variables such as cardiac output (r = -.68, p less than .001, SEE = 0.33), cardiac index (r = -.74, p less than .001, SEE = 0.31), and stroke volume index (r = -.68, p less than .001, SEE = 0.34). The interobserver agreement (derived by intraclass correlation analysis between two examiners) on the A/E ratio was high (r = .95, p less than .001, n = 26). We conclude that WP can be accurately determined noninvasively by tpDE. For the assessment of systolic ventricular function, tpDE is of limited diagnostic value. 
1	The management of malignant bone tumors in children and adolescents. A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma, fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978 to 1988. Ninety-eight percent of the patients received chemotherapy and 63% had a surgical resection. Sixty-five percent of all patients were alive at 30 months and were considered disease free. The functional results after surgery were evaluated according to the Musculoskeletal Tumor Society score. In all diaphyseal resections and resections of the upper extremity and pelvis, the results were excellent or good in 60% of the cases. In resections of the proximal femur, distal femur, or proximal tibia and reconstruction with nonexpansible prostheses, the results were excellent or good in 75%. On the other hand, when arthrodeses of the lower extremity were used, only 14% of cases had a good result. This correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth. 
3	Locked-in syndrome with bilateral ventral midbrain infarcts. We report a patient who was quadriplegic and mute, but retained consciousness and communicated by eye movements and blinks. EEG and SEPs were normal. BAEPs showed slight prolongation of latencies for waves IV and V. MRI showed bilateral infarcts only in the middle and lateral portions of the cerebral peduncles. 
1	Genetics of common diseases of adulthood. Implications for prenatal counseling and diagnosis. Genetic factors play an important role in the development of many common diseases of adulthood that result in early morbidity and mortality. Prevention of these disorders and their sequelae is best established through early detection and early intervention. Although it may be feasible to screen the entire population for some disorders (e.g., hypertension), this approach would be expensive and impractical for others (e.g., colon cancer). The family history provides an inexpensive and convenient method of identifying families at risk for premature diseases of adulthood. Family screening for a disorder should be recommended if there is increased risk for the disorder among family members, if screening methods are available to detect the condition at an early age or preclinical stage, and if early intervention will alter the course of the disease. For many disorders screening and intervention can prevent the occurrence of clinical disease. The prenatal counseling session affords an ideal setting for identifying families at risk for diseases of adulthood with major genetic components. By reviewing the family history, key family members can be identified and investigated, in order to establish a specific genetic diagnosis. At-risk relatives can then be counseled and screened for the disorder preclinically and premorbidly. The screening and intervention available for a disease depends on the nature of the disorder, our understanding of its physiology and etiology, and our current technology. The disorders discussed earlier are typical of conditions of adulthood that are influenced strongly by genetic factors, especially when they appear in younger adults. Atherosclerosis, colon cancer, and diabetes are complex phenotypes. Each can be caused by single-gene defects, but commonly the genetics are more complex. Empiric data help to establish the risk to an individual in the latter cases. In all three examples, early detection should lead to treatment, which can prevent more serious sequelae: by treating the dyslipidemia, coronary artery disease can be prevented; by removing the benign polyp, malignant cancer can be avoided; and when impaired glucose tolerance is detected, diet and exercise can prevent or delay frank diabetes and its complications. The complete evaluation of individuals at risk for disorders such as those in Table 1 and their families can be a complicated task. Referral to a center experienced in the genetics of common diseases often may be necessary.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Retrospective application of prognostic indices to pancreatitis discovered at necropsy. Six prognostic indices, which were developed to assess inpatients with acute pancreatitis, were evaluated for possible retrospective application. When applied to a series of 14 cases in whom pancreatitis was first diagnosed at necropsy, the index devised by Jacobs et al was found to be the most useful, because in nine of these cases eight or more of the variables required were available for assessment from the case records. In the other indices evaluated fewer than eight of the required variables were available for retrospective assessment in most cases. Although undiagnosed pancreatitis is probably uncommon as a sole cause of death, the retrospective use of one or more of these indices may help assess the severity of the patient's condition on admission to hospital. 
4	Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product. 
5	Effects of hypovolemia and transfusion on tumor growth in MCA-tumor-bearing rats. Pretransplant blood transfusion has been shown to significantly affect the outcome of renal transplantation. Evidence regarding the association of blood transfusions with growth or recurrence of solid tumors is still conflicting both in clinical and in experimental studies, although diminished survival has been suggested in several studies. To determine the influence of blood transfusions and hypovolemia, as separate or combined factors, on tumor growth, we evaluated the weight of a subcutaneously implanted sarcoma (methylcholanthrene-induced) in 35 rats. After reaching 1% tumor burden (day 0), the animals were separated into two groups: hypovolemia (shed volume, 15 ml/kg) or normovolemia. These groups were further divided according to resuscitation: OO (no resuscitation), BL (receiving syngeneic blood stored in citrate phosphate dextrose for 4 days, 15 ml/kg), SL (receiving 0.9% sodium chloride, 45 ml/kg). Tumor dimensions were determined daily by external measurement, and tumor weight was calculated. Hypovolemia exerted a significant influence on tumor growth, independent of the resuscitation modality. The rats that received blood transfusions showed an increased rate of tumor growth, compared to the animals that received saline solution or no treatment. No interaction was noted between the effects produced by hypovolemia and blood transfusion. We conclude that the hypovolemic event enhanced tumor growth independently of the resuscitation, and transfusion of citrate phosphate dextrose-blood stored for 4 days did influence tumor growth in this model. We suggest that the effect of blood transfusion in patients with cancer has to be redefined to account for the influence of possible hypovolemic events. 
2	Proximal esophageal pH-metry in patients with 'reflux laryngitis'. Fiberoptic laryngoscopic examinations were performed on 40 patients with gastroesophageal reflux disease, 25 of whom had persistent laryngeal symptoms (dysphonia, cough, globus sensation, frequent throat clearing, or sore throat) and 15 without laryngeal symptoms who served as disease controls. Ten patients with laryngeal symptoms but none of the controls had laryngoscopic findings consistent with reflux laryngitis. Dual-site ambulatory pH recordings were obtained with the pH electrodes spaced 15 cm apart and with the proximal sensor positioned just distal to the upper esophageal sphincter. Patients in the three groups (disease controls: group 1; patients with symptoms but without laryngoscopic findings: group 2; and patients with both laryngeal symptoms and findings: group 3) were comparable in terms of age, smoking habit, the presence of esophagitis, and distal esophageal acid exposure. Proximal esophageal acid exposure was, however, significantly increased in groups 2 and 3, and nocturnal proximal esophageal acidification occurred in over half of these patients but in none of the group 1 patients. We conclude that the subset of reflux patients who experience laryngeal symptoms show significantly more proximal esophageal acid exposure (especially nocturnally) and often have laryngoscopic findings of posterior laryngitis not observed in control reflux patients. 
1	Cloning of the cDNA for human 12-lipoxygenase. A full-length cDNA clone encoding 12-lipoxygenase (arachidonate:oxygen 12-oxidoreductase, EC 1.13.11.31) was isolated from a human platelet cDNA library by using a cDNA for human reticulocyte 15-lipoxygenase as probe for the initial screening. The cDNA had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 75,590. Three independent clones revealed minor heterogeneities in their DNA sequences. Thus, in three positions of the deduced amino acid sequence, there is a choice between two different amino acids. The deduced sequence from the clone plT3 showed 65% identity with human reticulocyte 15-lipoxygenase and 42% identity with human leukocyte 5-lipoxygenase. The 12-lipoxygenase cDNA recognized a 3.0-kilobase mRNA species in platelets and human erythroleukemia cells (HEL cells). Phorbol 12-tetradecanoyl 13-acetate induced megakaryocytic differentiation of HEL cells and 12-lipoxygenase activity and increased mRNA for 12-lipoxygenase. The identity of the cloned 12-lipoxygenase was assured by expression in a mammalian cell line (COS cells). Human platelet 12-lipoxygenase has been difficult to purify to homogeneity. The cloning of this cDNA will increase the possibilities to elucidate the structure and function of this enzyme. 
5	The role of etoposide in the treatment of poorly differentiated carcinoma of unknown primary site. Patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA) of unknown primary site comprise 25% to 35% of the patients with carcinoma of unknown primary site. Some of these patients have neoplasms that are highly responsive to combination chemotherapy, and a minority have potentially curable tumors. Between 1978 and 1982, 68 patients were treated with combination chemotherapy (most received cisplatin, vinblastine, and bleomycin [PVB] with or without doxorubicin). Thirty-eight patients (56%) responded to treatment, with 15 (22%) complete responder (CR) and 9 (13%) long-term, disease-free survivors. Since that time, we have incorporated etoposide into the treatment of these patients because of its synergism with cisplatin and its great activity against several other neoplasms, including germ cell tumors. Seventeen patients with PDC of unknown primary site received salvage therapy with etoposide and cisplatin after failing PVB. Ten of these patients had partial responses (PR), with a median response duration of 5 months (range, 2 to 12 months). Thirty-two previously untreated patients with PDC received etoposide and cisplatin combinations as initial treatment. Eighteen of 30 evaluable patients (60%) responded to therapy, and 11 patients (37%) had CR. Seven patients remain disease-free 39 to 63 months after the completion of therapy. Etoposide is an active drug in the treatment of PDC of unknown primary site. Preliminary results indicate that initial treatment with etoposide and cisplatin combinations produces results equivalent to or superior to those achieved with PVB. 
2	The ileosigmoid knot. The ileosigmoid knot (ISK) is a rare cause of intestinal obstruction. Unfamiliarity with the condition could have disastrous consequence at surgery. Over the past 20 years, we have encountered seven cases. Analyzing the data gathered from these, and on reviewing the literature, we found it possible to arrive at a preoperative diagnosis in two patients. Four patients were women, two of whom developed the obstruction in the postpartum period. One of the males was found to have an inflamed Meckel's diverticulum included in the knotting. The symptoms and the clinical findings were nonspecific. The characteristic x-ray findings of a double closed loop obstruction, was seen in only three patients. Resection of gangrenous bowel with anastomoses was feasible in four. Unlike in other series, primary anastomosis of the large gut was undertaken. There were two deaths early in the series. Guidelines to the management have been suggested. 
5	Cyst of the choroid plexus in the lateral ventricle: case report and review of the literature. We report an intraventricular cyst in a 2-year-old boy who had myoclonic jerks of the extremities. The cyst had no communication with the ventricular system or subarachnoid space. Total removal of the cyst adhering to the choroid plexus was accomplished. The glial cyst wall was lined in part by flattened or cuboidal epithelium. The preoperative and postoperative computed tomographic scans and magnetic resonance images are presented, and congenital benign cysts in the lateral ventricle are reviewed and discussed. 
4	Distribution of angiographic vasospasm after subarachnoid hemorrhage: implications for diagnosis by transcranial Doppler ultrasonography. A study was undertaken to determine how frequently angiographic vasospasm occurs outside the normal access range of transcranial Doppler ultrasound in patients who have suffered a subarachnoid hemorrhage. Vasospasm located in the basal vessels is readily identifiable using transcranial Doppler ultrasound whereas spasm affecting the more distal, vertically oriented arteries is outside the standard detection range. It is therefore speculated that the sensitivity of the technique would be adversely affected by a high incidence of distal vasospasm. A total of 136 angiograms performed on 68 patients after a subarachnoid hemorrhage from anterior circulation aneurysms were reviewed to determine the typical distribution of vasospasm. Of the 40 cases that showed greater than or equal to 25% vessel narrowing, 50.0% had spasm restricted to the basal vessels, 42.5% had spasm involving both basal and distal segments, and 7.5% had spasm of the distal segments only. None of the patients with distal vasospasm alone developed delayed ischemic deficits. It is concluded that most patients with anterior circulation aneurysms who develop vasospasm will have involvement of the basal vessels, but a small number of patients may develop vasospasm only in distal vessels. 
3	Persistence and remission of depressive symptoms in late life. OBJECTIVE: The relation of poor health to the onset of depression symptoms in late life is well recognized, but little attention has been given to characteristics that might predict persistence or remission of depressive symptoms. In previous analyses the authors found that increasing disability and declining health preceded the emergence of depressive symptoms in older community residents and accounted for 70% of the variance explained by discriminant analyses. The aim of the present analysis was to examine the relevance of changes in health and disability to the persistence of depressive symptoms. METHOD: A representative sample of 1,855 adults aged 65 or older were assessed with the Center for Epidemiologic Studies Depression Scale at baseline. Twenty-four months later, 1,577 individuals were available for a second assessment of depressive symptoms. The characteristics of the 97 community residents whose depressive symptoms persisted over 24 months were compared to those of the 114 whose symptoms remitted. RESULTS: Changes in health, differences in age, sleep disturbance, and added formal support services accounted for more than 30% of the variance between the persistently depressed and remission groups. Advanced age and worsening health were associated with persistent symptoms, improved health with remission. CONCLUSIONS: Previous studies have indicated that untoward changes in health and disability play a major role in the onset of depressive symptoms. These findings show a substantial contribution to chronicity as well. 
5	Peritoneal closure or non-closure at cesarean. The value of peritoneal closure at the time of cesarean birth was evaluated prospectively. Two hundred forty-eight women undergoing low transverse cesarean through a Pfannenstiel skin incision were assigned to one of two groups: peritoneum open (N = 127) or peritoneum closed (N = 121). The mean (+/- SEM) surgical time in the open group (48.1 +/- 1.2 minutes) was significantly less than for the closed group (53.2 +/- 1.4 minutes) (P less than .005). There were no postoperative differences between the groups in the incidence of wound infection, dehiscence, endometritis, ileus, and length of hospital stay. Our study suggests that leaving the parietal peritoneum unsutured is an acceptable way to manage patients at cesarean delivery. 
4	Mental stress as an acute trigger of ischemic left ventricular dysfunction and blood pressure elevation in coronary artery disease. Acute mental stress may be a frequent trigger of transient myocardial ischemia, myocardial infarction and sudden cardiac death. In an experimental setting, the effect of mental stress on hemodynamics and left ventricular wall motion abnormalities (as detected by radionuclide ventriculography) was measured in 29 patients with exercise-induced myocardial ischemia. Seventy-five percent of the patients demonstrated mental stress-induced wall motion abnormalities. Patients frequently exhibited greater increases in peak systolic arterial pressure during mental stress than during exercise. Personally relevant mental stress is the most potent type of mental stress, both in terms of frequency and magnitude of ischemia. Most mental stress-induced ischemic episodes are clinically and electrocardiographically silent and occur at heart rates significantly lower than those seen during exercise. Both systolic and diastolic blood pressure increased during mental stress-induced ischemia, suggesting that increased myocardial oxygen demand plays a role in the pathophysiology of mental stress-induced transient ischemia. The significant magnitude and acute onset of this mental stress-induced blood pressure elevation may in some manner contribute to atherosclerotic plaque rupture. These findings may provide a pathophysiologic link to the epidemiologic association between mental stress and acute ischemic coronary events. A new ambulatory radionuclide detector that can concurrently monitor left ventricular ejection fraction and electrocardiographic ST-segment change may enhance the detection and evaluation of transient myocardial ischemia in ambulatory coronary patients. 
2	Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis. We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis. 
4	Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals. Twenty hogs were administered the following procedures before, during, and after overdistraction of the spinal column at T5-T6: somatosensory (SEP) and neurogenic-motor evoked potentials (NMEPs), hydrogen clearance procedures, Stagnara wake-up tests, and aortic-injection of silastic plastic. To ensure that overdistraction was possible, a nonosseous, circumferential osteotomy was made at T5-T6 and distraction applied in one-ratchet increments using Harrington instrumentation. Overdistraction was maintained for 3, 5, 6, 10, 15, 20, 25, or 30 minutes. Results indicated that the duration of overdistraction, as represented by lost NMEPs, was always correlated with the animal's clinical status on wake-up test. If overdistraction was maintained more than 6 minutes, 100% of the animals demonstrated positive wake-up results; if maintained between 5 and 6 minutes, 75% demonstrated positive wake-up results; and if maintained less than 5 minutes, only 25% demonstrated positive wake-up results. Time-to-loss of the NMEPs and SEPs, after onset of overdistraction, fell within two groups: slow and fast. In the slow group, it required slightly more than 20 minutes (mean = 20.6) for the potentials to be lost, while in the fast-loss group data were lost in slightly less than 4 minutes (mean = 3.6). Blood flow studies and inspection of the spinal cord revealed that the mechanism of action for the slow group appeared to be ischemia of the spinal cord that extended several centimeters above and below the site of maximum distraction. In the fast-loss group, it appeared that gross structural damage, with some very localized ischemia, were the mechanisms of actions influencing the integrity of the spinal cord. 
4	Follow-up of patients who underwent arterial switch repair for transposition of the great arteries Thirty infants underwent arterial switch for transposition of the great arteries within the first week of life (mean age, 2.8 days). An additional three patients underwent repair at 5 1/2, 8, and 9 1/2 months of age. Six (18.2%) of 33 patients died. All the survivors were not receiving cardiac medications or diuretics at the time of the last follow-up visit. Examination of 24 of 27 survivors at 1 to 5 years of age revealed normal growth in 75% of the patients. Two patients had height, weight, and head circumference below the fifth percentile for age. Four patients had height and weight appropriate for age but head circumference below the fifth percentile. Neurodevelopmental testing yielded normal findings in 18 patients. Three patients were considered suspect and an additional three were abnormal neurodevelopmentally. Head circumference less than the fifth percentile, abnormalities on computed tomographic scans of the brain, and emergency balloon atrial septostomy or emergency switch operation were more likely to occur in patients who had low neurodevelopmental scores. We conclude that the majority of patients who undergo arterial switch repair demonstrate normal growth and development and no impairment of cardiovascular function. However, significant morbidity in the form of neurodevelopmental problems may occur. 
3	Central nervous system vasculitis after chickenpox--cause or coincidence? A 7.5 year old boy, known to have a seizure disorder, presented with an infarct in the left middle cerebral artery territory, 10 weeks after severe chickenpox. Immunofluorescent antibody titre to the varicella zoster virus in the cerebrospinal fluid was 1:32. Cerebral angiography showed evidence of focal vasculitis. He presented again seven months later with an acute exacerbation of seizures. Magnetic resonance imaging of the brain showed an old posterior extension of the infarct, but a repeated angiography demonstrated an improvement in the vasculitic process. Cerebrospinal fluid antibody titre was again 1:32. Although this may have been an unfortunate coincidence, a possible association between chickenpox and vasculitis, similar to that reported with herpes zoster, and with potentially significant clinical implications, should be considered. As a definite proof can be obtained only by a brain biopsy, however, which is generally not indicated in such cases, only additional clinical reports can lead to delineation of this association as a definite entity. 
1	Tenascin expression in hyperproliferative skin diseases. The expression of tenascin, a recently discovered extracellular matrix glycoprotein, was studied by immunohistochemistry in normal human skin and in a number of skin diseases with epidermal hyperproliferation such as psoriasis, basal cell carcinoma, Bowen's disease and solar keratosis. Tenascin expression in the upper dermis of normal skin was found to vary from almost absent to patchy along the basal membrane. Staining was continuous and intense around blood vessels, hair follicles and eccrine sweat ducts. In basal cell carcinoma a marked expression of tenascin was found in the tumour stroma, especially adjacent to the basal membrane surrounding the tumour cell nests. In Bowen's disease and solar keratosis, tenascin expression was found in the dermis next to the keratinocytes. In psoriasis the dermal papillae of clinically involved skin were intensely stained and a continuous band of tenascin was present in the upper dermis along the basal membrane. The distribution of tenascin differed from other known extracellular matrix components. 
2	Hepatobiliary manifestations of the acquired immune deficiency syndrome. Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections. 
5	Brain markers and suicide: can a relationship be found? Recent work suggests that some persons who commit suicide have altered neurochemistry in their brains. It remains unclear which of the many reported abnormalities are most reliably present and whether they reflect a specific psychiatric disorder or a disposition to violent impulsivity. A number of technical and interpretive problems must be clarified, but a postmortem test indicating that a subject was at high risk for suicide may eventually emerge. This approach would not be useful for ruling out suicide, since altered neurochemistry is not likely to be involved in every case. 
1	Myeloproliferative disorders. Classification and diagnostic features with special emphasis on chronic myelogenous leukemia and agnogenic myeloid metaplasia. Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow characterize the early stages of most of the CMPD, whereas extramedullary hematopoiesis (such as in the spleen or liver), peripheral cytopenias (anemia, leukopenia, or thrombocytopenia), and myelofibrosis, with or without osteosclerosis, reflect the changes seen in the later stages. Transitions among the different CMPD and termination in acute leukemia or marrow failure also are common. CML often is characterized by leukocytosis and the presence of the entire spectrum of granulocytes (mature and immature) in the blood and marrow, reduced LAP, hypercellularity with prominent granulocytic hyperplasia in the marrow, Ph chromosome, and bcr-abl gene rearrangement. Typical features of AMM include leukoerythroblastosis, teardrop poikilocytosis, anemia, increased or normal LAP, prominent megakaryocytic hyperplasia in the marrow, dyshematopoiesis, and hyperplastic or fibrotic/sclerotic marrow. 
1	Mucinous adenocarcinoma of the submandibular gland. A rare tumor not easily classifiable among published histologic categories for salivary gland tumors is reported. The neoplasm developed within the submandibular gland of a 78-year-old woman with invasion of the mandible and metastasis to regional lymph nodes. Histopathologically, cuboidal cells possessing clear cytoplasm and displaced round nuclei proliferated and exhibited an adenomatous pattern. Many cystic spaces surrounded by tumor cell strands were seen, mucus substance filled in the cystic spaces, and the tumor cells seemed mucus-secreting, but neither epidermoid cells nor papillary appearance could be observed. Electromicroscopically, numerous mucous droplets of low electron density were prominent in the cytoplasm, and the tumor cells had sparse irregular microvilli on the luminal surface. Mucin histochemistry, including paradoxical concanavalin A staining, revealed that the tumor cells contained neutral and acid mucins, and these were identified as class II and III mucosubstances. No other neoplastic lesion, except recurrent metastatic neck nodes, has been detected 6 years after the first examination, and it seems that the tumor is a rare primary mucinous adenocarcinoma of the submandibular gland. 
5	Recurrent laryngeal nerve avulsion for treatment of spastic dysphonia. Treatment of spastic dysphonia by recurrent laryngeal nerve section has resulted in reproducibly good results in the early postoperative period in most patients. However, critical long-term follow-up has shown a high recurrence rate of adductor spasms by the third year after initial nerve section. A patient who developed recurring adductor spasms 1 year after nerve section was reexplored, with identification of neural regrowth into the distal segment of the recurrent laryngeal nerve. The technique of neural avulsion removing the distal nerve up to its insertion into the laryngeal muscles is described. Neural regrowth, which is just one of the possible mechanisms for recurrence of spastic dysphonia, should be prevented by this surgical modification. Twelve patients who have undergone neural avulsion primarily for spastic dysphonia are being followed up without recurrence of symptoms thus far. Although these results appear promising, this short follow-up that averages 1.5 years must be extended to firmly support these concepts. 
4	Angiotensin I-forming angiotensinogenases in extrarenal vasculature and in the kidney. The intention of this study was to characterize angiotensin I-forming angiotensinogenases (AIFAs) in rat extrarenal arterial walls and to clarify whether these enzymes are also present in the kidney. A further aim was to identify AIFAs in human vasculature and to establish whether they are affected in essential hypertension. Sprague-Dawley rats and vascular sections of patients undergoing corrective surgery were studied. Enzyme kinetic assays were performed using angiotensin I radioimmunoassay and purified natural angiotensinogens. Fast protein liquid chromatography was employed for biochemical characterization. A series of AIFAs with various isoelectric points, molecular weights and pH optima was detected in rat extrarenal vascular and, with differing distributions of enzyme activities, in renal tissues. In extrarenal arteries the main form of renal renin was present with a relatively low activity only. AIFAs were also demonstrable in human extrarenal vasculature and behaved like plasma renin in essential hypertension. The results indicate the existence of an intrinsic human vascular RAS in extrarenal (and renal) arteries. Extrarenal arterial AIFAs are not generally stimulated in essential hypertensives, as previously postulated. 
3	Silent cerebrovascular disease in the elderly. Correlation with ambulatory pressure. Does the average daily blood pressure correlate with hypertensive cerebrovascular disease better than the casual pressure, as has been reported in other target organ involvement? We investigated the associations of two abnormal findings on brain magnetic resonance imaging suggestive of a vascular etiology, low intense foci (lacunae), and periventricular hyperintense lesions on T1- and T2-weighted images, with both office and average daily blood pressure values in a population of 73 healthy normotensive and hypertensive elderly individuals (70 +/- 6 years old). Lacunae were detected in 34 subjects (47%); the number per subject ranged from 0 to 19 and was significantly correlated with advancing age. Furthermore, these changes were supposedly related to the average of noninvasive ambulatory (24-hour and during awake and asleep periods) pressure recordings but not to office pressures. The grade of periventricular hyperintensity was also significantly associated with advancing age and the average of ambulatory systolic pressure recordings, particularly during sleep, but not with office blood pressure. In comparisons of normotensive, "office hypertensive," and hypertensive subgroups, abnormalities on magnetic resonance imaging were appropriate to the level of the 24-hour blood pressure measurements but not to that of clinic pressure. In hypertensive patients, the presence of electrocardiographic evidence of left ventricular hypertrophy was also associated with greater abnormalities on magnetic resonance imaging. We conclude that ambulatory blood pressure monitoring is superior to casual pressure measurements in predicting latent cerebrovascular disease, which is unexpectedly common in apparently healthy elderly subjects. 
3	Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures in the rat. The effects of acute changes in plasma magnesium concentration on the threshold for lidocaine-induced seizures were evaluated in mechanically ventilated rats receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were intravenously administered either 0.9% sodium chloride (group I) or 5.0% magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or 10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate, resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per minute) was begun in both experiments. Biparietal electroencephalographic activity was monitored continuously. At the onset of electroencephalographic seizure activity, arterial plasma magnesium and lidocaine concentrations were measured. In groups I and III (experiment 1), brain parenchymal magnesium was also assayed. There were no differences in plasma lidocaine concentrations (in experiments 1 or 2) between saline solution and hypermagnesemic groups at onset of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion. We conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures. 
5	Differences in health status between older and younger homeless adults. The Institute of Medicine has placed a priority on determining the special health-care needs of elderly homeless persons. As part of a community-based study of 521 homeless adults in two beach communities of Los Angeles, we compared the demographic characteristics and health of older (age rangek 50-78, n = 61) and younger (age range, 18-49, n = 460) homeless individuals. Compared with younger adults, older adults were more likely to be white (85% versus 61%), veterans (59% versus 27%), retired (36% versus 3%), and living in a vehicle (21% versus 8%). Older adults were more likely to report having a chronic disease (69% versus 49%), functional disabilities, no informal social contacts during the previous month (49% versus 27%), observed high blood pressure (42% versus 22%), elevated creatinine (11% versus 2%), and elevated cholesterol (57% versus 36%). Older adults were less likely to have a toothache (3% versus 30%), report psychotic symptoms (25% versus 42%), and to be illegal drug users (15% versus 55%). Although they are chronologically younger, the constellation of health and functional problems of older homeless adults resemble those of geriatric persons in the general population. We suggest that geriatricians could play a significant role in training other primary-care providers to evaluate and treat socially isolated older homeless adults in a more comprehensive way than is currently standard in practice (e.g., interdisciplinary team care and emphasis on functional status, rehabilitative medicine, and assessment for sensory impairment). 
2	Autoimmune enteropathy and colitis: is there a generalised autoimmune gut disorder? Children with protracted diarrhoea, circulating enterocyte autoantibodies, and an enteropathy showing features of inappropriate HLA molecule expression on the jejunal crypt epithelium, often present with persistent blood and mucus in their stools. Eight children with autoimmune enteropathy were investigated for the presence of associated colonic disease. Six children with protracted diarrhoea, no circulating autoantibodies, and an enteropathy (in five of them) undergoing colonoscopy were used as control subjects. In all eight patients, but not in the control subjects, there was macroscopic and microscopic evidence of an accompanying colitis of variable severity, thus indicating that a more generalised intestinal disorder was present, which might affect the whole intestine. Aberrant expression of DR molecules on the colonic surface and crypt epithelium was also detected. Autoimmunity may play a role in the colitis. 
4	Studies of myocardial protection in the immature heart. V. Safety of prolonged aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia. This study tests the hypothesis that multidose, hypocalcemic aspartate/glutamate-enriched blood cardioplegia provides safe and effective protection during prolonged aortic clamping of immature hearts. Of 17 puppies (6 to 8 weeks of age, 3 to 5 kg) placed on vented cardiopulmonary bypass, five were subjected to 60 minutes of 37 degrees C global ischemia without cardioplegic protection and seven underwent 120 minutes of aortic clamping with 4 degrees C multidose aspartate/glutamate-enriched blood cardioplegia ([Ca++] = 0.2 mmol/L), preceded and followed by 37 degrees C blood cardioplegic induction and reperfusion. Five puppies underwent blood cardioplegic perfusion for 10 minutes without intervening ischemia to assess the effect of the cardioplegic solution and the delivery techniques. Left ventricular performance was assessed 30 minutes after bypass was discontinued (Starling function curves). Hearts were studied for high-energy phosphates and tissue amino acids. One hour of normothermic ischemia resulted in profound functional depression, with peak stroke work index only 43% of control (0.7 +/- 0.1 versus 1.7 +/- 0.2 gm x m/kg, p less than 0.05). There was 70% depletion of adenosine triphosphate (7.6 +/- 1 versus control 20.3 +/- 1 mumol/gm dry weight, p less than 0.05) and 75% glutamate loss (6.6 +/- 1 versus control 26.4 +/- 3 mumol/gm, p less than 0.05). In contrast, after 2 hours of aortic clamping with multidose blood cardioplegia preceded and followed by 37 degrees C blood cardioplegia, there was complete recovery of left ventricular function (peak stroke work index 1.6 +/- 0.2 gm x m/kg) and maintenance of adenosine triphosphates, glutamate, and aspartate levels at or above control levels adenosine triphosphate 18 +/- 2 mumol/gm, aspartate 21 +/- 1 versus control 2 mumol/gm, and glutamate 25.4 +/- 2 mumol/gm). Puppy hearts receiving blood cardioplegic perfusion without ischemia had complete recovery of control stroke work index. We conclude that methods of myocardial protection used in adults, with amino acid-enriched, reduced-calcium blood cardioplegia, can be applied safely to the neonatal heart and allow for complete functional and metabolic recovery after prolonged aortic clamping. 
1	Multiple spinal epidural metastases; an unexpectedly frequent finding. In a prospective study, patients with known malignant disease who were suspected of having a spinal epidural metastasis, had myelography which was not confined to the clinically suspected site, but included at least the whole lumbar and thoracic spinal canal. Fifty four of the 106 myelograms revealed at least one epidural metastasis. Twelve of these 54 myelograms showed two separate lesions, and four myelograms showed three separate lesions. In all 16 cases with multiple lesions at least one of the lesions was asymptomatic at the time of the diagnosis. It is concluded that multiple spinal epidural metastases are of common occurrence and occur in about one third of the cases. This finding may have important clinical implications. Examination of the spinal canal for epidural metastases should not be confined to the clinically suspected site, but should include as extensive an area as possible of the spinal canal, whatever technique is to be used. 
1	Strong association between diabetes and displacement of mouse anti-rat insulinoma cell monoclonal antibody by human serum in vitro. In an attempt to identify novel pancreatic beta-cell surface antigens, mouse monoclonal antibodies (MoAbs) were raised against rat insulinoma (RIN5F) cells with standard techniques. Several clones were identified whose antibodies bound specifically to RIN5F cells but not to other rat, mouse, and human target cells. Each of these MoAbs was radiolabeled, and the specificity of binding of each MoAb was determined by the ability of excess cold homologous MoAb to displace the labeled MoAb. Six RIN5F cell-specific MoAbs of different epitopic specificities were identified. The relevance of these beta-cell epitopes to human insulin-dependent diabetes (IDDM) was demonstrated by the differential ability of human serums from control and diabetic children to displace the radiolabeled MoAbs from the RIN5F cells. Serums from 333 children without diabetes or a family history of diabetes and from 156 newly diagnosed IDDM patients were tested. Only one IgM MoAb was specifically displaced by the IDDM serums, i.e., 146 of 156, compared to serums from control children, i.e., 10 of 333. With immunofluorescence, the serum component responsible for the displacement of the mouse MoAb was identified as IgG. Most of the positive control serums were from children with active autoimmune thyroiditis. Serums from children with other forms of glucose intolerance did not displace MoAb 1A2. There was no correlation between age and the degree of displacement of 1A2. Thus, the displacement of 1A2 is a specific and sensitive marker of diabetes susceptibility easily applicable to mass screening. 
1	Ultrasound and ultrasound-guided fine needle aspiration biopsy of supraclavicular lymph nodes in patients with esophageal carcinoma. The use of ultrasound combined with ultrasound-guided fine-needle aspiration biopsy (UGFAB) of supraclavicular lymph nodes in the pretreatment staging of 37 patients with squamous cell carcinoma of the esophagus is described. All patients underwent computed tomography (CT) scans of the chest and the abdomen and ultrasound of the abdomen and supraclavicular regions. Supraclavicular lymph node metastases (Stage IV disease according to the tumor nodes metastasis [TNM] classification) were cytologically diagnosed in seven (18.9%) of the 37 patients. In two of these patients, no other metastases were found. In the other five patients, UGFAB replaced more invasive diagnostic procedures. Due to their superficial location, ultrasound and UGFAB of the supraclavicular lymph nodes was relatively simple to perform, and contributed to an improved staging of squamous cell carcinoma of the esophagus. 
2	Appendectomy in primary and secondary staging operations for ovarian malignancy. Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures. 
5	Mild head injury classification. Inconsistencies across studies concerning outcome after mild head injury may reflect differences in the diagnostic criteria used for selection of patients. Consequently, we compared the neurobehavioral outcome in three groups of consecutively hospitalized patients (aged 16 to 50 years) who sustained a closed head injury (CHI) and had a Glasgow Coma Scale (GCS) score in the 9 to 15 range. These groups included patients with uncomplicated CHI with mild impairment of consciousness as reflected by a GCS score in the 13 to 15 range (n = 78), patients with initially mild impairment of consciousness complicated by brain lesion or depressed skull fracture (n = 77), and patients with moderate CHI (n = 60). Tests of memory, information processing, and verbal fluency were administered within 1 to 3 months after injury, and the Glasgow Outcome Scale was completed at 6 months. Neurobehavioral functioning was impaired in the groups with complicated mild CHI and moderate CHI as compared to the group with uncomplicated mild CHI. Although moderate CHI produced longer durations of impaired consciousness and posttraumatic amnesia than complicated mild head injury, patients in these groups did not differ in neurobehavioral performance. Global outcome at 6 months was better in the patients with mild CHI than in patients with complicated mild and moderate injuries. Analysis of the various complications of mild CHI revealed that the presence of an intracranial lesion was related to more severe neurobehavioral sequelae than injuries complicated by a depressed fracture. 
3	Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome. We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F-fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p less than 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p less than 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p less than 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus. 
1	Anchorage-independent growth and the expression of cellular proto-oncogenes in normal human epidermal keratinocytes and in human squamous cell carcinoma cell lines. The expression of multiple cellular proto-oncogenes and the in vitro anchorage-independent growth of normal human epidermal keratinocytes and several human squamous cell carcinoma cell lines were studied and correlated. Squamous cell carcinoma cell lines KB, Si Ha, HEp-2, and Fa Du showed high anchorage independency, and MS 751 and A-253 cell lines had minimum independency. However, the normal keratinocytes and the A-431 cell line did not show anchorage-independent growth. Both the normal human epidermal keratinocytes and cancer cell lines expressed multiple proto-oncogenes such as src, erb B-1, abl, fos, raf, H-ras, and myc, and the amount of expression of these oncogenes was notably higher in the cancer cell lines than in the normal keratinocytes. The expression of proto-oncogenes from the monolayer cultures of the cancer cell lines is poorly correlated with the anchorage independency of the cells. These data indicate that the anchorage independency is not directly linked to the expression of specific cellular proto-oncogene(s) of the monolayer cancer cell cultures. 
4	Methodology of head-up tilt testing in patients with unexplained syncope Prolonged 60 degree head-up tilt has been shown to be valuable in the investigation of unexplained syncope, diagnosing neurally mediated bradycardia/hypotension or malignant vasovagal syndrome. To evaluate the methodology of tilt testing, the following were examined: reproducibility of results, tilt duration, angle of tilt, method of tilt support and effect of age in patients and control subjects. Seventy-one patients with recurrent unexplained syncope underwent 60 min of 60 degree tilt; 53 (75%) had an abnormal test with vasovagal syncope at 24 +/- 10 min (mean +/- SD). Tilting to 60 degrees resulted in an abnormal test in only 2 (7%) of 27 control subjects without cardiovascular symptoms (p less than 0.001); and 5 (15%) of 34 patients with syncope and documented conduction tissue disease (p less than 0.001). Of 15 youthful fainters, 3 (20%) had vasovagal reactions as did 1 (8%) of 12 asymptomatic youthful control subjects. These 12 control subjects also underwent tilting with a saddle support and 7 (67%) had vasovagal reactions. It is concluded that the duration of tilting at 60 degrees should be 45 min (mean time to syncope +2 x SD in the 53 patients with abnormal results). Twenty percent of patients with an abnormal tilt test may not demonstrate syncope with repeat tilting. Saddle tilt testing in unexplained syncope may result in a loss of specificity. Tilting at less than 60 degrees results in a loss of sensitivity. Head-up tilt may be less useful in youthful subjects with vasovagal syncope than in other subjects. 
5	An all-polyethylene cementless tibial component. A five- to nine-year follow-up study. An all-polyethylene cementless tibial component was used in 221 total knee arthroplasties. With one exception, failures did not occur before three years. Failure was characterized by medial subsidence of the tibial component. There was abrasion of the polyethylene on the undersurface of all components that failed. Survivorship was seven to nine years (87.1%). This study demonstrated that a flexible cementless component can function well when used with any type of bone. However, abrasion of the polyethylene that occurs from shearing forces is a concern. Polyethylene components need adequate provisions to prevent shearing or need surface treatment to prevent abrasion. 
4	Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial. Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively. 
3	Clinical-computed tomographic correlations of lacunar infarction in the Stroke Data Bank. Lacunar stroke was diagnosed in 337 (26%) of the 1,273 patients with cerebral infarction among the 1,805 total in the Stroke Data Bank. We analyzed the 316 patients with classic lacunar syndromes. Among these, 181 (57%) had pure motor hemiparesis, 63 (20%) sensorimotor syndrome, 33 (10%) ataxic hemiparesis, 21 (7%) pure sensory syndrome, and 18 (6%) dysarthria-clumsy hand syndrome. No striking differences were found among the risk factors for the lacunar subtypes, but differences were found between lacunar stroke as a group and other types of infarcts. Compared to 113 patients with large-vessel atherosclerotic infarction, those with lacunar stroke had fewer previous transient ischemic attacks and strokes. Compared to 246 with cardioembolic infarction, patients with lacunar stroke more frequently had hypertension and diabetes and less frequently had cardiac disease. We found a lesion in 35% of the lacunar stroke patients' computed tomograms, with most lesions located in the internal capsule and corona radiata. The mean infarct volume was greater in patients with pure motor hemiparesis or sensorimotor syndrome than in those with the other lacunar stroke subtypes. In patients with pure motor hemiparesis and infarcts in the posterior limb of the internal capsule, there was a correlation between lesion volume and hemiparesis severity except for the few whose infarct involved the lowest portion of the internal capsule; in these patients severe deficits occurred regardless of lesion volume. Taken together, the computed tomographic correlations with the syndromes of hemiparesis showed only slight support for the classical view of a homunculus in the internal capsule. 
5	Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage. Currently employed clinical indicators of perfusion provide inadequate warning of developing hazards caused by marginal perfusion in certain vital organs or "peripheral" tissues that are pivotal to postsurgical wound healing. In this study, mean arterial blood pressure, cardiac output, and transcutaneous and subcutaneous oxygen tensions (PtcO2 and PsqO2) were investigated during serial hemorrhage, as indicators of the degree of both hypovolemia and perfusion to specific tissues. Blood was removed in stages (10%, 20%, 30%, 40%, 55%, 60%, and 65% of original volume) from anesthetized dogs. Injections of variously radiolabeled microspheres allowed assessment of blood flow at each stage of hemorrhage in bone, brain, colon, heart, kidney, liver, muscle, pancreas, skin, small intestine, spleen, stomach, and subcutaneous tissue. PsqO2 was correlated more highly with blood volume lost than was PtcO2. Furthermore PsqO2 was more sensitive to blood loss than was either cardiac output or PtcO2 and, also during the early loss (0% to 40%), was more sensitive than mean arterial pressure. Some organs (e.g., pancreas) appeared to lose considerable blood flow with only small loss of blood volume, but their blood flow then stabilized at a low level despite further hemorrhage. Other organs, notably the kidney, appeared to be relatively unaffected by substantial loss of blood volume (20% to 40%), after which, however, their blood flow quite abruptly became sensitive to further hypovolemia. This explains why blood flow-related performance of the kidney (e.g., urine volume) may not adequately predict a developing hazard or peripheral perfusion. Some indicators were found to be better indexes of blood flow in some organs than in others (e.g., cardiac output and PsqO2 correlated more closely with skin, spleen, and intestinal flows [and one another] than with vital organ flows). 
1	Estrogen receptor localization in normal and neoplastic epithelium of the uterine cervix. To investigate the estrogen receptor (ER) status of cells during carcinogenesis of the uterine cervix, the immunohistochemical reactivity for a monoclonal anti-ER antibody (H 222) was studied in 26 normal cervical specimens, 21 cases of cervical intraepithelial neoplasia (CIN), and 21 cases of invasive cervical carcinoma. In addition, the presence of human papillomavirus (HPV) DNA (types 6/11, 16/18, or 31/33/35) was analyzed by in situ hybridization. In the normal cervix, basal cells of the squamous epithelium, metaplastic cells, and endocervical glandular cells were ER positive. In contrast, neoplastic cells of CIN (17 of 21 cases) and invasive carcinoma (19 of 21 cases) were ER negative. The remaining four cases of CIN and two cases of invasive carcinoma were focally ER positive. The HPV DNA analysis revealed that HPV DNA in ER-negative cases was either types 16/18 or undetectable, but all ER-positive neoplasms contained HPV DNA types 31/33/35. These results suggest that most neoplastic cells in CIN and invasive cervical carcinoma lose their ER expression and that this may be related to the HPV DNA types which they possess. 
5	Preoperative radiotherapy in operable rectal cancer. The effect of preoperative radiotherapy (31.5 Gy in 3.5 weeks) in operable rectal cancer was examined with respect to resectability and prognosis after two surgical procedures, abdominoperineal resection, or low anterior resection. Preoperative radiation did not influence the surgeon's selection of low anterior resection, which was similar (40 percent) in each group. Radiation improved five-year survival probability and decreased the incidence of local recurrence significantly after low anterior resection. In contrast, no improvement of treatment results was found in patients treated by abdominoperineal resection after radiotherapy. 
1	Progressive coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension: report of two cases. Two cases of neurological deterioration and coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension and invasion of the 3rd ventricle are presented. Emergency ventricular shunting led to prompt neurological improvement, which, supplemented by radiation therapy, allowed long-term amelioration of symptoms. Three possible explanations for this complication are offered: 1) traction of the attached 3rd ventricle into the decompression site, causing increased obstructive hydrocephalus, 2) vasopressin release by surgical manipulation of the pituitary stalk and circumventricular organs causing cerebral edema, and 3) edema in the residual tumor secondary to surgical manipulation causing further hydrocephalus. Subsequent patients with similar clinical and imaging criteria will have a planned perioperative ventricular shunting procedure performed. 
5	Prolonged confusion following convulsions due to generalized nonconvulsive status epilepticus. Among patients with a prolonged confusional state after convulsive seizure, we diagnosed 8 cases as generalized nonconvulsive status epilepticus. Six had a history of seizures, and 2 had new onset. The convulsive seizures were generalized in 6 and focal in two. The postictal confusion lasted up to 36 hours in the most prolonged case, and a delayed response to anticonvulsant medications occurred in all cases. The clinical symptoms ranged from mild confusion to coma. Psychiatric manifestations or automatisms were rare. The presumed etiology was due to diverse causes, but a withdrawal state was the most common. EEG demonstrated continuous or nearly continuous generalized ictal discharges of variable morphology. These cases call attention to the fact that some prolonged confusional states following convulsive seizures are in fact due to persistent seizure activity that can be diagnosed by EEG. 
4	Hemodynamic effects of renin inhibition by enalkiren in chronic congestive heart failure. Previous efforts to block the renin-angiotensin system in patients with chronic congestive heart failure (CHF) have focused on 2 distal sites in the system, the angiotensin-converting enzyme and the angiotensin II receptor. Recent work, however, has led to the development of agents that directly inhibit renin, the proximal step in the cascade. In this study, we investigated the hemodynamic effects of renin inhibition in 9 patients with chronic CHF by using enalkiren, a primate-selective, dipeptide renin inhibitor, which has been previously shown to suppress plasma renin activity and to lower blood pressure in hypertensive patients. The acute intravenous administration of enalkiren (1.0 mg/kg) produced increases in cardiac index (2.0 +/- 0.3 to 2.3 +/- 0.1 liter/min/m2) and stroke volume index (26 +/- 3 to 34 +/- 4 ml/m2) and decreases in left ventricular filling pressure (31 +/- 3 to 25 +/- 3 mm Hg), mean right atrial pressure (15 +/- 1 to 13 +/- 2 mm Hg), heart rate (78 +/- 5 to 72 +/- 6 beats/min) and systemic vascular resistance (2,199 +/- 594 to 1,339 +/- 230 dynes.s.cm-5) (all p less than 0.01 to 0.05). These observations indicate that renin inhibition produces hemodynamic benefits in patients with chronic CHF and could potentially provide a novel approach to interfering with the renin-angiotensin system in patients with this disorder. 
4	Serum lipids and lipoproteins are less powerful predictors of extracranial carotid artery atherosclerosis than are cigarette smoking and hypertension The effect of serum lipids and lipoproteins on extracranial carotid artery atherosclerosis (CAS) was studied in patients who underwent carotid arteriography. Serum lipid and lipoprotein values along with data on other potential predictors of extracranial CAS were determined in 240 patients who had at least one extracranial carotid artery visualized. In a multiple logistic regression analysis, the independently significant predictors of the presence of extracranial CAS were, in decreasing order of significance, duration of smoking of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I did not show an independent effect. Although low-density lipoprotein cholesterol was an independent predictor of the presence of extracranial CAS, its effect as a predictor was far outweighed by the effects of the duration of smoking of cigarettes and a history of hypertension. 
5	Different forms of chronic childhood thrombocytopenic purpura defined by antiplatelet autoantibodies. To determine whether detection of antiplatelet autoantibodies (AAb) to glycoproteins IIb/IIIa and Ib/IX may be useful in defining different forms of chronic thrombocytopenic purpura (TP) in children, we analyzed for AAb the platelet and plasma samples from 36 children with chronic TP (mean duration 4.4 years), from 31 children with normal platelet counts at the time of blood sampling but with chronic TP in the past (mean duration 2.9 years), and from 23 adults with chronic TP; the results were correlated with the clinical data. Antiplatelet autoantibodies were detected in 26 (72.2%) of 36 children with ongoing TP, 15 (48.4%) of 31 children with TP in the past, and 12 (66.7%) of 18 adults with TP. All children with high AAb ratios (greater than 5 times the control mean + 3 SD) were more than 8 years of age at diagnosis (mean age 12.4 years compared with 7.1 years in children with moderate or negative AAb levels; p = 0.003). The results suggest that the outcome for adolescents with high platelet-associated AAb levels may be similar to that of adults, whereas younger children may have a greater chance of spontaneous remission. The children with chronic TP in the past and elevated platelet-associated AAb levels may have a "compensated" TP and therefore may be at risk for relapses. Future studies aimed at serial AAb determination throughout the patients' courses may further define TP subgroups. 
2	Resolution of cirrhotic glomerulonephritis following successful liver transplantation. A 38-year-old man with liver failure due to Laennec's cirrhosis developed nephrotic range proteinuria and hematuria. Renal biopsy showed membranoproliferative glomerulonephritis with 2+ staining for IgA and complement consistent with cirrhotic glomerulonephritis. After orthotopic liver transplantation, proteinuria and hematuria rapidly resolved. This case indicates that glomerulonephritis associated with cirrhosis may be successfully treated with hepatic transplantation. Whether the improvement in glomerular abnormalities resulted from immunosuppression therapy or from restoration of normal hepatic function is unknown. 
5	Complications of extracorporeal membrane oxygenation in neonates. In cases of severe respiratory failure, cardiopulmonary bypass has been used as support until cardiac and pulmonary recovery occurs. We report the Wilford Hall USAF Medical Center experience with extracorporeal membrane oxygenation (ECMO) and its associated complications. From July 1985 to March 1989, 57 neonates were placed on membrane oxygenators. The overall survival was 79%. Technical complications encountered included catheter-related problems, mechanical complications of the pump apparatus, and hemorrhage. Hemorrhagic complications were the most frequent and devastating complications encountered. Intracranial hemorrhage accounted for six deaths associated with bypass. Extracorporeal membrane oxygenation is successful in significantly improving survival of neonates whose predicted mortality approaches 100% with conventional treatment. The rate of infant mortality using the membrane oxygenator is not affected by technical complications related to catheter position, mechanical problems with the circuit, or hemorrhage, excluding intracranial hemorrhage. The major cause of death of infants receiving extracorporeal membrane oxygenation is the underlying disease process leading to cardiopulmonary failure. 
5	Toxicology screening of the trauma patient: a changing profile. STUDY OBJECTIVES: To determine the current ingestants found in the multiply injured trauma patient and to determine if this select group of ingestants affected the resuscitation, evaluation, or convalescent management of these patients. DESIGN: A one-year retrospective analysis was performed on all patients who were admitted to an urban trauma center with a discharge diagnosis of multiple trauma and who received a comprehensive toxicology screening test. MAIN RESULTS: One hundred twenty-seven of the 177 patients (72%) who fulfilled the criteria had positive toxicology screens. Ethyl alcohol was the only drug present in 26 of these patients (20%); 57 (45%) were positive for drugs other than ethyl alcohol. A combination of ethyl alcohol and at least one other drug was quantified in 44 patients (35%). The most often encountered substances were ethyl alcohol (55%), marijuana (24%), and cocaine (21%). Twelve drug screens (9%) demonstrated pharmaceuticals (eg, acetylsalicylic acid, acetaminophen, or cyclic antidepressants) that may require specific antidotal treatment. CONCLUSION: The ingestant profile found in this subgroup of trauma patients differed from those of previous studies. Although a select group of these ingestants requires specific treatment or affects the physical assessment of the patient, none of these trauma patients received more than supportive care. 
1	Endometriosis of the abdominal wall. Endometriosis of the abdominal wall typically occurs as a painful mass in a lower abdominal incision from previous cesarean section or hysterectomy. Most patients are young and in their active reproductive years. The histologic diagnosis requires a combination of either endometrial-like glands, endometrial stroma, or hemosiderin pigment. The diagnosis must be considered in any woman with an abdominal wall mass and a history of transabdominal gynecologic surgery. Wide excision offers the best chance to prevent recurrence. 
4	Giant left atrium--a case report. A seventy-seven-year old woman, with mitral stenosis, presented with cardiomegaly evident on her chest roentgenogram. The cardiac enlargement was due to a giant left atrium that distorted the cardiac structures. An echocardiogram and a first-pass nuclear angiogram were able to delineate the huge left atrium. 
5	Cerebral glucose utilization during sleep in Landau-Kleffner syndrome: a PET study. Three right-handed male children (aged 5, 6, and 11 years) with signs, symptoms and/or history of the syndrome of acquired aphasia-epilepsy (Landau-Kleffner syndrome) were studied during drug-induced, electroencephalographically (EEG)-monitored sleep by positron-emission tomography (PET) and the [18F]fluorodeoxyglucose (FDG) method. Our data demonstrate that in Landau-Kleffner syndrome, cerebral glucose utilization is not normal during sleep. The metabolic pattern varied between the children but the metabolic disturbances always predominated over the temporal lobes. They were right-sided, left-sided, or bilateral. In the two first patients, EEG recordings showed continuous spike-and-wave discharges during sleep and a right-greater-than-left asymmetry was observed in temporal areas. In patient 1, the asymmetry was associated with a relative increase of glucose utilization of the right posterior temporal region. In patient 2, the glucose utilization was relatively decreased in the left anterotemporal and left perisylvian regions. In patient 3, the sleep EEG showed no discharge and no significant asymmetry was observed; however, glucose utilization of both temporal lobes was decreased. Lower metabolic rates in subcortical structures than in cortex were also noted in the three children. This metabolic pattern may be related to the maturation of the central nervous system (CNS). 
5	Surgical and prosthesis-related complications using the Groningen button voice prosthesis. Prosthesis-assisted tracheoesophageal speech has advanced speech rehabilitation appreciably. However, the surgical technique and the use of a prosthesis may give rise to complications. In a retrospective study on 132 consecutive patients rehabilitated with a Groningen button voice prosthesis, the complications were assessed, the average follow-up being 21 months. Surgical complications were not observed. Prosthesis-related complications, which were encountered in 28%, were all of a minor nature and mainly consisted of granulation formation and hypertrophic scarring; these appeared to be easily treatable. The complications found were few and insignificant in comparison with reports in the literature. This may be attributed to the uncomplicated surgical procedure for the insertion of the Groningen button. Moreover, the prosthesis is self-retaining and requires hardly any care from the patient. Permanent removal of the prosthesis usually requires surgical closure, which is a simple procedure performed under local anaesthesia. 
2	Markers of chronic alcohol ingestion in patients with nonalcoholic steatohepatitis: an aid to diagnosis. We report here the use of the biochemical marker desialylated transferrin to aid in the diagnosis of nonalcoholic steatohepatitis. Conventional biochemical tests used for the detection of chronic alcohol consumption fail to differentiate nonalcoholic steatohepatitis patients from alcoholic subjects. In addition, even in those alcoholic subjects with alcoholic liver disease in whom biopsy has been performed, it is impossible to differentiate these two disease states on the basis of morphological examination alone. In this study we have examined two new markers of excessive alcohol intake, desialylated transferrin and mitochondrial AST in subjects with nonalcoholic steatohepatitis and in patients consuming excessive amounts of alcohol. All nonalcoholic steatohepatitis patients consumed minimal or no alcohol and were diagnosed by morphological criteria based on liver biopsy specimens. Alcoholic subjects were consuming in excess of 80 gm/day ethanol, often with clinical evidence of overt alcoholism. Control subjects included both healthy controls and patient controls with liver diseases unrelated to alcohol. The ratio of desialylated transferrin/total transferrin was elevated only in patients who consumed excessive amounts of alcohol, whereas the ratio of mitochondrial AST to total AST (mitochondrial AST/total AST) was not significantly different between alcoholic subjects and patients with nonalcoholic steatohepatitis. The sensitivity and specificity for the ratio desialylated transferrin/total transferrin was 81% and 98%, respectively, whereas the sensitivity for the mitochondrial AST/total AST ratio was 92%; the specificity was only 50%, indicating that there were a large number of false-positives. All the conventional markers were less sensitive and less specific than the ratio desialylated transferrin/total transferrin. 
4	Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat. A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension. 
4	A frameshift mutation leading to type 1 antithrombin deficiency and thrombosis. Type 1 antithrombin III (ATIII) deficiency, which is the commonest form of inherited ATIII defect, is characterized by a quantitative reduction in both immunologically and functionally detectable protein. This condition is associated with a high incidence of thromboembolic disorder. Previous investigations have shown that the ATIII genes in the majority of cases are grossly intact, but the precise underlying molecular defects remain unknown. We have investigated the molecular basis of a type 1 ATIII deficiency in an Italian kindred by enzymatic amplification of the ATIII gene sequences in affected family members and direct sequencing of the amplified genomic DNA. A novel mutation, the deletion of a single T in the second position of codon 119, was identified in each of the affected individuals. The resulting frameshift leads to a premature termination in codon 126, effectively resulting in a null allele. 
5	Antibiotic therapy for common infections. Several important points regarding the treatment of urinary tract infections should be made. Single-dose and short-course antibiotic therapy is appropriate only for women with acute bacterial cystitis due to E. coli. Studies comparing single-dose to full-course therapy have not been sufficiently designed to draw valid statistical conclusions, and only TMP/SMX is recommended at this time. Recurrent UTI in women is almost always due to reinfection, which is best managed by prophylactic antibiotics. Acute bronchitis and acute exacerbations of chronic bronchitis are often due to viral infections, and therefore antibiotic therapy is not always needed. In acute exacerbations of chronic bronchitis, the clearest success rates for antibiotic therapy have been in patients, who have all three of the following symptoms: increased dyspnea, increased sputum production, and sputum purulence. Mupirocin is an important addition to the agents used to treat bacterial skin infections due to streptococcal and staphylococcal strains. In impetigo, mupirocin has been demonstrated to be as effective or superior to oral erythromycin. In prostatitis, data on the fluoroquinolones appears impressive, but further comparative trials are needed. They may become first-line, empiric therapy. The newer oral antibiotics are not recommended as initial, empiric therapy in the outpatient management of common infections, with the possible exception of the treatment of prostatitis. These newer agents may be more important in the treatment of recurrent or resistant infections. 
3	Nd:YAG-laser in the microsurgery of frontobasal meningiomas. Forty-three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor. The 1.32 microns Nd:YAG-laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments. Tumor shrinkage was achieved by radiating the tumor surface with the Nd:YAG-laser. This technique facilitated the microsurgical dissection and reduced the blood loss by half. The Nd:YAG-laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20% to zero. The postoperative quality of life was excellent with a complete rehabilitation in 76% of the patients. The use of the 1.32 microns Nd:YAG-laser improved significantly the results of microsurgery for frontobasal meningioma. 
4	The reproducibility of intravascular ultrasound imaging in vitro. To determine which factors may affect the image quality when an intravascular ultrasound catheter is used in vivo, the influence of blood, temperature change, and contrast media were evaluated. In addition, to confirm the reproducibility of intravascular ultrasound imaging to measure cross-sectional lumen area, intraobserver and interobserver variability were determined. The findings indicated that ultrasound images in blood are mildly attenuated, that changes from room temperature to body temperature do not have a significant impact on the image quality, that contrast media attenuates the image intensity in a dose-dependent manner, and that the intravascular ultrasound imaging catheter provides a reproducible method for measuring arterial lumen area with excellent intraobserver and interobserver correlation. 
5	Early magnetic resonance imaging in acute traumatic internuclear ophthalmoplegia. Adduction deficiency following acute head trauma may result not only from orbital damage but also from internuclear ophthalmoplegia, and in most instances this resolves over weeks to months. To date, noninvasive imaging studies during the acute phase following injury have not been definitive in localizing the pathology. Three cases of adduction deficiency following head trauma that were caused by internuclear ophthalmoplegia are reported. A lesion in the brain stem was found in all three cases by magnetic resonance imaging in the subacute post-traumatic period. These lesions were not visible on routine x-ray computed tomography obtained at the time of injury. 
1	Evidence for the functional binding in vivo of tumor rejection antigens to antigen-presenting cells in tumor-bearing hosts. Spleen cells of BALB/c mice bearing a syngeneic CSA1M fibrosarcoma were treated with anti-Thy-1.2 antibody plus C, yielding a T cell-depleted, APC-containing fraction. The APC-containing fraction was first tested for its capacity to present exogenous modified-self or another tumor (Meth A) Ag after in vitro pulsing. The results showed comparable Ag-presenting capacities to those obtained by APC-containing fraction from normal spleen cells, indicating that APC function is not affected in tumor-bearing mice. We next examined whether APC from CSA1M-bearing mice bind endogenously generated CSA1M tumor Ag onto its surfaces to stimulate tumor-specific T cells. Five rounds of inoculation of APC-containing fraction from CSA1M-bearing mice without further in vitro pulsing resulted in the induction of potent anti-CSA1M immune resistance. The involvement of anti-CSA1M T cells in the induction of anti-CSA1M immunity was excluded by the fact that the in vivo immunity was excluded by the fact that the in vivo immunity was delivered by Thy-1+ cell-depleted, but not by Thy-1+ cell-enriched fractions of spleen cells from CSA1M-bearing mice. Moreover, the failure of Sephadex G10-passed spleen cells to deliver anti-CSA1M resistance demonstrated the absolute requirement of APC for inducing the in vivo immunity. Finally, this in vivo resistance was found to be tumor specific, because APC fractions from CSA1M-bearing and Meth A-bearing BALB/c mice induced immune resistance selective against the corresponding tumor cell challenge. These results indicate that APC from tumor-bearing hosts can not only exert unaffected APC function against exogenous Ag, but also function to present tumor Ag generated endogenously in the tumor-bearing state and to produce tumor-specific immunity in vivo. 
3	Cerebrospinal fluid immune complexes in patients exposed to Borrelia burgdorferi: detection of Borrelia-specific and -nonspecific complexes. We analyzed cerebrospinal fluid (CSF) from 32 patients with neurological symptoms and evidence of Borrelia burgdorferi infection (29 were seropositive as determined by enzyme-linked immunosorbent assay, 2 were cell-mediated immune positive, and 1 had been seropositive as shown by enzyme-linked immunosorbent assay 9 months previously). CSF immune complexes were found in 22 (69%) of 32 patients; in 18, there was sufficient sample to isolate immune complexes. By enzyme-linked immunosorbent assay, isolated immune complexes from 10 of these 18 patients contained antibody specific for B. burgdorferi antigens. The isotypes were IgG (n = 8), IgM (n = 3), and IgA (n = 2). By immunoblot, these antibodies were directed against B. burgdorferi 41-kDa antigen and occasionally against the 33- and 17-kDa antigens. Anti-B. burgdorferi IgM was present in patients with acute neurological symptoms, was predominantly complexed rather than free, and decreased with clinical recovery in the one serial study. Three patients were nonreactive for free CSF antibodies, but had complexed antibodies to the organism. The preliminary finding of specific B. burgdorferi components in immune complexes in CSF suggests an active process triggered by the organism, even in the absence of other CSF abnormalities. 
5	Guidelines for transfusion support in patients undergoing coronary artery bypass grafting. Transfusion Practices Committee of the American Association of Blood Banks. We have reviewed the impact of evolving issues in coronary artery bypass grafting (CABG) on transfusion support for these patients. Issues include increased awareness of transfusion risks, reappraisal of traditional indicators triggering transfusion, and evolving alternatives to homologous blood transfusion such as autologous blood and pharmacologic therapy. These issues have been prompted by programs, such as the National Institutes of Health Consensus Conferences, to provide physicians with guidelines for appropriate use of blood components. However, evidence suggests that transfusion practice in coronary artery bypass grafting procedures remains variable and does not take into account the results of recently published clinical studies. We have therefore developed guidelines and recommendations for transfusion support in patients undergoing coronary artery bypass grafting. In summary, they are the following. 1. Institutions with coronary artery bypass grafting programs should establish a multidisciplinary approach to use a combination of interventions designed to minimize homologous blood exposure. 2. Prophylactic transfusion of plasma and platelets are of no benefit and therefore carry an unnecessary risk to the patient. 3. Special request products such as designated blood donation from first-degree relatives should not be used because of the risk of transfusion-associated graft versus host disease. 4. For support of intravascular volume, crystalloids or colloids should be used because they do not have the potential to transmit infection. 
1	Transurethral resection versus needle biopsy prior to radical prostatectomy for stage C prostate cancer. Influence on progression and survival. Previous reports have claimed that transurethral resection of the prostate (TURP) preceding definitive radiation therapy for patients with Stage C prostate cancer promotes the risk of distant metastasis and increases the mortality rate. A total of 490 patients with pathologic Stage C adenocarcinoma of the prostate treated by radical prostatectomy were studied. Median time to follow-up was 4.6 years. Comparison was made between patients who had TURP within the six months preceding prostatectomy (n = 54) and those who had needle biopsy (n = 437) prior to operation. No significant differences were noted in local recurrence of disease, systemic progression of disease, disease-free interval, and overall and cause-specific survival, even after adjustment for clinical (adjuvant treatment) and pathologic prognostic variables. Our data suggest that for patients with pathologic Stage C prostate cancer treated by radical surgery, preoperative TURP is not associated with unfavorable outcome. 
1	Gastric dysrhythmias following pylorus-preserving pancreaticoduodenectomy. Possible mechanism for early delayed gastric emptying. Transient delayed gastric emptying is reported as a frequent complication following pancreas-preserving pancreaticoduodenectomy (PPW). We placed serosal electrodes on the stomach of a patient undergoing PPW. Myoelectric recordings were obtained postoperatively and correlated with simultaneous radionuclide liquid gastric emptying studies. The patient developed early postoperative gastric atony, associated with frequent gastric dysrhythmias. These dysrhythmias may have been exacerbated by a perihepatic abscess. The gastric dysrhythmias correlated with alterations in liquid gastric emptying. Gastric dysrhythmias may be a mechanism for gastric dysfunction in the early postoperative period. 
4	Penetrating aortic ulcers: diagnosis with MR imaging. The authors studied seven patients with penetrating aortic ulcers with use of magnetic resonance (MR) imaging. All patients were evaluated for acute chest symptoms, and the presence of aortic ulcers was confirmed by means of angiography in all seven patients. Five patients also underwent computed tomography (CT). Three patients underwent surgical repair of the thoracic aorta. MR findings included intramural hematoma and focal aortic wall ulceration in four patients, focal ulceration in one, focal intramural hematoma in one, and focal intramural hematoma with rupture in one. The diagnosis of intramural hematoma was made by the detection of increased signal intensity on T1- and T2-weighted MR images. MR imaging was superior to angiography in depicting the extent of intramural thrombus, although one ulceration diagnosed at angiography was missed at MR imaging. MR imaging was superior to CT in differentiating acute intramural hematoma from atherosclerotic plaque and chronic intraluminal thrombus, although it did not depict displaced intimal calcification in one patient with extensive intramural hematoma. 
5	Effect of local inhibition of gamma-aminobutyric acid uptake in the dorsomedial hypothalamus on extracellular levels of gamma-aminobutyric acid and on stress-induced tachycardia: a study using microdialysis. Previous studies involving local microinjection of drugs that interfere with gamma-aminobutyric acid (GABA)A receptor-mediated synaptic inhibition have led to the suggestion that endogenous GABA suppresses the activity of a sympatho-excitatory mechanism in the dorsomedial hypothalamus in rats. In this study, microdialysis was used to assess and to alter pharmacologically extracellular-levels of GABA within this region while simultaneously monitoring heart rate and blood pressure. In anesthetized rats, local microdialysis for 15 min with 2.5, 10 and 40 mM nipecotic acid, an inhibitor of GABA uptake, caused concentration-related increases in GABA and taurine in the extracellular space, but no significant change in heart rate or arterial pressure. Similar perfusion with 37.5, 75 and 150 mM KCl caused concentration-related increases in GABA as well as aspartate, glutamate, taurine, glycine and alanine. Only modest, variable increases in heart rate and no effect on arterial pressure were observed during the perfusions with high potassium. In conscious rats, unilateral microdialysis of the dorsomedial hypothalamus with 0.5 mM nipecotic acid for 2 to 2.5 hr before stress coupled with contralateral microinjection of muscimol (88 pmol/250 nl) 5 min before stress significantly reduced air stress-induced tachycardia; this reduction in tachycardia was associated with markedly elevated levels of GABA in dialysates collected from the dorsomedial hypothalamus. Neither treatment alone significantly influenced stress-induced increases in heart rate, although perfusion with nipecotic acid alone evoked similar elevations in extracellular GABA. These results suggest that extracellular levels of endogenous GABA in the dorsomedial hypothalamus may regulate the cardiovascular response to stress. 
5	Expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas. The expression of ABH and Lewis antigens has been studied in a series of pulmonary carcinomas, in areas of squamous metaplasia, and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies. All respiratory epithelial cells can express antigens, with the exception of glandular serous cells. The expression of AB antigens is rather homogeneous, while Lewis antigens are expressed in a more irregular pattern, alternating positively stained cells with negatively stained cells in the same microscopic field. The expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms. Metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas. The most significant findings are the deletion of A antigen and the strong expression of Le antigen. Pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas. The most important findings are the deletion of AB antigens and the strong expression of Le(y) antigen. 
4	Kidney function and cardiovascular risk factors in non-insulin-dependent diabetics (NIDDM) with microalbuminuria. Microalbuminuria in non-insulin-dependent diabetes (NIDDM) is a strong predictor of increased mortality. The major causes of death are cardiovascular, whereas end-stage renal failure is of low frequency. To define kidney function and the presence of some assumed cardiovascular risk factors, we compared a group of 19 microalbuminuric NIDDM patients (M), of mean age (+/- SD) 65 +/- 4 years, and known duration of diabetes 8 +/- 7 years, with 19 randomly selected matched normoalbuminuric patients (N). Seven microalbuminuric patients (P) were also studied. Glomerular filtration rate (GFR) did not differ between N and M, whereas kidney volume was increased in M (260.3 +/- 54.1 ml 1.73 m-2) compared to N (220.4 +/- 44.8 ml 1.73 m-2; P = 0.018). The frequency of cardiac disease increased with increasing albuminuria. Glycaemic control did not differ between the groups, but fasting plasma C-peptide levels increased from 2.8 +/- 1.1 micrograms l-1 in N, to 3.7 +/- 1.7 micrograms l-1 in M (P = 0.08), and to 4.2 +/- 1.9 micrograms l-1 (P = 0.03) in P. The lipoprotein profile showed no significant differences, although the LDLcholesterol/HDLcholesterol (LDL-C/HDL-C) ratio tended to rise. A significant correlation was found between C-peptide and LDL-C/HDL-C (r = 0.5; P less than 10(-3]. In conclusion, GFR was not increased, and did not differ between N and M, whereas kidney volume was enhanced in M. Several assumed cardiovascular risk factors showed values of M intermediate between those of N and P. 
3	Neurologic complications in chronic renal failure: a retrospective study. We have retrospectively examined 324 patients with chronic renal failure and evaluated the probable underlying causes of neurologic complications, laboratory data and therapeutic interventions. The common neurologic problems in our patients were alterations in consciousness (40.7%) and convulsions (35.1%). When BUN concentration was above 135 mg/dl and creatinine clearance was below 8 m/min/1.73 m2, alteration of consciousness was observed and when BUN concentration was 200 mg/dl and creatinine clearance was below 7 m/min/1.73 m2, abnormal convulsives appeared. Changes in deep tendon reflexes and pathologic reflexes were associated with hypertension. All of the patients with cortical atrophy using computerized cranial tomography aluminum hydroxide at least for 18 months, and six of them had hemodialysis. Fourteen patients who underwent dialysis developed convulsions and were thought to have disequilibrium syndrome. These findings are consistent with the suggestion that the metabolic and biochemical derangements associated with CRF may be particularly detrimental to the still developing CNS of the child. 
5	Treatment of complicated prosthetic aortic valve endocarditis with annular abscess formation by homograft aortic root replacement. The outcome of 30 consecutive patients with active aortic prosthetic valve endocarditis and root abscesses treated by the technique of homograft aortic root replacement with reimplantation of the coronary arteries is detailed. The principles of this technique are the removal of all abscesses and infected areas likely to drain into the infected mediastinum, excision of infected tissues down to healthy noninfected tissue and replacement with an antibiotic-impregnated homograft aortic root. All patients had evidence of progressive cardiac failure and ongoing sepsis. Mean patient age (+/- SD) at the time of operation was 42 +/- 18 years. The mean number of previous aortic valve replacements per patient was 1.6 +/- 0.7; 14 patients (47%) had undergone greater than or equal to 2 previous replacements. At operation, aortic root abscesses were found in all patients; abscess extension to adjacent structures and partial valve dehiscence had occurred in 23. In-hospital death occurred in 9 (30%) of the 30 patients. The 21 hospital survivors have been followed up for a mean of 66 +/- 42 months (range 9 to 144). Overall, 17 (81%) of the 21 hospital survivors have remained free of major adverse events (recurrence of endocarditis, need for reoperation or death). The results of our study suggest that homograft aortic root replacement should be considered favorably in the treatment of patients with aortic prosthetic valve endocarditis and root abscesses. 
5	Bilateral vocal cord teflon injection. An ineffective treatment for recurrent aspiration pneumonia. Recurrent aspiration pneumonia is a potentially lethal problem, and its treatment is controversial. A variety of procedures have been advocated to prevent aspiration. These are reviewed briefly. We have been dissatisfied with established procedures because they usually require external approaches with considerable complexity and potential complications. Therefore, we attempted to obstruct the glottic airway by injecting both vocal cords with Teflon in a series of patients with recurrent aspiration pneumonia secondary to severe neurologic impairments. Since Teflon injection of the vocal cords bilaterally did not reliably prevent aspiration, we cannot recommend it for routine use in the treatment of chronic aspiration. 
5	Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia. OBJECTIVE: The authors sought to determine if an acute dose of dextroamphetamine might have positive effects on affect and cognition in schizophrenic patients maintained on a regimen of haloperidol and, if so, what variables might predict such improvements. METHOD: Twenty-one patients with chronic schizophrenia who were hospitalized on a research ward received a single oral dose of dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover study. All patients were receiving 0.4 mg/kg per day of haloperidol. Cognitive tests, motor tests, global ratings, mood ratings, and videotape ratings were used to determine the effect of the coadministration of these drugs. Ventricle-brain ratios derived from CT scans were used to predict response to the coadministration of these drugs. RESULTS: Amphetamine improved performance on a measure of concept formation on the Wisconsin Card Sorting Test but did not result in changes in performance on tests of memory or attention. As a group, the patients were more active and performed psychomotor tests more quickly while receiving amphetamine. Six patients were judged by clinical raters to have improved in terms of affect, cooperation, and engagement with the environment. Improvement was associated with enlarged cerebral ventricles and increases in blink rate from the placebo to the active drug condition. No patient unequivocally worsened. CONCLUSIONS: These results may be consistent with the theory that coadministration of amphetamine and haloperidol produces relatively selective enhancement of cortical dopaminergic activity. However, because of the acute nature of the trial and the specialized research environment in which it was conducted, the authors do not advocate amphetamine as a routine clinical treatment of schizophrenia. 
1	A cost-minimization study of cancer patients requiring a narcotic infusion in hospital and at home. We conducted a retrospective, non-randomized, cost-minimization study, from the perspective of the Ministry of Health, to compare the cost of managing cancer patients who required narcotic infusions, in hospital and at home. Our medical costs averaged $369.72 per inpatient day and $150.24 per outpatient day (saving $219.48 per diem, 1988 Canadian dollars), while narcotic costs were the same for any given patient in both settings. Sensitivity analysis showed that no reasonable changes in the quantity and cost of services reduced our savings by more than 50%. During incremental analysis, savings increased as more outpatient days were managed by our centre, from $0.00 for 318 days, to more than $500,000 for over 2000 days per annum. As this program has been extremely cost effective and preferred by our patients, other hospitals and central funding agencies might consider establishing a regional outpatient narcotic infusion program to reduce their costs. 
5	Unusual malignant neoplasms of the esophagus. Oat cell carcinoma, melanoma, and sarcoma. Primary noncarcinomatous malignant neoplasms of the esophagus are uncommon and data concerning treatment and results are sparse. To evaluate the results of therapy in this group, we reviewed the records of 32 patients with primary esophageal malignant tumors of unusual histologic type. Thirteen patients (41%) had sarcoma, eight (25%) melanoma, and 11 (34%) had oat cell carcinoma. Dysphagia was present in 78% (25/32) of the patients for a median of 13 weeks before diagnosis. Location of the esophageal primary tumor was upper third in four patients (12%), middle third in 12 (38%), and lower third in 16 (50%). Treatment consisted of esophagectomy in 10 of 13 patients with sarcoma (77%), seven of eight with melanoma (88%), and three of 11 with oat cell carcinoma (27%). Patients not undergoing resection received chemotherapy or radiation therapy, or both. The 3- and 5-year survival rates were 46% and 23% for sarcoma (median 20 months), 13% and 0% for melanoma (median 5 months), and 0% and 0% for oat cell carcinoma (median 5 months), respectively. Distant disease was the initial form of recurrence in 73% (11/15) of patients undergoing curative therapy. Surgical resection appears indicated for localized primary esophageal sarcoma. Optimum treatment of primary esophageal melanoma is less clear, but surgical resection may be of benefit in selected patients. Esophageal oat cell carcinoma is a systemic disease necessitating systemic therapy with local therapy reserved for palliation of dysphagia. 
5	Massive allografts in salvage revisions of failed total knee arthroplasties. Ten patients with failed total knee arthroplasties and severe bone loss were treated with massive whole distal femur and proximal tibial allografts in combination with prosthetic implants. Fourteen allografts were inserted either as invaginated or segmental grafts and were rigidly fixed to the host bone. Clinically and roentgenographically, 12 of 14 grafts (86%) seemed to have united to the host bone. The average range of motion was 92 degrees. Five patients developed complications; two of these involved the allograft (nonunion and fracture) and two were caused by inadequate healing at the ligament-allograft junction. One patient had a late infection. With careful planning and improved surgical techniques, these complications can be avoided. The massive allograft-prosthesis composite techniques is a viable reconstructive alternative worthy of further clinical trials. 
4	Late chronic hemolysis after valve replacement for aortic stenosis. Relation to residual hypertrophy and impaired left ventricular function. The relationship between intravascular hemolysis induced by aortic valve prosteses and patient status/left ventricular (LV) function (radionuclide cardiography) was examined in 63 patients of 65 who were alive ten to seventeen years after valve replacement (1965-1973) for aortic stenosis. Serum-lactic dehydrogenase (LDH) exceeded upper reference limit in 62 patients and S-haptoglobin (HAPTO) was reduced in 62. One patient with normal LDH had reduced HAPTO and elevated plasma-hemoglobin. Anemia was noted in 4 patients (6%). S-LDH was higher in men than in women (p less than 0.05), in patients with increased ECG hypertrophy score than in those with a normal score (p less than 0.05), in patients with NYHA class II-III than in those with class I (p less than 0.05), in patients with abnormal LV function than in those with a normal radionuclide study (p less than 0.05), in patients with a pathologic Q wave in the ECG than in those without (p less than 0.05), and in patients with a Starr Edwards cloth-covered (SECC) prosthesis than in those with other types (p = 0.07). ECG hypertrophy score correlated directly with LDH (r = 0.33, p = 0.008) and inversely with LV ejection fraction (r = -0.57, p less than 0.0001), peak ejection rate (r = -0.47, p less than 0.0001), and peak filling rate (r = -0.41, p less than 0.001). Multiple linear regression analysis revealed that LDH was accounted for by ECG hypertrophy score (p = 0.001), SECC prosthesis (p = 0.04), and male gender (p = 0.05). Hypertrophic malfunctioning left ventricles may be responsible for higher degrees of turbulent flow characteristics in the vicinity of prosthetic valves in the aortic position and, by inference, explain the increased tendency toward hemolysis in these patients. 
4	Wellness motivation in cardiac rehabilitation. Lack of patient adherence to prescribed regimens is a fundamental problem in cardiac rehabilitation programs. A causative factor in lack of patient adherence may be related to failure to address differences in individual health behavior motivation in cardiac rehabilitation. A group of 52 patients who had had myocardial infarction were sampled to test the relationship between social support systems, health locus of control, health value orientations, and wellness motivation. Pearson correlation coefficients indicated significant positive correlations between health locus of control variables, health value orientation variations, and wellness motivation. Health locus of control and health value orientation variables entered into a multiple regression equation to explain 32% of the variation in wellness motivation. Awareness of individual motivational responses that influence health behaviors in cardiac rehabilitation may enable nurses to develop intervention strategies for patients with cardiovascular disease who would benefit from modifying their risk-producing life-styles. 
4	Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort. A national sample of 1944 white menopausal women greater than or equal to 55 years old from the epidemiologic follow-up of participants in the National Health and Nutrition Examination Survey was reviewed to investigate the role of hormone therapy in altering the risk of death from cardiovascular disease. Women in the study were observed for up to 16 years after the baseline survey in 1971 to 1975. By 1987 631 women had died; 347 of these deaths were due to cardiovascular disease. History of diabetes (relative risk, 2.38; 95% confidence interval 1.73 to 3.26), previous myocardial infarction (relative risk, 2.12; 95% confidence interval 1.56 to 2.86), smoking (relative risk, 2.18; 95% confidence interval, 1.69 to 2.81), and elevated blood pressure (relative risk, 1.49; 95% confidence interval, 1.14 to 1.94) were strong predictors of cardiovascular disease-related death in this cohort. After adjusting for known cardiovascular disease risk factors (smoking, cholesterol, body mass index, blood pressure, previous myocardial infarction, history of diabetes, age) and education, the use of postmenopausal hormones was associated with a reduced risk of death from cardiovascular disease (relative risk, 0.66; 95% confidence interval, 0.48 to 0.90). The same protective effect provided by postmenopausal hormone therapy was seen in women who experienced natural menopause (relative risk, 0.69; 95% confidence interval, 0.45 to 1.06). 
4	Methodology of mental stress testing in cardiovascular research. Many issues related to the selection, reliability, and validity of mental stress testing in cardiovascular research are discussed. Five categories of mental stress testing are distinguished: problem-solving tasks, information-processing tasks, psychomotor tasks, affective conditions, and aversive or painful conditions. A series of practical and theoretical criteria are outlined for the selection of appropriate tests, and the measurement of a range of dependent variables is emphasized. The temporal stability of cardiovascular responses to mental stress tests is examined through an analysis of test-retest correlations (weighted for sample size) in 28 comparisons with intervals between sessions varying from 1 day to more than 1 year. Heart rate reactions to tasks show an average-weighted Z of 0.732 +/- 0.031 (r = 0.62), with Z = 0.575 +/- 0.034 (r = 0.52) for systolic blood pressure and Z = 0.313 +/- 0.035 (r = 0.30) for diastolic blood pressure. It is argued that the validity of mental stress tests can be judged in relation to several different aspects, specifically, methodological, ecological, diagnostic, prognostic, and therapeutic validities. The nature of these standards is described, and pertinent literature is presented. 
5	Adrenal medullitis in type I diabetes. To investigate whether cell-mediated immunity against the adrenal medulla occurs in type I diabetes (IDDM), we conducted a retrospective autopsy study of adrenal glands from IDDM and nondiabetic subjects using formalin-fixed tissue. Forty-four IDDM subjects, aged 4-67 yrs (mean +/- SD, 44.8 +/- 15.4) with a duration of IDDM from 0-55 yr (28.6 +/- 14.2), and 29 nondiabetic controls, aged 8-82 yr (51.8 +/- 18.6), were evaluated for a lymphocytic infiltrate using UCHL1, which recognizes a subpopulation of resting T-lymphocytes and most activated T-lymphocytes. Immunohistochemistry using antihuman B-cell antibody (L26) was also performed. Sections were scored for both lymphocytic infiltrates and fibrosis [none (0), small (1), moderate (2), or large (3)]. Blinded scoring was performed. A moderate to severe UCHL1 infiltrate was present in 9 of 44 (20%) IDDM, compared with 1 of 29 (3%) control subjects (P less than 0.04). Mild to severe fibrosis (score 1, 2, or 3) was present in 22 of 42 (52%) IDDM subjects compared with 4 of 25 (16%) control subjects (P = 0.003). Eight of 42 (19%) IDDM subjects had moderate to severe fibrosis (score 2 or 3) compared with 1 of 25 (4%) control subjects. Seventeen of 44 (39%) IDDM subjects had either a moderate to large cellular infiltrate or moderate to severe adrenal medullary fibrosis compared with 2 of 29 (7%) control subjects (P = 0.003). Staining of the adrenal medulla with L26 revealed a large cellular infiltrate in only one subject who was UCHL1 negative. Adrenal medullitis was observed in 20% of IDDM subjects, suggesting that the adrenal medulla may be another immunological target in IDDM. 
4	Detection of vascular complications in renal allografts with color Doppler flow imaging. One hundred ninety-five color Doppler flow (CDF) examinations were performed in 146 renal allografts to assess the capabilities of this technique in detecting intra- or extrarenal vascular complications. Conventional angiography was also performed in 44 transplants. In the group of transplants with angiographic correlation, CDF sonography enabled correct identification of 30 of 34 vascular complications. CDF showed 10 of 11 significant stenoses of the renal artery or of one of its main branches. There were two false-positive renal artery stenoses (one normal artery and one 40% stenosis). Nine of nine renal artery thromboses and the single pseudoaneurysm were also identified. Within the parenchyma, CDF sonography demonstrated five of five segmental infarcts, two of two postbiopsy arteriovenous fistulas, and three of six segmental or interlobar artery stenoses. Measurement of peak systolic velocity showed a significant difference (P less than .05) between a group (n = 8) with significant stenosis of the renal artery or one of its main branches (mean, 215.2 cm/sec +/- 32) and a group (n = 14) without stenosis (mean, 99.2 cm/sec +/- 19). 
3	L-tryptophan induced eosinophilia-myalgia syndrome. We describe the spectrum of clinical and histologic abnormalities of 11 women with L-tryptophan induced eosinophilia-myalgia syndrome. The illness is characterized by musculoskeletal symptoms including myalgias, arthralgias and paresthesias. The physical findings consist of muscle tenderness, neuropathies, rash, peripheral and periorbital edema. Electroneurography performed in 10 patients demonstrated a neuropathy in 5 and myopathic changes in 3. Skin and muscle biopsies showed fascial edema, inflammation and perivascular infiltrates in the skin, whereas perineural infiltrates and venulitis were identified in muscle. Seven patients were treated with prednisone; eosinophilia disappeared promptly although myalgias and neuropathy persisted. 
4	Progress report of the Stroke Prevention in Atrial Fibrillation Study. The Stroke Prevention in Atrial Fibrillation Study recently found and reported (SPAF Investigators, N Engl J Med, 1990;322:863-868) a beneficial effect of both warfarin and aspirin compared with placebo in the primary prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Among warfarin-eligible patients, the event rates were 1.6%/yr for those receiving active antithrombotic therapy (warfarin or aspirin) and 8.3%/yr for those receiving placebo (p less than 0.00005) (risk reduction 81%, 95% confidence interval 56-91). Ironically, we did not find a beneficial effect of aspirin in warfarin-ineligible patients. On the basis of these results, the study has been reshaped to directly compare these two antithrombotic agents. Insight into the apparent aspirin unresponsiveness noted in some patients also is being sought. Interpretation of the preliminary results and the reshaping of the study have been made more complex by the continued blinding of the investigators to certain portions of the data. Presented is an account of the study from its inception through its recent redesign. 
4	Left ventricular mass regression after aortic valve replacement measured by ultrafast computed tomography. Left ventricular mass and function were measured using ultrafast computed tomography, and were correlated with clinical status in 17 patients with aortic stenosis and/or insufficiency undergoing aortic valve replacement or balloon valvuloplasty. Wall mass was 159 +/- 38 gm/m2 initially, decreased 25% to 116 +/- 29 gm/m2 at 4 month (p less than 0.001), and decreased a total of 34% to 105 +/- 33 gm/m2 at 8 months after valve repair. By 8 months not only was the mean wall mass within the normal range, but only three patients retained abnormal hypertrophy. Ejection fraction increased 8% (p = 0.06). Clinical function improved in all patients, with only three patients remaining outside of New York Heart Association functional class 1 at 8 months. Regression of ventricular mass into the normal range correlated with attainment of class 1 functional status (p less than 0.02), despite a lack of increase of ejection fraction. The single patient followed for 8 months after valvuloplasty had minor wall mass regression and minor clinical improvement. 
4	Prehospital thrombolysis in acute myocardial infarction. The benefit and risk of prehospital thrombolysis for acute myocardial infarction (AMI) were evaluated in a double-blind randomized trial. Patients presenting less than 4 hours after symptom onset received 2 million units of urokinase as an intravenous bolus either before (group A, n = 40) or after (group B, n = 38) hospital admission. The mean time interval from onset of symptoms to thrombolytic therapy was 85 +/- 51 minutes in group A and 137 +/- 50 minutes in group B (p less than 0.0005). In 91% of the patients, thrombolytic therapy was administered less than 3 hours after symptom onset. Complication rates during the pre- and in-hospital period were low and did not differ between groups. Three patients died (1 in group A, 2 in group B) from reinfarction 7 to 14 days after admission. Left-sided cardiac catheterization before discharge revealed a patency rate in the infarct-related artery of 61% in group A and 67% in group B (difference not significant). Global left ventricular function and regional wall motion at the infarct site did not differ significantly between group A and B (ejection fraction 51 +/- 10%, n = 28 vs 53 +/- 14%, n = 28; wall motion -2.3 +/- 1.3 vs -2.2 +/- 1.1 standard deviation, respectively). Also, peak creatine kinase did not differ significantly (838 +/- 634 U/liter in group A vs 924 +/- 595 U/liter in group B). Prehospital thrombolysis using a bolus injection of urokinase has a low risk when performed by a trained physician with a mobile care unit. The saving of 45 minutes in the early stage of an acute infarction through prehospital thrombolysis did not appear to be important for salvage of myocardial function. 
5	Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse. From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years. 
3	Treatment of intractable arterial hemorrhage during stereotactic brain biopsy with thrombin. Report of three patients. Of 165 consecutive patients undergoing computerized tomography- or magnetic resonance imaging-guided stereotactic brain biopsies at the Cleveland Clinic between June, 1987, and November, 1989, four patients (2.4%) developed arterial hemorrhage refractory to conventional efforts to secure hemostasis. Craniotomy was performed in one of these patients to control the hemorrhage; in the other three, 0.5 to 2 cc of thrombin (5000 U/cc) was slowly injected via the biopsy cannula, resulting in immediate control of bleeding in all three cases. Postoperatively, the first two patients treated with 1 to 2 cc of thrombin were slow to awaken; one had evidence of vasospasm by transcranial Doppler ultrasound studies and multiple infarcts on cranial computerized tomography, while the other had a moderate-sized frontal hematoma with intracranial hypertension. After prolonged recovery periods, only mild neurological deficits persisted in both patients. The third patient, treated with 0.5 cc of thrombin, had an uneventful postoperative course. Thrombin is highly effective for stopping intractable arterial hemorrhage during stereotactic brain biopsy; however, it is a vasospastic agent and may have been responsible for the cerebral infarctions in one patient. Therefore, thrombin should be used only as a last resort, short of craniotomy, to control intractable arterial hemorrhage during stereotactic brain biopsy. 
1	The role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. I. Induction of regulatory macrophages in normal mice by the in vivo administration of rGM-CSF. Using a dimethylbenzanthracene-induced immunogenic nonmetastatic murine mammary adenocarcinoma in BALB/c mice, our previous work has shown that splenocytes from tumor bearers have reduced responses to both mitogens and Ag including tumor-associated Ag. NK and cytotoxic T cell activities are also reduced in splenocytes of tumor bearers. Mac-1+2+ macrophages induced in mammary tumor bearers are capable of down-regulating lymphocyte responses to mitogens and tumor-associated Ag by cell to cell contact interaction and increased PGE2 production. We have found that the tumor constitutively releases a granulocyte-macrophage (GM)-CSF-like factor in vivo and in vitro, which may be responsible for the systemic increase in cells of the macrophage lineage in tumor-bearing mice. A tumor cell line established from the in vivo tumor expresses and releases GM-CSF as shown by Northern and Western blot analyses. Daily i.p. injections for 3 wk of 10,000 U of rGM-CSF into normal mice induces hemopoietic and immunologic alterations similar to those observed in tumor bearers. Mac-1+ and/or Mac-2+ macrophages can also be detected in the spleens and bone marrow of the mice treated with rGM-CSF. Additionally, splenocytes from rGM-CSF-treated mice have reduced responses to mitogens and their peritoneal exudate cells can cause in vitro down-regulation of proliferative responses of lymphocytes from normal mice. The suppression can be partially reversed by the addition of indomethacin to the cultures suggesting that PGE2 may contribute to the effect. rGM-CSF enhances the in vitro release of PGE2 by the spleen, bone marrow, and peritoneal cells of normal mice. These data indicate that the high levels of GM-CSF constitutively produced by the tumor may be responsible for the hemopoietic changes and immunologic alterations observed in tumor-bearing mice. 
5	Gross and microscopic changes in the viscera induced by photodynamic therapy applied to the lower abdomen of intact rats. Photodynamic therapy (PDT) is a promising approach to the treatment of cancer. Preferential retention of the photosensitizer by malignant tissue has been considered a hallmark of this treatment modality. However, photosensitivity can be observed in normal, non-neoplastic tissues, and the present study investigated the effects of PDT treatment on the abdomen of intact rats. A circular region (1 cm diameter) on the shaved abdomen of Fischer rats, pretreated 24 h prior with Photofrin II, was irradiated for 30 min at 632 nm. Control animals received either photoradiation or Photofrin II administration. Subsequent lesions were observed in the irradiated skin, its associated abdominal wall, and the underlying gut in rats receiving Photofrin II and laser irradiation. All tissues were not equally sensitive to PDT treatment. Gut lesions were consistently more severe than were skin and abdominal wall injuries. By 24 hr after treatment, the gut manifested a transmural hemorrhagic necrosis, while the irradiated skin and abdominal wall were edematous, with an inflammatory infiltrate in the dermis and around occasional swollen myocytes. These results indicate that superficial lesions induced by PDT may not be reliable indicators of the extent of deeper PDT tissue damage. Further, it may be possible to take advantage of this discrepancy in tissue sensitivity and treat deep tissues through less sensitive superficial tissues. 
1	Adenocarcinoma of the prostate in a 41-year-old man with XXY karyotype and chronic lymphocytic leukemia: report of a case. We report a case of adenocarcinoma of the prostate in a 41-year-old man with 47XXY karyotype (Klinefelter's syndrome) and chronic lymphocytic leukemia. The increased incidence of malignancy in individuals with Klinefelter's syndrome has been well documented for certain neoplasms. Adenocarcinoma of the prostate has not been reported previously in a patient with Klinefelter's syndrome and a 47XXY karyotype. Absence of mosaicism was confirmed by peripheral lymphocyte, skin fibroblast, bone marrow cell and spleen stroma fibroblast cultures. Chronic lymphocyte leukemia, especially the T-cell cytotoxic/suppressive variant, may additionally add to an immunological deficit. Since carcinoma of the prostate, Klinefelter's syndrome and chronic lymphocytic leukemia are common, the lack of a previous report is interesting. Etiological aspects are discussed. 
5	Tissue expansion in the treatment of pressure ulcers. The authors report their experience using skin expanders in 11 patients with severe bed sores. The expanders, with different volumes, from 250 to 1000 cc, were generally overfilled using the cutaneous tonometer. In fact, with the information revealed by this apparatus on the skin in expansion, the authors were able to reduce the filling intervals without risking ulceration. In their experience, the results obtained were satisfactory: All patients treated achieved surgical recovery. The authors see a wide future for skin-expander use in pressure-ulcer treatment. They have a working hypothesis about using expanders to progressively advance sensitive skin in areas subject to ulceration. This hypothesis is based on the possibility of reexpanding the same flap several times, as has been seen in the treatment of other types of pathology. 
4	Effects of intravenous verapamil on left ventricular relaxation and filling in stable angina pectoris. Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right- and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 +/- 22 to 117 +/- 16 mm Hg, p less than 0.01) and the end-systolic pressure/volume ratio (2.4 +/- 1.3 to 1.6 +/- 0.5 mm Hg/ml, p less than 0.05), and increased LV end-diastolic (13 +/- 4 to 16 +/- 4 mm Hg, p less than 0.02) and pulmonary capillary pressures (10 +/- 5 to 12 +/- 5 mm Hg, p less than 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 +/- 0.7 to 3.9 +/- 0.6 liters/min/m2, p less than 0.02). The time constant of isovolumic relaxation shortened (63 +/- 14 to 47 +/- 9 ms, p less than 0.02); peak filling rate increased (370 +/- 155 to 519 +/- 184 ml/s, p less than 0.001; 2.6 +/- 1.1 to 3.3 +/- 0.9 end-diastolic counts/s, p less than 0.02; and 4.1 +/- 1.6 to 5.5 +/- 1.5 stroke counts/s, p less than 0.001). 
3	Gene mapping and other tools for discovery. Genetic mapping provides a means of understanding the molecular basis of inherited diseases whose biochemistry is unknown. Adequate pedigrees, informative genetic markers, and accurate identification of the disease phenotype are necessary. For dominant inheritance, mapping studies can be done in a single large pedigree; the larger the number of affected individuals sampled the better the estimate of recombination between the gene causing the disease and one or more nearby genetic markers. For recessive inheritance, nuclear families with more than one affected sibling provide the best information. The development of many polymorphic DNA markers on the human genome has contributed to the success of mapping unknown genes because, as the genome is now densely covered with markers, the probability is good that at least one marker will be linked to the disease locus in a family that is segregating a disease allele. Most genetic markers now in use depend upon restriction fragment length polymorphisms (RFLPs), which are either the result of single-base-pair substitution or the presence of a variable number of tandemly repeated oligonucleotide units at a locus (VNTRs). RFLPs can be recognized by digesting DNA with restriction enzymes and separating the fragments by size on an electrophoretic gel. VNTRs can vary widely among individuals, and they provide more linkage information than single-site polymorphic markers because family members are more likely to be heterozygous. Genetic maps of each chromosome, constructed from linkage data relating marker loci to one another in normal reference families, permit rational choices of markers for disease-mapping studies. 
5	Reduction of postoperative morbidity following patient-controlled morphine The present study examined the impact of two methods of pain management on recovery in 38 women undergoing hysterectomy. One group received IV morphine in the recovery room and IM morphine on the ward on a PRN basis (PRN group). In the other group, a loading dose of morphine 8 mg IV was given when the patient first complained of pain and patient-controlled IV morphine (PCA) was initiated and continued for 48 h (PCA group). Both groups received similar amounts of morphine overall, differently distributed over time. The PCA patients received 8 mg.h-1 in the recovery room (approximately 2.5 hrs) and less thereafter. The PRN patients received approximately 2 mg.h-1 for the entire 48-hr period. Pain control was better throughout convalescence and less variable across time with PCA management. Minute ventilation also recovered faster and by day four was 25 per cent above the preoperative baseline in the PCA group. In addition, oral temperature became normal one day earlier, ambulation recovered more rapidly and patients were discharged from hospital earlier. The data suggest that early treatment with relatively high, self-titrated morphine doses may alter the course of the metabolic response to surgery. 
5	Paraneoplastic brachial plexopathy in a patient with Hodgkin's disease. We describe a case of inflammatory brachial plexopathy that occurred in the context of a mild, diffuse sensorimotor peripheral neuropathy associated with Hodgkin's disease. Clinical, electrophysiologic, and pathologic studies helped distinguish this disorder from other causes of brachial plexopathy in patients with cancer. Treatment with corticosteroids seemed beneficial in this patient. We suggest that this may be another type of paraneoplastic condition associated with Hodgkin's disease. 
1	Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor. Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammatory responses. A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF. The cytotoxic effect of TNF on the fibrosarcoma cell line WEHI 164 was inhibited by 50% at a 10-fold excess of TNF-BP. The binding of TNF to the receptor was partially reversed after the addition of TNF-BP. Results from biosynthetic labeling of cells with 35S-cysteine followed by immunoprecipitation with anti-TNF-BP indicated that TNF-BP is formed and released at the cell surface by cleavage because no corresponding cellular polypeptide was observed. A cellular 60-kD polypeptide, which was immunoprecipitated with anti-TNF-BP, may correspond to the transmembrane TNF-receptor molecule and be the precursor of TNF-BP. Thus, TNF-BP appears to be a soluble form of a transmembrane TNF-receptor. Moreover our results demonstrate that the production of TNF-BP is increased when the TNF receptor is downregulated in cells by treatment with TNF or by activation of protein kinase C with phorbol esters. TNF-BP may be an important agent that blocks harmful effects of TNF, and, therefore, useful in clinical applications. 
1	Linkage of early-onset familial breast cancer to chromosome 17q21. Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. Mapping the genes responsible for inherited breast cancer may also allow the identification of early lesions that are critical for the development of breast cancer in the general population. Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease. Genetic analysis yields a lod score (logarithm of the likelihood ratio for linkage) of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-onset families and negative lod scores in families with late-onset disease. Likelihood ratios in favor of linkage heterogeneity among families ranged between 2000:1 and greater than 10(6):1 on the basis of multipoint analysis of four loci in the region. 
5	Spontaneous necrosis in osteosarcoma. The percentage of necrosis in a primary osteosarcoma after the patient has received preoperative chemotherapy is prognostic and is usually used to select subsequent chemotherapy. However, the percentage of necrosis that occurs spontaneously, without preoperative chemotherapy, has not been adequately studied. The examination of histologic macrosections of 76 osteosarcomas from patients who had not received preoperative treatment and of 20 patients who had received preoperative chemotherapy revealed a significant difference in the percentage of necrosis. There was minimal spontaneous necrosis, but necrosis after preoperative chemotherapy was usually extensive. The larger the tumor, the greater the percentage of spontaneous necrosis; however, size did not correlate with the percentage of necrosis with preoperative chemotherapy. Survival among those patients who did not receive preoperative treatment correlated with the size and percentage of necrosis. Necrosis in an osteosarcoma in a patient who has received preoperative chemotherapy can be considered the result of chemotherapy and not a spontaneous event. 
3	Presymptomatic and prenatal diagnosis of myotonic muscular dystrophy with linked DNA probes. Advances in neurogenetics are facilitating clinical care. Localization of the mutant gene that causes myotonic muscular dystrophy (DM) to chromosome 19 enabled our predictive testing using linked DNA probes in 74 members of 12 families at risk. Individuals sought either diagnostic confirmation or exclusion with childbearing in mind, or requested prenatal diagnosis. Valuable information was provided for 11 of 12 families. Of 14 individuals at 50% risk, 12 learned they did not have DM, two learned they did (although presymptomatic), and prenatal diagnoses of affected fetuses were made in three families--all with high degrees of certainty. The future opportunity for prenatal diagnosis was provided for 3 other families. The potential health risks to an affected female and her affected or nonaffected fetus provide cogent reasons for physicians to inform DM families in their care about these important advances and opportunities to avert grave complications. 
5	Role of angioplasty in myocardial infarction management strategies: a review. The role of angioplasty in acute myocardial infarction has been extensively studied in the past few years. Although angioplasty in some circumstances can be the primary reperfusion intervention, logistic problems and the excellent results of intravenous thrombolytic therapy have resulted in postlytic angioplasty being the preferred use of this interventional strategy. Clinical trials of this strategy have not supported its routine use, however, and a much more selective application of postthrombolytic coronary artery dilation is advocated at this time. 
2	Neonatal small bowel atresia, stenosis and segmental dilatation. In 8 years, 44 neonates were treated for small bowel atresia, stenosis or segmental dilatation by one surgical team. There was a single lesion in 30 infants and 14 had two or more sites of intestinal obstruction. Associated gastrointestinal abnormalities were found in 23 (52 per cent) patients. Resection of the atresia(s) and primary anastomosis were performed in 34 infants and staged procedures were carried out in ten patients with complicated lesions. Patients undergoing staged procedures had a higher complication rate than those having primary repair (six out of ten and 11 out of 34 respectively). The overall initial survival rate was 93 per cent, rising to 100 per cent in those without associated anomalies or prenatal complications, but more than a quarter (27 per cent) of survivors have long-term disabilities. 
5	Cerebral falciparum malaria mimicking thrombotic thrombocytopenic purpura. We have described a patient with cerebral falciparum malaria who had rapidly progressive CNS deterioration, renal failure, hemolytic anemia associated with striking and varied erythrocyte morphologic changes, and thrombocytopenia. The initial diagnosis was thrombotic thrombocytopenic purpura (TTP) of unknown origin. Reexamination of the peripheral smear of this comatose patient led to correct diagnosis and effective treatment in this case of cerebral falciparum malaria--another of medicine's great mimickers. 
2	Gallstone pancreatitis. Choosing and timing treatment. Patients with gallstone pancreatitis are often seen initially by primary care physicians. Prompt diagnosis and timely intervention are crucial in reducing morbidity and mortality. Initial management should include supportive medical care and surgical consultation. The timing of surgery is then dictated by serum enzyme levels and liver function test results as well as by the patient's condition. The role of endoscopic intervention is currently evolving. Whether surgery or endoscopic sphincterotomy is preferable as primary therapy for gallstone pancreatitis remains unresolved. However, sphincterotomy with stone extraction is a viable option in selected cases, especially in patients who have severe gallstone pancreatitis. 
4	Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages. 
5	Thoracoplasty: current application to the infected pleural space Thoracoplasty, once commonly used in the management of cavitary pulmonary disease, continues to find application in the obliteration of infected pleural spaces. This study reports a series of 13 patients receiving thoracoplasty between 1976 and 1989. Five patients had chronic apical empyema spaces without prior resection of lung tissue. Two of the empyemas were due to tuberculosis, two were due to atypical mycobacteria, and one was due to postpneumonic empyema. All patients had extensive destruction of upper lobe tissue. Eight patients had undergone prior pulmonary resection; 3 had persistent infected spaces in the early postoperative period, 3 had development of empyemas and bronchopleural fistulas late (5 to 19 years) after pulmonary resection, and 2 had postpneumonectomy empyema. All patients had rigid cavity walls preventing space obliteration by rib removal alone and required concomitant resection of the thickened pleura and intercostal muscle tissues. Bronchopleural fistulas were present in 11 patients and were closed with adjacent nonintercostal muscle. All patients survived and had successful obliteration of the infected spaces with acceptable physiological and cosmetic results. We conclude that thoracoplasty remains a useful procedure in the management of the infected pleural space in select patients. 
4	Dynamic association between artery shear flow condition and platelet cytosolic free Ca2+ concentration in human hypertension. 1. Blood cells and vascular endothelial cells are subjected to a wide range of haemodynamically generated shear stress forces. In vitro, membrane stretching or shear stress have been observed to activate ion channels and cell metabolism and to facilitate erythrocyte and platelet aggregation. 2. The present study was designed to evaluate the participation of shear stresses in the control of apparent platelet cytosolic free Ca2+ concentration in hypertensive patients. 3. Shear conditions and platelet cytosolic free Ca2+ concentration in vitro were studied after a dynamic perturbation induced by 3 months of double-blind treatment with one of two beta-antagonists, carteolol and atenolol. Brachial artery wall shear rate and stress were estimated by means of a pulsed Doppler velocimeter, and blood viscosity was measured by a co-axial viscometer at a shear rate of 96 s-1. Platelet cytosolic free Ca2+ concentration was simultaneously measured by using the Quin-2 fluorescent chelator. The direct effect of atenolol and carteolol on platelet cytosolic free Ca2+ concentration in vitro was also measured after addition of the beta-blockers to platelet-rich plasma. 4. Atenolol and carteolol decreased blood pressure similarly but their effects on shear rate (P less than 0.02), shear stress (P less than 0.01) and platelet cytosolic free Ca2+ concentration (P less than 0.05) differed after 3 months of therapy. In contrast, neither of the drugs significantly altered platelet cytosolic free Ca2+ concentration, in vitro per se. 5. In the overall population, strong positive correlations existed not only between changes in platelet cytosolic free Ca2+ concentration and those in shear rate (r = 0.81, P less than 0.001) and shear stress (r = 0.83, P less than 0.001), but also between their absolute values, suggesting a possible haemodynamic shear-dependent modulation of transmembrane Ca2+ transport. 
2	Oxygen free radicals in acute pancreatitis of the rat. This study aimed to assess the role of oxygen free radicals in acute pancreatitis. Acute pancreatitis was induced in rats by infusion of the CCK-analogue cerulein (5 micrograms/kg per hour) for 30 minutes, 3.5 hours, and 12 hours. After the infusion, serum enzymes and conjugated tissue dienes and malondialdehyde were measured and tissue samples were subjected to electron and light microscopy. Electron microscopy after 30 minutes showed moderate intracellular alterations. After 3.5 hours of cerulein infusion interstitial oedema and intravascular margination of granulocytes in the pancreatic gland were seen. After 12 hours histological evaluation showed pronounced zymogen degranulation, extensive tissue necrosis, and migration of granulocytes into the tissue. Amylase and lipase activities increased 15 and 35-fold respectively during this time. After 30 minutes of cerulein infusion conjugated dienes and malondialdehyde increased, they reached their peak after 3.5 hours and decreased to normal values after 12 hours. Treatment with superoxide dismutase (100,000 U/kg/hour) and catalase (400,000 U/kg/hour) either before or after the start of the cerulein infusion prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue oedema and inflammatory response, however, were not affected in any of the treated rats. Oxygen free radicals are instrumental in the development of acute pancreatitis. Even after its onset, scavenger treatment reduced the tissue damage normally observed. 
5	Remodeling of the rat right and left ventricles in experimental hypertension. Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles. 
2	Anorectal dysfunction in patients with urologic disturbance due to multiple sclerosis. Anorectal function was evaluated in 11 patients with voiding dysfunction due to multiple sclerosis. In six patients with constipation, three also had symptoms of obstructed defecation and one patient was incontinent due to stercoral diarrhea. One patient was only fecal incontinent and one patient had obstructed defecation as the only symptom. Three patients had no anorectal symptoms. Anal manometry in the women compared with a control group revealed significant lower anal resting and squeeze pressures, although no significant difference of rectal sensation to distention with air was found. Pudendal nerve terminal latencies were obtained in seven patients and were all normal. In four patients latency could not be demonstrated due to poor contraction of the sphincter on stimulation of the pudendal nerve. Two of these patients were incontinent and two had both constipation and obstructed defecation. It is concluded that patients with voiding symptoms due to multiple sclerosis often reveal anorectal symptoms or motility disorders. Although anal sphincter function is reduced, fecal incontinence is not prevalent in this group. The reason for this lies probably in the fact that many of the patients are constipated, thus securing fecal continence. 
5	Idiopathic and symptomatic trigeminal pain. The trigeminal reflexes (corneal reflex, blink reflex, masseter inhibitory periods, jaw-jerk) and far field scalp potentials (nerve, root, brainstem, subcortical) evoked by percutaneous infraorbital stimulation were recorded in 30 patients with "idiopathic" trigeminal neuralgia (ITN) and 20 with "symptomatic" trigeminal pain (STP): seven postherpetic neuralgia, five multiple sclerosis, four tumour, two vascular malformation, one Tolosa-Hunt syndrome, and one traumatic fracture. All the patients with STP and two of those with ITN had trigeminal reflex abnormalities; 80% of patients with STP and 30% of those with ITN had evoked potential abnormalities. The results indicate that 1) trigeminal reflexes and evoked potentials are both useful in the examination of patients with trigeminal pain, and in cases secondary to specific pathologies provide 100% sensitivity; 2) in "symptomatic" and "idiopathic" paroxysmal pain the primary lesion affects the afferent fibres in the proximal portion of the root or the intrinsic portion in the pons; 3) primary sensory neurons of the A-beta fibre group are involved in both paroxysmal and constant pain, but in the latter the damage is far more severe. 
5	Follow-up of patients who underwent arterial switch repair for transposition of the great arteries Thirty infants underwent arterial switch for transposition of the great arteries within the first week of life (mean age, 2.8 days). An additional three patients underwent repair at 5 1/2, 8, and 9 1/2 months of age. Six (18.2%) of 33 patients died. All the survivors were not receiving cardiac medications or diuretics at the time of the last follow-up visit. Examination of 24 of 27 survivors at 1 to 5 years of age revealed normal growth in 75% of the patients. Two patients had height, weight, and head circumference below the fifth percentile for age. Four patients had height and weight appropriate for age but head circumference below the fifth percentile. Neurodevelopmental testing yielded normal findings in 18 patients. Three patients were considered suspect and an additional three were abnormal neurodevelopmentally. Head circumference less than the fifth percentile, abnormalities on computed tomographic scans of the brain, and emergency balloon atrial septostomy or emergency switch operation were more likely to occur in patients who had low neurodevelopmental scores. We conclude that the majority of patients who undergo arterial switch repair demonstrate normal growth and development and no impairment of cardiovascular function. However, significant morbidity in the form of neurodevelopmental problems may occur. 
5	Carcinoma of the head of the pancreas. Optimal treatment for unresectable carcinoma of the pancreas remains controversial. This study was done to examine the relationship between perioperative jaundice and postoperative morbidity, and type of palliative biliary bypass and postoperative morbidity and jaundice clearance. Seventy-six patients with obstructive jaundice secondary to carcinoma of the head of the pancreas were studied. Forty-nine patients underwent one of four different types of palliative bypass: 1, cholecystojejunostomy (n = 22); 2, choledochojejunostomy (n = 11); 3, choledochoduodenostomy (n = 9), and 4, cholecystoduodenostomy (n = 7). Age, sex and preoperative health status were similar for all operative groups, as well as for those with and without postoperative morbidity. The postoperative complication rate was 33 per cent and there was one postoperative death. Length of preoperative jaundice and peak preoperative bilirubin levels were independent of morbidity. Postoperative morbidity was similar for each type of bypass used and no significant difference was found when cholecystoenteric (1 and 4) and choledochoenteric (2 and 3) bypass were compared. The results of this study support the view that postoperative morbidity is not directly related to the presence of jaundice preoperatively. Furthermore, the rate of jaundice clearance and the occurrence of postoperative complications are not dependent on the type of bypass used. 
5	Nonsurgical management of breast infections in nonlactating women. A word of caution. Management options for infectious mastitis have traditionally been limited to surgical drainage. With the advent of percutaneous fine needle aspiration (FNA), nonoperative treatment may be an alternative, though criteria for use have not been defined. During a 30-month period, 22 women presented with breast infection. Treatment was instituted based upon the clinical stage of infection. Patients with cellulitis (n = 8) were managed with diagnostic FNA/antibiotics. Those with focal abscess (n = 10) underwent FNA of the cavity/antibiotics. Patients with multiloculated abscess (n C = 3) underwent urgent surgical drainage. Of the 19 patients initially treated nonoperatively, resolution occurred in nine (47%); stage of infection did not effect outcome. Surgical drainage was required in the remainder; two cancers were found. FNA cytology in these (and all) patients was negative for malignancy. All underwent mammography during treatment. In 17 (77%) cancer was considered of low probability. The only patient with a mammogram highly suspicious for cancer had fat necrosis on biopsy. Bacterial cultures were positive in 79 per cent, virtually all with Gram (+) cocci. Four patients harbored Gram (-) organisms as well, two in concert with breast cancer. Conclusions: 1) select breast infections can be successfully managed nonoperatively, 2) the accuracy of FNA and mammography in the diagnosis of breast cancer may be impaired by coincident infection, 3) the finding of a Gram (-) breast infection warrants abandonment of nonoperative management in favor of tissue confirmation of the disease process. 
3	An evaluation of a 30-gauge needle for spinal anaesthesia for caesarean section. A 30-gauge spinal needle was evaluated for Caesarean section, using a combined epidural/spinal technique, in 50 mothers. Spinal anaesthesia failed in six mothers and was inadequate in another six. General anaesthesia was required on one occasion. A 25% overall failure rate suggests that a 30-gauge needle is not a practical proposition for routine clinical practice. 
4	Effect of delayed captopril therapy on left ventricular mass and myonecrosis during acute coxsackievirus murine myocarditis. The effect of captopril on coxsackievirus B3 murine myocarditis was investigated. Thirty-two, 3-week-old mice were infected with coxsackievirus B3 on day 0 of the study, then randomized into a placebo group or a captopril group starting on day 3 of infection. On day 9 of infection, the mice were put to death. Hearts were weighed and processed for light microscopic examination. Heart weight was 125 +/- 19 mg in the control group versus 102 +/- 14 mg in the captopril group (p less than 0.0003). Amount of necrosis as a percentage of left ventricular section was 3.5% (2.0% to 7.5%) in the placebo group versus 2.0% (0.0% to 5.0%) in the captopril group (p less than 0.01). The amount of dystrophic calcification was 5.0% (0.0% to 27.5%) in the placebo group versus 1.3% (0.0% to 20.0%) in the captopril group (p less than 0.01). The extent of the histopathologic involvement by planimetry was 10.2% in the placebo group versus 5.4% in the captopril group (p = 0.052). We conclude that captopril is beneficial in decreasing left ventricular mass and the amount of myocardial necrosis and calcification in the short term in the murine myocarditis model. 
4	Renal manifestations of NaCl sensitivity in borderline hypertensive rats. Compared with the normotensive Wistar-Kyoto rat, the spontaneously hypertensive rat exhibits exaggerated alterations in renal sympathetic nerve activity and excretory function during volume expansion (exaggerated natriuresis) and environmental stress (antinatriuresis). The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat and develops hypertension with increased dietary NaCl intake. The present investigation sought to determine whether the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. Borderline hypertensive rats fed a 1% NaCl diet remained normotensive and exhibited renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress that were similar to those of their Wistar-Kyoto parent. Borderline hypertensive rats fed an 8% NaCl diet developed hypertension and exhibited responses that were similar to those of their spontaneously hypertensive parent. Thus, the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. The results suggest that increased dietary NaCl intake is able to induce or unmask the capabilities for these responses, which are genetically conveyed to the borderline hypertensive rat by the spontaneously hypertensive rat parent in latent forms. 
4	The use of PTFE graft to correct anomalous drainage of persistent left superior vena cava. A new technique to correct persistent left superior vena cava (LSVC) drainage into the left atrium is described in a 14-year-old patient with situs inversus, left atrial isomerism common atrium, and mitral valve regurgitation. During surgery, occlusion of the LSVC markedly increased the venous pressure, precluding its ligation. Because of the malposition of the heart and the unusual atrial anatomy, correction with an intra-atrial baffle was not attempted. After correcting the intra-cardiac anomaly, the LSVC was divided and anastomosed to the "right" atrial appendage using a segment of PTFE graft. The postoperative course was uneventful and an angiogram demonstrated excellent performance of the graft. 
5	Efficacy and safety of intravenous nicardipine in the control of postoperative hypertension. IV Nicardipine Study Group. In a double-blind, randomized, multicenter study, the efficacy and safety of intravenous (IV) nicardipine was compared with placebo in the control of postoperative hypertension in cardiac and noncardiac surgical patients. One hundred twenty-two patients (17 cardiac and 105 noncardiac surgery) met the entry criteria (systolic BP greater than or equal to 140 mm Hg or diastolic BP greater than or equal to 95 mm Hg) and were randomized (3:2) to receive IV nicardipine (n = 71) or placebo (n = 51). Therapeutic response (greater than or equal to 15 percent reduction in BP from baseline) was achieved in 94 percent of patients treated with IV nicardipine vs 12 percent with placebo (p less than 0.001). The mean response time and infusion rate for IV nicardipine were 11.5 (+/- 0.8) minutes and 12.8 (+/- 0.3) mg/h, respectively. The magnitude of BP reduction was similar in both cardiac and noncardiac postsurgical patients. Blood pressure control was sustained with minimal dose adjustments of IV nicardipine (3.0 +/- 0.2 mg/h) during a prolonged maintenance infusion period of 6.8 +/- 0.5 h. A reflex mean increase in heart rate of 5 bpm was seen in patients treated with IV nicardipine. Sixteen patients (15 noncardiac and one cardiac surgery) had a sustained heart rate of greater than 100 bpm, with a mean increase of 24 bpm from the baseline. In all these patients except three, tachycardia was resolved while receiving nicardipine. None of these patients who had development of tachycardia during nicardipine therapy had exhibited ST segment changes indicative of ischemia. One patient with tachycardia at baseline had exhibited ST segment depression (3 to 4 mm) during nicardipine treatment, which was resolved following discontinuation of nicardipine therapy and application of nitroglycerin (Nitropaste). Hemodynamic evaluation revealed that IV nicardipine significantly decreased mean arterial pressure, systemic vascular resistance, and significantly increased cardiac index with no change in heart rate. These hemodynamic changes were similar in cardiac and noncardiac surgical patients. Adverse experiences reported with IV nicardipine included hypotension (4.5 percent), tachycardia (2.7 percent), and nausea/vomiting (4.5 percent). In the placebo group, the incidence of adverse experience was 6 percent, with an equal distribution of hypotension (2 percent), nausea/vomiting (2 percent), and headache (2 percent). No clinically important changes in laboratory variables related to IV nicardipine were reported. In conclusion, these findings indicate that nicardipine, a titratable intravenous calcium channel blocker, can rapidly and effectively control postoperative hypertension in cardiac and noncardiac surgical patients. 
3	Speech, velopharyngeal function, and hearing before and after orthognathic surgery. Articulation, voice, resonance, hearing sensitivity, and middle ear function were examined in 34 patients before and 3, 6, 9, and 12 months after orthognathic surgery. Thirty of the 34 patients had articulation errors before surgery. Errors on the sibilants /s/ and /z/ occurred most frequently, followed by those on /j,zh,ch/ and /sh/. Errors were predominantly distortions with both visual and acoustic components. After surgery, articulation improved spontaneously in the absence of intervention. Most of the preoperative articulation errors were eliminated by 3 months postoperative, but, thereafter, a gradual decline was noted so that by 12 months, errors occurred on /s/ and /z/. Voice, resonance, velopharyngeal port area, and hearing sensitivity were not altered by surgery. This study suggests that severe skeletal malocclusions requiring surgical correction have deleterious effects on the patients' articulation of consonants and that surgical alteration leads to the correction of most of these errors. 
5	Doppler assessment of pulmonary artery pressure and extrapulmonary shunting in the acute phase of hyaline membrane disease. The natural history of pulmonary artery pressure and extrapulmonary shunting in acute hyaline membrane disease was studied by serial Doppler echocardiography in 57 preterm infants, 38 with, and 19 without, hyaline membrane disease. Pulmonary artery pressure was assessed non-invasively by its inverse relationship with the ratio of pulmonary artery Doppler time to peak velocity: right ventricular ejection time. The mean ratio was significantly lower in the infants with hyaline membrane disease. The mean ratio for each infant with hyaline membrane disease varied widely and did not correlate with criteria of maturity or severity of disease. Individual ratios correlated with arterial pH. Between 60-80 hours after birth, 14 of 18 infants with hyaline membrane disease (78%) and one of 19 without (5%) had patent ductus arteriosus. Left to right and bidirectional shunting at ductal and atrial level were common; pure right to left shunting was uncommon. The mean ratio seen with bidirectional shunting was significantly lower than that seen with left to right shunting. Ratios and patterns of extra pulmonary shunting were similar when the fractional inspired oxygen (FIO2) was greater than 0.9 compared with when it was less than 0.9. Pulmonary artery pressure is high during the acute phase of hyaline membrane disease but varies widely among infants. A few infants have extrapulmonary right to left shunting, and these infants are difficult to detect clinically. 
2	An epidemic outbreak of cryptosporidiosis: a prospective community study from Guinea Bissau. In the first year of a prospective community study of childhood diarrhea conducted in a semiurban area in the capital of Guinea Bissau, Cryptosporidium sp. was found in 73 (6.0%) of 1216 episodes of diarrhea. The parasite was the second most prevalent intestinal parasite, and the only one significantly associated with diarrhea (OR = 2.79, P = 0.0006). The seasonal distribution was striking, with a peak prevalence in the beginning of the rainy season (May 17.6%) when an epidemic outbreak of diarrhea started. The prevalence was highest in children younger than 18 months, an age at which prevalences of other intestinal parasites were low. This reverse age pattern may possibly be explained by the small infective dose needed to create severe infections, by air-borne transmission and by the development of protective immunity. 
4	Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: a new marker of triple-vessel disease. To investigate the significance and mechanism of dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging, we performed both dipyridamole thallium-201 imaging and dipyridamole radionuclide angiography on 83 patients with known angiograms. The dipyridamole/delayed ratio of the left ventricular dimension from the thallium-201 image was defined as the left ventricular dilatation ratio (LVDR). An LVDR greater than the mean + two standard deviations in patients without coronary artery disease was defined as abnormal. Twenty-two of 83 patients showed an abnormal LVDR, and 18 of the 22 patients (82%) had triple-vessel disease. By defect and washout analysis, the sensitivity and specificity for correctly identifying the patients as having triple-vessel disease was 72% and 76%, respectively, whereas LVDR had a sensitivity of 72% and a specificity of 93%. When LVDR was used in combination with the defect and washout criteria, sensitivity increased to 84% without a loss of specificity. In those 22 patients with abnormal LVDRs, end-diastolic volume measured by radionuclide angiography did not change after dipyridamole infusion. Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging reflected relative subendocardial hypoperfusion induced by dipyridamole rather than actual chamber enlargement. The LVDR was moderately sensitive and highly specific for triple-vessel disease and provided complementary information to dipyridamole thallium-201 imaging. 
5	Synthesis of 70K stress protein by human leukocytes: effect of exercise in the heat. To determine whether reinduction of 70,000-Da (70K) stress protein synthesis could be used as an assay for thermal history and/or cellular levels of 70K stress protein in hyperthermic humans, leukocytes were obtained before and after 2 h of exercise and then incubated at 37 or 41 degrees C. Five healthy males completed 2 h of treadmill exercise consisting of running at 4-6 km/h for 30-45 min followed by 75-90 min of walking up a 2-10% grade. This exercise bout was performed by two subjects in hot (46 degrees C, 15% relative humidity) and by five subjects in cooler (30 degrees C, 40% relative humidity) environmental conditions. Exercise resulting in rectal temperature (Tre) less than 40 degrees C did not alter the amount of 70K stress protein synthesized by leukocytes incubated at 41 degrees C. In contrast, exercise resulting in Tre greater than 40 degrees C reduced the amount of 70K stress protein synthesized by leukocytes incubated at 41 degrees C. A protein immunoblot, probed with an antibody specific for the inducible 72K stress protein, showed that the reduction of 35S-labeled 70K stress protein in these postexercise leukocyte samples occurred without marked elevations of this protein. In vitro incubation of human leukocytes at 40 degrees C for 15-120 min reduced, in a time-dependent manner, the amount of 70K stress protein synthesized during a subsequent 41 degrees C heat stress. This reduction of 70K stress protein synthesis in 41 degrees C-treated leukocytes was abolished when cycloheximide was present during the 40 degrees C preincubation. 
5	Mechanisms of edema formation in experimental autoimmune encephalomyelitis. The contribution of inflammatory cells. Most of the central nervous system (CNS) endothelium regulates the passage of solutes and functions as a blood-brain barrier (BBB). During experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the CNS, loss of BBB function occurs. The authors have previously shown an increase in endothelial transcytotic activity associated with decreased mitochondrial content as evidence of BBB dysfunction in EAE. These changes occurred in the capillary bed and correlated with CNS edema and clinical signs. In the present report, a fixation procedure before infusion of the intravascular tracer horseradish peroxidase (HRP) in rats at the height of clinical EAE has been used. In these animals, tracer leakage was only noted in inflamed venules with diameters of 12 to 19 mu. The authors detected several mechanisms of passive leakage: 1) increased junctional permeability; 2) increased interendothelial space; 3) leakage alongside migrating inflammatory cells. Some small capillaries showed necrotic changes with minimal tracer leakage. This report demonstrates that BBB disruption also occurs via nonendocytic mechanisms that may be induced by inflammatory cells. 
4	Percutaneous popliteal approach for angioplasty of superficial femoral artery occlusions. Angioplasty using the percutaneous popliteal approach was utilized in 50 patients (PTS) to recanalize 59 occluded superficial femoral arteries which had been unsuccessfully canalized by using the antegrade approach because of either a flush origin occlusion or inability to maintain the guide wire in the true lumen. All PTS had claudication; 8 had rest pain; 3 had non-healing ulcers. The laser Probe was used in 17 cases and the Rotablator in 3 cases. Occlusion length varied between 1 and 40 cm: 7 lesions were less than 10 cm (group 1); 9 were between 10 and 20 cm (group 2); and 43 were greater than 20 cm (group 3). An angiographic success was obtained in 48/59 lesions (81%): 14/16 (87%) in groups 1 and 2 and 34/43 (79%) in group 3. Three PTS needed complementary common femoral endarterectomy and one required percutaneous aspiration of a thromboembolus. Complications included: arterial perforation and/or dissection (without clinical sequelae) in 11 and a popliteal hematoma in 1 PT. One patient with a severely ischemic leg underwent successful emergency vascular surgery, while another limb salvage patient required below-knee amputation. There was no worsening of limb ischemia from any popliteal approach attempt. At discharge, 39 patients (78%) whose outcome would have been unsuccessful with the traditional antegrade approach were clinically improved after utilizing the popliteal approach to achieve a successful angioplasty procedure. 
1	A population-based study of functional status and social support networks of elderly patients newly diagnosed with cancer. We assessed the functional status and social support networks of 799 men and women aged 65 years or older newly diagnosed with cancer and living in six New Mexico counties. Functional limitations included depending on others for transportation (33%) and mental incompetence or poor recent memory (42%). The percentage of patients with functional limitation increased sharply with increasing age. In a substantial number of patients there was also evidence for poor social support networks; 26.5% of subjects lived alone and 38.9% had no children living in the vicinity. In a multiple logistic regression analysis, the predictors of having a poor social support network included non-Hispanic white ethnicity, advanced age, low income, and being a recent migrant to the area. Subjects with functional limitations were more likely to have poor social support networks than subjects without such limitations. The deleterious combination of impaired functional status and a limited social support network may explain why elderly cancer patients are at increased risk for not receiving appropriate therapy. Given the potential complexities involving the evaluation and appropriate treatment of cancer, care must be taken to adequately assess functional status and support mechanisms of older patients, and to provide adequate support to ensure compliance with treatment. 
5	Late results with Carpentier-Edwards porcine bioprosthesis. From 1977 to 1984, 429 patients underwent aortic valve replacement (AVR), and 339 underwent mitral valve replacement (MVR) with a Carpentier-Edwards bioprosthesis. Early mortality for AVR was 4.6% (isolated AVR, 1.9%) and for MVR was 5.3% (isolated MVR, 4.1%). Follow-up was 99.3% complete at a mean of 5.9 years. Actuarial event-free rates at 10 years for AVR and MVR were, respectively, 1) for structural valve deterioration, 91.4 +/- 3.2% versus 75.1 +/- 4.0% (p less than 0.01); 2) for nonstructural dysfunction, 100% versus 97.8 +/- 1.6% (p = NS); 3) for thromboembolism, 90.6 +/- 2.3% versus 87.3 +/- 2.6% (p = NS); 4) for anticoagulant-related bleeding, 95.3 +/- 1.1% versus 88.6 +/- 2.4% (p = 0.05); 5) for endocarditis, 87.8 +/- 5.7% versus 90.6 +/- 2.4% (p = NS); 6) for reoperation, 91.0 +/- 2.5% versus 74.4 +/- 3.7% (p less than 0.01); 7) for valve-related mortality, 76.1 +/- 6.9% versus 71.4 +/- 5.2% (p = 0.01); 8) for permanent physical impairment, 85.0 +/- 3.0% versus 71.5 +/- 3.6% (p less than 0.01); and 9) for combined operative mortality, valve-related mortality, and reoperation, 68.7 +/- 6.4% versus 51.5 +/- 4.9% (p = 0.01). No structural valve dysfunction was observed in any AVR patient whose valve was inserted after age 70. Age at operation was the only factor that predicted structural valve deterioration (p less than 0.01). 
5	Steroid hormone abnormalities in women with severe idiopathic constipation. Patients with severe idiopathic constipation are almost exclusively women of reproductive age. To investigate the possibility of a sex hormone abnormality in this condition, we have compared a range of sex hormones during the follicular and luteal phases of the menstrual cycle in 23 healthy women (mean age 33 years) with those in 26 patients with severe idiopathic constipation (mean age 32 years, spontaneous bowel frequency less than one per week). In the patients there was a reduction in the follicular phase of progesterone (4.5 v 4 nmol/l, p = 0.006, median value, controls v patients), 17 hydroxyprogesterone (9.7 v 5.8 nmol/l, p = 0.01), cortisol (387 v 245 nmol/l, p = 0.008), testosterone (2.3 v 1.8 nmol/l, p less than 0.001), androstenedione (10.3 v 8.4 nmol/l, p = 0.02), and dehydroepiandrosterone sulphate (5.1 v 3.0 mumol/l, p = 0.03). In the luteal phase there was a reduction of oestradiol (483 v 350 pmol/l, p = 0.015), cortisol (322 v 242 nmol/l, p = 0.047), and testosterone (2.4 v 1.7 nmol/l, p = 0.003). The concentrations of sex hormone binding globulin, prolactin, luteinising hormone, and follicle stimulating hormone were not significantly different in either phase of the cycle. Women with severe idiopathic constipation have a consistent reduction in steroid hormones. 
2	Hepatitis B vaccination and interleukin 2 receptor expression in chronic renal failure. Only 50 to 60% of dialysis patients develop anti-HBs antibodies following hepatitis B vaccination. The nonresponder state correlates with impaired monocyte function, decreased interleukin-2 (IL-2) production of T cells, and an upregulation of the IL-2 receptor system. In the present study we examined anti-HBs production after hepatitis B vaccination and the in vitro expression of IL-2 receptors in nondialyzed patients with various degrees of chronic renal failure. Forty-four patients with impaired renal function were immunized with 2 micrograms recombinant hepatitis B vaccine and boostered after one and six months. Prior to the first injection IL-2 receptor expression of activated T cells was studied by an in vitro proliferation assay. Sixty-four healthy subjects served as controls. After completion of the third vaccination 55.0% of the patients acquired antibody titers greater than 10 U/liter. The seroconversion rate did not differ between patients with lower (less than 3.5 mg/dl) and higher (greater than 3.5 mg/dl) creatinine levels. In nonresponders IL-2 receptor expression (stimulation index, SI = 10.09 +/- 1.80) was elevated compared to healthy controls (SI = 4.62 +/- 0.35, P less than 0.002) or patients who responded with a high antibody titer (greater than 50 U/liter, SI = 3.12 +/- 0.43, P less than 0.001). Patients who produced low antibody titers (less than 50 U/liter) also presented with enhanced IL-2 receptor expression. These data show that an impaired antibody production following hepatitis B vaccination and an enhanced IL-2 receptor expression of T cells may already be present in early stages of chronic renal failure. 
5	Pregnancy-induced hypertension and acute fatty liver of pregnancy: atypical presentations. Severe pregnancy-induced hypertension and markedly elevated levels of serum alkaline phosphatase developed in a 29-year-old-woman in whom one pregnancy resulted in intrauterine death. Acute fatty liver of pregnancy developed with good fetal outcome in the next pregnancy. This case suggests that pregnancy-induced hypertension and acute fatty liver of pregnancy are part of a clinical spectrum. Moreover, classic abnormalities of liver function tests need not be present in acute fatty liver of pregnancy. 
1	Are three substages of clinical B prostate carcinoma useful in predicting disease-free survival? The B1 nodule, a 1.5 cm area of induration surrounded on at least two sides by prostatic tissue of normal consistency, was defined by Jewett in 1968 as the stage of prostatic cancer best suited for treatment and cure by radical prostatectomy (RP). The area of prostatic induration suitable for RP was subsequently extended to less than one lobe (Stage B1); this extension of induration was supported by the study of Walsh and Jewett in 1980 showing a 51 percent survival free-of-disease at fifteen-year follow-up. Subsequently, clinical staging systems evolved which substaged clinical B into three categories of induration: B1N = less than 1.5 cm nodule, B1 = greater than 1.5 cm but less than one lobe, and B2 = one lobe or both lobes. To determine if digital assessment of these progressively greater degrees of induration would translate into different intervals to first progression, whether local or distant, we reviewed prostate diagrams and descriptions of all Stage B patients treated by Iodine-125 interstitial implant and external beam radiation therapy between 1974 and 1985 at our institution. Forty-six patients had B1 nodules, 78 patients B1 (less than one lobe), and 52 patients B2 (one lobe or greater). Mean follow-up was fifty-five months. We found B1N, which was also associated with well-differentiated grade and a normal acid phosphatase, to have the longest interval to progression. 
4	A successful treatment of an intrarenal arteriovenous fistula by percutaneous embolization. A 37-year-old woman patient, known to have poorly controlled arterial hypertension that was diagnosed following a cerebrovascular accident at the age of 15 years, was referred to our outpatient clinic for investigation in 1987. An intrarenal arteriovenous fistula was diagnosed by selective renal angiography. Embolization of the fistula was performed using four 15-mm/5-cm coils, which induced thrombosis and obstructed the fistula. The vascularization of the affected kidney improved immediately. During the following 4 months, the antihypertensive treatment was stopped gradually, and the patient remained normotensive. This is an unusual case of a large intrarenal arteriovenous fistula, whose etiology was not clear, that was successfully treated by percutaneous embolization. 
2	Abdominal wall pain: an alternative diagnosis. The cause of abdominal pain need not necessarily reside in the viscera; the abdominal wall is another source of symptoms. Some causes of abdominal wall pain are obvious, e.g. hernias, but not so others such as nerve entrapment syndromes. This review is concerned with causes of abdominal wall pain which, although common, may be easily overlooked. 
5	Interferon alfa therapy in patients with chronic hepatitis B virus infection. Effects on hepatitis B virus DNA in the liver. Pretrial and posttrial liver biopsy samples from 124 adult patients who participated in two randomized, controlled trials of interferon alfa therapy for chronic hepatitis B virus (HBV) infection were analyzed to determine the effects of interferon on the replication of HBV in the liver. Replicative forms of HBV DNA were detected in the pretrial biopsy samples from all and posttrial biopsy samples from 74% treated patients and 86% controls. Replicative forms of HBV DNA were detected in the posttrial biopsy samples from all patients who remained positive for hepatitis B e antigen and HBV DNA in the serum, in 77% treated patients and 80% controls who cleared HBV DNA in the serum but who remained positive for hepatitis B e antigen, but in only 19% treated patients and 40% controls who cleared HBV DNA as well as hepatitis B e antigen in the serum. Serum alanine aminotransferase levels were significantly lower in patients whose posttrial biopsies did not contain replicative forms of HBV DNA. In summary, we demonstrated that in most patients with chronic HBV infection treated with interferon alfa, serological response was associated with the disappearance of replicative forms of HBV DNA in the liver. 
5	Intravenous but not intracolonic epidermal growth factor maintains colonocyte proliferation in defunctioned rat colorectum. The role of epidermal growth factor in the proliferation of normal and premalignant colonocytes in vivo is not fully understood. In particular, the relative importance of its possible systemic and intraluminal routes of action has not been fully clarified. Rats with surgically defunctioned distal colorectums were used, and mini osmotic pumps were implanted to study the effects of intraluminal and IV administration of epidermal growth factor on colonocyte proliferation. Within 2 weeks of bypass, colonocyte proliferation in defunctioned colorectum has decreased to about one third the rate in normal colorectum or in colorectum proximal to the defunctioning colostomy. Intraluminal epidermal growth factor, infused from the time of operation did not reverse this hypoplasia, whereas IV epidermal growth factor maintained colonocyte proliferation at approximately the normal rate in bypassed colorectum. This model is suitable for testing other putative colonic mitogens for possible intraluminal and systemic effects. 
5	Management of recurrent malignant pleural effusion in the United Kingdom: survey of clinical practice. Malignant pleural effusions are often symptomatic and tend to recur after simple aspiration. Pleurodesis may prevent recurrence of the effusion; many agents and techniques have been described. A questionnaire was sent to 448 clinicians in the United Kingdom to determine how pleurodesis is performed in practice. There was a 56% overall response, with replies from 101 respiratory physicians, 88 general physicians, 29 thoracic surgeons, and 35 general surgeons. General surgeons saw few cases of malignant pleural effusion and rarely performed pleurodesis. A patient with recurrent malignant pleural effusion would usually be managed with pleurodesis by 76 (76%) respiratory physicians, 26 (30%) general physicians, and 23 (81%) thoracic surgeons; a further 29 (33%) general physicians would refer such patients to another specialist. Most medical pleurodesis were performed by junior staff, whereas consultant thoracic surgeons were more likely to be concerned with the procedure. All the thoracic surgeons used an intercostal tube drain, usually with suction. An intercostal tube drain was used routinely by only 54 (54%) of the respiratory physicians and 28 (32%) general physicians. Thoracic surgeons preferred talc for pleurodesis whereas physicians most commonly used tetracycline. The variety of methods in use supports the need for randomised, controlled studies to determine the most effective technique of pleurodesis. 
1	Substance-P is present in a subset of thyrotrophs in the human pituitary. Substance-P immunoreactivity and tachykinin-like peptides are present in the pituitary gland of several mammalian species. In humans, however, the biochemical nature and cellular localization of pituitary substance-P has not been defined. We report here that substance-P-immunoreactive material is present in low concentrations in both the anterior and posterior lobes of the human pituitary gland. Gel chromatography and reverse phase high performance liquid chromatography indicate that the majority of the substance-P immunoreactivity in human pituitaries elutes as authentic substance-P and its oxidized derivative. Immunohistochemical studies showed substance-P-immunoreactive fibers and terminals in the posterior pituitary gland and occasional substance-P-immunoreactive cell bodies in the anterior lobe. The substance-P-immunoreactive cells were found to colocalize with a small subpopulation of TSH beta-immunoreactive cells (thyrotrophs). Substance-P immunoreactivity was also found in a pituitary microadenoma that contained numerous TSH beta-immunoreactive cells. These studies indicate that substance-P is present in the human pituitary gland, and they suggest a relationship between substance-P and thyroid function. 
4	Noninvasive estimation of left atrial pressure in patients with congestive heart failure and mitral regurgitation by Doppler echocardiography. A completely noninvasive method for estimating left atrial pressure in patients with congestive heart failure and mitral regurgitation has been devised with the use of continuous-wave Doppler echocardiography and brachial sphygmomanometry. Of 46 patients studied with mitral regurgitation, 35 (76%) had jets with distinct Doppler spectral envelopes recorded. The peak ventriculoatrial gradient was obtained by measuring peak mitral regurgitant velocity in systole and using the modified Bernoulli equation. This gradient was then subtracted from peak brachial systolic blood pressure, an estimate of left ventricular systolic pressure, to yield left atrial pressure (left atrial pressure = systolic blood pressure - mitral regurgitant pressure gradient). Noninvasive estimates of left atrial pressure from 35 patients were plotted against simultaneous recordings of mean pulmonary capillary wedge pressure resulting in the correlation y = 0.88x + 3.3, r = 0.88, standard error of estimate = +/- 4 mm Hg (p less than 0.001). Therefore, continuous-wave Doppler echocardiography and sphygmomanometry may be used in selected patients with congestive heart failure and mitral regurgitation for noninvasive estimation of left atrial pressure. 
1	Breast cancer screening: who should be included? The recommendations of the U.S. Preventive Services Task Force are reviewed in regard to screening for breast cancer. In contradistinction to those issued by some other national organizations, screening for breast cancer using mammography at ages 40-49 is not recommended. It is concluded that the scientific evidence is insufficient at present to recommend mammography screening for women aged 40-49. The recommendations of the task force are: all women over age 40 should receive an annual breast examination; all women should have mammography every one or two years beginning at age 50 and concluding at approximately age 75 unless disease has been detected; and it may be prudent to begin mammography at an earlier age for women at high risk of breast cancer. These recommendations are appropriate in light of the available evidence; though at present there is no evidence that clinical examination of the breasts at any age reduces breast cancer mortality; the upper age beyond which breast cancer screening no longer has a significant effect in reducing breast cancer mortality is unknown; and there is no evidence that women at high risk for breast cancer benefit to a different degree from screening than women not at high risk. 
5	Ichthyosis, mental retardation, and asymptomatic spasticity. A new neurocutaneous syndrome with normal fatty alcohol:NAD+ oxidoreductase activity. A number of inherited disorders of cornification have been related to abnormal lipid metabolism. In the recessively inherited Sjogren-Larsson syndrome, defined by the triad of ichthyosis, mental retardation, and spasticity, fatty alcohol:NAD+ oxidoreductase deficiency has recently been reported. These patients accumulate fatty alcohol in the plasma and cultured fibroblasts. A 19-year-old woman with ichthyosis, mental retardation, and mild spasticity is described in whom fatty alcohol metabolism was normal, as determined by plasma octadecanol level and fibroblast fatty alcohol:NAD+ oxidoreductase activity. Ultrastructural studies on skin from the patient revealed morphologically abnormal epidermal lamellar bodies, not unlike those seen in neutral lipid storage disease with ichthyosis. We postulate that this patient has a novel neurocutaneous syndrome that may be secondary to abnormal lipid metabolism. 
2	Clinical experience with biliary extracorporeal shock wave lithotripsy. Biliary lithotripsy is a new and important development in the nonsurgical management of gallbladder, cystic duct, and bile duct stones. Most patients do not require general or epidural anesthesia with newer second-generation machines. Patient selection and the use of adjuvant therapy to aid fragment clearance are important issues that are discussed. Results from different centers are compared but few long-term results are yet available, i.e., longer than 18 months. 
5	Internal mammary artery and saphenous vein graft patency. Effects of aspirin. As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD. 
4	Death at cardiac catheterization: coronary artery embolization of calcium debris from Ionescu-Shiley bioprosthesis. The case described is a death due to embolization of calcium debris from a bioprosthesis, dislodged at cardiac catheterization. As more bioprosthetic valves are implanted, and more of them fail long-term with calcification, such complications of the invasive study of these valves may be expected. 
1	Insulinomas: localization with selective intraarterial injection of calcium. To facilitate the noninvasive preoperative localization of islet cell tumors less than 15 mm in diameter, the authors examined the use of calcium as an insulin secretagogue in an arterial stimulation venous sampling (ASVS) technique. In four patients with episodic hypoglycemia, calcium gluconate (0.01-0.025 mEq Ca2+/kg) was injected directly into branches of the celiac plexus (gastroduodenal, splenic, and hepatic arteries) and the superior mesenteric artery. In all patients, serum levels of insulin rose abruptly in blood samples taken from the right hepatic vein 30 and 60 seconds after the infusion of calcium into the artery supplying the tumor; injection into an artery not supplying the tumor did not result in a similar rise. Accurate localization of the insulinomas was verified at surgery in three patients. In the fourth patient, who did not undergo surgery, arteriographic results were positive for insulinoma at the predicted site. On the basis of these results, the authors believe noninvasive ASVS may replace invasive portal venous sampling as the most effective method for the localization of occult insulinomas. 
3	EEG correlation of improvement in hemolytic-uremic syndrome after plasma infusion. We report a previously undescribed electroencephalographic pattern of epochs of diffuse delta background (85-240 sec) alternating with epochs of classic "burst suppression" (90-270 sec) in a 13-month-old girl with hemolytic-uremic syndrome. A dramatic electroencephalographic improvement was evident on continuous monitoring of cerebral function 3 hours after initiating fresh frozen plasma infusion, well before any clinical improvement was apparent. This patient, in addition to the unusual electroencephalographic findings, illustrates the role of continuous electrophysiologic monitoring of cerebral function and supports the use of fresh frozen plasma in hemolytic-uremic syndrome. 
5	Cluster headache: the effect of low oxygen saturation The present study concerns the possible relationship between hypoxia and the generation of cluster headache attacks. Fifteen controls and 25 cluster headache patients were studied. The patients were allocated into two groups according to cluster headache stage, i.e. cluster or remission period. During the tests, all the subjects were asked to inhale 12% oxygen (88% N2) for 30 min, and the decreasing oxygen saturation (SaO2%) was monitored. Patients in the remission period showed nearly the same decrement of SaO2% as controls. At the end of the test, patients in the bout showed significantly less reduction of SaO2% than the controls. In 5 patients, the test was carried out both in and outside the cluster periods. The tendency to less decrement in oxygen saturation in the cluster phase was as marked with this comparison, but the difference between the groups was not significant, probably partly due to the low number of tests carried out. Only one patient got a typical attack. It seems that hypoxia of this magnitude per se is not the cause of attacks. The different pattern with respect to SaO2% following 12% O2 inhalation in cluster headache may be due to an abnormality in central regulation and/or chemoreceptor sensitivity. 
5	Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group OBJECTIVE: To evaluate a single cycle of adjuvant chemotherapy compared with longer duration chemotherapy for premenopausal women or chemoendocrine therapy for postmenopausal women with operable breast cancer using a quality-of-life-oriented end point, Q-TWiST (quality-adjusted analysis of TWiST: Time Without Symptoms and Toxicity). DESIGN: Multicenter randomized clinical trial--International Breast Cancer Study Group (IBCSG: formerly Ludwig Group) Trial V. SETTING: IBCSG participating centers in Sweden, Switzerland, Australia, Yugoslavia, Spain, New Zealand, Italy, Germany, and South Africa. PATIENTS: Data were available for 1229 eligible patients with node-positive breast cancer who were randomized to receive one of three adjuvant treatments after at least a total mastectomy and axillary clearance. INTERVENTIONS: Patients received either a single cycle of perioperative chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and leucovorin; or six cycles (6 months) of a conventionally timed chemotherapy consisting of cyclophosphamide, methotrexate, fluorouracil, and prednisone for premenopausal women or this combination plus tamoxifen for postmenopausal women; or both perioperative and conventionally timed chemotherapy for a 7-month course of adjuvant therapy. RESULTS: At 5 years of median follow-up, patients who received the longer duration therapies had an improved 5-year disease-free survival percentage (53% compared with 36%; P less than 0.001) and 5-year overall survival percentage (73% compared with 63%; P = 0.001) compared with those who received the single perioperative cycle alone. By 3.5 years, the greater burden of toxic effects associated with the longer duration treatments was balanced by their superior control of disease. Within 5 years of follow-up, even after subtracting time with adjuvant treatment toxicity, patients gained an average of 2.2 months of Q-TWiST if treated with the longer duration therapies compared with the single cycle (P = 0.03). The gain for premenopausal patients was 2.8 months (P = 0.05), whereas the gain for postmenopausal women was 1.5 months (P greater than 0.2). CONCLUSIONS: Six or seven months of adjuvant chemotherapy or chemoendocrine therapy improve both the quantity and quality of life for patients with node-positive breast cancer compared with a single short course of perioperative combination chemotherapy. 
4	Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography [corrected and republished with original paging, article originally printed in J Am Coll Cardiol 1990 Oct;16(4):862-70] Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis. 
1	Vascular abnormalities in epidermal nevus syndrome. We report a patient with epidermal nevus syndrome and right hemispheric infarct and review 3 others with neurologic manifestations best explained by ischemia or hemorrhage. Each had a significant vascular abnormality such as occlusion or blood vessel dysplasia. None had hemimegalencephaly. We hypothesize that underlying vascular dysplasia is the cause of the neurologic lesions in these patients. 
5	Catecholaminergic systems in the medulla oblongata in parkinsonian syndromes: a quantitative immunohistochemical study in Parkinson's disease, progressive supranuclear palsy, and striatonigral degeneration. We investigated tyrosine-hydroxylase (TH)-immunoreactive neurons in the medulla oblongata corresponding to the A1 and A2 cell groups in autopsy tissue of patients with Parkinson's disease (PD) (n = 3), progressive supranuclear palsy (PSP) (n = 3), striatonigral degeneration (SND) (n = 2), and in controls (n = 4). The estimated total number of TH-positive neurons in the A1 and the A2 regions was normal in PD and PSP patients. The sparing of medullary catecholaminergic cells in PD and PSP may be related to their minor degree of melanization and the possibility that intermediate compounds associated with the oxidative catabolism of norepinephrine and epinephrine may be less cytotoxic than those generated by degradation of dopamine. Patients with SND showed a marked loss of TH-immunoreactive cells in the A1 and the A2 groups, which may contribute to the impairment of vasomotor control characteristic of the disease. 
1	Percutaneous urinary diversion in patients with hormone-refractory prostate cancer. Twenty-two patients with hormone-refractory prostate cancer underwent percutaneous urinary diversion; at the time, all but one had metastatic disease. Eleven patients received postnephrostomy therapy. The median survival time for all the patients was one hundred nineteen days. Overall, 41 percent of the patients' remaining lifetime was spent in the hospital. Six never left the hospital and 10 required rehospitalization; the remaining 6 patients were never rehospitalized. The median survival time for this group of patients was shorter than the expected survival of similar patients without ureteral obstruction. It appears that percutaneous urinary diversion does not improve the quality of life of these patients. 
4	Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography: a statement by a task force committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology. Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase. 
5	Hemorrhoids. A practical approach to an aggravating problem. Although hemorrhoids are considered a minor medical problem, they may cause considerable discomfort and anxiety. Fortunately, treatment is often simple and surgery is rarely necessary. In this practical article, Dr Cocchiara describes internal and external hemorrhoids, a classification system, and treatment choices based on the degree of involvement. 
4	Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = -0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure. 
3	Obstructive sleep apnoea in children undergoing routine tonsillectomy and adenoidectomy. Sleep screening was used to discover the incidence of sleep apnoea in 50 children undergoing routine adenotonsillectomy for recurrent upper respiratory tract infections, randomly selected from the waiting list. Preoperative assessment included a detailed parental history, physical examination, and lateral cephalometry, in order to identify factors that might alert the clinician to a diagnosis of obstructive sleep apnoea. There were 2 equal groups of snorers and non-snorers (grade 0); 1 patient was found to have the sleep apnoea syndrome (IV), 9 patients had obstructive snoring with apnoeic episodes (III), 3 patients had snoring with a disrupted sleep pattern (II), and 12 patients snored with no disruption of sleep (I). In identifying patients with apnoea, a history of snoring was unhelpful, whereas one of breathing irregularities was found to be highly specific. Nasal obstruction correlated poorly; however, there was a significant relationship between tonsillar position and size and sleep grade (Chi-squared P less than 0.01). Stepwise regression analysis showed a large contribution to the grading was made by the size of the oropharyngeal airway measured by lateral cephalometry. The children in grade II-IV were re-studied 3 months post-operatively and all reverted to grades 0 or I. 
3	Fulminating multiple sclerosis-like leukoencephalopathy revealing human immunodeficiency virus infection. A 66-year-old French homosexual man and a 42-year-old Brazilian man with no known risk factors for HIV infection developed headaches, asthenia, and neurologic episodes of abrupt onset. CT showed multiple hypodense, nonenhancing lesions. Serology for HIV was positive. They died respectively 2 months and 1 month after onset of the illnesses. Autopsy in both cases showed multiple, well-demarcated, demyelinating foci in the white matter of the cerebral hemispheres, brainstem, and cerebellum with histologic features characteristic of recent plaques of multiple sclerosis. There were no multinucleated giant cells or microglial nodules. Immunostaining for HIV was negative. Although a random coincidence of MS and HIV infection cannot be ruled out, the close temporal relationship between the 2 disorders suggests a possible etiologic association. 
5	Clinical outcome of emergency repeat coronary artery bypass surgery. To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time. 
3	Cholinergic deficiency and frontal dysfunction in Parkinson's disease. To investigate the influence of central cholinergic deficit on cognitive function in Parkinson's disease (PD), we compared the neuropsychological performance of a group of 20 patients who were treated with anticholinergic drugs (mean daily dose, 10.2 mg) with that of a group of 20 patients who received no anticholinergics. The two groups were matched for all the variables of parkinsonism and levodopa therapy. At the dose used, there was no significant difference between the two groups of patients for intellectual, visuospatial, instrumental, and memory function. In contrast, in the group that received anticholinergics severe impairment was observed on tests believed to assess frontal lobe function. These results suggest that the lesion of the ascending cholinergic neurons, which has been demonstrated post mortem in PD, may play a role in the subcorticofrontal behavioral impairment of this disease. 
5	Orbital inflammatory disease associated with systemic lupus erythematosus. Orbital inflammatory disease in a patient with systemic lupus erythematosus is rare and presents a diagnostic dilemma as well as a therapeutic challenge. Ours appears to be the sixth such case reported in the literature. 
1	Differential effects of the stimulation of complement receptors CR1 (CD35) and CR2 (CD21) on cell proliferation and intracellular Ca2+ mobilization of chronic lymphocytic leukemia B cells. The regulatory role of CR1 and CR2 on B cell activation and proliferation has been investigated by using B cells from patients with chronic lymphocytic leukemia. The chronic lymphocytic leukemia B cells are clonal expansions of B lymphocytes frozen at specific stages of activation. They displayed two patterns of response upon surface Ig (sIg) cross-linking in terms of in vitro proliferation and intracellular free Ca2+ mobilization: cells from patient F (first pattern) proliferated in the presence of mitogenic anti-mu antibodies, whereas cells from patient A (second pattern) did not respond to sIg cross-linking but proliferated in the presence of low m.w. B cell growth factor and IL-2. Coculture of A or F cells with C3b-bearing SRBC led to a two- to four-fold increase in thymidine incorporation in cultures containing low m.w. B cell growth factor but not in cultures containing rIL-2. This enhanced proliferation was inhibited by F(ab')2 polyclonal rabbit antihuman CR1 antibodies. Only cells which proliferated in the presence of anti-mu (cells F) responded to cross-linking of sIg with a rise in intracellular Ca2+. No increase in calcium mobilization was observed after co-cross-linking of CR1 and sIg on A and F cells with mAb or polyclonal anti-CR1 antibodies. Co-cross-linking of CR2 with sIg only led to an enhanced intracellular Ca2+ rise in F cells but not in A cells. The lack of CR2-mediated synergy in Ca2+ rise in A cells indicates that the synergy occurs only if there is a proper coupling of sIg to phospholipase C. CR1-induced proliferation of B cells does not involve the signaling pathways of sIg. These results provide additional evidences for the role of C3 fragments in modulation of human B cell activation. 
2	Pylorus preserving pancreatoduodenectomy: an overview. Pylorus preserving pancreatoduodenectomy (PPPD) was reintroduced 12 years ago. Since that time, over 400 patients have undergone PPPD with approximately 41 per cent having chronic pancreatitis and 54 per cent having pancreatic and other periampullary malignancies. Reported 5-year survivals in this latter group have been comparable to those achieved by the classic Whipple procedure. The postoperative mortality rate in 339 reported patients has been 3.8 per cent. Postoperative morbidity, including delayed gastric emptying, has been similar to that of the classic Whipple operation. However, PPPD has been associated with fewer late problems with dumping, diarrhoea, delayed gastric emptying (8.6 per cent), and marginal ulceration (3.6 per cent). Moreover, most patients undergoing PPPD have been able to return to their preoperative and preillness weight. The additional advantage of decreased operative time makes PPPD an attractive alternative to the classic pancreatoduodenectomy. 
4	Gastric outlet obstruction caused by traumatic pseudoaneurysm of superior mesenteric artery. Traumatic pseudoaneurysms of the superior mesenteric artery (SMA) are extremely rare. We describe two cases of posttraumatic proximal SMA pseudoaneurysms with symptoms of gastric outlet obstruction. Repair was accomplished by aorta-SMA bypass with saphenous vein. Injuries to the proximal SMA are easily missed at laparotomy, especially if intestinal ischemia or hematomas are absent. Recognition and repair are stressed to avoid the complications associated with pseudoaneurysm formation. 
4	Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy The acute hemodynamic effects of captopril were evaluated at cardiac catheterization in 16 children (age, 0.3-18 years) with cardiomyopathy. Twelve children had congestive cardiomyopathy, whereas four had restrictive cardiomyopathy. Hemodynamic measurements were obtained 30 and 60 minutes after the oral administration of captopril (0.5 mg/kg). Blood pressures were measured in the aorta, pulmonary artery, right atrium, and pulmonary capillary wedge position; cardiac outputs were measured by the thermodilution technique. Hemodynamic data could not be obtained after the administration of captopril in one child with congestive cardiomyopathy because of an immediate, severe hypotensive response. In 11 of 12 children with congestive cardiomyopathy, cardiac index increased by 22%, from 2.3 to 2.8 l/min/m2 (p less than 0.05), and stroke volume increased by 22%, from 23 to 28 ml/m2 (p less than 0.05). Systemic vascular resistance decreased from 32 to 21 units.m2 (p less than 0.01), but the mean aortic pressure did not change significantly. In contrast, four children with restrictive cardiomyopathy had no change in cardiac output after captopril, but there was a trend toward significant arterial hypotension (mean aortic pressure decreased from 78 to 59 mm Hg). Thus, captopril acutely reduced systemic vascular resistance and increased both cardiac output and stroke volume in children with congestive cardiomyopathy. In children with restrictive cardiomyopathy, however, captopril did not affect cardiac output, but it did decrease aortic pressure. These data indicate that captopril may benefit children with a congestive cardiomyopathy but that captopril probably should not be used in children with restrictive disease. 
1	Basal cell carcinoma arising in pemphigus vulgaris of the lower eyelid. A 59-year-old woman on continuous treatment with corticosteroids and immunosuppressive drugs for pemphigus vulgaris of 14 year's duration presented with an enlarging nodular lesion on the right lower eyelid. The neoplasm, diagnosed as basal cell carcinoma, was excised conserving the lid margin, and eyelid reconstruction was done with a rotated cheek flap. Wound healing proceeded without complications in spite of immunosuppressive treatment, and the final cosmetic and functional result was satisfactory. 
3	Liver failure occurring as a component of exertional heatstroke. An unusual case of an exertional heatstroke in a healthy 25-year-old man is presented. Initially, the patient was deeply comatose and developed severe rhabdomyolysis and massive hepatic necrosis. Subsequently, he received a liver transplant with remarkable improvement in his mental status, although the rhabdomyolysis continued. The patient died 41 days after the transplant due to a complicating infection. Providing that infections can be effectively controlled, liver transplants might be a promising therapeutic alternative for the few patients who survive the initial neurological consequences of this unusual event. 
4	Determinants of carotid intima-media thickness: a population-based ultrasonography study in eastern Finnish men. We investigated the determinants of maximal intima-media thickness of common carotid arteries in a population-based sample of 1224 Eastern Finnish men aged 42, 48, 54 or 60 years. A high-resolution B-mode ultrasonographic examination was performed as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). The maximal intima-media thickness (IMT) varied between 0.48 mm and 4.09 mm (mean value +/- SD, 0.94 mm +/- 0.38 mm). Age (standardized partial coefficient, beta = 0.238, P less than 0.0001), ambulatory pulse pressure (beta = 0.130, P less than 0.0001), cigarette-years of smoking (beta = 0.125, P less than 0.0001), serum LDL cholesterol concentration (beta = 0.125, P less than 0.0001), history of ischaemic heart disease (beta = 0.125, P less than 0.0001), pre-exercise systolic blood pressure (beta = 0.070, P = 0.0113) and diabetes (beta = 0.068, P = 0.0072) were most strongly associated with IMT. This study confirms the role of systolic blood pressure, smoking and serum LDL cholesterol levels as major risk factors for increased carotid intima-media thickness. 
4	The normal mediastinum in blunt traumatic rupture of the thoracic aorta and brachiocephalic arteries. In a review of 52 articles, published between 1953 and 1989, 656 patients with blunt traumatic rupture of the thoracic aorta or brachiocephalic arteries were identified. Of these, 608 (92.7%) had an abnormal mediastinum on initial chest radiographs obtained in the emergency department, thus allowing early detection of the vascular injury. Unfortunately, 48 (7.3%) of these patients had a normal mediastinum on their initial chest radiographs. This appears to occur when the traumatic pseudoaneurysm is not accompanied by associated mediastinal hemorrhage or hematoma formation, and the pseudoaneurysm is either small or is situated in such a way that it does not alter the mediastinal contour. The use of accessory clinical and radiographic signs to indicate the need for aortography has been shown to be of very low yield, but would have allowed the early detection of an additional 5.6% of the reported cases. Performing aortography solely on the basis of a history of major decelerating blunt trauma to the thorax remains the only way, in the acute emergency department setting, to detect the 1.7% of patients with aortic or brachiocephalic arterial rupture who have no mediastinal abnormality or accessory clinical or radiographic signs of vascular injury. There is evidence from the literature, however, to suggest that the evaluation of serial chest radiographs obtained at close intervals for the first month following trauma for the development of mediastinal abnormality or large hemothorax is an acceptable alternative to the routine performance of aortography in those blunt chest trauma victims with no clinical or radiographic suspicion of vascular injury. 
5	Antithrombotic efficacy of continuous extradural analgesia after knee replacement. We have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty. Forty-eight patients were allocated randomly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days. All patients wore compressive elastic stockings and no anticoagulant drugs were administered. Bilateral venography was performed 10 days after surgery. Continuous extradural analgesia did not impede mobilization of the patients. One case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia. The use of continuous extradural analgesia resulted in a significant difference in the total incidence of deep vein thrombosis (18% compared with 59% after general anaesthesia (P = 0.02]. The incidence of calf vein thrombosis was 12% compared with 45% after general anaesthesia (P = 0.05). 
1	In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Cloned integrin alpha 2 subunit complementary DNA was expressed on human rhabdomyosarcoma (RD) cells to give a functional VLA-2 (alpha 2 beta 1) adhesion receptor. The VLA-2-positive RDA2 cells not only showed increased adhesion to collagen and laminin in vitro, but also formed substantially more metastatic tumor colonies in nude mice after either intravenous or subcutaneous injection. These results show that a specific adhesion receptor (VLA-2) can markedly enhance both experimental and spontaneous metastasis. In contrast to the metastasis results, there was no difference in either the in vitro growth rate or apparent in vivo tumorigenicity of RD and RDA2 cells. 
1	Palliative operations for colorectal cancer. A review of 96 consecutive patients who underwent palliative surgery for primary colorectal cancer was undertaken to clarify the value of palliation achieved with surgical treatment. The overall rate of postoperative mortality was 8 percent (8 of 96) and the overall rate of postoperative morbidity was 24 percent (23 of 96). The mortality rate was 5 percent (3 of 66) after resective surgery and 17 percent (5 of 30) after nonresective surgery. Three deaths were related to the malignant disease, three were related to the intra-abdominal infection, and two were related to formation of intestinocutaneous fistulas. Of the 8 patients who died, 1 had a tumor with local visceral involvement only and 7 had a tumor with more distant spread. Median survival was 10 months for all patients, 15 months for patients treated with resective surgery, and 7 months for nonresected patients. Five patients (5 percent) have survived for longer than 5 years. The median relief of preoperative cancer symptoms was 4 months (4 months after resective surgery and 1 month after nonresective surgery). Twenty-five patients have undergone second surgery. It is concluded that palliative resective surgery for colorectal cancer can improve patient comfort with an acceptable postoperative mortality rate when cancer growth is localized and in favorable cases with more distant spread, whereas nonresective surgery fails to achieve symptom relief. 
1	Adult T-cell leukemia/lymphoma of the tongue. A case of posterior tongue lymphoma associated with adult T-cell leukemia (ATL) that occurred as a lesion in the lingual dorsal portion is reported in a 64-year-old woman. Initially, a diagnosis of Hodgkin's lymphoma was considered as no findings associated with ATL except lymphadenopathy and serum anti-ATLA antibodies were present. Combined radiotherapy and chemotherapy were administered with favorable results; however, 4 months later, Pneumocystis carinii pneumonia developed, and 2 months later, generalized lymphadenopathy and hypercalcemia evolved. At this time, a diagnosis of ATL was made. The patient died of renal dysfunction 6 months after the initial presentation. In suspected cases of ATL and malignant diseases of T-cell lineage, namely, malignant lymphoma and mycosis fungoides, the presence of HTLV-1 infection should be confirmed by testing for anti-ATLA antibodies. 
4	Coronary balloon angioplasty through diagnostic 6 French catheters. We investigated the use of ultralow profile balloon catheters (Scimed ACE, USCI Probe, Cordis, Orion) for coronary angioplasty through 6 French diagnostic catheters (Schneider, Cordis). Contrast injection was assisted with a Hercules pump (Cordis) in all cases. During 21 procedures, angioplasty of 27 lesions in 20 selected patients was attempted (1.3 lesion/procedure). Twelve lesions were in the right, 10 in the left anterior descending, and 5 in the left circumflex coronary artery. Balloon size varied between 2.5 and 3.5 mm. Twenty lesions could be successfully dilated (74%) through the 6 French catheter and 7 lesions required an exchange to a 7 French angioplasty guiding catheter. For 5 cases, another balloon was also necessary to complete the procedure. The final overall success rate was 100% per patient and per lesion and there were no major complications. Despite the small internal catheter lumen (1.22 mm) coronary visualization was adequate, and mechanical support was good. Failures of 6 French catheters were attributed to insufficient torque control and excessive friction when the balloon crossed the tapered end of the diagnostic catheter. Coronary angioplasty through a diagnostic 6 French catheter is feasible and may represent a reasonable alternative for simple cases that are done during the same session as the diagnostic angiography. Once available, 6 French high flow angioplasty guiding catheters without a tapered tip should improve success while retaining the advantage of a small femoral puncture site. 
1	Biology of basal cell carcinoma (Part II). Host-tumor relationships involve several factors that can enhance or suppress neoplastic growth. This second part of a review of basal cell carcinoma biology examines the role that hormones, cytokines, local and systemic immunity, congenital and genetic syndromes, and environmental factors play in the development of this neoplasm. Theories of etiology and pathogenesis are discussed, and transplantation and cell culture techniques used to study this cancer are explored. Valuable second-line therapies for treatment of multiple tumors are reviewed, and important areas of present and future research are emphasized. 
1	Dietary fat and risk of breast cancer. The relationship between dietary fat and subsequent risk of breast cancer was studied in 3988 initially cancer-free Finnish women aged 20-69 y. During a follow-up period of 20 y, 54 breast-cancer cases were diagnosed. Risk of breast cancer was significantly inversely related to energy intake and nonsignificantly inversely related to absolute fat intake. A positive association between energy-adjusted total fat intake and occurrence of breast cancer was also observed. The relative risk in the highest tertile as compared with the lowest tertile was 1.7 (95% confidence limits 0.6-4.8). The corresponding relative risks were 1.4 (0.5-3.7) for saturated fatty acids, 2.7 (1.0-7.4) for monounsaturated fatty acids, 1.2 (0.6-2.8) for polyunsaturated fatty acids, and 2.2 (1.0-5.0) for cholesterol intake. Adjustment for different potential confounding factors did not alter the results. The present data suggest that breast cancer is associated inversely with energy intake and weakly positively with energy-adjusted fat intake. 
1	Bronchoalveolar carcinoma: factors affecting survival. One hundred thirty-four consecutive patients (65 men and 69 women) underwent pulmonary resection for bronchoalveolar carcinoma. Mean age was 65 years. Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and wedge excision in 19. Only 10 patients had lymph node metastases (7.5%). The neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in stage II, 9 were in stage IIIa, and 1 was in stage IIIb. There were two operative deaths (1.5%). Thirty-nine complications occurred in 31 patients. Median follow-up was 5.1 years. Recurrent bronchoalveolar carcinoma developed in 45 patients. Five- and 10-year survival for patients in stage I was 75.2% and 62.0%, respectively. Survival for patients with T1 N0 M0 neoplasms was identical to expected survival and was 90.5% at 5 years, as compared with 55.4% for patients with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease, and 0.0% for patients with bilateral disease (p less than 0.0001). Other significant factors adversely affecting survival included the presence of signs and symptoms, diffuse malignant invasion, mucin-producing tumors, and the histological absence of scar. We conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases. Early aggressive pulmonary resection is safe and offers the potential for cure. The presence of bilateral cancer, however, is ominous. 
1	Pneumocystis carinii pneumonia complicating multiple myeloma. Pneumocystis carinii pneumonia complicated the course of two patients with multiple myeloma. The diagnosis was established in both cases by bronchoalveolar lavage, which demonstrated the typical pneumocysts. Clinical and roentgenographic improvement in both patients was observed following a course of trimethoprim-sulfamethoxazole. One patient had lymphocyte subsets performed with a CD4/CD8 ratio of 0.8; both patients were HIV antibody-negative by ELISA. Both patients tolerated prophylactic TMP-SMX given concurrently with the subsequent chemotherapy for myeloma. We suggest that the immune defect seen in multiple myeloma may have placed these patients at risk for opportunistic infections such as P carinii pneumonia; however, as opposed to patients with AIDS, our patients tolerated therapy with TMP-SMZ quite well. 
3	Induction, blockade and restoration of a persistent hypersensitive state. A new model of chronic hypersensitivity was developed in the rat by daily intraplantar administration of either prostaglandin E2 dopamine or isoprenaline, for a period of 2 weeks. Like other hyperalgesic mediators, dibutyryl-cAMP, when applied to the paws, caused an acute effect but did not produce persistent hypersensitivity. The persistent hypersensitive state was not affected by a typical non-steroidal anti-inflammatory drug (indomethacin), was temporarily inhibited by a centrally acting analgesic (morphine), was partially inhibited by a protein synthesis inhibitor (cycloheximide) and abolished by a single dose of peripherally acting analgesics such as dipyrone or N-methyl morphine. Once the residual hypersensitivity had been abolished with dipyrone or N-methyl morphine, a small dose of prostaglandin E2, dopamine or Interleukin-1 beta, which in normal animals causes a mild and short lived effect, restored the persistent hypersensitive state. This ability to restore the persistent effect was not observed with intraplantar administration of dibutyryl-cAMP. Our results suggest the existence of a peripheral trace of inflammatory pain, a phenomenon which may be associated with stimulation of neuronal adenylate cyclase and protein synthesis. This concept may explain part of the puzzle of chronic inflammatory pain and lead to the development of new analgesics. 
4	Distinguishable types of dyspnea in patients with shortness of breath. Dyspnea frequently accompanies a variety of cardiopulmonary abnormalities. Although dyspnea is often considered a single sensation, alternatively it may encompass multiple sensations that are not well explained by a single physiologic mechanism. To investigate whether breathlessness experienced by patients represents more than one sensation, we studied 53 patients with one of the following seven conditions: pulmonary vascular disease, neuromuscular and chest wall disease, congestive heart failure, pregnancy, interstitial lung disease, asthma, and chronic obstructive pulmonary disease. Patients were asked to choose descriptions of their sensation(s) of breathlessness from a dyspnea questionnaire listing 19 descriptors. Cluster analysis was used to identify natural groupings among the chosen descriptors. We found that patients could distinguish different sensations of breathlessness. In addition, we found an association between certain groups of descriptors and specific conditions producing dyspnea. These findings concur with those in an earlier study in normal volunteers in whom dyspnea was induced by various stimuli. We conclude that different types of dyspnea exist in patients with a variety of cardiopulmonary abnormalities. Furthermore, different mechanisms may mediate these various sensations. 
4	New operative method for distal aortopulmonary septal defect. A new technique is described for repairing distal aortopulmonary septal defect with aortic origin of the right pulmonary artery in a 26-day-old neonate. To prevent the narrowing of the proximal right pulmonary artery in the distal aortopulmonary septal defect caused by conventional intraluminal prosthetic patch reconstruction, rerouting of the right pulmonary artery using native aortic wall tissue without artificial material was performed. This method seems to be superior to the conventional method, especially during the neonatal period. 
1	When epilepsy masquerades as heart disease. Awareness is key to avoiding misdiagnosis. Autonomic neural impulses that accompany discharges during a seizure can cause a variety of cardiac manifestations, including cardiac arrhythmias, sudden death, anginal chest pain, neurogenic pulmonary edema, and symptoms of pheochromocytoma. Either generalized or focal seizures may generate such signs and symptoms. A better appreciation of cardiac problems caused by epilepsy is helpful in preventing misdiagnosis, because the clinical picture in such a patient may be confusing. 
5	China White epidemic: an eastern United States emergency department experience. STUDY OBJECTIVE: The purpose of this study was to isolate significant clinical or demographic findings concerning overdose patients treated during a China White (3-methyl fentanyl) epidemic and compare them with data for all unintentional narcotic overdose patients during a 24-month period. DESIGN: We reviewed charts from 85,246 patient visits to our emergency department during the 24-month period of January 1987 through December 1988 to study this narcotic epidemic. Data from the Allegheny County Coroner's Office pertaining to unintentional drug overdose deaths that occurred during this same period also were reviewed. SETTING: The first outbreak of narcotic overdoses in the eastern United States involving China White occurred in Allegheny County, Pennsylvania, in 1988. TYPE OF PARTICIPANTS: Patients were included if they met the criteria of a suspected unintentional narcotic overdose, but excluded if they were not given naloxone. INTERVENTIONS: Emergency physicians became suspicious of China White use after an unusual increase in narcotic overdoses presenting to the ED coupled with "routine drug of abuse" screens negative for opiates despite dramatic patient responses to naloxone. In most of the cases in which specific testing was done, there were positive indicators of fentanyl derivatives. Investigations found China White present in street drugs and paraphernalia. MEASUREMENTS AND MAIN RESULTS: A cluster was defined as a time period with a statistically significant increase in overdoses over the expected number for an interval of equal length. Although there were no significant clinical differences in case presentation during the 24-month period, there was a statistically significant 13-fold increase in overdoses during the September through November 1988 cluster (mean, 13 vs 0.95 per month, P less than .001 by Wilcoxon rank-sum test). A dramatic increase in unintentional drug overdose deaths occurred in the county during this cluster. A total of 18 fentanyl-positive unintentional drug overdose deaths, predominantly male (89%) and black (56%), with an age range of 19 to 44 years (mean, 34.9 years), were reported by the county coroner (13 during the cluster). Narcotic overdoses and unintentional drug overdose deaths declined sharply with confiscation of a clandestine China White laboratory. CONCLUSIONS: China White was responsible for a dramatic rise in unintentional drug overdose deaths in Allegheny County in 1988. There were no significant clinical differences between China White overdose survivors and other unintentional narcotic overdose victims. Overdoses responsive to naloxone with inconsistent routine toxicologic screens may be due to a fentanyl analogue. 
2	Norwalk virus genome cloning and characterization. Major epidemic outbreaks of acute gastroenteritis result from infections with Norwalk or Norwalk-like viruses. Virus purified from stool specimens of volunteers experimentally infected with Norwalk virus was used to construct recombinant complementary DNA (cDNA) and derive clones representing most of the viral genome. The specificity of the clones was shown by their hybridization with post- (but not pre-) infection stool samples from volunteers infected with Norwalk virus and with purified Norwalk virus. A correlation was observed between the appearance of hybridization signals in stool samples and clinical symptoms of acute gastroenteritis in volunteers. Hybridization assays between overlapping clones, restriction enzyme analyses, and partial nucleotide sequence information of the clones indicated that Norwalk virus contains a single-stranded RNA genome of positive sense, with a polyadenylated tail at the 3' end and a size of at least 7.5 kilobases. A consensus amino acid sequence motif typical of viral RNA-dependent RNA polymerases was identified in one of the Norwalk virus clones. The availability of Norwalk-specific cDNA and the new sequence information of the viral genome should permit the development of sensitive diagnostic assays and studies of the molecular biology of the virus. 
2	"Mini-perforation" of the colon--not all postpolypectomy perforations require laparotomy. In a 10-year experience with 4,784 consecutive colonoscopic polypectomies, the need for operative intervention in just two of seven perforations indicates that patients with specially defined, limited perforations can usually be treated nonoperatively. This specific complication, which has been termed "mini-perforation," is generally detected within 6-24 hours of polypectomy, and is characterized by local pain and tenderness, without signs of diffuse or spreading peritoneal irritation. Free intra-abdominal or retroperitoneal air on x-ray documents the actual perforation. Complete resolution of symptoms within 24-48 hours confirms the diagnosis of "mini-perforation." Success depends on good bowel preparation for colonoscopy, and early recognition of perforation, with institution of bowel rest and intravenous antibiotics. The "mini-perforation" spontaneously closes, probably by omental adherence. Frequent serial clinical examinations are mandatory so that frank perforation with advancing peritonitis will be promptly recognized and treated surgically. An understanding of the three levels of cautery injury to the colon wall--"serosal burn," "mini-perforation," and "frank perforation" are essential in managing the complications of colonoscopic polypectomy. 
4	Clinical results of femoropopliteal bypass using externally supported (EXS) Dacron grafts: with a comparison of above- and below-knee anastomosis. As of the end of September 1989, 52 EXS Dacron grafts had been implanted for femoropopliteal bypass operations. The distal ends of 27 grafts were anastomosed to above-knee popliteal arteries and those of 25 grafts to below-knee popliteal arteries. The cumulative patency rate of above-knee grafts was 71.3% at 54 months, and that of below-knee grafts was 78.8% at 48 months (n.s.). Kinking and stenosis of the arteriosclerotic proximal and/or mid popliteal artery when the knee was bent were angiographically remarkable. These changes may explain why some femoropopliteal grafts occlude with time and why the late results of above-knee grafts are not much better than those of below-knee grafts. 
5	High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment. 
1	Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors. The combination of carboplatin, etoposide, and bleomycin (CEB) was evaluated as initial chemotherapy in 76 patients with good-prognosis metastatic nonseminomatous germ cell tumors (NSGCT) between 1984 and 1988. The classification of eligible patients included Royal Marsden Hospital (RMH) stages IM, IIA, IIB, IIC, IIIA, IIIB, IV0ABCL1, and IV0ABL2. Four courses of combination chemotherapy were administered in a 21-day cycle, and surgical excision of residual mass was performed in 27 cases (23 laparotomies and four thoracotomies). At the time of analysis, median follow-up was 24 months from start of chemotherapy (range, 6 to 54 months). The 2-year cause-specific survival probability was 98.5%, the single cause-related mortality being caused by bleomycin pneumonitis. Five patients failed CEB chemotherapy, but all have been successfully salvaged with a combination of surgery and intensive chemotherapy, follow-up from completion of all treatment being 35 to 44 months. The toxicity of CEB included bone marrow suppression and alopecia in all patients but no significant neurotoxicity or ototoxicity, and minimal renal toxicity. Only four (5%) patients had a decrease in the glomerular filtration rate greater than 15%. In 51% of patients, the hemoglobin fell below 10 g/dL. The WBC count nadir was less than 1,500/microL in 11% of treatment cycles and in 16% the platelet nadir fell below 50,000/microL. Decreases in the WBC and platelet counts were of very brief duration. Only one of 310 CEB cycles was complicated by neutropenic sepsis, and there were no episodes of thrombocytopenic purpura or bleeding. We conclude that the CEB combination represents an effective alternative to cisplatin-based chemotherapy in good-prognosis NSGCT and that the replacement of cisplatin by carboplatin leads to reduced toxicity. 
5	Dissection of the aorta associated with congenital malformation of the aortic valve. The association of congenital aortic valve malformation and aortic dissection is analyzed. Over a 30 year period, 186 patients with non-iatrogenic aortic dissection were studied at necropsy. The aortic valve was tricuspid in 170 (91.4%), bicuspid in 14 (7.5%) and unicuspid in 2 (1.1%). Among the 16 patients with aortic dissection and a congenitally malformed valve, the age at death ranged from 17 to 82 years (mean 52) and 13 (81%) were men. The entrance tear of the aortic dissection was located in the ascending aorta in all 16 patients with a malformed valve but in only 68% of those with a tricuspid aortic valve. The aortic valve was stenotic in 6 of the 16 patients with a congenitally malformed valve. Fatal rupture of the false channel occurred after acute ascending aortic dissection in each of the 11 patients (none with healed dissection) who did not have operative therapy for the dissection. Two of the 16 patients with a malformed valve compared with no patient with a tricuspid aortic valve had aortic isthmic coarctation. Histologic sections of aorta from 10 patients disclosed severe degeneration of the elastic fibers of the media in 9 patients. Thus, a congenitally malformed aortic valve appears to be present at least 5 times more frequently in adults with than in those without aortic dissection, and in our patients the entrance tear was always in the ascending aorta, which usually had severe loss of elastic fibers in its media. 
2	Bleeding ectatic vascular lesion involving the sigmoid colon, endoscopically indistinguishable from angiodysplasia, in an 8-yr-old boy. An 8-yr-old Japanese boy was hospitalized, complaining of active hematochezia. He was shown to have a cherry-red, blood-oozing area of vascular dilation with mucosal prominence in the sigmoid colon by endoscopy, but had no other mucocutaneous vascular abnormalities. A family history was noncontributory. Under the clinical diagnosis of angiodysplasia of the sigmoid colon, he underwent an elliptical resection of the part, based on the intraoperative endoscopic findings. However, histological examination of the surgical specimen revealed a totally different picture from that seen in angiodysplasia: the thin-walled, markedly ectatic, nontortuous veins with hemorrhage were seen only just below the muscularis mucosae, around which the normal ones were shown to coexist. He has had no rebleeding for the past 3 yr. This lesion is considered to be an isolated congenital visceral telangiectasia involving veins. 
1	Serial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy. We prospectively performed magnetic resonance imaging (MRI) studies during the neonatal period, and at 4 and 8 months of age, on 15 term infants with hypoxic-ischemic encephalopathy, and compared the results with their neurodevelopmental outcome at 18 months of age. Cerebral palsy developed in nine infants, two infants were classified as having abnormalities of tone and delayed motor milestones that were suggestive of cerebral palsy, and four infants were normal. Structural abnormalities, delayed myelination, or a combination of the two were detected with MRI at 8 months of age in all nine infants with later development of cerebral palsy. Three of the four normal infants and one infant with suggestive abnormalities had normal serial MRI findings. Each of the remaining two infants (one normal, one with suggestive abnormalities) had isolated persistent ventricular dilation on all three MRI studies. Our results suggest that 8 months appears to be the earliest time at which MRI findings correlate well with later adverse neurodevelopmental outcome in this population. 
3	The efficacy of brainstem auditory evoked potentials in acoustic tumor surgery. As the identification of patients with small acoustic neuromas and salvageable hearing increases, intraoperative auditory nerve monitoring has been used increasingly in an attempt to improve the hearing preservation rate. Far-field recordings obtained by brainstem auditory evoked potentials (BAEP), at times enhanced by electrocochleography, have become a standard method of intraoperative auditory nerve assessment. To evaluate the usefulness of this monitoring technique, the hearing preservation results of a series of unmonitored acoustic tumor removals were compared to a series of patients monitored via the standard brainstem auditory evoked potentials. With comparable average tumor sizes, 4 of 7 unmonitored patients had hearing preserved at preoperative levels compared to 4 of 9 monitored patients. Neither preoperative BAEP assessments nor absolute tumor size were predictive of hearing preservation. This report brings into question the effectiveness of far-field intraoperative BAEP monitoring during acoustic tumor resection and suggests that direct auditory nerve monitoring may be more appropriate. 
2	Interferon alfa therapy in patients with chronic hepatitis B virus infection. Effects on hepatitis B virus DNA in the liver. Pretrial and posttrial liver biopsy samples from 124 adult patients who participated in two randomized, controlled trials of interferon alfa therapy for chronic hepatitis B virus (HBV) infection were analyzed to determine the effects of interferon on the replication of HBV in the liver. Replicative forms of HBV DNA were detected in the pretrial biopsy samples from all and posttrial biopsy samples from 74% treated patients and 86% controls. Replicative forms of HBV DNA were detected in the posttrial biopsy samples from all patients who remained positive for hepatitis B e antigen and HBV DNA in the serum, in 77% treated patients and 80% controls who cleared HBV DNA in the serum but who remained positive for hepatitis B e antigen, but in only 19% treated patients and 40% controls who cleared HBV DNA as well as hepatitis B e antigen in the serum. Serum alanine aminotransferase levels were significantly lower in patients whose posttrial biopsies did not contain replicative forms of HBV DNA. In summary, we demonstrated that in most patients with chronic HBV infection treated with interferon alfa, serological response was associated with the disappearance of replicative forms of HBV DNA in the liver. 
5	Evidence for motor neuropathy and reduced filling of the rectum in chronic intractable constipation. Subtotal colectomy with ileorectal anastomosis is now frequently offered to patients with slow transit constipation who have severe symptoms and no response to more conventional medical treatment. If this operation is to be successful, the underlying problem should be delay in the progress of contents through the colon but no mechanical or functional obstruction in the small bowel or rectum. We have used a recently described technique of prolonged ambulant manometry and electromyography to investigate anorectal function in these patients. Pressure data were collected using a 2 mm diameter intrarectal probe carrying microtransducers, and external anal sphincter activity was assessed by a pair of silver-silver chloride surface electrodes. Fourteen control subjects and eight patients with colonic inertia were studied. Sampling reflexes, indicative of rectal filling, occurred at mean (SEM) rates of 7.4 (2.0)/hour in controls but were significantly reduced in patients (2.4 (0.3)/hour (p less than 0.01]. Recurrent rectal motor complexes were seen to occur in both groups at intervals of 76 (1.8) minutes in controls and 64.9 (7.2) minutes in patients (p less than 0.1), and with amplitudes of 42.4 (2.1) mmHg and 9.2 (0.7) mmHg (p less than 0.001), respectively. External sphincter electromyographic spike activity did not differ between groups. Our results support the concept of reduced transit of faeces to the rectum from the colon over a 24 hour period in slow transit constipation and suggest that a motor neuropathy may also be present in the rectum. 
5	Periapical lesions of mandibular bone: difficulties in early diagnostics. It is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease. In this paper these problems are discussed, and some suggestions are made to overcome them. The discussion is based on cases of osteogenic sarcoma, histiocytic lymphoma, and chronic osteomyelitis. The patients were a boy and two middle-aged women, all of them with primary clinical symptoms of pain and swelling, diffuse roentgenologic changes in mandibular bone, uncertain response to treatment, and an unusual progress of the disease. 
2	Laparoscopic cholecystectomy. With more than 500,000 cholecystectomies performed per year, great interest has developed in laparoscopic cholecystectomy. The procedure offers the patient reduced hospital stay, faster return to work, less pain, and improved cosmetic results. In September 1988, we developed a technique of performing laparoscopic cholecystectomy that we have now performed in more than 800 cases with good results. The technique allows the surgeon to fully evaluate the common duct via operative cholangiography and has allowed us to use a laparoscopic approach in all patients who were candidates for cholecystectomy. The technique offers a minimally invasive alternative to open cholecystectomy. 
5	Maternal serum screening for aneuploid pregnancy by alpha-fetoprotein, hCG, and unconjugated estriol. A number of serum screening protocols are either currently in use or proposed to identify pregnant women under 35 years of age who are at increased risk for a Down syndrome fetus. It has been suggested that these same screening methods be applied to gravidas over 35 years of age to identify those women who should be offered amniocentesis. To evaluate the efficacy of screening for detection of aneuploid pregnancy in this age group, the serum samples of 34 women who underwent amniocentesis and who had confirmed fetal aneuploidy were assayed for alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3). These concentrations were compared with those of 85 women with known euploid pregnancy who underwent amniocentesis for advanced maternal age. The mean multiple of the median (MoM) for each of the three markers was significantly different from control values in cases of trisomy 21 (AFP median MoM = 0.82; unconjugated E3 median MoM = 0.77; and hCG median MoM = 1.89). These differences were not found when other aneuploidies were considered. Likelihood ratios were calculated for cases and controls and examined for their ability to predict the need for amniocentesis, based on currently recommended risk levels. There was a significant difference between the mean likelihood ratio for cases of trisomy 21 compared with that of controls (mean likelihood ratio = 13.48); there was no significant difference for other aneuploidies (mean likelihood ratio = 1.08). Of the 16 cases of trisomy 21 analyzed, four would not have been diagnosed antenatally if recommendation against amniocentesis had been made based on each woman's individual age-specific risk as modified by her likelihood ratio. 
1	Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer: prostate specific antigen is superior to all other clinical parameters. Presently, the standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers and a radionuclide bone scan. To evaluate the ability of local clinical stage, tumor grade, serum acid phosphatase, serum prostatic acid phosphatase (PAP) and serum prostate specific antigen (PSA) to predict bone scan findings, a retrospective review of 521 randomly chosen patients (mean age 70 years, range 44 to 92 years) with newly diagnosed, untreated prostate cancer was performed. Local clinical stage, tumor grade, acid phosphatase, PAP and PSA all correlated positively with bone scan findings (p less than 0.0001). Using receiver operating characteristic curves, however, PSA had the best over-all correlation with bone scan results. The median serum PSA concentration in patients with a positive bone scan was 158.0 ng./ml., whereas men with a negative bone scan had a median serum PSA level of 11.3 ng./ml. (p less than 0.0001). Using multivariate logistic regression analysis, local clinical stage, tumor grade, acid phosphatase and PAP were evaluated in combination with PSA to assess whether these parameters increased the ability of PSA alone to predict bone scan findings. None of these clinical parameters, irrespective of the combination used, contributed appreciably to the predictive power of PSA alone. A probability plot with 95% confidence intervals was constructed that allows the practicing urologist to estimate on an individual basis the probability of a positive bone scan for any given serum PSA value. The most significant finding of this study, however, was the negative predictive value of a low serum PSA concentration for bone scan findings. In 306 men with a serum PSA level of 20 ng./ml. or less only 1 (PSA 18.2 ng./ml.) had a positive bone scan (negative predictive value 99.7%). This finding would suggest that a staging radionuclide bone scan in a previously untreated prostate cancer patient with a low serum PSA concentration may not be necessary. 
4	Transesophageal Doppler color flow mapping assessment of atrial septal defect. Transesophageal Doppler color flow imaging was performed in 19 adult patients (mean age 35 years) with an atrial septal defect demonstrated by cardiac catheterization or at surgery, or both. The transesophageal study correctly identified and classified 19 of 19 shunts in contrast to 16 of 18 shunts identified by the transthoracic approach. The area of the atrial septal defect was calculated by assuming it to be circular and taking the maximal Doppler color flow jet width at the defect site as its diameter. The pulsed Doppler sample volume was placed parallel to the shunt flow direction at the defect site to obtain the mean velocity and flow duration. From these values, the shunt volume was calculated as a product of the defect area, mean velocity, flow duration and heart rate. The calculated shunt flow volume obtained by transesophageal study showed a good correlation with shunt flow volume (r = 0.91, p less than 0.001) and pulmonary to systemic blood flow ratio (r = 0.84, p less than 0.001) obtained at cardiac catheterization. The size of the defect by transesophageal Doppler color flow mapping correlated fairly well with the size estimated at surgery (r = 0.73, p = 0.004). It is concluded that transesophageal Doppler color flow imaging is useful in the detection and classification of atrial septal defects and in the assessment of shunt volumes. 
5	Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. In a prospective study of 148 consecutive breast adenocarcinomas, proliferative indices of the same surgical tumor sample were performed by immunohistologic staining (Ki67 index) with the use of the Ki67 monoclonal antibody, which binds to a nuclear antigen only expressed in cycling cells, and by flow cytometry-derived S-phase fraction (SPF). Measurable Ki67 and SPF indices were obtained in 142 cases and 99 cases, respectively, and in 96 cases by both methods. In aneuploid tumors, a significant but low (P less than 0.05, r = 0.3) relationship was observed between Ki67 index and SPF. When compared with clinical, pathologic, and biochemical parameters these two proliferative indices were shown to be associated with nuclear grading and mitotic index. Additionally, correlations were observed between Ki67 index and node involvement (P less than 0.02) and between SPF and estrogen receptors (P = 0.002). These results show that (1) proliferative indices are obtained in 96% of surgical samples with Ki67 versus 67% with SPF and that (2) Ki67 index and SPF may provide complementary data with respect to prognosis. 
3	Murine retroviral neurovirulence correlates with an enhanced ability ofvirus to infect selectively, replicate in, and activate resident microglial cells [published erratum appears in Am J Pathol 1991 May;138(5):1058] To determine the biologic basis of ts1 MoMuLV neurovirulence in vivo, newborn CFW/D mice were inoculated with neurovirulent ts1 MoMuLV and nonneurovirulent wt MoMuLV and the temporal response to virus infection in the central nervous system (CNS), spleen, and thymus was studied comparatively. Experimental procedures included single and double labeling in situ immunohistochemistry with selective morphometric analyses, and steady state immunoblotting of viral proteins. Cellular targets for virus infection were identical for both ts1 and wt MoMuLV and consisted sequentially of 1) splenic megakaryocytes, 2) splenic and thymic lymphocytes, 3) CNS capillary endothelial cells, and 4) CNS pericytes and microglia. Resident microglial cells served as the major reservor and amplifier of virus infection in the CNS of ts1 MoMuLV-infected mice; a similar but much less significant role was played by microglia in wt MoMuLV-infected mice. The genesis and progression of severe spongiform lesions in ts1 MoMuLV-infected mice were both temporally and spatially correlated with amplified virus infection of microglia, and hyperplasia and hypertrophy of both virus-infected and nonvirus-infected microglial cells. Direct virus infection of neurons was never observed. The development of clinical neurologic disease and spongiform lesions in ts1 MoMuLV-infected mice correlated with the accumulation of both viral gag and env gene products in the CNS; there was no selective accumulation of env precursor polyprotein Pr80env. When compared to wt MoMuLV-infected mice, the neurovirulence of ts1 MoMuLV-infected mice occurred by an enhanced ability to replicate in the CNS and to infect and activate more microglia, rather than by a fundamental change in cellular tropism or topography of virus infection. 
1	Endosonography of pararectal lymph nodes. In vitro and in vivo evaluation. One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent. 
4	Assessment and counseling of coronary risk factors by family practice residents. A study was undertaken to determine (1) the likelihood that patients seen for episodic health care in a family medical center have been assessed and counseled for coronary heart disease (CHD) risk factors, and (2) the likelihood that patients having an identified risk factor have been assessed and counseled regarding other CHD risk factors. One thousand five hundred twenty-eight medical records were randomly selected from all visits occurring over two periods in 1986 and 1987 to 122 residents in an eight-site family medicine residency network. Patients with cardiovascular disease and those younger than 20 or older than 65 years of age were excluded. Assessments were made of (1) smoking history, blood pressure, weight, physical activity, and dietary content during the previous 12 months; (2) family history of cardiovascular disease during the previous 12 months and in the initial patient history; (3) and blood cholesterol during the prior 5 years. Risk-factor counseling practices were examined for the previous 12 months. Blood pressure was assessed in 96% of patients, smoking in 40%, cholesterol in 26%, and family history in 52%. Ninety-six percent of hypertensive patients were counseled for hypertension, but only 45% of smokers and 20% of patients with hypercholesterolemia were counseled for those risk factors. Of patients having a given risk factor, assessment for any other risk factor occurred in fewer than 60% of cases. Patients having a documented positive family history were only slightly more likely than other patients to be assessed for additional risk factors. There is continued need for enhancing coronary risk-factor assessment and counseling by resident physicians. 
4	Ventricular late potentials and induced ventricular arrhythmias after surgical repair of tetralogy of Fallot. Ventricular tachycardia (VT) and sudden death are rare but recognized complications after surgical repair of tetralogy of Fallot. We prospectively studied 31 patients (19 boys and 12 girls, mean age +/- standard deviation 7 +/- 4 years) with postoperative tetralogy of Fallot, by means of right-sided cardiac catheterization, 24-hour Holter monitoring, body-surface and intracavitary signal-averaging (gain 10(5) to 10(6), filters of 100 and 300 Hz) and programmed ventricular stimulation (1 and 2 extrastimuli, 3 basic cycle lengths, right ventricular apex and outflow tract). All patients were asymptomatic and none had documented or suspected ventricular arrhythmias. Ventricular late potentials were detected in 10 of 31 patients (32%) and spontaneous ventricular arrhythmias in 12 of 31 patients (39%). No sustained VT was induced by programmed ventricular stimulation but nonsustained VT was induced in 3 patients (10%). Patients with inducible VT more often had late potentials (3 of 3 vs 7 of 28, p less than 0.01), and spontaneous ventricular premature complexes (VPCs) during Holter monitoring (3 of 3 vs 9 of 28, p less than 0.05). To predict VT inducibility, late potentials had a sensitivity of 100%, a specificity of 75%, a positive predictive value of 30% and a negative predictive value of 100%. For spontaneous VPCs, the figures were 100, 68, 25 and 100%, respectively. It is concluded that shortly after repair of tetralogy of Fallot, the presence of both spontaneous VPCs and ventricular late potentials are associated with an increased incidence of inducible VT. Conversely, the absence of VPCs and ventricular late potentials may identify patients at low risk of subsequent ventricular arrhythmias. 
1	The value of immunohistochemistry for collagen IV expression in colorectal carcinomas. The Dukes' classification has well-established prognostic value in colorectal cancer patients. Yet, in each Dukes' class, the survival of individual patients may vary considerably. Recent studies show prognostic significance of genetic alterations in colorectal carcinoma. However, the importance of tumor stromal components noted in the surrounding tissue may have been overlooked by the methods used. Therefore, in a longitudinal study of 154 patients with colorectal cancer operated on between 1967 and 1974, the authors determined the influence on prognosis of lymphocytic infiltration and expression of collagen type IV in tumor stroma. Also, age, sex, Dukes' classification, grade of tumor differentiation, vasoinvasion, and the number of positive lymph nodes were analyzed. Follow-up was at least 15 years. Lymphocytic infiltration and collagen IV expression were scored as mild, moderate, or severe. Survival was analyzed by a Cox proportional-hazards model. The density of lymphocytic invasion showed no significant influence on survival. Collagen IV expression analyzed as a single variable was significantly (P = 0.038) related to better prognosis in colorectal cancer patients. By multi-variate analysis collagen IV expression showed a trend toward better prognosis that was not statistically significant (P = 0.12). Dukes' classification (P less than 0.001), the presence of vasoinvasion (P = 0.009), and lymph node status (P = 0.04) significantly influenced survival. In conclusion immunohistochemistry for collagen IV is an important additional staining technique with prognostic value. In addition, collagen IV immunostaining facilitates recognition of vascular invasion by highlighting the basement membrane of vessels. 
3	Acute naming deficits following dominant temporal lobectomy: prediction by age at 1st risk for seizures. Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (less than or equal to 5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (greater than or equal to 25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks. 
5	Intraoperative assessment of cerebral ischemia during carotid surgery. One of the problems in carotid surgery is the intraoperative detection of brain ischemia. None of the methods (EEG; stump pressure) applied so far have been successful. Branston et al. (1974) found a threshold relationship between cortical cerebral blood flow and cortical somatosensory evoked potential (SEP). As the local blood flow fell below about 16 ml/100 g/min a progressive reduction occurred in the amplitude of the cortical evoked potential (N20/P25), implying a fundamental failure of neuronal function in the somatosensory cortex. We have monitored cortical SEP (somatosensory evoked potential) during 734 CEA's (carotid endarterectomies) in order to find an index of risk of incipient cerebral ischemia during carotid cross-clamping, to determine the need for shunting and the causes of early irreversible neurologic deficits. In 59 cases evaluation of SEP was not possible because of technical difficulties. During 586 CEA's no alteration of SEP occurred. However, 4 patients had an immediate postoperative neurologic deficit, while the SEP remained normal. Abnormal SEP occurred in 89 cases and in 6 of these an irreversible loss of SEP was seen. These patients awoke with a new neurologic deficit. We found a reversible abnormal SEP in 83 cases. Reversible changes of SEP occurred mainly during carotid clamping. The diagnostic sensitivity of intraoperative SEP monitoring in predicting neurologic outcome was 60% with a specificity of 100%. 
5	The butterfly rash and the malar flush. What diseases do these signs reflect? The butterfly rash and malar flush are common facial manifestations of several disorders. Systemic lupus erythematosus may produce a transient rash before any other signs. In pellagra, symmetric keratotic areas on the face are always accompanied by lesions elsewhere on the body. Erysipelas produces brawny, fiery red facial lesions, and scarlet fever causes facial eruptions as part of a generalized eruption. Lupus vulgaris and lupus pernio produce nodules that may spread in a butterfly pattern, and seborrheic dermatitis has a predilection for the malar prominences and other areas of the face. Carcinoid syndrome often causes flushing attacks that vary in duration, and facial flushing that lasts throughout treatment may accompany chemotherapy if the patient has a hypersensitivity reaction. Deep-red rashes and/or lichenoid lesions may be caused by graft-versus-host disease in a patient undergoing bone marrow transplantation. 
1	Familial ovarian cancer in Israeli Jewish women. Among 310 women with ovarian cancer of epithelial origin, eight ovarian cancer-prone families were identified, accounting for 24 cases. Five first-degree relatives underwent prophylactic oophorectomy, and early ovarian carcinoma was diagnosed in one of them. Familial aggregation of ovarian cancer occurs in the Israeli Jewish population. 
1	Use of various epithelial tumor markers and a stromal marker in the assessment of cervical carcinoma. The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, and the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, were evaluated in 111 cervical carcinoma patients. Squamous cell carcinoma antigen was pathologic in 47%, aminoterminal propeptide of type III procollagen in 40%, CA 125 in 13%, CA 15-3 in 30%, and TAG 72 in 9% of the 91 patients with squamous cell carcinoma. The squamous cell carcinoma antigen, aminoterminal propeptide of type III procollagen, and CA 125 correlated with the clinical stage. The predictive value of a pathologic squamous cell carcinoma antigen was 78% and that of a negative result 68%. Squamous cell carcinoma antigen and aminoterminal propeptide of type III procollagen further increased the detection rate by approximately 20% from that obtained by squamous cell carcinoma antigen alone. In 16 patients with advanced disease, squamous cell carcinoma antigen correlated with the behavior of the disease in eight, aminoterminal propeptide of type III procollagen in nine, and CA 125 in six patients. Pathologic squamous cell carcinoma antigen, CA 125, CA 15-3, TAG 72, and aminoterminal propeptide of type III procollagen appeared in 11, 32, 31, 31, and 47% of 19 patients with adenocarcinoma, respectively. Squamous cell carcinoma antigen is clinically useful in squamous cell carcinoma but poor in adenocarcinoma, for which the other markers are better. Squamous cell carcinoma antigen, CA 125, and aminoterminal propeptide of type III procollagen may be used for monitoring the behavior of advanced squamous cell carcinoma. 
4	Possible mechanisms of abnormal norepinephrine sensitivity and reactivity of resistance vessels and the development of hypertension in spontaneously hypertensive rats. A hypothesis. This study examined structural and functional changes of mesenteric resistance vessels in early, developing, and established stages of hypertension development in spontaneously hypertensive rats in an attempt to identify possible mechanisms of the development and maintenance of hypertension. Our results suggest that the development of hypertension in spontaneously hypertensive rats may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by hyperreactivity to norepinephrine through an altered signal transduction process, including the regulation of protein kinase C in smooth muscle cells of resistance vessels in spontaneously hypertensive rats. 
5	Artificial urinary sphincter insertion in congenital neuropathic bladder. A series of 44 patients with neuropathic bladder dysfunction due to congenital myelodysplasia underwent implantation of an artificial urinary sphincter (AUS); in 26 patients a reconstructive procedure was performed at the same time. Five patients who initially had AUS implantation alone developed detrusor hyper-reflexia and required a clam cystoplasty. Forty patients (90%) are continent, 2 are occasionally damp and 2 are wet and awaiting further surgery; 66% of patients who underwent AUS insertion and reconstruction were found to have significant residual urine and they perform intermittent self-catheterisation (ISC). In patients with a good bladder capacity and normal compliance and detrusor hyper-reflexia controlled by anticholinergic drugs, cystoplasty is not necessary at the time of AUS insertion. 
3	Delirium: masquerades and misdiagnosis in elderly inpatients. Delirium is an organic mental disorder defined as transient, fluctuating global dysfunction of cognition. It is common in elderly medical inpatients, yet its varied presentation is often missed or misdiagnosed. 
2	Colonic motor activity in acute colitis in conscious dogs. The changes in motor activity of the colon during acute colitis were investigated in six conscious dogs. The motor activity was recorded with seven strain-gauge transducers. Colitis was induced in the entire colon by luminal perfusion of acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. The mucosa was diffusely erythematous and friable and there were scattered ulcerations over the mucosal surface. The motor activity of the colon changed in several ways during colitis: (a) the total duration per hour and the mean duration of contractile states decreased significantly; (b) the cycle length of colonic migrating motor complexes was significantly prolonged, and the nonmigrating motor complexes were almost completely absent; and (d) the incidence of giant migrating contractions increased significantly. About half of the giant migrating contractions were followed by defecation. The remaining expelled mucus or gas. Sometimes, a migrating motor complex in the colon was also followed by defecation; this was never observed in the normal state. The motor activity of the colon was still decreased and the cycle length prolonged 21 days after induction of colitis. However, the dogs were asymptomatic at this time and the mucosa looked normal at colonoscopy. The incidence of giant migrating contractions was also normal at this time. It was concluded that the dog is a good model for the study of colitis because of the similarity of symptoms with human ulcerative colitis. The phasic contractions of the colon decreases during colitis but the incidence of giant migrating contractions is increased. The diarrhea in colitis may primarily be due to the large number of giant migrating contractions in the middle and the distal colon. 
4	Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep. In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury. 
5	A successful treatment of an intrarenal arteriovenous fistula by percutaneous embolization. A 37-year-old woman patient, known to have poorly controlled arterial hypertension that was diagnosed following a cerebrovascular accident at the age of 15 years, was referred to our outpatient clinic for investigation in 1987. An intrarenal arteriovenous fistula was diagnosed by selective renal angiography. Embolization of the fistula was performed using four 15-mm/5-cm coils, which induced thrombosis and obstructed the fistula. The vascularization of the affected kidney improved immediately. During the following 4 months, the antihypertensive treatment was stopped gradually, and the patient remained normotensive. This is an unusual case of a large intrarenal arteriovenous fistula, whose etiology was not clear, that was successfully treated by percutaneous embolization. 
5	Ovarian granulosa-stromal cell tumors are characterized by trisomy 12. Eleven ovarian granulosa-stromal cell tumors including 1 thecoma, 2 fibromas, 6 fibrothecomas, and 2 granulosa cell tumors, were karyotyped after direct harvest and/or short-term tissue culture. Bilateral fibrothecomas from one patient appeared to lack cytogenetic aberrations: the remaining nine tumors were characterized by trisomy for chromosome 12. Cytogenetic aberrations in the two granulosa cell tumors were much less complex than those described previously in undifferentiated carcinomas; accordingly cytogenetic analyses might be useful in distinguishing these categories. The consistent occurrence of trisomy 12 in different varieties of granulosa-stromal cell tumors suggests a common mechanism of oncogenesis within this diverse group of neoplasms. That mechanism probably involves promotion of low-grade, orderly cell proliferation. 
1	The management of pseudomyxoma peritonei. The management of nine patients with pseudomyxoma peritonei was reviewed. Aggressive surgical resection of tumor is the standard of treatment, with many patients requiring multiple laparotomies. Chemotherapy, including the use of cisplatin is not effective. Long-term nutritional support provides a better quality of survival for select patients. 
5	Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome. We treated two patients with presumed ocular histoplasmosis, subfoveal neovascular membranes, and progressive visual acuity loss to 20/400. Vitreoretinal surgical techniques were used to remove the subfoveal membranes. Visual acuity returned to 20/20 with seven months of follow-up in one patient (Case 1) and to 20/40 with three months of follow-up in the other patient (Case 2). No evidence of persistent or current subretinal neovascular membranes in either patient have been noted. These preliminary results suggest that vitreoretinal surgical techniques may be successful in mechanically removing subfoveal neovascular membranes with preservation of overlying neurosensory retina and thus preservation of central visual acuity. 
1	Multicentric cloacogenic carcinoma: report of a case with anogenital pruritus at presentation. A case of multicentric cloacogenic carcinoma of the perianal skin and vulva in a 79-year-old woman is presented, and the embryologic basis for the multicentricity is discussed. Histologically, cloacogenic carcinoma can be differentiated from other small cell neoplasms that affect the area. Cloacogenic carcinoma should be considered a rare cause of anogenital pruritus. It is important to perform an early biopsy of anogenital lesions that do not respond to conventional therapy. 
5	A comparative evaluation of the safety and efficacy of cefotetan and cefoxitin in surgical prophylaxis. Safety and efficacy were evaluated and compared retrospectively in 77 patients who received cefotetan (CTN) and 51 patients who received cefoxitin (CFX) for surgical prophylaxis. Both groups were similar with respect to age and gender. Surgical procedures were similar between groups (e.g., obstetric/gynecologic, renal transplant, colon, exploratory laparotomy, gastroduodenal, hernia repair). Postoperative infectious complications were more common in the CTN group (11.6 percent [9/77]) than in the CFX (7.8 percent [4/51]) group; however, this difference was not statistically significant. A higher incidence of wound infections was noted in the CTN group (5.2 percent [4/77]) than in the CFX group (2.0 percent [1/51]); this difference was also not significant. Patients receiving immunosuppressive therapy were more likely to develop infectious complications when CTN was used for prophylaxis (p = 0.0001). Clinically significant blood loss was not noted during surgery. Elevations in prothrombin times (greater than 1 sec) occurred in 27.3 percent (3/11) of CTN and 11.1 percent (1/9) of CFX patients (not significant). Except for the small subset of patients receiving concomitant immunosuppressive therapy, CTN appeared to be as safe and effective as CFX when used for surgical prophylaxis. Although not statistically significant, the increased incidence of wound infections in the CTN-treated patients requires further study in a prospective randomized comparison. 
1	High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study [published erratum appears in J Clin Oncol 1991 Jun;9(6):1094] We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace. 
1	Regulation of HLA class II molecule expressions by IFN-gamma. The signal transduction mechanism in glioblastoma cell lines. We examined the signal transduction mechanism responsible for the IFN-gamma-induced HLA class II molecule expressions on glioblastoma cell lines, T98G and A172. A series of experiments demonstrated that the activation of protein kinase C (PKC) is involved in the DR and DP molecule expressions on T98G cells. In addition to the activation of PKC, calcium influx appeared to be involved in the DR and DP molecule expressions on T98G. Northern blot analyses with actinomycin D or cycloheximide revealed that these second messengers induce the transcription of DRA and B and DPA and B genes without de novo protein synthesis. Furthermore, we examined the region of the DPB gene that is responsible for IFN-gamma-induced gene transcription by gene transfer of a series of 5' and 3' deletion mutants in which the upstream region of the DPB was linked to a reporter gene, chloramphenicol acetyltransferase. By using these deletion mutants, it appeared that the region between -152 and -126 bp contains a critical IFN-gamma-responsive element. Taken together, these results suggest that IFN-gamma activates PKC and stimulates calcium influx, resulting in the induction of transcription of DRA and B and DPA and B genes without de novo protein synthesis. In DPB gene, we speculate that preexiting protein(s) phosphorylated by PKC in the presence of Ca2+ might directly bind or indirectly interact with the region between -152 and -126 bp of the upstream sequence, leading to the induction of the transcription (possibly in concert with other nuclear protein(s) bound to the promoter sequences). 
4	Alcohol and pyruvate cardioplegia. Twenty-four-hour in situ preservation of hamster hearts. Isolated hamster hearts were first perfused with a normal Krebs-Henseleit medium to demonstrate comparable viability of hearts before perfusing and storing them for 24 hours in one of three solutions. The three solutions were a physiologic saline with pyruvate as the substrate and 4% alcohol to arrest the heart (group 1), a standard cardioplegic solution (group 2), and an alcohol-free physiologic saline with pyruvate as the substrate (group 3). Recovery in terms of rate/pressure product and oxygen consumption after 30 minutes of reperfusion was 81% and 93%, respectively, for group 1, 13% and 32% for group 2, and 70% and 72% for group 3. Percent of physiologic recovery was not related to recovery of adenosine triphosphate. The adenosine triphosphate level returned to approximately 40% control level in all three groups, and in all three groups inorganic phosphate remained approximately 320% over control level after 30 minutes of reperfusion. Phosphocreatine level significantly higher in groups 1 and 3 than in group 2, as a result of improved oxygen consumption. Intracellular pH, determined by phosphorous 31 nuclear magnetic resonance spectroscopy, was physiologic in groups 1 and 3 but alkaline in group 2. This alkalinity may have been caused by leaky membranes. Pyruvate helped preserve mitochondrial function during depressed oxygen delivery, such as was seen during the 24-hour storage period. Four percent alcohol arrested the heart; combined with pyruvate plus alcohol solution were better than a standard cardioplegic solution for maintaining functional capability. 
1	Extrahepatic metabolism of morphine occurs in humans. The pharmacokinetics of morphine was studied in six patients in whom a radiologic localization of an insulinoma was to be performed under general anesthesia. Sampling was done in the peripheral artery, the mesenteric vein in five of the six patients, the hepatic vein, and the peripheral vein, as well as in urine. Hepatic blood flow was estimated by an indocyanine green infusion technique at the end of the radiologic procedure. Morphine terminal half-life was 92 +/- 9 minutes, total body clearance was 1260 ml.min-1, and the hepatic extraction ratio was 0.65 +/- 0.11. No concentration gradient was observed between the artery and the superior mesenteric vein, showing that no gut wall metabolism of morphine occurred. The total body clearance exceeded the hepatic clearance by 38%. It was concluded that the extrahepatic extraintestinal clearance of morphine probably occurred through the kidney. 
5	Through-knee amputation in high-risk patients with vascular disease: indications, complications and rehabilitation. During a 10-year period 104 patients (mean age 72 years) had 106 through-knee amputations. Indications for surgery were: limb gangrene, 67 (64 per cent); ischaemic ulceration, 22 (21 per cent); rest pain, 9; knee contractures, 6. Thirty patients had had previous unsuccessful vascular reconstructive surgery and five had had a failed femoral embolectomy. The through-knee disarticulation used lateral skin flaps. The mortality was 21 (20 per cent). Of the 83 survivors, 59 (71 per cent) underwent uncomplicated primary wound healing; 36 (43 per cent) of the survivors were unsuitable for rehabilitation on a prosthesis. The remaining 47 (57 per cent) were walking before discharge 30-130 days (mean 68 days) after amputation. Through-knee amputation is a rapid, relatively bloodless, amputation and is a useful debridement procedure. The many surgical and functional advantages, in conjunction with the recent reports of better rehabilitation compared with the above-knee or Gritti-Stokes amputation, suggests that the through-knee amputation deserves greater consideration. 
4	Multiplexing studies of effects of rapid atrial pacing on the area of slow conduction during atrial flutter in canine pericarditis model. BACKGROUND. We report that rapid atrial pacing interrupts atrial flutter when the orthodromic wave front from the pacing impulse is blocked in an area of slow conduction in the reentry circuit. To characterize the area of slow conduction during atrial flutter and rapid pacing, we studied 11 episodes of induced atrial flutter, mean cycle length 157 +/- 20 msec, in eight dogs with sterile pericarditis. METHODS AND RESULTS. Atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the interruption of atrial flutter by rapid atrial pacing, mean cycle length 139 +/- 21 msec. Areas of slow conduction during atrial flutter were demonstrated at one to three sites in the reentry circuit. After rapid pacing captured the reentry circuit, one area of slow conduction either disappeared (10 episodes) or the degree of slow conduction in an area of slow conduction decreased (one episode). Both changes were in association with activation of the region by a wave front from the pacing impulse that arrived from a direction different than that during the induced atrial flutter. Interruption of atrial flutter during rapid pacing occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction that had either newly evolved during rapid pacing (seven episodes) or that was previously present (four episodes). CONCLUSIONS. Areas of slow conduction present during atrial flutter and rapid pacing of atrial flutter are functional and depend on both the atrial rate and the direction of the circulating wave fronts. Interruption of atrial flutter by rapid pacing results from block of the orthodromic wave front of the pacing impulse in an area of slow conduction in the reentry circuit. 
1	The recombinant immunotoxin anti-Tac(Fv)-Pseudomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukemia. Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin containing the heavy and light variable regions of the anti-Tac monoclonal antibody fused to a mutant form of Pseudomonas exotoxin (PE). Anti-Tac binds to the p55 subunit of the human interleukin 2 (IL-2) receptor, and anti-Tac(Fv)-PE40 kills human or monkey cell lines that contain either the intact IL-2 receptor or its p55 subunit alone. To assess the usefulness of anti-Tac(Fv)-PE40 in treatment of IL-2 receptor-positive leukemia, we tested peripheral blood mononuclear cells from six patients with adult T-cell leukemia. In each of the six patients, anti-Tac(Fv)-PE40 was extremely cytotoxic to the malignant cells. Metabolic activity and sensitivity of the fresh cells improved when a small amount of IL-2 (10 units per ml) was present during incubation. The toxin concentration necessary to inhibit protein synthesis by 50% after 16-hr incubation of cells with immunotoxin varied from 1.6 to 16 ng/ml (2.5-25 x 10(-11) M). In every case, binding was by means of the Tac antigen because anti-Tac(Fv)-PE40 cytotoxicity was prevented by adding excess anti-Tac antibody. Moreover, anti-Tac alone or an inactive mutant of anti-Tac(Fv)-PE40 without ADP-ribosylation activity had very little cytotoxic activity. Peripheral blood mononuclear cells from normal controls, from a patient with Tac-negative leukemia, and from adult T-cell leukemia patients without significant peripheral blood involvement were not sensitive to anti-Tac(Fv)-PE40. These results indicate that anti-Tac(Fv)-PE40 is a potent cytotoxin against adult T-cell leukemia cells in vitro and warrants clinical testing. 
4	Sequential or fixed sample trial design? A case study by stochastic simulation. The properties of Wilcoxon's rank sum test for fixed sample size and a Wilcoxon-type two-sample sequential test have been illustrated and compared by means of stochastic simulation. Data from a real fixed sample trial have been used, both for resampling from the original data, and for construction of an idealized theoretical distribution. The sequential and the fixed sample test obtain equal power, but the sequential test mostly includes considerably fewer patients to reach a conclusion, i.e. the mean and median number of patients included are both much lower than the fixed sample size. Under the hypotheses only a small fraction of the simulation runs exceed the fixed sample size. These findings exemplify results obtained in theoretical analyses and simulation studies covering a wide range of distributions. In our opinion sequential tests have obvious advantages and are in many cases better alternatives than fixed sample tests in clinical trials. 
1	Intracranial arachnoid cysts in children. A comparison of the effects of fenestration and shunting. The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. The cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported. Five children with mild symptoms and small cysts that remained stable on follow-up studies have not required surgical intervention. Of 15 patients with cysts initially treated by fenestration, 10 (67%) showed no clinical or radiographic improvement postoperatively and have undergone cyst-peritoneal (eight patients) or ventriculoperitoneal (VP) shunting (one patient), or revision of a VP shunt placed for hydrocephalus before cyst fenestration (one patient). Two other patients with existing VP shunts required no further procedures. Thus, only three (20%) of 15 patients initially treated by fenestration remain shunt-independent after a median follow-up period of 8 years. The 20 other patients were initially treated by cysts shunting and all improved postoperatively; shunt revision has been necessary in six (30%) of these 20 patients because of cysts recurrence. Cyst location influenced the success of shunt treatment; none of the seven middle cranial fossa cysts treated by shunting have required revision, but results with cysts in other locations were less favorable. In all locations, though, shunting was more successful than fenestration. It is concluded that cyst-peritoneal or cyst-VP shunting is the procedure of choice for arachnoid cysts in most locations, including those in the middle cranial fossa. 
5	Antiepileptic drug intoxication: factors and their significance. A retrospective chart review (1979-1985) was performed to identify probable causes of intoxication with antiepileptic drugs (AEDs). We identified 141 patients meeting clinical and laboratory criteria for intoxication and 17 with clinical signs but with serum concentrations within the therapeutic range. The majority were epileptic patients; almost half were treated with monotherapy, most with phenytoin (PHT). The causes of intoxication in the epileptic patients were iatrogenic (41%), inappropriate dose self-adjustment (34%), suicide attempt (18%), inappropriate caretaker dose adjustment (9%), accidental ingestion (8%), unrecognized drug interaction (6%), and association with intercurrent illness (2%). Twenty-two patients had more than one probable cause of intoxication. In nonepileptic patients the causes were suicide attempt (50%), accidental ingestion (27%), and iatrogenic (23%). Most patients had signs of ocularmotor and vestibulocerebellar dysfunction. Rarely described manifestations of intoxication, such as seizures or choreoathethosis, were observed in a few patients. The average hospital stay was 6.9 days; there was no mortality, and all patients recovered fully. We conclude that AED intoxication is a major but preventable cause of morbidity and that suicide attempts are an important and underrecognized contributor in both epileptic and non-epileptic patients. 
4	Vascular and calcemic effects of plasma of spontaneously hypertensive rats. Circulating substances that increase intracellular calcium, and other circulating substances that increase blood pressure, have been described in hypertensive animals and humans. In this study, we report the existence of a factor of the plasma of spontaneously hypertensive rats that does both. These effects were dose-dependent, and the time course for such effects was correlated with the time course for potentiation of pressor agents by the plasma. In addition, the plasma of spontaneously hypertensive rats was found to inhibit the depressor effects of parathyroid hormone. Our results confirm the presence of a circulating hypertensive factor in the plasma of spontaneously hypertensive rats, which may act by increasing calcium uptake in vascular smooth muscle. These findings may also help explain the secondary increase in parathyroid hormone noted in some forms of human and experimental hypertension. 
3	Non-drug related asystole associated with anaesthetic induction. A patient is presented where routine venepuncture associated with anaesthetic induction resulted in bradycardia and asystole. The case highlights the need for special caution with, and ECG monitoring throughout induction for, patients with a history of syncope. It also demonstrates the need for caution when attributing cardiovascular events during induction to the effect of the induction agents used. 
3	Effect of the topical anesthetic EMLA on the efficacy of pulsed dye laser treatment of port-wine stains. EMLA cream (Eutectic Mixture of Local Anesthetics) is a new topical anesthetic composed of 25 mg lidocaine and 25 mg prilocaine in an oil-in-water emulsion cream. It has been found to be very effective for local anesthesia prior to venepuncture, minor surgical procedures, and pulsed dye laser (PDL) therapy for port-wine stains (PWS) in children. However, since EMLA may cause vasoconstriction of cutaneous vessels, we tried to determine whether pretreatment with EMLA decreases the efficacy of subsequent PDL treatment. We report eight patients between the ages of 4 and 32 years with PWS who received two test site treatments prior to PDL treatment. One site was pretreated with EMLA cream under occlusion for 60 minutes and then left unoccluded for 15 minutes prior to PDL test treatment. The other site, in the same area of the PWS and patient's body, was not pretreated with EMLA. The test sites were compared 6-8 weeks later to determine whether EMLA decreased the degree of lightening of the PWS compared to the non-EMLA-treated site. We conclude that EMLA is an effective topical anesthetic for PDL treatment of PWS and does not adversely affect the efficacy of the treatment. 
2	Endoscopic retrograde cholangiopancreatography in infantile cholestasis. The difficulty of distinguishing surgically correctable causes of conjugated hyperbilirubinaemia in infants from other causes means that some infants may undergo laparotomy and intraoperative cholangiography unnecessarily, and others may be referred for surgery too late. In an attempt to improve the diagnostic accuracy in infants with conjugated hyperbilirubinaemia when standard methods produced equivocal results, we have been using prototype paediatric duodenoscopes (PJF 7.5 and XPJF 8.0; Olympus) to perform endoscopic retrograde cholangiopancreatography (ERCP). From 159 infants with conjugated hyperbilirubinaemia, 11 were referred for ERCP, which was performed in nine. In four in whom bile ducts were definitely visualised laparotomy was avoided. Operative cholangiography confirmed patent bile ducts in one in whom visualisation had been uncertain. Three of four in whom bile ducts were not seen had extrahepatic biliary atresia. Visible bile drainage in the fourth excluded atresia. No major complications ensued but there was radiological evidence of gall bladder perforation in one (common hepatic duct block) and overinflation with air was a problem until finer cannulae (Wilson-Cook) were introduced. In appropriately selected patients with conjugated hyperbilirubinaemia, ERCP with paediatric duodenoscopes in experienced hands may provide useful diagnostic information. 
5	Intrinsic vasodilation protects Wistar Kyoto rats from progressive glomerulosclerosis after unilateral nephrectomy. Genetically determined differences in functional and structural determinants that govern the development of progressive glomerulosclerosis (GS) were studied in aging sham-operated or unilaterally nephrectomized male rats of two strains. Wistar rats showed an increase of proteinuria and GS with age, which was enhanced by unilateral nephrectomy (UN). In contrast, intact and UN Wistar Kyoto rats did not show an increase of proteinuria with age and 7 months after UN, no GS was seen in these rats. Systemic blood pressure was comparable in both strains and was not affected by UN. Functional studies in a separate group of rats 1 month after UN showed an identical increase in glomerular filtration rate in both strains as compared with sham-operated controls. The Wistar rats did not show an effect of UN on renal plasma flow, and consequently, there was an increase in filtration fraction, in contrast to Wistar Kyoto rats, which showed an increase in renal plasma flow with an unchanged filtration fraction. Glomerular volume was increased in both strains at 1 month and 7 months after UN. Mesangial expansion was not observed at 1 month after UN in either strain, which indicates that this is not a decisive factor in the development of GS. These data indicate that the genetically determined susceptibility to the development of GS in these two rat strains may be related to the degree of vasoconstriction, whereas glomerular volume expansion per se does not lead to GS but can well be a consequence of hyperfiltration. These studies are concordant with previous studies that revealed the role of hemodynamics in the pathogenesis of GS irrespective of glomerular expansion. 
5	Renal artery stent placement with use of the Wallstent endoprosthesis. The Wallstent endoprosthesis was placed in 12 renal arteries of 11 patients; a total of 15 stents were placed. Indications for placement were restenosis after dilation and insufficient result after dilation. In two patients, malpositioning of the stent required placement of a second stent. Complications included a case of massive cholesterol embolization and a case of unexplained transient hematuria, proteinuria, and deterioration of renal function. At repeat angiography of seven renal arteries after stent placement, one was occluded and required thrombolysis and dilation. Another showed restenosis due to shortening of the stent and required redilation and, later, placement of another stent. This stent became occluded after 1 month. In this patient and in three other cases, angiography disclosed tissue buildup in the stent but without significant stenosis after this short-term follow-up. After a clinical follow-up of 6.7 months +/- 3.4 in 10 patients treated for hypertension, three were cured, four were improved, and three were unchanged when blood pressure levels before stent placement were compared with those obtained after stent placement. 
2	Iron and the liver. Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation. 
4	Incidence and clinical significance of ST segment elevation after electrical cardioversion of atrial fibrillation and atrial flutter. To study the incidence and clinical significance of postshock ST segment elevations, we recorded 12-lead ECGs immediately after transthoracic direct-current electrical cardioversion in 146 patients with atrial fibrillation or flutter. Among 23 patients (19%), acute ST segment elevations amounted to 1.4 +/- 0.8 mV (mean +/- SD) and occurred after 243 +/- 114 joules (cumulative dose) in the precordial leads only in 14, concomitantly in precordial and inferior leads in two, and in the precordial and anterolateral leads in seven. They normalized within 1.5 +/- 0.8 minutes. Occurrence of ST segment elevation was related to previous pericardiotomy (p less than 0.00001) and age (p = 0.01). Estimation of myocardial enzyme release did not show evidence of myocardial damage. Patients with ST segment elevations had a lower conversion rate (48% versus 76%, p = 0.005). Long-term maintenance of sinus rhythm was also diminished (35% versus 59%, p = 0.03). Results of this study show that postcardioversion ST segment elevation occurs predominantly in postpericardiotomy patients and may be associated with an unfavorable arrhythmia prognosis. 
3	Rehabilitation in brain disorders. 3. Intervention strategies. This self-directed learning module highlights advances in the principles of management of brain disorders. It is part of the chapter on rehabilitation in brain disorders for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. The chapter is composed of four articles, and each builds on principles established in the others. This article covers rehabilitation philosophy, management of cognitive remediation, and behavioral management, with attention to communication disorders, social factors, vocational/educational/avocational issues, treatment of motor deficits, dysphagia, sensory dysfunction, sexual dysfunction, and substance abuse. Advances that are covered in this section include pharmacologic and rehabilitative interventions for acute, chronic, and progressive brain injuries and diseases. The learner is directed to articles 1, 2, and 4 in this chapter for supporting information. 
2	The role of prostanoids in the production of acute acalculous cholecystitis by platelet-activating factor. Gallbladder tissue from patients with acute acalculous cholecystitis contains increased amounts of prostanoids when compared to normal gallbladder tissue. Platelet-activating factor (PAF) is a potent stimulus of eicosanoid formation. It has been implicated as a mediator of acute inflammatory processes and systemic responses to shock. In this study the role of PAF in acute acalculous cholecystitis was evaluated. Anesthetized cats underwent gallbladder perfusion with a physiologic buffer solution containing [14C]polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Platelet-activating factor was infused into the hepatic artery for 2 hours. Control experiments were performed when vehicle alone was infused. Experiments also were performed when indomethacin was administered intravenously and when indomethacin and PAF were administered. Gallbladder mucosal absorption/secretion and perfusate and tissue prostaglandin E (PGE) and 6 keto prostaglandin F1 alpha (6-keto PGF1 alpha) levels were evaluated. Gallbladder inflammation was evaluated by beta-glucuronidase and myeloperoxidase tissue concentrations and by a histologic scoring system. Platelet-activating factor eliminated gallbladder absorption and produced net fluid secretion associated with dose-related increases in perfusate PGE concentrations and gallbladder tissue PGE and 6 keto PGF1 alpha levels when compared to control values. Platelet-activating factor produced significant inflammation in the gallbladder with increases in the histologic score of inflammation and tissue lysosomal enzyme activities. Indomethacin significantly decreased the fluid secretion, prostanoid levels, and inflammation produced by PAF. The results suggest that PAF may induce acute gallbladder inflammation associated with systemic stress through a prostanoid-mediated mechanism. 
3	Peroxisomal disorders. Although peroxisomes were once considered a vestige, their importance in cellular metabolism is clearly established by the many inherited diseases that have been described in the past two decades. Unfortunately there is no definitive treatment for the various disorders, but based on the recognition of the biochemical abnormalities, prenatal testing and appropriate genetic counseling can be provided. It is essential for clinicians to be aware of this group of diseases, as diagnosis and further study of these patients are essential in understanding the basic etiologic mechanisms underlying these complex groups of disorders. Clearly, there is much to be learned about the relationship between biochemical abnormalities and the phenotypic variability of the peroxisomal disorders. 
1	Management decisions in laryngeal carcinoma in situ. Twenty-one patients with laryngeal carcinoma in situ (n = 12) or carcinoma in situ with microinvasion (n = 9) were treated with laser mucosal dissection of the vocal cords and/or superficial laser cordectomy. The normal architecture of the vocal cords was preserved because the depth of vaporization was usually superficial in these early cases. Five patients had recurrence, new tumor, or persistence of abnormal tissue that required additional laser surgical treatments. With a follow-up range of 6 months to 4 years, all patients currently are free of laryngeal abnormality, and no patient has needed open laryngeal surgery or radiation therapy. Transoral endoscopic laser resection of laryngeal carcinoma in situ with or without microinvasion should be the treatment of choice for these early lesions. 
5	Avascular necrosis of bone: a common serious complication of allogeneic bone marrow transplantation. PURPOSE: To describe the incidence, presentation, clinical course, and management of avascular necrosis of bone following bone marrow transplantation, and to identify risk factors related to its development and outcome. PATIENTS AND METHODS: All patients developing avascular necrosis after transplantation between March 1974 and May 1988 were identified by means of the Minnesota Bone Marrow Transplant Database and hospital records and included in analysis. Of 902 consecutive patients undergoing bone marrow transplantation, 28 developed avascular necrosis of bone. RESULTS: Twenty-eight of 642 allogeneic transplant recipients (10.4% by product limit estimate) developed avascular necrosis compared to zero of 260 autologous transplant recipients. Symptoms developed 1 to 62 months (median 12 months) after transplantation. In the 28 patients a total of 91 joints were affected (mean 3.3 per patient, range one to eight joints). The hip joint was most often involved (64% of patients), followed by knee (61%), ankle (29%), shoulder (21%), and elbow (7%). Initial standard radiographs were negative in 13 patients, while in nine patients, technetium-99 scans and/or magnetic resonance imaging demonstrated changes of osteonecrosis before changes on routine radiographs. Almost all patients had received steroid prophylaxis and therapy for graft-versus-host disease (GVHD). We observed a significant correlation between the total cumulative dose of steroids and number of joints involved (p less than 0.01). A multivariate analysis (allogeneic transplant patients only) identified acute or chronic GVHD requiring steroid therapy (p = 0.003), and increasing age (p = 0.002) as significant and independent risk factors. Fourteen patients required surgery, including joint replacement in 11 patients. In six of six patients, hip core decompression failed to halt disease progression, and total hip arthroplasty was subsequently required. CONCLUSION: Avascular necrosis of bone is a frequent late complication of bone marrow transplantation, causing significant morbidity and often requiring surgery; diagnosis using conventional imaging techniques may be difficult and treatment remains inadequate. 
3	Magnetic resonance imaging and tomographic evaluation of occlusal appliance treatment for advanced internal derangement of the temporomandibular joint. This study evaluates the positional relationship of the disc and mandibular condyle in patients with late opening clicks treated with appliance therapy. A total of 30 joints (18 patients) were studied. Twenty-seven of these 30 joints were treated with the appliance until the joints were silent to auscultation. The patients were then evaluated with axial corrected tomography and magnetic resonance imaging (MRI) in the centric occlusion position and with their bite appliance (Sved-type) in place. Comparisons were made between condyle position in centric occlusion and with the appliance in place. Magnetic resonance imaging was then used to evaluate disc positional changes. Each imaging procedure was made in the same sagittal plane. Only changes in condyle positioning could be identified. Evidence of disc repositioning with the appliance in place was seen in only three MRI examinations. The remaining 27 joints continued to exhibit disc displacement with various changes in disc morphology. It is concluded that the concept of "disc capture" is a clinical term only, and that such perceived clinical success should not lead to the assumption that an actual change in intra-articular anatomic relationships has occurred. Joint noises may decrease because joint space is increased, allowing smoother condylar translation beyond disc surface irregularities and positional abnormalities. 
4	Surgical presentation of Kawasaki disease (mucocutaneous lymph node syndrome). Five patients with Kawasaki disease (mucocutaneous lymph node syndrome) are reported whose varied presentations included acute abdominal pain, peripheral arterial aneurysms, digital gangrene and sterile pyuria and whose presenting pathology ranged from hydrops of the gallbladder to enteric pseudo-obstruction. As the complications of the disease can usually be managed without resort to surgery, which is associated with a mortality rate of up to 25 per cent, the recognition of Kawasaki disease will prevent hazardous and unnecessary laparotomy. 
4	Restoration of sinus rhythm during two consecutive pregnancies in a woman with congenital complete heart block. In a woman with congenital complete heart block atrioventricular conduction was normal during two successive pregnancies. Pregnancy, labour, and delivery were uncomplicated on both occasions and complete heart block returned post partum. 
2	Perianal streptococcal cellulitis with penile involvement. Perianal streptococcal cellulitis is described occurring in a 5-year-old boy. The condition also involved the penis and presented as a possible case of sexual abuse. The correct diagnosis was established by culturing beta-haemolytic streptococci group A from the penile and perianal skin. 
5	The management of aneurysms and arterio-venous fistulae of the popliteal artery arising from war trauma. Emphasis on sigmoid operative approach. Between 1986-1988, 600 vascular cases arising from the Iran-Iraq conflict were dealt with within an 18 month period and 60 cases of popliteal artery and/or venous disruption were encountered presenting at variable times after injury. A policy of management between the forward and base hospital surgical teams was introduced, observing the following broad categorizations: (a) assessment/referral, (b) assessment/fasciotomy/referral, (c) immediate operation/referral for further operation/review/management. Two types of incision were used to enter the popliteal fossa: (a) a medial incision and (b) a sigmoid posterior incision (which we now favor). The results of this strategy of management and operative technique (when compared with our previous experience within the same time frame) suggested an improved outcome. Fifty-four out of 60 cases had a satisfactory operative result with below-knee amputation being required in only four cases and higher amputations in two others. No operative or postoperative deaths occurred. The implementation of this "vetting policy" at the front line appeared to reduce the number of amputations and assisted the clarification of management criteria in assessing limb viability at the forward hospital when a large number of casualties were being received. Operative access using the sigmoid posterior incision was not associated with any complications, offered better exposure than the medial incision and was technically easier for the surgeon to perform. 
5	Prognostic indicators of the resolution of nonimmune hydrops fetalis and survival of the fetus. To delineate any possible prognostic indicators, we reviewed the ultrasonographic and nonmorphometric findings in 19 antenatally diagnosed cases of nonimmune hydrops fetalis in which it was chosen to continue the pregnancy. Thirteen fetuses died and six survived. Of all parameters examined, including associated anomalies, abnormal karyotype, location of serous fluid, anemia, and possible cause of nonimmune hydrops fetalis, the most sensitive prognostic indicator was the real-time-directed M-mode echocardiographic measurement of the biventricular outer dimension in diastole. All fetuses with biventricular outer dimensions greater than 95% died, whereas all but one with normal biventricular outer dimensions had resolution of nonimmune hydrops fetalis and survived. This was highly significant (p less than 0.001) with the predictive value of a normal biventricular outer dimension being 86% and the predictive value of an enlarged biventricular outer dimension being 100%. 
1	Hormonal and enzymatic parameters of hepatic regeneration in patients undergoing major liver resections. Thirteen patients who underwent 40% to 80% removal of their livers had blood samples drawn initially and daily on postoperative days 1 to 7. The enzyme marker of heightened polyamine metabolism, ornithine decarboxylase, and the indicator of DNA synthesis, thymidine kinase, were measured. In addition, the hormones (insulin, glucagon, estradiol and androgen), which in animals are known to reflect and possibly modulate regeneration, were measured. Changes in all these indices followed the same pattern as in rats, dogs and swine but at a slower rate. Ornithine decarboxylase and estradiol increased within 24 hr, but thymidine kinase and insulin rises did not become statistically significant until 3 to 5 days. Using these plasma or serum indices as surrogate measures of biochemical events in the liver itself, regeneration reached a maximum after 4 or 5 days. By computed tomography scan analysis, restoration of hepatic cell mass was not complete until 3 wk. 
1	Possible involvement of the retinoblastoma gene in undifferentiated sinonasal carcinoma. Retinoblastoma tumor formation is initiated by the loss of function of both alleles of the RB-1 gene on chromosome 13. Patients with the hereditary form of retinoblastoma carry a germ line mutation at one of the two homologous gene loci in all cells and have an increased risk for nonocular tumors (mainly osteosarcoma and other mesenchymal tumors) in later life. The authors studied a 38-year-old patient with sinonasal undifferentiated carcinoma (SNUC) who had been treated for bilateral retinoblastoma by enucleation (left eye) and irradiation (right eye), respectively. Using molecular probes for the RB-1 gene and other loci on chromosome 13, the authors detected a deletion at the RB-1 locus in metastatic SNUC cells that was not present in normal tissue. These findings indicate that somatic mutations at RB-1 locus may be involved in the formation or progression of ectodermal tumors. 
2	Pharmacokinetics and protein binding of cefpiramide in patients with alcoholic cirrhosis. The pharmacokinetics of cefpiramide, a new cephalosporin, were investigated after a single 1 gm intravenous injection in 11 patients with alcoholic cirrhosis and compared with those of 11 healthy subjects. In patients with cirrhosis the plasma elimination half-life was three times longer than that in normal subjects. The total plasma clearance was decreased significantly (p less than 0.001): 12.3 +/- 6.5 ml/min in patients and 25.6 +/- 4.6 ml/min in healthy volunteers, respectively. The urinary excretion of unchanged drug (percent of intravenous dose) for patients (69.8% +/- 29.9%) was statistically higher (p less than 0.01) than that for subjects (16.2% +/- 3.9%). The renal elimination became increasingly important with hepatic impairment. Protein binding of cefpiramide was reduced significantly in the group with cirrhosis. The average unbound fraction was 10.4% +/- 9.5% in patients with cirrhosis and 1.9% +/- 0.3% in normal subjects (p less than 0.01). Because the rate of elimination from plasma in patients is slower, the dosage regimen of cefpiramide would probably be modified in cirrhosis. 
3	Cognitive and behavioural impairment among elderly people in institutions providing different levels of care. OBJECTIVE: To compare the prevalence and degree of cognitive and behavioural impairment in elderly patients in institutions providing different levels of care. DESIGN: Prevalence study. SETTING: A nursing home, a home for the aged and psychogeriatric wards in a provincial psychiatric hospital. PATIENTS: Only subjects 65 years of age or older were eligible for inclusion. A random sample was selected comprising 25% of the residents in the nursing home and the home for the aged; of the 119 asked to participate 95 agreed (44 in the nursing home and 51 in the home for the aged). All 50 on the psychogeriatric wards agreed to participate. MAIN OUTCOME MEASURES: The Mini-Mental State Examination (MMSE) and the Kingston Dementia Rating Scale (KDRS). RESULTS: An MMSE score of less than 24 (cognitive impairment) was given to 37 (84%) of the residents in the nursing home, 43 (84%) of those in the home for the aged and 48 (96%) of the patients in the psychiatric hospital; the corresponding numbers for a KDRS score of more than 0 (cognitive impairment) were 41 (93%), 48 (94%) and 50 (100%). The seven patients receiving the highest level of care at the home for the aged (special care) had more behavioural problems than those in the psychiatric hospital did (p less than 0.001). CONCLUSIONS: Cognitive and behavioural impairment was widespread in the three institutions regardless of the level of care. When planning services and allocating resources government funding agencies should consider the degree and prevalence of such impairment among elderly people in institutions. 
2	Effect of race upon organ donation and recipient survival in liver transplantation. The effect of the race of the donor on organ donation and on the outcome of clinical liver transplantation has not been addressed previously. The aims of this study were to determine: (1) the number of organs donated by each of the major racial groups of the United States, (2) the outcome of transplantation of these organs across racial groups, and (3) the pattern of liver disease that required transplantation in each of these racial groups. A significantly higher proportion of organs were donated by white non-Hispanic Americans than either black or Hispanic Americans. There was no significant difference in survival when an organ was transplanted between black and white Americans and vice versa. Postnecrotic cirrhosis from a variety of causes was the most common indicator affecting black and white recipients, while primary biliary cirrhosis and primary sclerosing cholangitis were uncommon in the black population. While the number of organs donated by blacks was low, it was, however, proportional to the number of black recipients in this study. Reasons for the low rate of donation by the black and white Hispanic population are discussed. It is concluded that race is not a criteria to be used in selection of donors for liver transplantation. Educational programs addressing issues of organ donation and transplantation directed towards the black and Hispanic populations are recommended. 
5	Cytogenetic analysis of a granulocytic sarcoma in a patient without systemic leukaemia. Granulocytic sarcoma is a rare complication of leukaemia. Occasionally it presents before the development of systemic leukaemia when diagnosis may be difficult. A case of granulocytic sarcoma occurring in a patient with no overt evidence of leukaemia, but in whom cytogenetic analysis of the bone marrow showed a clonal t(12;13) translocation, is reported. Cytogenetic analysis of tissues in this disease may indicate evidence of systemic disease before overt morphological changes. 
5	Impedance tympanometry and acoustic reflectometry at myringotomy [published erratum appears in Pediatrics 1991 Jun;87(6):945] A total of 220 ears undergoing myringotomy and pressure-equalizing tube placement were studied with impedance tympanometry and acoustic reflectometry in a direct comparison for detection of middle-ear effusion. Impedance tympanometry and acoustic reflectometry were equally accurate, detecting the presence or absence of middle-ear effusion in 73% and 72% of ears, respectively. The presence of effusion in ears with tympanographic patterns other than type A and type B was not consistently and reliably predicted. The higher sensitivity of impedance tympanometry (90%) compared with that for acoustic reflectometry (58%) contrasted with the opposite findings for specificities (54% vs 88%). It is concluded that impedance tympanometry and acoustic reflectometry measure different events at the tympanic membrane and their utility lies in the fact that they complement each other. These instruments can aid the experienced otoscopist in confirming a clinical impression and assist the less experienced clinician in validating or improving otoscopic skills. 
5	An angiographic technique for three-dimensional determination of arterial supply patterns in cadaver soft tissue. A method for arterial tree mapping that can be used in cadaver soft tissue is presented. In situ angiograms and photographs are supplemented with profile angiograms of relatively narrow bands of tissue from the removed specimen. The described method was better suited for mapping the course and supply patterns of a soft-tissue arterial network than either in situ angiograms or dissection. While practical problems were encountered with most of the solutions used for providing radiopacity or structural support to the vessels, pure barium sulfate was found to be suitable because it filled the vascular tree to the capillary level without leakage during excision of the specimen. 
1	Risk factors for cancer of the tongue in Uruguay. From 1987 to 1989, a hospital-based case-control study of cancer of the tongue was conducted in Montevideo, Uruguay, as part of a large study to investigate a number of risk factors for cancer of the oral cavity, pharynx, and larynx. The study involved interviews with 57 cases and 353 controls and was restricted to men. Relative risks (RR) associated with tobacco smoking, alcohol drinking, and selected dietary items were obtained by unconditional logistic-regression analysis. Users of black tobacco had a RR fourfold higher than users of blond tobacco, and heavy drinkers of alcohol had a RR of 11.6. Infrequent consumption of vegetables was associated with a significant RR of 5.3, and heavy drinkers of the local infusion "mate" had a RR of 2.5. It was concluded that black tobacco smoking and alcohol drinking were the strongest risk factors for cancer of the tongue in Uruguay. Their effects combine according to a multiplicative model. Also, infrequent vegetable intake and mate ingestion contribute to the risk of cancer of the tongue. 
1	Metastasizing pleomorphic adenoma of the nasal septum. Pleomorphic adenoma is the most common benign tumor of glandular tissue occurring in the head and neck region. There have been several reports of metastasis of this benign-appearing tumor from the salivary glands to distant sites, suggesting hematogenous spread and implantation. Although occurrence of pleomorphic adenoma on the nasal septum has been described, to our knowledge this is the first reported case of recurrent septal pleomorphic adenoma with histologically benign tissue in an enlarged metastatic ipsilateral submandibular lymph node, suggesting lymphatic spread. The literature concerning the subject is reviewed. Wide septal excision and modified neck dissection is the recommended treatment. 
1	Long survival and prognostic factors in hepatocellular carcinoma. We studied survival and prognostic factors in all cases of hepatocellular carcinoma seen at a Midwestern teaching hospital from 1947 through 1986. Of the 70 cases, 56 were diagnosed during life and 14 at autopsy. There were 47 males and 23 females with age at diagnosis ranging from 14 to 88. Median survival for the 56 patients diagnosed during life was 106 days. Only 11 patients lived longer than one year. Two patients were long survivors and presumed cured, one living 27 years after diagnosis and surgical treatment and the other 19 years. Cox regression model showed young age at diagnosis and low stage of disease at diagnosis to be significant predictors of long survival. White patients survived nearly twice as long as black patients but the difference was not significant. Gender and year of diagnosis did not appear to be important determinants of survival. Pathologic material was still available for one of the two long survivors and the histology was that of fibrolamellar carcinoma of young adults. 
5	Increase in skin-flap survival by the vasoactive drug buflomedil. The effect of buflomedil to protect skin tissue from ischemia and necrosis was studied in random cutaneous flaps. Measurements were performed by intravital microscopy on the microcirculatory level of capillary perfusion in a flap model in the hairless mouse. In 30 hairless mice, single-pedicle flaps measuring 6 x 16 mm were raised perpendicular to the spine of the animal. This flap develops a reliable amount of necrosis at its distal edge over a period of 7 days. A group of 10 mice received intravenous injections of buflomedil in doses of 3 mg/kg per day diluted in 0.1 ml normal saline beginning 4 hours before flap elevation and for 6 consecutive days postoperatively. In addition, 10 further animals received the same treatment except that it was started 5 minutes after flap elevation. In 10 mice serving as controls, normal saline in equal volumes as in the experimental groups was applied. By means of intravital microscopy, functional vessel density (FVD) was determined in 2.5-mm increments from the flap's base to its distal edge at 1, 6, and 24 hours after elevation. Skin-flap survival was quantified by measuring the necrotic area on day 7 by means of digital planimetry. Functional vessel density was preserved in the distal flap of animals pretreated with buflomedil, revealing a higher functional vessel density at 10.0 mm (p less than 0.01), 12.5 mm (p less than 0.05), and 15.0 mm (p less than 0.001) from the flap's base as compared with controls. 
4	The role of protein kinase C and calcium in the regulation of norepinephrine release from the vascular adrenergic neurons in hypertension. This study was designed to investigate the role of protein kinase C and calcium in vascular adrenergic transmission in hypertension. In perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, 7 to 10 weeks old) and age-matched Wistar-Kyoto rats (WKY), we have examined the effects of the protein kinase C inhibitor H-7 on endogenous norepinephrine release and vascular responsiveness during nerve stimulation. Endogenous norepinephrine release and pressor responses during periarterial nerve stimulation were significantly greater in SHR than in WKY. The protein kinase C inhibitor H-7 inhibited the stimulation-induced norepinephrine release and pressor responses in a dose-dependent manner. The magnitude of these suppressive responses were more pronounced in SHR than in WKY. Calcium removal from extracellular fluid also reduced the norepinephrine release more strongly in SHR than in WKY. These results demonstrate that the regulation of norepinephrine release might be more dependent on protein kinase C and calcium in the blood vessels of SHR, which could contribute, at least partially, to the pathogenesis of this form of hypertension. 
3	Tarsal tunnel syndrome in athletes. Case reports and literature review. Tarsal tunnel syndrome is being seen in increasing frequency in the athletic population, especially in the running athlete. The sports medicine physician must be cognizant of this entity, including proper diagnostic testing and management. 
4	Response to diet and cholestyramine in a patient with sitosterolemia. In this report, an 11-year-old boy with diffuse tendinous and tuberous xanthomatosis and a plasma sterol concentration of 555 mg/dL, consisting primarily of cholesterol, is described. Three months after changing from an unrestricted diet to a cholesterol-lowering diet, his plasma sterol concentration decreased to 221 mg/dL. Because of the degree and rapidity of his response to diet, sitosterolemia was suspected. According to results of capillary gas-liquid chromatography of his plasma sterols, there was a sitosterol concentration of 31.3 mg/dL (normal less than 1.0 mg/dL), establishing the diagnosis of sitosterolemia. Addition of cholestyramine therapy (8 g/d) to a low sterol diet further lowered his plasma sterol concentration to 173 mg/dL and led to complete regression of all tuberous xanthomata. Tendinous xanthomata regressed at a slower rate. These findings show that the diagnosis of sitosterolemia should be suspected in severely hypercholesterolemic children (total cholesterol greater than 400 mg/dL) whose plasma cholesterol level is highly responsive to dietary manipulation. The rapid and sustained lowering of plasma cholesterol and regression of xanthomata after treatment with diet and cholestyramine suggest that sitosterolemia is a treatable cause of premature atherosclerosis. 
5	Inter-arytenoid glottic bar following intubation. Inter-arytenoid glottic bar is a rare complication of prolonged endotracheal intubation. We present two such cases and their treatment. The aetiology of this complication is multifactorial and involves local factors--local trauma, movement of the endotracheal tube within the larynx, infection, and anatomical influences--together with systemic factors such as in our two cases. The relative importance of these factors is discussed. A comment is also made on the use of a pre-operative topogram and the importance of an ENT assessment in patients with airway problems following prolonged intubation. 
3	Cerebral palsy: why we must plan for survival. The survival of children in the South East Thames region, born between 1970 and 1979 and diagnosed as having some form of cerebral palsy was investigated. Of the 732 children studied, 651 (90%) are still alive, and hence cerebral palsy must be regarded as a condition with which people live rather than a condition of which they die. Survival varies considerably among the different diagnostic groups: those suffering from spasic quadriplegia, dyskinetic and 'mixed' cerebral palsy are most severely affected. Our evidence suggests that, though immobility and severe mental subnormality are the strongest predictors of mortality in children with cerebral palsy, the majority of even the most severely affected patients survive to adulthood. It is therefore appropriate to plan for their survival by funding and evaluating programmes to maximise health, independence, and quality of life. 
3	Malignant glandular triton tumor. A case of left brachial plexus-related malignant peripheral nerve sheath tumor showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old Chinese man is reported. The authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component. The patient had extensive local recurrence comprising mainly the Schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation. The natural behavior of this tumor, as in other reported cases of malignant triton tumor, is extremely aggressive, unlike malignant schwannoma or glandular malignant schwannoma. The histogenesis of this tumor is likely to be from primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant Schwann's cells. 
5	Phenotypic heterogeneity in osteogenesis imperfecta: the mildly affected mother of a proband with a lethal variant has the same mutation substituting cysteine for alpha 1-glycine 904 in a type I procollagen gene (COL1A1). A proband with a lethal variant of osteogenesis imperfecta (OI) has been shown to have, in one allele in a gene for type I procollagen (COL1A1), a single base mutation that converted the codon for alpha 1-glycine 904 to a codon for cysteine. The mutation caused the synthesis of type I procollagen that was posttranslationally overmodified, secreted at a decreased rate, and had a decreased thermal stability. The results here demonstrate that the proband's mother had the same single base mutation as the proband. The mother had no fractures and no signs of OI except for short stature, slightly blue sclerae, and mild frontal bossing. As a child, however, she had the triangular facies frequently seen in many patients with OI. On repeated subculturing, the proband's fibroblasts grew more slowly than the mother's, but they continued to synthesize large amounts of the mutated procollagen in passages 7-14. In contrast, the mother's fibroblasts synthesized decreasing amounts of the mutated procollagen after passage 11. Also, the relative amount of the mutated allele in the mother's fibroblasts decreased with passage number. In addition, the ratio of the mutated allele to the normal allele in leukocyte DNA from the mother was half the value in fibroblast DNA from the proband. The simplest interpretation of the data is that the mother was mildly affected because she was a mosaic for the mutation that produced a lethal phenotype in one of her three children. 
4	Myotonic heart disease: a clinical follow-up. We followed 37 patients with myotonic dystrophy for a mean of 6 years. Two developed atrial flutter or fibrillation, 6 developed a new bundle branch block, 1 developed complete heart block requiring a pacemaker, and another with progressive 1st-degree heart block and a widening QRS interval had a sudden death. Most patients had predictable, gradually progressive disease of their cardiac conduction system. We recommend that patients with progressive atrioventricular block or widening QRS interval due to myotonic heart disease have yearly ECGs and be questioned about syncope or presyncope to determine the need for a cardiac pacemaker. 
3	Numb chin syndrome secondary to Burkitt's cell acute leukemia. We describe a case of Burkitt's cell acute lymphoblastic leukemia presenting with the bilateral numb chin syndrome as the initial symptom of the disease. Postmortem study of the trigeminal nerve showed heavy infiltrations of leukemic cells and destruction of axon and myelin by leukemic cells in the mandibular nerve. 
1	Mucogenic secondary open-angle glaucoma in diffuse epithelial ingrowth treated by block-excision. We treated a 40-year-old man with an acute, unilateral, open-angle glaucoma caused by a gelatinous translucent material in the anterior chamber. A clinical diagnosis of mucogenic secondary open-angle glaucoma caused by diffuse epithelial ingrowth after ocular trauma one year earlier was suspected, but a primary or secondary ciliary body or iris neoplasm could not be ruled out. A curative 9-mm block-excision was performed. Six years later, intraocular pressure was normal, and the visual function was unchanged. Light and electron microscopy disclosed an island of diffuse columnar epithelium with numerous goblet cells on the iris surface and copious mucinous material extending into the trabecular mesh-work. 
1	Time to recurrence varies inversely with thickness in clinical stage 1 cutaneous melanoma. The thickness of a tumor has been identified as the principal prognostic factor in cutaneous malignant melanoma. However, time to recurrence has not conclusively been related to thickness. A retrospective study of 216 patients with a primary cutaneous malignant melanoma that recurred was conducted to clarify this relationship and investigate possible independent relationships between age at diagnosis and sex of patients to time to recurrence. The results of analysis of linear regression revealed an inverse linear relationship between thickness and time to recurrence (p less than 0.001). Patients more than 50 years of age at the time of diagnosis were shown to relapse sooner than those less than 50 years of age (p = 0.014). Sex was not a significant factor in predicting time to recurrence (p greater than 0.10). These results suggest that thickness of tumor provides an indication of time to recurrence in those patients destined to recur and stress the need for long term surveillance in patients with a history of malignant melanoma because of the possibility of late relapse even with thin lesions. 
1	Impaired production of tumor necrosis factor in breast cancer. Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired. 
5	Desmopressin for diabetes insipidus, hemostatic disorders and enuresis. Arginine vasopressin preparations have been used in the treatment of diabetes insipidus for many years. Compared with older antidiuretic agents, the synthetic analog desmopressin is more potent, longer acting and easier to use. It is available for intravenous, subcutaneous and intranasal administration. Desmopressin may be useful in the treatment of hemostatic disorders such as von Willebrand's disease and hemophilia A. It has also been used for nocturnal enuresis. The vasopressor effects of arginine vasopressin preparations have been exploited for use as a temporizing measure in controlling acute gastrointestinal bleeding. Side effects such as hyponatremia and water intoxication are uncommon when these drugs are used with proper precautions. 
1	Primary rhabdomyosarcoma of the ileum in an adult. We report a case of primary rhabdomyosarcoma of the ileum occurring in a 45-year-old man. The rhabdomyoblastic nature was immunohistochemically confirmed by positivity with anti-myoglobin and anti-striated actin antisera. We discuss the differential diagnosis with similar tumors. To our knowledge, ileal rhabdomyosarcomas have not been previously reported in adults. 
3	Total knee arthroplasty fixation. Comparison of the early results of paired cemented versus uncemented porous coated anatomic knee prostheses. The results of 18 matched pairs of Porous Coated Anatomic knee prostheses were studied to compare the early clinical and functional performance of cemented versus uncemented fixation with an average five-year follow-up period for both. The knee score improved from a preoperative average of 35 points to a postoperative average of 90 points in the cemented group, and from 38 points to 93 points in the uncemented group. In particular, the individual pain scores and the range-of-motion values were well matched at the three-, six-, and 12-month follow-up visits and showed a steady improvement. Subjectively, all patients were pleased with the results of surgery; one-third preferred the cemented side, one-third preferred the uncemented side, and one-third found no difference in the performance of either knee. The clinical and functional performance of knee prostheses in patients who had one cemented knee and one uncemented knee were comparable and possibly unrelated to the type of fixation method. 
5	Paraileostomy hernia: a clinical and radiological study. Forty-six patients who underwent colectomy with end ileostomy for ulcerative colitis (n = 33) or Crohn's disease (n = 13) have been reviewed for paraileostomy hernia (PIH) formation 1-16 years after surgery. PIH developed in 13 of these patients (28 per cent) and was not related to the original disease or excessive weight gain. Twenty-eight patients underwent limited computed tomography (CT) scanning of the stomal region. Eight of these had a clinically detectable PIH, which was demonstrated on CT. A further two patients had PIH demonstrated on CT which was not detected by clinical examination. The rate of PIH was similar where the stoma emerged lateral to the rectus abdominis muscle (six out of 16 patients, 37 per cent) to where the stoma emerged through the rectus (four out of 12 patients, 33 per cent). Recurrence following operative repair of PIH was common. PIH occurs more frequently than previously supposed. CT can detect PIH and may be useful in evaluating a patient with stoma-related symptoms for occult PIH formation. 
3	Attitudes of major employers toward the employment of people with epilepsy: a 30-year study. Beginning in 1956, major San Francisco Bay area employers were sampled at 10-year intervals for a 30-year period to assess attitudes toward the employment of epileptic workers. In this time, we documented a trend of sustained positive change that appears to validate the efforts of organizations that have focused on raising public awareness of this disorder. 
5	Isoperistaltic intestinal lengthening for short bowel syndrome. Because of improvements in supportive care, many infants now survive massive intestinal loss and have short bowel syndrome. Unfortunately, some survivors are left with an insufficient amount of intestine and cannot be weaned from total parenteral nutrition. An isoperistaltic intestinal lengthening procedure was used to treat surgically two such infants with 25 centimeters of remaining small intestine and absent ileocecal valves. This surgical technique longitudinally divides the short, dilated small intestine into two smaller, parallel lumens that are anastomosed end to end. This procedure preserves all mucosa, prolongs transit time by doubling intestinal length and corrects the ineffective peristalsis by tapering the dilated intestine. The lengthening technique can be performed because of the anatomic division of the intestinal vasculature within two leaves of the mesentery. Longitudinal division between the two leaves maintains vasculature to each side of the intestine. The isoperistaltic intestinal lengthening procedure, as it was successfully applied to two infants, is described in detail. 
4	Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts. Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage. 
5	High ethanol consumption as risk factor for intracerebral hemorrhage in young and middle-aged people. We examined the prevalence of high ethanol intake, hypertension, and other risk factors for intracerebral hemorrhage in a case-control study of 24 young and middle-aged patients with intracerebral hemorrhage. We recorded ethanol consumption, history of hypertension, liver disease, cigarette smoking, and mild or severe coagulation disorder in each case of intracerebral hemorrhage and in 48 control patients matched by sex and age. In univariate matched analyses, the frequencies of high ethanol intake (p = 0.009), hypertension (p = 0.05), and coagulation disorder (p = 0.05) were higher in the cases than in the controls. After controlling for possible confounding factors, we found that high ethanol intake and hypertension were the only independent risk factors for intracerebral hemorrhage (p = 0.02 and p = 0.05, respectively). The hemorrhagic lesion found in cases with a high ethanol intake tended to be located in the cerebral lobes (p = 0.01), contrasting with the typical basal ganglia location of hypertensive hematomas (p = 0.009). We conclude that chronic, high ethanol intake should be considered as an important risk factor for lobar hematomas in young and middle-aged people. 
3	Musculoskeletal problems in association with cloacal exstrophy. The records of all thirteen patients for whom a diagnosis of cloacal exstrophy had been recorded in our hospitals were analyzed for evidence of musculoskeletal problems. All thirteen patients had spina bifida, four had congenital scoliosis, two had congenital kyphosis, and three had non-congenital scoliosis. All had a lipomeningocele, and eleven had paralysis of the lower extremities. Hydrocephalus and its associated problems were not found, but tethered-cord syndrome was diagnosed in eleven patients. Persistent diastasis of the symphysis pubis was found in all patients. Abduction and external rotation of the hips were more than normal. Mild dysplasia was seen in six of the twenty-six hips. Deformities of the foot were common, and twelve feet had been operated on for correction. Recurrent equinovarus deformity of the foot was associated with tethered-cord syndrome in two patients. 
4	Rigid spine syndrome with respiratory failure. The pathogenesis and therapy of respiratory failure in the rigid spine syndrome are discussed in two cases who improved with respiratory assistance. In both cases, the partial pressures of oxygen and carbon dioxide were reversed in arterial blood gas analysis and %VC was less than 30%. Remission from respiratory failure has been obtained by the use of a ventilator during the night. The cause of the respiratory failure in both cases was severe restrictive respiratory dysfunction due to extreme flattening of the chest and fixation of the thorax during respiration as a result of contracture of costovertebral joints. All the previously reported cases of the rigid spine syndrome with respiratory failure died. Appropriate use of the ventilator can improve the prognosis. 
4	Intraoperative coronary excimer laser angioplasty: preliminary clinical experience. Diffuse coronary artery atherosclerosis is generally recognized as a deterrent to successful revascularization if it cannot be adequately treated. Mechanical endarterectomy can be useful, but it is not the optimal solution owing to the associated higher incidences of perioperative infarction and mortality. The use of laser energy as an endarterectomy tool appears promising. To investigate the application of excimer laser radiation to intraoperative coronary artery endarterectomy, 15 stenotic lesions in 13 patients were treated with excimer irradiation during coronary artery bypass grafting. Eleven (73%) of the lesions were enlarged by the excimer probe (6 of the successes were in calcified lesions). The 4 arteries not enlarged by the excimer laser all demonstrated calcified lesions. There were 3 perforations and 2 dissections, all but 1 in heavily calcified arteries. The results of this phase 1 safety and efficacy study indicate that excimer irradiation can recanalize most arteries, including total and subtotal occlusions and some calcified lesions. Further evaluation with better delivery systems is needed to determine whether the perforation rate can be reduced. 
5	Localised endosteal bone lysis in relation to the femoral components of cemented total hip arthroplasties. Four cases are described of localised endosteal bone lysis in the femur occurring in association with cemented femoral components that were not obviously 'loose' radiologically. In each, the area of lysis was shown at operation to be related directly to a region in which there was a local defect in the cement mantle surrounding the stem. Via the space between the stem and cement, such defects provide a route through which the contents of the joint cavity may reach the endosteal surface of the femur, subsequently leading to localised bone lysis, and later to frank loosening. 
2	Short-term course of corticosteroids in the treatment of resistant ascites complicating schistosomal liver disease. The aim of this work was to evaluate the effect of short-term corticosteroids in resistant ascites complicating schistosomal liver disease after 4 wk or more on standard treatment. Thirty-seven patients were randomly allocated to two groups: Group I (18 patients) was put on 40 mg furosemide and 200 mg spironolactone, in addition to a 15-day, tapering dose of prednisone (15, 10, 5 mg). Group II (19) patients received the same diuretics without steroids, and served as controls. At the end of a 2-wk course of therapy, the mean variations were as follows: body weight in patients in Group I ("cases") decreased by 9.8 kg, compared with 4.3 kg in controls; abdominal girth decreased by 7.4 cm in cases, compared with 3.6 cm in controls; urine output increased by 635.9 ml in cases, compared with 364.6 ml in controls; urinary sodium excretion increased by 16.5 mEq/day in cases, compared with 4.1 mEq/day in controls. These differences between cases and controls were found to be statistically significant (p less than 0.01). On the other hand, there were insignificant differences as regards decrease in blood urea (3.2 g/dl for cases and 2.7 g/dl for controls), decrease in serum creatinine (0.2 mg/dl for both cases and controls), increase in serum albumin (0.3 g/dl in cases and 0.2 g/dl in controls), increase in serum sodium (3.2 mEq/L in cases and 2.7 mEq/L in controls), and increase in serum potassium (0.2 mEq/L in cases and 0.4 mEq/L in controls). We conclude that a short-term course of corticosteroids in conjunction with standard diuretics has proved to be an effective, safe, and economical modality to relieve resistant hepatic ascites. It can be considered a temporary alternative to paracentesis with albumin infusion. 
5	Prediction of risk in noncardiac operations after cardiac operations. To determine the preoperative variables affecting the mortality rate and the development of severe complications in patients who have had myocardial revascularization or a valve replacement and who then undergo a noncardiac operation, we retrospectively studied data from 120 such patients over the 5 years from 1982 through 1986. Thirty-six percent of patients had a noncardiac operation during the first month after the cardiac operation. The mortality rate was 11%, and the morbidity rate was 56%. The statistical comparison of the predictive accuracy of postoperative complications of three simple, widely used classifications (American Society of Anesthesiologists physical status, New York Heart Association classification, Massachusetts General Hospital cardiac risk index) demonstrated the superiority of the simplified three-class cardiac risk index (Massachusetts General Hospital-cardiac risk index; predictive accuracy of 84%). In a multivariate discriminant analysis of 21 variables in this population, five variables (myocardial infarction in previous 6 months, S3 gallop or jugular vein distention, arrhythmia on last preoperative electrocardiogram, emergency operation, delay between cardiac and noncardiac operation) were identified as being the most predictive of a postoperative complication. When these variables were used in the function (DF3) obtained by linear discriminant analysis, the prediction accuracy of a postoperative complication reached 83%. Performance of the new models in a prospective validation population remained satisfactory (75% for Massachusetts General Hospital-cardiac risk index three-class index and 72% for DF3). Extensive statistical analysis of our data tested by a validation study provided simple predictive models based on clinical variables easily available even in emergency situations. 
1	Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the oropharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended. 
5	Laser placement in noncontact Nd:YAG cyclophotocoagulation. We treated 40 eyes of 40 patients by using noncontact transscleral Nd:YAG cyclophotocoagulation to determine whether treatment 1.5 or 3.0 mm posterior to the corneoscleral lumbus was preferable. Patients were randomly assigned to one of the treatment groups, and all other variables, including power, number, and distribution of laser applications, were kept constant. Six months postoperatively, those treated 1.5 mm posterior to the corneoscleral limbus had a lower intraocular pressure (P = .0047) than those treated 3.0 mm from the corneoscleral limbus. The 1.5-mm group also required fewer retreatment (P = .017) and had a slightly lower occurrence of visual acuity loss after this procedure. We believe it may be advantageous to locate the laser application approximately 1.5 mm posterior to the corneoscleral limbus, rather than further posteriorly, when performing noncontact transscleral Nd:YAG cyclophotocoagulation. 
3	Effect of flumazenil on midazolam-induced amnesia. We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia. 
4	Presentation of breast carcinoma as Volkmann's contracture due to skeletal muscle metastases. Metastases to the skeletal muscles are extremely rare. They usually occur during the course of a pulmonary or digestive carcinoma. We describe a case of breast carcinoma presenting with forearm muscle metastases and Volkmann's type contracture. 
1	Diagnosing breast carcinoma in young women OBJECTIVE--To assess the individual and combined diagnostic accuracy of clinical examination, mammography, and fine needle aspiration biopsy in young women with breast cancer. DESIGN--Analysis based on case notes of patients presenting with breast cancer during 1971-89. SETTING--A combined breast clinic. PATIENTS--Consecutive series of 81 women aged less than 36 with histologically proved breast cancer presenting with a discrete mass over 19 years. MAIN OUTCOME MEASURES--Results of clinical examination, xeromammography or conventional mammography, fine needle aspiration biopsy, and examination of tissue removed by surgery. RESULTS--The clinical diagnosis was correct in 47 women and radiography in 35. Fine needle aspiration biopsy was correct in 47 of the 63 women in whom it was successfully performed. Fine needle aspiration was significantly more accurate than mammography (78% v 45%, p less than 0.01). Ten (16%) patients had negative results on clinical examination, mammography, and fine needle aspiration. CONCLUSION--Mammography alone seems inadequately sensitive to detect breast cancer in young patients. When all investigations give negative results excision biopsy is the only way of obtaining a definitive diagnosis. 
1	The elusive colonic malignancy. A need for definitive preoperative localization. Colonoscopy with biopsy is the standard of practice for the diagnosis of colonic malignancies. Unfortunately, the inability of endoscopy to obtain precise distance measurements from the anal verge can make localization of lesions at operation difficult. For this reason, preoperative barium enema or intraoperative colonoscopy have been advocated to further pinpoint the sites of those lesions not thought to be easily located at operation. Five patients are presented in whom malignant lesions of the colon were diagnosed and verified histologically, but were later undetectable at operation or subsequent colonoscopic examinations. Four of these patients underwent laparotomy and three received colon resections. None of these patients' tumors were identified during intraoperative colonoscopy, in the resected bowel on pathologic examination, or on follow-up colonoscopy. A fifth patient is presented who spontaneously passed a polyp containing invasive adenocarcinoma, but multiple colonoscopic examinations have failed to identify the site of the lesion. To date, none of these tumors have recurred with periods of follow-up ranging from 6 months to 2 years. These patients demonstrate a poorly documented and little understood aspect of the behavior of colonic malignancies, i.e., the ability to spontaneously regress or slough from the bowel wall. Based on these instances, localization of potentially malignant colon lesions is recommended with submucosal dye injections at initial endoscopy or with colonoscopy in the operating room immediately prior to operation. 
5	Association between urinary symptoms at 7 years old and previous urinary tract infection. The association between current micturition habits and previous urinary tract infection was analysed among 3553 school entrants aged 7 years by means of a questionnaire. A high incidence of urinary infection, confirmed by urine culture, was found (145 (8.4%) in the 1719 girls and 32 (1.7%) in the 1834 boys). There was a significant association between current symptoms that were suggestive of disturbed bladder function and previous urinary tract infection, but only among girls who were over 3 years of age at the time the first episode was diagnosed. 
3	Optic nerve sheath meningoceles. Clinical and radiographic features in 13 cases with a review of the literature Thirteen patients with dilated intraorbital optic nerve sheaths with an expanded, patulous cerebrospinal fluid (CSF) space were studied with high-resolution computed tomography (CT) or magnetic resonance imaging (MRI). Eleven patients had bilateral findings. Headache or visual complaints, or both, were present in all patients. Signs of optic nerve dysfunction were present in eight patients. Three patients had visual acuity worse than 20/200. Cerebrospinal fluid pressure was mildly elevated in two patients. Three patients underwent a surgical procedure; visual acuity improved in one. The authors propose the term meningocele for this condition and suggest MRI with fat-suppression techniques and off-axis sagittal views as the radiographic procedure of choice. 
3	Antinociception and cardiovascular responses produced by electrical stimulation in the nucleus tractus solitarius, nucleus reticularis ventralis, and the caudal medulla. In experiment 1, quantitative regional comparisons of the antinociceptive and cardiovascular responses produced by electrical stimulation in the caudal medulla, including regions such as the nucleus tractus solitarius (NTS), nucleus reticularis ventralis (NRV), nucleus reticularis gigantocellularis (NRGC), nucleus reticularis paragigantocellularis (NRPGC), nucleus raphe obscurus (NRO), and medial portions of the lateral reticular nucleus (LRN), were made in the rat. Electrical stimulation in all of these regions resulted in inhibition of the nociceptive tail-flick reflex, although the threshold intensity for inhibition was greater for sites in NTS compared to many sites ventral to the NTS. Antinociception was generally accompanied by an increase in mean arterial blood pressure, with the exception of sites in the NRO, where depressor responses were evoked by stimulation. Detailed comparisons between the NTS and NRV revealed that greater intensities of electrical stimulation were required to produce antinociception for sites in the NTS as compared to the NRV. There were no significant differences in threshold intensities for antinociception as a function of rostrocaudal subdivisions of the NTS, but the lateral subdivision of the NTS was significantly more efficacious than the medial subdivision. This mediolateral difference within NTS was primarily due to stimulation in medial sites producing overt movements in some animals, probably due to stimulation of adjacent midline nuclei or pathways. Within the NRV, thresholds for inhibition of the tail-flick reflex were greater for sites in the dorsal subdivision as compared to the ventral subdivision, which contains spinopetal projections from the NRM. The slopes of the lines of recruitment for inhibition of the tail-flick reflex at stimulation sites in either the NTS or NRV were both very steep, similar to other forms of antinociception. In experiment 2, the pulse duration of electrical stimulation was varied for sites of stimulation in the lateral NTS and NRV to generate strength-duration curves. This experiment confirmed that stimulation sites in the lateral NTS required greater current intensities to inhibit the tail-flick reflex than sites in the NRV. However, the chronaxies derived from the strength-duration functions for the NTS or NRV were both approximately 170 microseconds, indicating that the antinociceptive effects in these regions may not be exclusively due to the stimulation of fibers of passage. These results are discussed in terms of the role of the NTS, NRV, and caudal medulla in the modulation of nociceptive responses and cardiovascular function. 
5	Tumor factors predicting for prognosis in metastatic breast cancer. The presence of P24 predicts for response to treatment and duration of survival. Fifty-one patients with metastatic breast cancer were investigated to determine tumor parameters with prognostic significance. Investigations included determinations of P24 content by immunocytochemical means using a monoclonal antibody to P24 protein; immunocytochemical analysis of estrogen and progesterone receptors; ploidy analysis by flow cytometry, and histologic grading. There were significant correlations between the presence of P24 and estrogen receptor, between histologic grade and P24 expression, and between estrogen and progesterone receptors. Of the tumor factors investigated only P24 protein was, however, of prognostic significance. Patients with P24-positive tumors had a significantly higher rate of response to treatment as well as more prolonged duration of response and duration of survival from diagnosis of metastatic disease. None of the other variables investigated were significantly predictive of outcome. P24 protein may be a useful predictor of prognosis in metastatic breast cancer. 
1	An epithelial cyst in the cerebellopontine angle. Case report. A case of a benign epithelial cyst in the posterior cranial fossa is described. It had the unique histological feature of a double-layered cuboidal epithelial lining. Detailed immunohistochemical and electron microscopic studies supported an endodermal origin. The differential diagnosis and the histogenesis of epithelial cysts in the central nervous system are discussed. 
1	Recurrent pigmented melanocytic nevus. A benign lesion, not to be mistaken for malignant melanoma. Melanocytic nevi that recur after incomplete removal are pigmented lesions that may clinically and pathologically simulate malignant melanoma in situ. Five examples of recurrent pigmented melanocytic nevus, with emphasis on light microscopic and immunohistochemical findings, are reported herein. Prominent HMB-45 staining in these nevi may cause further confusion in differentiating them from malignant melanoma. The differential diagnosis of recurrent pigmented melanocytic nevi is discussed, with particular emphasis on distinguishing these lesions from malignant melanoma. Our immunohistochemical observations indicate that the recurrences most likely develop as a result of proliferation of melanocytes remaining in the epidermis and/or adnexae following incomplete removal. The approach and management of recurrent nevi are also discussed. 
5	Overestimation of myocardial infarct size by histologic measurement in a model of occlusion followed by reperfusion. We studied 32 transverse left ventricular slices of myocardium from 16 pigs after 45 to 100 minutes of coronary artery occlusion followed by 180 minutes of reperfusion. Infarct area for each slice was determined as follows: (1) grossly, by triphenyl tetrazolium chloride staining of each slice, and (2) microscopically, by complete histologic sectioning of the triphenyl tetrazolium chloride-stained surface of each slice. Planimetry of necrotic and nonnecrotic areas was performed from tracings and photographs of triphenyl tetrazolium chloride-stained slices and from actual histologic sections. When triphenyl tetrazolium chloride and histologic measurements were compared, necrotic tissue area had decreased 11.4% +/- 15.0% (2.59 +/- 1.04 vs 2.09 +/- 0.86 cm2). Nonnecrotic tissue area decreased 20.6% +/- 24.0% (8.31 +/- 3.79 vs 5.16 +/- 2.73 cm2). In this model of ischemia followed by reperfusion, with fixation and processing, viable tissue shrank almost twice as much as necrotic tissue. This differential shrinkage introduces an error resulting in overestimation of infarct size by histologic quantitation. 
5	Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners. This study investigated metabolic and nutritional factors in association with athletic menstrual dysfunction (AMD). Three groups of women were studied: amenorrheic runners (amenorrheic), eumenorrheic runners (eumenorrheic), and eumenorrheic sedentary controls (sedentary). Amenorrheic and eumenorrheic were similar in age, weight, percent body fat by hydrodensitometry, training pace and mileage, best 10 km race time, years running, and maximal oxygen consumption. When adjusted for body weight or for fat-free mass by analysis of covariance, RMR was significantly lower in amenorrheic than in eumenorrheic and sedentary. The daily caloric intakes of the groups did not differ significantly, but the amenorrheic scored significantly higher than the eumenorrheic and sedentary on a scale of aberrant eating patterns. Amenorrheic high mileage runners seem to have a less adequate diet than eumenorrheic runners but appear to maintain energy balance and stable weight through a reduction in RMR. 
3	Anticonvulsant and behavioral effects of two novel competitive N-methyl-D-aspartic acid receptor antagonists, CGP 37849 and CGP 39551, in the kindling model of epilepsy. Comparison with MK-801 and carbamazepine. The orally active competitive N-methyl-D-aspartate (NMDA) receptor antagonists CGP 37849 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid) and its ethyl ester CGP 39551 were evaluated in amygdala-kindled rats, a model for complex partial and secondarily generalized seizures. Anticonvulsant and behavioral effects of these novel compounds were compared with those of the noncompetitive NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] and the antiepileptic drug carbamazepine, one of the major drugs for treatment of partial and generalized seizures in humans. For comparative evaluation, the compounds were injected i.p. at the following doses: 1 to 10 mg/kg (CGP 37849 or CGP 39551), 0.05 to 0.3 mg/kg (MK-801) and 20 to 40 mg/kg (carbamazepine), respectively. In contrast to carbamazepine, CGP 37849, CGP 39551 and MK-801 exerted only weak anticonvulsant effects in fully kindled rats and did not increase the focal seizure threshold. The weak anticonvulsant effects of the NMDA receptor antagonists in kindled rats were associated with profound untoward behavioral effects. The behavioral syndrome induced by the NMDA receptor antagonists in kindled rats was characterized by marked ataxia, hyperactivity and, in case of CGP 37849 and MK-801, stereotypies, such as head weaving. The low or absent effectiveness of the novel NMDA receptor antagonists against kindled seizures suggests that these compounds will not be clinically useful antiepileptics against partial and secondarily generalized seizures. Furthermore, in view of the recent clinical findings on psychotomimetic effects of MK-801 in epileptic patients, the similarities in the excitatory effects produced by CGP 39551, CGP 37849 and MK-801 in kindled rats may indicate that competitive NMDA receptor antagonists may also produce psychotomimetic effects in humans. 
5	Treatment of traumatic rupture of the thoracic aorta. A 15-year experience. Traumatic rupture of the thoracic aorta is increasing in incidence and remains a highly lethal injury. The morbidity associated with this injury also remains high. We retrospectively reviewed the records of all patients admitted to our emergency department with ruptured thoracic aortas during a 15-year period to determine the reason for this persistently high morbidity and mortality and to identify any factors that might improve the outcome. We found that patients who are in unstable condition on arrival in the emergency department or who become unstable before reaching the operating room are not likely to survive. Patients who are injured in automobile accidents have a greater chance of survival than do those injured in motorcycle accidents or car-pedestrian accidents. Patients who are in hemodynamically stable condition after aortic injury survive only if diagnosis and treatment are prompt. Major complications of repair following thoracic aortic injury relate primarily to the length of cross-clamp time, and every effort should be devoted to keeping the cross-clamp time less than 30 minutes. 
4	Increased ischemic injury but decreased hypoxic injury in hypertrophied rat hearts. The purpose of this study was to compare the degree of ischemic and hypoxic injury in normal versus hypertrophied rat hearts to investigate basic mechanisms responsible for irreversible myocardial ischemic injury. Hearts from rats with bands placed on the aortic arch at 23 days of age (BAND) and sham-operated rats (SHAM, 8 weeks postoperative) were isolated, perfused with Krebs buffer, and had a left ventricular balloon to measure developed pressure. Hearts were made globally ischemic until they developed peak ischemic contracture and were reperfused for 30 minutes. Additional hearts were perfused for 15 minutes with glucose-free hypoxic buffer followed by 20 minutes of oxygenated perfusion. There was an 87% increase in heart weight of BAND compared with SHAM (p less than 0.01). During ischemia, lactate levels increased faster in BAND compared with SHAM, ischemic contracture occurred earlier in BAND than in SHAM despite no difference in ATP levels, and postischemic recovery of left ventricular pressure was less in BAND (26.8 +/- 5.6% of control left ventricular pressure, mean +/- SEM) compared with SHAM (40 +/- 4.6%, p less than 0.05). During hypoxic perfusion, lactate release was greater in BAND than in SHAM (48.8 +/- 1.2 versus 26.6 +/- 0.97 mumols/g, p less than 0.01), and with reoxygenation, lactate dehydrogenase release was less in BAND than in SHAM (13.2 +/- 0.7 versus 19.5 +/- 0.2 IU/g, p less than 0.01). After hypoxia and reoxygenation, left ventricular pressure recovery was greater in BAND than in SHAM (93 +/- 8.4% versus 66 +/- 5.3%, p less than 0.01). Thus, this study suggests that hypertrophied hearts have a greater potential for glycolytic metabolism, resulting in an increased rate of by-product accumulation during ischemia, which may be responsible for the increased susceptibility of hypertrophied hearts to ischemic injury. 
5	Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. Although work on class III antiarrhythmics remains at an early stage, these agents still appear to possess greater efficacy and less proarrhythmia than conventional class I agents in those experimental arrhythmia models considered to be most representative of the clinical situation. Although prolongation of repolarization carries with its own tendency for pause-dependent arrhythmogenesis (i.e., torsade de pointes), available data suggest that this may be a function of nonspecificity in potassium channel block rather than a general characteristic of class III activity. The availability of new and more selective blockers of specific cardiac potassium channels under development as class III agents have already helped to clarify basic questions about the ionic mechanism of repolarization in the heart, and one hopes that a growing clinical data base will eventually determine the relative safety and efficacy of these agents in preventing symptomatic and life-threatening arrhythmias. 
5	Physical and psychosocial consequences of total laryngectomy. The incidence and severity of respiratory symptoms after total laryngectomy and their influence on daily living were studied in 59 laryngectomized patients. Daily sputum production was the principal complaint of these patients (98%), followed by coughing (64%) and the need for frequent forced expectoration (more than 5 times a day) in order to clear the airway (57%). Frequent stoma cleaning (more than 5 times a day) was required by 37% of the patients. Significant correlation was found between respiratory symptoms, voice rehabilitation and several aspects of daily living, including fatigue, sleep problems, social contacts and psychological distress. These findings indicate that respiratory symptoms after total laryngectomy are both frequent and troublesome. The development of effective methods for minimizing and/or preventing such respiratory problems would contribute significantly to improving the quality of life of laryngectomized patients. 
1	Pheochromocytoma with electrocardiographic change mimicking angina pectoris, and cyclic change in direct arterial pressure--a case report. A forty-two-year-old man was admitted because of chest pain. Electrocardiograms at admission showed horizontal ST depression in leads, II, III, aVF, V4, V5, and V6. Direct blood pressure monitoring revealed cyclic change between 160/100 mmHg and 70/50 mmHg and heart rate between 80/sec and 120/sec at fifteen minute intervals. The plasma norepinephrine and epinephrine concentrations were elevated during the episodes of hypertension. Pheochromocytoma was found in the right adrenal gland. These cyclic changes in blood pressure and heart rate are an aid for diagnosis. 
3	Postlaminectomy ossified extradural pseudocyst. Case report. A large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53-year-old man. The cyst wall, histologically composed of mature bone tissue, was sparsely covered with connective tissue and lined with fibrocyte- or fibroblast-like cells on the inside. The ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation. 
5	Electroencephalographic changes during brief cardiac arrest in humans. Slowing and attenuation of the dominant frequency of the electroencephalogram (EEG) are changes commonly used to detect cerebral ischemia. To assess the validity of this method, the EEGs recorded during 93 episodes of circulatory arrest in ten normothermic, lightly anesthetized patients undergoing implantation of automatic internal cardioverting defibrillators (AICDs) were visually inspected for change. The number of events recorded for each patient varied from 5 to 18 and was a function of the duration and success of AICD testing in each patient. In 82 of 93 (88%) episodes, EEG changes were identified, and occurred an average of 10.2 s after the last normal heart beat. Of these 82, 67 (82%) illustrated slowing and attenuation. However, 15 (18%) of the hemodynamic events showed changes not previously described as indicative of cerebral ischemia: 6 (7%) showed a loss of delta-wave activity and 9 (11%) showed an increase in the amplitude of theta activity. Time to onset of these unusual changes (10.6 and 9.2 s, respectively) was not significantly different from that for EEG slowing and attenuation (10.2 s). Five of the ten subjects showed more than one pattern of EEG change. There was no significant difference in the time to onset of EEG change among individual patients, and neither were there differences in patterns of change associated with particular anesthetic agents. These results indicate that in normothermic, lightly anesthetized individuals, cerebral ischemia may cause changes in EEG pattern other than slowing and attenuation of dominant frequencies. These alternative patterns should be recognized as indicative of cerebral ischemia when intraoperative EEG monitoring is performed. 
1	The role of the immunogenetics laboratory in marrow transplantation. Allogeneic marrow transplants from genotypically HLA-identical siblings have become lifesaving therapy for patients with various congenital and acquired diseases of the immune and hematopoietic systems. Unfortunately, less than 30% of patients in the United States have an HLA-identical sibling; therefore, many are denied the opportunity for potentially curative treatment for otherwise fatal conditions. The results of marrow transplantation from haploidentical family members who were partially compatible for nonshared haplotypes with the patients demonstrated the relevance of HLA compatibility for engraftment and graft-vs-host disease. These results have provided the rationale for using HLA-identical unrelated volunteers as marrow donors. The recent development of a national registry of volunteer bone marrow donors (the National Marrow Donor Program in the United States) has made it possible to access a centralized file of more than 260,000 HLA-typed volunteers. Marrow transplants from an unrelated donor have become feasible. However, our preliminary clinical experience clearly demonstrated an increase in the incidence and severity of graft-vs-host disease. It is likely that standard HLA typing techniques are not adequate to provide data for sufficient donor and recipient matching. It is possible that currently available molecular technology could be applied to HLA typing and donor matching to improve on clinical results. 
4	Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. We describe a fatal case of systemic lupus erythematosus (SLE) developing cerebral and systemic necrotizing vasculitis during pregnancy. The patient was discovered to have SLE at 14 weeks' gestation. Although the symptoms disappeared without treatment with corticosteroid in the 2nd trimester, she presented with meningoencephalitis due to vasculitis in the 3rd trimester. Polyarteritis nodosa (PAN)-like necrotizing vasculitis of the small muscular arteries and arterioles, with acute and healing lesions in the leptomeninges, brain parenchyma and visceral organs was observed at postpartum autopsy. PAN-like vasculitis in the central nervous system is quite rare in SLE. This case is also suggestive in terms of the influence of pregnancy on the activity of SLE. 
5	Hamman-Rich syndrome revisited In this article, we retrospectively review 29 cases of Hamman-Rich syndrome. As in some other recent reports, we have used the term "acute interstitial pneumonia" to emphasize the clinical and pathologic features of these cases and to distinguish them from the more common chronic interstitial pneumonias, particularly idiopathic pulmonary fibrosis. Of the 29 patients, 12 survived, some after a long and complicated hospitalization. The histologic features were those of organizing diffuse alveolar damage, and some patients, including survivors, had extensive fibroblastic distortion of lung parenchyma. The overall survival among these patients was not appreciably different from the survival of patients with the adult respiratory distress syndrome in general. 
5	Diagnosis of Lyme disease based on dermatologic manifestations. Lyme disease, or Lyme borreliosis, is an infection caused by the spirochete Borrelia burgdorferi, which is most commonly transmitted to humans by a tick bite. Characterized by early and late phases, Lyme disease is a multisystem illness involving the skin, heart, joints, and nervous system. Diagnosis is based predominantly on clinical manifestations, the most specific being dermatologic. Thus, recognizing the dermatologic manifestations of Lyme disease is important for diagnosis and institution of appropriate, effective therapy. Approximately 75% of patients with Lyme disease present with the pathognomonic skin lesion erythema migrans, an expanding erythematous lesion. During early infection, secondary erythema migrans lesions or Borrelia lymphocytoma may occur. Borrelia lymphocytoma commonly presents as an erythematous nodule on the ear lobe or nipple. During late infection, acrodermatitis chronica atrophicans, an erythematous, atrophic plaque unique to Lyme disease may appear; it has been described in about 10% of patients with Lyme disease in Europe. Fibrotic nodules associated with acrodermatitis chronica atrophicans as well as other sclerotic and atrophic lesions, such as morphea, lichen sclerosus et atrophicus, anetoderma, and atrophoderma of Pasini and Pierini, have been seen late in the course of Lyme disease. In a few cases, other sclerodermatous lesions, such as eosinophilic fasciitis and progressive facial hemiatrophy, have been linked to B. burgdorferi infection. We review the cutaneous lesions associated with Lyme disease. 
1	Squamous cell carcinoma of the anus and HIV infection. We retrospectively reviewed six patients with squamous cell carcinoma of the anus (SCCA) and human immunodeficiency virus (HIV) infection treated between 1985 and 1988. All six patients were homosexual men. Five patients had AIDS and one was HIV-positive. The most common symptoms and signs were pain (n = 5), mass (n = 5), and bleeding (n = 5). The average tumor size was 3.2 cm with a range of 1-10 cm. Five tumors were located in the anal canal and one at the anodermal junction. One patient was treated with biopsy alone, one with local excision, one with wide local excision and radiation therapy, and two with diverting colostomy. The average follow-up was 8 months. Of the five AIDS patients, two died, one was transferred to a hospice facility, one was lost to follow-up, and one remains alive 1 year following treatment. The HIV-positive patient died secondary to metastatic SCCA. This group of patients raises the question of a possible association between HIV and SCCA. 
5	Acute dissection of the internal mammary artery: a fatal complication of coronary artery bypass grafting. A case of acute traumatic dissection of the right internal mammary artery is presented in a patient who had both IMAs grafted for recurrent angina 10 years after initial vein coronary revascularisation. The event was mistaken for spasm, but because of severe circulatory collapse no time was available to treat the patient appropriately. The purpose of this report is to facilitate the early recognition and avoidance of this potentially fatal complication. 
3	Prevention of cardiovascular disease: risks and benefits of aspirin. Aspirin has been tested for its benefit in preventing cardiovascular disease in randomized trials in three categories of patients. In secondary prevention among those with a history of myocardial infarction (MI), stroke or transient cerebral ischemia, or unstable angina pectoris, 25 randomized trials demonstrated significant reductions from aspirin of 25% for the occurrence of an "important vascular event" (nonfatal MI, nonfatal stroke, or vascular death), 32% for nonfatal MI, 27% for nonfatal stroke, and 15% for vascular mortality. Among those evolving an MI, the Second International Study of Infarct Survival (ISIS-2) showed a significant reduction of 23% in five-week vascular mortality among those started on a one-month regimen of daily aspirin within 24 hours of the onset of symptoms of suspected MI. Aspirin also significantly reduced reinfarction, nonfatal stroke, and important vascular events. Finally, in primary prevention, the US Physicians' Health Study (PHS) showed a significant 44% reduction in the occurrence of a first MI among apparently healthy male physicians; numbers of strokes and vascular deaths were insufficient to permit conclusions for these endpoints. Thus, aspirin is of clear benefit in reducing MI, stroke, and vascular death in secondary prevention and among those evolving an MI. It is also beneficial in the primary prevention of MI among men over 40, but data concerning its effects on stroke and vascular death remain inconclusive. 
1	Effect of bleomycin on hematoporphyrin derivative phototherapy of solid tumors. Hematoporphyrin derivative phototherapy (HpD-PT) has been successfully used to localize and treat superficial squamous cell cancers. Bleomycin sulfate is a glycopeptide antibiotic that has antineoplastic properties against squamous cell cancers. Because both HpD-PT and bleomycin chemotherapy are accepted forms of treatment for squamous cell cancer and their cytotoxicity is mediated by singlet oxygen and oxygen radicals, we studied the possibility of enhancing the response of solid tumors to HpD-PT by combining this modality with systemic bleomycin chemotherapy in a murine tumor model. Bleomycin did not enhance HpD-PT significantly. Also, we are not confident that HpD-PT alone or in combination with other agents can eradicate solid tumors; it certainly did not in this syngeneic murine tumor model. 
5	Control of hypertensive emergencies Although uncommon, hypertensive emergencies require prompt recognition and treatment to reduce very high morbidity and mortality rates. Admission to an intensive care unit for treatment and monitoring is essential for optimal care. A Swan-Ganz catheter is often helpful in management. Intravenous nitroprusside sodium (Nipride, Nitropress) is probably the drug of choice for hypertensive emergencies other than those due to eclampsia or pheochromocytoma. 
1	Risk of gastric cancer after gastric surgery for benign disorders. The objective of this review was to evaluate published evidence for the association between gastric resection for benign disorders and subsequent cancer of the gastric remnant. We searched the literature through Medline (1970 to 1988) and through the references of relevant articles. Fifty-eight studies consisting of case series, uncontrolled surveys, and case control or cohort analyses were identified and critically assessed using defined methodological criteria. There were no consistent differences between the expected and observed number of cancers occurring within 15 years after gastric resection. However, all case control studies and seven of the eight cohort analyses, in which the prevalence of cancer was stratified by time since gastric resection, indicated a twofold to fourfold increase in the risk of gastric cancer in patients who survived 15 or more years after gastric surgery. We conclude that most studies of the association of gastric surgery with subsequent gastric cancer have relatively weak designs. Still, the repetitive demonstration of this association by different investigators using different research designs supports the hypothesis that gastric resection increases the risk of cancer in the gastric remnant. 
5	Renal secretion and hepatic clearance of human multiple renin forms. Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity. 
5	Selected measures of health status for Mexican-American, mainland Puerto Rican, and Cuban-American children. The 1987 National Vital Statistics System and the Hispanic Health and Nutrition Examination Survey (1982 through 1984) were used to assess the health status of Mexican-American, mainland Puerto Rican, and Cuban-American children by examining the prevalences of pregnancy outcomes and chronic medical conditions. The low-birth-weight rate among Hispanics (7.0%) compared favorably with that of non-Hispanic whites (7.1%) despite the greater poverty and lower levels of education among Hispanics. When examined by Hispanic subgroup, however, significant differences were present, with mainland Puerto Ricans having the highest prevalences of low-birth-weight infants. Premature births were more common among all three Hispanic subgroups than among non-Hispanic whites. Mexican-American and Cuban-American children had a similar prevalence of (3.9% and 2.5%, respectively) chronic medical conditions compared with non-Hispanic white children; Puerto Rican children had a higher prevalence of chronic medical conditions (6.2%). When assessed by these health status indicators, Hispanic children seem to have a health status similar to non-Hispanic white children. However, mainland Puerto Rican children seem at greater risk for poor health, reflecting the US Hispanic population's heterogeneity. Health programs targeted at US Hispanics should appropriately consider these group differences. 
5	Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity. 
5	Selective evaluation and management of coronary artery disease in patients undergoing repair of abdominal aortic aneurysms. A 16-year experience. Reduction of cardiac mortality associated with abdominal aortic aneurysm (AAA) repair remains an important goal. Five hundred consecutive urgent or elective operations for infrarenal nonruptured AAA were reviewed. Patients were divided into three groups based on preoperative cardiac status: group I (n = 260, 52%), no clinical or electrocardiographic (ECG) evidence of coronary artery disease (CAD); group II (n = 212, 42.2%), clinical or ECG evidence of CAD considered stable after further evaluation with studies such as dipyridamole-thallium scanning, echocardiography, or coronary arteriography; group III (n = 28, 5.6%), clinical or ECG evidence of CAD considered unstable after further evaluation. Group I had no further cardiac evaluation and groups I and II underwent AAA repair without invasive treatment of CAD. Group III underwent repair of cardiac disease before (n = 21) or coincident with (n = 7) AAA repair. In all instances, perioperative fluid volume management was based on left ventricular performance curves constructed before operation. The 30-day operative mortality rate for AAA repair in all 500 patients was 1.6% (n = 8). There was one (0.4%) cardiac-related operative death in group I, which was significantly less than the five (2.4%) in group II (p less than 0.02). Total mortality for the two groups were also significantly different, with one group I death (0.4%) and seven group II deaths (3.3%), (p less than 0.02). These data support the conclusions that (1) the leading cause of perioperative mortality in AAA repair is myocardial infarction, (2) correction of severe or unstable CAD before or coincident with AAA repair is effective in preventing operative mortality, (3) patients with known CAD should be investigated more thoroughly to identify those likely to develop perioperative myocardial ischemia so that their CAD can be corrected before AAA repair, and (4) patients with no clinical or ECG evidence of CAD rarely die of perioperative myocardial infarction, and thus selective evaluation of CAD based on clinical grounds in AAA patients is justified. 
1	Osteoblastoma of the spine. A review of 75 cases. Clinical and radiologic features of 75 cases of osteoblastoma of the spine were reviewed. In addition to pain, which was the most frequent complaint, 18 patients demonstrated objective neurologic deficit, while scoliosis was observed in 17 patients. Aspirin yielded pain relief in 13 patients. Pathologic fracture was not encountered. The radiologic and histologic characteristics of osteoblastoma of the spine are indistinguishable from those arising in other sites. The typical lesion exhibited a well-defined, geographic margin with a sclerotic, frequently lobulated border. Approximately one half of the cases were predominantly lucent, the remainder displaying varying degrees of matrix mineralization. Distribution of the osteoblastomas through the spinal axis was as follows: cervical-29, thoracic-16, lumbar-17, sacral-13. Other significant findings included posterior element involvement in 73 of 75 cases, and a striking male to female ratio of 2.5 to 1. 
4	Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease. Leukotriene C4 is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4 release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II). To assess leukotriene C4 generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 microM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4 by radioimmunoassay. Patients in group I had a significantly lower release of leukotriene C4 from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 +/- 0.69 versus 5.92 +/- 0.54 ng/ml, p less than 0.025), whereas patients in group II had a similar release of leukotriene C4 by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 +/- 0.72 versus 6.4 +/- 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p less than 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4 released from neutrophils separated from coronary sinus blood as compared with leukotriene C4 produced by neutrophils separated from aortic blood. These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4 after stimulation by calcium ionophore A 23187. 
3	Widespread functional effects of discrete thalamic infarction. In order to investigate functional effects of various thalamic structures on metabolism in remote, morphologically intact cerebral regions, we used positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose to study regional cerebral metabolic rates of glucose (rCMRGlu) in 11 patients with chronic unilateral or bilateral infarcts strictly confined to the thalamus. Patients were grouped according to computed tomographic scans showing anterior (three), medial (four), or posterior (four) lesions. Compared with a matched group of 11 healthy subjects (hemispheric CMRGlu 35.2 +/- 3.49 mumol/100 g per minute), glucose metabolism was significantly lower in the hemisphere ipsilateral to the infarction (31.2 +/- 2.97 mumol/100 g per minute). Patients with bilateral infarcts had lower hemispheric CMRGlu (29.9 +/- 2.74 mumol/100 g per minute) than those with unilateral lesions (32.2 +/- 2.97 mumol/100 g per minute). Depending on infarct location within the thalamus, there was differential depression of rCMRGlu, with the largest effects on frontal and occipital areas in medial infarctions. Except for ipsilateral thalamic deactivation, metabolic patterns with anterior thalamic infarcts were close to normal, while posterior infarcts mostly depressed rCMRGlu in the visual and in the inferior limbic cortex. Cerebellar metabolic rates were within normal limits in most cases. These patterns of regional cerebral deactivation may be related to categories of thalamic projections--intrathalamic, to limbic system and basal ganglia, diffuse to most cortical areas, and specific to defined neocortical areas. Even small brain lesions may have widespread functional sequelae, potentially demonstrable by positron emission tomography. 
2	A five-year U.S. Army experience with 36,250 abdominal hernia repairs. Thirty-six thousand two hundred fifty abdominal hernia repairs were performed in U.S. Army medical treatment facilities during a five-year period. This study presents data about the type of hernia, incidence of complications by obstruction or strangulation, age, sex, and mortality. Hernias occurring with intestinal obstruction or gangrene (strangulation) are referred to as complicated hernias. Inguinal hernias in children less than two years of age, femoral hernias, and unusual (such as internal or obturator) hernias were found to have an increased incidence of complications. Surgical repair of ventral, umbilical, and femoral hernias was done with a low surgical risk and the presence of complications did not significantly increase this risk. An increased risk of mortality is associated with the repair of complicated unusual hernias and complicated inguinal hernias in patients more than 60 years of age. 
3	Sequencing in Parkinson's disease. Abnormalities in programming and controlling movement. Central programming deficits in Parkinson's disease (PD) were studied in two reaction time (RT) experiments. In Experiment 1, PD patients and controls performed sequences of hand postures that varied in length, the number of different postures (repetitive vs heterogeneous), and the delay interval before movement. Before movement, the PD group planned repetitive movements like controls whereas for heterogeneous sequences RT increased less with sequence length for the PD group, implying less preprogramming. The interresponse time (IRT) data from repetitive sequences showed that the PD group had difficulty controlling movement such that IRTs were faster when sequences were longer, thus allowing more time to schedule the termination of the sequence during the course of movement. For heterogeneous sequences, the PD group made more errors and were slower than controls when changing hand postures, suggesting a deficit in switching between different responses. While RT decreased with a longer delay similarly for both groups, IRT1 continued to improve only for the PD group but similarly for both types of sequences, suggesting a deficit specific to programming the first response. In Experiment 2, subjects made decisions about the number of different hand postures contained within a sequence. PD patients' decision times improved more with a longer delay only for heterogeneous sequences, suggesting a problem in identifying the number of different hand postures. The results have implications for levels of motor dysfunction in PD which emphasize the influence of sequence length and complexity. 
3	Motor-evoked potentials reflect spinal cord function in post-traumatic syringomyelia. The purpose of this study was to examine electrophysiologic abnormalities, including motor-evoked potentials, in a patient with post-traumatic syringomyelia before and after syringopleural shunting. A patient with C5 quadriplegia presented with pain, ascending sensory loss, and new weakness in the left upper extremity two yr after spinal cord injury. MRI revealed a syrinx extending from C2 to T12. We measured central motor conduction times (CMCTs) to the biceps, median F-wave latencies, needle electromyography and motor nerve conduction studies. Six days before surgery, CMCTs were 9.0 ms on the left and 7.8 ms on the right (normal less than 8.0), median F-waves were absent on the left and needle EMG revealed evidence of denervation in the left biceps. Fifteen days after syringopleural shunting at the T7 level, CMCTs had dropped to 6.9 ms on the left and 4.6 ms on the right; the left median F-wave reappeared with a normal latency. Repeat MRI revealed the syrinx to be smaller in diameter. These results suggest that CMCTs measured from magnetic stimulation of the motor cortex may be useful in the diagnosis of post-traumatic syringomyelia, as well as for following such patients postoperatively. 
2	Hepatocyte transplantation into the lung for treatment of acute hepatic failure in the rat. The lung was investigated as a matrix for transplanted hepatocytes in the rat model. Surgically induced fulminant hepatic failure was successfully treated by injection of 5 to 7 x 10(7) isolated hepatocytes into the pulmonary parenchyma in 86% of the animals. No animal, however, survived injection of hepatocytes into the jugular vein. It was found that liver failure is a prerequisite for the intrapulmonary survival of hepatocytes. After regeneration of the native liver, the majority of hepatocytes are cleared away within 6 months. 
3	The neuromuscular pathology of the Eosinophilia-Myalgia syndrome. The Eosinophilia-Myalgia Syndrome (EMS) is a recently reorganized disorder in patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was severe in four, moderate in two, mild in three and absent in three cases. The lesions contained many eosinophils, T-helper cells, mast cells and activated macrophages. Type 2 myofiber atrophy was present in five cases and in one, this was the only pathologic finding. Severe epineurial inflammation was seen in the three sural nerve biopsies. Indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs (two cases) and neurogenic atrophy (one case). Phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one. Fasciitis was present in three of four skin biopsies and dermal fibrosis in one. 
5	Occlusion of an "accessory" distal anterior cerebral artery during treatment of anterior communicating artery aneurysms. Report of two cases. Two cases are presented in which clip occlusion of a third distal anterior cerebral artery segment occurred during treatment of anterior communicating artery aneurysms. Case histories, angiograms, operative descriptions, and postmortem findings are presented. The incidence of this anomalous vessel is reviewed. Preoperative and intraoperative vigilance in determining the presence of this anomaly prior to clip placement is emphasized. 
5	Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy. OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open-label, dose-finding phase followed by a randomized, double-blind, placebo-controlled, crossover phase, with each treatment period lasting up to 60 days. SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial fibrillation (n = 17) were enrolled. Their arrhythmias were documented by electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were randomized and the data obtained from these patients were used in the efficacy analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300 mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching placebo tablets were administered in a randomized sequence. MEASUREMENTS: Symptomatic arrhythmia was documented by telephone transmission of the electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for the overall group of 23 patients while they received propafenone (P = 0.004). The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo. CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal supraventricular arrhythmias. 
5	Total perinatal wastage. A clarification of priorities. The pregnancy outcome of 16,971 women carrying 17,352 living fetuses after 16 weeks gestation was studied. As well as recording perinatal deaths, all losses before 28 weeks and up to one year after delivery were recorded to give a total perinatal wastage rate of 21.6 per 1000 fetuses alive at 16 weeks compared with a perinatal mortality rate (stillbirths plus early neonatal deaths) of 7.8 per 1000 births. All deaths were then classified according to pathological sub-groups. The concept of auditing perinatal care using perinatal mortality was then compared with that using total perinatal wastage. 
2	Surgical management of islet cell dysmaturation syndrome in young children. Islet cell dysmaturation syndrome (ICDS) encompasses the causes of infantile hyperinsulinemic hypoglycemia histologically described as islet cell hyperplasia, pancreatic adenomatosis and nesidioblastosis. Eleven infants underwent 14 pancreatic resections for ICDS from 1965 to 1990 at the University of California at Los Angeles Medical Center for severe hypoglycemia unresponsive to medical therapy. Seizures were the presenting symptoms of hypoglycemia in eight infants. Six patients had nesidioblastosis, four had islet cell hyperplasia and one patient had an adenoma with histologically normal pancreatic islet cells. Four neonates underwent 80 per cent pancreatic resection; three with nesidioblastosis required reoperation (90 to 95 per cent resection). Four older infants underwent 80 per cent pancreatic resection but required diazoxide for less than six months postoperatively. Three infants underwent 90 to 95 per cent pancreatic resection. None have required reoperation or postoperative medications. All infants are normoglycemic without pancreatic exocrine insufficiency and none had postoperative complications. Five infants had preoperative neurologic impairment, with three having severe retardation; all showed some improvement postoperatively, but only one infant now has normal findings on neurologic examination. Early diagnosis and aggressive surgical resection should minimize neurologic complications of the ICDS. 
3	Multimodality evoked potential testing in acute mild closed head injury. Multimodality evoked potential (MEP) testing, including brainstem auditory, visual, and somatosensory evoked potentials, have been reported to be useful in predicting outcome in severe closed head injury. Brainstem auditory evoked potentials have been demonstrated to be abnormal in 10% to 40% of acute mild head injury. A prospective study of 18 patients with mild closed head injury was undertaken to determine the usefulness of MEP screening within two weeks of the acute event. Long latency event-related potentials (P300s), in response to auditory stimuli with an oddball paradigm, were included in the screening. The subjects had several symptoms consistent with the postconcussive syndrome at the time of the evoked potential testing. Only one patient had an abnormal evoked potential response (greater than three standard deviations from the mean) from all the testing done. The standard methods of MEP testing were insensitive to quantifying the possible physiologic changes that are associated with memory deficits, lethargy, and emotional irritability after mild closed head injury. 
4	Increased endothelin in experimental heart failure. Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced. 
5	Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa Hepatocellular carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia. Hepatitis B virus and aflatoxins are risk factors for HCC, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines, and allelic losses from chromosome 17p have been found in HCCs from China and Japan. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G----T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa, which is both a mutagen that induces G to T substitution and a liver-specific carcinogen. 
4	Silent cerebrovascular disease in the elderly. Correlation with ambulatory pressure. Does the average daily blood pressure correlate with hypertensive cerebrovascular disease better than the casual pressure, as has been reported in other target organ involvement? We investigated the associations of two abnormal findings on brain magnetic resonance imaging suggestive of a vascular etiology, low intense foci (lacunae), and periventricular hyperintense lesions on T1- and T2-weighted images, with both office and average daily blood pressure values in a population of 73 healthy normotensive and hypertensive elderly individuals (70 +/- 6 years old). Lacunae were detected in 34 subjects (47%); the number per subject ranged from 0 to 19 and was significantly correlated with advancing age. Furthermore, these changes were supposedly related to the average of noninvasive ambulatory (24-hour and during awake and asleep periods) pressure recordings but not to office pressures. The grade of periventricular hyperintensity was also significantly associated with advancing age and the average of ambulatory systolic pressure recordings, particularly during sleep, but not with office blood pressure. In comparisons of normotensive, "office hypertensive," and hypertensive subgroups, abnormalities on magnetic resonance imaging were appropriate to the level of the 24-hour blood pressure measurements but not to that of clinic pressure. In hypertensive patients, the presence of electrocardiographic evidence of left ventricular hypertrophy was also associated with greater abnormalities on magnetic resonance imaging. We conclude that ambulatory blood pressure monitoring is superior to casual pressure measurements in predicting latent cerebrovascular disease, which is unexpectedly common in apparently healthy elderly subjects. 
5	Simultaneous bilateral hernia repair. A case against conventional wisdom. The timing of bilateral hernia repair remains controversial. Because of reported high recurrence rates after simultaneous bilateral repair, staged procedures have been suggested. This study determined recurrence and complication rates of unilateral versus simultaneous bilateral repair. Of 659 patients undergoing hernia repair between 1974 and 1980, 333 underwent unilateral repair and 329 had simultaneous bilateral repair. More than 90% of patients were followed until death or a minimum of 60 months (median, 104 months). Perioperative complications were associated with 18% of repairs. More morbidity occurred in the bilateral group. However complication rates for specific events were not significantly different, except for urinary retention, which occurred in 20 patients (6.1%) of the unilateral group and 49 (15%) of the bilateral group (p less than 0.001). Overall 25 recurrences occurred in the unilateral group and 31 in the bilateral group. Recurrence rates at 5 and 9 years were, respectively, 4.8% and 8.8% in the unilateral group and 5.0% and 9.1% in the bilateral group (p = 0.861). These data suggest that simultaneous bilateral inguinal herniorrhaphy does not result in increased rates of most postoperative complications or recurrence when compared with unilateral repair. 
3	Diagnostic evaluation of syncope Syncope is a common medical problem and is caused by a wide variety of diseases ranging from physiologic derangements with few consequences to conditions that may be immediately life-threatening. Because of the large differential diagnosis, many diagnostic tests are available for its evaluation. However, a cause of syncope is not established in 38% to 47% of patients despite these tests. In those patients in whom a diagnosis can be assigned, the history and physical examination identify a potential cause in 49% to 85%. Furthermore, in 8% of additional patients, history and physical examination are suggestive of causes that need confirmation by specific tests. Routine blood tests rarely yield diagnostically helpful information. In those patients in whom a potential cause for syncope is identified, arrhythmias are diagnosed by electrocardiogram in 2% to 11% of patients, cardiac monitoring in 3% to 27% (telemetry or Holter), stress test in less than 1%, carotid massage in less than 1%, and electrophysiologic studies in less than 3%. Diagnosis of arrhythmias as a cause of syncope is problematic because symptomatic correlation during electrocardiographic monitoring is rarely found (approximately 4%), and as a result, there is no uniform agreement on diagnostic criteria for abnormalities. Similar problems exist in the use of electrophysiologic studies. Upright tilt testing and psychiatric examination may be useful in evaluation of recurrent syncope of unknown cause in patients without organic heart disease. Based on the results of recent studies, strategies for evaluation of patients with syncope are possible that utilize selective and goal-directed diagnostic testing. 
4	Spontaneous dural carotid-cavernous fistula with central retinal vein occlusion and iris neovascularization. Spontaneous dural carotid-cavernous fistulas are dural vascular malformations that usually run a benign course. We present a case of a spontaneously occurring dural carotid-cavernous fistula complicated by central retinal vein occlusion and iris neovascularization that led to progressive visual failure. 
4	Influence of right bundle branch block on short- and long-term survival after acute anterior myocardial infarction The impact of right bundle branch block on long-term prognosis after anterior wall myocardial infarction is unclear. In 932 patients with Q wave anterior infarction, the short- and long-term prognostic significance of the presence of right bundle branch block was analyzed. Compared with 754 patients without block, 178 patients with right bundle branch block after myocardial infarction showed an increased incidence of left ventricular failure (72% versus 52%, p less than 0.001) and increased in-hospital (32% versus 8%, p less than 0.001) and 1 year after hospital discharge (17% versus 7%, p less than 0.001) cardiac mortality rates. The presence of right bundle branch block was an independent predictor of increased in-hospital and 1-year mortality when entered in a multivariate analysis. However, the absence of left ventricular failure identified a subgroup of patients with right bundle branch block with low in-hospital (4%) and 1 year postdischarge (5%) cardiac mortality rates comparable with those of patients with neither failure nor right bundle branch block (1.7% and 4.8%, respectively). In the presence of left ventricular failure, patients with associated right bundle branch block had higher in-hospital (43% versus 14%, p less than 0.01) and 1 year postdischarge (24% versus 9%, p less than 0.01) cardiac mortality rates than those of patients with failure but no right bundle branch block. Thus, the presence of right bundle branch block after anterior myocardial infarction is an independent marker of poor prognosis. 
1	Erythropoietin receptors induced by dimethyl sulfoxide exhibit positive cooperativity associated with an amplified biologic response. Erythropoietin triggers the differentiation of erythrocyte progenitors by binding to receptors on their plasma membrane. We report here that pretreatment of erythropoietin-responsive murine erythroleukemia cells with chemical inducers resulted in a striking increase in erythropoietin-specific hemoglobinization. This amplification of the erythropoietin biologic response was accompanied by the induction of a new population of high-density receptors (approximately 20,000 per cell) exhibiting marked positive cooperativity. Erythropoietin binding to new receptors displayed a convex upward Scatchard plot and a Hill coefficient (nH) of 6.75. Measurement of erythropoietin receptor mRNA demonstrated an initial decrease in receptor transcript followed by an approximately 2- to 3-fold increase after 24-48 hr. This increase in receptor message does not appear to account for the magnitude of the receptor up-regulation by dimethyl sulfoxide. We propose that this positive cooperativity reflects the interaction (clustering) of receptors, presumably through the formation of homooligomers or heterooligomers, and that this receptor interaction may amplify the erythropoietin signal transduction pathway. 
2	Acute porphyria presenting with hyperamylasemia. An elevation of serum amylase and lipase has not been reported previously to occur with porphyria. In this report, we describe a patient who presented with the clinical and laboratory picture of pancreatitis: elevated amylase, lipase, amylase-creatinine clearance ratio, and with abdominal pain. Only after extensive evaluation, was the patient found to have porphyria. On two separate occasions, with hematin therapy, her serum amylase decreased, as did her clinical symptoms of porphyria and her urinary quantitative porphyrins. This suggests an association between elevation of the serum amylase and lipase with acute porphyria. Moreover, this association can lead to delay in establishing the diagnosis of acute porphyria. 
3	A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features. Twelve infants (six boys, six girls) with severe hypocalcaemic tetany or convulsions were seen over a three year period. Nine patients were symptomatic in the newborn period. Their hypocalcaemia was associated with hyperphosphataemia and very low concentrations of immunoreactive parathyroid hormone. None of the babies suffered from congenital cardiac disease. Cell mediated immunity, measured in five patients, was normal. There were no chromosomal abnormalities but all patients shared several dysmorphic features including deep set eyes, microcephaly, thin lips, beaked nose tip, external ear anomalies, micrognathia, and depressed nasal bridge. Mental retardation of varying degree was found in all patients. All had severe intrauterine and postnatal growth retardation. Four patients have died. The remaining eight patients are on treatments with vitamin D and calcium supplements with no change in their growth pattern. We believe that this association of congenital hypoparathyroidism with severe growth failure and dysmorphism represents a new syndrome. 
1	The effect of somatostatin on 5-hydroxytryptamine release from a carcinoid tumor. One of the major manifestations of the carcinoid syndrome is secretory diarrhea thought to be due to overproduction of 5-hydroxytryptamine (5-HT). Synthetic somatostatin analogues have proved to be clinically effective in controlling this diarrhea. We have established a continuous cell line from a human pancreatic carcinoid tumor that secretes 5-HT. We examined the ability of the somatostatin analogue, SMS 201-995, to inhibit 5-HT release in vitro. Tumor cells were exposed to SMS 201-995 (10(-6) mol/L), pentagastrin (10(-9) mol/L), acetylcholine (10(-5) mol/L), and isoproterenol (10(-5) mol/L) alone and in combination; 5-HT release was assayed with high pressure liquid chromatography. We found that pentagastrin (6.43 +/- 0.64 ng/ml), isoproterenol (20.24 +/- 2.17 ng/ml), and acetylcholine (12.39 +/- 1.10 ng/ml) each stimulated release of 5-HT compared to control values (4.38 +/- 0.42 ng/ml). SMS 201-995 significantly reduced release of 5-HT in response to isoproterenol and acetylcholine but did not inhibit the effect of pentagastin. These data suggest that different agents do not act through the same pathway to stimulate 5-HT release from human pancreatic carcinoid cells. 
3	Neuroleptic malignant syndrome. When levodopa withdrawal is the cause. Neuroleptic malignant syndrome has been described in patients receiving dopamine antagonists and in a few patients after withdrawal of dopaminergic antiparkinson therapy. Complications affect almost all organ systems and can be life-threatening. Most patients have fever, altered level of consciousness, bradykinesia, and rigidity. Treatment includes withdrawal of the causative agent and supportive therapy for complications. When withdrawal of a dopaminergic medication is the suspected cause, the agent should be reinstated. 
1	Clinical study of intracranial nongerminomatous germ cell tumors producing alpha-fetoprotein. We present six patients with intracranial nongerminomatous germ cell tumors that produced alpha-fetoprotein (AFP). Their ages ranged from 8 to 20 years (average, 11.5 years old); two were male and four were female. Four of the tumors originated in the pineal region and two in the suprachiasmatic region. One patient treated with only radiation therapy died within 3 months of admission as a result of intraperitoneal metastasis via a ventriculoperitoneal shunt. Another patient, treated with radiation therapy and intrathecal administration of neocarzinostatin, died after 12 months because of tumor progression and subarachnoid dissemination. Two patients who received radiation and combination therapy with cisplatin, vinblastine, and bleomycin died after 13 and 25 months. The remaining two patients treated with radiation therapy and adjuvant chemotherapy (cisplatin and etoposide) are now alive without recurrence after 16 and 19 months from admission. Adjuvant chemotherapy with cisplatin and etoposide appears to be efficacious in the treatment of intracranial nongerminomatous germ cell tumor. 
5	Blockade of prostaglandin production increases cachectin synthesis and prevents depression of macrophage functions after hemorrhagic shock. Although hemorrhage severely depresses macrophage functions, it is not known whether the increased TNF-alpha or PGE2 production is responsible for it. To study this C3H/HeN mice were bled to mean blood pressure of 35 mmHg for 60 minutes, resuscitated, and treated with either ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage increased plasma prostaglandin E2 (PGE2) levels by 151.7% +/- 40.0% (p less than 0.05) and significantly decreased peritoneal macrophage (pM phi) antigen presentation (AP) by 60.5% +/- 7.3%, Ia expression by 52.3% +/- 7.6%, and interleukin-1 (IL-1) synthesis by 60.5% +/- 12.3% compared to shams. However ibuprofen treatment reduced PGE2 plasma levels by 61.3% +/- 12.1% and significantly increased AP (+237.0% +/- 95.3%), Ia expression (+72.8% +/- 27.5%), IL-1 synthesis (+235.7% +/- 134.7%), and cachectin synthesis (+485.8% +/- 209.0%) compared to vehicle-treated animals. These results indicate that prostaglandins but not cachectin are involved in the suppression of pM phi functions following hemorrhage because blockade of prostaglandin synthesis improved depressed macrophage functions despite enhanced cachectin synthesis. 
4	Percutaneous transluminal angioplasty of crural arteries. The authors dilated 103 stenosed crural arteries in 71 patients. Primary success was defined as traversing and reducing the lesion to a residual stenosis of less than 30%. This was achieved in 96% of cases. Complications included one vessel rupture and one occluding intimal flap, which were treated by the vascular surgeon with bypass and venous patch, respectively. One hematoma at the puncture site was treated surgically because of its size. With modern materials such as steerable guide wires and low-profile balloon catheters, dilation of crural arteries has become safe. Until now, the indications for percutaneous transluminal angioplasty (PTA) of crural arteries have been limited to Fontaine stages III and IV disease. The authors believe that the indications for PTA in Fontaine stage IIb disease are justified, especially if intervention improves outflow after a more proximal recanalizing procedure is performed. 
4	Effect of indecainide in patients with left ventricular dysfunction. Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 +/- 32 mg; half of the responders achieved achieved efficacy at serum drug concentration greater than or equal to 600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p less than 0.04) and inversely related to creatinine clearance (r = 0.74, p less than 0.05) and ejection fraction (r = 0.71, p less than 0.02). Indecainide prolonged mean PR and QRS intervals (p less than 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r = 0.80, p less than 0.001) and QRS (r = 0.66, p less than 0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects. 
1	Evolution of in vitro transformation and tumorigenesis of HPV16 and HPV18 immortalized primary cervical epithelial cells. Cervical carcinoma develops through a progressive spectrum of premalignant intraepithelial lesions (CIN I-III), the majority of which are associated with human papillomavirus (HPV) types 16 and 18. We established HPV16 and HPV18 immortalized human cervical epithelial cell lines and used them as a model to investigate the genesis and progression of cervical malignancy. The cell lines when cultured in vitro in a system mimicking their in vivo environment exhibit cytologic atypia and a variety of defects in morphologic differentiation at early passage compared to their normal counterparts. With increased passage, these alterations progress to more severe grades, histologically similar to CIN III; however only a limited number of the cell lines are tumorigenic, mimicking the epidemiologic evidence on the rate of conversion from premalignant to invasive carcinoma. The observed changes are not associated with alterations of viral DNA integration or expression and may reflect specific cellular events or changes in virus-host interactions associated with malignant progression. 
2	Biphasic modulation of acetaminophen bioactivation and hepatotoxicity by pretreatment with the interferon inducer polyinosinic-polycytidylic acid. Interferons and interferon induction can inhibit cytochromes P-450 and reduce the bioactivation and hepatotoxicity of acetaminophen. However, since P-450 inhibition often is followed by P-450 induction, which would enhance acetaminophen hepatotoxicity, the possibility of a biphasic modulation of acetaminophen hepatotoxicity by interferons was investigated. Outbred male CD-1 mice of various ages, and young inbred male C57BL/6 mice were given the interferon inducer, polyinosinic-polycytidylic acid (Poly I-C), 10 mg/kg intraperitoneally, followed 1 to 48 days later by a single dose of acetaminophen, 300 to 450 mg/kg intraperitoneally. Hepatotoxicity was assessed by the peak plasma concentration of alanine aminotransferase (ALT) occurring between 0 and 48 hr after acetaminophen treatment. Poly I-C inhibited the hepatotoxicity of acetaminophen given within 8 days, with maximal inhibition between 1 and 4 days. Conversely, a maximal 7-fold enhancement of ALT concentration was observed in CD-1 mice when 300 mg/kg of acetaminophen was given 32 days after Poly I-C (P less than 0.05). In the C57BL/6 strain, Poly I-C inhibited the hepatotoxicity of acetaminophen when given within 16 days, whereas a maximal 20-fold enhancement of ALT concentration was observed when 300 mg/kg of acetaminophen was given 24 days after Poly I-C (P less than 0.05). The mechanism of toxicologic enhancement was examined in male C57BL/6 mice using the same treatment regimen. Biochemical assessment of hepatotoxicity was confirmed by detailed histologic evaluation. Plasma concentrations of acetaminophen and metabolites were determined by high-performance liquid chromatography. Acetaminophen bioactivation was quantified by production of the glutathione-derived cysteine and mercapturic acid conjugates of acetaminophen. Poly I-C pretreatment produced a 5-fold increase in acetaminophen-induced ALT release (P less than 0.05), which correlated with histologic evidence of centrilobular necrosis. Poly I-C pretreatment produced respective 3-fold and 1.3-fold increases in the production of cysteine and mercapturic acid conjugates (P less than 0.05), which correlated with peak ALT concentrations (cysteine, r = 0.92, P less than 0.001; mercapturic acid, r = 0.75, P = 0.006). Thus, the hepatotoxicity of acetaminophen can be inhibited when given within days after interferon induction, and conversely enhanced when given after several weeks. The toxicologic enhancement appears to be due to increased P-450-catalyzed bioactivation of acetaminophen. 
5	Identification, prevention, and treatment of silicone oil pupillary block after an inferior iridectomy. We treated two patients in whom silicone oil pupillary block developed despite a patent inferior iridectomy. The clinical characteristics of this complication were a deep anterior chamber, specular reflexes from the iris surface, identification by biomicroscopy of aqueous trapped inferiorly in the vitreous cavity, and no convection currents in the anterior chamber. This complication may be prevented by early face-down positioning of the patient after the operation, and the avoidance of large, centrally located, inferior iridectomies. We recommend that the iridectomy be placed peripherally no larger than 2 mm and propose a new technique for breaking the silicone oil block, which was clearly successful in one of the patients. 
5	Deep venous thrombosis: longitudinal study with duplex US. Forty-nine patients with deep venous thrombosis (DVT) of the lower limb were studied with repeated duplex ultrasound (US) for at least 1 year or until the vein became normal at US. Standard anticoagulant therapy was given for 3 months. In 36 patients, the veins became normal within 1 year. The likelihood of normalization increased if the lesion was located in only one site, if the pelvic veins were unaffected, if the affected leg was the left one, if the initial clot was nonocclusive, if there was no history of DVT, and if the symptoms had lasted less than than 24 hours. The average time before normalization was shorter if the symptoms had lasted less than 24 hours, that is, 11 weeks versus 25 weeks (P less than .02). The rate of sequelae at 1 year was lower if the US scan was normal or showed regression at 3 months, 6% versus 83% (P less than .00005). 
5	Role of leukotriene C4 in mucosal damage caused by necrotizing agents and indomethacin in the rat stomach. Intragastric ethanol stimulates mucosal formation of leukotriene C4 in the rat stomach. The present study demonstrates that the increase in leukotriene C4 formation begins within 30 seconds and is maximal within 5 minutes, closely paralleled by the appearance of hemorrhagic lesions. Leukotriene C4 formation returns to prechallenge levels within 3 hours, although erosions still persist. Intragastric 0.2N NaOH, acidified 100 mmol/L taurocholate, 25% NaCl, or 0.6N HCl did not consistently increase leukotriene C4 formation despite severe mucosal injury. A number of sulfhydryl-containing or sulfhydryl-blocking agents as well as metals protected against mucosal damage and simultaneously prevented the stimulation of leukotriene C4 formation induced by ethanol. None of the agents increased and some virtually abolished mucosal formation of prostaglandin E2, indicating that gastroprotection can occur completely independently of the endogenous prostaglandin system. The leukotriene biosynthesis inhibitor MK-886 markedly suppressed gastric leukotriene C4 formation but did not protect against damage caused by ethanol, NaOH, NaCl, or acidified taurocholate. Oral indomethacin reduced the ex vivo formation of both prostaglandin E2 and, to a lesser extent, leukotriene C4 in the gastric mucosa, inducing a shift in the balance from protective prostaglandins to proulcerogenic leukotriene C4. Pretreatment with MK-886, however, did not significantly diminish indomethacin-induced lesions. These data suggest that leukotriene C4 is not the exclusive mediator of gastric injury caused by necrotizing agents or indomethacin. On the other hand, certain protective compounds exhibit a striking parallelism between protection and inhibition of ethanol-induced leukotriene C4 formation, suggesting that they may affect a target crucial for both mucosal injury and stimulation of 5-lipoxygenase. 
5	Persistent neutrophilic meningitis. Persistent neutrophilic meningitis is an unusual but distinct clinical variant of chronic meningitis characterized by CSF neutrophilia with hypoglycorrhachia which persists for more than 1 week on serial CSF studies. Documented etiologies include selected bacteria and higher bacteria such as Brucella, Nocardia and Actinomyces as well as "opportunistic" fungi such as Candida, Aspergillus, the Zygomycetes, and Pseudallescheria. Recognition of the syndrome is important, as empiric therapy (e.g., cotrimoxazole and amphotericin B) may differ significantly from that used for classic chronic meningitis. 
3	Hyponatraemia in patients with cirrhosis. Hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites, and is due to the excessive retention of free water which results from the kidney's inability to excrete it normally. The morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances. The degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms. Altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy, symptoms of which overlap with hepatic encephalopathy and uraemia. The occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia. The appearance of hyponatraemia in cirrhotic patients, long regarded as a poor prognostic sign, may be a function of unrecognized underlying impaired renal function. Therapy for hyponatraemia remains suboptimal. 
3	Mandibular osteomyelitis in a patient with sickle cell anemia: report of case. A case is presented in which mandibular osteomyelitis and mental nerve paresthesia developed in a patient with sickle cell anemia. This infection appeared to precipitate a sickle cell crisis. The mechanisms for these patients' propensity to infection and the diagnosis and management of sickle cell osteomyelitis of the jaws are discussed. 
2	Cytologic criteria to distinguish hepatocellular carcinoma from nonneoplastic liver. The authors reviewed a series of fine-needle aspiration biopsy (FNAB) specimens of the liver to identify useful cytologic criteria to distinguish hepatocellular carcinoma (HCC) from nonneoplastic liver. Ten cytologic features were examined in this study: high cellularity, acinar pattern, trabecular pattern, hyperchromasia, pleomorphism, irregularly granular chromatin, uniformly prominent nucleoli, multiple nucleoli, increased nuclear/cytoplasmic ratio, and atypical naked hepatocytic nuclei. These features were examined in a series of 82 FNAB specimens from 52 patients with HCC and 30 patients with nonneoplastic lesions. With the use of a step-wise logistic regression analysis, three features were identified as predictive of HCC: increased nuclear/cytoplasmic ratio (P = 0.001), trabecular pattern (P = 0.002), and atypical naked hepatocytic nuclei (P = 0.03). When these three criteria were used, the sensitivity of diagnosing HCC by FNAB was 100%, and the specificity was 87%. 
2	In vitro model of intestinal crypt abscess. A novel neutrophil-derived secretagogue activity. In order to model crypt abscesses, a histological finding which correlates with disease activity in intestinal inflammation, human polymorphonuclear leukocytes (PMN) were layered onto monolayers of the human intestinal epithelial cell line T84, a crypt-like epithelium which is capable of Cl- secretion. Such PMN-epithelial interaction had no substantial effect on monolayer integrity or function. However, when PMN were stimulated by conditions including those present naturally in the human colonic lumen, monolayers responded with a bumetanide-sensitive short circuit current (Isc) indicative of Cl- secretion, the basis of secretory diarrhea. This Isc response was induced by a neutrophil-derived secretagogue (NDS), which was only active when applied to the luminal surface of monolayers and did not require PMN-epithelial contact. NDS activity is resistant to boiling, acid, and trypsin and passes a 500 nominal mol wt cutoff filter. NDS activity is not secondary to the respiratory burst products O2- or H2O2 and does not appear to be a myeloperoxidase product. We speculate NDS elicited Cl- secretion may contribute to the secretory diarrhea seen in patients with intestinal inflammation and crypt abscesses. 
5	Right-to-left shunt across a patent foramen ovale caused by cardiac tamponade: diagnosis by transesophageal echocardiography. Cardiac tamponade can manifest as profound hypoxemia from intracardiac shunting across a patent foramen ovale. As a consequence, pulmonary embolus can be erroneously diagnosed. As demonstrated in the case described herein, transesophageal echocardiography can be useful in determining the correct diagnosis, especially if transthoracic echocardiography is technically limited. In our patient, the findings on transesophageal echocardiography also helped determine the appropriate treatment. The relative inaccessibility of the pericardial effusion to needle drainage prompted open surgical drainage. 
2	Radiographic evaluation of suspected small bowel obstruction. Plain abdominal radiographs and enteroclysis studies were reviewed blindly in 117 consecutive patients undergoing enteroclysis for suspected small bowel obstruction. Plain radiographs were unreliably predictive of the presence of obstruction as determined by enteroclysis and surgery. Among patients with normal or abnormal nonspecific plain radiographs, varying degrees of small bowel obstruction were demonstrated by enteroclysis in 22%. Conversely, of patients with obstruction on plain radiographs, 42% had either normal enteroclysis studies or only minor adhesions. Enteroclysis correctly predicted the presence of obstruction in 100%, the absence of obstruction in 88%, the level (proximal vs distal) of obstruction in 89%, and the etiology of obstruction in 86% of operated patients. Enteroclysis is advocated as the definitive study in patients with clinical uncertainty about the diagnosis of small bowel obstruction. 
4	An overview of intimal hyperplasia. Many hypotheses have been postulated for the development of intimal hyperplasia in vein and prosthetic grafts. In these hypotheses, the central theme seems to be endothelial injury, but not always denuding injury. As we progress into the biologic era with more sophisticated research tools, the study of the endothelial cell may give us the answers to the problem of intimal hyperplasia. In addition, the leukocyte is still a relatively unknown entity and further modification of their function may hold promise. 
5	Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent. 
3	Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study. Thirty-nine falciparum malaria autopsy cases from the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand were divided into two groups that had had either cerebral malaria (CM) or non-cerebral malaria (NCM). We then studied significant pathological differences between these groups in order to investigate the correlation between parasitized erythrocyte (PRBC) sequestration in small blood vessels in the brain, heart, lungs and small intestines. We found that the percentage of PRBC sequestration in the organs which we studied was higher in the CM patients than in the NCM patients. The difference of PRBC sequestration among the organs of two groups was significant (P less than 0.05). In the CM group, the average percentage of PRBC sequestration in the brain was significantly higher than in the heart, lungs and small intestines (P less than 0.05). No statistically significant difference was found between PRBC sequestration in the brains, hearts, lungs and small intestines in the NCM group (P greater than 0.05). Our study indicates that severity of malaria in the CM patients depends on PRBC sequestration, especially in the brain. A combination of functional disturbances of the other organs, in addition to the cerebral pathology, may augment the severity of the disease. 
3	Traumatic asphyxia. Traumatic asphyxia is a distinctive clinical syndrome characterized by cervicofacial cyanosis and edema, multiple petechiae, and subconjunctival hemorrhage after a severe crush injury of the thorax or of the upper part of the abdomen. A case of traumatic asphyxia is reported, and its clinical and pathophysiologic features are discussed. 
5	Image cytophotometric DNA analysis of atypical hyperplasias and intraductal carcinomas of the breast. With the use of image analysis, DNA content was quantified on paraffin-embedded tissue sections of 25 atypical hyperplasias and 35 intraductal carcinomas of the breast by comparison of integrated gray levels of Feulgen-stained control and ductal cell nuclei. The mean full-peak (G0/G1) control cell DNA histogram coefficient of variation was 5.5%. DNA aneuploidy was more common in intraductal carcinomas compared with atypical hyperplasias (71% of intraductal carcinomas vs 36% of atypical hyperplasias) and correlated with a lack of cytologic (nuclear) and architectural differentiation (63% moderate vs 93% poor and 38% cribriform vs 82% solid). In addition, multiple DNA stemlines were observed in 40% of intraductal carcinomas. We conclude that (1) some atypical hyperplasias demonstrate abnormal DNA content consistent with neoplastic transformation, (2) aggressive forms of intraductal carcinoma are more frequently associated with DNA content abnormalities, and (3) frequent DNA stemline heterogeneity in intraductal carcinoma supports the hypothesis that multiple genetic events occur in the development of mammary intraepithelial neoplasia. 
1	Intraosseous lipoma within the femoral head. A case report. Intraosseous lipoma occurring within the femoral head seems not to have been previously reported. Symptoms associated with the tumor included slowly increasing pain and a cystic lesion shown on roentgenograms. Management was by total hip arthroplasty. Pathologic examination of the specimen showed that the tumor was composed almost entirely of mature adipose tissue in keeping with a diagnosis of Stage 1 intraosseous lipoma. A sclerotic border and osteoid seams were noted, two features that seem not to have been previously reported in early lesions. Recent papers suggest intraosseous lipomas are more common than previously thought, and the femur now accounts for 25% of reported cases. 
5	Restenosis after directional coronary atherectomy: differences between primary atheromatous and restenosis lesions and influence of subintimal tissue resection. Rates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions. After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01). Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histologically identical to restenotic tissue developing after balloon angioplasty (n = 37). These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions. 
5	Post-traumatic basal ganglia hemorrhage: analysis of 52 patients with emphasis on the final outcome. A series of 52 patients suffering post-traumatic basal ganglia hemorrhage (BGH) after closed head injury is reviewed. Post-traumatic BGH was associated with other intracranial lesions in most cases. The outcome in this series is rather good, with 53.8% of patients having a functional survival. Radiologically, the post-traumatic intraventricular hemorrhage (IVH) and brainstem hemorrhage usually coexisted with a poor outcome. Old age (greater than 60), abnormal pupil reaction, impaired oculocephalic response, and abnormal motor response to pain stimuli are reliable clinical hallmarks for poor prognosis. 
3	Seizures and other neurologic sequelae of bacterial meningitis in children. BACKGROUND. Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS. We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS. One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS. After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy. 
5	Cavernous-carotid thrombosis and ocular motor paresis A 64-year-old man presented with the acute onset of unilateral blindness and ipsilateral ocular motor paresis. Occlusion of the central retinal artery associated with thrombosis of the internal carotid artery in the cavernous sinus was demonstrated by angiography and magnetic resonance imaging. Cases of carotid thrombosis associated with ipsilateral ocular motor paresis are rare. The pathophysiology of intracavernous carotid thrombosis is discussed in connection with blood supply of the cranial nerves in the cavernous sinus. 
1	Titrated intravenous barbiturates in the control of symptoms in patients with terminal cancer. Patients with terminal cancer may have a series of severe and dehumanizing physical and psychologic symptoms. To improve symptom control in the final days and hours of life, we administer intravenous barbiturates continuously to provide heavy sedation or continuous somnolence. Titrated dosage is then reduced to a minimum, after a desired steady-state has been achieved. Improved symptom control is provided, and the patient's dignity is maintained until death. 
5	Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. BACKGROUND. Malignant soft-tissue tumors often present substantial diagnostic challenges. Chromosome aberrations that might be diagnostic have been identified in some types of soft-tissue tumors, but the overall frequency and diagnostic relevance of these aberrations have not been established. METHODS. We attempted to determine the karyotypes of a series of 62 consecutive, unselected malignant spindle-cell or small round-cell soft-tissue tumors (from 46 adults and 16 children) after direct harvesting of cells or short-term culture. All tumors were examined independently by immunohistochemical staining in addition to routine light-microscopical evaluation, and all but two tumors were examined by electron microscopy. RESULTS. Metaphases were obtained from 61 of the 62 tumors, and clonal chromosome aberrations were identified in 55 (89 percent). In the six tumors that yielded metaphases but lacked apparent clonal aberrations, the normal metaphases were found to originate from non-neoplastic stromal elements within the tumor specimens. Thus, all tumors in which karyotyping was successful contained clonal chromosome aberrations. Forty of 62 tumors (65 percent) contained clonal chromosome aberrations that either suggested or confirmed a specific diagnosis; in 15 of these tumors (24 percent of all tumors), the aberrations were important in establishing the final diagnosis. Cytogenetic analyses were particularly informative about small round-cell tumors from children: 8 of 14 round-cell tumors contained diagnostically important chromosome aberrations. Using the combined approaches of light and electron microscopy, immunohistochemistry, and cytogenetics, we established an unambiguous diagnosis for 60 of 62 tumors. CONCLUSIONS. Cytogenetic analyses reveal clonal chromosome aberrations in virtually all malignant soft-tissue tumors. These clonal chromosome aberrations, particularly in small round-cell tumors in children, often have diagnostic relevance. 
1	Adjuvant topical chemotherapy versus immunotherapy in primary superficial transitional cell carcinoma of the bladder. In a prospective randomised controlled study, the efficacy of ethoglucid was compared with that of keyhole-limpet haemocyanin (KLH) in preventing recurrent tumours following transurethral resection of primary superficial transitional cell carcinoma of the bladder. Patients treated with ethoglucid (n = 39) received 0.565 g (1% solution) ethoglucid weekly for 6 weeks and then monthly for 1 year. Patients treated with KLH (n = 38) were immunised subcutaneously with 1 mg KLH; bladder instillations of 30 mg were then given weekly for 6 weeks and thereafter monthly for 1 year. The recurrence rates, disease-free intervals and tumour progression rates were evaluated. The end-point of the study was either progression in stage or grade or more than 1 recurrence during the observation period. The minimum length of follow-up was 1 year. The recurrence rates, mean disease-free intervals and progression rates in the 2 groups showed no statistically significant differences. 
4	Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study [published erratum appears in JAMA 1991 Jun 26;265(24):3249] We report here the 14-year sex-specific effect of non-insulin-dependent diabetes mellitus on the risk of fatal ischemic heart disease in a geographically defined population of men and women aged 40 through 79 years. There were 207 men and 127 women who had diabetes at baseline based on medical history or fasting hyperglycemia. They were compared with 2137 adults who had fasting euglycemia and a negative personal and family history of diabetes. The relative hazard of ischemic heart disease death in diabetics vs nondiabetics was 1.8 in men and 3.3 in women, after adjusting for age, and 1.9 and 3.3, respectively, after adjusting for age, systolic blood pressure, cholesterol, body mass index, and cigarette smoking using the Cox regression model. The sex difference in the independent contribution of diabetes to fatal heart disease was largely explained by the persistently more favorable survival rate of women (than men) without diabetes. 
2	Intestinal pseudoobstruction secondary to amyloidosis responsive to cisapride. A case of chronic intestinal pseudoobstruction secondary to systemic amyloidosis in a patient with multiple myeloma is described. Gastrointestinal symptoms and indices of nutrition improved markedly after commencing treatment with cisapride, which may have been responsible for relatively prolonged survival compared with similar reported cases. 
4	Current status of antitachycardia devices. With the limitations of currently available modalities for treating clinically important tachycardias, the role of implanted antitachycardia devices will continue to expand. The challenge of the future will not only involve continued technological advances but the socioeconomic impact of this efficacious but expensive mode of therapy in an era of increasing financial restraints. Further studies to definitively prove the efficacy of more widespread use of antitachycardia device therapy will be needed. 
3	Superiority of transesophageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology. The diagnostic yield of transesophageal and transthoracic echocardiography for identifying a cardiac source of embolism was compared in 79 patients presenting with unexplained stroke or transient ischemic attack. There were 35 men and 44 women with a mean age of 59 years (range 17 to 84); 52% had clinical cardiac disease. Both transthoracic and transesophageal echocardiograms were performed using Doppler color flow and contrast imaging. Transesophageal echocardiography identified a potential cardiac source of embolism in 57% of the overall study group compared with only 15% by transthoracic echocardiography (p less than 0.0005). Compared with transthoracic echocardiography, transesophageal echocardiography more frequently identified atrial septal aneurysm associated with a patent foramen ovale (9 versus 1 of 79 patients, p less than 0.005), left atrial thrombus or tumor (6 versus 0 of 79 patients, p less than 0.05) and left atrial spontaneous contrast (13 versus 0 of 79 patients, p less than 0.0005). All cases of left atrial thrombus or spontaneous contrast were identified in patients with clinically identified cardiac disease. In the 38 patients with no cardiac disease, transesophageal echocardiography identified isolated atrial septal aneurysm and atrial septal aneurysm with a patent foramen ovale more frequently than transthoracic echocardiography (8 versus 2 of 38 patients, p less than 0.05). The two techniques had a similar rate of identifying apical thrombus and mitral valve prolapse. Overall, transesophageal echocardiography identified abnormalities in 39% of patients with no cardiac disease versus 19% for transthoracic echocardiography (p less than 0.005). Thus, transesophageal echocardiography identifies potential cardiac sources of embolism in the majority of patients presenting with unexplained stroke. 
5	High-frequency oscillatory ventilation compared with conventional intermittent mechanical ventilation in the treatment of respiratory failure in preterm infants: neurodevelopmental status at 16 to 24 months of postterm age. The HIFI Study Group. The High-Frequency Intervention Trial was a 10-center randomized clinical trial to test the efficacy and safety of high-frequency oscillatory ventilation (HFO) in the treatment of neonates weighing 750 to 2000 gm; 327 infants were assigned to HFO and 346 to conventional intermittent mechanical ventilation (IMV). Survival and lung morbidity rates were the same in the two groups. Bayley psychometric evaluations and CNS examination were performed at 16 to 24 months of postterm age in 77% of the survivors (185 HFO and 201 IMV). There was no difference in growth or respiratory status at follow-up. Cerebral palsy was diagnosed in 19 (10%) HFO-treated infants and 23 (11%) IMV-treated infants. There was no difference in severity between the two groups. A significantly higher incidence of hydrocephalus (12% vs 6%) was present in the HFO group (p less than 0.05). Bayley index scores greater than 83 were scored in 57% of HFO-treated infants compared with 66% of IMV-treated infants. The proportion of children at follow-up with a normal neuro-developmental status (i.e., Bayley score greater than 83 and no major CNS defect) was significantly less in the HFO than in the IMV group (54 vs 65%; p less than 0.05). Both treatment groups showed a strong association between the presence of grade 3 or 4 intraventricular hemorrhage and the development of major CNS or cognitive defects. No significant long-term beneficial or deleterious effects were demonstrated in the use of HFO versus IMV for the treatment of respiratory failure in low birth weight premature infants, except that there were slightly more neurologic deficits in the HFO group related to the higher proportion of survivors with major intraventricular hemorrhage. 
5	Ehrlichiosis in children. Tick-borne rickettsiae of the genus Ehrlichia have recently been recognized as a cause of human illness in the United States. In the years 1986-1988, 10 cases of ehrlichiosis were diagnosed in children in Oklahoma. Fever and headache were universal: myalgias, nausea, vomiting, and anorexia were also common. Rash was observed in six patients but was a prominent finding in only one. Leukopenia, lymphopenia, and thrombocytopenia were common laboratory abnormalities. Six patients were treated with tetracycline, three with chloramphenicol, and one was not treated with antibiotics: all recovered. The onset of illness in spring and early summer for most cases paralleled the time when Amblyomma americanum and Dermacentor variabilis are most active, suggesting that one or both ticks may be vectors of human ehrlichiosis in Oklahoma. 
5	Squamous carcinoma of the posterior pharyngeal wall. We have reviewed a 12-year experience with 295 patients treated for squamous carcinoma of the pharynx in order to focus on 78 patients whose lesions arose in the posterior wall. Surgery was the definitive therapy for the primary tumor in 57 (73%), including 3 treatment groups. Thirty-two patients had limited resections that preserved the larynx, involving local excision (7 patients), anterior pharyngotomy (7 patients), lateral pharyngotomy (6 patients), median labiomandibular glossotomy (6 patients), or median mandibulotomy with paralingual extension (6 patients). The second group consisted of 21 patients with more extensive tumors who required a laryngectomy and complex reconstruction, often with postoperative radiotherapy. Finally, there were four patients who developed metachronous second primaries in the pharynx subsequent to a laryngectomy. All required flap reconstruction. Of the 21 patients whose primary treatment was radiotherapy, 5 had lesions that were implanted after access was provided by a mandibulotomy. Cumulative 5-year survival was 32% and ranged from 44% in those with favorable lesions to 15% in those with extensive tumors. Our experience highlights the variety of treatment approaches available in patients with pharyngeal carcinomas confined to the posterior wall. Surgery in this setting carries acceptable morbidity and yields survival rates that compare favorably with those achieved by external radiation therapy alone. Results in patients with extensive lesions still leave much to be desired, despite radical surgery and aggressive radiotherapy. Innovative brachytherapy techniques using surgery for access deserve further investigation. 
2	CT diagnosis of acquired small bowel volvulus. Small-bowel volvulus is an uncommon but important cause of small-bowel obstruction and often results in ischemia or infarction. Clinical examination and plain film radiography may be nondiagnostic, leading to delay in surgical intervention with subsequent increase in morbidity and mortality. We present two patients in whom the diagnosis of strangulating small-bowel volvulus was made by computed tomography (CT), allowing rapid surgical correction of this potentially life-threatening condition. 
2	A pitfall in azygos vein cannulation in cirrhotic patients: mistaken cannulation of the mammary vein. Azygos venous flow can be measured by a thermodilution catheter in patients with cirrhosis. This is a useful technique since azygos flow is thought to reflect the superior portosystemic collateral flow in these patients. The authors report 3 cases in which mistaken internal mammary vein cannulation mimicked azygos vein cannulation in the supine fluoroscopic view. A lateral fluoroscopic view confirmed internal mammary cannulation. They suggest that if the azygos arch is unpronounced or flow measurements are unexpectedly low in patients with portal hypertension due to cirrhosis, a lateral view be performed to rule out internal mammary vein cannulation. 
5	Adenocarcinoma arising in a foregut cyst of the mediastinum. A case of malignant transformation in a mediastinal cyst of the esophageal reduplication type is presented. The cyst had been recognized 39 years previously, but remained asymptomatic until sudden growth occurred. It was resected totally from the esophagus and the patient recovered well. A review of the literature showed that malignancy in mediastinal foregut cysts is extremely rare. 
1	Flow cytometric evaluation of chemosensitive and chemoresistant head and neck tumors. For patients with head and neck squamous carcinoma, a clinical response to induction chemotherapy has correlated with a survival advantage. Similarly, patients with diploid tumors have displayed a survival advantage when compared with patients with aneuploid tumors. This study examined DNA content in 33 patients who had undergone induction chemotherapy as part of two clinical protocols to determine if there was a correlation between the patients with diploid tumors and the patients with a clinical response to chemotherapy. Although patients with stage III tumors had a longer disease-free survival than stage IV patients (p less than 0.0002), the addition of DNA content information did not improve the ability to predict response. Specifically, there was no correlation between DNA content and the response to chemotherapy. In addition, for this group of patients, a diploid DNA content was not correlated with a survival advantage. We conclude that DNA content information did not add significantly to the prediction of clinical outcome in these patients who received induction chemotherapy. 
5	An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval. 
5	Rapid percutaneous tracheostomy We describe a new method of performing percutaneous tracheostomy rapidly and safely using a specialized instrument kit. The technique permits the safe insertion of a full-sized 7.0 (ID) or 7.5 mm (ID) cuffed cannula into the trachea within 1-2 min, through the membranous second intercartilagenous space. Animal studies have demonstrated a superior healing process compared to that seen after conventional tracheostomy techniques. 
4	Portal venous gas in a patient with Crohn's disease. Portal venous gas usually occurs in the setting of an acute abdomen. Several causes for benign portal venous gas (PVG) have been reported. We describe the finding of PVG by computed tomography in a febrile patient with Crohn's disease and discuss the clinical implications of such a finding. 
3	Medicare Peer Review Organization preprocedure review criteria. An analysis of criteria for three procedures The Medicare Peer Review Organization (PRO) program includes preprocedure review using explicit criteria to assess the appropriateness of specific procedures. This study evaluates the variability in the PRO preprocedure criteria for the three procedures most frequently reviewed by PROs: carotid endarterectomy, cataract removal, and cardiac pacemaker implants. In August 1989, the PRO review criteria were received from the Health Care Financing Administration. To provide a reference point for reviewing the PRO criteria, national practice guidelines for these three procedures were identified. Wide variability was demonstrated in the PRO procedure-specific carotid endarterectomy and cataract removal review criteria among PROs, and the criteria differed significantly from the identified practice guidelines. The criteria for cardiac pacemaker implants were somewhat less variable, and were based, to varying degrees, on practice guidelines developed by the American College of Cardiology (ACC). Greater attention is needed to improve the development of review criteria, including the use of relevant practice guidelines, to ensure that review criteria are optimal. 
1	Adjuvant antiestrogen therapy for breast cancer. Past, present, and future. Laboratory investigations using animal models of breast cancer growth have indicated that the antiestrogenic compound tamoxifen is a tumoristatic agent. It is therefore effective in suppressing, rather than destroying, the breast tumor. Its use as an adjuvant in breast cancer management has been successful, with a proportion of women benefiting from long periods of tamoxifen treatment. All the initial studies recruited postmenopausal women, but tamoxifen is now proposed for the treatment of premenopausal women for an extended time. Naturally, there are many aspects of the toxicology of tamoxifen to consider; however, careful monitoring of clinical trials will determine the safety of the drug for the general patient population. 
4	A positron emission tomographic comparison of pulmonary vascular permeability during the adult respiratory distress syndrome and pneumonia. We measured extravascular density (EVD) and the pulmonary transcapillary escape rate (PTCER) for 68Ga-transferrin using positron emission tomography in 14 normal volunteers and 29 patients with radiographic infiltrates, including six patients with congestive heart failure (CHF), eight patients with the adult respiratory distress syndrome (ARDS), and 15 patients with focal pneumonia. Contralateral, radiographically normal regions were also evaluated in the patients with focal pneumonia. Mean EVD was elevated in the patients with CHF, ARDS, and pneumonia in regions of radiographic infiltrate compared with values from normal subjects (p less than 0.05), but it was not significantly different among the three patient groups. PTCER in normal subjects and in patients with CHF was not significantly different (21 +/- 11 versus 44 +/- 16 x 10(-4) min-1, respectively, p = NS). PTCER was elevated in regions of infiltrate because of either pneumonia (173 +/- 99) or ARDS (170 +/- 79). PTCER was also elevated in regions contralateral to those with focal infiltrate during pneumonia, even though these regions were radiographically normal and had normal EVD values. These results suggest that PTCER is a sensitive but nonspecific index of abnormal pulmonary vascular permeability, which may be useful for classifying patients in clinical studies of pulmonary edema. 
4	Effects of fish-oil ingestion on cardiovascular risk factors in hyperlipidemic subjects in Israel: a randomized, double-blind crossover study. Effects of a daily fish-oil supplement on serum lipids, apolipoproteins, and some platelet functions and hemorheologic variables were examined in 27 hyperlipidemic subjects in a randomized, controlled, double-blind, crossover fashion with an identically encapsulated vegetable oil serving as the control treatment. Despite the habitual high linoleic acid intake of the study population, significant incorporation of n-3 (omega-3) fatty acids into the serum, platelet, and erythrocyte lipids was observed after the fish-oil supplement. Ingestion of fish oil resulted in a 40% decrease in the triglyceride concentration, a 12% increase in HDL cholesterol, and a significant decrease in plasma viscosity, whereas the vegetable-oil placebo had no significant effect. We conclude that a moderate intake of fish oil (15 g/d) is a feasible treatment for hypertriglyceridemia even in patients with a background of high linoleic acid intake and that it may have a beneficial effect on several cardiovascular risk factors. 
5	Mesial temporal sclerosis: pathogenesis, diagnosis, and management. Mesial temporal sclerosis (MTS) is probably the most common symptomatic pathologic entity--alone or mixed with other pathologic features--for seizures of temporal lobe origin. The pathophysiology of MTS, including any genetic influence, needs clarification. A characteristic ictal expression for seizures of MTS origin appears not to exist. The majority of patients (78%) with postresection MTS who are seizure-free have tightly localized interictal abnormalities restricted to F7/F8, Sp1/Sp2, T3/T4, and T5/T6 more than 96% of the time. MRI abnormalities may be seen in 55% of patients with MTS if both "hard" and "soft" criteria are used or in 20% when only "hard" criteria are used. The neuropsychologic evaluation of patients with MTS, which includes intracarotid amobarbital test (IAT), may prove to be increasingly useful in identifying patterns of cognitive deficit that correlate with enhancement of both lateralizing and localizing preoperative information. 
3	Cerebrospinal fluid dynamics in the tardive cauda equina syndrome of ankylosing spondylitis. Typical cauda equina syndrome secondary to long-standing ankylosing spondylitis is reported in a 63-year-old man. Radionuclide cisternography demonstrated a resorption defect of cerebrospinal fluid in the enlarged lumbosacral dural sac. After transient symptomatic improvement with acetazolamide, a lumboperitoneal shunt was placed. The rate of cerebrospinal fluid, isotope resorption became normal. In the 5 years of follow-up, partial remission has been observed. 
5	Infrarenal abdominal aortic disease: a review of the retroperitoneal approach. Transabdominal exposure is the most widely used surgical approach to the infrarenal aorta. Over the last 30 years a number of surgeons have championed the retroperitoneal approach for repair of abdominal aortic aneurysms and aortoiliac occlusive disease using a variety of incisions. Several studies attest to the clinical superiority of this approach over the transabdominal route and recent evidence demonstrates reduced physiological disturbance with this technique. The retroperitoneal approach is suitable for all elective operations on the abdominal aorta, particularly in patients with high-risk aneurysms and in selected patients with symptomatic and ruptured aneurysms. 
2	Perirectal abscess in Crohn's disease. Drainage and outcome. The role of surgical intervention in the treatment of patients with anorectal Crohn's disease is controversial. To clarify the success of aggressive drainage and the subsequent clinical course of patients with Crohn's disease and perirectal abscesses, the authors reviewed the records of 38 patients who presented with this condition during an eight-year period. Twenty-two male and 16 female patients (median age, 32 years; range, 17 to 61 years) with clinically or pathologically confirmed Crohn's disease of the bowel underwent operation for perirectal abscesses. Thirty-two percent of patients had no previous history of anorectal Crohn's disease. Thirty simple abscesses and 8 complex horseshoe abscesses were treated. At operation, 53 percent of patients underwent incision and drainage whereas 26 percent received loop indwelling drains and 21 percent had mushroom catheters placed. After resolution of the index abscess, recurrent abscesses occurred in 45 percent of the patients who underwent catheter drainage and 56 percent of the patients who underwent incision and drainage. More importantly, 44 percent of the incision and drainage group and only 31 percent of the catheter drainage group required subsequent proctectomy to control perineal sepsis. The healing time of the perineal wound was longer than six months in 83 percent of patients requiring rectal excision. We concluded that long-term catheter drainage may offer substantial benefit in the overall outcome of the treatment of patients with Crohn's disease and perirectal abscess. 
5	Changes in the postenteropathic form of the hemolytic uremic syndrome in children. An analysis was made of clinical and laboratory findings in children with the diarrheal form of the hemolytic uremic syndrome (HUS) treated at The Children's Hospital, Birmingham between 1970 und 1987. From 1982 the rate of referral increased, the prodromal illness more often consisted of bloody diarrhea, and the mean age at presentation doubled from 2 to 4 years. For patients with a good outcome there was an excess of males in the period 1970-81, and females in the period 1982-87. Moreover, in the years 1982-87 the disorder was distinguished from that of the earlier time by a positive correlation between adverse outcome and both neutrophil leukocytosis and a higher hemoglobin concentration at presentation. Prognostic scores obtained by logistic regression analysis were specific for each period. From July 1983 stool samples were analyzed for verocytotoxin-producing Escherichia coli (VTEC) and neutralizable verotoxin. Positive results were obtained in 39% of cases. The nature of HUS has changed and the new form of the disorder is associated with VTEC infection. 
5	Surgical presentation of Kawasaki disease (mucocutaneous lymph node syndrome). Five patients with Kawasaki disease (mucocutaneous lymph node syndrome) are reported whose varied presentations included acute abdominal pain, peripheral arterial aneurysms, digital gangrene and sterile pyuria and whose presenting pathology ranged from hydrops of the gallbladder to enteric pseudo-obstruction. As the complications of the disease can usually be managed without resort to surgery, which is associated with a mortality rate of up to 25 per cent, the recognition of Kawasaki disease will prevent hazardous and unnecessary laparotomy. 
1	Role of mastectomy in breast cancer. The surgical management of breast cancer continues to evolve in an attempt to define the ideal line between therapeutic efficacy and morbidity. It is clear that breast cancer is a biologically heterogeneous group of diseases, and no single hypothesis explains its behavior. The surgical options proposed to the individual patient must draw from the experience of retrospective clinical studies and prospective randomized trials in an attempt to optimize the treatment plan. Most patients without distant disease are eligible to consider mastectomy, which can accomplish excellent local control and significantly improve survival for earlier stages of disease. However, breast conservation remains an appropriate alternative for a carefully defined subset of patients. Today, with early-stage disease, no patient need leave the operating room without a breast. Recent advances in reconstructive surgery make mastectomy with immediate reconstruction or limited resection plus axillary dissection with postoperative radiation therapy the two principal treatment choices available. Future studies will focus on the integration of other treatment modalities. Clinical research into the use of preoperative chemotherapy to downstage the disease to permit less extensive surgery is of interest. Recent application of molecular biologic techniques such as oncogene analysis, cytogenetic studies, proliferative indices, and the highly sensitive detection of distant micrometastases using monoclonal antibodies may assist in the design of innovative approaches to surgery, radiation therapy, and systemic drug treatment. These advances show great promise for improving the quality of life and the cure rate for patients with breast cancer. Today, surgical treatment options have evolved that fulfill some of the objectives outlined by Dr. James Ewing of Memorial Hospital some 50 years ago. His concerns about breast cancer remain as relevant today as they were half a century ago: "I have drawn the impression that in dealing with mammary cancer, surgery meets with more peculiar difficulties and uncertainties than with almost any other form of the disease. The anatomical types are so numerous, the variations in clinical course so wide, the paths of dissemination so free and diverse, the difficulties of determining the actual conditions so complex, and the sacrifice of tissues so great, as to render impossible in the majority of cases a reasonably accurate adjustment of a means to an end.". 
3	Fetal alcohol syndrome in adolescents and adults. Fetal alcohol syndrome is a specific recognizable pattern of malformation. Manifestations in 61 adolescents and adults suffering from alcohol teratogenesis are presented. After puberty, the faces of patients with fetal alcohol syndrome or fetal alcohol effects were not as distinctive. Patients tended to remain short and microcephalic, although their weight was somewhat closer to the mean. The average IQ was 68, but the range of IQ scores widely varied. Average academic functioning was at the second- to fourth-grade levels, with arithmetic deficits most characteristic. Maladaptive behaviors such as poor judgment, distractibility, and difficulty perceiving social cues were common. Family environments were remarkably unstable. Fetal alcohol syndrome is not just a childhood disorder; there is a predictable long-term progression of the disorder into adulthood, in which maladaptive behaviors present the greatest challenge to management. 
3	From disease to delirium: managing the declining elderly patient. Many geriatric patients have concurrent physical and psychiatric illnesses, but at times it may be difficult to determine which is primary. Delirium, a transient syndrome that presents with psychiatric symptoms, is usually the manifestation of an organic disorder and, if undetected and untreated, can be fatal. Clinicians, therefore, must learn to recognize the syndrome, search diligently for the underlying etiology, and treat accordingly. 
4	A comparison of coarctation resection and subclavian flap angioplasty using ultrasonographically monitored postocclusive reactive hyperemia The reported relatively high incidence of early restenosis at the coarctation repair site with subclavian flap angioplasty, especially in infants less than 3 months of age, prompted a physiologically oriented analysis of relief of obstruction from coarctation after subclavian flap angioplasty versus resection and end-to-end anastomosis in infancy. Twenty-one patients who had undergone repair of coarctation in infancy by either subclavian flap angioplasty (nine patients) (median age 8 years) or resection and end-to-end anastomosis (12 patients) (median age 8 years) were evaluated by Doppler spectrum analysis of the blood flow velocities in the femoral artery at rest and during reactive hyperemia. The median resting right upper to lower limb systolic pressure difference (with interquartile range) was similar in the angioplasty, resection and anastomosis, and control groups: -5 mm Hg (18 mm Hg), 0 mm Hg (12 mm Hg), and -2.5 mm Hg (10 mm Hg), respectively. Also, similar resting values for the maximum frequency of the advancing curve and the pulsatility and resistance indices were measured in the three groups. During reactive hyperemia of the leg, however, a significant hemodynamic obstruction across the repair site became clinically manifest in the angioplasty group only, as documented by a lower pulsatility index in comparison with the control group (p = 0.01, Mann-Whitney U test). Comparison of the hemodynamic results between the angioplasty and resection and anastomosis groups in subdivisions of infants operated on at an age of less or greater than 3 months, both at rest and during reactive hyperemia, showed, already at rest, a significantly lower value for the pulsatility index in the former angioplasty subdivision (p = 0.05, Student's t test), indicating a significant resistance at the coarctation repair site in the angioplasty patients operated on before the third month of life. A disadvantage of angioplasty (compared with resection and anastomosis) was noted when angioplasty was performed before the third month of life, and an unequivocal lack of advantage was noted when performed beyond that period regarding relief of obstruction from coarctation. In addition, a definite potential for adverse long-term effects on the hemodynamics of the left upper limb after subclavian flap angioplasty in infancy has been documented. For these reasons we prefer to perform resection and end-to-end anastomosis for repair of coarctation in infancy. 
2	Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation. A newly identified condition. A newly identified myopathy of the internal anal sphincter is described. In the affected family, at least one member from each of five generations had severe proctalgia fugax; onset was usually in the third to fifth decades of life. Three members of the family have been studied in detail. Each had severe pain intermittently during the day and hourly during the night. Constipation was an associated symptom, in particular difficulty with rectal evacuation. Clinically the internal anal sphincter was thickened and of decreased compliance. The maximum anal canal pressure was usually increased with marked ultraslow wave activity. Anal endosonography confirmed a grossly thickened internal anal sphincter. Two patients were treated by internal anal sphincter strip myectomy; one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain. The hypertrophied muscle in two of the patients showed unique myopathic changes, consisting of vacuolar changes with periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium, and electrical-field stimulation. Immunohistochemical studies for substance P, calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue. A specific autosomal-dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized. 
1	Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer. Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. Complications from bacillus Calmette-Guerin therapy are usually minor but serious and even fatal reactions can occur. Five recent cases illustrate the gravity of bacillus Calmette-Guerin sepsis. One man with severe debility and the organic brain syndrome died acutely with a fever of 40 C. Two men had frank sepsis that progressed to multiorgan failure and death. Sepsis progressed despite the use of isoniazid, rifampin and streptomycin. Two men who had equally progressive sepsis with intravesical bacillus Calmette-Guerin survived with the use of cycloserine for the first 72 hours of treatment. Triple antituberculous antibiotics, including cycloserine, may be lifesaving. Sepsis resulted from intravenous absorption through inflamed or disrupted urothelium. Bacillus Calmette-Guerin treatment should not be administered in the presence of severe cystitis or after grossly traumatic catheterization. 
4	Results of intracoronary stents for management of coronary dissection after balloon angioplasty. Dissections after coronary balloon angioplasty are risk factors for acute or subacute vessel closures. Intracoronary stenting was developed to avoid these complications by pressing the intimal and medial flaps against the vessel wall, thus reducing the risk of acute thrombosis. A total of 22 stents were implanted into the coronary arteries of 15 patients with dissections after balloon angioplasty causing angina pectoris or ischemic electrocardiographic changes. Stent delivery was successful in all cases. In 1 patient acute stent thrombosis was documented and treated successfully by thrombolytic therapy. Another patient underwent coronary artery bypass surgery 24 hours later because of persisting angina. Angiograms after 24 hours documented vessel patency in the remaining 14 patients. Late control angiograms after 4 to 6 months were obtained in 12 of 14 patients. Vessel patency without significant restenosis was observed in 8 patients, restenosis in 3 and reocclusion in 1 patient. All 3 patients with multiple stent implantation had restenosis (n = 2) or reocclusion (n = 1), compared with 1 patient with single stent implantation. Thus, intracoronary stenting appears to be a secure and effective method of handling bailout situations caused by dissection after balloon angioplasty, with good long-term results when only a single stent is implanted. 
1	Estimation of PR and ER by immunocytochemistry in breast cancer. Comparison with radioligand binding methods. Immunocytochemical assays for progesterone receptor (PR) using monoclonal antirabbit PR antibodies (PR-ICA) and for estrogen receptor (ER) (ER-ICA) were compared with radioligand binding (dextran-coated charcoal [DCC]) methods for receptor determination in patients with breast cancer. Immunocytochemical staining for PR was exclusively nuclear in localization. In this regard, PR staining is similar to previous findings for ER; PR-ICA showed a sensitivity of 89% and specificity of 100%. ER-ICA was also 89% sensitive and similarly specific. There was good correlation between the degree and intensity of staining and quantitative binding of radioligand. Receptor-positive tumors, however, show considerable variation of immunocytochemical staining, suggesting heterogeneity of cellular PR content. The availability of an immunocytochemical assay for PR increases the discriminatory potential for these methods of receptor determination. 
2	Cimetidine suppresses chemically induced experimental hepatic porphyria. The ability of cimetidine to reduce the activity of hepatic aminolevulinic acid synthase (ALA-S) was examined in allylisopropyl acetamide (AIA) treated porphyric adult rats. A dose of 20 mg cimetidine/100 gm body weight resulted in a 50% decrease in the AIA-induced hepatic ALA-S activity compared to rats treated with AIA alone. Heme oxygenase activity was decreased 25% compared to rats treated with AIA alone. The effects of AIA and cimetidine on cytochrome P-450 were not additive, suggesting competition for a common site of interaction. The results suggest that cimetidine may prove to be useful in treating porphyria in humans. 
4	Primary malignant fibrous histiocytoma of the aorta associated with aortic dissection. We report a unique case of primary aortic malignant fibrous histiocytoma presenting clinically as aortic dissection. To our knowledge, this occurrence is the first ever reported. The magnetic resonance imaging technique may provide superiority in the differential diagnosis between tumor and hematoma of aortic dissection. Aortic tumor, although rare, should be included among the causes of aortic dissection. 
4	The influence of elastic compression stockings on deep venous hemodynamics. To determine the effect of elastic compression stockings on deep venous hemodynamics we measured ambulatory venous pressure, venous refill time, maximum venous pressure with exercise, amplitude of venous pressure excursion, and duplex-derived common femoral and popliteal vein diameter and peak flow velocities with and without stockings in 10 healthy subjects and 16 patients with chronic deep venous insufficiency. The effects of below-knee and above-knee 30 to 40 torr and 40 to 50 torr gradient stockings were studied. Despite documentation of substantial stocking compressive effects by skin pressure measurements, neither below-knee or above-knee elastic compression stockings significantly improved ambulatory venous pressure, venous refill time, maximum venous pressure with exercise, or the amplitude of venous pressure excursion in healthy patients or in patients with deep venous insufficiency (p greater than 0.05). In patients with deep venous insufficiency stockings modestly increased popliteal vein diameter and flow velocity in the upright resting position (p less than 0.02). After tiptoe exercise without stockings deep venous peak flow velocity increased in healthy patients and in patients with deep venous insufficiency by a mean of 103% in the popliteal vein and 46% in the common femoral vein (p less than 0.01). With the application of elastic compression stockings only modest augmentation of deep venous flow velocity occurred in both groups above that seen in the bare leg after exercise. Thus elastic compression stockings did not improve deep venous hemodynamic measurements in patients with deep venous insufficiency. The beneficial effects of stockings in the treatment of deep venous insufficiency must relate to effects other than changes in deep venous hemodynamics. 
5	Stressful experience and cardiorespiratory disorders. Ever since Selye's time, the belief has persisted that the outcome of stressful experience is disease. The likelihood of this eventuality is increased when the experience is damaging, unavoidable, or uncontrollable. However, in most stressful instances, these conditions do not occur. The experience either is overcome or produces disturbances in physiological functions without structural change. The prevalence of "functional" disorders are far more common in medical practice than is disease. Among the most interesting of these is the hyperventilation syndrome, which may mimic or be confused with ischemic heart disease. Its symptomatology and physiology are complex. The syndrome may produce coronary vasospasm, but it may also complicate ischemic heart disease. It is even believed that chronic hyperventilation may be a risk factor for ischemic heart disease. Stressful experience consisting of various tasks and challenges may also produce myocardial perfusion deficits in ischemic heart disease, presumably secondary to vasospasm. These deficits are in turn considerably more frequent in any one patient than ST segment changes in the electrocardiogram or the incidence of angina pectoris. Vasospasm is in turn related to cardiac arrhythmias, which may occur with ischemic heart disease during a variety of stressful experiences and during outbursts of anger. Finally, the role of stressful experience in inciting ischemic heart disease and its complications remains moot. 
5	Rupture of coronary vasa vasorum as a trigger of acute myocardial infarction. Some controversy has always existed regarding the presence and extent of the vasa vasorum--the nutrient vessels in the wall of the human aorta--in the coronary arteries. Now, cinemicrographic studies using silicone polymer injections in cleared human hearts have identified the vasa vasorum of coronary arteries, revealing evidence of neovascularization in the region of atherosclerotic plaques. These studies suggest an important role for the vasa vasorum in the pathogenesis of coronary atherosclerosis and its sequelae, especially intramural hemorrhage and vascular spasm. The wall of the human coronary artery in regions of atherosclerotic injury may be particularly rich in capillary vessels of the vasa vasorum. From this, the evidence suggests that with the morning increase in blood pressure, fragile neovascular structures of the vasa vasorum may be more prone to rupture and may be responsible, in part, for the circadian variation in myocardial infarction. 
5	Histologic evaluation of the width of soft tissue necrosis adjacent to carbon dioxide laser incisions. This study evaluated the width of tissue necrosis lateral to carbon dioxide laser incisions on human intraoral excisional biopsy specimens. Measurements were made on specimens including epithelium, muscle, dense and loose connective tissue, and salivary gland. Results showed a mean width of tissue necrosis of 86 microns in epithelium, 85 microns in muscle, 51 microns in loose connective tissue, 96 microns in dense connective tissue, and 41 microns in salivary gland. The range of thermal necrosis in different tissue types is probably based on the water content within each type. A cellular partially homogenized zone of reversible thermal damage up to 500 microns in width was visible adjacent to the zone of thermal necrosis. The relatively narrow width of tissue necrosis with this technique may account for the claimed superior properties of laser-induced wounds compared with those created by electrosurgery. 
3	Sleep disturbances in HIV-infected homosexual men. To provide a better understanding of the etiology of subjective sleep complaints in HIV-infected individuals, a study to evaluate sleep/wake disturbances in 10 healthy HIV-infected male volunteers was performed. All subjects were HIV-infected but had no history of AIDS-related infections, and considered clinically asymptomatic. Interviews and sleep questionnaires revealed sleep complaints in nine subjects. Five healthy HIV-seronegative male subjects, with no history of sleep complaints, were also evaluated. Sleep architecture analyses detected that, in comparison to published normative data and to negative controls, there was a significant increase in the total percentage of slow wave sleep (SWS) and an increase in the percentage of SWS in the later sleep cycles. When compared with normative data, an increase in stage 1 shifts, rapid eye movement (REM) periods, and arousals were also observed in the HIV-infected group. Significant decreases in sleep latency, total percentage stage 2 sleep, and average REM durations were also observed in the HIV-infected group compared with normative data. These sleep architecture abnormalities could not be attributed to known sole primary sleep disorders, first night effect, medications, anxiety or depression. This study indicates that sleep disturbances occur early in the course of HIV infection and suggests that the observed alterations of sleep physiology may be a consequence of central nervous system involvement and/or immune defense mobilization in the early phases of HIV infection. 
5	The role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation. In a variety of animal models of acute pancreatitis, cholecystokinin-receptor antagonists have ameliorated the injury response. These results suggest that cholecystokinin may play a primary role in the pathogenesis of pancreatitis initiated by multiple stimuli. In an effort to test this theory, a sensitive and high affinity cholecystokinin-receptor antagonist L364,718 was administered to four different models of acute pancreatitis that were produced in the ex vivo perfused canine pancreas preparation. The four models of pancreatitis were initiated by cerulein infusion, partial duct obstruction with secretin stimulation, oleic acid infusion, and a 2-hour period of ischemia. In each model, pancreatitis was manifest by edema formation, weight gain, and hyperamylasemia during a 4-hour perfusion. In cerulein infusion-induced pancreatitis L364,718 inhibited edema formation and weight gain (31 +/- 5 gm versus 7 +/- 6 gm; p less than 0.05) and significantly decreased plasma amylase activity (36,605 +/- 21,216 U/dl versus 9421 +/- 5149 U/dl; p less than 0.05). The acute pancreatitis induced by the other three stimuli was not ameliorated by L364,718 treatment. We conclude that in the ex vivo-perfused canine pancreas preparation cerulein-induced pancreatitis is mediated at least in part by the cholecystokinin receptor. Early blockade of the cholecystokinin receptor was of no benefit in treating the other models of pancreatitis, suggesting that cholecystokinin is not involved in the early pathogenesis. 
4	Quantification of the reversibility of stress-induced thallium-201 myocardial perfusion defects: a multicenter trial using bull's-eye polar maps and standard normal limits A multicenter trial was performed on 140 patients from four centers to determine the accuracy of quantitative analysis of stress/delayed thallium-201 myocardial tomograms using normal limits to assess the relative amount of reversibility of stress-induced defects. The patients were found to have 85 fixed and 124 reversible defects, as determined by visual interpretation. Reversibility bull's-eye polar maps were compared to gender-matched normal limits from 36 normals. Regions were identified as reversible if their normalized difference between stress and 4 hr greater than 1.5 s.d.s. from the mean normal limits. Overall agreement between experts at multicenter sites and reversibility maps was 73% for reversible defects and 80% of fixed defects. Sensitivity in detecting reversibility was highest for the left circumflex (88%) and lowest for the right coronary (60%). These results indicate that reversibility polar maps and normal limits offer an objective, accurate technique for determining the reversibility of stress-induced perfusion defects. 
3	Recurrent thoracic outlet syndrome after first rib resection. Seventy-seven patients with 84 operated limbs participated in a follow-up examination on an average of about six years after the resection of the first rib for thoracic outlet syndrome (TOS). Forty-two limbs (50%) were totally asymptomatic one month after the operation and remained so for at least half a year postoperatively. In the follow-up examination, 31 limbs were still asymptomatic, whereas 11 limbs had the same symptoms as before the operation. Of the nine patients with recurrent TOS (two with bilateral resection), seven were women and two were men. These nine patients were on average 38 years old (range = 19 to 51 years) and their jobs consisted of monotonous desk work. Seven of 11 stumps of the first rib were subluxated disclosed by the cervical rotation-lateral-flexion test. The occurrence of a subluxated stump of the first rib in the group of asymptomatic patients was far lower, only 3% (p less than .001). Of the 42 patients with persistent problems, a subluxated stump was encountered in seven (17%). Results of this follow-up examination suggest that monotonous desk work is an important factor causing kinesiologic abnormalities in the thoracic aperture. This abnormal kinesiology contributes to the recurrence of TOS symptoms even after the resection of the first rib. 
4	Effect of hydralazine on the mesenteric vasculature of hypertensive rats. To test whether structural alterations observed in the mesenteric vasculature of Wistar-Kyoto spontaneously hypertensive rats (SHR) were dependent on the presence of hypertension, male SHR and Wistar-Kyoto normotensive (WKY) rats were treated in utero and postnatally with hydralazine up to 28 weeks of age. Treated SHR, WKY, and untreated WKY rats had comparable blood pressures that were less than those of untreated SHR. Treatment altered the dimensions of the superior mesenteric, intermediate-sized, and small arteries of the mesenteric vasculature. In the case of the superior mesenteric artery and intermediate vessels, hydralazine treatment increased the lumen and medial cross-sectional areas of the arteries in WKY rats and slightly decreased both parameters in SHR. Within the small arteries, treatment significantly increased the lumen size in SHR but not WKY rats and had no significant effect on the media of the vessels. Despite the above alterations, the media-to-lumen cross-sectional area ratios remained significantly elevated in SHR over WKY rats in both the treated and control groups of animals within all classes of arteries. The results indicate that there is an inherent increase in the quantity of media surrounding the arteries of SHR when compared with WKY rats that cannot be abolished by normalizing the blood pressure in utero and postnatally with hydralazine treatment. In SHR, such changes persist not only in arteries that exhibit an increase in the media-to-lumen ratio before hypertension but also in the superior mesenteric artery in which an increase in the ratio occurs after hypertension development. 
3	Swimmer's migraine. Three cases of sudden, severe headache occurring during swimming are described. A 51-year-old female had been engaging in a swimming exercise for about 20 minutes when she suddenly experienced a pulsating headache in the parietotemporal region, accompanied by nausea. A few days later, she experienced a similar episode, again during swimming practice. A 45-year-old male developed a pulsating headache with nausea immediately after diving into a swimming pool, and had a similar attack during diving practice 1 week later. A 32-year-old male developed a pulsating headache accompanied by nausea while swimming in the sea. In all three cases, blood pressure, pulse rate, neurological findings, cervical spinal x-rays, brain CT scans, and hematological findings were normal and the outcome was good. Although these patients' headaches were diagnosed as benign exertional headache, pathophysiologically they appeared to resemble the headache associated with sexual activity. 
1	A comparative study of histopathology, hormone receptors, peanut lectin binding, Ki-67 immunostaining, and nucleolar organizer region-associated proteins in human breast cancer. The current study was performed on 71 cases of human female breast cancer and compares the results of five morphologic methods developed for the detection of estrogen receptors (ER), progesterone receptors (PgR), lectin Peanut agglutinin (PNA) binding sites, monoclonal antibody Ki-67 immunoreactivity, and the mean number of argyrophilic nucleolar organizer regions (Ag-NOR). All the parameters were evaluated on serial cryostat sections representative of a closely related, if not identical, neoplastic population. A significant positive correlation was found between the occurrence of estrogen, progesterone, and peanut receptors and between Ki-67 immunoreactivity, mean number of NOR, and mitotic index. Furthermore, ER, PgR, and PNA receptors showed a significant, inverse correlation with Ki-67 immunoreactivity, mitotic index, and mean number of Ag-NOR. These results provide further data that support the hypothesis that (1) progesterone and PNA receptors are estrogen-induced and indicate a metabolic response of the target cells to functioning estrogen receptors; (2) the mean number of NOR reflects the cell kinetics of the tumor; and (3) metabolic differentiation of neoplastic cells is inversely correlated to the proliferation index. 
5	Morbidity associated with incompletely erupted third molars in the line of mandibular fractures. A retrospective analysis of 105 mandibular fractures associated with incompletely erupted third molars was undertaken. It was found that there was no difference in the rates of complication if the teeth were retained or extracted, or if an open or closed reduction was performed. The combination of tooth retention with open reduction, however, shows a trend toward being the treatment most prone to postoperative complications. 
5	Grinspan's syndrome: a drug-induced phenomenon? Three cases of apparently drug-induced Grinspan's syndrome involving the triad of oral lichen planus, diabetes mellitus, and hypertension are reported. Because drug therapy for diabetes mellitus and hypertension is capable of producing lichenoid reactions of the oral mucosa, the question arises as to whether Grinspan's syndrome is an iatrogenically induced syndrome. 
1	The use of bromodeoxyuridine cytokinetic studies as a prognostic indicator of cancer of the head and neck. Traditional measures of head and neck tumors often fail to predict patient outcome or clinical course, particularly in nonadvanced disease. This problem of unpredictable tumor behavior has been one focus of cell proliferation studies. Such studies, however, have been limited by difficult methodology. A newer method of quantifying tumor cell proliferation using bromodeoxyuridine is applicable for head and neck squamous cell carcinomas, as shown in the present study. The relative ease with which cell proliferation can be evaluated using this technique will allow large numbers of head and neck tumors to be studied, enabling correlations with tumor behavior to be made. 
1	Melanoma in pregnancy. The clinical course of malignant melanoma in pregnancy has been a subject of controversy, but current evidence indicates that it is similar to the clinical course in non-pregnant patients. Early detection and biopsy of localized disease is crucial because early treatment provides an excellent prognosis. Surgical excision is the primary therapy for this disease. As the primary care provider for many women in the reproductive age group, obstetrician-gynecologists have an opportunity to detect these lesions at their earliest stages when they are amenable to cure. Overall, maternal metastases to the fetus and placenta are very rare events and do not warrant elective termination based on the maternal diagnosis. However, a thorough examination of the infant and placenta should be done in all cases of melanoma complicating pregnancy. After treatment, long-term follow-up is recommended. Since most recurrences develop within 3 years after the diagnosis, it remains prudent to recommend that these patients avoid a subsequent pregnancy during this interval. 
1	High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients. Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain. 
5	Clustered tRNA genes in Schizosaccharomyces pombe centromeric DNA sequence repeats. The centromere-associated B' and B DNA sequence repeats of Schizosaccharomyces pombe chromosomes I and II have been found to contain clusters of tRNA genes. The centromere II region (cen2) includes at least 22 tRNA genes distributed among five copies of the B sequence repeat containing genes specifying tRNA(Ile), tRNA(Ala), and tRNA(Val). Individual B repeats are variously associated with other tRNA genes, including those specifying tRNA(Lys), tRNA(Arg), and tRNA(Glu2). The centromere I region (cen1) contains at least six tRNA genes in two copies of the B' repeated element, including genes specifying tRNA(Ile), tRNA(Ala), and tRNA(Glu3). Multiple tandemly arranged clusters of tRNA genes are presumably conserved due to restricted recombination frequencies in the centromere regions. 
3	Intradural spinal cord tumor presenting as a subarachnoid hemorrhage: magnetic resonance imaging diagnosis. Negative findings on four-vessel angiography after a subarachnoid hemorrhage are seen in 5 to 30% of patients. A previously silent lesion in the spinal canal may be responsible for the ictus in a small percentage of this group. The etiological factors include tumors and arteriovenous malformations; however, investigations of such lesions have been limited to patients with signs and symptoms of spinal cord or nerve root pathological processes. This report describes the management of a 56-year-old woman with clinical findings typical of an aneurysmal subarachnoid hemorrhage and negative findings on cerebral angiography, in whom magnetic resonance imaging with gadolinium enhancement revealed an intradural extramedullary cervical schwannoma. For this reason, cervicothoracic magnetic resonance imaging with gadolinium enhancement should be considered as an adjunctive scanning examination in all patients with a subarachnoid hemorrhage and negative findings on angiography. 
2	Gluten challenge in patients with celiac disease: evaluation of alpha 1-antitrypsin clearance. Our aim in this study was to monitor changes of the intestinal structure by alpha 1-antitrypsin clearance (alpha 1-ATCL) in order to offer an alternative to the gluten challenge biopsy. In addition, we evaluated the possibility of reducing the time of gluten challenge. Twelve patients had a presumptive diagnosis of celiac disease based on clinical and histological grounds. They were studied when the jejunal histology was normal after gluten-free diet and an alpha 1-ATCL was normal. The gluten was introduced by returning to a normal diet. The challenge lasted 4 wk. We measured alpha 1-ATCL at the end of the 1st and 4th wk, and a new jejunal biopsy was obtained at the end of the 4th wk. By wk 1, alpha 1-ATCL was abnormal in 11 patients but normal in one. By wk 4, alpha 1-ATCL was abnormal in 10 patients and still normal in one. The post-challenge biopsies showed atrophy in 11 and was normal only in the patient with normal alpha 1-ATCL at wk 1 and 4. One patient with abnormal alpha 1-ATCL had to stop the challenge at the first week. The patient with normal clearance at wk 1 and 4 and normal biopsy at wk 4 had abnormal results at 6 months. These data support our hypothesis that alpha 1-ATCL can be used as evidence of gluten toxicity after gluten challenge, and that this test can be abnormal as early as 1 wk after gluten is reintroduced. 
5	The use of risk factors in medical diagnosis: opportunities and cautions. We discuss in this paper the extent to which disease risk factors may assist in the diagnostic process. We caution that disease risk factors need not be very sensitive or specific. Risk factor specificity and sensitivity may be further reduced if, in the former case, the risk factor is related to other illnesses having the same clinical presentation as the disease of interest, or if, in the latter case, the risk factor disappears with the onset of illness. We illustrate these points in a discussion of the utility of smoking as a diagnostic test for malignancy in two clinical situations, the patient with asymptomatic microscopic hematuria and the patient with a solitary pulmonary nodule. Risk factors hold great promise as aids to medical diagnosis, as this information is readily available to clinicians at little or no cost. Clinicians, however, should exercise caution when using risk factors of unproven diagnostic utility in medical diagnosis, as their presence may have little or no effect on disease probability. 
5	Management of postoperative inflammation: dexamethasone versus flurbiprofen, a quantitative study using the new Flare Cell Meter. A consecutive, random, prospective study was conducted to compare the effect of topical dexamethasone and flurbiprofen drops on postoperative inflammation in patients undergoing extracapsular cataract extraction with lens implantation. Objective, quantitative measurements were made postoperatively, using the Kowa FC-1000 Flare Cell Meter. The two treatments were equally effective. 
4	Klinefelter's syndrome with anomalous origin of left main coronary artery Klinefelter's syndrome is a rare entity. Even rarer is an anomalous origin of the Left Main Coronary Artery. For both conditions to occur in the same patient is hence exceedingly rare. Reported here is a never previously reported case of a coronary congenital anomaly in a patient with Klinefelter's syndrome together with the proper angiographic approach. 
4	Pulse oximetry: a new non-invasive assessment of peripheral arterial occlusive disease. Peripheral skin perfusion reflects the level of vascularity and viability of a limb and may help in planning the site of amputation or bypass surgery in patients with vascular disease. This study used peripheral pulse oximetry in 20 healthy volunteers and in 20 patients with limb ischaemia. Pulse oximetry saturation levels (Psa,O2) were compared with ankle artery Doppler pressures and transcutaneous oxygen measurements (Ptc,O2). Recordings were taken at two standard sites distally and referenced to finger and forearm to calculate an index. A significant correlation was found between Ptc,O2 and Psa,O2 in patients with ischaemia (r = 0.68, P less than 0.01). A further group of 12 patients with acute limb ischaemia was similarly assessed before and after revascularization. After revascularization mean(s.d.) Ptc,O2 increased from 38(13) to 44(1) mmHg (P greater than 0.05) and mean(s.d.) Psa,O2 increased from 86(3) to 90(4) per cent (P less than 0.01). These data suggest that pulse oximetry is a more sensitive index of peripheral perfusion than Ptc,O2 or ankle artery Doppler pressure and that, because of its accuracy and simplicity, it merits further use. 
4	Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension. OBJECTIVE: To study the effects of milrinone on pulmonary vasculature. BACKGROUND: It has been suggested that bipyridines or their derivatives may have a selective pulmonary vasodilation effect. METHODS: Preliminary study: milrinone administration to 12 normal dogs (low dose [bolus 75 micrograms/kg for 5 min followed by a continuous infusion at 0.75 micrograms/kg.min, n = 6]; high dose [bolus 150 micrograms/kg for 5 min followed by continuous infusion at 1.5 micrograms/kg.min, n = 6]). Main study: milrinone administration to 18 dogs with pulmonary hypertension due to pulmonary embolism induced by a massive injection of autologous muscle cubes. The pulmonary hypertension dogs were divided into three groups: a) group E (n = 6) received embolization only, as control; b) group L (n = 6) received low-dose milrinone; and c) group H (n = 6) received high-dose milrinone, equivalent to the preliminary study group. Hemodynamic measurements and blood samplings were obtained at baseline and at 15, 30, and 60 min after start of milrinone infusion. RESULTS: Milrinone did not change mean pulmonary artery pressure (MPAP) in normal dogs. Milrinone decreased MPAP significantly in dogs with pulmonary hypertension. Pulmonary vascular resistance index remained at an almost constant level in normal dogs, but decreased significantly in dogs with pulmonary hypertension. Mean arterial pressure was maintained at a constant level in all groups. High-dose milrinone administration decreased systemic vascular resistance index (SVRI) significantly; low-dose milrinone administration decreased SVRI slightly. CONCLUSIONS: Milrinone may have a selective pulmonary vasodilatory effect only in dogs with pulmonary hypertension. The mechanism that produced a selectivity on pulmonary vasculature in dogs with pulmonary hypertension is unknown. However, an inhibition of platelet aggregation may decrease the MPAP resulting from an increase in cAMP caused by milrinone. Further studies are needed to resolve the pulmonary vasodilatory effect of milrinone in dogs with pulmonary hypertension. 
4	Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy. To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 +/- 3.0 to 16.1 +/- 2.5 ml/kg/min, p less than 0.05) as did the oxygen pulse (9.0 +/- 2.2 to 12.6 +/- 1.8 ml/beat, p less than 0.02). Resting heart rate (87 +/- 18 to 62 +/- 9 beats/min, p less than 0.05) and peak exercise heart rate (133 +/- 13 to 105 +/- 30 beats/min, p less than 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 +/- 0.06 to 0.25 +/- 0.11 and peak exercise ejection fraction also tended to increase (0.19 +/- 0.11 to 0.28 +/- 0.15, difference not significant). Both resting plasma norepinephrine (613 +/- 706 to 303 +/- 142 pg/ml, p less than 0.05) and epinephrine (71 +/- 50 to 40 +/- 21 pg/ml, p less than 0.05) were reduced. Circulating lymphocyte beta-adrenergic receptor number was unchanged (1,334 +/- 292 to 1,344 +/- 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity. 
5	Benefit of bicarbonate dialysis during CAVHD. The effect of bicarbonate dialysate (BD) on acid-base status in six pediatric CAVHD patients was examined during seven episodes of metabolic acidosis. When metabolic acidosis was not corrected with CAVHD, a sterile BD was substituted for either acetate- or lactate-based dialysate. Pre- and post-BD substitution levels of lactate, HCO3, PCO2, anion gap, and pH were recorded, as well as dose of intravenous (i.v.) bicarbonate. Improvements in pH and serum HCO3 were seen in all seven cases. Anion gap decreased in all but one of the patients who were switched from lactate to bicarbonate dialysate, with improvement most marked in those patients with marked elevation of the anion gap. No adverse effect on PCO2 was noted. Lactate dialysate may be less effective when serum lactate levels are high, and may contribute to further elevation of lactate levels and anion gap. These data suggest that bicarbonate dialysate may be preferable to lactate or acetate dialysate in CAVHD patients with persistent metabolic acidosis. 
2	Ascending cholangitis: surgery versus endoscopic or percutaneous drainage. A retrospective review of 61 patients with calculous cholangitis was carried out. There were 31 men and 30 women and their mean age was 75.8 years. All patients had abdominal pain, 87% had chills and fever, 65% had clinical jaundice, 23% were in shock, and 54% had positive blood cultures. Because intravenous hydration and antibiotics did not help, 33 patients underwent surgery, 25 patients underwent endoscopic papillotomy (EP), and three patients underwent percutaneous transhepatic drainage of the common bile duct (PTD). Morbidity in the surgery group included two wound infections, one respiratory failure, and one renal failure. Morbidity in the EP-PTD group was one case of arterial bleeding requiring surgery and one of pancreatitis treated conservatively. Two patients (6%) died in the surgery group, one of sepsis and the other of cardiorespiratory arrest. In the EP-PTD group nine patients (32%) died of sepsis and multisystem organ failure. These patients were considered too ill to undergo surgery and thus repeat EP-PTD was carried out. Cholangitis persisted, and retained common bile duct stones with sepsis was the cause of death. Thus when initial EP or PTD is unsuccessful, surgical exploration of the common bile duct should be carried out to control sepsis. 
3	Meningitis in the neurosurgical patient. In the patient with a basilar skull fracture and CSF leak, the risk of meningitis is greatly increased. The diagnosis of both leak and infection can be obscured by the patient's other injuries, and requires aggressive investigation of symptoms that suggest infection. Although the diagnosis is made with CSF cultures, when clinically suspected, treatment should begin after appropriate cultures have been obtained. Treatment should be directed against the most likely organisms, Streptococcus pneumoniae, Haemophilus influenzae, and the other organisms common to the upper respiratory tract. There are no good indications for prophylactic antibiotic usage in patients with known CSF leaks. The patient with a shunt or other CNS prosthetic device may have various manifestations of infection, depending on the type of device and its termination. Frank meningitis or ventriculitis is not always present. Diagnosis requires direct culturing of the shunt milieu, with the most frequent isolates being staphylococcal species and gram-negative enteric bacilli. The most effective therapy, for both eradication of the infection and minimization of the duration and morbidity of therapy, involves removal of the infected shunt, external drainage during parenteral antibiotic therapy, and complete replacement of hardware at the time of internalization. The postsurgical patient will not develop meningitis very frequently, but like the posttrauma patient, concurrent factors can make the diagnosis difficult. Differentiating infectious from chemical meningitis must often be initially based on CSF cell counts and chemistries alone. Treatment to cover the most likely organism, staphylococcal species and respiratory flora, should be started before the culture results are finalized. 
5	Childhood deaths from toy balloons. We describe four children who died of suffocation by rubber balloons in Canada between 1983 and 1988. In the United States, at least 121 children have died in a similar manner in the 15 years between 1973 and 1988 according to a report by the US Consumer Product Safety Commission. Although the highest mortality occurred among infants, 30 (25%) of the 121 deaths occurred in children 6 years of age or older. Balloons account for 43% of the approximately 15 childhood deaths related to children's products that are documented each year by the Consumer Product Safety Commission. Toy rubber balloons are thus the leading cause of pediatric choking deaths from children's products. Preventive efforts should be directed toward a ban on this type of balloon and the development of safer alternatives. Meanwhile, public information campaigns should alert parents, physicians, and policymakers to the dangers of toy rubber balloons. 
1	Impact of enucleation for choroidal melanoma on the performance of vision-dependent activities. We report a functional outcome assessment of 71 patients who underwent enucleation for choroidal melanoma. Each was interviewed to evaluate his her self-reported ability to perform four vision-dependent activities--working, driving, reading, and television viewing--before enucleation and when interviewed. The interval between enucleation and the interview varied between 2 and 25 years. Eighty-seven percent (62/71) reported no change in their ability to perform these important vision-dependent tasks. At 15 years after enucleation, 90% (18/20) retained the ability to drive and 96% (25/26) retained the ability to read. These results are reassuring for those with choroidal melanoma who are faced with enucleation, because most of these patients seem likely to continue at a level of visual function comparable with their preenucleation status. 
4	Clinical and anatomic considerations for surgery in femoropopliteal disease and the results of surgery. From 1980 to 1988 we performed 288 femoropopliteal bypass operations in 231 patients at the Oregon Health Sciences University. The indication for the procedure was claudication in 31% and the relief of limb-threatening ischemia in 64%. Operative mortality occurred after four of these operations (1.4%), including three deaths from myocardial infarction and one death from stroke. The femoropopliteal bypass patients were divided into groups for patency analysis, including those undergoing bypass surgery with a good quality greater saphenous vein versus alternate bypass conduits and patients undergoing primary limb bypass versus those undergoing repeat bypass after prior bypass failure. Our overall primary graft patency for all femoropopliteal grafts was 79% at 5 years. Patients undergoing bypass with a good quality greater saphenous vein had primary graft patency of 85% at 5 years. Patients undergoing bypass using a conduit other than greater saphenous vein had a 5-year patency of 73%. Patients undergoing repeat bypass after a prior failed bypass had a 5-year patency of 57%. 
4	Elapsed time from symptom onset and acute myocardial infarction in a community hospital. STUDY OBJECTIVE: Previous reports have emphasized that thrombolytic therapy for acute myocardial infarction should be initiated within three or four hours of symptom onset to obtain the best clinical outcomes. However, our clinical impression was that late arrivers, who often do not receive thrombolytic therapy, have a good short-term prognosis. Therefore, we investigated the relationships among the elapsed time from symptom onset, thrombolytic therapy, and short-term prognosis in acute myocardial infarction patients. The research hypothesis was that late arrivers have a better in-hospital prognosis because they have less severe disease that may involve spontaneous thrombolysis. DESIGN: Observational cohort study based on reviewing medical records and emergency department service logs. SETTING: 500-bed teaching hospital with medical school affiliation in northeastern Ohio. TYPE OF PARTICIPANTS: Four hundred consecutive patients with acute infarction confirmed by chest pain and positive ECGs or elevated cardiac enzymes. MEASUREMENTS AND MAIN RESULTS: Patients arriving early (elapsed time less than or equal to 1.5 hours) were more likely to be in Killip class III or IV (P = .04) or to have hypotension (P = .0004); and they experienced twofold increased odds of ventricular tachycardia (P = .007), cardiac arrest (P = .03), or death (P = .01). Patients arriving late (elapsed time greater than 3.5 hours) were more likely to have a history of angina (P = .002) and had a better short-term prognosis. CONCLUSIONS: Time of ED arrival after onset of acute myocardial infarction symptoms distinguishes two patient groups that differ in their risk of in-hospital complications. Late arrivers have better short-term prognoses and less (acutely) severe disease, and may have less need for thrombolytic therapy because of possible spontaneous thrombolysis. Patients with prior angina may need education on seeking care if their symptoms change. 
5	Prostate cancer: transrectal ultrasound and pathology comparison. A preliminary study of outer gland (peripheral and central zones) and inner gland (transition zone) cancer. A study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A cancer; one patient had cancer detected by palpation and not detected by ultrasound. Cancers in the outer gland (peripheral and central zones) were compared with cancers in the inner gland (transition zone) by both ultrasound and pathology. Forty-eight percent (52 of 108) of cancers originating in the outer gland showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the outer gland were the prostatic capsule (38%), anterior fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of cancers originating in the inner gland (transition zone) showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled. Gleason scores were significantly different for inner and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9, respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic extension for outer gland cancer. Outer gland cancers showed increased aggressive behavior of both histologic and biologic nature. The difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options. Use of other diagnostic parameters, such as DNA ploidy, may help to determine which cancers to treat and when to treat them; this may have more relevance for cancers originating in the inner gland. Strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known. Thus, transrectal ultrasound may be our "window of observation" through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers. 
5	Primary total knee arthroplasty in patients with psoriasis. Between 1976 and 1988, 50 primary total knee arthroplasties were performed on 34 patients with psoriasis vulgaris. The skin lesions were graded for severity in all patients and the extent of affected body surface was mapped. All patients received peri-operative antibiotics. Only one deep infection, with Staphylococcus aureus, occurred 25 months after operation. The average length of follow-up was nearly four and a half years, being to a minimum of two years or until failure of the arthroplasty. There appears to be no increased risk of deep infection in patient with psoriasis vulgaris undergoing primary total knee arthroplasty. 
4	Adjacent solid boundaries alter the size of regurgitant jets on Doppler color flow maps. Recent studies have attempted to predict the severity of regurgitant lesions from jet size on Doppler flow maps. Jet size is a function of both regurgitant volume and fluid entrained from the receiving chamber and, for a free jet, is a function of its momentum at the orifice. However, regurgitant jets often approach or attach to cardiac walls, potentially altering their momentum and ability to expand by entrainment. Therefore, this study addressed the hypothesis that adjacent walls influence regurgitant jet size as seen on Doppler flow maps. Steady flow was driven through circular orifices (0.02 to 0.05 cm2) at physiologic velocities of 2 to 5 m/s. At a constant flow rate and orifice velocity, orifice position was varied to produce three jet geometries: free jets, jets adjacent to a horizontal chamber wall lying 1 cm below the orifice and wall jets with the orifice at the level of the wall. Doppler color flow imaging was performed at identical instrument settings for all jets. Two long-axis views of the jet were obtained: a vertical view perpendicular to the wall, resembling that most commonly used in patients to image the length of the jet, and a horizontal view parallel to the chamber wall. Velocities along the jet were also measured by Doppler mapping. 
1	Primary non-Hodgkin's T-cell lymphoma of the esophagus. A case with peculiar endoscopic ultrasonographic pattern. We report a case of primary esophageal non-Hodgkin's T-cell lymphoma in a young white female. At admission, endoscopy revealed large, irregularly shaped, esophageal ulcerations with super imposed candidiasis. Endoscopic ultrasonography to assess submucosal alterations and periesophageal involvement revealed a diffuse hypoechogenic thickening (up to 5 mm) of the esophageal wall, a pattern consistent with lymphomatous infiltration. Definitive diagnosis was made with the aid of histology and immunohistochemistry. 
1	Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens. Intraoperative pathologic examination with frozen section (FS) was performed on 504 specimens of thyroid tissue obtained from 457 patients over a period of 9 years. After examination of permanent sections (PS) a malignant neoplasm was diagnosed in 57 specimens (11.3%); 50 (87%) of these were primary thyroid carcinoma, four (8%) metastatic carcinoma, and three (5%) malignant lymphoma. The FS diagnosis was "benign" in 448 (88.9%), "malignant" in (30) 5.9%, and "deferred" in 26 (5.2%). The sensitivity of FS diagnosis of malignancy was 53% and the specificity and positive predictive value 100%. The negative predictive value was 97.8% and overall accuracy 97.9%. The PS disclosed a malignant neoplasm in 62% of specimens in which FS diagnosis was "deferred." Sixty-eight percent of papillary carcinomas, 87% of undifferentiated carcinomas, and a single case of medullary carcinoma were diagnosed with FS examination. A FS diagnosis of malignancy was not made in any of the ten specimens containing follicular carcinoma; in all ten the neoplasms were well-differentiated and eight were encapsulated and minimally invasive. The inability to diagnose follicular carcinoma intraoperatively with FS is the most significant factor accounting for the relatively low sensitivity of FS diagnosis of malignant thyroid neoplasms. 
1	Role of laparoscopy in the evaluation of patients with suspected hepatic or peritoneal malignancy. The purpose of this study was to determine the role of laparoscopy in patients with suspected hepatic or peritoneal malignancy and a normal computerized tomograph (CT). Twenty-five consecutive patients with a normal liver and no peritoneal lesions on CT were evaluated. Patients with a documented primary neoplasm or a positive ascitic fluid cytology were excluded. At laparoscopy, malignancy was documented by biopsy in 12 patients for an incidence of 48%. Of the patients with exudative ascites, 75% had peritoneal metastases. In addition seven patients had benign liver disease documented by laparoscopic biopsy. Liver enzymes were not helpful in distinguishing benign and malignant disease in this group of patients. This study indicates that a negative CT does not exclude liver or peritoneal malignancy. Laparoscopy has a significant yield in patients with a negative CT suspected of having hepatic or peritoneal malignancy and is the procedure of choice in evaluating these patients. 
4	Cardiotoxicity of interferon. A review of 44 cases. Cardiovascular complications have occurred in clinical trials of interferon. We review herein experience to date of cardiotoxicity with all types of interferons in cancer patients. The most common presentations of cardiotoxicity were cardiac arrhythmia, dilated cardiomyopathy, and symptoms of ischemic heart disease, including myocardial infarction and sudden death. The cardiac effects were not related to the daily dose, cumulative total dose, or period of therapy. Some of the patients in whom interferon has caused cardiovascular sequelae have had a history of coronary heart disease or have previously been given chemotherapy with drugs known to be cardiotoxic. In most of the patients, cardiac toxicity was reversible following the cessation of the drug therapy. 
2	Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers. In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable. 
4	Repair of flail anterior leaflets of tricuspid and mitral valves by cusp remodeling. We present an alternative approach to extensive rupture of the chordae tendineae leading to flail anterior leaflets. Resection of the affected cusp segment, suture of the cut edges, and extensive plication of the segment of annulus devoid of leaflets abolished massive regurgitation while maintaining an adequate valve orifice. 
2	GI symptoms, function, and psychophysiological arousal in dysmenorrheic women. In a previous study, gastrointestinal (GI) symptoms and stool characteristics were found to be influenced by menstrual cycle phase. The current study was designed to replicate initial work regarding GI symptoms and stool characteristics and to explore the relationships between GI symptoms, stool characteristics, ovarian hormone levels, and indicators of psychophysiological arousal. Fifty women (dysmenorrheic, N = 22; nondysmenorrheic, N = 28) maintained a daily dairy for recording stool characteristics, GI symptoms, and daily anxiety level. First morning void urine specimens for catecholamine assays and serum samples for ovarian hormone and cortisol determinations were obtained at menses, follicular, and luteal phases. Results showed menstrual cycle-related differences in stool characteristics and report of GI symptoms, with the greatest changes occurring at menses in the total sample. Dysmenorrheic women reported higher levels of all GI symptoms at menses as compared to nondysmenorrheic women. In addition, cycle-related differences in serum cortisol, urine catecholamines, and report of anxiety were also noted, particularly in dysmenorrheic women. However, looser stools and GI symptoms at menses were not correlated with absolute levels of ovarian hormones or indicators of psychophysiological arousal. 
1	Clinical features and natural history of von Hippel-Lindau disease The clinical features, age at onset and survival of 152 patients with von Hippel-Lindau disease were studied. Mean age at onset was 26.3 years and 97 per cent of patients had presented by aged 60 years. Retinal angioma was the first manifestation in 65 patients (43 per cent), followed by cerebellar haemangioblastoma (n = 60, 39 per cent) and renal cell carcinoma (n = 15, 10 per cent). Overall, 89 patients (59 per cent) developed a cerebellar haemangioblastoma, 89 (59 per cent) a retinal angioma, 43 (28 per cent) renal cell carcinoma, 20 (13 per cent) spinal haemangioblastoma and 11 (7 per cent) a phaeochromocytoma. Renal, pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed. Mean age at diagnosis of renal cell carcinoma (44.0 +/- 10.9 years) was significantly older than that for cerebellar haemangioblastoma (29.0 +/- 10.0 years) and retinal angioma (25.4 +/- 12.7 years). The probability of a patient with von Hippel-Lindan disease developing a cerebellar haemangioblastoma, retinal angioma or renal cell carcinoma by age 60 years was 0.84, 0.7 and 0.69, respectively. A comprehensive screening protocol for affected patients and at-risk relatives is presented, based on detailed analysis of age at onset data for each of the major complications. Median actuarial survival was 49 years, with renal cell carcinoma the leading cause of death. 
3	Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. The lack of effective therapy for many of the chronic neuromuscular diseases such as amyotrophic lateral sclerosis, hereditary motor sensory neuropathy (Charcot-Marie-Tooth disease), spinocerebellar degenerations and idiopathic polyneuropathy has led to a search for substances that may stimulate peripheral nerve regeneration. Two such agents that have been proposed are gangliosides (mixed purified bovine brain gangliosides, Cronassial) and thyrotropin releasing factor (TRH). Studies on both of these agents were initially reported with enthusiasm to be successful, but later double-blind controlled studies have failed to confirm these findings. This review provides critical analysis of the designs of studies of potentially effective agents in chronic neuromuscular diseases, and emphasizes the power of the placebo response, and the importance of designing placebos which are indistinguishable from the trial medication other than in the active effect. 
1	Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Vascular permeability factor (VPF), a tumor-secreted heparin-binding protein (Mr approximately 38,000), is responsible for increased vessel permeability and fluid accumulation associated with tumor growth. Vascular permeability factor also promotes the growth of human umbilical vein endothelial cells (EC) and bovine pulmonary ECs in vitro. It is shown for the first time that guinea pig VPF (half-maximal and maximal dose approximately 0.4 and 22 pmol/l (picomolar), respectively), as well as human VPF, are potent stimuli for human ECs resulting in [Ca2+]i increases (maximal three- to fourfold) and inositol triphosphate (IP3) formation. Unlike the maximal responses to thrombin and histamine, the [Ca2+]i response to a maximal VPF dose was preceded by a characteristic 10- to 15-second delay. Guinea pig VPF also selectively increased [Ca2+]i in cultured aortic and pulmonary artery ECs, but not aortic smooth muscle cells, human fibroblasts, or neutrophils. Affinity-purified rabbit antibody (raised to a synthetic peptide representing VPF N-terminal amino acids 1 to 24) adsorbed all vessel permeability-increasing activity, EC growth-promoting activity, and specifically all activity responsible for increasing EC [Ca2+]i. Similar to other mediators that increase [Ca2+]i in cultured ECs, VPF also induced a 200% increase in von Willebrand factor release. Together these data indicate that VPF acts directly on ECs and that rapid cellular events in its in vivo/in vitro actions are likely to involve phospholipase C activation, [Ca2+]i increase, and von Willebrand factor release. 
4	Plasma prolactin and clinical outcome in preterm infants. Plasma prolactin was measured weekly in 280 preterm infants. The complex gestational age dependent pattern of postnatal prolactin release has been defined and reference standards provided. Plasma prolactin was higher in girls, with increasing divergence between the sexes from the third week onwards, and higher after two weeks, in infants of mothers with pregnancy related hypertension. Diet, assigned randomly, exerted a major effect on plasma prolactin, with significantly higher values in infants fed donor breast milk or standard formula than in those fed a protein, energy, and mineral enriched preterm formula. After adjusting for confounding factors, infants with the lowest plasma prolactin concentrations (less than 1000 mU/l, 32.9 micrograms/l) occurring usually at a nadir between days 5 and 12, showed a 120% increase in the duration of ventilatory assistance required, a 20% increase in the number of days to attain full enteral feeds, and a 30% decrease in length gain. We suggest preterm birth disrupts the normal perinatal pattern of prolactin release and that those infants who develop relatively low plasma concentration have an adverse outcome. Our data add to the broader debate on whether preterm infants require multiple endocrine replacement treatment. 
1	Aggressive primary gastrointestinal lymphomas: review of 91 patients treated with the LNH-84 regimen. A study of the Groupe d'Etude des Lymphomes Agressifs. PURPOSE: Patients with aggressive primary gastrointestinal lymphoma undergoing the LNH-84 chemotherapy regimen were analyzed to determine the efficacy of intensive combination chemotherapy, the role of surgical debulking in patients treated with combination chemotherapy, and the toxicity associated with each of these modalities. PATIENTS AND METHODS: Ninety-one patients with primary gastrointestinal lymphoma who participated in the prospective multicenter LNH-84 combination chemotherapy trial (total number of patients in trial, 737) were analyzed. These 91 patients included 69 (76%) with diffuse large cell, nine (10%) with diffuse mixed, and seven (8%) with small noncleaved cell lymphoma. Two patients (2%) had stage IE, 54 patients (59%) stage IIE, and 35 patients (38%) stage IV disease; all patients with stage IE, 22 with stage IIE, and 18 with stage IV disease had bulky (greater than or equal to 10 cm) tumors. Specific sites of gastrointestinal involvement included stomach (47%), small bowel (38%), ileocecum (14%), colon (11%), and rectum (7%). Although surgical resection was attempted in 71 patients (78%), only 28 (31%) had complete tumor excision. All patients received three or four cycles of ACVB (defined in text) induction therapy followed by sequential consolidation as previously described. RESULTS: Responses to treatment in the 91 patients included 71 (78%) complete remissions, six (7%) partial remissions, five (5%) nonresponses, and nine (10%) deaths. With a median follow-up of 3 years, 10 patients (14%) have had relapses; predicted 4-year disease-free survival of complete responders is 85% and predicted 4-year survival of the entire group is 62%. In patients with stage IE or IIE disease, the complete response, survival, and disease-free survival rates were similar in those who underwent complete surgical resection or incomplete or no surgical resection prior to the administration of combination chemotherapy. Prognostic factors predicting for survival in the 91 patients with primary gastrointestinal lymphoma were similar to those in the 646 other patients treated with the LNH-84 regimen. CONCLUSIONS: Patients with aggressive gastrointestinal lymphoma treated with intensive chemotherapy have outcomes and prognostic factors comparable to those of patients with similar-stage aggressive lymphoma without primary gastrointestinal involvement. Surgical resection prior to the administration of combination chemotherapy did not influence the complete response rate, survival rate, or disease-free survival rate in this small group of patients. 
4	Pulmonary artery balloon counterpulsation for intraoperative right ventricular failure. Two cases of severe low cardiac output and right ventricular failure after coronary artery bypass grafting necessitated pulmonary artery balloon counterpulsation after intraaortic balloon pumping and maximal inotropic/pressor support were unsuccessful in maintaining a satisfactory cardiac output. Hemodynamic improvement was sufficient to allow removal of the device 2 and 3 days postoperatively, with survival in 1 patient. Pulmonary artery counterpulsation is less morbid in comparison with other mechanical methods of right ventricular support and is applicable in right ventricular failure of intermediate severity. 
2	Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones. One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm). 
4	Intrapericardial extralobar pulmonary sequestration in a neonate. A huge pericardial effusion was diagnosed during fetal ultrasound examination performed in the 42nd week of pregnancy on a healthy 25-year-old woman. Immediately after the birth, a two-dimensional echocardiogram confirmed this finding in the infant, and an intrapericardial kidney-shaped solid mass measuring 45 x 56 x 15 mm, completely surrounded by pericardial effusion, was visualized to the left part of the heart. The heart was normal. No signs of cardiac tamponade were seen. At the age of two days, the mass was surgically resected and the pericardial fluid evacuated. Microscopic examination revealed that the mass was formed totally of normal lung tissue surrounded by normal pleura. To the best of our knowledge, this is the first case of intrapericardial extralobar sequestration consisting of an accessory lung with completely normal lung tissue. 
4	Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats. To determine the effects of myocardial infarction-induced left ventricular failure on the regulation of surface alpha-1 adrenoreceptors and signal transduction, large infarcts were produced in rats and the animals killed seven days later. After the documentation of impaired left ventricular pump performance, radioligand binding studies of the alpha-1 adrenoreceptor, norepinephrine-stimulated phosphoinositol turnover, and ADP ribosylation of 41 kD substrate by pertussis toxin were examined in the hypertrophying unaffected myocardium. Moreover, the expression of sarcomeric actin isoforms was analyzed by Northern blots and hybridization with specific oligonucleotide probes. Alpha-1 adrenoreceptor density was found not to be altered in membranes obtained from the spared left ventricular tissue, whereas phosphoinositol turnover was increased 3.1-fold in the viable myocytes of infarcted hearts. Furthermore, pertussis toxin substrate was augmented 2.5-fold in membranes prepared from the surviving left ventricular myocardium. Finally, an upregulation of the skeletal actin isoform was detected in the tissue of the failing left ventricle. In conclusion, the possibility is raised that in the presence of severe myocardial dysfunction and ongoing reactive hypertrophy, effector pathways linked to the alpha-1 adrenoreceptor may stimulate the myocyte hypertrophic response which would tend to normalize cardiac hemodynamics. The reexpression of alpha skeletal actin may be a molecular indicator of the persistance of an overload on the myocardium. 
5	Unusual cause of 'piriformis muscle syndrome'. The piriformis muscle syndrome is a controversial "clinical" syndrome primarily characterized by signs and symptoms of sciatic nerve compression at the region of the piriformis muscle as it passes through the greater sciatic notch. The syndrome is often referred to; however, cases are rarely reported, and it is generally an uncommon diagnosis. Of those cases reported, the incidence is six times more frequent in females than in males, and is typically temporally related to minor pelvic or buttock trauma. We describe a case of a 40-year-old woman presenting with signs and symptoms suggestive of piriformis muscle syndrome following a gynecologic procedure performed in the dorsal lithotomy position. Electromyographic findings were consistent with this clinical entity. Operative exploration, however, revealed the source of neural compression to be a pseudoaneurysm of the inferior gluteal artery adjacent to the piriformis muscle. The diagnostic features of this clinical syndrome are discussed. 
1	Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now. 
5	Extracorporeal membrane oxygenation for the circulatory support of children after repair of congenital heart disease. We have treated 39 infants and children with congenital heart disease with extracorporeal membrane oxygenation during the past 5 years. Thirty-six were treated for low cardiac output or pulmonary vasoreactive crisis after repair of congenital heart defects. Twenty-two (61%) survived. Most patients were cannulated from the neck via the right internal jugular vein and the right common carotid artery. Six patients were cannulated from the chest, including three who had separate drainage of the left side of the heart with a left atrial cannula. Two of these patients survived and were the only survivors of the nine patients cannulated in the operating room because they could not be weaned from cardiopulmonary bypass after open cardiac operations. We also reviewed 312 patients (the predictor study series) having open cardiac operations before the availability of extracorporeal membrane oxygenation; 27 of these patients died. Data were collected at 1 and 8 hours postoperatively to determine if any parameters might predict early mortality. With these parameters used as criteria, patients who went on extracorporeal membrane oxygenation were as sick as those who died before extracorporeal membrane oxygenation was available. The most common complication was bleeding related to heparinization. The mean transfusion requirement in survivors was 1.50 +/- 1.13 ml/kg/hr, 5.63 +/- 7.0 ml/kg/hr in the nonsurvivors, and 7.46 +/- 8.29 ml/kg/hr in those cannulated in the operating room because they could not be weaned from bypass. Four children had intracranial hemorrhage, and two of them died. There was one late death. Nine of the 22 survivors are entirely normal. All survivors who do not have Down's syndrome are considered to have normal central nervous system function. We conclude that extracorporeal membrane oxygenation can improve survival in patients with both pulmonary artery hypertension and low cardiac output after operations for congenital heart disease. 
3	Status epilepticus in infancy and childhood. Status epilepticus implies a prolonged seizure or recurrent seizures with persistent decreased consciousness, lasting at least 30 minutes. Both convulsive and nonconvulsive forms exist, either of which may lead to death or additional neurologic deficit. Therapy involves careful supportive care plus some combination of benzodiazepines, phenytoin, or phenobarbital. The outcome depends first on the etiology and second on the rapidity with which seizures are controlled. 
5	Abscess of the sphenoid sinus after transsphenoidal surgery. A case of a bacterial abscess developing in the sphenoid sinus 2 weeks after transsphenoidal surgery is presented. Although abscesses within the sella turcica have been reported as rare complications of transsphenoidal surgery, this is the first reported case of the postoperative formation of an abscess of the sphenoid sinus. The patient sought treatment for severe headaches, nausea and vomiting, and marked temperature elevation. A computed tomographic scan demonstrated soft tissue and air within the sphenoid sinus. A regimen of stress doses of hydrocortisone and antibiotics was prescribed, and the patient underwent transsphenoidal drainage of the sphenoid sinus. The sella turcica was not involved. Anaerobic cultures were positive for Fusobacterium necrophorum. 
5	Trapped-lung syndrome after cardiac surgery: a potentially preventable complication of pleural injury. A case of trapped-lung syndrome after coronary artery bypass grafting (CABG) is presented. A significant pleural injury occurred during the bypass operation resulting in intrapleural hemorrhage, pleural fibrosis, and trapped-lung syndrome. The physicians caring for the patient when she was first seen with the trapped-lung syndrome were unaware of the potential relationship between the two prior bypass surgeries to this pulmonary complication. Recognition of the potential for pleural injury to occur after cardiac operations is important and may allow for earlier diagnosis and institution of appropriate therapeutic interventions. Early recognition and treatment with pleural fluid drainage and reexpansion of the collapsed lung may help prevent this potentially serious pleuropulmonary complication from occurring. In addition, the presentation of this pleuropulmonary complication may be delayed after the cardiac surgery, making early diagnosis more problematic. 
5	Mast cell heterogeneity in chronic idiopathic urticaria. Patients with chronic urticaria are more sensitive to codeine skin testing than other allergic individuals. Nonlesional skin in most patients with chronic urticaria was found to contain increased numbers of both total and atypical mast cells. The presence of increased mast cell density was found to correlate with the degree of clinical (dermatographism) and functional (codeine skin test) skin sensitivity. 
5	Combined hemorrhagic shock and head injury: effects of hypertonic saline (7.5%) resuscitation. Hypertonic saline resuscitation was compared to isotonic fluid resuscitation in a large animal model combining hemorrhagic shock with head injury. Sheep were subjected to a freeze injury of one cerebral hemisphere as well as 2 hours of hypotension at a mean arterial pressure (MAP) of 40 mm Hg. Resuscitation was then carried out (MAP = 80 mm Hg) for 1 hour with either lactated Ringer's (LR, n = 6) or 7.5% hypertonic saline (HS, n = 6). Hemodynamic parameters and intracranial pressure (ICP) were followed. At the end of resuscitation brain water content was determined in injured and uninjured hemispheres. No differences were detected in cardiovascular parameters; however, ICPs were lower in animals resuscitated with HS (4.2 +/- 1.5 mm Hg) compared to LR (15.2 +/- 2.2 mm Hg, p less than 0.05). Additionally, brain water content (ml H2O/gm dry weight) in uninjured brain hemispheres was lower after HS resuscitation (HS = 3.3 +/- 0.1; LR = 4.0 +/- 0.1; p less than 0.05). No differences were detected in the injured hemispheres. We conclude that hypertonic saline abolishes increases in ICP seen during resuscitation in a model combining hemorrhagic shock with brain injury by dehydrating areas where the blood-brain barrier is still intact. Hypertonic saline may prove useful in the early management of multiple trauma patients. 
1	Diagnosis of thymoma in myasthenics using anti-striated muscle antibodies: predictive value and gain in diagnostic certainty. Assay of anti-striated muscle antibodies (StrAb) is used as a diagnostic test for thymoma in individuals with myasthenia gravis. Unfortunately, false positive results are common, and their effect on test accuracy is magnified by the relatively low frequency of thymoma in myasthenics. We estimated the predictive values of positive and negative StrAb assays (PV+ and PV-) and gain in diagnostic certainty using values for sensitivity, specificity, and thymoma frequency previously reported in the literature. Sensitivity for indirect immunofluorescence assays ranged from 0.83 to 0.84 (pooled estimate = 0.84; n = 68). Specificity ranged from 0.73 to 0.88 (pooled estimate = 0.77; n = 898). Frequency of thymoma ranged from 0.07 to 0.17 (pooled estimate = 0.12; n = 4,515). The expected gain in diagnostic certainty from StrAb was minimal in those aged 0 to 20 and those aged 60+. In those aged 20 to 60, a negative test helped to exclude thymoma, and a positive test raised diagnostic suspicion but was not sufficient to establish a diagnosis of thymoma (PV+ = 0.46). 
5	Unusual posterior retinal holes associated with high myopia in XYY syndrome. A 49-year-old XYY man was found to have high myopia OU with unusual multiple retinal atrophic holes located in the posterior pole, unrelated to a posterior staphyloma or any other myopic degenerative changes. Most of the retinal holes showed signs of self-healing, with no evidence of vitreous traction or retinal detachment. High myopia and atrophic retinal holes have been found in other chromosomal disorders and in one sex-chromosomal abnormality. 
5	The surgical treatment of ingrowing toenails. Two prospective studies of ingrowing toenail management were conducted. In the first, 163 patients (204 ingrowing nail edges) who had not had previous surgery were randomised and treated by total nail avulsion, nail edge excision, or nail edge excision with phenolisation of the germinal matrix; recurrence rates one year postoperatively were 73%, 73% and 9% respectively. In the second study, 63 ingrowing nail edges which had recurred after previous operations underwent nail edge excision and phenolisation. There was a 5% recurrence rate and 5% incidence of dystrophy of the nail one year after operation. 
4	New horizons in the treatment of coronary artery thrombosis. The application of recombinant DNA methodology to clinical medicine offers the clinician a new generation of more potent and specific therapies. Recombinant methods offer great promise in the treatment of coronary artery thrombosis. This review focuses on the characterization of 1) molecules that activate plasminogen locally (in the vicinity of a thrombus) rather than systemically, and 2) molecules that offer new approaches to the inhibition of platelet activation and thrombin activity. We first describe the methods used to uncover these molecules and their characterization at the molecular level. The ways in which this knowledge can lead to the development of agents tailored to clinical needs are then explored. 
5	Primary inflammatory reaction in synovial fluid and tissue in rabbit immobilization osteoarthritis. The kinetics and composition of the primary cellular inflammatory process were studied in the synovial fluid (SF) and synovial tissue (ST) compartments of a rabbit knee immobilization osteoarthritis model. Immobilization induced rapid migration of neutrophils (59% +/- 26% of all cells) into SF in three days, which was accompanied by nonspecific esterase-positive monocytes (71% +/- 8% of all mononuclear cells). This finding suggests that non-specific inflammation mediated by phagocytic leukocytes predominates the cellular response in the SF compartment. In contrast, morphometric analysis of ST proper showed an inflammatory mononuclear cell response, the intensity of which diminished over time during the study period from Day 3 (416 +/- 59 cells per 0.049 mm2 ST tissue) through Day 10 (305 +/- 32 cells) to Day 35 (174 +/- 36 cells). A dotlike T-pattern alpha-naphthyl acetate esterase (ANAE) was found in the T-cell-dependent areas of secondary lymphatic tissue in the spleen, enabling immunocytologic ANAE marker studies. The ST response in situ was predominated by tissue macrophage, though infiltrates rich in T lymphocytes were present in the immediate sublining stroma. There was a significant correlation between the intensity of the SF cell response (total recovery) and the percentage of neutrophils, but there was no correlation between the intensity of the ST response and the proportion of T lymphocytes. These T-cell accumulations together with the local proliferation of fibroblastlike lining cells and stromal fibroblasts suggest that the primary inflammatory cell response is not caused by either wear and tear or mechanically by cartilage fragments. 
1	Central neurogenic hyperventilation: pharmacologic intervention with morphine sulfate and correlative analysis of respiratory, sleep, and ocular motor dysfunction. Central neurogenic hyperventilation (CNH), for which there is no effective therapy, can eventually result in respiratory fatigue and death. This report describes a patient with CNH due to a brainstem anaplastic astrocytoma who also exhibited disturbances of sleep and ocular motor function. The CNH responded clinically to morphine sulfate and methadone. Analysis of ventilatory response to CO2 before and after morphine demonstrated a depression of ventilatory response (49 to 53% of baseline) and occlusion pressure response (35 to 50% of baseline) to CO2, with a requirement for high doses of naloxone (10 mg IV) to reverse the effect. Polysomnography revealed sustained hyperventilation, elevated O2 saturation, and low end-tidal CO2 throughout all stages of non-rapid eye movement (NREM) sleep, and absence of rapid eye movement (REM) sleep. Ocular motor evaluation disclosed absence of horizontal and reflexive saccades with compensatory head thrusts. Correlation of the clinical and physiologic data with the MRI abnormalities suggested that the lesion responsible for CNH in this patient might reside in the medial tegmental parapontine reticular formation. Since recurrent episodes of hyperventilation responded in a sustained fashion to IV and oral opiates, this treatment may warrant consideration in other patients with CNH. 
4	Arteriovenous fistula as a complication of temporary pacemaker insertion: treatment with percutaneous embolization. Arteriovenous fistula is a rare complication of central venous catheterization. We present a case of right internal mammary artery-to-right innominate vein fistula resulting from emergent insertion of a temporary pacemaker. Percutaneous management is discussed and the literature is reviewed. 
4	Temporal arteritis presenting as a submandibular swelling. Temporal arteritis (giant cell arteritis) is a disease of protean manifestation. A case which presented as a submandibular swelling is reported. 
3	Pneumocephalus secondary to a high-pressure water injury to the nose. We report a case of pneumocephalus following a water jet injury to the nose incurred during a water-skiing fall. Pneumocephalus due to this type of injury has not been previously reported, to our knowledge. Since this unusual injury may be associated with serious complications, it must be promptly recognized and treated. 
1	Cervical lymph node metastasis: assessment of radiologic criteria. To estimate the accuracy of different radiologic criteria used to detect cervical lymph node metastasis in patients with head and neck carcinoma, seven different characteristics of 2,719 lymph nodes in 71 neck dissection specimens from 55 patients were assessed. Three lymph node diameters, their location, their number, the presence of a tumor, and the amount of necrosis and fatty metaplasia were recorded. The minimal diameter in the axial plane was found to be the most accurate size criterion for predicting lymph node metastasis. A minimal axial diameter of 10 mm was determined to be the most effective size criterion. The size criterion for lymph nodes in the subdigastric region was 1 mm larger (11 mm). Groups of three or more borderline nodes were proved to increase the sensitivity but did not significantly decrease the specificity. Radiologically detectable necrosis (3 mm or larger) was found only in tumorous nodes and was present in 74% of the positive neck dissection specimens. Shape was not a valuable criterion for the radiologic assessment of the cervical lymph node status. 
3	Magnetic resonance in pediatric and adolescent neuroimaging. With improved availability and a practical understanding of the principles of utilization, MRI will continue to replace CT and US in pediatric neuroimaging, just as it has impacted upon the more invasive modalities. In general, US remains the procedure of choice for screening of fetal and infant CNS abnormalities, and CT continues as the principal screening modality beyond infancy and especially for acute, emergent presentations. MRI has now emerged as a primary option for screening as well as for more definitive assessment of many intracranial and most intraspinal conditions. 
5	Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham Heart Study experience). The baseline electrocardiograms of 5,125 original subjects of the Framingham Heart Study were measured to examine the relation of the QT interval corrected for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43 and greater than or equal to 0.44 were studied in relation to these outcomes. There were no significant differences in the risk of total mortality, sudden cardiac death or death due to coronary artery disease according to QTc. A similar lack of significant association between QTc and these 3 outcomes was observed among all persons studied and in the 2 sexes after using a multiple regression analysis to control for several potentially confounding characteristics including age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood pressure and Framingham relative weight. The results of this study fail to demonstrate an association between baseline QTc and overall mortality, and deaths due to sudden cardiac events or coronary artery disease in a large population-based cohort of essentially healthy persons in whom pathologic forms of QTc prolongation are uncommon. 
4	Posttachycardia T-wave changes. A 25-year-old previously healthy man presented to the emergency department with a tachydysrhythmia. After pharmacological intervention, the patient's rhythm converted to normal sinus and symmetrically inverted T-wave changes were noted. Although asymptomatic after conversion, the patient was admitted to the hospital and monitored for two days to rule out cardiac ischemia correlating with the T-wave changes. The patient was ultimately discharged in good health. A review of the emergency medical literature fails to reveal examples of post-tachycardic T-wave changes that may simulate myocardial ischemia but be of no clinical significance. 
5	Efficacy and toxicity of sodium stibogluconate for mucosal leishmaniasis. OBJECTIVE: To determine the efficacy and toxicity of the World Health Organization's (WHO) recommended treatment for mucosal leishmaniasis: antimony, 20 mg/kg body weight per day for 28 days. DESIGN: Open trial with 12-month follow-up. SETTING: Inpatient unit of a regional referral hospital in a developing country. PATIENTS: Twenty-nine consecutive eligible patients with culture-confirmed infection of the mucosa with Leishmania species who were otherwise healthy. Eight patients (28%) had mild to moderate disease (confined to the nasal mucosa). Twenty-one patients (72%) had severe disease (including the oropharynx as well as the nasal mucosa). INTERVENTION: Antimony, 20 mg/kg body weight intravenously every day for 28 days. Patients received antimony in the form of sodium stibogluconate. MEASUREMENTS AND MAIN RESULTS: Initial results of therapy were as follows: 63 of 72 lesions (88%) healed or markedly improved; all lesions were culture-negative for parasites; and 18 of 29 patients (62%) showed complete clinical and parasitologic cure of all lesions. By the 12-month follow-up examinations, however, 37 lesions had recurred, 8 new lesions had appeared, and only 8 patients (30%) showed clinical cure of all lesions. Of the 8 patients with mild to moderate disease, 6 were cured compared with only 2 of the 21 patients with severe disease. Side effects of this treatment regimen included T-wave inversion on electrocardiogram (4 patients), abnormal liver function tests (10 patients), and musculoskeletal pain (24 patients). No side effects occurred during week 1 of therapy. CONCLUSIONS: The only recommended treatment for mucosal leishmaniasis is ineffective in patients with severe disease. The acceptable toxicity of the regimen suggests that longer courses of therapy with antimony, or that trials with other antileishmanial agents alone or combined with antimony be evaluated as initial therapy for this disease. 
5	Osteonecrosis of the knee after arthroscopic surgery: diagnosis with MR imaging. Spontaneous osteonecrosis about the knee typically is a disease of the elderly characterized by an acute onset of pain. The exact cause of this condition has long been debated, although a causative relationship between meniscal tears and spontaneous osteonecrosis about the knee has been postulated. Seven patients with knee pain, meniscal tears, and chondromalacia without initial evidence of osteonecrosis at magnetic resonance (MR) imaging underwent arthroscopic surgery with meniscal recontouring or repair and cartilage shaving. These patients returned within 2-14 months with recurrent pain in the treated knee. MR imaging then demonstrated abnormalities consistent with osteonecrosis. Osteonecrosis of the femoral condyle or tibial plateau may be a late sequela of meniscal injury in association with chondromalacia and arthroscopic surgery. This diagnosis should be suspected in patients with recurrent knee pain after arthroscopic repair of meniscal tears. The precise relationship of this pattern of osteonecrosis to that previously described as spontaneous requires further investigation. 
5	Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction. To determine how accurately several methods of height prediction estimate adult height, we compared height predictions calculated by the Bayley-Pinneau, Roche-Wainer-Thissen (RWT), target height, and Tanner-Whitehouse Mark I (TW-MI), and Mark II (TW-MII) methods with final adult height in 37 boys and 32 girls with short stature and constitutional delay of growth and puberty. They were first seen at a chronologic age (mean +/- SD) of 14.80 +/- 1.70 years (boys) and 12.87 +/- 2.56 years (girls). Adult height at 23.14 +/- 1.95 years and 21.05 +/- 2.02 years was 170.4 +/- 5.4 cm (boys) and 157.8 +/- 4.2 cm (girls), respectively, and thus within the lower range of normal. Height predictions were calculated for the total group and for patients with parents of normal (group 1) as well as short stature (group 2). For boys, the RWT method gave very accurate results, underestimating adult height by -0.6 cm for the total group. The prediction errors for the other methods were -7.3 cm (TW-MI), -4.2 cm (TW-MII), and +3.1 cm (Bayley-Pinneau method) or +1.7 cm (target height). For girls, no method was superior in estimating adult height. The mean prediction error was -0.8 cm, -2.1 cm, and -1.8 cm with the Bayley-Pinneau, TW-MI, and TW-MII methods, respectively. In contrast, adult height was overpredicted by +2.3 cm and +1.2 cm with the RWT and target height methods. We conclude that patients with short stature and constitutional delay of growth and puberty reach an adult height in the lower range of normal. Height prediction methods differ with respect to their accuracy and their tendency to overestimate or underestimate adult height. 
3	Pontine supranuclear facial palsy. Two patients presented with a unilateral supranuclear facial palsy. Additional dysarthria was attributed to the pontine origin documented by magnetic resonance imaging on the contralateral side. The pontine disorder also was indicated by an isolated delay of the blink reflex R1 component or of the masseter reflex. We attribute the facial palsy to a lesion of a supranuclear fiber bundle supplying the facial nucleus. The location of the lesions favors these fibers taking a separate course from the main pyramidal tract at the mid- to upper pontine level. 
3	Combination of Anandron with orchiectomy in treatment of metastatic prostate cancer. Results of a double-blind study. A multicenter, randomized double-blind study was carried out in 203 patients with metastatic prostate cancer, in order to compare the efficacy of complete suppression of androgens achieved with surgical castration and nilutamide (Anandron), 100 mg t.i.d. The combined therapy was well-tolerated by patients, and they noted a better relief of bone pain after six months than those in the control group. There was a greater number of favorable responses in the combined treatment group. In addition, despite a similar median progression-free actuarial rate, the combined treatment (nilutamide plus orchiectomy) offered an improved survival time over orchiectomy alone. 
5	Gastrointestinal bleeding in a 15 month old male. A presentation of Munchausen's syndrome by proxy. Munchausen's syndrome by Proxy is a well-described entity that may not always be immediately considered in a complicated case. We describe this syndrome being portrayed through the guise of gastrointestinal bleeding in a 15 month old male and discuss not only the difficulty involved in solidifying this diagnosis but also the consequences that may occur should this diagnosis not be entertained. Failure to diagnose Munchausen's syndrome by proxy often results from failure to consider the diagnosis. These cases frequently have specific characteristics that allow seasoned clinicians to suspect the diagnosis. Once the diagnosis is considered, it is crucial to take steps to protect not only the index patient but also siblings who not infrequently are also recipients of this life threatening form of child abuse. 
5	Reverse coitus: mechanism of urethral injury in male partner. Reverse coitus, a rarely used sexual position, makes the male urethra more vulnerable to injury from the pubic arch and symphysis pubis of the female partner. Severe pain, bleeding and immediate detumescence were observed in 3 patients. The lesion usually occurred at the fossa navicularis, responded well to conservative management and did not hinder micturition. Potency has been well preserved in all 3 patients. 
1	Hypercalcemia in malignancy. The pathogenesis of hypercalcemia in malignancy has been enigmatic until recent years. Since the realization in 1980 that bioassays for parathyroid hormone detected a cross-reacting substance in malignancy, progress has been remarkably rapid. A parathyroid hormone-related protein was purified and identified by molecular cloning as a 141-amino acid peptide with limited homology to parathyroid hormone itself. Nonetheless, both peptides activate the parathyroid hormone receptor to produce hypercalcemia. It is now clear that the parathyroid hormone-related protein is the cause of hypercalcemia in most solid tumors, particularly squamous and renal carcinomas. New assays for the hormone as well as the related peptide have greatly simplified the differential diagnosis of hypercalcemia. At the same time, new agents for the treatment of hypercalcemia are becoming available, most notably the bisphosphonate drugs. 
4	Gallbladder varices: imaging findings in patients with portal hypertension. A retrospective review of the medical and imaging records of 50 patients with portal hypertension examined in the authors' department during a 2-year period identified six patients with gallbladder wall varices. Imaging studies performed in these patients included computed tomography (CT) (four patients), duplex and color Doppler flow (five patients), and magnetic resonance (MR) (four patients). Five of six patients with gallbladder varices had portal vein thrombosis. Anechoic areas within the gallbladder wall detected with ultrasonography could be distinguished from intramural edema by using duplex or color Doppler flow imaging in all five patients in whom it was used. Contrast material enhancement of these varices was detected with CT in three patients, two of whom also had adjacent mesenteric collaterals. Gradient-echo MR imaging (fast imaging in steady precession/fast low-angle shot) showed flow-related enhancement within the gallbladder wall in two patients. The presence of gallbladder wall varices may imply the presence of portal vein thrombosis. Since these varices can be a source of major blood loss, surgeons must be made aware of them when operating on patients with portal hypertension. 
5	Serial ultrasonographic evaluation of neonatal vein of Galen malformations to assess the efficacy of interventional neuroradiological procedures. Two-dimensional echocardiography complemented with color-flow imaging and pulsed Doppler ultrasound was used to evaluate one fetus and five neonates with a vein of Galen malformation who had severe high-output congestive heart failure and cranial bruits at birth. Intracranial blood flow through the vein of Galen malformations, cardiac status, and direction of aortic blood flow were assessed before and after staged interventional neuroradiological treatment with transarterial and transvenous embolization procedures. Color-flow imaging in each infant displayed the major vascular anatomy including feeding vessels and the patterns of filling of the vein of Galen malformations. Pulsed Doppler ultrasound performed on the descending aorta above the diaphragm showed the degree of diastolic flow reversal indicative of runoff into the vein of Galen malformations. A reduction in blood flow through the vein of Galen malformation was seen on color-flow imaging in four patients treated successfully by embolic procedures. The ratio of diastolic retrograde flow velocity in the descending aorta to systolic antegrade velocity decreased from 0.51 +/- 0.15 (mean +/- standard deviation) to 0.15 +/- 0.20 (P less than 0.05). Color-flow imaging and pulsed Doppler ultrasonography provided anatomical and pathophysiological information regarding cardiac hemodynamics and intracranial blood flow; with the patient's clinical status, these methods provided a reliable, noninvasive means to evaluate the effectiveness of therapy and the need for further treatment in neonates with vein of Galen malformations. 
5	Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system: I. Intraventricular and extracerebral lesions. The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project. 
5	The modified Schollner costoplasty. The modified Schollner costoplasty is a cosmetic procedure for the correction of rib prominence deformity in scoliosis. We present the results of the procedure in 21 patients who had previously undergone spinal fusion for scoliosis. We found the procedure to be well tolerated without major complications. Objective cosmetic improvement was achieved in all but one case. All but one patient considered the procedure to have been of cosmetic benefit. 
4	Cholesterol screening in a black inner-city pediatric population. A screening for total blood cholesterol levels was conducted by the University of Louisville Department of Family Practice in association with the National Youth Sports Program in Louisville, Kentucky. On May 30, 1987, 224 inner-city children between 10 and 16 years of age were tested; 109 (49%) were girls and 115 (51%) were boys. All participants were black. Of the entire population, the girls had a slightly lower mean level of cholesterol than the boys (160 mg/dL vs 165 mg/dL, respectively). Because of the large number of participants aged 10 to 14 years (211), this subset of children was studied more closely. In this age group, 47 (22%) of the children were at moderate risk for future cardiovascular disease and 48 (23%) were at high risk. The serum cholesterol levels were relatively constant in all children until age 12, after which a slight reduction occurred. This decrease is more evident in boys. Our study also showed a correlation between increased blood cholesterol and above normal weight/height indices (ie, Quetelet scores), with nearly 70% of all children having elevated cholesterol levels also exhibiting above normal Quetelet scores. We observed no correlation between high cholesterol levels and high blood pressure in this study population. Dietary intervention is recommended as the initial treatment for elevated cholesterol levels in children. 
1	Inositol phosphate formation in the human squamous cell carcinoma line SCC-12 F: studies with bradykinin, the calcium ionophore A23187, and sodium fluoride. The phospholipase C (PLC)-mediated hydrolysis of membrane phosphoinositides is an important signal transduction pathway coupled to the cell-surface receptors for several hormones and growth factors. In addition, PLC activity can be modulated by changes in intracellular calcium and activation of GTP binding proteins. In this report, differential activation of PLC in the human keratinocyte cell line SCC-12F was studied as judged by specific patterns of inositol phosphate formation. Several hormones and growth factors previously shown to stimulate PLC in a variety of cell types were screened for activity in SCC-12F cells. Only bradykinin was active, stimulating the PLC-dependent generation of inositol (1,4,5) triphosphate (Ins(1,4,5)P3). Ins(1,4,5)P3 was rapidly metabolized to inositol(1,4)biphosphate (Ins(1,4)P2) and inositol(1,3,4,5)tetrakisphosphate (Ins(1,3,4,5)P4), and subsequently degraded to inositol monophosphates. The response elicited by bradykinin was concentration dependent (EC50 value of 50 nM), suggesting involvement of a specific bradykinin receptor. Treatment of these cells with the calcium ionophore A23187 appeared to result in the direct formation of Ins(1,4)P2 without Ins(1,4,5)P3 as precursor. Treatment of the cells with AIF4-, a putative activator of GTP binding proteins, resulted in the generation of inositol monophosphates as the major metabolites in the absence of detectable Ins(1,4,5)P3 formation. Taken together, these observations suggest that the PLC complex present in SCC-12F cells can be differentially activated to yield either Ins(1,4,5)P3, Ins(1,4)P2, or InsP. The observed effects may be due to a direct PLC-dependent hydrolysis of the appropriate membrane phosphoinositide. 
4	Respiratory muscle strength in congestive heart failure. In experimental animals, conditions which drastically decrease cardiac output may reduce the strength and endurance of respiratory muscles leading to hypercapnic respiratory failure. Because patients with chronic CHF have reduced cardiac output and vital capacity (FVC), we measured PImax and PEmax and maximal handgrip force in 16 patients with CHF and 18 AMNs. The patients with CHF had a mean left ventricular ejection fraction of 26 +/- 7 percent. Maximal respiratory pressures were significantly reduced; group mean values (+/- SD) for PImax at FRC were 41.4 +/- 5.6 cm H2O (CHF) and 102.1 +/- 27.4 cm H2O (AMN) (p less than 0.001), with PImax values in five patients with CHF as low as 20 to 30 cm H2O. In most patients, PEmax was comparably reduced. Handgrip force was less dramatically reduced, suggesting selective respiratory muscle weakness. Possible explanations include reduction in respiratory muscle blood flow or generalized muscular atrophy and weakness related to cardiac cachexia. 
5	Growth hormone inhibits tumor metastasis. The effect of growth hormone on tumor growth and metabolism in the tumor-bearing host is unknown. This study was done to determine the effect of recombinant growth hormone on primary tumor growth, tumor metastasis, and carcass weight in tumor-bearing animals. Twenty-seven female Lobund/Wistar rats with subcutaneous prostate tumor implants (PA-III) were randomized to receive a standard protein diet (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.27 kcal/g) ad libitum orally. One half of the animals in each group were randomized to receive daily injections of either recombinant growth hormone (1000 mU/kg/day intramuscularly) or placebo (saline) for 14 days. A significant increase in body weight was observed in growth hormone-treated animals without acceleration of primary tumor growth. Spontaneous pulmonary metastasis was inhibited significantly in animals in both dietary groups treated with growth hormone. Thus, growth hormone selectively supports host growth and inhibits pulmonary metastasis in this tumor-bearing animal model. The potential metabolic effects and clinical consequences of treating cancer patients with growth hormone is discussed. 
5	Does auxiliary heterotopic liver transplantation reverse hypersplenism and portal hypertension? In this study, performed to assess the effect of auxiliary heterotopic liver transplantation on portal hypertension and hypersplenism, eight patients with chronic liver disease who underwent the procedure and had functioning grafts for at least 6 months were analyzed. The transplantation resulted in (a) normalization of platelet and leukocyte counts, (b) reduction of splenomegaly by 20% +/- 3% (P less than 0.02), (c) disappearance of ascites, and (d) diminution of esophageal varices in all patients. Intraoperatively, the mean portacaval pressure gradient decreased with 54% +/- 7% after recirculation of the graft (P less than 0.05). In conclusion, a functioning auxiliary heterotopic liver graft decompresses portal hypertension and reverses hypersplenism. 
3	Multicenter long-term safety and efficacy study of vigabatrin for refractory complex partial seizures: an update. We followed 66 patients with refractory complex partial seizures and a favorable initial response to vigabatrin for 5 to 72 (median, 43) months. Thirty-seven patients discontinued vigabatrin for the following reasons: benefit-to-risk evaluation, 8; seizure breakthrough, 6; adverse events, 6; seizure breakthrough and adverse events, 5; moved or lost, 4; no longer eligible for study, 2; non-drug-related death, 2; narcotic abuse, 1; and patient request, three. There were no clinically significant abnormalities in laboratory studies including SMA 12, complete blood count, ECG, EEG, and visual evoked response testing, and no toxicity other than reversible, dose-dependent side effects. Based on this and other long-term data, clinical trials of vigabatrin have resumed in the United States and Canada. 
4	Elevated insulin, norepinephrine, and neuropeptide Y in hypertension. To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels. 
4	Patency rate of implantable devices during long-term intraarterial chemotherapy. Intraarterial implantable drug delivery systems have been considered as an alternative method for treating patients with unresectable liver malignancies. However, catheter problems with external implanted devices have resulted in limited application of chemotherapy. The introduction of subcutaneous devices offers an opportunity for long-term locoregional chemotherapy. Twelve external intraarterial catheters were implanted into 12 patients and 52 subcutaneously placed devices into 51 patients, all with various hepatic malignancies. Retrospective analyses comparing those two intraarterial systems were conducted taking into account the function and complication rate (hepatic artery thrombosis, infection, leaking, hemorrhage, and dislocation). The follow-up time for the external system was two to eight months (median five weeks), the thrombosis rate 33.3%, and the infection rate 25%. One instance of severe bleeding from the hepatic artery occurred during chemotherapy. One catheter dislocated. For the subcutaneously implanted intraarterial devices the follow-up time was five to forty-one months (median sixteen months), the thrombotic complication rate 17.3%, and the infection rate 7.6% (all patients with simultaneous bowel surgery). Catheter dislocation one year later required reimplantation; in 1 patient therapy had to be discontinued because of a catheter leak. The overall function rate was 71.3% with a median follow-up time of eight months. Anticoagulation therapy for subcutaneously implanted devices starting from the beginning of intraarterial chemotherapy is recommended to achieve long-term patency. No implantation should be preformed simultaneously with bowel surgery. The subcutaneously placed intraarterial devices had a higher function rate and were available for a longer period as compared with external implanted catheters. 
4	Usefulness of blood lactate as a predictor of shock development in acute myocardial infarction [published erratum appears in Am J Cardiol 1991 Apr 15;67(9):912] Data were obtained and analyzed in 229 patients admitted to the coronary care unit from November 1988 through July 1989. The patients were classified into 2 groups: patients without or with only mild left ventricular failure (Killip class I or II) during their hospital stay (group I), and patients who were in Killip class I or II on admission but developed cardiogenic shock during hospitalization (group II). Discriminant function analysis was performed using the following variables: patients' age, history of previous myocardial infarction, diabetes mellitus, blood lactate, urea, creatinine, creatine kinase, aspartate aminotransferase, lactate dehydrogenase concentrations, and chest x-ray cardiothoracic ratio. Variables that were found to significantly discriminate the 2 groups of patients were age, previous infarction, x-ray cardiothoracic ratio, blood urea and lactate concentrations. The risk index was computed, and blood lactate was the variable with the greatest predictive power for shock development. The sensitivity, specificity and predictive value of the risk index, taking various cutoff points, were calculated. With a cutoff value of 1, sensitivity was 65%, specificity 91%, positive predictive value 36% and negative predictive value 97%. With a cutoff value of 2, sensitivity was 53%, specificity 99%, positive predictive value 82% and negative predictive value 96%. 
4	Doxazosin in the treatment of mild or moderate essential hypertension: an echocardiographic study. Sixteen patients with mild or moderate essential hypertension received 1 to 8 mg/day of doxazosin (mean daily dose, 2.7 mg). Blood pressure reduction (supine and standing) was highly significant (p less than 0.001), and no significant changes in heart rate were observed. A significant reduction (p less than 0.01) in left ventricular mass was seen without a change in left ventricular systolic function. All side effects were mild, and only one patient withdrew from the study. 
1	Effects of hypothyroidism on bronchial reactivity in non-asthmatic subjects. The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects. 
1	Expression of enzymatically active sucrase-isomaltase is a ubiquitous property of colon adenocarcinomas. Adenocarcinoma of the colon is one of the most prevalent and lethal of all human malignancies. The early diagnosis and management of this disease could be improved if biological markers, whose expression was restricted to malignant colon cells, were identified. Sucrase-isomaltase is a glycoprotein hydrolase expressed throughout the small intestine and fetal colon but not in the normal adult colon. This study shows that the expression of enzymatically active sucrase-isomaltase is a ubiquitous property of primary and metastatic colon adenocarcinoma. Significant sucrase enzyme activity (i.e., greater than 5 mU/mg protein) was observed in 16 colon carcinomas but not in adjacent normal colon mucosa. Sucrase-isomaltase messenger RNA was identified in all tumors using reverse transcriptase polymerase chain reaction. Using a quantitative polymerase chain reaction analysis, this study shows that the amount of sucrase-isomaltase messenger RNA in tumors examined (3.4 x 10(-8) to 3.19 x 10(-7) micrograms/micrograms total RNA) was greater than in adjacent mucosa (0 to 3.4 x 10(-8) micrograms/micrograms total RNA). This induction of sucrase-isomaltase messenger RNA and enzyme activity was corroborated by immunostaining. Of 30 colon adenocarcinomas examined, 80% were positive for sucrase-isomaltase. In addition, all colon carcinoma metastases examined were positive for sucrase-isomaltase. The staining pattern was distinct and demarcated tumor cells from the surrounding histologically normal tissue. No sucrase-isomaltase staining was seen in normal mucosa from the same patients. With the exception of lung, no sucrase-isomaltase immunostaining was observed in a variety of examined noncolonic adenocarcinomas. Thus, the specificity and ubiquity of sucrase-isomaltase expression in adenocarcinomas of the colon can be exploited to improve the clinical management of this disease. In addition, studies on the structure of the sucrase-isomaltase gene and its regulatory elements should contribute toward understanding the alteration of gene expression by oncogenic transformation of the colonic mucosa. 
4	Early detection and treatment of hyperlipidemia: physician practices in Canada. We surveyed primary care physicians in Canada to determine their current practices regarding the detection and treatment of hyperlipidemia in asymptomatic adults 20 years of age or more and to determine the role of selected patient characteristics (age, sex and the presence of coronary heart disease [CHD] risk factors) in their management decisions. The self-administered questionnaire was completed by 428 of 804 family physicians and general practitioners. The proportion of physicians who reported having tested at least 50% of their adult patients varied from 29% to 85% and was related to the number of CHD risk factors present and the patient's age. The proportion of respondents who reported starting dietary or drug therapy among patients with a cholesterol level of 6.2 mmol/L or less increased as the number of CHD risk factors increased and was not related to patient age or sex. According to the factors examined our results suggest that primary care physicians in Canada select patients for screening and treatment mainly on the basis of CHD risk factors present and that their approach is more conservative than that recommended by the Canadian and US consensus conferences. 
1	Free alpha subunit of the pituitary glycoprotein hormones. Measurement in serum and tissue of patients with pituitary tumors. A solid-phase radioimmunoassay was developed that measures the free alpha subunits of pituitary glycoprotein hormones (alpha PGpHs) and has negligible cross-reactivity with the intact hormones (less than 0.014% for thyroid-stimulating hormone [TSH], less than 0.1% for human chorionic gonadotropin [hCG], 0.8% for luteinizing hormone [LH], and 2.0% for follicle-stimulating hormone [FSH]). The assay is standardized with the alpha subunit of hCG but also reacts well with the alpha subunits of the other glycoprotein hormones (84% for alpha TSH, 77% for alpha FSH, and 64% for alpha LH). Concentrations as low as 0.3 micrograms/L can be reliably measured, and the 97.5% reference range in 27 healthy adults, including postmenopausal females, is less than or equal to 1.2 micrograms/L. Elevated preoperative alpha PGpH concentrations were found in 45 (9.4%) of 479 sera from patients with pituitary adenoma and 3 (4.5%) of 66 patients with nonadenomatous sellar lesions. Postoperative alpha PGpH levels were lower in 30 of 39 adenoma patients and 2 of 3 nonadenoma patients. In five (1%) of the patients with pituitary adenomas, alpha PGpH was the only elevated serum hormone marker. Serum values of alpha PGpH correlate weakly with alpha subunit immunocytochemical staining--95% of those with negative staining have normal alpha PGpH values, but only 18% of those with positive staining have elevated alpha PGpH values. 
1	Elevated serum levels of soluble interleukin-2 receptors in small cell lung carcinoma. The presence of the soluble form of the interleukin-2 receptors (sIL-2R) was evaluated in the serum of 21 patients with small cell lung carcinoma (SCLC) and 37 patients with non-small cell lung carcinoma (non-SCLC) by means of an enzyme-linked immunosorbent assay. The sIL-2R level was measured serially in patients with SCLC both during and after therapy. The mean serum level of sIL-2R in patients with SCLC was 3.8 times higher than that of 47 healthy controls and was 1.9 times higher than in 37 patients with non-SCLC. Six patients with SCLC had very high levels of sIL-2R, ranging from five to 52 times the mean level observed in normal controls. Tumor cells in the pleural fluid of the patient with highest levels were positive with monoclonal antibodies to IL-2R (CD25), NKH-1, OKDR, and OKT9. A longitudinal study in this patient showed a good correlation between tumor activity and sIL-2R levels. Also, the sIL-2R levels decreased in patients responding to therapy. These results suggest that some SCLCs secrete sIL-2R and that the serial measurements of the serum sIL-2R levels can be used as a noninvasive tumor marker in this disease. 
1	Hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas. Retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation (BMT) was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease (VOD). Twelve patients (4.1%) developed a clinical syndrome of right upper quadrant (RUQ) tenderness or hepatomegaly, jaundice, and ascites, with or without encephalopathy, within 40 days of marrow reinfusion. Evidence of metastatic liver disease was the only pretransplant characteristic predictive for VOD (P = .0002). Sex, age, histology, hepatitis B serology, and elevated liver function tests were not predictive. No individual preparative agent had a significant effect on the development of VOD. However, a single 2-hour infusion of carmustine (BCNU) (greater than or equal to 450 mg/m2) led to an increased incidence of VOD when compared with the same dose administered in a fractionated schedule (P = .0258) when given with two other chemotherapeutic agents. Seven of eight autopsy specimens confirmed the clinical diagnosis of VOD. The four patients in whom clinical VOD resolved had lower median peak bilirubins (7.3 v 15.9 mg/dL), lower median peak creatinines (2.1 v 4.1 mg/dL), and relatively quick engraftment of neutrophils (mean, 18.7 days). One of the four patients in whom VOD resolved had other grade 4 (life-threatening) toxicities in contrast to eight of eight who succumbed. In summary, VOD is an uncommon complication in autotransplantation of solid tumors and lymphomas. Our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated BCNU schedule especially in combination with other alkylating agents. 
5	A simple method to improve the accuracy of non-invasive ultrasound in selecting TIA patients for cerebral angiography. A prospective study is reported of the ability of B mode ultrasound imaging and continuous wave Doppler flow studies to detect different degrees of stenosis of the extracranial internal carotid artery (ICA) in 186 arteries in 99 patients with transient ischaemic attacks (TIA) and minor ischaemic stroke. A simple mathematical equation has been developed which combines the image and flow data to provide a single predictor of the degree of angiographic stenosis which has advantages over either ultrasonic modality used alone. The sensitivity and specificity of the predictive model in the detection of stenosis greater than or equal to 25% was 73% and 98%, of stenosis greater than or equal to 50% was 90% and 93%, of stenosis greater than or equal to 75%, 65% and 99% and occlusion 100% and 94% respectively. The principal clinical value of ultrasound screening is to spare patients with "non-significant" stenosis the risk of unnecessary angiography. Thus a simple measure of the Duplex screening tests' performance is the proportion of all strokes occurring as a complication of angiography that are avoided by changing the investigation policy from "angiograms for all carotid TIA and minor ischaemic stroke patients" to "angiograms for all patients with abnormal ultrasound results". If Duplex scanning were used to select patients most likely to have a significant abnormality on angiography, depending on the degree of stenosis to be detected, 52-85% of angiographic strokes might be avoided. If the predictive equation were used 62-88% of angiographic strokes might be avoided. 
5	Limits of brain tolerance to daily increments in serum sodium in chronically hyponatraemic rats treated with hypertonic saline or urea: advantages of urea. 1. At present there is no consensus about the optimal management of hyponatraemia to prevent demyelinating brain lesions. We have evaluated in a large series of rats (n = 136) the protective role of urea for the brain in the treatment of severe chronic hyponatraemia. Urea (group I, n = 51) was compared with hypertonic saline in boluses (group II, n = 46) and with hypertonic saline in divided doses (group III, n = 39). Treatment was administered intraperitoneally over 48 h. The severity of brain lesions was assessed by histological scoring. 2. For 95% of the injured animals treated with hypertonic saline, brain lesions appeared for an absolute increment in serum Na+ concentration (delta SNa+) of 20 mmol day-1 l-1. Above this limit neurological injuries gradually worsened, and beyond a transition zone (delta SNa+ greater than or equal to 20 less than or equal to 23 mmol day-1 l-1) 89% (group III) to 100% (group II) of the animals were injured. This limit can be reached rapidly, as attested by the comparable severity of brain lesions observed in group II (mean delta SNa+ 1 h after a bolus injection, 19 mmol/l) and in group III (mean delta SNa+ 1 h after an injection, 2 mmol/l), both groups achieving similar daily delta SNa+. 3. A correction above the threshold of 20 mmol day-1 l-1 is as toxic during the first 24 h as during the second day of the treatment. 
5	Heart and lung transplantation for terminal cystic fibrosis. A 4 1/2-year experience. From among 112 patients with cystic fibrosis who were assessed for heart-lung transplantation, 83 were accepted. Twenty-six died while awaiting heart-lung transplantation and 32 had the operation. The management and the outcome of these 32 patients is reported. Survival, infection, and rejection rates among these patients were compared with those of 61 patients without cystic fibrosis who underwent heart-lung transplantation between 1984 and 1990. The cumulative survival rate was 72.29% +/- 94.91% at 1 year and 55.59% +/- 7.50% at 3 years. The mortality rate was slightly higher in the group with cystic fibrosis during the first year after the operation but it was lower at 3 years. The difference, however, could have been due to chance alone (p = 0.308). The same was true for the prevalence of rejection (up to 6 months: chi 2 = 1.8141, p = 0.17), and infection (up to 6 months: chi 2 = 2.20, p = 0.14), between the two groups. It is concluded that cystic fibrosis does not constitute an additional risk in terms of survival and morbidity after heart-lung transplantation. 
4	Exposing patients with chronic, stable, exertional angina to placebo periods in drug trials. Because the safety of withholding standard therapy and enrolling patients with stable angina in placebo-controlled trials is not known, we identified all events leading to dropout from trials of 12 antianginal drugs submitted in support of new drug applications to the US Food and Drug Administration. Persons who dropped out of the trials were classified as cause due to adverse cardiovascular events or other causes without knowledge of drug assignment. There were 3161 subjects who entered any randomized, double-blind phase of placebo-controlled protocols; 197 (6.2%) withdrew because of cardiovascular events. There was no difference in risk of adverse events between drug and placebo groups. A prospectively defined subgroup analysis showed that groups who received calcium antagonists were at an increased risk of dropout compared with placebo groups (P = .04), primarily because of a disproportionate number of adverse events in studies of one drug. In conclusion, there were few adverse experiences associated with short-term placebo use. Withholding active treatment does not increase the risk of serious cardiac events. 
5	Recurrent lateral rectus palsy in childhood. Five patients with recurrent, lateral rectus palsy in childhood, examined at the University of Iowa Hospitals over a period of 22 years, are reported. During the same period, 131 abducens nerve palsy patients, younger than 18 years of age, were evaluated. Eighteen similar patients, most single case reports, are reviewed from the literature. All reported patients, including our own, shared the following features: spontaneous recovery within 6 months in the majority of patients, ipsilateral recurrence, and painless palsy. There is female and left-sided preponderance. Etiology is undetermined. Hypotheses include viral etiology, neurovascular compression by aberrant artery, and migraine. 
2	Interventional radiologic alternatives to cholecystectomy. It has been estimated that 20 million people in the United States have gallstone disease. The choice of the optimal management strategy for a patient with symptomatic gallstones in the 1990s will take into account the clinical status of the patient, the characteristics of the gallstones, and the patient's preference. Only patients whose doctors understand the advantages and disadvantages of the newer methods can make properly informed choices. When interventional radiologic alternatives to cholecystectomy are being contemplated, one approach is to first consider the patient's clinical presentation (acute or nonacute) and then their risk of death after cholecystectomy (low or high). Figure 5 shows an algorithmic approach to the management of gallbladder stones based on this concept. This algorithm also can be used as a framework for discussion of treatment options with any individual patient. 
5	Hole preparation techniques for transpedicle screws. Effect on pull-out strength from human cadaveric vertebrae. In each of eight thoracolumbar human cadaveric vertebrae, a hole was made through one pedicle into the vertebral body with a drill bit and through the contralateral pedicle with a probe. Identical metal screws were implanted into the holes to equal depths, and maximum pull-out force was determined for each screw. Using a paired Student t test, no significant difference (P = 0.87) was found in pull-out strength between the screws implanted into drilled holes and those implanted into probed holes. In fact, the average pull-out strengths for the two groups differed by less than 2%. The pedicular cortex was broken through during hole preparation in 5 of the 16 pedicles: 3 as a result of drilling and 2 secondary to probing. The average pull-out strength of the screws in these five pedicles was 11.0% less than the average pull-out strength of the screws implanted into the contralateral intact pedicles. Although this does not represent a statistically significant difference (P = 0.15), it suggests that damaging the pedicular cortex may weaken pedicle screw fixation. 
5	Molecular defect in siblings with prolidase deficiency and absence or presence of clinical symptoms. A 0.8-kb deletion with breakpoints at the short, direct repeat in the PEPD gene and synthesis of abnormal messenger RNA and inactive polypeptide. Prolidase deficiency is an autosomal recessive disorder with highly variable symptoms, including mental retardation, skin lesions, and abnormalities of collagenous tissues. In Japanese female siblings with polypeptide negative prolidase deficiency, and with different degrees of severity of skin lesions, we noted an abnormal mRNA with skipping of 192 bp sequence corresponding to exon 14 in lymphoblastoid cells taken from these patients. Transfection and expression analyses using the mutant prolidase cDNA revealed that a mutant protein translated from the abnormal mRNA had an Mr of 49,000 and was enzymatically inactive. A 774-bp deletion, including exon 14 was noted in the prolidase gene. The deletion had termini within short, direct repeats ranging in size of 7 bp (CCACCCT). The "slipped mispairing" mechanism may predominate in the generation of the deletion at this locus. This mutation caused a 192-bp in-frame deletion of prolidase mRNA and was inherited from the consanguineous parents. The same mutation caused a different degree of clinical phenotype of prolidase deficiency in this family, therefore factor(s) not related to the PEPD gene product also contribute to development of the clinical symptoms. Identification of mutations in the PEPD gene from subjects with prolidase deficiency provides further insight into the physiological role and structure-function relationship of this biologically important enzyme. 
5	Trisomy 13: a new recurring chromosome abnormality in acute leukemia. A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias. 
4	A cellist with arm pain: thermal asymmetry in scalenus anticus syndrome. We report on a cellist with pain and coldness of the upper extremity. Abnormal thermographic studies were instrumental in uncovering intermittent compression of the subclavian artery, and this prompted us to study the effects of cello playing on skin temperature asymmetry. Temperature asymmetry was defined as the temperature difference (delta-T) from one hand to the other. In 57 controls, mean delta-T at rest was .309 +/- .254C. Exercising the upper extremities by prolonged elbow flexion or by movements mimicking cello playing in controls did not significantly affect delta-T. In our patient, delta-T was ten times control (3.6C). Angiography showed extrinsic compression of the subclavian artery occurring only after cello playing; sympathetic ganglion block relieved the pain. Our patient's abnormal skin temperature may have reflected sympathetic vasomotor hyperactivity. Intermittent neurovascular compression and sympathetic hyperactivity appear to be factors in scalenus anticus syndrome. 
4	Neuroendocrine activity in congestive heart failure. The increased neuroendocrine activity in patients with congestive heart failure appears to be a generalized attempt to maintain blood pressure at the expense of reduced cardiac performance and salt and water retention. It is likely that baroreceptor dysfunction contributes to increased sympathetic nervous system activity in patients with congestive heart failure. The usual tonic inhibitory messages emanating from baro- and mechanoreceptors in the great vessels and heart fail to adjust sympathetic traffic from the brain to the periphery, leading to uninhibited sympathetic tone. Arginine vasopressin and plasma renin activity may be increased secondarily; however, plasma renin activity activation could also be induced by a low-salt diet and diuretic use. Preliminary baseline data indicate that patients with left ventricular dysfunction (ejection fraction less than or equal to 35%) but no or very mild symptoms of heart failure have increased plasma levels of norepinephrine, atrial natriuretic factor and arginine vasopressin, while plasma renin activity is normal, suggesting that neuroendocrine activity contributes to the pathogenesis of congestive heart failure. Neurohormones such as angiotensin II may alter gene expression, leading to changes in the shape and size of the cell. Remodeling of the heart and blood vessels is associated with both heart failure and hypertension. Angiotensin-converting enzyme inhibitors have been demonstrated to retard or reverse the remodeling process under certain experimental conditions. Studies are currently under way to test this possibility in patients. 
4	Tricuspid valve incompetence caused by nonpenetrating thoracic trauma. Tricuspid valve incompetence from ruptured papillary muscle or chordae as a result of nonpenetrating trauma is uncommon. Blunt trauma causing partial detachment of a leaflet from the annulus is very rare. We report the case of a young adult involved in a car accident who had these findings. Operative repair with resuture of the leaflet to the annulus and annuloplasty using a Carpentier ring resulted in complete recovery. 
1	Sequential connection of flaps: a logical approach to customized mandibular reconstruction. Microsurgery has improved the success rate for reconstruction of composite defects in the head and neck. Restoration of mandibular continuity alone is not adequate for reconstruction. Replacement of the oral lining with thin tissue is necessary to improve tongue mobility and to set the stage for later dental restoration. There is currently no ideal osteocutaneous free flap that provides unlimited length of bone, can undergo multiple osteotomies to produce the proper curve to the reconstructed mandible, and provides thin skin for oral lining. Combining free flaps can take advantage of the strengths of the individual donor sites and eliminate some of the problems with current osteocutaneous flaps. In six patients, a fibular osseous free flap was combined with either a radial forearm flap or a lateral arm flap to provide bone and oral lining in reconstruction of mandibular composite defects. In these selected patients, the fibula provided the blood supply for the second free flap, which was placed sequentially. The distal peroneal vessels were used to anastomose to the radial forearm vessels or the lateral arm pedicle. This approach allows the surgeon to customize the defect by improving both the functional and aesthetic aspects of reconstruction and is of use in cases where vascular access is limited, such as following head and neck surgery and radiation. 
2	Prevalence of Helicobacter pylori in specific forms of gastritis. Further evidence supporting a pathogenic role for H. pylori in chronic nonspecific gastritis. Helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis; moreover, there is evidence to suggest that H. pylori may cause this form of gastritis. However, there is little or no information on the prevalence of H. pylori in specific forms of gastritis. Our hypothesis was that if H. pylori was pathogenic in chronic nonspecific gastritis, organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis. Prevalence rates of H. pylori were determined independently in patients with eosinophilic and Crohn's gastritis, Menetrier's disease, and chronic nonspecific gastritis. The prevalence of H. pylori in patients with chronic nonspecific gastritis was 71%, whereas the organism was not identified in patients with any form of specific gastritis. This finding further supports the accumulating evidence that H. pylori is a primary pathogenic factor in chronic nonspecific gastritis. 
1	Late effects of treatment for Wilms' tumor. A report from the National Wilms' Tumor Study Group. The National Wilms' Tumor Study (NWTS) was initiated in 1969. One of its objectives was to modulate treatments according to risk factors to minimize the number and severity of treatment-related short-term and long-term iatrogenic complications. The NWTS has therefore incorporated a Long Term Follow-up Study (LTFS) within its framework to monitor late effects. The LTFS is confined to relapse-free survivors alive 5 years or longer after initial surgery, and data are collected using specifically designed forms. A total of 787 patients registered on NWTS-1 or NWTS-2 (1969 to 1979) were eligible, of whom 680 (86%) were available for analysis regarding musculoskeletal, cardiovascular, and neuropsychologic status, and the presence of benign and malignant tumors. Patients with early-stage disease who were treated with radiation had scoliosis reported, along with other musculoskeletal abnormalities (32 versus 2), nearly seven times as often as did the members of the cohort population who did not undergo radiation (35 of 57 versus 5 of 53, respectively). The difference in cardiovascular problems recorded in survivors who did and did not receive Adriamycin (Adria Laboratories, Columbus, OH) (2.4 versus 1.1 per 100-person years at risk) had borderline statistical significance (P = 0.06). No excess in neuropsychologic events was reported for those given the neurotoxin vincristine. When considering patients with disease of all stages, all 5 second malignant tumors occurred in the 623 patients who underwent radiation (RT patients); benign tumors were also more frequent in RT patients than in those patients who did not undergo radiation (41 of 486 or 8% versus 4 of 194 or 2%). Continuing study of this unique body of patients is needed, especially for those given Adriamycin, because of the known long interval needed for latent cardiomyopathy to become clinically manifest in some patients. 
1	Soluble interleukin-2 receptors in patients with nasopharyngeal carcinoma. The authors performed a retrospective analysis of serum soluble interleukin-2 receptor (sIL-2R) levels in 72 patients with nasopharyngeal carcinoma (NPC) using an enzyme immunoassay. Their objectives were to determine the value of serum sIL-2R in estimating the tumor burden, and its predictive value in response to therapy and prognosis. The data showed that serum sIL-2R levels in patients were significantly higher than that of healthy controls. The serum levels correlated with clinical staging and hence the tumor burden of NPC. Serial measurement of serum sIL-2R provided an accurate prognostic index of the clinical response to radiotherapy in at least 89% of patients with raised serum sIL-2R at initial diagnosis (defined as mean + 2 SD of healthy controls) and a reliable predictive index in all patients who subsequently developed distant metastasis despite initial radiotherapy. Simultaneous measurement of Epstein-Barr virus-related serology (IgA-VCA and IgG-EA) failed to demonstrate predictive value comparable with that of serum sIL-2R. The authors conclude that monitoring serum sIL-2R levels has clinical and prognostic significance in patients with NPC and that prospective studies are indicated. 
5	The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. We have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke. All had a single well-defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered. Each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest, 2 during movement of fingers of the recovered hand, and 2 during movement of fingers of the normal hand. When the normal fingers were moved, regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere. When the fingers of the recovered hand were moved, significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other regions, namely, insula, inferior parietal, and premotor cortex, were also bilaterally activated with movement of the recovered hand. We have also demonstrated, by using a new technique of image analysis, different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements. Our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke. 
5	Ruptured mature cystic teratoma of the ovary with recurrence in the liver and colon 17 years later. A case report. A mature cystic teratoma of the ovary occurred in a 51-year-old woman and recurred as a large intrahepatic tumor mass as well as a small mass in the transverse colon 17 years after rupture, intraperitoneal spillage of tumor contents and subtotal surgical removal of the ovarian lesion and peritoneal implants. The patient was treated with a partial hepatectomy and a segmental transverse colectomy. The recurrent lesions, which contained histologically fully mature teratomatous elements only, were excised; the result was a complete cure. To our knowledge this is the first documented report on such a complication of mature cystic teratoma of the ovary. 
3	Evaluation of vigabatrin as an add-on drug in the management of severe epilepsy. The effects of the addition of Vigabatrin, a new anti-epileptic drug, to the therapy of 128 patients with severe medically refractory epilepsy is reported. Forty two (33%) of patients experienced side effects, which were predominantly neurotropic. In 28 (22%), the drug was withdrawn because of these side effects. The commonest side effects were drowsiness and behavioural change. The remaining 100 patients were followed for a mean of 30 weeks (range 12-75). Forty one of these patients showed a marked improvement in seizure frequency (a 50% or more reduction when compared with the pre-trial period), and nine (7%) were rendered seizure free. Apparent tolerance to the effects of the drug were noted in five patients. An exacerbation of seizures may occur if the drug is withdrawn too quickly. Vigabatrin appears to be a promising new anti-epileptic drug. 
4	The post-occlusive hyperemic response in patients with systemic sclerosis. We investigated post-ischemic hyperreactive cutaneous blood flow in patients with primary Raynaud's phenomenon and Raynaud's phenomenon secondary to systemic sclerosis (SSc). Reactive hyperemia was measured over a locally warmed area of skin, using a laser Doppler flowmeter, following 5 minutes of suprasystolic occlusion of blood flow. We found that patients with primary Raynaud's phenomenon had normal post-ischemic blood flow compared with normal controls. In contrast, patients with SSc had reduced levels of baseline and peak blood flow compared with either the primary Raynaud's phenomenon patients or the normal subjects. Infusion of carbaprostacyclin, a potent prostacyclin analog vasodilator, did not increase blood flow in the SSc patients, nor did it restore the reactive hyperemic response. These findings are consistent with the hypothesis that patients with the nonvasoconstricted condition of SSc have fixed structural defects that limit cutaneous microvascular blood flow. 
4	Electrophysiologic characteristics of manifest and latent retrograde conduction in dogs. Atrioventricular (AV) nodal reentry requires intact retrograde ventriculoatrial (VA) conduction. The purpose of this study was to assess the contribution of various pacing and pharmacologic techniques to uncover VA conduction during apparent unidirectional VA block, and to evaluate the role of several biologic and electrophysiologic factors in concealment of retrograde conduction. Forty healthy dogs underwent catheter-electrophysiologic studies of AV and VA conduction. Group I (20 animals) had intact VA conduction. Group II (six animals) had VA dissociation with ventricular pacing initiated during sinus rhythm, but the presence of VA conduction was confirmed by isoproterenol infusion or by premature ventricular stimulation. In group III (14 animals), the above techniques failed to uncover VA conduction. Eight of 14 group III animals underwent thoracotomy and crushing or freezing of the sinoatrial (SA) node. Ventricular pacing initiated during sinus standstill was associated with 1:1 VA conduction in each experiment. VA conduction time and retrograde Wenckebach cycle length, both in the baseline state and during isoproterenol infusion, were significantly longer in the eight animals in group III than in those in group I. Age, gender, weight, breed, sinus cycle length, and anterograde AV conduction properties were not significantly different between groups I, II, and III. The data suggest that (1) in normal dogs, complete unidirectional VA block probably does not exist; (2) in the presence of anterograde input to the AV node, even sophisticated pacing and pharmacologic maneuvers may fail to uncover the presence of VA conduction; (3) although anterograde input is essential for concealment of VA conduction, the phenomenon is more closely associated with depressed retrograde than with anterograde AV nodal characteristics. 
5	Clinical-computed tomographic correlations of lacunar infarction in the Stroke Data Bank. Lacunar stroke was diagnosed in 337 (26%) of the 1,273 patients with cerebral infarction among the 1,805 total in the Stroke Data Bank. We analyzed the 316 patients with classic lacunar syndromes. Among these, 181 (57%) had pure motor hemiparesis, 63 (20%) sensorimotor syndrome, 33 (10%) ataxic hemiparesis, 21 (7%) pure sensory syndrome, and 18 (6%) dysarthria-clumsy hand syndrome. No striking differences were found among the risk factors for the lacunar subtypes, but differences were found between lacunar stroke as a group and other types of infarcts. Compared to 113 patients with large-vessel atherosclerotic infarction, those with lacunar stroke had fewer previous transient ischemic attacks and strokes. Compared to 246 with cardioembolic infarction, patients with lacunar stroke more frequently had hypertension and diabetes and less frequently had cardiac disease. We found a lesion in 35% of the lacunar stroke patients' computed tomograms, with most lesions located in the internal capsule and corona radiata. The mean infarct volume was greater in patients with pure motor hemiparesis or sensorimotor syndrome than in those with the other lacunar stroke subtypes. In patients with pure motor hemiparesis and infarcts in the posterior limb of the internal capsule, there was a correlation between lesion volume and hemiparesis severity except for the few whose infarct involved the lowest portion of the internal capsule; in these patients severe deficits occurred regardless of lesion volume. Taken together, the computed tomographic correlations with the syndromes of hemiparesis showed only slight support for the classical view of a homunculus in the internal capsule. 
4	Exclusion of the Na(+)-H+ antiporter as a candidate gene in human essential hypertension. The primary abnormalities that contribute to the pathogenesis of human essential hypertension are unknown. The known genetic contribution to this disorder suggests the possible use of genetic linkage analysis to test whether specific candidate genes contribute to the pathogenesis of either essential hypertension or intermediate phenotypes. Among such phenotypes, elevated erythrocyte Na(+)-Li+ countertransport (SLC) is the best known, supporting major gene inheritance by pedigree analysis. Striking similarities between SLC and Na(+)-H+ exchange suggest that mutations at the Na(+)-H+ antiporter gene locus (APNH) might result in elevated SLC and contribute to the subsequent pathogenesis of hypertension. We have tested these hypotheses by genetic linkage analysis, with APNH as a candidate gene. By determining genotypes at APNH and flanking loci in pedigrees that support major gene segregation of elevated SLC, we have excluded linkage of APNH and the major SLC locus with a LOD score of -5.91, an odds ratio of almost 1,000,000:1 against linkage. In the analysis of 93 hypertensive sibling pairs, we have further demonstrated that APNH explains none of the variance in SLC in hypertensive individuals (r2 = 6 x 10(-7), p greater than 0.99). Finally, we have directly tested for linkage of APNH to genes predisposing toward hypertension by linkage in hypertensive sibling pairs. Mean allele sharing at APNH is not greater than expected from random assortment in hypertensive siblings (0.92 versus 1.0, p greater than 0.80), and the upper 95% confidence limit of this value (1.04) indicates that mutations at APNH rarely if ever contribute to the pathogenesis of hypertension in this population. 
2	Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to pre-S- and S-encoded viral surface antigens. The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis B virus carriers. Hepatitis B virus DNA was detectable in the serum of HBsAg-positive virus carriers using aliquots as small as 100 al. The detection limit for cloned hepatitis B virus DNA was 100 ag. Primer pairs for different regions of the HBV genome resulted in different sensitivity. Detection of the amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay. Using several primer pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80% of HBe antibody-positive symptomatic HBsAg carriers and 57% of asymptomatic HBe antibody-positive HBsAg carriers were found to have hepatitis B virus DNA in the serum. During antiviral therapy hepatitis B virus DNA disappeared by the polymerase chain reaction assay in patients who became HBeAg negative, but polymerase chain reaction detected a relapse earlier than did the conventional dot blot. Pre-S antigens were assayed in serum and liver samples from most chronic carriers by enzyme-linked immunosorbent assay and/or immunoblot. Although most viremic carriers were strongly positive for pre-S1 and pre-S2 antigens, some hepatitis B virus DNA-positive HBsAg carriers did not have detectable pre-S antigens, and vice versa. Our data show that assay of hepatitis B virus DNA in the serum by polymerase chain reaction is by far more proficient than by dot blot and that it cannot be replaced by serological assays of HBeAg or pre-S antigen. 
4	Risk factors for gestational diabetes in black population. In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension. Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy. The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects. Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene. Restriction-fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C-III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis. 
2	Pathogenesis and therapy of peptic ulcer disease. The epithelial cells of the stomach and duodenum are normally protected from the damaging effects of acid and pepsin by a balancing mechanism of mucosal resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching has emphasized the importance of acid (and pepsin) as the cause of this imbalance; however, it is clear that acid and pepsin are not the only important factors in the pathogenesis of peptic ulcer. More recent investigative efforts have been directed at what constitutes mucosal resistance and how it can be disrupted to produce, in the presence of gastric acid, a peptic ulcer. Depletion of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as prominent theories. As evidence exists both to support and refute these theories in humans, any definitive conclusions cannot be made at this time. The acute management of peptic ulcer disease is directed at relieving pain, accelerating ulcer healing, and preventing complications. Peptic ulcers can be healed with antisecretory agents (i.e., H2-receptor antagonists, omeprazole), antacids, prostaglandins, and sucralfate. Because they are effective, safe, and convenient, the H2-receptor antagonists are the most widely used agents for the management of peptic ulcer disease. Because the H2-receptor antagonist agents are equally effective in their indicated uses and are equally safe based on scientifically valid data, selection should be based primarily on cost. Omeprazole is the newest antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for 24 h. The agent offers little advantage over H2-receptor antagonists for the majority of patients with peptic ulcer. 
1	Carotid body tumors. The surgical management of carotid body tumors requires identification and preservation of neural and vascular structures without compromising resection of the neoplasm. Fifteen patients were examined and treated for carotid body tumors at the Cleveland (Ohio) Clinic Foundation from 1979 through 1987. The benchmark of diagnosis is bilateral carotid angiography. When neural structures are free of tumor, meticulous dissection facilitates their preservation. Large tumor size increases risk for arterial resection necessitating reconstruction. The use of a vascular shunt minimizes the risk of cerebral ischemia. Postoperative intravenous digital subtraction angiography allows for evaluation of arterial repair. A retrospective review of 15 carotid body tumor resections performed in 14 patients revealed no evidence of tumor recurrence, no mortality associated with surgical intervention, no postoperative cerebrovascular accident, and limited morbidity associated with unavoidable sacrifice of neural elements. 
5	Glaucoma triple procedures: efficacy of intraocular pressure control and visual outcome. Sixty-three glaucoma triple surgeries [combined trabeculectomy, extracapsular cataract extraction (ECCE), and posterior-chamber intraocular lens (PC-IOL) implantation] were reviewed. Intraocular pressure (IOP) was controlled satisfactorily in all cases; 25% required additional glaucoma therapy but fewer glaucoma medications. Eighty-six percent achieved 6/12 or better visual acuity. Postoperative IOP and visual acuity results were similar to those achieved by trabeculectomy or ECCE/PC-IOL, respectively. Cumulative years of preoperative glaucoma therapy had an adverse effect on postoperative IOP control. 
3	Fibrillation potential amplitude and muscle atrophy following peripheral nerve injury. Maximum peak-to-peak fibrillation potential amplitude was measured in 69 subjects between 7 days and 10 1/2 years post complete or partial peripheral nerve injury. Mean amplitude during the first 2 months was 612 muV; third and fourth months 512 muV, fifth and sixth months 320 muV. After the first year, no population of fibrillation potentials greater than 100 muV was recorded. The sciatic nerve was sectioned in 13 guinea pigs and animals studied up to 17 weeks. Fibrillation potential amplitude in gastrocnemius muscles declined paralleling that in humans. By the end of the study, type I fibers had lost almost half of their initial diameter and type II fibers had atrophied more than twice this amount. Fibrillation potential amplitude may be useful in estimating the time post nerve injury and appears to correlate with the surface area and fiber diameter of a type I muscle fiber. 
1	Subclinical vulvar papillomavirus infection. Eighty-eight cases of subclinical human papillomavirus (HPV) vulvar infection were detected in a consecutive colposcopic series of 968 women. Three patterns of acetowhite lesions had a 72% predictive value (88/122) for histologically assessed HPV. The prevalence of subclinical vulvar HPV in self-referred patients was 7.9% (73/918); it was 9% (88/968) in the overall series and significantly higher in younger patients (age less than 25 years: 21/106, or 19.8%) or in those with cervical HPV or cervical intraepithelial neoplasia (CIN) (40/100, or 40%). Routine inspection of the vulva after acetic acid lavage in association with a Papanicolaou test might help identify Papanicolaou-test-negative patients at high risk of developing cervical HPV or CIN. Treatment with beta-interferon (2,000,000 IU daily intramuscularly for 10 days) was given to 30 consecutive patients, but the results were poor: regression was observed in only 2 cases. 
5	Vesicular changes in the myopathies of AIDS. Ultrastructural observations and their relationship to zidovudine treatment. Six patients with AIDS and AIDS related complex (ARC) who developed neuromuscular symptoms associated with vesicular changes in muscle fibres are reported. Two patients in the advanced stages of AIDS, who did not receive zidovudine, developed proximal limb weakness and wasting: both had a necrotising myopathy with an unusual segmental vesicular change of myofibres. There were numerous vesicles 0.1 to 2 microns in diameter produced by dilatations of the sarcoplasmic reticulum in fibres depleted of myofibrils. Four patients developed a myopathy while receiving zidovudine for AIDS. One of these had an inflammatory myopathy which showed the development of vesicular change due to enlargement and electron lucency of mitochondria. The three other patients with ARC developed muscle pains or weakness and elevated serum CK while on zidovudine. These patients also showed vesicular changes due to enlargement and electron lucency of mitochondria associated with disruption of sarcomeres and the presence of cytoplasmic bodies. The muscular symptoms resolved when ziduvodine was stopped and repeat biopsy in one case revealed no abnormalities. 
4	Identification of the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation. We continuously observed successive pairs of R-R intervals during atrial fibrillation and hypothesized that the shortest R-R interval for a given preceding R-R interval in a pair represents the functional refractory period of the atrioventricular node at that preceding interval. To test this hypothesis we simulated atrial fibrillation in 28 isolated cross-perfused canine hearts and obtained an R-R interval scatterplot by plotting the R-R intervals as a function of the immediately preceding R-R interval. This scatterplot enabled us to detect a series of the shortest R-R intervals for a wide range of preceding R-R intervals, and this allowed us to estimate the rate-dependent functional refractory period of the atrioventricular node in simulated atrial fibrillation. The estimated functional refractory periods correlated well with those measured by the conventional method (r = 0.93). We conclude that the proposed method makes it possible to estimate the rate-dependent functional refractory periods of the atrioventricular node in atrial fibrillation. 
5	A prospective evaluation of the effectiveness of temporomandibular joint arthroscopy. This is a prospective study to evaluate therapeutic arthroscopy for internal derangement of the temporomandibular joint (TMJ). Fifty-nine patients with 76 abnormal joints were evaluated preoperatively for pain, noise, maximal incisal opening (MIO), and deviation on opening. Preoperative and postoperative magnetic resonance imaging (MRI) scans were obtained for 29 joints. Patients were treated by superior joint arthroscopy, lysis of adhesions, lavage, and steroid injection, along with preoperative and postoperative splint and physiotherapy. Pain, noise, and motion were evaluated at three time periods: 1) early (10 to 30 days); 2) intermediate (1 to 6 months); and 3) late (greater than 6 months). At early, intermediate, and late follow-up, increase in MIO was statistically significant (P less than .05). Noise did not return in the majority of patients. Disc position, evaluated by MRI, did not appear to change in 25 of 29 joints and did not correlate with clinical outcome. The results of this study indicate that TMJ arthroscopy is effective in reducing pain and increasing motion in patients with TMJ internal derangement. 
2	Crypt cell proliferation and HLA-DR expression in pelvic ileal pouches. To investigate the nature of the morphological changes that occur in ileal pouches, 26 biopsy specimens from patients with functioning ileo-anal pouches (eight with pouchitis) were studied. Normal ileum (n = 10) was used as a control. Mucosal morphometry (using linear measurements), crypt cell proliferation (CCP) (using the monoclonal antibody Ki67), and epithelial HLA-DR expression (monoclonal antibody CR3/43) were assessed. CCP (expressed as the percentage of Ki67 positive nuclei for each crypt) was significantly higher in pouches with pouchitis, compared with those without, and in pouches without pouchitis compared with normal ileum. CCP values in some pouches without pouchitis approached values found in those with pouchitis. CCP was related inversely to villous height and an index of villous atrophy (VH/TMT), and directly to crypt depth. In the presence of pouchitis there was intense epithelial HLA-DR expression that extended into the crypts. In some pouches with high CCP values, but without clinically important inflammation, surface epithelial HLA-DR expression was weak and patchy. It is concluded that villous atrophy and crypt hyperplasia in ileal pouches are associated with high CCP values. These may be increased even in the absence of active inflammation, and this increase may occur as a response to the new luminal environment. 
5	Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children ages one to nine years presenting at the hospital. Seventy-four children ages 1 to 9 years hospitalized because of severe pneumonia were investigated using blood cultures, lung aspirates, nasopharyngeal aspirates, serology and antigen detection procedures. A bacterial infection was identified in 57 (77%), a viral infection was seen in 25 (34%) and 18 (24%) had mixed viral-bacterial infections. The bacterial pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae found in 61 and 15% of patients, respectively. The viral pathogen most frequently recovered was respiratory syncytial virus (12%). Evidence of Chlamydia pneumoniae strain TWAR and Mycoplasma pneumoniae infection was found in 12 and 4% of cases, respectively. Overall a potential pathogen was identified in 60 (81%) children, with evidence of polymicrobial infection in 30 cases (40.5%). The study provides information on the relative role of different infectious agents in the etiology of severe pneumonia in children in a developing country. 
3	Radiology for cochlear implants. One fifth of patients selected for cochlear implants have such bony irregularities in the cochlear duct that full insertion of a multichannel electrode array is impossible. Three cases of cochlear deafness are presented where pre- and post-operative radiology played an important part in the management. Standard CT at 2 mm cuts is compared with ultra high resolution CT at 1 mm cuts. The pitfall of poor definition is that the inexperienced surgeon may find himself unexpectedly drilling out an obliterated cochlear duct. Sections 30 degrees caudal to Reid's infra orbito-meatal base line at 1 mm intervals give maximum information for minimum radiation. Plain films show the placement of individual platinum electrode contacts in relation to the spiral 'frequency map' of the cochlea. This is vital information for the audiologist who has to route specific frequencies to specific sites within the ear for a good hearing result. 
4	Hypertension and diabetes in blacks. This article summarizes the current state of knowledge on the interrelationship between non-insulin-dependent diabetes mellitus, obesity, insulin resistance, and hypertension in our attempt to explore the pathophysiology of the high incidence of diabetes and hypertension in the Black population in the United States. A central role for hyperinsulinemia is proposed, and questions are raised that are suitable for investigative clinical trials. 
5	Defective oral tolerance promotes nephritogenesis in experimental IgA nephropathy induced by oral immunization. Oral tolerance, an important feature of the mucosal immune system, appears to protect against immune-mediated disease by blunting production of systemic IgG and IgM antibody directed toward immunogens chronically present at mucosal surfaces. In this study, we explored the role of oral tolerance and mucosal immunoregulation in an experimental model of IgA nephropathy (IgAN), an important form of nephritis in humans. Cyclophosphamide and estradiol were used to inhibit the expression of oral tolerance, which otherwise develops after chronic oral presentation of Ag. BALB/c mice given drinking water containing 0.1% bovine gamma globulin (BGG) continuously for 14 wk were randomly assigned to groups given either 2 mg of cyclophosphamide i.p., 2 mg of estradiol s.c. or both drugs. Groups of control mice received neither BGG nor drugs. In three separate experiments, a low percentage of saline-treated orally immunized mice had microscopic hematuria (0 to 20%), as did nonimmunized controls (0 to 20%). However, 58 to 83% of mice given estradiol and/or cyclophosphamide at appropriate times developed significant hematuria. If drugs were given at suboptimal times, only 25 to 56% of mice developed hematuria. Drug-treated immunized mice also had more serum IgG and IgM anti-BGG antibodies than control and saline groups. Immunofluorescence showed significantly more glomerular deposits of IgG, IgM, and C3 in drug-treated immunized mice compared to saline-treated immunized and normal untreated control mice. Hematuria and glomerular deposits of IgG, IgM, and C3 paralleled serum IgG and IgM antibody. All immunized mice showed significant mesangial IgA and BGG deposits and there were no differences in such deposits between saline- and drug-treated immunized mice. We suggest that blunting of oral tolerance with promotion of systemic IgG and IgM antibody production leads to nephritis in chronically orally immunized mice and that glomerular immune complexes containing IgG and/or IgM promote complement deposition and hematuria in IgAN. Analogous defects in oral (or more generally mucosal) tolerance could play a role in the genesis of symptomatic human IgAN. 
5	The use of the Jarvik-7 total artificial heart and the Symbion ventricular assist device as a bridge to transplantation. The proliferation of transplantation programs has not been paralleled by a similar increase in the availability of organ donors. Between 1984 and 1987, 104 orthotopic heart transplantations were performed at Loyola University Medical Center. During the same period, 25 patients died while awaiting a donor organ. To reduce the mortality, we began using the total artificial heart (TAH) and a ventricular assist device (VAD) as a bridge to transplantation in 1988. Of 29 patients who underwent transplantation, 15 patients required a TAH and three patients required a VAD as a bridge. The underlying heart conditions were ischemic cardiomyopathy (11 patients), dilated cardiomyopathy (5 patients), giant cell myocarditis (1 patient), and allograft failure (1 patient). The average duration of mechanical support was 10 days (range, 1 to 35 days). Of the 17 patients who successfully underwent transplantation, 1 patient died at 17 days because of acute rejection of the transplanted heart, and another patient died at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long-term survivors. Nine patients required reoperation for bleeding. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with heparin. Dipyridamole was given. We conclude that the TAH and VAD are excellent mechanical bridges to transplantation. 
3	Hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis. A case is presented of 14 year old female with hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis. Evidence of hypothalamic obesity included 1) acute hyperphagia and weight gain, 2) neuroradiology showed hydrocephalus with focal enlargement of the third ventricle, 3) endocrinological studies revealed hyperinsulinaemia and impaired growth hormone (GH) response to arginine, but normal GH response to growth hormone-releasing factor (GRF) and 4) Torkildsen's ventriculo-cisternal shunting resulted in improvement in hyperphagia and obesity. 
1	Lung cancer histology in Jews and Arabs in Israel, 1962-1982. Lung cancer rates in Israel are lower than in Western countries, not explainable by smoking habits. Because of the different relations of squamous cell carcinoma and adenocarcinoma to smoking it was of interest to study the histologic distribution in Israel. A total of 7,871 histologically confirmed lung cancer cases were studied in the period 1962-1982. Squamous cell carcinoma was the leading tumor type in Jewish men and adenocarcinoma in Jewish women. Rates of both adenocarcinoma and squamous cell carcinoma increased throughout the period in both Jewish men and women, but the increase in adenocarcinoma was more pronounced in the last study period than that in squamous cell carcinoma. In 1977-1982 the rate ratio of squamous cell carcinoma to adenocarcinoma among Jewish men was 1.7. In Arab men it was 2.9, and in Jewish women 0.57. The Kreyberg I/II ratio among Jewish men was about 2.7 with no clear trend throughout the study period, and among Arab men this gradually decreased from 8.1 to 3.5. Jewish women had a constant Kreyberg I/II ratio of about 1 through the whole study period, but the ratio in Arab women was significantly higher than 1, with a mean overall ratio of 3.2. Jews and Arabs in Israel are different from each other in their patterns of lung cancer histology and are different to some extent from other populations in the Western world. 
4	Heart disease in Asians and Pacific-Islanders, Hispanics, and Native Americans. Heart disease is the leading cause of death for Asian-Americans and Pacific-Islanders, Hispanic-Americans, and Native Americans. Generally, heart disease death rates are lower in these population groups than in Caucasians, with the notable exception of Native Americans under the age of 35. Of particular interest are data for southwestern US Native Americans and Mexican-Americans, which indicate low CHD prevalence rates despite high rates of obesity, diabetes mellitus, increasing hypertension, and low socioeconomic status. Much more research is needed to explain these and other observations. Intervention in those risk factors already identified is necessary, particularly in prevention of obesity and diabetes. 
1	Fine-needle aspiration cytology and flow cytometry of intracystic papillary carcinoma of breast To define criteria for cytologic diagnosis of intracystic papillary carcinoma (ICPC), the authors retrospectively reviewed the fine-needle aspiration (FNA) cytologic specimens of eight cases of histologically proven ICPC of breast. The patients were five black and three white women, 56-87 years of age. The FNA specimen was cyst fluid in four cases (bloody in three, clear in one). All the aspirates showed cellular smears with small and large clusters of cells with papillary and/or cribriform configurations and numerous single epithelial cells. The cells were cuboidal to columnar with minimal atypia. ICPC was suggested by FNA in each case, and all the patients underwent surgical excision or mastectomy. Flow cytometry, performed on fresh FNA specimen in one case and on paraffin-embedded surgical tissue in all eight cases, showed seven tumors to be aneuploid and one to be diploid. The authors contend that ICPCs of breast have distinct cytomorphologic features that can be recognized by FNA. Because ICPC may present in cyst fluid, either bloody or clear, all breast cyst fluids from postmenopausal women should be examined cytologically. Flow cytometric demonstration of an aneuploid population may assist in confirming malignancy in this lesion. 
5	Host genetic influences on fetal susceptibility to murine cytomegalovirus after maternal or fetal infection. Genetically determined resistance to murine cytomegalovirus is observed in adult mice and is mediated in part by genes of the H-2 complex, with the H-2k haplotype conferring resistance. This model was used to examine the effect of primary maternal infection on fetal outcome. The severity of fetal growth retardation and death after primary maternal infection on day 8 of pregnancy was found to be genetically determined. Fetal viability and weight were significantly lower in infected BALB/c mothers (H-2d) than in CBA(H-2k) and BALB.K(H-2k) mothers. However, fetal infection was not detected, suggesting that the resistance mechanisms operate at the level of the mother or placenta. By directly inoculating fetuses in utero, it was shown that genetic factors in the fetus can influence the level of fetal infection and viability. These results point to the possibility that host genetic factors may modulate maternal and fetal cytomegalovirus infections in humans. 
5	Factors associated with hemorrhage in cesarean deliveries. A case-control study was performed to study risk factors for hemorrhage in cesarean deliveries. Hemorrhage was defined by a pre- to post-delivery hematocrit decrease of 10 points or more or by the need for red-cell transfusion. Patients with antenatal bleeding were excluded. Among 3052 cesarean deliveries, hemorrhage occurred in 196 cases (6.4%). Three controls were matched to each case and multiple logistic regression was used to control for covariance among predictor variables. Factors having a significant association with hemorrhage were: general anesthesia (adjusted odds ratio 2.94), amnionitis (odds ratio 2.69), preeclampsia (2.18), protracted active phase of labor (2.40), second-stage arrest (1.90), and Hispanic ethnicity (1.82). After adjustment for these variables, a classic uterine incision had a small but significant association (odds ratio 1.06) with hemorrhage. Previous cesarean, parity, gestational age, and several other factors had no association with hemorrhage. These data allow one to anticipate hemorrhage in patients at risk and may be useful in planning appropriate use of blood bank resources, including antepartum autologous blood donation. 
5	Clinical experience with the Medtronic-Hall valve prosthesis. Medtronic-Hall valves were implanted during 204 procedures performed between 1982 and 1988. Mean population age was 54.4 years; 96% of patients were in New York Heart Association functional class III or greater. Emergency operations constituted 16% of the procedures. Rheumatic heart disease was the single most common indication for valve replacement. In 18% of patients, operation was performed to replace a previous prosthetic valve. The mean follow-up was 3.2 years. Overall operative mortality was 10.3%, the highest mortality being for double-valve replacements (24%). Valve-related mortality, by position, was 5.3% for aortic valves, 6.0% for mitral valves, and 4.0% for multiple-valve replacements. Actuarial 5-year freedom from events were: survival, 68%; thromboembolism, 90%; prosthetic valve endocarditis, 98%; paravalvular leak, 95%; and reoperation, 92%. Complications with the highest mortality were thromboembolism (36%) and endocarditis (33%). The complication rates in this series are high but the patients were more severely ill than in other reports, and operative survivors experienced a considerable improvement in New York Heart Association functional class. 
5	Role of beta-adrenergic blockers after percutaneous transluminal coronary angioplasty. Restenosis after percutaneous transluminal coronary angioplasty (PTCA) cannot currently be prevented. Different medical regimens have been largely unsuccessful. Experimental studies suggest roles for beta-adrenergic blockers and calcium antagonists. Controlled clinical studies have failed to show any decrease in restenosis rate for calcium antagonists. Corresponding studies for beta blockers are lacking. This study evaluates 541 consecutive PTCA procedures, 455 (86%) in patients treated with beta blockers after PTCA (76% metoprolol, 14% atenolol, 4% sotalol, 6% others) and 86 (14%) in patients without beta blockers. Angiographic success was achieved in 483 of 620 lesions (78%), and was not significantly different with or without beta blockers (79 vs 73%, p greater than 0.05). The procedure success rate and the complication rates (myocardial infarction, emergency coronary artery bypass grafting, death) did not differ with or without beta blockers (p greater than 0.05). Follow-up angiograms for 426 of the 483 successfully dilated lesions (88%) revealed that a total of 155 stenoses had recurred (36%). The restenosis rate was not significantly different with (368) or without (58) beta blockers (36 vs 38%, p greater than 0.05). For beta blockers with calcium antagonists (84% nifedipine, 13% diltiazem, 2% verapamil, 1% others), the restenosis rate was 97 of 250 (39%) vs 36 of 118 (31%) (p greater than 0.05). This retrospective study indicates that treatment with beta-adrenergic blockers after PTCA, alone or in combination with calcium antagonists, does not influence either the success rate or the restenosis rate and can be continued if indicated from an antiischemic viewpoint. 
4	Triggers of transient myocardial ischemia: circadian variation and relation to plaque rupture and coronary thrombosis in stable coronary artery disease. The phenomenon of transient myocardial ischemia is common in patients with stable coronary disease and appears to be due both to increases in myocardial demand and to episodic coronary vasoconstriction. The circadian variation of transient ischemic episodes closely parallels the circadian variation of acute coronary syndromes associated with plaque rupture, such as myocardial infarction and sudden death. These concordant temporal patterns of transient ischemia, myocardial infarction and sudden cardiac death probably represent independent manifestations stemming from the consequences of increased sympathetic activity. 
2	Gallbladder surgery following cholecystlithotripsy: suggested guidelines for treatment Twenty-three of 229 symptomatic patients undergoing cholecystlithotripsy underwent surgical intervention: 22 of the patients had cholecystectomy performed (five also undergoing choledochotomy) and one patient had a cholecystostomy. Of these 23 patients, five were lithotripsy failures, five developed acute pancreatitis, one had acute cholecystitis, and one had cholangitis. One patient had her gallbladder removed incidentally at the time of surgery for a bleeding gastric ulcer. Ten patients underwent surgery for recurrent biliary pain, probably related to fragment passage via the cystic duct. We suggest that up to 16 of these 23 patients did not necessarily require cholecystectomy, i.e. five patients with pancreatitis, one patient with cholangitis and ten patients with recurrent biliary colic. Conservative and/or endoscopic management may be successful in the first instance to allow further treatment with lithotripsy in the majority of patients. If, however, the expertise to perform endoscopic sphincterotomy is not available or the patient declines further lithotripsy, then resort to surgery may be necessary. We propose that it is the responsibility of the management team in charge of the lithotripsy unit to inform both the patient and the referring clinicians of the possible side-effects and outcome of treatment in an attempt to avoid unnecessary surgical procedures. 
4	Neurovascular mechanisms and sodium balance in the pathogenesis of hypertension. Physiological studies have clarified the role that the brain has in the interplay between salt balance and hypertension. Neural mechanisms and endocrine secretions play a pivotal role in the adaptation of mammals to changes in the intake and excretion of sodium. Maneuvers that alter the concentration of sodium in the plasma modify the sensitivity of baroreceptor reflexes and alter vascular reactivity. These changes may be mediated in part by the release of vasopressin. The research also suggests that the brain indirectly modulates the ability of the vascular endothelium to release vasoactive factors. Collectively, these studies illustrate the multiple effects of the sodium ion on the peripheral neural and central endocrine mechanisms that participate in the regulation of arterial pressure. 
2	Upper gastrointestinal bleeding in dengue fever. Twenty-six virologically and serologically confirmed Dengue patients with signs of upper gastrointestinal tract bleeding (13.1%) were studied during the 1987 outbreak in southern Taiwan. Within a 1-yr period from 1987 to 1988 in Kaohsiung Chang Gung Memorial Hospital, there were 198 patients with Dengue fever confirmed. Viral isolation and serological studies indicated that type I Dengue was the cause. There was no evidence of sequential secondary infection among them. The 26 patients were evaluated gastroduodenoscopically. Most of the Dengue patients who developed upper gastrointestinal bleeding had gastric ulcers or duodenal ulcers; superficial and hemorrhagic gastritis are the other relevant endoscopic findings. Thirteen patients (50%) had a past history of peptic ulcer symptoms, whereas the other 13 did not. Dengue infection is a precipitating factor in inducing peptic ulcer bleeding because of hemostatic derangements. Supportive therapy and blood transfusions alone were adequate treatment, except for one patient who required surgery due to massive bleeding of a duodenal ulcer. No mortality was observed in this study. 
5	Anorectal dysfunction in patients with urologic disturbance due to multiple sclerosis. Anorectal function was evaluated in 11 patients with voiding dysfunction due to multiple sclerosis. In six patients with constipation, three also had symptoms of obstructed defecation and one patient was incontinent due to stercoral diarrhea. One patient was only fecal incontinent and one patient had obstructed defecation as the only symptom. Three patients had no anorectal symptoms. Anal manometry in the women compared with a control group revealed significant lower anal resting and squeeze pressures, although no significant difference of rectal sensation to distention with air was found. Pudendal nerve terminal latencies were obtained in seven patients and were all normal. In four patients latency could not be demonstrated due to poor contraction of the sphincter on stimulation of the pudendal nerve. Two of these patients were incontinent and two had both constipation and obstructed defecation. It is concluded that patients with voiding symptoms due to multiple sclerosis often reveal anorectal symptoms or motility disorders. Although anal sphincter function is reduced, fecal incontinence is not prevalent in this group. The reason for this lies probably in the fact that many of the patients are constipated, thus securing fecal continence. 
1	Vaginal mullerian cyst presenting as an anterior enterocele: a case report. A case is discussed of an extremely large vaginal mullerian cyst that presented as an anterior enterocele. Sonographic and radiologic studies are described. The patient underwent operative excision of the cyst with reconstructive vaginoplasty. 
4	Effects of long-term treatment with metoprolol and hydrochlorothiazide on plasma lipids and lipoproteins. In order to evaluate the effects of one-year antihypertensive treatment on plasma lipids and lipoproteins, 65 patients whose diastolic blood pressure was in the range 95-120 mmHg were randomly allocated to groups that received either hydrochlorothiazide or metoprolol, or both drugs when the response to one of them was insufficient to control blood pressure. Blood pressure was effectively reduced in all groups. Patients on hydrochlorothiazide showed a significant increase (P less than 0.01) in low-density lipoprotein cholesterol (LDL-C) after 3 months of treatment. A significant increase in triglycerides was observed after 6 and 12 months, together with a decrease in high-density lipoprotein cholesterol (HDL-C) after 12 months (P less than 0.05) of treatment in patients on metoprolol. In patients treated with both hydrochlorothiazide and metoprolol, total cholesterol increased after 3 (P less than 0.001) and 6 months (P less than 0.05), triglycerides increased after 6 (P less than 0.01) and 12 months (P less than 0.01), and LDL-C increased after 3 (P less than 0.05), 6 (P less than 0.001) and 12 months (P less than 0.01) of treatment, respectively. In 61% of the patients, three or more lipid parameters were affected during the study period. We conclude that long-term antihypertensive treatment with hydrochlorothiazide, metoprolol, and particularly with both drugs, can induce lipid effects that deserve recognition, because in some cases these might counteract the possible benefit of a reduction in blood pressure on the prevention of coronary heart disease. 
1	Subsite distribution and incidence of colorectal cancer in New Zealand, 1974-1983. The purpose of this study was to examine changes in subsite distribution and incidence of colorectal cancer within different age groups. Registration of colorectal cancer by the National Cancer Registry of New Zealand approached 100 percent by 1974. The present study was based on 15,395 individuals aged 25 years and over and registered for colorectal cancer between 1974 and 1983. Subsite distribution (right colon, left colon, rectum) for different age groups (25-49, 50-69, 70+ years) was significantly skewed, with an excess of right colonic cancer in individuals aged 25-49 years and 70+ years. This right colonic excess was accompanied by a relative reduction in left colonic cancer. Age adjusted incidence rates for the periods 1974-78 and 1979-83 were compared and stratified by age group and subsite. Incidence rates increased in all subsites in individuals aged 50+ years. This was particularly evident for right sided cancer in the elderly of both sexes. There was a marked reduction in the incidence of left colonic cancer and rectal cancer in individuals under 50 years. In contrast, the incidence of right colonic cancer remained relatively stable in young individuals. Time trend studies indicate that the skewed subsite distribution of large bowel cancer in different age groups may increase with time and is probably due to varying etiological factors acting on different cohorts. 
4	Prognostic value of thallium-201 myocardial perfusion imaging in patients with unstable angina who respond to medical treatment [published erratum appears in J Am Coll Cardiol 1991 Sep;18(3):889] Although the prognostic value of thallium-201 imaging is well established, its ability to risk stratify patients who present with unstable angina is unclear. Fifty-two consecutive patients admitted with unstable angina who responded to medical treatment and underwent stress thallium-201 imaging within 1 week of discharge were studied. Patients were followed up for 39 +/- 11 months. Cardiac events included cardiac death (n = 3), nonfatal myocardial infarction (n = 4) and admission for unstable angina or revascularization (n = 17). The ability of thallium-201 data (redistribution, fixed defects, normal) to predict cardiac events was compared with clinical data (age, gender, prior myocardial infarction, anginal syndrome, rest and stress electrocardiogram) and cardiac catheterization data using logistic regression. Thallium-201 redistribution was the only significant predictor of cardiac death or nonfatal myocardial infarction (p less than 0.05). The number of myocardial segments with thallium-201 redistribution (p less than 0.0005) and a history of prior myocardial infarction (p less than 0.05) were the only significant predictors of all cardiac events. Cardiac death or nonfatal myocardial infarction occurred more frequently in patients with thallium-201 redistribution (6 [26%] of 23) than in those without redistribution (1 [3%] of 29, p less than 0.05). Similarly, total cardiac events developed more frequently in patients with thallium-201 redistribution (p less than 0.001). Stress thallium-201 imaging has important prognostic value in patients admitted with unstable angina who respond to medical therapy and can identify subgroups at high versus low risk for future cardiac events. 
1	Type II oestrogen binding sites in human colorectal carcinoma. Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors. The tumours specifically bound oestradiol. This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites. Oestrogen receptors were absent or present at very low concentrations. Immunohistochemical investigation of nuclear oestrogen receptors gave negative results. This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites. The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma. 
2	Candidacidal activity of Crohn's disease neutrophils. The ability of normal and Crohn's disease neutrophils to kill Candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10(6) cells per ml. C albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10(7) organisms/ml. Neutrophils and Candida were then incubated together at 37 degrees C in a shaking water bath in the presence of fresh serum. At 30 and 60 minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed by colony counting. Results were compared with control suspensions of Candida incubated with serum alone. After 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more Candida than Crohn's disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005). The results did not alter significantly when normal neutrophils were incubated with Candida in the presence of Crohn's disease serum instead of normal serum. When Crohn's disease neutrophils were incubated with Candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at 60 minutes. Phagocytosis, measured using a radiometric assay, was normal. Neutrophils from patients with Crohn's disease have an impaired ability to kill this granuloma provoking organism. It is not due to serum inhibitors or defective phagocytosis. 
2	Extrahepatic biliary obstruction by lymphoma. Extrinsic compression of the common bile duct by enlarged lymph nodes is an unusual cause of obstructive jaundice. We describe two patients with such a manifestation of lymphoma and the use of endoscopic retrograde cholangiopancreatography in distinguishing this rare complication from other causes of jaundice in lymphoma. Patients may have rapid resolution of both symptoms and biochemical abnormalities by nonoperative biliary bypass combined with chemotherapy and/or radiotherapy. Lymphomatous obstruction should be considered a cause of potentially treatable jaundice in patients with known lymphoma; endoscopic retrograde cholangiopancreatography can be valuable as a diagnostic and therapeutic tool. 
1	Relationship of transfusion and infectious complications after gastric carcinoma operations. To determine the effect of transfusion on the incidence of postoperative infection, a retrospective cohort study of 196 patients who underwent surgery for gastric carcinoma in the period from 1985 through 1989 was carried out. Seventy-one patients (36.2%) developed postoperative septic complications; they had received an average of 4.2 blood units, as compared with 2.7 units received by patients not affected (p less than 0.0053). The hypothesis of dose-response relationship is supported by the Mantel-Haenszel test, as applied to the overall results (p less than 0.01) and the results grouped by duration of operation (p less than 0.02). Furthermore, logistic regression analysis shows transfusion to be an independent risk factor in the incidence of infection (p less than 0.01), as are antibiotic prophylaxis (p less than 0.015), urinary tract catheterization (p less than 0.002), and the duration of surgery (p less than 0.027). This significance is attained after adjustment for age, gender, period of evolution of symptoms; preoperative infection(s), number of white cells, hemoglobin level and total proteins on diagnosis, location of tumor, tumor, nodes, and metastasis staging, operative technique, drainage of the area of operation, enteral nutrition, and the histologic studies and macroscopic appearance of the tumor. This study is further evidence that transfusion may cause an increased incidence of postoperative infection. 
5	Time course of improvement in ventricular function after ablation of incessant automatic atrial tachycardia. A patient with dilated cardiomyopathy and supraventricular tachycardia presumed to be of sinus origin was referred for cardiac transplantation. The extreme rate of the tachycardia during exercise, profound fluctuations in heart rate, and the presence of an abnormal P wave axis suggested the diagnosis of incessant ectopic atrial tachycardia rather than compensatory sinus tachycardia. Electrophysiologic study with endocardial activation sequence mapping confirmed the diagnosis of an ectopic left atrial automatic tachycardia, after which surgical cryoablation of the left atrial focus was carried out successfully and sinus rhythm was restored. Serial radionuclide angiocardiograms obtained before and after surgery demonstrated a very rapid recovery of left ventricular function to nearly normal within the first month after surgery, followed by further improvement to normal over the next several months. The diagnosis of tachycardia-related cardiomyopathy should be seriously considered in any patient with apparently end-stage dilated cardiomyopathy and persistent resting tachycardia. 
5	Quantification of biomedical findings of chronic pain patients: development of an index of pathology. Difficulties in assessing and quantifying the biomedical signs and symptoms that may be related to patients' reports of pain are well recognized. Although there appears to be some consensus among physicians as to the potential utility of examination and diagnostic tests frequently used to evaluate chronic pain patients, little attention has been paid to the reliability of interpreting the results of these procedures. Moreover, the integration of biomedical findings to form a general index of pathology associated with chronic pain has been a difficult problem to solve because not all biomedical procedures used to evaluate pain patients are necessarily relevant or indicated for a specific patient. Two studies are presented that were designed to evaluate the reliability of 23 biomedical procedures commonly used to evaluate chronic pain patients and to determine if findings on these procedures can effectively be combined to form a reliable index of physical pathology. The results of study 1 suggest that 17 of the 23 procedures can be applied in clinical setting with acceptable levels of reliability. Study 2 provides evidence that an innovative weighted scoring approach, based on current medical consensus, can be used to produce a reliable, general index of pathology that is independent of the number of procedures used to evaluate patients. The utility of this quantification approach to biomedical findings for clinical and research purposes is discussed. 
5	Microvascular pedal bypass for salvage of the severely ischemic limb Bypass to the pedal arteries was performed with use of the operating microscope and standard microsurgical technique in 37 patients with severe, chronic ischemia of a lower extremity. Twenty-one patients (57%) had three or more cardiovascular risk factors, and 22 (59%) had diabetes. Preoperative arteriography identified a pedal artery suitable for bypass in all but one patient. The greater or lesser saphenous vein was used in all patients, most frequently as a nonreversed, translocated vein graft. An arm vein was used as part of a composite graft in only one patient. No early deaths occurred, and only one patient had a perioperative myocardial infarction. Although five grafts occluded within 30 days, four were successfully revised, and 36 patients had a patent graft at the time of dismissal from the hospital. At 1 year, the primary graft patency rate (patency without revision) was 60.8%, and the secondary patency rate was 68.8%. One early and six late amputations were performed; the cumulative 1-year limb salvage rate was 82.4%. Grafts with an intraoperative flow rate of 50 ml/min or more had a better patency rate than those with a lower flow rate. The presence of diabetes did not adversely affect long-term patency. Of the 34 patients who were alive at the time of this report, 27 (79%) had a functional foot that allowed ambulation, had no rest pain, and had no substantial loss of tissue. Pedal bypass should be considered for critical, chronic ischemia, even if the patient has an increased surgical risk and advanced distal atherosclerotic disease. 
5	Argon versus krypton panretinal photocoagulation side effects on the anterior segment. The modification of corneal sensitivity, accommodation, pupillary diameter and endothelial cell density after argon versus krypton panretinal photocoagulation were studied prospectively in 88 eyes of 64 diabetic patients with proliferative diabetic retinopathy, randomized for one of the two laser treatments. In both groups a marked internal ophthalmoplegia and reduction of corneal sensitivity occurred after laser photocoagulation. At no time, 2, 90 and 180 days after PRP, were these parameters significantly different. Endothelial cell loss was non significantly greater in the krypton group. The results indicated that the side effects commonly observed on the anterior segment after PRP are comparable using argon or krypton lasers. 
1	Cytologic features of poorly differentiated 'insular' carcinoma of the thyroid, as revealed by fine-needle aspiration biopsy. The authors report on the cytologic features of six cases of poorly differentiated "insular" carcinoma (IC) of the thyroid, a recently described variety of thyroid tumor intermediate between well-differentiated and anaplastic neoplasms. It is characterized by trabecular and/or alveolar growth patterns, merging with follicular areas, and by the absence of pleomorphism in the tumor cells. Fine-needle aspiration biopsy (FNAB) materials (both smears and cell-block preparations) from six patients were reviewed after the diagnosis of IC was confirmed on the surgical specimen. The following cytologic features were consistently found: high cellularity and necrotic background; low grade of atypia; trabeculae and/or clusters, possibly associated with microfollicles, of cells with poorly defined cytoplasm; and cytoplasmic vacuoles containing thyroglobulin. Nuclear inclusions and grooving of the nuclear surface were additional features. Preoperative diagnosis suggestive of IC might be of value for planning surgical treatment and subsequent therapy. 
5	The influence of calcium alginate haemostatic swabs upon operative blood loss in adenotonsillectomy. Although adenotonsillectomy is regarded as a minor procedure, it has been shown that 18% of patients may experience an operative blood loss of 10-20% of the total blood volume. The aim of this study was to determine whether calcium alginate haemostatic swabs reduce operative blood loss in adenotonsillectomy. Seventy-two patients (ages 2-12 years) entered a prospective trial in which the operation was performed either with normal gauze swabs or calcium alginate swabs. Thirty-six children were randomized to each group. The mean blood loss was found to be 34.9 ml (2.07% of total blood volume) and 47.8 ml (2.97% of total blood volume) respectively. Although there was no significant reduction in operative blood loss using calcium alginate, in both groups the blood loss was much smaller than that stated by the majority of previous workers. 
2	Can clinicians accurately assess esophageal dilation without fluoroscopy? This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation. 
5	Significance of discordant ST alternans in ventricular fibrillation. With the use of epicardial mapping, we investigated the electrical alternans of the ST segment during acute myocardial ischemia and studied the difference in ST alternans between dogs with resultant ventricular fibrillation and those without it. During the 7-minute occlusion of the left anterior descending coronary artery below its first diagonal branch, 60 epicardial unipolar electrograms were recorded simultaneously at 1-minute intervals by a computerized mapping system. ST alternans was found in the eight dogs we observed. The amplitude of ST alternans (difference in the ST segment elevation of two consecutive electrograms) was greater in dogs with ventricular fibrillation (n = 4) than in those without it (n = 4) (3.92 +/- 1.24 versus 0.58 +/- 0.49 mV, p less than 0.05). Three of the four dogs with ventricular fibrillation demonstrated discordant ST alternans (i.e., adjacent leads were out of phase). Results from the present study indicate that an increased amplitude and discordance of ST alternans during acute myocardial ischemia are related to ventricular fibrillation and act as indicators of time and spatial unevenness of ventricular repolarization. 
4	Coronary artery aneurysm without stenosis in association with Osler-Weber-Rendu disease--a case report. A fifty-three-year-old woman presented with coronary artery aneurysm in association with Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia) manifested also by large pulmonary arteriovenous fistulas. The arterial dye dilution curves were unusually distorted owing to the right-to-left shunts. The coronary artery aneurysm was located in multiple sites but was not accompanied by stenotic lesions. Coronary artery aneurysm without stenosis is a rare pathologic state and has not been previously reported in association with hereditary telangiectasia. 
5	Ectopic retinoblastoma within the 3rd ventricle: case report. Ectopic intracranial retinoblastomas are rare. These tumors usually occur in the pineal, parasellar, or suprasellar regions several years after the successful treatment of ocular retinoblastomas with no evidence of direct extension or distant metastasis. We report here a case of ectopic retinoblastoma occurring within the third ventricle. The tumor was surgically excised by the transventricular approach. Ectopic retinoblastomas exhibit greater differentiation than one would expect to observe in a metastatic lesion of this tumor. The distinction of ectopic retinoblastomas and metastasis from ocular retinoblastomas is important, since ectopic retinoblastomas, unlike metastasis, can be successfully managed by intensive therapy including radical excision. 
5	Mobile knee reconstructions after resection of malignant tumors of the distal femur. Limb-salvage surgery involving mobile knee reconstructions for malignant tumors about the distal femur is a desirable and achievable goal. With limb salvage, the survival rate does not decrease significantly, and the resulting function is superior to when an amputation plus a prosthesis are used. Immediate and delayed morbidity is greater after limb-salvage surgery than after amputation. However, with thorough preoperative planning, use of neoadjuvant chemotherapy as indicated, and an experienced team of surgeons, limb-salvage surgery can provide a mobile knee with excellent function in the vast majority of cases for patients with malignant tumors of the distal femur. 
5	Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures. Malignant strictures of the extrahepatic bile ducts are difficult to distinguish from benign strictures, particularly in patients with primary sclerosing cholangitis. Because attempts at diagnosing small cancers with fine-needle aspiration biopsy are not possible in the absence of an associated mass lesion and because the sensitivity of exfoliative biliary cytology is controversial, brush cytology has been used as a potential means of establishing a specific diagnosis of bile duct carcinoma. Herein we report our experience with this technique when performed on 65 patients over a 5-yr period. Each had at least one brushing. Thirty-seven were found to have bile duct carcinoma and 28 were found to have benign strictures. Of these 37, the first brushing was positive for malignancy in 15 (40%), whereas four (11%) had cells suspected but not diagnostic of malignancy. Thirteen patients with bile duct carcinoma whose initial brushings were negative for malignancy had second brushings. Of these, five (38%) had malignant cells, whereas three (24%) yielded suspicious cells. Three of the eight whose first two brushings were negative for malignancy were found to have malignant cells on the third brushing. In contrast, of the 28 patients with benign strictures, malignant cells were never found. However, in two patients, suspicious cells were reported with the first but not the second brushing. A single negative or suspicious cytological finding decreased the probability of bile duct carcinoma to 43%. Two and three sequential negative tests reduced the probability to 32% and 0%, respectively. 
5	Alanine-based oral rehydration therapy for infants with acute diarrhea. Twenty male infants less than 1 year of age with acute diarrhea and dehydration were randomly assigned to a study group and studied in blind fashion in a metabolic unit to assess the efficacy of the addition of 30 mmol/L alanine to the standard World Health Organization (WHO) oral rehydration solution (ORS). Patients were exclusively rehydrated with one of two types of ORS during the first 24 hours of treatment. On the second day, oral feedings were started with a lactose-free formula, and ORS was given to replace stool losses. Body weight, ORS, food intake, vomitus, stool, and urine output were recorded at 6-hour intervals. Blood was drawn at the time of admission, after rehydration, and at 24 and 48 hours of hospitalization to monitor blood gases and electrolytes. Rehydration was satisfactory in both groups of patients. ORS that contained alanine did not reduce the purging rates of the infants compared with those who received standard ORS. Clinically no adverse effect of the alanine-based ORS was observed during hospitalization. None of the patients had significant hypernatremia or hyponatremia, and serum amino acid levels were not altered. These data show that the addition of 30 mmol/L alanine to the standard WHO-ORS produces no further improvement in the outcome of the infants with acute diarrhea compared with those fed the standard WHO-ORS. 
3	Mastalgia refractory to drug treatment. Management of the patient with mastalgia who fails to respond to first line therapy is a difficult problem and there is a group of patients who do not respond to any therapy. A group of 126 patients with mastalgia who failed to respond to first line therapy and completed further treatment options was studied. The response rate of those with cyclical mastalgia fell to 57 and 25 per cent for second and third line therapy respectively. Equivalent figures for non-cyclical mastalgia were 24 and 21 per cent. Danazol maintains a high response rate after the failure of other drugs, whereas the second line response to bromocriptine and evening primrose oil is poor. Unresponsive patients were matched to a group of patients who responded to first line therapy, and reproductive and historical factors were compared using the chi 2 test, but failed to identify which patients would respond to therapy. 
3	Dementia: what to do. Dementia is a syndrome of acquired intellectual deterioration that interferes with personal or social functioning. Diagnosis requires historical information from the family and the mental status evaluation of orientation, recent memory, comprehension, calculation, and abstraction. Most dementias create permanent, even progressive cognitive deterioration, yet there are some presentations for which remission exists. Common reversible conditions include depression, drug toxicity, normal-pressure hydrocephalus, hypothyroidism, subdural hematoma, and neoplasm. Screening laboratory studies consist of urinalysis, chemistry profile, blood count, thyroid survey, vitamin B12 and folate measurements, serology, chest roentgenogram, computerized tomographic scan of the head, electroencephalogram, and electrocardiogram. Treatment focuses on potential reversibility, psychosocial issues, restoring deficits, and specific symptoms. 
1	Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors. The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B-CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B-CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL-2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings. 
5	Extravesical versus Leadbetter-Politano ureteroneocystostomy: a comparison of urological complications in 320 renal transplants. The urological complications of 320 consecutive renal transplants performed at our institution between October 17, 1985 and November 10, 1989 are reviewed. The Leadbetter-Politano technique of ureteroneocystostomy was used in the first 160 patients (group 1) and an anterior extravesical technique modified from the methods of Witzel, Sampson and Lich was performed in the second 160 patients (group 2). Urological complications occurred in 15 patients (9.4%) in group 1 and 6 (3.7%) in group 2 (p = 0.04). Ureterovesical junction obstruction occurred in 6 patients (3.7%) in group 1 and 1 (0.6%) in group 2 (p = 0.05). Complications of leakage, ureteral necrosis and ureteral stricture were comparable in the 2 groups. Therefore, we advocate the use of the anterior extravesical technique over Leadbetter-Politano ureteral reimplantation based on the lower incidence of urological complications and various technical advantages, including less operative time, avoidance of a separate cystotomy, less hematuria and ability to use short donor ureters. 
3	Immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction. Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and lower motoneurons of unknown etiology. In support of the potential role of autoimmunity in ALS, two immune-mediated animal models of motoneuron disease have been developed that resemble ALS with respect to the loss of motoneurons, the presence of IgG within motoneurons and at the neuromuscular junction, and with respect to altered physiology of the motor nerve terminal. To provide direct evidence for the primary role of humoral immunity, passive transfer with immunoglobulins from the two animal models and human ALS was carried out. Mice injected with serum or immunoglobulins from the animal disease models and human ALS but not controls demonstrated IgG in motoneurons and at the neuromuscular junction. The mice also demonstrated an increase in miniature end-plate potential (mepp) frequency, with normal amplitude and time course and normal resting membrane potential, indicating an increased resting quantal release of acetylcholine from the nerve terminal. The ability to transfer motoneuron dysfunction with serum immunoglobulins provides evidence for autoimmune mechanisms in the pathogenesis of both the animal models and human ALS. 
4	Acebutolol effects on lipid profile [published erratum appears in Am J Cardiol 1990 Dec 1;66(19):A8] The relation between lipid profile and the incidence of coronary artery disease has been confirmed by the results of epidemiologic and intervention studies. Among antihypertensive agents, beta blockers, particularly those without intrinsic sympathomimetic activity (ISA), are generally reported to have negative effects on lipids, which may increase the risk of coronary artery disease. The ongoing Treatment of Mild Hypertension Study, now in its third year, has evaluated 847 patients to date with regard to lipid profile. Additional end points measured in this multicenter, randomized, controlled, double-blind study include blood pressure reduction and target organ deterioration. During the trial, all patients received nutritional and behavioral counselling to modify their diet, exercise habits and alcohol and sodium consumption to control their hypertension by nonpharmacologic means. In addition, some patients were randomized to receive low doses of 1 of the 5 classes of antihypertensive medication: acebutolol, a beta blocker with ISA (n = 124); amlodipine, a calcium channel blocker (n = 122); chlorthalidone, a diuretic (n = 125); doxazosin, an alpha blocker (n = 128); enalapril, an angiotensin-converting enzyme inhibitor (n = 127) or placebo (n = 221). At 1 year, acebutolol showed a statistically significant (p less than 0.001) decrease in total cholesterol (-12.7 mg/dl) compared with placebo (-5.2 mg/dl) and with chlorthalidone (1.0 mg/dl); a significant (p less than 0.001) decrease in low-density lipoprotein cholesterol (-6.0 mg/dl) compared with placebo (+0.7 mg/dl) and with chlorthalidone (+8.0 mg/dl) and no change in high-density lipoprotein cholesterol (-0.4 mg/dl). 
5	Endothelial cell adhesiveness for human T lymphocytes is inhibited by transforming growth factor-beta 1. Recombinant human transforming growth factor-beta (TGF-beta) was found to inhibit the adhesive phenotype of human umbilical vein endothelial cells for human PBL, purified T lymphocytes, and PHA-activated lymphoblasts. TGF-beta inhibited lymphocyte attachment to resting human umbilical vein endothelial cells and also to endothelial monolayers stimulated with the pro-inflammatory cytokines TNF-alpha and IL-1 beta. Our investigations also show that the ability of endothelial cells to respond to TGF-beta by altering their adhesiveness is lost with prolonged culture of the cells. However, this loss is selective as TGF-beta inhibits cell proliferation in both early and late passage endothelial cells. These results suggest that in vivo TGF-beta may inhibit the adhesive phenotype of endothelial cells and also may limit the immunologic response occurring at the endothelial cell barrier. 
3	The relationship between viral RNA, myelin-specific mRNAs, and demyelination in central nervous system disease during Theiler's virus infection. The DA strain of Theiler's murine encephalomyelitis virus (DAV) causes a chronic demyelinating disease in susceptible mouse strains. To elucidate the pathogenesis of DAV-induced demyelination, the authors investigated the spatial and chronologic relationship between virus (antigen and RNA), myelin-specific mRNAs, and demyelination in DAV-infected mice using immunohistochemistry, in situ hybridization, and slot blot hybridization analyses. In spinal cord white matter, viral RNA was detected easily in ventral root entry zones 1 to 2 weeks after infection. Viral RNA increased to maximum levels by 4 weeks after infection, which was associated with inflammation and mild demyelination. At 8 to 12 weeks after infection, when demyelination became most extensive, viral RNA was significantly decreased. Demyelination did not chronologically or spatially parallel the presence of viral RNA within the spinal cord. Decrease of myelin-specific mRNAs, including myelin-basic protein and proteolipid protein mRNAs, was observed within the demyelinating lesions with or without detectable viral RNA. These results indicate that a viral infection of white matter in the early phase of the infection initiates spinal cord disease leading to demyelination, but later an ongoing immunopathologic process contributes to the presence of extensive demyelination. 
5	Infantile acute hemorrhagic edema of the skin: study of ten cases. Infantile acute hemorrhagic edema of the skin is not included as a separate entity in the current English-language literature as it is in continental Europe. Therefore we have attempted to clarify the nosologic position of acute hemorrhagic edema among cutaneous vasculitides in children, on the basis of our experience in 10 cases. Our study confirms that acute hemorrhagic edema affects infants between 4 and 24 months of age. The two main features are an ecchymotic purpura, often in a cockade pattern, and an inflammatory edema of the limbs and face. Visceral involvement is uncommon. Spontaneous and complete resolution occurs within 1 to 3 weeks; one to four attacks may occur. Histopathologic examination demonstrates a leukocytoclastic vasculitis. Perivascular IgA deposits can occasionally be found. Besides typical acute hemorrhagic edema, some cases in 2- to 4-year-old children appear to overlap with Schonlein-Henoch purpura. We suggest that typical acute hemorrhagic edema should be regarded as a separate clinical entity. This allows an appropriate prognosis to be made for this generally benign disease of infants. 
1	Vascular lesions of the intestines. This article reviews the pathology, pathophysiology, diagnosis, and treatment of vascular lesions of the intestine as a cause of gastrointestinal bleeding. In addition, a modified system for classifying such lesions, based on the author's personal experience with such lesions, is presented. 
3	Headache and acquired immunodeficiency syndrome. Because the acquired immunodeficiency syndrome (AIDS) virus is neurotropic, physicians will continue to see a rise in the number of neurologic complications of this syndrome. Much of this increase will be accompanied by headache, not only as a primary symptom of HIV infection or opportunistic disease but also as a result of diagnostic tests and therapeutic efforts. Complete understanding of the ramifications of headache in AIDS will be important in the 1990s as we continue to treat a younger population, usually affected by benign vascular and muscle contraction-type headache. 
4	Right pulmonary artery obstruction after pulmonary artery banding. Serial assessment of pulmonary artery flow by Doppler echocardiography was carried out in 15 infants after pulmonary artery banding. Three infants were identified as having branch pulmonary artery obstruction based on diastolic pulmonary artery flow. It is concluded that this flow profile may be specific for branch pulmonary artery obstruction after pulmonary artery banding. 
3	Complications of lateral C1-2 puncture myelography. This study reviewed the technical complication of 112 cases of lateral C1-2 puncture myelography for cervical spinal cord disorders. Spinal cord puncture and contrast injection, puncture between the occiput and C1, and blood vessel puncture were the main complications. These principally depended on the positioning of the patient's neck (hyperextension) and misdirection of the x-ray beam. For preventing major arterial puncture, the authors also reviewed 164 vertebral angiograms and determined the pathway of the vertebral arteries and the incidence of anomaly. 
5	Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study. Endoscopic, clinical, and laboratory parameters including presence of varices in the gastric fundus, red color sign, diameter and number of variceal columns, platelet count, and the Child status were assessed in 109 patients with cirrhosis and esophageal varices without previous variceal bleeding. During a mean follow-up period of 21 months, the predictive values of these parameters with regard to first bleeding incidence and mortality rate were studied. The incidence of bleeding was 29%, and the mortality rate 46%. Endoscopic criteria (presence of varices in the gastric fundus, presence of the red color sign, and size of the largest varix) as well as alcoholic etiology of cirrhosis showed a significant positive correlation with the bleeding incidence but not with mortality. Contrary to this, two factors of the Child classification (encephalopathy and ascites) and age positively correlated with mortality but not with the bleeding incidence. 
3	Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA). We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications. 
5	Hypoxemia in the postanesthesia care unit: an observer study To determine the incidence and duration of hypoxemia in the postanesthesia care unit (PACU), 200 patients were investigated in a single-blind observer study. The number of unrecognized hypoxemic episodes, as well as risk factors and possible association between hypoxemia and postoperative morbidity, were studied. Oxygenation was monitored continuously with a pulse oximeter. One or more hypoxemic episodes (SpO2 less than or equal to 90%) were noted in 55% of the patients. SpO2 values less than or equal to 80% were noted in 13% of the patients. Supplementary oxygen was given during 55% of the 447 hypoxemic episodes registered. The hypoxemic episodes were unrecognized by the staff in 95% of the cases. With stepwise multiple logistic regression analyses, risk factors associated with a higher incidence of hypoxemia were: duration of anesthesia (P less than 0.0001), age (P less than 0.002) and a history of smoking (P less than 0.01). Patients who had undergone regional anesthesia had a lower risk of hypoxemia (P less than 0.0002). The occurrence of hypoxemia in the PACU could not be correlated to postoperative morbidity. We conclude that hypoxemic episodes in our PACU are common and that the routine use of supplemental oxygen combined with normal clinical surveillance did not prevent hypoxemic episodes. 
3	Diagnostic utility of lower extremity radiographs of young children with gait disturbance. The diagnostic utility of lower extremity radiographs was evaluated using 84 outpatients 1 to 5 years of age with gait disturbance whose lower extremities appeared physically normal. Chief complaints included limp (65 children [77%]), refusal to walk or stand (37 children [44%]), and frequent falling (6 children [7%]). A total of 43 children (51%) had more than one complaint. The mean age of patients was 26 months and the median duration of symptoms was 1 day. Trauma was reported in 43 (51%) cases and fever in 14 (17%). Results of radiographical studies appeared normal in 81 children (96%), demonstrated soft tissue swelling in 2 children, and revealed a bony island in 1 child. In 1 patient admitted to the hospital for failure to thrive and irritability, and whose radiographic results appeared normal, findings consistent with osteomyelitis later developed. Of the remaining children, 68 (81%) were available for follow-up observation 4 to 28 months after the initial visit and all reported spontaneous resolution of the initial complaint. It was concluded that in a well-appearing child with an otherwise normal physical examination results, an acute gait disturbance is likely to be a self-limiting condition and radiographs are unlikely to contribute to the diagnosis. 
4	Comparison of sublingual captopril and nifedipine in immediate treatment of hypertensive emergencies. A randomized, single-blind clinical trial. Sublingual captopril (25 mg) was compared with sublingual nifedipine (10 mg) to determine their effectiveness and safety in the treatment of hypertensive emergencies. In nine of 10 patients who received sublingual captopril, mean (+/- SD) systolic blood pressure and diastolic blood pressure dropped from 245 +/- 39 to 190 +/- 25 mm Hg (P less than .0025) and from 144 +/- 8 to 115 +/- 8 mm Hg (P less than .001) at 50 minutes, respectively. The hypotensive effect of the drug was maintained for a mean of 4 hours. In six of nine responders to sublingual captopril, blood pressure-lowering effect was associated with a clear improvement of end-organ failure within 60 minutes. There were no side effects, including a dangerous fall in blood pressure or reflex tachycardia. Sublingual nifedipine lowered diastolic blood pressure and systolic blood pressure in eight of 10 patients. The hypotensive effect of nifedipine was more rapid than that of captopril (10 vs 20 minutes for diastolic blood pressure and 20 vs 30 minutes for systolic blood pressure, respectively), but no difference was observed in the time or in the magnitude of peak hypotensive effect between the two treatments, nor was a difference observed in the duration of hypotensive effect. In six of eight responders to nifedipine therapy, a clear improvement of symptoms and signs of end-organ failure was observed within 60 minutes. In three patients, minor side effects were observed. We conclude that sublingual captopril effectively and safely lowers arterial blood pressure in patients with hypertensive emergencies. 
4	Systolic Hypertension of the Elderly Program (SHEP). Part 10: Analysis. The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses. The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death. The sample size achieved (4,736 participants) should be adequate to address the proposed questions. Monitoring procedures have been described and established. A data and safety monitoring board that uses these procedures is closely following the data from the trial. The board will periodically examine the data to determine whether termination of the study is warranted. 
1	Long-term follow-up of patients with recurrent malignant gliomas treated with adjuvant adoptive immunotherapy. Between August 1986 and October 1987, the Denver Brain Tumor Research Group conducted a clinical trial using autologous human recombinant interleukin-2 (rIL-2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas. The trial involved surgical resection and/or decompression followed by intracavitary implantation of lymphokine-activated killer (LAK) cells and autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot. One month later, stimulated lymphocytes and rIL-2 were infused through a Rickham reservoir attached to a catheter directed into the tumor bed. The LAK cells were rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days. Of the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range, 15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at entry, 14 mg/d, range, 0-32). The average number of lymphocytes implanted was 7.6 x 10(9) (range, 1.9-27.5 x 10(9], together with 1 to 4 x 10(6) U of rIL-2. To date, 10 of the 11 patients died, all from recurrent tumor growth. The median overall survival time was 63 weeks (range, 36-201; mean, 86). The median survival time after immunotherapy was 18 weeks (range, 11-151; mean, 39). No significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not. The use of steroids or prior chemotherapy did not influence the in vitro generation of ASL or LAK cells. 
1	Basic studies on a new material for inducing antitumor immune cells. Recently, adoptive immunotherapy for cancer with lymphokine activated killer (LAK) cells has been widely used experimentally. The therapy has several problems, including difficulty in handling, sterilization, and time consumption. To solve these problems, new materials able to induce antitumor immune cells were investigated. Pokeweed mitogen (PWM) and PWM-conjugated materials (CMC-1) could induce strong killer cells by short-term stimulation of human peripheral blood lymphocytes (PBL). The induced killer cells showed a wide killing spectrum in vitro against human tumor cell lines (MKK-1, PRMI4788, NBT-2, ZR-7530, H-1, Hela, KB, HMV-1, PC-10, C-1). Human PBL stimulated for a short time by CMC-1 also showed a tumoricidal effect on tumor bearing (MKN-1, MKN-45) nude mice. These results suggest that CMC-1 may solve the problems with currently used LAK therapy and may provide easily applicable extracorporeal immunotherapy for cancer. 
5	Anaesthetic problems in ex situ resection of the liver. Ex-situ resection of the liver is a new surgical technique for treatment of liver tumours not amenable to conventional surgery. This paper describes the cardiovascular and metabolic changes that occurred in nine consecutive such patients. No severe haemodynamic or pulmonary complications occurred. Specific problems were encountered during the prolonged anhepatic period, which lasted an average of 5.96 (SD 1.46) hours. Significant metabolic and coagulation disorders occurred 2 to 3 hours after hepatectomy because of complete loss of hepatic function. The predominant findings during the anhepatic period were hypoglycaemia and severe metabolic acidosis, mainly from increased levels of lactic acid. Exogenous administration of dextrose 5% at an average rate of 188 ml/hour was necessary to maintain normoglycaemia, while correction of metabolic acidosis required 403 (SD 159.79) mmol of sodium bicarbonate, supplemented by hyperventilation. Tris-hydroxymethylaminomethane was used when sodium overload was thought to be a problem. There was a marked decrease of Factor V and fibrinogen, a moderate thrombocytopenia and fibrinolysis. The severity of these alterations was dependent on the duration of the anhepatic period and the primary function of the re-implanted liver. 
1	Obesity and body fat distribution and breast cancer prognosis. This study addresses the effect of obesity and body fat distribution on axillary lymph node involvement, tumor size, and estrogen receptor (ER) level in breast cancer patients. Anthropometric measurements were prospectively obtained on 248 consecutively and newly diagnosed women with invasive breast cancer. The anthropometric measurements evaluated were abdomen, thigh, subscapular, and midaxillary skinfolds; weight; and height. Weight and Quetelet Index (kg/m2) were significantly (P = 0.001) associated with lymph node involvement in postmenopausal patients. The abdomen:thigh skinfold ratio was significantly higher in premenopausal patients (P = 0.004) and postmenopausal (P = 0.03) without axillary node involvement compared with women with 4+ axillary node involvement. The abdomen:thigh skinfold was higher (P = 0.05) in women with smaller breast cancers (less than 2.0 cm) and higher ER levels. Weight and Quetelet Index did not affect tumor size or ER level. This study demonstrated that obese postmenopausal women who developed breast cancer tend to have more axillary node involvement than their leaner counterparts. Generalized obesity did not affect tumor size or ER level. Premenopausal and postmenopausal women with upper body fat distribution appear to be a subset of women who have a more favorable prognosis as measured by less lymph node involvement, smaller tumors, and higher levels of ER in their tumors. 
4	Adventitial red blood cells produce intimal platelet accumulation in cerebral arteries of cats following subarachnoid hemorrhage. After dividing 21 cats into three equal groups, we exposed their right middle cerebral arteries transorbitally and adventitially irrigated them with 2 ml washed red blood cells, blood plasma, or saline. To determine arterial intimal platelet accumulation in each cat, we injected [111In]oxine-labeled platelets intravenously immediately before injecting the various experimental solutions. Animals were sacrificed 2 or 4 hours following the injection of labeled platelets. Irrigation with washed red blood cells produced a significantly greater intraluminal accumulation of platelets than irrigation with saline (p less than 0.05). Plasma tended to have less of an effect on platelet accumulation than washed red blood cells, but this difference was not significant. These data suggest that the adventitial blood fraction responsible for intimal platelet accumulation in cerebral arteries following subarachnoid hemorrhage may be derived mainly from the red blood cell fraction. 
5	The Maylard incision in gynecologic surgery The transverse muscle-splitting Maylard incision was used in 175 gynecologic patients who required pelvic-abdominal surgery. One hundred fifty-three patients (87%) had pelvic malignancy; other indications for operation included uterine myomas, endometriosis, tuboovarian abscess, and benign ovarian cysts. Exposure was excellent: 54% of patients underwent pelvic lymphadenectomy and 17% underwent paraaortic lymphadenectomy. Twelve patients (6.9%) had wound complications, but there was neither long-term morbidity nor mortality associated with the incision. Fifty-six patients (32%) received preoperative or postoperative pelvic radiation therapy with no detrimental effect on wound healing. The Maylard incision is cosmetic, strong, easily learned, and has an acceptable complication rate. Unless a vertical incision is indicated, the Maylard technique is preferred when optimal exposure and accessibility to the pelvis are required. 
5	Coronary angioplasty following cardiac transplantation: a case report and review of the literature. A 23-year-old man underwent successful percutaneous transluminal coronary angioplasty of a severe stenosis of the left anterior descending artery 25 months after orthotopic heart transplantation. Four months later restenosis of the same lesion was treated by repeat PTCA. Angiography 11 months later showed no restenosis. In selected cases, PTCA may be useful in treating allograft coronary disease. 
1	Ampullary hamartoma: endoscopic diagnosis and treatment. This study shows a patient who presented with intermittent biliary tract obstruction caused by ampullary hamartoma. Endoscopic retrograde cholangiopancreatography showed a large ulcerated papilla and dilated biliary ducts. Tissue diagnosis was established by a large particle biopsy obtained with a snare. The patient underwent a successful endoscopic sphincterotomy and has remained symptom free for 4 years. 
5	Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I BACKGROUND. As part of an interdisciplinary study of medical injury and malpractice litigation, we estimated the incidence of adverse events, defined as injuries caused by medical management, and of the subgroup of such injuries that resulted from negligent or substandard care. METHODS. We reviewed 30,121 randomly selected records from 51 randomly selected acute care, nonpsychiatric hospitals in New York State in 1984. We then developed population estimates of injuries and computed rates according to the age and sex of the patients as well as the specialties of the physicians. RESULTS. Adverse events occurred in 3.7 percent of the hospitalizations (95 percent confidence interval, 3.2 to 4.2), and 27.6 percent of the adverse events were due to negligence (95 percent confidence interval, 22.5 to 32.6). Although 70.5 percent of the adverse events gave rise to disability lasting less than six months, 2.6 percent caused permanently disabling injuries and 13.6 percent led to death. The percentage of adverse events attributable to negligence increased in the categories of more severe injuries (Wald test chi 2 = 21.04, P less than 0.0001). Using weighted totals, we estimated that among the 2,671,863 patients discharged from New York hospitals in 1984 there were 98,609 adverse events and 27,179 adverse events involving negligence. Rates of adverse events rose with age (P less than 0.0001). The percentage of adverse events due to negligence was markedly higher among the elderly (P less than 0.01). There were significant differences in rates of adverse events among categories of clinical specialties (P less than 0.0001), but no differences in the percentage due to negligence. CONCLUSIONS. There is a substantial amount of injury to patients from medical management, and many injuries are the result of substandard care. 
5	Anorectal malignant melanoma in Sweden. Report of 49 patients. Clinicopathologic features and prognosis of 49 patients with anal malignant melanoma were investigated in the total Swedish population between 1970 and 1984. Median age was 71 years (range, 50 to 87 years), and there was a female predominance (31 females, 18 males). The most common symptom at presentation was bleeding. The majority of tumors ranged between 2 and 5 cm in diameter and all invaded at least into the submucosa and/or the lamina propria. At diagnosis, one third of the patients had either regional or distant metastasis with a median survival of 5 months. The remaining patients were surgically treated with curative intent, either by abdominoperineal resection (APR) or local excision. Median survival was poor in both treatment groups (APR, 12 months; local excision, 13 months). Most patients died with distant metastasis. Our results confirm the opinion that APR offers no more curative potential than a more conservative surgical approach. However, tumor sizes were on average smaller in the group treated by local excision. This could indicate that, in the absence of known distant metastasis, radical surgery should be performed, particularly since local recurrences tended to be more common after a local excision. 
5	Correction of subclavian artery stenosis by percutaneous angioplasty. Subclavian artery stenosis is an infrequently recognized cause of left-sided chest and arm pain that can mimic the signs and symptoms of angina pectoris. In addition, more proximal subclavian artery stenoses can be associated with cerebrovascular symptoms in the "subclavian steal syndrome." This article reviews the clinical experience in four patients who presented with different manifestations of subclavian artery stenosis and who were all successfully treated by percutaneous angioplasty. Their clinical presentation, angiographic findings, and post-angioplasty results are documented. In conclusion, it is felt that nonsurgical correction of critical subclavian artery stenosis, using current angioplasty techniques, is the preferred method of treatment. 
4	Amiloride blocks the onset of ACTH-induced hypertension in the sheep. This study investigated the ability of two diuretics, amiloride and frusemide, to prevent the development of ACTH induced hypertension in conscious sheep. Infusion of amiloride (20 mg/day) or frusemide (50 mg/day) for three days into normotensive sheep did not have any significant effects on blood pressure. Amiloride blocked ACTH-induced hypertension and the sodium retention and hypokalemia which is usually associated with ACTH administration. Frusemide failed to completely block the hypertension and potassium loss, however it blocked the transient initial urinary sodium retention associated with ACTH-induced hypertension. As frusemide failed to completely block the hypertension it is unlikely that the amiloride effect is due primarily to effects on urinary Na excretion. It is possible that amiloride is exerting its antihypertensive effects by blocking sodium channels. 
5	Diagnostic modalities in abdominal trauma. Peritoneal lavage, ultrasonography, computed tomography scanning, and arteriography. Numerous algorithms encompassing the diagnostic studies described above have been published in recent years. For practical purposes, diagnostic peritoneal lavage and CT scanning are the diagnostic studies most commonly used in patients without obvious indications for celiotomy after blunt or penetrating abdominal trauma. Diagnostic peritoneal lavage is invasive, rapidly performed, cheap, and accurate and has a primary role in documenting intra-abdominal bleeding or contamination in hypotensive patients with blunt trauma or selected stable patients with penetrating stab wounds. It misses small and large injuries to the diaphragm and cannot rule out injury to retroperitoneal structures. Computed tomography is noninvasive, time consuming to perform, expensive, and accurate and has a primary role in defining the location and magnitude of intra-abdominal injuries in stable patients with blunt trauma or with penetrating trauma to the flank or back. In many hospitals, it misses gastrointestinal perforations or ruptures. Both studies may be needed in the same stable patient, and both should be available and used in a complementary fashion in the modern trauma center. 
1	Surgical strategy for early gastric cancer. The diagnostic and therapeutic options in early gastric cancer are reviewed. In Japan, the rate of detection of early gastric cancers has increased so that minute gastric cancers can now be identified as a result of advances in diagnostic methods. The results of histopathological staging of a large number of resected specimens have led to three surgical options based on size and depth of the primary lesion, namely classical R2 resection, radical resection with limited lymphadenectomy and endoscopic surgery. 
2	Achalasia of the cardia: long-term results of oesophagomyotomy and posterior partial fundoplication. Forty-eight patients with achalasia of the cardia were treated by Heller's myotomy with a posterior fundoplication of approximately 270 degrees, suturing the gastric fundus to the edges of the myotomy. The mean(s.d.) postoperative follow-up period was 5.4(2.8) years. The clinical results were good to excellent in 44 cases (92 per cent) and fair in four cases (8 per cent) (two with residual dysphagia and two with gastrooesophageal reflux). Barium studies showed a decrease in oesophageal diameter and disappearance of distal narrowing but normal oesophageal emptying did not occur. Postoperative manometric studies (29 patients) revealed a significant decrease in lower oesophageal sphincter pressure and a significant increase in the length of the infradiaphragmatic segment. In the oesophageal body a recovery of peristaltic waves in the proximal third was seen in ten of the patients (34 per cent). Twenty-four-hour pH monitoring showed pathological reflux in only three of 25 patients studied, and one of these was asymptomatic. This technique is effective, improving oesophageal symptoms and controlling long-term reflux. 
5	A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer. The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit. 
2	The prevalence of Helicobacter pylori infection in the Peoples Republic of China. Meta-analysis on data from 16 (two volunteer and 14 endoscopic) studies ahs been performed to investigate the prevalence of Helicobacter pylori infection in the stomachs of individuals within the Peoples Republic of China. In this survey covering 2216 cases (89 volunteers and 2127 endoscopy patients), the incidence of H. pylori infection in 15- to 22-yr-old healthy volunteers, and in 13- to 88-yr-old symptomatic patients undergoing gastroscopy was 49.4% and 64.5%, respectively. The frequency of H. pylori infection in chronic gastritis (63.6%), gastric ulcer (71.9%), and duodenal ulcer disease (73.1%) differed significantly from that in histologically normal individuals (8.2%), confirming the relationship of H. pylori infection with those disease states. We found no significant association between H. pylori infection and symptoms. 
5	Dystrophin analysis in Duchenne and Becker muscular dystrophy carriers: correlation with intracellular calcium and albumin. Immunocytochemical localization and immunoblot analysis of dystrophin in muscle fibers of 11 obligate and probable, and 7 possible carriers of Duchenne and Becker muscular dystrophy revealed an abnormal expression of the protein in 3 of them. Localization of calcium and albumin, as endogenous markers of extracellular fluid penetration, showed the presence of both molecules inside some fibers lacking dystrophin. Our morphological studies show that the initial stages leading to fiber necrosis in Duchenne muscular dystrophy are present in carriers with mosaicism. Comparison of dystrophin studies with restriction fragment length polymorphism analysis and creatine kinase levels showed that neither immunocytochemical nor immunoblot techniques for dystrophin are sensitive enough to provide a basis for genetic counseling. 
3	Neurologic complications of alcoholism. Neurologic and myopathic complications of alcoholism are multiple and diverse, affecting both the central and peripheral nervous systems. In the ED, initial concern is for diagnosing readily reversible causes and ruling out possible life- or limb-threatening etiologies. A rapid assessment of the ABCs, a fingerstick blood glucose determination, and, in cases of AMS, the administration of intravenous naloxone is indicated. In almost every instance of a potential neurologic complication, intravenous thiamine replacement is indicated initially, along with the parenteral administration of folic acid and the other B vitamins, including nicotinic acid and pyridoxine. Metabolic screening with electrolytes, glucose, blood urea nitrogen, creatinine, calcium, magnesium, liver enzymes (AST, alkaline phosphatase), bilirubin, arterial blood gases with carboxyhemoglobin determination, and a complete blood count are often warranted. Special tests such as CT scan, CK, ammonia, or toxicologic screens are indicated in specific instances. In terms of physical examination, attention to the presence of focal neurologic findings is paramount because of the possibility of a subdural or epidural hematoma. It is important not to miss meningitis and a low threshold for treatment or lumbar puncture should be maintained. Specialized consultation and referral are needed only after stabilization and appropriate tests are performed. If an organized approach to the evaluation of an alcoholic with neurologic symptoms is undertaken, occult disease will not be missed and outcomes will be improved. 
5	Pulmonary aspiration during emergency endoscopy in patients with upper gastrointestinal hemorrhage. OBJECTIVE: To evaluate the frequency and significance of aspiration and its clinical importance in patients with upper GI bleeding undergoing esophagogastroduodenoscopy in the ICU. DESIGN: Thirty consecutive patients with active and severe upper GI bleeding were studied. SETTING: ICU. PATIENTS: Ranged in age from 20 to 78 yr with an equal number of males and females. INTERVENTIONS: All patients had continuous pulse oximetry monitoring and had chest radiographs obtained less than 12 hr before endoscopy and less than 4 hr after endoscopy. MEASUREMENTS: Six (20%) of 30 patients developed new lung infiltrates after esophagogastroduodenoscopy. In this group of patients, preendoscopy chest radiographs were obtained after less than 4 hr. In five of these patients, infiltrates were accompanied by fever and/or leukocytosis and oxygen desaturation to less than 90% during the esophagogastroduodenoscopy. CONCLUSION: Clinically significant aspiration pneumonia frequently complicates esophagogastroduodenoscopy in upper GI bleeding patients and is an important mechanism of esophagogastroduodenoscopy-induced hypoxia. 
3	An objective score to predict upper tract deterioration in myelodysplasia. Bladder dysfunction in myelodysplasia may present a significant hazard to the upper tract and a threat to kidney function. Urodynamic features of high leak pressure and detrusor-sphincter dyssynergia have been associated with an increased risk. We have developed an objective score to describe urodynamic findings in myelodysplasia. The score includes consideration of bladder compliance, detrusor contractility and reflux, in addition to leak pressure and sphincter behavior. In 171 myelodysplastic patients a significant correlation was demonstrated between the score and upper tract studies at the time of urodynamics and the score and the management decision. Of 73 myelodysplasia patients with normal upper tracts at the first urodynamics study hydronephrosis later developed in 14. The score was a potent predictor of outcome (p = 0.0006). 
1	Surgical therapy in Barrett's esophagus. Seventy-six patients with Barrett's esophagus were cared for during a 10-year period. Fifty-six patients (74%) presented with complications of the disease. There were 20 strictures, 7 giant ulcers, 11 cases of dysplasia, and 29 patients with carcinoma. In patients with benign disease, 93% had mechanically defective sphincters and 83% had peristaltic failure of the lower esophageal body. Esophageal pH monitoring showed excessive esophageal exposure to pH less than 4 in 93% and excessive exposure to pH more than 7 in 34% of the patients tested. Ninety-three per cent of patients with excessive alkaline exposure had complications, compared to only 44% with normal alkaline exposure (p less than 0.01). Gastric pH monitoring, serum gastrin levels, and gastric acid analysis supported a duodenal source for the alkaline exposure. Antireflux surgery was performed using Nissen fundoplication in 30, Belsey partial fundoplication in 3, and Collis-Belsey gastroplasty in 2. Six required resection with colon interposition. Good symptomatic control was achieved in 77% after antireflux surgery. Four patients had symptoms and signs of duodenogastric reflux; three required a bile diversion procedure. Fifteen patients had an en bloc curative resection with colon interposition. One patient with high-grade dysplasia on biopsy was found to have intramucosal carcinoma after simple esophagectomy. Five tumors were intramucosal, seven were intramural, and four were transmural. Lymph node involvement occurred only in the latter two. Actuarial survival 5 years after curative resection was 53%. Median survival time for patients after palliative resection or no resection was 12 months. Study of en bloc specimens indicated that extent of resection should be adapted to extent of disease: esophagectomy for intramucosal disease, en bloc esophagectomy with splenic preservation for intramural and transmural disease. Serum CEA was useful in detecting recurrent disease after surgery when the primary tumor stained positively for CEA. 
4	Effects of n-3 fatty acids in essential hypertension. We examined the effects on blood pressure, plasma lipoproteins, and platelet function when marine oil supplements (rich in n-3 fatty acids) or vegetable oil supplements (rich in n-6 fatty acids) were added to the usual diets of patients with mild essential hypertension. In a randomized, double-blind, parallel-group study, patients received 50 g of either marine oil (n = 8) or vegetable oil (n = 8) daily for 6 weeks following a baseline observation period. Diastolic blood pressure declined during treatment with fish oil (mean +/- SEM, 96 +/- 2 v 89 +/- 2 mm Hg, P = .02), but did not change with vegetable oil (92 +/- 1 v 94 +/- 1 mm Hg). Systolic blood pressure did not change significantly during either treatment. Serum triglycerides declined (by approximately 30%) in patients receiving only marine oil, but total cholesterol, LDL-, HDL-, HDL2-, and HDL3-cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups. Bleeding time increased by 33% during treatment with marine oil but did not change with vegetable oil supplements. Marine oil did not alter in vitro platelet aggregation thresholds. The lack of a significant correlation between blood pressure changes and platelet membrane fluidity, plasma renin activity, aldosterone, norepinephrine, or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil. We conclude that large doses of marine oil reduce diastolic blood pressure, lower triglycerides, and increase bleeding time in patients with mild hypertension. 
5	Lumbar intervertebral disc prolapse in teenage twins. A case report and review of the literature. We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect. 
5	In vitro and in vivo effects within the coronary sinus of nonarcing and arcing shocks using a new system of low-energy DC ablation. DC shocks within the coronary sinus have been abandoned because of the risk of cardiac rupture and tamponade. Catheter ablation using DC energy to electrodes straddling the ostium of the coronary sinus, when used clinically, has been reported to result in cardiac tamponade in as many as 16% of patients. A new system of energy delivery maximizes voltage while decreasing the undesirable effects caused by barotrauma. This system includes 1) a low-energy ablation power supply with a brief time-constant capacitive discharge that delivers up to 40 J and 3,000 V and 2) a low-energy ablation catheter with a contoured distal electrode. We performed in vitro and in vivo studies of this new system and compared arcing shocks with nonarcing shocks. Ablations were performed using unipolar distal shocks (D) and unipolar shocks to both electrodes made electrically common (P-D). In vitro studies were done in a large tank filled with physiological saline while recording voltage, current, and pressure. High-speed cinematography (32,000 frames/sec) of shocks of 10-40 J permitted detailed analysis of the vapor globe. Anodal shocks of less than 20 J showed no arcing or only minimal vapor globe formation. For D and P-D anodal shocks of 40 J, the diameters of the vapor globe were 31 and 22 mm, respectively, corresponding to pressure recordings of 11 and 4.9 atm. The pressure rise lasted less than 50 mu sec. In vivo studies involved 18 dogs that received nonarcing shocks (one to six shocks of 15 J) and 18 dogs that received arcing shocks (one to three shocks of 40 J). Each group was divided between D and P-D shocks; catheter ablation was performed at a mean +/- SEM distance of 2.94 +/- 0.92 cm within the coronary sinus. All dogs tolerated the procedure without cardiac rupture or tamponade. When killed 2-4 days later, the dogs had edema and hyperemia or hemorrhage in the area of the coronary sinus. We compared the effects of multiple (three to six) nonarcing shocks with the effects of one to three arcing shocks. Disruption or rupture of the coronary sinus within the epicardial fat space occurred in two of 12 dogs (17%) with multiple nonarcing shocks but in 13 of 18 dogs (72%) with arcing shocks (p less than 0.003). Occlusion of the coronary sinus occurred in two of 12 dogs (17%) with multiple nonarcing shocks and in nine of 18 dogs (50%) with arcing shocks (p less than 0.06).(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Osteotomy for osteoarthritis of the hip. A survivorship analysis. We have reviewed 368 osteotomies carried out for osteoarthritis of the hip at the Nuffield Orthopaedic Centre. Survivorship analysis showed that 10 years after osteotomy 47% had required no further surgery, and even after 20 years 23% had still not had a hip replacement. Hips with moderate arthritic change showed significantly better results than those with more severe degeneration. Osteotomies with varus angulation as well as medial displacement showed longer survival. 
5	Vitamin E in gastric mucosal injury induced by ischemia-reperfusion. To clarify the relationship among vitamin E, oxygen radicals, and lipid peroxidation in ischemia-reperfusion, we produced an experimental model of gastric mucosal injury in rats by ischemia-reperfusion with clamping of the celiac artery and measurements of the area of gastric erosion, thiobarbituric acid (TBA)-reactive substances, and alpha-tocopherol in serum and gastric mucosa during ischemia-reperfusion. The area of gastric erosions and TBA-reactive substances in gastric mucosa were significantly increased after 30 and 60 min of reperfusion. The serum alpha-tocopherol-cholesterol ratio and gastric mucosal alpha-tocopherol were significantly decreased after 30 and 60 min of reperfusion. On the other hand, in vitamin E-deficient rats, gastric mucosal injury induced by ischemia-reperfusion was more severe than that in vitamin E-nondeficient rats. These results indicate that vitamin E is consumed in the process of lipid peroxidation induced by oxygen radicals in ischemia-reperfusion to prevent the development of tissue damage. 
4	Transient left ventricular filling abnormalities (diastolic stunning) after acute myocardial infarction. A variety of experimental studies suggest that diastolic left ventricular (LV) function changes after acute myocardial infarction (AMI), but limited data exist on these changes in humans. To assess diastolic filling after AMI, 60 patients underwent Doppler echocardiographic examination within 24 hours of AMI. Of 54 patients who also underwent catheterization, 45 (83%) were successfully reperfused. A subgroup of 17 patients underwent a follow-up Doppler examination at 7 days after infarction, whereas 15 patients with stable exertional angina served as control subjects. There was no significant difference in age, gender, incidence of systemic hypertension or diabetes mellitus, heart rate, mean arterial pressure or severity of coronary artery disease between the infarct and control groups. The infarct group had a lower velocity time integral total (9.9 +/- 0.4 cm vs 12.0 +/- 0.9 cm, p less than 0.001), a lower velocity time integral E (5.8 +/- 0.3 cm vs 6.8 +/- 0.5 cm, p less than 0.01) and a lower velocity time integral 0.333 (3.5 +/- 0.4 cm vs 6.1 +/- 0.5 cm, p less than 0.01) than the control group. In addition, velocity time integral A/total was significantly greater in the infarction group (0.44 +/- 0.03 vs 0.35 +/- 0.04, p less than 0.01) compared to the control group. The follow-up subgroup showed an increase in velocity time integral total (p less than 0.01), velocity time integral E (p less than 0.05) and velocity time integral 0.333/total (p less than 0.05) over the first 7 days after infarction. The final recovery values at 7 days were not significantly different from those of the coronary artery disease group. 
1	Squamous carcinoma metastatic to the sternum. A 63-year-old man had a 10 x 16-cm sternal mass 18 months after a second aortocoronary bypass operation. The resected lesion was a metastatic tumor of squamous histology. No primary tumor was found. The diagnostic work-up and treatment options are presented. 
2	Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole. The magnitude and duration of changes in nocturnal intragastric acidity caused by 25 days of dosing with the antisecretory drugs ranitidine and omeprazole were investigated in a double-blind study of 22 healthy subjects. Nocturnal intragastric acidity was studied before (twice), during (on day 25), and after (every 3 days for 21 days) dosing with either 300 mg ranitidine at night or 40 mg omeprazole every morning. Three and six days after withdrawal of dosing with ranitidine, median integrated nocturnal intragastric acidity was increased significantly (17% and 14%, P = 0.01 and P = 0.05, respectively) compared with before dosing. Three days after withdrawal of dosing with omeprazole, median integrated nocturnal intragastric acidity was decreased significantly (-23%, P = 0.003). Compared with before dosing, no significant differences were seen in the ranitidine group between days 9 and 21 or the omeprazole group between days 6 and 21 after cessation of dosing. Fasting plasma gastrin concentration was measured on the morning of each study; compared with before treatment, the only significant elevations occurred on the last day of dosing with omeprazole (before, 4 pmol/L; during, 7 pmol/L). It is concluded that rebound intragastric hyperacidity after dosing with 300 mg ranitidine at night or sustained hypoacidity after dosing with 40 mg omeprazole every morning reflect transient disturbances of gastric function that are unlikely to be of clinical importance. 
2	Biliary and pancreatic metastases of breast carcinoma: is surgical palliation indicated? Obstructive jaundice developed in a patient concomitantly with the diagnosis of breast carcinoma. Abdominal exploration disclosed a metastatic tumor in the head of the pancreas, the distal bile duct, and the gallbladder. A cholecystectomy and choledochojejunostomy were performed and later, because of intestinal obstruction, the patient underwent gastrojejunostomy. Pathological examination demonstrated metastatic lobular carcinoma of breast with strongly positive staining for estradiol. Additional hormonal therapy has been given to the patient since the operation. The patient is alive 16 months after the diagnosis of her disease. This case suggests that a vigorous diagnostic approach should be adopted in every jaundiced patient with metastatic breast cancer in order to exclude causes of jaundice other than diffuse metastatic involvement of the liver. Patients with extrahepatic biliary metastasis should be treated by aggressive surgical treatment, combined with systemic therapy which can offer them significant palliation and better survival. 
4	Assessment of myocardial perfusion in patients after the arterial switch operation. In 21 patients who had undergone the arterial switch operation, the adequacy of myocardial perfusion was evaluated by thallium-201 computed scintigraphy 2.6 +/- 2 (0.3-7) yr after surgery. Fourteen patients had undergone the arterial switch procedure after pulmonary artery banding and seven as a primary repair. Isoproterenol stress increased the heart rate by at least 55%. Tomographic imaging was performed at peak stress and 3 hr later in the reperfusion phase. Nine patients had perfusion defects. The perfusion defects were located at the left ventricular apex in four (with extension to the inferolateral wall in one), left ventricular anterolateral wall in two, ventricular septum in one, left ventricular inferior wall in one, and right ventricular free wall in one. Some of these defects could be due to myocardial damage at the time of surgery, but these results also raise concern about long-term adequacy of myocardial perfusion following the arterial switch procedure. 
3	Sleep apnoea syndrome associated with maxillofacial abnormalities. Four cases with Obstructive Sleep Apnoea Syndrome (OSAS) are presented. They consisted of two cases with TMJ ankylosis with micrognathia, one case with Treacher Collins Syndrome, and one case with the Long Face Syndrome. Standard and specific cephalometric parameters were obtained to detect the site of the obstruction. Polysomnographic studies yielded information regarding the patient's sleep-wake state, respiratory and cardiac functioning, pre- and post-operatively. A temporary tracheostomy corrected the symptoms in one patient but the syndrome recurred when it was closed. Surgical correction of the maxillofacial anomalies will re-establish normal sleep patterns preventing OSAS. 
3	Periventricular hyperintensity detected by magnetic resonance imaging in infancy. Twenty-one infants younger than 12 months of age were diagnosed as having periventricular hyperintensity (PVH) on T2-weighted magnetic resonance imaging. Ten infants had experienced neonatal asphyxia, 6 intracranial hemorrhage, 2 bacterial meningitis, and 3 apnea. PVH was classified according to its extent. Round foci of PVH surrounding the frontal and occipital horns of the lateral ventricles were observed in 4 infants (PVH pattern I). Continuous PVH was observed in 17 infants (PVH patterns II and III). Fourteen infants with continuous PVH had spastic diplegia or quadriplegia. Developmental delay was demonstrated in 15 infants with continuous PVH. No PVH pattern I infants had cerebral palsy; only 1 such infant had mild developmental delay. Our study suggests that the extent of PVH reflects the severity of brain damage in neonates with cerebral injuries. 
4	Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries. A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures. 
5	Detecting arrhythmia by exercise electrocardiography in pediatric patients: assessment of sensitivity and influence on clinical management. We studied 49 patients with suspected arrhythmias (group 1) and 92 patients with previously documented arrhythmias (group 2) who underwent exercise electrocardiography (EECG) at our institution between 1979 and 1987. Among group 1 patients, all of whom had sinus rhythm before exercise, 10 (20%) had abnormal findings on EECG, and treatment was modified in 4 of these 10 (8% of group 1). Further testing (24-hour ambulatory or transtelephonic electrocardiographic monitoring or electrophysiologic study) of the 39 patients with normal EECG findings revealed 8 additional patients with arrhythmias. In group 1, the sensitivity of EECG was 56%, and its negative predictive value was 79%. Group 2 consisted of 38 patients with atrial arrhythmias, 31 with ventricular arrhythmias, and 23 with atrioventricular conduction abnormalities before EECG. Of these 92 patients, 68 (74%) had abnormal EECG findings. All but 1 of the 24 patients with normal findings underwent further testing, and rhythm abnormalities were induced in 16. Patients with atrial arrhythmias were more likely to have normal EECG results (42%) than were those with ventricular arrhythmias (23%) or an atrioventricular conduction abnormality (4%). Of the 35 patients who had been referred for suppression of an arrhythmia, 25 (71%) had abnormal rhythm suppressed during exercise. Clinical management was modified in 27% of group 2 patients on the basis of EECG findings. 
2	Colonic lipomas: outcome of endoscopic removal. Colonic lipomas are benign adipose tumors which are usually submucosal. With the increase in the number of endoscopic procedures being performed, these tumors are often detected incidentally at colonoscopy. Although the risks of removing these tumors have been recognized, numerous reports have documented safe removal by snare electrocautery. We have reviewed the clinical outcome and the endoscopic and histopathologic features of seven lipomas that were endoscopically removed over a 5-year period. Four patients recovered uneventfully, while three patients (42.8%) developed colonic perforation after the polypectomy. In the latter group, the lipomas were significantly larger than they were in the patients who did not develop colonic perforation (1.9 +/- 0.4 and 4.2 +/- 0.7 cm, respectively; p = 0.048). Furthermore, the polypectomy specimens from those patients who developed perforation all contained significant muscularis propria. Lipomatous polyps that are identified at endoscopy to be greater than or equal to 2 cm in diameter and to have a limited pedicle are at the greatest risk for endoscopic perforation. 
5	Rotator cuff lesions: signal patterns at MR imaging. The signal intensity patterns of rotator cuff lesions at magnetic resonance (MR) imaging were evaluated in 80 patients who had surgical correlation and in 13 asymptomatic individuals (14 shoulders). Six cadaver shoulders were examined with MR, and histologic correlation was obtained in four. All studies were performed at 1.5 T with a flexible circular surface coil. The accuracy of MR imaging in detection of full-thickness cuff tears (31 patients) was 0.95 and of partial thickness tears (16 patients), 0.84. The most common and accurate pattern for full-thickness cuff tears (22 of 31 tears) was a region of intense signal seen on T2-weighted images. Less often the torn region consisted of an extremely degenerated and attenuated tendon with moderate signal intensity or was obscured by low-signal-intensity scar. The intense signal pattern on T2-weighted images was also accurate, although a less common finding (seven of 16 cases), in the diagnosis of partial tears. Tendinitis was recognized as focal or diffuse regions of increased signal intensity or a nonhomogeneous pattern of increased signal often associated with tendinous enlargement. In some patients, manifestations of subacromial-subdeltoid bursitis was present. Tendon degeneration was also manifested as regions of increased signal intensity. Some similarity and overlap of signal patterns of partial interstitial tears, tendinitis, and tendon degeneration are observed. 
3	Cerebral blood flow velocities in the anterior cerebral arteries and basilar artery in hydrocephalus before and after treatment. We studied Pourcelot's index (PI), which shows cerebral vascular resistance, in the anterior cerebral arteries and basilar artery, and the PI ratio (Pourcelot's index in the anterior cerebral artery/Pourcelot's index in the basilar artery) in 11 measurements of hydrocephalus. The mean values of PI in the anterior cerebral artery, basilar artery, and the PI ratio before treatment were significantly higher than those after treatment and those in normal infants. Before treatment, the mean PI in the anterior cerebral arteries was significantly higher than the mean PI in the basilar artery. All PI ratios increased to 1.00 or more. After treatment and in normal infants, the mean PI in the anterior cerebral arteries was significantly lower than the mean PI in the basilar artery. All PI ratios decreased to less than 1.00. We believe that the PI ratio is useful to evaluate the need or effect of treatment in hydrocephalus. 
5	Long-term results of the Belsey Mark IV antireflux operation in relation to the severity of esophagitis A retrospective analysis of the results of the Belsey Mark IV operation has been conducted, relating these to the degree of esophagitis present preoperatively. Analysis of 89 patients showed a 91.7% success rate in patients without esophagitis. Good results diminished steadily as the severity of esophagitis increased, giving 76.5%, 75%, 66.7%, and 50% success rates for first-, second-, third-, and fourth-degree esophagitis, respectively. We believe that shortening of the esophagus is an important factor in this. Shortening is obvious in third- and fourth-degree esophagitis but subtle in first- and second-degree esophagitis. We conclude that the Belsey operation is adequate for patients without esophagitis, but for patients with any degree of esophagitis more effective reflux control is needed. 
4	Ischemic colitis. An ever-changing spectrum? Ischemic colitis, or more properly colonic ischemia, became a clear clinical entity in the past 25 years. Yet, early diagnosis of this disease with its various presentations remains a difficult task. A 10-year review at our hospital identified 38 patients with colonic ischemia for comparison with the authors' previous experience and with data from the literature. Several important factors emerge: (1) Twice as many cases occurred after operations (34% in this series vs. 16% in the past), probably because fewer and fewer spontaneous cases were hospitalized. (2) Sixteen patients required operative intervention for colonic ischemia with a mortality of 62 per cent, while those treated nonoperatively had a mortality of 14 per cent. Seven of eight postoperative patients who required a second operative procedure for their colonic ischemia died. A high clinical suspicion is necessary in the postoperative patient, as colonic ischemia appears to be more severe among these patients. Moreover, the high incidence of associated cardiovascular disease indicates that early diagnosis, as well as monitoring of the "at-risk" patient, is needed for improvement in survival to occur. New monitoring methods, such as tonometry, may help accomplish this goal. 
5	Linear scleroderma associated with ptosis and motility disorders. A case is reported in which an 11-year-old girl developed progressive ptosis and a subsequent motility disorder of the right eye. The diagnosis linear scleroderma en coup de sabre was established. Atrophy of the upper levator palpebral and superior rectus muscle could be shown on CT scan. 
3	An estimate of the incidence of dementia in idiopathic Parkinson's disease. The proportion of patients with idiopathic Parkinson's disease (PD) who are considered demented ranges from 10% to 15%. Because dementia may affect survival in PD, the incidence rate of dementia, rather than proportion, would be a more accurate measure of disease frequency. We previously estimated the proportion of patients with PD and dementia to be 10.9% from the records of a cohort with the idiopathic form of PD in a major medical center. We reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia. We identified 65 new cases of dementia from the 249 patient-records available. Using the number of person-years of follow-up for each case as the denominator, we estimated the overall incidence rate to be 69 per 1,000 person-years of observation. The mean age of this cohort was 71.4 years. The cumulative incidence of dementia increased with age. By 85 years of age, over 65% of the surviving members of the cohort were demented. The age-specific incidence rates for dementia in this cohort of PD were significantly greater than for a similarly aged cohort of healthy elderly people. The age-specific standard morbidity ratios indicated that, compared with people of similar ages, patients with PD have the highest increase in risk for dementia between ages 65 and 75. 
3	Motion analysis of the cervical spine in athetoid cerebral palsy. Extension-flexion motion. Frequently instability and premature onset of spondylosis of the cervical spine are found in athetoid cerebral palsy (CP) patients. These structural abnormalities appear to be related to athetoid motion of the neck in CP. Through motion analysis, the authors aimed to clarify the abnormalities of cervical motion that could precipitate structural abnormalities. The gross characteristic feature of cervical motion in athetoid CP is "whip movement." Both velocity and acceleration during extension-flexion motion were greater than in normal subjects, especially at the upper cervical levels. Also, a sudden increase in velocity and acceleration occurred during rapid motions at certain levels, followed by a larger range of motion of the cervical spine. Such kinematic abnormalities were thought to generate a greater shearing force and bending moment exerted on the corresponding cervical articulations-discs and facets. Olisthetic instability often accompanied disc degeneration at the upper cervical levels. A large range of extension--flexion motion of the cervical spine, analogous to a cantilever, caused a repeated bending moment of extraordinary magnitude and was regarded as a precipitative factor for disc degeneration and osteophytosis common at the middle and lower levels of the disc. 
3	The relationship of headache symptoms with severity and duration of attacks. Efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes. An alternative conceptual approach, the "severity model" of headache, considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms. A population-based telephone interview was carried out among 10,169 subjects aged 12-29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks. In an analysis of frequency of occurrence, pain and duration of recent (within 4 weeks prior to interview) headache attacks, the data revealed that common symptoms (such as forehead pain and pain in the back of the head, neck and shoulders) were reported frequently, but headaches with these symptoms were generally characterized by low levels of pain and short duration. Although not an original study objective, the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types. Symptoms of migraine were frequently experienced concomitant with tension-type symptoms; the resultant headaches were usually characterized as moderate in intensity. In contrast, symptoms usually associated with migraine in the absence of concomitant tension-type symptoms were infrequently experienced, but resulted in headaches causing the greatest disability. The data provide some support for the severity model of headache. 
1	Interphase cytogenetic analysis in the diagnosis and study of neoplastic disorders. Cytogenetic information usually is obtained through the direct analysis of chromosomes from cells arrested in metaphase. Recently, advances in molecular genetics have made it possible to acquire cytogenetic information through the study of interphase and terminally differentiated cells. By using chromosome-specific DNA probes or probes that are specific for certain chromosomal regions, and by employing techniques of in situ hybridization along with nonradioactive detection methods, it is now possible to detect numerical and structural chromosomal abnormalities from nonmetaphase cells. When used as an adjunct to conventional cytogenetic analysis or when used together with knowledge of established cytogenetic findings for a particular malignancy, this new technology can serve to broaden the scope and utility of cytogenetic analysis beyond the limits of the present metaphase-based technology. Interphase cytogenetic analysis has application to the diagnosis and study of neoplastic disorders and, thus, has particular importance in pathology. 
1	Adverse mortality experience of a southwestern American Indian community: overall death rates and underlying causes of death in Pima Indians. As part of an ongoing epidemiologic study, the death rate and causes of death during 1975 through 1984 were determined in Pima Indians who resided in the Gila River Indian Community (GRIC) in 1965 and later. Death certificates were available for 677 of the 681 deaths. In 78% of the deaths, the underlying cause recorded on the death certificate agreed with the cause determined after review of all available relevant records. The age- and sex-adjusted average annual death rate for the GRIC population (1639/100,000) was 1.9 times (95% CI 1.7-2.0) the 1980 rate for the U.S. all races (878/100,000). In Pima males, whose death rate was substantially higher than that of Pima females, the age-adjusted death rate was 2.3 times that in U.S. males, all races. Moreover among males 25-34 years of age, the Pima death rate was 6.6 times that for the U.S. all races. Diseases of the heart and malignant neoplasms caused 59% of U.S. deaths in 1980, but only 19% of GRIC deaths. By contrast, the age- and sex-adjusted mortality rate in the GRIC Pima was 5.9 times the rate of the U.S. all races for accidents, 6.5 times for cirrhosis, 7.4 times for homicide, 4.3 times for suicide, and 11.9 times for diabetes. Tuberculosis and coccidioidomycosis were important causes of death in the Pima, for whom infectious diseases was the tenth leading cause of death. The findings indicate that programs to improve the adverse mortality experience of the GRIC population should emphasize factors related to fatal accidents, alcoholic cirrhosis, homicide, suicide, diabetes mellitus, and infectious diseases. Young Pimas, especially the males, should be the primary focus of such preventive efforts. These findings and recommendations probably apply to many Native American populations. 
1	Prevention of renal disease and conservation of renal function. In summary, we have reviewed some of the most frequently encountered areas of prevention of renal failure in the elderly. They include obstruction, hypertension, drug interaction, and inappropriate use of drugs and the silent killer of the elderly, renal carcinoma. Only by a thorough understanding of the altered physiology of the aging kidney can the physician avoid making the same mistakes when new drugs are developed or new types of diseases are encountered. Proper early diagnosis and understanding the guidelines to therapy in these conditions, can save huge human costs in terms of mortality, morbidity, and money. 
5	Giant sclerosing leiomyoma of bladder presenting as chronic renal failure. The clinical and pathologic features of a case of giant sclerosing leiomyoma of the bladder in a male Polynesian patient are reported. The presenting complication of chronic renal failure due to tumor envelopment of both ureters and consequent bilateral renal obstruction appears to be unique in the literature. 
4	Translumbar arch aortography: a retrospective controlled study of usefulness, technique, and safety. Subclavian and axillary artery stenoses may lead to axillofemoral bypass graft failure. These arteries were assessed preoperatively with arch aortography performed after conventional high translumbar peripheral aortography by exchanging the initial 16-gauge sheath for a 5-F pigtail catheter. Thirty-two diagnostic translumbar runoff and arch (TLR-arch) aortograms were obtained in 30 patients with advanced lower extremity ischemia. In six patients (20%), the results of the arch study influenced the choice of an inflow site. These patients were compared with 70 control subjects who underwent conventional translumbar aortography without arch studies. In the TLR-arch group, two major complications occurred in one patient, while in the control group 11 major complications occurred in 10 patients. One retroperitoneal hematoma occurred in the TLR-arch group; two occurred in the control group. The mean change in hematocrit for the TLR-arch group was -3.81% (-0.0381), and for the control group it was -4.17% (-0.0417). This difference was not statistically significant. Arch aortography is a valuable adjunct to the translumbar aortofemoral study. It can be simply performed without increasing the morbidity of the peripheral study. 
5	Antiarrhythmic efficacy of a new class III agent, UK-68,798, during chronic myocardial infarction: evaluation using three-dimensional mapping. UK-68,798 is a potent class III antiarrhythmic agent that selectively lengthens the effective refractory period (ERP) in isolated tissue without affecting conduction velocity. The present study was performed to evaluate the antiarrhythmic efficacy of UK-68,798 (30 micrograms/kg i.v.) in dogs with a previous myocardial infarction. UK-68,798 did not alter the PQ interval or QRS duration of the surface electrocardiogram but did increase the Q-Tc interval significantly. The ventricular ERP was increased significantly (P less than .01) at a basic cycle length of stimulation of either 300 ms (ERP increased 24 +/- 10 ms) or 250 ms (ERP increased 20 +/- 12 msec), indicating that the response was preserved at more rapid rates. UK-68,798 prevented the induction of sustained ventricular tachycardia in six of seven animals (86%, P = .03). However, UK-68,798 failed to prevent the induction of ventricular fibrillation (VF) in dogs where VF was the only arrhythmia induced. To evaluate the mechanisms responsible for the prevention of ventricular tachycardia and lack of efficacy against inducible VF, detailed three-dimensional activation mapping of the heart in vivo was used. Induction of ventricular tachycardia was prevented by UK-68,798 due to a lengthening of the ERP in the epicardial region surrounding the infarct with no effect on conduction velocity even in periinfarct regions bordering the infarct. In contrast, the induction of VF was dependent on a rapid nonreentrant or focal mechanism that was not altered by the lengthening of ERP with UK-68,798. Thus, UK-68,798 is a selective class III antiarrhythmic agent that is likely to be efficacious in preventing arrhythmias due to a reentrant mechanism in patients with a previous myocardial infarction. 
3	Driving and epilepsy. A review and reappraisal Driving and epilepsy is a problem that involves physicians as both care providers to patients and consultants to regulatory authorities. Driving restrictions for people with seizure disorders are intended to ensure the public's safety, but such restrictions may unduly harm the welfare of many people with seizures. In the United States, all states now permit some people with epilepsy to drive. In general, only people whose seizures are adequately controlled are licensed to drive. Adequate control has been judged principally by the seizure-free interval, but individual state standards widely vary. There is a trend toward greater liberalization of driving standards for people with seizure disorders, but the appropriateness and application of these standards continue to raise questions, as does the role physicians should have in the licensing process. Our responsibilities to persons with disabilities and advances in our understanding of seizures and the nature of driving risks warrant a reappraisal of the current medical, legal, and social implications of driving and epilepsy. 
4	Evaluation and management of supraventricular tachycardia in children. Emergency physicians may be called on to resuscitate acute complications in pediatric patients with congenital heart disease. Supraventricular tachycardia, with or without hemodynamic decompensation, is one of the most serious complications. We present the case of a 22-month-old boy with a history of single ventricle who presented to our institution with a history of syncope and hemodynamically stable supraventricular tachycardia. Initial attempts at pharmacologic conversion with propranolol and verapamil failed. The arrhythmia was terminated in response to an IV fluid bolus and dopamine infusion and probably resulted from a combination of anemia, hypovolemia, and impaired contractility. Appropriate evaluation and management relating to the cre of acute supraventricular tachycardia in children are discussed. 
1	An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome. Neurologic sequelae of Paget's disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae, ischemia caused by a spinal artery, steal syndrome or neoplasm. We describe a patient with Paget's disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma. Clinicians need to recognize this entity since surgical intervention may result in a favorable outcome. 
1	Nonspecific magnetic resonance appearance of renal oncocytomas: report of 3 cases and review of the literature. We report the magnetic resonance appearance of 3 cases of solitary renal oncocytomas. All lesions were of low to moderate signal intensity on T1-weighted images and became considerably brighter on the more heavily T2-weighted images. One lesion contained a large central area of cystic degeneration, while the other 2 were solid. A central stellate scar was present in the smaller of the 2 solid lesions. Our observations lend further support to earlier reports on the nonspecific magnetic resonance features of oncocytomas. 
5	An outpatient anticoagulation protocol managed by a vascular nurse-clinician. Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events. 
5	Transient mitral regurgitation due to mitral valve prolapse accompanied by systolic anterior motion of the mitral valve. A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure. 
1	An epitope on the transferrin receptor preferentially exposed during tumor progression in human lymphoma is close to the ligand binding site. We have previously reported an anti-transferrin receptor antibody, Trump, which was originally selected for its ability to discriminate low- and high-grade lymphomas. This feature was distinct from the other anti-transferrin receptor antibodies such as OKT9. In the present study, further immunochemical analysis was performed to define the nature of the antigenic site recognized by the Trump antibody. Trump was found to block the binding of transferrin both to solubilized and to surface transferrin receptors; conversely, transferrin could block the binding of Trump only to surface transferrin receptors. Therefore, the epitope recognized by Trump is near but not identical to the transferrin binding site. Stimulation of peripheral blood lymphocytes with phytohemagglutinin induced both the OKT9 epitope and the Trump epitope, but 12-phorbol 13 myristate acetate induced only the OKT9 epitope. Growth of some cell lines was inhibited by Trump but not by OKT9. No structural difference was found between transferrin receptor molecules reactive with Trump and those reactive with OKT9. In support of these results, Trump was able to immunoprecipitate transferrin receptor molecules solubilized from low-grade follicular lymphoma cells even though it did not bind to the receptors exposed on the surface of these cells. These findings imply that low-grade lymphoma cells differ from high-grade lymphoma cells not in the structures of their transferrin receptors but in their exposure of the molecule on the cell surface. 
1	A surgical approach to the cervicothoracic spine. We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care. 
5	Mechanisms of vein graft atherosclerosis: LDL metabolism and endothelial actin reorganization. We have explored the effect of arterial hemodynamics on endothelial cell morphology and low-density lipoprotein metabolism in human saphenous vein segments harvested from tissue donors. An arterial pulsatile perfusion system was used to impose physiologic pressures and flows for 20 hours on saphenous vein and companion (control) femoral artery segments. A venous perfusion apparatus was also employed for the perfusion of a second (control) saphenous vein segment for the same period of time. Calculations of fluid shearing and wall tensile stresses were performed and related to induced changes in endothelial cell geometry and cytoskeletal actin organization and the incorporation, degradation, and localization of intact low-density lipoprotein within the vessel wall. Our results indicate that, compared with native arteries and veins, a 20-hour exposure of test saphenous veins to arterial hemodynamics induced (1) a significant increase in endothelial cell luminal surface area and perimeter independent of alignment with flow, (2) disassembly of the dense peripheral band of actin with a concomitant assembly of stress fibers, and (3) a two- to fourfold elevation in the undegraded low-density lipoprotein content, localized primarily within the subendothelial intima. Although the exact mechanisms underlying these results are uncertain, the focal accumulation of intramural low-density lipoprotein may be related to the loss of normal barrier function during endothelial cell enlargement, which is accompanied by transient cytoskeletal reorganization during the adaptation to arterial flow. 
5	Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. Eighty-one patients with acute myeloid leukemia (ANLL, n = 44) or acute lymphoblastic leukemia (ALL, n = 37), aged 10 to 50 years were randomized to receive 1 mg/kg per day (n = 41, group A) or 5 mg/kg per day (n = 40, group B) of cyclosporine A (CyA) from day -1 to day +20 after bone marrow transplant (BMT). All patients received CyA orally thereafter. All patients were prepared with cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TBI), and received unfractionated BM from an HLA-identical sibling. The two groups were comparable for diagnosis, disease status, French-American-British (FAB) classification, WBC count at diagnosis, cytogenetic abnormalities, extramedullary disease before BMT, donor/recipient age and sex, number of cells infused, and number of days with intravenous (IV) CyA. Median follow-up for surviving patients in group A was 983 v 632 days in group B. Patients in group A had lower serum levels of CyA (295 v 686 ng/mL, P = .004), lower bilirubin levels (1.9 v 2.6 mg/dL, P = .07), lower creatinine levels (0.9 v 1.4 mg/dL, P = .06), and a lower proportion of CD8+ cells in the peripheral blood (PB) within day +21 (19% v 28%, P = .07). First day to 0.5 x 10(9)/L neutrophils was comparable in the two groups (13 v 14 days; P = .1). In a Cox model, the actuarial risk of acute graft-v-host disease (GVHD) grade II+, after stratification for age (less than 20 years greater than) was significantly lower in group B patients (0.54, P = .04). The actuarial risk of developing chronic GVHD was comparable (P = .9). Actuarial transplant-related mortality (TRM) at 240 days was 28% and 26% (P = .8) in group A and B: the major cause of death was GVHD in group A (P = .02) and multiorgan toxicity in group B (P = .07). The actuarial risk of relapse at 2 years overall was 20% in group A and 52% in group B (P = .001); it was 9% v 43%, respectively, for patients in first remission (P = .0001) and 48% v 63% for patients in non-first complete remission (CR) (P = .1). Actuarial 2-year disease-free survival (DFS) in group A and B was 58% v 32% (P = .02) for all patients, 71% v 35% (P = .01), in first remissions, and 30% v 23% (P = .2) in advanced disease.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Acute lower respiratory tract infections in hospitalized patients with diarrhea in Dhaka, Bangladesh. This study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection (ALRI) and diarrhea in Dhaka, Bangladesh, and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens. The most common manifestations of ALRI were pneumonia (374 cases), bronchiolitis (12 cases), and tracheobronchitis (11 cases). The majority (77%) of the illnesses were in children less than 2 years of age, and 88% of the children were malnourished. A respiratory tract pathogen was identified in 30% of the patients, and a diarrheal pathogen was identified in 34%. The overall case-fatality rate in children with ALRI and diarrhea was 8%. The case-fatality rate was 14% in children with bacterial pneumonia and diarrhea, 3% in those with viral pneumonia and diarrhea, and 14% in malnourished children with shigellosis and ALRI. The most common respiratory tract pathogens were respiratory syncytial virus, Streptococcus pneumoniae, influenza viruses, and Haemophilus influenzae type b. 
3	Anteromedial tibial tubercle transfer without bone graft. We followed 30 patients for more than 2 years after anteromedial tibial tubercle transfer for persistent patellofemoral pain associated with patellar articular degeneration. Twelve of these patients were followed more than 5 years. We report 93% good and excellent results subjectively and 89% good and excellent results objectively. The quality of improvement was sustained in all 12 of the patients who were evaluated again after more than 5 years from surgery. When examined separately, 75% of those patients with advanced patellar arthrosis achieved a good result; none of these patients achieved an excellent result. Postoperative continuous passive motion has markedly reduced the incidence of stiffness. Serious complications such as compartment syndrome, infection, and skin slough were avoided completely in 51 consecutive cases. Patellofemoral contact pressure studies in five cadaver knees have shown that anteromedial tibial tubercle transfer can provide substantial reduction of patellofemoral contact stress while helping to balance medial and lateral facet pressures. This surgical procedure is mechanically and clinically successful for alleviating intractable pain related to patellar malalignment and articular degeneration. This procedure enables the majority of appropriately selected patients with malalignment and patellar articular degeneration to resume increased levels of activity with substantially diminished pain. 
5	Spontaneous rupture of an aortic aneurysm into the left renal vein. A diagnostic challenge. Rupture of an aortic aneurysm into a renal vein presents a rare and difficult diagnostic problem. Often, therapy is delayed because the patient is thought to have a urologic problem. In this instance, CT scan provided useful clues leading to the diagnosis of this entity, and its rapid treatment. To our knowledge, this is the first CT scan done in a patient with aorto-renal vein fistula. 
2	Angiodysplasia: characterization, diagnosis, and advances in treatment. Gastrointestinal bleeding accounts for 2% of all adult hospital admissions each year. Angiodysplasia is one of the most frequently reported causes of lower gastrointestinal bleeding. In 80% of patients with bleeding angiodysplasia, the bleeding will stop spontaneously, but will often recur. Although angiography may detect bleeding in 86% of actively bleeding patients, the bleeding rate must be at least 0.5 mL/min. The treatment of choice for control of bleeding has been resection of the suspected segment of bowel, but this procedure is associated with a 10% rebleeding rate and 7% to 8% mortality. Superselective catheterization with infusion of vasoconstrictors has been used to control bleeding, but effects are short-lived. Superselective embolization occludes an offending vessel, but is difficult to perform accurately and is associated with risk of infarction. Laser photocoagulation controls bleeding in 84% of patients, with a 6% complication rate. This method of controlling bleeding offers distinct advantages, especially for the hemodynamically unstable patient. Except for cases in which surgical resection is indicated, Nd:YAG laser photocoagulation is the safest, least invasive, and probably most effective means of treating angiodysplasia. 
5	Landau-Kleffner syndrome: a clinical and EEG study of five cases. In five children with normal initial psychomotor development, a Landau-Kleffner syndrome appeared at age 3-7 years. No neuroanatomic lesions were noted. Aphasia and hyperkinesia were isolated in three patients and associated with global regression of higher cortical functions in one patient. Massive intellectual deterioration and psychotic behavior were associated with transient aphasia in one patient. The epilepsy (focal motor and generalized tonic-clonic seizures, subclinical EEG focal seizures during sleep, and atypical absences) always regressed spontaneously or with antiepileptic drug (AED) treatment. The EEG in waking patients showed focal and generalized spike-wave discharges on a normal background rhythm. Discharge topography and pattern changed frequently. During sleep, discharges always increased. At some time during syndrome development, all patients had bilateral spike-waves for greater than 85% of the sleep period, while at other times the discharges were discontinuous or continuous but focal or unilaterally hemispheric. Discharge topography and abundance changed from night to night. The abnormal EEG and the impaired higher functions developed and regressed together, but not with strict temporal correlation. Our own experience suggests that the Landau-Kleffner syndrome and epilepsy with continuous spike-wave activity in slow-wave sleep cannot be clearly differentiated. They may be different points on the spectrum of a single syndrome. 
1	Genetics and biology of human ovarian teratomas. II. Molecular analysis of origin of nondisjunction and gene-centromere mapping of chromosome I markers. Chromosomal heteromorphisms and DNA polymorphisms have been utilized to identify the mechanisms that lead to formation of human ovarian teratomas and to construct a gene-centromere map of chromosome 1 by using those teratomas that arise by meiotic nondisjunction. Of 61 genetically informative ovarian teratomas, 21.3% arose by nondisjunction at meiosis I, and 39.3% arose by meiosis II nondisjunction. Eight polymorphic marker loci on chromosome 1p and one marker on 1q were used to estimate a gene-centromere map. The results show clear linkage of the most proximal 1p marker (NRAS) and the most proximal 1q marker (D1S61) to the centromere at a distance of 14 cM and 20 cM, respectively. Estimated gene-centromere distances suggest that, while recombination occurs normally in ovarian teratomas arising by meiosis II errors, ovarian teratomas arising by meiosis I nondisjunction have altered patterns of recombination. Furthermore, the estimated map demonstrates clear evidence of chiasma interference. Our results suggest that ovarian teratomas can provide a rapid method for mapping genes relative to the centromere. 
4	Caloric expenditure, life status, and disease in former male athletes and non-athletes. This study examined the association between aerobic, caloric exercise expenditure and life status (living vs deceased) as well as the prevalence rates of hypertension (HBP) and cardiovascular disease (CVD) in former male athletes (ATH) and non-athletes (N-ATH). The initial survey for this study was done in 1952. Follow-up surveys of respondents were done in 1960, 1968, 1976, and 1984. The present study used all subjects who responded fully to activity and health questions in 1976 and who were reported as either dead or alive (not lost to follow-up) in 1984. A total of 348 subjects (185 ATH, 163 N-ATH) were assessed and caloric expenditure groups were established by kilocalories (kcal) of aerobic exercise per week; 0 kcal (group 1), 1-399 kcal (group 2), 400-899 kcal (group 3), 900-1499 kcal (group 4), 1500-2499 kcal (group 5), and 2500+ kcal (group 6). Only activity considered to be aerobic was used in the establishment of the aerobic categories. Death rate was highest in groups 1 and 2. Subjects in group 1 tended to be the oldest. Year of birth (age) (P less than 0.001) and CVD (P less than 0.05) as reported in 1976 were significantly related to mortality between 1976 and 1984. College athletic status and 1976 exercise level were not significantly related to mortality. Prevalence of CVD and HBP was highest in groups 1 and 6, suggesting a moderate amount of aerobic activity as optimal. 
1	Changes in gastric mucosa that antedate gastric carcinoma. Endoscopic biopsy specimens of the gastric mucosa from 13 patients who were found at follow-up examination to have gastric carcinoma were compared for abnormal histologic features, type of intestinal metaplasia, and presence of immunoreactive carcinoembryonic antigen (CEA), with specimens from 40 tumor-free controls. Villus-like changes and angular infolding, cytologic nuclear pleomorphism, distinct nuclear border, irregular thickness of the nuclear membrane, irregular chromatin clumping, prominent nucleoli, and distinct nucleoli were manifestations of the carcinoma group. Angular infolding, distinct nuclear border, irregular thickness of the nuclear membrane, and distinct nucleoli were also observed in the latent stage before detection of carcinoma. The individual features, however, lacked specificity. Histochemically, a IIB subtype of intestinal metaplasia, and immunoreactive CEA in the cytoplasm of foveolar epithelium appeared exclusively in the patients with carcinoma. These findings indicate that the gastric epithelium of patients with gastric carcinoma tends to be morphologically and histochemically abnormal even before the recognition of classical dysplasia. This can be described as abnormal epithelium and is believed to provide the soil on which gastric carcinoma develops. 
1	Chondrosarcomas of the synovium. Chondrosarcoma of the synovium, either primary or secondary to synovial chondromatosis, is rare. Ten cases of synovial chondrosarcoma were studied (four from the Mayo Clinic files and six from the authors' consultation files). Two were considered primary. In five cases there was evidence of preexisting synovial chondromatosis, and in the remaining three, there was a suggestion of preexisting disease. Several histologic features were found that were helpful to diagnose malignancy. The most important ones were loss of the "clustering" growth pattern typical of synovial chondromatosis, myxoid change in the matrix, areas of necrosis, and spindling at the periphery of chondroid lobules. Pulmonary metastasis developed in five of nine patients; three of these patients died. 
5	Hypoxic events in the surgical intensive care unit. An oxygen-monitoring protocol was established in the surgical intensive care unit (SICU) at the Denver General Hospital in July 1988. A 3-month surveillance audit ending March 1989 prospectively documented 100 consecutive hypoxic events in 51 of 241 (21%) SICU patients. These episodes occurred during mechanical ventilation in 46 patients, during spontaneous ventilation in 15 patients with artificial airways, and the remaining 39 occurred in nonintubated patients. Hypoxemia was recognized by pulse oximetry in 59, arterial blood gas analysis in 24, mixed venous oximetry in 15, and transcutaneous oxygen monitoring in 2. These events were due to problems with the ventilator or airway in 42, recent interventions in 21, new pulmonary process in 19, progression of underlying disease in 11, and unknown causes in 7. Two thirds resulted from mechanical problems amenable to simple intervention; there were two adverse outcomes. In conclusion, acute hypoxia is a frequent potentially morbid SICU event. Advances in continuous oxygen monitoring permit early identification and thereby may limit adverse outcomes, but should not prompt an expensive diagnostic work-up. 
4	Double-peaking circadian variation in the occurrence of sustained supraventricular tachyarrhythmias. We studied 251 patients less than or equal to 65 years of age admitted for treatment of symptomatic supraventricular tachyarrhythmia to assess whether these arrhythmias begin evenly throughout the day or manifest circadian variation in occurrence. The arrhythmias included 152 episodes of atrial fibrillation, 50 episodes of supraventricular reentry tachycardia, 30 episodes of atrial flutter, and 19 cases of ectopic atrial tachycardia. A total of 209 patients could tell the exact time their symptoms had started. In 38 of them (18%), the arrhythmia had begun between midnight and 6:00 AM, in 63 (30%) between 6:01 AM and noon, in 46 (22%) between noon and 6:00 PM, and in 62 (30%) between 6:01 PM and midnight. This distribution differed significantly from uniform occurrence (chi square 8.7, p less than 0.05). Fifty patients were using beta-adrenoceptor blocking agents when the arrhythmia occurred. Compared with the other 159 patients, they had no morning surge of arrhythmias (20% versus 33.3% of episodes between 6:01 AM and noon), but instead a much higher incidence at night (34% versus 13.2% of episodes between midnight and 6:00 AM) (chi square 14.4, p less than 0.005). We conclude that the frequency of onset of sustained supraventricular tachyarrhythmias varies with the time of day, showing nearly equal peaks in the morning and in the evening and a trough at night. The modifying effect of beta-adrenoceptor blockage suggests that many morning arrhythmias are of adrenergic origin while other, probably vagal arrhythmogenic mechanisms, prevail at night. 
4	Surgical augmentation of skin blood flow and viability in a pig musculocutaneous flap model. A porcine rectus abdominis musculocutaneous (TRAM) flap model was designed and validated in nine pigs. This TRAM flap was based on the deep inferior epigastric (DIE) vessels with an 8 x 18 cm transverse skin paddle at the superior end of the rectus abdominis muscle. The model was subsequently used to test our hypothesis of surgical augmentation of flap viability by vascular territory expansion. Specifically, we observed that ligation of the superior epigastric (SE) vessels at 4, 7, 14, and 28 days (N = 6 to 8) prior to raising the TRAM flaps significantly increased (p less than 0.05) the length and area of the viable skin in the transverse skin paddles of the treatment flaps compared with the contralateral shammanipulated control flaps. This significant increase in skin viability was seen to be accompanied by a significant increase (p less than 0.05) in skin and muscle capillary blood flow in the treatment TRAM flaps compared with the controls (N = 9). The mechanism of vascular territory expansion is unclear. We postulate that hypoxia resulting from the ligation of the superior epigastric vessels prior to the flap surgery may play a role in the triggering of the deep inferior epigastric artery to take over some of the territory previously perfused by the superior epigastric artery. This would then increase the skin and muscle capillary blood flow in the transverse paddle when the TRAM flap was raised on the deep inferior epigastric vascular pedicle. 
4	Atrial septal occlusion improves the accuracy of mitral valve area determination following percutaneous mitral balloon valvotomy. We investigated the impact of the atrial communication on the mitral valve area calculation after percutaneous mitral balloon valvotomy in 17 patients (15 women, 2 men; mean age 56 +/- 4 years). The hemodynamic measurements and mitral valve area calculations were performed with and without balloon occlusion of the atrial septal puncture site. The mitral valve area determined with balloon occlusion was significantly smaller than the mitral valve area determined without occlusion (1.6 +/- 0.1 vs. 1.9 +/- 0.1 cm2, P less than 0.01), and was similar to the echocardiographically determined valve area (1.6 +/- 0.1 cm2). This decrease in the calculated mitral valve area with occlusion was associated with a decrease in the measured cardiac output, without a change in the mitral valve gradient or the diastolic filling period. Occlusion of the atrial septal puncture site may permit more accurate determination of the mitral valve area and thus provide a better reference point for future comparison should the question or restenosis arise. 
5	Low-dose almitrine bismesylate enhances hypoxic pulmonary vasoconstriction in closed-chest dogs. The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose-related. 
4	Central retinal vein obstruction and axial length. The axial lengths of 24 consecutive adult eyes with unilateral central retinal vein obstruction (CRVO) were compared with those of contralateral unaffected eyes and those of a control population. The lengths of the two eyes of persons with a unilateral CRVO were not significantly different. By contrast, eyes of persons with CRVO averaged 0.67 mm (approximately 2 diopters) shorter than their control counterparts (P = .03). This anatomic difference may be a factor in the development of CRVO. 
5	Angiographic follow-up and clinical outcome of 126 patients after percutaneous directional atherectomy (Simpson AtheroCath) for occlusive peripheral vascular disease. Angiographic and clinical follow-up data were obtained in 115/126 patients who underwent directional atherectomy for peripheral vascular disease; of the 126, ten were excluded for appropriate reasons and one was lost to follow-up. Thus, 115/116 successful atherectomy patients (99%) had follow-up of 182/213 lesions (86%): 74 patients (64%) with angiography (mean time 5.4 mon), and 41 patients (36%) clinically. One hundred twenty-eight of 183 lesions (70%) had angiographic follow-up; the lesion recurrence as a stenosis or as an occlusion was 53%. Lesion distribution did not differ between angiography and clinical follow-up groups: nearly 85% were within the superficial femoral or popliteal arteries. Despite data stratification, angiographic follow-up indicated that patients after successful directional atherectomy, at a mean follow-up time of 5 mos, have more than a 50% lesion recurrence rate. Although directional atherectomy (Simpson AtheroCath) utilizing present techniques has excellent primary success and acceptable complication rates, angiographic follow-up statistics are bothersome. 
2	A new technique of surgical treatment of chronic duodenal ulcer without laparotomy by videocoelioscopy. We performed truncal posterior right vagotomy with lesser curve anterior gastric myotomy by videocoelioscopy on 10 patients (5 men and 5 women, ranging in age from 19 and 54 years, with a mean age of 32 years). All had a long history of chronic duodenal ulcer with a mean duration of symptoms of 3.8 years. The mean length of the operation was 60 minutes (range: 55 to 110 minutes). There was no morbidity, and all patients were discharged after 5 days. The acid secretion tests under basal conditions and under insulin stimulation preoperatively and 1 month postoperatively showed a mean decrease in the basal output of 79.3% and a mean decrease of 83.04% in the maximal output. The fibroscopic control at the second postoperative month showed a complete healing of the ulcer in nine patients and a residual ulcer scar in one. No patients had any abdominal complaints. Right truncal vagotomy and anterior lesser curve seromyotomy by videocoelioscopy is an efficient and elegant method of treating chronic duodenal ulcer, but it needs thorough experimental practice. 
5	Surgical procedures in the management of Takayasu's arteritis. Takayasu's arteritis is an inflammatory arteriopathy that often progresses to obliteration of multiple large arteries. Variable results have been reported after medical and surgical management. Twenty female patients with Takayasu's arteritis were treated from 1973 to 1989. Eleven (55%) patients had hypertension. Upper or lower extremity ischemia was present in 12 (60%) patients and cerebrovascular insufficiency in seven (35%). Nine patients initially managed with corticosteroids had no improvement in signs or symptoms of arterial insufficiency. Eleven patients had 16 vascular procedures for the following indications: renovascular hypertension (6), extremity ischemia (5), cerebrovascular insufficiency (2), dilation ascending aorta with aortic insufficiency (1), thoracic aortic aneurysm (1), abdominal aortic aneurysm (1). Procedures included aortorenal bypass (5), carotid-subclavian, axillary, or brachial bypass (4), aorto-carotid bypass (2), aneurysm resection (2), supra-celiac aorto-femoral bypass (1), ascending aorta/aortic valve replacement (1), and nephrectomy (1). Clinical improvement occurred in all patients. There were no operative deaths. All are alive at a mean follow-up of 5.75 years (6 months to 16 years). Revision of the initial reconstruction has been required for recurrent renovascular hypertension in one patient and extremity ischemia in another. The other nine patients remain symptomatically improved. Symptomatic Takayasu's arteritis frequently requires arterial reconstruction. Symptomatic improvement and excellent long-term graft patency can be expected after arterial reconstruction. 
4	Ventricular arrhythmias in ischemic heart disease. Ventricular arrhythmias remain the leading cause of death from coronary artery disease. This review summarizes current thinking in several areas relating to the pathophysiology, prognosis, and therapy of ventricular arrhythmias associated with acute and chronic coronary artery disease syndromes. The experimental basis of arrhythmias in the setting of acute myocardial ischemia and chronic myocardial infarction is described, stressing the important pathophysiologic differences between these two conditions. The effects of the autonomic nervous system as a key modulator of ischemic arrhythmogenesis are discussed. Insights, derived from endocardial mapping studies, into the nature of ventricular tachycardia in humans with chronic myocardial infarction are described, including implications for risk stratification and therapy to prevent arrhythmia recurrence. Current therapeutic principles are discussed in the management of ventricular arrhythmias associated with coronary artery disease, including pharmacologic approaches, surgical and catheter ablation, and automatic implantable cardioverting and defibrillating devices. 
5	Biliary pain in postcholecystectomy patients without biliary obstruction. A prospective radionuclide study. Biliary pain without obvious biliary obstruction is common in postcholecystectomy patients. We studied 20 symptomatic patients with episodes of biliary-type pain after cholecystectomy (all having undergone endoscopic retrograde cholangiography), and in 18 asymptomatic postcholecystectomy controls. We performed quantitative hepatobiliary radionuclide analysis with dimethyl-imidodiacetic acid. From a series of 90 dynamic images at 1-min intervals using a gamma camera coupled to a computer, time-activity curves were produced in regions of interest in the liver, intrahepatic biliary tree, common duct, and heart, from which quantitative biliary excretion indexes were obtained. The results demonstrate a biliary kinetic dysfunction in patients with postcholecystectomy pain without morphological abnormalities. 
2	Surgical presentation of Kawasaki disease (mucocutaneous lymph node syndrome). Five patients with Kawasaki disease (mucocutaneous lymph node syndrome) are reported whose varied presentations included acute abdominal pain, peripheral arterial aneurysms, digital gangrene and sterile pyuria and whose presenting pathology ranged from hydrops of the gallbladder to enteric pseudo-obstruction. As the complications of the disease can usually be managed without resort to surgery, which is associated with a mortality rate of up to 25 per cent, the recognition of Kawasaki disease will prevent hazardous and unnecessary laparotomy. 
2	Helicobacter pylori and gastric acid output in peptic ulcer disease. Helicobacter pylori is associated with peptic ulcer, and a causal relationship has been postulated. We investigated the association between Helicobacter pylori and gastric acid output. Two hundred forty-one patients were studied: 173 with duodenal ulcer, 51 with gastric ulcer (41 corpus, 10 prepyloric), and 17 with combined gastric and duodenal ulcer. In 194 patients (80%), Helicobacter pylori could be demonstrated histologically from gastric antral biopsies. The presence or absence of Helicobacter pylori was not influenced by age, sex, or use of tobacco or analgesics. Patients with duodenal ulcer or combined gastric and duodenal ulcer had similar gastric acid outputs irrespective of the presence or absence of Helicobacter pylori. However, gastric ulcer patients with Helicobacter had higher basal and maximal acid outputs when compared to patients without Helicobacter (mean basal output: 4.1 mmol/hr vs 2.4, P less than 0.05; mean maximal output 19.5 mmol/hr vs. 14.4, P less than 0.05). Although Helicobacter pylori is associated with both gastric ulcer and duodenal ulcer, its significance may be different in the two diseases. 
4	Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? OBJECTIVE: To explore the role of endothelin-1, a potent endothelial-derived vasoconstrictor peptide, in pulmonary hypertension, by measuring its concentration in arterial and venous plasma. DESIGN: A survey, case series study. SETTING: University-affiliated hospitals and outpatient clinics. PATIENTS: Twenty-seven patients with pulmonary hypertension: 7 with primary, and 20 with secondary pulmonary hypertension of various causes. The control groups (n = 16) comprised 8 healthy volunteers and 8 patients with coronary artery disease but without evidence of pulmonary hypertension. MEASUREMENTS AND MAIN RESULTS: Pulmonary artery pressure was markedly increased (94/43 +/- 23/13 mm Hg) in the patients with pulmonary hypertension. Venous plasma immunoreactive endothelin-1, measured by a specific radioimmunoassay, was significantly higher in patients with pulmonary hypertension (3.5 +/- 2.5 pg/mL, P less than 0.001) than in normal subjects (1.45 +/- 0.45 pg/mL), or patients with coronary disease (0.75 +/- 0.64 pg/mL). The arterial-to-venous ratio of immunoreactive endothelin-1 was significantly greater than unity in primary pulmonary hypertension (2.21 +/- 0.72, P = 0.01), whereas the patients with secondary pulmonary hypertension had a mean ratio not different from 1 (0.97 +/- 0.42). In contrast, the mean arterial-to-venous ratios were significantly less than unity in both control groups (0.59 +/- 0.35, and 0.54 +/- 0.64; P less than 0.02, for normal subjects and coronary disease patients, respectively), indicating a possible clearance of endothelin-1 across the healthy lung. CONCLUSIONS: Patient with pulmonary hypertension have substantial alterations in plasma immunoreactive endothelin-1, which may reflect changes in net release or clearance of endothelin-1 by the lung. In patients with primary pulmonary hypertension, the high levels in arterial compared with venous plasma suggest pulmonary production of endothelin-1, which may contribute to elevated pulmonary vascular resistance. 
5	Hilar malignancy: treatment with an expandable metallic transhepatic biliary stent. An expandable metallic transhepatic biliary endoprosthesis was used to treat 20 patients with hilar malignancy and isolated right and left intrahepatic ducts. In 12 patients, only one intrahepatic ductal system was drained; in eight patients, both systems were drained. In five patients, both systems were drained through a single transhepatic track by arrangement of two stents in a T configuration. The initial technical success rate in placing the stents and achieving internal drainage was 100%. Complications necessitating further intervention occurred in two of the 20 patients. Short-term clinical follow-up was available for 19 of the 20 patients. Two months after stent insertion, two patients complained of persistent jaundice, two patients died without jaundice, and 15 patients were free of symptoms of biliary obstruction. A variety of geometric configurations are possible with this endoprosthesis. The relative merits of these stent arrangements are discussed, and a new technique for placing the stents in a T configuration is described. 
2	Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate. They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin. In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen. Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p less than 0.005). They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells. Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells. These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol. Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect. 
1	Intraoperative pressure profile measurement and continence mechanism adjustment in the Indiana pouch urinary reservoir. We have described herein a simple pressure transducer system which helps the surgeon to tailor suture placement and achieve a continent ileocecal reservoir. It seems that fewer Lembert sutures than previously recommended are necessary to create a continent reservoir, although further study is needed. 
1	Cutaneous malignant melanoma metastatic to the choroid. Cutaneous malignant melanoma metastatic to the eye is a well-documented occurrence in the ophthalmic literature. Typically, ocular metastatic disease occurs concomitantly with or following the documentation of disseminated metastases. We present the clinical and histopathologic findings in a 62-year-old man whose first manifestation of metastatic cutaneous melanoma was his choroidal lesion. 
1	Marjolin's ulcer: a review and reevaluation of a difficult problem. The formation of an epidermoid carcinoma in nonhealing scar tissue, a Marjolin's ulcer, is a well described neoplasm. These lesions are, however, frequently overlooked and often inadequately treated. This paper reviews six cases of scar-tissue carcinoma. All lesions were secondary to various kinds of burns. Four of the Marjolin's ulcers were well-differentiated squamous cell carcinomas. One was a moderately differentiated squamous cell carcinoma, and one was a malignant melanoma. The average age at presentation was 59 years, and the mean interval from time of burn injury to appearance of neoplasm was 36.8 years. The lesions varied in anatomic location and involved the upper extremities, lower extremities, and scalp. In addition to the case studies, this paper reviews the literature and provides a logical treatment plan for a patient with a Marjolin's ulcer. Because these lesions can be very aggressive, a well thought-out treatment plan is necessary to optimize care and assure patient survival. 
5	Acute obstructive jaundice in the multiple trauma patient. The appearance of acute jaundice in the multiple trauma patient may result from obstruction of the common bile duct by clot. Management of this problem may be hindered by a delay in diagnosis, especially where alterations in pigment load and hepatic clearance may have produced the jaundice. A high index of suspicion combined with the judicious use of various noninvasive imaging modalities may be helpful in making the diagnosis. The progression of jaundice in a patient suspected of having acute obstructive hemobilia should prompt rapid operative intervention. At laparotomy, cholangiography or common bile duct exploration should be done. Persistent bleeding should be managed initially with angiographic localization and transcatheter embolization; its failure would necessitate surgical control of the source. 
5	Duodenal stricture: a complication of chronic fibrocalcific pancreatitis. Over the past 10 years, one of us (M.C.A.) has treated 92 patients who required operation for symptoms associated with alcohol-induced chronic fibrocalcific pancreatitis. Four of these patients had duodenal obstruction. All four had had lateral pancreaticojejunostomy to relieve pancreatic ductal obstruction and associated chronic abdominal pain; three of the four also required biliary diversion for stenosis of the intrapancreatic portion of the common bile duct. Each duodenal stricture required reoperation and gastrojejunostomy to bypass the site of obstruction. A review of the English language literature revealed that duodenal obstruction in patients with chronic fibrocalcific pancreatitis is uncommon, only 58 previous cases having been reported. All of those patients had pancreatic ductal obstruction, and more than half had concomitant distal biliary stenosis. Two thirds of the duodenal obstructions were treated by gastroenterostomy, and one third were resected. Duodenal obstruction in patients with chronic pancreatitis and biliary stricture appears to reflect an advanced form of the disease. Combined lateral pancreaticojejunostomy and biliary diversion has emerged as the preferred surgical procedure for this problem. Careful preoperative assessment for evidence of duodenal stenosis also is needed in this group of patients, and gastroenterostomy is indicated in appropriate cases. 
3	Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. A patient is described who has features of Pearson syndrome and who presented in the neonatal period with a hypoplastic anemia. He later developed hepatic, renal, and exocrine pancreatic dysfunction. At the age of 5 years he developed visual impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia, and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 4.9 kb. The deleted region was bridged by a 13-nucleotide sequence occurring as a direct repeat in normal mtDNA. Both Pearson syndrome and Kearns-Sayre syndrome have been noted to be associated with deletions of mtDNA; they have not previously been described in the same patient. These observations indicate that the two disorders have the same molecular basis; the different phenotypes are probably determined by the initial proportion of deleted mtDNAs and modified by selection against them in different tissues. 
5	Right hemothorax: an unusual presentation of ruptured aortic dissection. This report presents the case of a 55-year-old male with rupture of a descending thoracic aortic dissection into the right hemithorax who successfully underwent prosthetic graft replacement of the involved segment of the aorta through left thoracotomy. 
1	Spinal coning after lumbar puncture in prostate cancer with asymptomatic vertebral metastasis: a case report. A 60-year-old man was admitted to our hospital for complete urinary retention. Prostate cancer was diagnosed and anti-cancer chemotherapy was administered. Regression of prostatic enlargement was appreciated and difficult urination improved. At 6 months after the initial treatment vertebral metastasis of T10-11 was noted on a bone scintigram but there were no symptoms induced by bone metastasis. Orchiectomy was performed with the patient under lumbar anesthesia. Complete paralysis of both lower extremities occurred postoperatively. Computerized tomography and myelographic findings demonstrated complete subarachnoid block with an extramedullary spinal cord tumor. It was concluded that traction on the spinal cord producing neurological deterioration (spinal coning) occurred after removal of the cerebrospinal fluid by lumbar puncture. 
3	Intracranial complications of paranasal sinusitis: a combined institutional review. Intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies. The charts of all patients (n = 649) admitted for acute or chronic sinusitis to the University of Minnesota Hospital and to the University of Michigan Medical Center during a 13-year period (1975 to 1988) were retrospectively reviewed to determine the incidence of complications. The clinical presentation, bacteriology, involved sinuses, influencing host factors, white blood cell count on presentation, length of hospitalization, and postinterventional complications are presented. Twenty-four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3.7%. Aggressive medical and semi-emergent surgical intervention are required to prevent excessive morbidity and/or mortality. Intracranial complications included subdural empyema, frontal lobe abscesses, intrahemispheric abscesses, cavernous and superior sagittal sinus thrombosis, and osteomyelitis. 
1	Altered protein tyrosine kinase levels in human colon carcinoma. To further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis, the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues. Total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine (Gly) (E11-G1), as an artificial substrate. Tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration. The average specific activity ratios were 1.95 +/- 0.27 (normal cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma particulate) for tyrosine kinase activity. Cellular distribution (% cytosol) of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to 91.2% and from 7.0% to 61.4%, respectively. In nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues. There was no difference due to histologic type or the presence of adenomatous components. A significant decrease of cytosolic tyrosine kinases was correlated with Dukes' Stage A. With advancing Dukes' stage, the average specific activity ratios (normal cytosol/carcinoma cytosol) were decreased. This study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with colonic tumor growth. 
5	Detection of human papillomavirus-genomic DNA in oral epithelial dysplasias, oral smokeless tobacco-associated leukoplakias, and epithelial malignancies. Human papillomavirus (HPV) is an infectious agent that is increasingly associated with mucosal cancers, in particular cancer of the cervix. The present investigation was undertaken in an attempt to determine whether HPV could be easily detected in biopsies of oral tissues, specifically oral squamous cell carcinomas, oral epithelial dysplasias, smokeless tobacco keratoses, verrucous hyperplasia, and verrucous carcinoma. In situ DNA hybridization methods were used to isolate specific HPV genomes. Among 100 instances of benign leukoplakia, only 4% of non-tobacco-related and 10% of smokeless tobacco-related lesions harbored viral sequences. We were able to detect viral sequences in dysplastic lesions 3% of the time. Alternatively, 17% and 20% of the verrucous hyperplasias and verrucous carcinomas were positive for viral nucleic acids. Six percent of the squamous cell carcinomas harbored HPV. On the basis of these findings, it is concluded that HPV of known genotype can be identified in oral premalignant and malignant neoplasms. 
3	Unusual cerebral manifestations in hereditary fructose intolerance. Five children with hereditary fructose intolerance developed symptoms of neurological impairment. In three of them, neurological involvement was related to the acute hepatic toxicity of fructose (hypoglycemia, abnormal coagulation, cardiovascular collapse); in the other two, such a relationship could not be demonstrated. Neurological impairment is not classic in hereditary fructose intolerance, but its occurrence in the acute phase of the disease is possible and does not constitute an argument against the diagnosis. 
4	Hepatic arterial embolization in cases of extensive celiac arterial stenosis. Transarterial hepatic embolization was attempted in 10 and succeeded in nine patients with hepatocellular carcinoma accompanied by extensive celiac arterial stenosis. All catheterization was done through the femoral artery. In six cases, the tip of the catheter (2.5-F ball-tip microcatheter in three cases, 4-F ball-tip supple catheter in three cases) was placed in the proper hepatic artery through the pancreaticoduodenal collaterals. In three cases, a ball-tip microcatheter was injected from the guiding catheter, which was placed in a pinhole of the celiac trunk. These techniques involving flow-guided ball-tip catheters are of great value for hepatic arterial catheterization in cases of extensive celiac arterial stenosis. 
5	Hearing loss in elderly patients in a family practice. OBJECTIVE: To investigate hearing loss in elderly patients. DESIGN: Cohort study. SETTING: Family practice. PATIENTS: All ambulatory patients 65 years of age or older who attended the practice from June to August 1989. OUTCOME MEASURES: The Hearing Handicap Inventory for the Elderly--Screening Version (HHIE-S) and the Welch-Allyn Audioscope. Patients who failed one or both of the screening tests were referred to a speech and hearing clinic for audiologic assessment and treatment recommendations. Those with hearing aids were excluded from the main study but were given the opportunity to have them assessed at the clinic. MAIN RESULTS: Of 157 eligible patients 42 were excluded: 16 refused to participate, 13 already had hearing aids, and 13 could not be contacted. Of the remaining 115, 34 failed one or both of the tests (14 failed the HHIE-S, 9 failed the audioscope test, and 11 failed both). Of the 34, 25 completed the audiologic assessment at the clinic. Fifteen were found to have severe hearing impairment; the recommendation was hearing aids for 12, further assessment for 2 and no treatment for 1. Of the remaining 10 patients it was thought that 6 would benefit from hearing aids. Ten of the 11 patients with hearing aids who agreed to undergo testing at the clinic were found to need an adjustment or replacement of their devices. CONCLUSIONS: Hearing loss is a significant problem in elderly patients in primary practice. Further study is required to determine which of the two screening tools is most effective. Most elderly patients with hearing aids may require modification or replacement of their devices. 
5	Narrow excision (1-cm margin). A safe procedure for thin cutaneous melanoma. We analyzed the results at 8 years of an international, randomized, prospective study carried out by the World Health Organization Melanoma Programme aimed at evaluating the efficacy of 1-cm-margin excision of primary melanomas not thicker than 2 mm. Data for 612 patients were assessable; 305 were randomized to receive 1-cm-margin excision and 307 to receive wide excision (margins of greater than or equal to 3 cm). The major prognostic criteria were similar in the two groups. Breslow thickness was 0.99 mm in the narrow excision group and 1.02 mm in the wide excision group. Disease-free and overall survival rates (mean follow-up period, 90 months) were similar in the two groups. Only four patients had a local recurrence as a first relapse. All underwent narrow excision, and each had primary melanomas thicker than 1 mm. 
5	Rupture of a benign mediastinal teratoma into the right pleural cavity. A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid. The activity of the amylase is thought to be the most likely cause of the rupture. High levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors. 
3	Suppression of carbamazepine-induced rash with prednisone. We report our experience with 20 patients who developed a rash shortly after the introduction of carbamazepine and were treated with prednisone and an antihistamine. Sixteen patients were successfully continued on carbamazepine while 4 had to discontinue the drug. 
2	Long-term remission of chronic hepatitis B after alpha-interferon therapy. OBJECTIVE: To evaluate whether remissions of chronic hepatitis B induced by alpha-interferon therapy are of long duration. DESIGN: Cohort study. SETTING: Clinical Center of the National Institutes of Health, a tertiary referral center. PATIENTS: Sixty-four patients with chronic hepatitis B were treated with alpha-interferon between 1984 and 1986. MAIN OUTCOME MEASURES: Patients were followed with frequent examinations and determinations of serum liver biochemical tests and hepatitis B virus (HBV) markers including hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA using blot hybridization and polymerase chain reaction. RESULTS: Among 64 patients with chronic hepatitis B who were treated with alpha-interferon, 23 (36%) responded to treatment with loss of HBeAg and improvement in serum aminotransferases. All 23 have been followed for 3 to 7 years (mean, 4.3 years). During follow-up, 3 of 23 patients relapsed, with reappearance of HBeAg and abnormal serum aminotransferases, all within 1 year of therapy. The remaining 20 patients continued to have no detectable HBeAg or HBV DNA (using blot hybridization) in serum and to be asymptomatic for liver disease, although 3 had minimal elevations in serum aminotransferases. Thirteen patients (65%) became negative for HBsAg between 0.2 and 6 years (mean, 3 years) after loss of HBeAg. Although no patient had HBV DNA that was detectable by blot hybridization, the 7 patients who remained HBsAg positive all had HBV DNA in serum detected by polymerase chain reaction, but only 2 of 13 HBsAg-negative patients had viral genome using this method. Testing sequential samples indicated that HBV DNA detected by polymerase chain reaction usually disappeared at or around the time that test results for HBsAg became negative. CONCLUSIONS: Remissions in chronic hepatitis B induced by alpha-interferon are of long duration and are followed, in most patients, by the loss of HBsAg and all evidence of residual virus replication. 
4	Role of endogenous angiotensin II in the control of vasopressin secretion during hypovolemia and hypotension in conscious rabbits. In order to investigate the physiological role of angiotensin II (ANG II) in the control of vasopressin (VP) secretion, the VP responses to hypotension induced by hemorrhage (20 ml/kg, n = 10) or nitroprusside infusion (1-10 micrograms/kg.min, n = 9) were studied with or without blockade of ANG II formation by the converting enzyme inhibitor captopril in conscious rabbits. Administration of captopril (5 mg/kg, iv) caused a small decrease in mean arterial pressure but did not enhance the hypotensive response to subsequent hemorrhage or nitroprusside infusion. The renin response to both stimuli was enhanced by captopril, whereas the increase in plasma ANG II concentration was attenuated. Plasma VP (PAVP) concentration increased during hemorrhage (2.0 +/- 0.2-113.6 +/- 47.7 pg/ml, P less than 0.01) and nitroprusside infusion (2.1 +/- 0.3-5.1 +/- 1.0 pg/ml, P less than 0.01). Captopril did not change basal plasma PAVP, nor did it attenuate the VP responses to hemorrhage or nitroprusside. Indeed, captopril tended to enhance the VP responses to hemorrhage (2.3 +/- 0.3-147.1 +/- 65.9 pg/ml) and nitroprusside infusion (1.9 +/- 0.2-15.4 +/- 6.0 pg/ml). The relationship between log PAVP and mean arterial pressure during hemorrhage and nitroprusside infusion in the presence of captopril was not different than in the absence of captopril. These results indicate that in conscious rabbits, the renin-angiotensin system does not contribute to the increase in VP secretion during hypotension induced by hemorrhage or nitroprusside infusion. 
5	Induced abortions, contraceptive practices, and tobacco smoking as risk factors for ectopic pregnancy in Athens, Greece. A case-control study of the role of induced abortion and other factors on the subsequent occurrence of ectopic pregnancy was undertaken in 1986-1987 in Athens, Greece, where a similar study 20 years ago found a tenfold risk of ectopic pregnancy among women with one or more illegal induced abortions. Seventy women residents of Athens, consecutively admitted to the major state maternity hospital with a diagnosis of ectopic pregnancy, were individually matched with women with a newly diagnosed pregnancy of the same order as the ectopic index pregnancy. Two control women were found for each of 63 cases, but only one control for each of the remaining seven cases. All cases and controls were interviewed by the same qualified obstetrician. Statistical analysis was undertaken with stratification of individual matched triplets and pairs, as well as through conditional multiple regression procedures. The relative risk of recurrence of an ectopic pregnancy was 6.39 with 95% confidence interval (CI) 1.96-21.04. Miscarriages did not increase the risk of ectopic pregnancy. The relative risk for subsequent ectopic pregnancy among women with one or more induced abortion, compared to women without such abortions, was 1.87 (CI 0.84-4.16) controlling only for the matching factors, and 1.71 (CI 0.69-4.27) when marital status (a possible selection factor) was also accounted for in the conditional logistic regression. There was no evidence for increasing risk with increasing number of induced abortions. Past use of an intrauterine device (IUCD) was associated with a relative risk of 3.89 (0.72-21.02); the relative risk increased with the duration of use of the IUCD. 
4	Current status of organ preservation with University of Wisconsin solution. A retrospective analysis of all organs that were preserved with University of Wisconsin solution was undertaken to assess the impact of this solution on early allograft function. From May 1987 until June 1990, 181 livers, 92 pancreata, and 92 kidneys were preserved with University of Wisconsin solution for extended periods of time. The mean (+/- SD) preservation times were as follows: liver, 12.6 +/- 4.5 hours; pancreas, 16.7 +/- 4.4 hours; and kidney, 18.3 +/- 4.3 hours. The overall rate of primary nonfunction and hepatic artery thrombosis were 6.1% and 3.9%, respectively. No differences in the rates of primary nonfunction and hepatic artery thrombosis were noted for combined liver-pancreas procurement vs isolated liver retrievals or when reduced-size liver transplants were compared with nonreduced liver transplants. Likewise, no difference in primary nonfunction or hepatic artery thrombosis was seen in livers that were preserved for less than 6, 6 to 12, and greater than 12 hours. However, serum aminotransferase levels and prothrombin times were lower on the first postoperative day in livers that were preserved for less than 6 hours when compared with 6 to 12 or greater than 12 hours. Early pancreatic allograft function was also excellent for up to 24 hours of cold-storage preservation. All patients were immediately insulin independent, and there were no cases of initial nonfunction or graft pancreatitis. There were only two cases (2.2%) of pancreatic vascular thrombosis in this series. No difference in pancreatic function was noted for organs that were preserved for less than 6, 6 to 12, or greater than 12 hours. Likewise, renal allograft function was excellent, with only two patients (2.2%) requiring postoperative hemodialysis. The actuarial 1-month patient survival for liver and pancreas-kidney transplant recipients was 91.5% and 98.9%, respectively. Actuarial 1-month allograft survival for liver, pancreas, and kidney transplants was 83.0%, 96.7%, and 97.8%, respectively. In conclusion, University of Wisconsin solution represents a significant advancement in cold-storage organ preservation and is ideally suited as a universal intra-abdominal aortic-flush and cold-storage solution. 
5	Transvaginal approach for repair of rectovaginal fistulae complicating Crohn's disease. The management of rectovaginal fistulae complicating Crohn's disease is difficult and often unsatisfactory. Between December 1983 and November 1988, 13 patients with Crohn's disease underwent repair of rectovaginal fistulae via a transvaginal approach. All patients had a diverting intestinal stoma either as part of the initial step in the staged management of intractable perianal disease or concurrent with the repair of the rectovaginal fistula. Each of the patients had low or mid septal fistulae; high fistulae generally are treated transabdominally and are not the focus of this discussion. Fistulae were eradicated in 12 of the 13 women and did not recur during the follow-up period, which averaged 50 months (range, 9 to 68 months). The only treatment failure was a patient who had a markedly diseased colon from the cecum to the rectum and a very low-lying fistula. It is concluded that a modified transvaginal approach is an effective method for repair of rectovaginal fistulae secondary to Crohn's disease. 
2	Irritable bowel syndrome in women having diagnostic laparoscopy or hysterectomy. Relation to gynecologic features and outcome. We identified irritable bowel syndrome (IBS) in 47.7% of 86 women having diagnostic laparoscopy for chronic pelvic pain, 39.5% of 172 women having elective hysterectomy, and 32.0% of 172 controls age-matched for the hysterectomy group (P = NS). Constipation and pain subtype IBS were more common in hysterectomy patients than controls (P less than 0.05). In laparoscopy patients, dyspareunia was more common in those with IBS than in those without it (P less than 0.05). In the hysterectomy group, more IBS patients had chronic pelvic pain (P less than 0.005), and abnormal menses (P less than 0.01). Chronic pelvic pain was more frequently the only prehysterectomy diagnosis in IBS patients (P less than 0.05), and IBS was present more often when pain was a reason for hysterectomy (P less than 0.01). One year after laparoscopy, IBS patients gave lower overall status ratings (P less than 0.01) and lower pain improvement ratings (P less than 0.05) than non-IBS patients. In women who had a hysterectomy for pain, there was less pain improvement one year later in those with the pain subtype of IBS than in non-IBS patients (P less than 0.05). IBS is associated with gynecologic symptoms and affects the symptomatic outcome of diagnostic laparoscopy and hysterectomy. 
1	Anaesthetic problems in ex situ resection of the liver. Ex-situ resection of the liver is a new surgical technique for treatment of liver tumours not amenable to conventional surgery. This paper describes the cardiovascular and metabolic changes that occurred in nine consecutive such patients. No severe haemodynamic or pulmonary complications occurred. Specific problems were encountered during the prolonged anhepatic period, which lasted an average of 5.96 (SD 1.46) hours. Significant metabolic and coagulation disorders occurred 2 to 3 hours after hepatectomy because of complete loss of hepatic function. The predominant findings during the anhepatic period were hypoglycaemia and severe metabolic acidosis, mainly from increased levels of lactic acid. Exogenous administration of dextrose 5% at an average rate of 188 ml/hour was necessary to maintain normoglycaemia, while correction of metabolic acidosis required 403 (SD 159.79) mmol of sodium bicarbonate, supplemented by hyperventilation. Tris-hydroxymethylaminomethane was used when sodium overload was thought to be a problem. There was a marked decrease of Factor V and fibrinogen, a moderate thrombocytopenia and fibrinolysis. The severity of these alterations was dependent on the duration of the anhepatic period and the primary function of the re-implanted liver. 
1	Prognostic value of DNA flow cytometry in paragangliomas of the carotid body. A carotid body tumor is a paraganglioma of the carotid bifurcation. Histologic appearance does not correlate with the malignant potential of the lesion, and thus a reliable prognostic marker for these tumors is lacking. To determine whether flow cytometric analysis of paraffin block specimens by DNA index and synthetic phase fraction (SPF) would be of prognostic value, a retrospective chart review of 14 patients with carotid body tumors was performed. Three of 14 tumors were aneuploid and were the only tumors with SPF greater than 15%. One of 3 patients (33%) with an aneuploid tumor (SPF = 22%) developed a local recurrence; no patient with a diploid tumor developed a recurrence. Two of 3 (67%) patients with aneuploid tumors (SPF = 18%) but only 1 of 11 (9%) with a diploid tumor were symptomatic preoperatively (P = 0.03). DNA index and SPF may help select a subgroup of patients with more aggressive tumors who are at increased risk for recurrence and therefore require closer follow-up. 
2	Resolution of the adult respiratory distress syndrome following colectomy and liver transplantation. A 32-year-old woman with liver failure from end-stage cirrhosis and ulcerative colitis developed septicemia and severe ARDS. Subtotal colectomy and a successful liver transplantation resulted in complete resolution of the ARDS. 
1	Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients. To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials. 
3	Cerebellar syndrome caused by isoniazid. Treatment of tuberculosis in a hemodialysis patient with isoniazid, rifampin, and pyrazinamide resulted in the development of acute cerebellar dysfunction. This resolved rapidly following the discontinuation of isoniazid and pyrazinamide, reinstitution of isoniazid at a lower dose, and addition of pyridoxine. We discuss why we believe this syndrome was caused by isoniazid. Patients with renal failure who undergo antituberculous therapy with isoniazid should receive supplemental pyridoxine to reduce the likelihood of isoniazid-related neurotoxicity. 
4	Pharmacological reversibility of experimental cerebral vasospasm. Using a morphometric technique, the pharmacological reversibility of luminal narrowing after experimental subarachnoid hemorrhage (SAH) was investigated. For vasodilation, a "cocktail" consisting of 10(-4) M papaverine, 2 x 10(-4) M sodium nitroprusside, and 10(-5) M adenosine was administered intra-arterially. Forty-two rabbits were divided into six groups: control (normal animals); control plus cocktail (normal animals perfused with the cocktail before fixation); SAH (animals sacrificed 48 hours subsequent to intracisternal injection of 1.5 ml/kg of arterial blood); SAH plus cocktail (SAH plus perfusion with the cocktail); BaCl2 (animals sacrificed 10 minutes after intracisternal injection of 2 ml of 3 x 10(-3) M BaCl2); and BaCl2 plus cocktail (BaCl2 animals perfused with the cocktail). The diameter of the basilar arteries in the control and the control plus cocktail groups was not significantly different. BaCl2 reduced the diameter 44% and SAH reduced the diameter 27%. There were no significant differences between the diameter of the BaCl2 plus cocktail group and SAH plus cocktail group when compared with the control or the control plus cocktail group. Morphological examination by light and transmission electron microscopy showed luminal narrowing and corrugation of the elastic lamina with few degenerative or proliferative changes of the vessel wall in animals with SAH. These results suggest that cerebral vasospasm is caused initially by smooth muscle contraction rather than by proliferative vasculopathy and that it is not an irreversible process. 
4	The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. Computerized mapping of atrial fibrillation was performed in animals and man. To study atrial fibrillation in a systematic manner, we developed a clinically relevant experimental model of atrial fibrillation. Chronic mitral regurgitation was created surgically in 25 dogs without opening the pericardium. After several months of chronic mitral regurgitation, the atria became enlarged and sustained atrial fibrillation could be induced by standard programmed electrical stimulation techniques. Computerized isochronous activation maps of the atria were recorded during atrial fibrillation from 208 bipolar electrodes simultaneously. In a parallel study, human atrial fibrillation was mapped with a separate 160-channel intraoperative mapping system in patients with paroxysmal atrial fibrillation who were undergoing surgical correction of the Wolff-Parkinson-White syndrome. The canine activation sequence maps demonstrated a spectrum of rhythm abnormalities ranging from simple atrial flutter to complex atrial fibrillation. They also showed that macroreentrant circuits within the atrial myocardium were responsible for the entire spectrum of arrhythmias. Atrial reentry was also documented during human atrial fibrillation. All patients had nonuniform conduction around regions of bidirectional block in both atria resulting in multiple discrete wave fronts. In addition, six patients had a single reentrant circuit in the right atrium in which bidirectional block of the activation wave front occurred along the sulcus terminals between the venae cavae. The left atrium in all patients demonstrated multiple wave fronts and conduction block, but left atrial reentry could not be detected. Both the experimental study and the clinical study demonstrated that multiple wave fronts, nonuniform conduction, bidirectional block, and large (macroreentrant) reentrant circuits occur during atrial fibrillation. The presence of macroreentrant circuits and the absence of either microreentrant circuits or evidence of atrial automaticity suggests that atrial fibrillation should be amenable to surgical ablation. 
5	Enhanced anaphylatoxin and terminal C5b-9 complement complex formation in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Complement activation was studied in ten consecutive pregnant women developing hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) and ten other women with normal pregnancies. Blood samples for anaphylatoxin (C3a/C3a desArg and C5a/C5a desArg) and terminal C5b-9 complement complex determinations were drawn at delivery and 24 hours and 7 days later. Women developing HELLP syndrome had higher plasma levels of anaphylatoxins with delivery than did women with uneventful pregnancies. The plasma levels of terminal C5b-9 complement complexes at the time of delivery were increased as compared with levels 1 and 7 days after delivery in women with HELLP syndrome. The plasma concentrations of the anaphylatoxins and the terminal C5b-9 complement complexes returned to normal levels within 1 week after delivery in the HELLP group. The formation of C5b-9 complement complex indicates that the terminal part of the complement cascade has been activated and that C5a has been formed and eliminated. Complement activation with release of anaphylatoxins and terminal C5b-9 complement complexes may be one etiologic factor behind the elevated blood pressure, hemolysis, liver insufficiency, and platelet consumption seen in these patients. 
4	Long-term impact of smoking cessation on the incidence of coronary heart disease. Using a simulation model of the US male population, we estimated the long-term impact that future smoking cessation programs would have on the distribution and occurrence of coronary heart disease in males ages 35-84. For interventions that reduce the number of smokers by 25 percent in 1990, the number of men free of coronary heart disease is projected to increase by 416,787 (0.7 percent) in 2015, and the age-standardized absolute incidence to decline by 2.3 percent. Incidence rates and absolute incidences are projected to fall in men under age 65, but absolute incidence would rise in men over age 65, in large part because of the increased number of men who were at risk for coronary heart disease because of a reduction in non-coronary smoking-related mortality. These trends were more marked for greater smoking reductions and were generally unaffected in a variety of analyses using alternative assumptions, which considered smoking as a risk factor in the elderly, a lag-time before benefits from smoking cessation were realized and secular declines in smoking prevalence. Subject to the assumptions of our model, we conclude that smoking reductions will markedly reduce coronary heart disease, especially in younger age groups, and that this benefit will be slightly offset by a small increase in absolute incidence in elderly men. 
5	Acute central nervous system symptoms caused by ibuprofen in connective tissue disease. We describe 2 cases of acute encephalopathy in patients with connective tissue disease caused by small doses of ibuprofen. In addition to aseptic meningitis, both patients had altered mental status and focal neurologic signs, ophthalmoplegia in one and hemiparesis in the other. The spectrum of neurologic manifestations of ibuprofen hypersensitivity is reviewed. 
5	Association of anterior ectopic anus and partial absence of levator musculature in a woman with impaired defecation. Report of a case. A 25-year-old nulliparous woman with adult onset constipation and slight anterior displacement of the anus underwent pelvic magnetic resonance imaging and was diagnosed with congenital hemiabsence of the levator ani sling. Impaired defecation was confirmed by anorectal function studies and defecography demonstrated an anterior rectocele, perineal descent at the upper limit of normal, and partial obstruction of defecation, which appeared related to the levator sling abnormality. To our knowledge, this combination of findings has not been previously described as a cause of adult onset constipation. 
1	History of cigarette smoking and risk of leukemia and myeloma: results from the Adventist health study. The risks of leukemia and myeloma associated with cigarette smoking were evaluated in a cohort study of 34,000 Seventh-day Adventists. Although Seventh-day Adventists do not smoke by church proscription, many are adult converts who smoked cigarettes prior to their baptism into the church. In comparison with those who never smoked, ex-smokers experience a relative risk of 2.00 (95% confidence interval = 1.01-3.95) for leukemia and 3.01 (95% confidence interval = 1.13-8.05) for myeloma. Risks increased in a dose-response fashion with increasing numbers of cigarettes smoked daily for both leukemia (trend P = .009) and myeloma (trend P = .005). Also, the risks of both leukemia and myeloma increased with the total duration of cigarette smoking. The cigarette smoking-leukemia relationship was strongest for myeloid leukemia, for which ex-smokers experienced a relative risk of 2.24 (95% confidence interval = 0.91-5.53). These data lend support to the hypothesis that cigarette smoke may induce malignant degeneration in bone marrow and its products. 
4	The accuracy of CT scanning in the diagnosis of abdominal and thoracoabdominal aortic aneurysms. As CT scanning has evolved as a reliable clinical tool, the use of angiography in the diagnosis of aortic aneurysmal disease has diminished. Fewer than 25% of patients with aortic aneurysmal disease undergo aortic angiographic evaluation at our institution. A prospective clinical study was undertaken to assess the validity of this policy. One hundred patients with clinical or ultrasonographic evidence of aortic aneurysms were evaluated prospectively during the period July 1987 to December 1989. All patients underwent CT scanning as an initial evaluation. Patients were selected for angiography if they fulfilled any of the following criteria: radiographic evidence of thoracoabdominal or juxtarenal aneurysms, or horseshoe kidney; or clinical suggestion of renal artery stenosis, mesenteric arterial insufficiency, aortoiliac occlusive disease, or lower extremity aneurysmal disease. During this period 19 patients (19%) underwent both CT scanning and angiography. The indications for angiography were thoracoabdominal aneurysms (7), juxtarenal aneurysms (2), clinical evidence of mesenteric insufficiency (1) or renal insufficiency (2), evidence of lower extremity aneurysmal disease (3), or severe aortoiliac occlusive disease (4). Eighty-one patients (81%) underwent CT scanning as the only radiographic evaluation. No patient was adversely affected by elimination of angiographic evaluation. CT scanning revealed inflammatory aneurysms (4), retroaortic renal veins (2), and horseshoe kidney (1). This study suggests that most (81%) patients with aortic aneurysmal disease can be adequately evaluated by CT scanning, and that a very selective policy of angiographic evaluation is indicated. 
4	Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats. We investigated the effects of nilvadipine, a calcium antagonist, on cerebral ischemia in rats. Under halothane anesthesia, 30 rats had a 3-0 nylon suture introduced through the extracranial internal carotid artery to occlude the left middle cerebral artery. Nilvadipine was dissolved in polyethylene glycol 400. Immediately following occlusion, group 1 rats (n = 10) were treated subcutaneously with vehicle and group 2 and 3 rats were treated with 1.0 (n = 10) and 3.2 (n = 10) mg/kg nilvadipine, respectively. Perfusion fixation was performed 24 hours later, and the histopathologic outcomes were quantified. In group 1 infarct volume was 28.2 +/- 11.4% of the total cerebral volume; in groups 2 and 3 infarct volumes were 25.5 +/- 11.6% (NS) and 13.9 +/- 9.2% (p less than 0.05 different from group 1), respectively. Nilvadipine decreased ischemic neuronal injury in a dose-dependent manner and may be of use in the treatment of cerebral ischemia. 
2	Bronchobiliary fistula detected by cholescintigraphy. We present a case of a bronchobiliary fistula initially detected by hepatobiliary scintigraphy. The patient developed bilioptysis 18 mo after undergoing a right hepatic lobectomy and resection of the common bile duct for cholangiocarcinoma. The procedure was complicated by the development of a subphrenic abscess that required percutaneous biliary drainage. 
2	Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. The protective effect of ursodeoxycholate conjugates against bile salt hepatotoxicity was studied in chronic bile fistula rats. Taurochenodeoxycholate or taurodeoxycholate, infused intraduodenally at 24 or 16 mumols/100 g rat per hour, respectively, caused cholestasis and severe hepatocellular necrosis within 8 hours. In contrast, tauroursodeoxycholate or taurocholate at 48 mumols/100 g rat per hour were choleretic. Tauroursodeoxycholate was not hepatotoxic, whereas taurocholate produced moderate hepatocellular necrosis. Simultaneous infusion of tauroursodeoxycholate to rats receiving taurochenoxycholate or taurodeoxycholate preserved bile flow and ameliorated hepatic injury in a dose-dependent manner. Tauroursodeoxycholate protected equally by intravenous and intraduodenal routes. Intravenous glycoursodeoxycholate also was protective. The hydrophobicity index of infused bile salts correlated well with their toxicity. Concurrent administration of ursodeoxycholate conjugates did not reduce biliary recovery of intraduodenally infused [24-14C]-taurocholate. Biliary alkaline phosphatase secretion was stimulated by infusion of taurocholate, taurodeoxycholate, or taurochenodeoxycholate; simultaneous infusion of ursodeoxycholate conjugates failed to prevent this increase. We conclude that ursodeoxycholate counteracts hepatoxicity of more hydrophobic bile salts via a direct effect at the level of the liver. 
1	The potential and limitations of laser photoablation of colorectal adenomas. Ablation of colorectal adenomas by Nd:YAG laser energy was investigated in 271 patients. Two hundred and forty-one patients, selected because of poor surgical and medical condition or refusal of surgery, presented with incompletely removed polyps or with lesions unsuitable for endoscopic polypectomy. Thirty patients with polyposis coli were treated for rectal stump polyps after subtotal colectomy and ileorectal anastomosis. Because of insufficient follow-up (28) or malignant degeneration (23), full evaluation was possible in 196 colon adenoma and 24 polyposis patients. Complete ablation with histologic confirmation for at least 12 weeks was achieved in 150 (82%) of the 183 colon adenomas. This declined to 141 (77%) because of later recurrences in prolonged follow-up. Treatment of large adenomas was less successful than that of intermediate and small lesions: ultimate ablation in 56, 85, and 93%, respectively. Impressive was the immediate relief in 100 symptomatic elderly patients, who were bothered by frequent diarrhea, excessive mucous discharge, and incontinence. All patients survived despite major complications (7%) that mainly consisted of stenosis and hemorrhage. Rectal stump polyps were eliminated in 20 patients with polyposis coli. The remaining four had an uneventful ileoanal anastomosis for ultimately uncontrollable growth of polyps. Malignancy was discovered in 22 adenoma patients and in 1 polyposis patient. We recommend laser ablation of colorectal adenomas for small and medium-sized polyps, that cannot be removed by endoscopic polypectomy in inoperable patients or in patients refusing operation. Laser treatment for extensive adenomas seems only appropriate for symptomatic relief. 
3	Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement. To assess the role of alpha-tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha-tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C-1 (20) of the Centers for Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha-tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p less than 0.05) and 22 of 30 cerebrospinal fluid (p less than 0.0002) samples from clinically more advanced patients (group IV B and group IV C-1). Alpha-tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C-1 patients. 
4	Socioeconomic conditions in childhood and ischaemic heart disease during middle age OBJECTIVE--To examine the association between socioeconomic conditions in childhood and ischaemic heart disease in middle aged men, including the role of physiological and behavioural risk factors. DESIGN--Prevalence study with extensive examination and testing and with recall of childhood conditions. SETTING--Population based study in Kuopio, Finland. SUBJECTS--Representative sample of 2679 men aged 42, 48, 54, and 60. MAIN OUTCOME MEASURES--Ischaemic findings on progressive maximal exercise test. RESULTS--Low socioeconomic style in childhood was associated with significantly higher prevalence of findings indicating ischaemias. Compared with those in the highest tertile of childhood socioeconomic conditions, the age adjusted odds ratio for subjects in the lowest tertile was 1.44 and for those in the middle tertile 1.35. Adjustment for years of cigarette smoking times the average number of cigarettes smoked, ratio of high density lipoprotein to low density lipoprotein cholesterol, fibrinogen and serum selenium concentrations, and adult height did not appreciably weaken the association. Adjustment for adult socioeconomic state resulted in a 16% decline in the association. The association was reduced to non-significance by adjustment for measures of prevalent cardiovascular illness. CONCLUSIONS--Socioeconomic state in childhood was significantly associated with ischaemic heart disease in middle aged men. Levels of risk factors measured at middle age did not account for this association, nor did adult height. Because childhood socioeconomic conditions precede the development of ischaemic heart disease the substantial impact of prevalent illness on the observed association suggests that ischaemic heart disease develops earlier in those with lower socioeconomic state during childhood. 
1	The relationship of nasopharyngeal carcinomas and second independent malignancies based on the Radiation Therapy Oncology Group experience. The authors sought to learn if the incidence of second independent malignancies after the irradiation of carcinomas of the nasopharynx is similar to that observed after treatment of tumors arising in other head and neck sites. One hundred twenty-one patients who had primary carcinomas of the nasopharynx who were treated solely by ionizing radiation (according to the specifications of a Radiation Therapy Oncology Group protocol) were identified and their subsequent well-being was reviewed. Overall there was a 4.1% incidence of second malignancies (2% after 3 years, 5% after 5 years, and 8% after 8 years) with most arising in the upper aerodigestive tract. This rate is significantly less than the rate associated with other head and neck sites. It is not significantly different from the rate of first malignancies observed in an age-matched and sex-matched population. When only those patients who were free of all evidence of neoplastic disease 6 months after the completion of radiotherapy are considered, similar analysis leads to similar outcomes. The authors conclude that the risk of second malignancies after the successful irradiation of carcinomas of the nasopharynx is substantially less than after treatment of tumors at other head and neck sites. 
4	The effects of tumor necrosis factor on intestinal structure and metabolism. Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study. 
4	Orthostatic hypotension following right ventricular myocardial infarction corrected with mineralocorticoid therapy. Severe hypotension while standing became a problem in a patient after discharge from the hospital following right ventricular myocardial infarction. Hemodynamic studies showed that right ventricular systolic function did not maintain adequate left ventricular preload and that the patient did not compensate for cardiac dysfunction by increasing blood volume. Volume expansion by mineralocorticoid therapy corrected the orthostatic hypotension and ameliorated symptoms. Hypotension eventually resolved and therapy was stopped four months after the myocardial infarction. 
2	Enteroclysis and small bowel series: comparison of radiation dose and examination time. Respective radiation doses and total examination and fluoroscopy times were compared for 50 patients; 25 underwent enteroclysis and 25 underwent small bowel series with (n = 17) and without (n = 8) an examination of the upper gastrointestinal (GI) tract. For enteroclysis, the mean skin entry radiation dose (12.3 rad [123 mGy]) and mean fluoroscopy time (18.4 minutes) were almost 1 1/2 times greater than those for the small bowel series with examination of the upper GI tract (8.4 rad [84 mGy]; 11.4 minutes) and almost three times greater than those for the small bowel series without upper GI examination (4.6 rad [46 mGy]; 6.3 minutes). However, the mean total examination completion time for enteroclysis (31.2 minutes) was almost half that of the small bowel series without upper GI examination (57.5 minutes) and almost four times shorter than that of the small bowel series with upper GI examination (114 minutes). The higher radiation dose of enteroclysis should be considered along with the short examination time, the age and clinical condition of the patient, and the reported higher accuracy when deciding on the appropriate radiographic examination of the small bowel. 
5	Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Cancer and Leukemia Group B studies. In premenopausal women with metastatic breast cancer, differences in survival curves early during follow-up can be misleading. The authors therefore analyzed long-term survival in 378 patients, entered in three randomized trials, started between 1973 and 1978. Combined data from the three trials were used to increase the power for identifying prognostic variables. Cancer and Leukemia Group B (CALGB) trial 7382 randomized patients to oophorectomy plus either cyclophosphamide or combination chemotherapy or observation. Eastern Cooperative Oncology Group (ECOG) 2174 randomized patients who had not progressed 3 months after oophorectomy to combination chemotherapy or combination chemotherapy or observation. Trial ECOG 2177 randomized estrogen receptor (ER) positive or ER-unknown patients to oophorectomy plus combination chemotherapy or immediate combination chemotherapy, and ER-negative patients were directly assigned to combination chemotherapy. Hence ER-negative patients need not have been healthy enough to be randomized to oophorectomy. With only 14% of the patients still alive, median survival on the three studies was 30, 24, and 28 months. The median survival of individual treatments changed noticeably in ECOG 2174 and ECOG 2177 with long-term follow-up. At this time there are no differences in survival between randomized regimens in any of the three trials. In a multivariate model, factors associated with significantly poorer survival were visceral-dominant disease, nodal metastases, breast metastases, age younger than 45 years, ER negativity, and not receiving chemotherapy immediately after oophorectomy. This treatment difference was thus not due to imbalances in the prognostic variables used in the model, but it may be due to imbalances of unknown prognostic factors or differences in patient selection. 
3	Discontinuation of antiepileptic drugs in children who have outgrown epilepsy: effects on cognitive function. Cognitive function is frequently impaired in children with epilepsy, compared with age-matched controls. It can be hard to evaluate the significance of various contributory factors. The effects of antiepileptic drugs may be studied in children who have outgrown their epilepsy but are still being treated. A multicenter study to assess various aspects of cognitive function in children with different forms of epilepsy, both during and after treatment with antiepileptic drugs, is currently under way. Definitive results are not yet available; interim analysis of the findings suggests that short-term memory is decreased in all subgroups of children being treated for epilepsy, compared to controls. 
1	Prospective randomized comparison of intravesical with percutaneous bacillus Calmette-Guerin versus intravesical bacillus Calmette-Guerin in superficial bladder cancer. Conflicting reports of the necessity for percutaneous bacillus Calmette-Guerin (BCG) administration with intravesical BCG prompted us to evaluate its benefit in a randomized prospective comparison of intravesical versus intravesical with percutaneous BCG therapy. Intravesical Tice BCG was given in a dose of 50 mg. with or without percutaneous BCG weekly for 6 weeks, at 8, 10 and 12 weeks, at 6 months and every 6 months thereafter. Tumor recurrence was documented in 13 of 30 patients (43%) receiving only intravesical BCG and in 15 of 36 patients (42%) receiving intravesical plus percutaneous BCG. The addition of percutaneous BCG to intravesical therapy did not increase treatment efficacy in this study. 
1	Effect of antileukemia chemotherapy on marrow, blood, and oral granulocyte counts. This study was designed to elicit the effects of antileukemia chemotherapy on marrow production, blood carriage, and oral extravasation of granulocytes, and on the phagocytic activity of those harvested from the mouth. Fifteen adult patients with various morphologic forms of acute leukemia were followed through one to four courses of chemotherapy. Oral saline rinse samples were obtained thrice weekly and prepared for enumeration in a hemocytometer. The oral granulocyte counts were compared with concurrent counts in the bone marrow and peripheral blood. Phagocytic activity of the oral granulocytes was measured by the method of Smith and Rommel. The 15 patients were followed through 30 courses of chemotherapy and recovery. During each, there was a drug-induced decrease in marrow, blood, and oral granulocytes that was reversed when therapy was discontinued and bone marrow activity was restored. Phagocytic activity of the oral granulocytes was not perceptibly affected by the antileukemic drugs. Oral granulocyte counts provide a noninvasive method for monitoring the onset and recovery of chemotherapy-induced myelosuppression and granulocytopenia in patients with leukemia. 
1	The development of neutralizing antibodies in a patient receiving subcutaneous recombinant and natural interleukin-2. Systemic administration of interleukin-2 (IL-2) in humans may induce antibodies specific to IL-2. The case is reported of a patient with metastatic rectal carcinoma who was treated with long-term subcutaneous IL-2 and a combination of subcutaneous IL-2 and interferon-alpha 2b (IFN-alpha 2b). This patient developed nonneutralizing and neutralizing anti-IL-2 antibodies recognizing both the recombinant and natural cytokine. Detectable serum levels of neutralizing antibodies were accompanied by the inhibition of immune responsiveness to systemic IL-2 in vivo. 
2	Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study. Endoscopic, clinical, and laboratory parameters including presence of varices in the gastric fundus, red color sign, diameter and number of variceal columns, platelet count, and the Child status were assessed in 109 patients with cirrhosis and esophageal varices without previous variceal bleeding. During a mean follow-up period of 21 months, the predictive values of these parameters with regard to first bleeding incidence and mortality rate were studied. The incidence of bleeding was 29%, and the mortality rate 46%. Endoscopic criteria (presence of varices in the gastric fundus, presence of the red color sign, and size of the largest varix) as well as alcoholic etiology of cirrhosis showed a significant positive correlation with the bleeding incidence but not with mortality. Contrary to this, two factors of the Child classification (encephalopathy and ascites) and age positively correlated with mortality but not with the bleeding incidence. 
1	Spinal cord hemangioblastoma with subarachnoid hemorrhage. A case of subarachnoid hemorrhage caused by a cervical hemangioblastoma is presented. The clinical picture was indistinguishable from that of a subarachnoid hemorrhage from an intracranial lesion. The diagnosis was established by angiography and water-soluble contrast myelography followed by cervical computed tomographic scan. At surgery, the tumor was completely removed, and no neurological deficit was observed after the operation. 
4	Relationship between blood pressure, plasma insulin and triglyceride concentration, and insulin action in spontaneous hypertensive and Wistar-Kyoto rats. Previous results have shown that spontaneously hypertensive rats (SHR) are insulin resistant, hyperinsulinemic, and hypertriglyceridemic as compared to Wistar-Kyoto rats (WKY). Since SHR rats also have higher blood pressures than WKY rats, the current study was initiated in an attempt to evaluate the relationship between the magnitude of blood pressure and the differences in insulin and lipid metabolism seen in SHR and WKY rats. The experimental variables to be compared were determined in three groups of SHR and WKY rats, varying in age: Group I rats were 6 to 7 weeks of age; Group II rats were 8 to 9 weeks old; whereas Group III rats were 12 to 13 weeks of age. Maximal insulin-stimulated glucose transport by adipocytes isolated from SHR rats was significantly lower (P less than .005) than isolated adipocytes from WKY rats in all three groups, whereas plasma insulin and triglyceride concentrations were significantly higher (P less than .005). Blood pressure was also higher in SHR than in WKY rats within each group. Since absolute values for maximal insulin-stimulated glucose uptake did not change statistically as the rats grew older, the magnitude of the decrease in SHR rats was similar in each group. The increase in plasma insulin and triglyceride concentration observed in SHR rats was also the same in each group, but the absolute values increased with age in both SHR and WKY rats. However, blood pressure rose significantly with age in SHR, but not WKY rats, leading to a progressive increase in the degree of hypertension in SHR rats. These results support the view that hypertension, per se, does not lead to insulin resistance, hyperinsulinemia, and hypertriglyceridemia. 
1	Granulocyte-macrophage colony-stimulating factor synergizes with interleukin-6 in supporting the proliferation of human myeloma cells. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the growth of multiple myeloma (MM) was investigated in 21 patients with MM. In 17 patients with proliferating myeloma cells in vivo, recombinant GM-CSF significantly increased the endogenous-IL-6-mediated spontaneous myeloma cell proliferation occurring in 5-day cultures of tumor cells in vitro (P less than .01). Furthermore, GM-CSF was detected in 5-day culture supernatants of myeloma bone marrow cells. This endogenous GM-CSF was produced by the myeloma bone marrow microenvironment but not by myeloma cells and contributed to the spontaneous myeloma-cell proliferation observed in 5-day cultures. In fact, this proliferation was partially blocked (67%) by anti-GM-CSF monoclonal antibodies. The stimulatory effect of rGM-CSF was mediated through IL-6 because it was abrogated by anti-IL-6 monoclonal antibodies. rGM-CSF did not reproducibly increase the endogenous IL-6 production in short-term cultures of bone marrow cells of MM patients. Using an IL-6-dependent myeloma cell line (XG-1 cell line), rGM-CSF was shown to act directly on myeloma cells stimulating by twofold their IL-6 responsiveness. rGM-CSF did not induce any IL-6 production in XG-1 cells, nor was it able to sustain their growth alone. Although no detectable GM-CSF levels were found in the peripheral or bone marrow blood of MM patients, it is possible that GM-CSF, produced locally by the tumoral environment, enhances the IL-6 responsiveness of myeloma cells in vivo in a way similar to that reported here in vitro. 
5	Recurrence rate after discontinuation of long-term mebendazole therapy in alveolar echinococcosis (preliminary results). The recurrence rate was investigated in 19 patients with non-resectable alveolar echinococcosis after discontinuation of a long-term therapy with mebendazole (average treatment 4.3 years). A control group consisted of 14 patients who underwent radical surgery and finished a course of prophylactic postoperative mebendazole treatment of 2 years. In the controls, no recurrence was observed after a post-therapy period averaging 3.5 years. In contrast, recurrence occurred in 7/19 patients (37%) with non-resectable alveolar echinococcosis an average of 1.6 years after discontinuation of the long-term mebendazole therapy. The absence of clinically detectable recurrence in the remaining 12 patients seems to be due either to spontaneous inactivation of alveolar echinococcosis preceding chemotherapy or too short post-therapy surveillance. The patients with recurrence responded favorably to reintroduction of chemotherapy. The data indicate that mebendazole therapy is parasitostatic rather than parasiticidal. 
5	National survey of the pattern of care for carcinoma of the lung. A national survey of the patterns of care for carcinoma of the lung sponsored by the Commission on Cancer of the American College of Surgeons has documented continuing changes in epidemiology, treatment, and outcome. The project consisted of a long-term study of 15,219 patients whose diagnosis was made in 1981 and a short-term study of 19,074 patients whose diagnosis was made in 1986. The male/female incidence ratios have continued to decrease and the decrease has moved into the older age groups. Although the percentage of adenocarcinoma is increasing at the expense of squamous carcinoma, the latter is still the most prevalent histologic type. The accuracy of percutaneous needle biopsy and transbronchial biopsy of lung nodules reported from this group of 941 hospitals was high and equal to that reported by single institutions. The percentage of patients having a resection did not increase from 1981 to 1986, but for smaller lesions a move was apparent toward more lung-sparing resections. Little change has occurred in the use of adjuvant radiotherapy, particularly in stage III disease, where approximately 50% of the patients received postoperative irradiation. An improvement in the overall 5-year survival when compared with Surveillance, Epidemiology, and End Results data was noted. Whether this is a true improvement in survival or is the result of selection because of an unrecognized change in the pattern of care for patients with a carcinoma of the lung is unknown. 
4	Atrioventricular septal defects. Analysis of short- and medium-term results. Atrioventricular septal defects were repaired in 87 patients from 1981 to 1988. Interventricular communications were present in 73 patients, and major associated anomalies were present in 17 (tetralogy of Fallot in four, double-outlet right ventricle in two, multiple ventricular septal defects in 11). Five deaths occurred in the hospital (5.7%; 70% confidence limits, 3.2% to 9.7%). A preoperative New York Heart Association class V functional condition was the only incremental risk factor (p = 0.02) for death in the hospital. No patient (0%; 70% confidence limits, 0% to 2.15%) had complete heart block. Actuarial survival rate at 80 months was 81.4%. The only incremental risk factor (p = 0.005) leading to reoperation was a preoperative valve incompetence. Actuarial rate at 80 months for freedom from reoperation was 84.2% in the overall group of patients after repair of atrioventricular septal defect. We conclude that an improvement in survival and success rates should be found when a policy of earlier repair is followed. 
5	Chronic rupture of the Achilles tendon: a new technique of repair. A new operative technique is described for the treatment of patients who have a rupture of the Achilles tendon. The large gap between the proximal and distal stumps of the Achilles tendon in seven patients was bridged by use of the tendon of the flexor digitorum longus as the graft. At the most recent follow-up examination (average follow-up, thirty-nine months; range, two to six years), the result was excellent or good in six patients and fair in one. Postoperatively, two patients needed an adjuvant procedure: one, a local rotation flap and the other, a split-thickness skin graft. Both patients had excellent restoration of function. The patient who had a fair result had a persistent limp and residual discomfort. There were no re-ruptures. 
5	Cardiac arrhythmias in critically ill patients: epidemiologic study The general prevalence of cardiac arrhythmias in 2,820 consecutive patients was 78%, ranging from 44% in multiple trauma patients to 90% in primary cardiovascular patients. Patients without recorded arrhythmias (22%, n = 621) were used as control subjects. No clinical group was free from cardiac arrhythmias. Atrial tachyarrhythmias had the highest prevalence in the population as a whole (28%) and in all clinical groups except multiple trauma. Atrial fibrillation was the most common atrial arrhythmia (52%); ventricular arrhythmias followed. Patients with atrial tachyarrhythmias, nodal rhythm ventricular bradyarrhythmias, and ventricular rapid rhythms had significantly (p less than .01) increased mortality rates (40%, 44%, 77%, and 51%, respectively) when compared with patients without arrhythmias (35%). The relative risk of dying (RRD) of these clinical groups was increased by 1.16, 1.27, 2.20, and 1.47, respectively. Patients with cardiorespiratory precipitating disease and any arrhythmia except atrial bradyarrhythmia had a mortality rate between 32% and 74%, significantly (p less than .05) different from that of patients within the same clinical groups without arrhythmias. The RRD was increased by 1.67 to 3.40. Septic patients with atrial tachyarrhythmia or nodal rhythm and neurologic patients with nodal or ventricular arrhythmias also had significantly (p less than .01 and .05, respectively) increased mortality and were at higher RRD (1.53 to 2.81). Our data suggest that severe illness may be present in some clinical groups of critically ill patients with cardiac arrhythmias. 
5	Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts. Changes in hemodynamic load cause alterations in cardiac myocyte size, with regional variations in myocyte size distribution possible within the ventricular wall. We studied regional changes in cellular dimensions and their distribution in two models of cardiac hypertrophy and in cardiac atrophy in the rat. Combined volume-pressure overload was produced by 3,3',5-triiodo-L-thyronine (T3) treatment; atrophy was produced by heterotopic isotransplantation. Our previous data from long-term pressure overload after aortic constriction were used for comparison. Isolated ventricular myocytes were obtained after in vitro coronary perfusion with collagenase. Cell volume and its distribution were determined; cell length was directly measured by image analysis, and cross-sectional area was estimated from the cell volume/cell length ratio, assuming a cylindrical model. Myocyte hypertrophy resulting from hyperthyroidism and aortic constriction was primarily due to increased cross-sectional area. In both cases, the relative response was greater in the right ventricle than in the left ventricle. Within the left ventricle, epimyocardial myocytes enlarged the most. Aortic constriction and T3 treatment predominantly increased the size of smaller myocytes. Heterogeneity in myocyte size increased after constriction but remained relatively unaffected after T3 treatment. Atrophy of left ventricular myocytes was due to a proportional decrease in cell length and cross-sectional area, with the greatest decrease in the left ventricular endomyocardium. Atrophy predominantly affected larger myocytes, resulting in a more homogeneous overall population of smaller myocytes. We conclude that various alterations in load lead to diverse remodeling in the myocyte population throughout the ventricular wall. In general, smaller myocytes show the highest growth potential, whereas larger myocytes exhibit the highest potential to atrophy. 
3	A critical appraisal of mitogen-induced lymphocyte proliferation in depressed patients. OBJECTIVE: The authors' goal was to evaluate the utility of mitogen-induced lymphocyte proliferation assays in clinical research in psychoimmunology. METHOD: They examined 23 depressed patients and 23 matched comparison subjects with this assay. There were no significant differences between these groups. They then combined the results of this study with the results of their previous study of 20 depressed patients and 20 comparison subjects to examine possible determinants of lymphocyte proliferation in depression. RESULTS: Depressed patients with lower proliferative responses than their matched comparison subjects had lower depression subscale, anergia subscale, and total scores on the Brief Psychiatric Rating Scale than did patients with higher proliferative responses than their matched comparison subjects. This finding was unexpected and unexplained. Depressed patients with lower proliferative responses than their matched comparison subjects also had fewer obsessions and compulsions and less psychomotor agitation according to the Schedule for Affective Disorders and Schizophrenia interview than did patients with higher proliferative responses than their matched comparison subjects. Stepwise discriminant analysis and cluster analysis contributed little further understanding of the determinants of in vitro lymphocyte proliferation of cells from depressed patients. CONCLUSIONS: Longitudinal studies using multiple serial determinations of mitogen-induced lymphocyte proliferation are the minimal design needed to make this assay useful in further evaluating any immune system changes in depression. 
2	Infectious diarrhea. Managing a misery that is still worldwide. Infectious diarrhea is the largest single cause of morbidity and mortality in the world. Bacteria, viruses, and protozoan parasites are the most common causative agents. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Antimicrobial therapy is reserved for very ill patients only. With the exception of Cryptosporidium, for which no effective agent is yet available, all protozoan infections are treatable with metronidazole. 
4	Temporal relation between left ventricular dysfunction and chest pain in coronary artery disease during activities of daily living. Forty-three ambulatory patients with angina of increasing frequency underwent continuous monitoring of left ventricular (LV) function for an average of 2.9 +/- 1.9 hours to determine the incidence and temporal sequence of LV dysfunction, ST-segment depression and chest pain. Indicators of ischemia were: a decrease in ejection fraction greater than 5% lasting greater than 1 minute; horizontal or downsloping ST-segment depression of greater than or equal to 1 mm; or onset of the patient's typical chest pain complex, or a combination of these. During the monitoring interval, subjects performed daily activities such as sitting, walking, climbing stairs and eating. In 11 patients, 22 episodes of chest pain or ST-segment depression, or both, were observed. Eighteen episodes were accompanied by a decrease in ejection fraction (9 patients); chest pain accompanied the decrease in ejection fraction during 13 episodes, whereas ST-segment changes occurred during 7. In 12 of 13 episodes the decrease in ejection fraction began earlier than the onset of chest pain, whereas in 1 patient ejection fraction decrease and chest pain onset started at the same time. The average interval from a decrease in ejection fraction to the onset of chest pain was 56 +/- 41 seconds (range 0 to 120). ST changes occurred after the onset of a decrease in ejection fraction in 6 of 7 episodes. The average interval from the onset of ejection fraction decrease and the onset of ST change was 99 +/- 91 seconds. These data suggest that LV dysfunction manifested by a decrease in ejection fraction is an earlier indicator of myocardial ischemia than is angina pectoris or electrocardiographic evidence of ischemia. 
4	Echocardiographic measurement of left ventricular mass and volume in normotensive and hypertensive rats. Necropsy validation. Although rats are commonly used to study left ventricular (LV) hypertrophy, measurement of LV mass and dimensions has required killing the rat. To determine the accuracy of echocardiography in rats, blinded crossectional area (CSA) and LV mass measurements using either the cube function (LVM) or an elliptical model (LVMel) from high resolution M-mode echocardiograms were compared to necropsy LV weight (0.28 to 1.5 g), in 41 normotensive (body weight 116 to 762 g) and 17 hypertensive rats (350 to 560 g). Postmortem chamber volumes in 28 normal rats (0.02 to 0.19 mL) were also compared to echocardiographic volumes derived from the elliptical model. Correlation with LV weight was r = 0.87 for LVM, 0.90 for CSA and 0.93 for LVMel (all P less than .00001). Comparison of hypertensive and body-weight-matched normotensive rats revealed the upper normal limit for both LVMel and CSA to have 89% sensitivity and 100% specificity for detection of post mortem LV hypertrophy. Necropsy LV volumes were more closely related to systolic echocardiographic volumes than to diastolic volumes (r = 0.78 v 0.71, both P less than .00001), compatible with the effects of post mortem contracture. Stroke volume determined invasively in 5 Wistar rats by thermodilution was similar to that obtained using elliptical model echo volumes in 5 rats of the same body size (0.35 +/- 0.05 v 0.30 +/- 0.06 mL/beat). Echocardiography can be used to evaluate LV structure and function in rats and to detect in vivo LV anatomic differences induced by hypertension. 
4	Screening for total cholesterol. Do the National Cholesterol Education Program's recommendations detect individuals at high risk of coronary heart disease? BACKGROUND. The National Cholesterol Education Program (NCEP) has provided guidelines for identification of persons at high risk of coronary heart disease (CHD) because of lipid abnormalities. These recommendations are based on total cholesterol as the initial screening tool and have become the stimulus for clinic- and community-based screening programs nationwide. However, the use of the guidelines may be problematic because individuals may have total cholesterol levels in the desirable range but low density lipoprotein (LDL) or high density lipoprotein (HDL) levels considered at high risk. This study evaluates the ability of the NCEP screening recommendations to identify correctly persons at high risk of CHD because of lipid abnormalities. METHODS AND RESULTS. Using the NCEP guidelines, we simulated a population-based screening program with data from visits 1 and 2 of the Lipid Research Clinics Program Prevalence Study. Individuals were considered to be at high risk of CHD if they had LDL levels greater than 160 mg/dl or HDL levels less than 35 mg/dl. Following the NCEP process, 21% of those with high LDL concentrations and 66% of those with low HDL concentrations would not be routinely referred for immediate treatment. Overall, 41% of those at high risk of CHD would not be promptly evaluated. The sensitivity of the guidelines for promptly identifying individuals with lipoprotein abnormalities is 59%. CONCLUSIONS. This relatively low sensitivity of total cholesterol as a screening tool should be the impetus for rethinking the screening guidelines. Specifically, the cost-benefit ratio of routine screening for lipoproteins, particularly HDL cholesterol, needs to be carefully considered. 
1	The Merkel cell and associated neoplasms in the eyelids and periocular region. Merkel cells are clear oval cells in the epidermis and outer root sheaths of hair follicles, which are probably of epithelial origin, share ultrastructural features with neuroendocrine cells, and are found in association with touch receptors. In the eyelid, they occur singly in the epidermis and external root sheaths of hairs and eyelashes, and in specialized touch spots alternating with eyelashes. Their typical electron microscopical and antigenic features include dense-core granules, intranuclear rodlets, spinous processes, and a positive reaction for specific cytokeratins, epithelial membrane antigen, neuron-specific enolase, chromogranin and synaptophysin. Merkel cell carcinoma probably develops from precursor cells which give rise to keratinocytes and Merkel cells, and nearly one out of ten Merkel cell carcinomas occur in the eyelid and periocular region. They tend to be bulging lesions near the lid margin of elderly patients, reddish in color, and erythematous with telangiectatic vessels. The diagnosis is based on the frequent presence of neurofilaments and paranuclear aggregates of intermediate filaments in addition to features typical of normal Merkel cells. The tumor often mimics lymphoma or undifferentiated carcinoma and frequently invades lymphatic vessels. One third of Merkel cell carcinomas recur, almost two thirds give rise to regional node metastases, and up to one half metastasize widely and result in death. Initial treatment should be prompt and aggressive, with wide resection and routine postoperative irradiation. Although metastatic lesions often respond to radiation therapy and cytostatic drugs, these treatments are mainly of palliative value. 
1	Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Regulation of insulin secretion involves the coordinated control of ion channels in the beta-cell membrane. We have isolated and characterized cDNA and genomic clones encoding a voltage-dependent K+ channel isoform expressed in human islets and in a human insulinoma. This K+ channel isoform, designated hPCN1, with a deduced amino acid sequence of 613 residues (Mr = 67,097), is related to the Shaker family of Drosophila K+ channels. hPCN1 is homologous to two other human K+ channel isoforms we have isolated, hPCN2 and hPCN3, with 55% and 65% amino acid sequence identity, respectively. The electrophysiological characteristics of hPCN1 were determined after microinjection of synthetic RNA into Xenopus oocytes. Two-microelectrode voltage-clamp recordings of oocytes injected with hPCN1 RNA revealed a voltage-dependent outward K+ current that inactivated slowly with time. Outward currents were inhibited by 4-aminopyridine with a Ki less than 0.10 mM and were relatively insensitive to tetraethylammonium ion or Ba2+. A delayed rectifier K+ channel such as hPCN1 could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion. 
1	A T-cell neoplasia showing clinicopathologic features of malignant histiocytosis with novel chromosomal abnormalities and N-ras mutation. Malignant histiocytosis (MH) is a distinct disease entity defined clinically and morphologically. However, the neoplastic origin of MH is not well established. The authors report a 26-year-old woman who showed the typical clinicopathologic features of so-called MH. Cytogenetic and molecular genetic examinations were performed in addition to the morphologic and immunologic approach. The expression of CD2 and T-cell receptor gene rearrangements indicated the T-cell origin of this case. CD30, which is positive for anaplastic large cell lymphoma (Ki-1 lymphoma), was not expressed. The cytogenetic study revealed a clonal chromosome abnormality involving 3q25, 6p21, 11p15, and 11q21. An N-ras point mutation within codon 12 (GGT----GCT) was also detected. These finding indicate that MH defined clinically and morphologically is not a tumor of true histiocytic origin and that it should be reclassified on the basis of immunologic, cytogenetic, and molecular genetic data. 
1	Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis. Recently the formation of bile acid glucosides has been described as a novel conjugation mechanism in vitro and in vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 +/- 0.03 mumol/24 hr (mean +/- S.E.M.)-in the range of bile acid glucuronide excretion (0.41 +/- 0.06 mumol/24 hr; mean +/- S.E.M.). A gas chromatography-mass spectrometry-characterized trihydroxy bile acid glucoside of still-unknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 +/- 0.13 mumol/24 hr (mean +/- SEM), yet significantly lower than bile acid glucuronide excretion (1.53 +/- 0.13 mumol/24 hr; mean +/- SEM; p less than 0.001). In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation. The data establish the composition and quantity of urinary bile acid glucosides in healthy controls and cholestasis and constitute a quantitative comparison with another glycosidic conjugation reaction, bile acid glucuronidation. 
4	Immunoreactivity of anti-streptococcal monoclonal antibodies to human heart valves. Evidence for multiple cross-reactive epitopes. Association of group A streptococci with acute rheumatic fever and valvular heart disease is well established; however the basis of valve injury remains unclear. In this study, anti-streptococcal monoclonal antibodies (MAbs) cross-reactive with myocardium were reacted with sections from 22 rheumatic valves, nine normal, five endocarditic, one 'floppy,' and one Marfan valve. In immunohistochemical studies, MAb reactivity was observed with cardiac myocytes, smooth muscle cells, cell surface and cytoplasm of endothelial cells lining valves, and valvular interstitial cells. Endothelial basement membrane and elastin fibrils reacted with the MAbs, whereas collagen was unreactive. Similar reactivity was seen with sera from acute rheumatic fever patients. The anti-streptococcal MAbs reacted with intravalvular myosin and vimentin in Western blots, and purified elastin competitively inhibited the binding of the anti-streptococcal MAbs to whole group A streptococci. The data show that human heart valves have numerous sites of immunoreactivity with anti-streptococcal MAbs and acute rheumatic fever sera of potential importance in the pathogenesis of rheumatic valvular injury. 
1	Microcystic adnexal carcinoma following radiotherapy in childhood. A 36-year-old man was treated by radiotherapy for tinea capitis many years before discovery of microcystic adnexal carcinoma (MAC). Because of patient's refusal of any surgical intervention, we were able to follow the natural course of this tumor for 13 years. This case emphasizes the typical slow development of (MAC). The implication of the association of MAC and radiotherapy are discussed. 
5	Immunohistochemical interpretation of early epithelial disorders of pyriform sinus. Expression of cytokeratins (CKs) was investigated immunohistochemically by use of monospecific monoclonal anti-CK antibodies in normal epithelia of pyriform sinus and epithelial lesions such as simple hyperplasia, different degrees of dysplasia, in situ carcinoma, and invasive carcinoma. In normal epithelium, strong expression of CK-19 was consistently observed only in the basal layer as basic CK, while expression of CK-13 showed a completely reverse pattern, being expressed only in suprabasal layers as stratification-related CK. Characteristic changes in expression pattern of these two CKs were observed in accordance with the degree of epithelial disorders and differentiation of carcinoma. Cytokeratin 1, as keratinization-associated CK, was observed only in keratinized cells of hyperplastic epithelia and well-differentiated carcinomas. These findings may be useful in evaluating epithelial disorders and classifying carcinomas more objectively, and may assist earlier detection of carcinoma when used with standard histologic techniques. 
4	Relation between lipids and atherosclerosis: epidemiologic evidence and clinical implications. Coronary artery disease (CAD) is the leading cause of death in most developed countries. Therefore, elucidation of risk factors and associated mechanisms for CAD has been a high priority. Data from the Framingham Heart Study and other large-scale epidemiologic studies have identified major risk factors associated with CAD, demonstrating the adverse effects of increased total and low-density lipoprotein cholesterol levels and the protective effect of high-density lipoprotein cholesterol. Other more recent investigations, including the Lipid Research Clinics Trial and the Helsinki Heart Study, have shown that lowering total cholesterol and raising high-density lipoprotein cholesterol significantly reduce the risk for CAD. Because hypertension is also a significant risk factor for CAD, the assumption has been that blood pressure reduction should offer significant benefits in terms of CAD risk. However, despite their antihypertensive efficacy, diuretics and beta blockers have failed to significantly reduce CAD morbidity or mortality. The adverse effects of these antihypertensive agents on lipid profiles, glucose metabolism and other metabolic parameters may account for their disappointing performance in reducing CAD morbidity and mortality. As a result, newer agents such as angiotensin-converting enzyme inhibitors and calcium antagonists that appear to be free of such adverse effects have garnered considerable attention for their potential to reduce CAD risk. 
3	Why are autism and the fragile-X syndrome associated? Conceptual and methodological issues. Investigations of the association between autism and the fragile-X syndrome have yielded conflicting results with some studies indicating a strong correlation and others indicating no relation between the disorders. In this paper, we review the relevant research on this controversy and discuss the conceptual and methodological problems involved in such an inquiry. We conclude that autism and fragile X are associated and that this relation will prove fruitful in understanding the role of the X chromosome in a variety of behavior disorders and in unraveling various theoretical accounts on the etiology of autism. 
4	High-risk reparative surgery. A neglected alternative to heart transplantation. The selection of patients for either high-risk reparative operations on the heart or for transplantation has become increasingly difficult as a result of improved results with both modalities. A retrospective review was done of patients referred for heart transplantation who were not considered candidates for conventional cardiac surgery, yet instead underwent reparative procedures rather than transplantation. Of 23 adult patients referred during a 7-year period, 18 had coronary artery disease, and five had valvular heart disease. All had New York Heart Association class IV symptoms. Preoperative left ventricular ejection fractions were in the range 0.08-0.63 (mean, 0.28). Ten of 18 patients with coronary artery disease required insertion of an intra-aortic balloon pump for hemodynamic support perioperatively. Seven patients had primary coronary artery bypass grafts, and 10 had reoperative coronary bypass procedures. One patient had a left ventricular aneurysmectomy, and one had endocardial stripping in addition to myocardial revascularization procedures. Of the patients with valvular disease, three had aortic valve replacement, of which two were reoperations, and two others had mitral valve replacements with tricuspid annuloplasties. With a mean follow-up of 25 months, 1-, 3-, 12-, and 24-month actuarial survival rates were 91%, 87%, 82%, and 76%, respectively. One patient who underwent aortic valve replacement in this study successfully received heart transplantation 19 months postoperatively. These results compare favorably with the current results for patients undergoing first-graft heart transplantation. All survivors enjoy New York Heart Association class I or II functional capacity. 
3	Haemorrhagic shock encephalopathy and sudden infant death In 2 pairs of non-identical twins, haemorrhagic-shock encephalopathy syndrome developed in 1 co-twin while the other died of sudden infant death syndrome. The twin pairs were aged 3 and 4 months, respectively, and no cause was identified. We suggest that stress protein deficiency may underlie both syndromes. 
3	Developmental dysmnesia in a poor reader. A 22-yr-old subject with moderate developmental dyslexia experienced poor memory from an early age. In spite of normal intelligence he had great difficulty in learning historical and geographical names, mathematical formulae, poems and songs, and verbal series such as the letters of the alphabet and the months of the year. His recognition of familiar faces was also faulty at times. A battery of memory tests confirmed a moderate deficit of verbal as well as visual memory, whereas spatial memory was preserved. Other cognitive functions were intact, except for a mild reading disability. No evidence of brain pathology was provided by his history, neurological examination and CT scanning. 
5	A three-year retrospective study of synovectomies in children. The aim of this study was to evaluate the results of synovectomies in children with juvenile arthritis. Five hundred twenty-eight synovectomies and tenosynovectomies were performed over a period of 13 years. The patients were followed for one, two, three, five, and ten years postoperatively. The evaluation after three years was chosen as the basis for this article. One hundred twenty-five children with arthritis who were not evaluated three years postoperatively had less severe arthritis, both locally and generally, than the evaluated group of 389. The rate for good results and tolerability was high at one, two, and three years postoperatively but decreased with time; more patients went from good results to poor rather than vice versa. Global assessment, soft-tissue swelling, and limitation of movement seemed to be the best parameters for evaluating the results of synovectomies. It appears necessary to wait at least three years to evaluate the long-term effect of synovectomies. 
4	Unsuspected mitral stenosis. PURPOSE AND PATIENTS AND METHODS: We observed a series of patients in whom the diagnosis of mitral stenosis was first discovered in the echocardiography laboratory. Because of this experience, we examined the records of 152 patients with echocardiographic evidence of rheumatic mitral stenosis to determine the clinical characteristics and course of patients with unsuspected mitral stenosis as well as those factors that may have obscured the diagnosis. RESULTS: Of these 152 patients, 18 had mitral stenosis that was unsuspected clinically until the echocardiogram. These patients were elderly, with a median age of 72 years. They were all referred for echocardiography because of cardiac symptoms. Eight patients were referred for evaluation of congestive heart failure. Five patients were referred for evaluation of aortic valve disease. Three patients were referred because of cerebrovascular accidents and atrial fibrillation. The Doppler-determined mean diastolic mitral gradient ranged from 4 to 15 mm Hg (mean: 7 mm Hg). Mitral stenosis ranged in severity from trivial to very severe. Eight patients had moderate to severe mitral stenosis with estimated mitral valve areas less than or equal to 1.5 cm2. Seven had mild or trivial mitral stenosis with estimated mitral valve areas greater than 1.5 cm2. After further evaluation, two patients underwent mitral valve surgery with improvement of congestive failure. In three patients, warfarin therapy was begun to prevent emboli. Thus, five of 18 patients had a significant immediate change in therapy because of the discovery of mitral stenosis. CONCLUSION: The diagnosis of mitral stenosis may not be suspected in the presence of advanced age, other serious cardiac and medical conditions, or mechanical factors that complicate the physical examination. In these patients, mitral stenosis may be hemodynamically significant and may cause significant symptoms. 
3	Central nervous system bioaminergic responses to mechanical trauma. An experimental study. Changes in biogenic amines in the brain and spinal cord following penetrating injury were studied in male Wistar rats using high-performance liquid chromatography with electrochemical detection. Rapid increase in hemispheric concentration of these substances was noted beginning shortly after trauma. This trend continued until they were about three to four times control levels by about 24 to 48 hours postinjury. In the spinal cord, however, there was an initial sharp reduction in regional concentrations 2 hours postinjury followed by a slow rise thereafter. By 48 hours postinjury, levels of norepinephrine, dopamine, and serotonin of the cords of injured animals were still less than those of nontraumatized controls. This variation in the central nervous system bioaminergic response with the level of injury raises questions as to its precise role in neurological damage following mechanical insult. 
5	Alteration of platelet serotonin in patients with chronic tension-type headache during cold pressor test. Change of 5-hydroxytryptamine (5-HT) concentrations in platelets from patients with chronic tension-type headache (TH) and controls were observed during cold pressor test (CPT). Before cold stimulation, 5-HT concentrations in platelets from patients with TH were significantly lower than those found in controls. One minute after the start of cold stimulation, 5-HT levels in platelets from patients with TH were significantly much lower than in the controls, as control levels rose and TH levels fell. The results show that, under stress, the absorbance of 5-HT into the platelets in patients with TH is reduced. It is suggested that, in patients with TH, there are abnormalities of 5-HT uptake into platelets and factors which cause release of 5-HT from platelets. 
5	Treatment of anorectal abscess with or without primary fistulectomy. Results of a prospective randomized trial. To determine whether primary fistulectomy should be performed or not at the time of incision and drainage, a prospective, randomized study in 70 patients with anorectal abscess was conducted. Thirty-six patients underwent incision, drainage and fistulectomy with primary partial internal spincterectomy (group I), whereas in 34 patients anorectal abscess was treated by incision and drainage alone (group II). After a median follow-up of 42.5 months, the combined recurrence or persistence rate was 2.9 percent in group I and 40.6 percent in group II (P less than 0.0003, log-rank test). Recurrent abscesses or persistent fistulas were treated by secondary partial internal sphincterectomy. Comparing anal continence before and 1 year after definite treatment, we found increased anal function disturbances in 39.4 percent of the patients in group I and in 21.4 percent of the patients in group II (P less than 0.106, Fisher-exact test). The combined recurrence or persistence rate of 40.6 percent indicates that more than half of the patients with anorectal abscess will have no further problems after simple incision and drainage. This finding, as well as the increased anal function disturbances after partial internal sphincterectomy (either primary or secondary) are the main reasons to reserve fistulectomy as a second stage procedure if necessary. 
2	Artificial urinary sphincters around intestinal segments--are they safe? Artificial urinary sphincters (AUS) were implanted around intestinal segments to achieve urinary continence in 8 patients and faecal continence in 1. In 6 patients the cuff was placed around the lower end of the cystoplasty following bladder neck (5) or urethral (1) erosion. Four are completely dry, 1 on self-intermittent catheterisation (SIC). One has mild stress incontinence. In 1 patient the cuff eroded at 8 months. Two patients had cuffs implanted parastomally to create continent diversion. One is satisfactory on SIC and the other had her AUS explanted because of life-threatening metabolic acidosis. The rectal cuff was explanted because of faecal impaction above the cuff. As an absolute last resort, placing an AUS round a cystoplasty appears little more hazardous than round bladder neck. The use of the AUS for continent diversion has not been pursued because of reliable techniques of non-prosthetic continent diversion. The current model of the AUS is unsuitable for the treatment of faecal incontinence. 
4	Components of delay time in suspected acute myocardial infarction with particular emphasis on patient delay. Two hundred and thirty-four patients admitted to a coronary care unit (CCU) were interviewed a few days after arrival in hospital to determine reasons for patient delay and the various components of total delay time from onset of symptoms to arrival in CCU. Of the three major components of delay, decision time (time from onset of symptoms to decision to go to hospital), and hospital procedure time (time from arrival in hospital to arrival in the CCU), were of the same magnitude, 1 h 15 min and 1 h 30 min (median), whereas the median time for preparation and transportation to hospital was somewhat shorter, being 45 min. Decision time appeared to be similar in patients with confirmed and non-confirmed acute myocardial infarction (AMI) and was not associated with intensity of pain or infarct size. Half of the patients hesitated to go to hospital, which resulted in a prolonged decision delay (3 h). It is concluded that patient indecision to seek medical help is the most important reason for delay in hospital arrival in patients with suspected AMI. 
4	Experimental and clinical percutaneous angioscopy experience with dynamic angioplasty. The authors have used ultrathin angioscopes with high optical resolution to assess the effects of dynamic angioplasty in vitro and in vivo. Experimentally, angioscopy was used to study the effects of the 5F "Kensey" catheter in "normal" porcine coronary arteries (NPCA) and postmortem human coronary arteries (PMHCA). In NPCA, the catheter keeps a coaxial position. Intimal flaps (IFs) were seen in 21/23 NPCAs. They occurred with all cam rotation speeds and were usually single and small (less than 25% of lumen). Perforations in patent arteries were rare (1/23). However, when the catheter was forced against the wall by passing through a narrowing of 5F diameter (made by a band ligature), perforations were more common at higher cam speeds. The epicardium remained intact in two thirds of perforations. Angioscopy visualized perforations in only 10% of cases (1/10), the common sign being that of large and multiple intimal flaps, which were often obstructive (5/10). In PMHCAs, angioscopy was more sensitive than angiography in detecting atheromatous lesions. The authors were able to give a better assessment of the effect of dynamic angioplasty on treated lesions, including the demonstration of intimal flaps that were not visible on angiography. In vivo, they have performed percutaneous angioscopy before and after dynamic angioplasty using 8 French Kensey catheters. Angioscopy revealed features that were not shown angiographically. 
3	Tamoxifen therapy for painful idiopathic gynecomastia. We have evaluated the efficacy of the antiestrogen tamoxifen in six men with painful idiopathic gynecomastia. Subjects were given either tamoxifen or placebo for 2 to 4 months and then were given the other agent for an identical period. Breast size was considered to have been reduced only if it had decreased by one or more Marshall-Tanner stages during the treatment period. Pain reduction with tamoxifen therapy was statistically significant for the group, occurring in five of six subjects during tamoxifen treatment and in only one of six during the placebo period. Size reduction with tamoxifen was only marginally significant for the entire group, but occurred in all three subjects who were initially in Marshall-Tanner stage III and in none of the three subjects who were initially in stage V. During tamoxifen treatment, there was a significant increase in the serum levels of luteinizing hormone and total estradiol and a marginally significant increment in the total testosterone level. 
3	Sleep disturbances in survivors of the Nazi Holocaust. OBJECTIVE AND METHOD: Sleep disturbances are commonly reported by victims of extraordinary stress and can persist for decades. This study was designed to test the hypothesis that survivors of the Nazi Holocaust would have significantly more and different sleep problems than depressed and healthy comparison subjects and that the severity of the survivors' problems would be correlated with length of time spent in a concentration camp. Forty-two survivors, 37 depressed patients, and 54 healthy subjects of about the same age, all living in the community, described their sleep patterns over the preceding month on the Pittsburgh Sleep Quality Index, a self-rating instrument that inquires about quality, latency, duration, efficiency, and disturbances of sleep, use of sleep medication, and daytime dysfunction. RESULTS: The survivors had significantly greater sleep impairment than the healthy comparison subjects, as measured by all subscales of the index, but had less impairment than the depressed patients except on the sleep disturbances and daytime dysfunction subscales. However, for specific items within these subscales, survivors had significantly more frequent awakenings due to bad dreams and had less loss of enthusiasm than the depressed subjects. Sleep disturbances and frequency of nightmares were significantly and positively correlated with the duration of the survivors' internment in concentration camps. CONCLUSIONS: These findings suggest that for some Holocaust survivors, impaired sleep and frequent nightmares are considerable problems even 45 years after liberation. 
1	Preferential localization of human adherent lymphokine-activated killer cells in tumor microcirculation. The efficacy of adoptive immunotherapy for solid tumors with lymphokine-activated effector cells presumably depends on the ability of these cells to localize adequately in tumor tissues. We present here the first quantitative study of the in vivo movement of fluorescently labeled adherent lymphokine-activated killer (A-LAK) cells. These cells were injected intra-arterially along with low-dose interleukin-2 into normal (mature granulation) tissue and an implant of VX2 carcinoma grown in the rabbit ear chamber. A small proportion of A-LAK cells accumulated preferentially in the tumor microcirculation in vivo because of an increased frequency of long-term adhesive interactions with the tumor vasculature. Stasis of blood flow in the tumor vasculature was observed 1 to 2 days after injection. Subsequent necrosis of the tumors was observed, along with diffuse infiltrates of lymphocytes, monocytes, and granulocytes in the interstitial space within the tumor. Development of necrosis despite low ratios of effector cells to target cells suggests that in addition to direct cytotoxicity, the response to adoptive immunotherapy is mediated via the tumor vasculature. This novel mechanism for adoptive immunotherapy must be taken into account in the development of improved strategies for cancer treatment. 
3	Higher incidence of carpal tunnel syndrome in oophorectomized women. To determine whether the hormonal changes of the menopause are related to the onset of carpal tunnel syndrome (CTS), 53 healthy women, younger than 44 years, and subjected to bilateral oophorectomy between 1 and 4 years before the study, were evaluated. Seventy healthy menstruating women matched for age were used as controls. In those complaining of symptoms and presenting signs suggestive of CTS, sensory and motor nerve conduction studies were done. In the oophorectomized group, 17 of 53 (32%) had clinical CTS, while only seven of 70 of the control group (10%) did so (relative risk for the oophorectomized group = 4.25; 95% confidence intervals 1.47 and 12.61). The nerve conduction studies were abnormal in 14 of 16 oophorectomized women (87.5%), and in only one of seven of the control group (14.2%; P less than 0.002). Symptoms tended to be milder in the controls. Symptoms developed in the first year after oophorectomy in 14 of the 17 women with CTS. This suggests that women develop CTS after oophorectomy more frequently than controls. 
2	The emergence of hepatitis B as a sexually transmitted disease. In the United States, approximately 300,000 cases of hepatitis B virus infection occur annually, and heterosexual activity is one of the most commonly reported risk factors for acquiring disease. Until the number of infections transmitted through heterosexual contact can be reduced through hepatitis B vaccination, there is little chance of controlling this infection. 
4	Transient ischaemic attacks in young patients: a thromboembolic or migrainous manifestation? A 10 year follow up study of 46 patients. Forty six patients aged 18-39 years with transient ischaemic attacks (TIA) were studied; two thirds were women. Twenty five patients had attacks accompanied by headache, and seven gave a history of common migraine. Only four of 27 angiograms were abnormal; no operable carotid lesion was demonstrated. Over a mean follow up period of 10 years stroke or myocardial infarction (AMI) occurred in all four patients who presented major cerebrovascular risk factors, but in only two of the remaining 42 patients. Thus irrespective of age thromboembolic TIA is a harbinger of stroke or AMI. However, most TIAs under the age of 40 years are caused by a non-embolic benign vascular disorder. The clinical characteristics, long-term prognosis, and possible pathogenesis, for such attacks are often indistinguishable from those of classical migraine. In the absence of cardiovascular risk factors, arteriography does not provide much diagnostic and prognostic information. 
3	Hospitalization and the cognitive deficits of schizophrenia. The influences of age and education. The study investigated the relationship between length of hospitalization and increasing cognitive deficit in schizophrenics. Using Halstead-Reitan Battery data obtained from 245 schizophrenic patients, multiple regression analyses were performed using age, education, and length of hospitalization as independent variables and various summary test indices as dependent variables. These analyses showed that there was not a statistically significant change in percentage of explained variance when length of hospitalization was entered into the multiple regression equations. On the basis of these analyses, it was concluded that the association between increasing deficit and length of hospitalization experienced by schizophrenic patients is no greater than what would be anticipated on the basis of aging. 
3	Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. We compared T-cell proliferative responses to acetylcholine receptor (AChR) and to purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, and blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus cells gave significantly higher and more consistent responses to AChR than parallel cultures of autologous blood cells, whereas responses to PPD showed an opposite trend. Thus there was a preferential localization of AChR-reactive T cells in the hyperplastic MG thymus. Furthermore, there was a strong correlation between blood and thymus cell responses to PPD (but not to AChR), arguing that the hyperplastic MG thymus contains a sample of sensitized peripheral T cells. By contrast, both AChR- and PPD-responsive T cells were almost undetectable in thymus from nonmyasthenic patients, which is evidently much less receptive to circulating T cells. Cells from MG thymomas showed the highest stimulations by AChR but did not consistently react to PPD. However, the uninvolved thymus adjacent to these thymomas behaved almost identically to the hyperplastic samples described above. Our interpretation is that AChR-specific T cells are initially sensitized in the MG thymoma but are selectively trapped in the hyperplastic thymus after being primed elsewhere. 
1	Complications of the pectoralis major myocutaneous flap in head and neck reconstruction. A retrospective review of the complications in 211 patients undergoing pectoralis major myocutaneous flap reconstruction is presented. The flap was used for mucosal lining of the oral cavity or oropharynx in 109 patients, for pharyngoesophageal reconstruction in 44, for skin coverage in 47, and for other locations in 14 patients. Flap-related complications developed in 63% of the patients. These included flap necrosis, suture line dehiscence, fistula formation, infection, and hematoma. Analysis of risk factors for the development of flap complications showed the following factors to be significant: age over 70; female gender; nomographic overweight; albumin less than 4 g/dL; use of the flap in reconstruction of the oral cavity after major glossectomy; and presence of other systemic diseases. The median length of hospitalization for those developing complications was 33 days compared with 16 days for those who did not develop any complications. Thirty-five (26%) of the 135 patients developing complications required reoperation and only 2 among these required a second flap. Similarly, only 13 of the 61 patients who developed fistulas required surgical closure. 
2	Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study. It is now generally accepted that Campylobacter pylori is closely associated with peptic ulcer disease and chronic type B gastritis. Whether C. pylori is the direct etiologic cause of either or both of these illnesses remains unclear. Possible pathophysiologic effects of C. pylori are still a matter of debate and conjecture. Utilizing a small group of patients with gastric ulcers and chronic gastritis, we examined the ultrastructural relationship between C. pylori and gastric cells. Forty-eight percent of our gastric ulcer patients and 57% of our chronic gastritis patients had C. pylori in their lower corpus mucosa. Examination with the transmission electron microscope indicated a very close proximation by C. pylori to the surface epithelial cells strongly suggesting adherence. We also describe for the first time the invasion of gastric cells by C. pylori. Although an uncommon occurrence, we had repeated observations of C. pylori invading surface epithelial cells, parietal cells, and chief cells. Most of the intracellular C. pylori were intact but other forms appearing to be degenerating organisms were also seen. We suggest that cell invasion may be one mechanism by which C. pylori causes pathologic changes in the gastric mucosa. These observations may also explain why C. pylori chronically infects gastric cells and frequently recurs after treatment. 
4	Silicone pouch for protection of automatic implantable cardioverter-defibrillator leads. Automatic implantable cardioverter-defibrillator has become routine treatment for recurrent, drug-resistant ventricular tachycardia. Although there is documentation regarding clinical experience and device performance, there is little information on how to avoid complications related to the retrieval of sensing and defibrillation leads from the subcutaneous space. We are reporting our experience with a silicone pouch for protection of automatic implantable cardioverter-defibrillator leads that allows immediate and simple retrieval of the leads in case an automatic implantable cardioverter-defibrillator generator is needed. 
4	Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease. Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse. 
4	Severe mitral insufficiency post-balloon valvuloplasty: the late changes found in a disrupted mitral valve. The case of a 45-yr-old woman who had balloon valvuloplasty for rheumatic mitral stenosis is presented. An anterior mitral leaflet tear occurred as a complication of the procedure. Both partial healing of the anterior mitral leaflet and gradual dilatation of the left atrium occurred which allowed the damaged valve to remain in situ for several months. Some of the late changes which occur after such a complicated valvuloplasty are illustrated here, as this patient eventually required surgery and valve excision for definitive repair. 
1	Hereditary ovarian cancer. Heterogeneity in age at diagnosis. An unknown fraction of the ovarian cancer burden occurs in women with a family history indicative of a putative autosomal dominantly inherited cancer susceptibility syndrome. The results from a five-generation, extended, hereditary breast-ovarian cancer kindred are described 10 years after it was initially ascertained. Significantly more cancers were observed in high-risk family members during this decade than were expected (P less than 0.001). The age of ovarian cancer diagnosis was studied in additional ovarian cancer-prone families of three types: site-specific ovarian cancer syndrome, the breast-ovarian cancer syndrome, and Lynch syndrome II. The age of onset in each of the three sets was significantly (P less than 0.001) earlier than the general population mean of 59, and there were significant differences in the age of onset (P = 0.050) among these three cohorts. Ovarian cancer histology was similar to that of patients with negative family histories. There may be clinically significant heterogeneity in the age at diagnosis of ovarian cancer among these ovarian cancer-prone syndromes. This has important implications for understanding its natural history and targeting surveillance-management strategies. 
5	Bilateral sudden deafness and acute acquired toxoplasmosis. An 18-year-old woman, while suffering from acute acquired toxoplasmosis, experienced sudden deafness and a total loss of vestibular function first in the right ear and three months later also in the left. Following treatment with sulphadiazine and pyrimethamine, hearing was retrieved to such a degree that the patient was enabled to communicate by means of a body-worn hearing aid and lip-reading. Taking the differential diagnostic possibilities into account, we believe that toxoplasmosis was the cause of the severe hearing loss. Since effective treatment seems to be available, we recommend that patients with acute bilateral sensorineural hearing loss of unknown origin are examined for acute toxoplasmosis with a view to instituting chemotherapy. 
2	A study of HTLV-I and its associated risk factors in Trinidad and Tobago. Seroprevalence of human T-lymphotropic virus type 1 (HTLV-I) among a sample of persons selected from a government register of businesses in Trinidad was 3.2% in 1,025 persons of African descent compared to 0.2% among 487 persons of Asian descent and 0% among 46 persons of European-descent. In Tobago, from a coastal village, among persons of African ancestry ascertained as part of a cardiovascular survey, the rate was 11.4%, which was significantly higher when corrected for age and race than the rate in Trinidad. The seroprevalence rate of antibodies to hepatitis A and B was also significantly elevated in Tobago compared to Trinidad. HTLV-I seroprevalence rates were higher in females than males while hepatitis A and B rates were not significantly different in the two sexes. For males, age was a significant determinant of HTLV-I seropositivity, while for females, age, markers of poor sanitation, and hepatitis B were each independently linked to HTLV-I seropositivity. The frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to HTLV-I infection. 
4	Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram. To determine whether patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm, the signal-averaged electrocardiogram triggered by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf group) and in 50 control patients. The root mean square voltages (LP10, LP20, and LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40-300 Hz) P wave of the spatial magnitude were measured. LP10 and LP20 were significantly lower in the Paf than in the control group (LP10, 1.92 +/- 0.58 versus 2.49 +/- 0.78 microV, p less than 0.001; LP20, 2.47 +/- 0.78 versus 3.46 +/- 1.20 microV, p less than 0.0001), although no significant difference in LP30 was found between groups. Ad was also significantly longer in the Paf than in the control group (137.0 +/- 14.3 versus 118.6 +/- 11.3 msec, p less than 0.001). These differences between the Paf and control groups remained significant even after dividing by the presence or absence of organic heart diseases. The criteria of "LP20 = 3.5 microV or less" and "Ad greater than 120 msec" as defining "atrial late potential" gave a sensitivity of 91% and a specificity of 76%. These findings suggest that patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm by using the P wave-triggered signal-averaged electrocardiogram. 
4	Angiographic progression to total coronary occlusion in hyperlipidemic patients after acute myocardial infarction. POSCH Group. The progression of coronary artery stenosis to total occlusion was assessed in 413 hyperlipidemic patients with a previous myocardial infarction. Coronary angiograms were recorded at baseline, 3 (n = 312), and 5 years (n = 248) after initial study and analyzed by 2 independent readers. There were 177 (43%) patients with 1-, 130 (31%) with 2-, and 61 (15%) with 3-vessel disease (greater than or equal to 50% diameter narrowing), whereas 45 (11%) did not have significant disease within a major coronary vessel at baseline. A new finding of total occlusion occurred in 4% (30 of 748) and 7% (40 of 605) of major coronary artery segments at 3 and 5 years, respectively. The risk of progression to total occlusion was higher if the initial stenosis was greater than 60% compared to lesions less than or equal to 60% both at 3 years (19 of 143 = 13% vs 11 of 605 = 2%; p less than 0.001) and 5 years (27 of 91 = 30% vs 13 of 514 = 3%; p less than 0.001). The frequency of occlusion was highest for the right coronary artery by 5 years (18 of 167 = 11% for right vs 8 of 225 = 4% for circumflex vs 14 of 213 = 7% for left anterior descending coronary arteries; p less than 0.02). Clinical and laboratory data revealed that myocardial infarction was associated with a new total occlusion in 23% of patients (7 of 30) at 3 years and in 64% (25 of 39) at 5 years. 
5	Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system. II. Lesions associated with hypoxic-ischemic encephalopathy. One hundred neonates determined prospectively to be at risk for neurologic handicap underwent magnetic resonance imaging with a high-field (1.5 T) imager. Thirty-three demonstrated a total of 37 lesions consistent with hypoxic-ischemic encephalopathy, including periventricular leukomalacia (n = 12), basal ganglia hemorrhage (n = 5), multicystic encephalomalacia (n = 5), and focal parenchymal hemorrhage (n = 15). Diagnoses by ultrasonography and computed tomography were compared with those by magnetic resonance imaging in 29 and 17 infants, respectively. Ultrasonography agreed more frequently with magnetic resonance imaging than did computed tomography. Ultrasonography detected 79% of lesions demonstrated by magnetic resonance imaging whereas computed tomography detected only 41%. Periventricular leukomalacia was seen most often in preterm infants, basal ganglia hemorrhage and multicystic encephalomalacia primarily occurred in term infants, and focal parenchymal hemorrhage occurred at all gestational ages. Basal ganglia hemorrhage and multicystic encephalomalacia were strongly associated with histories of perinatal asphyxia, seizures, and early abnormal neurological status. All infants with basal ganglia hemorrhage (5/5) and multicystic encephalomalacia (5/5) and the majority with periventricular leukomalacia (9/12) and focal parenchymal hemorrhages (9/15) had developmental abnormalities at discharge. 
1	Detection and typing of human papillomavirus using the Vira Type "in situ" kit: comparison with a conventional dot blot technique. A new commercial kit (Vira Type "in situ", Life Technologies, Inc., Molecular Diagnostics Division, Guithersburg, Maryland, USA) for the detection of human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33 and 35 in routinely processed human anogenital tissue was compared with a conventional dot blot assay for HPV 6, 11, 16 and 18. Both systems use double-stranded genomic DNA probes for the detection of type specific HPV DNA. The probes used on the dot blots were labelled with 32P and visualised autoradiographically. The Vira Type probes were labelled with biotin and visualised using a streptavidin-alkaline phosphatase conjugate with NBT-BCIP substrate. Biopsy specimens from the cervix, vagina, and vulva of 46 women were processed by both methods and compared. The histological diagnoses ranged from benign changes, to dysplasia, and invasive carcinoma. Overall, 50% of biopsy specimens were positive for HPV DNA by dot blot hybridisation; only 39% were positive by Vira Type in situ hybridisation. Three of the specimens positive by the Vira Type "in situ" kit showed no cross hybridisation and were the same HPV type as the dot blot. A further 13 showed hybridisation, but the showed cross hybridisation, but the to the dot blot results. One biopsy specimen was positive for different HPV types by the two tests and one was positive by Vira Type and negative by dot blot. Six biopsy specimens were negative by Vira Type but positive by dot blot. It is concluded that the Vira Type "in situ" kit has a similar specificity but lower sensitivity than the dot blot hybridisation method for the detection of HPV DNA. 
4	Experience with the Sarns centrifugal pump as a ventricular assist device. The authors used the Sarns centrifugal pump (Sarns 3M, Ann Arbor, MI) as a ventricular assist device (VAD) in 30 patients between May 1985 and February 1990. Sixteen patients were unweanable from cardiopulmonary bypass at the time of surgery; nine were patients who developed cardiogenic shock postoperatively in the intensive care unit. One was a donor organ failure; one had a failed PTCA; and one an acute myocardial infarction with cardiogenic shock preoperatively. Two patients were bridged to cardiac transplantation. Of the 28 nontransplant candidates, 20 (71.4%) were weaned successfully, 14 (50%) were discharged from the hospital, and 13 (46%) are alive from 1 to 46 months postoperatively (mean, 21.1 months). Three patients received right ventricular support alone; all three were weaned, and two (66.7%) were discharged. Ten patients received left ventricular assistance alone. Six (60%) were weaned, and four (40%) were discharged. Two patients received left ventricular support initially but were taken back for right VAD insertion because of right-sided heart failure; one (50%) is alive. Fifteen patients received biventricular support. Eleven (77.3%) were weaned, and eight (53.3%) were discharged. Patient ages ranged from 19 to 73 years, with a mean age for men of 59 years and 50.5 years for women. There were no thromboembolic events. Various clinical parameters were evaluated to determine effect on weanability and survival. These results show survival equivalent to any other VAD at this time. The centrifugal pump is a convenient and effective means of maintaining ventricular support in individuals who are believed to have salvageable myocardium. 
5	Percutaneous nephrolithotomy and the solitary kidney. We reviewed 53 patients with stones in a solitary kidney who had undergone percutaneous nephrolithotomy. Previous surgery on that kidney had been performed in 35.8%, and 50.9% had other medical conditions including 26.4% who had impaired renal function. Staghorn or partial staghorn calculi were present in 52.9% and an additional 18.8% had multiple stones. Postoperative complications in 18.8% of the patients included sepsis, the need for transfusion and 1 death of bronchopneumonia. Percutaneous nephrolithotomy alone resulted in a 77.3% rate free of stone or fragments of 2 mm, or less. This rate increased to 86.8% with the addition of extracorporeal shock wave lithotripsy, ureteroscopy or open surgery (2 patients). Only 1 patient suffered long-term deterioration in renal function. Percutaneous nephrolithotomy is a safe procedure in the solitary kidney. It should be considered in those patients with complex stone burdens and impaired renal function when reduction in stone bulk and improved renal function may allow other treatment modalities to be used. 
2	Influence of hepatitis delta virus replication in the presence of hepatitis B virus DNA in peripheral blood mononuclear cells. The presence of hepatitis B virus DNA was studied in peripheral blood mononuclear cell samples from 259 HBsAg carriers (229 anti-hepatitis delta negative, 30 anti-hepatitis delta positive), 16 anti-HBc-positive HBsAg-negative patients and 30 patients without hepatitis B virus markers. Hepatitis B virus DNA sequences were detected in peripheral blood mononuclear cell from 115 (44.4%) of the chronic HBsAg carriers and from two (12%) of the anti-HBc-positive, HBsAg-negative patients. In anti-hepatitis delta-negative patients, viral DNA was positive in peripheral blood mononuclear cell from 74 (46%) and from 24 (35.5%) with and without serum HBV-DNA, respectively. With respect to anti-hepatitis delta-positive patients, viral DNA was found in peripheral blood mononuclear cell in 8 of 13 (61.5%) of the patients with circulating hepatitis delta virus RNA and in 9 of 17 (53%) of the hepatitis delta virus RNA-negative subjects. Regarding hepatitis B virus DNA in serum and peripheral blood mononuclear cell, 71% (5 of 7) of the patients with serum hepatitis B virus DNA had this marker in peripheral blood mononuclear cell, whereas 52% (12 of 23) of the patients without serum hepatitis B virus DNA had hepatitis B virus DNA in peripheral blood mononuclear cell. A Southern blot analysis was also carried out on peripheral blood mononuclear cell samples from 30 patients. Hepatitis B virus DNA was detected in 16 patients as free forms, in 12 patients as dimers and free forms and as free circular together with free linear forms in the remaining two patients. 
1	New chemotherapies for ovarian cancer. Systemic and intraperitoneal podophyllotoxins. The epipodophyllotoxin derivatives etoposide and teniposide have been evaluated intermittently for possible use in the treatment of ovarian cancer. Conflicting studies suggest that variables such as dose and prior treatment have a major influence on outcome. Response rates ranged from 0% to 40% in five series with teniposide, and from less than a 10% overall response rate to greater than a 10% complete response rate in nine studies with etoposide. One study documented activity with oral etoposide. However, because all patients had received various prior chemotherapies, firm conclusions regarding the activity of etoposide could not be drawn. These results, and the expectation of synergy with etoposide and cisplatin, led to several studies that combined etoposide with platin compounds by the systemic and intraperitoneal (IP) routes. Various studies have used intravenous drug combinations of these agents in both previously treated and untreated patients. One study, which used carboplatin instead of cisplatin, reported only seven failures among 26 previously untreated patients. Conversely, the prominent toxicities reported by another study were discouraging, and responses did not exceed what might be expected from cisplatin alone. Studies of analogous combinations administered IP are ongoing. A favorable experience, which was initially reported by the University of California (San Diego group), is being confirmed by other investigators. This has prompted the incorporation of etoposide into first-line strategies. The pharmacologic advantage of etoposide by the IP route (related to its high protein binding) may provide appropriate dose intensity against IP disease while sparing systemic toxicities. Finally, systemic dose intensity with autologous bone marrow support indicates some promise for etoposide in combination with high-dose alkylating drugs. 
4	Value of electrophysiologic studies in hypertrophic cardiomyopathy treated with amiodarone. The relation of electrophysiologic effects of amiodarone to long-term outcome was studied in 35 patients with hypertrophic cardiomyopathy (HC). Indications for electrophysiologic studies were: cardiac arrest (n = 3), syncope/presyncope (n = 27) and asymptomatic ventricular tachycardia (VT) (n = 5). Twenty-eight patients (80%) had VT, 3 (9%) atrial tachycardia and 3 (9%) paroxysmal atrial fibrillation during 24-hour Holter monitoring. The studies were repeated after a total amiodarone dose of 58 +/- 122 g and during a maintenance median daily dose of 400 mg. Amiodarone abolished paroxysmal atrial arrhythmias in all 6 patients. However, it caused marked atrioventricular nodal conduction abnormality in 3 patients and heart block or marked HV interval prolongation (to greater than or equal to 100 ms) in 4 patients. Sustained VT was induced in 26 patients (74%) at baseline study and in 23 patients (66%) taking amiodarone therapy. With amiodarone, VT was no longer inducible or was more difficult to induce in 11 patients (31%), and the drug abolished VT during Holter monitoring in all patients. However, VT was easier to induce with amiodarone or was induced only with amiodarone in 18 (51%) patients. Amiodarone significantly slowed the rate of induced VT (from 248 +/- 29 to 214 +/- 37 beats/min, p less than 0.001). This was associated with a change in its morphology from polymorphic to monomorphic VT in 7 patients. During a follow up of 18 +/- 14 months (range 2 to 56), amiodarone was discontinued because of adverse effects in 8 patients (23%). 
1	Papanicolaou smear cell recovery techniques used by primary care physicians. Nine hundred Tennessee-based internists, family physicians, and obstetrician-gynecologists were randomly selected and surveyed to identify Papanicolaou smear cell recovery methods used in their practices. This 16-item survey also requested typical laboratory reporting procedures on Papanicolaous smears. The most frequently reported cell sampling technique was the combination cotton-tipped applicator and spatula, which was used by 47 percent of all physicians. Use of the cervical cytobrush for Papanicolaou smears, which has been shown to improve the detection of cervical dysplasia, was used alone or in combination by 19 percent of those surveyed, of whom 72 percent were gynecologists. Cervical sampling should contain cells from the transformation zone as evidenced by an adequate number of endocervical cells on the smear. Laboratories reporting the presence of endocervical cells were significantly different (P less than 0.05) among the specialties, with 26 percent of the internists', 18 percent of the family physicians', and 15 percent of the obstetricians' laboratories not providing this information in their reports. Reporting inadequate smears is a necessary first step toward improved sampling technique. Without this information, physicians risk missing pathology through reports of false-negative Papanicolaou smears. 
1	Mutational hotspot in the p53 gene in human hepatocellular carcinomas Human hepatocellular carcinomas (HCC) from patients in Qidong, an area of high incidence in China, in which both hepatitis B virus and aflatoxin B1 are risk factors, were analysed for mutations in p53, a putative tumour-suppressor gene. Eight of the 16 HCC had a point mutation at the third base position of codon 249. The G----T transversion in seven HCC DNA samples and the G----C transversion in the other HCC are consistent with mutations caused by aflatoxin B1 in mutagenesis experiments. No mutations were found in exons 5,6,8 or the remainder of exon 7. These results contrast with p53 mutations previously reported in carcinomas and sarcomas of human lung, colon, oesophagus and breast; these are primarily scattered over four of the five evolutionarily conserved domains, which include codon 249 (refs 4-9). We suggest that the mutant p53 protein may be responsible for a selective clonal expansion of hepatocytes during carcinogenesis. 
5	Effect of nisoldipine on hemodynamic responses to defibrillation. Sequences of ventricular fibrillation-defibrillation cause transient hypertension; we hypothesized that this "adrenergic overshoot" might be blunted by the functional antiadrenergic effect of the calcium channel blocking drug nisoldipine, with a potentially beneficial reduction in myocardial oxygen requirements. However, other calcium channel blocking drugs have been shown to reduce shock success for defibrillation, a deleterious effect. Thus the purposes of this study were to assess the effect of nisoldipine on the hemodynamic responses to the sequences of ventricular fibrillation-defibrillation, and its effect on the energy requirements for defibrillation. In 16 dogs we administered intravenous nisoldipine (1 microgram/kg bolus followed by an infusion of 0.075 to 0.50 microgram/kg/min) to lower mean blood pressure 10% and 20% below baseline. Ventricular fibrillation was induced electrically, and shocks of varying energy levels (30, 50, and 100 joules) were administered to determine defibrillation energy requirements. Heart rates and blood pressures were recorded up to 3 minutes after each shock to determine hemodynamic responses. Measurements were made before nisoldipine administration and again at the two levels of drug-induced blood pressure decline. We found that the usual systolic blood pressure "overshoot" after defibrillation (typically maximum at 15 to 30 seconds after shocks) was significantly blunted after nisoldipine administration (p less than 0.05). Heart rate slowing after defibrillation (a cholinergic response) was not affected. Nisoldipine did not alter shock success rates, which varied from 12 +/- 7%SE at 30 joules to 68 +/- 12% at 100 joules. Thus nisoldipine blunted the "adrenergic overshoot" of systolic blood pressure following defibrillation, a potentially beneficial effect, without altering the energy requirements for transthoracic defibrillation. 
4	Scleroderma and central nervous system vasculitis. We describe a patient with scleroderma (CREST syndrome) and central nervous system vasculitis. While angiography demonstrated segmental symmetrical arterial narrowing characteristic of vasculitis, results of leptomeningeal biopsy were normal. There was no evidence of systemic vasculitis, renal failure, or malignant hypertension previously thought to be required to explain central nervous system dysfunction in patients with scleroderma. Signs and symptoms attributable to vasculitis were reversible with aggressive immunosuppressive therapy. 
4	Kinetic abnormalities of the red blood cell sodium-proton exchange in hypertensive patients. The present study was designed to examine the kinetics of Na(+)-H+ exchange in red blood cells of normotensive and hypertensive subjects and its relation to the previously reported abnormalities in Na(+)-Li+ exchange. The Na(+)-H+ antiporter activation kinetics were studied by varying cell pH and measuring net Na+ influx (mmol/l cell x hr = units) driven by an outward H+ gradient. The Na(+)-Li+ exchange was determined at pH 7.4 as sodium-stimulated Li+ efflux. Untreated hypertensive patients (n = 30) had a higher maximal rate of Na(+)-Li+ exchange (0.43 +/- 0.05 versus 0.26 +/- 0.02 units, p less than 0.0003), a higher maximal rate of Na(+)-H+ exchange (62.3 +/- 6.2 versus 47 +/- 4 units; p less than 0.02), but a similar affinity for cell pH compared with normotensive subjects (n = 46). The cell pH activation of the Na(+)-H+ antiporter exhibited a lower Hill coefficient than that of normotensive subjects (1.61 +/- 0.12 versus 2.56 +/- 0.14; p less than 0.0001). This index of occupancy of internal H+ regulatory sites was found reduced in most of the hypertensive patients (73%) whether their hypertension was untreated or treated. Hypertensive patients with Na(+)-Li+ exchange above 0.35 units (0.68 +/- 0.057 units, n = 16) did not exhibit elevated maximal rates of Na(+)-H+ exchange (57.3 +/- 10 units, NS) in comparison with those with Na(+)-Li+ exchange below 0.35 units (66.4 +/- 7.6 units, n = 26), but both groups exhibited reduced Hill coefficients. Hypertensive patients with enhanced Na(+)-H+ exchange activity (more than 90 units) had normal maximal rates of Na(+)-Li+ exchange. 
2	Psychological characteristics of children with Shwachman syndrome. Twelve children and young adults with Shwachman syndrome were compared with their unaffected siblings and with controls suffering from cystic fibrosis in terms of intellectual ability, motor skills, and behaviour. There were highly significant differences in intelligence quotient between those with Shwachman syndrome and the other two groups. Four of the index subjects but none of the control subjects were below the normal range. The differences between groups on other tests of cognitive and motor skills were not significant, though those with Shwachman syndrome tended to have the lowest scores. There was no evidence that those with Shwachman syndrome had more behavioural difficulties than the control subjects. We suggest that the intellectual difficulties of patients with Shwachman syndrome may be of neurological rather than social origin and that they may originate before birth. 
2	Plasma vasoactive intestinal polypeptide concentration determination in patients with diarrhea. Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course. 
5	Endothelialization of vascular prostheses by transplantation of venous tissue fragments. A method to accelerate the endothelialization of vascular prostheses by seeding venous tissue fragments was developed. A piece of peripheral vein was obtained, chopped into small fragments, and stirred into 20 ml of saline, making a tissue suspension. This suspension was sieved through the wall of a highly porous vascular prosthesis (water porosity: 3,600-4,000). The prostheses, (7 mm ID and 5.7 cm in length) seeded with tissue fragments, were implanted into the thoracic descending aortae of 20 dogs, and were removed from 1 to 371 days after implantation. Ten prostheses, preclotted with fresh blood, were used as controls. In the seeded grafts, an infinite number of endothelial cells migrated and proliferated from the fragments. These had produced numerous capillaries by 5 days after implantation that had reached and opened onto the luminal surface of the prosthesis. From these openings, numerous endothelial cells spread out and formed colonies. With the increase in the size of the colonies, the inner surface was completely endothelialized within 5 weeks. This quick neointimal formation by seeding venous tissue fragments might be applicable to several artificial organs. 
1	Ki-67 immunostaining in uveal melanoma. The effect of pre-enucleation radiotherapy. The reactivity of 33 choroidal and ciliary body melanomas with monoclonal antibody Ki-67, which recognizes a proliferation associated nuclear antigen, has been assessed and compared with clinicopathologic parameters. In 23 cases, 8 Gy irradiation was given 2 days before enucleation. Nonirradiated melanomas had a significantly higher proliferation rate as defined by staining with monoclonal antibody Ki-67 as compared with irradiated tumors (P = 0.007). Similarly, a strong relationship was found between pre-enucleation irradiation and low mitotic activity (P = 0.001). There was no significant correlation between the presence of Ki-67-positive nuclei and histologic classification, largest tumor diameter, localization of the tumor, age, sex, scleral invasion, pigmentation, and lymphocytic infiltration. The relevance of Ki-67 immunohistochemistry for the assessment of the life prognosis of patients with uveal melanoma has to be studied prospectively. 
5	Randomized, double-blind, placebo-controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding. A randomized, double-blind, placebo-controlled trial of somatostatin was conducted among 120 patients admitted for bleeding esophageal varices (59 placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin followed by a 5-day continuous infusion of 250 micrograms/h and an identical administration of placebo were evaluated for both the control of bleeding and prevention of early rebleeding from varices. Failure to control bleeding occurred in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to failure occurring earlier with placebo (P = 0.036). blood and plasma transfused per hour during drug infusion of trial drug was reduced in the somatostatin group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was halved in somatostatin-treated patients. The average effect of somatostatin was a 41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P = 0.0545) after adjustment for the severity of liver disease, which was the only other variable having a significant influence on time to failure. There was no difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or complications. It is concluded that somatostatin is safe and more effective than placebo for the control of variceal bleeding. 
5	Traumatic vulvar hematomas. Assessing and treating nonobstetric patients. Management of the vast majority of vulvar hematomas is conservative. Most resolve spontaneously when simple measures are taken. Serial examinations are necessary to distinguish uncomplicated hematomas from those requiring surgery. The clinician must also be vigilant for the possibility of sexual abuse and respond with appropriate workup and referral if this situation is suspected. 
4	Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system: I. Intraventricular and extracerebral lesions. The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project. 
1	Screening for neuroblastoma at 3 weeks of age: methods and preliminary results from the Quebec Neuroblastoma Screening Project. A large neuroblastoma screening study was recently started in the province of Quebec, Canada. This project, a collaboration between the Quebec Network for Genetic Medicine and the University of Minnesota, is studying the impact of screening infants for the preclinical detection of neuroblastoma on the population-based mortality caused by this tumor. All infants born in Quebec during a 5-year period will be screened twice, at 3 weeks and at 6 months. Urinary homovanillic acid and vanillylmandelic acid determination from dried filter paper samples is used for screening. Initial qualitative screening is done by means of thin-layer chromatography with confirmatory quantitative screening by gas chromatography-mass spectrometry (GC-MS). During the initial 6 months of 3-week screening, 41,673 neonates (92% compliance rate) were screened and 10.6% of them were tested also by GC-MS. Nine of these neonates had positive results on two GC-MS tests and were referred for evaluation to rule out the presence of neuroblastoma. Four had the tumor, 1 had a calcified adrenal gland, and 4 had no tumor detected. Three additional neonates had clinical diagnosis of neuroblastoma before they reached the screening age of 3 weeks. A neuroblastoma that did not secrete homovanillic acid or vanillylmandelic acid was diagnosed clinically in 1 additional patient who tested negative by screening. 
4	Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group Investigators in eight communities collected aortas, right coronary arteries, blood, and associated information from 390 males, 15 to 34 years of age, who died of violent causes. Pathologists at central laboratories graded the arteries for atherosclerotic lesions, and serum lipoprotein cholesterol and thiocyanate concentrations were measured. The percentage of intimal surface involved with atherosclerotic lesions in both the aorta and the right coronary artery was positively associated with serum very low-density lipoprotein + low-density lipoprotein cholesterol concentration and negatively associated with serum high-density lipoprotein cholesterol concentration. The serum thiocyanate concentration, a marker for smoking, was strongly associated with prevalence of raised lesions, particularly in the abdominal aorta. The effect of smoking was not explained by lipoprotein levels. Blacks had more extensive total surface involvement of the aorta after adjustment for lipoprotein cholesterol levels and smoking. These associations indicate that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults. 
1	Diffuse sclerosing variant of papillary carcinoma of the thyroid. Clinical importance, surgical treatment, and follow-up study. A diffuse sclerosing variant is not very rare among papillary carcinomas of the thyroid when the patients are female and younger than 30 years of age. The variant is characterized by diffuse involvement of one or both thyroid lobes, with dense sclerosis, patchy lymphocytic infiltration, and abundant psammoma bodies. Controversy still exists concerning its prognosis. We reviewed our experience with 14 patients treated between 1958 and 1988. All patients were young females, their age being from 10 to 28 years with a mean of 19.6. Hashimoto's thyroiditis had been suspected in nine patients before they came to our clinic. Nowadays the diagnosis of this cancer is possible when we have this entity in mind and detect abundant psammoma bodies either by ultrasonography or by soft-tissue roentgenography of the neck. Total thyroidectomy with modified neck dissection was carried out in eight patients, subtotal thyroidectomy with neck dissection in five, and lobectomy with neck dissection in one. All of them are alive and well without distant metastasis at a mean follow-up of 16 years. Because most of the patients with this variant of papillary carcinoma are young women and the prognosis is favorable, a complete resection without causing later recurrence, but also cosmetic and complication-free surgery, should be considered. 
5	Antibiotic compared with antiseptic prophylaxis for prostatic surgery. Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association between the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of post-operative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per-operative urinary infection or catheterisation. 
4	Experience with the use of coronary autoperfusion catheter during complicated angioplasty. Between February and July of 1989, 22 patients underwent the use of the Stack autoperfusion catheter following acute occlusion or obstructive dissection during coronary angioplasty; in 20 cases conventional balloon was used in an attempt to correct the angiographic appearance followed by the use of Stack catheter when results were sub-optimal. Only 1 patient (4.5%) required surgical revascularization. Although our study is not prospective or randomized, our observations suggest a significant impact in decreasing the need for emergency surgical revascularization after complicated coronary angioplasty with the use of this approach. 
5	Reversal of cardiac and vascular hypertrophy by antihypertensive therapy. Cardiovascular hypertrophy, such as left ventricular hypertrophy, and arteriolar hypertrophic changes are common in established hypertension. Left ventricular hypertrophy, in particular, markedly increases the risk of cardiovascular complications and death. The ability of an antihypertensive agent to reverse hypertrophic changes could, therefore, be greatly advantageous. Clinical studies with beta-blockers have shown them able to substantially reduce left ventricular hypertrophy. For reversal of arteriolar hypertrophy, vasodilatory beta-blockers have been shown to be preferable to ordinary beta-blockers, possibly because vasodilation reduces vascular smooth-muscle tone, which may facilitate reversal of hypertrophy. Theoretically, a vasodilatory beta-blocker, such as celiprolol, would therefore appear to offer advantages because of its ability to reverse left ventricular and arteriolar hypertrophy in addition to its antihypertensive action. The practical and clinical effects of cardiovascular hypertrophy reversal remain to be fully evaluated; however, it is logical to assume that they would be of considerable benefit to the hypertensive patient. 
5	Is routine preoperative hemodynamic evaluation of nonagenarians necessary? An Incidence of co-morbid cardiac disease in the elderly surgical patient as high as 66% has been previously reported. Even in the absence of clinically significant cardiac disease, advanced age alone is often considered sufficient indication for Swan-Ganz placement, hemodynamic evaluation, adjustment of fluid states, and inotropic support. Yet data clearly documenting the need for this evaluation and therapy are difficult to obtain. All major general surgical and orthopedic operations in non-agenarians were reviewed in our institution from July 1, 1987 through December 31, 1988. Fifty-one procedures were performed on 46 patients. None of these patients had preoperative Swan-Ganz catheterization or hemodynamic evaluation. Eighteen general surgical, 30 orthopedic, 2 neurosurgical, and 1 gynecological procedures were performed. Forty-three were performed under general anesthesia, 7 under spinal anesthesia, and 1 with local anesthesia. Seven out of 51 patients (14%) experienced major complications, and 16 out of 51 (31%) experienced minor complications. Thirty-day mortality was 0%, and 6-month survival was 92%. Only one complication occurred within 48 hours of surgery that might possibly have been prevented with hemodynamic evaluation, adjustment of fluid status, inotropic support, and intensive care unit monitoring. 
1	IgE receptor-mediated phosphatidylinositol hydrolysis and exocytosis from rat basophilic leukemia cells are independent of extracellular Ca2+ in a hypotonic buffer containing a high concentration of K+. In isotonic buffer, IgE receptor-mediated exocytosis from rat basophilic leukemia cells is dependent on extracellular Ca2+, with half-maximal degranulation requiring 0.4 mM Ca2+. No significant exocytosis occurs in the absence of extracellular Ca2+. This absolute requirement for Ca2+ is eliminated by suspending the cells in a hypotonic buffer containing 60 to 80 mM K+; Na+ cannot substitute for K+. Optimal Ca2(+)-independent exocytosis occurs in a buffer containing 20 mM dipotassium Pipes, pH 7.1, 40 mM KCl, 5 mM glucose, 7 mM Mg acetate, 0.1% BSA, and 1 mM EGTA. The cells maintain this Ca2(+)-independent exocytosis even if they are preincubated with 1 mM EGTA for 40 min at 37 degrees C before triggering. Exocytosis is eliminated as isotonicity is approached by adding sucrose, NaCl, KCl, or potassium glutamate to the buffer. Quin 2 fluorescence measurements reveal only a very small rise in [Ca2+]i when the cells are triggered in hypotonic buffer in the absence of extracellular Ca2+ and the presence of 1 mM EGTA. In isotonic buffer, degranulation does not occur under conditions that lead to such a small rise in [Ca2+]i. Sustained IgE receptor-mediated phosphatidylinositol hydrolysis, which is also Ca2+ dependent in isotonic buffer, becomes independent of Ca2+ in the hypotonic buffer. In fact, the rate of phosphatidylinositol hydrolysis in hypotonic buffer in the absence of Ca2+ (and presence of 1 mM EGTA) is twice that observed in isotonic buffer in the presence of 1 mM Ca2+. These data show that in hypotonic buffer, the requirement of IgE receptor-mediated PI hydrolysis for extracellular Ca2+ is eliminated, and degranulation proceeds with a [Ca2+]i of 0.1 microM, the baseline level of [Ca2+]i found in resting cells. These results are consistent with the hypothesis that, in isotonic buffer, the Ca2+ requirement for mast cell degranulation is for the generation of second messengers via hydrolysis of membrane phosphatidylinositols. 
5	Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. The experimental metastatic potential of 13762NF mammary adenocarcinoma clone MTLn3 was tested after pretreatment in serum-free medium containing transforming growth factor (TGF) beta 1 at 0-5000 pg/ml. Lung colonies were measured 2 weeks after inoculation in syngeneic F344 rats, and a bell-shaped dose-response curve with 2- to 3-fold increase in number of surface lung metastases was seen. Maximal enhancement occurred at the 50 pg/ml dose level. The effect was specific because addition of neutralizing anti-TGF-beta antibody blocked the stimulatory activity at all levels of TGF-beta 1 pretreatment, but when antibody was given alone, neutralizing anti-TGF-beta antibody had no effect on untreated cells. Increased metastatic potential appears to be from an increased propensity of cells to extravasate as tested in the membrane invasion culture system. MTLn3 cells penetrated reconstituted basement-membrane barriers 2- to 3.5-fold more than did untreated control cells, depending upon length of TGF-beta 1 exposure. Increased invasive potential is apparently due, in part, to a 2- to 6-fold increase in type IV collagenolytic (gelatinolytic) and a 2.4-fold increase in heparanase activity. TGF-beta 1 treatment of MTLn3 cells did not alter their growth rate or morphology in the presence of serum; however, growth was inhibited in serum-free medium. Likewise, adhesion to human umbilical vein endothelial cell monolayers or to immobilized reconstituted basement membrane or fibronectin matrices was unchanged. These results suggest that TGF-beta 1 may modulate metastatic potential of mammary tumor cells by controlling their ability to break down and penetrate basement-membrane barriers. 
4	Congestive heart failure, coronary events and atherothrombotic brain infarction in elderly blacks and whites with systemic hypertension and with and without echocardiographic and electrocardiographic evidence of left ventricular hypertrophy. Hypertension was present in 50% of 196 blacks and in 36% of 382 whites (p less than 0.001). A prospective study of 84 elderly blacks (70% women) and 326 elderly whites (73% women) with hypertension correlated echocardiographic and electrocardiographic left ventricular (LV) hypertrophy with incidences of congestive heart failure (CHF), coronary events and atherothrombotic brain infarction (ABI). Echocardiographic LV hypertrophy (p less than 0.02) and concentric LV hypertrophy (p less than 0.001) were more prevalent in hypertensive blacks than in hypertensive whites. Hypertensive blacks were younger (78 +/- 9 years) than hypertensive whites (82 +/- 7 years) (p less than 0.001). Other coronary risk factors were similar, except for higher serum triglycerides in whites than in blacks (p less than 0.02). Follow-up was 37 +/- 18 months in blacks and 43 +/- 18 months in whites (p less than 0.01). Incidences of CHF and coronary events were not significantly different in blacks and whites. ABI incidence was 38% in blacks and 21% in whites (p less than 0.005). Multiple logistic regression analysis showed that prior CHF (p = 0.000), concentric LV hypertrophy (p = 0.018) and echocardiographic LV hypertrophy (p = 0.022) were independent risk factors for CHF. Echocardiographic LV hypertrophy (p = 0.001), serum total cholesterol (p = 0.002), concentric LV hypertrophy (p = 0.005) and prior coronary artery disease (p = 0.042) were independent risk factors for coronary events. Prior ABI (p = 0.001), echocardiographic LV hypertrophy (p = 0.001) and electrocardiographic LV hypertrophy (p = 0.034) were independent risk factors for ABI. 
5	Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus. The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg. We have investigated whether this antigen is a target structure for human T-lymphocytes. Using recombinant HBxAg protein, we found HBxAg-specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals. With HBxAg-specific synthetic polypeptides, several T-cell epitopes were identified. Most were located in the carboxyterminal half of the HBxAg protein. Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CD8-negative subtype. These data establish for the first time HBxAg as an antigen in the cellular immune response. 
4	Treatment of recurrent ischemia after thrombolysis and successful reperfusion for acute myocardial infarction: effect on in-hospital mortality and left ventricular function. To determine the effect of treatment of recurrent ischemia after reperfusion for acute myocardial infarction on in-hospital mortality and left ventricular function recovery and to identify patients at highest risk of serious consequences in the event of recurrent ischemia in this setting, 405 consecutively treated patients were studied retrospectively. All patients received intravenous thrombolytic therapy within 6 h of ST segment elevation-documented infarction and had angiographic confirmation of their reperfusion status performed within 120 min of treatment. Three hundred three patients had successful reperfusion with or without rescue angioplasty and had no recurrent ischemia (group 1), 74 patients had initially successful reperfusion but subsequent recurrent ischemia (group 2) and 28 patients had failed reperfusion (group 3). The in-hospital mortality in groups 1 to 3 was 2.0%, 14.9% and 32.1%, respectively (p less than 0.001) and the change from baseline to prehospital discharge left ventricular ejection fraction was 1.2 +/- 9.3%, -0.8 +/- 8.7% and -4.3 +/- 5.3%, respectively (p = NS). Within the recurrent ischemia group (group 2), multiple regression analysis found absence of cardiogenic shock at presentation (p = 0.002) and successful treatment initiated within 90 min of recurrent ischemia (p = 0.045) to be the only variables independently correlated with in-hospital survival. Later successful reperfusion was not associated with improved hospital survival. The timing and success of treatment did not affect recovery of global or regional left ventricular function in the patients with paired angiographic studies. 
3	Lymphomatous polyneuropathy. Biopsy of clinically involved nerve and successful treatment. We present a patient with large-cell lymphoma in remission who, over several weeks, developed widespread multifocal polyneuropathy. There was involvement of all four limbs, most severely the left upper extremity that had become useless. Biopsy of the left saphenous nerve within an area of sensory loss showed lymphoma in the endoneurium. There was no other evidence of recurrent lymphoma despite extensive investigation, including bone marrow, lumbar puncture, magnetic resonance imaging of the spine, and computed tomography of the abdomen and pelvis. Intensive systemic chemotherapy was accompanied by nearly complete recovery. Biopsy of a symptomatic nerve is preferable to routine sural nerve biopsy in this condition because of its patchy distribution. Treatment with systematic chemotherapy can be effective. 
5	The analysis of erythrocyte morphologic characteristics in urine using a hematologic flow cytometer and microscopic methods. Three methods for the examination of erythrocyte morphology in urine are described: phase contrast microscopy, microscopy of cytocentrifuged and stained preparations, and erythrocyte analysis with the Technicon H1. Analysis with the H1 has not been described until now. All methods can be used to discriminate between dysmorphic and isomorphic erythrocytes. The red cell distribution width was the best H1 parameter for this discrimination. The authors have found a good correlation between the microscopic methods. The clinical impact of the three methods was studied with urine samples from patients with a confirmed diagnosis. The discrimination between renal and nonrenal hematuria is similar with phase contrast microscopy and cytocentrifuged preparations. The use of the H1 for this discrimination is not recommended. 
4	Coronary arterial remodeling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis. Coronary arterial remodeling is a compensatory mechanism that may limit the adverse effects of coronary obstructive lesions by expansion of the entire vascular segment. To determine if this compensatory anatomic change occurs in patients, high-frequency epicardial echocardiography using a 12 MHz transducer was performed during open heart surgery in 33 patients (10 with normal coronary arteries undergoing valvular surgery and 23 with coronary atherosclerosis). From stop-frame videotape high-frequency epicardial echocardiographic images, cross-sectional measurements of luminal area and total arterial area (lumen, intima, media and dense adventitia) were made in the patients with atherosclerosis at the site of arterial lesions and from the most proximal portion of the same artery. Remodeling was defined as enlargement of the total arterial area. In normal arteries measurements were made from proximal and midarterial locations. In the patients with normal coronary arteries, total arterial area, as determined by high-frequency echocardiography, decreased from the proximal site to the midportion of the artery (from 10.4 +/- 0.9 to 8.4 +/- 1.0 mm2, p less than 0.05); luminal area also decreased (from 6.0 +/- 0.6 to 4.5 +/- 0.7 mm2, p less than 0.05). In patients with coronary arterial lesions, luminal area also decreased from the proximal site to the arterial lesion site (from 5.3 +/- 0.6 to 2.3 +/- 0.3 mm2, p less than 0.05), but total arterial area increased (from 11.6 +/- 1.0 to 13.0 +/- 1.0 mm2, p less than 0.05). Of the 25 coronary arteries evaluated, only 4 had angiographic evidence of coronary collateral formation. These data indicate that coronary arterial remodeling is an important compensatory mechanism in obstructive coronary disease. 
3	Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume. Between 1982 and 1989, 19 patients with gynecologic carcinoma, paraneoplastic cerebellar degeneration, and seropositivity for anti-Purkinje cell cytoplasmic antibodies were identified at our institution. Seven of the patients had no clinical, computed tomographic, or magnetic resonance imaging evidence of cancer but had undergone laparotomy solely because anti-Purkinje cell antibodies were found in their serum; all had high-grade adenocarcinoma. Cerebellar symptoms preceded or coincided with the initial cancer diagnosis in 15 patients and preceded the diagnosis of recurrent cancer in 4 patients. The cancers were 14 ovarian, 2 fallopian tube, 2 surface papillary, and 1 poorly differentiated metastatic adenocarcinoma in a periaortic lymph node. Two remarkable surgical observations in patients with high-grade ovarian and tubal cancers were the conspicuous lack of peritoneal implants and the small metastatic volume. A comparison of the 8 patients who had primary stage III cancer with 24 matched control patients without paraneoplastic cerebellar degeneration revealed no difference in primary tumor volume but a significantly smaller volume of metastatic tumor in the seropositive group (P = 0.05). Anti-Purkinje cell antibodies were not detected in 111 neurologically normal patients with advanced ovarian cancer. The small metastatic volume in the face of high-grade and advanced stage malignancy in seropositive patients with paraneoplastic cerebellar degeneration suggests that an immune response to the tumor (presumably cross-reactive with cerebellar cells) may impair the metastatic process. Earlier diagnosis and treatment of cancer, based on prompt serologic testing, may offer an improved neurologic and oncologic prognosis. 
5	Identification and preliminary characterization of protein-cysteine farnesyltransferase. Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity. Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group. Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin. These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue. This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested. Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa. Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway. 
5	The value of preoperative estimation of haemoglobin in children undergoing tonsillectomy. Preoperative estimation of haemoglobin in children undergoing tonsillectomy is routinely practised in most centres. To assess the value of this investigation the haemoglobin of 250 consecutive children undergoing tonsillectomy was estimated. Two children were clinically found anaemic preoperatively, and this was confirmed on blood testing. Since the prevalence of anaemia is low, it is proposed that the practice of routine preoperative estimation of haemoglobin is unnecessary, traumatic and expensive, and therefore requires reconsideration. 
5	Oxygen free radicals in acute pancreatitis of the rat. This study aimed to assess the role of oxygen free radicals in acute pancreatitis. Acute pancreatitis was induced in rats by infusion of the CCK-analogue cerulein (5 micrograms/kg per hour) for 30 minutes, 3.5 hours, and 12 hours. After the infusion, serum enzymes and conjugated tissue dienes and malondialdehyde were measured and tissue samples were subjected to electron and light microscopy. Electron microscopy after 30 minutes showed moderate intracellular alterations. After 3.5 hours of cerulein infusion interstitial oedema and intravascular margination of granulocytes in the pancreatic gland were seen. After 12 hours histological evaluation showed pronounced zymogen degranulation, extensive tissue necrosis, and migration of granulocytes into the tissue. Amylase and lipase activities increased 15 and 35-fold respectively during this time. After 30 minutes of cerulein infusion conjugated dienes and malondialdehyde increased, they reached their peak after 3.5 hours and decreased to normal values after 12 hours. Treatment with superoxide dismutase (100,000 U/kg/hour) and catalase (400,000 U/kg/hour) either before or after the start of the cerulein infusion prevented lipid peroxidation and reduced zymogen degranulation and tissue necrosis. Tissue oedema and inflammatory response, however, were not affected in any of the treated rats. Oxygen free radicals are instrumental in the development of acute pancreatitis. Even after its onset, scavenger treatment reduced the tissue damage normally observed. 
5	Respiratory epithelium in a cystic choristoma of the limbus. A female newborn had a cystic, whitish gray mass at the inferotemporal limbus of the left eye. At age 3 weeks, the newborn underwent excision of the tumor, corneal patch grafting, and superior sector optical iridectomy. Histopathologic and electron microscopic examination of the excised tissue revealed a choristoma consisting of cysts lined with respiratory epithelium. To our knowledge, respiratory epithelium in a limbal choristoma has not been previously reported. 
5	The effect of muscle-sparing versus standard posterolateral thoracotomy on pulmonary function, muscle strength, and postoperative pain. Increased interest in alternative approaches to thoracotomy has developed because of the considerable morbidity associated with the standard posterolateral technique. We conducted a prospective, randomized, blinded study of 50 consecutive patients to compare postoperative pain, pulmonary function, shoulder strength, and range of shoulder motion between the standard posterolateral and the muscle sparing thoracotomy techniques. Pulmonary function (forced expiratory volume in 1 second and forced vital capacity), shoulder strength, and range of motion were measured preoperatively and at 1 week and 1 month postoperatively. Pain was quantitated by postoperative narcotic requirements, the visual analogue scale, and the McGill pain questionnaire. Morbidity, mortality, and hospital stay were compared between the standard posterolateral and muscle-sparing techniques. There were no differences in postoperative pulmonary function, shoulder range of motion, extent of lung resection, surgical approach time, mortality, or hospital stay. There was significantly less postoperative pain in the muscle-sparing group. The narcotic requirement was less in the first 24 hours (p = 0.0169), and visual analogue scale scores were significantly lower (p less than 0.05) throughout the first postoperative week. Shoulder girdle strength was decreased at 1 week in the standard incision group whereas the strength was preserved with the muscle-sparing approach. Muscle strength had returned to preoperative levels by 1 month in both groups. Morbidity was identical in the two groups with the exception of postoperative seromas. The prevalence of seroma was 23% in the muscle-sparing group and 0% in the standard incision group (p = 0.0125). We have demonstrated that the muscle-sparing incision may be a reasonable alternative to the standard posterolateral approach. 
3	Neuro-ocular Lyme borreliosis. Any patient who has a Bell's palsy (unilateral or bilateral), aseptic meningitis, chronic fatigue syndrome, atypical radiculoneuropathy, presenile dementia, atypical myopathy, or symptoms of atypical rheumatoid arthritis should be asked specifically about the following: visits to highly endemic areas, any known tick bites, any skin lesion suggestive of erythema migrans, any history of palpitations or of prior Bell's palsy, aching in joints (especially the knees), paresthesias, chronic fatigue and depression, forgetfulness, and eye problems. Any patient showing a chronic iritis with posterior synechiae, vitritis in one or both eyes, an atypical pars planitis-like syndrome, big blind spot syndrome, and swollen or hyperemic optic discs should be asked the same questions. The physician should send one red-top tube of blood containing 2 to 3 ml serum to Microbiology Reference Laboratory, 10703 Progress Way, Cypress, CA 90630-4714, requesting a Lyme/treponemal panel. For $90 the patient will receive an RPR test with titer, serum FTA-ABS test, serum Lyme IFA IgG and IgM, and a serum Lyme ELISA test. If these tests are within normal limits and the physician is still suspicious, a Western blot can be ordered on serum. A green top tube with fresh white blood cells sent out by overnight express on a Monday or Tuesday will produce a Lyme PCR and a lymphocyte stimulation test. Finally, R.K. Porschen, director of MRL Laboratory, will provide information on the urine antigen test on an investigational basis. A careful history with emphasis on the specific questions noted above, a complete neuro-ophthalmological and physical examination ruling out other causative problems, and the laboratory studies here discussed will usually provide sufficient data to choose therapy. Much further active research into Lyme borreliosis is an important priority in medicine. 
2	Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: an operator-blind echo-Doppler study. In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity. 
3	Clentiazem reduces infarct size in rabbit middle cerebral artery occlusion. We assessed the value of pretreatment with clentiazem (8-chlorodiltiazem), a diltiazem derivative with cerebroselective properties, on the consequences of surgical occlusion of the middle cerebral artery via a transorbital approach in 38 rabbits. Nineteen rabbits received 1.7 (n = 5), 5 (n = 8), or 15 (n = 6) mg/kg clentiazem orally four times a day for 24 hours before and 48 hours after occlusion. Upon sacrifice, a segment of the right middle cerebral artery distal to the occlusion and a corresponding segment from the nonoccluded left middle cerebral artery were mounted on myographs for in vitro study of their reactivity to histamine, acetylcholine, serotonin, norepinephrine, and electrical stimulation of intramural sympathetic nerves. Morphometric measurements of 2,3,5-triphenyltetrazolium chloride-stained brain slices permitted us to estimate infarct volume. Pretreatment with 1.7, 5, and 15 mg/kg clentiazem significantly reduced infarct volume (p less than 0.05, p less than 0.01, and p less than 0.01, respectively). Mean infarct volume of the 15 mg/kg-treated group was only 4% that of the untreated group. There were no postoperative deaths in any treated group compared with a death rate of 36% in the untreated group. Mean values for vascular smooth muscle contractility to histamine and relaxation to acetylcholine were significantly enhanced in vessels from treated rabbits. These studies indicate that pretreatment with clentiazem offers cerebral protection and significantly reduces infarct volume as well as arterial wall damage beyond the occlusion. 
4	The entrainment of low frequency breathing periodicity. It has been predicted by mathematical models of the respiratory control system that the delay between the lung and the respiratory controller may determine the cycle time found in periodic breathing. We examined cycle time of periodic breathing and circulation time in 11 patients known to have circulation delay due to heart failure. We did not find a significant relationship between the amount of periodic breathing and circulation delay, but found a very high correlation between circulation delay and the cycle time of periodic breathing (r2 = 0.825; p = 0.0001). 
2	Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones. One hundred and twenty-six patients with radiolucent gallstones in 'functioning' gallbladders were treated with 8-10 mg ursodeoxycholic acid (UDCA) kg/day and followed to a treatment conclusion. Complete or partial gallstone dissolution was achieved in 74 (59 per cent). However, only 22 achieved complete gallstone dissolution, as judged by two normal oral cholecystograms; ultrasonograms were performed in 16 of these patients, and all were normal. UDCA was stopped in 76 patients: because of cystic duct obstruction (n = 12), severe biliary pain (n = 13), non-response (n = 25) or partial stone dissolution with arrested progress (n = 26). Life-table analysis showed that complete gallstone dissolution rates at four years were 25-30 per cent (two normal oral cholecystograms) and 17-19 per cent (two normal oral cholecystograms plus one ultrasonogram). All patients with complete gallstone dissolution had shown partial stone dissolution at 6-12 months; of those with partial stone dissolution at six months, only 25 per cent went on to complete gallstone dissolution, and then always within two years. Efficacy correlated inversely with stone size but not with age, sex, obesity or on-treatment saturation indices. Acquired surface gallstone calcification developed in 13 patients (life-table analysis 22 +/- 7 per cent at four years); none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution. Thus, despite relatively high partial gallstone dissolution rates, the ultimate efficacy of UDCA in achieving complete gallstone dissolution is low. 
5	Usefulness of tomographic thallium-201 imaging for detection of restenosis after percutaneous transluminal coronary angioplasty. The role of tomographic thallium-201 exercise and redistribution imaging in the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 116 patients: 61 (53%) with 1- and 55 (47%) with multivessel PTCA, with a total of 185 dilated vessels. Complete revascularization was performed in 89 (77%) and partial revascularization in 27 (23%) of the patients. Restenosis was angiographically demonstrated in 69 (60%) of the patients and 85 (46%) of the vessels 6.4 +/- 3.1 months after PTCA. Disease progression in previously normal vessels was noted in 11 patients. The results were: (1) for detection of restenosis in the group of patients, single-photon emission computed tomographic (SPECT) versus exercise electrocardiographic sensitivity was 93 vs 52% (p less than 0.001), specificity 77 vs 64%, and accuracy 86 vs 57% (p less than 0.001). The results were similar in the complete and partial revascularization groups. (2) SPECT was 86% sensitive, specific and accurate for restenosis detection in specific vessels with comparable results for 1-versus multivessel PTCA and complete versus partial revascularization. Sensitivity, specificity and accuracy were: 89, 95 and 92% for the left anterior descending coronary artery; 88, 79 and 82% for the right coronary artery; and 76, 83 and 85% for the left circumflex coronary artery. Eighty-one percent of the diseased nondilated vessels were correctly identified. (3) Disease progression to greater than 50% stenosis was detected with 91% sensitivity, 84% specificity and 85% accuracy. SPECT thallium-201 imaging is an excellent tool for the detection of restenosis and disease progression after PTCA in the settings of 1- and multivessel angioplasty and complete and partial revascularization. 
3	Acetylsalicylic acid vs. metoprolol in migraine prophylaxis--a double-blind cross-over study. In a double blind cross-over study, 28 patients, 5 male and 23 female, aged 31 +/- 14 years, after a run-in period of 8 weeks, were treated for 3 months with acetylsalicylic acid and for another 3 months with metoprolol, both in a prophylactic mode. Attack frequency was reduced significantly with both therapeutic regimens (ASA p less than 0.001, metoprolol p less than 0.00005). Reduction of attacks below 50% was seen with metoprolol in 14 cases, and with ASA in three cases. Even though ASA was of statistically significant efficacy in migraine prophylaxis, it clearly is not the drug of first choice in migraine prophylaxis. 
4	Sustained improvement in left ventricular function after successful coronary angioplasty. The short and long term effects of successful percutaneous transluminal coronary angioplasty on left ventricular function, at rest and on exercise were investigated in 49 patients. Thirty-four had had no previous infarction (group 1) and 15 had (group 2). Technetium-99m gated blood pool images were obtained at rest and during exercise before, six weeks after, and a mean of fifteen months after successful angioplasty. Before angioplasty the mean (SD) ejection fraction fell significantly on exercise in both groups from 58 (10)% to 53 (13)% in group 1 and from 48 (10)% to 40 (16)% in group 2. This change was paralleled by a worsening wall motion score (from 0.6 (0.4) to 1.6 (1.2) in group 1 and from 2.3 (1.9) to 3.3 (2.4) in group 2). Six weeks after the procedure there was little change in resting ejection fraction but it increased significantly on exercise (to 62 (11)% in group 1 and to 53 (13)% in group 2). There was a concomitant significant improvement in the exercise wall motion score (to 0.4 (0.6) in group 1 and to 1.8 (1.1) in group 2). This improvement in exercise ejection fraction and wall motion was maintained at later follow up with no significant deterioration in either variable and a clearly sustained improvement in ejection fraction (60 (10)% in group 1 and 51 (10)% in group 2) and wall motion score (0.2 (0.2) in group 1 and 1.3 (0.8) in group 2) compared with values before angioplasty. 
1	Effect of selective elimination of the oral flora on mucositis in irradiated head and neck cancer patients. Recently it has been reported that chlorhexidine 0.1% rinsing was not successful in eradication of gram-negative bacilli in patients who have head and neck cancer. These bacilli could play a role in irradiation mucositis. This study reports the effect of lozenges containing 2 mg polymyxin E, 1.8 mg tobramycin, and 10 mg amphotericin B qid on the oropharyngeal flora in 15 irradiated head and neck cancer patients. The results were compared with those of a previous study in two groups of 15 patients comparing chlorhexidine rinsing with placebo. In all patients using lozenges, eradication of gram-negative bacilli and yeasts was achieved within 3 weeks. A significant increase of enterococci was found. Mucositis was significantly reduced compared with the previous two groups. All patients showed erythema only, whereas 80% of both the placebo and chlorhexidine rinsing patients suffered from severe mucositis, with signs of pseudomembranes developing from the third week of conventional irradiation protocol. The effect of selective elimination of gram-negative bacilli from the oropharynx and the prevention of severe mucositis may be explained by the eradication of these bacteria and/or neutralization of salivary endotoxin, released by gram-negative bacilli, mediating the inflammatory processes. 
5	Pneumocystis carinii pneumonia complicating somatostatin therapy of Cushing's syndrome in a patient with metastatic pancreatic islet cell carcinoma and Zollinger-Ellison syndrome. Described is the case of a 73-yr-old woman with metastatic pancreatic islet carcinoma that manifested initially as Zollinger-Ellison syndrome followed by onset of endogenous Cushing's syndrome, who developed Pneumocystis carinii pneumonia while on therapy with a long-acting somatostatin analog. Although P. carinii pneumonia has been observed in patients with Cushing's syndrome associated with other conditions, this is the first reported case in a patient with Zollinger-Ellison syndrome. Heightened awareness of the possibility of opportunistic infections in patients receiving somatostatin therapy for Cushing's syndrome of any cause, particularly Zollinger-Ellison syndrome, may be warranted. 
5	Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-beta 1 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission. TGF-beta 1 prevents the occurrence of relapses in REAE. The results suggest that TGF-beta 1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models of autoimmune disease, but without discernable adverse effects. 
1	Treatment of anovulation due to polycystic ovarian syndrome by laparoscopic ovarian electrocautery. Our experience of ovarian electrocautery for the treatment of polycystic ovarian syndrome (PCOS) in ten women is described. We found that nine responded favourably, either ovulating spontaneously or becoming more responsive to ovulation induction. There was a significant and persistent fall in serum testosterone levels, and a transient fall with subsequent rise in inhibin. We recommend that laparoscopic ovarian electrocautery is considered as an alternative to ovulation induction with gonadotrophins, in women with PCOS who fail to respond to clomiphene citrate. 
3	Attenuated neuropathology by nilvadipine after middle cerebral artery occlusion in rats. We investigated the effects of nilvadipine, a calcium antagonist, on cerebral ischemia in rats. Under halothane anesthesia, 30 rats had a 3-0 nylon suture introduced through the extracranial internal carotid artery to occlude the left middle cerebral artery. Nilvadipine was dissolved in polyethylene glycol 400. Immediately following occlusion, group 1 rats (n = 10) were treated subcutaneously with vehicle and group 2 and 3 rats were treated with 1.0 (n = 10) and 3.2 (n = 10) mg/kg nilvadipine, respectively. Perfusion fixation was performed 24 hours later, and the histopathologic outcomes were quantified. In group 1 infarct volume was 28.2 +/- 11.4% of the total cerebral volume; in groups 2 and 3 infarct volumes were 25.5 +/- 11.6% (NS) and 13.9 +/- 9.2% (p less than 0.05 different from group 1), respectively. Nilvadipine decreased ischemic neuronal injury in a dose-dependent manner and may be of use in the treatment of cerebral ischemia. 
1	Pancreatic tumor pathogenesis reflects the causative genetic lesion. Transgenic mice in which c-myc expression is targeted to pancreatic acinar cells develop mixed acinar/ductal pancreatic adenocarcinomas between 2 and 7 months of age. This contrasts with the effect on pancreas of the simian virus 40 tumor antigen or activated ras, which in adult mice causes lesions composed exclusively of acinar-like cells. Furthermore, during an early stage of myc-induced pathology, transformed acinar-derived cells appear within islets, suggesting that islet hormones may influence the progression of these exocrine pancreatic tumors. These findings demonstrate that the initial oncogenic alteration can influence the pattern of subsequent tumor pathogenesis and, given that human exocrine pancreatic tumors are predominantly ductal adenocarcinomas, support the suggestion that transformed acinar cells may contribute to the genesis of this serious disease in man. 
4	Changes in cardiac function during extracorporeal membrane oxygenation for persistent pulmonary hypertension in the newborn infant. The effects of extracorporeal membrane oxygenation (ECMO) on cardiac function and its determinants (preload, afterload, contractility, and heart rate) are largely unknown, although some evidence exists that function may decrease. To determine whether cardiac function decreases and what changes in the determinants take place during and after ECMO, we observed 26 newborn infants with persistent pulmonary hypertension. Serial echocardiograms were performed before ECMO, during maximum cardiopulmonary bypass, and after ECMO. Cardiac function was assessed by using standard echographic ejection phase indices (shortening fraction and cardiac output). Heart rate, preload (left ventricular end-diastolic dimension and area), afterload (left ventricular end-systolic wall stress), and contractility (relationship between velocity of circumferential fiber shortening and wall stress) were also measured. Ejection phase indices significantly decreased during ECMO (shortening fraction 33% to 25%, cardiac output 205 to 113 ml/kg/min; p less than 0.05) and returned to normal after ECMO (shortening fraction 26% to 34%, cardiac output 107 to 240 ml/kg/per minute; p less than 0.05). Heart rate also significantly decreased during ECMO (158 to 118 beats/min; p less than 0.05). Preload significantly increased after ECMO (left ventricular end-diastolic dimension 1.4 to 1.6 cm, left ventricular end-diastolic area 1.9 to 2.2 cm2; p less than 0.05). There were no significant changes in contractility and afterload during any study period. We conclude that, although left ventricular ejection phase indices and heart rate decreased during ECMO, these changes were transient and resolved when bypass was terminated. Contractility and afterload did not appear affected by bypass. 
5	Mechanism of glucoregulatory responses to stress and their deficiency in diabetes. During exercise, increased energy demands are met by increased glucose production that occurs simultaneously with the increased glucose uptake. We had previously observed that, during exercise, metabolic clearance rate of glucose (MCR) increases markedly in normal, but only marginally in poorly controlled diabetic dogs. We wished to determine (i) whether in a more general model of stress matched increases in rate of appearance of glucose and MCR also occur, or if MCR is suppressed, as during catecholamine infusion; and (ii) whether diabetes affects stress-induced changes in rate of glucose appearance and MCR. Therefore, we injected carbachol (27 nmol/50 microliters), an analog of acetylcholine, intracerebroventricularly in seven conscious dogs before and after induction of alloxan diabetes. In normal dogs, plasma epinephrine and cortisol increased 4- to 5-fold, whereas norepinephrine and glucagon doubled. Plasma insulin, however, remained unchanged. Tracer-determined hepatic glucose production increased rapidly, but transiently, by 2.5-fold. This increment can be fully explained by the observed increments in the counterregulatory hormones. Surprisingly, however, MCR also promptly increased, and therefore, plasma glucose changed only marginally. After induction of diabetes, the animals were given intracerebroventricular carbachol while plasma glucose was maintained at moderate hyperglycemia (9.0 +/- 0.4 mM). Increments in counterregulatory hormones were similar to those seen in normal dogs, except for exaggerated norepinephrine release. Peripheral insulin levels were higher in diabetic than in normal dogs; however, MCR was markedly reduced and the lipolytic response to stress increased, indicating insulin resistance. Interestingly, the hyperglycemic response to stress was 6-fold greater in diabetic than normal animals, relating mainly to the failure of MCR to rise. Plasma lactate increased equivalently in diabetic and normal animals despite suppression of MCR in the diabetics, indicating either greater muscle glycogenolysis and/or impairment in glucose oxidation. We conclude that in this stress model MCR increases as in exercise in normal but not in diabetic dogs. We speculate that glucose uptake in stress could be mediated through an insulin-dependent neural mechanism. 
3	Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. BACKGROUND. In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS. Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS. There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences. 
1	Aetiology of pancreatic cancer Curative surgery is possible in only a small minority of patients with pancreatic cancer and, to date, responses to chemotherapy and radiotherapy have been disappointing. To make any impact on the incidence of the disease a clearer understanding of its aetiology is required. This review explores present knowledge of the aetiology and epidemiology of pancreatic cancer. 
1	Selenium in forage crops and cancer mortality in U.S. counties. The potential protective effect of selenium status on the risk of developing cancer has been examined in animal and epidemiologic studies. This ecological study investigated the association between U.S. county forage selenium status and site- and sex-specific county cancer mortality rates (1950-1969) using weighted least squares regression. Consistent, significant (p less than .01) inverse associations were observed for cancers of the lung, rectum, bladder, esophagus, and cervix in a model limited to rural counties and for cancers of the lung, breast, rectum, bladder, esophagus, and corpus uteri in a model of all counties. No consistent significant positive associations were observed in the rural county models. This remarkable degree of consistency for the inverse associations strengthens the likelihood of a causal relationship between low selenium status and an increased risk of cancer mortality. 
5	Aortic dissection with the entrance tear in transverse aorta: analysis of 12 autopsy patients. Clinical and autopsy findings are described in 12 patients who had fatal aortic dissection with the entrance tear in the transverse aorta. The 12 patients represent 7% of 182 autopsies of spontaneous aortic dissection studied by us. The ages of the 12 patients at death ranged from 37 to 87 years (mean, 67 years). Eight were men; 8 had a history of systemic hypertension, and 10 had hearts of increased weight. Diagnosis of aortic dissection was made during life in only 4 of the 12 patients. All 12 patients died of rupture of the false channel within 2 weeks of onset of signs or symptoms compatible with dissection. The direction of aortic dissection from the entrance tear was entirely retrograde in 4 patients, entirely anterograde in 4 patients, and in both directions in 4 patients. Hemopericardium occurred in the first group, left hemothorax in the second group, and either in the last group. Of the 8 patients in whom the ascending aorta was involved, the retrograde dissection in each extended to the aortic root, 6 had pulmonary adventitial hemorrhage, and 4 had involvement of the arch arteries by dissection. In the 4 patients with strictly anterograde dissection, none had dissection in the arch arteries. Thus, tear in the transverse aorta causes a dissection that is usually fata, that often dissects retrogradely, and that may mimic dissection from a tear in ascending aorta. Aortic dissection from a tear in transverse aorta requires early operative intervention. 
3	The floppy infant: recent advances in the understanding of disorders affecting the neuromuscular junction. The clinician is often asked to evaluate the floppy infant. Numerous conditions that cause hypotonia in infancy are briefly outlined in this article. These conditions may affect the brain, spinal cord, or motor unit. Several disorders of neuromuscular transmission, including four distinct and recently described congenital myasthenic syndromes and infant botulism, are discussed thereafter. 
4	Deep venous thrombosis in intravenous cocaine abuse mimicking septic arthritis of the shoulder. We describe two patients with deep venous thrombosis of the upper extremity who initially were thought to have septic arthritis of the shoulder. These patients had a history of recent intravenous cocaine abuse. The diagnosis of deep venous thrombosis should be considered when a patient with a swollen shoulder has an appropriate history. 
3	Influence of amphetamine treatment on somatosensory function of the normal and infarcted rat brain. The consequences of acute amphetamine administration on the metabolic responsiveness of the cerebral cortex to physiologic activation were studied in normal and infarcted rats. Treated rats received a 4 mg/kg intravenous injection of d-amphetamine 1 hour before unilateral vibrissae stimulation and 2-deoxyglucose study. In nontreated normal rats, metabolic activation was restricted to the major relay stations of the vibrissae-barrel circuit. In amphetamine-treated rats, stimulation-induced increased glucose utilization was widespread, including ipsilateral and contralateral cortical regions outside the barrel field circuit. For example, an 84% increase in glucose utilization above control was seen in cortical areas anterior to the barrel field region. Increased glucose utilization induced by stimulation was severely depressed in nontreated rats that had undergone infarction of the left cortical barrel field 2 weeks previously. Vibrissae stimulation failed to increase glucose utilization significantly in cortical areas remote from the infarct. In contrast, bilateral increases in glucose utilization were observed within cortical regions of treated infarcted rats. For example, a 50% increase in glucose utilization was detected in cortical areas bordering the infarct. Thus, in the normal and infarcted rat, amphetamine appears to promote alternate circuit activation--a pharmacologic property that may be advantageous for recovery after injury. 
2	Follow-up of infants treated with extracorporeal membrane oxygenation for newborn respiratory failure. Follow-up studies were conducted to assess the medical and developmental outcome of 92 infants treated with extracorporeal membrane oxygenation at the University of Michigan. Of 118 near-term (greater than 34 weeks' gestation) infants who received extracorporeal membrane oxygenation, 103 (87%) were surviving and available for follow-up at between 1 and 7 years of age. Ninety-two of these children were seen on at least one occasion. Each visit included a history and physical examination, an evaluation by a physical therapist, and developmental testing by a pediatric psychologist. Medical outcome during year 1 found 31% of the children rehospitalized, primarily with respiratory illness. Outpatient-treated lower respiratory tract illness was seen in an additional 31% of the children. New or nonstatic neurologic problems were noted in 6% of the children. Abnormal growth during year 1 occurred in 26% of the children. At last clinic visit 16% of the children exhibited moderate-to-severe neurologic abnormalities, and 8% had moderate-to-severe cognitive delay. Sensorineural hearing loss occurred in 4% of children. Nine percent of the children were receiving speech and language therapy; screening tests showed that an additional 6% had speech and language delay. Overall, at last visit 16 (20%) of the children exhibited some type of handicap. A review of the literature on follow-up studies of non-extracorporeal membrane oxygenation-treated infants with persistent pulmonary artery hypertension produced an impairment rate of 18.5%. Outcome post-extracorporeal membrane oxygenation appears similar to that seen in less ill cohorts of infants treated with more "conventional" therapy. Long-term follow-up of all such infants remains essential. 
2	Maternal outcome after open fetal surgery. A review of the first 17 human cases. A few fetal diseases may benefit from surgical treatment before birth, but hysterotomy and subsequent delivery by cesarean section pose a risk to the otherwise unaffected mother. To assess maternal risk of mortality, morbidity, and reproductive potential after fetal surgery, we reviewed our experience with 17 highly selected women who underwent fetal surgery. Fifteen of these procedures were performed for one of two congenital anomalies: severe bilateral hydronephrosis and congenital diaphragmatic hernia. There were no deaths or serious maternal injuries. In the 14 women who continued pregnancy after hysterotomy, uterine irritability and preterm labor were frequent complications, requiring early confinement in most cases. There has been no detectable effect on future fertility, as indicated by eight subsequent normal pregnancies. We conclude that hysterotomy for fetal surgery can be accomplished without unduly endangering the mother's life or her future reproductive potential. However, morbidity related to premature labor remains a serious problem, and our ability to control uterine contractions after hysterotomy remains the limiting factor in human fetal surgery. 
5	The surgical treatment of atrial fibrillation. II. Intraoperative electrophysiologic mapping and description of the electrophysiologic basis of atrial flutter and atrial fibrillation. Computerized mapping of atrial fibrillation was performed in animals and man. To study atrial fibrillation in a systematic manner, we developed a clinically relevant experimental model of atrial fibrillation. Chronic mitral regurgitation was created surgically in 25 dogs without opening the pericardium. After several months of chronic mitral regurgitation, the atria became enlarged and sustained atrial fibrillation could be induced by standard programmed electrical stimulation techniques. Computerized isochronous activation maps of the atria were recorded during atrial fibrillation from 208 bipolar electrodes simultaneously. In a parallel study, human atrial fibrillation was mapped with a separate 160-channel intraoperative mapping system in patients with paroxysmal atrial fibrillation who were undergoing surgical correction of the Wolff-Parkinson-White syndrome. The canine activation sequence maps demonstrated a spectrum of rhythm abnormalities ranging from simple atrial flutter to complex atrial fibrillation. They also showed that macroreentrant circuits within the atrial myocardium were responsible for the entire spectrum of arrhythmias. Atrial reentry was also documented during human atrial fibrillation. All patients had nonuniform conduction around regions of bidirectional block in both atria resulting in multiple discrete wave fronts. In addition, six patients had a single reentrant circuit in the right atrium in which bidirectional block of the activation wave front occurred along the sulcus terminals between the venae cavae. The left atrium in all patients demonstrated multiple wave fronts and conduction block, but left atrial reentry could not be detected. Both the experimental study and the clinical study demonstrated that multiple wave fronts, nonuniform conduction, bidirectional block, and large (macroreentrant) reentrant circuits occur during atrial fibrillation. The presence of macroreentrant circuits and the absence of either microreentrant circuits or evidence of atrial automaticity suggests that atrial fibrillation should be amenable to surgical ablation. 
5	Patterns of dyspepsia in patients with no clinical evidence of organic diseases. We studied 2000 dyspeptic patients with no obvious signs of organic disease at their first examination, in order to (1) verify how many diagnoses of idiopathic dyspepsia had really been made after exhaustive diagnostic procedures and (2) evaluate the diagnostic power of the symptoms in distinguishing organic from idiopathic dyspepsia. This latter was considered only when no structural abnormalities were found. In all the other cases, a distinction was made between "related" and "associated" organic dyspepsia according to whether or not there was a certain relationship between the abnormalities and the dyspeptic symptoms. The patients were referred to us as follows: (1) spontaneously, (2) sent by physicians collaborating with us, (3) referred to our open access endoscopic service. The results show the frequency of idiopathic dyspepsia was 26%, whereas associated structural abnormalities were present in 45.4%. Obvious organic causes of dyspepsia were seen in 28.6% (24% benign and 4.6% malignant diseases). When considered separately, no symptom alone allows a correct diagnosis. The simultaneous evaluation of the symptoms with linear discriminant analysis distinguishes between idiopathic and organic dyspeptic patients in about 70% of the cases. A higher discrimination percentage in about 70% of the cases. A higher discrimination percentage could probably be obtained using a wider range of clinical parameters and/or a more complex statistical analysis of the interrelationships which exist between the clinical symptoms and the final diagnosis. 
1	Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. The safety of administering the live attenuated Oka/Merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children. Susceptible well children were eligible for vaccination if the child with malignancy had leukemia, lymphoma, or solid tumor in remission for 3 months or longer. No evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine. Varicella-zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings. None of the 30 immunocompromised children had vaccine-related rashes or showed immunologic evidence of subclinical varicella-zoster virus infection based on testing for varicella-zoster virus IgG antibodies and T-lymphocyte proliferation to varicella-zoster virus. Four healthy vaccinees eventually had mild breakthrough cases of varicella, with transmission to the high-risk sibling in 3 cases. However, even in these families, the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment. 
2	Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit. Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease. Colonic mucosal inflammation was induced in rats, guinea pig and rabbits by rectal instillation of a dilute solution of acetic acid. Twenty-four hours later, mucosal levels of myeloperoxidase (a marker enzyme for neutrophil infiltration) and extravasation of i.v. administered Evans blue dye (a marker of vascular disruption and increased permeability) were measured. Tissues were also evaluated histologically. The animals received either SC-41930 or vehicle, intrarectally, 30 min after or 1 hr before and 1 hr after the acetic acid. When given 30 min after acetic acid instillation SC-41930 prevented the rise in myeloperoxidase and dye extravasation observed in the acetic acid inflammed tissue. The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space. Median effective dose (ED50) values for vascular protection were approximately 20 mg/kg for both rat and guinea pig. ED50 values for inhibition of granulocyte accumulation were 20 mg/kg for rat, 24 mg/kg for guinea pig and 30 mg/kg for rabbit. These data indicate that SC-41930 is effective locally to prevent acute colonic inflammation. 
1	Primary CT diagnosis of abdominal masses in a PACS environment Whether the display medium--film versus cathode ray tube (CRT)--affects observer performance during interpretation of computed tomographic (CT) images is an important research issue in these times of implementation and growth of picture archiving and communications systems in radiology. The authors performed a multiobserver receiver operating characteristic (ROC) study to determine the performance of radiologists who read abdominal CT studies displayed on film, as well as on a high-resolution workstation (video monitor) that made use of three different display modes. A total of 166 examinations were evaluated by eight radiologists, who recorded their ordinal confidence ratings of the demonstration of presence or absence of abdominal masses. ROC analysis showed small differences in the confidence ratings assigned by individual readers for the detection and interpretation tasks. Results for the group as a whole showed no significant reduction or improvement in observer performance when ratings for any one of the workstation display modes were analyzed. The results of this study demonstrate that current CRT display technology is adequate for enabling the primary detection of abdominal masses with CT examinations. 
5	Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures in the rat. The effects of acute changes in plasma magnesium concentration on the threshold for lidocaine-induced seizures were evaluated in mechanically ventilated rats receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were intravenously administered either 0.9% sodium chloride (group I) or 5.0% magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or 10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate, resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per minute) was begun in both experiments. Biparietal electroencephalographic activity was monitored continuously. At the onset of electroencephalographic seizure activity, arterial plasma magnesium and lidocaine concentrations were measured. In groups I and III (experiment 1), brain parenchymal magnesium was also assayed. There were no differences in plasma lidocaine concentrations (in experiments 1 or 2) between saline solution and hypermagnesemic groups at onset of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion. We conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures. 
4	Comparison of supraannular and subannular pledgeted sutures in mitral valve replacement Ten fresh canine hearts were used to compare the peak left ventricular pressure required to disrupt prosthetic mitral valves sutured in place with horizontal mattress sutures with either subannular or supraannular pledgets. Each group consisted of 5 animals. A 29-mm Medtronic mitral valve was secured in the mitral position with ten pledgeted sutures. The aorta was cannulated and normal saline solution was infused into the left ventricle until valvar disruption occurred. The peak pressure and the location and mechanism of disruption were then noted. At the peak left ventricular pressure required for valvar disruption, no individual sutures were broken. Instead, in all specimens a subannular myocardial rupture occurred in the posterior portion of the mitral annulus along the extent of the atrioventricular groove. In addition, the posterior wall of the left atrium dissected upward subsequently. Significantly greater pressures were required in the group with subannular suture placement as compared with the supraannular group (354 +/- 37 versus 236 +/- 33 mm Hg; p less than 0.0007). These data suggest that placement of horizontal mattress sutures with pledgets in the subannular position is superior to the currently recommended method of supraannular suture placement in mechanical valves. 
2	Segmented turboFLASH: method for breath-hold MR imaging of the liver with flexible contrast. A method called segmented turboFLASH imaging allows high-resolution, multisection, short-inversion-time (TI) inversion-recovery (STIR), T1- or T2-weighted magnetic resonance (MR) studies of the liver to be completed within a breath-hold interval. The method was applied in a phantom and in 19 patients with hepatic lesions. Sequence comparisons were performed among segmented turboFLASH, single-shot turboFLASH, T1-weighted gradient-echo with ultrashort echo time, and T2-weighted spin-echo (SE) techniques. Signal from fat and liver could be nulled with the segmented turboFLASH method, with TIs of 10 and 300 msec, respectively; signal from these tissues could not be eliminated with the single-shot approach. Signal-difference-to-noise ratios and contrast for the best segmented sequences were comparable with those of the best T2-weighted SE and T1-weighted gradient-echo techniques. It is concluded that it is feasible to obtain breath-hold images with arbitrary tissue contrast by means of segmented turboFLASH imaging. The method may prove helpful for the detection and characterization of hepatic lesions and will likely have applications to other anatomic regions such as the chest and pelvis. 
5	Treatment of infection after total knee arthroplasty by debridement with retention of the components. Thirty-one total knee arthroplasties were followed by infection in twenty-seven patients who were subsequently treated with debridement, retention of the components, and intravenous administration of antibiotics. The results were reviewed retrospectively in an effort to evaluate the function of the prostheses that had been salvaged successfully and to identify the causes of failure of those around which an infection had recurred. At the most recent follow-up (average duration, 8.8 years), infection had recurred around twenty-four (77 per cent) of the thirty-one arthroplasties. Seven knees (23 per cent) remained free of infection. Function remained satisfactory, although revision was subsequently needed in two knees for reasons other than infection. One cause of failure was the duration of the infection before debridement. This averaged twenty-one days for the seven knees in which the prosthetic arthroplasty had been salvaged and thirty-six days for the twenty-four knees in which treatment had failed. Another cause of failure was the type of organism: Staphylococcus aureus had caused the infection in fourteen (58 per cent) of the twenty-four knees in which the treatment failed but in only two of the seven knees in which the prosthetic arthroplasty was salvaged. In addition, eight infections in the first group were resistant to penicillin, whereas both infections in the second group were sensitive to penicillin. The four infections with gram-negative organisms in the series were all in knees in which the treatment failed. All six hinged prostheses that were used failed. 
3	Effect of nimodipine on acute ischemic stroke. Pooled results from five randomized trials. In a review of pooled data from five double-blind, placebo-controlled studies of nimodipine in acute ischemic stroke, we compared the effect of 120 mg nimodipine given orally with that of placebo. In the five studies, 871 patients were followed, and 781 adhered to entry and inclusion criteria. End points were mortality and outcome at the end of the treatment period (21 or 28 days). Outcome was assessed with Mathew's scale and the physician's clinical judgement. The treatment and control groups were well matched with respect to demographic data, risk factors, and baseline Mathew scores. In the treatment group, 34 patients (7.9%) died during the treatment period, whereas 54 (12.3%) in the control group died, corresponding with a mortality reduction of 36%. Significantly less neurologic impairment at the end of the treatment period was documented under nimodipine treatment, and this impairment improved more in patients with moderate-to-severe stroke (baseline Mathew score less than 66) if administration of nimodipine occurred within 12 hours after stroke onset or if the patient was more than 65 years old. The overall incidence of adverse reactions was relatively modest, and these were of minor severity; only a few appeared to have more than a remote relation to the study medication. 
5	Isolated lung transplantation for pulmonary fibrosis. The peri-operative anaesthetic management of 11 patients with pulmonary fibrosis undergoing single-lung transplantation is presented. Intra-operative problems, the early postoperative phase of recovery and intensive care, and other incidents in which general anaesthesia was required for the management of complications, are featured. Results, both short- and long-term, are mentioned. Major intra-operative events that cause concern appear to be related to the severity of the presenting illness and the development of respiratory failure. Others have reported the development of intra-operative cardiac failure. All cases were successfully managed operatively using conventional one-lung anaesthesia, although resort to partial cardiopulmonary bypass may have been indicated in some. The indications and attitudes to utilising cardiopulmonary bypass in the evolution of techniques for facilitating single-lung transplantation are reviewed. 
3	Cerebral palsy and rhizotomy. A 3-year follow-up evaluation with gait analysis. A recent increase in the popularity of selective rhizotomy for reduction of spasticity in cerebral palsy has led to a demand for more objective studies of outcome and long-term follow-up results. The authors present the results of gait analysis on 14 children with spastic cerebral palsy, who underwent selective posterior rhizotomy in 1985. Sagittal plane gait patterns were studied before surgery and at 1 and 3 years after surgery using a digital camera system. The parameters measured included the range of motion at the knee and thigh, stride length, speed of walking, and cadence. The range of motion at the knee was significantly increased at 1 year after surgery and further improved to a nearly normal range at 3 years after surgery. In contrast, postoperative measurements of thigh range exceeded normal values at 1 year, but decreased toward normal range at 3 years. While improvements in range of motion continued between Years 1 and 3, the children developed a more extended thigh and knee position, which indicated a more upright walking posture. Stride length and speed of walking also improved, while cadence remained essentially unchanged. This 3-year follow-up study, the first to examine rhizotomy using an objective approach, has provided some encouraging results regarding early functional outcome. 
2	Sjogren's syndrome and primary biliary cirrhosis: presence of autoantibodies to purified mitochondrial 2-OXO acid dehydrogenases. Sjogren's syndrome is well known for the presence of antibodies directed at specific nuclear antigens. However, the presence of antibodies reacting with a variety of other self antigens, including antimitochondrial antibodies, has often been reported although their significance is unknown. Moreover, patients with Sjogren's syndrome have been occasionally reported to be concordant with primary biliary cirrhosis. To address this issue we studied in a group of 96 patients with Sjogren's syndrome the presence of autoantibodies to the dihydrolipoamide acetyltransferases of both pyruvate dehydrogenase and branch chain ketoacid dehydrogenase and to alpha-ketoglutarate dehydrogenase; these latter enzymes are the mitochondrial target antigens of primary biliary cirrhosis. We report that 7 of the 96 patients reacted with the mitochondrial antigens that are prominent in primary biliary cirrhosis. Moreover, in those patients showing reactivity with mitochondrial antigens, the autoantibodies were directed at the same immunodominant epitopes that have been previously characterized in primary biliary cirrhosis. One of the 7 positive patients was known to have primary biliary cirrhosis. We hypothesize that the remaining 6 patients are at clinical risk for the development of primary biliary cirrhosis and/or that abnormalities would be found on liver biopsy. 
1	Molecular phenotype of a pediatric small round cell tumor. Molecular probes were used to characterize an unusual small round cell abdominal tumor arising from the fallopian tube of a 15-year-old girl. DNA and RNA extracted from the tumor and adjacent normal tissue was subjected to Southern and Northern blot analysis using a variety of different probes. N-myc oncogene RNA was greatly expressed in the tumor, but was not expressed in normal tissue or amplified in chromosomal DNA. Insulin-like growth factor II RNA was similarly overexpressed in the neoplasm, but not in normal tissue. While histopathologic studies could not distinguish between a neuroectodermal neoplasm and Wilms' tumor, electron microscopy and the pattern of gene expression was most consistent with Wilms' tumor. 
5	Rapid control of refractory atrial tachyarrhythmias with high-dose oral amiodarone. To shorten the delay in the onset of antiarrhythmic effect when using amiodarone for the conversion of refractory atrial tachyarrhythmias to sinus rhythm, 19 patients were given oral amiodarone according to a high-dose loading protocol. In 18 of 19 patients (95%), sinus rhythm was restored 36 hours (range, 0 to 96 hours) after starting amiodarone. The conversion occurred as a result of amiodarone therapy alone within 48 hours in 12 patients (63%), and by amiodarone therapy plus electrical cardioversion at 48 to 96 hours in six patients (32%). Minor side effects were noted in eight patients (42%). No major side effects were encountered. The length of hospital stay after initiating amiodarone therapy was 3.6 days (range, 2 to 5 days). High-dose oral amiodarone loading is a safe and effective method for the rapid conversion of atrial tachyarrhythmias to sinus rhythm. 
5	Elective resection for diverticular disease of the sigmoid colon. From 1966 to 1987, 177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were: colovesical fistula (n = 12), suspicion of residual abscess (n = 39), two or more previous attacks of acute inflammation (n = 52), chronic symptoms (n = 72) and suspicion of carcinoma (n = 2). An abscess was found at operation in 76 patients (43 per cent) and this was extracolic with local peritonitis in 52 patients (29 per cent). An unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms. Colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess. There were no postoperative deaths and no clinical anastomotic leakages. Long-term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms. The results of this series suggest that a one-stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease, even if an extracolic abscess is found. The good long-term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications. 
3	Asymptomatic ulnar neuropathy in carpal tunnel syndrome. Quantitative assessment of the vibration threshold of the second and fifth fingertips at 125Hz was performed on 28 affected limbs of 17 patients with carpal tunnel syndrome (CTS) together with a median and ulnar sensory nerve conduction velocity (SNCV) study. Twenty-six limbs of 26 age-matched healthy subjects were used as controls. Both the vibration threshold elevation of the second finger and the delay of median SNCV were significant in CTS patients as compared with controls (p less than .001). Although the ulnar SNCVs of all affected limbs were within the normal range, ten affected limbs (36%) were found to have a concomitant vibration threshold elevation of the fifth finger, and eight of those limbs were found to be exposed to chronic occupational mechanical stimulation at the wrist. These findings appear to support the presence of subclinical traumatic damage to the ulnar nerve at the wrist. In summary, digital vibration measurement can elucidate subclinical ulnar neuropathy in CTS which cannot be detected by SNCV studies. 
4	Long-term effects of delapril on renal function and urinary excretion of kallikrein, prostaglandin E2, and thromboxane B2 in hypertensive patients. The effects of delapril, an angiotensin converting enzyme (ACE) inhibitor, on renal function and the renin-angiotensin and kallikrein-prostaglandin systems were investigated in 10 hypertensive patients who were treated for between 4 months and 1 year. There was a significant (P less than .05) increase in renal blood flow (RBF) without affecting glomerular filtration rate. Filtration fraction increased, while renal vascular resistance decreased. There were also significant (P less than .05) increases in urinary kallikrein and prostaglandin excretion, while thromboxane excretion decreased. There was no change in urinary aldosterone excretion. These results suggest that renal hemodynamic changes seen during long-term therapy with delapril are caused, in part, by activation of the kallikrein-prostaglandin system, as well as suppression of the renin-angiotensin system. 
5	Histologic evaluation of the larynx in sudden infant death syndrome. Seventy-four larynges removed at death from children who died of sudden infant death syndrome (SIDS) have been studied by serial sectioning in the transverse plane. An increase in subepithelial glandular tissue is seen in many specimens, and the reduction in the available subglottic area has been measured with the Measuremouse Image Intensifying system. This preliminary report confirms that in some of these children with SIDS, particularly around the age of 3 months, there is a potentially lethal reduction in subglottic airway secondary to an increase in mucus-secreting glands, possibly from an associated mild upper respiratory tract infection. Accepting that adequate control infants within this age group who have not had any trauma to the laryngotracheal area are not available, these findings offer a possible explanation for what are always tragic events. 
4	Pivotal role of early and sustained infarct vessel patency in patients with acute myocardial infarction. Thrombolytic therapy in acute myocardial infarction unequivocally has improved short- and long-term mortality. The fundamental goal of therapy for evolving myocardial infarction is early and sustained infarct vessel recanalization. The mechanisms linking an open artery with improved long-term survival and other clinical outcomes are presented with use of data from extensive clinical trials. 
1	Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway. A randomized, multicenter clinical trial was conducted in Western Norway to study the effectiveness of preoperative radiation therapy in operable rectal cancer, given at a dosage of 3150 cGy in 18 fractions, 2 to 3 weeks before radical surgery. Three hundred nine patients were entered into the trial between May 1976 and December 1985. After radiation no tumor was seen in 4.5% of the patients. There was no increased morbidity or mortality at surgery. The 5-year survival for evaluable patients was 57.5% in the control group and 56.7% in the radiotherapy group. For patients operated on for cure the 5-year survival was 60.9% and 64.2% in the control group and radiotherapy group, respectively. Radiation significantly delayed both local and distant recurrences in patients in the radiation group who had curative resection from 13.3 months in controls to 27.1 months. The local recurrence rate in the corresponding groups was 21.1% and 13.7%, respectively. We conclude that higher preoperative radiation doses should be used in new trials as a higher dosage may transform the observed positive effects into a survival benefit. 
1	Multicentric endobronchial granular cell myoblastoma. Granular cell myoblastoma (GCM) is a rare benign neoplasm involving the tracheobronchial tree. It is believed to arise from the Schwann cell. Four cases of tracheobronchial GCM, all of which were multicentric, are presented and a conservative therapeutic approach is suggested. 
1	A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience. Pheochromocytoma is an unusual but potentially devastating tumor. Although a high index of suspicion is necessary, the likelihood of a pheochromocytoma is lower in the absence of the typical symptoms and findings. Nonetheless, screening must be broadened to include patients with a lower risk of the disease, such as those with resistant or labile hypertension who are minimally symptomatic. Extensive diagnostic evaluations should be reserved for those whose clinical or laboratory findings are more suggestive. Symptoms in a group of patients in whom a pheochromocytoma was seriously considered but excluded overlap symptoms in patients with a pheochromocytoma. Certain symptoms are useful: flushing to suggest a non-pheochromocytoma illness; visual symptoms, flank pain, and pallor to suggest that a pheochromocytoma is more likely. Combinations of symptoms can be of value: 2 or more symptoms from the triad of headache, palpitations, and diaphoresis were present in the majority of pheochromocytoma patients, but in a smaller number of non-pheochromocytoma patients. The presence of the entire triad is more specific, but less sensitive. New hypertension, or hypertension associated with unexplained orthostatic hypotension, are suggestive of an underlying pheochromocytoma. Twenty-four-hour urine studies are consistently abnormal in patients with a pheochromocytoma, but are also elevated in a significant proportion of non-pheochromocytoma patients. Values greater then 1.5-2-fold above the upper limit of normal are very suggestive that a pheochromocytoma is present, and warrant a more intensive subsequent evaluation. Imaging studies are reliable in the diagnosis of pheochromocytoma, and can help to confirm or exclude the disease. Patients with a higher clinical likelihood and any elevated urinary testing, or with a lower clinical likelihood and persistently and/or significantly elevated urinary testing, should have imaging studies performed. This combination of clinical screening, 24-hour urinary testing, and imaging studies is a useful and reliable approach to patients suspected of harboring a pheochromocytoma. 
3	An improved photochemical model of embolic cerebral infarction in rats. To provide further evidence that the multiple cerebral infarcts found in rats following photochemical damage to the carotid artery are caused by emboli and to eliminate the systemic hypotension and heating of the blood reported with the previous photochemical embolic stroke model (rose bengal and a green laser), I have modified the photochemical technique. Brain pathology was studied in 18 Wistar rats following carotid artery irradiation with a red laser (632 nm) at powers ranging from 100 to 800 mW/cm2 for 10 or 20 minutes following the injection of the photosensitizing dye Photofrin II. Multiple cerebral arterioles were occluded by platelet aggregates containing frequent erythrocytes and leukocytes, identical to the thrombotic material in the carotid artery but different from the platelet aggregates seen in the carotid artery and the brain in the rose bengal model. Eighty infarcts were distributed randomly throughout the brain ipsilateral to the nonocclusive carotid thrombus. Significant heating (0.5 degree C or more) of the blood occurred only with laser powers higher (1,600 mW/cm2) or laser irradiations longer (25 minutes) than those used in the improved model of embolic stroke. This model mimics one mechanism of stroke in humans and provides a means to study systematically the morphological evolution of small cerebral infarcts. 
2	Effects of vasopressin on portal pressure during hemorrhage from esophageal varices. Vasopressin is often used to treat variceal hemorrhage. However, its efficacy is uncertain, and its portal hemodynamic effects in this setting are unknown. Eleven patients with alcoholic liver disease and bleeding varices were given vasopressin (0.2 U/min for the first hour, then 0.4 U/min for 24 hours). Portal pressure was monitored using an indwelling hepatic vein balloon catheter. Seventeen patients with variceal bleeding who remained stable over 26 hours of initial treatment with crystalloid and blood products served as a comparison group. Vasopressin infusion (0.2 U/min) produced a significant decrease in wedged hepatic venous pressure, hepatic venous pressure gradient (wedged minus free hepatic venous pressure), and heart rate. Increases in the rate of infusion did not produce further decreases in the parameters measured, but the changes were sustained over the course of the infusion. Hemodynamics remained stable in the control group. Portal pressure did not increase when vasopressin was abruptly discontinued in the 3 patients in whom postinfusion measurements were made. Vasopressin retains its portal hypotensive effects in the setting of variceal hemorrhage. Tachyphylaxis does not develop over 26 hours, and a "rebound" increase in portal pressure probably does not occur when the infusion is discontinued. 
2	Helicobacter pylori infection in patients with acquired immune deficiency syndrome. A controlled study was conducted on patients with human immunodeficiency virus (HIV) infection referred for upper endoscopy to evaluate the prevalence of Helicobacter pylori (H. pylori) infection. Four different stains and culture for H. pylori were performed on biopsy specimens from the gastric antrum. Sixteen (40%) of 40 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were diagnosed to be infected with H. pylori versus 14 (39%) of 36 age-matched control patients. Eight of 15 AIDS/ARC patients without AIDS-related esophagogastroduodenal findings (53%) were infected with H. pylori versus 8/25 (32%) with endoscopic findings typical of AIDS. No invasion of the lamina propria by H. pylori was noted in any patient. Active chronic gastritis was present in 60% of AIDS/ARC patients and 61% of controls. Fifty-eight and 59%, respectively, of active chronic gastritis cases were infected with H. pylori. All the H. pylori infections, except one, were found in patients with chronic gastritis. In AIDS/ARC patients, H. pylori infection and active chronic gastritis are as common as in other patients referred for upper endoscopy. They may play a pathogenic role, especially when endoscopic AIDS-related findings are lacking. Cell-mediated immune deficiency does not appear to increase the risk of infection with H. pylori. 
5	Recurrent pain, illness intrusiveness, and quality of life in end-stage renal disease. Repeated episodes of headache and muscle cramp were hypothesized to contribute to increased patient perceptions of illness intrusiveness and to compromised quality of life. Standard measures of pain, illness intrusiveness, and quality of life were obtained on 2 occasions, each 6 weeks apart, from 100 end-stage renal disease patients. The impact of recurrent muscle cramps on perceptions of illness intrusiveness was conditional upon the occurrence of headache symptoms. Perceptions of illness intrusiveness were significantly higher when both muscle cramp and headache symptoms occurred during one or more assessment intervals as compared to when muscle cramps or headaches, only, occurred. Illness-related concerns and general feelings of pessimism were also significantly higher among patients who experienced recurrent episodes of muscle cramp. Although no direct relations were observed between pain and other quality of life indicators, previous research has documented a relation between illness intrusiveness and quality of life. Recurrent pain problems, thus, appear to contribute to increased illness intrusiveness and to reduced quality of life in end-stage renal disease patients. 
2	Reoperative surgery for the morbidly obese. A university experience. Patients who undergo surgery for morbid obesity are often subjected to reoperation for a wide array of indications. To evaluate outcome following revisional procedures, we reviewed the records of 32 such patients treated at UCLA between April 1986 and May 1989. Twenty-five women (78%) and 7 men (22%) with a mean age of 44 years underwent 76 reoperations (2.4 per patient) for complications of prior obesity surgery. Indications for initial surgical revision consisted primarily of metabolic derangements (12 patients) and weight-related problems (11 patients). In contrast, indications for the patients' final surgical procedure were commonly for bowel obstruction (41%), intra-abdominal sepsis (12%), and gastrointestinal bleeding (6%). Following initial revision, 23 patients (71.8%) required further surgery for major complications and four patients died (12.5%). While initial revisions are frequently indicated for metabolic problems, final reoperations are more frequently undertaken for urgent, life-threatening complications. Revisional procedures for morbid obesity should be carefully considered, and the potential for major complications and/or death should be weighted heavily against proposed benefits. 
3	Cerebral circulation and metabolism in patients with septic encephalopathy. Cerebral circulation and metabolism in septic encephalopathy have not been well documented. The authors measured cerebral blood flow (CBF) and metabolic rate for oxygen (CMRO2) in six patients with septic encephalopathy associated with multiple organ failure (three to five organs). They found that CBF and CMRO2 were significantly lower than awake control values of 46 +/- 2 to 28 +/- 3 mL/100g/min (mean +/- SEM) and 3.1 +/- 0.2 to 1.2 +/- 0.2 mL/100g/min, respectively. Cerebral vascular resistance (CVR) and cerebral circulatory index (CCI:CBF/CMRO2) were significantly higher than the control values of 2.0 +/- 0.1 to 3.0 +/- 0.4 mm Hg/mL/100g/min and 15.1 +/- 0.8 to 24.2 +/- 3.3, respectively. At the time of cerebral circulatory and metabolic measurements, their consciousness varied between 4 and 10 as evaluated by the Glasgow coma scale. The electroencephalogram showed diffuse slow wave activity and the latency of the auditory brain stem evoked response was prolonged in four of six patients. Computed brain tomography showed either no abnormality or mild atrophy. It is concluded that CBF and CMRO2 are disproportionally decreased during septic encephalopathy in association with dysfunction of the CNS and decreased electrical activity. 
1	Impaired polymorphonuclear leucocyte function in patients undergoing hepatectomy: adenylate energy charge and superoxide anion production in relation to hepatic mitochondrial redox state. Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studied the energy metabolism of the polymorphonuclear leucocyte (PMN), focusing on energy charge and function, especially superoxide anion (O2-) generation, in relation to the hepatic mitochondrial redox state. By labelling the PMN adenine nucleotide pool with radioactive adenine and by superoxide dismutase-inhibitable reduction of ferricytochrome c, the energy charge and O2- production was measured in 18 patients with hepatoma (non-cirrhotic, seven; cirrhotic, 11) undergoing hepatectomy. Their arterial ketone body ratios (KBRs), reflecting the hepatic mitochondrial redox potential, were above 0.7 before operation. After surgery, the 18 patients were divided into two groups: group A, KBR greater than 0.7, n = 10; and group B, KBR less than 0.7, n = 8. The energy charge and O2- release in group B decreased significantly from preoperative values (P less than 0.001 and P less than 0.01 respectively) and when compared with group A (P less than 0.05 and P less than 0.01 respectively). These results suggest that impaired hepatic energy metabolism (KBR less than 0.7) in hepatectomized patients leads to impaired energy charge and O2- production in the PMNs. 
2	Hemoperitoneum as a result of coital injury without associated vaginal injury. Hemoperitoneum as a result of coital injury without associated vaginal injury is an extremely rare entity, and evidence by only five cases that have been reported in the medical literature to date. We report five additional cases encountered in two medical centers. Two of these were ruptured corpus luteum cysts, one was a laceration of the round ligament, another was a laceration of an ovary, and the fifth was rupture of a serous cystadenoma. This diagnosis should be considered in patients with hemoperitoneum after coitus. 
4	Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience. Fifty-six patients affected with hereditary angioedema have been followed during long-term prophylaxis with attenuated androgens. The treatment was started in patients who had one or more severe attacks per month. In 24 patients, the therapy lasted for more than 5 years. The minimal effective dose usually did not exceed 2 mg/day of stanozolol or 200 mg/day of danazol. Only in two patients were these doses not sufficient to achieve the complete disappearance of symptoms. Irregular menstruation, but rarely amenorrhea, was the only significant side effect. One patient had to stop the therapy because of laboratory signs of hepatic cell necrosis. In one patient, danazol was administered during the last 8 weeks of pregnancy without side effects for the mother but with transient signs of virilization for the female baby. To find a biochemical marker for the minimal effective dose of androgen derivatives, we measured the plasma levels of C1 C1 INH complexes at different doses of stanozolol in four patients with hereditary angioedema. We found that these complexes, elevated before treatment, promptly reverted to normal values during androgen therapy and remained normal with any reduction of the dose of the drug as long as the patient remained symptom free. Therefore, the measurement of C1 C1 INH complexes appears to reflect the activity of the disease and not the amount of androgen that is administered. 
4	Reappraisal of the mechanism for cerebrospinal fluid hypertension during aortic surgery. Cerebrospinal fluid (CSF) hypertension during aortic surgery is a poorly understood, multifactorial event that may increase the risk of spinal cord injury. To assess the factors that may contribute to changes in CSF pressure during aortic surgery, measurements of ascending arterial and CSF pressures were made in 17 anesthetized mongrel dogs. Changes in CSF patterns were monitored under several conditions tested in random sequence. These included systemic hypertension produced by an infusion of phenylephrine, cross-clamping of the descending thoracic aorta, and manual, superior displacement of the transverse aortic arch (arch elevation), either alone or in conjunction with the cross-clamp. Hypertension, cross-clamping, and cross-clamping combined with arch elevation all produced significant increases in ascending mean arterial pressure (204 +/- 20, 170 +/- 8, and 158 +/- 11 mm Hg, respectively, vs. 117 +/- 8 mm Hg [control]; (p less than 0.01). Small, nonsignificant increases in CSF pressure were detected in the cross-clamp group, but none were detected with hypertension alone, despite significant increases in ascending arterial blood pressure in both groups. Thus, neither arterial hypertension nor cross-clamping alone could be demonstrated directly to cause significant CSF hypertension. However, when aortic elevation (displacement) was combined with cross-clamping, the rise in CSF pressure increased to significant levels, even though the ascending arterial hypertension was least severe in this group. In contrast, arch elevation alone did not produce any significant increase in ascending arterial pressure but did produce an approximately 114% increase in CSF pressure (15.2 +/- mm Hg vs. 7.7 +/- 1 mm Hg [control]; p less than 0.01. 
1	A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients. Patients were stratified according to whether or not there were bone metastases only. Four hundred twelve patients entered this trial; 378 were assessable for tolerability and 365 for efficacy. The overall response rates were comparable between FEC 50 (44.6%) and FEC 75 (44.7%), but both were better than the epirubicin alone (30.6%) (P = .04 and P = .0006, respectively). The complete response rate was better in FEC 75 (15.5%) than in FEC 50 (7%) (P = .025) or epirubicin (4%) (P = .002). Similar results were obtained in the group of patients without bone-only metastases. No difference in the three treatments was observed in the patients with bone metastases only. Mean durations of response were similar in the three groups, being 412 days, 440 days, and 350 days for FEC 50, FEC 75, and epirubicin, respectively. Patients without previous adjuvant chemotherapy fared better than those with previous treatment (without anthracyclines). Tolerability was fair in the three groups. Overall, the epirubicin-alone group showed better tolerance than the two other groups, which did not differ significantly. Time to progression and survival were not different among the three groups, but more early relapses occurred in the epirubicin and FEC 50 groups; survival seemed to be better during the first 8 months in the FEC 75 group, and the survival difference between the epirubicin group and the FEC 75 group was of borderline significance. No difference in survival was observed between epirubicin- and FEC 50-group patients, even though the response rate was significantly worse in the monochemotherapy group. 
5	Changes in circulating norepinephrine with hemofiltration in advanced congestive heart failure. In congestive heart failure (CHF), hemofiltration is associated with an obvious decrease in circulating norepinephrine. This method was used for investigating the mechanisms whereby plasma norepinephrine is increased in chronic CHF. In 23 cases of advanced CHF, hemofiltration (2,983 +/- 1,228 ml) lowered plasma norepinephrine by 515 +/- 444 pg/ml. This effect was prompt, persisted or became greater in the next 24 hours. It was not associated with significant changes in cardiac output, aortic pressure or systemic vascular resistance. It did not appear to depend on variations in parameters related to the sympathetic activity, such as plasma renin, right atrial, wedge pulmonary artery and renal perfusion pressures, and was independent of duration and amount of hemofiltration. These observations did not support the concept that the norepinephrine decrease was the main consequence of a neural sympathetic inhibition. Hemofiltration increased diuresis by 606 +/- 415 ml; changes were prompt and correlated inversely (r = -0.7; p less than 0.01) with those in plasma norepinephrine. The same unknown mechanism of the increased urinary output might potentiate the norepinephrine removal from the blood by the kidney, or hemofiltration and the augmented diuresis might result in a regression of congestion of lungs and kidneys, leading to an improved extraction of norepinephrine. In CHF, a relation may exist between fluid retention and norepinephrine and in advanced stages, circulating norepinephrine, although strikingly increased, is devoid of important cardiovascular effects. At these stages, plasma norepinephrine is probably unreliable as an index of the sympathetic neural activity. 
5	Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy. In miniature pigs, retinal veins were experimentally occluded using argon laser coagulation. Microvascular modifications leading to retinal hemorrhages and retinal edema were observed some hours after the occlusion. These lesions resolved progressively within 3 weeks after the occlusion, but in most cases ischemic retinal territories persisted. Preretinal partial pressure of oxygen (PO2) measurements, using double barrelled O2-sensitive microelectrodes, showed that all the ischemic areas were indeed hypoxic. In half of the experiments, preretinal and intravitreal new vessels grew on the ischemic territories. Tissue hypoxia appears to be a key step in triggering neovascularization. However, the critical level of hypoxia was not determined. 
3	Development of a traumatic intracranial hematoma after a "minor" head injury. We have analyzed features of patients who had what appeared initially to be a minor head injury but who developed an acute traumatic intracranial hematoma. Over a 10-year period, 183 patients who were able to open their eyes spontaneously, were oriented to person, place, and time, and who obeyed commands when they were first seen at a hospital subsequently underwent operation for an acute intracranial hematoma. The hematoma was extradural in 54% of these patients. A history of altered consciousness or symptoms of headache and vomiting were present in 61% of the patients; 33% had a focal neurological deficit, and 43% had either focal deficit or signs of a basal skull fracture. A skull fracture was shown radiologically in 60% of patients, including 52% of those not clinically suspected of having an intracranial lesion. Six months after injury, 77% of the patients had made a moderate or good recovery. The possibility that a patient who has recently sustained a head injury might develop an acute intracranial hematoma can never be completely discounted, even when there are no abnormal clinical signs, and a skull x-ray retains a useful place in the investigation of selected patients with a minor head injury. 
1	Increased epidermal growth factor receptors in seborrheic keratoses and acrochordons of patients with the dysplastic nevus syndrome. Seborrheic keratoses and acrochordons may change in biologic behavior with pregnancy or during treatment with sex steroids. Because epidermal growth factor receptor localization may change in hyperproliferative skin diseases, we compared epidermal growth factor receptor immunolocalization in seborrheic keratoses and acrochordons from women who were or were not pregnant or taking oral sex steroid hormones. Epidermal growth factor receptor was further investigated in growing and quiescent seborrheic keratoses and acrochordons from women with and without the dysplastic nevus syndrome. The epidermal growth factor receptor concentration was strikingly elevated in suprabasilar keratinocytes of growing seborrheic keratoses and acrochordons from patients with the dysplastic nevus syndrome who were pregnant or taking sex steroid hormones and less elevated in growing seborrheic keratoses from other patients. In contrast, the epidermal growth factor receptor distribution pattern in acrochordons did not correlate as well with the history of growth of these lesions in normal patients. These data suggest sex steroids may affect epidermal growth factor receptor metabolism in benign epidermal hyperproliferative lesions, particularly in patients with the dysplastic nevus syndrome. 
5	Effect of delayed captopril therapy on left ventricular mass and myonecrosis during acute coxsackievirus murine myocarditis. The effect of captopril on coxsackievirus B3 murine myocarditis was investigated. Thirty-two, 3-week-old mice were infected with coxsackievirus B3 on day 0 of the study, then randomized into a placebo group or a captopril group starting on day 3 of infection. On day 9 of infection, the mice were put to death. Hearts were weighed and processed for light microscopic examination. Heart weight was 125 +/- 19 mg in the control group versus 102 +/- 14 mg in the captopril group (p less than 0.0003). Amount of necrosis as a percentage of left ventricular section was 3.5% (2.0% to 7.5%) in the placebo group versus 2.0% (0.0% to 5.0%) in the captopril group (p less than 0.01). The amount of dystrophic calcification was 5.0% (0.0% to 27.5%) in the placebo group versus 1.3% (0.0% to 20.0%) in the captopril group (p less than 0.01). The extent of the histopathologic involvement by planimetry was 10.2% in the placebo group versus 5.4% in the captopril group (p = 0.052). We conclude that captopril is beneficial in decreasing left ventricular mass and the amount of myocardial necrosis and calcification in the short term in the murine myocarditis model. 
5	Medical treatment and prevention of peptic ulcer disease. Many agents seem to be equally effective for the treatment of peptic ulcer disease. This is true despite the drugs' varied mechanisms of action, and this observation has caused investigators to shift their focus from aggressive to defensive factors when studying ulcer pathogenesis. Patients with a healed ulcer are always at risk for recurrence, and guidelines are available for management of these patients. Ulcer prevention becomes a crucial issue in intensive care units where critically ill patients have many known risk factors. Maintaining a gastric pH above 4.0 appears to reduce the morbidity and mortality associated with such stress-induced ulcers. Use of nonsteroidal anti-inflammatory drugs increases ulcer risk and complications in the elderly, in women with rheumatoid arthritis, and in smokers and abusers of alcohol. Prophylaxis with the synthetic prostaglandin analogue misoprostol (Cytotec) appears to reduce this risk. 
5	Esophageal involvement in pemphigus vulgaris: a clinical, histologic, and immunopathologic study. Eleven newly diagnosed patients and one patient with pemphigus vulgaris who relapsed underwent endoscopy of the upper gastrointestinal tract. Three patients had blisters or erosions and two had longitudinal lines of erythema in the esophageal mucosa. In four patients histopathologic examination showed findings of pemphigus vulgaris but direct immunofluorescence was positive in all patients. This study demonstrates that the immunopathologic disturbance in pemphigus vulgaris involves the entire length of the esophagus, although only some patients have clinical or histologic involvement. To the best of our knowledge this is the first histopathologic and direct immunofluorescence study of esophageal involvement in patients with untreated pemphigus vulgaris. 
2	Endoscopic findings in Yersinia enterocolitica enterocolitis. The endoscopic findings in the colon and terminal ileum in eight cases of Yersinia enterocolitica enterocolitis infection were studied. The diagnosis was based on the isolation of Y. enterocolitica in the feces and/or elevated serum antibody titers to the organism. Total colonoscopy was performed between 7 and 38 days (mean, 24 days) after the onset of symptoms. In all patients, the terminal ileum was affected, followed by frequent involvement of the ileocecal valve and the cecum, and less frequently, the ascending colon. In the terminal ileum, round or oval elevations with or without ulcers were detected. Small ulcers were detected on the ileocecal valve and in the cecum. These findings were observed even 4 to 5 weeks after the onset of symptoms, suggesting a relatively long course for this disease. 
5	Estrogen receptor level determines sex-specific in vitro transcription from the Xenopus vitellogenin promoter. Female-specific expression of the Xenopus laevis vitellogenin gene was reconstituted in vitro by addition of recombinant vaccinia-virus-produced estrogen receptor to nuclear extracts from male livers, in which this gene is silent. Transcription enhancement was at least 30 times and was selectively restricted to vitellogenin templates containing the estrogen-responsive unit. Thus, in male hepatocytes, estrogen receptor is the limiting regulatory factor that in the female liver controls efficient and accurate sex-specific expression of the vitellogenin gene. Furthermore, the Xenopus liver factor B, which is essential in addition to the estrogen receptor for the activation of this gene, was successfully replaced in the Xenopus extract by purified human nuclear factor I, identifying factor B of Xenopus as a functional homolog of this well-characterized human transcription factor. 
5	Left ventricular diastolic dysfunction presenting as ascites: the importance of clinically assessing central venous pressure. A 66-year-old man without history of heart disease or symptoms of left ventricular (LV) failure was admitted with transudative ascites. Echocardiography showed no valvular or pericardial disease and normal LV function. Gated pool scintigraphy confirmed normal LV systolic function but demonstrated severe right ventricular systolic dysfunction. Catheterization revealed left ventricular diastolic dysfunction as the cause of right-sided failure. The clinician evaluating transudative ascites cannot exclude LV failure on the basis of noninvasive assessment of systolic function alone. Appreciation of an elevated central venous pressure remains the most important evidence of a cardiac source of ascites. 
5	The relationship of "high risk" mammographic patterns to histological risk factors for development of cancer in the human breast. In the UK Trial for the Early Detection of Breast Cancer in Nottingham, 119 women were identified as having fibrocystic change with epithelial hyperplasia or in situ carcinoma. Their mammograms were classified according to Wolfe's criteria and the corresponding histology for each patient was classified for degrees of epithelial hyperplasia, atypia and in situ neoplasia using Page's criteria. A control population of patients presenting for breast screening was used to represent the general population. No correlation was found between the four mammographic Wolfe patterns, N1, P1, P2 and DY and histological evidence of epithelial hyperplasia, atypia or in situ carcinoma. A further study was carried out to determine histological features of Wolfe pattern, using radiological examination of resected breast tissue. The variation in Wolfe pattern was related to the distribution of fibrous and adipose tissue in the breast interlobular stroma and appeared to have no relationship to epithelial parenchymal content. This information does not support the hypothesis that radiographic densities of P2 and DY patterns correspond to high risk epithelial proliferation. 
4	Five-year experience with triple-drug immunosuppressive therapy in cardiac transplantation. Although triple-drug immunosuppression with a combination of cyclosporine, prednisone, and azathioprine has been shown to improve short-term survival after cardiac transplantation, its long-term effects still are unknown. From December 1983 through December 1988, all patients (N = 139) who underwent orthotopic cardiac transplant at our institution received triple-drug immunosuppressant therapy. Follow-up averaged 32.2 +/- 15.8 months. Twenty-one patients died; 134 survived more than 30 days. Actuarial survival was 92% at 1 year, 85% at 3 years, and 78% at 5 years. Twenty-five episodes of acute graft rejection were diagnosed in 21 of the 139 recipients (0.18 episode per patient). In patients, the incidence of infection was 0.82 episode; 72% of infections were viral, with 10% due to cytomegalovirus. The incidence of coronary artery disease was 10% at 1 year, 25% at 3 years, and 36% at 5 years. Coronary artery disease was responsible for 60% of late deaths. Arterial hypertension developed in 81% of patients, despite relatively well-maintained renal function (serum creatinine, 1.7 +/- 0.3 mg/dl). Skeletal complications occurred in 15.8% and lymphoma in 1.4% of recipients. Complete long-term rehabilitation was achieved in all but two of the surviving patients. These data support the short- and long-term effectiveness of triple-drug therapy. This regimen reduces the incidence of rejection, infection, and lymphoma, as well as the degree of renal failure. However, the incidence of posttransplant coronary artery disease has not been reduced, and graft atherosclerosis represents the major cause of late graft failure and death. 
1	Nephrotic syndrome complicating adenocarcinoma of the lung with resolution after resection. Nephrotic syndrome is an uncommon complication of lung cancer. We present a case in which adenocarcinoma was complicated by the nephrotic syndrome, which resolved after resection of the cancer. 
4	Effects of felodipine on urinary albumin excretion and metabolic control in hypertensive non-insulin-dependent diabetics. The effect of a blood pressure reduction by 10 mg extended release felodipine once daily on urinary albumin excretion (UAE) as well as the possible diabetogenic effect of felodipine was studied. A 2 X 12 week placebo-controlled double-blind crossover study was performed in 12 hypertensive non-insulin-dependent diabetic (NIDDM) patients without nephropathy on concomitant treatment with beta-blocker and/or a diuretic agent. Metabolic control as estimated by fasting plasma glucose, hemoglobin A1c and fasting plasma C-peptide was unaltered after felodipine. Blood pressure was significantly reduced by felodipine: systolic 166 +/- 26 mm Hg (placebo) v 153 +/- 26 mm Hg (felodipine) (P less than .05) and diastolic 95 +/- 7 mm Hg v 90 +/- 8 mm Hg (P less than .05). Heart rate was unchanged. There was no correlation between blood pressure and UAE, but the relative change in UAE expressed as UAE placebo/UAE felodipine was significantly correlated to the fall in systolic blood pressure (r = 0.64, P = .03) and mean blood pressure (r = 0.66, P = .02). Since microalbuminuria predicts proteinuria and reduced survival, early antihypertensive treatment may be beneficial in NIDDM as it is in IDDM. Long-term consequences on kidney function and mortality remains, however, to be elucidated. 
5	Experimental oral foreign body reactions: vegetable materials. Foreign bodies and tissue reactions to foreign materials are commonly encountered in the oral cavity. Exogenous materials most commonly causing foreign body reactions are metallic in origin (usually amalgam). Of the nonmetallic materials seen during biopsies, suture materials and vegetable matter are most often observed. Since many foodstuff foreign materials are unidentifiable histologically, common vegetables were experimentally implanted subcutaneously in rats to assess local host responses and to characterize the nature of these materials microscopically. The histologic characteristics of these vegetable foreign body reactions are detailed herein. The implanted materials correspond to reactions seen in human subjects. 
5	Estimation of Reynolds stresses within the Penn State left ventricular assist device. Fluid velocities were measured using a two-component laser Doppler anemometery (LDA) system at 129 locations within a Plexiglas model of a 70 cm3 Penn State electric Left Ventricular Assist Device (LVAD). The LVAD was driven by a pulsatile piston pump acting on an attached segmented polyurethane diaphragm. Bjork-Shiley tilting disc valves were used to provide unidirectional flow through the inlet and outlet ports. A seeded blood analog fluid, which matched the kinematic viscosity of blood at high shear rates and the refractive index of Plexiglas, was used to make the measurements. At each location, 250 instantaneous velocity realizations were collected at eight instances during the pump cycle. The maximum Reynolds shear and normal stresses were calculated for each pump cycle time and location after filtering the data. The results reveal that the highest Reynolds shear and normal stresses occur in the near wall region just proximal to the aortic valve during diastole, and reach values of 5,300 dynes/cm2 and 10,800 dynes/cm2, respectively. The elevated turbulent stresses are observed during the period of regurgitant flow through the aortic valve, with peak stress values arising during the period of peak regurgitant flow. This supports the hypothesis that a regurgitant turbulent jet is formed near the wall of the prosthetic aortic valve and may be contributing to blood damage. 
4	Intestinal permeability in patients with chronic urticaria-angioedema with and without arthralgia. We evaluated the clinical response to oligoallergenic dietary treatment and the intestinal absorption of a protein antigen, cow milk beta-lactoglobulin (BLG) in 24 patients with chronic urticaria/angioedema syndrome 13 of whom also suffered from joint symptoms. Sixteen patients (77% of those with arthralgia) responded to diet (RD) with marked reduction of symptoms; the others did not respond (NR). Ten (all but one RD with arthralgia) had increased permeability to BLG after oral administration of cow milk. Four with high titers of IgG to BLG showed the highest absorption of BLG and the groups with arthralgia showed higher BLG levels than those without arthralgia. In all cases, specific IgE to cow milk was absent. These data suggest that the symptoms of a subgroup of patients with chronic urticaria, and especially patients with joint complaints that subside with diet, are related to excess intestinal permeability. The measurement of gut permeability to food proteins may be useful to define those who may benefit from dietary restriction. 
5	Balloon catheter tamponade in cardiovascular wounds. From 1980 to 1990, operative balloon catheter tamponade was used in 12 patients with cardiac or vascular injuries from penetrating wounds. In nine patients, a balloon catheter was passed into a bleeding site through a bullet track or proximal artery and inflated with saline or radiologic dye. In two of these patients, the proximal balloon catheter was folded on itself, tied in that position, and left in the patient permanently. In the other seven patients in this group, the balloon catheter was attached to a three-way stopcock and left temporarily inflated postoperatively. These patients were then observed in the intensive care unit for 3 to 4 days, at which time the balloon was withdrawn. Eight of nine patients survived without recurrent hemorrhage after removal of the balloon catheter, while one patient with a Fogarty balloon placed in the carotid siphon died of a cerebral infarction. Balloon catheter tamponade was also used on a temporary basis in one patient with a posterior cardiac wound and in one patient with an anterior stab wound of the inferior vena cava at the renal veins, whereas in two patients with high cervical arteriovenous fistulas, one had permanent placement of the balloon catheter while the other had temporary placement. One of the latter patients also had acute hemorrhage. Although all four patients survived, one of the patients with a fistula developed a recurrence and another required two separate operative procedures for correct placement of the balloon to cure the fistula. 
5	The role of the facial nerve latency test in the prognosis of Bell's palsy. Eighty patients with idiopathic facial nerve palsy were evaluated by the facial nerve latency test. Depending on the latency time, the patients were classified into the following four groups: group A patients had normal latency times (3.25 msec); group B patients had slightly extended latency times (4 to 7 msec) and a mean of 5.6 msec; group C patients had extended latency times (10 to 14 msec) and a mean of 10.2 msec; and group D patients displayed complete disappearance of evoked compound muscle action potential (no responses). Under the same therapeutic regimen, it was determined that, when the latency time was normal or close to normal, the functional recovery of the nerve was complete or almost complete, and the recovery time was short. When the latency time was extended or there was no response, the functional recovery of the nerve was either incomplete or absent. 
5	Adenoidectomy in otitis media. A review. For many years adenoids were thought to affect adversely middle ear (ME) aeration by obstructing the eustachian tube opening, leading to ME infections and effusions. Consequently, the adenoids have often been removed in children suffering from ME diseases; indeed, adenoidectomy is still performed around the globe on millions of children annually. Opinions vary, however, on the usefulness of the operation in various ME diseases. The purpose of this study is to review the available studies concerning the relationship of adenoids to the ME as well as the effect and benefit of adenoidectomy on ME effusions and ME infections. 
1	DNA analysis of multiple synchronous renal cell carcinomas. The authors used retrospective quantitative DNA analysis to study interrelationships between multiple synchronous renal cell carcinomas in seven patients. DNA content was determined by image analysis on Feulgen-stained nuclear smears prepared from multiple paraffin blocks from each tumor. Tumors were unilateral in four cases and bilateral in three. Ten tumors had homogeneous, and four heterogeneous DNA stemlines. Intertumoral heterogeneity in four cases suggested multifocal origin. Identical DNA aneuploid indices in bilateral tumors in one case suggested metastasis from a solitary origin. Abnormal DNA content and heterogeneous populations began to appear in the size range 2.0 to 5.0 cm. All tumors over 5.0 cm contained nondiploid populations. Although the interrelationships between these multiple synchronous neoplasms are not entirely clear, the DNA analysis suggests that the occurrence of nondiploid stemlines and heterogeneous DNA content may parallel both tumor growth and more aggressive behavior. 
2	Rectopexy is an ineffective treatment for obstructed defecation. The symptoms of obstructed defecation have been attributed to rectal intussusception, and thus rectopexy has been advocated in the surgical management. In this study, patients with obstructed defecation underwent manometry and proctography before and after rectopexy. Seventeen patients (16 females and one male, mean age 51.6 years) were studied. Eleven underwent anterior and posterior fixation of the rectum and six had posterior fixation only. Preoperatively five patients demonstrated rectoanal intussusceptions. Fifteen had significant pelvic descent. No significant change in maximum resting pressure, maximum voluntary contraction, pelvic descent, or anorectal angle was seen postoperatively. In the initial follow-up, many patients had significant amelioration of symptoms. However, on longer follow-up (mean 30.8 months) only two had long-term improvement. The remainder had a poor clinical result in spite of complete resolution of rectal intussusception. Many reported a worsening of symptoms as reflected by an increase in tenesmus and stool frequency. In the two cases with a satisfactory result, both could empty the rectum completely and demonstrated rectoanal intussusception on preoperative evacuation proctography. In those with poor results, four had complete emptying and three had rectoanal intussusception. In conclusion rectopexy is an ineffective treatment for obstructive defecation in most patients. 
1	Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1-weighted magnetic resonance imaging: case report. A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography. 
1	Growth hormone inhibits tumor metastasis. The effect of growth hormone on tumor growth and metabolism in the tumor-bearing host is unknown. This study was done to determine the effect of recombinant growth hormone on primary tumor growth, tumor metastasis, and carcass weight in tumor-bearing animals. Twenty-seven female Lobund/Wistar rats with subcutaneous prostate tumor implants (PA-III) were randomized to receive a standard protein diet (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.27 kcal/g) ad libitum orally. One half of the animals in each group were randomized to receive daily injections of either recombinant growth hormone (1000 mU/kg/day intramuscularly) or placebo (saline) for 14 days. A significant increase in body weight was observed in growth hormone-treated animals without acceleration of primary tumor growth. Spontaneous pulmonary metastasis was inhibited significantly in animals in both dietary groups treated with growth hormone. Thus, growth hormone selectively supports host growth and inhibits pulmonary metastasis in this tumor-bearing animal model. The potential metabolic effects and clinical consequences of treating cancer patients with growth hormone is discussed. 
3	LDH isoenzymes in cerebrospinal fluid in various brain tumours. This study examined the isoenzymatic pattern of LDH in the cerebrospinal fluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage. 
1	Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a. A heterogeneous group of five patients with progressive, invasive angiomatous diseases including pulmonary hemangiomatosis, angiosarcoma, or massive hemangioma with associated consumptive coagulopathy were treated with interferon alfa-2a for periods of 17 to 33 months. One patient with a large thoracic hemangioma, cardiorespiratory failure, and consumptive coagulopathy died after less than 2 months of treatment. The remaining four patients have shown beneficial responses, including (1) regression of abnormal vessels on pulmonary angiogram and improved exercise tolerance in pulmonary hemangiomatosis (two patients), (2) decreased corticosteroid and/or platelet transfusion requirements in consumptive coagulopathy (two patients), and (3) decreased size and number of tumor nodules in the one patient with angiosarcoma arising in preexisting angiomatous lesions. Responses occurred during periods of 2 to 20 months of treatment. There was no measurable progression of angiomatous lesions in any patient receiving interferon at the therapeutic dose, except possibly in the one who died. Each of the four surviving patients had improved linear growth and weight gain during interferon treatment. 
1	Continuity of cancer care. The importance of providing continuity in the care of all patients with major medical problems, such as cancer, has widespread acceptance in our current health care system. From the perspective of an oncology social work clinician, this article offers a definition of the concept of continuity of care, examines factors influencing its provision in oncology, and reviews key components in continuity of cancer care planning and implementation. It also examines some innovative efforts in practice to improve continuity. 
5	Penetration of lanthanum through the main pancreatic duct epithelium in cats following exposure to infected human bile. The main pancreatic duct epithelium acts as a barrier to the diffusion of molecules from the duct lumen into pancreatic acinar and interstitial tissue. We studied sequential ultrastructural characteristics of the loss of epithelial barrier function in the cat using lanthanum, an electron-opaque tracer, following perfusion of the duct from the tail to the duodenum with infected human bile. Tight junctions between duct epithelial cells were found to become permeable to the tracer as early as after 15 min of exposure. Later, there was progressive disintegration of intercellular junctions and epithelial loss. Lanthanum penetrated the duct epithelium exclusively on an intercellular path. Loss of barrier function of the pancreatic duct epithelium was consistently associated with subsequent development of acute interstitial edematous pancreatitis. There was no association between the degree of duct epithelial damage and the severity of acute pancreatitis. Both bile and a suspension of bacteria alone were not harmful to the pancreas. Sequential perfusion produced acute pancreatitis only when at first bile and then the bacterial suspension was perfused. A reversed succession of perfusates produced no morphologic alterations. We conclude: (1) Increased tight junction permeability is an early lesion in acute bile-induced pancreatitis: (2) loss of duct epithelial barrier function is important for the initiation but not for the severity of the inflammation; and (3) bile renders duct epithelial intercellular junctions vulnerable to Escherichia coli bacteria. 
4	Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage. Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe. 
5	Diagnostic significance of flow separation within the carotid bifurcation demonstrated by digital subtraction angiography. The presence of an area of reversed blood flow due to flow separation in the interval carotid artery is a normal finding in Doppler ultrasound studies in vivo as well as in model carotid bifurcations. This flow separation phenomenon is caused by the geometry of the carotid bifurcation and the fluid dynamics of blood. We demonstrated the flow separation phenomenon on lateral-projection intra-arterial digital subtraction angiograms in 99 of 100 carotid bifurcations. The mean duration of flow separation was 5.8 seconds, with values up to 14 seconds in normal carotid bifurcations. The presence of this flow separation phenomenon is almost independent of atherosclerotic lesions and is not correlated with cerebral ischemia. Therefore, the angiographic finding of a flow separation has no diagnostic value. However, our results refer to a factor that may be important in the genesis of atherosclerosis at the carotid bifurcation, namely the duration of the stay of blood and its components within the area of flow separation. 
5	Functional and metabolic effects of bupivacaine and lignocaine in the rat heart-lung preparation. We have examined the effects of bupivacaine and lignocaine on myocardial metabolism in the rat isolated heart-lung preparation. Bupivacaine 1, 5 or 25 micrograms ml-1 or lignocaine 4, 20 or 100 micrograms ml-1 was administered 5 min after the start of perfusion. Both bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 reduced heart rate significantly. Bupivacaine 25 micrograms ml-1 was associated with a higher incidence of arrhythmias than the other groups. Three hearts in the bupivacaine 25 micrograms ml-1 group (n = 8) and two hearts in the lignocaine 100 micrograms ml-1 group (n = 8) failed (zero cardiac output) at the end of the experiment. Although there were no significant differences in myocardial lactate and glycogen concentrations between groups, ATP content in the bupivacaine 25 micrograms ml-1 and lignocaine 100 micrograms ml-1 groups was significantly less than that in the control group. The results suggest that myocardial depression and subsequent metabolic deterioration occurred with both the high doses of local anaesthetics; these findings do not account for the apparent increased cardiotoxicity of bupivacaine. 
3	Events associated with rupture of intra-aortic balloon counterpulsation devices. Nineteen intra-aortic balloon (IAB) ruptures occurred in sixteen patients during a three-year period. Perforation occurred secondary to abrasion with material failure or mishandling of the device during insertion. To avoid serious sequelae, it is important to be aware of the possibility of IAB rupture and to remove any defective device immediately upon recognition of an event. 
5	Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement. A prospective, randomized study of compression alone, compression and aspirin, and compression and low-dose warfarin. A prospective, randomized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression, alone or in combination with oral administration of either aspirin or low-dose warfarin, was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old. All patients began walking by the third postoperative day. One hundred and ninety-six patients who had 217 total hip arthroplasties were included. Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis, and the remainder were primary arthroplasties. Patients were randomized as to the type of prophylaxis that they received: intermittent pneumatic compression alone, seventy-six hips; intermittent pneumatic compression and aspirin, seventy-two hips; or intermittent pneumatic compression and low-dose warfarin, sixty-nine hips. Before discharge from the hospital, and at an average of seven days after the operation, all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography. The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups; the over-all relative frequency was 10 per cent. Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement. With the number of patients in our study, the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin. 
4	Detection of restenosis after successful coronary angioplasty: improved clinical decision making with use of a logistic model combining procedural and follow-up variables. A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 +/- 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with greater than 50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of greater than 50% of luminal diameter. Restenosis occurred in 40% of the patients. The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p less than 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p less than 0.0001), exercise thallium-201 scintigram score (p less than 0.0001), difference between exercise and rest ST segment depression (p less than 0.001), postangioplasty exercise ST segment depression (p less than 0.001), absolute postangioplasty stenosis diameter (p less than 0.003), postangioplasty exercise work load (p less than 0.03) and postangioplasty exercise heart rate (p less than 0.05). 
5	Genetics of cerebrovascular disease. Stroke is a complex disease, with both genetic and environmental factors having a role in its pathogenesis. A review of past studies shows some evidence of genetic influences in the development of stroke. This is supported by studies of cardiovascular disease, which indicate major genetic influences at several levels including the development of risk factors. New approaches to phenotypic classifications, patient ascertainment, and genetic analysis will stimulate research into the role of genetics in cerebrovascular disease. 
4	Treatment of ventricular tachycardia induced cardiogenic shock by percoronary chemical ablation. Incessant ventricular arrhythmias pose an especially challenging therapeutic dilemma. We describe the successful treatment and follow-up of a patient with refractory ventricular tachycardia-induced cardiogenic shock with percoronary chemical ablation. After endocardial mapping was used to identify the "tachycardia-related" coronary artery, temporary termination of the arrhythmia with balloon occlusion and subselective intracoronary installation of iced saline as previously advocated was unsuccessful. This was probably due to a dual arterial blood supply to the arrhythmogenic focus. However, infusion of 2 cc ethanol (99%) permanently terminated the arrhythmia. Contrary to previous experience, ethanol-induced arrhythmia termination did not result in arterial occlusion, further supporting a direct toxic effect on the myocardium as its mode of action. Use of standard angioplasty balloon inflation prevents "backwash" of distally infused ethanol and more generalized cell death. The only complication of this procedure was temporary third-degree AV block, requiring permanent pacemaker implantation. 
4	Coronary angioplasty in patients with severe left ventricular dysfunction. The applications for coronary angioplasty have greatly expanded and the procedure is now increasingly used in complex and potentially high risk conditions. This report describes the short- and long-term effects of coronary angioplasty in 61 patients with severely depressed left ventricular function (ejection fraction less than or equal to 35%) with unstable or refractory anginal symptoms, or both, in whom revascularization was necessary despite increased risk. In a retrospective analysis of 1,260 patients undergoing angioplasty between January 1985 through December 1987, 61 had an ejection fraction less than or equal to 35%. The common clinical presentation was unstable angina (70%) with or without recent myocardial infarction. Mean left ventricular ejection fraction was 27 +/- 6%. Forty-five patients (74%) had multivessel disease. Clinical success after angioplasty was achieved in 55 patients (90%). Major complications (death, infarction and emergency bypass surgery) occurred in five patients (8.2%), with death in two (3.2%). During long-term (mean 21 +/- 11 months) follow-up study of the 55 patients with successful angioplasty, 13 (23%) died, including 3 of noncardiac causes, and 11 (20%) had clinically symptomatic recurrence. Continued clinical success was present in 39 patients (71%), of whom 28 (51%) were event-free patients and 11 (20%) had clinical recurrence; a successful second angioplasty procedure was performed in 9 because of restenosis. Thus, in patients with depressed left ventricular function, coronary angioplasty can be performed with a short-term success rate comparable to that of routine angioplasty or surgical procedures. However, acute complications are more frequent and the late mortality rate is higher than in patients with less depressed function. 
2	Absorption of carbon 13-labeled rice in milk by infants during acute gastroenteritis. To determine whether rice cereal could be used to complement a cow milk-based diet in the nutritional management of infants with acute diarrhea, we assessed its digestion and absorption in eight affected male infants, 69 to 131 days of age. They received cow milk formula with 5.4% lactose (diluted 1:1 with water and precooked rice cereal) 5 to 22 hours after admission and rehydration. The first feeding consisted of milk diluted with carbon 13-enriched rice cereal. A 48-hour fecal collection and balance study was performed. Rice cereal was reasonably well absorbed (84.0% to 95.8%) by seven of the eight infants. The study was repeated in seven of the infants after they had recovered. Our results indicated that rice cereal is well absorbed by young infants with acute diarrhea and that it is an adequate nutrient supplement for this patient population. 
5	Fine-needle aspiration evaluation of lymphoproliferative lesions in human immunodeficiency virus-positive patients. A multiparameter approach. Forty-six fine-needle aspirates of lymphoproliferative lesions from 31 human immunodeficiency virus (HIV)-positive patients were reviewed using cytomorphologic, immunocytochemical, flow cytometric (FCM), cytogenetic, and molecular studies. There were 29 lymphomas (15 small non-cleaved cell [SNCL], 11 large cell [LCL], one small lymphocytic, and two Hodgkin's), 14 reactive hyperplasias, and three "atypical lymphoid proliferations." The reactive hyperplasias were characteristically polymorphic and polyclonal lymphoid populations; six of seven were diploid on FCM, the seventh was hypodiploid. Higher proliferative indices (mean, 11.6%) and higher RNA indices (mean, 1.2) characterized this subgroup compared with published reactive lymphoid hyperplasias from patients without HIV positivity. Aspirates of SNCL showed monotonous populations of intermediate-sized cells except in one patient where a giant cell syncytial variant occurred. Nine of 13 SNCL aspirates showed light chain restriction. JH rearrangement revealed B-cell lineage in one aspirate in which immunocytochemical study was negative for Kappa, lambda, B1, and Leu-4. Nine of 12 SNCL were diploid; the mean proliferative index was 25.6% and the mean RNA index 2.3. Chromosomal translocations involving the c-myc locus were demonstrated in five of seven SNCL aspirates karyotyped. Five of eight LCL showed light chain restriction the remaining three showed null cell phenotype. Large cell lymphomas were diploid on tetraploid with the mean proliferative index of 22.0% and mean RNA index of 2.2. One of two LCL aspirates karyotyped demonstrated c-myc translocation. Despite the multiparameter approach, a definitive diagnosis could not be reached in three aspirates. 
1	Radiologic staging of chest in testicular seminoma. We investigated the usefulness of chest x-ray (CXR), conventional planar tomography (TOM), and computerized axial tomography (CAT) in evaluating patients with Stages I and II testicular seminoma. All patients had a CXR, and 22 patients had either TOM or CAT as part of initial staging. No occult pulmonary or mediastinal nodal disease was found during initial staging, and none of the patients manifested recurrence of tumor in these sites as a first event. Review of the literature corroborates our finding of a very small thoracic failure rate in early stage seminoma. Routine use of CAT or TOM is not indicated in staging these patients. 
5	Nasal augmentation with split calvarial grafts in Orientals. This study reports on my experience with autogenous split calvarial grafts in nasal augmentation in 62 Orientals. In 78 percent of patients, the procedure was performed under local anesthesia in an outpatient setting. Total operating time for harvesting of split calvarial grafts ranged from 20 to 55 minutes, with a mean of 32 minutes. Patients ranged in age from 16 to 48 years, with a mean of 27 years. Follow-up was from 6 months to 8 years, with an average of 3.1 years. Intraoperative discomfort was uniformly low and well tolerated when local anesthesia was used. The complication rate was 8.0 percent, with three cases of minor seroma-hematoma formation at the bone-graft donor site. These were treated with aspiration. There were two recipient-site complications, with one case of complete bone resorption that occurred in a densely fibrotic nose with preexisting septal perforation and a case of overcorrection that was successfully rasped 1 year later. Because of their easy accessibility beneath the scalp, split calvarial grafts to the nose are useful in various types of nasal augmentation, and the technique is offered as a practical alternative to the use of alloplastic materials. 
5	Prognosis and prognostic factors of retinal infarction: a prospective cohort study. OBJECTIVE--To determine the prognosis and adverse prognostic factors in patients with retinal infarction due to presumed atheromatous thromboembolism or cardiogenic embolism. DESIGN--Prospective cohort study. SETTING--University hospital departments of clinical neurology. PATIENTS--99 patients with retinal infarction, without prior stroke, referred to a single neurologist between 1976 and 1986 and evaluated and followed up prospectively until death or the end of 1986 (mean follow up 4.2 years). INTERVENTIONS--Cerebral angiography (55 patients), aspirin treatment (37), oral anticoagulant treatment (eight), carotid endarterectomy (13), cardiac surgery (six), and peripheral vascular surgery (two). MAIN OUTCOME MEASURES--Death, stroke, coronary events, contralateral retinal infarction; survival analysis confined to 98 patients with retinal infarction due to presumed artheromatous thromboembolism or cardiogenic embolism (one patient with giant cell arteries excluded), and Cox's proportional hazards regression analysis, including age as a prognostic factor. RESULTS--During follow up 29 patients died (21 of vascular causes and eight of non-vascular or unknown causes), 10 had a first ever stroke, 19 had a coronary event, and only one developed contralateral retinal infarction. A coronary event accounted for more than half (59%) of the deaths whereas stroke was the cause of only one death (3%). Over the first five years after retinal infarction the actuarial average absolute risk of death was 8% per year; of stroke 2.5% per year (7.4% in the first year); of coronary events 5.3% per year, exceeding that of stroke; and of stroke, myocardial infarction, or vascular death 7.4% per year. Prognostic factors associated with an increased risk of death were increasing age, peripheral vascular disease, cardiomegaly, and carotid bruit. Adverse prognostic factors for serious vascular events were increasing age and carotid bruit for stroke, and increasing age, cardiomegaly, and carotid bruit both for coronary events and for stroke, myocardial infarction, or vascular death. CONCLUSIONS--Patients who present with retinal infarction due to presumed atherothromboembolism or cardiogenic embolism are at considerable risk of a coronary event. The risk of stroke, although high, is not so great. Not all strokes occurring after retinal infarction relate directly to disease of the ipsilateral carotid system, although this is probably the most common cause. Few patients experience contralateral retinal infarction. Non-arteritic retinal infarction should be diagnosed or confirmed by an ophthalmologist, and the long term care of patients with the condition should involve a physician who has an active interest in managing vascular disease. 
5	Fulminant pseudomonal keratitis and scleritis in human immunodeficiency virus-infected patients. Patients with human immunodeficiency virus infection are predisposed to fungal, parasitic, and viral infections. Bacterial infection can also be seen, although ocular bacterial infections have not been reported in patients with acquired immunodeficiency syndrome until recently. We present two cases of Pseudomonas corneoscleritis and one case of Pseudomonas keratitis in patients with human immunodeficiency virus infection that failed to respond to antibiotic treatment. Predisposing factors included extended-wear soft contact lens use in one patient and exposure secondary to Bell's palsy in another patient. All three patients had neutropenia that may have contributed to their poor response to treatment. Enucleation was required to treat two patients with overwhelming infection. Enucleation has been rarely required for treatment of corneoscleritis in immunocompetent patients treated at our institution. Pseudomonas keratitis in human immunodeficiency virus-infected patients represents a serious ocular infection requiring early diagnosis and aggressive treatment. 
5	Scleroderma and central nervous system vasculitis. We describe a patient with scleroderma (CREST syndrome) and central nervous system vasculitis. While angiography demonstrated segmental symmetrical arterial narrowing characteristic of vasculitis, results of leptomeningeal biopsy were normal. There was no evidence of systemic vasculitis, renal failure, or malignant hypertension previously thought to be required to explain central nervous system dysfunction in patients with scleroderma. Signs and symptoms attributable to vasculitis were reversible with aggressive immunosuppressive therapy. 
1	Use of cytoplasmic 5'nucleotidase for differentiating malignant from benign monoclonal gammopathies. Bone marrow smears from 15 patients with multiple myeloma, 15 patients with monoclonal gammopathy of undetermined significance (MGUS), and 15 control subjects were examined for the presence of cytoplasmic 5'nucleotidase (c5NT) in plasma cells. Plasma cell positivity for c5NT (mean and 95% confidence interval) in patients with multiple myeloma numbered 46.4% (38.0-54.8%), in those with MGUS it was 15.3% (11.1-19.6%), and in control subjects it was 1.2% (0.3-2.1%). These findings indicate that c5NT can be used to differentiate benign from malignant monoclonal gammopathies. 
3	Rupture of atheromatous plaque as a cause of thrombotic occlusion of stenotic internal carotid artery. We analyzed the clinical profiles and autopsy findings of five patients who died shortly after developing cerebral infarction following thrombotic occlusion of the internal carotid artery. In all five cases, thrombotic occlusion was caused by rupture of the fibrous lining over the gruel of atheroma at the origin of the internal carotid artery showing tight stenosis of the lumen. The mean +/- SD shorter diameter of the lumen at the site of occlusion was 1.5 +/- 0.4 mm. Our results show that an internal carotid artery with tight stenosis of the lumen by atheroma containing gruel harbors a risk of thrombotic occlusion, which may give rise to cerebral infarction by artery-to-artery embolism or by reduced cerebral perfusion. 
1	Argon green (514 nm) versus krypton red (647 nm) modified grid laser photocoagulation for diffuse diabetic macular edema. Between 1984 and 1988, 225 eyes of 132 patients were entered in a prospective, randomized clinical trial to determine if any significant differences exist between treatment with argon green (514 nm) and krypton red (647 nm) modified grid laser photocoagulation for patients with diffuse diabetic maculopathy with or without cystoid macular edema. At the 12- and 24-month follow-up visits, no statistically significant difference was found between the two groups with respect to all of the following: reduction or elimination of macular edema, improvement in visual acuity, worsening of visual acuity, number of treatments per eye, and effect on the visual field. At the 12-month follow-up visit, none of the following factors statistically affected the visual outcome in either of the two groups: a history of systemic hypertension, systemic vascular disease, cystoid macular edema, or initial poor visual acuity. 
5	Etiologic and clinical evaluation of acute lower respiratory tract infections in young Argentinian children: an overview. This paper summarizes the first study on clinical, etiologic, and epidemiologic features of acute lower respiratory tract infection (ALRI) in children in Argentina. A total of 1,003 children less than 5 years of age (805 inpatients and 198 outpatients) presenting with ALRI were studied during a 40-month period. Nasopharyngeal aspirate (NPA), blood, urine, and throat-swab samples were collected when each child was first seen for care. Virologic studies were performed on the NPA by means of indirect immunofluorescence and isolation of virus in cell culture. Bacteriologic studies primarily were done by means of culture of blood or pleural fluid (when available); Bordetella pertussis and Mycoplasma pneumoniae, however, were searched for by the use of immunofluorescence and complement-fixation testing, respectively, in paired sera. Respiratory syncytial virus was the most commonly isolated virus, followed by adenovirus, parainfluenza virus, and influenza virus. Streptococcus pneumoniae was the most frequently isolated bacterium, followed by B. pertussis and Haemophilus influenzae type b. Overall, the patient fatality rate was 3.8% among inpatients with pneumonia or bronchiolitis. 
3	Patient compliance--a factor in facial trauma repair. The clinical records of 25 consecutive patients who were treated for facial trauma were reviewed and analyzed to ascertain what effect patient cooperation had on the outcome of facial fracture repair. The study was designed to establish the incidence of complications and to discover what factors contributed to untoward sequela in such patients. Overall, 15 patients (60%) were noncompliant in one or more aspects of their care. Six patients (24%) had significant postoperative complications associated with their facial injuries. Four of these patients were not fully cooperative. 
2	Plasma thrombomodulin in health and diseases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis of plasma thrombomodulin concentrate revealed that four degraded forms of thrombomodulin with different molecular weights are present in plasma. Plasma concentrations of thrombomodulin in patients with various diseases were measured by two methods of enzyme-linked immunosorbent assay using monoclonal antibodies. One method measures intact thrombomodulin and degraded forms of thrombomodulin; the other does not detect the two smaller degraded forms of thrombomodulin present in plasma. The results indicated that thrombomodulin was increased in the circulating blood of patients with disseminated intravascular coagulation syndrome, pulmonary thromboembolism, adult respiratory distress syndrome, chronic renal failure, or acute hepatic failure. The different values obtained by the two methods indicate that the increase of plasma thrombomodulin found in these patients was mainly due to an increase of the smaller fragments of degraded forms, suggesting that the release of thrombomodulin from endothelial cells was accelerated in various disease states by proteolytic activity generated on the surface of the endothelium and may be removed from the circulation mostly by the kidneys and liver. 
5	The importance of calcium ions for in vitro malignant hyperthermia testing. Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine. 
2	Serum ferritin and stomach cancer risk among a Japanese population. Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset. 
1	Endodermal sinus tumor of the ovary during pregnancy: a case report. Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy. After surgery, chemotherapy was postponed. In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks' gestation. After delivery, the patient received four chemotherapy courses (cisplatin, etoposide, and bleomycin). Mother (24 months after last chemotherapy) and child are doing well. 
4	Renal autotransplantation in children: a successful treatment for renovascular hypertension. Renovascular hypertension in children is not a common disease. With improved surgical technique the incidence of nephrectomy has decreased and renovascular reconstruction is currently the preferred method to manage this entity. Between 1977 and 1988, 21 patients with renovascular hypertension were treated at our hospital: 7 patients 6 to 16 years old underwent renal autotransplantation. Of the children 4 had unilateral and 3 had bilateral disease requiring bilateral autotransplantation. Autotransplantation was performed by anastomosis of each renal artery end-to-side to the common iliac artery. The renal veins were anastomosed end-to-side to the common iliac veins. The ureters were left intact in all but 1 patient who required a bench operation. Of the 4 patients who had a unilateral procedure 3 are cured and 1 is improved with a normal blood pressure on a small dose of antihypertensive medication. The 3 patients with bilateral autotransplants are cured. These results, with normalization of the blood pressure in 86% of the patients and improvement in blood pressure in 14% with a patency rate of 87%, are similar to other reported reconstructive modalities in children. 
3	Changes of hippocampal glucose utilization subsequent to amygdaloid-kindled generalized seizures. Local changes in cerebral glucose utilization during the postictal phase of amygdaloid-kindled generalized seizures were studied with the quantitative autoradiographic 2-[14C]deoxyglucose method in conscious rats. Measurement was initiated either just after termination of a behavioral seizure (GS-I) or 30 s after seizure termination (GS-II) to determine dynamic metabolic changes in the postictal phase. Although glucose utilization of the neocortex was remarkably depressed in both GS-I and GS-II, that of the hippocampus significantly increased in GS-I and then decreased in GS-II as compared with control. These changes of hippocampal glucose utilization were observed in all sectors of the pyramidal cell layer (CA 1-4) and in the molecular layer. Because metabolic changes associated with development of amygdaloid-kindled seizures begin in the limbic structures including the hippocampus, the transient increase in hippocampal glucose utilization observed in the early postictal phase indicates that the hippocampus is one of the key structures not only for initiating and maintaining but also for terminating kindled seizures. 
5	Experience with childhood urolithiasis. Report of 196 cases. A total of 196 children with urinary calculi were treated surgically. Their ages ranged from 1 to 14 years. The male:female ratio was 3:1. Stones were located in the kidney in 96 patients, in the bladder in 52 and in the ureters in 32. Multiple organ involvement was present in 16 patients and associated urinary tract anomalies were found in 11. Stone analysis revealed calcium oxalate and phosphate stones in 121 patients, struvite stones in 60 and uric acid stones in 15. 
5	Failure of nutritional recovery after total gastrectomy. Malnutrition is reported to be an inevitable consequence of total gastrectomy, although there are few data to support this contention. Six patients of median age 63 years underwent total gastrectomy for malignancy. At follow-up (median 45 months, range 25-60 months) each patient was clinically tumour-free and underwent dietary assessment, faecal fat and nitrogen measurement and routine haematological testing. Protein and fat stores, measured by neutron activation analysis and the tritiated water dilution technique, were compared with the same measurements made before operation and with predicted values. Mean (s.d.) dietary intake (2224(381) kcal day-1 and 81(15)g protein day-1) met the patients' estimated requirements. Mean(s.d.) serum albumin and faecal nitrogen values were normal but there was notable steatorrhoea (21(17) g day-1). Body composition measurements revealed profound deficiencies of body-weight (P less than 0.02), protein (P less than 0.01) and fat (P less than 0.02) before operation which were not corrected by an apparently curative total gastrectomy (P less than 0.05), although further deterioration was prevented. 
4	An open, noncomparative study of doxazosin in essential hypertension: experience in general practice in The Netherlands. The antihypertensive efficacy, safety, and lipid effects of doxazosin, a selective alpha 1-inhibitor, were assessed in a general practice setting. Three hundred twenty-six patients were entered into the study, which involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received 1 to 8 mg of doxazosin once daily, and (3) a 4-week maintenance period. After 12 weeks, 78.8% of efficacy-evaluable patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline or greater than or equal to 10 mm Hg reduction from baseline). The mean daily dose in patients considered a therapy success was 2.8 mg. By the final visit, sitting systolic/diastolic blood pressures of these patients were reduced by 16.4/13.5 mm Hg from a mean baseline of 170/106 mm Hg. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 70% of patients. Of the 326 patients, 30.7% reported a total of 160 side effects; 78% of the side effects were mild or moderate in severity, and 24 patients (7.4%) discontinued treatment because of adverse experiences. The investigators' global assessment of toleration was excellent or good for 87% of patients. Doxazosin produced a significant decrease in total cholesterol (p = 0.02) and triglyceride (p less than 0.001) levels. From baseline to final visit there was also a highly significant reduction of 17% (p less than 0.001) in calculated risk score for coronary heart disease on the basis of the Framingham Heart Study risk equation. 
5	Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 4, 12, 20, and 29 months of age. Mean arterial pressure, left ventricular pressure and its first derivative (dP/dt), and heart rate were comparable in rat groups up to 20 months. During the interval from 20 to 29 months, elevated left ventricular end-diastolic pressure and decreased dP/dt indicated that a significant impairment of ventricular function occurred with senescence. In the period between 4 and 12 months, a reduction of nearly 19% in the total number of myocytes was measured in both ventricles. In the subsequent ages, similar decreases in myocyte cell number were found in the left ventricle, whereas in the right ventricle, the initial loss was fully reversed by 20 months. Moreover, from 20 to 29 months, a 59% increase in the aggregate number of myocytes occurred in the right ventricular myocardium. In the left ventricle, a 3% increment was also seen, but this small change was not statistically significant. These estimations of myocyte cellular hyperplasia, however, were complicated by the fact that cell loss continued to take place with age. The volume fraction of collagen in the tissue, in fact, progressively increased from 8% and 7% at 4 months to 16% and 22% at 29 months in the left and right ventricles, respectively. In conclusion, myocyte cellular hyperplasia tends to regenerate the ventricular mass being lost with age in the adult mammalian rat heart. 
5	Cellular and molecular basis of the asbestos-related diseases. Asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated, at least in part, by cytokines released by "activated" alveolar macrophages. The process of phagocytosis and "activation" of alveolar macrophages is poorly understood. Are all macrophages activated or only subpopulations? Which cytokines are up-regulated? How does the local milieu modulate profibrotic and antifibrotic mediators? Is protein release accompanied by up-regulation of gene transcription? Is there an ordered sequence of cytokine activity? What roles do neutrophils and lymphocytes play? How can disease progression best be quantified absent further exposure? Answers to these questions are important to direct rational strategies at interdicting the fibrotic process. The question of cancer and asbestos is more vexing. The processes of inflammation, fibrosis, and carcinogenesis appear to be closely intertwined. For example, proto-oncogenes such as c-sis (PDGF B-chain) are up-regulated in activated alveolar macrophages from fibrotic lungs; these and possibly others may play an important role in asbestos carcinogenesis. Second, asbestos can transfect DNA into cells. Furthermore, DNA can adhere to asbestos fibers, and these fibers are capable of direct transmigration into cells. The questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain. Lastly, if the bronchial epithelium is highly metaplastic throughout from cigarette smoking, what triggers a single (or several) nidus of cells to transform into carcinoma? Malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history. Mesothelial cells are susceptible to minute environmental manipulations, and changes occur after exposure to all fiber types. Yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk. To test this hypothesis, experimental data must be generated differentiating tumorigenesis risk from short, chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue. Despite the future decreasing numbers of clinical cases of asbestos-related disease, solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer. 
1	Cell lineage markers in human pancreatic cancer. The normal pancreas consists of three major cell types or lineages that share a common embryologic origin from pluripotent endodermal precursors. The type of cell that undergoes neoplastic transformation to form a pancreatic carcinoma is controversial and may influence the phenotype and biologic behavior of the tumor. In this study, immunohistologic techniques were used to determine the cell lineage differentiation expressed in 29 primary exocrine pancreatic adenocarcinomas, five metastatic exocrine pancreatic adenocarcinomas, and five islet cell neoplasma. Specimens of normal pancreas and chronic pancreatitis were used for comparison. The cell lineage markers consisted of monoclonal and polyclonal antibodies against trypsin and lipase (acinar cells); secretory component, carbonic anhydrase II, and pancreatic cancer mucin SPan-1 (ductal cells); and chromogranin-A and somatostatin (islet cells). The expression of carcinoembryonic antigen (CEA) and lysozyme were also determined. This collection of markers allowed the differentiation between acinar, ductal, and islet cells of normal pancreas and chronic pancreatitis specimens. The expression of cell lineage markers in islet cell tumors was homogeneous and restricted to chromogranin-A. In contrast, the expression of these markers in primary and metastatic exocrine pancreatic adenocarcinomas was variable. Reactivity with monoclonal anti-CEA was absent in normal pancreas, and was present in 83% of chronic pancreatitis specimens as well as 90% of exocrine pancreatic adenocarcinomas. In addition, lysozyme reactivity was absent in normal pancreas; however, lysozyme was expressed in one case of chronic pancreatitis, 17 cases of primary carcinoma, and three cases of metastatic carcinoma. These findings support the concept that the original transformed cell type in many pancreatic exocrine carcinomas resemble endodermal "stem cells" that retain the capability of differentiation along more than one cell lineage pathway. 
1	Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be characterized, is associated with adult T-cell leukaemia and a chronic progressive disease of the central nervous system termed tropical spastic paraparesis, or HTLV-I-associated myelopathy. Only 1% of individuals infected with HTLV-I develop clinical disease however. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals, infection with variant strains of HTLV-I, differences in viral tropism or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized, little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes. Here we report the presence of high levels of circulating HTLV-I-specific cytotoxic T lymphocytes in patients with HTLV-I associated neurological disease but not in HTLV-I seropositive individuals without neurological involvement. These cytotoxic T lymphocytes are CD8+, HLA class I- restricted and predominantly recognize the HTLV-I gene products encoded in the regulatory region pX. These findings suggest that HTLV-I-specific cytotoxic T lymphocytes may contribute to the pathogenesis of associated neurological disorders associated with HTLV-I. 
5	A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features. Twelve infants (six boys, six girls) with severe hypocalcaemic tetany or convulsions were seen over a three year period. Nine patients were symptomatic in the newborn period. Their hypocalcaemia was associated with hyperphosphataemia and very low concentrations of immunoreactive parathyroid hormone. None of the babies suffered from congenital cardiac disease. Cell mediated immunity, measured in five patients, was normal. There were no chromosomal abnormalities but all patients shared several dysmorphic features including deep set eyes, microcephaly, thin lips, beaked nose tip, external ear anomalies, micrognathia, and depressed nasal bridge. Mental retardation of varying degree was found in all patients. All had severe intrauterine and postnatal growth retardation. Four patients have died. The remaining eight patients are on treatments with vitamin D and calcium supplements with no change in their growth pattern. We believe that this association of congenital hypoparathyroidism with severe growth failure and dysmorphism represents a new syndrome. 
5	Regulatory elements of the erythropoietin gene. Because the human hepatoma cell line Hep3B produces erythropoietin (Epo) in a regulated fashion, it can be used to investigate the cis-acting regulatory elements of the Epo gene. Comparison of primate and mouse sequences shows strong homology not only in the coding sequence but also within the 5' flanking region, the first intron, and the 3' flanking region. These portions of the Epo gene were inserted 5' and 3' to a reporter gene, human growth hormone (GH). 5A is a 1,192-base pair (bp) HindIII-Xbal fragment that extends from 378 bp 5' to the cap site through the first intron. To obviate the problem of false initiation of translation from the Epo ATG start codon, this site was changed to TAG by site-directed mutagenesis. 3A is a 255-bp Accl-BglII fragment that extends 67 bp upstream from the Epo termination codon and covers most of the 3' noncoding region of homology. The plasmid DNAs were transfected by electroporation into Hep3B cells with RSVCAT as an internal standard to correct for transfection efficiency. One aliquot of cells was exposed to 50 mumol/L CoCl2 or to 1% O2. At the end of the incubations, GH and Epo were measured in the cell media and the cell pellet was assayed for CAT. Production of GH was stimulated 1.7-fold by cobalt or hypoxia. Furthermore, addition of 3A to the GH gene, irrespective of orientation, stimulated GH production 2.6-fold with CoCl2 and 2.3-fold with hypoxia. Stable cell lines were produced by cotransfection of the above constructions, along with the selectable marker pSV-Neo. In two clones, exposure to hypoxia resulted in much more marked (16-fold) induction of GH. Stimulus of both GH and Epo production by hypoxia was partially abrogated by carbon monoxide. These results demonstrate the presence of promoter and enhancer elements within the human Epo gene that are appropriately responsive to hypoxia and cobalt. 
4	Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram. 
5	Therapeutic options in acute diverticulitis. Diverticulitis is a serious intra-abdominal infection that ultimately afflicts about one in four patients having colonic diverticulosis. The illness may be indolent or fulminant, depending on the degree of colonic spillage and its containment. Most patients require hospitalization, and medical therapy suffices in about three fourths. Those who fail aggressive medical management and those with recurrent acute attacks, diffuse peritonitis, abscess, persistent obstruction, or fistulization require surgical intervention. Abdominal CT scanning has supplanted the contrast enema as the acute diagnostic procedure of choice and allows guided percutaneous drainage of large abscesses in selected cases. This approach helps realize the surgical ideal of a single elective operation without a temporary colostomy. For those patients still requiring emergency surgery, the two-stage approach employing resection of the diseased colon at the initial operation is far superior to the older three-stage approach. 
3	The pathophysiology of anoxic injury in central nervous system white matter. White matter of the mammalian brain is susceptible to anoxic injury, but little is known about the pathophysiology of this process. We studied the mechanisms of anoxic injury in white matter using the isolated rat optic nerve, a typical central nervous system white-matter tract. Optic nerve function, measured as the area under the compound action potential, rapidly failed when exposed to anoxia. Postanoxic recovery was variable, depending on duration of the anoxic insult; after a standard 60-minute period of anoxia, the compound action potential recovered to 28.5% of control. Irreversible anoxic injury was critically dependent on extracellular Ca2+; maintaining the tissue in zero [Ca2+] solution throughout the anoxic period resulted in 100% compound action potential recovery. Increasing perfusate [Ca2+] during anoxia from zero to 4 mM resulted in progressively less recovery. Anoxic damage to the optic nerve appears to depend on the gradual accumulation (over tens of minutes) of Ca2+ in a cytoplasmic compartment. The inorganic Ca2+ channel blockers Mn2+ (1 mM), Co2+ (1 mM), or La3+ (0.1 mM) had no effect on recovery of the compound action potential after anoxia; only Mg2+ (10 mM) significantly improved recovery. Treatment with the dihydropyridine Ca2+ channel blockers nifedipine (1-10 microM) or nimodipine (1-40 microM) also had no effect on recovery from anoxia. Thus, Ca2+ influx during anoxia does not occur via conventional Ca2+ channels. Preliminary evidence suggests that this Ca2+ influx may occur via other cation channels that are imperfectly selective for Ca2+ or via the Na(+)-Ca2+ exchanger. 
3	Emergency portosystemic shunt in patients with variceal bleeding. Thirty-five patients for whom emergency sclerotherapy or conservative treatment, or both, failed to arrest variceal bleeding, or who had early rebleeding and required emergency portosystemic shunts (EPSS) were studied. EPSS permanently controlled the variceal bleeding in all but one patient. In this patient, the shunt was patent as demonstrated by angiography. Esophageal varices disappeared in 18 patients and were reduced in 14. Three patients died before the endoscopic examination could be performed. The causes of death were hepatic failure in two and bleeding ulcerations of the gastric fundus in the other patient. One patient was classified in Child's category B and two in Child's category C. Thirty-two patients submitted to EPSS and were discharged alive. Twelve of these patients subsequently died, at an average of 11.2 months after undergoing the shunt procedure. Four of 12 patients died of hepatic failure; two patients died of hepatomas; two, other neoplasia; three, hemorrhaging duodenal ulcers, and one patient, renal failure. Analysis of actuarial survival rates showed that the five year survival rate was 43 per cent. The long term survival rates were fewer for patients with Child's category C than for those with combined Child's categories A and B (five year survival rates were 21 versus 55 per cent; p less than 0.05). During the follow-up period, none of the patients had variceal bleeding. Chronic encephalopathy developed in six, which was mild in three, moderate in one instance and severe in two. It developed soon after EPSS, with onset in the first month after discharge in three. Thus, when conservative treatment fails to arrest variceal bleeding, EPSS should be performed to guarantee definitive control of hemorrhage and prolong the survival period. 
5	The efficacy of methylprednisolone in reducing flap edema. It has been suggested that systemic steroids reduce postoperative flap edema. This has been poorly documented by several reports based on subjective clinical observations. In an effort to provide quantitative data on methylprednisolone and edema, a flap edema model in the rat was developed based on the inferior epigastric vessels. Significant edema developed after 48 hours. Differing intraoperative doses of methylprednisolone were studied, producing a dose-response curve. A single low dose of intraoperative steroid is effective in reducing flap edema; previously recommended doses are probably excessive. 
2	Pneumatosis intestinalis and pneumoperitoneum complicating mixed connective tissue disease. A case of a young woman with a 3-year history of mixed connective tissue disease who developed secondary pneumatosis intestinalis and pneumoperitoneum and died shortly after of rapidly progressive disease is reported. The pathogenesis, treatment and prognosis of this unusual complication in mixed connective tissue disease are discussed. 
4	Is hyperglycemia associated with cardiovascular disease? The Framingham Study. The association of nonfasting blood glucose levels with CVD incidence was determined prospectively in 1382 men and 2094 women aged 45 to 84 years participating in the Framingham Heart Study. For this study, all patients were classified in 1970 as diabetic or nondiabetic. Every 2 years they were examined, categorized according to causal blood glucose samples obtained at the clinic visit, reclassified for development of CVD and diabetes mellitus, and followed 10 years for CVD. During the follow-up period, 350 men and 369 women developed CVD. Age-adjusted CVD rates were positively associated with glucose levels in nondiabetic women who did not develop diabetes during follow-up. No such associations were seen in men. Multivariate analyses confirmed the independent association of blood glucose levels with later CVD in nondiabetic women. This study shows that hyperglycemia in the original Framingham cohort is an independent risk factor for CVD in nondiabetic women, but not among men. 
4	Experience with photocoagulation in Behcet's disease. Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behcet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others. 
2	Nosocomial outbreak of cryptosporidiosis in AIDS patients. OBJECTIVE--To describe a nosocomial outbreak of cryptosporidiosis during four months after June 1989. SETTING--A department of infectious diseases in Copenhagen, seeing about half the patients with AIDS in Denmark. SUBJECTS--73 HIV antibody negative subjects and 60 antibody positive subjects admitted as inpatients during the transmission period of the outbreak (20 June-14 August), of whom 18 (17 with AIDS, one with AIDS related complex), developed cryptosporidiosis. Two further HIV negative subjects (one departmental secretary, one visiting relative) developed cryptosporidiosis. MAIN OUTCOME MEASURES--Cryptosporidia in stool samples, clinical symptoms, CD4 cell count, HIV antigen concentration, chemotherapeutic treatment. RESULTS--The source of the outbreak was identified as ice from an ice machine in the ward, contaminated by an incontinent, psychotic patient with cryptosporidiosis picking out ice for cold drinks. The mean incubation time was at least 13 days-that is, twice that in HIV-negative patients. Of the 18 patients with AIDS who developed cryptosporidiosis, five recovered, two were symptomless carriers, three died of unrelated causes, and eight died after prolonged diarrhoea. Among the 57 exposed HIV antibody positive inpatients (excluding two patients and the index case with cryptosporidiosis diagnosed elsewhere), significantly more of those who developed symptomatic cryptosporidiosis received oral sulphonamides than those who did not (91%, 10/11 v 48%, 21/44, p less than 0.05). CONCLUSIONS--The clinical and epidemiological findings indicate that infection was the consequence of very small inocula. Increased sensitivity to cryptosporidiosis may be an unrecognised side effect of oral sulphonamide treatment in patients with AIDS. 
4	Management of multiple risk factors for coronary heart disease in patients with hypertension. Hypertension intervention trials, which have involved mainly the use of diuretics and beta-blockers, have demonstrated a disappointing benefit in terms of reduction of coronary heart disease (CHD). Rather than suggesting that elevated blood pressure and CHD are not causally related, these data suggest that the antihypertensive agents used were not optimal for the management of hypertension and a review of the currently recommended therapies is needed. Major risk factors for CHD, which include increased blood pressure, elevated serum cholesterol levels, and smoking, are highly prevalent in the general population and appear to cluster in patients with hypertension. Therefore the treatment of hypertension demands a multifactorial approach, one that takes into consideration all the risk factors for CHD. Diuretics and beta-blockers adversely affect the serum lipid profile, and this could negate some of the CHD benefit afforded by blood pressure reduction. 
4	Differential protective effects of halothane and isoflurane against hypoxic and reoxygenation injury in the isolated guinea pig heart. The authors investigated the effects of halothane (HAL) and isoflurane (ISO) on cardiac depression produced by global hypoxia and the recovery of function following reoxygenation is isolated guinea pig hearts perfused with Krebs' solution at constant pressure. Isovolumetric left ventricular systolic (LVSP) and end-diastolic pressures (LVEDP) were measured by placing a saline filled, latex balloon into the left ventricle. Bipolar electrodes were placed in the right atrium and right ventricle for measurements of heart rate (HR), atrioventricular conduction time (AVCT), and determination of the incidence and severity of dysrhythmias occurring during hypoxia and reoxygenation. Hearts were divided into three groups: control (n = 20), halothane (n = 12), and isoflurane (n = 13). All hearts were exposed in sequence to oxygenated perfusate (PO2, 530 mmHg), moderately hypoxic perfusate (PO2, 91 mmHg) for 30 min, and then to oxygenated perfusate for 40 min. Halothane (1%, 0.4 mM) or isoflurane (1.5%, 0.5 mM) were administered 10 min before hypoxia, during hypoxia, and during the first 10 min of reoxygenation. Exposure to halothane and isoflurane before hypoxia produced a 14 and 11% decrease in heart rate, a 32 and 23% increase in AVCT, and a 47 and 28% decrease in LVSP (all P less than or equal to 0.001) for halothane and isoflurane, respectively, and no significant change in LVEDP. During hypoxia, HR decreased and AVCT increased similarly in both groups. Left ventricular systolic pressure (LVSP) decreased sharply with a narrowing of the prehypoxic differences among the groups. In the control and isoflurane groups, LVEDP increased during hypoxia but remained unchanged in the halothane group. 
2	From Leningrad to the day-care center. The ubiquitous Giardia lamblia. Giardiasis is recognized as a worldwide public health problem. Seroprevalence data from both the developing and developed world show high rates of carriage in populations at risk for fecal-oral transmission, such as children in day-care centers. Outbreak investigation has expanded our understanding of reservoirs for Giardia lamblia and of the routes of transmission. Various host factors have been associated with infection. The pathogenesis of giardial infections is being elucidated, in particular the role of lectin activation in producing disease. Three standard chemotherapeutic agents are available in the United States. The institution of community-wide prevention measures is equally important. Current areas of investigation including antigenic composition and enzymatic variants should result in effective forms of immunotherapy, while more effective forms of chemoprophylaxis could assist in eradicating the pathogen from institutional settings. 
1	The value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast. Specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over-all course of the disease. Sixty-four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis. Those patients with a new complaint at an interval between scheduled follow-up visits and who went on to have tests to document a recurrence were categorized as interval follow-up. Those who were seen at a prearranged regular follow-up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow-up. Thirteen patients presented with new contralateral primary disease and 51 with metastatic disease (16, bone; 13, lung; 11, local; three, liver, and eight, multiple). The median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups, respectively. Ninety per cent of the failures occurred by 53 months. The survival time after recurrence was significantly greater in those patients diagnosed routinely (p = 0.003). However, the over-all survival time (from primary therapy to death) was only significantly improved for the routine group when the contralateral new primary diseases were included (p = 0.009). The method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram. Strong recommendations for follow-up testing can be limited to mammogram and physical examination. 
5	Loss of photosynthetic and chlororespiratory genes from the plastid genome of a parasitic flowering plant. Photosynthesis is the hallmark of plant life and is the only plastid metabolic process known to be controlled by plastid genes. The complete loss of photosynthetic ability, however, has occurred on several independent occasions in parasitic flowering plants. Some of these plants are known to lack chlorophyll and certain photosynthetic enzymes, but it is not known to what extent changes have occurred in the genes encoding the photosynthetic apparatus or whether the plants even maintain a plastid genome. Here we report that the nonphotosynthetic root parasite Epifagus virginiana has a plastid chromosome only 71 kilobases in size, far smaller than any previously characterized land plant plastid genome. The Epifagus plastid genome has lost most, if not all, of the 30 or more chloroplast genes for photosynthesis and most of a large family of plastid genes, the ndh genes, whose products may be involved in a plastid respiratory chain. The extensive changes in Epifagus plastid gene content must have occurred in a relatively short time (5-50 x 10(6) yr), because Striga asiatica, a related photosynthetic parasite, has a typical complement of chloroplast genes for photosynthesis and chlororespiration. The plastid genome of Epifagus has retained transcribed ribosomal RNA and ribosomal protein genes, suggesting that it expresses one or more gene products for plastid functions not related to photosynthesis. 
1	Human papillomavirus in women with vulvar intraepithelial neoplasia III. Untreated cases of vulvar intraepithelial neoplasia (VIN) III may progress to invasive vulvar carcinoma. Tissues from 29 New Zealand women with VIN III were examined for the presence of human papillomavirus (HPV) types 6, 11, 16 and 18 by in situ hybridization and polymerase chain reaction. HPV 16, the only HPV type detected in the lesions, was identified in about half the cases. HPV-positive women were younger than HPV-negative women, and their lesions displayed koilocytosis more often. In four of five cases in which there was a progression to invasive cancer, HPV 16 was detected in both the VIN III and invasive cancer tissue. 
4	Transesophageal echocardiography during percutaneous balloon mitral valvuloplasty. To ascertain the value of transesophageal echocardiography during percutaneous balloon mitral valvuloplasty, the present study was undertaken in 26 anesthesized patients (21 women and 5 men; mean age, 47 years) with symptomatic rheumatic mitral valve stenosis. In all but one patient the balloon dilation of the mitral valve was successful and Doppler-derived valve area increased (0.9 +/- 0.3 to 1.9 +/- 0.4 cm2). Transesophageal echocardiography provides continuous monitoring, as well as guidance of the procedure. Crossing the arterial septum, as well as delivery of the sheath through the mitral valve orifice and correct positioning of the balloon, was highly facilitated and reduced x-ray exposure time. The degree of mitral regurgitation and the presence of interatrial shunting at the end of the procedure could be readily assessed, making cineangiography not necessary. Complications of the procedure, such as pericardial effusion, could be detected before hemodynamic deterioration had occurred (one patient). The advantages of transesophageal echocardiography for routine monitoring of percutaneous mitral valvuloplasty, however, should be weighted against the added risk and expense of this support. 
5	Assessment of Proplast-Teflon disc replacements [published erratum appears in J Oral Maxillofac Surg 1991 Feb;49(2):220] This retrospective study reports the findings in the follow-up of 31 temporomandibular joints in which Proplast-Teflon (Vitek Inc, Houston, TX) replacements were used. Among the problems noted were pain, malocclusion, restricted opening, and degenerative changes in the condyle and fossa. 
3	Facial bone fracture associated with carotid-cavernous sinus fistula. Out of 989 cases of facial bone fracture, ten patients had carotid-cavernous sinus fistulas (1.01%). Their ages ranged from 25 to 48 years. Seven were male and three female. Two of the ten patients had lower third, three patients had middle third, three patients had upper third, and two patients had combined middle and lower third facial bone fractures. The signs and symptoms of a fistula appeared from the first postinjury day up to 50 days after the injury (mean, 21 days). Four patients had symptoms after operation for facial bone fracture. Most fistulae were identified by arteriography before treatment. Followup ranged from 1 year, 8 months, to 5 years, 9 months (mean, 2 years, 9 months). One patient had a malocclusion. Nine patients had complete resolution of their bruits. Complications included unilateral complete visual loss (two), CSF rhinorrhea (two), and stroke in one of the two CSF rhinorrhea patients. One patient expired due to a severe head injury, and there was one death from an unrelated cause. 
1	Retinal vasculitis as a complication of rheumatoid arthritis. Two middle-aged women developed retinal vasculitis in the moderately active phase of classical rheumatoid arthritis. Fluorescein angiography disclosed diffuse leakage from the retinal capillaries and cystoid macular edema, which subsided in response to oral steroid. They did not show any clinical signs of vasculitis in other parts of the body. Retinal vasculitis should be included in the list of complications observed in rheumatoid arthritis. 
1	Astroblastoma: electron microscopy and immunohistochemical findings: case report. The clinical, histological, immunohistochemical, and electron microscopic features of a cerebral astroblastoma are reported. The patient is a young woman with a superficial parietal tumor. Macroscopic findings include a well-delineated superficial nodule with a hard central core. Histological study disclosed a predominantly papillary tumor with hyalinized vessels. Tumor cells were scarcely positive with immunohistochemical stain for glial fibrillary acidic protein, extensive and diffusely positive with vimentin and neuron-specific enolase, and intensely positive with S-100 and epithelial membrane antigen in the papillary areas. Ultrastructural study showed abundant intermediate filaments forming bundles in tumoral cytoplasms, membrane junctions, and external laminae when cells were in contact with collagen fibers. Based on immunohistochemical and ultrastructural characteristics, we believe that the filaments seen in tumor cells are mainly vimentin filaments. These peculiar immunohistochemical patterns in a glioma may aid in the histological diagnosis of this rare tumor type. 
4	Relative importance of activation sequence compared to atrioventricular synchrony in left ventricular function. This study evaluated the relative hemodynamic importance of a normal left ventricular (LV) activation sequence compared to atrioventricular (AV) synchrony with respect to systolic and diastolic function. Twelve patients with intact AV conduction and AV sequential pacemakers underwent radionuclide studies at rest and Doppler echocardiographic studies at rest and during submaximal exercise, comparing atrial demand pacing (AAI) to sequential AV sensing pacing (DDD) and ventricular demand pacing (VVI). Studies at rest were performed at a constant heart rate between pacing modes, and the exercise study was performed at a constant heart rate and work load. Cardiac output was higher during AAI than during both DDD and VVI (6.2 +/- 1 vs 5.6 +/- 1 and 5.3 +/- 1 liters/min, p less than 0.05). LV ejection fraction was likewise higher during AAI (55 +/- 12 vs 49 +/- 11 vs 51 +/- 13, p less than 0.05). VVI with or without AV synchrony was associated with a paradoxical septal motion pattern, resulting in a 25% impairment of regional septal ejection fraction. In addition, LV contraction duration was more homogenous during AAI. Peak filling rate during AAI and VVI was higher than during DDD (2.86 +/- 1 and 2.95 +/- 1 vs 2.25 +/- 1 end-diastolic volume/s; p less than 0.05). During VVI, the time to peak filling was significantly shorter than during both AAI and DDD (165 +/- 34 vs 239 +/- 99 and 224 +/- 99 ms; p less than 0.05). 
1	Improved early detection of recurrence in prostatic carcinoma following hormonal therapy. Combined use of palpation and fine needle aspiration cytology. Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal examination and fine needle aspiration cytology at six-month intervals for periods ranging from six to one hundred twenty months (median follow-up 48 mos). The cytologic findings and clinical impressions were divided into four or five categories, respectively, ranging from benign to clearly malignant. Cytologic material and clinical descriptions suitable for evaluation were available for 306 follow-up examinations. Of these, 209 were cytologically benign (including 191 without and 18 with clinical evidence of malignancy). The remaining 97 examinations showed cytologic evidence of malignancy of which 50 were clinically apparent (51.5%). While the correlation of clinical and cytologic findings was good (91.4%) in cases with no evidence of disease activity, our findings indicate that many recurrences which are occult to clinical examination may be detected by cytologic examination. 
1	Chromosomes in childhood acute lymphoblastic leukaemia: karyotypic patterns in disease subtypes. To define further the clinical importance of cytogenetic analysis in acute lymphoblastic leukaemia (ALL) a prospective study was performed on 139 unselected children. Analyses were considered adequate in 104, of whom 35 were normal and 69 had clonal abnormalities. Abnormalities were categorised according to banded chromosome analysis as well as chromosome count. Karyotypes were correlated with clinical and laboratory features at diagnosis and with survival. Of the successful analyses, thirty five (34%) children had no abnormalities; this group contained an excess of T cell disease. Twenty five (24%) had a "characteristic" hyperdiploid karyotype and as a group had lower presenting white counts, a tendency to CD10, and periodic acid schiff positivity of the blast cells and smaller spleens. None was an infant and only one was over 10 years old. Seven (7%) children with t(9; 22), t(8; 14), or t(4; 11) translocations were grouped together as "specific" translocations. Collectively they had a significantly worse prognosis than the remainder. Nine children developed central nervous system relapse, six of whom had either t(4; 11) or abnormalities of 9p or 19p. A descriptive classification taking into account chromosome bonding pattern is cytogenetically more appropriate and may be more clinically useful than grouping children simply by chromosome number. As knowledge and techniques improve, the classification of cytogenetic abnormalities in ALL will need to be kept under frequent review. 
5	Acute upper airway obstruction following Teflon injection of a vocal cord; the value of nebulized adrenaline and a helium/oxygen mixture in its management A 67-year-old man presented with a 45-year history of a week voice. This was result of polio which had left him with a right vocal cord palsy. The patient underwent a Teflon injection of the right vocal cord under general anaesthesia to improve the quality of his voice. In the immediate post-operative period, he suffered acute upper airway obstruction. The problem of acute upper airway obstruction following Teflon injection is considered and its management with nebulized adrenaline and a helium/oxygen mixture is discussed. 
5	Assessment of patient laboratory data in the acutely ill. Laboratory test results are a valuable source of information. Nurses need to assess laboratory test results as part of the physical assessment of their patients. Comparison of laboratory test results and changes with abnormal physical findings provides the basis for changes in the nursing care plan. Progressive monitoring of laboratory results and prompt interventions might lessen the seriousness of the health problem. In acute care units, the initial group of laboratory tests serves as a baseline for assessing additional test results. Several reference values should be remembered, particularly the electrolytes (potassium, sodium, and calcium), glucose, BUN, creatinine, and albumin. Specific group profiles assist in identifying and in monitoring the patient's health status. Incorporating laboratory test results into the plan and evaluation of care will result in safer and more effective patient care. Referring to laboratory test findings and comparing them with physical assessment findings are required for the delivery of professional nursing care. 
3	Fluctuations of interictal brain imaging in repeated 123I-IMP SPECT scans in an epileptic patient. Single photon emission computed tomography (SPECT) brain scans with N-isopropyl-(iodine 123) p-iodoamphetamine (123I-IMP) were performed three times in interictal periods in a 35-year-old man with intractable frontal lobe epilepsy and normal X-ray CT findings. The first scan showed decreased 123I-IMP uptake in the right frontal lobe. This abnormal image was regarded as the primary focus of his epilepsy on the basis of its regional agreement with focal epileptic discharges on EEGs. In the second scan, he showed normal imaging, while the third scan showed the same abnormal image as before, in the right frontal lobe. The frequency of his clinical seizures was almost unchanged during the intervals between scans and further EEGs recorded soon after each scan showed almost no changes in the basic activities and frequency of the epileptic discharges. Such fluctuations in SPECT brain imaging suggest that the severity of functional inactivation underlying the focal hypoperfusion image as an epileptic focus may fluctuate considerably in the interictal state with no relation to the clinical features of epilepsy. 
5	Incidental demonstration of pericardial fistula during hepatobiliary scintigraphy. Biliary vomiting developed 16 mo after resection of adenocarcinoma of the esophagus in a patient with a complex postoperative course. A biliary scan revealed an outline of the pericardium, suggesting a fistula. The potential role of radionuclide imaging in this rare and potentially fatal complication is discussed. 
3	The efficacy of suction drains after routine total joint arthroplasty [published erratum appears in J Bone Joint Surg [Am] 1991 Jun;73(5):791] A prospective study of thirty-eight patients (seventy-six knees) who had had a primary bilateral total knee replacement and twelve patients (twenty-four hips) who had had a primary bilateral total hip replacement was conducted to assess the effect of postoperative suction drainage on wound-healing. A suction drain was placed on each patient's right operative wound, while no drains were used on the left. Otherwise, the same operative technique and method of closure were used in all wounds. Statistical analysis of the results showed no difference between the two sides with regard to the incidences of swelling or persistent drainage. Return of active function of the quadriceps and of range of motion of the knee in patients who had had a total knee replacement was also unaffected by the use of suction drains. We concluded that the routine use of suction drains for wounds is unnecessary after uncomplicated total joint arthroplasty. 
5	Congenital angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type. The autopsy of a stillborn infant showed an extensive intravascular proliferation of atypical cells throughout the body. There was no infiltration by these cells of the parenchyma of the bone marrow, lymph nodes, or thymus. By histochemistry, these cells were negative for naphthol-ASD-chloroacetate esterase, a marker of granulocytes. By immunohistochemistry, they were reactive with MT-1 and anti-Leu-22, but unreactive with MB-1, L26, anti-Leu-M1, Tu-9, and antihemoglobin antibodies. A few cells reacted with antileukocyte common antigen and UCHL-1. Based on these findings, the lesion was diagnosed as angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type, which occurred congenitally. Most angiotropic lymphomas in the literature are of the B-cell type, and no leukemia virus type I antibody was negative in the mother. 
1	Thyroid carcinoma with mixed tall-cell and columnar-cell features. Tall-cell and columnar-cell carcinomas have been regarded as aggressive variants of papillary thyroid carcinoma. In the present case report the authors describe a composite tumor where these forms of differentiation coexisted, with transitional changes occurring within single follicular structures. This finding indicates that the two variants are closely related. In local recurrences, one or the other feature appeared in separate lesions. Lung metastases developed, and the patient died 5 1/2 years after diagnosis and primary treatment. 
2	The auditory P300 event-related potential: an objective marker of the encephalopathy of chronic liver disease. Recently many variants of electroencephalogram-evoked responses have been studied as potential diagnostic aids in the detection and evaluation of hepatic encephalopathy. This study assesses the value of the auditory P300 event-related potential--a slow component of the auditory evoked response--as a tool in this field. Twenty-one nonencephalopathic and 12 encephalopathic (grade 1/2) cirrhotic patients and 26 controls were assessed clinically and psychometrically. Electroencephalogram spectral analysis and visual evoked response recordings were also conducted. An auditory P300 wave was elicited using the standard two-tone discrimination paradigm. The latency and amplitude of this wave were measured. The latency of the P300 was found to be significantly increased in the encephalopathic patients compared with both nonencephalopathic cirrhotic and control groups (p less than 0.05). Amplitude of the wave was decreased in both nonencephalopathic and encephalopathic patients, but this was not statistically significant. This study suggests that the latency of the P300 is a good marker of grades 1 and 2 clinical hepatic encephalopathy. The delays in the P300 latency may indicate that encephalopathic patients have a deterioration of their stimulus evaluation abilities. 
5	Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox. The two mouse genes, En-1 and En-2, that are homologs of the Drosophila segmentation gene engrailed, show overlapping spatially restricted patterns of expression in the neural tube during embryogenesis, suggestive of a role in regional specification. Mice homozygous for a targeted mutation that deletes the homeobox were viable and showed no obvious defects in embryonic development. This may be due to functional redundancy of En-2 and the related En-1 gene product during embryogenesis. Consistent with this hypothesis, the mutant mice showed abnormal foliation in the adult cerebellum, where En-2, and not En-1, is normally expressed. 
5	Analysis of programmed stimulation methods in the evaluation of ventricular arrhythmias in patients 20 years old and younger. The purpose of this study was to systematically evaluate programmed ventricular stimulation in patients less than 21 years of age undergoing electrophysiologic testing. A standardized protocol was applied in 55 consecutive patients (mean age 14 years) with the following clinical presentations: sustained ventricular tachycardia (VT) (n = 17); ventricular fibrillation (VF) (n = 7); syncope with heart disease (n = 10); nonsustained VT (n = 6); and syncope with an ostensibly normal heart (n = 15). The stimulation protocol consisted of 1 and 2 ventricular extrastimuli during sinus rhythm, followed by 1 to 4 (S2, S3, S4, S5) extrastimuli during pacing at 2 ventricular sites. Of the 17 patients with sustained VT, 12 had induction of the arrhythmia (sensitivity = 71%). Overall, 18 of 55 patients had inducible sustained VT, with this response significantly enhanced by use of S4 or S5 protocols (p = 0.02). Although no syncope patients with an ostensibly normal heart had inducible sustained VT, 7 had polymorphic nonsustained VT in response to ventricular stimulation. The mean number of extra-stimuli preceding the induction of nonsustained or sustained VT or VF did not differ. The induction of VF in 5 cases during this study was preceded in each case by extrastimuli intervals less than or equal to 190 ms. Thus, data indicate that aggressive stimulation protocols appear to be required for induction of sustained VT in most young patients, nonsustained polymorphic VT as a response to aggressive programmed stimulation is of uncertain significance, and that coupling intervals less than or equal to 190 ms may correlate with the induction of VF. 
1	Radiobiological studies in the naevoid basal cell carcinoma syndrome. The naevoid basal cell carcinoma syndrome is described in a 43-year-old male. The response of dividing fibroblasts from this patient to the lethal effects of ionizing radiation was indistinguishable from that of a normal control: mean inactivation dose (D) = 1.74 Gy and 1.68 Gy, respectively. However, these cells were defective in the repair of potentially lethal damage (D = 2.36 Gy and 3.26 Gy, respectively). The response to radiation of Go T lymphocytes derived from the patient was similar to that of the control. The frequency of mutant circulating T lymphocytes resistant to 6-thioguanine was 17 x 10(-6) which was elevated when compared with age-matched controls. These results suggest an abnormality in the response of the fibroblasts to ionizing radiation damage. 
5	Use of recombinant human erythropoietin to enhance autologous blood donation in a patient with multiple red cell allo-antibodies and the anemia of chronic disease. We treated a patient with alcohol-induced cirrhosis, intractable pain from a defective hip prosthesis, and multiple red cell allo-antibodies with recombinant human erythropoietin (EPO) in order to facilitate collection of blood for autologous transfusion during an elective total hip revision. This patient had experienced a delayed transfusion reaction 4 months earlier after receiving least incompatible packed red cells for gastrointestinal bleeding. His blood could not be crossmatched because of the development of multiple antibodies to homologous blood given during previous surgery and several episodes of gastrointestinal hemorrhage. Following initiation of EPO therapy, there was a prompt and persistent increase in the reticulocyte count from a baseline of 1.6% to a maximum of 8.6%. This was accompanied by maintenance of the hematocrit between 32% and 38.5% despite withdrawal of seven units of autologous blood over the 45-day treatment period. Poor venous access and availability of blood bank personnel, not hematocrit level, were the limiting factors that determined how frequently blood could be collected. We conclude that EPO stimulated erythropoiesis in this patient with underlying anemia of chronic disease and facilitated harvest of autologous blood for elective surgery. 
1	Breast cancer screening in older women: practices and barriers reported by primary care physicians. Annual mammography, in combination with clinical breast examinations, can reduce mortality from breast cancer. However, surveys of both patients and physicians suggest that mammography is underutilized. This study examined whether physicians' reported breast cancer screening practices and barriers to mammography varied with patients' age. Data from 576 primary care physicians (internal medicine, family/general practice, and obstetrics/gynecology) who participated in a mailed statewide survey were analyzed. Physicians reported screening elderly women significantly less often than younger women, regardless of family history of breast cancer. With the exception of medical specialty, physicians' demographic and practice characteristics were not associated with reported screening practices. However, physicians' knowledge and beliefs about breast cancer in older women were associated with reported screening practices. When analyzing barriers to ordering mammography, cost to the patient was viewed as a barrier for women of all ages, and pain was viewed as a greater barrier for younger women; otherwise, physicians consistently believed that their elderly patients faced considerably more barriers compared with younger women. Further investigation is required to examine why primary care physicians report age-related differences in both breast screening and barriers to mammography. 
3	Observation of cerebrospinal fluid flow with echo-planar magnetic resonance imaging. Using echo-planar (EP) magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) flow patterns have been demonstrated in the normal subject and patients with pathological conditions including communicating hydrocephalus, aqueduct stenosis and syringohydromyelia. Snap-shot imaging times of 128 ms allow detailed demonstration of transient intraventricular CSF flow patterns, which is not possible with conventional MRI. The potential of EPI as a method for qualitative and quantitative assessment of CSF dynamics is illustrated. 
5	Pneumatic chest wall compression. A cause of respiratory failure from massive subcutaneous emphysema. Subcutaneous emphysema rarely causes significant adverse clinical consequences. Two patients had development of massive subcutaneous emphysema during positive-pressure ventilation that resulted in chest wall compression and respiratory failure. Drainage of the subcutaneous air produced dramatic improvement. Subcutaneous emphysema is potentially fatal in ventilated patients. Specific decompression of subcutaneous tissues is indicated in such extreme cases. 
1	Factors related to and consequences of weight loss in patients with stomach cancer. The Norwegian Multicenter experience. Norwegian Stomach Cancer Trial. Of 1165 patients with stomach cancer included in a national, prospective multicenter study with 51 surgical units participating, information about weight loss before diagnosis was available for 855 patients (73%). Median weight loss was 5 kg; 259 patients (31%) experienced no weight loss. By logistic regression analysis the authors found that weight loss increased with age and advancing stages of disease (TNM Stage I-IV), with decreasing Karnofsky index, in Lauren's diffuse versus intestinal tumor type, and with tumors located at the cardia/esophagus. Increasing weight loss reduced the resectability rate significantly, but no association between weight loss and postoperative complication rate was found. The odds ratio for postoperative mortality was 2.5 to 1 for the weight loss group 5 to 10kg versus 0 kg. In conclusion, weight loss reflects a less favorable tumor status. Weight loss did not increase postoperative morbidity but did lead Weight to a higher death rate after surgery. 
4	Sudden appearance of coronary thrombus observed by angiography--a case report. A sudden coronary thrombus formation was documented by chance during cardiac catheterization in a patient with postinfarction angina. The thrombus was successfully treated with intravenous urokinase and heparin infusions, and thereafter, coronary angioplasty was performed without any complication. 
5	Surgical treatment for severe slipping of the upper femoral epiphysis. We have used a modified technique of cervical osteotomy to treat a consecutive series of 23 patients with chronic slip of the upper femoral epiphysis. It has been successful in correcting both moderate and severe deformities with a low incidence of avascular necrosis, comparable to that seen after subtrochanteric osteotomies. We describe the operative details and discuss the features which make cervical osteotomy technically superior to intertrochanteric and subtrochanteric procedures. 
1	Synthesis of type I collagen in healing wounds in humans. To quantify wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured with specific radioimmunoassays. The mean concentration of PICP in would fluid on day 1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less than 0.001, signed rank test). On day 7, the mean concentration reached was 380 times higher than that of day 1 (79,330 +/- 54,151 micrograms/L). Only one peak of PICP antigenicity, corresponding to the intact propeptide as set free during synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration analysis of wound fluid samples. The mean concentration of PIIINP was 70 +/- 61 micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129 micrograms/L on day 3 (p less than 0.001 when compared with day 1). Finally on day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day 1, was reached. Methods described in the present paper allow separate and repetitive quantification of the synthesis of both type I and type III procollagen during human wound healing. 
2	Vaccines and milk immunoglobulin concentrates for prevention of infectious diarrhea. Considerable progress has been made in the last decade in developing vaccines against the most important enteric infections. Two new, widely licensed vaccines (oral Ty21a and parenteral Vi) are available against typhoid fever, and new attenuated Salmonella typhi strains are ready for testing. An engineered live orally administered cholera vaccine, CVD 103-HgR, is undergoing clinical trials for safety, immunogenicity, and transmissibility in children in areas where cholera is endemic. Multiple candidate vaccines against rotavirus, Shigella, and enterotoxigenic Escherichia coli are in clinical trials. Newly acquired knowledge about pathogenesis and mucosal and cellular immunology, coupled with application of biotechnology, has already resulted in many candidates for vaccines, and more are expected to appear within the next few years. 
5	Porokeratoses: immunohistochemical, light and electron microscopic evaluation. Punch biopsy specimens of 14 patients with porokeratosis of Mibelli (n = 1), disseminated superficial porokeratosis (n = 6), disseminated superficial actinic porokeratosis (n = 4), porokeratosis plantaris, palmaris et disseminata (n = 2), and punctate porokeratosis (n = 1) were obtained for light and electron microscopy for evaluation of possible differences between these clinical variants. Langerhans cells in close contact with early degenerating keratinocytes could be observed in the epidermis. To study the cellular composition of the epidermal inflammatory infiltrate immunohistochemistry was performed. These studies demonstrated that the predominant cell type in these infiltrates are helper T cells, intermingled with Leu-6+ Langerhans cells. Despite the clinical variation and possible different etiologic or triggering mechanisms, the immunohistochemical and morphologic changes in all types of porokeratosis are the same and seem to represent a uniform reaction pattern. 
5	Is thioridazine retinopathy progressive? Relationship of pigmentary changes to visual function. Thioridazine toxicity has been described as a 'progressive chorioretinopathy', but this designation can be misleading. During the first year after thioridazine exposure retinal pigmentation evolves from a granular to a patchy or nummular appearance. However, visual function and the electroretinogram typically improve during this period. Some cases may show chorioretinal atrophy and functional loss many years later, but there is little evidence for ongoing drug-related progression. Late atrophy may represent degeneration of cells that were injured subclinically at the time of initial drug exposure. Although thioridazine toxicity produces an evolving pigmentary disturbance, functional changes must be monitored independently of fundus appearance. 
5	Role of percutaneous fine-needle aspiration biopsy in suspected intrathoracic malignancy. Percutaneous fine-needle aspiration (PFNA) biopsy is an accepted technique for the diagnosis of suspected intrathoracic malignancy, but the appropriate indications for its use have not been clearly defined. To help establish guidelines, we performed a retrospective analysis of 188 patients who underwent PFNA biopsy for suspected intrathoracic malignancy. Biopsy led to a diagnosis in 72% (135/188) of the patients, but in 27% (50/188) samples were inadequate for cytological diagnosis, and in 2% (3/188) samples were adequate but failed to yield a diagnosis. Fifty-three patients underwent surgical intervention, thus allowing histological confirmation of the cytological diagnosis. In patients with a diagnosis from PFNA biopsy, operation confirmed malignancy in 97% (37/38) and a specific cell type in 79% (30/38). In patients without a diagnosis after biopsy, a malignancy was found in 73% (11/15) at the time of operation. This suggests a high rate of accuracy when PFNA biopsy provides a diagnosis. However, it also illustrates that a substantial percentage of PFNA biopsy attempts fail to yield a diagnosis in patients ultimately found to have malignancies. This implies that PFNA biopsy might best be reserved for patients who are not surgical candidates. 
5	Cesarean section before the onset of labor and subsequent motor function in infants with meningomyelocele diagnosed antenatally Background. Meningomyelocele can now be detected before birth. Few data are available on its natural history, however, and optimal management at the time of delivery is controversial, although it has been suggested that labor and vaginal delivery may cause pressure on exposed nerve roots, resulting in additional loss of neural function. Methods. To assess the effect of labor and the type of delivery on the level of motor function in fetuses with uncomplicated meningomyelocele, we identified 200 cases of this disorder, accounting for 95 percent of the cases that occurred in the state of Washington during our 10-year study period. We compared the outcomes of 47 infants delivered by cesarean section before labor began, 35 delivered by cesarean section after a period of labor, and 78 who were delivered vaginally (another 40 were ineligible for the study). In cases of meningomyelocele detected prenatally, cesarean section was performed before the onset of labor if isolated meningomyelocele without severe hydrocephalus was present. The infants delivered in this manner were compared with those who were delivered either vaginally or by cesarean section after labor began. Results. At two years of age, the infants who had been exposed to labor were 2.2 times more likely to have severe paralysis than those delivered by cesarean section without labor (95 percent confidence interval, 1.7 to 2.8). Infants delivered by cesarean section before the beginning of labor had a mean (+/- SD) level of paralysis 3.3 +/- 3.0 segments below the anatomical level of the spinal lesion at two years of age, as compared with 1.1 +/- 2.3 for infants delivered vaginally and 0.9 +/- 4.1 for infants delivered by cesarean section after the beginning of labor (P less than 0.001 for both comparisons). Exposure to labor did not affect the frequency of neonatal complications or later intellectual performance. Conclusions. For the fetus with uncomplicated meningomyelocele, delivery by cesarean section before the onset of labor may result in better subsequent motor function than vaginal delivery or delivery by cesarean section after a period of labor. 
5	Beagle pup germinal matrix maturation studies. Intraventricular hemorrhage, or hemorrhage into the germinal matrix tissues of the developing brain, remains a common problem of preterm infants. The "risk period" for this insult is the first 3-4 postnatal days. We hypothesized that this risk period for hemorrhage is related to rapid perinatal maturation of the germinal matrix vasculature and employed the newborn beagle pup model for the study of this maturation. Newborn beagle pups (n = 30) were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density between postnatal days 1 and 4. Germinal matrix sections were also stained for antibodies to alpha-smooth muscle actin, collagen IV, collagen V, desmin, factor VIII-related antigen, fibronectin, glial fibrillary acidic protein, laminin, transferrin, and vimentin. Vasculature staining by alpha-smooth muscle actin was not noted until postnatal day 10, and differential staining was detected for antibodies to laminin and collagen V. Quantification of staining intensity by confocal microscopy demonstrated a significant increase in both extracellular matrix components at postnatal day 4 compared with day 1 (p less than 0.05 for both). These basement membrane proteins may add sufficient structural integrity to germinal matrix vessels to prevent capillary rupture and thus intraventricular hemorrhage. 
5	Hypertrophic pyloric stenosis: volumetric measurement of nasogastric aspirate to determine the imaging modality The authors postulated that volumetric measurement of residual gastric aspirate in neonates and infants with nonbilious projectile vomiting could enable differentiation between patients with hypertrophic pyloric stenosis (HPS) and those with gastroesophageal reflux (GER) and help to determine whether ultrasound (US) or fluoroscopy of the upper gastrointestinal tract would best confirm the diagnosis. In the 38 patients (all but two of whom had been fasting for 3-4 hours), 10 mL or more of nasogastric aspirate was considered indicative of obstruction. HPS occurred in 91.7% of patients with 10 mL of aspirate or more, whereas GER occurred in 85.7% of patients with less than 10 mL. The differences between the two groups were statistically significant. Solely on the basis of residual volume (greater than or equal to 10 mL), the cause of vomiting could be differentiated, prior to standard radiologic studies, 89.4% of the time. It is concluded that patients with projectile vomiting who have 10 mL or more of residual aspirate in the stomach should undergo US for confirmation of HPS; those with less than 10 mL should undergo fluoroscopy for confirmation of GER. 
4	Financial impact of a rapid CK-MB-specific immunoassay on the diagnosis of myocardial infarction. The purpose of this study was twofold. First, we evaluated the financial impact of a rapid, monoclonal antibody-based CK-MB mass assay (Stratus, Dade Division, Baxter Laboratories, Miami, Fla) for the direct measurement of CK-MB in serum samples from 65 patients admitted to the coronary care unit with the possible diagnosis of acute myocardial infarction. Second, we evaluated retrospectively the Stratus assay and an activity assay (electrophoresis) for CK-MB in the following patient categories: acute myocardial infarction treated with and without thrombolytic therapy, angina, congestive heart failure, skeletal muscle trauma, and the acutely ill without acute myocardial infarction. The advantageous features of the Stratus mass assay were as follows. First, the laboratory was able to perform the assay more frequently because of the short assay time per specimen (less than 10 minutes) without additional personnel. This had a substantial impact on the clinician's ability to diagnose acute myocardial infarction and to move patients out of an intensive care unit at substantial financial savings to the patient, the hospital, or the third-party payer. Second, the Stratus assay was able to detect low levels of CK-MB (1 to 2 micrograms/L) in the presence of low total creatine kinase activity (less than 100 U/L). Third, the Stratus assay showed no interference due to very-high-total creatine kinase activities (greater than 100,000 U/L), CK-BB, macro-creatine kinase, and mitochondrial creatine kinase. 
2	Diarrhea in ciguatera fish poisoning: preliminary evaluation of pathophysiological mechanisms. Ciguatera fish poisoning is a clinical syndrome consisting of a combination of gastrointestinal and neurological symptoms occurring after eating toxin-containing tropical reef fish; it is a major cause of morbidity in Hawaii, the South Pacific, Australia, and the Caribbean. In an effort to define pathophysiological mechanisms responsible for the diarrheal component of the illness, we examined the effect of crude and fractionated toxin preparations on isolated rabbit ileal tissue in a Ussing chamber model. Both the crude toxin preparation (prepared from toxic Ctenochaetus strigosus) and 10% and 50% methanol-chloroform toxin fraction (prepared from a pool of toxic fish samples) gave a striking increase in transepithelial electrical potential difference and short-circuit current. Enterotoxic activity seemed to be mediated by calcium. When examined by light microscopy, the intestinal mucosa was not damaged by the toxin preparations used. Our data demonstrate that toxins involved in ciguatera fish poisoning directly stimulate intestinal fluid secretion without accompanying tissue damage and suggest that calcium is the "second messenger" mediating the process. 
5	Doppler echocardiographic evaluation of streptokinase lysis of thrombosed right-sided St. Jude Medical valves in patients with congenital heart defects. Four episodes of St. Jude Medical prosthesis leaflet thrombosis were serially evaluated by two-dimensional and Doppler echocardiography during treatment with streptokinase. Three patients aged 4, 11, and 24 years with congenital heart disease had St. Jude Medical valves in pulmonary positions (two cases) for tetralogy of Fallot and in the tricuspid position (one case). The duration of thrombosis was not known in any patient. Leaflet immobility and its resolution were demonstrated by echocardiography and were confirmed fluoroscopically. Continuous wave Doppler echocardiography showed abnormal stenotic gradients in thrombosed valves that were reduced after thrombolysis. These studies demonstrate the utility of two-dimensional and Doppler echocardiography in serial evaluation of prosthetic pulmonary and tricuspid valve thrombosis during thrombolysis. 
1	Unusual variants of adrenal pseudocysts with intracystic fat, myelolipomatous metaplasia, and metastatic carcinoma. Five previously unreported cases of adrenal pseudocysts are described that demonstrate a wider range of histologic appearances than has been previously recognized in these lesions. One pseudocyst removed from an asymptomatic 59-year-old female contained intracystic nests of cytologically malignant cells of unknown origin. Workup revealed a left breast mass, which on biopsy showed an infiltrating ductal carcinoma with neoplastic cells that were cytologically similar to those found within the cyst contents. Four other pseudocysts are described with variable numbers of intracystic vascular structures and benign adrenal cortical cells. In addition, intracystic mature adipose tissue was observed in all four cases, with myelolipomatous metaplasia found in one. Awareness of the wide histologic variability of these lesions should improve diagnostic accuracy and allow distinction from adrenocortical neoplasia and myelolipoma. 
1	Late metastases of cutaneous melanoma: case report and literature review. The development of delayed metastases, although rare, is well documented in patients with invasive cutaneous melanoma. Only 24 cases, including ours, are clearly documented in the literature. We describe a 56-year-old woman who had an acral lentiginous melanoma of the right hand (thickness 1.2 mm). Thirteen years after excision and postoperative irradiation, a subcutaneous metastasis developed in the right arm. One year later the patient died with disseminated bone metastases. This case, as with most of those with delayed metastases, has typical features: female sex; location at a site other than the back, arm, neck, or scalp; and primary tumor thickness between 1.2 and 2.5 mm. 
4	Reappraisal of surgical treatment of traumatic transection of the thoracic aorta. Since Crawford's report in 1973, repair of traumatic transection of the thoracic aorta without shunt or bypass has emerged as a popular technique which simplifies the operation and avoids use of heparin. Growing evidence, however, indicates that the incidence of paraplegia is higher with this method and may outweigh its advantages. With this in mind, we have examined our experience with 40 patients who underwent repair of aortic transection from 1975-1988. The operated patients in our series all survived. Fourteen were repaired using some type of bypass or shunt, none of whom developed paraplegia. The remaining 26 patients were repaired without a shunt and 9 (34.6%) developed paraplegia or paraparesis (p less than 0.02). Paraplegia was related to aortic occlusion time (p less than 0.002). It did not occur in 11 patients with times less than 27 minutes, but happened in 2 of 8 patients with times between 28 and 35 minutes and in all 7 patients with clamp times over 35 minutes. These data suggest that shunt or bypass should be used in most cases of aortic transection. 
1	Cathepsins D and E in normal, metaplastic, dysplastic, and carcinomatous gastric tissue: an immunohistochemical study. Immunohistochemical distributions of cathepsins D and E were determined in normal mucosa, metaplastic, dysplastic, and cancerous lesions of the human stomach. Cathepsins D and E were localised in the foveolar epithelium and parietal cells of the normal gastric mucosa, but their intracytoplasmic distributions were different - cathepsin E distribution was even and diffuse in the cytoplasm while cathepsin D was found in coarse intracytoplasmic granules. Chronic inflammation and ulcer did not influence the distribution of these enzymes. No positive staining was obtained in the incomplete type of intestinal metaplasia, dysplasia, and well differentiated adenocarcinoma. Tumour cells of signet ring cell carcinoma and poorly differentiated adenocarcinoma cells, however, gave strong and diffuse stainings for cathepsins D and E in the cytoplasm. The results suggest that the distribution of cathepsins D and E is related to each specialised function of the foveolar epithelium and the parietal cells, and that their disappearance is associated with development of well differentiated adenocarcinoma from intestinal metaplasia. 
5	Left ventricular pseudoaneurysm complicating mitral valve replacement in a 4-year-old child with acute bacterial endocarditis. A 4-year-old child with acute bacterial endocarditis required mitral valve replacement. A left ventricular pseudoaneurysm developed following surgery. The etiology and diagnosis of this complication are discussed. 
4	Transoesophageal pacing for perioperative control of neonatal paroxysmal supraventricular tachycardia. The perioperative management of a 16-day-old infant with recurrent supraventricular tachycardia (SVT) is discussed. Vagal manoeuvres and medication were not adequate in controlling the SVT. Since the patient was scheduled for extensive surgery in the prone position, it was decided to use transoesophageal pacing as the method of choice for conversion of SVT. Transoesophageal pacing succeeded several times in overriding the SVT and restoring normal heart rate and haemodynamic variables. The advantages and disadvantages of various methods of treating SVT in the newborn are discussed. 
5	Postangiographic femoral artery injuries: nonsurgical repair with US-guided compression Ultrasound-guided compression repair (UGCR) of catheterization-related femoral artery injuries was evaluated as a possible new imaging-guided interventional procedure. Thirty-nine femoral artery injuries (35 pseudoaneurysms, four arteriovenous fistulas) were detected with color Doppler flow imaging in patients with enlarging groin hematomas and/or groin bruits 6 hours to 14 days after catheterization procedures. UGCR was not performed in 10 patients due to spontaneous thrombosis (n = 4), infection (n = 1) or skin ischemia (n = 1), unsuitable anatomy (n = 3), or excessive discomfort (n = 1). The remaining 29 patients underwent a full trial of compression therapy, and the lesion was eliminated in 27. Follow-up color flow scans were obtained after 24-72 hours in all 27 successful cases and at 1-15 months in 19; no recurrences or complications occurred. UGCR for acute injuries is safe and technically simple and is promising as a cost-effective, first-line treatment for uncomplicated catheterization-related femoral artery injuries. UGCR is probably not appropriate for long-standing injuries. 
5	Postarthroscopy analgesia with bupivacaine. A prospective, randomized, blinded evaluation. The analgesic effect of intraarticular bupivacaine injected at the conclusion of knee arthroscopy done under general anesthesia was investigated in a prospective, randomized, and blinded fashion. Pain scores, the use of analgesic medications, crutch use, weight-bearing, activity level, and difficulty sleeping the night after surgery were all unaffected by the use of bupivacaine. The apparent lack of effect is most likely due to rapid clearance from the knee, leaving only a transient, 1 to 2 hours of potential benefit. In this study, the patients were already quite comfortable during this time period due to the routine use of intraoperative narcotics. The preoperative level of knee discomfort was found to be a major determinant of postoperative discomfort. Other much less important factors were synovial and chondral shaving, sex of the patient, and experience of the surgeon. 
1	The intraoperative incidence of detectable bilateral and multicentric disease in papillary cancer of the thyroid. This is a prospective study to determine the incidence of grossly detectable multicentric and bilateral cancer at operation in patients who, before surgery, were believed to have a unilateral lesion. The opposite lobe was inspected at the time of operation and the surgeon made a determination as to whether there was bilateral and/or multicentric disease present. A total thyroidectomy was then carried out and the accuracy of the surgeon's judgment was established by permanent-section pathologic examination. Fifteen of the 44 patients were assessed to have gross bilateral disease. Thirteen of these were confirmed by pathologic examination. One case of microscopic bilateral disease was not recognized by the surgeon. Seventeen patients were thought to have unilateral multicentric disease. Fifteen of these cases were confirmed by microscopy and an additional seven cases were documented to have secondary foci. It is obvious from this study that most disease that is called microscopic disease is actually palpable. A review of the literature confirms this. It was very unlikely for a patient who did not have unilateral multicentric disease to have a contralateral focus of carcinoma. The incidence of bilateral disease was 32%, and the incidence of multicentric disease was 50%; the surgeon was very accurate in assessing this. We believe that surgeons who advocate lobectomy as the primary treatment for thyroid cancer are recognizing grossly detectable disease in a significant number of patients and thus are doing total thyroidectomies in most patients with bilateral disease. 
5	Circus movement atrial flutter in the canine sterile pericarditis model. Differential effects of procainamide on the components of the reentrant pathway. To evaluate the mechanisms of action of procainamide on the components of the reentrant pathway, drug-induced changes in activation patterns, effective refractory periods (ERPs), and stimulation thresholds were analyzed in nine dogs with sterile pericarditis and sustained atrial flutter. Activation maps were based on 127 close bipolar recordings from a special "jacket" electrode. From the control map, 22 +/- 2 sites covering the slow zone and the normal zone of the reentrant circuit were selected to measure ERPs and thresholds. The excitable gap was estimated from the longest ERP during pacing at the tachycardia cycle length. During atrial flutter, epicardial activation proceeded as a single wave around an arc of functional conduction block in the proximity of the atrioventricular (AV) ring or around a combined functional/anatomic obstacle, with the arc being contiguous with one of the venae cavae. An area of slow conduction, which accounted for 53 +/- 15% of the revolution time within 35 +/- 15% of the total length of the reentrant pathway, was bordered by the arc of block and the AV ring or a caval vein and the AV ring, respectively. Procainamide (5-10 mg/kg i.v.) prolonged the cycle length of atrial flutter from 144 +/- 17 to 190 +/- 24 msec (p less than 0.05) and then terminated the arrhythmia in all studies. The increase in cycle length was due to an increase in conduction time in the slow zone by 37 +/- 11 msec (86 +/- 17% of the total cycle length increase). During the last reentrant beat, conduction failed in the slow zone, with the arc of block joining the AV ring. At termination, procainamide had prolonged conduction time, stimulation threshold, and ERP in the normal zone by 11 +/- 18%, 40 +/- 80%, and 5 +/- 15%, respectively, compared with 51 +/- 16%, 86 +/- 93%, and 14 +/- 21%, respectively, in the slow zone (p less than 0.05 for all three parameters). The duration of the excitable gap did not change significantly. We conclude that procainamide preferentially affected the slow zone of single loop reentrant circuits. The drug terminated circus movement atrial flutter without abolishing the excitable gap, and its effect on conduction seemed the major determinant of the antiarrhythmic action. 
5	Enlarged adenoid and adenoidectomy in adults: endoscopic approach and histopathological study. Adenoid enlargement is uncommon in adults and because examination of the nasopharynx by indirect posterior rhinoscopy is inadequate, many cases of enlarged adenoid in adults are misdiagnosed and accordingly maltreated. This study was conducted on 35 cases of enlarged adenoid aged between 20 and 42 years. The nasal endoscope was utilized to identify the adenoid mass. Adenoidectomy under transnasal endoscopic control was performed and all the excised material was sent for histopathological examination. Adenoidectomy resulted in marked improvement in 94 per cent of cases without major complications. Histopathological examination revealed non-specific inflammatory reaction in 15 cases (43 per cent), pure reactive changes, predominantly follicular hyperplasia, in two cases (6 per cent) and mixed pattern in 18 cases (51 per cent). Endoscopic follow-up for an average 17 months identified recurrence in only two patients. It was concluded that enlarged adenoid tissue in adults has some histopathological differences from that in children and adenoidectomy under transnasal endoscopic control is safe and reliable. 
4	Therapeutic embolization: enhanced radiolabeled monitoring. Radiolabeling of Ivalon (polyvinyl alcohol sponge) particles permits localization of injected particles during embolization through the use of a portable gamma camera and provides a means to prevent potentially fatal complications such as pulmonary embolization. A more efficient technique of labeling Ivalon particles with technetium-99m sulfur colloid was developed. An increase in labeling efficiency allowed more accurate determination of the distribution of injected Ivalon particles. Scanning electron microscopy demonstrated the stability of the Ivalon particles during this new labeling process. Two patients with arteriovenous malformations underwent therapeutic embolization with radiolabeled Ivalon particles; gamma camera imaging of the lesion and chest was performed throughout the procedure. 
5	Lipolytic factors associated with murine and human cancer cachexia. We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells. 
4	Role of beta-adrenergic blockers after percutaneous transluminal coronary angioplasty. Restenosis after percutaneous transluminal coronary angioplasty (PTCA) cannot currently be prevented. Different medical regimens have been largely unsuccessful. Experimental studies suggest roles for beta-adrenergic blockers and calcium antagonists. Controlled clinical studies have failed to show any decrease in restenosis rate for calcium antagonists. Corresponding studies for beta blockers are lacking. This study evaluates 541 consecutive PTCA procedures, 455 (86%) in patients treated with beta blockers after PTCA (76% metoprolol, 14% atenolol, 4% sotalol, 6% others) and 86 (14%) in patients without beta blockers. Angiographic success was achieved in 483 of 620 lesions (78%), and was not significantly different with or without beta blockers (79 vs 73%, p greater than 0.05). The procedure success rate and the complication rates (myocardial infarction, emergency coronary artery bypass grafting, death) did not differ with or without beta blockers (p greater than 0.05). Follow-up angiograms for 426 of the 483 successfully dilated lesions (88%) revealed that a total of 155 stenoses had recurred (36%). The restenosis rate was not significantly different with (368) or without (58) beta blockers (36 vs 38%, p greater than 0.05). For beta blockers with calcium antagonists (84% nifedipine, 13% diltiazem, 2% verapamil, 1% others), the restenosis rate was 97 of 250 (39%) vs 36 of 118 (31%) (p greater than 0.05). This retrospective study indicates that treatment with beta-adrenergic blockers after PTCA, alone or in combination with calcium antagonists, does not influence either the success rate or the restenosis rate and can be continued if indicated from an antiischemic viewpoint. 
2	Gender differences in Manning criteria in the irritable bowel syndrome. The objective of this study was to determine if gender differences exist when using the Manning criteria for diagnosis of irritable bowel syndrome. In an outpatient setting, 61 women and 36 men with entry complaints of abdominal pain, altered bowel habits, or both underwent full evaluation by board-certified/eligible gastroenterologists who also systematically rated the presence or absence of the six Manning criteria. Irritable bowel syndrome was defined as the absence of an organic disease explanation for the entry complaints. This determination was made by two other board-certified gastroenterologists after patients had been in the study for 9 months. These raters were independent of the study and rated the transcripts of patients' clinic visits, all other available clinical data from this and other clinics, all laboratory data obtained during the 9-month study period, and the results of a 9-month telephone follow-up to patients and their physicians. Sixty-five percent of the study population had no organic disease explanation for the entry symptoms, thereby representing irritable bowel syndrome for this study. A similar proportion and type of organic disease and irritable bowel syndrome were experienced by men and women. For the total sample of 97 subjects, the correlation of the Manning criteria with irritable bowel syndrome was 0.22 (P less than 0.01). In the 61 women, correlation between the Manning criteria and irritable bowel syndrome was significant (r = 0.47; P less than 0.01). In the 36 men, however, the correlation was in the opposite direction, although it was not significant (r = -0.16). It was concluded that significant gender differences exist when using the Manning criteria for the diagnosis of irritable bowel syndrome and that the Manning criteria were not of diagnostic value in men. 
1	De novo carcinoma of the lower urinary tract in renal allograft recipients. Immunocompetence has been postulated as an important defense against the progression of urothelial carcinoma. Three cases of de novo lower urinary tract carcinoma in renal transplant recipients demonstrated the potential for unusually rapid urothelial extension and invasion in chronically immunosuppressed patients. Two patients had a history of perineal condyloma acuminata; tumors from 1 of these harbored the genetic sequences of human papillomavirus type 6. One patient had multiple manifestations of cyclophosphamide-related urothelial injury, including bladder carcinoma. Treatment of 2 patients culminated in a radical operation during which the remaining native urinary system was resected completely, with sacrifice of the allograft kidney in 1 and diversion into an ileal conduit in 1. The remaining patient underwent urethrectomy and partial cystectomy with a sigmoid conduit. 
3	Clinicopathological experience with pineocytomas: report of five surgically treated cases. The clinicopathological experience associated with five cases of pineocytoma is presented. All patients were treated by surgical removal without postoperative radiotherapy. In three individuals, 2000 cGy was administered to the tumor as a presurgical diagnostic test, with no evidence of response. All cases demonstrated histological features of pineocytoma, according to the criteria of Borit et al., and of the so-called "pineocytoma with neuronal differentiation," according to the criteria of Rubinstein. The experience obtained from the present series reveals that these tumors can occur in the initial decades of life, that a cystic appearance and the presence of calcifications are distinctive features of their radiological evaluation, and that they have a good prognosis after surgical removal, even when the histological data indicate local invasion. The convenience of reserving the term "pineocytoma" for these tumors, and of including the so-called "pineocytomas without further differentiation" within the group of pineoblastomas, is suggested in order to achieve a practical clinicopathological assessment of parenchymatous pineal tumors. 
4	Orthostatic hypotension in human immunodeficiency virus infection may be the result of generalized autonomic nervous system dysfunction. We used an autonomic nervous system (ANS) testing battery to determine if generalized ANS dysfunction was present in five human immunodeficiency virus-positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All five patients had abnormal ANS testing, which demonstrated both sympathetic and parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with fludrocortisone effectively reversed the OH in four of the five patients. The OH was transient in these four patients. We believe it is important to recognize that OH may be the result of generalized ANS dysfunction in HIV-positive patients and that it can be effectively treated. 
1	Immunocytochemical localization of progesterone receptors in endocrine cells of the human pancreas. Progesterone receptors (PgR) have been immunocytochemically localized in the nuclei of several (40% to 75%) endocrine cells of the human pancreas and in a more variable number of neoplastic cells of 7 of 18 endocrine pancreatic tumors. Conversely the exocrine epithelial cells of the pancreas did not exhibit any PgR immunoreactivity in normal as well as in different pathologic conditions, including pancreatic adenocarcinomas. Estrogen receptors were not detected in any of the pancreatic samples investigated. Double immunocytochemical experiments have documented that PgR immunoreactivity in normal Langerhans islets is a consistent feature of most (75%) glucagon-producing A cells, of approximately 5% to 20% of insulin-producing B cells, and of a variable percentage of pancreatic polypeptide (PP)-producing cells, ranging from 5% to 70%. These figures were not affected by the sex, age, or underlying disease of the patients. The reported findings corroborate previous clinical and experimental evidence indicating that sex steroid hormones may have some regulatory effects on the functional activity of the endocrine pancreas. 
1	Prostate tumour markers and differentiation grade in prostatic cancer. Serum acid phosphatase activity, prostate specific phosphatase and prostate specific antigen were measured in 100 patients with prostatic cancer. The patients were divided according to the differentiation grade into 3 groups: G1 (well), G2 (moderately) and G3 (poorly differentiated) carcinoma. Bone metastases were identified by scintigraphy. Among the 76 M0 patients the mean levels of all 3 markers were slightly higher in patients with moderately differentiated prostatic carcinoma. Among the 24 M1 patients the primary tumour was either G2 (18 patients) or G3 (6 patients); none had G1 lesions. Significantly higher serum ACP and PAP levels were found in patients with G2 tumours than in those with G3 lesions. It was concluded that the histological differentiation grade of prostatic carcinoma did affect serum levels of prostatic tumour markers; the tendency towards higher levels in the G2 group was noticeable in both non-metastatic and metastatic cases despite the limited number of patients in the latter category. In clinical practice this information may be an important additional tool in staging prostatic cancer. 
4	Effect of subarachnoid hemorrhage on serotonin uptake and release in the rabbit basilar artery. This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the serotonin (5-hydroxytryptamine, 5-HT) uptake and release evoked in rabbit basilar arteries by tyramine. Rabbits were injected with 5 ml of autologous arterial blood into the cisterna magna to produce SAH. Tritium accumulation in basilar arteries was measured after 30 minutes of incubation with 10(-7) M [3H]5-HT and a subsequent 120-minute superfusion (1 ml/min) period. The uptake of 5-HT by arteries 1, 2, 3, and 7 days after SAH was found to be 109%, 69%, 57% (P less than 0.05), and 67% (P less than 0.05) (n = 4, 4, 9, and 6; P less than 0.05) of control (n = 13; 16.8 +/- 1.2 X 10(2) dpm/mg tissue), respectively. The neuronal (cocaine-sensitive) uptake of 5-HT in the arteries 3 days after SAH decreased to approximately 38% of control, whereas the extraneuronal (cocaine-insensitive) uptake of both groups had almost the same absolute value (n = 6 and 6; 4.4 +/- 0.4 and 4.8 +/- 0.4 X 10(2) dpm/mg). Autoradiographic study disclosed that dense clusters of silver grains in the adventitia were not observed after treatment with cocaine (3 X 10(-5) M), although a diffuse distribution of grains was present throughout the vascular wall. The labeled arteries were stimulated by superfusion of tyramine, which is known to replace amines in the sympathetic nerve ending. Tyramine (10(-6) and 10(-4) M)-induced 3H efflux was significantly potentiated by SAH (n = 6) and was suppressed by treatment with cocaine. 
3	Reflex sympathetic dystrophy syndrome: consensus report of an ad hoc committee of the American Association for Hand Surgery on the definition of reflex sympathetic dystrophy syndrome. This report proposes that reflex sympathetic dystrophy be defined as a pain syndrome in which the pain is accompanied by loss of function and evidence of autonomic dysfunction. In the clinical setting, this diagnosis is usually associated with other anatomic and psychological diagnoses and may be associated with a variety of systemic illnesses and medicolegal factors. All components should be assessed before a treatment plan is established. Priorities should go to emergency care, acute injuries, and systemic illness, psychiatric problems, and chronic anatomic problems, in that order. Early, accurate diagnosis improves prognosis. 
5	Coronary angioplasty of diffuse coronary artery disease. From January 1983 through December 1987, 98 patients underwent angioplasty of at least one diffusely diseased coronary artery. Diffuse coronary disease was described as: group I, narrowing greater than or equal to 50% that involved the entire vessel (40 patients), group II, long lesions greater than or equal to 2 cm in length (39 patients), group III, three or more lesions in the same vessel (19 patients). There were 65 men and 33 women, with a mean age of 60 years; 64 patients (65%) had unstable angina, 23 patients (23%) were diabetic, 31 (32%) had prior myocardial infarctions, and 12 had prior bypass surgery. Multivessel disease was present in 89% of patients. Angioplasty of only the diffusely diseased vessel was performed in 41 patients, and additional vessels were dilated in 57 patients. Overall, of 396 lesions (four per patient) and 197 vessels (two per patient) attempted, success was achieved in 382 lesions (96%) and 187 vessels (95%); angiographic success was achieved in 112 of 120 diffusely diseased vessels (93%). Clinical success was achieved in 91 patients (93%). The overall complication rate (death, myocardial infarction, urgent bypass surgery) was 8% (8 of 98): six patients (6%) had myocardial infarction (one Q wave, five non-Q wave), one patient (1%) had urgent bypass surgery, and two patients (2%) died (one during bypass surgery). The majority of complications (7 of 8 or 87%), including the two deaths, occurred in group I patients, with a 17.5% rate, versus 2.5% in group II and 0% in group III, p less than 0.002. 
3	Resolution of the adult respiratory distress syndrome following colectomy and liver transplantation. A 32-year-old woman with liver failure from end-stage cirrhosis and ulcerative colitis developed septicemia and severe ARDS. Subtotal colectomy and a successful liver transplantation resulted in complete resolution of the ARDS. 
3	Volume conduction of the parietal N20 potential to the prerolandic frontal area. Somatosensory evoked potentials were recorded from the frontal and parietal areas in patients with various lesions in the central nervous system on stimulation of the median nerve. Five representative cases who showed a selective loss of the positive potential from the frontal area are reported. In each case, the parietal N20 potential was relatively well preserved, and the midposition between the frontal and central areas (FC area) showed a negative potential following P14. The peak of this negative potential was synchronous with that of the parietal N20 potential. This negativity on the FC area is considered to be a volume conducted potential from the parietal N20 to the prerolandic frontal area. Such an anterior volume conduction of the parietal N20 would not be explained by the concept of a tangentially oriented dipole generated in the posterior bank of the central sulcus. Instead, for the generator of the parietal N20 potential, a radically oriented dipole generated mainly in the parietal area is postulated. 
1	Granulomatous prostatitis and poorly differentiated prostate carcinoma. Their distinction with the use of immunohistochemical methods. Granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic each other both clinically and histologically. To develop criteria useful in resolving problem cases, the authors compared the reactivities of these conditions (nine cases of granulomatous prostatitis and six cases of poorly differentiated carcinoma) with a panel of antibodies to cytokeratin (AE1/3), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), lysozyme, antimacrophage M, and leukocyte common antigen (LCA). In granulomatous prostatitis, histiocytes were not immunoreactive for PAP, PSA, or cytokeratin; however, histiocytes reacted to lysozyme in nine of nine cases, antimacrophage M in seven of nine cases, and LCA in one of nine cases. Tumor cells from all six carcinoma cases reacted with PAP, PSA, and cytokeratin; all failed to react with lysozyme, LCA, and antimacrophage M. The authors conclude that granulomatous prostatitis and poorly differentiated carcinoma can be reliably distinguished with immunohistochemical methods. 
5	Hepatic portal venous gas identified by computed tomography in a patient with blunt abdominal trauma: a case report. An abdominal computed tomographic (CT) scan in a middle-aged man injured in a high-speed motor vehicle accident demonstrated the presence of portal venous gas. Findings on initial peritoneal lavage were entirely negative. Exploratory celiotomy performed because of increasing abdominal pain and leukocytosis revealed gangrene of the cecum. This report illustrates the importance of the finding of portal venous gas on CT scan in patients with blunt abdominal trauma. 
5	Erythropoietin response to anemia as a function of age. The erythropoietin (EPO) response to anemia was assessed for 244 subjects aged 1-64 years (mean 45.2 years) and 121 subjects aged 65-94 years (mean 68.3 years). Subjects included non-anemic individuals as well as those with anemia of various etiologies, excluding renal disease and pregnancy. Significant inverse correlations between serum immunoreactive EPO and hematocrit were noted for both groups. Regression lines failed to show a significantly lower slope or y-intercept for older compared to younger subjects. EPO levels were not significantly lower for older compared to younger subjects when controlled for hematocrit level. These results suggest that the EPO response to anemia in older subjects is similar to that of younger subjects. 
4	Renovascular hypertension. Difficulties in diagnosis and treatment. Renovascular hypertension is not easily identified clinically, and most tests are not totally reliable in detecting its presence. The condition may be due to fibromuscular dysplasia or congenital anomalies in patients younger than age 30 or to atherosclerosis in patients older than 50. The goal of treatment is to lower blood pressure and improve or maintain renal function. Cure or improvement of hypertension is more likely in patients with fibromuscular dysplasia than in those with atherosclerosis. Interventional procedures include percutaneous transluminal angioplasty, surgical revascularization, and nephrectomy. 
1	Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa. Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer. 
1	A community study of delay in presenting with signs of melanoma to medical practitioners. In the absence of more effective treatment for advanced tumors, early diagnosis and treatment of localized tumors is the most effective way of reducing the burden of illness associated with melanoma. This study examined the following factors: prevalence of signs of melanoma (a mole changing in size, shape, appearance, or color, itching or tingling, bleeding or weeping, becoming raised) in 1344 individuals in a randomly selected sample of 1075 households; the length of delay in seeking medical advice; the factors associated with either going to a medical practitioner or not going/delaying; and the actions of the medical practitioners when first presented with these signs. The results indicate that a large proportion of the sample (11.9%, n = 156) had observed signs of melanoma in the previous 12 months. Of the sample reporting signs that had first appeared in the previous 5 years, only 32% sought medical advice about the signs within the recommended period. Of the sample either not seeking advice at all or delaying, 49% reported that they thought the sign "wasn't serious/would clear up." Furthermore, 30% of the sample either did not known or underrated the importance of early detection and treatment of lesions. These results indicate that there is a deficit in the knowledge of the general public about the signs of melanoma, the severity of the disease, and the possible risks associated with delay. 
1	Adenocarcinoma of the colon occurring with intussusception in an adolescent. Hydrostatic reduction of intussusception is definitive therapy in most infants with this abnormality. In the older child, adolescent, and adult, a polyp or tumor is often present. Operative intervention should be considered earlier in the clinical course both to relieve the intussusception and to define the nature of the lead point. 
5	Influence of high-dose aprotinin treatment on blood loss and coagulation patterns in patients undergoing myocardial revascularization. Intraoperative administration of the proteinase inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 x 10(6) kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 x 10(5) KIU/h during surgery. Additionally, 2 x 10(6) KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P less than 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P less than 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P less than 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly increased until heparin was neutralized after cardiopulmonary bypass (CPB). 
4	High-dose epinephrine improves outcome from pediatric cardiac arrest. STUDY OBJECTIVE: Animal studies suggest that the standard dose of epinephrine (SDE) for treatment of cardiac arrest in human beings may be too low. We compared the outcome after SDE with that after high-dose epinephrine (HDE) in children with refractory cardiac arrest. DESIGN: Prospective intervention versus historic control groups. TYPE OF PARTICIPANTS: Two similar groups of 20 consecutive patients each (median ages, 2.5 and 3 years) with witnessed cardiac arrest who remained in arrest after at least two SDEs (0.01 mg/kg). INTERVENTIONS: Treatment with an additional SDE versus HDE (0.2 mg/kg). MEASUREMENTS AND MAIN RESULTS: The rates of return of spontaneous circulation and long-term survival were compared. Fourteen of the HDE group (70%) had return of spontaneous circulation, whereas none of the SDE group did (P less than .001). Eight children survived to discharge after HDE, and three were neurologically intact at follow-up. No significant toxicity from HDE was observed. CONCLUSION: HDE provided a higher return of spontaneous circulation rate and a better long-term outcome than SDE in our series of pediatric cardiac arrest. HDE may warrant incorporation into standard resuscitation protocols at an early enough point to prevent irreversible brain injury. 
1	Intralaryngotracheal thyroid. A case of intralaryngotracheal thyroid in a 57-year-old man is presented. The treatment modalities are considered and the previous literature is reviewed. 
4	Spinal cord compression from a thoracic paraganglioma: case report. A 34-year-old man with a 4-month history of midthoracic back pain sought treatment for a recent onset of lower extremity paresthesia and stiffness. A myelogram and computed tomographic myelogram disclosed an extradural block at the level of the 8th thoracic vertebral body with involvement of the pedicles, lamina, and spinous process. A posterior decompression of the spinal cord with subtotal resection of a highly vascular tumor was performed. The tumor was identified as a paraganglioma. In a second stage, the remainder of the tumor was embolized preoperatively, and gross total excision and sequential stabilization of the spine with a Luque rectangle and sublaminar wires were performed. The patient has been symptom free and without signs of a recurrence in the spine for over 13 months. A large abdominal paraganglioma was recently resected from its probable origin from the adventitia of the abdominal aorta. 
1	True hermaphrodite with bilateral ovotestes, bilateral gonadoblastomas and dysgerminomas, 46,XX/46,XY karyotype, and a successful pregnancy. The first case (to the authors' knowledge) is reported of a true hermaphrodite with bilateral ovotestes, bilateral gonadoblastomas and dysgerminomas, a 46, XX/46,XY karyotype, and a successful pregnancy. The true hermaphroditism was diagnosed during infancy. The patient was subsequently found to have a gonadoblastoma and a microscopic dysgerminoma in the gonad diagnosed as an ovotestis and excised during infancy. The successful pregnancy occurred when the patient was 29 years old. A year later a large gonadal tumor affecting the remaining gonad was excised. The gonad was found to be an ovotestis, and the tumor was a dysgerminoma arising from a gonadoblastoma. This case further emphasizes the malignant potential of the Y chromosome in patients with abnormal gonads. 
5	Subarachnoid hemorrhage of unknown etiology: early prognostic factors for long-term functional capacity. Forty-one patients suffering subarachnoid hemorrhage (SAH) of unknown etiology were re-investigated at an average of 91 months after the bleed to determine functional capacity. Nineteen patients were performing at their previous level of work, five were employed part-time, and four could not work due to the SAH. Five patients showed a moderate disability in activities of daily living but were not dependent on help, one patient was severely disabled, and two had died. There was one rebleed. Early prognosis of an unfavorable outcome was possible on the basis of three clinical variables on admission: a history of hypertension, a Hunt and Hess grade of greater than II, and the presence of focal neurological deficits. In addition, the presence of an organic mental syndrome at discharge was identified as a predictive factor for reduced functional capacity later on. Other clinical variables in the acute stage, including sex, age, history of headache, interval between SAH and admission, impaired consciousness, and cognitive deficits, were not related to a limited functional level. Residual neurological deficits and the Glasgow Outcome Scale score on discharge were also not predictive of restrictions in global functions evaluated by means of the Karnofsky Performance Scale status at follow-up review. 
5	Litigation and employment status: effects on patients with chronic pain. In order to study the effects of compensation and litigation, 201 chronic pain patients were selected from a sample of 444: 99 were working, 15 were working and litigating, 53 were receiving Worker's Compensation, and 34 were receiving Worker's Compensation and litigating. Employment (working vs. Worker's Compensation) and litigation status (litigating vs. not litigating) were analyzed in a 2 x 2 factorial design with measures of pain, disability, psychological distress, and selected demographics as dependent variables. Compared to Worker's Compensation patients, working patients reported significantly less disability (down-time, days spent in bed, interference of pain in daily activities) and pain of a longer duration. Compared to litigating patients, non-litigating patients reported less pain (on the McGill Pain Questionnaire) and less disability (stopping activity, interference of pain in daily activities). On two measures of psychological distress (depression, anxiety), there were significant interactions: Worker's Compensation patients who were litigating reported less distress than non-litigants, while working patients who were litigating reported more distress than non-litigants. The results indicate clear differences in self-reports of disability associated with both employment and litigation status. They also suggest that litigation may function as a coping response for patients who are distressed by the adversarial nature of the Worker's Compensation system. Limitations of the study as well as suggestions for further research also are discussed. 
3	Transient hyperprolactinemia is associated with a midcycle luteinizing hormone surge. This study demonstrates that LH surge cycles in IVF patients were associated with significantly higher serum PRL concentrations than cycles in which a spontaneous LH surge did not occur. Our findings support the hypothesis of concomitant LH and PRL release at the time of the midcycle gonadotropin surge, as well as that of estrogen sensitization of pituitary lactotropes, and suggest a possible mechanism for transient midcycle hyperprolactinemia. 
3	An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome. Neurologic sequelae of Paget's disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae, ischemia caused by a spinal artery, steal syndrome or neoplasm. We describe a patient with Paget's disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma. Clinicians need to recognize this entity since surgical intervention may result in a favorable outcome. 
3	Familial trigeminal neuralgia and Charcot-Marie-Tooth neuropathy. Report of two families and review. Typical trigeminal neuralgia has occasionally occurred in multiple members of the same family over several generations. The clinical features of such cases, including the increased incidence in females, and the absence of other apparent hereditary, neurologic, metabolic, or structural abnormalities were identical to those of sporadic cases. More rarely, familial trigeminal neuralgia has been described in the setting of hereditary peripheral neuropathy, especially Charcot-Marie-Tooth disease. We describe patients from two different families with Charcot-Marie-Tooth disease and medically intractable trigeminal neuralgia. Both patients were successfully treated by percutaneous retrogasserian glycerol rhizolysis. The occurrence of cranial nerve symptoms in patients with demyelinating peripheral neuropathies is discussed in light of the current hypotheses regarding the etiology of trigeminal neuralgia. 
5	Rigid spine syndrome with respiratory failure. The pathogenesis and therapy of respiratory failure in the rigid spine syndrome are discussed in two cases who improved with respiratory assistance. In both cases, the partial pressures of oxygen and carbon dioxide were reversed in arterial blood gas analysis and %VC was less than 30%. Remission from respiratory failure has been obtained by the use of a ventilator during the night. The cause of the respiratory failure in both cases was severe restrictive respiratory dysfunction due to extreme flattening of the chest and fixation of the thorax during respiration as a result of contracture of costovertebral joints. All the previously reported cases of the rigid spine syndrome with respiratory failure died. Appropriate use of the ventilator can improve the prognosis. 
5	Recurrent transient ischemic attacks and stroke in association with an internal carotid artery web Fibromuscular dysplasia is a nonatherosclerotic vascular disease that most commonly affects cervical carotid arteries at the C1-C2 level when cephalic arteries are involved. Several histopathologic and angiographic subtypes of fibromuscular dysplasia exist; most have a benign natural history. We describe the third reported case of a pathologically proven, symptomatic proximal internal carotid artery web and suggest that patients with this lesion are at a higher risk for stroke. 
3	Eosinophilia-myalgia syndrome (L-tryptophan-associated neuromyopathy). Histopathologic study of skeletal muscle biopsy in a patient with eosinophilia-myalgia syndrome following L-tryptophan use showed prominent lymphocytic perineuritis, neuritis, and perimysial fasciitis. The presence of perineuritis and neuritis provides a histopathologic basis for clinical features of neuropathy in eosinophilia-myalgia syndrome and occurred in conjunction with a fasciitis or interstitial myositis that was predominantly perimysial and focally endomysial. 
1	Papillary adenocarcinoma of the middle ear. A case of papillary adenocarcinoma of the middle ear is presented. The patient had an unusually short history of otalgia, aural discharge and facial palsy, and, at presentation the tumour was too large for surgical resection to be a feasible option. The management of this rare tumour is discussed and the relevant literature reviewed. 
1	Sarcoid reaction mimicking intrathoracic dissemination of testicular cancer. The close observation of patients treated for testicular cancer led to the suspicion of intrathoracic and/or mediastinal metastases on radiologic examination in a number of patients without other evidence of relapse. This report presents two patients with combined seminomatous and nonseminomatous germ cell tumors with isolated sarcoid reactions of hilar and interlobular lymph nodes, detected concomitant with diagnosis and 12 months after diagnosis, respectively. Histologic examination appears to be imperative in these cases to avoid unnecessary chemotherapy. 
1	Local-regional breast cancer recurrence following mastectomy. Local-regional recurrence patterns were investigated in 1392 patients with breast cancer. Primary treatment for all patients included a mastectomy. Nine hundred seventeen patients had negative nodes and did not receive systemic therapy. Four hundred seventy-five patients had node metastases and were randomized to receive different combinations of chemoendocrine therapy. Follow-up ranged between 5 and 16 years. Two hundred thirty (25.8%) node-negative patients have had recurrences, with the initial recurrence being local-regional in 9.2%. Two hundred forty-two (50.9%) node-positive patients have had recurrences, with the initial recurrence being local-regional in 17.1%. Larger tumors and more extensive node involvement were associated with more first local-regional recurrences. The relative percent of first local-regional recurrence among patients in whom cancer recurred was similar for node-negative and node-positive patients (35.4% and 33.5%, respectively). In 63.6% of patients in whom cancer recurred, first local-regional recurrence were distant. Larger tumors, more extensive node involvement, and a shorter disease-free interval after mastectomy were associated with more rapid appearance of distant recurrence among these patients. 
5	Closure of refractory perineal Crohn's lesion. Integration of hyperbaric oxygen into case management. A case is reported in which a comprehensive program of hyperbaric oxygen (HBO), surgical debridement and reconstruction, and continuing medical management resulted in complete and sustained closure of an extensive perineal Crohn's lesion refractory to conventional medical and surgical management. It is emphasized that in this case healing occurred in the setting of previous removal of all diseased intestinal tissue and only with the combined use of all three treatment modalities. HBO may be a useful adjunct in the therapy of large nonhealing perineal lesions post-proctocolectomy in patients who are unresponsive to metronidazole or to immunosuppressant therapy or who experience limiting side effects from continued medical therapy. 
5	Allopurinol and thiazide effects on new urinary stone formed after discontinued therapy in patients with urinary stones. We treated 87 patients with calcium-containing urinary stones with either allopurinol alone (44 patients) or in combination with thiazide (43 patients) and studied new stone formation before, during, and after the discontinuation of the drug therapy. The number of stones formed were 1.18, 0.24, and 0.13 before, during, and after discontinuation of the drug therapy, respectively, in the patients treated with allopurinol alone and 1.32, 0.20, and 0.09 in those treated in combination with thiazide. No differences were observed in these values and the duration of each observation period between the two groups. Decreases in the incidence of stone formation even after interruption of drug therapy suggested that recurrence-preventive effects observed following administration of these drugs include the effects of medical guidance. However, allopurinol therapy was effective in preventing recurrence in patients with hyperuricosuria. 
1	A cytotoxic T-lymphocyte clone derived from mice with progressively growing tumors. Tumor-specific T-cell clones were derived from spleen cells of mice bearing a syngeneic PHS-5 tumor (a P815 mastocytoma mutant). Cells were expanded in vitro and characterized and assayed for activity against the relevant tumor in vivo. Clone cells were CD4-, CD8+ T lymphocytes, as determined by fluorescence activated cell sorting analysis and were specifically cytotoxic against P815 tumor cells in vitro, as shown in chromium 51 release assays. These cells require both antigen and interleukin 2 to proliferate; neither alone is sufficient, even with the addition of interleukin 1. In an experimental P815 liver metastasis model, the adoptive transfer of GD11 or GD11.17 clone cells and injection of recombinant interleukin 2 (7500 U intraperitoneally) 3 days after infusion of tumor cells reduced the number of tumor nodules, while the adoptive transfer of lymphokine-activated killer cells was ineffective. 
2	Longitudinal histopathologic assessment of rejection after bladder-drained canine pancreas allograft transplantation. In preparation for assessment of percutaneous biopsies in our clinical pancreas transplant program, a working knowledge of the histopathologic changes after transplantation was obtained in a longitudinal open biopsy study of 16 dogs receiving bladder-drained whole pancreas allografts. Edema, extravasation of polymorphs, and lymphocytes associated with focal parenchymal injury were early, invariable, and probably nonspecific findings. The initial feature of unmodified rejection was the appearance of capillary and small vein endothelial changes with mainly perivascular inflammatory cell infiltration. Acinar cell loss occurred early and was progressive, whereas islets and ducts were relatively preserved, indicating that acinar tissue may be more vulnerable to lytic necrosis when damaged. Functional rejection, determined by fasting urinary amylase levels, was at a stage of extensive and irreversible necrosis. Functioning grafts in immunosuppressed dogs had minor and transient endothelial changes with absence of class II antigen staining of parenchymal cells. 
2	The long-term effects of radiation therapy on patients with ovarian dysgerminoma. A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder. 
2	Protein-losing enteropathy in systemic lupus erythematosus associated with intestinal lymphangiectasia. This case report concerns a young woman with systemic lupus erythematosus who presented with a protein-losing enteropathy. Intestinal biopsy revealed lymphangiectasia. Mesenteric lymph nodes showed paracortical lymphoid depletion and multiple small sinusoids. Elevated cholesterol levels and normal lymphocyte counts characterized the peripheral blood samples. Lymph nodes, though enlarged, showed no evidence of obstructive pathology. No secondary cause of lymphangiectasia could be identified. The patient exhibited antinuclear antibodies and antibodies to dsDNA at the onset, and then, 5 yr later, the classic features of systemic lupus erythematosus (SLE). The lymphocytopenia and hypolipidemia that characterizes lymphangiectasia is not a feature of the SLE cases reported to date. Furthermore, the mechanism for the dilated lymphatics and villous edema is more likely immunological than mechanical disruption of lymphatics. 
4	Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction. The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036. 
5	Restriction fragment length polymorphism analysis to study the genetic origin of complete hydatidiform mole. To determine the genetic origin of the complete hydatidiform mole, 20 abnormal pregnancies were studied with restriction fragment length polymorphism with five genomic probes: EJ 6.6, beta-globin gene, 3'alpha-hypervariable region, J-Bir, and St14. In the 12 cases of molar pregnancy, pure paternal origin was proved in 11 cases, but both maternal and paternal inheritance were shown in only one case. In the cases with pure paternal origin, all of the restriction fragment length polymorphisms were homozygous, although those of the fathers were heterozygous at 15 loci. In the four cases that mimicked hydatidiform mole but were diagnosed as hydropic change of villi, both paternal and maternal inheritance were noted. In the four pregnancies with blighted ovum, both paternal and maternal inheritance were shown in three cases; and in one case with a balanced translocation between chromosomes 13 and 14, only paternal inheritance was noted. This study showed that most of the complete hydatidiform moles were caused by fertilization of an empty egg by a duplicated haploid sperm, but rare exceptions may exist. 
2	Choledochotomy for calculous disease in the elderly. To determine the risk of operations on the biliary tract in the elderly, we retrospectively examined 56 patients 80 years of age or older undergoing choledochotomy for calculous disease and compared their outcomes with those of a contemporary group of 257 patients undergoing similar surgery. Thirty of 56 elderly patients (54%) required urgent surgery for acute cholangitis, acute cholecystitis, or obstructive jaundice (serum bilirubin greater than 5 mg/dL), compared with 97 of 257 younger patients (38%) (p = 0.029). Mortality in elderly patients was significantly higher (5 of 56) than in younger (6 of 257) patients (p = 0.015). In three of the five patients who died, urgent surgery was performed for obstructive jaundice, reflecting the higher mortality experienced by jaundiced patients in the entire series (9.4%). Biliary cultures grew organisms in 25 of 27 elderly patients (93%). This is in contrast to findings of bactibilia in 62 of 118 patients (53%) under the age of 80 (p = 0.001). Similarly, preoperative blood cultures were positive more often in elderly (63%) than in younger patients (26%) (p = 0.007). Mean postoperative hospital recovery was longer in the elderly group (16.2 +/- 8.5 days) than in the younger group (12.2 +/- 9.3 days) (p = 0.002). In conclusion, elderly patients, particularly those with obstructive jaundice, are at higher risk for complicated biliary tract disease necessitating choledochotomy. They appear to be more susceptible to bactibilia and bacteremia, and require longer hospital recovery than younger patients. 
5	Broad spectrum penicillin as an adequate therapy for acute cholangitis. In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction. 
1	Immunochemical studies on the differential binding properties of two monoclonal antibodies reacting with Tn red cells. Two monoclonal antibodies (MoAbs), BRIC 66 (IgM) and BRIC 111 (IgG1), were produced by immunizing mice with ovarian cyst blood group A1 glycoprotein and Tn red cells (RBCs), respectively. Their specificities were determined by inhibitions using Tn sialoglycoproteins (SGPs), mucins (armadillo [ASG] and ovine [OSG] submaxillary glycoproteins), and monosaccharides. BRIC 66 agglutinated both Tn and group A RBCs and reacted immunohistochemically with both the vascular endothelium and tumor cells from a group A adenocarcinoma, BRIC 66 was inhibited by N-acetylgalactosamine (GalNAc), Tn SGPs, and mucins on both hemagglutination inhibition tests and radioimmunoassay. BRIC 111 agglutinated Tn RBCs only, and it specifically stained tumor cells from a group O patient's breast carcinoma and a group A patient's adenocarcinoma. In hemagglutination inhibition tests, BRIC 111 was readily inhibited by Tn SGPs, only partially inhibited by GalNAc, and not inhibited by mucins. In a sensitive radioimmunoassay, BRIC 111 was inhibitable by GalNAc. Tn SGP was 2000-fold more effective as an inhibitor than the mucins (ASG and desialized OSG), which contain a high content of terminal alpha-GalNAc-O-serine (threonine) residues. It is postulated that BRIC 66 is specific for terminal alpha-GalNAc units in carbohydrate chains. The exclusive reaction of BRIC 111 with Tn SGP indicates a combining site larger than GalNAc alpha-1, which probably includes amino acid residues in juxtaposition to GalNAc in Tn SGP. In view of its specific agglutination of Tn RBCs, BRIC 111 is a useful reagent for the examination of polyagglutinable RBCs. 
1	Intraoral adenoid cystic carcinoma. The presence of perineural spread in relation to site, size, local extension, and metastatic spread in 22 cases. Twenty-two patients with an intraoral adenoid cystic carcinoma (ACC), initially treated by surgery with or without postoperative radiotherapy, were examined for the presence of perineural spread in relation to primary site, size, local extension, histologic status of the surgical margins, and metastatic spread of the tumor. There seems to be no correlation between perineural spread and the primary site or size of the tumor. However, perineural spread occurred more often in tumors with local extension and in cases with surgical margins with positive results. There seems to be no statistically significant correlation between perineural invasion and distant metastatic disease. 
1	Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. The nm23 gene was identified in murine melanoma cells, in which its expression is associated with the cells' metastatic potential. Expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry. We measured nm23 mRNA in 71 patients with primary breast cancer and found variable levels of nm23 expression. The nm23 gene was expressed at higher levels in well-differentiated tumors (P less than .02). There was a significant inverse relationship between nm23 expression and nodal status (P less than .02). Expression of nm23 was positively associated with longer disease-free survival and overall survival, and the relationships were significant (P less than .002 and P less than .003, respectively). This study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype. 
1	Resection and reconstruction for soft-tissue sarcomas of the extremity. Soft-tissue sarcomas are uncommon malignant tumors, and when a diagnosis is made early, the patient has up to an 80% chance of surviving. In treating soft-tissue sarcomas, the goal of the surgeon is the prolongation of patient survival, the total eradication of local disease, and the minimization of functional deficits. In addition to treatment, this article discusses evaluation, histology, and staging. 
1	Hormonal treatment of functional ovarian cysts: a randomized, prospective study. Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re-evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment. 
1	Symptomatic pineal cyst: case report. Pineal cysts are being described with increasing frequency since the advent of magnetic resonance imaging. Although pineal cysts are incidental findings in as many as 4% of magnetic resonance imaging studies, symptomatic pineal cysts are quite rare. We present a case of pineal cyst causing aqueductal obstruction with symptomatic hydrocephalus and resultant headache and syncope, which was treated by surgical resection. A review of the relevant literature and discussion follow. 
1	Mechanism of antitumor activity of tumor necrosis factor alpha with hyperthermia in a tumor necrosis factor alpha-resistant tumor. Cells from a radiation-induced fibrosarcoma (RIF-1) are exceedingly resistant to tumor necrosis factor alpha (TNF-alpha) in vitro. We tested whether the addition of mild hyperthermia (42.5 degrees C, 30 minutes) could enhance TNF-alpha activity against RIF-1 tumors growing in syngeneic hosts (C3H mice). TNF-alpha was administered intratumorally. Tumor cell killing essentially was not measurable following TNF-alpha, hyperthermia, or a combination of the two. Single-modality treatments also had no effect on tumor growth delay or on the x-ray dose (given 24 hours after the primary treatment) required to sterilize 50% of the tumors. The combination of TNF-alpha and hyperthermia, however, resulted in a marked increase in tumor doubling time and a highly significant reduction in the x-ray dose required to sterilize the tumors. Syngeneic lymph nodal lymphocytes and blood leukocytes did not appear to mediate the action of TNF-alpha on RIF-1 cells in vitro. Necrosis and hemorrhage were the most prominent histopathological alterations in the treated tumors. Electron microscopic studies 6 hours after therapy showed increased damage to capillary endothelial cells and accumulation of neutrophils in the capillaries of tumors treated with TNF-alpha with or without heat, suggesting that neutrophils may mediate the endothelial cell injury. These observations indicate a greater than additive tumoricidal effect of TNF-alpha with hyperthermia. Furthermore, they support the concept that the interaction between the two agents damages the vasculature, compromising the microcirculation and ultimately causing ischemic tumor necrosis. 
1	Boronate affinity chromatography of gamma-glutamyltransferase in patients with hepatocellular carcinoma. We analyzed the serum gamma-glutamyltransferase (gamma-GT) by boronate affinity chromatography to ascertain the presence or absence of any changes in the binding properties of gamma-GT toward boronate gels in patients with hepatocellular carcinoma and liver cirrhosis, and in normal controls. The mean gamma-GT activity ratio of the bound (peak 2) and nonbound (peak 1) fraction in patients with hepatocellular carcinoma was significantly higher than that in patients with liver cirrhosis or in normal controls. Thus, the gamma-GT, which has adjacent cis-hydroxyl groups in its carbohydrate moieties, was found to increase in the serum of patients with hepatocellular carcinoma. The positivity rate was examined in patients with hepatocellular carcinoma and liver cirrhosis, using a cut-off level for the peak 2:peak 1 ratio of 1.05 (mean + 2 SD of liver cirrhosis). Nineteen (42.2%) patients with hepatocellular carcinoma had a ratio of peak 2:peak 1 higher than 1.05. Nine of the 19 patients who had serum alpha-fetoprotein levels below 100 ng/ml had an elevated peak 2:peak 1 ratio. In total, 77.8% of the occurrence of hepatocellular carcinoma could be detected by a combination of these two markers. Three patients who had developed hepatocellular carcinoma during the course of cirrhosis but remained negative for alpha-fetoprotein throughout the course developed higher levels of peak 2:peak 1 ratio when hepatocellular carcinoma occurred. These results indicate that the two markers, the peak 2:peak 1 ratio of serum gamma-GT activity and serum alpha-fetoprotein level, may be considered to serve as complementary markers for the diagnosis of hepatocellular carcinoma. 
1	Magnetic resonance imaging for assessment of vena caval tumor thrombi: a comparative study with venacavography and computerized tomography scanning. We assessed the accuracy of magnetic resonance imaging in demonstrating the presence and extent of vena caval tumor thrombi. The study group included 20 patients with vena caval thrombi from renal cell carcinoma (18), renal pelvic transitional cell carcinoma (1) and adrenal pheochromocytoma (1). Preoperative diagnostic studies included magnetic resonance imaging in all patients, inferior venacavography in 16 and computerized tomography scanning in 15. All patients underwent an operation in which the presence and extent of the vena caval thrombus were confirmed. Magnetic resonance imaging accurately delineated the presence and extent of the thrombus in all 20 patients (100%). Venacavography was accurate in 15 patients (94%) but 8 (50%) required a retrograde and antegrade study. Computerized tomography scanning demonstrated the presence of a tumor thrombus in all 15 patients but accurately delineated the cephalad extent of the thrombus in only 5 (33%). In patients with vena caval tumor thrombi magnetic resonance imaging can provide accurate information regarding the extent of vena caval involvement while avoiding the need for an invasive contrast imaging study. 
1	Perforation and tumor formation of the intestine in primary amyloidosis. We report a case of primary amyloidosis with repeated bowel perforations. This patient also had localized amyloid deposition creating a tumorous region mimicking malignancy in the rectum. Perforation of the intestine is common in systemic amyloidosis. The ischemic change due to amyloid infiltration into the vessel wall may lead to perforation of the affected bowel. Amyloid tumors occur more often in localized amyloid than in systemic amyloidosis. Macroscopically, it is difficult to distinguish amyloid tumor of the intestine from neoplasia. 
2	Ascites revealing peritoneal and hepatic extramedullary hematopoiesis with peliosis in agnogenic myeloid metaplasia: case report and review of the literature. A 61-year-old man presented with ascites in the course of agnogenic myeloid metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia. Subsequently, portal hypertension was demonstrated by hepatic transjugular catheterization. Complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock. A review of the literature and an analysis of mechanisms of ascites occurring in AMM, especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders, are presented. 
1	Microinvasive carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics Stage IA). In 1985 the International Federation of Gynecology and Obstetrics (FIGO) subdivided Stage IA cervical cancer and specified metric criteria to demarcate Stage IA from Stage IB. Early stromal invasion (Stage IA1) denotes the first invasive protrusions of a carcinoma in situ into the stroma. Microcarcinomas (Stage IA2) are small cancers a number of orders of magnitude larger than Stage IA1 lesions and with a maximum depth of invasion of 5 mm and a maximum horizontal spread of 7 mm; larger lesions are classified as Stage IB. This study reviews 486 patients previously classified as having Stage IA disease. This yielded 344 Stage IA1 and 101 Stage IA2 lesions; 41 cancers were reclassified as Stage IB. Three hundred nine, 89, and 38 patients were followed for greater than or equal to 5 years. One (0.3%) patient with Stage IA1 disease re-presented with Stage IIB disease 12 years after conization. Five (5.6%) patients with Stage IA2 lesions developed invasive recurrences; three died. None of the 38 patients reclassified as having a Stage IB lesion, including 16 who were treated conservatively, developed a recurrence. The FIGO classification is not a guideline for treatment. Stage IA1 lesions can be treated conservatively, but treatment in Stage IA2 must be individualized. Risk factors such as vascular space involvement and confluency are of high sensitivity but low specificity. 
1	Composite reconstruction for chest wall and scalp using multiple ribs-latissimus dorsi osteomyocutaneous flaps as pedicled and free flaps. A composite flap is presented based on the latissimus dorsi myocutaneous unit together with the underlying ninth to eleventh ribs. Three patients are presented. In two, a full-thickness chest-wall defect was present. In one, a full-thickness scalp and cranial defect was present. Use of the composite osteomyocutaneous latissimus dorsi free flap as a pedicled flap in two patients and as a free flap in one patient resulted in successful definitive reconstruction in all with no complications. This procedure necessitates no transplantation of soft tissue prior to bone grafting to maintain local vascularity, so the simultaneous one-stage reconstruction of an osseous-soft-tissue defect becomes possible easily. 
4	Decreased operative risk of surgical treatment of mitral regurgitation with or without coronary artery disease. The consecutive 2 year experience with patients undergoing first-time surgery for mitral regurgitation with and without coronary artery disease was reviewed. From January 1988 to January 1990, 127 patients with pure mitral regurgitation undergoing first-time operation were surgically treated. No other valve lesion, no reoperation and no congenital defects were included. The mean patient age was 62 years with 26% of the patients greater than 70 years. Twenty-six percent of the entire group was in functional class IV. Seventy-five patients received mitral valve repair and 52 underwent mitral valve replacement with a St. Jude or Hancock valve. In patients undergoing mitral valve repair, there was a higher incidence of those greater than 70 years old and of coronary artery disease and in patients undergoing mitral valve replacement there was a higher incidence of functional class IV. The operative mortality rate was 2.3% (3 of 127 patients). No patient failed to be discontinued from cardiopulmonary bypass and all three deaths occurred after mitral valve replacement, with one from complications of chronic renal failure and dialysis. There was no significant difference in patients who either did or did not have a concomitant coronary artery bypass graft and there was no difference related to age or functional class. Postoperative complications occurred in five patients in the valve repair group, including recurrent mitral regurgitation in two necessitating reoperation, and in three patients in the valve replacement group. With newer operative and postoperative management techniques, especially preservation of the papillary muscle annular continuity, the risk of mitral valve surgery, particularly of valve repair, is considerably lower than in previous years. 
1	The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome. Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins. 
5	Helicobacter pylori and Zollinger-Ellison syndrome. Helicobacter pylori (previously Campylobacter pylori) is almost invariably associated with chronic duodenal ulcer disease. The relationship between H. pylori infection and duodenal ulcer in Zollinger-Ellison syndrome is unknown. We investigated the frequency of H. pylori infection in Zollinger-Ellison syndrome and also what effect H. pylori infection had on gastric function in patients with Zollinger-Ellison syndrome. H. pylori infection was diagnosed based on a specific serologic (ELISA) assay based on high-molecular-weight cell-associated proteins of H. pylori. We studied 20 patients with Zollinger-Ellison syndrome; 15 men and 5 women ranging in age from 24 to 71 years, median age 51. Six Zollinger-Ellison syndrome patients had H. pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease (P less than 0.05). Pretreatment basal acid output in Zollinger-Ellison syndrome patients ranged from 7.9 to 95.0 mmol/hr, median 35.2. Pentagastrin-stimulated maximal acid output ranged from 8.5 to 132 mmol/hr; median 52.7. Acid secretion was lower in the H. pylori-infected patients than the uninfected patients (BAO 24.5 +/- 6.5 vs 45.4 +/- 6.6, and MAO 44.3 +/- 11.8 vs 67.9 +/- 10.7, for H. pylori infected vs uninfected patients, respectively). The difference in BAO was statistically significant (P less than 0.05). The present results indicate that H. pylori is not a major contributing factor in duodenal ulcer associated with Zollinger-Ellison syndrome. The association of a reduced BAO with H. pylori suggests that these findings may be related. 
4	Pulmonary effects of ischemic limb reperfusion: evidence for a role for oxygen-derived radicals. OBJECTIVE: To evaluate the lung as a reperfusion target after limb ischemia-reperfusion, and to measure specifically the oxygen radical response to this reperfusion. DESIGN: Paired simple randomized, with continuous interval data in dependent variable and both continuous and nominal independent variables. SUBJECTS AND INTERVENTION: Sprague-Dawley male rats (n = 195) were anesthetized and both hind limbs occluded for 3.75 hr, the overnight LD50. Alveolar lavage was performed on the animals 1 hr after reperfusion or on survivors 20 hr after reperfusion. Groups were either undosed or pretreated with alpha-tocopherol as an antioxidant (50 mg/kg.day) 2 days before ischemia. MEASUREMENTS AND MAIN RESULTS: Luminol-enhanced chemiluminescence was measured in both phorbol myristate acetate-stimulated and unstimulated macrophages. Nanomoles of superoxide radicals per 10(6) alveolar cells/min were also measured using a cytochrome c reduction assay. A significant (p less than .01, Student's t-test), time-dependent increase in response of cells from ischemic-reperfused rats was seen. Pretreatment with antioxidant had no effect at 1 hr, but significant differences were seen in the 20-hr survivors. CONCLUSIONS: These studies show that alveolar lavage cells, 95% macrophages, reflect the reperfusion of ischemic-reperfused hind limbs by a significant increase in oxygen radical activity, an effect partly suppressed in antioxidant-dosed survivors. 
2	A rational attitude toward serum alanine aminotransferase measurement by blood banks, based on a longitudinal study of a cohort of repeat blood donors. A cohort of 879 blood donors was followed over a 3-year period. Of the 3858 units of blood collected, 112 (2.9%), obtained from 64 donors, had an alanine aminotransferase (ALT) activity over 45 IU per L; of these, 39 had a single ALT elevation. The incidence of ALT increase was 2.01 per 100 units, or 5.1 per 100 donors, per year. The pattern of elevated ALT was followed in 72 donors, 54 of whom were from the 64 cited above. At the second blood donation (BD2), about 5 months later, 62.5 percent had a normal ALT value, and most (91%) retained those values at blood donation 3 (BD3). However, 19 (70.3%) of the 27 whose ALT levels had not returned to normal at BD2 had an increased value at BD3. These results led to the formulation of the following algorithm to improve the management of blood donors; at the first donation, the ALT assay is done after the blood collection, but, at the next donation, the ALT level is measured before donation if the preceding ALT activity had been abnormal. If ALT is elevated, blood is not collected. Three consecutive ALT elevations are a criterion for permanent exclusion of the donor. 
5	Persistent and recurrent hyperparathyroidism: assessment with gadopentetate dimeglumine-enhanced MR imaging. The effect of gadopentetate dimeglumine on signal intensity of abnormal parathyroid glands was assessed in 14 patients with persistent and recurrent hyperparathyroidism. Non-contrast material-enhanced T1- and T2-weighted spin-echo images were compared with T1-weighted images obtained 1 minute and 10 minutes after administration of gadopentetate dimeglumine. Percentage of contrast between the abnormal gland and surrounding tissue was determined with the use of skeletal muscle, subcutaneous fat, and thyroid gland as reference tissues. All 11 abnormal parathyroid glands showed low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Gadopentetate dimeglumine significantly increased the signal intensity enhancement ratio of all abnormal parathyroid glands, causing increased percentage of contrast relative to the thyroid gland and skeletal muscle on T1-weighted images. However, the percentage of contrast relative to these tissues was even greater on nonenhanced T2-weighted images. Thus, gadopentetate dimeglumine can substantially enhance the signal intensity of abnormal parathyroid glands and improve differential contrast with some neighboring tissues on T1-weighted images, but it does not improve contrast with surrounding tissue beyond that achieved on T2-weighted images. 
5	Temporal bone findings in two cases of head injury. Temporal bone findings in two cases of head injury are reported. In one patient, longitudinal fractures occurred in both temporal bones, and extended to the middle ear bilaterally. Bleeding was seen in the tympanic cavity, mastoid air cells, internal auditory meatus and facial nerve canal. Bleeding was observed in the scala tympani, cochlear aqueduct and endolymphatic sac, but there were no fractures. In the other patient, bleeding was seen in the internal auditory meatus and facial nerve canal. In the right ear, endolymphatic hydrops was observed in all turns of the cochlea. 
2	Spontaneous rupture of the spleen in initial presentation of Hodgkin's disease. A 46-year-old man presented with a four-week history of fevers, occasional chills, and a two-week history of sweats and poor appetite. He also complained of progressive weakness and lethargy. After initial evaluation, while awaiting further consultation, the patient developed rapidly progressing abdominal pain and light-headedness. He was moved immediately into the emergency treatment area. He was noted to have an acute abdomen and was taken to surgery. An enlarged Hodgkin's-infiltrated spleen with an actively bleeding hematoma was removed. The patient denied any history of trauma. 
1	Magnetic resonance imaging of fourth ventricular epidermoid tumors. Two pathologically proved cases of epidermoid tumor of the fourth ventricle are presented; clinical history and computed tomographic, magnetic resonance imaging, and histopathologic findings are included. 
2	Use of plasmid profiles in the investigation of a patient with Helicobacter pylori infection and peptic ulcer disease. Plasmids may effect bacterial virulence and antibiotic resistance, and serve as epidemiologic markers. In this study, plasmid DNA profiles of serial isolates of Helicobacter pylori showed persistence of an identical strain of this organism in a patient with duodenal ulcer disease. Three control strains of H. pylori isolated from other patients contained plasmids different from each other and from that of the original patient; two of these strains had two plasmids each. These data have important implications for further study of the epidemiology and pathogenesis of H. pylori-related diseases. 
1	Cystic rheumatoid arthritis: description of a nonerosive form. In a study of patients with rheumatoid arthritis (RA), 9% (n = 70) were found to have a cystic form. At radiologic examination of these patients with cystic RA, the first abnormality seen consisted of periarticular intraosseous cysts without erosions. The cysts were distributed symmetrically, most often located at the proximal side of the joints and predominantly around the proximal interphalangeal, metacarpophalangeal, and wrist joints of the hands and the first interphalangeal and metatarsophalangeal joints of the feet. Computed tomographic scans showed the peripheral intraosseous location of the cysts. Magnetic resonance images showed that the cysts may contain fluid, inflamed synovia, or both. Cysts can be an important feature in the diagnosis of RA and a supplement to the criteria of the American Rheumatism Association. Osteoporosis, joint-space narrowing, and joint destruction occurred less frequently in patients with cystic RA than in patients with classic RA. Of the patients with cystic RA, 54% were male, and 50% were seronegative. This study is a supplement to and an enlargement on earlier descriptions of cyst predominance in RA. 
5	Congenital craniofacial anomalies of ophthalmic importance. Congenital craniofacial abnormalities frequently require ophthalmic evaluation and surgical management. Called upon to perform as part of the craniofacial team managing the often severely deformed craniofacial patient, the ophthalmologist must bring a basic knowledge of craniofacial syndromes and developmental anatomy, as well as clinical acumen to help preserve or improve ocular and adnexal function. As an introduction to this area of ophthalmology, the clinical features, classification, appropriate facial embryology, assessment and surgical considerations of the various congenital craniofacial abnormalities are reviewed. The expanding availability of craniofacial surgeons and surgical teams along with improved surgical results will ultimately require an increasing involvement by many more ophthalmologists in the evaluation and management of these congenital abnormalities. 
5	Pathophysiologic changes in the critically ill patient: risk factors for ulceration and altered drug metabolism. Virtually all patients who are under the physiologic stress of an intensive care unit (ICU) are vulnerable to stress-related mucosal damage and ulceration. Although clinically significant hemorrhage from stress ulceration occurs in only 5-20 percent of patients in the ICU, the associated mortality is greater than 50 percent. The pathophysiologic mechanisms of stress ulcer are not well understood; however, a number of risk factors such as intraluminal gastric acidity and mucosal ischemia have been implicated. To prevent the development of stress ulcers and subsequent complications, it is important to identify and correct these underlying risk factors. Improving mucosal blood flow (i.e., fluid resuscitation and low-dose dopamine) and providing adequate nutritional support are invaluable adjuncts in minimizing the risk of stress ulcer formation. The use of pharmacologic prophylaxis controls the gastric acidity and prevents the formation of stress ulcers. The potential for drug-induced adverse effects and drug-drug interactions are of particular concern in the care of critically ill patients. Multiple organ system dysfunction or failure, malnutrition, fluid and electrolyte abnormalities, as well as the use of multiple pharmacologic agents predispose these patients to alterations in drug pharmacokinetics, drug-induced adverse effects and drug-drug interactions. These changes may alter the pharmacodynamic response to therapy and must be considered when designing drug dosage regimens for critically ill patients. 
1	Endometrioma of the liver. Hepatic endometriosis is extremely rare. We describe a patient sent to us with epigastric pain as the only symptom and who was found to have associated endometrioma of the liver and left ovary. We suggest a gynecologic evaluation before surgery for hepatic cyst of unknown cause. 
3	Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain. Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging. 
4	Videodensitometry versus digital calipers for quantitative coronary angiography. Single-plane left coronary angiograms in 18 patients were prospectively analyzed using videodensitometry (XR-70 system) and handheld digital calipers to compare arterial dimensions, stenosis dimensions, intraobserver variability and interobserver variability for the methods. A total of 648 arterial segments were measured, yielding a highly significant correlation between videodensitometry and caliper-determined cross-sectional area (r = 0.96, p = 0.0001). Similarly, a highly significant linear relation was observed between videodensitometry and caliper-determined diameter (r = 0.95, p = 0.0001). When data subsets for small, medium and large arterial segments were examined, higher variability in the correlation between videodensitometry and caliper-determined area was observed in the large segments (greater than 10 mm2). In addition, caliper-estimated areas tended to be slightly smaller than videodensitometry-estimated areas in these segments. For diameter estimations, correlations between caliper and videodensitometry data were similar for the entire range of arterial segment sizes. Intra- and interobserver variability was low for both caliper and videodensitometry determination of diameter or area. Thus, over a wide range of arterial dimensions, results obtained with caliper estimates of luminal area and diameter are comparable to those obtained with videodensitometry using the XR-70 system. 
1	Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors. Thirty-eight histologically confirmed desmoid tumors were treated with conservative surgical resection and interstitial iridium 192. Patients included in this series constituted a poor prognostic group. Seventy five percent (75%) had previous recurrences of their disease and 50% had tumors 8 cm or greater in size. In addition, 16% of the patients had gross residual disease after surgical excision and 79% had positive or close margins of resection. With a median follow-up of 5.5 years, the 5-year actuarial in-field local control rate was 75% and the overall local control rate was 66%. Four of the 12 local recurrences developed at the periphery of the implant volume and four patients failed at least 3 cm or more beyond the treated volume. After salvage therapy, the 5-year actuarial local control rate was 95%. Two patients required amputation for recurrent disease. Thirty of 34 patients remain free of disease with an excellent functional result achieved. The authors conclude that surgical resection and postoperative interstitial iridium 192 is effective therapy for patients with desmoid tumors. Despite the fact that most patients in this series had bulky, recurrent tumors, excellent long-term local control and limb function were achieved. 
4	Effect of age on the efficacy of blood pressure treatment strategies. To study whether the proportion of excess cardiovascular events attributable to various levels of systolic blood pressure varies with age, we calculated the population-attributable risk of all-cause mortality, fatal and nonfatal cardiovascular events (stroke, coronary heart disease, angina, congestive heart failure, and peripheral vascular disease), and stroke incidence due to systolic blood pressure in men and women 45 years of age or older in the United States during 1980. Our estimates are based on US census counts, blood pressure prevalence distributions from the second National Health and Nutrition Examination Survey, and the annual risk of cardiovascular complications during 18 years of follow-up in the Framingham cohort. We then determined the impact of age on the relative efficacy of mass treatment and case-finding strategies in preventing systolic blood pressure-related events. At 45-54 years of age, only 30-40% of systolic blood pressure-related excess events occur in hypertensive individuals (systolic blood pressure greater than or equal to 160 mm Hg). With increasing age, however, the percentage of systolic blood pressure-related events that occur in hypertensive individuals rose substantially; in the older age group (greater than or equal to 75 years), 65-70% of fatal and nonfatal cardiovascular disease events occur in hypertensive persons. The pattern is similar for men and women. The potential impact of a mass treatment strategy designed to shift the distribution of blood pressure downward by a small amount is greater in younger than in older groups, whereas an opposite trend is seen for a high-risk, hypertensive case-finding and treatment approach. 
5	Human immunodeficiency virus associated with thrombotic thrombocytopenic purpura: successful treatment with zidovudine. Thrombocytopenia associated with human immunodeficiency virus (HIV) is well described, and two recent reports show a beneficial effect with the antiretroviral agent zidovudine (ZDV). HIV-associated thrombotic thrombocytopenic purpura (TTP) has recently been observed, but the use of ZDV for it has not been previously described. We have reported a case of relapsing TTP in an HIV-positive man who achieved remission with plasmapheresis and antiplatelet therapy initially, but multiple relapses necessitated the addition of vincristine and ZDV to induce a sustained remission. 
1	Resection and reconstruction for bone tumors in the proximal tibia. The proximal tibia is a common site for both benign and malignant tumors. This article reviews pertinent anatomy, clinical presentation, and staging methods for tumors of this area. Discussion is given to various methods of resection and reconstruction with useful guidelines for procedure selection. The use of allografts for reconstruction is discussed in depth. 
4	DMPO and reperfusion injury: arrhythmia, heart function, electron spin resonance, and nuclear magnetic resonance studies in isolated working guinea pig hearts. With the use of isolated working guinea pig hearts with normothermic global ischemia, it was shown that 5,5-dimethyl-pirroline-N-oxide (DMPO), an organic spin trap agent designed specifically to form stable adducts with oxygen free radicals in electron spin resonance studies, can dramatically reduce the vulnerability of the heart to reperfusion-induced arrhythmias. Studied in concentrations ranging from 10 to 500 mumol/L, DMPO exerted a dose-dependent protective effect. Thus, after 30 minutes of global ischemia, the incidence of ventricular fibrillation (total) and tachycardia was reduced from control values of 100% and 100% to 100% and 100%, 91% and 100%, 25% (p less than 0.001) and 50% (p less than 0.05), and 25% (p less than 0.001) and 41% (p less than 0.05), respectively, with DMPO concentrations of 10, 30, 100, and 500 mumol/L. Maximum signals of DMPO-OH adduct, with the use of electron spin resonance studies, were observed after 3 minutes of reperfusion in fibrillated hearts but were not detected in nonfibrillated hearts. Results of nuclear magnetic resonance studies of myocardial adenosine triphosphate, creatine phosphate, pH, and inorganic phosphate showed that these parameters were not significantly changed by treatment with DMPO, and consequently myocardial heart function was not improved, although there was a dissociation between myocardial adenosine triphosphate content and left ventricular developed pressure during reperfusion. The data presented here indicate that oxygen free radicals play an important role in the development of reperfusion-induced arrhythmias but trapping these cytotoxic free radicals does not improve the recovery of postischemic heart function and high-energy phosphate contents in isolated working guinea pig hearts. 
2	Alternation of gastric mucosal glycoprotein (lectin-binding pattern) in gastric mucosa in stress. A light and electron microscopic study. Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells. 
5	Pathogenesis and treatment of intra-abdominal infection. Intra-abdominal infection is considered potentially life-threatening. Such infection is frequently secondary to perforated viscera, trauma or inflammatory disease. Simple abscesses may be drained percutaneously with roentgenologic guidance; complex abscesses often require open surgical drainage. Secondary peritonitis is usually polymicrobial; broad-spectrum antimicrobial therapy effective against aerobic and anaerobic gram-negative bacteria, as well as gram-positive organisms, is essential. Newer antibiotics, administered either singly or in combination, have been used successfully to treat intra-abdominal infection while avoiding the toxicity of aminoglycosides. 
2	Pneumococcal peritonitis complicating CAPD--was the indwelling intrauterine device to blame? A 45-year-old woman on CAPD developed pneumococcal peritonitis. This is the second such case of Streptococcus pneumoniae peritonitis complicating CAPD. The role of an indwelling intrauterine device (IUD) in producing ascending infection into the peritoneum is discussed, especially in women with evidence of retrograde menstruation. A review of the literature concerning pneumococcal peritonitis associated with IUD is given. Possible contraception to women on CAPD is briefly mentioned. 
1	Spontaneous infarction of placental chorioangioma and associated regression of hydrops fetalis. We report a case of a large chorioangioma diagnosed prenatally with concomitant meconium peritonitis and hydrops fetalis in the second trimester. Spontaneous regression of the tumor occurred, associated with some resolution of the fetal hydrops and delivery near term with good neonatal outcome. 
4	Effects of mental stress on myocardial perfusion in patients with ischemic heart disease. The purpose of the present study was to determine whether and to what extent mental stress can reproduce the perfusion defects that are known to be induced by exercise. Twenty-four patients with recent myocardial infarction (New York Heart Association functional class I) and evidence of ischemic response were evaluated by means of SESTAMIBI scintigraphy performed once after exercise and then again within 2 days after mental arithmetic. Baseline, exercise, and mental stress planar scintigrams were divided into 15 segments, and each segment was reviewed and scored on a scale of 0 to 3 by experienced observers using circumferential profile analysis. Conflicting scores were resolved by consensus. Electrocardiographic abnormalities were found in 15 of 24 patients during exercise and in none during mental arithmetic. Chest pain was experienced by five patients during exercise and by none during mental stress. Twenty patients showed reversible perfusion defects during mental stress. Of the 360 pooled scintigram segments, 99 evidenced uptake defects during exercise, and 48 of these showed the same defects during mental stress. Twenty of the remaining 51 of 99 segments were adjacent to segments showing reversible hypoperfusion, suggesting milder hypoperfusion in these segments during mental arithmetic than during exercise. Furthermore, 10 segments showed reversible defects only during mental stress such that seven of these occurred in areas adjacent to those that had shown exercise-induced reversible perfusion defects, two occurred in areas that had shown fixed SESTAMIBI defects during exercise, and one occurred in a segment that had shown completely normal uptake during exercise. 
5	Maximal O2 uptake of in situ dog muscle during acute hypoxemia with constant perfusion. We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max. 
4	Blood rheology after cardiac valve replacement with mechanical prostheses or bioprostheses. Arterial thromboembolism is a serious complication in patients after heart valve replacement. Abnormalities in blood rheology may contribute to this complication. Therefore, the aim of this study was to compare various determinants of blood rheology in patients with substitute heart valves with those in healthy controls; furthermore, differences between patients with mechanical valves and those with bioprostheses should be investigated. The hemorrheologic determinants--fibrinogen, plasma viscosity, red cell aggregation, hematocrit and platelet aggregation--were studied in 92 patients with mechanical bileaflet valves, in 28 patients with bioprostheses and in 29 control subjects; the time since valve replacement was greater than or equal to 9 months. Fibrinogen, plasma viscosity, red cell and spontaneous platelet aggregation were found to be increased in all patients after heart valve replacement compared with normal subjects (fibrinogen: 348 +/- 87 vs 267 +/- 66 mg/dl, p less than 0.01; plasma viscosity: 1.71 +/- 0.1 vs 1.66 +/- 0.1 mPas, p less than 0.05; red cell aggregation: 9.9 +/- 2 vs 7.8 +/- 2 U, p less than 0.01; platelet aggregation: 22 +/- 15 vs 13 +/- 13%, p less than 0.01); among patients, fibrinogen, plasma viscosity and spontaneous platelet aggregation were higher in mechanical valves than in bioprostheses (fibrinogen: 359 +/- 95 vs 314 +/- 41 mg/dl, p less than 0.01; plasma viscosity: 1.72 +/- 0.1 vs 1.68 +/- 0.1 mPas, p less than 0.1; platelet aggregation: 23 +/- 15 vs 16 +/- 11%; p less than 0.05), whereas no difference could be found for red cell aggregation (9.7 +/- 2 vs 10.5 +/- 2%, p greater than 0.05). 
3	Posterior transfer of the adductors in children who have cerebral palsy. A long-term study. Seventy-eight posterior transfers of the adductors of the hip in forty-two children who has spastic cerebral palsy were reviewed an average of 5.7 years after the operation (range, two to 14.6 years). The results were assessed on the basis of the patient's ability to walk, the range of motion of the affected hip or hips, and the radiographic measurements. In 88 per cent of the patients, the transfer was successful in improving or maintaining abduction, extension, functional walking, and stability of the hip. The failures were all in patients who were unable to walk and who had spastic quadriplegia. Tenotomy of the iliopsoas tendon at the time of the transfer procedure resulted in an improved range of motion of the hip. 
4	The placebo effect in heart failure. Many patients who are enrolled in controlled clinical trials of new drugs for the treatment of heart failure show favorable hemodynamic and clinical responses to placebo therapy. This "placebo effect" results from both the creation of a supportive therapeutic environment and the spontaneous improvement that is commonly seen when measurements of symptoms and cardiac function are repeated frequently over long intervals of time. Three months of treatment with a placebo produces a reduction in symptoms in 25% to 35% of patients, an increase in cardiac output and a decrease in pulmonary wedge pressure, and an increase in exercise tolerance of up to 90 to 120 seconds. Physicians commonly seek to maximize the "placebo effect," since the goal of treatment in the clinical setting is to improve the quality of the patient's life. On the other hand, clinical investigators seek to minimize the "placebo effect," since the goal of a research study is to test the hypothesis that the new drug is superior to a placebo. 
4	Effects of pressure and volume of the receiving chamber on the spatial distribution of regurgitant jets as imaged by color Doppler flow mapping. An in vitro study. Regurgitant jet dimensions imaged by color Doppler flow mapping have been used to evaluate the severity of valvular insufficiency in clinical studies. To study the effect of pressure and volume within the receiving chamber on the magnitude of spatial distribution of regurgitant jets assessed by color Doppler techniques, we designed a simple constant-flow model in which a jet was driven through a known orifice (1.5 mm2) into a compliant receiving chamber by a steady-flow pump. A distal tube at the outflow closed the system and maintained the volume of the chamber constant during pump operation. We varied flow rate from 60 to 270 ml/min into elastic balloons with different static compliances of 1, 2, 4.5, and 9 ml/mm Hg (pressures of 57, 28, 18, and 8 mm Hg, respectively); the balloons served as receiving chambers at the constant volume of 150 ml. We also evaluated the effect of different volumes of a receiving chamber (110, 130, and 150 ml and pressures of 5, 15, and 24 mm Hg) with a static compliance of 2 ml/mm Hg over the same range of flow rates. For each of the different balloons, jet area correlated linearly with the jet velocity across the orifice (r = 0.98, 0.99, 0.98, and 0.97) and also with flow rate (r = 0.97, 0.99, 0.98, and 0.99). At the same flow rate and volume of receiving chamber, however, the jet area imaged by color Doppler decreased as the pressure in the receiving chamber increased, although receiving-chamber volume was constant. 
4	Cardioprotective effects of carnitine in extensive aortocoronary bypass grafting: a double-blind, randomized, placebo-controlled clinical trial. The cardioprotective effects of carnitine were tested in patients undergoing multiple aortocoronary bypass grafting. Intermittent aortic cross-clamping at 28 degrees C was used. Mean total cross-clamping time was 30 +/- 11 min. Patients were randomized into three groups: a control group receiving placebo (group 1), a group pretreated with 3 g carnitine intravenously before cardiopulmonary bypass (CPB) (group 2), and a group pretreated with 6 g carnitine intravenously (group 3). The markers of myocardial ischemia included levels of adenosine triphosphate, its catabolites, and creatine phosphate in transmural left ventricular biopsy specimens taken at the beginning and end of CPB, as well as hemodynamic recovery during weaning from CPB and for the next 24 h. The intravenous infusion of carnitine (3 or 6 g) had no hemodynamic effect. At the end of CPB myocardial tissue levels of adenosine triphosphate and creatine phosphate did not differ significantly among the groups (P greater than 0.05). Recovery of cardiac function during weaning from CPB and for the following 24 h was similar in all three groups (P greater than 0.05). It is concluded that pretreatment with carnitine neither facilitates weaning from cardiopulmonary bypass in patients undergoing aortocoronary bypass surgery nor favorably affects hemodynamic function during the next 24 h. 
5	Peripheral arterial occlusive disease of the extremities in the United States: hospitalization and mortality. PAODE is an important cause of morbidity and health care expenditures among the elderly. Data from the NHDS and National Vital Statistics System were used to assess its impact in the U.S. In 1985 to 1987, an estimated 229 thousand men and 184 thousand women per year were discharged with any diagnosis of chronic PAODE. Discharge rates were much higher in men and increased sharply with age. Lower extremity arteriography was performed during 88 thousand hospitalizations and aorta-iliac-femoral bypass procedures were done during 31 thousand hospitalizations per year. Numbers of procedures increased markedly since 1979. An estimated 60 thousand men and 50 thousand women per year were discharged with any diagnosis of acute PAODE. Embolectomy or thrombectomy of lower limb arteries was listed for 28 thousand discharges per year. Few deaths were attributed to PAODE. Although these data are limited by likely incomplete reporting and by the nonspecificity of diagnostic codes, they provide an indication of the magnitude of the problem. An aging population and advances in surgical techniques suggest continued monitoring using multiple data sources. Vigorous primary prevention programs are needed to lessen the impact of all atherosclerotic diseases. 
5	Mechanical circulatory support as a bridge to transplantation: current status of total artificial heart in 1989 and determinants of survival. Since April 1986, 40 total artificial hearts (TAH) were implanted as a bridge to transplantation in our institution. In an attempt to identify factors affecting survival of TAH recipients we reviewed our experience over 1000 days of mechanical support. There was no postoperative bleeding requiring surgery nor were there any clinical episodes of thromboembolic complications. Over a total functioning period greater than 3 years there were no mechanical failures in the driving system but one artificial ventricle had to be replaced because of mechanical dysfunction. Infections and multiple organ failure were the primary causes of morbidity and mortality during mechanical support. When the patients who underwent staged transplantation (no. 17) were compared with those who died during mechanical support (no. 23) there were no differences in TAH driving mode or hemodynamic variables between the groups. Although preoperative pulmonary, hepatic and renal functions were found to be similar between the groups, there were significant differences in the early evolution (3 days) of hepatic and renal functions following TAH implant (p less than 0.01). Urinary output was found to be the earliest variable discriminating recovery and survival (p less than 0.01). Finally, univariate analysis indicated age (less than 40 vs greater than 40 years) and modality of cardiac decompensation (acute vs chronic) as the most important factors affecting survival after TAH implantation. Since young patients (less than 40 years of age) with acute decompensation were successfully transplanted in 82% of cases while 100% of older patients with chronic decompensation died before or after transplantation, TAH should be advised in young patients with acute or chronic heart failure and in selected older candidates with recent, acute cardiac failure. 
2	Effect of marked peripheral leukocytosis on the leukocyte count in ascites. Patients with high peripheral leukocyte counts are sometimes found to have high leukocyte counts in ascitic fluid in the presence of negative cultures. To determine if peripheral leukocytosis (greater than or equal to 20 x 10(9)/L) by itself can result in high leukocyte or neutrophil counts in ascites, 29 patients were studied. A total of 31 paracenteses were performed in these patients as soon as the high peripheral leukocyte count was determined. Culture of ascitic fluid was performed using blood-culture bottles. The mean peripheral leukocyte count was 29.3 +/- 9.3 x 10(9)/L, with a mean neutrophil count of 19.9 +/- 6.5 x 10(9)/L. The mean ascitic fluid neutrophil count was 0.064 +/- 0.054 x 10(9)/L (range, 0.007 to 0.197 x 10(9)/L). No significant correlation was found between peripheral neutrophil (or leukocyte) count and neutrophil (or leukocyte) count in ascitic fluid. Marked peripheral leukocytosis (or neutrophilia) does not seem to have an effect on the leukocyte or neutrophil count in ascitic fluid. 
4	Streptokinase treatment for femoral artery thrombosis after arterial cardiac catheterisation in infants and children. Data on 205 children who underwent retrograde arterial catheterisation were studied to assess the frequency of femoral artery thrombosis and the safety and efficacy of systemic streptokinase treatment for this complication. In 29 (14%) a transarterial balloon dilatation was performed. In 15 (7.3%) patients impaired arterial perfusion due to vascular spasm with or without thrombus formation was seen in the cannulated leg after catheterisation. Despite heparinisation, signs of impaired arterial circulation persisted in nine patients (4.4% of the total). In these patients femoral artery thrombosis was strongly suspected. Six (53%) of these had undergone a balloon dilatation. Therefore in this study the risk of femoral artery thrombosis developing was 12 times greater after transarterial balloon dilatation than after arterial catheterisation without dilatation (20.6% v 1.7%). Systemic infusion of streptokinase was started in all patients with femoral artery thrombosis. Arterial perfusion became normal in all patients, though in one this was delayed. Haematological monitoring showed lengthening of the thrombin time and a decrease of the fibrinogen concentration during streptokinase treatment. There were no serious complications. Systemic infusion of streptokinase is a safe and useful treatment in children with persistent femoral artery thrombosis after arterial cardiac catheterisation. 
1	Atheroemboli to the lower urinary tract: a marker of atherosclerotic vascular disease--a case report. Atheroemboli to the lower genitourinary tract may serve as a marker for disseminated atheroembolic disease, a highly lethal condition. A case presentation and review of our institional experience is presented. 
3	Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. Autografts of adrenal medulla were implanted into preformed cavities in the caudate nuclei of four rhesus monkeys with hemiparkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Five other hemiparkinsonian monkeys underwent caudate cavitation, but received no tissue implant. All of the animals had marked bradykinesia of the affected arm and stable apomorphine-induced turning before cavitation or implantation. Moderate behavioral recovery was seen in all five monkeys with cavitation and two of the three monkey with long-term adrenal autografts (the fourth adrenal recipient was sacrificed 10 days after grafting). The improvement occurred months after the procedure and was not as early or as complete as that seen after fetal dopaminergic grafts. Surviving adrenal tissue was found only in the animal that showed no behavioral recovery. The other two adrenal autograft recipients (with no surviving adrenal medulla) and all of the animals with cavitation had ingrowth of dopaminergic fibers from the area olfactoria and nucleus accumbens into the caudate, oriented toward the cavity. These findings show that the mechanism of improvement after adrenal medullary implants for parkinsonism is not dopamine secretion by chromaffin cells, but may be related to the sprouted host fibers. The results also indicate that the limited recovery after adrenal implants in parkinsonian patients may be a result of the cavitation, and not necessarily the result of tissue implantation. 
4	Skeletal muscle metabolism in heart failure: a 31P nuclear magnetic resonance spectroscopy study of leg muscle. 1. The gastrocnemius muscle of seven patients with mild to moderate chronic heart failure and of five healthy control subjects was studied using 31P nuclear magnetic resonance spectroscopy. Spectra were collected at rest and during an incremental, symptom-limited, exercise protocol. Blood flow was measured in the same study during brief interruptions to exercise. 2. The phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio was lower in patients with heart failure than in control subjects at an exercise rate of 1.5 W, although intracellular pH and blood flow were similar. 3. The cytosolic free adenosine 5'-diphosphate concentration was markedly increased in patients with heart failure exercising at 1.5 W compared with control subjects exercising at the same workload. 4. Although the maximum workload achieved by patients with heart failure was less than half of that reached by control subjects, the pH and the phosphocreatine/(phosphocreatine plus inorganic phosphate) ratio were lower in patients with heart failure at maximal load. Blood flow was less at maximal exercise in patients with heart failure than in control subjects in keeping with the reduced work load. 5. The phosphocreatine depletion induced in the gastrocnemius muscle by exercise was more severe than previously described in the forearm of patients with heart failure. 6. Metabolic abnormalities in skeletal muscle may contribute to exercise intolerance in heart failure, particularly during submaximal exercise. 
3	Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. The vagus is a mixed nerve carrying somatic and visceral afferents and efferents. The majority of vagal nerve fibers are visceral afferents and have a wide distribution throughout the central nervous system (CNS) either monosynaptically or via the nucleus of the solitary tract. Besides activation of well-defined reflexes, vagal stimulation produces evoked potentials recorded from the cerebral cortex, the hippocampus, the thalamus, and the cerebellum. Activation of vagal afferents can depress monosynaptic reflexes, decrease the activity of spinothalamic neurons, and increase pain threshold. Depending on the stimulation parameters, vagal afferent stimulation in experimental animals can produce electroencephalographic (EEG) synchronization or desynchronization and has been shown to affect sleep states. The desychronization of the EEG appears to depend on activation of afferent fibers that have conduction velocities of less than or equal to 15 m/s. Vagal afferent stimulation can also influence the activity of interictal cortical spikes produced by topical strychnine application, and either attenuate or stop seizures produced by pentylenetetrazol, 3-mercaptoproprionic acid, maximal electroshock, and topical alumina gel. The mechanisms for the antiepileptic effects of vagal stimulation are not fully understood but probably relate to effects on the reticular activating system. The vagus provides an easily accessible, peripheral route to modulate CNS function. 
5	Measuring crackles. Crackles heard on auscultation can be represented graphically as a time-amplitude plot of the associated waveform. To assess the relative merits of several measures which might be considered for machine implementation in diagnostic instruments, we compared the reproducibility of those based on the initial voltage deflection which begins a crackle with those based on the largest deflection. The latter group showed less interobserver and less intraobserver variability when the same crackles were measured twice by each of two observers. Crackles from a teaching tape, categorized as fine and coarse, were used in this study. The ability of the various measures tested to distinguish between fine and coarse crackles on an individual basis was assessed and found to favor the measures based on the largest deflection. They showed an average of 9.96 percent incorrectly classified crackles, as opposed to 19.53 percent for the two measures based on the initial deflection. 
5	Microstaging of squamous cell carcinomas. The clinical classification of squamous cell carcinoma, which was established primarily by the International Union Against Cancer (UICC), does not permit optimal estimation of expected metastasis. The authors' results indicate that metastasis can be more accurately estimated on the basis of invasion depth, histopathologic grading, and especially tumor thickness. One essential advantage of these criteria is that they can be established by a histopathologist. It is interesting to note that in the authors' collective no carcinoma less than 2 mm thick metastasized, that is, a relatively high percentage of carcinomas (48%) can be graded as no-risk carcinomas. The risk of metastasis for undifferentiated carcinomas greater than 6 mm thick that have infiltrated the musculature, the perichondrium, or the periosteum, however, is quite high. Tumors between 2 and 6 mm thick with moderate differentiation and a depth of invasion that does not extend beyond the subcutis can be classified as low-risk carcinomas. 
4	Cardiorespiratory effects of endoscopic esophageal variceal sclerotherapy. Endoscopic variceal sclerotherapy (EVS) is an effective means of controlling variceal hemorrhage, which develops as a consequence of portal hypertension. While esophageal perforation, ulceration, strictures, and mediastinitis are potential complications associated with this procedure, it is not clear whether isolated pleuropulmonary events such as pleuritis, pneumonitis, and adult respiratory distress syndrome are causally related to the EVS. Endoscopy and sedation with the attendant risk of aspiration, particularly in the background of hepatic encephalopathy, may account for some of these events. Recent controlled studies of respiratory function demonstrate that EVS as such results in minor changes in gas exchange, lung volumes, and pulmonary and systemic hemodynamics. Most pulmonary complications have been reported with the use of sodium morrhuate sclerosant. Comparative studies among different sclerosants are necessary to evaluate relative safety. Finally, there have been rare reports of myocardial ischemia and pericarditis reported in association with EVS, but these are of a transient nature. Chest symptoms, roentgenographic pleuropulmonary changes, pulmonary hemodynamics, and cardiac perturbations are transient and should not preclude offering EVS to patients with variceal hemorrhage. 
3	Transient ischaemic attacks in young patients: a thromboembolic or migrainous manifestation? A 10 year follow up study of 46 patients. Forty six patients aged 18-39 years with transient ischaemic attacks (TIA) were studied; two thirds were women. Twenty five patients had attacks accompanied by headache, and seven gave a history of common migraine. Only four of 27 angiograms were abnormal; no operable carotid lesion was demonstrated. Over a mean follow up period of 10 years stroke or myocardial infarction (AMI) occurred in all four patients who presented major cerebrovascular risk factors, but in only two of the remaining 42 patients. Thus irrespective of age thromboembolic TIA is a harbinger of stroke or AMI. However, most TIAs under the age of 40 years are caused by a non-embolic benign vascular disorder. The clinical characteristics, long-term prognosis, and possible pathogenesis, for such attacks are often indistinguishable from those of classical migraine. In the absence of cardiovascular risk factors, arteriography does not provide much diagnostic and prognostic information. 
2	CD8+ T cell homing to the pancreas in the nonobese diabetic mouse is CD4+ T cell-dependent. The adoptive transfer of type I diabetes in nonobese diabetic mice requires the contribution of both CD4+ and CD8+ T cells. To further elucidate the cellular pathway(s) of beta-cell destruction and the responsibility of each subset, high doses of committed T cells from diabetic mice purified to single subsets, were injected into syngeneic nonobese diabetic neonates. The recipients of single or mixed subsets were followed for clinical manifestations of diabetes and examined at 30 days of age for in situ lesions. None of the animals injected with either CD4+ or CD8+ T cells became overtly diabetic during the 30 days of observation whereas 8 of 23 mice inoculated with a mixture of the two subsets developed glycosuria and hyperglycemia. However, insulitis was found in 6 of the 13 mice injected with CD4+ T cells whereas only 1 of the 9 mice injected with CD8+ T cells showed marginal infiltration of the pancreas. The lesions initiated by CD4+ T cells alone were considerably less severe than those induced by the mixture of both subsets, corroborating the fact that overt disease did not occur in the former group. Together, these results suggest a distinct function for each diabetogenic T cell subset. CD4+ T cells, which have the capacity to home to the pancreas, promote in turn the influx of CD8+ effector T cells that do not by themselves accumulate in this organ. These results illustrate a novel form of T-T cell interactions leading to organ specific autoimmune lesions. 
1	Expression of c-erbB-2 gene product in urinary bladder cancer. Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer. 
1	Mononuclear phagocytes: a major population of effector cells responsible for rejection of allografted tumor cells in mice. To understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells, the types of cells that infiltrated into the rejection site were examined. When Meth A cells (H-2d) were given i.p. to an allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on the 6th day, accompanied by an i.p. infiltration of leukocytes. The tumor cells were totally eliminated from the peritoneal cavity around the 12th day. The highest cytotoxic activity against Meth A cells was obtained with the peritoneal exudate cells harvested on day 8. On this day, the exudate cells consisted of three populations when examined by flow cytometry, and each was isolated by sorting. Each of them appeared to be homogeneous, and they were morphologically identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less-granular cells. The cytotoxic activity was confined exclusively to the last population. The effector cells (H-2b) were cytotoxic against not only Meth A cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of mouse]. The effector cells were totally inert against concanavalin A-activated syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse]. The effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4- immunoglobulin- asialo GM1-), morphologically, and functionally distinct from cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells but were adherent mononuclear phagocytes. 
5	Survey of the use of thrombolysis for acute limb ischaemia in the UK and Ireland. A total of 156 vascular surgeons from the UK and Ireland responded to a postal questionnaire on the use of thrombolysis in acute limb ischaemia. Almost half had used thrombolysis in the previous 12 months. Low dose intra-arterial streptokinase (89 per cent) was the regimen most frequently used, but 33 per cent had used intravenous streptokinase. Detailed results for 103 patients (limb salvage rate 60 per cent, amputation rate 35 per cent, mortality rate 5 per cent) were similar to those of previously published reports. Complications in most series were infrequent, but in the entire survey there were six bleeding-related deaths and one death from anaphylaxis. A total of 67 per cent of surgeons with working experience indicated that selected patients with acute arterial thromboses were most suitable for thrombolysis, particularly if there was no neurological deficit and no run-off for surgical bypass. Distal or late emboli and graft occlusions were regarded as appropriate by some surgeons. This study demonstrated that many vascular surgeons currently use thrombolysis, although sparingly and in selected cases. Patients with acute limb ischaemia should be managed by experienced vascular surgeons who are aware of the new therapeutic alternatives, an ideal supported by almost three-quarters of respondents to this survey. 
1	Malignant glandular triton tumor. A case of left brachial plexus-related malignant peripheral nerve sheath tumor showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old Chinese man is reported. The authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component. The patient had extensive local recurrence comprising mainly the Schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation. The natural behavior of this tumor, as in other reported cases of malignant triton tumor, is extremely aggressive, unlike malignant schwannoma or glandular malignant schwannoma. The histogenesis of this tumor is likely to be from primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant Schwann's cells. 
5	Rejection of multivisceral allografts in rats: a sequential analysis with comparison to isolated orthotopic small-bowel and liver grafts. Multivisceral isografts and allografts were transplanted to Lewis rats, and the histopathologic changes were studied in the liver, intestine, and other constituent organs. Rats receiving isografts had indefinite survival with maintenance of weight. With multivisceral allografts (from Brown-Norway donors), the intestinal component was rejected more severely than the companion liver and with about the same severity as when intestinal transplantation was performed alone. Intestinal rejection in either circumstance was a lethal event, causing death in 10 to 12 days. The earliest (by day 4) and most intense cellular rejection was in the Peyer's patches and mesenteric lymph nodes. This was associated with or followed by cryptitis, epithelial cell necrosis, focal abscess formation, mural necrosis, and eventual perforation. Liver allografts transplanted alone or as part of multivisceral grafts also had histopathologic evidence of rejection, but this was self-limiting and spontaneously reversible when the liver was transplanted alone. Thus the Achille's heel of multivisceral grafts is the intestinal component that is not protected by the presence of the liver in the organ complex. Better immunosuppression should permit successful experimental and clinical transplantation of such grafts. 
4	Efficacy of nimodipine in cerebral ischemia or hemorrhage. Our studies showed that in an appropriate dose, nimodipine increased local cerebral blood flow with no corresponding increase in local metabolism. Nimodipine treatment given before experimental ischemic insult, resulting from either vascular occlusion or intracranial hemorrhage or after subarachnoid hemorrhage, maintained or improved blood flow and minimized the severity of subsequent brain damage. Lack of benefit from nimodipine treatment after the insult may occur because the inexorable progression of events leading to ischemic neuronal damage, once initiated, cannot be arrested. On the other hand, pharmacokinetic factors may be important, and post-treatment efficacy may depend on administration protocols that achieve an adequate concentration in ischemic tissue sufficiently soon after an insult. Our findings are compatible with the benefit of nimodipine being due to an improvement in blood flow that reduces the severity of ischemia. However, they do not exclude the possibility that treatment may minimize the accumulation of calcium in damaged cells as a result of "cytoprotective" effects. 
5	Effect of nontransmural necrosis on epicardial potential fields. Correlation with fiber direction. The effect of nontransmural necrosis on epicardial potential distributions was studied in 13 dogs. In previous studies, left ventricular epicardial pacing generated epicardial potential maps at QRS onset with a negative central area and two positive areas that faced the portions of the wavefront propagating along fibers. Subsequently, the positive areas expanded in a counterclockwise direction by 90 degrees to 120 degrees. In those studies, the rotatory expansion of the positive areas was tentatively attributed to the spread of excitation through deep myocardial layers, where fiber direction rotated counterclockwise from epicardium to endocardium. To test this hypothesis, we tried to interrupt the counterclockwise expansion of the positive area by creating localized, nontransmural necrosis at various depths in the left ventricular wall by injection of formalin or application of laser energy. Epicardial potential maps were obtained from a grid of 12 x 15 electrodes on a 44 x 56-mm area. Epicardial pacing from selected sites generated epicardial maps in which some positive areas were missing compared with controls. The direction of the straight line joining the pacing site to the site of missing positivity correlated well with the average fiber direction in the necrotic mass (r = 0.82, p less than 0.01). Angle between epicardial fiber direction and the straight line described above correlated well with the average depth of the necrosis, expressed as percent of the wall thickness (r = 0.95, p less than 0.01). These data support the hypothesis that the counterclockwise expansion of the epicardial positivity occurring after epicardial pacing results from excitation spreading along deep fibers. 
1	Peripheral ameloblastoma with clear cell differentiation. This report details a case of mandibular peripheral ameloblastoma having a clear cell component. The latter consisted of ovoid cells with vacuolated or clear cytoplasm and vesicular or pyknotic nuclei that may be disposed as discrete clusters or show direct transition from typical acanthomatous areas. Comparison of this lesion with other odontogenic and nonodontogenic tumors that contain clear cells is discussed in the context of the differential diagnosis. 
3	Posttraumatic torticollis. We report six cases of torticollis precipitated by neck trauma. The dystonia began 1 to 4 days after the trauma and differed clinically from idiopathic torticollis by marked limitation of range of motion, lack of improvement after sleep ("honeymoon period"), and absence of geste antagonistique. Worsening with action was not present; nor was there improvement with support as seen with idiopathic torticollis. Onset of pain immediately after the trauma and marked spasms of the paracervical muscles were other predominant features. Anticholinergic therapy was without benefit; however, some improvement occurred with botulinum toxin injection. It is concluded that torticollis can be caused by peripheral trauma and that it has unique clinical characteristics. 
1	Bone cancer incidence rates in New York State: time trends and fluoridated drinking water. BACKGROUND: Recent animal studies of the potential carcinogenicity of fluoride prompted an examination of bone cancer incidence rates. METHODS: Trends in the incidence of primary bone cancers, including the incidence of osteosarcomas were examined among residents of New York State, exclusive of New York City. Average annual osteosarcoma incidence rates in fluoridated and non-fluoridated areas were also compared. RESULTS: Among persons less than 30 years of age at diagnosis, bone cancer incidence among males demonstrated a significant increase since 1955, while incidence among females has remained unchanged. A significant decrease in bone cancer incidence rates since 1955 was observed among both males and females age 30 years and over at time of diagnosis. Osteosarcoma incidence rates have remained essentially unchanged since 1970, among both younger and older males and females. The average annual age adjusted incidence of osteosarcomas (1976-1987) in areas served by fluoridated water supplies was not found to differ from osteosarcoma incidence rates in non-fluoridated areas. CONCLUSIONS: These data do not support an association between fluoride in drinking water and the occurrence of cancer of the bone. 
4	Hepatic lesions in the rabbit induced by acoustic cavitation. Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma. 
5	Hyperadrenergic orthostatic intolerance as a result of postpartum blood loss. This article describes a young women in whom orthostatic intolerance developed as a result of protracted postpartum vaginal bleeding. The cardiovascular abnormalities were unresponsive to usual treatment measures, and she required combination therapy directed at increasing plasma volume and decreasing sympathetic nervous system activity. After resolution of her symptoms, the patient required no long-term therapy. Chronic blood loss has not been reported as a cause of this syndrome. 
4	Acute coronary artery occlusion during and after percutaneous transluminal coronary angioplasty. Frequency, prediction, clinical course, management, and follow-up [published erratum appears in Circulation 1991 Jul;84(1):446] BACKGROUND. Acute coronary artery occlusion after percutaneous transluminal coronary angioplasty (PTCA) continues to remain a serious complication despite significant improvement in operator performance and technological advancements. This retrospective study was performed to ascertain the frequency, predictive variables, management, and outcome of acute coronary artery occlusion. METHODS AND RESULTS. The study was based on data from 1,423 consecutive patients who underwent an elective coronary angioplasty between January 1986 and December 1988. Acute coronary artery occlusion occurred in 104 patients (7.3%). Acute occlusion developed during the dilatation procedure in 80 patients (5.6%) and within 24 hours after the procedure in 24 patients (1.7%). Four clinical and 14 angiographic variables predictive for acute coronary artery occlusion were analyzed in these 104 patients with a complicated procedure and were compared with those in 104 representative patients with successful attempts. Multivariate analysis found three independent predictive variables: unstable angina, multivessel disease, and complex lesions. The overall clinical outcome after management of acute coronary artery occlusion including immediate repeat dilatation (95 patients), use of intracoronary streptokinase (34 patients), or autoperfusion catheter (12 patients) was successful (reduction of lumen diameter to less than 50%, no death, no myocardial infarction [MI], and no emergency surgery) in 42 patients (40%), was a failure without major complication in four patients (4%), and was a failure with major complication (death, MI, and emergency surgery) in 58 patients (56%). The overall mortality rate was 6% (six patients), the overall MI rate was 36% (37 patients), and emergency bypass surgery was required in 30% of patients (31 patients). At 6 months' follow-up of 42 patients with successful management, recurrent angina pectoris due to restenosis occurred in 10 patients (24%), and a late MI occurred in one patient (3%). At 6 months' follow-up of 56 survivors with unsuccessful management (development of MI or need for emergency bypass surgery), recurrent angina occurred in nine patients (16%), and cardiac death in two patients (4%). However, the majority of patients in both groups were either symptom free or had mild angina pectoris. CONCLUSION. Acute coronary artery occlusion during PTCA is often unpredictable, but its frequency is higher in patients with unstable angina, multivessel disease, and complex lesions. Despite immediate redilatation, use of intracoronary streptokinase, and emergency bypass surgery, PTCA is associated with a high mortality and morbidity. 
1	A case of classical mycosis fungoides associated with human T-cell lymphotropic virus type I. A 72-year-old male patient from north-eastern Iran developed the typical clinical and histopathological features of mycosis fungoides with lymphadenopathy, but without any other systemic involvement. Human T-cell lymphotropic virus (HTLV-I) antibodies were detected in the patient's serum by two different ELISAs and by Western blot using purified viral particles from MT-2 culture supernatants. Cultured peripheral blood lymphocytes were positive for labelling with anti-HTLV-I serum. Southern blot hybridization of DNA extracted from a skin tumour and from an involved lymph node revealed integrated proviral DNA with identical restriction patterns. This case supports a relationship between mycosis fungoides and HTLV-I and may indicate a new region of endemic HTLV-I infection. 
5	Analysis of antigen expression at multiple tumor sites in epithelial ovarian cancer. The question of whether the antigenic phenotype of human epithelial ovarian cancer varies in a given patient between the primary tumor and metastatic sites or among metastatic sites themselves is an important issue in planning potential therapeutic strategies for ovarian cancer. We have obtained tumor specimens from at least two separate sites during operations on 12 patients with epithelial ovarian cancer, and we have typed these specimens with a group of 18 monoclonal antibodies that react with cell-surface glycoprotein and carbohydrate antigens, including blood group antigens. Antibodies with relative specificity for malignant cells as well as those that detect more widely distributed epithelial antigens were used. A total of 31 specimens from 12 patients with advanced adenocarcinoma (8 serous, 3 undifferentiated, 1 endometrioid) of the ovary were studied, including fresh ascites cells in two patients. Frozen sections of tumor specimens were stained with the antibodies by the indirect immunoperoxidase technique and graded semiquantitatively. Little difference was seen in antigenic expression of tumors that were obtained from various sites in the same patient for either the epithelial cell markers or blood group markers. Intratumoral antigenic heterogeneity was seen, but this was generally quite consistent within a given patient's specimens. As anticipated, variations in antigen expression were seen among specimens from different patients. The antigenic phenotype of the tumor specimens in a given patient, as determined immunohistochemically by our group of antibodies, showed only minor variation among primary and metastatic sites. 
5	Decrease in mean platelet survival time in acute poststreptococcal glomerulonephritis (APSGN). In an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), we studied the platelet survival time, as an index of platelet activation, in 22 patients with APSGN. Mean platelet survival time was computed from the disappearance of radioactivity from blood, sampled serially after injection of autologous 51Cr-labelled platelets. C1q solid phase ELISA and conglutinin (K) solid phase ELISA were used to measure the serum levels of immune complexes. The platelet survival time in APSGN patients was 113 +/- 10 h vs 197 +/- 10 h in the control group (p less than 0.001); 68% of the patients had a shortened platelet survival, lower than 95% confidence limit. There was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome. There was no significant association between the mean platelet times survival and CICs (circulating immune complexes). Similarly, no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease, as assessed by the serum creatinine level and the proteinuria. These results support evidence of platelet activation and consumption in APSGN and we suggest that this activation occurs in the glomeruli capillary wall, due to platelet-vascular wall interaction. 
3	Brain water content, brain blood volume, blood chemistry, and pathology in a model of cerebral edema. STUDY OBJECTIVES: The objective was to correlate regional changes during brain water content with alterations in blood chemistry and cerebral pathology during hypo-osmotic edema. PARTICIPANTS: Sprague-Dawley male adult rats were used in these studies. DESIGN: Animals were block-randomized to receive either an intraperitoneal distilled water injection equivalent to 5% or 15% of their body weight or no injection (controls). Rats were sacrificed 15 or 60 minutes after water injection or at an equivalent time for controls. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: Water content of cerebral cortical gray and white matter was calculated from measurements of tissue specific gravity. Blood plasma osmolality and sodium and potassium concentrations were determined at various times after water injection. An index of blood-brain barrier permeability was obtained by measuring brain red blood cell and plasma volumes. A qualitative assessment of edema was made from light and electron micrographs of the cerebral cortex. We found that water injection produced a dose-dependent decrease in plasma osmolality and sodium concentration within 15 minutes. Cortical water content was unchanged after this period. An influx of water into cerebral gray, and, less readily, into cerebral white matter occurred during the next 15 minutes. Whole blood specific gravity and brain blood content were unchanged and thus did not confound the measurement of cerebral water content. Hematocrit was increased 60 minutes after a 15% water injection. The blood-brain barrier remained intact throughout this period. Microscopy revealed astrocytic swelling with slight extracellular fluid accumulation 60 minutes after the water injection. CONCLUSIONS: Homeostatic mechanisms in the cerebral cortex can maintain constant water content for at least 15 minutes during maintained intravascular hypo-osmolality. Fluid that subsequently moves into the tissue primarily enters an intracellular compartment. This model will be useful in investigating physiological mechanisms of brain water regulation and the pathogenesis of brain edema, a common clinical entity in emergency conditions. 
4	Prostacyclin and prostaglandin E2 mediate reduction of increased mean arterial pressure during cardiopulmonary bypass by aspiration of shed pulmonary venous blood. Increased mean arterial pressure during the aortic crossclamp period while on cardiopulmonary bypass was usually treated by us with hypotensive drugs. We noticed, however, that aspirating shed excess pulmonary venous blood from the open pleural cavities causes an immediate reduction in mean arterial pressure, obviating the need for any further pharmaceutical intervention. In this study we investigated the relationship between the reduction in mean arterial pressure and the levels of prostacyclin and prostaglandin E2 in the peripheral and pulmonary venous blood. Ten men undergoing coronary bypass operations had 21 episodes of increased mean arterial pressure (106.9 +/- 11.4 mm Hg) during aortic crossclamping, which was reduced to 67.4 +/- 11.4 mm Hg (p less than 0.001) only by aspirating a mean of 490 ml (range 150 to 1100 ml) of pulmonary venous blood from the pleurae back into the circulation. Mean peripheral prostacyclin level, measured as 6-keto-prostaglandin F1 alpha, and prostaglandin E2 level, both measured by radioimmunoassay technique, were significantly lower at peak mean arterial pressure (419 +/- 180 and 59.5 +/- 21.2 pg/ml) than at lowest mean arterial pressure (632 +/- 271 and 96.7 +/- 52.4 pg/ml for 6-keto-prostaglandin F1 alpha and prostaglandin E2, respectively; p less than 0.001). Prostaglandin F1 alpha and prostaglandin E2 levels in the aspirated pulmonary venous blood were 2309 +/- 3098 pg/ml and 749 +/- 909 pg/ml, respectively. The hypotensive effect of shed pulmonary venous blood that is aspirated back from the pleurae into the circulation seems to be mediated by the high levels of prostacyclin and prostaglandin E2, both powerful vasodilators. 
1	Desmoplastic variant of ameloblastoma: report of a case and review of the literature. A case of desmoplastic variant of ameloblastoma is reported. The lesion, in a 36-year-old Japanese woman, was successfully treated by partial maxillectomy. Reconstruction was carried out with a block of hydroxyapatite about 7 years and 6 months later. Six cases, including our case, reported up to the present are summarized and reviewed. 
5	Comparison of coffee intake and coffee-induced symptoms in patients with duodenal ulcer, nonulcer dyspepsia, and normal controls. Coffee and decaffeinated coffee stimulate acid secretion. In addition, many patients experience dyspepsia after coffee ingestion. Therefore, coffee is often prohibited by physicians in patients with peptic diseases. However, the association between peptic disease and symptoms remains unclear. This study compares coffee intake and the induction of symptoms by coffee in patients with duodenal ulcer disease, nonulcer dyspepsia, and normal controls. We have studied the coffee drinking habits of 58 duodenal ulcer patients, 55 nonulcer dyspepsia patients, and 55 normal controls. The use of coffee on a daily basis was not significantly different between duodenal ulcer patients (64%) and controls (56%), or between nonulcer dyspepsia patients (55%) and controls. There was also no difference between the three groups in the use of decaffeinated coffee, the number of cups per day, the method of preparation, the length of time of coffee use, or any change in coffee intake in the previous year. The intake of tea, caffeinated carbonated beverages, and aspirin or nonsteroidal anti-inflammatory drugs was also similar in the three groups. The duodenal ulcer patients were more likely to be cigarette smokers (45%) than either the controls (16%) or the nonulcer dyspepsia patients (24%). Daily alcohol intake was not significantly different in the three groups. The prevalence of coffee induction of dyspeptic symptoms was similar in duodenal ulcer patients (29%) and controls (22%), but was much more common in nonulcer dyspepsia patients (53%) than in controls (22%), p = 0.0036. In conclusion, there was no difference in coffee intake between patients with duodenal ulcer, nonulcer dyspepsia, or normal controls. However, patients with nonulcer dyspepsia, but not duodenal ulcer, were more likely to experience dyspeptic symptoms after coffee ingestion. 
1	An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings. The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome. Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months. Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ less than 3.0 mmol/l and HCO3 greater than 30 mmol/l; serum cortisol at 9 a.m. or midnight of greater than 800 nmol/l; urine free cortisol greater than 1300 nmol/24 hours; plasma ACTH greater than 100 ng/l. In the high-dose dexamethasone suppression test, suppression by less than 50 per cent of 9 a.m. serum cortisol, urine free cortisol or 17-oxogenic steroids was usually indicative of an ectopic source of ACTH. A mean suppressed value of greater than 450 nmol/l for the 9 a.m. and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease. For urine free cortisol, a mean suppressed value of less than 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of less than or equal to 3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was greater than 3-fold in all but one of the patients with Cushing's disease. Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease (Patient 16); in the ectopic group, all patients except Patient D failed to respond to either test. It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measurable plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH. 
4	Comparison of standard one-minute treadmill exercise and strandness test (absolute walking distance) in relation to site of lesion, walking distance, and diastolic blood flow velocity (Doppler curves). In 215 outpatients suffering from occlusive arterial disease of the lower limbs the authors compared the decrease in the ratio of ankle systolic pressure to brachial systolic pressure according to whether the treadmill exercise was limited to one minute or extended until pain forced the patient to stop. After a one-minute walk the pressure index always decreased significantly, especially when walking was restricted. The decrease in the pressure index was generally greater when the exercise was continued until the absolute walking distance, and the recovery time was usually twice as long. The fall in the pressure index was significantly greater for patients with single and multiple iliac stenoses than for those with stenoses at lower levels. In patients having a diastolic blood flow velocity on Doppler curves at rest, not modified by walking, a maximum drop in peripheral pressure was recorded after walking for one minute. In this instance there was no intensification of the decrease in peripheral pressure, unlike in patients without a diastolic blood flow velocity at rest. This one-minute test is not a maximal hemodynamic response, but it is sufficient for the appreciation of ischemia during exercise, according to the different parameters measured. 
1	Control of interleukin-1 beta expression by protein kinase C and cyclic adenosine monophosphate in myeloid leukemia cells. We have examined the signal transduction pathways leading to the expression of the interleukin-1 beta (IL-1 beta) gene in human myeloid leukemia cells lines. Two cell lines representing different stages of differentiation were used (HL-60, promyelocytic, and THP-1, mature monocytic). In accordance with previous studies, it was observed that a protein kinase C (PKC) activator, phorbol myristate acetate (PMA), was a sufficient stimulus for induction of the IL-1 beta messenger RNA (mRNA) expression and IL-1 beta protein production in both of these cell lines. A structural analog of cyclic adenosine monophosphate (dbcAMP) or agents elevating the endogenous cAMP levels (prostaglandin E2, forskolin) were not alone able to induce IL-1 beta expression, but they strongly enhanced the PMA-induced IL-1 beta production and IL-1 beta mRNA accumulation. Nuclear run off analysis showed that this elevation in IL-1 beta mRNA levels was due to an increased rate of transcription. If dbcAMP was added 6 hours before PMA to the cultures, no enhancement in the IL-1 beta production was seen, implying that for this enhancing effect both of these signals must be present simultaneously. PKC inhibitor, H7, also blocked effectively the PMA plus dbcAMP induced IL-1 beta production, while the protein kinase A (PKA) inhibitor, HA1004, had no effect, suggesting that PKA activation is not involved in the mechanism of action of cAMP in this case. Collectively, the present findings show that cAMP-dependent signals can have a positive regulatory effect on the PKC-dependent activation of the IL-1 beta gene in cells derived from different stages of myeloid differentiation. 
5	Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. Torulopsis glabrata is second only to Candida albicans in frequency of isolation from the vagina in both asymptomatic women and patients with yeast vaginitis. We retrospectively studied 33 patients from whom vaginal isolates of T glabrata were obtained. Torulopsis glabrata caused symptomatic vaginitis in 42% of the patients but was unassociated with symptoms in 30%; in 27% of patients, its importance was uncertain because of concomitant pathology. Antifungal susceptibility testing was performed on 39 T glabrata strains isolated from 39 patients. The minimal inhibitory concentrations (MICs) of the majority of T glabrata isolates fell within the sensitive range of the antimycotic drugs tested; however, no correlation was found between in vitro antifungal MICs and the response to azole drug therapy. Clinical success was achieved in 67% of the patients although mycologic cure occurred in only 33%. A small number of patients developed recurrent and often chronic Torulopsis vaginitis unresponsive to conventional therapy. Limited experience suggests that vaginal boric acid therapy may be of value in these recalcitrant cases. 
1	Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy. A report from the Study Group of Japan. One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989. The eligible patients included infants younger than 12 months of age with Stage IVA disease (bone cortex, distant lymph node, and/or remote organ metastases) and patients aged 12 months or older with Stage III or IV disease (IVA plus IVB with tumor crossing the mid-line and with metastases confined to bone marrow, liver, and skin). The patients first received six cyclic course of intensive chemotherapy (regimen A1), consisting of cyclophosphamide (1200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (pyrarubicin; 40 mg/m2), and cisplatin (90 mg/m2). Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy. The patients were further divided into three groups. Patients in course 1 received alternating treatment by regimen B (cyclophosphamide and ACNU) and intensified regimen A1, and those in course 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in course 3 were treated with bone marrow transplantation (BMT) preceded by high-dose preconditioning chemotherapy. Survival rates were 77% in Stage III and 54% in Stage IV at 2 years, and 70% in Stage III and 45% in Stage IV at 3 years. The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3, mild cystitis, and hearing impairment. The 2-year survival rate was 78% in 21 patients who underwent BMT when complete remission was achieved. We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response, and in widening the indications for and achieving improved results of treatment with BMT. 
3	Radiation-induced cranial nerve palsy: hypoglossal nerve and vocal cord palsies. Cranial nerve palsies are an unexpected complication of radiotherapy for head and neck tumours. We present a case of this radiation-induced cranial palsy. An 18-year-old female with nasopharyngeal carcinoma developed a right hypoglossal nerve palsy 42 months after cancericidal doses of radiotherapy. In addition, she developed a bilateral vocal cord palsy 62 months after therapy. Follow-up over four years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement. 
5	Choroid plexus tumors in the breast cancer-sarcoma syndrome. Choroid plexus neoplasms are rare epithelial tumors of the central nervous system. A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome (Li-Fraumeni or SBLA syndrome), an inherited condition characterized by the development of diverse neoplasms (sarcoma, breast cancer, brain tumors, leukemia, adrenal cortical carcinoma, and others). Choroid plexus carcinomas were identified in two kindreds previously reported with the syndrome. The literature contains reports of choroid plexus neoplasms occurring in families and in individuals with multiple primary tumors. Choroid plexus neoplasm may be a manifestation of the inherited proclivity to tumor development in the breast cancer-sarcoma syndrome. 
5	The Baltimore experience with laparoscopic management of acute cholecystitis. Laparoscopic cholecystectomy has rapidly emerged as a popular alternative to traditional laparotomy and cholecystectomy. Acute cholecystitis has been considered to be a relative or absolute contraindication to laparoscopic surgery. After gaining extensive experience in laparoscopic biliary tract surgery, this procedure was attempted in 15 patients with acute cholecystitis. All patients were operated on within 72 hours of admission. In five patients, the laparoscopic procedure was converted to an open laparotomy; in one patient, a localized abscess was found, and in the other four patients, extensive inflammation and edema precluded a safe dissection of the vascular and ductal structures. Laparoscopic cholangiography was performed in 14 patients and proved valuable in demonstrating the ductal anatomy. Patients were discharged an average of 2.7 days after the laparoscopic procedure. Laparoscopic cholecystectomy may be safely performed by experienced surgeons in patients with acute cholecystitis. To ensure a low complication rate, a low threshold for converting the procedure to an open laparotomy must be maintained if the ductal and vascular anatomy cannot be safely demonstrated. 
4	Senile cardiac amyloidosis associated with homozygosity for a transthyretin variant (ILE-122). Senile cardiac amyloidosis, also known as senile systemic amyloidosis, is a sporadic disease of late onset but with increasing incidence with age. Recently it has been shown in one case that amyloid deposits contained a transthyretin variant with an isoleucine for valine substitution at position 122. A second case with the transthyretin isoleucine 122 variant is reported here. This individual, who died with restrictive cardiomyopathy, was found to be homozygous for this transthyretin variant and his son heterozygous for the variant. A brother of the propositus was also homozygous for the variant but died of a cerebral vascular accident without being evaluated for amyloidosis. These studies show genetic transmission of the isoleucine-122 transthyretin variant associated with this form of cardiac amyloidosis. 
2	Gastrointestinal intraluminal pH in normal subjects and those with colorectal adenoma or carcinoma. Recent evidence suggests that the production of colorectal carcinogens is facilitated when the pH of the colonic contents is alkaline. It follows that the colonic intraluminal pH of patients with colorectal neoplasms should be higher than in normal subjects. Gastrointestinal pH has been measured in 30 patients with colorectal cancer and 37 patients with benign colorectal adenomas (using a pH sensitive radiotelemetry capsule). These values have been compared with those recorded in 66 normal subjects. No differences in gastrointestinal pH were found and the results did not support the hypothesis that colonic pH plays a role in the aetiology of colorectal neoplasia. 
1	Use of the levator scapulae muscle flap in head and neck reconstruction. There are numerous techniques available for reconstruction of defects following composite resection of oral cavity and oropharyngeal tumors. No single technique is applicable in all situations. The levator scapulae muscle flap is well known for its application in carotid protection. Little attention is paid to its usefulness in other aspects of head and neck reconstruction. We have been using the levator scapulae muscle flap for a variety of reconstructive problems. The flap is useful for buttressing intraoral suture lines, closing intraoral defects, and providing soft tissue to fill in dead spaces and bulk out lateral and anterior oral defects. The levator flap was found to be easy to elevate, safe, and reliable with a minimum of wound complications. A review of 18 patients, representative case studies, and a discussion of surgical technique and relevant anatomy and blood supply is presented. 
4	Heart weights of white men 20 to 39 years of age. An analysis of 218 autopsy cases. Review of autopsy data for 218 white men between 20 and 39 years of age who died of injuries or suddenly and unexpectedly indicated a mean heart weight of 371 g. The mean for those dying of external causes was 364 g whereas the mean for those dying of natural causes was 446 g. A coefficient for heart weight expressed as a percentage of body weight was lower in heavy individuals than lightweight individuals; it ranged between 0.38% and 0.55%, with a mean of 0.48%. Heart weight, including epicardial fat, increased with age and body weight. These data may be useful to those who are called upon to investigate sudden and unexpected deaths. 
1	Myofibroblastoma of the tongue. An immunohistochemical, ultrastructural, and flow cytometric study. A case of myofibroblastoma arising in the tongue of a 77-year-old man is described. The patient presented with a submucosal tongue mass without other associated symptoms. The tumor was 2 cm in diameter, well circumscribed, and composed of uniform spindle cells arranged in fascicles. Electron microscopic examination and immunohistochemistry demonstrated a myofibroblastic origin for the tumor cells. DNA flow cytometric analysis showed a diploid DNA content of this tumor. To the authors' knowledge, this is the first report of myofibroblastoma occurring in the tongue. 
5	Postoperative sore throat: topical hydrocortisone Forty patients undergoing tracheal intubation and controlled ventilation of the lungs for elective surgical procedures were studied. They were allocated randomly into one of two groups. The tracheal tubes used for group A patients were lubricated before insertion with water-soluble 1% hydrocortisone cream. Those for group B patients were lubricated with KY jelly. The incidence of postoperative sore throat was found to be significantly greater in group A. Topical 1% hydrocortisone cream is therefore ineffective in the prevention of postoperative sore throat. 
2	Diagnostic fine-needle puncture of the gallbladder with US guidance From February 1988 to January 1990, 118 fine-needle diagnostic punctures of the gallbladder (DPG) were performed under continuous ultrasound (US) guidance on symptomatic patients with gallstones. The first attempt at gallbladder puncture and aspiration was successful in every patient with use of a 22-gauge needle and continuous US visualization of the needle tip. The aspirated volume varied between 3 and 88 mL (average +/- standard deviation, 25.0 mL +/- 15.3). Biliary analysis revealed an elevation of the cholesterol saturation index in patients with cholesterol gallstones (attenuation at computed tomographic examination of 50 HU or less) relative to that in patients with pigment stones (attenuation more than 50 HU) (1.3 +/- 0.2 vs 1.0 +/- 0.1, P less than .05). The nucleation time was prolonged in patients with pigment stones (19.3 days +/- 3.5 vs 1.8 days +/- 0.8 for patients with cholesterol stones, P less than .001). All patients remained hospitalized for 24 hours after DPG and were reexamined on an outpatient basis at 1 and 3 months thereafter. No complications were detected during either short-term observation or long-term follow-up. The authors conclude that DPG is a safe and valuable technique in the diagnostic work-up of gallstone patients to establish their suitability for nonoperative treatment. 
5	Morbidity and disability in older persons in the years prior to death. BACKGROUND: A large proportion of the disease and disability which affects older persons occurs in the years just prior to death. Little prospective evidence is available which quantifies the burden of morbidity and disability during these years. METHODS: In three community-based cohorts of persons age 65 and older, chronic conditions and disability were evaluated for the three years prior to death in 531 persons who had three annual assessments and then died within one year of the third assessment. Number of chronic conditions, prevalence of disability in activities of daily living (ADLs), and prevalence of disability on a modified Rosow-Breslau scale were determined for these decedents and compared to 8821 members of the cohorts known to have survived. RESULTS: Prevalence rates of disease and disability increased during the follow-up for both decedents and survivors, with decedents generally having higher rates than survivors. Disability rates prior to death, but not the number of diseases, increased with increasing age at death. The odds ratio for disability in ADLs at any of the three assessments for decedents versus survivors ranged from 3.0 to 4.2 in the three communities. In each community the odds ratio for ADL disability was higher in women decedents versus survivors than in men decedents versus survivors. CONCLUSIONS: These results have important implications for disability levels in future older populations in which death is projected to occur at increasingly higher ages. 
3	The association of carotid artery stenosis with carotid sinus hypersensitivity. Transitory cerebral ischaemic attack provoked by carotid sinus reflex The association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity. Transitory cerebral ischaemic attack (TIA) will usually be manifested by activation of carotid sinus reflex. Eighteen patients were observed suffering from both carotid sinus hypersensitivity and TIA. The patients had had TIA's for many years. Unilateral internal carotid stenosis was detected in 15 cases, while 3 patients had bilateral carotid stenosis. On carotid sinus stimulation, syncope appeared and a TIA could be provoked. The mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree AV block in 4 cases. In all patients carotid artery disobliteration was performed; in 14 patients pacemaker implantation was necessary, while 4 patients could be treated by atropine medication. The development of a TIA could be abolished in every patient and 14 patients remained totally symptom free. 
5	The role of sphincteroplasty for fecal incontinence reevaluated: a prospective physiologic and functional review. Sixteen female patients (mean age 54.1 years; range 34-74 years) with a 9.8-year (range 1-25 years) history of incontinence to solid stool underwent overlapping sphincteroplasty with internal sphincter imbrication without fecal diversion. All patients were prospectively evaluated with preoperative anorectal manometry, electromyography, and pudendal nerve motor latency assessment, postoperative anorectal manometry, and preoperative and postoperative functional evaluation. Mean and maximal resting pressures increased from 30 mm Hg and 49 mm Hg preoperatively to 40 mm Hg and 57 mm Hg, respectively, postoperatively. Likewise, mean and maximal squeeze pressures increased from 27 mm Hg and 48 mm Hg preoperatively to 39 mm Hg and 73 mm Hg, respectively, postoperatively (P less than 0.01). Furthermore, anal canal high pressure zone length was increased by sphincteroplasty from a mean of 0.9 cm (range 0-3 cm) to a mean of 2.1 cm (range 1-4 cm). These objective physiologic improvements correlated well with subjective functional improvement. Subjectively, functional outcome was rated by patients as excellent in 38 percent, good in 38 percent, fair in 19 percent, and poor in only 5 percent of cases. Overlapping sphincteroplasty with internal sphincter imbrication improves both the anal sphincter physiologic profile and fecal continence. 
5	False aneurysm of the internal mammary artery. Iatrogenic false aneurysm of a branch of the internal mammary artery after sternal wire closure is a very rare occurrence. We describe a case which appeared in a 62 year old woman operated upon for mitral valve replacement and diagnosed after Digital Subtraction Angiography. 
4	Intravascular ultrasound: a new potential modality for angioplasty guidance. Current angioplasty devices are limited by significant rates of arterial perforation and dissection, due to inadequate techniques of guidance, and by restenosis, which may be partly attributed to inadequate debulking of lesions. This paper describes the authors' initial experience in-vitro and in-vivo with intravascular ultrasound as a possible method of enhancing the three-dimensional guidance of devices through atherosclerotic obstructions. Using an in-vitro model they correlated the dimensions and histologic morphology of animal and human arteries with ultrasound images of the specimens. Additional in-vivo evaluations of this technology in canine arteriosclerotic and human atherosclerotic arteries preliminarily support the hypothesis that intravascular ultrasound defines the transmural arterial morphology and may enhance the accuracy of angioplasty procedures. Simultaneous imaging with angioscopy and intravascular ultrasound is demonstrated as a potential method of accurately defining both intraluminal and transmural arterial wall characteristics. 
4	Dietary salt and blood pressure. A perspective. Although dietary salt restriction is often valuable as sole or adjunctive therapy of hypertensive disorders, it is abundantly clear that hypertensive patients comprise a heterogeneous group with regard to salt sensitivity of blood pressure. This is apparent despite the many methodological obstacles to defining salt sensitivity in an individual patient. Currently, dietary trial is the only sure means of defining a given patient as responsive to salt restriction. Easily definable markers of salt sensitivity would allow appropriate targeting of this rather ponderous therapy. Promising leads include the assessment of membrane ion transporters such as sodium-lithium exchange and of the activity of the renin-angiotensin system, including the phenomenon of "non-modulating" hypertension and other volume regulatory hormones such as atrial natriuretic factor. Although less intensively studied than in hypertensive patients, the blood pressure response of normal subjects to salt restriction is also marked by great variability. Given the possibility of deleterious consequences of population-wide salt restriction for at least some people in a setting such as the United States, it seems imprudent to recommend such a policy before its proven worth has been demonstrated by clinical trial. Pending such evidence and the development of markers, salt restriction should be reserved for those in whom it is of demonstrated efficacy. 
5	Murine mast cells synthesize basement membrane components. A potential role in early fibrosis. Mast cells are resident in tissues, particularly in association with endothelial and epithelial cell basement membranes, and increase at sites of inflammation, injury, and fibrosis. Although mast cells are known to both release and generate proinflammatory molecules in response to inflammatory stimuli, little is known about their normal biologic function. Here we demonstrate that IL-3-dependent mouse PT18 mast cells, mouse bone marrow-derived mast cells, and rat basophilic leukemia cells express large amounts of mRNA for collagen IV, laminin, and heparan sulfate proteoglycan. Western blot analysis confirmed that mast cells synthesize and secrete significant amounts collagen IV and laminin B1 and B2 chains. These data suggest that mast cells may contribute to normal tissue repair and/or the early overproduction of basement membrane components seen in a variety of fibrotic conditions. 
5	Functional upper airway obstruction in adolescents. Functional upper airway obstruction is an uncommon manifestation of a conversive reaction characterized by recurrent stridor attacks caused by adduction of the vocal cords during inspiration. The oxygen saturation never drops to pathologic levels. The stridor is not accompanied by an appropriate degree of anxiety and is not associated with other symptoms. Patients benefit from verbal reassurance and speech therapy, but stridor attacks tend to recur and psychiatric consultation seems necessary in most cases. We present the case histories of three adolescent patients with nonorganic upper airway obstruction and describe the features that may facilitate the diagnosis of this condition. Early diagnosis and intervention may prevent unnecessary and potentially harmful investigations and therapy. 
3	Relaxation training in school classes does not reduce headache complaints. The effect of teacher-presented Progressive Relaxation Training (PRT) on headaches, fear of failure and school problems was studied in school students. During ten physical education lessons, students received either PRT (n = 110) or placebo training (n = 92). The effect of the training was investigated in students who indicated the presence of headaches in a pre-training diary. No significant differences were found between both training groups regarding headache frequency, duration and intensity and the psychological variables. On the basis of these and previous findings, it is recommended to present PRT to fairly small groups of self-selected subjects instead of complete classes. 
5	Are measurements of height made by health visitors sufficiently accurate for routine screening of growth? To find out whether measurements of height made by health visitors are sufficiently accurate for use in routine screening of children we carried out an interobserver and intraobserver reliability study. Height measurements were made on a group of 10 children aged 3 years old and 10 aged 4.5 years old by two sets of four health visitors. They used a Microtoise or wall chart and the measurements were compared with those made by a trained auxologist with a Harpenden stadiometer. For a single assessment of height both pieces of equipment gave reasonably accurate results. In a child aged 3 years, with height measured on the Microtoise as 100 cm, the true height could be expected--with 95% probability--to lie between 99.2 cm-101.8 cm. At the age of 4.5 years, if the measurement was 110 cm, the child's true height could be expected to lie between 108.9 cm and 111.9 cm. The narrowest confidence interval for the growth rate from 3 to 4.5 years was achieved with the Microtoise, taking the mean of three measurements. We conclude that measurements made by health visitors are sufficiently accurate for routine screening of height, and the use of such measurements for the calculation of height velocity could be improved by more structured training. 
4	Diltiazem overdose: pharmacokinetics of diltiazem and its metabolites and effect of multiple dose charcoal therapy. We describe a 38 year-old female who ingested 900 mg of diltiazem. She experienced hypotension, bradycardia and heart block but responded well to supportive care that included normal saline infusion and vasopressors. Calcium administration was not beneficial. Serial plasma concentrations of diltiazem, N-demethyldiltiazem and desacetyldiltiazem were quantified. By comparing the elimination half-life for diltiazem with historical controls, it is concluded that multiple dose charcoal therapy was not beneficial for our patient. 
1	Cervical rotation flaps for midface resurfacing. The midface has long served as a focus for creativity in surgical reconstruction. Full-thickness skin grafts, split-thickness grafts, and distal flaps have long been used to attempt to reduplicate existing anatomy in this area. Recent reconstruction efforts have focused on the creative use of microvascular free flaps for this purpose. This article reports on the use of extensively developed regional rotation flaps as an excellent reconstructive modality for use in this area of the face. The details of surgical incisional planning are given. The nuances of surgical creation of these flaps and their rotation and suspension into place are given. The cases we have done using this technique for the past 3 years are reviewed. Our present indications for use of these flaps and their limitations are given. 
4	Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: an operator-blind echo-Doppler study. In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity. 
5	Total hip arthroplasty with cement. A long-term radiographic analysis in patients who are older than fifty and younger than fifty years. The long-term performance of a total of 712 Charnley and STH prostheses was evaluated as a function of the patient's age (older than fifty years or younger than fifty years) and of the underlying disease (osteoarthrosis, rheumatoid arthritis, or avascular necrosis). In patients who were older than fifty years, there were lower incidences of continuous cement-bone radiolucency about the acetabular component (p = 0.04), wear of the polyethylene acetabular cup (p = 0.03), and resorption of the calcar (p = 0.03). However, larger percentages of younger patients had rheumatoid arthritis or avascular necrosis. In the cohort of patients who had osteoarthrosis, the performance of the prosthesis did not differ significantly between older and younger patients; therefore we attributed the differences that were observed to the disease--that is, to rheumatoid arthritis or avascular necrosis. 
3	Atrial fibrillation after stroke in the elderly. To examine the relationship between atrial fibrillation and mortality after stroke, we studied 186 men and 167 women from the Waikato Stroke Registry whose mean age was 75.2 +/- 7.5 years. Twenty-three percent (82 of 353) had atrial fibrillation or flutter on their admission electrocardiogram. This group differed significantly from that with sinus rhythm in three respects: 1) They were older (p less than 0.01); 2) they had more severe current stroke deficit as evidenced by lower limb power (p less than 0.05) and Mini-Mental State Score (p less than 0.001), higher incidence of homonomous hemianopia (p less than 0.05), and lower incidence of lacunar syndrome stroke (p less than 0.001); and 3) they had a significantly higher incidence of cardiomegaly and congestive heart failure (p less than 0.01). Functional outcome was insignificantly better in the group with sinus rhythm. During a mean follow-up period of 18 months, mortality was significantly higher in the group with atrial fibrillation (p = 0.001). Proportional hazards modeling, however, showed that the apparently poorer survival in those patients with atrial fibrillation could be explained by factors other than cardiac rhythm, such as age, Mini-Mental State Score, level of consciousness, and interstitial edema on admission chest radiograph. Thus, atrial fibrillation was not an independent predictor of survival after stroke. 
3	Sudden blindness after thermocoagulation of the trigeminal ganglion. Sudden blindness during percutaneous thermocoagulation of the gasserian ganglion occurred in a 72-year-old woman with trigeminal neuralgia. Considered a safe procedure, we highlight the possibility of this serious complication which was probably due to direct damage of the optic nerve. 
4	Clinical significance of simple heart rate-adjusted ST segment depression in supine leg exercise in the diagnosis of coronary artery disease. To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease. 
1	Elderly men with histories of heavy drinking: correlates and consequences. Recognition that the physical, psychological and social consequences of substance abuse may persist throughout the life span has led to increased study of the impact of lifetime drinking habits on the elderly. We examined the characteristics of elderly men with self-reported histories of having ever been heavy drinker (H+) in a population-based (N = 1,155, mean age = 73.7 years) longitudinal survey of community-dwelling elders; 10.4% of the men reported that they had been heavy drinkers at some time during their lives. H+ men were younger and less educated than non-heavy drinkers (H-) or never drinkers (N). Mortality was higher among H+ men who were current drinkers than among H- or N men. H+ men reported more major illnesses, poorer self-perceived health status, more physician visits, more depressive symptoms, lower levels of life satisfaction and smaller social networks than did H- or N men. Self-reported ability to perform activities of daily living and instrumental activities of daily living was poorest among H+ men, who also scored the lowest on a mental status examination. Thus, a history of having ever been a heavy drinker is predictive of widespread impairments in physical, psychological and social health and functioning among elderly men. 
4	Plasma homocyst(e)ine levels in men with premature coronary artery disease. Plasma homocyst(e)ine (that is, the sum of free and bound homocysteine and its oxidized forms, homocystine and homocysteine-cysteine mixed disulfide) levels were determined in 170 men (mean age +/- SD 50 +/- 7 years) with premature coronary artery disease diagnosed at coronary angiography and in 255 control subjects clinically free of coronary artery disease (mean age 49 +/- 6 years). Patients with coronary artery disease had a higher homocyst(e)ine level than control subjects (13.66 +/- 6.44 versus 10.93 +/- 4.92 nmol/ml, p less than 0.001). High density lipoprotein (HDL) cholesterol levels were lower (32 +/- 10 versus 46 +/- 13 mg/dl, p less than 0.001) and triglycerides levels were higher (193 +/- 103 versus 136 +/- 106 mg/dl, p less than 0.001) in the coronary disease group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels were not significantly different between patients with coronary disease and control subjects. The presence of hypertension, smoking or diabetes mellitus did not significantly alter homocyst(e)ine levels in the patient or the control group. Patients who were not taking a beta-adrenergic blocking drug (n = 70) had a nonsignificantly higher homocyst(e)ine level than did patients taking this class of drugs (n = 100) (14.67 +/- 8.92 versus 12.95 +/- 3.77 nmol/ml, p = 0.087). By design, none of the control subjects were taking a beta-blocker. No significant correlations were observed between homocyst(e)ine and age, serum cholesterol, LDL cholesterol, HDL cholesterol or triglyceride levels. It is concluded that an elevated plasma homocyst(e)ine level is an independent risk factor for the development of premature coronary atherosclerosis in men. 
5	Musculoskeletal abnormalities in a patient with juvenile hypothyroidism. Abnormalities in growth and development are the most striking clinical features of juvenile acquired hypothyroidism. Therefore, physicians should consider the diagnosis of hypothyroidism in any child with musculoskeletal growth dysfunction. Drs Kilpatrick and Fincher describe a case demonstrating the severe and potentially irreversible effects of prolonged, untreated hypothyroidism. 
4	Blood pressure response to dietary calcium intervention in humans. Epidemiological and experimental studies have suggested that dietary calcium deficiency may lead to the development of hypertension. This article reviews findings in human trials on calcium intervention with special reference to the responses of blood pressure and biochemical variables. Calcium supplementation consistently resulted in decreased blood pressure in a subset of hypertensive and normotensive subjects, but led to increased blood pressure in some hypertensive patients. The variable blood pressure responses to calcium supplementation could not be predicted on the basis of routine biochemical parameters and appeared to be due to differences in the backgrounds of the subjects and/or the design and size of the trials. It is concluded that further studies are required on the hypotensive effect of calcium supplementation. 
3	Articulatory impairment associated with tardive dyskinesia. The speech of two patients with tardive dyskinesia was studied, and one neuroleptic-treated patient having no signs of overt tardive dyskinesia served as control. A structured interview, including reading, repetition of sentences, and spontaneous conversation, was performed. A phonetic transcription and analysis of abnormal phonemes was done by a linguist under blind conditions. Both patients with tardive dyskinesia had abnormal phonemes whereas the control patient had none. These differences could not be explained by age, direct neuroleptic effect, or neuroleptic exposure time. The abnormal phonemes were all consonants. The authors conclude that tardive dyskinesia may cause articulatory communication problems. 
5	Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure. Ten patients with parenchymal acute respiratory failure (ARF) underwent computed tomography (CT) scans while in the supine and prone positions. At equal levels of positive end-expiratory pressure, the authors measured the changes of CT density in dorsal and ventral basilar lung regions induced by the change of position as well as alterations of gas exchange. The level of venous admixture did not change with body position. The CT scan image of each lung was fractionated into ten levels from dorsal to ventral, each constituting 10% of the lung height. After measuring each lung fraction, the volume, the average CT number, its frequency distribution, and the expected normal value, we computed the lung tissue mass, the excess tissue mass, and the fraction of normally inflated tissue (excess tissue mass = amount of "tissue," which includes edema, cells, and blood in excess of the expected normal value). We also estimated the superimposed hydrostatic pressure on each lung region. We found that the excess lung tissue mass is independent of position. However, in patients in the supine position, lung CT density increased and regional inflation decreased from ventral to dorsal, suggesting progressive deflation of gas-containing alveoli along the gravity gradient. A similar ventral-dorsal deflation pattern occurred within 10 min in patients in the prone position. We conclude that the lung in patients with ARF behaves like an elastic body with a diffusely increased mass; dependent lung regions are compressed by the pressure of overlying structures. 
5	Role of cell-mediated immunity to staphylococci in blepharitis. We studied cell-mediated immunity to staphylococcal antigens in 116 patients with chronic blepharitis and eight normal subjects. Antibodies in tears and blood were measured. Enhanced cell-mediated immunity to Staphylococcus aureus was demonstrated in 46 of 116 patients (40%) in the absence of antibodies to teichoic acid but not among normal subjects. Symptoms of grittiness and morning stickiness were more frequent among patients without enhanced responses. Folliculitis occurred more commonly among patients with enhanced immunity. Marginal keratitis occurred equally among patients with and without enhanced systemic immunity, but patients with enhanced response more commonly required topical corticosteroid therapy. Desensitization to staphylococcal antigens could be investigated as a potential therapeutic approach in selected patients. 
5	Afferent nipple valve malfunction caused by anchoring collar: an unexpected late complication of the Kock continent ileal reservoir. In the construction of a Kock continent ileal reservoir for urinary diversion, significantly high rates of late postoperative complications regarding nipple valves, the efferent limb in particular, have been reported. There are only a few reports on afferent nipple valve malfunction. A total of 42 patients who underwent a Kock pouch operation and were observed for more than 12 months (mean 38 months) was evaluated in terms of afferent nipple valve malfunction. Late afferent nipple valve complications were observed in 10 of the 42 patients (24%). These complications included erosion of the polyester fiber fabric used as a collar (5 patients), stenosis of the afferent limb (2) and obstruction of the afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications were due to mechanical or dynamic obstruction of urine flow caused by a nonabsorbable collar. None of the 10 patients had problems with efferent nipple valve function. Our results suggest that the peristaltic direction of the intestine and the use of nonabsorbable material as a collar are primarily responsible for the late afferent nipple valve complications. Further modifications are needed to produce a stable nipple valve. Otherwise, simpler and more reliable alternative techniques of antireflux anastomosis should be considered. 
1	Decalcification of a choroidal osteoma. A 56-year-old man presented with a clearly defined orange tumour in the posterior pole of his left eye. A choroidal osteoma was suspected, and ultrasonography confirmed the diagnosis. Fluorescein angiography demonstrated subretinal neovascularisation on the nasal edge of the tumour, which was treated with krypton laser photocoagulation twice. Recurrent subretinal neovascularisation occurred one year later and was not amenable to treatment. Three years after the patient first presented, thinning of the tumour was noted on follow-up examination. During the next 15 months the tumour completely disappeared, leaving an area of retinal pigment epithelial and choroidal atrophy. Total decalcification of the choroidal osteoma was demonstrated by ultrasonography. 
5	Ultrastructural evidence of the effects of shear stress variation on intimal thickening in dogs with arterially transplanted autologous vein grafts. Based on our findings that changes in wall shear stress, not the rate of blood flow, were the main hemodynamic factor related to intimal hyperplasia of autologous vein grafts, we further investigated the effect of wall shear stress variation on sequential ultrastructural changes in the intimal hyperplasia of arterially transplanted autovein grafts, using canine models. As noted, wall shear stress variation (tau-variation) could be defined by the variation in wall shear stress within a cardiac cycle, using a desktop flow waveform analyzer. In Group I, which had a high flow rate of 78.4 +/- 4.6 ml/min and low tau-variation of 36.1 +/- 2.2 dynes/cm2, intimal hyperplasia was significant. Ultrastructurally, there was a marked transformation of intimal smooth muscle cells to secretory cells 2 to 4 weeks after implantation. The surface of the intima was lined with modified smooth muscle cells at 2 weeks after implantation. In Group II, which had a low flow rate of 5.6 +/- 2.2 ml/min and normal tau-variation value (174.6 +/- 13.0 dynes/cm2), intimal hyperplasia was minimal, and there were several layers of contractile type smooth muscle cells, with characteristic myofibrillae. The surface of the intima was lined with endothelial cells at 2 weeks after implantation. These findings suggest that, in regions of low wall shear stress variation, intimal smooth muscle cells of autovein grafts may well become secretory cells, and enhanced platelet adherence could occur during early intimal repair, causing intimal hyperplasia to develop. 
4	Cardiac tamponade and contralateral hemothorax after subclavian vein catheterization. A patient developed life-threatening cardiac tamponade and contralateral hemothorax after insertion of a subclavian catheter in the operating room. Contrast was infused through the catheter, demonstrating its malposition in the pericardial space. Contrast infusion was valuable in evaluating this complication of central line placement. 
4	Effect of naproxen and sulindac on blood pressure response to atenolol. Twenty-eight patients with mild to moderate essential hypertension well controlled by atenolol entered a five-week, double-blind, placebo-controlled trial of the effects of sulindac and naproxen on blood pressure (BP) control. Atenolol alone was administered during weeks 1, 3, and 5. Naproxen or sulindac was administered with atenolol during week 2, with crossover during week 4. Data were analyzed for 27 of the patients (one dropped out after developing a skin rash). Naproxen significantly increased the systolic BP compared with placebo (mean 4.0 mm Hg; 95 percent confidence interval, 1.1-7.0; p less than 0.05). There were no significant differences in systolic BP during sulindac administration compared with placebo or naproxen. No significant effects on diastolic BP were observed. Weight was increased by naproxen and sulindac compared with placebo (mean 0.6-0.8 kg, p less than 0.05), although not to a clinically significant extent. One-week therapy with naproxen has a greater potential than sulindac to increase systolic BP in well-controlled hypertensive patients receiving atenolol; however, the increase is minor and unlikely to be of clinical significance. 
4	Inhibitory role of the coronary arterial endothelium to alpha-adrenergic stimulation in experimental heart failure. The role of the endothelium in regulating coronary alpha-adrenergic tone was evaluated in isolated coronary arterial rings from dogs with and without pacing-induced congestive heart failure (CHF). The maximal contractile response to methoxamine was attenuated approximately 43% (p less than 0.05) in both intact and denuded CHF rings compared with control. Conversely, norepinephrine-induced contractions were diminished 58% in intact CHF vessels and 39% in denuded CHF vessels (p less than 0.05). Denudation did not alter responses to methoxamine but significantly (p less than 0.05) augmented the tension generated by norepinephrine in both control (1.7-fold) and CHF (2.4-fold) arteries. In both intact control and CHF coronary arteries, norepinephrine elicited rapid, transient relaxations that preceded slow, sustained contractions; the initial relaxation phase was endothelium dependent, because denudation eliminated the response. Relaxations to the selective alpha 2-adrenoceptor agonist BHT 920 were also dependent on the presence of an endothelium. At peak CHF, endothelium-dependent relaxations to norepinephrine and BHT 920 were enhanced, whereas relaxations to nitroglycerin and acetylcholine were unaltered. The data suggest that alpha-adrenergic tone in canine coronary arteries is diminished by pacing-induced CHF because of a decrease in alpha 1-adrenoceptor-mediated constriction and an enhanced capacity of the endothelium to antagonize the direct vascular smooth muscle response of norepinephrine through endothelium-dependent, alpha 2-adrenoceptor-mediated relaxations. 
5	Ultrastructural demonstration of peroxidase expression in acute unclassified leukemias: correlation to immunophenotype and treatment outcome. The lineage affinity of 57 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping and analysis of immunoglobulin gene configuration. Twenty-three cases of myeloid and three cases of megakaryocytic differentiation were identified by detection of ultrastructural myeloperoxidase (UMPO) and platelet peroxidase (UPPO). No significant correlation was noted between myeloid marker expression and POEM positivity, whereas presence of CD 19 or CD 24 antigen significantly correlated with POEM negativity (P = .001 and .023, respectively). Ig gene rearrangements including oligoclonal patterns were also recorded in 8 of 14 UMPO+ patients tested. Fourteen UMPO+ patients responded poorly to an ALL/AUL chemotherapy regimen with a low complete remission (CR) rate of 29% and a short median remission duration (MRD) of 5 months. The POEM- patients proved very heterogenous with respect to immunophenotype and Ig gene rearrangement. Seventeen of 21 patients tested had Ig gene rearrangements, including oligoclonal patterns. Combined data suggest that a proportion of these cases probably derive from a very immature lymphoid progenitor cell, particularly because 15 POEM- AUL patients showed a response to ALL/AUL chemotherapy comparable to that observed in patients with definitive acute lymphoblastic leukemia (ALL) (CR rate 80%, MRD 20 months). Thus, ultrastructural analysis of peroxidase expression can provide decisive prognostic information in AUL patients. 
5	Fluorosilicone oil in the treatment of retinal detachment. We evaluated the use of a heavier-than-water fluorinated silicone oil in the treatment of 30 selected cases of complicated retinal detachment from January 1988 to July 1989. Proliferative vitreoretinopathy grade C-2 or greater accounted for 19 cases, proliferative diabetic retinopathy with traction detachment for two cases, giant retinal tears five, ruptured globe with retinal detachment two, massive choroidal effusion with retinal detachment one, and acute retinal necrosis with retinal detachment one. Initial retinal reattachment was achieved in all cases. Complications included redetachment seven (23%), cataract six (75% of phakic patients), raised intraocular pressure four (13%), hypotony four (13%), keratopathy three (10%), uveitis-synechia formation three (10%), phthisis two (3%), choroidal haemorrhage one (3%), and vitreous haemorrhage one (3%). Postoperative visual acuities with at least six months' follow-up range from no light perception to 20/50, with seven patients (23%) 20/400 or better. 
1	Oral manifestations of HIV infection and their management. II. Less common lesions. This second of two articles reviews the many uncommon and rare oral lesions that have arisen in persons infected with human immunodeficiency virus (HIV). The various drug-related oral disorders of HIV disease are also considered. 
4	Incidence of myocarditis. A 10-year autopsy study from Malmo, Sweden. Although myocarditis has been known for almost two centuries, data in regard to its incidence have varied widely. Autopsy studies have reported an incidence of 3.5% to as high as 10%. The main reason for such diversity of data appears to be the lack of unanimity as to what constitutes myocarditis. Recently, definitions of myocarditis have been proposed and precise criteria for the morphologic recognition of myocarditis have been published. In this study an analysis of 12,747 consecutive autopsies performed from 1975 to 1984 at Malmo (Sweden) General Hospital was carried out. Applying the newly proposed histologic criteria, the diagnosis of myocarditis was made in 136 cases, which constitute 1.06% of the autopsy population studied. This rate of myocarditis incidence at postmortem is lower by far than rates previously published. 
5	Multivessel coronary angioplasty from 1980 to 1989: procedural results and long-term outcome From June 1980 to January 1989, 3,186 patients had coronary angioplasty of two (2,399 patients) or three (787 patients) of the three major epicardial coronary systems. A mean of 3.6 lesions (range 2 to 14) were dilated per patient, with a 96% success rate. Acute complications were seen in 94 patients (2.9%) and included Q wave infarction in 47 (1.4%), urgent coronary artery bypass surgery in 33 (1%) and death in 31 (1%). Multivariate correlates of in-hospital death included impaired left ventricular function, age greater than or equal to 70 years and female gender. Complete long-term follow-up data were available for the first 700 patients and the follow-up period averaged 54 +/- 15 months in duration. Actuarial 1 and 5 year survival rates were 97% and 88%, respectively, and were not different in patients with two or three vessel disease. By Cox regression analysis, age greater than or equal to 70 years, left ventricular ejection fraction less than or equal to 40% and prior coronary artery bypass surgery were associated with an increased mortality rate during the follow-up period. Repeat revascularization procedures were required in 322 patients (46%). Restenosis resulted in either repeat angioplasty or bypass surgery in 227 patients (32%). Repeat coronary angioplasty was performed for isolated restenosis in 126 patients (18%), for restenosis and disease progression at new sites in 85 patients (12%) and for new disease progression alone in 54 patients (8%). Coronary bypass surgery was required in 110 patients (16%) during the follow-up period. 
5	Pulmonary tolerance of prophylactic aerosolized pentamidine in human immunodeficiency virus-infected patients. The effects of primary and secondary long-term prophylaxis of Pneumocystis carinii pneumonia with aerosolized pentamidine on pulmonary function in HIV+ patients were evaluated. Eighty-one patients, none of whom were drug addicts or had pulmonary Kaposi's sarcoma, were studied. Fifty patients were receiving AP as secondary prophylaxis, 36 monthly and 14 twice-monthly; eight patients with a history of PCP served as control subjects. Twenty-three patients were receiving AP as primary prophylaxis, 12 monthly and 11 twice-monthly. Pulmonary function tests, including spirometry, lung transfer capacity for carbon monoxide (Tlco) and alveolar-arterial oxygen gradient (P[A-a]O2) were evaluated at M1, ie, one month after the diagnosis of PCP, or at the beginning of the AP prophylaxis, and then at three-month intervals (M4 to M13). No differences were observed in the results of spirometry or P(A-a)O2. Among the patients receiving secondary prophylaxis, a significant increase (paired Student's t-test) in Tlco occurred at M7 compared to M1 in the group receiving monthly administrations (p less than 0.01) and in the untreated control group (p less than 0.05); there was no significant difference in Tlco at M13 compared to M1 in the 12 patients who received monthly administrations for this period or at M7 in the 14 patients receiving AP twice-monthly. No significant difference in Tlco was observed at M7 in the primary prophylaxis groups. These results indicate that pulmonary tolerance of AP, as reflected by pulmonary function tests, is good. 
2	Modified Kraske approach for disease of the mid-rectum. A modification of Dr. Paul Kraske's approach for removal of mid-rectal lesions has been used in 11 patients from 1977 to 1988 by the senior authors. Patients ranged in age from 56 to 89 yr, with an average of 67 yr. There were seven male and four female patients. Indications for surgery were as follows: villous adenoma (seven), carcinoid (one), recurrent dysplasia in a previous endoscopic polypectomy site (one), positive distal margin for neoplasm following low anterior sigmoid resection (one), and adenocarcinoma in one elderly poor-risk patient. All lesions were in the middle rectum (7-11 cm from the anal verge, average 9 cm). The postoperative stay ranged from 6 to 12 days with a mean of 8 days. The average follow-up for the 11 patients is 3 1/2 yr (1 month to 7 yr), with only one patient having a local recurrent lesion. There was no morbidity or mortality. We conclude that this modification of the Kraske approach offers a good alternative for excision of mid-rectal lesions in terms of technical ease, efficacy, safety, and patient tolerance. The modified Kraske approach is indicated in certain situations and should be a part of the surgeon's armamentarium. 
3	Striatonigral degeneration. A clinicopathological study. The clinical and pathological features of 10 cases of striatonigral degeneration are described: 5 were misdiagnosed in life as Parkinson's disease. Retrospectively, helpful early pointers to the diagnosis in these cases included unexplained falls, autonomic dysfunction, absence of rest tremor and failure to respond to L-dopa, but these were not always present. The pathological diagnosis could not be excluded on macroscopic examination of the striatum. Relative preservation of the putamen occurred in the 4 patients who benefited from L-dopa. The caudate nucleus was involved in all cases and there was no sparing of the large striatal neurons. In mild cases, involvement of the putamen was confined to its posterior two-thirds, dorsolaterally. With increasing severity this extended in a dorsal to ventral and posterior to anterior direction. Seven of the cases had evidence of olivopontocerebellar damage, but only 2 of these had clinical evidence of cerebellar disease. Correlation was found between the neuronal counts in caudate:putamen, striatum:nigra compacta, globus pallidus:nigra compacta, nigra compacta:locus coeruleus. The most severely involved part of the substantia nigra pars compacta was the ventrolateral zone, which projects to the dorsal putamen, the earliest site of striatal disease. 
4	Arterial blood pressure. Correlation with erythrocyte count, hematocrit, and hemoglobin concentration. The relationship between arterial blood pressure and red blood cell variables was investigated in 1013 unselected persons with a blood pressure range of 90 to 225 mm Hg systolic and 50 to 145 mm Hg diastolic. Statistically significant correlations were demonstrated between mean (as well as systolic and diastolic) arterial blood pressure and red blood cell count (r = 0.27; P less than .0001), hematocrit (r = 0.28; P less than .0001), and hemoglobin concentration (r = 0.29; P less than .0001). Average arterial blood pressure was higher in men than in women (133 +/- 16/83 +/- 10 v 124 +/- 16/79 +/- 9 mm Hg, P less than .0001) and this was associated with higher values for erythrocyte count, hemoglobin concentration, and hematocrit in men as compared to women. The significant correlation of blood pressure and hematocrit, which represents one important determinant of blood viscosity, points to a role for rheological factors in the long-term control of blood pressure. Moreover, it might be speculated that the sex difference in blood pressure as observed in the present study may be due, at least in part, to stimulated erythropoiesis in men as compared to women. 
1	Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2. 
4	Morphologic comparison of patients with mitral valve prolapse who died suddenly with patients who died from severe valvular dysfunction or other conditions. Clinical and necropsy findings are described in 56 patients with mitral valve prolapse: 15 patients, aged 16 to 69 years (mean 39), died suddenly and mitral valve prolapse was the only cardiac condition found at necropsy (hereafter called isolated mitral valve prolapse); the remaining 41 patients had other conditions that were capable of being fatal. Of the latter 41 patients, 7, aged 17 to 59 years (mean 45), had associated congenital heart disease, and 34 patients, aged 17 to 70 years (mean 52), had no associated congenital cardiac abnormalities. Compared with the 34 patients without associated congenital heart disease and with nonmitral valve prolapse conditions capable in themselves of being fatal, the 15 patients who died suddenly with isolated mitral valve prolapse were younger (mean age 39 +/- 17 versus 52 +/- 15 years; p = 0.01), more often women (67% versus 26%; p = 0.008) and had a lower frequency of mitral regurgitation (7% versus 38%; p = 0.02). The 15 patients dying suddenly with isolated mitral valve prolapse also were less likely to have evidence of ruptured chordae tendineae (29% versus 67%; p = 0.04). The frequency of increased heart weight (67% versus 59%), a dilated mitral valve anulus (80% versus 81%), a dilated tricuspid valve anulus (17% versus 17%), an elongated anterior mitral leaflet (86% versus 54%), an elongated posterior mitral leaflet (79% versus 77%) and fibrous endocardial plaque under the posterior mitral leaflet (73% versus 63%) was similar between the two groups. The severity of the prolapse (mild 20% versus 11%; moderate 27% versus 58%; severe 53% versus 32%) also was similar between the two groups. Thus, persons with mitral valve prolapse dying suddenly without another recognized condition tend to be relatively young women without mitral regurgitation. 
1	Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women [published erratum appears in JAMA 1991 Apr 10;265(14):1828] We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years since last [corrected] use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk. 
5	The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity. The purpose of this study was to (1) evaluate the relative cost effectiveness of the central venous pressure and flow-directed pulmonary artery catheters used to maintain normal hemodynamic values as therapeutic goals in the control groups vs supranormal values empirically observed in critically ill postoperative survivors in the protocol groups, and (2) to evaluate tissue perfusion and oxygenation in relationship to organ failure and mortality. In two prospective clinical trials there were no significant differences in outcome between the central venous pressure and pulmonary artery control groups that used normal values as therapeutic goals. However, there were marked and significant reductions in morbidity and mortality of the protocol groups using the supranormal cardiac index, oxygen delivery, and oxygen consumption values as goals. The cumulative oxygen debt was less and organ failures were fewer and less severe in the protocol groups than in the control groups. 
4	Hypertension during pregnancy in insulin-dependent diabetic women. Insulin-dependent diabetic patients are at increased risk for hypertensive disorders of pregnancy. This study was designed to study prospectively the rate of pregnancy-induced hypertension (PIH) in 175 insulin-dependent diabetic pregnancies (88 White classes B-C, 87 classes D-RT). Pregnancy-induced hypertension was defined as two or more occurrences after 20 weeks' gestation of a mean arterial pressure (MAP) of 105 mmHg or greater or an increase of 20 mmHg or greater from the baseline MAP. The rate of PIH in the diabetic population was 15.4% and was significantly associated with nulliparity, poor glycemic control in the first and second trimesters, and advanced White class. Neonatal outcome was not significantly altered in the presence of PIH. We speculate that improved glycemic control throughout pregnancy might reduce the rate of this complication in diabetic patients. 
5	Ileal duplication cyst causing massive bleeding in a child. Intestinal duplication is a rare congenital anomaly; nonetheless, it comprises more than half of all alimentary duplication disorders. Our case report describes the hemorrhagic sequelae of this entity with surgical and pathologic findings. A review of anatomical classification, embryology, and natural history of duplication cyst follows; differentiating characteristics of duplication cyst versus Meckel's diverticulum are outlined. Intestinal duplication cyst should be considered in the differential diagnosis of GI bleeding, especially in children. 
3	Disturbances in the cerebral perfusion of human immune deficiency virus-1 seropositive asymptomatic subjects: a quantitative tomography study of 18 cases. Quantitative measurements of cerebral blood flow (CBF) by xenon-133 (133Xe) tomography, together with magnetic resonance imaging (MRI), electroencephalography (EEG), psychometric tests, and laboratory analyses were performed on 18 human immunodeficiency virus 1 (HIV-1) seropositive asymptomatic subjects. Abnormalities of cerebral perfusion were observed in 16 cases (88%). These abnormalities were particularly frequent in the frontal regions (77% of cases). MRI demonstrated leucoencephalopathy in only two cases. EEG showed only induced diffuse abnormalities in two cases. Psychometric tests showed restricted moderate disturbances in 55% of patients. These disturbances mostly concerned those sectors involved in cognitive functions and memorization. These results indicate that quantitative measurements of CBF by 133Xe-SPECT is capable of detecting abnormalities of cerebral perfusion at a very early stage (Phase II) of HIV-1 infection. These abnormalities are indications of disturbances resulting from unidentified metabolic or vascular lesions. This technique appears to be superior to MRI at this stage of the disease's development. It could provide objective information leading to earlier treatment, and prove useful in evaluating potential antiviral chemotherapy. 
5	Local failure and related complications after definitive treatment of carcinoma of the prostate by irradiation or surgery. The authors review their institution's experience with the failure of definitive treatment to achieve local tumor control and with the distant dissemination and local morbidity associated with such failure. The causes of local failure are various: incomplete resection, implantation of spilled cells, and, possibly, selective implantation of circulating tumor cells in traumatized tissues after surgery and totally or partially resistant cells, new tumors, or radiologic misses after radiation. Treatment of local failure may be prophylactic or therapeutic and differs depending on the stage of the disease. Failure to control the tumor locally in the presence of distant metastases does not alter the length of survival, but it can profoundly affect the quality of survival. 
5	Recurrent wheezy bronchitis and viral respiratory infections Fifty four patients aged from 1 to 6 years who had had recurrent attacks of wheezy bronchitis were prospectively followed up for three months to find out if there was an association between different viral respiratory infections and episodes of wheezing. Of the 115 episodes of upper or lower respiratory tract symptoms, virus or Mycoplasma pneumoniae infection were diagnosed in 52 (45%). Thirty four of rhinoviruses. The patients had an average of 2.1 episodes of respiratory tract symptoms the total mean (SD) duration of which was 30 (2) days of the 92 days that followed. Wheezing occurred during 76 (66%) of the 115 episodes and during a third of these the patient was admitted to hospital because of severe dyspnoea. Wheezing started a mean (SD) of 43 (7) hours after the first symptoms of respiratory infection and persisted for 3.8 (4.2) days in patients in whom virus infection was diagnosed. The incidence of wheezing was not associated with IgE mediated atopy, with positive virological tests, or with fever during virus infection, but was associated with parental smoking and more than one sibling. 
5	A community-based study of acute respiratory tract infections in children in Uruguay. Acute respiratory tract infection (ARI) was investigated in children less than 5 years old in a longitudinal community-based study of 166 families living in a socioeconomically depressed area in Montevideo, Uruguay. Pediatricians made home visits every 10 days from May 1985 to December 1987, and symptoms and signs of ARI were recorded. The incidence of ARI was 5.8 episodes per child-year during the first 12 months of life and decreased with increasing age of the index children; the rate was highest in children 1-5 months old. Children observed from birth were ill during 21% of the visits. According to the definitions of the study, the incidence of lower respiratory tract infection was 11.6% higher than the incidence of upper respiratory tract infections. The rates of ARI were higher during the colder months. Most risk factors for ARI were only marginally statistically significant. 
1	Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth. We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL. 
4	Case-control study of coronary heart disease risk factors in the elderly. We undertook a case-control study utilizing a large coronary arteriography database to determine if traditional cardiovascular risk factors are as predictive of the presence of angiographically-proven coronary artery disease (CAD) in elderly patients as in younger patients. Among the patients aged 65 years or more, there were 2120 cases and 193 controls, while for the patients aged 35-49 years there were 1493 cases and 707 controls. Odds ratios obtained from logistic regression indicated that age, male sex, diabetes, cigarette smoking, hypertension, total cholesterol and left ventricular hypertrophy were all significant risk factors for CAD in both age groups, although the odds ratios tended to be somewhat lower in the elderly. Logistic regression analysis for gender subgroups generally revealed similar findings when compared with the combined (males + females) age groups, although power was limited for the subgroup of elderly males which had few controls. We conclude that most of the traditional cardiovascular risk factors which have been described as correlated with the presence of CAD in younger populations are also correlated with angiographically-proven CAD in older patients. 
1	Effect of morphine on growth of metastatic colon cancer in vivo. Control of colon cancer depends, in part, on intact immune defense mechanisms. Since opiates are known to affect some components of immune function, this study was conducted to determine the effect of high-dose subcutaneous morphine sulfate and of low-dose intrathecal morphine on the postoperative growth of metastatic colon cancer. Five groups of 15 Fischer 344 rats were given intraportal injections of colon cancer cells as follows: group 1, control; group 2, daily subcutaneous injections of 20-mg/kg morphine the day before and for 2 days after colon cancer cell inoculation; group 3, daily subcutaneous injections of saline; group 4, daily intrathecal injections of 20 micrograms of morphine; and group 5, daily intrathecal injections of saline. There was a significant decrease in the hepatic tumor burden in group 2 compared with groups 1 and 3 and a significant increase in the hepatic tumor burden in groups 4 and 5 compared with group 1. This study demonstrates that intermittent injections of a narcotic may decrease the growth of tumor cells that gain access to the circulation during a surgical procedure. In addition, the results support the concept that tumor cells entering the circulation during a vulnerable period of postoperative immunosuppression are more likely to survive as metastatic tumor. 
2	Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum. Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia. Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity. This has been demonstrated in uremic children treated with aluminum-containing antacids. The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use. Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids. The study patients consumed 123 +/- 16 mg/kg per day (mean +/- SEM) of elemental aluminum for an average of 4.7 weeks. Their plasma aluminum level (37.2 +/- 7.13 micrograms/L) was significantly greater than that of the control group (4.13 +/- 0.66 micrograms/L) (P less than .005). It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids. The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level. 
3	Intrapartum, intranasal cocaine use and acute fetal distress. A case report. Intrapartum, intranasal cocaine was used for relief of labor pains by a healthy woman with an uncomplicated pregnancy. Fetal hypoxemia and distress followed the event. A causal relationship between the intrapartum use of cocaine and the fetal distress was postulated. Cocaine abusers could benefit from hospitalization early in labor for close surveillance and monitoring, thus avoiding exposure to cocaine and its unpredictable systemic effects. 
5	Hypocalcemia and hypercalcitoninemia in critically ill children. To study Ca metabolism in critically ill children, we measured ionized Ca (Ca2+), parathyroid hormone (PTH), calcitonin, 25 hydroxycholecalciferol (25[OH] D3), 1-25 dihydroxycholecalciferol (1-25[OH]2D3, and gastrin levels in critically ill children and in healthy controls. Patients were considered hypocalcemic if Ca2+ was less than 1.1 mmol/L. Six (14%) of 45 patients were hypocalcemic. Five hypocalcemic patients were studied and were found to have higher calcitonin levels than normocalcemic patients and healthy controls and higher PTH levels than healthy controls. 25(OH)D3 and 1-25(OH)2D3 were not significantly different in the three groups of patients. Gastrin levels were low in critically ill patients, whether or not they were hypocalcemic. We conclude that hypocalcemia occurs frequently in critically ill children. It is associated with raised levels of calcitonin and PTH. The mechanism for the increase in calcitonin is unknown. 
5	Thromboxane A2 biosynthesis in acute asthma and after antigen challenge. Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has been implicated in airway inflammation and in the genesis of bronchial hyperresponsiveness in asthma. We have examined the urinary excretion of a variety of products derived from thromboxane A2 (thromboxane B2, 2,3-dinor, and 11-dehydro-thromboxane B2) and prostacyclin (6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha) using gas chromatography-mass spectrometry in patients admitted acutely to hospital with severe asthma and in atopic volunteers after bronchial antigen challenge. Urinary excretion of all thromboxane-derived products was markedly increased in a number of patients with severe acute asthma compared with that in a nonsmoking control population, in some cases approaching those previously described in myocardial infarction: TXB2, 31.6 +/- 12.0 versus 6.5 +/- 0.9; 2,3-dinor-TXB2, 79.0 +/- 19.2 versus 29.5 +/- 2.7; and 11-dehydro-TXB2, 234.3 +/- 65.3 versus 25.0 +/- 2.1 ng/mmol creatinine (p less than 0.001). Urinary prostacyclin-derived products were also significantly raised in acute asthma. In contrast, after inhaled allergen challenge in atopic volunteers, which caused significant bronchoconstriction, urinary excretion of thromboxane-derived products was not significantly elevated: TXB2, 5.6 +/- 1.1 versus 5.7 +/- 1.0; 2,3-dinor-TXB2, 41.2 +/- 12.5 versus 28.5 +/- 6.9; and 11-dehydro-TXB2, 69.8 +/- 17.6 versus 39.7 +/- 11.2 ng/mmol creatinine. In a separate experiment, less than 2% of exogenously administered TXB2 to the airway appeared as urinary thromboxane-derived products, suggesting that production of greater than or equal to 1 microgram of TXA2 in vivo would be required to increase urinary thromboxane excretion twofold. 
5	Cerebral atrophy in habitual cocaine abusers: a planimetric CT study. We compared cranial CTs of 35 habitual cocaine abusers, 16 self-reported 1st-time users, and 54 headache patients using linear planimetric measures. All patients met the following criteria: age 20 to 40 years, no polydrug abuse (including alcohol), HIV seronegativity, normal albumin level, and no history of any other neurologic disease. The sex ratios and ages were not significantly different in the 3 groups. The planimetric measurements and calculated indices of cerebral atrophy were significantly different in the habitual cocaine abusers compared with the 2 other groups of patients. There were no differences between 1st-time cocaine users and controls. Among the habitual cocaine abusers there was a positive correlation between the approximate duration of cocaine abuse and the calculated atrophy indices. The findings suggest that cerebral atrophy develops in chronic cocaine abusers, and the severity correlates with the duration of abuse. 
2	Melanosis of the esophagus. An endoscopic, histochemical, and ultrastructural study. Endoscopic, histological, and ultrastructural features of 21 cases of esophageal melanosis are described. These cases were detected during 1000 consecutive routine upper gastrointestinal endoscopies. Staining characteristics and ultrastructure of the pigment contained in the endoscopically visible lesions were found to be similar to those of true melanin. 
2	Hyponatraemia in patients with cirrhosis. Hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites, and is due to the excessive retention of free water which results from the kidney's inability to excrete it normally. The morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances. The degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms. Altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy, symptoms of which overlap with hepatic encephalopathy and uraemia. The occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia. The appearance of hyponatraemia in cirrhotic patients, long regarded as a poor prognostic sign, may be a function of unrecognized underlying impaired renal function. Therapy for hyponatraemia remains suboptimal. 
5	Ocular motor abnormalities from head trauma. Head injuries cause the hospitalization of 200-300 persons per 100,000 population per year. Ophthalmologists provide diagnostic and therapeutic care to those trauma victims with damage to the globe, optic nerve, orbit, and ocular motor system. Eye movements can be affected by damage at any level of the central nervous system or peripheral motor unit. Comprehensive ocular motor assessment of the trauma patient can substantially contribute to the understanding of the patient's injury, recovery, and rehabilitation. This review examines all aspects of head and face trauma that can lead to ocular motility disturbances. 
5	Genetic determination of cytomegalovirus-induced and age-related cardiopathy in inbred mice. Characterization of infiltrating cells. Carditis developed 7 days after the administration of murine cytomegalovirus to neonatal, young adult or aged mice of varying sensitivity to lethal infection with this virus. The inflammation persisted for up to 80 days, but infected myocardial cells were rare and were not seen after day 10. The inflammatory cells comprised macrophages (up to 30%) and T cells (up to 80%), with a high ratio of Lyt2+ to L3T4+ cells throughout. Although the H-2 genotype affects murine cytomegalovirus replication at the level of individual cells, and hence resistance to lethal infection, it did not determine resistance to cardiopathy per se. However BALB/c, BALB.B, and BALB.K mice developed persistent myocarditis regardless of age at infection, and age-related cardiopathy was frequent and severe in infected and uninfected mice. B10 and B10.BR mice also developed myocarditis after neonatal infection, but inflammation resolved rapidly after adult infection and age-related cardiopathy was correspondingly mild. C3H mice exhibited minimal carditis after neonatal or adult infection. However neonatal infection appears to accelerate age-related cardiopathy, which is severe in retired breeders of this strain. 
1	Cartilage removal prior to skin grafting in the triangular fossa, antihelix, and concha of the ear. Skin grafting onto a large area of exposed ear cartilage with irregular contours poses an increased risk of inadequate re-establishment of circulation. Removal of cartilage not needed for structural support before grafting following Mohs surgery on the triangular fossa, antihelix, and concha of the ear decreases the risk of recurrence of the carcinoma, and increases the chances for survival of the graft. 
4	Circadian rhythm of heart rate variability after acute myocardial infarction and its influence on the prognostic value of heart rate variability. This study examined heart rate (HR) variability in patients surviving acute myocardial infarction (AMI) to find the optimum time and duration of recording of the ambulatory electrocardiogram for the prediction of the risk of sudden cardiac death, or serious arrhythmic events, or both. Twenty patients (group I) who initially survived an AMI but later experienced serious events (death or symptomatic sustained ventricular tachycardia) during a 6-month follow-up were compared with 20 patients (group II) who remained free of complications for greater than 6 months after discharge. Groups I and II were matched with regard to age, gender, infarct site, ejection fraction, and beta-blocker treatment. HR variability was assessed in the 24-hour electrocardiograms recorded during the first 2 weeks after an AMI and in various portions of the complete 24-hour recording, with both the beginning and the length of the analyzed portion varied by 20 minutes (a total of 5,113 possibilities). The maximum reduction of HR variability in group I patients was systematically found when assessing HR variability in recordings starting approximately at 6 A.M. and lasting for approximately 8 hours. In the low-risk patient, the diurnal rhythm of HR variability is more marked than in the high-risk patient and the long-term components of HR variability due to the diurnal variation must be included in the measurement of HR variability when using it as a long-term predictor of risk from arrhythmic events after an AMI. 
1	Tanning salons: an area survey of proprietors' knowledge of risks and precautions. An area survey of tanning salon proprietors was conducted in a medium-sized midwestern city. Proprietors reported they were in compliance with federal safety regulations, but not all had age, frequency, or duration restrictions. Similarly, proprietors were not uniformly informing patrons of potential tanning hazards, including the possibility of skin cancer, and were not knowledgeable about the risk and benefits of tanning. Some establishments reported selling psoralens to patrons to enhance tanning. More explicit guidelines regarding the use of tanning equipment and more accurate consumer information are needed. 
4	Treatment of obstructive pneumatosis coli with endoscopic sclerotherapy: report of a case. The case of an 86-year-old man with cardiac and pulmonary failure, in whom pneumatosis cystoides intestinalis caused segmental obstruction of the sigmoid colon is described. The patient was treated with endoscopic puncture and sclerotherapy of the cyst walls in four sessions, giving endoscopic and radiologic regress of the lesions and symptomatic relief. 
5	Subtrochanteric fractures treated with interlocking nailing. In a prospective study of 31 subtrochanteric fractures treated with Grosse-Kempf interlocking nails with a followup period of at least 1 year, there was a 87.1% (27/31) union rate, and a union period of 4.2 +/- 1.8 months. Knee range of motion in 28 acute traumatic cases was on average 127.5 +/- 23.0 degrees. The significant complications included: nail breakage, 3.2% (1/31); nonunion without nail breakage, 9.7% (3/31); neglected femoral fracture with malunion, 3.2% (1/31). The interlocking nailing has the advantages of: a) closed method, b) weight-sharing principle, c) shortening prevention, d) non-rigid fixation. From the theoretical and clinical comparison among the various implants, we conclude that closed interlocking nailing is one of the better instruments for subtrochanteric fracture treatment, and moreover, the most reasonable of all. However, for the higher level subtrochanteric fractures, reconstruction-style locking nails should be chosen. 
5	Extensor tendon rupture after osteoarthrosis of the wrist associated with nonrheumatoid positive ulnar variance. Rupture of the extensor tendon after osteoarthrosis of the wrist associated with nonrheumatoid, positive ulnar variance is uncommon. Eight cases were seen in the last five years. They included five men and three women, whose ages ranged from 54 to 82 years (average, 70 years). In all the cases, roentgenograms revealed osteoarthrotic changes in the wrist and dorsal subluxation or dislocation of the ulnar heads. Seven cases had operations. Friction with the dorsally subluxated or dislocated ulnar head and the osteophytes surrounding it caused these tendons to rupture. It was impossible to use end-to-end sutures, so tendon transfers or tendon grafts were performed. The patients were evaluated one to four years after surgery. Three patients complained of some disability in their daily lives, notably, limited flexion of their fingers. It is important that during surgery the reconstructed tendons should not be strained excessively. 
5	Outcomes of pregnancy in a national sample of resident physicians BACKGROUND. Physically demanding, highly stressful work during pregnancy has been reported to cause a variety of adverse outcomes. It has been difficult, however, to separate the effects of work from those of socioeconomic status. METHODS. By means of a national questionnaire-based survey, we studied the outcomes of pregnancy during residency for 4412 women who graduated from medical school in 1985 and for the wives of 4236 of their male classmates, who served as controls. RESULTS. The rate of response to our survey was 87 percent (4412 of 5079) for the women residents and 85 percent (4236 of 4968) for the wives of the male residents. There were no significant differences in the proportion of pregnancies ending in miscarriage (13.8 percent for residents vs. 11.8 percent for their classmates' wives, P = 0.12), ectopic gestations (0.5 percent vs. 0.8 percent, P = 0.69), and stillbirths (0.2 percent vs. 0.5 percent, P = 0.20). There were 989 women residents and 1238 residents' wives whose first pregnancy during residency resulted in the live birth of a singleton infant. Although during each trimester the women residents worked many more hours than the wives of the male residents, the frequency of preterm births (less than 37 weeks' gestation) was similar: 6.5 percent for residents and 6.0 percent for residents' wives (odds ratio = 1.1; 95 percent confidence interval, 0.7 to 1.5). Infants who were small for gestational age (with birth weights less than the 10th percentile for gestational age) were born to 5.3 percent of the residents and 5.8 percent of the residents' wives (odds ratio = 0.9; 95 percent confidence interval, 0.6 to 1.3). Adjustment for factors that differed between the women residents and the wives of male residents resulted in odds ratios of 1.2 (95 percent confidence interval, 0.8 to 1.7) for preterm delivery and 0.9 (95 percent confidence interval, 0.6 to 1.3) for the delivery of an infant who was small for gestational age. However, the women residents more frequently reported having had preterm labor (11 percent vs. 6 percent), but not preterm delivery (6.5 percent vs. 6.0 percent); preeclampsia was also more common among the women residents (8.8 percent vs. 3.5 percent). CONCLUSIONS. These results suggest that working long hours in a stressful occupation has little effect on the outcome of pregnancy in an otherwise healthy population of high socioeconomic status. 
4	High output failure in patients with peripartum cardiomyopathy: a comparative study with dilated cardiomyopathy. Although few studies have reported on relatively preserved ventricular function in patient with peripartum cardiomyopathy, the condition is usually believed to have the typical low-output congestive hemodynamic pattern of the dilated congestive cardiomyopathies. Two groups of patients, 14 with peripartum cardiomyopathy and 12 with dilated congestive cardiomyopathy who were matched for gender and age, were studied. They had normal blood pressure and similar New York Heart Association functional class, nutritional status, thyroid function and routine laboratory evaluation. All patients were catheterized during stable in-hospital compensation of heart failure, which was achieved by bed rest, sodium restriction, and administration of digoxin and diuretics long (more than 3 months) after delivery. Significant differences (p less than 0.05) between patients with peripartum cardiomyopathy and those with dilated congestive cardiomyopathy were observed in regard to: (1) cardiac index: 3.34 +/- 1.36 L/min/m2 versus 2.24 +/- 0.72 L/min/m2, (2) systemic vascular resistance: 1713 +/- 567 dynes.sec.cm-5 versus 2194 +/- 603 dynes.sec.cm-5, (3) right ventricular stroke work index: 8.6 +/- 4.2 g.M/m2 versus 14.8 +/- 8.2 g.M/m2 in the peripartum cardiomyopathy and the dilated congestive cardiomyopathy groups, respectively. Three of the patients with peripartum cardiomyopathy had resting cardiac index values that were even higher than the normal upper limit for our laboratory (4.5 L/min/m2): 4.80, 5.70, and 5.63 L/min/m2. They also had nearly normal left ventricular ejection fractions: 0.68, 0.41, and 0.51, respectively. These results indicate that, unlike the common dilated cardiomyopathy, the hemodynamic pattern in patients with peripartum cardiomyopathy is not homogeneous, and some patients have high-output failure and near normal left ventricular function. 
3	Auras and subclinical seizures: characteristics and prognostic significance. The characteristics and prognostic significance of subclinical seizures and independent auras were studied in 40 patients with partial epilepsy who had long-term electroencephalographic (EEG) monitoring with intracranial electrodes. Focal, restricted subclinical seizures were noted in 23 patients, and 11 patients experienced auras that were accompanied by ictal EEG discharges. Auras and subclinical seizures usually were identical in EEG appearance, but were distributed differently among patients. The subclinical seizures and auras usually had the same origin as complex partial seizures, but did not always reliably indicate complex partial seizure origin. Subclinical seizures and auras were of favorable prognostic significance for patients undergoing temporal lobectomy. A majority (greater than 80%) of individuals with subclinical seizures and auras were free of complex partial seizures after surgery, whereas a minority (29%) of patients without subclinical seizures and auras became free of complex partial seizures. 
1	Philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study. During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph1/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, although four were in hematologic remission at the time of the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7 showed the chronic myelogenous leukemia breakpoint. The induction failure rate was much higher in this subgroup (31%) as compared with Ph1-negative cases, and the projected duration of event-free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years. ALL with both the 9;22 translocation and -7 appears to represent a unique and previously undescribed subgroup of childhood ALL associated with a particularly adverse outcome. Leukemic transformation in such patients may involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene (-7). 
4	Non-invasive monitoring of finger arterial pressure in patients with Raynaud's phenomenon: effects of exposure to cold. We studied the effects of exposure to cold on finger arterial pressure (FAP) measured by a finger arterial pressure monitor in 15 patients with Raynaud's phenomenon and in 15 healthy volunteers. The cold exposure induced vasoconstriction of the peripheral vascular bed as judged by the plethysmograph of a pulse oximeter and had marked effects on FAP values compared with upper arm arterial pressure. Immediately after the cold exposure, FAP decreased significantly (P less than or equal to 0.01) in both groups. However, during the subsequent 20 min, FAP values increased in relation to upper arm pressure. Finally, FAP values were greater than upper arm pressure in the control individuals, but not in patients with Raynaud's phenomenon. These results have implications for non-invasive monitoring of arterial pressure by the finger pressure device. Clinically, significant problems may arise in the monitoring of FAP in patients with a systemic connective tissue disease affecting peripheral circulation. 
1	Left superior vena cava: a pitfall in computed tomographic diagnosis with surgical implications. We report 2 cases in which computed tomography of the mediastinum demonstrated an abnormality originally misinterpreted as lymphadenopathy but subsequently shown to represent a left superior vena cava. Misinterpretation may result in errors in optimum treatment and may complicate surgical exploration of the mediastinum. These 2 cases are presented to remind radiologists and surgeons of the possibility of this unusual anatomy. 
3	Pituitary hemorrhage into a Rathke's cleft cyst This report describes a case of symptomatic pituitary hemorrhage into a Rathke's cleft cyst in a 25-year-old woman. The literature on pituitary hemorrhage in nonadenomatous sellar tumors is reviewed. 
5	Pterygia: single-fraction postoperative beta irradiation. A retrospective evaluation was performed with records of 128 patients with 146 eyes that underwent applications of strontium-90 after pterygium excisions performed between 1982 and 1988. With a median follow-up of 13 months, 135 eyes were evaluable. Most pterygia (127 of 135) were treated with a single postoperative application of Sr-90 that delivered 3,000 cGy of beta radiation in one fraction. The actuarial freedom from relapse was 87%; all recurrences occurred within the first 18 months, and 46% of these within the first 3 months. Of the 13 recurrences, 10 have been re-treated with surgery and a second course of beta irradiation with excellent results. All eight eyes for which follow-up was available had no evidence of disease. The ultimate control rate was 96.3% for the series. Correlation of various treatment parameters, including age, bilaterality, prior recurrence, and interval from surgery to irradiation, was performed, and no statistically significant difference was seen. No serious complications have developed. Transient conjunctivitis and photophobia were almost universally seen, with five cases lasting beyond 5 months. The authors conclude that a single application of Sr-90 after surgery is effective and safe in managing pterygia. 
5	Interruption of professional and home activity after laparoscopic cholecystectomy among French and American patients. With a laparoscopic approach, patients can undergo cholecystectomy with a shorter hospitalization, minimal pain, and quicker recovery. It has not been demonstrated, however, that patients actually return to work after laparoscopic cholecystectomy faster than the traditional 4- to 6-week absence from work after a standard open procedure. A survey of 104 French and 84 American patients undergoing laparoscopic cholecystectomy revealed that postoperative discomfort was completely resolved in 2 weeks in 73% of French and 93% of American patients. All but 11 French and 5 American patients were back to normal home activities by 2 weeks after the operation. Of the 35 American and 40 French patients who had professional activity outside the home, 63% and 25%, respectively, returned to work within 14 days. Five (14%) of the American patients and 12 (30%) of the French patients returned to work 4 weeks or more after the operation. The amount of physical activity on the job correlated with the period off work, but, interestingly, at least six patients with very hard physical activity at work (including construction workers) were able to return to full work activity within 1 week. These data suggest that early return to work is possible and that pain resolves quickly after laparoscopic cholecystectomy. The economic benefit of having patients back on the job quickly, however, may be less than expected until cultural norms change with regard to leave of absence after major surgery. 
1	Intraluminal pressure adjacent to left colonic anastomoses. A cumulative total of 89 h of pressure data was acquired from both sides of a left colonic anastomosis in 15 patients over a median period of 7 postoperative study days. Patients had a colonic ileus lasting 3-10 days and during this proximal and distal inactivity the intraluminal pressure remained within 6 mmHg of atmospheric pressure. After recovery of activity, pressures proximal to the anastomosis in excess of 10 mmHg occurred during less than 1 per cent of the recording time. Distal peak pressures were significantly elevated with respect to the proximal site (P less than 0.001). Two-thirds of the distal pressures recorded were between 10 and 20 mmHg and 98 per cent were less than 50 mmHg; the peak distal pressure was 90 mmHg. Four patients had distal repetitive tonic contractions creating a pressure difference across the anastomosis with a mean of 20 mmHg and a peak of 45 mmHg. Each contraction persisted for 15-20 min. Intraluminal pressures are unlikely to play a role in anastomotic dehiscence. 
4	Sudden death associated with undiagnosed Graves' disease. Hyperthyroidism may result in multiple symptoms attributable to an excess of thyroid hormone. We report a case of Graves' disease in association with sudden death in a previously healthy, undiagnosed young female. This case illustrates an unusual initial presentation of Graves' disease. 
3	Posterior interosseous nerve palsies. One hundred seventy patients with radial nerve disorders were reviewed at the Louisiana State University Medical Center over a 15-year period. Of these, 32 had involvement of the posterior interosseous nerve exclusively. Findings included weak wrist extension with a radial drift, inability to extend the fingers, paralysis of thumb extension, and weak thumb abduction. Causes included entrapment at the arcade of Froshe (14 patients), laceration (6 patients), fracture (6 patients), compression or contusion (3 patients), and loss associated with tumor (3 patients). The ratio of men to women was 2:1, and the right arm was involved twice as often as the left. Preoperative evaluation included physical examination, electrophysiological testing (electromyogram/nerve conduction velocity), and roentgenograms of the elbow and forearm. Of the 30 patients (2 patients had bilateral lesions), 26 underwent operation. In the operative series, all 28 nerves had a function of Grade 3 or more of a possible 5 after 4 years of follow-up. Seventeen had achieved Grade 4/5, and 7 had obtained Grade 5/5. At operation, 23 nerves were found to be in continuity. Fourteen lesions of nerves in continuity were associated with entrapment and, not unexpectedly, transmitted a nerve action potential with slowed conduction and low amplitude across the lesion. Four nerves in continuity that had lesions caused by injury had nerve action potentials and were treated by neurolysis, and another 4 had no nerve action potentials and were treated by graft or suture repair. Five injured nerves were not in continuity. Two could be repaired by end-to-end suture, and 3 required graft repair. A large ganglion cyst involving the posterior interosseous nerve was also resected. 
1	Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. In 58 breast cancer patients with meningeal carcinomatosis (MC) pretreatment characteristics, clinical course, and response to treatment were evaluated. Forty-four patients were uniformly treated with intraventricular chemotherapy. Fourteen patients did not receive intraventricular treatment. In the intraventricularly treated group the median survival was 12 weeks. Multivariate analysis of the pretreatment characteristics of the intraventricularly treated patients demonstrated a prognostic significance with respect to survival for age older than 55 years, lung metastases, cranial nerve involvement, cerebrospinal fluid (CSF) glucose less than 2.5 mmol/l, and CSF protein 0.51 to 1.0 g/l. Based on the significance of these predicting factors a prognostic index (PI) identified four groups of patients with a median survival of 43 weeks, 22 weeks, 11 weeks, and 3 weeks, respectively. After 6 weeks of intraventricular treatment 22 patients showed a neurologic improvement or stabilization, and nine patients showed a worsening of the neurologic signs, whereas 13 patients (30%) had already died. The responders had a median additional survival of 5 months versus 1 month for nonresponders. No relation was found between survival and intensity of the intraventricular treatment after the first 6 weeks of treatment. Almost all long survivors had also received systemic treatment for systemic disease, whereas most patients who died within 6 months did not receive systemic therapy. Radiation therapy had no influence on the survival time. Early death due to the intensive treatment occurred in three patients. In 11 of the 17 patients who survived more than 4 months an often seriously debilitating late neurotoxicity developed. The survival curve of the nonintraventricularly treated patients appeared to be essentially the same as the curve of the intraventricularly treated patients. Using the same PI the predicted survival time was also the same as in the intraventricularly treated group. It is concluded that survival in MC from breast carcinoma may be more dependent on some pretreatment characteristics than on treatment intensity. On the basis of these pretreatment characteristics the survival time seems to be predictable. Finally, late neurotoxicity due to aggressive treatment leads to impairment of the quality of life in more than 50% of the long survivors. The exact value of intraventricular and systemic therapy in patients with MC still has to be determined. 
1	Periapical lesions of mandibular bone: difficulties in early diagnostics. It is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease. In this paper these problems are discussed, and some suggestions are made to overcome them. The discussion is based on cases of osteogenic sarcoma, histiocytic lymphoma, and chronic osteomyelitis. The patients were a boy and two middle-aged women, all of them with primary clinical symptoms of pain and swelling, diffuse roentgenologic changes in mandibular bone, uncertain response to treatment, and an unusual progress of the disease. 
1	Evaluation of in vitro bromodeoxyuridine labeling of breast carcinomas with the use of a commercial kit. The prognostic significance of S-phase fraction analyses of breast carcinomas has been reported by several investigators. The Cell Proliferation Kit (Amersham Corporation, Arlington Heights, IL), which uses in vitro bromodeoxyuridine (BRDU) labeling to evaluate cell cycle kinetics without a flow cytometer or radioisotopes, simplifies this assay for the clinical-based laboratory by providing standardized reagents and recommended methods. This study was performed to determine whether data derived from its use were comparable to published S-phase data from the use of thymidine labeling, BRDU, or other methods on breast carcinomas. Primary infiltrating ductal carcinomas (n = 142) and primary lobular carcinomas (n = 6) showed mean and median BRDU labeling of 4.63% and 3%, 1.3% and 1%, respectively, with a range of 0-28%. Benign lesions always had less than 3% BRDU uptake (n = 21). Estrogen receptor (ER) and progesterone receptor (PR) status correlated with BRDU labeling (P less than 0.05), with the highest S-phase fractions in ER- and PR-negative tumors. Correlations between BRDU uptake and histologic tumor type or size were observed. Significant correlations between BRDU uptake and lymph node status, patient age, or histologic tumor grade were not observed. S-phase studies of breast carcinomas using other techniques have shown similar data, therefore, the Cell Proliferation Kit appears to be a practical and useful method for in vitro S-phase analysis that allows concomitant histologic examination of the same tumor tissue sample. 
5	Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death The pathophysiology of recurrent cyanotic episodes has been investigated in 51 infants and children. Episodes began at a median age of 7 weeks (range 1 day to 22 months, 39 at less than 4 months). They were characterised by the rapidity of onset and progression of severe hypoxaemia with early loss of consciousness from cerebral hypoxia. The most common precipitating factor was a sudden naturally occurring stimulus from pain, fear, or anger. In uncontrolled trials, cyanotic episodes were reduced in frequency and severity by tetrabenazine (n = 15) and additional inspired oxygen (n = 10). Eight patients died suddenly and unexpectedly (four during cyanotic episodes). Twenty eight patients underwent physiological studies during cyanotic episodes. There was no evidence of seizure activity at the onset and although prolonged absence of inspiratory effort with continued expiratory efforts was common, breathing sometimes continued. Episodes were not caused by upper airway obstruction and sometimes occurred during positive airway pressure ventilation. The rapidity of fall in arterial oxygen pressure and continued breathing suggested a right to left shunt of sudden onset. The results of contrast echocardiography and lung imaging studies confirmed that this was occurring within the lungs. These cyanotic episodes included both intrapulmonary shunting and prolonged expiratory apnoea. They are best explained by interactions between central sympathetic activity, brainstem control of respiration and vasomotor activity, reflexes arising from around and within the respiratory tract, and the matching of ventilation to perfusion in the lungs. They are a cause of sudden unexpected death in infancy and early childhood. 
4	Clentiazem reduces infarct size in rabbit middle cerebral artery occlusion. We assessed the value of pretreatment with clentiazem (8-chlorodiltiazem), a diltiazem derivative with cerebroselective properties, on the consequences of surgical occlusion of the middle cerebral artery via a transorbital approach in 38 rabbits. Nineteen rabbits received 1.7 (n = 5), 5 (n = 8), or 15 (n = 6) mg/kg clentiazem orally four times a day for 24 hours before and 48 hours after occlusion. Upon sacrifice, a segment of the right middle cerebral artery distal to the occlusion and a corresponding segment from the nonoccluded left middle cerebral artery were mounted on myographs for in vitro study of their reactivity to histamine, acetylcholine, serotonin, norepinephrine, and electrical stimulation of intramural sympathetic nerves. Morphometric measurements of 2,3,5-triphenyltetrazolium chloride-stained brain slices permitted us to estimate infarct volume. Pretreatment with 1.7, 5, and 15 mg/kg clentiazem significantly reduced infarct volume (p less than 0.05, p less than 0.01, and p less than 0.01, respectively). Mean infarct volume of the 15 mg/kg-treated group was only 4% that of the untreated group. There were no postoperative deaths in any treated group compared with a death rate of 36% in the untreated group. Mean values for vascular smooth muscle contractility to histamine and relaxation to acetylcholine were significantly enhanced in vessels from treated rabbits. These studies indicate that pretreatment with clentiazem offers cerebral protection and significantly reduces infarct volume as well as arterial wall damage beyond the occlusion. 
5	Ear involvement in the yellow nail syndrome. Recognized features of the yellow nail syndrome include yellow nails, lymphedema, and pleural effusions. We report a patient with the additional feature of keratosis obturans, which may be a manifestation of this syndrome in the external ear. 
5	Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography. Renal ultrasonography was performed in 45,905 adults, including 41,364 without any signs suggesting urinary tract malignancies, 1,667 with microscopic hematuria only and 2,874 with some signs of malignancy. Renal lesions were found in 355 adults (0.858%) in the asymptomatic, 39 (2.3%) in the microscopic hematuria and 75 (2.6%) in the symptomatic groups, respectively. Renal cell carcinoma was found in 35 (7.5%) lesions: 19 (5.4%) in the asymptomatic, none in the microscopic hematuria and 16 (21.3%) in the symptomatic groups. A total of 47 patients, including 12 other renal cell carcinoma patients transferred from related hospitals, was grouped into 28 without and 19 with symptoms. Primary tumor size and clinical stages were significantly smaller and lower, respectively, in the asymptomatic group than in the symptomatic group. Radical nephrectomy was performed in all but 2 asymptomatic patients. The 5-year survival rates after nephrectomy were 94.7 and 60.9% for the asymptomatic and symptomatic groups, respectively (p less than 0.01). The results indicate that ultrasonography is a useful tool to detect low stage asymptomatic renal cell carcinoma at low cost. 
1	Squamous carcinoma of the distal esophagus: a survival study. A survival study for squamous carcinomas of the distal esophagus treated by the Southern California Permanente Medical Group in the interval of 1954 to 1988 was undertaken. We found radiation therapy and surgery equally efficacious in terms of cure for patients without distant disease and performance status sufficient to tolerate treatment. We did not find survival benefit for patients treated with palliative surgery, and plan less invasive endoscopic means along with chemotherapy and radiation for palliation, reserving surgery for special circumstances. 
1	Primary hepatic carcinoid tumor. An electron microscopic and immunohistochemical study. A case of primary carcinoid tumor of the liver with striking morphologic and electron microscopic features is reported. Conventional histologic examination showed a prominent paranuclear clear zone in numerous tumor cells. By electron microscopic examination, this clear zone corresponded to a paranuclear mass of intermediate filaments admixed with neurosecretory granules and other cytoplasmic organelles. 
4	The failure of serial pneumatic cuff venous occlusion plethysmography to predict patients at risk for pulmonary emboli after trauma. Over a three month period, attempts to perform serial Pneumatic Cuff Venous Occlusion Plethysmography (VP) were carried out in 51 severely injured patients felt to be at risk for Pulmonary Embolus (PE). Studies could not be performed in 25 of these patients due to the nature of their injuries. Of the remaining 26 patients, two showed evidence of deep vein thrombosis (DVT). Venography confirmed the diagnosis in only one of these patients. Serial VP failed to predict PE in all five patients in whom it was diagnosed. This article concludes that serial VP is not an effective predictor of PE in these patients. 
3	Is it correct to correct? Developmental milestones in 555 "normal" preterm infants compared with term infants. To determine whether correction for preterm birth should be applied during developmental assessment, we conducted a prospective national survey of very premature infants (born at less than 32 weeks of gestation); neurodevelopment in the first 2 years was studied with the Dutch child health care developmental assessment. In 555 preterm children who had no evidence of handicap at 2 years of age, the age at which developmental milestones were reached was established. The results were compared with the results of the same assessment in Dutch children born at term. During the first year, the development of the very premature children equaled the development of normal children when full correction was applied. At 2 years of age, development was equal to or better than normal children's development without correction. We conclude that full correction for prematurity should be applied in the first year to avoid overreferral for developmental stimulation, whereas at 2 years of age correction is not necessary. 
4	Assessment of right ventricular oxidative metabolism by positron emission tomography with C-11 acetate in aortic valve disease. Evaluation of right ventricular (RV) oxidative metabolism is limited by the inability to easily determine oxygen extraction by the RV myocardium and the complex morphology of this ventricle. Because left ventricular C-11 clearance rate constants closely correlate with myocardial oxygen consumption, it was postulated that C-11 clearance rate constants for the RV free wall should also reflect its oxygen consumption. Therefore, RV C-11 clearance rate constants were compared with RV loading in 21 patients with aortic valve disease to assess the possible use of this technique for noninvasive evaluation of RV oxidative metabolism. RV free wall C-11 clearance rate constants correlated with the product of systolic pulmonary artery pressure and heart rate for all patients (r = 0.65, p = 0.002), but the relation was stronger if 2 patients with overt RV dysfunction were excluded (r = 0.83, p = 0.001). On the basis of mean pulmonary artery pressures, patients were stratified into subgroups with normal (group I, n = 8) and elevated (group II, n = 13) pulmonary pressures and were compared with 10 normal control subjects. RV C-11 clearance rate constants were significantly higher in group II than in group I and in normal control subjects (p less than 0.05). These data suggest that RV C-11 acetate clearance rate constants can provide noninvasive evaluation of RV oxidative metabolism. This technique may allow serial assessment of RV performance in various cardiac and pulmonary diseases, and particularly of changes associated with therapeutic interventions. 
1	Epstein-Barr virus transformation of B lymphocytes from IgA nephropathy patients and first-degree relatives results in increased immunoglobulin synthesis not restricted to IgA. In order to study B-cell activation patterns independent of T-cell regulation in patients with IgA nephropathy (IgAN), peripheral blood mononuclear cells from 67 patients with IgAN, 15 first-degree relatives of patients with familial disease, and 13 normal controls were transformed with Epstein-Barr virus (EBV). Culture supernatants of these transformed cells were assayed for levels of IgG, IgA, and IgM, and results obtained on the three populations were compared. EBV-transformed cells of IgAN patients, as well as the population of first-degree relatives, secreted significantly elevated levels of all three isotypes as compared with the normal controls. However, in comparing ratios of secreted isotypes, it was determined that more IgA relative to IgG and IgM was synthesized by cells of these two populations as compared with the normal controls. Our results imply that (1) the population of B cells susceptible to EBV activation is increased in IgAN patients; (2) this population of "activatable" B lymphocytes is polyclonal and not restricted to the IgA class; and (3) even though there may be a primary B-cell abnormality in IgAN, an additional defect(s) is probably operative in the pathogenesis, since cells of clinically unaffected relatives behaved in a pattern similar to that of patients. 
5	New horizons in management of hypothermia and frostbite injury. Diagnosing hypothermia requires a high index of suspicion. Restoring lost heat with careful attention to hemodynamics usually results in complete recovery. Frostbite is best treated by physicians who are cognizant of the pathophysiology of cold injury. Although alternative methods of intervention are being tested, rapid rewarming and anti-inflammatory agents are integral to treatment protocols. 
1	A phase I clinical trial of 2-chlorodeoxyadenosine in pediatric patients with acute leukemia. To evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia, we performed a phase I trial of 2-chloro-2'-deoxy-adenosine (2-chlorodeoxyadenosine; 2-CDA) given as a continuous 5-day infusion at doses of 3 to 10.7 mg/m2/d. In this study of 31 children with acute leukemia, the only dose-limiting toxicity was myelosuppression. At the highest dose level, three of seven patients developed fatal systemic bacterial or fungal infections. At dose levels above 6.2 mg/m2/d, significant oncolytic responses occurred in all patients. In addition, there was a significant correlation between both the responsiveness by cell type and dose of 2-CDA, such that more oncolytic responses were noted in acute myeloid leukemia (AML) patients than acute lymphoblastic leukemia (ALL) patients (P = .02). Although this was a phase I trial in heavily pretreated patients with refractory disease, two AML patients treated at 5.2 and 10.7 mg/m2/d, respectively, had complete hematologic responses, and one patient treated at 10.7 mg/m2/d had a partial response. In addition, there was a dose-response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2-CDA. In vitro evaluation of 2-CDA uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2-chloro-2'-deoxyadenosine (Cld-AMP) and 2-chloro-2'-deoxyadenosine 5'-striphosphate (CldATP) reached concentrations close to steady-state levels within 1 hour. Intracellular nucleotide disappearance rates were high with half-lives of 1.29 and 2.47 hours for CldAMP and CldATP, respectively. This suggests that continuous infusion is necessary to maintain the desired plasma concentration. The results of this study confirm the antileukemic activity of 2-CDA and the lack of prohibitive nonhematologic toxicity. Phase II trials in patients with AML and ALL are warranted. 
4	Sinus node-atrioventricular node isolation: long-term results with the "corridor" operation for atrial fibrillation The "corridor" operation is designed to restore sinus rhythm to patients with atrial fibrillation by electrically isolating the sinus node, a band of atrial tissue and the atrioventricular (AV) node from the remaining atrial tissue. Nine patients with drug-refractory atrial fibrillation underwent this operation; four patients had chronic atrial fibrillation and five had paroxysmal atrial fibrillation; the mean duration of symptoms was 12 +/- 8 years. Patient ages ranged from 25 to 68 years (mean 48 +/- 12). At preoperative electrophysiologic study, no patient had evidence of an accessory AV pathway or AV node reentry. Sinus node recovery time could not be determined in five patients because of recurrent atrial fibrillation during or before programmed stimulation. At operation the corridor of atrial tissue connecting the sinus and AV nodes was successfully isolated from the remaining left and right atrial tissue in all patients. One patient required early reoperation for recurrent atrial fibrillation before hospital discharge. At the predischarge electrophysiologic study, the corridor remained isolated in all patients except for one patient who had intermittent conduction between the corridor and excluded right atrium. One patient had nonsustained atrial fibrillation and one had atrial tachycardia evident in the corridor. Atypical AV node reentry of uncertain significance was induced in one other patient. Over a total follow-up of 191 patient months (mean 21 +/- 20), seven patients remained free of atrial fibrillation. Two patients had recurrent atrial fibrillation, which in one patient was effectively controlled by a single antiarrhythmic agent. A permanent pacemaker was implanted in four patients for sinus node dysfunction. 
5	Environmental risk factors in siblings with Parkinson's disease. To investigate possible risk factors in Parkinson's disease, we conducted a case-controlled study of 19 families having two or more siblings with Parkinson's disease. Demographic data were collected, including lifetime histories of places of residence; sources of drinking water; occupations, such as farming; and exposure to herbicides and pesticides. Rural living and drinking well water, but not farming and herbicide exposure, were significantly increased in 38 parkinsonians compared with 38 normal control subjects. A comparison of parkinsonian siblings with siblings with essential tremor revealed no differences in any risk factors for the years of shared environment. These data suggest that living in a rural environment and drinking well water are risk factors for Parkinson's disease and that the total life exposure to an environmental toxin may be more important than exposure in early life. 
4	Lipids, vascular disease, and dementia with advancing age. Epidemiologic considerations. Elevated plasma lipid and lipoprotein levels are associated with an increased risk of cardiovascular disease in middle-aged men and women. It is still not clear, however, whether lipid and lipoprotein abnormalities continue to be risk factors for cardiovascular disease in the elderly population. It is not even clear what normal lipid values are in the elderly, and whether diet or drug therapy should be advised on the basis of lipid values established in middle-aged populations. Ischemic heart disease does remain the leading cause of death in the elderly, and there is now preliminary evidence from epidemiologic studies that relative elevations of levels of lipid and lipoprotein fractions in an elderly population might be associated with an independent and increased risk of coronary heart disease, stroke, and possibly dementia. Intervention studies are about to begin that will assess various lipid-and lipoprotein-modifying therapies and their ability to reduce vascular disease risk in the elderly. 
2	Preventive therapy of first gastrointestinal bleeding in patients with cirrhosis: results of a controlled trial comparing propranolol, endoscopic sclerotherapy and placebo. Propranolol and endoscopic sclerosis of esophageal varices are the two approaches currently used in prophylaxis of the first gastrointestinal hemorrhage in the cirrhotic patient. One hundred twenty-six cirrhotic patients with esophageal varices and no histories of bleeding were included in the trial regardless of the gravity of the cirrhosis or the size of the esophageal varices. Patients with hepatocarcinomas or other cancers, clearly impossible follow-up, previous treatment for portal hypertension or contraindication to beta-blockers were excluded. After randomization, 43 patients received propranolol twice daily at a dose reducing the heart rate by 25%; 42 patients were treated with intravariceal and extravariceal injections of Polidocanol; 41 control patients received vitamin K orally as placebo. The patients were seen at 3-mo intervals for 2 yr. On entry to the trial the three groups were comparable in terms of clinical and biological parameters, including size of esophageal varices (grade I = 51, grade II = 54, grade III = 17), Child-Pugh classification (A = 29, B = 61, C = 32) and the origin of cirrhosis (alcoholic in 79% of cases). Twenty-four patients bled (two bled in the propranolol group, nine bled in the endoscopic sclerosis of esophageal varices group and 13 bled in the placebo group). Actuarial estimates (Kaplan-Meier) of the time of onset of first bleeding showed that the differences were significant between propranolol and placebo (p less than 0.004) and between propranolol and sclerotherapy (p less than 0.03) but not between sclerotherapy and placebo. 
1	Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides. The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and gamma interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides. 
2	Serum gastrin and blood glucose levels during halothane-nitrous oxide anaesthesia and strabismus surgery in children. The purpose of this study was to determine whether serum gastrin levels are increased by reflexogenic stimuli applied to the extrinsic muscles of the eye. Serum gastrin and blood glucose concentrations were measured in ten normal children aged between 5 and 12 yr during general anaesthesia with halothane and nitrous oxide and during strabismus surgery. Fasting basal concentrations of gastrin (33.6 +/- 14.8 pg.ml-1) and of glucose (4.43 +/- 0.72 mmol.L-1) were in the normal range of values for children. Intravenous atropine (0.01 mg.kg-1), general anaesthesia with halothane in nitrous oxide and oxygen by mask for three minutes, tracheal intubation, extraocular muscle stimulation and surgical stress did not cause any variation in the mean serum gastrin concentration. On the contrary, tracheal intubation and surgical stress increased blood glucose concentrations (P less than 0.05). There was no difference in the serum gastrin levels after extraocular muscle stimulation between children with positive or negative oculocardiac reflexes (44.5 +/- 16.7 pg.ml-1 vs 38 +/- 14.7 pg.ml-1, respectively). The incidence of vomiting predischarge was 60 per cent. Serum gastrin levels did not differ between children who vomited and children who did not (44.3 +/- 18.5 pg.ml-1 vs 47.1 +/- 16.9 pg.ml-1, respectively). Vomiting after strabismus surgery cannot be attributed to high gastrin serum levels. Consequently, it is unlikely that vomiting after strabismus surgery is linked to an "oculogastric reflex" with the vagus nerve as the efferent pathway. 
3	Serial neurobehavioral assessments in preterm infants. The purpose of this study was to compare serial neurobehavioral assessments in a sample of preterm infants with intraventricular hemorrhage (IVH) to those of a group of unaffected preterm infants. Of the 30 infants included in the study, 5 infants had a grade III or IV/VI intraventricular hemorrhage. Infants with IVH demonstrated more abnormalities in mental status and a cluster of abnormal neurologic findings (persistent ankle clonus, tremulousness, and brisk deep tendon reflexes). Of the 30 infants, 20 infants were included in a brain metabolism study. Infants who had experienced an IVH had significantly different brain metabolism findings, as measured by nuclear magnetic resonance spectroscopy (NMR). There was a significant correlation between one measure of brain metabolism (PCr/PI) and the neurobehavioral assessment rating for infants with IVH. 
4	Coronary sinus occlusion: effect on ischemic left ventricular dysfunction and reactive hyperemia. Pressure-controlled intermittent coronary sinus occlusion (PICSO) has been shown to reduce experimental infarct size. To examine the role of PICSO in limiting the consequences of brief ischemia on left ventricular function, we studied the effect of PICSO in nine open-chest anesthetized dogs. PICSO was performed using a pump-inflated, balloon-tipped catheter in the coronary sinus until coronary sinus occlusion pressure reached a plateau (10 +/- 3 seconds). The balloon was then rapidly deflated (2 seconds) and the cycle was repeated. Regional left ventricular function in the ischemic zone was assessed by sonomicrometry. Coronary blood flow was measured with a flow probe around the left anterior descending artery (LAD) proximal to an occluding suture. Measurements were obtained at baseline, during a 3-minute LAD occlusion, and for 10 minutes of reperfusion. In an additional five dogs, this sequence was repeated during an infusion of adenosine at a dose that abolished reactive hyperemia following LAD occlusion. The addition of PICSO beginning 15 minutes prior to ischemia and continuing throughout LAD occlusion and reperfusion did not prevent, reduce, or shorten ischemic left ventricular dysfunction. PICSO uniformly blunted reactive hyperemia during reperfusion. However, PICSO also reduced coronary blood flow during maximal vasodilatation achieved by adenosine infusion prior to LAD occlusion. Therefore, it is likely that PICSO decreases reactive hyperemia due to mechanical factors arising from venous engorgement rather than by reducing the ischemic stimulus causing vasodilation. 
4	Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns. Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic modality for newborn respiratory failure, but there is little information available regarding the prognostic determinants with this technique. One hundred thirty-five newborns treated with ECMO over a 4-year period were critically analyzed with regard to the influence that birth weight, gestational age, age at initiation of ECMO, best blood gases before ECMO, number of hours on ECMO, renal failure, intracerebral hemorrhage, and long-distance air transport had on survival. Infants with meconium aspiration and those undergoing long-distance transfer showed significant differences in blood gases before ECMO, with survivors having more normal pH and carbon dioxide tension values. Intracerebral hemorrhage and renal failure that developed during ECMO were grave prognostic signs, with few survivors in either group. These data show that ability to ventilate patients before ECMO, giving normal carbon dioxide tension and pH values, is an important prognostic sign in infants with meconium aspiration and undergoing long-distance transfer for ECMO, whereas renal failure and intracerebral hemorrhage are usually lethal complications of ECMO. Each center performing ECMO should continually reevaluate this invasive technique and its results and complications. 
4	Insulin as a mitogenic factor: role in the pathogenesis of cardiovascular disease. Evidence has been accumulating that insulin has actions that may promote the development of atherosclerosis. Research has involved three broad areas: actions of insulin on cultured arterial cells, the effect of insulin on isolated artery preparations, and the development of lipid-containing lesions in the arteries of experimental animals. Insulin, in concentrations similar to those found in physiologic conditions, stimulates proliferation of cultured arterial smooth muscle cells from a number of species, including humans. Insulin also stimulates migration of smooth muscle cells. Cholesterol synthesis and low-density lipoprotein interaction with its receptor in smooth muscle cells are stimulated by insulin. Insulin's mitogenic action appears to be mediated by the insulin-like growth factor receptor. Endothelial cells cultured from large vessels are resistant to the actions of insulin, but hyperglycemia inhibits their proliferation. Insulin deficiency protects animals from experimental atherosclerosis; this protection is lost with insulin treatment. Insulin administration results in lipid-containing lesions in chickens and rats fed a normal diet, and in increased lipid synthesis in the arteries of pigs and dogs. Isolated artery preparations from insulin-deficient or insulin-treated animals undergo lipid metabolism at a rate that correlates with the insulin concentrations in the donor animals. The biological actions of insulin (and glucose) on arterial tissue suggest that hyperglycemia and hyperinsulinemia may promote the development of atherosclerosis. 
2	Congenital tracheoesophageal fistula associated with carcinoma of the lung in an adult. A rare case of adult congenital H-type tracheoesophageal fistula was diagnosed. Subsequently, at operation, large cell, undifferentiated carcinoma of the right middle lobe with extension to the right lobe and adherence to the diaphragm was documented. The diagnosis, surgical intervention, and 4-year follow-up are presented. 
5	Posterior nuchal cystic hygroma [published erratum appears in Clin Perinatol 1990 Dec;17(4):viii] When cystic hygroma is detected antenatally, the prognosis is usually poor, and intrauterine or neonatal death are common. This seems especially true for Turner syndrome (the largest etiologic group associated with cystic hygroma) and the lethal multiple pterygium syndromes. However, some fetuses with Turner syndrome, and also with certain other diagnoses, had a good outcome, and further study of these conditions is required before more definite prognostic indicators and risk figures will be available. Increasing numbers of syndromes are being reported in association with fetal cystic hygroma, and lymphedema may be a common element in their pathogenesis. Mild, short-lived, or otherwise uncomplicated jugular lymphatic obstruction may be a cause of the neck webbing seen in the Noonan, familial pterygium colli, and distichiasis-lymphedema syndromes. With earlier and more widespread fetal ultrasonography, and more sensitive techniques, a greater number of resolving fetal cases may be reported. This may clarify the natural history and provide prospective criteria for the conditions that have better prognoses. The associated conditions include autosomal dominant and recessive genetic traits. Careful ultrasound study for other malformations, polyhydramnios and fetal growth parameters, a fetal karyotype, and, if appropriate, pathologic examination are required to determine the etiology and recurrence risk. The parents should be asked about exposure to alcohol or other agents and should be examined for signs of pterygium colli or Noonan syndrome. If the decision is made to continue the pregnancy, and there is doubt about the natural history and prognosis, multi-disciplinary supervision should include social services, neonatology, pediatric surgery, cardiology, and genetics specialties when indicated. 
5	Transient renal acidification defect during acute infantile diarrhea: the role of urinary sodium. We studied urinary acidification daily during the hospital course of 16 infants with acute gastroenteritis and metabolic acidosis. Urine pH value on admission was higher than 5.5 in 14 (87%) patients. We hypothesized that inappropriate urinary acidification was due to sodium deficiency and inadequate sodium delivery to the distal nephron. Forty-one urinary samples were collected during metabolic acidosis. The mean pH of 24 urine samples with sodium concentration less than 10 mmol/L was significantly higher than the pH of 17 samples with sodium concentration greater than 10 mmol/L (6.04 +/- 0.06 vs 5.19 +/- 0.1; p less than 0.001). The urine ratios of titratable acid to creatinine and of total acidity to creatinine were significantly higher in urine samples containing more sodium (p less than 0.02), whereas the ammonium/creatinine ratio was not. After administration of furosemide or correction of the sodium deficit, appropriate acidification was observed. We conclude that impaired urinary acidification is frequently found during metabolic acidosis in infants with acute gastroenteritis and results from a sodium deficit rather than from transient distal renal tubular acidosis. 
3	Abnormal single motor unit behavior in the upper motor neuron syndrome. We studied the discharge pattern of single motor units (SMUs) in the left and right biceps muscles from a patient with nonspastic weakness of the left arm. Detailed statistical analysis of the behavior of discharge patterns of 4 of 4 single motor units on the affected side showed abnormalities with characteristic features of an upper motor neuron lesion. Five out of 5 single motor units recorded from the right biceps were normal. An upper motor neuron lesion affecting the left arm, predicted by our results, was confirmed by magnetic resonance imaging (MRI), which showed a lesion in the right precentral gyrus. It appears that changes in single motor unit firing characteristics, caused by an upper motor neuron lesion, can be detected at a time when there is no evidence of increased "tone" and/or hyperreflexia (spasticity) in the affected extremity. 
3	Sexual behavior of a sample of females with epilepsy. A sample of 700 female epileptic outpatients was examined between 1985 and 1987. The incidence of psychosexual disorders was 18%. Epileptic females with psychosexual disorders were compared with epileptic females without sexual disorders and with normal female controls on selected clinical and EEG parameters. Epileptic females with sexual disorders showed: lower marriage rates, a longer duration of illness, sexually colored prodromata, predominance of partial complex seizures (83%) and a higher incidence of menstrual abnormalities. Hyposexuality and exhibitionism were the psychosexual disorders most frequently noted. Temporal lobe EEG abnormalities were significantly higher. 
4	Pressure-length loop area: its components analyzed during graded myocardial ischemia. The changes in total pressure-length loop area were compared with changes in effective shortening area, systolic lengthening area and postsystolic shortening area (defined with respect to end-diastolic and end-systolic lengths) of the pressure-length loop during myocardial ischemia in seven anesthetized dogs instrumented for measurement of left ventricular pressure and regional segmental wall motion (sonomicrometry) in the minor axis of the apical region of the left ventricle. Ischemia was induced by gradual tightening of a micrometer-controlled snare around the left anterior descending coronary artery, which supplied the apical myocardium. Data were obtained at normal flow, after critical constriction (loss of pulsatile coronary flow), mild ischemia (ischemia 1: onset of regional dysfunction, i.e., postsystolic shortening and mild hypokinesia) and moderate ischemia (ischemia 2: marked hypokinesia). At each stage, acute afterloading was performed by partially occluding the descending thoracic aorta. The pressure-length loops were analyzed in terms of four areas: total loop area, effective shortening area, postsystolic shortening area and systolic lengthening area. Total loop area decreased only when marked hypokinesia was present (176 +/- 18.3 mm Hg x mm at ischemia 2 versus 245.1 +/- 26.9 mm Hg x mm at ischemia 1, p less than 0.05). However, effective shortening area (98.2 +/- 0.8% of total loop area at baseline; 93.8 +/- 2.4% at critical constriction; 76.3 +/- 7.2% at ischemia 1; 51.9 +/- 12.2% at ischemia 2) and postsystolic shortening area (1.8 +/- 0.8% of total loop area at baseline; 5.2 +/- 1.9% at critical constriction; 14.3 +/- 3/4% at ischemia 1; 23.8 +/- 5.1% at ischemia 2) changed significantly with each progressive stage of ischemia. 
3	A surgical approach to the cervicothoracic spine. We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care. 
3	Magnetic resonance imaging in motor neuron disease. Magnetic resonance imaging (MRI) of the brain was evaluated in 20 patients with motor neuron disease (MND) and in a control group of 11 healthy people. Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, internal capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in 8 out of 20 patients. Three out of 4 patients with progressive bulbar paralysis and 5 out of 11 cases of amyotrophic lateral sclerosis had abnormal MRI. Such MRI abnormalities have neither been found in patients with progressive muscular atrophy nor in controls, suggesting that they may be the hallmark of pyramidal tract degeneration in motor neuron disease. 
5	Ascites after rupture of dissecting aortic aneurysm into the right atrium. We report successful repair of an aneurysmal aorta-right atrial fistula causing intractable ascites. The clamped "ascending aorta" was drained for mixed return after perfusion through the femoral vessels and opened during hypothermic arrest. Return cannulation through the fistula permitted definitive repair. 
3	Human olfactory discrimination after unilateral frontal or temporal lobectomy. Olfactory discrimination and detection was studied in 106 patients with unilateral cerebral excision in the right or left temporal lobe, right or left frontal lobe, left parietal lobe, or right frontal and temporal lobes, and in 20 normal control subjects. Detection thresholds for n-butyl alcohol, measured separately in each nostril, did not differ across subject groups or across nostrils, thus excluding any primary sensory loss. The discrimination task involved monorhinal presentation of repairs of unfamiliar odorants, which the subjects judged as same or different in quality. The results showed a significant deficit in discrimination confined to the nostril ipsilateral to the lesion in patients with temporal lobe removals. Patients with frontal lobe excisions were also impaired and, for patients with right frontal lesions including the orbital cortex, the impairment was found in both nostrils. Patients with left parietal lesions did not demonstrate any significant deficits. Normal subjects showed consistently better performance in the right than in the left nostril. The results are interpreted as reflecting the importance of the orbitofrontal cortex in olfactory discrimination. Temporal lobe lesions may disrupt the input to the orbitofrontal cortex, thereby producing poorer performance. The nostril difference in the normal subjects, together with the birhinal impairment in patients with right orbitofrontal damage, suggest a relative advantage of the right orbital region in olfactory processing. 
4	Warm induction blood cardioplegia in the infant. A technique to avoid rapid cooling myocardial contracture. The use of profound hypothermia and total circulatory arrest for repair of heart defects in neonates usually involves a period of systemic and myocardial bypass cooling. Rapid cooling of muscle (skeletal, smooth, and myocardial) can result in contracture through elevation of cytosolic calcium levels. The increased myocardial tone caused by cooling might render the heart more vulnerable to a subsequent period of cardioplegic ischemic arrest. Infants may be more susceptible to contracture because their small body mass allows more rapid myocardial temperature change when prearrest bypass cooling is used. The influence of avoiding rapid myocardial cooling before induced cardioplegic arrest was analyzed in a group of infants weighing less than 6 kg at the time of open cardiac operation. Myocardial ischemic arrest by warm (37 degrees C) induction blood cardioplegia was used in 57 infants and compared with results in 440 infants treated with standard blood cardioplegia. Multivariate logistic regression analysis revealed that patient diagnosis, weight, and age at operation were significant risk factors for operative mortality. The use of warm induction blood cardioplegia had a strongly positive independent effect on survival (p = 0.0003) for any patient weight, age, or diagnostic group. We recommend the avoidance of rapid myocardial cooling on bypass in all patients before induction of cardioplegic ischemic arrest. 
4	Repair of posterior left ventricular aneurysm in a six-year-old boy. Left ventricular aneurysms and diverticula are rarely encountered in the pediatric age group. This paper reports a case of congestive heart failure and mitral regurgitation in a 6-year-old boy with a large posterolateral left ventricular aneurysm. Complete repair was successfully performed by excision of the aneurysm and Dacron patch reconstruction of the left ventricular free wall. The patch extended onto the posterior annulus of the mitral valve, thus restoring the mitral valve to normal geometry and correcting the mitral insufficiency. The surgical literature on congenital cardiac diverticula and acquired aneurysms in children is reviewed and summarized. 
5	The Senior Care Study. The optimal use of medications in acutely ill older patients. Geriatric assessment units have improved pharmacotherapy for their patients by decreasing the number of medications prescribed. The Senior Care Study, a randomized controlled trial, compared a multidisciplinary-team approach to patient care to the standard medical practice of the institution. As a part of the trial, the effectiveness of an interdisciplinary team intervention in improving the use of medications was studied. Study goals were to decrease medications used, decrease unnecessary medications, and improve medication choices in our acutely ill inpatient population. A pharmacist interviewed all experimental patients and patient records, and presented medication concerns and recommendations at a team conference. Medications were counted on admission and on the third day, sixth week, and third month after randomization. Medications were paired with patient problems. Medication:problem pairs were judged as inappropriate choices if there were potential side effects that would affect patient function, and if better alternatives were available. The 215 control and 221 experimental patients in the study were similar in age, sex, place of origin, and number of medications on admission. Experimental patients took fewer medications than controls on the third day (5.3 versus 5.9, P less than .05). Experimental patients received fewer multiple unpaired medications (11% versus 19%, P less than .025) and fewer inappropriate medication choices (20% versus 37%, P less than .005). The results suggest that the team intervention was effective in improving pharmacotherapy in the acute-care setting. 
1	Prostate-specific antigen for staging prior to surgery and for early detection of recurrence after surgery. The exact usefulness of prostate-specific antigen for staging before radical prostatectomy is still unclear. Perhaps the marker's most exciting feature is its value in detecting residual disease after radical prostatectomy. The author also discusses the technical questions in testing and interpretation. 
5	Abdominal aortic aneurysm with perianeurysmal fibrosis: experience from 11 Swedish vascular centers. Case records of 2026 patients operated on because of abdominal aortic aneurysms from 11 Swedish Vascular Centers were reviewed and revealed 98 cases (4.8%) of inflammatory abdominal aortic aneurysm. Also included in this case-control study was an analysis of a randomized group of 82 patients from the same centers who had noninflammatory abdominal aortic aneurysms. Four inflammatory aneurysms were ruptured, compared with 16 in the noninflammatory group (p less than 0.01). A higher proportion of patients with inflammatory abdominal aortic aneurysms had symptoms that led to radiographic investigations. The median erythrocyte sedimentation rate was 39 mm versus 19 mm (26% of patients with inflammatory abdominal aortic aneurysms had erythrocyte sedimentation rates greater than 50 mm; p less than 0.001), and the serum creatinine level was increased in 27 and 8 patients (p less than 0.01) in the inflammatory and noninflammatory groups, respectively. Preoperative investigations revealed ureteral obstruction in 19 patients with inflammatory abdominal aortic aneurysms, of whom 12 had preoperative nephrostomy or ureteral catheter placement. At operation, 20 additional patients exhibited fibrosis around one or both ureters. Although ureterolysis was performed in 19 patients, preoperative and postoperative creatinine levels did not differ between these patients and the conservatively treated ones. Duration of surgery (215 vs 218 minutes), intraoperative blood loss (2085 vs 2400 ml) and complications did not differ significantly between the groups. Overall operative (30-day) mortality was equal (11% vs 12%) but was increased for patients undergoing elective surgery for inflammatory abdominal aortic aneurysms (9% vs 0%; p = 0.03). 
1	The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma. One hundred fifty-one patients with colorectal polyps containing invasive adenocarcinoma treated by resection were studied to determine the incidence of lymph node metastasis and whether lymph node metastasis was related to the depth of invasion. Other variables evaluated included size and configuration of the polyp, grade of adenocarcinoma, presence or absence of lymphovascular invasion, and degree of differentiation. In patients with sessile polyps, the incidence of lymph node metastasis was 10 percent. Eighty percent of these lesions had lymphovascular invasion. For pedunculated polyps, the overall incidence of lymph node metastasis was 6 percent. However, there was no incidence of lymph node metastasis when the depth of invasion was limited to the head, neck, and stalk of the polyp (Levels 1, 2, and 3). Only when the depth of invasion reached to the base of the stalk (Level 4) was the risk of lymph node metastasis high (27 percent). The other risk factors were not associated with lymph node metastasis. We concluded that the most significant risk factor for lymph node metastasis in patients with invasive carcinoma in a polyp was invasion into the submucosa of the bowel wall (Level 4). 
1	Effects of FUdR on primary-cultured colon carcinomas metastatic to the liver. Hepatic arterial infusion of fluorodeoxyuridine (FUdR) has demonstrated efficacy in the treatment of metastatic colorectal carcinoma of the liver. In this study, the direct cytotoxic effect of FUdR was measured on ten metastatic and two primary-site colorectal carcinomas in a primary culture assay system. Overall, clinically achievable concentrations of FUdR (0.4 to 4 microM) induced partial cell kill in 75% of tumors, including a greater than 50% reduction in viable tumor cell number in only two tumors and less than 50% in the remaining seven. Total cell kill was not observed in any tumor. Three tumors were resistant to these FUdR concentrations. Tumor sensitivity correlated with the size of the tumor growth fraction. Increasing the exposure time to FUdR from 3 to 7 days approximately doubled the magnitude of the response. 5-Flurouracil and cisplatin, at clinically achievable concentrations, were more toxic to metastatic tumor cells than FUdR. Because of the limited chemosensitivity of metastatic colorectal tumor cells to FUdR in vitro, we postulate that other mechanisms besides direct cytotoxicity contribute to the clinical efficacy of FUdR in vivo. 
1	Flexible sigmoidoscopy as a screening procedure in rural patients. In this study of flexible sigmoidoscopy as a screening procedure for rural, impoverished patients, 16% of asymptomatic patients who were screened by sigmoidoscopy and 23% of patients with a positive test for fecal occult blood were found to have a polyp or carcinoma. Flexible sigmoidoscopy appears to be an important part of the physical examination of patients older than 50. It is a test that can readily be done by primary care physicians in a rural setting. 
5	Intracatheter streptokinase for recurrent peritonitis in CAPD. Intracatheter streptokinase (SK) is advocated as effective treatment with minimal adverse effects in both recurrent bacterial peritonitis and catheter fibrin blockage in continuous ambulatory peritoneal dialysis (CAPD) patients. We reviewed 35 instillations in 20 patients noting a high (86%) side effect profile consisting of fever, onset of turbid dialysis effluent and/or abdominal pain. SK probably releases fibrin clot containing bacteria, leukocytes and debris from the colonized catheter into the peritoneal cavity causing a "peritonitis-like syndrome" of 1 to 3 days duration. Fungal peritonitis occurred after SK in 2 patients. Failure of SK therapy was encountered in Staphylococcus epidermidis infection (p less than 0.05 versus other organisms), which may be related to its protective capsular polysaccharide slime and ability to adhere to plastic prosthetic devices. SK, in this study, was useful treatment in relapsing bacterial peritonitis (50% overall cure) but failed to correct catheter malfunction. 
1	Capillary hemangioma of the maxilla. A report of two cases in which angiography and embolization were used. This article presents two clinical cases of capillary hemangiomas of the maxilla. Such lesions are rare, as demonstrated by the review of the literature included in this article. The presentation, differential diagnosis, histopathology, management, and follow-up for each case are discussed. Our rationale for approaching these types of lesions, as well as our opinion that microembolization should be considered as a first line approach to treatment, is presented. 
5	Pathological observations of intrahepatic peribiliary glands in 1,000 consecutive autopsy livers. III. Survey of necroinflammation and cystic dilatation. Pathological changes and significance of intrahepatic peribiliary glands, hitherto poorly recognized intrahepatic elements, have been evaluated in our laboratory. In this report, we surveyed necroinflammatory and cystic changes of the peribiliary glands in 1,000 consecutive autopsy livers because these two changes coexisted frequently in the same liver. The necroinflammatory change was found in 228 livers (22.8%) and the cystic change in 202 livers (20.2%), and 103 cases showed both changes in the same liver. The necroinflammatory change was frequently found in intrahepatic cholangitis and extrahepatic biliary obstruction with bacterial infection, suggesting that biliary bacterial inflammation extends into these peribilary glands. This change was also frequent in systemic infection or septicemia without biliary bacterial infection, implying that the peribiliary glands were also damaged in such conditions without direct infection. The cystic change was frequent in livers with portal hypertension or obstruction, adult polycystic disease and necroinflammation of the glands, suggesting that the cystic change of the glands could occur as the result of the disturbance of intrahepatic circulation or as the result of inflammatory destruction of the glandular conduits. Some of peribiliary cysts may be of congenital origin. Dysfunction related to these pathological changes in the glands may diminish seromucous secretion and cause alterations in hepatic bile composition. The cystic change of the glands may retard bile flow by compressing bile duct lumina. 
5	Neonatal small bowel atresia, stenosis and segmental dilatation. In 8 years, 44 neonates were treated for small bowel atresia, stenosis or segmental dilatation by one surgical team. There was a single lesion in 30 infants and 14 had two or more sites of intestinal obstruction. Associated gastrointestinal abnormalities were found in 23 (52 per cent) patients. Resection of the atresia(s) and primary anastomosis were performed in 34 infants and staged procedures were carried out in ten patients with complicated lesions. Patients undergoing staged procedures had a higher complication rate than those having primary repair (six out of ten and 11 out of 34 respectively). The overall initial survival rate was 93 per cent, rising to 100 per cent in those without associated anomalies or prenatal complications, but more than a quarter (27 per cent) of survivors have long-term disabilities. 
2	Disorders of esophageal motility. Patients with esophageal motility disorders usually have dysphagia and many also have chest pain similar to angina. The diagnosis is suggested by the clinical presentation, and supporting evidence is often provided by contrast roentgenography. Esophageal manometry is usually necessary to confirm the diagnosis. Conservative therapy using pharmacologic agents is often useful as an initial trial, although many patients who continue to be symptomatic ultimately require surgical intervention. 
4	Successful treatment of an excimer laser-associated coronary artery perforation with the Stack perfusion catheter. A 64-year-old woman underwent excimer laser angioplasty of the right coronary artery. The procedure was complicated by perforation, which was successfully managed without complication with a Stack perfusion catheter. This report describes successful nonsurgical treatment of laser-induced coronary perforation and makes recommendations for avoiding this complication in other patients. 
2	Extracorporeal cholecystolithotripsy without oral chemolitholysis. One hundred thirty-six patients completed extracorporeal biliary lithotripsy (EBL) for symptomatic cholecystolithiasis. Sonographic evidence of complete clearance of all stone fragments was the only criterion for treatment success, which occurred in 32 of the 71 patients (45%) followed up for 24 weeks and in 36 of the 59 patients (61%) followed up for 52 weeks. The authors' protocol varied from protocols of other researchers primarily in that no adjuvant chemolitholysis was used. However, the number of treatment sessions and total number of shock waves (a maximum of 4,000 shock waves per treatment session, 12,000 shock waves in a patient demonstrating no significant fragmentation, and 20,000 shock waves in a patient whose stones responded well to fragmentation) was higher than those in other reports. The results of treatment and complication rates in this study are comparable with those at centers using both shock-wave lithotripsy and chemotherapy. The authors conclude that EBL is developing into an important alternative to surgery, which was obviated in all patients with complete clearance of fragments from the gallbladder. 
4	Cardiogenic hepatorenal syndrome. A variant of hepatorenal syndrome occurring in patients with chronic congestive heart failure following an episode of cardiogenic pulmonary edema, and in the absence of hypotension, is described. This was observed in 13 patients during an eleven-year period. The clinical picture is characterized by hepatic injury and functional renal impairment. Increase of serum glutamic oxaloacetic transaminase levels as high as 2100 IU; prolongation of prothrombin time; elevation of serum bilirubin, creatinine, blood urea nitrogen, and potassium levels; decrease in urinary sodium excretion; and a normal urinary sediment are the salient laboratory abnormalities of this entity. Treated with conventional medication, the patients' course was fatal in 4 cases. When the splanchnic vasodilator dopamine was added to the patients' management, 5 of 9 patients recovered. Cardiogenic hepatorenal syndrome is a severe but potentially reversible complication of heart failure. The apparently beneficial effect of low-dose dopamine needs further evaluation. 
4	Complications in percutaneous transluminal angioplasty: relationships with patient age. Five hundred consecutive attempted lower limb angioplasties for ischaemic disease (370 patients, mean age 65.6 years, range 33-91 years) were reviewed. Significant complications occurred in 44 cases (8.8%). Nine patients (1.8%) underwent emergency surgery related to a complication. A further 12 patients (2.4%) underwent elective surgery related to a complication. In addition, four patients died within 30 days of the procedure; one following surgery performed because of a complication of angioplasty, one following a myocardial infarction, one following severe bleeding associated with subsequent thrombolytic therapy and one during emergency surgery related to a complication of angioplasty. A correlation was found between complication rate and age. This relationship was independent of the approach to, the position of, and the severity of the treated lesion. Elderly patients are at increased risk of complication in lower limb angioplasty. 
5	Detection of active intraabdominal arterial hemorrhage: value of dynamic contrast-enhanced CT. Contrast-enhanced dynamic CT was used prospectively to diagnose and locate the site of active arterial intraabdominal hemorrhage in 18 patients. Active arterial extravasation was confirmed by angiography in five patients and by immediate surgery in nine. Two patients not undergoing surgery or angiography required multiple blood transfusions to correct rapidly falling hematocrit due to a coagulopathy. One patient died of hypovolemic shock, and autopsy confirmed a large acute retroperitoneal hematoma. Another patient with a splenic laceration and massive hemoperitoneum on CT had no active bleeding at the time of surgery, which was delayed 1 hr from the time of the CT. All patients were clinically thought to be hemodynamically stable and had systolic blood pressures greater than 110 mm Hg at the time of CT. In seven patients, hypotension developed either during (two patients) or immediately after (five patients) CT scanning, necessitating either immediate surgery or angiographic embolization. Contrast-enhanced dynamic CT is valuable in the diagnosis and localization of active arterial intraabdominal hemorrhage. Identification of the anatomic site of this potentially life-threatening hemorrhage is critical in determining whether immediate laparotomy or angiographic embolization is the preferred method of treatment. 
5	Tumorigenic 3T3 cells maintain an alkaline intracellular pH under physiological conditions. One of the earliest events in the response of mammalian cells to mitogens is activation of Na+/H+ exchange, which increases intracellular pH (pHin) in the absence of HCO3- or at external pH values below 7.2. The proliferative response can be blocked by preventing the pHin increase; yet, the proliferative response cannot be stimulated by artificially raising pHin with weak bases or high medium pH. These observations support the hypothesis that optimal pHin is a necessary, but not sufficient, component of the proliferative-response sequence. This hypothesis has recently been challenged by the observation that transfection of NIH 3T3 cells with yeast H(+)-ATPase renders them tumorigenic. Although previous measurements indicated that these transfected cells maintain a higher pHin in the absence of HCO3-, whether H(+)-ATPase transfection raised the pHin under physiologically relevant conditions was not known. The current report shows that these transfected cells do maintain a higher pHin than control cells in the presence of HCO3-, supporting the possibility that elevated pHin is a proliferative trigger in situ. We also show that these cells are serum-independent for growth and that they glycolyze much more rapidly than phenotypically normal cells. 
5	The significance of gastrinomas found in peripancreatic lymph nodes. A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma. 
1	Prognostic factors in craniofacial surgery. From 1979 to 1989, 21 patients underwent craniofacial resection for malignancies involving the anterior skull base. Histologic types included 8 squamous cell carcinomas, 3 chondrosarcomas, 2 melanomas, 2 basal cell carcinomas, 2 adenocarcinomas, 2 poorly differentiated carcinomas, 1 malignant schwannoma, and 1 malignant hemangiopericytoma. Survival was 57%, with follow-up of 41 months. A 50% complication rate included osteomyelitis, cerebrospinal fluid rhinorrhea, meningitis, brain abscess, epidural abscess, and syndrome of inappropriate antidiuretic hormone. Recurrent disease occurred in 9 patients (41%), the most reliable predictor being dural invasion indicated preoperatively by CT scan or at operation. Patients demonstrating dural involvement (N = 9) had a 22% survival rate, while patients without (N = 12) had a survival rate of 83%. The impact of dural invasion on long-term survival is emphasized. Though complications were frequent, long-term results were favorable. 
5	Supplemental emergent chest computed tomography in the management of blunt torso trauma. The efficacy of conventional chest X-ray (CXR) in comparison to chest computed tomography (CCT) in acutely injured blunt trauma patients was examined. Over a 21-month period, 50 patients underwent CXR and CCT according to a standard protocol, and their films and records were reviewed retrospectively. Hemo- and/or pneumothorax (HPTX) was noted in 12 patients (five by CXR, 12 by CCT). Pulmonary contusion (PC) was identified in ten patients (four by CXR, ten by CCT). Three additional false positive PC were diagnosed by CXR. Therapy changes based upon CCT findings occurred in seven of seven HPTX and five of six PC. The two imaging techniques were complementary in detecting fractures. Atelectasis was a common CCT finding (58% incidence). Chest X-ray is less sensitive than chest computed tomography in the detection of HPTX (42% vs. 100%) and PC (40% vs. 100%). Emergent chest computed tomography is recommended in stable patients with: 1) blunt high-energy torso trauma, 2) "cross-body" injury pattern, and/or 3) a mechanism of injury suggestive of chest trauma. 
5	Saccular aneurysms of the distal anterior cerebral artery. We report a series of 42 consecutive patients with aneurysms of the distal anterior cerebral artery (ACA). Of these, 36 patients had one aneurysm, 5 had two aneurysms, and one had three aneurysms. Thirty patients had a ruptured distal ACA aneurysm; among these patients, the size of the aneurysm was less than 5 mm in diameter in 20, 6 to 10 mm in 7, and larger than 11 mm in 3. Eighteen patients (42.9%) had multiple aneurysms, and distal ACA aneurysms were responsible for a subarachnoid hemorrhage in 10. Thirty-four patients underwent direct surgery, and 30 of these had excellent outcomes 3 months after surgery. The treatment of patients with distal ACA aneurysms is often technically difficult, because of their broad neck configuration and the coexistence of other aneurysms. Nevertheless, the present study emphasizes that distal ACA aneurysms tend to bleed, irrespective of their size, and that excellent outcomes are obtainable by direct surgery. 
4	Does isoflurane lead to a higher incidence of myocardial infarction and perioperative death than enflurane in coronary artery surgery? A clinical study of 1178 patients To examine if the choice of volatile agents influences cardiac outcome in coronary artery surgery, 1178 patients undergoing elective coronary artery bypass grafting without additional operations received enflurane (608) or isoflurane (570) as their primary anesthetics. The inspired concentration of volatile agent (administered with 50% nitrous oxide) was adjusted depending on the level of blood pressure at the discretion of the anesthesiologist. In addition to the volatile agent assigned, each patient received small doses of fentanyl at induction and before sternotomy (total 0.006-0.008 mg/kg). The groups did not differ in preoperative and surgical characteristics except for a more frequent history of renal dysfunction in patients given isoflurane. The rates of postoperative myocardial infarction, administration of positive inotropic agents at the time of weaning from cardiopulmonary bypass, and in-hospital deaths in the enflurane and isoflurane groups were 1.8% and 4.0% (P less than 0.05), 4.9% and 8.1% (P less than 0.05%), and 0.3% and 2.1% (P less than 0.01), respectively. Although the mechanism of the adverse effects of isoflurane could not be clarified in this study, these results demonstrate that the use of isoflurane could be inappropriate in patients undergoing coronary artery bypass grafting. 
5	The morbidity and financial impact of colostomy closure in trauma patients. During a 10-year period, 87 patients who had undergone elective colostomy closure at Bellevue Hospital were retrospectively reviewed in order to evaluate the morbidity of colostomy closure after traumatic injury and its financial impact. Sixty-two per cent of the colostomies were in the left colon and 38% were right sided. The interval from the original injury to colostomy takedown varied from 20 to 465 days, with a mean of 144 days. The mean postoperative hospital stay for the entire group was 15.13 days at a cost of $13,995. There were no deaths and no anastomotic leaks in the entire series, but a morbidity rate of 25% ensued. Small bowel obstruction was the most frequent significant complication, occurring in ten patients (11.5%) and resulting in a prolongation of hospital stay by 7 days at an additional cost of $6,500 per patient. One additional patient developed a subphrenic abscess which required operative drainage, necessitating an additional 24 days in the hospital at an increased cost of $22,200. Other complications which did not prolong hospital stay included eight superficial wound infections, one transient respiratory failure, and two patients who returned at a later date with incisional hernias at the stoma site. The 25% morbidity encountered in this series suggests that colostomy closure is not a low-morbidity procedure and should be considered as an important factor favoring primary repair. Coupled with the significant financial impact of both colostomy formation and takedown, ample justification exists for greater efforts in avoiding colostomy formation whenever feasible. 
1	Reversible hearing loss from cerebellopontine angle tumors. We report two patients who presented with a dramatic recovery from severe sensorineural hearing loss after total surgical removal of cerebellopontine angle tumors (meningioma and jugular foramen neurinoma). The factors that differentiate these "non-acoustic tumors" in relation to the prognosis for hearing are discussed. A surgical approach that maintains the labyrinthine structure and preserves the arachnoid membrane of the superior cerebellopontine angle cistern during tumor removal is stressed. 
5	Fine needle aspiration of pancreatic fluid collections. The complications of pancreatitis remain diagnostic and therapeutic challenges. Patients with simple pancreatitis, pancreatic necrosis, pseudocyst, noninfected fluid collection or abscess may all have similar clinical pictures. During the last decade computerized tomography (CT)-guided needle aspiration of peripancreatic fluid collections has been increasingly used as a diagnostic tool for pancreatic abscesses. This study reviewed the effectiveness of CT-guided needle aspiration of peripancreatic fluid collections at our institution in terms of diagnostic accuracy, correlation with eventual outcome, and safety. Charts of patients who underwent needle aspiration of de novo peripancreatic fluid collections over the past 2 years were reviewed. Thirty-five patients underwent 50 aspirations. Eleven patients (31%) had a positive aspirate culture; seven of these had a positive Gram's stain. There were no false positive Gram's stains but four false negatives. Twenty-four (69%) patients had negative aspirate Gram's stains and cultures. Patients with positive aspirate cultures were treated with antibiotics only (2), CT-guided drain placement (7), or surgical drainage (3). The mortality related to each of these therapeutic modalities was 50 per cent, 0 per cent, and 33 per cent, respectively. Of the 24 patients with negative aspirate cultures, five had no further treatment, 12 received antibiotics, and six underwent CT drain placement. All these patients survived. There was one false negative aspirate culture. This patient underwent delayed surgical drainage but expired. There were no major complications from CT-guided aspiration. CT-guided aspiration appears to be a safe and reliable method of diagnosing infection in peripancreatic fluid collections. 
2	Atracurium decay and the formation of laudanosine in humans. Several groups of investigators have reported that the plasma concentrations of laudanosine, a metabolite of atracurium, are high immediately after administration of atracurium and thereafter decline. Such a time profile of a metabolite in plasma is very unusual. The authors describe a model of atracurium decay and laudanosine disposition that satisfactorily explains these data. The model reveals the following: 1) each atracurium molecule is degraded into two of laudanosine; 2) the generation of laudanosine occurs through two processes--a rapid one, involving approximately 31% of the atracurium dose and proceeding with a half-life of 0.25 min, and a slower one, involving the residual 69% and proceeding with a half-life of 51 min; 3) atracurium degradation by Hofmann elimination proceeds in the central and the noncentral compartments; 4) laudanosine formed from atracurium gains access to its central compartment and disappears from plasma in a biexponential pattern; 5) in cirrhotic patients, only 18% of the atracurium dose is degraded rapidly and laudanosine is disposed of more slowly. The authors propose that the rapid degradation of atracurium in plasma proceeds through a nucleophilic substitution reaction, with plasma nucleophiles substituting for the laudanosine moiety in atracurium. Because both laudanosine moieties in atracurium are required to establish and sustain plasma concentrations of laudanosine, excretion of atracurium or its degradation through pathways not generating laudanosine must be small. 
4	Different plasma ionized calcium correlations with blood pressure in high and low renin normotensive adults in Utah. Plasma ionized calcium levels have been shown to be lower than normotensive control levels in hypertensive patients with low plasma renin activity and higher than control levels in hypertensive patients with high renin activity; they did not differ between high and low plasma renin activity groups of normotensive controls. To see if ionized calcium may have different relationships with blood pressure across renin categories in normotensive individuals, plasma ionized calcium was measured on 875 healthy individuals, ages 3 to 83, who had never been diagnosed as having hypertension. Blood pressures were measured in the sitting, standing, and supine positions, along with pressures measured during two stress maneuvers: isometric handgrip and a 50 degrees tilt from a supine position. There was no linear correlation of blood pressure with plasma ionized calcium in the entire sample of youths or adults. However, after dividing the adults into tertiles based on plasma renin activity, there were significant inverse correlations between ionized calcium and systolic and diastolic blood pressure in the low renin group (r = -0.16 to -0.25, P less than or equal to .05), while the systolic blood pressure correlations were significantly positive in the high renin group (r = 0.14 to 0.22, P less than or equal to .05). Adults with normal renin levels did not have any significant correlations of plasma ionized calcium with blood pressure. These confounding effects of renin were greater for systolic than for diastolic blood pressure. These correlations within renin tertiles occurred even though there were no differences in mean blood pressure, plasma ionized calcium, total plasma protein and plasma sodium across renin categories. 
5	Infection with HIV as a risk factor for adverse obstetrical outcome. We carried out a case-control study to investigate the role of sexually transmitted diseases (STDs), including infection with HIV, as risk factors for adverse outcome of pregnancy. Overall, 1507 women were enrolled within 24 h of delivery. Cases (n = 796) were mothers of low-birthweight infants (less than 2500 g) or of stillborns. Low-birthweight infants were divided into preterms (n = 373) and neonates small for gestational age (n = 234). Stillborns were separated into intrauterine fetal deaths (n = 120), and intrapartum fetal deaths (n = 69). Controls were selected from mothers delivering a live baby of greater than or equal to 2500 g (n = 711). The maternal HIV seroprevalence in the control group was 3.1%. Prematurity was associated with maternal HIV antibody [8.6% seropositive; adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.1-4.0], as was being born small for gestational age (7.7% seropositive; adjusted OR 2.3; 95% CI 1.2-4.2). In mothers who delivered a stillborn baby, both intrauterine fetal death (11.7% seropositive; adjusted OR 2.7; 95% CI 1.3-5.5) and intrapartum fetal death (11.6% seropositive; adjusted OR 2.9; 95% CI 1.3-6.5) were independently associated with HIV seropositivity in the mother. Maternal syphilis was confirmed as an important risk factor for intrauterine fetal death (14.3% positive; adjusted OR 4.8; 95% CI 2.4-9.5). No significant association was found between other STDs, including gonococcal and chlamydial infection, and adverse obstetrical outcome. These results suggest an association between maternal HIV infection and adverse obstetrical outcome, defined as low birthweight and stillbirth. 
1	Preliminary studies for an immunotherapeutic approach to the treatment of human myeloma using chimeric anti-CD38 antibody. Multiple myeloma is a disease in which conventional chemotherapy has only limited value, but which may be ideal for treatment with passive antibody against a suitable cell surface antigen on the neoplastic plasma cell. The CD38 antigen is known to be present on the majority of neoplastic plasma cells, and this was confirmed by detailed examination of bone marrow aspirates from three patients. Strong expression of CD38 was confined to cells which, by the criteria of light-scattering profiles and possession of cytoplasmic Ig, were plasma cells. The vast majority of neoplastic plasma cells appeared to be involved. Using a cell line as a model, it was found that the CD38 antigen acts as a target for a chimeric antibody prepared from the antibody OKT10. The chimeric antibody consists of the Fab portion of the mouse monoclonal antibody linked by a stable thioether bond to an Fc molecule derived from human IgG1, thereby forming mouse Fab-human Fc. In contrast to the parent antibody, the chimeric molecule mediates antibody-dependent cellular cytotoxicity (ADCC) very efficiently with human blood mononuclear effector cells, and is effective at low concentration. Also, even though the CD38 antigen is present on natural killer cells, there appears to be little deleterious action of the antibody on effector cell function. The antibody also failed to affect the growth of progenitor cells of the granulocyte/macrophage or erythroid lineages present in normal bone marrows, despite the suspicion that these cells express the antigen. Other advantages of the CD38 molecule are that it is not found in the serum of patients with myeloma, and it does not appear to modulate in vitro. Fourteen patients with florid myeloma and on various chemotherapeutic regimes had an undiminished capacity to mediate ADCC with the chimeric antibody, when compared with normal individuals. The maintenance of ADCC activity, coupled with the known suppression of the antibody response in these patients, augers well for treatment with chimeric antibody. 
2	Immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa. Specimens of normal and neoplastic colonic mucosa from 52 patients were analysed by immunohistochemistry using a monospecific polyclonal antiserum against human pancreatic secretory trypsin inhibitor (PSTI). In normal colonic mucosa PSTI was found in the goblet cells in the basal parts of the crypts. In adenomas of tubular, villous, and tubulo-villous types PSTI was also found in the upper parts of the polyps, usually occurring in the regeneration zone. There was a more intense staining reaction in polyps with increased atypia. Carcinomas of different types and of various grades of differentiation and of in situ type did not contain PSTI. These findings indicate that PSTI could be a marker for adenomatous rather than carcinomatous epithelium in the colon. Furthermore, the absence of the inhibitor in malignant cells might facilitate tissue invasion by malignant cells because of deficient protease inhibition. 
3	Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial. Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively. 
4	Alterations in aldosterone secretion and metabolism in low renin hypertension. Low renin essential hypertensives (LRH) have normal plasma aldosterone levels which are inappropriately high in relation to their PRA. Posture is the major determinant for plasma aldosterone and PRA levels, but it is not known whether postural increments (delta) of plasma aldosterone and (delta) PRA are also abnormal in LRH. To evaluate this, LRH (n = 8), normal renin hypertensives (NRH; n = 9), normotensive controls (n = 18), and subjects with idiopathic hyperaldosteronism (IHA; n = 5) were studied in a metabolic unit on a controlled diet over 7 days. Overnight supine and 4-h upright PRA, plasma aldosterone, and 24-h urinary tetrahydroaldosterone (THA) and aldosterone secretion rates (ASR) were measured. The delta in plasma aldosterone after 4 h of upright posture was not different in the four groups. The ratio of delta plasma aldosterone/delta PRA, however, was elevated in both IHA and LRH compared to that in NRH and normals. THA excretion was also elevated in IHA and LRH, but LRH had a normal ASR. This resulted in a higher fractional THA excretion (THA/ASR) in LRH compared to the other three groups. These data further support enhanced adrenal angiotensin-II sensitivity in LRH. Aldosterone was preferentially metabolized to THA in LRH. Since THA has reduced biological activity, this may be a compensatory mechanism to reduce mineralocorticoid activity in LRH. 
5	Flow cytometric detection of tumor metastases during urologic surgery. Flow cytometric studies were performed on peripheral blood obtained before, during, and subsequent to urologic surgery. The results suggest that 7 of 11 patients had a brief period during surgical manipulation when they had cells from the primary surgical site in the peripheral blood. Concentration of such cells was generally less than 10(2)/mL even during the intraoperative period. These findings suggest that perioperative tumor seeding is a real concern, and that flow cytometry can be used to study maneuvers to reduce its incidence. 
1	Occupational sunlight exposure and melanoma in the U.S. Navy. Melanoma is the second most common cancer, after testicular cancer, in males in the U.S. Navy. A wide range of occupations with varying exposures to sunlight and other possible etiologic agents are present in the Navy. Person-years at risk and cases of malignant melanoma were ascertained using computerized service history and inpatient hospitalization files maintained at the Naval Health Research Center. A total of 176 confirmed cases of melanoma were identified in active-duty white male enlisted Navy personnel during 1974-1984. Risk of melanoma was determined for individual occupations and for occupations grouped by review of job descriptions into three categories of sunlight exposure: (1) indoor, (2) outdoor, or (3) indoor and outdoor. Compared with the U.S. civilian population, personnel in indoor occupations had a higher age-adjusted incidence rate of melanoma, i.e., 10.6 per 100,000 (p = .06). Persons who worked in occupations that required spending time both indoors and outdoors had the lowest rate, i.e., 7.0 per 100,000 (p = .06). Incidence rates of melanoma were higher on the trunk than on the more commonly sunlight-exposed head and arms. Two single occupations were found to have elevated rates of melanoma: (1) aircrew survival equipmentman, SIR = 6.8 (p less than .05); and (2) engineman, SIR = 2.8 (p less than .05). However, there were no cases of melanoma or no excess risk in occupations with similar job descriptions. Findings on the anatomical site of melanoma from this study suggest a protective role for brief, regular exposure to sunlight and fit with recent laboratory studies that have shown vitamin D to suppress growth of malignant melanoma cells in tissue culture. A mechanism is proposed in which vitamin D inhibits previously initiated melanomas from becoming clinically apparent. 
5	Effect of dietary alpha-linolenic acid on growth, metastasis, fatty acid profile and prostaglandin production of two murine mammary adenocarcinomas. The purpose of this study was to determine whether dietary (n-3) fatty acids would affect mammary tumor growth and metastasis. Weanling female BALB/c mice were fed diets that contained 10% corn oil (CO), linseed oil (LO) or a fish oil-corn oil mix (FO) for 3-8 wk prior to receiving subcutaneous injections of one of two syngeneic mammary tumor cell types (410 and 410.4). Tumor growth was assessed by monitoring mean tumor diameter and tumor weight upon removal. Feeding LO, but not FO, reduced the growth (p less than 0.05) of 410.4 mammary tumors compared with growth in those fed CO. Metastasis data paralleled the tumor growth rate. Feeding LO and FO enhanced (p less than 0.005) incorporation of (n-3) fatty acids into tumors. Tumor prostaglandin E (PGE) production was reduced (p less than 0.005) by LO and FO, compared with CO. FO feeding reduced 410.4 tumor PGE synthesis more (p less than 0.05) than LO feeding, yet tumor growth was only inhibited by LO. These data suggest an inhibitory effect of dietary linolenic acid [i.e., 18:3 (n-3)] on mammary tumor growth and metastasis. However, this effect did not directly correlate with diet-induced changes in PGE synthesis. 
4	A note on the measurement of hypertension in HHANES Using data from the HHANES, we found the rates of elevated blood pressure readings on clinical examination to be extremely low for a sample of Mexican American and Puerto Rican women. The prevalence rates were one-fourth to one-fifth the rates found for a comparable sample of White women from NHANESII. These findings are discrepant with the little that is known about hypertension prevalence among Hispanics and with estimates of hypertension prevalence for Mexican Americans and Puerto Ricans drawn from NHANESII. While our HHANES samples women had much lower rates of clinical high blood pressure than Whites, they reported hypertension histories in excess of Whites. Rates of medicine usage among Hispanics were insufficiently large for effective treatment to explain the disparity. The prevalence estimates increased, but the relative discrepancies remained when we altered our sample specifications and clinical high blood pressure measure. A possible explanation for these discrepancies is that few physicians performed the majority of blood pressure readings in our HHANES sample. This may have been statistically inefficient. The discrepancies noted suggest that HHANES may not be a reliable source of information on hypertension among Hispanic women. 
5	Brachial-jugular polytetrafluoroethylene fistulas for hemodialysis. A retrospective analysis was made of 16 patients who had received a brachial-jugular polytetrafluoroethylene (PTFE) graft for hemodialysis. In four patients, the procedure was used to treat malfunctioning brachio-axillary fistulas due to long venous stenosis in the axillary vein. In 12 other patients, the operation was chosen in cases of exhaustion of the veins in the upper extremity because of previous multiple failed fistulas. Two patients died with a functioning fistula 7 and 10 months after placement of the graft of causes unrelated to the vascular access. The other 14 patients retained functioning fistulas between 8 and 26 months after construction of the shunt. Three patients needed graft thrombectomy to treat occlusive episodes. No venous stenosis was found in a postoperative fistulography made in those patients. One patient needed substitution of a graft segment due to stenosis of the prosthesis crossing over the clavicle. We believe that the brachial-jugular graft is a procedure that can be considered as vascular access for hemodialysis in cases where the use of veins in the upper extremity and the axilla is not possible. 
5	Potential value of hormone receptor assay in carcinoma in situ of breast. The estrogen receptor (ER) expression of invasive breast cancer has been extensively studied both biochemically and with specific monoclonal antibodies against ER. Relatively few studies have attempted to characterize ER pattern in breast carcinoma in situ (CIS) and in other premalignant lesions. In the current study, the authors investigated the pattern of ER expression in 62 cases of breast CIS, 30 of which had a component of invasive cancer, and 36 cases of atypical hyperplasia. Paraffin sections of formalin-fixed breast tissue underwent enzyme pretreatment to expose nuclear antigenic sites as previously described. Breast tissues then underwent estrogen immunocytochemical assay using specific monoclonal antibodies (Abbott Laboratory, Chicago, IL). The cases were evaluated for heterogeneity, intensity of staining, and percentage of ER-positive cells. An attempt was made to study the relation between the pattern of ER expression, nuclear pleomorphism, and type of CIS. The results of ER immunocytochemical assay showed positive nuclear staining for ER in 75% of the CIS, 73% of CIS with invasive cancer, and 100% of atypical hyperplasias. ER expression in CIS agreed with that in the invasive carcinoma in 29 of 30 cases. This study also suggests that comedocarcinoma has a higher incidence of negative ER expression than the other types of CIS, particularly when it is associated with significant nuclear pleomorphism. There was no significant difference in ER tumor heterogeneity between premalignant and malignant lesions. 
4	Two-way factorial study of alcohol and salt restriction in treated hypertensive men. The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01). 
3	Plasticity in the aging brain. Reversibility of anatomic, metabolic, and cognitive deficits in normal-pressure hydrocephalus following shunt surgery. The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year-old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease. 
1	Data compression: effect on diagnostic accuracy in digital chest radiography. High-resolution digital images make up very large data sets that are relatively slow to transmit and expensive to store. Data compression techniques are being developed to address this problem, but significant image deterioration can occur at high compression ratios. In this study, the authors evaluated a form of adaptive block cosine transform coding, a new compression technique that allows considerable compression of digital radiographs with minimal degradation of image quality. To determine the effect of data compression on diagnostic accuracy, observer tests were performed with 60 digitized chest radiographs (2,048 x 2,048 matrix, 1,024 shades of gray) containing subtle examples of pneumothorax, interstitial infiltrate, nodules, and bone lesions. Radiographs with no compression, with 25:1 compression, and with 50:1 compression ratios were presented in randomized order to 12 radiologists. The results suggest that, with this compression scheme, compression ratios as high as 25:1 may be acceptable for primary diagnosis in chest radiology. 
2	A simple score for the identification of patients at high risk of organic diseases of the colon in the family doctor consulting room. The Local IBS Study Group. In order to develop a scoring system for selecting patients at high risk of organic diseases of the colon, who would need a colonoscopy or a barium enema, we conducted a study with 14 GPs in the local health care district of Modena. Over one year, 254 consecutive patients who consulted their GP for chronic abdominal pain were asked to answer a guided questionnaire. A checklist of simple parameters suggestive of the presence of organic diseases of the colon was also registered by the GP. For the final diagnosis, the patients underwent either a colonoscopy or a barium enema. Data collected were analysed by means of a stepwise logistic regression analysis to obtain a weighted score for the diagnosis of either irritable bowel syndrome (score less than 0) or organic disease (score greater than 0). Out of the 25 parameters explored, six were significantly more common among patients with organic disease and weighted as positive score (namely ESR greater than 17 mm, first hour, history of blood in the stool, leukocytosis greater than 10,000 cm3, age greater than 45 years, slight fever and presence of neoplastic colonic diseases in first-degree relatives). On the contrary, five parameters were more frequent among patients with irritable bowel syndrome and weighted as negative score (namely visible distension of the abdomen, feeling of distension, presence of irritable bowel syndrome in first degree relatives, flatulence and irregularities of bowel movement). Our scoring system correctly classified 83.5% of the cases, and it was very sensitive (82.4%) for the diagnosis of organic disease. 
3	Vagus nerve stimulation in humans: neurophysiological studies and electrophysiological monitoring. Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus-nerve-evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 microV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep. 
5	Clinical evaluation of an acetaminophen meter for the rapid diagnosis of acetaminophen intoxication. STUDY OBJECTIVES: To test the accuracy of a newly developed meter that determines serum acetaminophen concentration after a 30-second analysis of one drop of whole blood. DESIGN: Sixty-six blood samples from patients with known or suspected drug overdose were analyzed for the presence of acetaminophen. In all cases determination of serum acetaminophen concentration was performed simultaneously with the meter and by a reference laboratory. SETTING: Eligible patients were those who presented during a nine-month period to the emergency departments of two tertiary care hospitals (including a pediatric hospital). RESULTS: Thirty-one specimens had a laboratory-confirmed detectable acetaminophen concentration. The meter identified these toxic specimens in all cases; there were no false-negatives (sensitivity, 100%). Among the 35 specimens not containing acetaminophen, the meter invariably confirmed a nondetectable serum acetaminophen concentration (specificity, 100%). Acetaminophen measurements by the meter correlated strongly with laboratory determinations (r = .985, P less than .001). Repeated testing of one specimen documented the precision and reproducibility of the meter's analysis; mean coefficient of variation was .08 in measuring toxic acetaminophen concentrations. Drug coingestion had no significant effect on the accuracy of the meter. Instrument accuracy was maintained after more than 100 uses without recalibration. CONCLUSIONS: This meter identifies the possibility of rapid and accurate determinations of serum acetaminophen concentration. The instrument is ideally suited for patients with acetaminophen poisoning in whom expeditious and appropriate administration of antidotal therapy is desired. 
2	Modulation of mediator release from human intestinal mast cells by sulfasalazine and 5-aminosalicylic acid. Intestinal mast cells are thought to contribute to the mucosal inflammation in ulcerative colitis and Crohn's disease through release of inflammatory mediators. Since sulfasalazine and its metabolite 5-aminosalicylic acid are effective therapeutic agents in inflammatory bowel disease and have been shown to inhibit generation of inflammatory products in other cells, we examined the effect of these agents in vitro on human intestinal mast cell mediator release. Sulfasalazine (5 x 10(-4)-10(-3) M) was found to significantly enhance goat anti-human IgE-induced histamine release from intestinal mast cells, which is the same response as seen in human blood basophils, whereas its metabolite 5-aminosalicylic acid was an effective inhibitor of stimulated histamine release in both mast cells and basophils. 5-Aminosalicylic acid also inhibited production of prostaglandin D2 by the stimulated intestinal mast cells. Sulfasalazine alone, without immunologic stimulation, did not induce histamine release from mast cells or basophils, but the enhancement of ongoing mast cell activation by sulfasalazine may explain some cases of adverse reactions to the drug. The inhibition of mast cell histamine release and prostaglandin generation by 5-aminosalicylic acid demonstrates a potential therapeutic modality of this agent. 
2	Somatostatin prevents acute pancreatitis after pancreatic duct sphincter hydrostatic balloon dilation in patients with idiopathic recurrent pancreatitis. The purpose of this study was to determine whether prophylactic somatostatin infusion can prevent pancreatitis after hydrostatic balloon dilation of the pancreatic duct sphincter segment in 16 patients with idiopathic recurrent pancreatitis. This study demonstrated that prophylactic administration of somatostatin before, during, and after the procedure diminished the incidence and severity of acute pancreatitis. We recommend consideration of such prophylaxis in patients undergoing this procedure. 
4	Evidence for decreased coronary flow reserve in viable postischemic myocardium. To try to unravel the complexity and heterogeneity of the "no-reflow" phenomenon and its underlying mechanisms, we studied tissue perfusion in reperfused heart muscle by using tracer microspheres in an anesthetized dog model of 90-minute coronary occlusion followed by reperfusion for 2 1/2 hours, 24 hours, or 1 week. Regional myocardial blood flow was determined both in basal flow conditions and during reactive hyperemia. The effect of intracoronary adenosine administration was examined, and the ultrastructure of postischemic myocardium was analyzed. In viable reperfused tissue (as delineated by triphenyltetrazolium chloride staining), reflow in basal conditions is unimpaired. Coronary flow reserve (as approximated by peak reactive hyperemic flow) is intact at the start of reperfusion, decreases by more than half after 2 1/2 hours, and recovers completely within 1 week. This impairment of coronary reserve can be relieved by intracoronary adenosine administration. On ultrastructural examination, the capillaries are patent. On the other hand, in irreversibly damaged myocardium, both the basal reflow impairment and the decrease in coronary flow reserve are severe and permanent. Coronary flow reserve is already decreased at the start of reperfusion, and the pharmacological intervention has no beneficial effect. Ultrastructurally, extracellular and intracellular edema invariably are present, whereas the vascular endothelium is damaged and the capillaries are packed with red blood cells. We conclude that the no-reflow phenomenon (i.e., mechanical obstruction to blood flow) is limited to infarcted tissue. In viable myocardium, however, coronary flow reserve is transiently diminished, probably because of washout and subsequent insufficient availability of the chemical mediator adenosine after breakdown and slow recovery of the precursor ATP pool. 
4	Prevention of renal disease and conservation of renal function. In summary, we have reviewed some of the most frequently encountered areas of prevention of renal failure in the elderly. They include obstruction, hypertension, drug interaction, and inappropriate use of drugs and the silent killer of the elderly, renal carcinoma. Only by a thorough understanding of the altered physiology of the aging kidney can the physician avoid making the same mistakes when new drugs are developed or new types of diseases are encountered. Proper early diagnosis and understanding the guidelines to therapy in these conditions, can save huge human costs in terms of mortality, morbidity, and money. 
4	Greenfield filter as primary therapy for deep venous thrombosis and/or pulmonary embolism in patients with cancer. In 1985, as a result of the high complication rate associated with anticoagulants in patients who have cancer and deep venous thrombosis (DVT) and/or pulmonary embolism (PE), we established a policy of placing Greenfield filters (GFs) as primary therapy instead of anticoagulation. Since 1985 we have been asked to consult in the treatment of 18 patients with cancer and with DVT and/or PE, and we have placed a GF in each of these patients. This represented 34% (18/53) of the filters placed during that same period. Over the same 4-year period, 11 patients with cancer and DVT and/or PE underwent anticoagulation therapy. The purpose of this study was to compare the results of anticoagulation versus GF insertion in these two groups of patients. A significantly higher number of major complications (n = 4) occurred in the anticoagulation group (p less than 0.05, Fisher's exact test) than in the GF group (n = 0). The four complications that occurred in the anticoagulation group included three bleeding episodes (tumor bleeding, gastrointestinal bleeding, and hip hematoma) and one PE, despite adequate anticoagulation. Two patients died as a direct result of these complications (PE and gastrointestinal bleeding). The three patients with bleeding complications each required a transfusion of more than 3 units of blood. All four of the patients with complications had metastatic disease (pancreatic carcinoma, chronic lymphocytic leukemia, prostate carcinoma, and uterine carcinoma). Although this is a small, nonrandomized, nonprospective study, the data seem to indicate that GF placement is safer than anticoagulation for DVT or PE in patients with cancer and particularly in patients with metastatic disease. We conclude that GF insertions may be a better primary treatment than anticoagulation. 
3	Perception and action in 'visual form agnosia'. A single case study of a patient with 'visual form agnosia' is presented. A severe visual recognition deficit was accompanied by impairments in discriminating shape, reflectance, and orientation, although visual acuity and colour vision, along with tactile recognition and intelligence, were largely preserved. Neuropsychological and behavioural investigations have indicated that the patient is able to utilize visual pattern information surprisingly well for the control of hand movements during reaching, and can even read many whole words, despite being unable to make simple discriminative judgements of shape or orientation. She seems to have no awareness of shape primitives through Gestalt grouping by similarity, continuity or symmetry. It is proposed that many of these perceptual disorders might be the combined result of (1) a selective loss of the cortical elaboration of the magnocellular visual processing stream, and (2) a selective output disconnection from a central processor of visual boundaries and shape primitives in the occipital cortex. 
1	"Pinch modification" used to repair a large surgical defect on the scalp: other proposed uses. Dr Peng's "pinch modification" of the linear advancement flap, a reconstructive technique used to correct surgical wounds on the nose and suggested as a surgical alternative in other non-hair-bearing skin, was used successfully to correct a surgical defect of 55 mm in diameter located on the occipital area, on hair-bearing skin. Other possible uses for this technique are suggested. 
1	Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides. A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity. Dose calculations are performed using a radionuclide-specific absorbed dose point kernel in the form of a lookup table. The method described yields the spatially varying dose delivered to tumor and normal tissue volumes from a patient-specific cumulated activity distribution in a clinically implementable manner. This level of accuracy in determining normal tissue and tumor doses may prove valuable in the evaluation and implementation of radionuclides and radiolabeled compounds for therapeutic purposes. 
2	Isolated ventral pancreatitis in a patient with pancreas divisum. A previously healthy 22-yr-old woman was found to have chronic pancreatitis restricted to the ventral pancreas in association with pancreas divisum. When conservative treatment failed, sphincteroplasty of both papillae was performed with good results. This well-documented case represents a clear exception to the commonly held concept that obstruction of the dorsal duct is the essential pathogenic factor in the development of pancreatitis associated with pancreas divisum. The importance of visualizing both the dorsal and ventral pancreatic ducts to direct therapy for patients with idiopathic pancreatitis is discussed. Theories of the pathogenesis of concomitant pancreatitis and pancreas divisum are reviewed. 
4	Pulmonary hypertension after heparin-protamine: roles of left-sided infusion, histamine, and platelet-activating factor. Severe pulmonary hypertension after protamine neutralization of heparin is an infrequent but life-threatening event following cardiopulmonary bypass. The effect of left ventricular infusion of protamine on pulmonary hypertension as well as a possible role of platelet-activating factor (PAF) or histamine in the heparin-protamine reaction was investigated in 30 pigs in four different groups during general anesthesia. Group 1 animals received 250 IU/kg heparin, followed by 100 mg protamine intravenously after 15 min. In group 2 protamine was infused into the left ventricle. Group 3 animals received the histamine H1- and H2-antagonists clemastine and ranitidine 5 min before protamine infusion. In group 4 the PAF receptor blocker WEB 2086 was given 5 min before protamine. Platelet-activating factor was measured by a bioassay in serum samples of group 1 and group 4 animals. In all four groups protamine caused severe pulmonary hypertension, thromboxane A2 release, and a transient decrease in leukocyte counts. No PAF release was detected after protamine infusion. Neither left ventricular infusion of protamine nor histamine or PAF antagonists prevented or attenuated the reactions after protamine infusion. The authors conclude that left ventricular infusion of protamine provides no protection from pulmonary hypertension, and that histamine and PAF are not involved in the acute pulmonary vasoconstriction after protamine neutralization of heparin. 
3	Litigation and employment status: effects on patients with chronic pain. In order to study the effects of compensation and litigation, 201 chronic pain patients were selected from a sample of 444: 99 were working, 15 were working and litigating, 53 were receiving Worker's Compensation, and 34 were receiving Worker's Compensation and litigating. Employment (working vs. Worker's Compensation) and litigation status (litigating vs. not litigating) were analyzed in a 2 x 2 factorial design with measures of pain, disability, psychological distress, and selected demographics as dependent variables. Compared to Worker's Compensation patients, working patients reported significantly less disability (down-time, days spent in bed, interference of pain in daily activities) and pain of a longer duration. Compared to litigating patients, non-litigating patients reported less pain (on the McGill Pain Questionnaire) and less disability (stopping activity, interference of pain in daily activities). On two measures of psychological distress (depression, anxiety), there were significant interactions: Worker's Compensation patients who were litigating reported less distress than non-litigants, while working patients who were litigating reported more distress than non-litigants. The results indicate clear differences in self-reports of disability associated with both employment and litigation status. They also suggest that litigation may function as a coping response for patients who are distressed by the adversarial nature of the Worker's Compensation system. Limitations of the study as well as suggestions for further research also are discussed. 
1	Embryonic stem cell virus, a recombinant murine retrovirus with expression in embryonic stem cells. The expression of Moloney murine leukemia virus and vectors derived from it is restricted in undifferentiated mouse embryonal carcinoma and embryonal stem (ES) cells. We have developed a retroviral vector, the murine embryonic stem cell virus (MESV), that is active in embryonal carcinoma and ES cells. MESV was derived from a retroviral mutant [PCC4-cell-passaged myeloproliferative sarcoma virus (PCMV)] expressed in embryonal carcinoma cells but not in ES cells. The enhancer region of PCMV was shown to be functional in both cell types, but sequences within the 5' untranslated region of PCMV were found to restrict viral expression in ES cells. Replacement of this region by related sequences obtained from the dl-587rev retrovirus results in MESV, a modified PCMV virus that confers G418 resistance to fibroblasts and ES cells with similar efficiencies. Expression of MESV in ES cells is mediated by transcriptional regulatory elements within the 5' long terminal repeat of the viral genome. 
5	Computerized tomography in acute gastrointestinal disorders. In recent years, computerized tomography (CT) has become one of the most important imaging modalities in evaluation of patients with acute gastrointestinal disorders. Its role, diagnostic accuracy, indications, and limitations in some of the most commonly encountered acute abdominal conditions are succinctly presented and reviewed. CT should not be used indiscriminantly, but is best considered a valuable primary or complimentary diagnostic tool in critically ill patients. Its selective use in a variety of emergency abdominal diseases will significantly improve accuracy of clinical diagnoses, leading to a prompt and adequate medical or surgical management. 
5	Molecular and hematologic characterization of Scottish-Irish type (epsilon gamma delta beta)zero thalassemia. The DNA deletion associated with an example of (epsilon gamma delta beta)zero thalassemia (Scottish-Irish type) was characterized. The deletion is approximately 205 kb in length and involves the epsilon, G gamma, A gamma, delta, and beta globin genes. The breakpoint is located 263 bp 3' to exon 3 of the beta globin gene. An LI (KpnI) repeat element approximately 320 bp in size is found at the 3' end of the novel DNA sequence. Different clinical phenotypes for three heterozygous neonates suggest that the deletion alone does not predict severity of (epsilon gamma delta beta)zero thalassemia at this age. 
3	The molecular biology of occlusive stroke in childhood. It is very likely that many of the same factors involved in occlusive disease in the adult are operative in the child. The major difference may be in the factors that damage endothelium in these two age groups and thereby initiate this catastrophe (atherosclerosis versus "other" causes of endothelial changes). Our task in this next decade is the rational exploration of the effects of endothelium-mediated kinins, endothelial secretory products, angiospasm, platelet aggregration, prostaglandins, and lipoproteins on pediatric stroke. 
5	The pathophysiology of anoxic injury in central nervous system white matter. White matter of the mammalian brain is susceptible to anoxic injury, but little is known about the pathophysiology of this process. We studied the mechanisms of anoxic injury in white matter using the isolated rat optic nerve, a typical central nervous system white-matter tract. Optic nerve function, measured as the area under the compound action potential, rapidly failed when exposed to anoxia. Postanoxic recovery was variable, depending on duration of the anoxic insult; after a standard 60-minute period of anoxia, the compound action potential recovered to 28.5% of control. Irreversible anoxic injury was critically dependent on extracellular Ca2+; maintaining the tissue in zero [Ca2+] solution throughout the anoxic period resulted in 100% compound action potential recovery. Increasing perfusate [Ca2+] during anoxia from zero to 4 mM resulted in progressively less recovery. Anoxic damage to the optic nerve appears to depend on the gradual accumulation (over tens of minutes) of Ca2+ in a cytoplasmic compartment. The inorganic Ca2+ channel blockers Mn2+ (1 mM), Co2+ (1 mM), or La3+ (0.1 mM) had no effect on recovery of the compound action potential after anoxia; only Mg2+ (10 mM) significantly improved recovery. Treatment with the dihydropyridine Ca2+ channel blockers nifedipine (1-10 microM) or nimodipine (1-40 microM) also had no effect on recovery from anoxia. Thus, Ca2+ influx during anoxia does not occur via conventional Ca2+ channels. Preliminary evidence suggests that this Ca2+ influx may occur via other cation channels that are imperfectly selective for Ca2+ or via the Na(+)-Ca2+ exchanger. 
1	Phase I clinical and pharmacokinetic trial of flavone acetic acid. Flavone acetic acid is a synthetic benzopyrone derivative with an unknown mechanism of action. Thirty-eight patients (30 men and 8 women) were treated once a week for 4 weeks every 5 weeks with doses of flavone acetic acid ranging from 0.33 to 12.5 g/m2. At doses less than or equal to 3.9 g/m2, the drug was administered intravenously over 1 hour; at doses greater than or equal to 5.28 g/m2, the infusion period was lengthened to 6 hours. Treatment of all patients included hydration before and after treatment and alkalization to maintain urine pH at greater than or equal to 6.5. A dose-limiting toxic effect was hypotension at 10 g/m2. Pharmacokinetic studies revealed linear behavior in the eight patients studied, beginning at 3.9 g/m2. Peak plasma levels ranged from 125 to 630 micrograms/mL, with a mean terminal half-life of 22.4 hours. Immunologic monitoring was performed in three patients at 10 g/m2. A transient increase in CD16- and/or Leu-19-positive cells was noted in all three patients. In one patient, this increase correlated with a 10-fold increase in K562 cell killing. There were no objective tumor responses seen in this trial. The recommended phase II dose on this schedule is 8 g/m2. Further studies to elucidate the drug's mechanism of action and to define its immunologic properties are recommended. 
5	Similar time course of ST depression during and after exercise in patients with coronary artery disease and syndrome X. To assess whether the time course of ST segment depression differs in patients with coronary artery disease and patients with angina and normal coronary arteries, the exercise tests of 54 patients with documented coronary artery disease and 25 patients with syndrome X (angina, positive exercise test, no evidence of coronary artery spasm, and normal coronary arteries) were compared. All tests were performed with therapy withheld, using the modified Bruce protocol. In each test, time, heart rate and blood pressure were measured at the onset and at 1 mm of ST segment depression, and at peak exercise. Recovery (return of the ST segment to baseline +/- 0.2 mm) time was also assessed. Peak ST segment depression was similar in coronary artery disease and syndrome X patients (1.5 +/- 0.3 versus 1.6 +/- 0.4 mm). In 42 coronary artery disease patients, ST segment depression developed early (less than or equal to 6 minutes) during exercise; this was associated with a short recovery (less than or equal to 3 minutes) in 17 (40%) and with a long recovery (greater than 3 minutes) in 25 (60%) patients. In 17 patients with syndrome X, ST segment depression developed early; it was associated with a short recovery in six (35%) and with a long recovery in 11 (65%) patients. Late (greater than 6 minutes) onset of ST segment depression was observed in 12 coronary artery disease patients; of these, eight (67%) had a short recovery and 4 (33%) had a long recovery. Late onset of ST segment depression occurred in eight patients with syndrome X; six (75%) had a short recovery and two (25%) had a long recovery. 
5	Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin. The records of 42 patients who had axillary metastases compatible with a clinically occult breast primary were reviewed. Forty patients had mammography performed as part of their evaluations. Mastectomy yielded the primary tumor in one of 13 patients; biopsy yielded positive results in one of five. Among the 29 patients who did not undergo mastectomy, 16 received breast irradiation, and 13 were simply observed for signs of the primary tumor. For the patients who did not undergo mastectomy, the 5-year actuarial risk for appearance of a primary was 17% in the irradiated group versus 57% in the nonirradiated group (P = 0.06). Patterns of failure are correlated with stage and local and systemic therapy. The results affirm our belief that patients with axillary metastases histologically consistent with breast tumor should be treated identically to patients with similar nodal stages and proven breast primaries. 
1	Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft. Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature. Cultured human PBL distributed in moderate concentrations to intraperitoneal tumor when administered i.p., but not when administered i.v. The poor localization of i.v. injected PBL to tumor may reflect species disparity in homing receptors and/or endothelial ligands, a problem which may be overcome with a syngeneic model. These results suggest that regional therapy with HA antibodies and PBL may offer advantages over systemic therapy for initial clinical trials. 
4	Prolonged anginal perceptual threshold in diabetes: effects on exercise capacity and myocardial ischemia. Anginal perceptual threshold (the time from onset of 0.1 mV of ST segment depression to onset of angina during treadmill exercise) is prolonged in diabetic patients with coronary artery disease. In the present study, the functional significance of this perceptual abnormality was evaluated by analysis of its effect on exercise capacity and the severity of myocardial ischemia. Treadmill exercise in 32 diabetic patients and 36 nondiabetic control patients showed a close linear correlation between the time to onset of electrical ischemia (ST segment depression) and exercise capacity in both groups (r = 0.8 and 0.9, respectively; p less than 0.001). However, the slope of the relation was flatter in the diabetic group because prolongation of the anginal perceptual threshold permitted continued exercise as ischemia intensified. The anginal perceptual threshold itself showed a close linear correlation with exercise capacity in the diabetic group (r = 0.8, p less than 0.001), although in the nondiabetic group these variables were unrelated. The permissive effect of a prolonged anginal perceptual threshold on exercise capacity is undesirable as reflected by its correlation with ischemia at peak exercise (r = 0.6, p less than 0.001): the longer the threshold, the greater the exercise capacity and the more severe the ischemia. Indeed, the inverse relation between the severity of ischemia at peak exercise and exercise capacity in the nondiabetic group (r = 0.4, p less than 0.02) was completely lost in the diabetic group. Thus, in diabetic patients with coronary artery disease, anginal perceptual threshold is a major determinant of exercise capacity. 
4	Timing and mechanism of in-hospital and late death after primary coronary angioplasty during acute myocardial infarction. The effect of early myocardial reperfusion on patterns of death after acute myocardial infarction (AMI) is unknown. Thus, the mechanism and timing of in-hospital and late deaths among a group of 614 patients treated with coronary angioplasty without antecedent thrombolytic therapy for AMI were determined. Death occurred in 49 patients (8%) before hospital discharge. Four patients died in the catheterization laboratory. Death was due to cardiogenic shock in 22 patients, acute vessel reclosure in 5 patients, was sudden in 8 patients and followed elective coronary artery bypass surgery in 8 patients. Cardiac rupture was observed in only 2 patients after failed infarct angioplasty, and did not occur among the 574 patients with successful infarct reperfusion. Intracranial hemorrhage did not occur. Multivariate predictors of in-hospital death included failed infarct angioplasty, cardiogenic shock, 3-vessel coronary artery disease and age greater than or equal to 70 years. During a follow-up period of 32 +/- 21 months (range 1 to 87), 55 patients died. The cause of death was cardiac in 36 patients, including an arrhythmic death in 23 patients and was due to circulatory failure in 13 others. One patient died of reinfarction due to late reclosure of the infarct artery. Actuarial survival curves demonstrated overall survival after hospital discharge of 95 and 87% at 1 and 4 years, respectively. Freedom from cardiac death at 1 and 4 years was 96 and 92%. Multivariate predictors of late death included 3-vessel disease, a baseline ejection fraction of less than or equal to 40%, age greater than 70 years and female gender. 
1	Medical comorbidity of major depressive disorder in a primary medical practice. Despite much speculation about the relationship between depression and medical comorbidity in primary care settings, few investigators have examined this issue empirically. Using a two-stage screening procedure, we assessed 618 patients aged 18 to 64 years in an academic general medicine clinic. Forty-one patients (6.6%) suffered from a current episode of major depressive disorder (MDD). We compared this group with a 20% random sample of nondepressed patients. While patients with MDD were younger (mean age, 41.1 vs 47.2 years), they were assessed by the Duke University Severity of Illness Scale as having more severe medical illness. Patients with MDD were more likely to have malignant tumors and "ill-defined conditions" than nondepressed patients. The 18 patients with MDD (44%) who were correctly diagnosed by their physicians had less severe medical illness than those whose depression was clinically undetected. A logistic regression model predicting MDD group membership included female gender, younger age, higher Duke University Severity of Illness Scale score, and more frequent inactive ill-defined diagnoses. These findings are consistent with assertions: (1) patients with MDD have more physical illness than nondepressed patients and/or (2) somatic symptoms and disability caused by MDD add to the burden of physical illness. 
2	Motility changes in primary achalasia following pneumatic dilatation. The changes in esophageal motility after pneumatic dilatation were evaluated prospectively in 51 patients with achalasia. The patients were evaluated for a median of 14 months. Pneumatic dilatation led to a clinical improvement in 41 patients. On manometric evaluation, a significant decrease in lower esophageal sphincter pressure was observed (28.4 +/- 14.9 mmHg vs. 13.5 +/- 7.2 mmHg; p = 0.001); the resting pressure of the esophageal body dropped from 4.8 +/- 4.2 mmHg above gastric baseline to 0.1 +/- 3.9 mmHg below gastric baseline. After therapy, peristaltic activity was present in 10/51 (20%) patients; in 1 case, complete relaxation of the lower esophageal sphincter was recorded. Treatment-induced motility changes could not be predicted by clinical history or the lower esophageal sphincter pressure before or after therapy. However, the resting pressure of the esophageal body before and after therapy was significantly lower in these patients in whom peristalsis recurred after therapy than in patients with an unchanged motility pattern. The reappearance of peristaltic activity after pneumatic dilatation was unrelated to lower esophageal sphincter pressure. In conclusion, motility disturbances of the esophageal body in patients with achalasia do not simply reflect the functional obstruction of the lower esophageal sphincter. These findings support the hypothesis that achalasia is not a distinct motility disturbance but should be regarded as part of a broad spectrum of different interrelated esophageal motility disorders. 
4	Regression of the left main trunk lesion by steroid administration in Takayasu's aortitis. A 62-year-old man with unstable angina due to severe narrowing of the left main trunk (LMT) was examined. Emergency bypass surgery was performed with an internal mammary artery graft, instead of a saphenous vein graft, because of the thickened, edematous ascending aorta. Postoperative coronary angiography showed the lesion of the LMT markedly regressing. Presumably, this stenotic lesion of the LMT was caused by active aortitis and was partially reversible by steroid administration both during and after surgery. Steroid therapy can be added to the list of treatments for cases of LMT disease associated with Takayasu's aortitis, if signs of active inflammation are present. 
5	Long-term clinical results with the Ionescu-Shiley pericardial xenograft. From 1977 to 1987, 829 Ionescu-Shiley pericardial valves (Shiley, Inc., Irvine, Calif.) were implanted in 766 patients at the University of Ottawa Heart Institute. There were 476 patients who had aortic valve replacement, 234 who had mitral valve replacement, and 44 who had double valve replacement. The standard-profile design was used in 508 patients and the low-profile design in 321 patients. Follow-up was obtained for 97% of patients, with calculation of event-free probabilities. At 10 years the overall probability of freedom from structural failure was 48% +/- 7% after aortic valve replacement, 44% +/- 15% after mitral valve replacement, and 79% +/- 11% after double valve replacement. Although at 5 years the probability of failure was statistically lower with the low-profile design, this favorability was lost by 6 years. Freedom from structural failure was only 47% +/- 7% for the standard-profile valve at 10 years. Thus the probability of freedom from reoperation was only 46% +/- 7% after aortic valve replacement, 39% +/- 6% after mitral valve replacement, and 65% +/- 20% after double valve replacement at 10 years. Thromboembolism occurred in 69 patients, for a predicted freedom from this complication at 10 years of 79% +/- 3% after aortic, 73% +/- 7% after mitral, and 96% +/- 4% after double valve replacement. There were 31 cases of endocarditis. The 10-year predicted freedom from endocarditis, therefore, was 86% +/- 3% after aortic, 98% +/- 1% after mitral, and 97% +/- 1% after double valve replacement. A total of 221 operative and late deaths were recorded in this series. Prosthetic valve failure accounted for 27% of late deaths. The 10-year survival rates were estimated to be 56% +/- 5% (aortic valve replacement), 54% +/- 6% (mitral valve replacement), and 51% +/- 8% (double valve replacement). We concluded that the Ionescu-Shiley pericardial xenograft provides less than optimal clinical performance and its use has been discontinued. 
4	The spectrum of portal vein thrombosis in liver transplantation. Thrombosis of the portal vein with or without patency of its tributaries used to be a contraindication to orthotopic liver transplantation (OLTX) until quite recently. Rapid progress in the surgical technique of OLTX in the last few years has demonstrated that most patients with portal vein thrombosis can be safely and successfully transplanted. Presented here is a series of 34 patients with portal vein thrombosis transplanted at the University of Pittsburgh since 1984. The various techniques used to treat various forms of thrombosis are described. The survival rate for this series was 67.6% (23 of 34 patients). Survival was best for patients who underwent phlebothrombectomy or placement of a jump graft from the superior mesenteric vein. The survival rate also correlated with the amount of blood required for transfusion during surgery. Overall it is concluded that a vast majority of the patients with thrombosis of the portal system can be technically transplanted and that their survival rate is comparable to that of patients with patent portal vein. 
5	Indigenous cases of Lyme disease diagnosed in North Carolina. Between January 1984 and December 1989, 102 indigenous cases of Lyme disease were reported in North Carolina. Lyme disease was reported in each of the three major geographic regions of the state: mountain, piedmont, and coastal plain. One or more diagnoses were made in 42 of 100 counties. Patients ranged in age from 5 months to 78 years (median, 27 years); 58 patients (57%) reported a history of tick exposure within 1 month of the onset of symptoms. Erythema migrans was reported by 93 patients (91%). Arthritis (30%), neurologic symptoms (10%), and cardiac abnormalities (7%) were observed. Thirty of the 102 cases were confirmed serologically by indirect fluorescence microscopy or enzyme-linked immunosorbent assay. 
2	Alanine aminotransferase in clinical practice. A review. Alanine aminotransferase is an enzyme produced mainly in the liver. When serum activity is measured, it provides a marker of hepatic disease. This review explores the biochemistry and laboratory analysis of alanine aminotransferase in terms of its significance in human health and disease. Cut-off levels that define abnormality are rather arbitrary and this decreases the specificity of the test in apparently healthy patients. A small, but important, group of patients with alanine aminotransferase abnormality have underlying liver disease that may be treatable. Most can be diagnosed based on history, physical examination, and biochemical-serological profiles. Liver biopsy can complement the diagnostic process in selected circumstances. Literature pertaining to this is critically reviewed. 
4	Left ventricular diastolic dysfunction limits use of maximum systolic elastance as an index of contractile function. We tested the hypothesis that maximum systolic elastance (Emax) fails to detect a decline in left ventricular (LV) contractile function when diastolic dysfunction is present. Canine hearts were studied in an isolated blood-perfused heart apparatus (isovolumic LV); contractile dysfunction was produced by 60 or 90 minutes of global ischemia, followed by 90 minutes of reperfusion. Nine normal hearts underwent 60 minutes of ischemia, and five underwent 90 minutes of ischemia. After the ischemia-reperfusion sequence, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 14 hearts. In the group undergoing 60 minutes of ischemia, LV diastolic pressure did not increase, whereas Emax decreased from 5.2 +/- 2.5 to 2.9 +/- 1.4 mm Hg/ml (p less than 0.05). In the group undergoing 90 minutes of ischemia, diastolic pressure increased (from 10 +/- 2 to 37 +/- 20 mm Hg, p less than 0.05), and Emax did not change significantly (from 5.1 +/- 4.3 to 4.3 +/- 2.5 mm Hg/ml). A second series of experiments was performed in 13 hearts with pressure-overload hypertrophy (aortic-band model with echocardiography and catheterization studies before the ischemia-reperfusion protocol). Five had evidence for pump failure, whereas eight remained compensated. After 60 minutes of ischemia and 90 minutes of reperfusion, developed pressure, pressure-volume area, and myocardial ATP level were significantly less than those at baseline in all 13 hearts. In the group with compensated LV hypertrophy, LV diastolic pressure did not change, whereas Emax decreased from 6.9 +/- 3.0 to 3.1 +/- 2.3 mm Hg/ml (p less than 0.05). 
4	Coronary angioplasty in young adults: initial results and late outcome. The initial and late outcome of coronary angioplasty was studied in 148 patients less than 40 years of age (mean 36.4 +/- 3). Angioplasty was performed on a single vessel in 70% of patients and on multiple vessels in 30%; it was performed on a totally occluded vessel in 20%. Angioplasty was successful in 90.5% of patients, unsuccessful but uncomplicated in 7.4% and complicated by myocardial infarction in 0.7%, emergency bypass surgery in 0.7% and death in 0.7%. At late (mean 3.7 +/- 3 years; range 0.5 to 11.5) follow-up study after successful angioplasty, 94% of patients were alive, 79% were free of angina and 85% had returned to work; late myocardial infarction occurred in 4%. Actuarial survival at 5 years was 95%, and 85% of patients were free from death, infarction or bypass surgery. A second angioplasty was performed in 29 patients (22%) (mean 6.1 +/- 8.4 months) and was successful in 27 (93%), with no deaths. Elective coronary bypass surgery was performed in 8.5% of patients, with perioperative infarction in 9% and no deaths. By univariate analysis, late death was more likely to occur in hypertensive patients (15% versus 2.5%; p less than 0.01) and diabetic patients (21.4% versus 3.6%; p less than 0.01). Cox proportional hazard regression analysis identified hypertension (p = 0.007) and diabetes (p = 0.04) as independent time-related predictors of subsequent death. Thus, early and late results after coronary angioplasty in young adults are favorable, but certain risk factors are important predictors of outcome. Late revascularization procedures (repeat angioplasty or surgery) for restenosis or disease progression are common. 
3	Grading white matter lesions on CT and MRI: a simple scale. We developed and tested a simple three-point scale for grading white matter lesions in anterior and posterior regions of the brain. Twenty four CT scans and 24 MRI scans were separately judged by 11 and five observers, respectively, on the presence and severity of white matter lesions. The observers were radiologists and neurologists. For CT scans, these periventricular changes were graded according to their extent as absent, or partly involving the white matter, or extending up to the subcortical region. The MRI lesions were graded as no lesion or only a single one, multiple focal lesions, and multiple confluent lesions. The pairwise agreements of all possible combinations of observers for each scan were corrected for chance (kappa statistics; maximal agreement 1.0). The weighted kappa value, for anterior and posterior regions combined, was 0.63 for CT scans, and 0.78 for MRI scans. This three-point scale for two separate regions seems suitable as a basis for cross-sectional or longitudinal studies of large series of patients. 
1	Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis? Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells. 
4	Doxazosin therapy in the treatment of diabetic hypertension. The incidence of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) has not been reduced by the control of hyperglycemia alone. Hypertension and dyslipidemia may be the major determinants of macrovascular disease in these patients. With the high prevalence of hypertension in NIDDM, antihypertensive drugs are likely to be important determinants of an atherogenic lipid profile. To date, there is no completed major randomized controlled trial of antihypertensive treatment outcome in a diabetic population, and as such, drug choice for the treatment of diabetic hypertension is often based on evidence extrapolated from studies in nondiabetic groups. However, two short-term studies have assessed the effects of doxazosin antihypertensive therapy in subjects with NIDDM. Both studies showed that the significant reduction in blood pressure with doxazosin treatment was associated with favorable effects on the serum lipid profile. In one study, contrasting adverse effects of atenolol treatment on glycemic control, lipids, and lipoproteins were observed. Doxazosin therapy was associated with a trend toward correcting the disturbances of lipoprotein metabolism characteristic of NIDDM. These metabolic effects, combined with effective lowering of blood pressure by doxazosin, may be important determinants of cardiovascular disease in the long term. 
4	Dietary sodium reduction for hypertension prevention and treatment. Nutritional-nonpharmacological approaches for the treatment and prevention of hypertension are of great interest. Sodium reduction is one of the primary methods recommended for these purposes. The general public is interested in the reduction of dietary sodium intake and has responded with a decrease in table salt use, the purchase of lowered sodium food products, and the use of food labels to help guide food purchases. Countervailing trends in the use of convenience foods and dining out increase the difficulty for individuals to lower sodium intake. Clinical trials that have used sodium reduction alone or in combination with other lifestyle therapies have demonstrated the feasibility of reducing dietary sodium intake from 30% to 50% for up to 4 years, in a variety of populations. Trials that used lifestyle and weight loss interventions have also achieved significant reductions in body weight and alcohol consumption and increases in physical activity. A variety of studies indicate that long-term sodium reduction is feasible and that it is acceptable to patients. No negative consequences of these interventions have been observed, and in some cases improvement in the intake of other nutrients has occurred. Nonpharmacological interventions have resulted in hypertension control in significant proportions of the trial populations. These studies demonstrate that the foregoing types of interventions can significantly contribute to hypertension treatment and prevention. 
3	Frontal impairment and hypoperfusion in neuroacanthocytosis. Cerebral blood flow tomography, by xenon 133 inhalation or HMPAO (99mTc-d, l-hexamethyl-propylene amine oxime) technetium Tc 99m injection, revealed a severe hypoperfusion in both frontal lobes of a 40-year-old woman with confirmed neuroacanthocytosis. This finding occurred in conjunction with neuropsychological deficits consistent with selective frontal lobe dysfunction. This observation is the first documentation of this type of dementia in neuroacanthocytosis. 
1	Comparison of myelography with CT follow-up versus gadolinium MRI for subarachnoid metastatic disease in children. We evaluated 17 children with primary intracranial neoplasms for subarachnoid metastatic disease (SAMD) using myelography with computed tomographic follow-up (Myelo + CT) and cerebrospinal fluid (CSF) histopathologic examination, as well as magnetic resonance imaging with gadolinium DTPA (MRI + Gd), between December 1988 and December 1989. There were 12 boys, and the median age was 5.7 years (range, 0.8 to 21.8 years). Tumor histology included 8 primitive neuroectodermal tumors (PNETs), 3 ependymomas, 2 low-grade astrocytomas, 1 anaplastic astrocytoma, 1 glioblastoma multiforme, 1 atypical rhabdoid tumor, and 1 malignant fibrous histiocytoma. Thirteen tumors originated in the posterior fossa, 2 were supratentorial, and 2 were in the spinal cord. The median interval between the 2 diagnostic tests was 2 days. MRI + Gd was positive in 11 (65%), Myelo + CT in 8 (47%), and CSF in 5 (29%) cases. MRI + Gd was superior in delineating spinal cord nodules and "sugar coating" whereas Myelo + CT more readily revealed nerve root sleeve filling defects. There was no case in which Myelo + CT was positive that MRI + Gd did not reveal SAMD. MRI + Gd is a safe, noninvasive test that should be used as the initial imaging modality for the presence of SAMD. 
1	Benign parotid tumour enucleation--a reliable operation in selected cases. The method of surgical treatment for benign tumours of the parotid gland had not yet been rationalized, but many authors recommend parotidectomy as the most appropriate procedure. A series of 289 operations for parotid swelling is reported; the majority of mixed and Warthin's tumours underwent enucleation without either complications or recurrence. The rationale of parotidectomy versus enucleation is discussed but in fast growing, deeply infiltrating and recurrent tumours, parotidectomy appears to be the best choice. In the other group of more commonly occurring tumours, enucleation represents a reliable time saving option. 
2	Geographic variation of inflammatory bowel disease within the United States. One approach to learn about possible environmental risks in inflammatory bowel disease relates to studying its geographic pattern of occurrence. The geographic variation of inflammatory bowel disease within the United States was analyzed using the accumulated 17.5 million hospital discharges of all U.S. Medicare beneficiaries during two consecutive years. To validate the geographic pattern shown by the Medicare data, hospitalization was compared with mortality from inflammatory bowel disease among different states. Mortality and hospitalization statistics both suggested that the occurrence of inflammatory bowel disease was determined by environmental factors that had a marked geographic variation within the United States. Both Crohn's disease and ulcerative colitis appeared to be more frequent in northern parts of the United States than in southern and in urban more than rural parts. These trends were observed for men and women and for blacks and whites alike. Similar geographic patterns of Crohn's disease and ulcerative colitis suggested the influence of one or more identical risk factors for both diseases. 
5	Regional H2O2 concentration in rat brain after hyperoxic convulsions. O2 toxicity of the central nervous system (CNS) may be a result of enhanced generation of reactive O2 species such as superoxide and H2O2 at high PO2. In this study, we measured H2O2 production in six regions of the rat brain before and after convulsions induced by hyperbaric hyperoxia (HBO). H2O2 concentration was determined ex vivo using a method based on the H2O2-dependent decline in catalase activity in the presence of the irreversible inhibitor of compound I, 3-amino-1,2,4-triazole. Regional catalase activity in the brain ranged from 0.029 +/- 0.004 to 0.055 +/- 0.004 mumol O2.min-1.micrograms DNA-1 in cerebellum and medulla-pons, respectively. In the presence of aminotriazole, catalase activity declined after HBO-induced convulsions to 26-45% of normoxic values. The rates of inactivation of catalase were used to predict average steady-state values for H2O2 concentration in different brain structures. Estimated H2O2 concentrations during HBO varied from 31 to 51 pM in cerebellum and posterior subcortex and represented increases of 2.2-7.3 times normoxic values. These findings suggest that H2O2 is an important mediator of selective neuronal vulnerability to CNS O2 toxicity. 
4	Functional status after coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. Two cohorts of consecutive patients of comparable age with similar preprocedure cardiac function who underwent either coronary artery bypass grafting (CABG; n = 106) or percutaneous transluminal coronary angioplasty (PTCA; n = 64) were entered into a prospective comparison study examining functional status and return to work during the first year of recovery. Patients were evaluated using standardized functional status instruments for activities of daily living, work performance, social activity, mental health and quality of social interaction at 1, 6 and 12 months after the procedure. Within the CABG group, statistically significant improvements of functional status on every subscale were noted over the 1-year follow-up. Patients undergoing PTCA demonstrated significant improvement in all dimensions except for the quality of interaction at 1 year as compared with baseline. When the 2 groups were compared, the PTCA group demonstrated greater participation than the CABG group in routine daily physical and social activities at 1 and 6 months, but this apparent advantage disappeared by 1 year. Measures of psychological functioning were better after CABG than after PTCA. A reduction in the number of those with employment occurred in both the CABG and PTCA groups, independent of physical functional status measures, which improved in both groups after the procedures. For those with employment, the CABG group reported the greatest improvement in work performance. 
5	Effects of changes in level and pattern of breathing on the sensation of dyspnea. Breathing during hypercapnia is determined by reflex mechanisms but may also be influenced by respiratory sensations. The present study examined the effects of voluntary changes in level and pattern of breathing on the sensation of dyspnea at a constant level of chemical drive. Studies were carried out in 15 normal male subjects during steady-state hypercapnia at an end-tidal PCO2 of 50 Torr. The intensity of dyspnea was rated on a Borg category scale. In one experiment (n = 8), the level of ventilation was increased or decreased from the spontaneously adopted level (Vspont). In another experiment (n = 9), the minute ventilation was maintained at the level spontaneously adopted at PCO2 of 50 Torr and breathing frequency was increased or decreased from the spontaneously adopted level (fspont) with reciprocal changes in tidal volume. The intensity of dyspnea (expressed as percentage of the spontaneous breathing level) correlated with ventilation (% Vspont) negatively at levels below Vspont (r = -0.70, P less than 0.001) and positively above Vspont (r = 0.80, P less than 0.001). At a constant level of ventilation, the intensity of dyspnea correlated with breathing frequency (% fspont) negatively at levels below fspont (r = -0.69, P less than 0.001) and positively at levels above fspont (r = 0.75, P less than 0.001). These results indicate that dyspnea intensifies when the level or pattern of breathing is voluntarily changed from the spontaneously adopted level. This is consistent with the possibility that ventilatory responses to changes in chemical drive may be regulated in part to minimize the sensations of respiratory effort and discomfort. 
3	Progressive degeneration of the right temporal lobe studied with positron emission tomography. A 79 year old man with a twelve year progressive history of prosopagnosia and recent naming difficulty, in whom other intellectual skills were preserved, is described. Positron emission tomography (PET) revealed an area of right temporal lobe hypometabolism, with an additional area of less severe hypometabolism at the left temporal pole. This may represent an example of progressive focal cortical degeneration similar to that associated with primary progressive dysphasia, but affecting the right temporal lobe. 
4	Increased Ca2+ signaling after alpha-adrenoceptor activation in vascular hypertrophy. In an effort to explain the increased sensitivity to agonists of hypertrophic vascular muscle, intracellular Ca2+ concentration ([Ca2+]i)-signaling mechanisms were studied in normal and hypertrophic rat aortas from normotensive and coarctation-hypertensive rats. Based on both fura 2 fluorescence and aequorin luminescence measurements, qualitatively different patterns of Ca2+ mobilization occur in normal and hypertrophic rat aortic muscle. Normal rat aortic muscle contracts to phenylephrine with little or no increase in [Ca2+]i, whereas the angiotensin II-induced contraction is accompanied by a marked [Ca2+]i transient. In contrast, hypertrophic rat aortic muscle shows a dramatic increase in Ca2+ signaling after phenylephrine stimulation. Moreover, both the amplitude of the angiotensin-induced [Ca2+]i transient and the contractile sensitivity to this agonist are decreased in the hypertrophic muscle. Our results strongly suggest that the amplitude of the [Ca2+]i transient after agonist stimulation determines the contractile sensitivity and that there is an altered coupling of the alpha-adrenoceptor in the hypertrophic vascular muscle. 
1	Occurrence of beta-hexachlorocyclohexane in breast cancer patients. The residues of polycyclic aromatic hydrocarbon (PAH) and neutral organochlorine compounds in breast fat of 44 breast cancer patients and 33 women free of cancer were determined. No statistically significant differences appeared between the two comparison groups with regard to occurrence of PAH compounds. Of the neutral organochlorine compounds, residues of beta-hexachlorocyclohexane (HCH) were found more frequently in breast cancer patients. After adjusting for age and parity by stepwise logistic regression, beta-HCH remained a significant risk factor of breast cancer. Using a cutoff point for the residue level of beta-HCH in breast adipose tissue of more than 0.1 mg/kg fat, the odds ratio was 10.51 (95% CI, 2.00-55.26). 
1	Adenoid cystic carcinoma of the esophagus. A clinicopathologic study of three cases. In a group of 245 cases of primary carcinoma of the esophagus the authors found three cases of adenoid cystic carcinoma (ACC). Clinical and pathologic data of those patients (one female and two male; age range, 49-74 years) were analyzed. Tumors were localized in the middle third of the esophagus. One patient lived 15 months after surgery. Another is a case of early ACC who has been living 4.5 years after surgery and is without specific symptoms. The third patient had not had surgery and died 13 months after the onset of dysphagia. An autopsy showed only a locally invasive tumor growing into the surroundings of the esophagus, and regional lymph node metastases without distant parenchymal metastases. These findings support pathologic and biologic similarities between ACC of the esophagus and ACC of the salivary glands. There are synchronous tumors of the esophagus and the vital localization which makes the prognosis of ACC of the esophagus worse than ACC of the salivary glands. 
4	Penetration of the pericardium by a gastric ulcer--survival after pericardiocentesis. Elderly patients often have unusual manifestations of common illnesses. We describe a geriatric patient having a pneumopericardium from pericardial penetration by a gastric ulcer. Benign gastric ulceration causing perforation of the pericardium or other cardiac structures was recognized as early as 1854; however, until 1964, the condition was invariably fatal. Our patient survived the episode after early pericardiocentesis and medical treatment. Aspects of this uncommon clinical entity and a brief review of the literature are described. 
1	Renal vein leiomyosarcoma. The 11th case of primary leiomyosarcoma of the renal vein is reported. Unique features of this case included concomitant resection of an isolated hepatic metastasis, intraoperative radiation therapy, and the use of electron microscopy and immunohistochemical stains in confirming the diagnosis. A review of the previously reported cases shows a tendency toward slow tumor growth and infrequent recurrence (18%). Metastases are common (82%), primarily to the lung and liver. Aggressive surgical resection and adjuvant radiation therapy, including intraoperative radiation therapy, are recommended. Adjuvant chemotherapy should be considered, although its benefits at present are unclear. 
2	Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations. Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms. 
1	Serous papillary adenocarcinoma of the tunica vaginalis of the testis with metastasis. Testicular or paratesticular neoplasms that resemble the common epithelial type of ovarian tumor are quite rare. The authors report the case of a 29-year-old man with a metastatic serous papillary adenocarcinoma arising from the tunica vaginalis. To the authors' knowledge, this is the first reported case of a serous carcinoma of the tunica vaginalis behaving in a malignant fashion. The fact that clinically apparent metastatic disease occurred 4 years after initial presentation suggests that development of metastases is a late event. Unfortunately, the tumor has been refractory to therapy with chemotherapeutic agents with activity against ovarian malignancies. 
1	Solitary thyroid nodule: a prospective evaluation of nuclear scanning and ultrasonography. The aim of this study was to assess prospectively the value of thyroid nuclear scans and ultrasound examination in the preoperative investigation of patients with a solitary thyroid nodule. Total thyroid lobectomy for a solitary thyroid nodule was performed in 68 cases. Each patient had a thyroid isotope scan (except two women who were pregnant) and thyroid ultrasound examination. There were 10 (15 per cent) malignant nodules, 11 (16 per cent) benign neoplastic nodules and 47 (69 per cent) benign non-neoplastic nodules. All of the patients with malignant nodules who were scanned had a solitary cold nodule on thyroid scan, as did 40 (69 per cent) of those with benign solitary nodules. Ultrasound examination of the thyroid suggested correctly that one of 16 (6 per cent) cystic lesions, four of 16 (25 per cent) complex solid-cystic lesions and three of 18 (17 per cent) of solid lesions were malignant. One lesion reported as multinodular on ultrasonography and one reported as normal also turned out to be malignant. Thyroid isotope scans and ultrasound do not accurately differentiate between benign and malignant conditions and their routine use in the investigation of a solitary thyroid nodule should be abandoned. 
4	Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy. To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation. 
2	Surgical aspects of sclerosing cholangitis. Results in 178 patients. Of 178 patients with sclerosing cholangitis treated since 1950, 88 patients had associated inflammatory bowel disease, 72 had no such history, and 18 had iatrogenic injury or stone disease. A total of 233 biliary operations were performed, with a 75% rate of temporary improvement after initial operation. Subsequent operations resulted in a lower success rate and a higher mortality rate. Radiologic findings included predominant extrahepatic, intrahepatic, and diffuse disease in 29%, 28%, and 43% of patients, respectively; no survival differences were noted. Seventy-five of one hundred three deaths (73%) were related to liver failure, bleeding, or sepsis. Of 14 patients undergoing portosystemic shunt, 13 died of surgical complications or related disease. Orthotopic liver transplantation was performed in 16 patients and resulted in eight deaths, mainly in patients who had previously undergone extensive surgical treatment. No survival differences were seen between the patients with inflammatory bowel disease, those without the condition, or those who had colectomy. Surgical treatment in patients with sclerosing cholangitis should be minimized. Orthotopic liver transplantation should be offered as the treatment of choice for patients with portal hypertension, refractory cholangitis, advanced cirrhosis, or progressive liver failure. 
4	Studies on the pathogenesis of hypertension in Cushing's disease and acromegaly. The pathogenesis of the hypertension associated with Cushing's syndrome and with acromegaly is poorly understood. We have investigated the possible roles of sodium retention, activation of the renin-angiotensin system and increased sympathetic nervous system activity in untreated patients. In 11 patients with Cushing's disease, seven of whom were hypertensive, total exchangeable sodium was normal despite increased levels of the mineralocorticoid hormones, 11-deoxy-corticosterone and corticosterone. The renin-angiotensin system was also normal. Cardiac sensitivity to the beta-receptor agonist isoprenaline was increased, but this was not due to an increase in beta-adrenoceptor density. Hypertension in Cushing's disease is neither sodium-dependent nor angiotensin II-mediated, but increased cardiac sensitivity to catecholamines, by increasing cardiac output, may contribute to the pathogenesis of hypertension. In nine patients with acromegaly (three of whom were hypertensive) total exchangeable sodium was elevated. Although no correlation between blood pressure and exchangeable sodium was found, hypertension in acromegaly is probably sodium dependent. No evidence was found for a pathogenetic role for either the renin-angiotensin-aldosterone or the sympathetic nervous system. 
2	Endoscopic management of retained cystic duct stones. The finding of residual common bile duct stones after cholecystectomy is a relatively frequently encountered problem for which effective nonoperative therapy exists. Retained stones in a cystic duct remnant are very rare. We present a case of multiple retained stones in a long variant cystic duct remnant following cholecystectomy and common duct exploration, which was successfully managed with endoscopic sphincterotomy and balloon extraction. 
1	Response by women aged 65-79 to invitation for screening for breast cancer by mammography: a pilot study [published erratum appears in BMJ 1991 Jul 27;303(6796):234] OBJECTIVE--To determine whether there is sufficient benefit to be gained by offering screening for breast cancer with mammography to women aged 65-79, who are not normally invited for screening. DESIGN--Pilot study of women eligible for screening but not for personal invitation. The results of this study were compared with the results of routinely screened younger women (aged 50-64) from the same general practice. SETTING--One group general practice in south Manchester. PATIENTS--The 631 women aged 65-79 on the practice list. A total of 42 (7%) were excluded by the general practitioner, and 22 (4%) invitation letters were returned by the post office. MAIN OUTCOME MEASURES--Response rates to invitation for screening assessed by three indices: crude population coverage ratio, crude invited population coverage ratio, and corrected invited population coverage ratio. RESULTS--344 Patients aged 65-79 (61% of those invited, excluding those who could not be traced) were screened compared with 77% of women aged 50-64. The three response indices were higher for younger women than older: crude population coverage ratio = 66.5%, crude invited population coverage ratio = 69.3%, corrected invited population coverage ratio = 76.8% for women aged 50-64, compared with 54.5%, 58.4%, and 60.7% respectively for women aged 65-79. All four biopsies done in the older women gave positive results, giving a cancer detection rate of 11.6/1000 compared with 4.1/1000 among younger women. CONCLUSIONS--These results show that there is a potential for high attendance at routine screening by older women if they are invited in the same way as younger women. If these results are found elsewhere the costs and benefits of screening older women should be reassessed. 
2	Visceral protothecosis mimicking sclerosing cholangitis in an immunocompetent host: successful antifungal therapy. A healthy 39-year-old man who had clinical findings consistent with sclerosing cholangitis was found to have systemic protothecosis at surgery. Severe granulomatous inflammation and palpable nodules were found in the gallbladder, on the surface of the liver, and in the duodenum. Prototheca wickerhamii was detected in biopsied specimens and stool; the titer of indirect fluorescent antibody to this organism was 1:2,000. The patient recovered after a short course of treatment with amphotericin B and 3 months of oral therapy with ketoconazole. He had no other concurrent illness and had no abnormality in his immune system. This is the second reported human case of systemic protothecosis. An elevated IgG level, an elevated erythrocyte sedimentation rate, eosinophilia, and abnormal levels of enzymes in the liver were found in both cases. Protothecosis should be considered in the differential diagnosis of hepatic and biliary inflammatory diseases of uncertain etiology. 
5	Physician response to notification of acute problems in nursing homes. A frequently cited example of physicians' alleged disinterest in nursing home patients is their failure to respond rapidly or appropriately to telephone calls about acute events or important changes in patient status. This study of 45 SNFs and their 15 attached ICFs evaluated the length of time required to reach physicians by phone about significant clinical changes in patients' conditions and the appropriateness and timeliness of action taken by the physicians once contact was made. Calls on administrative matters, updating of orders, and similar routine calls were excluded. Seven hundred and fifty calls were identified from 24-hour nursing reports; the nature of the problem and the time and details of physicians' responses were recorded from patient charts. Judgment on the quality of physicians' responses was made by consensus of the regional UR committee except in the case of infections where decisions were based on detailed criteria developed in a previous study. The most frequent clinical problems were acute infections (32%), trauma (12%), GI tract disorders (11%), cardiorespiratory problems (10%), neurological disorders (7%), and diabetic control (7%). Results were very encouraging: 96% of physicians' call-backs and actions were judged to be timely, and 87% of physicians' actions taken were judged to be appropriate. However, actions taken were judged inappropriate for certain specific clinical problems, ie, in 22% (54/243) of infections, 24% (4/17) of CVA's, and 12% (6/49) of diabetic control problems. Implications for nursing home care and recommendations for improving the response to acute problems are discussed. 
1	Clinical, radiographic, and pathological features of symptomatic Rathke's cleft cysts. The clinical, radiographic, and pathological findings in 155 patients with symptomatic Rathke's cleft cysts are discussed. Eight patients were treated by the authors and 147 were collected in a review of the literature. This lesion occurred more often in female than male patients by a 2:1 margin, and the mean age at presentation was 38 years. The average patient had been symptomatic for nearly 3 years at the time of treatment, with the most common symptoms and signs being pituitary dysfunction, visual disturbances, and headaches. Affected children generally were pituitary dwarfs. The sella was enlarged in 80% of cases, and the cyst was situated in both an intrasellar and a suprasellar location in 71%. Computerized tomography revealed a low-density cystic mass with capsular enhancement in one-half of the cases. A variable appearance was seen with magnetic resonance imaging. Partial excision and drainage of the cyst by the transsphenoidal approach is the recommended treatment, as the recurrence rate is low. Most symptoms and signs improved or resolved following surgery with the exception of hypopituitarism and diabetes insipidus. The cyst lining was usually composed of ciliated cuboidal or columnar epithelium. Theories as to the origin of Rathke's cleft cysts are also discussed. 
5	Inpatient theophylline toxicity: preventable factors. OBJECTIVE: To identify preventable factors contributing to inpatient theophylline toxicity. DESIGN: Case series. SETTING: Tertiary care public hospital. PATIENTS: Forty consecutive adult inpatients (mean age, 56.5 years) with theophylline levels greater than 140 mumol/L (25.0 mg/L). MEASUREMENTS AND MAIN RESULTS: A retrospective chart audit was done. Toxicity was produced in 27 of 40 patients by inpatient or emergency department theophylline administration. Management errors found included delay (greater than 10 hours) in taking action from time toxic blood levels were drawn (20 patients), inappropriately high dosing of patients with congestive heart failure (17 patients), failure to recognize obvious symptoms (16 patients), recurrent toxicity (11 patients), additional emergency department treatment of already toxic patients (7 patients), overlap of intravenous and oral therapy (6 patients), patient discharged with no physician awareness of toxicity or dosage change (5 patients). CONCLUSIONS: A set of recurring management errors was identified as contributing to inpatient theophylline toxicity. Effective preventive mechanisms could have prevented most toxicity and associated morbidity. Theophylline's overall risk-benefit ratio in the inpatient setting may be less than that measured in well-controlled studies of the drug's efficacy because of these management errors. 
4	Alterations in collateral blood flow produced by isoflurane in a chronically instrumented canine model of multivessel coronary artery disease. The actions of isoflurane and adenosine on left ventricular myocardial perfusion during a total occlusion of the left anterior descending coronary artery and concomitant stenosis of the left circumflex coronary artery were investigated in dogs chronically instrumented for measurement of systemic and coronary hemodynamics, regional myocardial contractile function (via ultrasonic sonomicrometers), and myocardial blood flow (via the radioactive microsphere technique). An Ameroid constrictor was implanted on the left circumflex coronary artery to produce a slowly progressive stenosis that gradually depleted the coronary reserve of the distal vascular bed. The reductions in reserve were evaluated by daily measurement of baseline left circumflex coronary blood flow velocity and the hyperemic response to injection of adenosine. At a stage of moderate or severe left circumflex stenosis development, the left anterior descending coronary artery was totally occluded via a hydraulic occluder to simulate multivessel coronary artery disease, and control measurements of hemodynamics, regional contractile function, and myocardial blood flow were completed. In separate groups of experiments, either adenosine (0.64 and 1.28 mg/min) or isoflurane (1.6-1.8 and 2.3-2.5%, end-tidal) was administered and measurements remade during steady state hemodynamic conditions. Finally, diastolic aortic pressure and heart rate were adjusted to levels present in the control state during administration of adenosine or isoflurane, and additional measurements were recorded. Isoflurane reduced mean arterial pressure, left ventricular systolic pressure, and the rate of increase of left ventricular pressure at 50 mmHg (positive dP/dt50) without change in heart rate. Administration of isoflurane decreased blood flow in normal, stenotic, and occluded regions; however, when arterial pressure and heart rate were restored to levels present in the conscious state, myocardial perfusion in all regions was maintained at control levels. Ratios of flow between occluded and normal or stenotic zones remained unchanged from the conscious state during a constant aortic pressure and heart rate. Similar results were obtained in dogs with either a moderate or severe left circumflex coronary artery stenosis. In contrast, adenosine produced a dose-related decrease in collateral flow and occluded-to-normal or occluded-to-stenotic zone flow ratio. The results of this investigation indicate that adenosine but not isoflurane redistributes blood flow away from collateral-dependent myocardium to other regions in a chronically instrumented canine model of multivessel coronary artery disease.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Simultaneous superior oblique sheathectomy and inferior oblique tuck in congenital Brown's syndrome. Since Harold Brown, in 1950, described the superior oblique tendon sheath syndrome, numerous surgical techniques have been explored to treat this condition. Tenectomy of the homolateral superior oblique, alone or in combination with a weakening procedure on the homolateral inferior oblique, has been the technique most advocated. However, good functional results are rarely achieved in a single procedure, and delayed complications are frequent. Taking advantage of the improved dissection and reduced trauma afforded by the use of a surgical microscope, one of the techniques first recommended and later abandoned by Brown was reappraised. The technique consists of dissection of the sheath and attachments of the superior oblique, while preserving its tendon, combined with a 10mm tuck of the homolateral inferior oblique. Both a typical and a severe atypical congenital case, according to the classification of Brown, were treated in this fashion. Full correction was achieved in both. 
4	Orthopedic complications. Compartment syndrome, fat embolism syndrome, and venous thromboembolism. Specialized education in the care of orthopedic patients includes an understanding of the common complications for which patients require monitoring. With a socioeconomic backdrop of decreasing hospital stays and prospective payment, patient care must be managed proactively. For all three complications presented, there are unique sets of risk factors that, when present, contribute to a high index of suspicion for morbidity. Clusters of symptoms have also been discussed representing the expected normal patterns. With this knowledge as a foundation, clinical application is essential to incorporate other salient aspects of individual situations. Nurses diagnose and treat human responses to health problems. The end result of human responses to injury or orthopedic conditions can be the development of complications. Stringent adherence to patient monitoring protocols can promote timely nursing interventions to prevent, minimize, or detect complications or treatment side effects. Although definitive treatment is often physician directed, nurses are in a key role to impact final patient outcomes. 
2	The effect of ambulation on recovery from postoperative ileus. To determine whether ambulation hastens recovery from ileus following laparotomy, 34 patients were studied, 10 of whom followed an ambulatory regimen beginning on postoperative day 1 (group A). The other 24 patients (group C) did not become ambulatory until postoperative day 4. All patients underwent placement of seromuscular bipolar recording electrodes on the Roux limb, if present, stomach, jejunum, and colon at laparotomy. Group A was recorded before and after ambulation so comparisons could be made to determine if ambulation had an acute effect on myoelectric activity. Group A preambulation and group C recordings were compared to judge whether there was an over-all effect of ambulation on myoelectric recovery. No effect on slow wave frequency or percentage of slow waves with associated spike potentials was noted acutely or overall in the stomach, colon, or jejunum in continuity with the duodenal pacemaker. Transient increases in phase II spike activity in patients having a Roux limb and their jejunum distal to the enteroenterostomy were noted on postoperative days 1 to 2, but these differences resolved by postoperative days 3 or 4. The data suggest that ambulation as a means to help resolve postoperative ileus and its accompanying cramps and bloating may be more perceived than real. 
5	Peripheral nerve function in sepsis and multiple organ failure Forty-three patients who had sepsis and multiple organ failure (critical illness) were studied prospectively to determine the incidence and severity of peripheral nerve function and to correlate such function with a number of variables. Electrophysiologic studies indicated a primary axonal degeneration of motor and sensory fibers in 30 (70 percent). Fifteen (30 percent) had the clinical signs of difficulty in weaning from assisted ventilation, weakness of limb muscles, and reduced or absent deep tendon reflexes. Full recovery from the polyneuropathy occurred among the 23 (53 percent) who survived, except three who had a very severe polyneuropathy. A peripheral nerve function index, computed from electrophysiologic measurements, showed statistically significant (p less than 0.01) negative correlations with the time in the critical care unit, and the serum glucose value; the serum albumin level showed a positive correlation. Multiple regression analyses indicated all three factors accounted for 47 percent (r2 = 0.4678) of all potential variables. In a separate analysis, the nerve function index correlated with the amplitude of the diaphragm compound muscle action potential (p less than 0.01). The results were consistent with the polyneuropathy being due to the same mechanisms that are currently postulated to cause dysfunction in this syndrome of other organ systems (including the neuromuscular respiratory system). 
1	Magnetic resonance imaging of facial nerve neuromas. Facial nerve neuromas are uncommon tumors often confused with other tumors of the temporal bone and cerebellopontine angle. Radiologically, it may be impossible to differentiate an intracanalicular facial nerve neuroma from an acoustic neuroma. We present three case reports of facial nerve neuromas arising within the internal auditory canal to show the important magnetic resonance imaging features of these tumors. One tumor extended into the cerebellopontine angle, middle cranial fossa, and middle ear. Another filled the internal auditory canal and extended through the cerebellopontine angle to the brain stem. The third occurred in a patient who had neurofibromatosis as well as numerous other intracranial tumors. We feel that gadolinium-enhanced magnetic resonance imaging provides the most useful information in the preoperative assessment of this disorder. 
1	Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer. Eighty-nine patients with carcinoma of the head of the pancreas underwent pancreaticoduodenectomies. The actuarial 5-year survival for all 89 patients was 19%, with a median survival of 11.9 months. The 81 hospital survivors were analyzed in an effort to determine factors influencing long-term survival. Negative lymph nodes and the absence of blood vessel invasion both favored long-term survival. The strongest predictive factor was negative lymph node status with a median survival of 55.8 months, compared with 11 months with lymph nodes involved with tumor (p less than 0.05). Blood transfusions were also predictive, with patients receiving two or fewer units having a median survival of 24.7 months, compared with 10.2 months for those receiving three or more units (p less than 0.05). The most important determinant of long-term survival after pancreaticoduodenectomy for pancreatic cancer is biology of the tumor (lymph node status, blood vessel invasion). However, performance of the resection (units of blood transfused) also appears to be an important factor influencing survival. 
5	Surgical management of cervical soft disc herniation. A comparison between the anterior and posterior approach. Anterior cervical fusion was initially described in the 1950s for cervical spondylotic radiculopathy. The indications for this procedure in the management of soft disc herniation have not been clearly defined. In addition, controversy exists as to whether a cervical soft herniation should be managed by an anterior approach or a posterior cervical laminotomy-foraminotomy. The authors report the results of a prospective study comparing anterior discectomy and fusion to posterior laminotomy-foraminotomy for the management of soft cervical disc herniation. Twenty-eight patients underwent anterior discectomy and fusion (Robinson horseshoe graft) while 16 patients underwent posterior laminotomy-foraminotomy. The disc herniations were classified into two types. Type I were single level anterolateral herniations (33 patients) while type II were central soft disc herniations (11 patients). Clinically, patients with type I herniations manifested signs and symptoms of radiculopathy while patients with type II herniations manifested signs of myelopathy or neck pain and bilateral upper extremity paresthesias in 4 patients. Confirmatory studies were myelography in 12 patients, myelography combined with computed tomography (CT) in 26 patients, and magnetic resonance imaging (MRI) in 6 patients. For type I herniations, 17 patients underwent anterior fusion while 16 patients had a posterior laminotomy-foraminotomy. The 11 patients classified as type II herniation all underwent anterior discectomy and fusion. There were 27 men and 17 women. The age range was 21 to 52 years (mean, 41 years). The follow-up was 1.6 to 8.2 years (mean, 4.2 years). 
1	Regressing atypical histiocytosis. Aberrant prothymocyte differentiation, T-cell receptor gene rearrangements, and nodal involvement. Two cases of regressing atypical histiocytosis were studied. New findings reported include the presence of CD1 epitope on large atypical histiocytoid cells and apparent early lymph node involvement. Because regressing atypical histiocytosis may demonstrate aberrant thymic differentiation antigen expression and T-cell receptor gene rearrangements, initial lymph node involvement, and eventuation in conventional lymphoma in some cases, the alternative term regressing-phase anaplastic lymphoma is proposed as a more accurate designation for this entity. 
4	Reperfusion arrhythmias after thrombolysis. Electrophysiologic tempest, or much ado about nothing. Arrhythmias that may accompany myocardial reperfusion have generated significant clinical interest. First, there were concerns, based on animal studies, that high-grade ventricular tachyarrhythmias would pose a serious threat following thrombolytic therapy to treat an evolving myocardial infarction. Second, lower-grade arrhythmias, such as accelerated idioventricular rhythm, were cited as useful, noninvasive markers of successful reperfusion. Critical review of the current data, however, indicates that arrhythmias following thrombolytic therapy for acute myocardial infarction are usually neither dangerous clinical events nor consistent markers of reperfusion. 
4	Hyperadrenergic orthostatic intolerance as a result of postpartum blood loss. This article describes a young women in whom orthostatic intolerance developed as a result of protracted postpartum vaginal bleeding. The cardiovascular abnormalities were unresponsive to usual treatment measures, and she required combination therapy directed at increasing plasma volume and decreasing sympathetic nervous system activity. After resolution of her symptoms, the patient required no long-term therapy. Chronic blood loss has not been reported as a cause of this syndrome. 
5	Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns. Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic modality for newborn respiratory failure, but there is little information available regarding the prognostic determinants with this technique. One hundred thirty-five newborns treated with ECMO over a 4-year period were critically analyzed with regard to the influence that birth weight, gestational age, age at initiation of ECMO, best blood gases before ECMO, number of hours on ECMO, renal failure, intracerebral hemorrhage, and long-distance air transport had on survival. Infants with meconium aspiration and those undergoing long-distance transfer showed significant differences in blood gases before ECMO, with survivors having more normal pH and carbon dioxide tension values. Intracerebral hemorrhage and renal failure that developed during ECMO were grave prognostic signs, with few survivors in either group. These data show that ability to ventilate patients before ECMO, giving normal carbon dioxide tension and pH values, is an important prognostic sign in infants with meconium aspiration and undergoing long-distance transfer for ECMO, whereas renal failure and intracerebral hemorrhage are usually lethal complications of ECMO. Each center performing ECMO should continually reevaluate this invasive technique and its results and complications. 
5	Ruling out acute myocardial infarction. A prospective multicenter validation of a 12-hour strategy for patients at low risk BACKGROUND. Although previous investigations have suggested that 24 hours is required to exclude acute myocardial infarction in patients who are admitted to a coronary care unit for the evaluation of acute chest pain, we hypothesized that a 12-hour period might be adequate for patients with a low probability of infarction at the time of admission. METHODS. Using a Bayesian model, we developed a strategy to identify candidates for a shorter period of observation from an analysis of a derivation set of 976 patients with acute chest pain who were admitted to three teaching and four community hospitals. In the derivation set, patients whose clinical characteristics in the emergency room predicted a low (less than or equal to 7 percent) probability of myocardial infarction had only a 0.4 percent risk of infarction if they had neither abnormal levels of cardiac enzymes nor recurrent ischemic pain during the first 12 hours of hospitalization. In an independent testing set of 2684 patients from the seven hospitals, 957 admitted patients (36 percent) were classified as candidates for this 12-hour period of observation according to a previously published multivariate algorithm. Few of these patients were actually transferred from a monitored setting at 12 hours. RESULTS. Of the 771 candidates for a 12-hour period of observation who did not have enzyme abnormalities or recurrent pain during the first 12 hours, 4 (0.5 percent) were subsequently found to have acute myocardial infarction, and only 3 (0.4 percent) died after primary cardiac arrests, all of which occurred three to five days after admission. Rates of other major cardiovascular complications were low in the patients who might have been transferred from the coronary care unit after 12 hours with this strategy. In patients with a higher initial risk of infarction, the standard strategy of 24-hour observation identified all but 11 of 739 acute myocardial infarctions (1 percent). CONCLUSIONS. Emergency room clinical data can be used to identify a large subgroup of patients for whom a 12-hour period of observation is normally sufficient to exclude acute myocardial infarction. Patient-specific evaluation and treatment can then proceed without the restrictions imposed by "rule-out" protocols for myocardial infarction. 
5	Intraoperative management of severe endobronchial hemorrhage Endobronchial hemorrhage due to pulmonary artery perforation by a Swan-Ganz catheter developed during coronary artery bypass grafting while weaning from cardiopulmonary bypass. After reinstitution of cardio-pulmonary bypass with pulmonary artery venting, bleeding was localized to the right lower lobe bronchus using fiberoptic bronchoscopy. A Fogarty embolectomy catheter was inflated in the bronchus to tamponade successfully only the right lower lobe. This case illustrates a method of distal bronchial blockade for maximal retention of pulmonary function and avoidance of pulmonary resection. 
5	From chimney sweeps to oncogenes: the quest for the causes of cancer. Over the past 200 years, a bewildering array of chemical, physical, and viral agents has been identified that can cause cancer, but the mechanisms involved are only now becoming clear. In the leukemias and lymphomas, it appears that the activation of cellular oncogenes is important. The genes involved are present in all normal cells and are often associated with cell growth and regulation. When activated, they act in a dominant fashion to cause a cell to express the malignant phenotype. There is increasing evidence that in solid tumors, a more important mechanism may be the loss of a suppressor gene. The classic example is retinoblastoma, in which the retinoblastoma gene has been cloned and is also found to be associated with several other common cancers including sarcomas and small cell lung cancer. It is likely to be one of a family of such genes. It may well be that the activation of one or more oncogenes or the loss of one or more suppressor genes, or both, is required for a tumor to progress from initiation through promotion to a metastasizing malignancy. 
1	Roentgenographic evaluation of the augmented breast. We performed a retrospective study to determine the sensitivity of mammography in detecting breast cancer arising in women with augmented breasts. Of eight women with breast implants in whom breast cancer developed, six had mammograms before biopsy. Only two of the six cancers were identified mammographically (sensitivity = 33%), and one of these two was seen only in retrospect. In both cases, the mammographic findings suggested a benign rather than a malignant process. All eight women had a palpable mass and early disease, and all are clinically disease-free at present. The sensitivity of mammography in detecting palpable cancers in a control group of women without implants was 92% (118 of 128). For tumors of 2 cm or less, the sensitivity was 88% (58 of 66). These results suggest that the sensitivity of mammography in detecting breast cancer is decreased when implants are present. Further investigations are needed to determine the effects of prostheses on mammographic evaluations. 
2	Serological evidence of infection with Helicobacter pylori may predict gastrointestinal intolerance to non-steroidal anti-inflammatory drug (NSAID) treatment in rheumatoid arthritis. Specific circulating antibodies to the spiral gastric organism, Helicobacter pylori (HP) were detectable in 43% of 68 patients with rheumatoid arthritis by complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA), a frequency comparable with that of a normal, age-matched population. Presence of these antibodies correlated strongly with a previous history of peptic ulcer disease (PUD) and to the severity of NSAID-related dyspeptic symptoms, the latter often leading to multiple drug intolerance. This contrasts with short term, prospective NSAID toxicity data, which show little relationship between ulceration and HP carriage. This result suggests, however, that HP may have a definite role in the pathogenesis of symptomatic PUD associated with more chronic NSAID usage, and may have important implications for ulcer prophylaxis in these patients. 
2	Typhlitis due to Balantidium coli in captive lowland gorillas. Typhlitis caused by Balantidium coli and requiring surgical resection occurred in three captive lowland gorillas over a 30-month period. Not one of the other gorillas in the colony or their keepers was ill. B. coli is distributed widely geographically and widely among mammals. Asymptomatic commensalism predominates, but invasion of the colonic mucosa can produce diarrhea and dysentery and set the stage for local or systemic spread. 
2	Prevention of a false diagnosis of sexually acquired reactive arthritis by synovial lymphocyte responses. Three cases are reported in which a diagnosis of sexually acquired reactive arthritis might have been made erroneously from the history, but the enteric origin of the reactive arthritis was evident from synovial lymphocyte responses. The importance of making the correct diagnosis and the avoidance of unwarranted spousal dysharmony is stressed. 
4	Limitation of retinal injury by vitreoperfusion initiated after onset of ischemia. We tested whether vitreoperfusion, a new method of perfusing the vitreous cavity with solutions containing nutrients, can limit retinal injury if initiated after the onset of ischemia. Severe bilateral ocular ischemia was induced in cats with healed lensectomy-vitrectomy wounds; 30, 60, 90, or 120 minutes later, one eye from each of 18 cats underwent vitreoperfusion while the ischemia continued for 120 minutes. The other eye simultaneously underwent either continued untreated ischemia or reinstated circulation. The histopathologic abnormalities evident after 8 days depended on the duration of ischemia. Reinstated circulation yielded less retinal damage than continued ischemia. Nine additional cats underwent bilateral ischemia for at least 210 minutes. Vitreoperfusion was initiated in one eye after 30 minutes. In each cat, the vitreoperfused eye fared significantly better as observed histopathologically and electroretinographically. We believe that no other treatment has similarly limited retinal injury in vivo when initiated so long after total ocular ischemia has developed. 
4	Heparin as the cause of coagulopathy which may complicate grafting of the liver. Disposal of heparin is accomplished rapidly by the normal liver, but the effects of ischemia, flushing and hypothermia during hepatic transplantation have not been investigated before. The results of the present study showed that neither laparotomy, hypothermia nor insertion of the portosystemic bypass seemed markedly to affect the coagulation profile, but autograft associated with 30 to 45 minutes of warm ischemia resulted in a twofold prolongation of the t1/2 heparin as calculated from sequential measurements of the activated clotting time. Unexpectedly, the storage of livers for four hours in EuroCollins solutions seemed to result in more rapid disappearance of heparin than in animals after laparotomy. After hepatectomy, the clearance of heparin was delayed for two hours but, thereafter, the slope of the disappearance resembled that in sham operated animals. Autograft and allograft of livers in normal pigs that did not receive transfusion were also associated with changes in fibrinolysis and declining levels of fibrinogen together with severe intraoperative bleeding problems and rapid death on the operating table in 30 per cent of the pigs. While administration of heparin alone did not appear to precipitate these changes, use of the drug after dissection, mobilization and storage of the liver may release other tissue factors that activate fibrinolysis. 
1	Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. We evaluated the outcome in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS) associated with histologically verified small-cell carcinoma (SCC). Thirteen patients received specific tumor therapy (chemotherapy, radiation therapy, or resection) and most also received pharmacologic and immunologic treatment for LEMS. Seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement (1 patient being in complete remission at 7 years); in 3 of 11 improvement was transient. An EMG index of disease severity (compound muscle action potential amplitude in abductor digiti minimi) was significantly increased at final follow-up (p less than 0.01; n = 11). A pretreatment amplitude greater than 3.0 mV was a good prognostic sign. We conclude that a combined treatment approach in SCC-LEMS usually results in neurologic improvement. 
5	Management of perineal wounds following abdominoperineal resection with inferior gluteal flaps. Our experience treating perineal wounds secondary to abdominoperineal resection, either for inflammatory bowel disease or cancer, is presented. A total of 16 patients were treated either on a delayed basis or at the same time as the abdominoperineal resection. All wounds were closed using the inferior gluteal myocutaneous flap. Fifteen of 16 patients have achieved healing, eight of whom had no complications. Only minor revisions or local wound care were required in the remaining patients, with only one patient failing to heal. Our results compare favorably with previous reports of treatment of this difficult problem. 
4	Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients BACKGROUND. Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium. To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease. METHODS. We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter. Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per kilogram of body weight per minute, for two minutes). We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium. RESULTS. In patients with normal coronary arteries, the highest dose of serotonin increased cross-sectional area by 52 percent (P less than 0.001) and blood flow by 58 percent (P less than 0.01). The effect was significantly potentiated by administration of ketanserin. In patients with coronary-artery atherosclerosis, serotonin reduced cross-sectional area by 64 percent (P less than 0.001) and blood flow by 59 percent (P less than 0.001). Ketanserin prevented this effect. CONCLUSIONS. Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect. When considered with other evidence, these data suggest that platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes. 
3	Survey of adolescents with severe intellectual handicap. A diagnostic survey was undertaken of children aged 11 to 19 years in Tameside with severe learning difficulties (intelligence quotient less than or equal to 50). Eighty-two children were identified and their medical records reviewed. A specific diagnosis for the retardation was documented in 25 (30%) of the children, 18 of whom had Down's syndrome. A probable aetiology or a disorder of unknown aetiology had been identified in a further 21 (26%) children. To confirm the existing diagnosis, identify new diagnoses, and offer genetic counselling, the parents of 63 children were offered detailed reassessment of their child. Fifty three children were reviewed, and a specific disorder identified in 25 out of 31 previously undiagnosed children. The most frequent diagnoses made were fragile X syndrome and Rett's syndrome. On completion of the survey, 61 of the 82 children (74%) had a specific diagnosis or probable aetiology identified, 12 (15%) had associated disorders such as cerebral palsy, and in only nine of the 82 children (11%) were there no clues at all to the cause of their retardation. 
4	Ultrasonic evaluation of early carotid atherosclerosis. We investigated the prevalence of carotid atherosclerosis, including mild early lesions, and its association with cervical bruits and various risk factors (age, male sex, hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking) in 232 consecutive Japanese patients. High-resolution real-time B-mode ultrasonography was performed to determine the extent of atherosclerosis, and it was quantified by using a scoring system. The prevalence of carotid atherosclerosis was 49%, 59%, and 41% in all 232 patients, the 100 symptomatic patients, and the 132 asymptomatic patients, respectively. Although carotid lesions were detected frequently (87%) in the 30 patients with cervical bruits, bruits were noted in only 30% of the 88 examined patients with carotid atherosclerosis. Independent risk factors for carotid atherosclerosis in these patients were found to be age, male sex, and hyperlipidemia; diabetes mellitus was a possible risk factor for carotid atherosclerosis. Our study did not show a close association between hypertension and carotid atherosclerosis, and this might be caused by the high prevalence of hypertension in our patients. Our findings suggest an increasing prevalence of carotid atherosclerosis in the Japanese, though this should be confirmed in a population-based study. Our study demonstrates the clinical usefulness of high-resolution B-mode ultrasonography for the evaluation of early carotid atherosclerosis. 
1	Granular cell tumor of the esophagus: endoscopic ultrasonographic demonstration and endoscopic removal. A 35-yr-old Japanese man with a granular cell tumor of the esophagus that was removed by endoscopic polypectomy is presented. Radiography and endoscopy showed a 20 x 12 mm sessile protrusion in the distal esophagus. Endoscopic ultrasonography demonstrated the hypoechoic mass in the submucosa without continuity to the muscularis propria. The lesion was successfully treated by endoscopic polypectomy without complications. The cross-sections of the resected specimen were quite in agreement with the ultrasonographic findings. Endoscopic ultrasonography is valuable to assess the exact location and extent of the tumor, and to determine the indication for endoscopic polypectomy. 
1	Coexpression patterns of vimentin and glial filament protein with cytokeratins in the normal, hyperplastic, and neoplastic breast. The authors studied by immunohistochemistry the intermediate filament (IF) protein profile of 66 frozen samples of breast tissue, including normal parenchyma, all variants of fibrocystic disease (FCD), fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies (MAbs) to cytokeratins included MAb KA 1, which binds to polypeptide 5 in a complex with polypeptide 14 and recognizes preferentially myoepithelial cells; MAb KA4, which binds to polypeptides 14, 15, 16 and 19; individual MAbs to polypeptides 7, 13, and 16, 17, 18, and 19, and the MAb mixture AE1/AE3. The authors also applied three MAbs to vimentin (Vim), and three MAbs to glial filament protein (GFP). Selected samples were studied by double-label immunofluorescence microscopy and by staining sequential sections with some of the said MAbs, an MAb to alpha-smooth muscle actin, and well-characterized polyclonal antibodies for the possible coexpression of diverse types of cytoskeletal proteins. Gel electrophoresis and immunoblot analysis also were performed. All samples reacted for cytokeratins with MAbs AE1/AE3, although the reaction did not involve all cells. Monoclonal antibody KA4 stained preferentially the luminal-secretory cells in the normal breast and in FCD, whereas it stained the vast majority of cells in all carcinomas. Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas. Vimentin-positive cells were found in 8 of 12 normal breasts and in 12 of 20 FCD; in most cases, Vim-reactive cells appeared to be myoepithelial, but occasional luminal cells were also stained. Variable subpopulations of Vim-positive cells were noted in 9 of 20 ductal and in 1 of 7 lobular carcinomas. Glial filament protein-reactive cells were found in normal breast lobules and ducts and in 15 of 20 cases of FCD; with rare exceptions, GFP-reactivity was restricted to basally located, myoepithelial-appearing cells. Occasional GFP-reactive cells were found in 3 of 31 carcinomas. Evaluation of sequential sections and double-label immunofluorescence microscopy showed the coexpression of certain cytokeratins (possibly including polypeptides 14 and 17) with vimentin and alpha-smooth muscle actin together with GFP in some myoepithelial cells. The presence of GFP in myoepithelial cells was confirmed by gel electrophoresis and immunoblotting. Our results indicate that coexpression of cytokeratin with vimentin and/or GFP is comparatively frequent in normal basal-myoepithelial cells of the breast.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	Carotid artery disease in patients with head and neck carcinoma. Irradiation has been shown experimentally to cause accelerated development of atherosclerosis in exposed large arteries. However, occurrence of such an entity in carotid arteries of patients after treatment for head and neck carcinoma is unknown. Therefore, we reviewed 179 patient charts who had undergone head and neck operations with or without irradiation between 1979-1987. Of these 179 patients, 107 (59.8%) were dead at time of follow-up. Cause of death was unknown in 42 (40%) patients; in the remainder included: respiratory arrest--33; carcinoma-related--18; cardiac--6;pneumonia--7; and trauma--1. Average interval from treatment to death was 23.5 months. Of the 72 patients known to be alive, follow-up was obtained in 52 patients. Their average age was 64.9 years. Risk factors for atherosclerosis included: male gender--43; smoking--50; hypertension--9; diabetes--4; coronary artery disease--12; and peripheral vascular disease--4. Seventy-five per cent of these patients received postoperative irradiation. Average follow-up was 64.5 months. Duplex scans were performed on 34 patients. Three patients had common or internal carotid stenoses greater than 75 per cent. All of these patients had received irradiation and none of them were symptomatic. Seven patients had carotid stenoses between 50 to 75 per cent; five of these had received irradiation. Of these five patients, one had a stroke 60 months postoperatively, and one had a TIA 36 months postoperatively. The remaining 58 patients (of which 48 had irradiation) had carotid stenoses less than 50 per cent and none were symptomatic. 
2	Hepatic fibrin-ring granulomas in a patient with hepatitis A. Hepatic fibrin-ring granulomas were found in a 30-year-old patient with serologically confirmed hepatitis A. Other causes associated with the presence of fibrin-ring granulomas in the liver, such as Hodgkin's and non-Hodgkin's lymphoma, cytomegalovirus infection, visceral leishmaniasis, and consumption of allopurinol, were ruled out. It is suggested that hepatitis A must be included in the differential diagnosis of a patient with hepatic fibrin-ring granulomas. 
4	Neurogenic control of the cerebral circulation during global ischemia. The influence of the trigeminal nerve on the cerebral circulation was investigated in chronically denervated cats during and after reversible four-vessel occlusion for 10 minutes combined with controlled hypotension (50 mm Hg). Postocclusive hyperemia 30 minutes after reperfusion was attenuated by up to 48% in cortical gray matter of the anterior, middle, and posterior cerebral artery territories on the side of trigeminal ganglionectomy. Similar results were observed for denervation accomplished by direct surgical ablation and by the topical application of capsaicin to a cortical branch of the middle cerebral artery. Denervation did not alter basal cerebral blood flow or the duration of hyperemia, nor did it impair the cerebrovascular response to hypercapnia. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion and suggest that strategies directed at blocking axon reflex-like mechanisms may be beneficial in reducing the morbidity that follows severe cortical hyperemia. 
5	Bronchiolar inflammation and fibrosis associated with smoking. A morphologic cross-sectional population analysis. The lungs of 42 smokers and 13 nonsmoking males of various ages who died suddenly and unexpectedly were examined grossly using Gough-Wentworth whole-lung sections and by microscopic planimetry to assess the severity and prevalence of emphysema. The bronchioles in representative histologic sections were evaluated for inflammation and epithelial metaplasia as well as for fibrosis and muscular hypertrophy. Postmortem interviews with next of kin established a history of cigarette smoking and excluded possible occupational exposures to toxic or particulate inhalants. Emphysematous changes were not prominent in members of the study group, but they tended to be more severe in smokers (p = 0.059) and increased in severity with age (p less than 0.001). Inflammatory changes (so-called smoker's bronchiolitis) were evident in smokers of all ages, although they were significantly less prominent in the lungs of older smokers. On the other hand, respiratory and membranous bronchiolar wall fibrosis was increasingly evident in older smokers (p less than 0.05). Muscular hypertrophy in the bronchiolar walls was significantly greater in smokers, but a change with age was not observed. These findings strongly suggest that bronchiolar fibrosis is associated with chronic cigarette use. These lesions occur independently of emphysema and may account for some of the subtle physiologic alterations observed in smokers. 
1	Intramuscular hemangioma in the oral region: report of three cases. The occurrence of intramuscular hemangioma in an intraoral or perioral localization is rare, and a thorough knowledge of these tumors is necessary for adequate diagnosis and treatment. Three cases are presented with discussion, and their histopathology and differential diagnosis are discussed. An adequate primary excision is necessary to avoid recurrence. 
5	Rupture of a giant carotid aneurysm after extracranial-to-intracranial bypass surgery. We report a case of a fatal rupture of a previously unruptured giant aneurysm of the bifurcation of the internal carotid artery (ICA), which occurred after an extracranial-intracranial (EC-IC) bypass and the partial occlusion of the ICA. Interim angiography showed retrograde filling of the proximal middle cerebral artery to the aneurysm. There have been four previously reported cases of giant aneurysms rupturing after treatment with an EC-IC bypass and carotid ligation, and it appears likely that a change in pressure/flow dynamics produced by the bypass may have been the cause. The technique of carotid ligation with an EC-IC bypass is used frequently to treat unclippable intracranial aneurysms, and the resulting hemodynamic changes need to be considered carefully to prevent this type of complication. To minimize hemodynamic stress on the aneurysm, we suggest that 1) the bypass caliber should be as small as possible consistent with sufficient cerebral blood flow after ICA occlusion, and 2) complete ICA occlusion should be performed as soon as possible after the bypass. 
5	Colon cancer in pregnancy with elevated maternal serum alpha-fetoprotein level at presentation. A case of colon cancer in pregnancy is presented in which the maternal serum alpha-fetoprotein level was elevated. Failure to evaluate colon cancer as a cause of the elevated maternal serum alpha-fetoprotein may have accounted for the poor outcome. 
4	The origin and fate of complex coronary lesions. Complex irregular coronary artery stenoses, representing plaque rupture/thrombosis, are associated with the acute coronary syndromes. However, the natural history (origin and fate) of these lesions is not known. To examine this issue we studied 255 patients who had had two to four arteriograms within a mean interval of 2.6 +/- 1.7 years. Of 53 irregular lesions that had progressed on a later arteriogram, 35 (66%) originated from areas that were smooth and less than 50% in stenosis diameter. Of 44 irregular lesions on an earlier study, 10 (23%) became totally occluded, five (11%) progressed in severity (all remained irregular), 25 (57%) showed no change in severity (all remained irregular), and four (9%) regressed (two became smooth). Nine of the 10 lesions progressing to occlusion were greater than or equal to 95% stenosed on the earlier study. Only 2 of 44 lesions (5%) showed smoothing. These findings are in agreement with the concept that irregular lesions represent ruptured atherosclerotic plaques and demonstrate that they usually originate from mildly occlusive smooth plaques. Markedly narrowed irregular lesions (greater than or equal to 95% stenosis) frequently progress to occlusion. Irregular lesions less than 90% narrowed commonly remain angiographically stable, and irregular over several years. They were found rarely to evolve into smooth-walled plaques. 
5	Absent or minimal cerebrospinal fluid abnormalities in Haemophilus influenzae meningitis. A case of Haemophilus influenzae type b (Hib) meningitis in which the diagnosis and treatment were delayed because of normal cerebrospinal fluid analysis is presented. A retrospective review was conducted at two children's hospitals to determine the frequency and clinical characteristics of patients with Hib meningitis whose spinal fluid had a normal total white blood cell count, normal chemistries, and negative Gram stain, but subsequent growth of Hib in culture. Of 379 cases of Hib meningitis, two had completely normal CSF, and two had CSF containing small numbers of polymorphonuclear cells as the sole abnormality. In three of the four cases, the duration of symptoms was less than 24 hours, and appropriate therapy was significantly delayed because of benign-appearing CSF. Normal CSF cell counts, chemistries, and Gram stain do not exclude the possibility of bacterial meningitis, and one should remain suspicious when a child has clinical findings suggesting meningitis. 
2	Hypophosphatemia and renal tubular dysfunction in alcoholics. Are they related to liver function impairment? The study was designed to evaluate (a) the role of reduced renal phosphate reabsorptive capacity assessed as the ratio of maximum capacity for renal phosphate reabsorption (TmPO4) to glomerular filtration rate (GFR) in the pathogenesis of hypophosphatemia in alcoholics, (b) possible mechanisms leading to reduced TmPO4/GFR, and (c) the effect of liver function impairment on TmPO4/GFR. The TmPO4/GFR, its major extrarenal determinants, ratios of urinary excretion gamma-glutamyl transpeptidase and of alpha-glucosidase to GFR (uGGT/GFR and uAGL/GFR), indices of structural damage of renal tubular cells, and fractional clearance of lysozyme, an index of proximal renal function, were evaluated in 31 alcoholics with alcohol-related liver disease, 24 alcoholics without alcohol-related liver disease, 14 patients with non-alcohol-related liver disease, and 25 control subjects. Hypophosphatemia was found in 35% of alcoholics with alcohol-related liver disease, 29% of alcoholics without alcohol-related liver disease, and no patients with non-alcohol-related liver disease. A reduced TmPO4/GFR was the major determinant of hypophosphatemia in both groups of alcoholics. No difference in extrarenal determinants of TmPO4/GFR was found between alcoholics with and without hypophosphatemia. Alcoholics with and without alcohol-related liver disease had increased uGGT/GFR and normal uAGL/GFR regardless of serum phosphate level. Fractional clearance of lysozyme, instead, was increased only in hypophosphatemic alcoholics with and without alcohol-related liver disease. The TmPO4/GFR correlated inversely with the fractional clearance of lysozyme in both groups of alcoholics (P less than 0.01). The TmPO4/GFR and urinary enzymes were normal in patients with non-alcohol-related liver disease. It was concluded that a reduced TmPO4/GFR is involved in the pathogenesis of hypophosphatemia in alcoholics. A proximal tubular dysfunction seems to be responsible for the reduced TmPO4/GFR. Liver function impairment is not required for the expression of this tubular dysfunction. 
3	A retrospective study of spontaneous remission and long-term outcome in patients with infantile spasms. The spontaneous remission rate and long-term outcome in 44 patients with infantile spasms not treated with hormonal drugs were studied. The cumulative spontaneous remission rate during the first 12 months after onset of infantile spasms, as determined by retrospective analysis, was as follows: 1 month, 2%; 2 months, 2%; 3 months, 5%; 4 months, 7%; 5 months, 9%; 6 months, 11%; 7 months, 11%; 8 months, 14%; 9 months, 16%; 10 months, 18%; 11 months, 25%; 12 months, 25%. The average age at follow-up was 80 months. Nine percent of patients had normal development or only mild impairment. The remainder showed various degrees of retardation. These data should be useful in the design and interpretation of therapeutic drug trials in patients with infantile spasms. 
5	Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Intestinal perforation due to cytomegalovirus (CMV) infection in patients with AIDS is the most common life-threatening condition requiring emergency celiotomy in these patients. The authors describe a patient with AIDS with intestinal perforation due to CMV infection, and review 14 additional cases reported in the English-language surgical literature. The diagnostic triad of pneumoperitoneum on x-ray, evidence or history of CMV infection, and AIDS occurred in 70 percent of patients. The most common site of intestinal perforation was the colon (53 percent), followed in frequency by the distal ileum (40 percent) and appendix (7 percent); perforation usually occurred between the distal ileum and splenic flexure of the colon. Colonoscopy, rather than sigmoidoscopy, is recommended as a screening examination in patients with AIDS suspected of having colonic ulceration due to CMV infection. Multiple biopsies of ulcerated tissue should be obtained. Gross and microscopic analyses of involved intestinal tissue reveal the characteristic findings of ulceration and CMV infection. Despite aggressive therapy, the operative mortality rate in patients with AIDS with intestinal perforation due to CMV infection was 54 percent and the overall mortality rate was 87 percent. Postoperative complications occurred in most patients and consisted mainly of systemic sepsis and pneumonia caused by Pneumocystis carinii infection. An increased awareness of this syndrome by physicians frequently called on to manage patients with AIDS is recommended. 
5	Clinical and anatomical considerations for nonoperative therapy in tibial disease and the results of angioplasty. For a 6-year period, 96 patients had 146 below-knee angioplasties. There were 31 total occlusions and 95 multiple stenoses. All patients had distal ischemia, and 40% had gangrene. The primary success rate was 97%, and the 2-year limb salvage rate was 83%. The ankle/brachial index increased from a mean of 0.25 before the procedure to 0.62 afterward. At 2 years (35 patients), the mean ankle/brachial index was 0.55. For the same period, 320 femorodistal bypasses were performed. The results of angioplasty are comparable to those of surgery, but angioplasty is only suitable in about 20-30% of patients presenting with isolated tibial disease. Suitable lesions are five or fewer stenoses and occlusions 5 cm or less in length. 
2	Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. To investigate the effect of human immunodeficiency virus type 1 (HIV-1) infection on subsequent hepatitis B virus (HBV) infection, HIV antibody was sought in homosexual men who developed HBV infection during a hepatitis B vaccine trial. Among 134 unvaccinated HIV-1-negative men, 7% became HBV carriers, 64% had viremia, and 42% had clinical illness. Among vaccinated HIV-1-negative men, HBV infection severity decreased with number of vaccine doses administered. When adjusted for prior hepatitis B vaccination status, persons with HIV-1 infection preceding HBV infection had a significantly higher risk of developing HBV carriage, viremia, prolonged ALT elevation, and clinical illness. Among HIV-1-infected men, the risk of HBV carriage was increased in unvaccinated persons (21%) and those who failed to respond to vaccination (31%) and further increased in those who received vaccine doses at the time they developed new HBV infection (56%-80%), suggesting inactivated hepatitis B vaccine may temporarily impair the immune response to HBV infection in HIV-1-infected persons. HIV-1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow-up of men who became HBV carriers. 
5	Peripheral neuropathy associated with eosinophilia-myalgia syndrome. In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations. 
4	Metabolic considerations in hypertension. The frequent concurrence of other cardiovascular risk factors in hypertensive patients, such as obesity and diabetes mellitus, suggests that overlapping genetic and environmental factors may contribute to the common metabolic and cardiovascular derangements observed in these populations. Hypertension and hyperglycemia accelerate atherosclerosis in diabetics, and play an important role in associated morbidity and mortality. Several abnormalities in blood pressure regulatory systems such as the renin-angiotensin system, the sympathetic nervous system, and sodium/volume control have been described in diabetes mellitus. Sodium retention and cardiovascular hyperreactivity appear to occur early in the course of diabetes mellitus, even at normal blood pressure levels and before onset of renal failure, and could set the stage for the development of hypertension. The relationship between obesity and hypertension is also well-established, and may reflect metabolic and cardiovascular adaptations in obese subjects which predispose to blood pressure elevations. Obese subjects display changes in sympathetic nervous system activity, sodium metabolism, and vascular hemodynamics. Sodium-sensitive blood pressure responses in the obese may be secondary to increased cardiac output or fluid volume, and are directly related to circulating insulin levels. Certain metabolic and vascular characteristics of obesity and diabetes mellitus are found in patients with essential hypertension. It has been suggested that insulin and insulin resistance may be the common link between these risk factors. Improved understanding of metabolic considerations in the treatment of obese and diabetic hypertensives should lead to more careful selection of medications that avoid metabolic complications. Although diuretics and beta-blockers may be useful in some patients, there are several reasons not to recommend their use as initial therapy in obese and diabetic hypertensives. On the other hand, calcium channel blockers and angiotensin converting enzyme inhibitors are highly effective, with minimal effects on metabolic parameters, and are well-suited as first-line therapy in the treatment of obese and diabetic hypertensives. 
5	Morphologic comparison of patients with mitral valve prolapse who died suddenly with patients who died from severe valvular dysfunction or other conditions. Clinical and necropsy findings are described in 56 patients with mitral valve prolapse: 15 patients, aged 16 to 69 years (mean 39), died suddenly and mitral valve prolapse was the only cardiac condition found at necropsy (hereafter called isolated mitral valve prolapse); the remaining 41 patients had other conditions that were capable of being fatal. Of the latter 41 patients, 7, aged 17 to 59 years (mean 45), had associated congenital heart disease, and 34 patients, aged 17 to 70 years (mean 52), had no associated congenital cardiac abnormalities. Compared with the 34 patients without associated congenital heart disease and with nonmitral valve prolapse conditions capable in themselves of being fatal, the 15 patients who died suddenly with isolated mitral valve prolapse were younger (mean age 39 +/- 17 versus 52 +/- 15 years; p = 0.01), more often women (67% versus 26%; p = 0.008) and had a lower frequency of mitral regurgitation (7% versus 38%; p = 0.02). The 15 patients dying suddenly with isolated mitral valve prolapse also were less likely to have evidence of ruptured chordae tendineae (29% versus 67%; p = 0.04). The frequency of increased heart weight (67% versus 59%), a dilated mitral valve anulus (80% versus 81%), a dilated tricuspid valve anulus (17% versus 17%), an elongated anterior mitral leaflet (86% versus 54%), an elongated posterior mitral leaflet (79% versus 77%) and fibrous endocardial plaque under the posterior mitral leaflet (73% versus 63%) was similar between the two groups. The severity of the prolapse (mild 20% versus 11%; moderate 27% versus 58%; severe 53% versus 32%) also was similar between the two groups. Thus, persons with mitral valve prolapse dying suddenly without another recognized condition tend to be relatively young women without mitral regurgitation. 
1	Human papillomavirus in oesophageal squamous cell carcinoma. Thirty seven cases of oesophageal squamous cell carcinoma were studied by applying DNA slot blot analysis and in situ hybridisation using type specific probes for HPV 6, 11, 16 and 18. Cases of condyloma accuminata, cervical carcinoma, and laryngeal papilloma were used as controls. Blocks including areas of invasive carcinoma, intraepithelial neoplasia, and normal epithelium were studied in each case. No HPV genome was detectable in any of the oesophageal cases. It is concluded that these types of HPV do not have an association with oesophageal squamous cell carcinoma. 
1	The effects of interleukin-6 on tumor-infiltrating lymphocytes derived from human renal cell cancer. Tumor-infiltrating lymphocytes (TIL) are a heterogeneous population of T cells with potent antitumor activity against a wide variety of tumors. TIL from renal cell cancer (RCC) typically exhibit diminished growth and antitumor activity after four weeks in vitro. We have therefore investigated effects of varying doses of interleukin-6 (IL-6) (0, 25, 100 units/ml.) on in vitro expansion, proliferation, cytotoxicity, and expression of cell surface phenotypes of long term renal TIL cultures from three RCC patients. Among the various conditions tested, three of three TIL cultures displayed a mild increase in cell expansion when grown in IL-2 with the addition of 100 units/ml. of IL-6. Two of three TIL cultures grown in IL-2 and 100 U/ml. of IL-6 demonstrated enhanced proliferation as determined by 3H-thymidine uptake. TIL could not be isolated or maintained in vitro when grown in the presence of IL-6 alone without IL-2. IL-6 was also found to enhance the long term non-specific cytotoxicity against an allogeneic nonrenal tumor target. No consistent effect on autologous tumor-specific cytotoxicity was demonstrated. We conclude that IL-6, when used in combination with IL-2, may modestly enhance the long-term growth of RCC-derived TIL. 
3	Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits. Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed platelets to be elevated by approximately 20-fold in spinal cord injured by 25 minutes of ischemia and 2 hours of reperfusion (2.80 +/- 0.98 ng/g) compared with that in normal spinal cord (0.15 +/- 0.06 ng/g, p less than 0.01). Given during ischemia to seven rabbits, 10 mg/kg i.p. of a highly selective and potent antagonist of platelet-activating factor (BN 50739) accentuated the early postischemic hyperemia and prevented the delayed hypoperfusion measured by on-line laser-Doppler flowmetry (-35 +/- 7% of baseline [n = 7] without versus 33 +/- 14% with treatment, p less than 0.01) and the edema formation measured as the increase in tissue water content (4.4 +/- 0.7% without [n = 6] versus 2.1 +/- 0.6% with [n = 7]treatment, p less than 0.05) after 2 hours of reperfusion. This neurochemical and pharmacologic evidence emphasizes a new perspective of ischemia-induced phospholipid degradation and suggests an important role for platelet-activating factor in the early manifestations of stroke. 
3	Cardiovascular responses to arm cranking and FNS-induced leg exercise in paraplegics. Twelve spinal cord-injured males performed arm-crank exercise (ACE) with and without concurrent functional neuromuscular stimulation (FNS) of paralyzed leg muscles to investigate the hypothesis that FNS would augment cardiovascular performance during submaximal ACE. Six men who exhibited vigorous isometric contractions of thigh and calf muscles were classed as "responders" to FNS (R), and the remaining subjects with poor or nonexistent contractions served as "nonresponder controls" (C). Steady-state heart rate and oxygen uptake during ACE at 30, 60, and 90 W were not appreciably different from the ACE + FNS condition. However, cardiac outputs in R were augmented by 30% during FNS at rest (from 4.9 to 6.4 l/min), by 18% during 30-W ACE + FNS (from 8.6 to 10.1 l/min), and by 28% during 90-W ACE + FNS (from 12.1 to 15.6 l/min). Similarly, resting stroke volumes were increased by 18% (9 ml) and by 23% (19 ml) at 60 W during FNS in the R group. Calculated total peripheral resistance was reduced at rest and during 90-W ACE + FNS by approximately 24%. In contrast, no alterations of circulatory hemodynamics were observed for C subjects. These data indicate that FNS-induced contractions of paralyzed leg muscles augment venous return to aid central cardiovascular control during upper-body submaximal exercise in paraplegics. 
1	Chondrosarcoma of the soft tissues. Two different sub-groups. Chondrosarcomas arising from soft tissues are rare. Two different varieties are described, myxoid and mesenchymal. We have collected nine cases of the tumour, five myxoid and four mesenchymal, from a review of 513 cases of chondrosarcoma seen between 1904 and 1988. We report the principal clinical, radiographical and histological differences between the two varieties and discuss their surgical treatment and prognosis. 
1	Cerebral venous thrombosis: new causes for an old syndrome? The range of disorders affecting the cerebral veins and sinuses is increasing and now includes blood disorders, abnormalities in the patterns of blood flow, and infiltrative or inflammatory conditions, all of which may promote thrombosis. We describe 10 patients with cerebral venous thrombosis: two had protein S deficiency, one had protein C deficiency, one was in early pregnancy, and there was a single case of each of the following: dural arteriovenous malformation, intracerebral arteriovenous malformation, bilateral glomus tumours, systemic lupus erythematosus, Wegener's granulomatosis, non-Hodgkin's lymphoma. The recognition of such diverse aetiology may be importance since clinical features are non-specific, and may consist only of raised intracranial pressure, allowing confusion with 'benign intracranial hypertension'. The existence of effective treatment both for the thrombosis and for many of the underlying disorders makes early diagnosis essential. The prognosis of treated patients may be favourable. 
1	Central neurogenic hyperventilation in invasive laryngeal carcinoma. We describe a patient with central neurogenic hyperventilation secondary to extension of a laryngeal tumor into the base of the brain, resulting in extrinsic compression of the medulla. Such an association has not been previously described. Unique features which distinguish this patient from previously reported cases are emphasized. Possible mechanisms involved in pathogenesis, as well as types of therapy, are outlined. 
1	'Locked-in syndrome' for 27 years following a viral illness: clinical and pathologic findings. We describe a man who, after a presumed encephalitic illness, was "locked-in" for 27 years. His CT and autopsy findings showed atrophy of the brainstem and a cystic lesion at the base of the pons. He survived longer than most other patients in a similar state. 
5	Snow skiing for the physically disabled. The sport of snow skiing by the physically disabled, which originated in Europe in 1935 and first received attention in the United States in the 1940s, is reviewed in terms of opportunities available, instructions, adaptive equipment necessary, and benefits provided. Persons with a wide variety of disabilities (such as cerebral palsy, multiple sclerosis, spinal cord injury, hemiplegia, amputation, blindness, spina bifida, and muscular dystrophy) can participate. Accordingly, a wide range of adaptive equipment is available--including outrigger skis, flip-skis, canting wedges, ski bras, "toe spreaders," sit-skis, and mono-skis--to allow safe enjoyment of the sport. Programs for instruction of the disabled skier are increasing in number and popularity, and numerous opportunities are available to enter competitive events sponsored by National Handicapped Sports. Both the participants and the instructors relate the numerous physical and psychologic benefits that can be derived from skiing; the sport provides an almost universal enjoyment of the sense of freedom and independence. Snow skiing is an enjoyable, beneficial, outdoor cold-weather activity that the disabled population can safely learn with proper instruction. 
5	Improved biocompatibility by postfixation treatment of aldehyde fixed bovine pericardium. Long-standing release of locally cytotoxic aldehyde concentrations is responsible for lack of spontaneous endothelialization and increased calcification of glutaraldehyde fixed bovine pericardium. Postfixation treatment with amino acids made in vitro endothelialization of bioprosthetic heart valves possible. Such treated pericardium calcified significantly less (13 +/- 4 micrograms/mg dry weight) than did conventionally processed pericardium (114 +/- 25 micrograms/mg) after 63 days of subcutaneous implantation in rats. To test the ability for spontaneous in vivo endothelialization, 5 sheep had 6 mm grafts made from postfixation treated pericardium (PTP) implanted into the carotid artery, compared to PTFE grafts on the contralateral side, which spontaneously endothelialize in animal models. In a pregnant animal, both grafts occluded. All remaining pericardial grafts remained patent, but one additional PTFE graft occluded and another one was stenosed. The area covered with red thrombus was significantly smaller in the PTP grafts (3.05 +/- 3.9%) than in the PTFE grafts 42 +/- 14% (p = 0.0036); TEM and SEM showed endothelial cells growing directly on the PTP, but only on myofibroblasts in PTFE grafts. Postfixation treatment of glutaraldehyde fixed pericardium aids spontaneous endothelialization and decreases tissue calcification. 
5	Early hospital discharge of children with cancer treated for fever and neutropenia: identification and management of the low-risk patient. Children with leukemia and solid tumors are often hospitalized for empiric broad-spectrum antibiotic therapy because of fever during periods of chemotherapy-induced neutropenia. Conventional practice dictates that parenteral antibiotics be continued until the patient is afebrile and has recovered from neutropenia, ie, until the absolute neutrophil count (ANC) exceeds 500 cells per cubic millimeter. However, the practice in our center has been to discontinue parenteral antibiotic therapy and discharge many such patients before resolution of neutropenia. Since the feasibility and safety of this approach has not been studied, we reviewed the records of 114 consecutive hospitalizations for fever and neutropenia in 61 patients during a 13-month period. Seventy-seven children (68%) were discharged to their homes while still neutropenic after they had been afebrile for 1 to 2 days on parenteral antibiotics, had negative blood cultures, appeared well, and usually had some evidence of bone marrow recovery. Five patients (4.4%) developed recurrent fever and required rehospitalization within 7 days of discharge. Only three of the 77 patients (3.9%) who were sent home with neutropenia had recurrent fever. Each had a brief and uneventful second hospitalization. Two of the 37 children discharged with an ANC over 500 cells per cubic millimeter required rehospitalization. A declining ANC and advanced malignancy were risk factors in predicting recurrence of fever following discharge. A rising monocyte count was a predictor of imminent recovery from neutropenia. These results suggest that "early" discharge of an afebrile yet still neutropenic patient is safe when the patient is in remission, has no evidence of serious infection, appears clinically stable, and has indications of bone marrow recovery. The conventional approach of routinely continuing the hospitalization until resolution of neutropenia may be unnecessary in such low-risk patients. 
4	Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons. To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi, we evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide was studied because it inhibits thrombin cleavages of fibrinogen by simple competition without blocking enzyme catalytic-site function. When an exteriorized arteriovenous access shunt model was used in baboons (Papio anubis), thrombus formation was induced by placing a thrombogenic device made of (i) a segment of tubing coated covalently with type I collagen, which generated platelet-rich thrombi under arterial flow conditions, and (ii) two subsequent annular regions of flow expansion that produced fibrin-rich thrombi typically associated with venous valves and veins. Thrombus formation was quantified by measurements of 111In-labeled platelet and 125I-labeled fibrinogen deposition in both arterial-flow and venous-flow portions of the device. Continuous infusion of H peptide (0.5, 15, and 75 mg/kg) proximal to the device for 40 min interrupted, in a dose-response fashion, formation of fibrin-rich thrombus in the regions of disturbed flow and generation of fibrinopeptide A. In contrast, H peptide did not inhibit the capacity of platelets to deposit on the collagen surface (P greater than 0.2 at all doses) or to form hemostatic plugs (as assessed by measurements of bleeding time; P greater than 0.1 at all doses). These findings suggest that, by competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type thrombus formation may be selectively prevented. This strategy may be therapeutically attractive for preserving normal platelet function when conventional anticoagulant therapy is contraindicated. 
1	Reconstruction of mandibular defects in irradiated patients. In this prospective study, mandibular reconstruction using titanium plates was evaluated in 31 patients treated between July 1988 and January 1990. Sixteen patients had prior surgery; 13 had prior radiotherapy. In 11 patients, prior radiation and surgery had failed. Sixteen patients received postoperative radiotherapy either in standard or accelerated fractions. Twelve patients had complications of either intraoral (8), extraoral (5), or combined (1) plate exposure or fistula formation (2). Factors significantly related to complications were poor nutrition, accelerated radiation, and recurrence. Sixty-one percent of all patients healed uneventfully. When patients with complications secondary to recurrence who subsequently died were excluded, the success rate was 73%. Only one patient had an unacceptable result that produced a cosmetic and functional deformity despite secondary repair. 
2	Utility of upper endoscopy in the evaluation of noncardiac chest pain. The diagnostic yield of esophagogastroduodenoscopy, esophageal manometry, and Bernstein testing was assessed in 100 consecutive patients being evaluated for non-cardiac chest pain. Manometric studies revealed the nutcracker esophagus in 21 patients; non-specific esophageal motility disorders in 19 patients; a hypertensive lower esophageal sphincter in 4 patients; diffuse esophageal spasm in 2 patients; and normal motility in 54 patients. Endoscopy was normal in 38 patients; but revealed grades II to IV esophagitis in 24 patients; gastritis and/or duodenitis in 18 patients; a sliding hiatal hernia without evidence of esophagitis in 14 patients; and gastric or duodenal ulcers in 6 patients. Twenty-five individuals were found to have normal manometric studies in combination with a negative Bernstein test. Among these 25 patients, however, 7 patients had esophagitis (grade II or higher); 6 patients had gastritis and/or duodenitis; five patients had a sliding hiatal hernia without esophagitis; 1 patient had peptic ulcer disease; and only 6 patients had a normal endoscopic exam. Our results indicate that endoscopy can identify a significant number of patients with acid-peptic disease who present with non-cardiac chest pain, that would not have been otherwise diagnosed by esophageal manometry or Bernstein testing alone or in combination. 
1	Aspiration biopsy cytology of occult breast lesions by use of the "scouting needle". A prospective study of 261 cases. The increased use of mammography for the detection of impalpable breast lesions has resulted in a need for new diagnostic techniques. In a prospective study of 261 occult breast lesions, aspiration biopsy was done with a standard fine needle and syringe. This "scouting needle" technique permits the collection of diagnostic cytologic material in the clinician's office without specialized radiologic equipment. Thirty of 53 malignant lesions (57%) were detected cytologically. A benign cytologic diagnosis, which was made in 220 patients, did not preclude additional investigation. Aspiration biopsy using the "scouting needle" is a rapid, low-cost, easily performed, initial procedure which complements "watchful waiting." When diagnostic of carcinoma, it results in immediate surgical intervention and may obviate two-stage surgical treatment. 
5	Perioperative myocardial ischemia in patients undergoing noncardiac surgery--I: Incidence and severity during the 4 day perioperative period. The Study of Perioperative Ischemia (SPI) Research Group. To determine the incidence and characteristics of perioperative myocardial ischemia, the electrocardiographic (ECG) changes consistent with ischemia during the 4 day perioperative period were documented and characterized in 100 patients with or at risk for coronary artery disease undergoing noncardiac surgery. Using continuous two channel ECG monitoring (leads CC5 and CM5), the frequency and severity of ECG ischemic episodes defined by ST segment depression greater than or equal to 1 mm or elevation greater than or equal to 2 mm during the preoperative (up to 2 days), intraoperative and early postoperative (first 2 days) periods were compared. Preoperatively, 28 patients (28%) exhibited 105 episodes of ischemia; intraoperatively, 27 patients exhibited 39 episodes and postoperatively, 42 patients exhibited 187 episodes. There was no difference between the pre- and intraoperative episode characteristics. However, postoperative ischemic episodes were the most severe. The mean ST change was 1.5, 2 and 2.6 mm for pre-, intra- and postoperative episodes, respectively (p less than 0.0001 postoperative versus pre- or intraoperative); duration of ischemic episodes was 69, 45 and 207 min, respectively (p less than 0.005 postoperative versus preoperative, p less than 0.001 versus intraoperative) and area under the ST curve was 88, 74 and 383 mm.min (p less than 0.009 postoperative versus preoperative, p less than 0.005 versus intraoperative). Ninety-four percent of all postoperative ischemic episodes were silent; 80% of all episodes occurred without acute change (+/- 20% of control) in heart rate and 77% of intraoperative episodes occurred without acute change in blood pressure. 
3	The management of the painful first metatarsophalangeal joint in the older patient. Arthrodesis or Keller's arthroplasty? We report a prospective randomised trial comparing Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint for the management of symptomatic hallux valgus and hallux rigidus in the older patient. In 81 patients (110 feet), with a minimum of two years follow-up, both procedures gave a similar degree of patient satisfaction and symptom relief. The incidence of metatarsalgia was also similar. As there were no obvious advantages to arthrodesis, and since six out of 50 arthrodesed toes required revision, we suggest that Keller's arthroplasty is the better operation in these patients. 
5	Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection. BACKGROUND. Contraction of obliquely oriented left ventricular (LV) fibers results in a twisting motion of the left ventricle. The purpose of this study was to assess the effects of acute human cardiac allograft rejection on LV twist pattern and the twist-volume relation. METHODS AND RESULTS. Tantalum markers were implanted into the LV midwall in 15 transplant recipients to measure time-varying, three-dimensional chamber twist using computer-assisted analysis of biplane cinefluoroscopic images. Twist was defined as the mean longitudinal gradient of circumferential rotation about the LV long axis. When plotted against normalized percent ejection fraction (%EF), the resulting twist-normalized %EF relation could be divided into three phases. In systole, LV twist was linearly related to ejection of blood. In contrast, diastolic untwist was characterized by early rapid recoil with little change in LV volume, followed by more gradual untwisting when the bulk of diastolic filling occurred. During 10 acute rejection episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope of the systolic twist-normalized %EF relation did not change. In contrast, the slope of the early (first 15% of filling) diastolic twist-normalized %EF relation (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus -0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2 (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p = 0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/- 11% versus 36 +/- 13%, p = 0.0003). Therefore, a greater proportion of LV untwisting occurred later in diastole during rejection, as reflected by an increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling) diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010 rad/cm, p = 0.0015). Peak rate of untwist was not affected. With resolution of rejection, M(early-dia) and percent untwist during early diastole returned to baseline levels (p = NS versus baseline). There was also a trend for M(mid-dia) to return toward prerejection values (p = NS versus baseline), but this change did not reach statistical significance compared with rejection values. CONCLUSION. Acute cardiac allograft rejection is associated with altered diastolic twist mechanics in the absence of any demonstratable systolic abnormalities. During rejection, myocardial edema and other factors may result in intrinsic changes of the elastic properties of the myocardium, thereby leading to modification of recoil forces responsible for the early, rapid unwinding of the deformed ventricle. 
5	Expression and characterization of TCA3: a murine inflammatory protein. TCA3 is a cDNA originally isolated from activated T cells. Transcription of this gene has been shown to correlate with Ag-induced cellular activation of both T cells and mast cells. Based on the predicted amino acid sequence encoded by the cDNA, we previously proposed that TCA3 represents a cytokine. In this report we have used rDNA technology to express TCA3 in two mammalian cell lines. In both cases, TCA3 was expressed as a secreted molecule with an apparent molecular mass of 16 kDa. Digestion of the (rTCA3) with the enzyme N-glycanase revealed that approximately 8 kDa is caused by N-linked glycosylation. Intradermal injection of rTCA3 into mouse footpads resulted in a rapid swelling response. The sites of injection were characterized histologically by a local accumulation of neutrophils. These findings are discussed with particular attention to a family of related proteins, some of whose members also have inflammatory properties. 
5	Role of dopamine and arterial chemoreceptors in thermal tachypnea in conscious cats. In mammals submitted to a warm environment, intracerebral injection of dopamine (DA) produces no change or an increase in body temperature accompanied by an increase in metabolic heat production, but its effect on heat loss mechanisms such as vasodilation and tachypnea is not clear. Because the principal mechanism of heat loss in the conscious cat is thermal tachypnea, we studied the influence of DA on thermal tachypnea in response to heat stress (ambient temperature = 33-36 degrees C) in five conscious cats. We first studied the steady-state response to a DA agonist, apomorphine, which crosses the blood-brain barrier. Intravenous injection of apomorphine greatly reduced thermal tachypnea by decreasing respiratory frequency (from 94.9 to 52.5 breaths/min) and increasing tidal volume (from 13.2 to 20.4 ml). The subsequent injection of the DA antagonist haloperidol, which also crosses the blood-brain barrier, restored the initial tachypnea. To further investigate the mechanism involved in thermal tachypnea, we studied the influence of peripheral chemoreceptors by transiently stimulating or inhibiting carotid body (CB) activity during tachypneic breathing. CB stimulation by intravenous injection of NaCN or domperidone reduced thermal tachypnea mainly by decreasing the respiratory frequency, whereas CB inhibition by DA tended to increase frequency and thus tachypnea. It is concluded that 1) in a warm environment, central DA receptors are also greatly involved in heat loss mechanisms, 2) arterial chemoreceptor input appears to counteract this tachypneic breathing, and 3) thermal and hypoxic tachypnea may be controlled by the same mechanism in which a DA-like system has a key role. 
5	Normalization of ventilation/perfusion relationships after liver transplantation in patients with decompensated cirrhosis: evidence for a hepatopulmonary syndrome. To examine the effect of liver transplantation on the respiratory and cardiovascular functions, ventilation/perfusion relationships were determined by multiple inert gas elimination technique in six patients with end-stage liver disease 1 to 19 mo before and 2 to 6 mo after liver transplantation. Cardiac output and pulmonary vascular pressures were measured after catheterization of the pulmonary artery. All patients had normal spirometry and chest x-ray films before transplantation. PaO2 before transplantation was 78.8 +/- 7.4 mm Hg (range = 51.8 to 102.8 mm Hg). All patients had perfusion of poorly ventilated lung regions (low ventilation/perfusion relationships) varying from 3% to 19% of cardiac output (mean = 8.5% +/- 2.4% of cardiac output) and two patients had intrapulmonary shunting (3% and 20% of cardiac output). Measured and calculated PaO2 agreed closely, indicating absence of pulmonary diffusion abnormality, as well as of extrapulmonary shunting. After transplantation, PaO2 normalized in all patients, and both shunting and low ventilation/perfusion relationships disappeared. Cardiac output decreased from 9.1 +/- 1.4 to 6.6 +/- 0.5 L/min (p less than 0.05), and the pulmonary vascular resistance increased from 0.69 +/- 0.14 to 1.64 +/- 0.43 mm Hg/L/min (p less than 0.05). The systemic vascular resistance also increased (before = 8.7 +/- 1.0; after = 15.3 +/- 1.1 mm Hg/L/min; p less than 0.001). Normalization of respiratory and cardiovascular alterations, after liver transplantation, in patients with end-stage liver disease indicates that these changes have a direct functional relationship to the diseased liver. It is hypothesized that this is part of a "hepatopulmonary syndrome,' which in similarity to the hepatorenal syndrome disappears with improved liver function. 
2	Clinical management of gastric cancer and concomitant esophagogastric varices. We report the late results of treatment of 13 consecutive patients with gastric cancer and concomitant esophagogastric varices. Of seven good-risk patients classified as Child's class A or B, gastrectomy together with selective shunt operation was performed in two, total gastrectomy with splenectomy in three, and distal partial gastrectomy with paraesophageal devascularization without splenectomy in one. The remaining patient with early gastric cancer underwent distal partial gastrectomy following repeated endoscopic injection sclerotherapy (EIS) for treatment of the esophageal varices. Although the majority of patients who underwent surgical repair of varices (i.e., shunt, splenectomy, or devascularization) died, total gastrectomy with splenectomy was the only procedure that led to control of the esophageal varices. Since partial gastrectomy combined with EIS limits the morbidity and mortality of an extensive resection and at the same time controls esophageal variceal bleeding, it is probably the procedure of choice for patients with a carcinoma in the lower two-thirds of the stomach. Concerning non-surgical cases, two patients were effectively treated using laser endoscopy and EIS, without the occurrence of variceal bleeding. The remaining four patients, given chemotherapy or irradiation for treatment of gastric carcinoma, died within 4 months with variceal bleeding or liver failure. For the poor-risk patients with evidence of severe liver dysfunction, laser treatment and EIS would be the treatment of choice. 
1	Occurrence of uveal melanoma in contact with a chorioretinal cryocoagulation scar. A case of a uveal melanoma arising in an eye previously treated with cryocoagulation for a horseshoe retinal tear is described. In the anterior border of the tumor, a notch, clearly fitting the curve of the chorioretinal scar was observed. Possible mechanisms which may be responsible for the local arrest of the tumor extension are discussed. 
1	Esophageal ultrasound and the preoperative staging of carcinoma of the esophagus. Esophageal ultrasound allows the esophageal wall to be viewed as five discrete layers. Lymph nodes are easily identified, and their size, shape, margin, and internal structure can be assessed. This provides an alternative method of preoperative (clinical) evaluation of the primary tumor [T] and the regional lymph nodes [N] of patients with carcinoma of the esophagus. Esophageal ultrasound was attempted in the clinical staging of 28 patients with carcinoma of the esophagus. Six patients (21%) were not assessed because of the inability to pass the esophageal ultrasound probe through the malignant stricture. The staging system for carcinoma of the esophagus developed by the International Union Against Cancer and the American Joint Committee on Cancer was used. Twenty-two patients had the true T determined by pathologic review of the resected esophagus. Esophageal ultrasound correctly identified T in 13 patients (59% accuracy). In four patients (18%) the disease was overstaged by esophageal ultrasound; all these patients had early T1 tumors confined to the submucosa. In five patients (23%) the disease was understaged by esophageal ultrasound; all of these patients had advanced tumors (four T3 and one T4) that invaded beyond the esophageal wall. Seven of the nine incorrect esophageal ultrasound determinations were called T2 (three T1, three T3, one T4), which suggests that the borders of the muscularis propria require careful attention when evaluated by esophageal ultrasound. Twenty patients had the true N determined by pathologic review of the resected specimen. Esophageal ultrasound correctly identified N in 14 patients (70% accuracy). Three patients were falsely identified as having N1 disease and three were falsely identified as having N0 disease. The sensitivity, specificity, positive predictive value, and negative predictive value for N assessment by esophageal ultrasound were 70%. Esophageal ultrasound provides an alternative method of visualization of the esophageal wall and regional lymph nodes. Our early experience shows promise for esophageal ultrasound in the clinical staging of carcinoma of the esophagus. 
2	Gastrointestinal tuberculosis. Report of four cases. Gastrointestinal tuberculosis is a rare disease in the United States. Correct identification is often delayed because it is not considered early on in the differential diagnosis. Four patients with gastrointestinal tuberculosis and the symptoms, diagnosis, complications, and treatment of the disease are discussed. Gastrointestinal tuberculosis should be considered in Asian immigrant patients who present with symptoms and signs of inflammatory bowel disease. 
1	Multimodal therapy in locally advanced breast carcinoma. Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease. 
1	Preliminary characterization of growth factors secreted by human pituitary tumors. To investigate the secretion of mitogenic factors by human pituitary tumors we have cultured cells from 54 adenomas in serum-free medium. Conditioned media from 28 (52%) elicited dose-dependent stimulation of [3H]thymidine incorporation into rat GH3 cells (22-338% above control), while 14 (26%) inhibited GH3 proliferation. Stimulating activity was observed more frequently in nonfunctional tumor-conditioned medium (73%; n = 22) than in secretory tumor-conditioned medium (37%; n = 32). Of 10 tumour-conditioned media with mitogenic activity for GH3 cells, only 4 produced modest stimulation of HEp2 (human laryngeal carcinoma) cells. In contrast, [3H]thymidine incorporation into A431 (human squamous carcinoma) and PC12 (rat adrenal pheochromocytoma) cells was enhanced by each of 15 tumor-conditioned media (up to 342% and 275%, respectively), 8 of which had shown stimulatory and 2 inhibitory effects on GH3 cells. Gel filtration of pooled conditioned media from 10 nonfunctional tumors showed significant growth-promoting activity for GH3 cells in fractions corresponding to mol wt of 2-3 and 11-18 kDa. Proliferative activity on A431 cells also eluted in two positions; one corresponded to the higher mol wt peak seen with GH3 cells, while the other, not observed with GH3 cells, was in the 3- to 6-kDa range. These findings suggest that cells derived from human pituitary adenoma tissue synthesize and secrete several growth factors, each of which may have its own target cell specificities. These factors have yet to be characterized, but we suggest that they may have a role in stimulating the development or maintenance of human pituitary adenomas. 
4	Characteristics of a new angiotensin converting enzyme inhibitor: delapril. Delapril, a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, which has an indanylglycine moiety differing from the proline moiety of captopril or enalapril, is an esterified prodrug that is converted in vivo to its active metabolites. Delapril effectively inhibits rabbit lung ACE activity and lowers blood pressure in spontaneously hypertensive rats. Delapril has several characteristics that differ from captopril and enalapril, including high lipophilicity and weak bradykinin potentiating action. Delapril is a more potent inhibitor of vascular wall ACE activity than enalapril or captopril. It also shows a weaker potentiating action on the citric acid-induced cough in the guinea pig model compared with captopril and enalapril. In 12 out of 150 patients with essential hypertension who complained of cough during treatment with enalapril, changing to delapril resulted in resolution of the cough in 6 out of 12 of these patients: the percentage of patients in the total population with cough decreased from 8% to 4%. 
1	Cryoprobe as a "handle" for resection of metastatic liver tumors. Resection of metastatic liver tumors can be a difficult and risky procedure. Using a cryoprobe as a "handle" can greatly facilitate resection by providing a taut surface for transection and improving visualization of ductal and vascular structures. In addition, this technique may decrease the risk of contaminating surrounding tissues with cancer cells, and may inhibit tumor recurrence within the margins of resection. 
1	Toxic dermatitis induced by 10-ethyl-10-deaza-aminopterin (10-EdAM), a novel antifolate. A new methotrexate analog, 10-ethyl-10-deaza-aminopterin (10-EdAM), was found to induce a particular form of skin toxicity different than the skin rash reported to result from methotrexate. At histologic examination, it was found to be a toxic dermatitis that clinically most often first appears on the lower legs but can occur anywhere in the body, especially if treatment is continued. Nine cases are reported. A specific risk factor could not yet be identified. Discontinuation of 10-EdAM administration leads to complete healing; concomitant corticosteroid treatment also induces healing. 
4	Experience with esmolol for the treatment of cocaine-associated cardiovascular complications. The authors report their experience using esmolol, an ultra-short acting beta-adrenergic antagonist, for the treatment of seven patients with cocaine-associated cardiovascular complications. No consistent hemodynamic benefit was found with the use of this drug. Although there was a decline in mean heart rate of 23% (range 0% to 35%), they were unable to show a consistent antihypertensive response. Adverse effects occurred in three patients. This included one patient with a marked exacerbation of hypertension and one who became hypotensive. Another patient developed emesis and lethargy during esmolol therapy and required endotracheal intubation. They do not recommend the routine use of esmolol for cocaine cardiotoxicity. 
4	Prevalence of hemodynamically significant stenosis of the carotid artery in an asymptomatic veteran population. The results of previous studies have suggested that significant stenosis of the carotid artery occurs in less than 6 per cent of asymptomatic patients. However, some populations studied were not representative of those seen by most vascular surgeons. Accordingly, we examined two cohorts of patients at the Veterans Administration Medical Center using Duplex scanning. There were 153 volunteers in group 1, all more than 50 years of age, who were being treated at our outpatient department for nonvascular problems. There were 116 patients of similar age in group 2 but who were known to have significant arterial occlusive disease of the lower extremity. The majority of patients were men with a mean age of 64.4 years. Risk factors in the total population included hypertension, diabetes mellitus, coronary arterial disease, peripheral vascular disease and smoking. Over-all, significant (greater than 50 per cent diameter) stenosis of the carotid artery was discovered in 25 of 269 patients. The prevalence for those in group 1 was 6.5 per cent versus 12.9 per cent for those in group 2 (p = 0.058). The prevalence in patients with cardiac disease was 15.2 per cent compared with 6.8 per cent in those without cardiac disease (p = 0.032). Smoking was associated with a 10.6 per cent rate of significant disease compared with a 2.3 per cent rate in nonsmokers (p = 0.065). Hypertension and diabetes were not significant risk factors. Significant stenosis of the carotid artery was found in seven of 40 patients in whom coronary arterial disease, peripheral vascular disease and smoking were all present. 
5	Asymmetric growth of the lateral cerebral ventricle in infants with posthemorrhagic ventricular dilation. Lateral cerebral ventricular volume in 36 preterm infants with or without an intraventricular hemorrhage, and with or without posthemorrhagic hydrocephalus, was measured longitudinally and compared with the ventricular index measurements of the same ventricles. A poor correlation was found (r2 = 0.67). To determine a reason for this poor relationship, we analyzed the volumes of the regions of the ventricles by a segmental volume analysis. The occipital region of the lateral cerebral ventricle enlarged at a much faster rate (1.904 +/- 0.477 ml/day) than either the anterior region (0.546 +/- 0.253 ml/day; p less than 0.01) or the middle region (-0.209 +/- 0.334 ml/day; p less than 0.01) in infants with posthemorrhagic hydrocephalus. The rate of growth of the middle region of the lateral cerebral ventricles was the same for all infants. Linear indexes, such as the ventricular index and the lateral ventricular ratio, do not allow for accurate serial estimates of ventricular size in posthemorrhagic hydrocephalus because of asymmetric growth of the lateral cerebral ventricle. We conclude that sequential volume measurements are more useful than ventricular index measurements to follow ventricular size sequentially in infants with posthemorrhagic hydrocephalus. 
5	Surgical complications with the cochlear multiple-channel intracochlear implant: experience at Hannover and Melbourne. The surgical complications for the first 153 multiple-channel cochlear implant operations carried out at the Medizinische Hochschule in Hannover and the first 100 operations at the University of Melbourne Clinic, The Royal Victorian Eye and Ear Hospital, are presented. In the Hannover experience the major complications were wound breakdown, wound infection, electrode tie erosion through the external auditory canal, electrode slippage, a persistent increase in tinnitus, and facial nerve stimulation. The incidence of wound breakdown requiring removal of the package was 0.6% in Hannover and 1.0% in Melbourne. The complications for the operation at both clinics were at acceptable levels. It was considered that wound breakdown requiring implant removal could be kept to a minimum by making a generous incision and suturing the flap without tension. 
3	Acute urinary retention secondary to Herpes simplex meningitis. We report a case of acute urinary retention in a 24-year-old man with Herpes simplex meningitis without genital lesions. Since the differential diagnosis in young patients who present with acute urinary retention also includes multiple sclerosis, lumbosacral disk herniation, rheumatological disorders and drug intoxication, a thorough history and careful neurological examination are of paramount importance in distinguishing these syndromes. As part of a directed neurological evaluation prompt performance of lumbar puncture is indicated; a lymphocytic pleocytosis is suggestive of herpetic meningitis. Culture of Herpes simplex virus from the cerebrospinal fluid should be attempted. We recommend conservative management only, typically with intermittent catheterization, since bladder function usually normalizes within 10 to 14 days. 
4	Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Intracranial hemorrhage (ICH) from an intracranial aneurysm or arteriovenous malformation is a grave complication of pregnancy and is responsible for 5 to 12% of all maternal deaths. We critically analyzed 154 cases of verified ICH during pregnancy from an identified intracranial lesion, including 2 patients treated at our institution and 152 cases previously reported in the literature in English. Aneurysms were responsible for ICH in 77% of patients, and arteriovenous malformations in 23%. Hemorrhage occurred antepartum in 92% of patients and postpartum in 8%. Women with angiomatous hemorrhage were younger than those with aneurysmal hemorrhage; however, in contrast to previous reports, we found no differences between angiomatous and aneurysmal hemorrhage with respect to parity or gestational age at the time of the initial hemorrhage. Hypertension and/or albuminuria were present at some time during the pregnancy in 34% of patients with documentation, which sometimes made it difficult to differentiate angiomatous or aneurysmal ICH from that associated with eclampsia. In a logistic regression analysis, surgical management of aneurysms, but not arteriovenous malformations, was associated with significantly lower maternal and fetal mortality, independent of other covariants. For those patients with a lesion not operated on, cesarean delivery afforded no better maternal or fetal outcome than did vaginal delivery. We conclude that the decision to operate after ICH during pregnancy should be based upon neurosurgical principles, whereas the method of delivery should be based upon obstetrical considerations. The perioperative and anesthetic management of the pregnant patient with a neurosurgical complication is discussed. 
5	ST segment alternans during percutaneous transluminal coronary angioplasty--a case report. The occurrence of electrical alternans of the ST segment has been reported in patients with variant angina. The authors encountered a patient with typical electrical alternans of the ST segment in leads V4 through V6, which developed during percutaneous transluminal coronary angioplasty (PTCA) of the proximal left anterior descending artery. Hemodynamic pulsus alternans of the aortic pressure tracing was not observed during electrical alternans, and a Ca2+ blocker could not prevent this phenomenon during PTCA. 
5	Irritable bowel syndrome in women having diagnostic laparoscopy or hysterectomy. Relation to gynecologic features and outcome. We identified irritable bowel syndrome (IBS) in 47.7% of 86 women having diagnostic laparoscopy for chronic pelvic pain, 39.5% of 172 women having elective hysterectomy, and 32.0% of 172 controls age-matched for the hysterectomy group (P = NS). Constipation and pain subtype IBS were more common in hysterectomy patients than controls (P less than 0.05). In laparoscopy patients, dyspareunia was more common in those with IBS than in those without it (P less than 0.05). In the hysterectomy group, more IBS patients had chronic pelvic pain (P less than 0.005), and abnormal menses (P less than 0.01). Chronic pelvic pain was more frequently the only prehysterectomy diagnosis in IBS patients (P less than 0.05), and IBS was present more often when pain was a reason for hysterectomy (P less than 0.01). One year after laparoscopy, IBS patients gave lower overall status ratings (P less than 0.01) and lower pain improvement ratings (P less than 0.05) than non-IBS patients. In women who had a hysterectomy for pain, there was less pain improvement one year later in those with the pain subtype of IBS than in non-IBS patients (P less than 0.05). IBS is associated with gynecologic symptoms and affects the symptomatic outcome of diagnostic laparoscopy and hysterectomy. 
4	Clinical perspective on celiprolol: cardioprotective potential. beta-Adrenergic blockers have had widespread use in the treatment of cardiovascular disease. Some agents of this class have been shown to reduce the incidence of total mortality, cardiovascular mortality, sudden death, and nonfatal reinfarction in survivors of acute myocardial infarction. The mechanism for this cardioprotective action is not known. Antiarrhythmic action and hemodynamic alterations have been suggested as possible mechanisms. An anticoagulant mechanism is another possibility, although the antiplatelet effects of beta-blockers are weak. It is now believed that antithrombotic effects may be related to the prevention of coronary artery plaque rupture and the subsequent propagation of an occlusive arterial thrombus rather than a direct anticoagulant action. The therapeutic ability beta-blockers to attenuate the hemodynamic consequences of catecholamine surgers, as they do in aortic dissection, may protect a vulnerable plaque from fracture, reducing the risk of coronary thrombosis, myocardial infarction, and death. Celiprolol, a third-generation beta 1-selective adrenergic blocker with partial beta 2-agonist activity, is comparable to other beta-blockers in antihypertensive and antianginal activity. It has additional actions that may be beneficial to patients: (1) it does not adversely affect lipids and lipoproteins; (2) it does not appear to depress the myocardium in patients with left ventricular dysfunction; (3) it can lower serum fibrinogen levels; and (4) it can cause regression of myocardial mass in patients with left ventricular hypertrophy. 
4	Ultrasound screening of first-degree relatives of patients with an abdominal aortic aneurysm. The pedigrees were constructed of 43 patients (probands) who underwent resection of an abdominal aortic aneurysm. Seven probands (16.2%) had a first-degree relative (parent, sibling, child) known to have had an abdominal aortic aneurysm (multiplex family). To determine the prevalence of undiagnosed abdominal aortic aneurysm, ultrasound screening of first-degree relatives over age 40 years was undertaken. Of 202 eligible relatives, 103 (51.0%) were screened. An occult abdominal aortic aneurysm was defined as an infrarenal aortic diameter greater than 3.0 cm or an infrarenal/suprarenal aortic diameter ratio of greater than 1.5. An incipient abdominal aortic aneurysm was defined as a clear focal bulge of the infrarenal aorta, which was less than 3.0 cm in greatest diameter. Four of 103 relatives (3.9%) were found to have an occult abdominal aortic aneurysm (age/sex: 57M, 60M, 62F, 65M), and three (2.9%) were found with an incipient abdominal aortic aneurysm (age/sex: 56M, 60M, 67F). These smaller abdominal aortic aneurysms were in patients younger than the operated probands (average age men, 67 years; women, 69 years). Six of seven individuals were in families previously considered simplex, increasing the actual multiplex family frequency from 16.2% to 27.9%. All seven new abdominal aortic aneurysms were found in the 49 siblings age 55 years or older. There were no abdominal aortic aneurysms found in the 39 relatives under age 55 years, in 14 children ages 50 to 59 years or in one parent. Therefore of the siblings age 55 years or older, 5/20 men (25.0%) and 2/29 women (6.9%) were found to have a previously undiagnosed abdominal aortic aneurysm. 
1	The vascularized fibula graft in mandibular reconstruction. The use of a vascularized graft from the fibula for mandibular reconstruction is presented. The great strength, pliability, and long vascular pedicle that characterize such grafts make them particularly suitable for this type of repair. The results in six cases were highly satisfactory. Masticatory function was well restored, without alteration of the facial contour, and with minimal sequelae at the donor site. 
5	Reduced allergen-induced nasal congestion and leukotriene synthesis with an orally active 5-lipoxygenase inhibitor BACKGROUND AND METHODS. The clinical importance of leukotrienes in human allergy has not been defined, in part because there have been no selective 5-lipoxygenase inhibitors that have been effective and safe for use in humans. To address the hypothesis that stimulated leukotriene synthesis causes symptoms of immediate-hypersensitivity reactions in vivo, I investigated the effects of a new 5-lipoxygenase inhibitor, A-64077, on provoked allergic nasal symptoms and mediator release in a double-blind, randomized, placebo-controlled study. Eight subjects with allergic rhinitis underwent nasal challenge on two occasions after an oral dose of 800 mg of A-64077 or an identical-appearing placebo. RESULTS. Allergen-induced nasal congestion was significantly attenuated (P less than 0.02) by A-64077; peak levels of leukotriene B4 (median, 684 pg per milliliter) and 5-hydroxyeicosatetraenoic acid (median, 704 pg per milliliter) in nasal-rinse fluids were markedly reduced (to 67 and 185 pg per milliliter, respectively; P less than 0.01), whereas levels of prostaglandin D2 were not. Histamine release and sneezing were not reduced significantly by A-64077, but there was a significant correlation (P less than 0.01) between the changes in these variables within subjects. The mean (+/- SEM) stimulated synthesis of leukotriene B4 in whole blood ex vivo was markedly reduced by A-64077 (from 153 +/- 19 to 20 +/- 9 ng per milliliter, P less than 0.01), and the specificity of A-64077 for 5-lipoxygenase inhibition was verified by its lack of effect on the synthesis of serum thromboxane B2 or 12-hydroxyeicosatetraenoic acid. CONCLUSIONS. These results provide direct evidence of an important role for the 5-lipoxygenase products of arachidonic acid in allergic rhinitis and support the notion that further experiments in this area may lead to new therapeutic approaches to allergic disorders. 
4	Fish oil amplifies the effect of propranolol in mild essential hypertension. Forty-seven male patients with mild essential hypertension were randomly allocated to three subgroups. After a run-in period of 4 weeks, the first subgroup (n = 16) received propranolol (80 mg/day) for 36 weeks followed by a placebo period of 4 weeks. The second subgroup (n = 15), after a run-in period of 4 weeks, was given a supplement of encapsulated fish oil (9 g/day) for 36 weeks with a subsequent period of 4 weeks in which fish oil placebo was given. The third subgroup (n = 16), after a run-in period of 4 weeks, was given propranolol (80 mg/day) for 12 weeks, propranolol (80 mg/day) plus fish oil capsules (9 g/day equivalent to 1.8 g/day of eicosapentaenoic acid and 1.1 g/day of docosahexaenoic acid) for 12 weeks, propranolol plus fish oil placebo (same doses for 12 weeks) with a subsequent period of 4 weeks when propranolol placebo was administered. The results indicate a blood pressure-lowering effect of fish oil, which was comparable with that of propranolol. The simultaneous intake of fish oil plus propranolol was more effective than propranolol or fish oil alone. Propranolol treatment resulted in a decrease of plasma norepinephrine, plasma renin activity, and thromboxane B2 formation. After fish oil supplementation, plasma norepinephrine and thromboxane B2 formation were likewise reduced, whereas plasma renin activity appeared increased. The decrease of serum triglycerides, total and low density lipoprotein cholesterol as well as the rise of high density lipoprotein cholesterol are concomitant beneficial effects, which justify the consideration of fish oil alone or in combination with antihypertensive drugs for the treatment of mild hypertension. 
1	The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract. Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty-four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life. 
3	Horner's syndrome from hypothalamic infarction. We report a case of Horner's syndrome due to ipsilateral posterior hypothalamic infarction, occurring in the absence of other signs of hypothalamic dysfunction. Associated symptoms of contralateral faciobrachial weakness and dysarthria correlated with the extension of the infarct into the posterior limb of the internal capsule seen by magnetic resonance imaging. The likely vascular anatomy of this lesion is discussed. 
5	Thyroid antibodies as a risk factor for Down syndrome and other trisomies. To test whether the presence of thyroid antibodies in a parent is a risk factor for meiotic nondisjunction, we measured the levels of thyroid antibodies in serum samples drawn during early pregnancy from 101 gravidas who delivered a child with a trisomy, from 11 gravidas who had had a trisomic child in a previous pregnancy, and from 44 of their husbands. For each case mother, three controls were randomly selected from the same population and matched for age, race, sex of the child, and hospital of birth. Cases and controls came from two longitudinal populations, the Child Health and Development Studies (CHDS) and the national Collaborative Perinatal Project (CPP), together comprising more than 70,000 live births. All cases with both a definite diagnosis of trisomy-Down syndrome (DS) or other-and available serum were included. Overall, there was no association between the presence of thyroid antibodies in a mother and a trisomy in her offspring (odds ratio [OR] = .98, confidence interval [CI] = .54-1.85). The lack of association was seen in all three subgroups (DS only, other trisomies, and DS in a previous pregnancy), in all ethnic groups, and in the age groups of white mothers either less than 30 years of age (OR = .80, CI = .40-1.6) or greater than or equal to 30 years of age (OR = 1.26, CI = .82-1.9). In the CHDS population, case fathers, as compared with control fathers, did not have a higher prevalence of thyroid antibodies. 
5	Natural death as viewed by the medical examiner: a review of 1000 consecutive autopsies of individuals dying of natural disease. A study of 1000 consecutive autopsies of individuals dying of natural disease was conducted. Cardiovascular disease was responsible for 60.9% of all deaths with coronary artery disease--not only the main cause of cardiovascular death but also the main cause of all natural deaths--accounting for 45.1% of such cases. Diseases of the central nervous and respiratory systems accounted for 8.7 and 8.6%, respectively, of the natural deaths. Seizure disorders and pneumonia were the main causes of death in these organ systems. There were 124 deaths of children less than one year in age, 91 of which were due to sudden infant death syndrome (SIDS). All of the SIDS deaths were in children less than 10 months old. 
5	Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome. In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency. 
2	Serum amylase in patients with renal insufficiency and renal failure. Results vary with regard to the upper limits of serum amylase seen in patients with renal failure, and very little has been reported with patients with renal insufficiency not yet requiring dialysis. To determine the level of serum amylase elevation in renal insufficiency and renal failure, we determined serum amylase values in 128 subjects with creatinine clearances less than 90 ml/min. Serum amylase remained in the normal range when creatinine clearance was greater than 50 ml/min, and did not become elevated until creatinine clearance was less than 50 ml/min. The highest serum amylase recorded in the absence of acute pancreatitis was 503 IU/L (normal, less than 128 IU/L). Serum lipase and trypsin values paralleled those for serum amylase; values remained normal when creatinine clearance was greater than 50 ml/min, and were normal or elevated when creatinine clearance was less than 50 ml/min. These results indicate that elevations of serum amylase (i.e., amylase greater than 128 but less than 500 IU/L) in asymptomatic patients with impaired renal function are not evident until creatinine clearances fall below 50 ml/min, and probably do not represent acute pancreatitis. 
5	Leukoaraiosis, intracerebral hemorrhage, and arterial hypertension. To investigate whether the observed association of leukoaraiosis with intracerebral hemorrhage is direct or mediated by risk factors, we compared 116 patients with intracerebral hemorrhage confirmed by computed tomography and 155 controls without intracerebral hemorrhage, evaluating the prevalence of leukoaraiosis and vascular risk factors. Leukoaraiosis was observed in 21 (18%) of the 116 patients and in 12 (8%) of the 155 controls (p less than 0.01). Only two (6%) of the 31 patients with lobar hemorrhage had leukoaraiosis on computed tomograms, compared with 17 (24%) of the 71 patients with basal ganglionic hemorrhage (p less than 0.05). Leukoaraiosis was significantly correlated with intracerebral hemorrhage after controlling for age and sex by using multiple logistic regression analysis, while the correlation disappeared after controlling for hypertension. Our results indicate that leukoaraiosis is not an independent risk factor for intracerebral hemorrhage. 
5	New approaches in the rehabilitation of the traumatic high level quadriplegic. The use of noninvasive alternatives to tracheostomy for ventilatory support have been described in the patient management of various neuromuscular disorders. The use of these techniques for patients with traumatic high level quadriplegia, however, is hampered by the resort to tracheostomy in the acute hospital setting. Twenty traumatic high level quadriplegic patients on intermittent positive pressure ventilation (IPPV) via tracheostomy with little or no ability for unassisted breathing were converted to noninvasive ventilatory support methods and had their tracheostomy sites closed. Four additional patients were ventilated by noninvasive methods without tracheostomy. These methods included the use of body ventilators and the noninvasive intermittent positive airway pressure alternatives of IPPV via the mouth, nose, or custom acrylic strapless oral-nasal interface (SONI). Overnight end-tidal pCO2 studies and monitoring of oxyhemoglobin saturation (SaO2) were used to adjust ventilator volumes and to document effective ventilation during sleep. No significant complications have resulted from the use of these methods over a period of 45 patient-years. Elimination of the tracheostomy permitted significant free time by glossopharyngeal breathing for four patients, two of whom had no measurable vital capacity. We conclude that noninvasive ventilatory support alternatives can be effective and deserve further study in this patient population. 
4	Diagnosis of left atrial thrombi in mitral valve disease by coronary arteriography. Arteriographic findings of neovascularity and fistula formation between coronary arteries and left atrium have occasionally been described in association with left atrial thrombosis in patients with mitral valve disease. The validity of these coronary arteriographic findings in diagnosis of atrial thrombi has been evaluated in 112 patients with mitral valve disease. Comparison was made with surgery. The study furnished these diagnostic values: sensitivity 70%, specificity 85%, positive predictive value 72%. Even if this angiographic finding is complementary in diagnosis of atrial thrombosis, its identification during coronary arteriography in patients with mitral valve disease is useful. Its detection could improve diagnostic prediction of thrombosis, especially in patients without previous embolic events or where echocardiography failed to reveal thrombi. 
5	Nasolacrimal obstruction after inferior meatus nasal antrostomy. Transient epiphora following rhinoplasty or intranasal procedures is a common occurrence. Permanent nasolacrimal duct obstruction, however, is rare. This article documents four cases of nasolacrimal duct obstruction following intranasal antrostomy. Three patients were cured by dacryocystorhinostomy and a fourth refused surgery. The anatomy of the nasolacrimal duct in the inferior meatus has considerable variation. Although the duct typically opens in the inferior meatus immediately under the insertion of the inferior turbinate, the orifice can be a single hole, a slit, multiple holes, or a trough, and can be located anywhere from 30 to 40 mm dorsal to the anterior nares. We review the embryology and anatomy of the nasolacrimal orifice in the nose and make recommendations for safe surgery in the inferior meatus. 
2	The role of methanethiol in the pathogenesis of hepatic encephalopathy. Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant. In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy. 
5	Nd:YAG-laser in the microsurgery of frontobasal meningiomas. Forty-three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor. The 1.32 microns Nd:YAG-laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments. Tumor shrinkage was achieved by radiating the tumor surface with the Nd:YAG-laser. This technique facilitated the microsurgical dissection and reduced the blood loss by half. The Nd:YAG-laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20% to zero. The postoperative quality of life was excellent with a complete rehabilitation in 76% of the patients. The use of the 1.32 microns Nd:YAG-laser improved significantly the results of microsurgery for frontobasal meningioma. 
5	Salvage from cardiogenic shock by atherectomy after failed emergency coronary artery angioplasty. In this case report of a patient undergoing angioplasty for cardiogenic shock during acute myocardial infarction, recurrent occlusion resulted in recurrence of shock. Atherectomy reestablished lasting patency and reversed the patient's hemodynamic collapse. Atherectomy deserves further investigation as a means to salvage vessel patency during unsuccessful coronary angioplasty. 
1	Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas. Cell culture and biochemical techniques have been employed to examine the effects of steroids, bromocriptine, and epidermal growth factor (EGF) on the growth and proliferative potential of meningiomas. In cell culture, the growth of meningiomas was not altered by progestogens, antiprogestogens, or 17beta-estradiol. The progestogen, norethisterone, had no effect on the uptake by meningiomas cell cultures of 3H-thymidine. Furthermore, cytosolic deoxyribonucleic acid (DNA) polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors. In contrast, the androgen antagonists, cyproterone acetate and 11-alpha-hydroxyprogesterone, and the dopamine agonist, bromocriptine, all inhibited the in vitro growth of meningioma cells. The growth of meningioma cell cultures was stimulated by EGF, and there was a positive correlation between the EGF content and DNA polymerase activity in meningioma cytosols. These results demonstrate that female sex steroids do not influence growth of meningiomas in vitro, whereas antiandrogens and bromocriptine have an antiproliferative effect. Consequently, bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas. In addition, these results suggest that EGF may be involved in the genesis and/or progression of meningiomas. 
4	Prognostic importance of delayed Q-wave evolution 3 to 24 hours after initiation of thrombolytic therapy for acute myocardial infarction. The timing of Q-wave evolution and its prognostic significance was studied in 201 patients who received thrombolytic therapy for a first acute myocardial infarction (AMI). One hundred forty-one patients (70%) had evidence of a Q-wave AMI within 3 hours of the initiation of thrombolytic therapy, 31 (16%) developed Q waves after 3 hours but before hospital discharge, and 29 (14%) were discharged with a non-Q-wave AMI. Laboratory indicators of myocardial damage and in-hospital morbidity and mortality were greater among patients with Q-wave AMIs than with non-Q-wave AMIs. When these indexes were examined with respect to the timing of Q-wave evolution, the prognosis of patients with delayed Q-wave development was similar to that of patients with non-Q-wave AMIs. Thus, compared to patients with early (less than or equal to 3 hours) Q-wave evolution, patients with delayed Q-wave evolution or with a non-Q-wave AMI had a smaller creatine kinase peak (mean 661 to 1,081 vs 1,251 to 1,541 IU; p = 0.005), better preservation of left ventricular function as measured by radionuclide ventriculography before discharge (mean +/- standard deviation 54 +/- 11% vs 47 +/- 13%; p less than 0.01), and a lower incidence of congestive heart failure at discharge (3 vs 15%; p = 0.02). In-hospital mortality was lower among patients with delayed Q-wave evolution or with a non-Q-wave AMI (5 of 141 vs 0 of 60; difference not significant). 
4	Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. Supraventricular tachyarrhythmias are reported in up to 40% of patients early after coronary artery bypass graft operations. In a randomized study, we compared the efficacy and safety of the class III antiarrhythmic beta-blocking drug sotalol versus propranolol at low and high doses in the prevention of supraventricular tachyarrhythmias in 429 consecutive patients after coronary artery bypass graft operations. Patients with severely depressed left ventricular function and other contraindications for beta-blockers were excluded. From the fourth hour up to the sixth day after coronary artery bypass, 74 patients received low-dose sotalol (40 mg every 8 hours), 66 patients low-dose propranolol (10 mg every 6 hours), 133 patients high-dose sotalol (80 mg every 8 hours), and 156 patients high-dose propranolol (20 mg every 6 hours). Baseline characteristics were comparable in all groups. Supraventricular tachyarrhythmia was observed in 10 of 72 (13.9%) who received low-dose sotalol, 12 of 64 (18.8%) who received low-dose propranolol, 13 of 119 (10.9%) who received high-dose sotalol, and 19 of 139 (13.7%) who received high-dose propranolol (not significant). Drug-related adverse effects necessitating discontinuation of the drug occurred in four receiving low doses (2.9%) and in 31 receiving high doses (10.7%) (p less than 0.02). In conclusion, no medication was found to be superior, although supraventricular tachyarrhythmias tended to be less prevalent in patients treated with sotalol than in those treated with propranolol. Moreover, significantly fewer adverse effects were noted in both low-dose groups. Therefore, low-dose beta-blocking treatment, especially low-dose sotalol, seems preferable. 
4	Nephrotoxicity of allopurinol is enhanced in experimental hypertension. Hyperuricemia is present in 20-40% of pediatric and adult patients with essential hypertension. This metabolic abnormality may represent an additional risk factor for the development of cardiovascular disease. Therefore, we performed the following studies to determine 1) whether hyperuricemia is more prevalent in the spontaneously hypertensive rat (SHR) and 2) whether allopurinol treatment has a beneficial effect on the development of hypertension in this strain, based on its capacity to lower the serum uric acid concentration and to act as an antioxidant agent. SHR and control Wistar-Kyoto (WKY) rats were assigned to two groups, one given tap water to drink and the other provided water containing allopurinol (400 mg/l) to furnish an approximate daily dose equal to 100 mg/kg body wt. This treatment was maintained for 15 weeks. The serum uric acid levels were similar in untreated SHR and WKY rats (1.85 +/- 0.10 versus 1.66 +/- 0.14 mg/dl; p = 0.28). In the control WKY rat strain, allopurinol therapy did not adversely affect weight gain or hematocrit and did not cause an increase in mortality. It resulted in a moderate decrement in kidney function (creatinine clearance: allopurinol-treated group 0.32 +/- 0.09 versus control group 0.46 +/- 0.04 ml/min/100 g body wt, in conjunction with mild-to-moderate tubulointerstitial inflammation (allopurinol-treated group 0.9 +/- 0.4 versus control group 0). 
3	Extrageniculate vision in hemianopic humans: saccade inhibition by signals in the blind field. The functional competence of extrageniculate visual pathways in hemianopic humans was demonstrated by showing that distractor signals in the blind half of the visual field could inhibit saccades toward targets in the intact visual field. This inhibitory effect of unseen distractors in patients occurred only when distractors were presented in the temporal half of the visual field, was specific to oculomotor responses, and did not occur in normal subjects. These results show that a peripheral visual signal activates retinotectal pathways to prime the oculomotor system and that these pathways can mediate orienting behavior in hemianopic humans. 
3	Long-term morphology of spastic or flaccid muscles in spinal cord-transected rabbits. Despite difficulty in long-term maintenance of spinalized rabbits, muscular pathologic changes in chronic spinalized rabbits could be observed for a period of four weeks. Rabbits were prepared by spinal cord transection at T10 (spastic paralysis) or by spinal cord removal below L7 (flaccid paralysis). Spastic preparations showed hind-limb spasticity and reflex incontinence one to two days after operation. Hypertrophic fibers began to appear in spastic muscles after two weeks. This hypertrophy, thought to be caused by phasic repetitive contraction, was verified by electron microscopy to be different from normal exercise hypertrophy. Flaccid preparations maintained hind-limb flaccidity and overflow incontinence. In flaccid muscle, marked muscle fiber necrosis indicated rapid atrophy. Spinal deformity and joint contracture inactivate spinalized rabbits, and cause pressure sores. However, feeding assistance and avoidance of complications make long-term maintenance possible. 
5	Embryo reduction in multifetal pregnancies after infertility therapy: obstetrical risks and perinatal benefits are related to operative strategy. To assess the benefits that can be expected from embryo reduction of multiple pregnancies after infertility therapy, we report 58 consecutive cases of selective termination using either a transcervical or a transabdominal approach. The initial number of embryos was five or more in 13 patients, four in 29 patients, and three in 15 patients. The miscarriage rate after transabdominal procedures (23%) was one half of that after transcervical aspiration. Forty pregnancies resulted in the live birth of one child or more. The rate of prematurity was strongly related to the number of embryos left. Mean gestational age at birth was 35.5 weeks but reached 37.7 weeks when only one embryo was left. A reduction in premature birth after selective termination appeared clear for pregnancies with four or more embryos but was less significant for triplets. 
1	Clear cell adenocarcinoma of the vagina and cervix. A report of the Central Netherlands Registry with emphasis on early detection and prognosis. The Central Netherlands Registry (CNR) of women with vaginal or cervical clear cell adenocarcinoma (CCAC) was established in 1985. An overview is presented of clinical and pathologic data of 55 patients who were registered at the CNR until July 1, 1988. All Netherlands Departments of Pathology (NDP) maintain a patient registry and 95% of the Institutes are connected with a Central Archive via a computer network. The histologic slides and clinical status were reviewed at the CNR. Twenty-five tumors were classified as vaginal carcinoma and 30 as cervical carcinoma. The mean age of the patients was 22 years. Fifty-five percent of patients (63% of patients with known maternal history) were exposed to diethylstilbestrol (DES) in utero. The majority of cases was initially diagnosed after 1980. Cytologic examination before the initial histologic diagnosis indicated that cervical tumors were detected in 80% of cases, but vaginal tumors were detected only in 33% of cases. It was concluded that an examination of DES-exposed women should consist of colposcopic inspection of the cervix and vagina, cytologic examination of the cervix and four quadrants of the vagina, and careful palpation of the cervix and the entire vaginal wall. The most important prognostic parameter for patients with CCAC was stage and grade of nuclear atypia. The results of a statistical analysis showed that these features were the most effective to distinguish between nonsurvivors and patients surviving more than 5 years. 
1	Epithelial cyst of the fourth ventricle. Case report. A case of epithelial cyst in the fourth ventricle of a 4-year-old child is described. A single epithelial layer with a clear basement membrane lining the cyst wall was observed. There were no prominent histological findings to suggest a pathogenesis for this cyst based on immunohistochemical or ultrastructural studies; however, the cyst fluid contained significant amounts of carcinoembryonic antigen. It is considered that the epithelial layer lining the cyst wall was possibly of endodermal origin. 
4	Comparison of pulse oximeters: accuracy at low arterial pressure in volunteers. A laboratory model was developed of limb hypoperfusion in volunteers, using parital occlusion of the brachial artery with consequent reduction in radial artery pulse pressure. This was used to compare the function of 13 pulse oximeters and the effect of reduced pulse pressure and mild hypoxia on these devices. With the exception of one device, all the pulse oximeters studied demonstrated similar accuracies at pulse pressures exceeding 20 mm Hg. There were however, significant differences between several of the pulse oximeters in both ability to display readings and accuracy of readings displayed when brachial artery occlusion reduced radial artery pulse pressures equal to or less than 20 mm Hg. 
3	Glucagon: prehospital therapy for hypoglycemia. STUDY OBJECTIVE: This study evaluated the efficacy of glucagon for prehospital therapy of hypoglycemia in patients without IV access. DESIGN: Prospective clinical trial. SETTING: Prehospital in a busy, urban emergency medical services system. TYPE OF PARTICIPANTS: Fifty consecutive patients presenting with documented hypoglycemia (ChemStrip BG less than or equal to 80 mg/dL) and symptoms of decreased level of consciousness, syncope, or seizure were enrolled. MEASURES AND MAIN RESULTS: Data collected included pretreatment (ChemStrip BG) and post-treatment serum glucose (hospital assay) as well as assessment of level of consciousness by a quantitative measure, the Glasgow Coma Score, and by a qualitative scale (0 to 3). The mean pretreatment blood glucose of 33.2 +/- 23.3 mg/dL increased after treatment to 133.3 +/- 57.3 mg/dL. Qualitative level of consciousness increased from a mean of 1.26 +/- .96 to 2.42 +/- .94 and Glasgow Coma Score increased from a mean of 9.0 +/- 4.19 to 13.04 +/- 3.68. The mean time until response was 8.8 minutes in those who responded to both level of consciousness criteria 82% (41 of 50). Glucagon administered for hypoglycemia resulted in a glucose increase in 98% (49 of 50) with headache as the only side effect noted in 4% (two of 50) of patients (P less than .0001). CONCLUSION: Glucagon is safe and effective therapy for hypoglycemia in the prehospital setting. 
5	Hemolytic transfusion reaction following transfusion of frozen and washed autologous red cells A case of hemolytic transfusion reaction, accompanied by hypotension and followed by transient renal failure, occurred after the transfusion of 1 unit of previously frozen autologous red cells. Subsequent investigation revealed the probable cause of the hemolysis to be inadequate deglycerolization of the unit. The cause of the associated symptoms is unknown. Possibilities include nephrotoxic effects of hemoglobin or stroma, toxic effects of glycerol, or release of vasoactive or thrombogenic substances from lysed red cells. This case of a hemolytic reaction adds to the known risks of autologous transfusion. 
5	Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. We describe a fatal case of systemic lupus erythematosus (SLE) developing cerebral and systemic necrotizing vasculitis during pregnancy. The patient was discovered to have SLE at 14 weeks' gestation. Although the symptoms disappeared without treatment with corticosteroid in the 2nd trimester, she presented with meningoencephalitis due to vasculitis in the 3rd trimester. Polyarteritis nodosa (PAN)-like necrotizing vasculitis of the small muscular arteries and arterioles, with acute and healing lesions in the leptomeninges, brain parenchyma and visceral organs was observed at postpartum autopsy. PAN-like vasculitis in the central nervous system is quite rare in SLE. This case is also suggestive in terms of the influence of pregnancy on the activity of SLE. 
1	Expression of class II molecules on intestinal epithelial cells in humans. Differences between normal and inflammatory bowel disease. Expression of class II antigens on human intestinal epithelial cells was assessed using a sensitive avidinbiotin-peroxidase technique. HLA-DR was present predominantly in the normal small bowel with diminished but evident expression in the colon. HLA-DP staining was less prominent, and HLA-DQ was absent. In inflammatory bowel disease the expression of both HLA-DR and HLA-DP was increased, but that for HLA-DQ remained absent, suggesting an inherent defect in the ability of intestinal epithelial cells to express HLA-DQ. In related experiments, an interferon gamma-treated malignant epithelial cell line T84 also failed to stain for HLA-DQ and HLA-DP despite the presence of HLA-DR. Isolated RNAs for all three subclasses of HLA-D were detectable by slot-blot analysis, suggesting that the lack of HLA-DQ expression relates to posttranscriptional defects in intestinal epithelium. These and other differences with conventional class II antigen-positive accessory cells (macrophages/B cells) may help to explain the unique properties of intestinal epithelial cells as antigen-presenting cells. 
5	Effect of intraesophageal location and muscarinic blockade on balloon distension-induced chest pain. Intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain. In order to examine the effect of balloon location and muscarinic blockade on distension-induced pain, 10 asymptomatic male volunteers were studied on two separate days using a low-compliance perfused manometry system that incorporated a silicone rubber balloon. Five-second-duration balloon distensions using balloon volumes of 2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES) before and after administration of atropine (10 micrograms/kg intravenously) or placebo in a randomized double-blind fashion. A standardized scoring system was used to assess the balloon distension-induced pain. Pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site. This was not associated with any differences in intraballoon pressures between the two sites; however, contraction amplitude orad to the balloon was greater with balloon distension at the proximal site. Atropine significantly decreased pain sensation scores with the balloon located distally but not proximally. This attenuation was not associated with significant changes in intraballoon pressures; however, contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension. These studies indicate that balloon distension-induced pain varies depending on the location of distension. This difference is not explained by differences in esophageal wall tension at the site of distension. 
5	Chloroprocaine antagonism of epidural opioid analgesia: a receptor-specific phenomenon? Sixty healthy patients scheduled for elective cesarean delivery under epidural anesthesia were randomized to receive either lidocaine or 2-chloroprocaine as the primary local anesthetic agent. When patients first complained of postoperative pain in the recovery room, they were given either fentanyl 50 micrograms or butorphanol 2 mg, epidurally, in a randomized, blinded fashion. Postoperative analgesia, quantitated on a visual analogue scale, as well as time elapsed until first request for supplemental opioid, did not differ for patients receiving butorphanol after either 2-chloroprocaine or lidocaine anesthesia. In contrast, epidural fentanyl produced a shorter and lesser degree of sensory analgesia after 2-chloroprocaine use, whereas epidural fentanyl after lidocaine anesthesia provided pain relief similar to that seen in the butorphanol groups. Side effects were limited to somnolence with butorphanol and pruritus with fentanyl. No evidence of respiratory depression was seen in any patient. We conclude that 2 mg of butorphanol epidurally provides approximately 2 to 3 h of effective analgesia after cesarean delivery with either lidocaine or 2-chloroprocaine anesthesia. Epidural fentanyl seems to be antagonized when 2-chloroprocaine, but not lidocaine, is used as the primary local anesthetic agent. We suggest a possible mu-receptor-specific etiology for this effect. 
5	Diagnosis of obstructive sleep apnea. The diagnosis of obstructive sleep apnea is frequently made by taking a meticulous history coupled with a high index of suspicion. Snoring and hypersomnolence are clinical features common to individuals with sleep apnea. Since snoring is said to be a "disease of listeners," it is not uncommon that bed partners reported an increased incidence of depression and marital displeasure. It is for this reason that the spouse or bed partner should be interviewed, since the patient may not be aware of any sleeping problems. Physicians should also be alert to complaints of excessive daytime somnolence, because studies have shown that patients with obstructive sleep apnea are at increased risk for automobile crashes. It has been estimated that approx 58,000 motor vehicle accidents involving people with sleep apnea will occur in the US each yr. By proper diagnosis and treatment, the physician is in a unique position to prevent at least some of the automobile accidents that result from falling asleep while driving. Polysomnography is the only definitive way to obtain a diagnosis of sleep apnea. This allows the physician not only to diagnosis the disorder, but also helps in the evaluation of the severity of the syndrome and selection of therapy. An ENT evaluation is also important in ruling out anatomic disorders that can cause upper airway obstruction. Certain factors, such as alcohol and sedative ingestion, may aggravate the condition in a person predisposed to sleep apnea, and subtle changes, such as unexplained hypertension, polycythemia, and cor pulmonale, should lead one to investigate the possibility of sleep apnea as the etiology. 
5	Transformed and nontransformed cells differ in stability and cell cycle regulation of a binding activity to the murine thymidine kinase promoter. A DNA binding activity to an upstream region of the murine thymidine kinase gene is regulated differently in a transformed and nontransformed cell line pair. Differences in regulation were observed (i) after serum levels were reduced, (ii) when serum levels were returned to initial high levels, and (iii) while protein synthesis was inhibited. After reduction of serum levels, the binding activity was unstable in nontransformed BALB/c 3T3 clone A31 cells but was significantly more stable in benzo[a]pyrene-transformed BALB/c 3T3 cells. After serum concentration was returned to high levels, the kinetic pattern of the binding activity differed between nontransformed and transformed cells. While protein synthesis was inhibited, the binding activity was unstable in nontransformed cells and stable in transformed cells. Partial inhibition of protein synthesis--a more stringent condition to test instability--prevented the induction of the binding activity in nontransformed cells. Previously, the labile protein hypothesis set forth the criterion that a protein regulating the onset of DNA synthesis should be unstable in nontransformed cells and stable in transformed cells. The DNA binding activity described here satisfies this criterion. 
1	Mucinous cystadenoma of the lung. A report of two cases with immunohistochemical and ultrastructural analysis. We describe two patients who presented with solitary pulmonary masses that consisted of unilocular cysts lined by columnar mucinous epithelium. The cysts contained copious mucus. The epithelial lining of the cysts showed foci of stratification and papillary infolding. Histologically identical lesions have previously been termed unusual mucous cysts or mucinous cystadenomas. We believe that these tumors are true neoplasms differentiating toward the respiratory epithelial mucous cell. They should be distinguished from a variety of pulmonary neoplasms including bronchoalveolar carcinoma, bronchial mucous gland adenoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma. 
3	Brain death and organ donation in a neurosurgical unit: audit of recent practice OBJECTIVE--To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit. DESIGN--Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989. SETTING--A regional neurosurgical unit serving 2.7 million population. RESULTS--Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation. Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated. Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these. Half those with permission for multiorgan donation had only the kidneys removed. CONCLUSIONS--More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients. The estimated size of the pool of potential donors depends on what types of patients might be considered. Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors. Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues. 
1	Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer. 
3	Modification of stroke susceptibility by genotype-dependent maternal influences. The influence of the prenatal and postnatal maternal environment on stroke susceptibility was evaluated by reciprocally crossing the spontaneously hypertensive (SHR) and the Dahl salt-sensitive (SS/Jr) inbred rat strains to produce reciprocal F1 hybrids that were nurtured, respectively, during prenatal and postnatal life by SHR or SS/Jr mothers. Following placement on a high-salt diet containing 8% NaCl at 35 days of age, F1 rats reared by SHR mothers had shorter survival times and were more likely to die with cerebral hemorrhage than F1s reared by SS/Jrs. Across reciprocal F1 female groups, enhanced susceptibility to stroke was associated with greater elevations of systolic blood pressure, but this association was not seen across reciprocal F1 male groups. There was also an association between blood pressure and stroke within each F1/gender subgroup: Rats eventually suffering strokes developed higher blood pressure after placement on the high-salt diet than rats that did not suffer stroke. Lower day 35 body weights (before exposure to the high-salt diet) were associated with greater likelihood of stroke both across the reciprocal F1 groups, and within three of the four F1/gender subgroups. The differences in stroke susceptibility between the reciprocal F1 groupings may be due to systematic differences in the prenatal and/or postnatal environments of SHR and SS/Jr mothers and may be mediated by variations in the nutritive capacity of the two inbred mothers. 
1	Absence of estrogen receptors in dysplastic nevi and malignant melanoma. Benign nevi, dysplastic nevi, and primary and metastatic malignant melanomas were evaluated for the presence of sex hormone binding and estrogen receptor protein. We have confirmed the observation of Ellis et al. that some pigmented lesions possess sex hormone-binding proteins. We could not demonstrate a true estrogen receptor in any benign nevi, dysplastic nevi, primary melanomas, or metastatic melanomas. Thus the ability to bind estrogen or progesterone does not correlate with the presence of a true estrogen receptor. Lack of nuclear estrogen receptors suggests that the influence of estrogen on the pathophysiology of melanoma or of benign melanocytic nevi may not be significant. 
5	Memory-contingent saccades and the substantia nigra postulate for essential blepharospasm. Essential blepharospasm and cranial dystonia are related focal dystonias of unknown aetiology. Blepharospasm induced by acute dopamine depletion in parkinsonism restricts saccade initiation possibly via the substantia nigra pars reticulata (SNpr). If essential blepharospasm and cranial dystonia similarly restrict saccades, then a selective, somatotopically arranged pathway such as the SNpr may be involved. To test this possibility memory-contingent and visually-guided saccades were measured in patients with essential blepharospasm and cranial dystonia. The latency of both forms of saccades was either significantly prolonged or excessively variable, while the accuracy and peak velocity of these fast eye movements were similar to age-matched control subjects. Essential blepharospasm and cranial dystonia alter the initiation of saccadic eye movements. Subcortical brain regions or pathways where eyelid, saccade and cranial/cervical motor control are somatotopically approximated, such as the SNpr, may be involved in blepharospasm. 
5	Itraconazole therapy for nonmeningeal coccidioidomycosis: clinical and laboratory observations. Itraconazole, a new oral triazole antifungal agent, was administered in 75 courses to patients with chronic coccidioidomycosis at dosages of 50 to 400 mg/day for a median duration of 10 months. Assessment of efficacy was made with a standardized scoring system. Responses were seen in 42 of 58 assessable courses (72%). Nonresponse occurred exclusively in patients who had failed previous therapy and was most common in pulmonary disease. Toxicity was minimal at the doses studied. Pharmacokinetic analysis of itraconazole in serum at steady state showed negligible circadian variation; differences in serum concentrations among patients were large. Clinical isolates of Coccidioides immitis showed uniform in vitro susceptibility to itraconazole. Itraconazole shows impressive activity in this series of patients with refractory coccidioidomycosis. Further evaluation of itraconazole in this and in other systemic mycoses is in order. 
2	Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction. In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid ([99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of [99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl). 
3	Local anesthesia for neonatal circumcisions: are family practice residents likely to use it? Dorsal penile nerve block with lidocaine (DPNB) is a local anesthetic technique for neonatal circumcision which is both effective and consistent with ethical concerns for infant welfare. As such, it should be included in training programs that prepare residents to care for newborns. To assess the current level of DPNB use by residents in a family practice training program and to identify attitudes and other factors that relate to use, a survey was sent to 127 residents in the Department of Family Practice and Community Health, University of Minnesota. Of the 101 respondents, 55% had used DPNB, and 17% could be characterized as high users, employing the technique for over one half of the circumcisions they performed. Residents with comprehensive understanding of the newborn's capacity to feel pain were more likely to be using DPNB than their less well-informed counterparts. Four factors were identified as predicting use: cooperation of nursery staff for the procedure, accessibility of instruction in PNB technique, belief that PNB is effective in reducing infant pain, and likelihood of parents giving consent for PNB. These results suggest strategies which may be implemented by family practice educators who wish to promote the principles and techniques of DPNB. 
3	Choroid plexus tumors in the breast cancer-sarcoma syndrome. Choroid plexus neoplasms are rare epithelial tumors of the central nervous system. A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome (Li-Fraumeni or SBLA syndrome), an inherited condition characterized by the development of diverse neoplasms (sarcoma, breast cancer, brain tumors, leukemia, adrenal cortical carcinoma, and others). Choroid plexus carcinomas were identified in two kindreds previously reported with the syndrome. The literature contains reports of choroid plexus neoplasms occurring in families and in individuals with multiple primary tumors. Choroid plexus neoplasm may be a manifestation of the inherited proclivity to tumor development in the breast cancer-sarcoma syndrome. 
5	Blue breath holding is benign. In their recent publication in this journal, Southall et al described typical cyanotic breath holding spells, both in otherwise healthy children and in those with brainstem lesions and other malformations. Their suggestions regarding possible autonomic disturbances may require further study, but they have adduced no scientific evidence to contradict the accepted view that in the intact child blue breath holding spells are benign. Those families in which an infant suffers an 'apparently life threatening event' deserve immense understanding and help, and it behoves investigators to exercise extreme care and self criticism in the presentation of new knowledge which may bear upon their management and their morale. 
5	Surgical treatment of the retethered spinal cord after repair of lipomyelomeningocele. In a series of 75 patients with surgically treated lipomyelomeningoceles, the neurological condition of six patients deteriorated 6 months to 14 years after the operation due to repeat tethering of the spinal cord. The tethering resulted from postoperative dense adhesion between the cord and the overlying dura mater. Two of the six patients underwent conventional repeat untethering procedures, and the remaining four were successfully treated with a new surgical technique developed by the authors to prevent such dural adhesion. For this procedure, after complete untethering of the spinal cord, the lumbosacral cord is retained in the center of the dural sac by fine stay sutures between the pia mater of the conus medullaris and the ventral dura mater. In addition, the dura mater is tacked to the posterior arch which is reconstructed with bone grafts at one or two bifid vertebral levels. During a postoperative follow-up period of 1 to 3 years, no further deterioration has been observed and magnetic resonance studies have demonstrated a space filled with cerebrospinal fluid (CSF) around the lumbosacral cord. The authors conclude that long-term observation, both neurological and radiological, is essential even after successful repair of a lipomyelomeningocele. This new surgical procedure can maintain a CSF bath around the lumbosacral cord, thus preventing dural adhesion. Application of this technique will hopefully be beneficial in lipomyelomeningocele patients with a high risk of cord retethering after initial repair. 
4	Clinical and Doppler echocardiographic follow-up after percutaneous balloon valvuloplasty for aortic valve stenosis. Percutaneous balloon valvuloplasty has been shown to increase the aortic orifice area and to improve clinical symptoms. However, there are only few data concerning long-term results after balloon valvuloplasty. In this study, 36 patients (11 men, 25 women, mean age 75 +/- 8 years) were followed after balloon valvuloplasty for a period of up to 18 months by means of clinical parameters and repeated Doppler echocardiographic measurements after 1, 3, 6, 12 and 18 months. Invasive measurements revealed a decrease of the systolic peak gradient from 78 +/- 24 to 38 +/- 13 mm Hg (p less than 0.001), and an increase in the aortic orifice area from 0.58 +/- 0.23 to 0.93 +/- 0.2 cm2 (p less than 0.001). The Doppler echocardiographic approach revealed that the maximal instantaneous gradient decreased from 96 +/- 26 to 67 +/- 22 mm Hg (p less than 0.001). The aortic orifice area increased from 0.49 +/- 0.16 to 0.73 +/- 0.21 cm2 (p less than 0.001). Three patients (8%) died in the hospital. After hospital discharge, 16 patients (44%) died and 8 patients (22%) underwent successful aortic valve replacement after a mean follow-up of 8 +/- 6 months. Nine patients (25%) were alive after a follow-up period of 18 months. Seven of these (19%) remained clinically improved. During follow-up, the Doppler echocardiographic results revealed a continuous trend toward the preprocedural severity of the aortic valve stenosis. Progression of restenosis assessed by Doppler echocardiographic measurements was accelerated in the group of patients who subsequently died or underwent repeat balloon valvuloplasty or aortic valve replacement. 
5	Severe tricuspid regurgitation after mitral valve repair: diagnosis by intraoperative transesophageal echocardiography. Transesophageal echocardiography facilitates the evaluation of valvular repair in the operating room. The functional valvular morphology and degree of valvular regurgitation can be assessed before and after repair. This technique can also identify unsuspected findings--in this case, severe tricuspid regurgitation complicating cardiopulmonary bypass. We report a previously undescribed cause of traumatic tricuspid regurgitation. 
3	Calcium antagonists in the management of patients with aneurysmal subarachnoid hemorrhage: a review. Cerebral arterial vasospasm and infarction is the leading cause of death and disability among patients who reach a major medical center after aneurysmal subarachnoid hemorrhage (SAH). Recent evidence suggests that two calcium antagonists, nimodipine or nicardipine, may be useful in preventing this important complication of SAH. This paper reviews the current status of these two calcium antagonists in the management of SAH. 
1	Postoperative follow-up of patients with early breast cancer. Patterns of care among clinical oncologists and a review of the literature. Eighty clinical oncologists in the southeastern United States were surveyed to determine their strategies for follow-up care after primary treatment of early-stage breast cancer. The frequency of use of the history and physical examination, complete blood count, liver function tests, carcinoembryonic antigen levels, chest x-ray, skeletal survey, bone scan, liver scan, and mammogram for observing hypothetical low- and high-risk patients was assessed. Yearly mammograms were recommended by more than 95% of respondents. History and physical examination were the modalities used most often, whereas periodic bone and liver scans were used only in a minority of patients. A review of the literature supported the strategy of the respondents in this survey and further underscored the cost-effectiveness of the history and physical examination in detecting recurrence during follow-up. Based on this survey and supporting literature, recommendations for reasonable yet cost-conscious follow-up are presented. 
4	Prognostic significance of Doppler measures of diastolic function in cardiac amyloidosis. A Doppler echocardiography study. BACKGROUND. We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis. METHODS AND RESULTS. We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening. CONCLUSIONS. Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis. 
4	Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection BACKGROUND. Peliosis hepatis is characterized by cystic, blood-filled spaces in the liver and is seen in patients with chronic infections or advanced cancer and as a consequence of therapy with anabolic steroids. Cutaneous bacillary angiomatosis is a bacterial infection that occurs in patients with human immunodeficiency virus (HIV) infection; its histologic appearance is that of a pseudoneoplastic vascular proliferation. METHODS. We studied liver tissue from eight HIV-infected patients with peliosis hepatis, two of whom also had cutaneous bacillary angiomatosis. For comparison we examined tissue from four patients who had peliosis hepatis without HIV infection. Tissues were examined histologically on routine sections and with special stains and electron microscopy. RESULTS. The histologic features seen in peliosis hepatis associated with HIV infection, but not in the four cases unrelated to HIV infection, were myxoid stroma and clumps of a granular purple material that on Warthin-Starry staining and electron microscopy proved to be bacilli. The bacilli, which could not be cultured, were morphologically identical to those found in the skin lesions of cutaneous bacillary angiomatosis. The clinical courses of two of the patients with this "bacillary peliosis hepatis" indicate that it responds to antibiotic treatment. CONCLUSIONS. HIV-associated bacillary peliosis hepatis is an unusual, treatable opportunistic infection, probably caused by the same organism that causes cutaneous bacillary angiomatosis. Our failure to find bacilli in non-HIV-associated cases implies that other pathogenetic mechanisms may also be responsible for peliosis hepatis. 
1	Cyclosporine enhances the growth of carcinogen-induced enzyme-altered foci in rat liver. Cyclosporine, a powerful immunosuppressant, has been used successfully for organ transplantation. Its efficacy on liver transplants of patients with primary hepatic tumors remains controversial because of a high rate of recurrence of the original tumors in the transplanted livers. In this study, we experimentally tested whether cyclosporine exerts any effects on the growth of carcinogen-initiated liver cells using the short-term assays of rat liver carcinogenesis. Dietary cyclosporine, which maintained sufficient levels of blood cyclosporine and suppressed host immune functions, enhanced the development of the glutathione S-transferase, placental form-positive hepatocyte foci in the liver of male F-344 rats treated with a single weekly dose of diethylnitrosamine (75 mg/kg) for 3 wk. Dietary cyclosporine also accelerated the growth of preformed glutathione S-transferase, placental form-positive foci induced by a single dose of diethylnitrosamine (250 mg/kg) followed by the promoting regimen of a choline-deficient diet. It is possible that the enhancement of the size of hepatocyte foci by cyclosporine could be due to stimulation of growth or inhibition of regression. The mechanisms by which cyclosporine modifies the growth of preneoplastic lesions in the liver are not yet fully understood. Possible involvement of immunologically relevant cells in the liver, Kupffer cells and pit cells in the process is suggested. 
3	A cellist with arm pain: thermal asymmetry in scalenus anticus syndrome. We report on a cellist with pain and coldness of the upper extremity. Abnormal thermographic studies were instrumental in uncovering intermittent compression of the subclavian artery, and this prompted us to study the effects of cello playing on skin temperature asymmetry. Temperature asymmetry was defined as the temperature difference (delta-T) from one hand to the other. In 57 controls, mean delta-T at rest was .309 +/- .254C. Exercising the upper extremities by prolonged elbow flexion or by movements mimicking cello playing in controls did not significantly affect delta-T. In our patient, delta-T was ten times control (3.6C). Angiography showed extrinsic compression of the subclavian artery occurring only after cello playing; sympathetic ganglion block relieved the pain. Our patient's abnormal skin temperature may have reflected sympathetic vasomotor hyperactivity. Intermittent neurovascular compression and sympathetic hyperactivity appear to be factors in scalenus anticus syndrome. 
3	Cauda equina syndrome associated with multiple lumbar arachnoid cysts in ankylosing spondylitis: improvement following surgical therapy. A case of cauda equina syndrome with multiple lumbar arachnoid cysts complicating ankylosing spondylitis (AS) is described. The value of computerised tomography (CT) and magnetic resonance imaging (MRI) as a non-invasive means of establishing the diagnosis is emphasised. In contrast to previously reported cases the patient showed neurological improvement following surgical therapy. Surgery may be indicated in some patients, particularly when there is nerve root compression by the arachnoid cysts and when the patient is seen early before irreversible damage to the cauda equina has occurred. 
5	Carotid-cavernous sinus fistula associated with a primitive trigeminal artery. Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery. 
2	Apical secretion of lysosomal enzymes in rabbit pancreas occurs via a secretagogue regulated pathway and is increased after pancreatic duct obstruction. Lysosomal hydrolases such as cathepsin B are apically secreted from rabbit pancreatic acinar cells via a regulated as opposed to a constitutive pathway. Intravenous infusion of the cholecystokinin analogue caerulein results in highly correlated apical secretion of digestive and lysosomal enzymes, suggesting that they are discharged from the same presecretory compartment (zymogen granules). Lysosomal enzymes appear to enter that compartment as a result of missorting. After 7 h of duct obstruction is relieved, caerulein-stimulated apical secretion of cathepsin B and amylase is increased, but the ratio of cathepsin B to amylase secretion is not different than that following caerulein stimulation of animals never obstructed. These findings indicate that duct obstruction causes an increased amount of both lysosomal and digestive enzymes to accumulate within the secretagogue releasable compartment but that duct obstruction does not increase the degree of lysosomal enzyme missorting into that compartment. Pancreatic duct obstruction causes lysosomal hydrolases to become colocalized with digestive enzymes in organelles that, in size and distribution, resemble zymogen granules but that are not subject to secretion in response to secretagogue stimulation. These organelles may be of importance in the development of pancreatitis. 
5	Acute experimental allergic encephalomyelitis in SJL/J mice induced by a synthetic peptide of myelin proteolipid protein. Clinical, histologic, and ultrastructural characteristics of acute experimental allergic encephalomyelitis (EAE) induced by sensitization with a synthetic peptide corresponding to mouse myelin proteolipid protein (PLP) residues 139-151 HCLGKWLGHPDKF were studied in SJL/J mice. Groups of mice were immunized with 20, 50, or 100 nmol of the peptide and were killed from seven to 28 days after sensitization or when they were moribund. Beginning on Day 9, the mice showed signs of EAE and the disease progressed rapidly to paralysis. Central nervous system (CNS) inflammation, edema, gliosis, and demyelination were found in all mice killed between Days 10 and 28 and white matter lesion areas correlated with clinical score at the time the mice were killed. Peripheral nerve roots and the cauda equina did not have lesions. Within the range studied, the severity of clinical or histologic disease was the same regardless of the PLP peptide dose. Two of ten mice immunized with 100 nmol and none of 14 mice given smaller doses of a synthetic peptide of mouse myelin basic protein (MBP) showed clinical EAE. These mice had small numbers of CNS lesions that were indistinguishable from those in PLP peptide-sensitized mice. These findings demonstrate that immunization of SJL/J mice with PLP peptide 139-151 produces a disease with the clinical and morphologic features of CNS tissue-, whole PLP-, whole MBP-, and MBP peptide-induced acute EAE. Thus, PLP is a major encephalitogen and immune reactions to epitopes of different myelin proteins may induce identical patterns of injury in the CNS. 
2	Six physicians with inflammatory bowel disease. This essay tells the stories of six physicians with inflammatory bowel disease (IBD) to emphasize how important denial and control become when a physician is a patient. Guilt at the supposed psychosomatic "origin" of IBD suggests that we as physicians should never blame our patients for getting sick. 
4	The variable extent of jeopardized myocardium in patients with single vessel coronary artery disease: quantification by thallium-201 single photon emission computed tomography To assess the extent of jeopardized myocardium in patients with single vessel coronary artery disease of variable severity and location, quantitative exercise thallium-201 single photon emission computed tomography was performed in 158 consecutive patients with angiographically proved single vessel coronary artery disease. The extent of abnormal left ventricular perfusion was quantified from computer-generated polar maps of three-dimensional myocardial radioactivity. Patients with only a moderate (51% to 69%) stenosis tended to have a small perfusion defect irrespective of the coronary artery involved. Whereas a perfusion defect measuring greater than or equal to 10% of the left ventricle was found in 78% of patients with no prior infarction and severe (greater than or equal to 70%) stenosis, this was observed in only 24% of patients with moderate stenosis. Perfusion defect size increased with increasing severity of stenosis for the entire group without infarction and for those with left anterior descending, right and circumflex coronary artery stenosis. However, the correlation between stenosis severity and perfusion defect size was at best only modest (r = 0.38, p = 0.0001). The left anterior descending artery was shown to be the most important of the three coronary arteries for providing left ventricular perfusion. Proximal stenosis of this artery produced a perfusion defect approximately twice as large as that found in patients with a proximal right or circumflex artery stenosis. However, marked heterogeneity in perfusion defect size existed among all three vessels despite comparable stenosis severity. This was most apparent for the left anterior descending coronary artery, where mid vessel stenosis commonly produced a perfusion defect similar in size to that found in proximally stenosed vessels. 
5	Are cystgastrostomy and cystjejunostomy equivalent operations for pancreatic pseudocysts? To compare the effectiveness of cystgastrostomy and cystjejunostomy for treatment of pancreatic pseudocysts, 39 patients with cystgastrostomy were compared to 59 patients with cystjejunostomy. The groups were comparable in age, sex, cause of pancreatitis, pseudocyst location, symptoms, and preoperative serum amylase level. Cysts treated with cystgastrostomy were larger (mean diameter, 11.1 +/- 0.9 cm) than cysts treated by cystjejunostomy (mean diameter, 6.7 +/- 0.7 cm) (p less than 0.05). Mean duration of surgery was 148 +/- 11 minutes for cystgastrostomy versus 265 +/- 15 minutes for cystjejunostomy (p less than 0.05). Mean blood loss was 397 +/- 82 ml for cystgastrostomy versus 703 +/- 80 ml for cystjejunostomy (p less than 0.05) Mean intraoperative fluid requirements were 2640 +/- 313 ml for cystgastrostomy and 4403 +/- 362 ml for cystjejunostomy (p less than 0.05). Cyst recurrence was 10% for cystgastrostomy versus 7% for cystgastrostomy. Postoperative gastrointestinal bleeding occurred in 8% of patients with cystgastrostomy and in 2% of patients with cystjejunostomy. Infection problems with cystjejunostomy included two wound infections and one case of septicemia; infection problems with cystjejunostomy included five intraabdominal abscesses, two wound infections, and one case of pneumonia. Two patients died with cystgastrostomy (both from gastrointestinal bleeding); two patients died with cystjejunostomy (one from intraabdominal sepsis and one from pulmonary embolus). Cystgastrostomy was used for significantly larger pseudocysts and was associated with significantly less blood loss and operating time than cystjejunostomy (p less than 0.05). Morbidity and mortality from cystgastrostomy and cystjejunostomy were comparable, although gastrointestinal bleeding was more common with cystgastrostomy and intraabdominal abscess was more common with cystjejunostomy. Since cystgastrostomy can usually be performed more quickly and with less blood loss, it should be considered whenever anatomically feasible. 
5	Increased susceptibility to hypoxia of prolonged action potential duration in ventricular papillary muscles from diabetic rats. The action potential duration (APD) of ventricular muscles obtained from diabetic animals is reported to be prolonged. We studied the effect of varied periods of diabetes on APD prolongation using isolated ventricular papillary muscles from streptozocin-injected rats. We found that a diabetic period greater than 30 wk was necessary for the evolution of significant prolongation of APD. We then studied the effect of repeated hypoxia (PO2 40 mmHg) and normoxia (PO2 300 mmHg) on prolonged APD of diabetic muscles and compared the findings with those from control rats. Transmembrane potentials were recorded with conventional glass microelectrodes. Under normoxic conditions, the APDs of diabetic muscles were significantly prolonged, the maximum upstroke velocity of action potentials tended to be decreased, and the resting membrane potential was not changed significantly compared with controls. The first hypoxia (20 min) shortened the APD in both diabetic and control rats but more so in diabetic rats, thereby making the APD of diabetic rats virtually identical to the control rat APD during the hypoxia. On subsequent reoxygenation (30 min), these hypoxia-induced changes were almost recovered. The second hypoxia (20 min) produced more severe shortening of the APD in both muscle types, and the effect was again far greater in diabetic rats than controls, ending with a reversed sequence of APDs and the APD of diabetic muscles much shorter than the controls. Excessive shortening of APD in diabetic muscles during hypoxic conditions was speculated to be due to greater increases in the outward K+ current through ATP-regulated K+ channels that may be secondary to the more severe reduction of intracellular ATP concentrations in diabetic versus control hearts. 
5	Differences between florid osseous dysplasia and chronic diffuse sclerosing osteomyelitis. Florid osseous dysplasia (FOD) is confused in the literature with chronic diffuse sclerosing osteomyelitis. Two cases of each condition are presented to demonstrate the differences between them. In FOD, there are multiple lobulated sclerotic masses in several quadrants of the jaws, usually in black females. In some cases, the sclerotic masses are exposed to the oral cavity, resulting in a secondary osteomyelitis. Periapical cemental dysplasia is often found in association with FOD. Chronic diffuse sclerosing osteomyelitis is a primary inflammatory condition of the mandible. Patients have cyclic episodes of unilateral pain and swelling. The affected region of the mandible exhibits a diffuse opacity with poorly defined borders. Although women are affected more often than men, black persons are not particularly susceptible. 
5	The IVH complex of lesions: cerebrovascular injury in the preterm infant. The term intraventricular hemorrhage has become associated with a variety of cerebrovascular insults in preterm infants. Because of a shared pathophysiology and timing, these are the neurologic lesions to search for when evaluating sick preterm infants. This complex of lesions is common and, when parenchymal injury occurs, likely to result in neurologic sequelae. A review of the variety of injuries, their pathophysiology, their diagnosis by cranial ultrasonography, and their prognosis is offered. Emphasis is placed on the need for assessment over time when evaluating parenchymal lesions in preterm infants. 
1	Colorectal cancer: have we identified an effective screening strategy? Three currently used screening methods are aimed at detecting colorectal cancer when it is asymptomatic and curable, and at detecting polyps so that they can be removed before they can progress to cancer. Digital rectal examinations are relatively cheap and easy but can detect only a small fraction of large-bowel cancers. Sigmoidoscopy is more sensitive, but its low acceptability to patients has been only partially mitigated by the introduction of the 35-cm flexible instrument. Fecal occult blood testing has limited sensitivity because blood from cancers and polyps is neither continuously shed nor uniformly distributed in feces; specificity and positive predictive value are also low because of other sources of blood in the stool. Prudent judgment suggests that all of these screening tests may prevent death from colorectal cancer in some patients. However, none has been proven effective in general use by well-controlled studies. Case-control studies can provide timely and valuable new evidence in this regard; the authors' investigations in progress are described. The current lack of strong evidence in support of these screening tests should not be interpreted as evidence against their use. 
2	Estrogen receptors in the external anal sphincter. Inasmuch as anal competence in women is reduced after the age of 50 years, it may be dependent on effects of estrogens. In this study, samples of the external anal sphincter were analyzed for the presence of estrogen receptors and were found to be present at a median concentration of 5.0 fmol per milligram of protein (range, 1.9 to 13) in women (n = 7), and 1.1 fmol per milligram of protein (range, 0 to 3.2) in men (n = 7). These findings are of interest with regard to the treatment of idiopathic anal incontinence. 
4	Turner's syndrome, fibromuscular dysplasia, and stroke. We report a 43-year-old woman who presented with a right frontoparietotemporal ischemic stroke. She had been diagnosed with Turner's syndrome during childhood and had a history of chronic estrogen therapy. Cerebral angiography showed lesions characteristics of fibromuscular dysplasia involving the right internal carotid and right vertebral arteries. We are not aware of any previous reports describing an association between fibromuscular dysplasia and Turner's syndrome. Although chronic estrogen therapy cannot be ruled out as a cause of this patient's stroke, we suggest a possible etiologic relation between these two entities. 
1	The role of gastric resection in the management of multicentric argyrophil gastric carcinoids. A patient with pernicious anemia, atrophic non-antral gastritis, hypergastrinemia, and widespread hyperplasia of enterochromaffin-like cells and manifest enterochromaffin-like cell carcinoma was followed up during 39 months, including 15 months after gastric resection. In this case normalization of gastrin levels did not prevent the development of multiple gastric carcinoids in the fundic mucosa, suggesting that factors other than gastrin are of importance in the pathogenesis. 
1	The potential of 2-deoxy-2[18F]fluoro-D-glucose (FDG) for the detection of tumor involvement in lymph nodes. To assess the potential of FDG for PET imaging of nodal tumor metastases, we evaluated its uptake into normal lymph nodes, tumor-involved lymph nodes, and subcutaneous tumor xenografts in rodents. Normal lymph nodes in mice and rats accumulate FDG moderately, developing node/blood ratios of 1.3-11.9/1 at 2 hr following i.v. injection. By contrast, FDG given subcutaneously to healthy Sprague Dawley rats developed very high normal draining lymph node/blood ratios (272/1) versus 7.7/1 by i.v. injection. In nude mice, subcutaneous human ovarian cancer xenografts had 1.27-fold more uptake relative to blood than did normal popliteal lymph nodes. Subcutaneous tumor xenografts of rat breast cancer developed tumor/normal node uptake ratios of 4.91 +/- 0.43/1 and tumor/blood ratios of 6.6 +/- 0.9 at 2 hr postinjection. Mouse nodes involved with 38C13 murine B-cell lymphoma had mean node/blood ratios of 42.9 +/- 6.7/1 and tumored node/normal lymph node uptake of 6.3/1. Thus, FDG given intravenously but not subcutaneusly (due to high normal nodal uptake) has potential as an agent for the detection of metastatic tumors in regional lymph nodes using PET scanning. 
4	Pathophysiology of hypertension in blacks. The pathophysiology of hypertension in the black population differs to some extent from that of the nonblack population. Although black hypertensives exhibit enhanced sodium retention, expanded plasma volume, lower plasma renin activity, and a greater increase in blood pressure in response to high levels of Na+ intake compared with nonblack hypertensives, there is considerable heterogeneity in these studies. Alterations in ion transport mechanisms, such as a decrease in Na+K(+)-ATPase activity and Na+K+ cotransport, have been demonstrated in the black hypertensive population. Those features provide the physiologic basis for the differential response to monotherapy with diuretics and, perhaps, with calcium channel blockers, that is observed in black hypertensives, particularly when compared with responses to beta-blockers or angiotensin converting enzyme inhibitors. 
2	Increased uptake of bromodeoxyuridine by hepatocytes from early stage of primary biliary cirrhosis. The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001). These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes. 
5	Fine surface structure of an intraspinal neurenteric cyst: a scanning and transmission electron microscopy study. The case of an 11-year-old boy with an intraspinal neurenteric cyst, which recurred 8 years and 3 months after surgery, is presented. Scanning and transmission electron microscopy of the cyst epithelium revealed marked resemblance to that of the respiratory tract, despite the presence of numerous goblet cells mimicking intestine on light microscopy study. Detailed ultrastructural findings are described. 
5	Acid aspiration prophylaxis in 288 obstetric anaesthetic departments in the United Kingdom. The choice of drugs for acid aspiration prophylaxis in 288 obstetric anaesthetic departments in the United Kingdom was determined by questionnaire. The results are compared with a similar survey of anaesthetic departments 5 years ago. The prescription of sodium citrate and the H2 receptor antagonist ranitidine has superseded that of Mist. magnesium trisilicate. 
3	Advances in the treatment of complex cerebrovascular disorders by interventional neurovascular techniques. Treatment of complex cerebrovascular disorders, including intracranial aneurysms, carotid cavernous sinus fistulas, vertebral fistulas, arteriovenous malformations, atherosclerosis of brachiocephalic vessels, and arterial vasospasm, is being performed in selected cases by interventional neurovascular techniques. Recent advances in microballoon technology, permanent solidifying polymers, newer embolic agents, high-resolution digital subtraction angiography with road-mapping technique, and steerable micro-guide wires and catheters have greatly improved access in the distal intracranial circulation and markedly reduced the morbidity associated with these procedures. Interventional neuroradiology is emerging as an important adjunct to neurosurgery for selected cerebrovascular disorders. 
5	Transfer function of sound transmission in subglottal human respiratory system at low frequencies. The amplitude of sound transmission from the mouth to a site overlying the extrathoracic trachea and two sites on the posterior chest wall was measured in eight healthy adult male subjects at resting lung volume over the 100- to 600-Hz frequency range. The ratios of the estimated magnitude spectra of transmission of each of the chest wall sites to the tracheal site were determined, with the resulting spectra representing effective transfer functions of transmission in the subglottal system. For the group, the transfer functions exhibited a single peak, which occurred at 143 +/- 13 Hz (mean +/- SD) with a quality factor (Q) of 2.0 +/- 0.2 for the upper chest wall site and at 129 +/- 6 Hz with a Q of 2.2 +/- 0.4 for the lower site. The trend of decreasing spectral energy with increasing frequency was indicated by roll-offs of -10 +/- 4 and -17 +/- 5 dB/octave from 300 to 600 Hz at the two sites, respectively. The fundamental radial mode of a model thoracic cavity, which is a large rigid cylinder filled with lossless lung tissue, provides a good estimate of the observed low-frequency resonance. This agreement suggests that thoracic cavity resonances may have particularly important effects on sound transmission at frequencies below approximately 250 Hz, where the magnitude of parenchymal attenuation appears to be small. 
4	Results of repeat percutaneous balloon valvuloplasty for pulmonary valvar restenosis. Follow-up cardiac catheterization studies were used to evaluate 105 patients who had undergone percutaneous balloon pulmonary valvuloplasty. Fifteen of those patients who had peak systolic pulmonary valve gradients greater than = 40 mm Hg at follow-up underwent repeat balloon valvuloplasty. For the initial balloon pulmonary valvuloplasty, the mean ratio of the balloon diameter to pulmonary valve annulus diameter was 0.98 +/- 0.2; at repeat valvuloplasty the mean was 1.19 +/- 0.12. The immediate post-repeat balloon valvuloplasty results showed a reduction in the peak systolic gradient from a mean of 70.2 +/- 17.8 to 29.1 +/- 19.0 mm Hg (p less than 0.001). This reduction in the gradient was maintained at a mean of 14.3 +/- 5.0 mm Hg in 8 of the 10 patients who underwent further follow-up studies. We conclude that successful repeat balloon pulmonary valvuloplasty with the use of larger sized balloons is feasible in patients who have restenosis after the initial percutaneous balloon valvuloplasty--including partial but not complete dysplasia of the pulmonary valve. 
4	Double-blind comparison of doxazosin and enalapril in patients with mild or moderate essential hypertension. The antihypertensive efficacy and safety of doxazosin and enalapril were compared in the general practice setting (n = 54). Both agents produced comparable, statistically significant (p less than 0.05) reductions in mean blood pressure with no clinically relevant changes in heart rate. Side effects in the two groups were mild or moderate and disappeared or were tolerated with continued treatment. Doxazosin, in contrast to enalapril, produced a significant (p less than 0.05) reduction in the total serum cholesterol concentration, a reduction in the level of triglycerides, and a favorable increase in the high-density lipoprotein/total cholesterol ratio. The reduction in calculated coronary heart disease risk produced by doxazosin (-27.58%) was highly significant (p less than 0.0002) and greater than that produced by enalapril (-18.49% p less than 0.02). 
5	Bilateral reexpansion pulmonary edema following unilateral pleurocentesis. Acute ipsilateral pulmonary edema following reexpansion of the lung after pleurocentesis or pneumothorax is a well described entity. We report the unusual occurrence of bilateral pulmonary edema following unilateral pleurocentesis in a young male without heart disease. Various hypotheses regarding the mechanism of reexpansion pulmonary edema include increased capillary permeability due to hypoxic injury, decreased surfactant production, altered pulmonary perfusion and mechanical stretching of membranes. This case suggests that forces leading to ipsilateral reexpansion pulmonary edema also affect the contralateral lung. 
4	Payment mechanism and patterns of use of medical services: the example of hypertension. This study explores the relationship between the use of medical services by hypertensive patients and mechanisms for payment within a single primary care practice. Three payment mechanisms were explored: public assistance, a capitated health maintenance organization (HMO), and fee-for-service. Patterns were examined across reimbursement type for the following variables: age, sex, visit reason, number of visits, medications, tests ordered, referrals made, and recommendations for follow-up visits. Illness severity was controlled in two ways: (1) by the study being focused on one diagnosis--mild to moderate hypertension, and (2) by concurrent chronic illnesses being enumerated and included in the analysis. Medical visits to the physician were examined over a 2-year period for 25 to 30 patients randomly sampled from each of the three payment mechanisms. Statistically significant differences were found for patient behaviors (total number of patient visits) and physician behaviors (number of medications and recommendations for revisits). The highest visit frequency was found for those on public assistance, followed closely by those covered by an HMO, and more distantly by those choosing fee-for-service. In a climate of cost consciousness, further study is needed to explore the impact of reimbursement mechanisms on the use of health care services. 
3	Effects of neuro-developmental treatment and orthoses on knee flexion during gait: a single-subject design. The interactive effects of neuro-developmental treatment and inhibitive ankle-height orthoses on gait were examined via a single-subject research design. Knee flexion during gait at initial contact, mid-stance, heel-off, and mid-swing were measured in a 2-year-old girl with diplegia by use of a goniometer and freeze-frame videography. During the treatment and treatment/orthoses phases, a decrease in excessive knee flexion was noted. Changes in trend over time were greater in the 3-week treatment phase than in the 3-week treatment/orthoses phase. Changes in level at the initiation of the treatment/orthoses phase were greater than in the treatment phase. The described neuro-developmental treatment activities were conducted correctly 92% of the time according to an independent observer. The interrater reliability of goniometric data measured by videography was .93 using intraclass correlation coefficients. The results of this study suggest that both methods of treatment can be used to decrease excessive knee flexion during gait in a child with diplegia. 
5	Indications and results of relaxing retinotomy. The authors report their results of a consecutive series of 40 eyes undergoing relaxing retinotomy during vitrectomy to achieve retinal reattachment for the following indications: proliferative vitreoretinopathy (PVR), 21 eyes (52%); trauma, 10 eyes (25%); diabetic retinopathy, 6 eyes (15%); and expulsive choroidal hemorrhage, 3 eyes (8%). Thirty eyes (75%) had undergone previous vitreoretinal procedures. Extended tamponade was achieved in all cases with either silicone oil (27 eyes, 68%) or long-acting gas (13 eyes, 32%). Retinotomy size ranged from 45 degrees to 360 degrees. Intraoperative retinal attachment was possible in all eyes with 33 (83%) achieving total or subtotal retinal attachment including the macula for 5 months or more. Twenty-seven eyes (68%) achieved 3/200 visual acuity or better and 10 (37%) achieved 20/400 or better. Thirteen eyes (32%) failed to achieve 3/200 visual acuity secondary to recurrent detachment (18%), corneal decompensation (8%), macular dysfunction (5%), and glaucoma (3%). 
5	Increased septic complications with three-drug sequential immunosuppression for cadaver renal transplants. In 152 renal transplant recipients, the results of immunosuppression with three-drug sequential (Minnesota antilymphocyte globulin, prednisone, azathioprine, and cyclosporine) immunosuppression (n = 107) were compared with those of a two-drug sequential protocol (Minnesota antilymphocyte globulin, prednisone, and cyclosporine) that excluded azathioprine (n = 45). The study groups were comparable by age, sex, etiology of renal failure, incidence of diabetes, and degree of HLA matching. Patient survival at 1 year was not significantly different in the two groups (two drug, 93% versus three drug, 86%; p = 0.19). One-year graft survival was superior in the two-drug group (two drug, 93% versus three drug, 75%; p = 0.02). Analysis of primary transplants only (n = 116) yielded the same results. During the first year, the serum creatinine level remained stable in both groups. As expected, the three-drug therapy group had significantly more bacterial and viral infections. For low-risk primary cadaveric renal transplants, two-drug sequential immunosuppression is superior. 
5	Effects of salt, race, and hypertension on reactivity to stressors. Blood pressure and heart rate reactivity to a psychological stressor and to a cold pressor test were examined in a group of 51 normotensive and 37 unmedicated hypertensive men. All were studied twice, once while the participants were maintained on a moderately high salt (200 meq sodium/day) diet and once while the participants were maintained on an extremely low salt (10 meq sodium/day) diet. Dietary salt had no effect on blood pressure or heart rate responses to the two stressors. The systolic and diastolic responses of the white participants to the psychological stressor were greater than those of the black participants (both p less than 0.05); however, there was no difference between blacks and whites in reactivity to the cold pressor challenge. As compared with the normotensive group, the hypertensive group reacted to the psychological stressor with increased responses in systolic blood pressure, diastolic blood pressure, and heart rate (all p less than 0.05). The hypertensive group also hyperresponded in terms of the systolic pressure response to the cold pressor task (p less than 0.05). Plasma norepinephrine and epinephrine responses were not significantly different across the two diets, races, or diagnoses. 
5	Percutaneous cholangioscopic or transpapillary insertion of self-expanding biliary metal stents. Fifty-two self-expanding metal stents were implanted in 39 patients with malignant (35 patients) or benign (4 patients) biliary stenoses. The stents were inserted and properly released by means of a 7 or 9 French gauge delivery catheter via the percutaneous (20 patients) or transpapillary (19 patients) route. In all cases the endoprostheses expanded to a diameter of 7 to 10 mm and achieved complete biliary tract drainage. Jaundice disappeared in 36 of the 39 patients. No early complication was observed. After a median follow-up of 121 days (range, 30 to 422 days), 19 of 36 patients are still alive and 17 died of non-procedure-related causes. Biliary re-obstruction occurred in five patients due to tumor overgrowth above or below the prosthesis (four patients) or bile encrustation (one patient). In patients with malignant stenoses, the probability of stent patency is 78% after 200 days. We conclude that large-bore metal stents are safe, effective, and provide better long-term patency than conventional endoprostheses. 
5	Incisional parapubic hernias. A parapubic hernia, distinct from other lower abdominal wall hernias, is identified as a particular type of incisional hernia. This hernia results from the disruption of the musculotendinous elements of the abdominal wall as they insert into the pubis. This disruption is brought about by either the destruction of these musculotendinous tissues at their lower end or the resection of portions of the pubic bone as is sometimes done in suprapubic radical prostatectomies for easier access to the prostate. Seven cases have been identified and reported. Men and women were seen to make up a clinical picture that is suggestive of the diagnosis, namely, multiple previous operations through the lower abdominal wall, procedures of a gynecologic or urologic nature, a herniation that mimics an incisional or inguinal hernia, and a defect that cannot possibly be corrected without the use of a prosthesis. When the diagnosis is accurately established, the polypropylene mesh is inserted in the preperitoneal space and anchored laterally to the ligaments of Cooper and in between to the arcuate pubic ligament and the periosteum of the posterior aspect of the pubis. Excellent results have been obtained, and the success must be ascribed to the recognition of the parapubic hernia as a distinct entity. 
1	Diagnostic imaging and surgical treatment of dumbbell tumors of the mediastinum. We describe the diagnostic procedures and surgical approaches employed in 5 patients with dumbbell tumors of the mediastinum. Magnetic resonance imaging accurately described the existence and longitudinal extension of the intraspinal component of the tumor and assisted in choosing the appropriate surgical approach. Both the intrathoracic and intraspinal components of the tumor were resected at one time by a thoracic and neurosurgical team. We employed the Grillo technique three times and a separate laminectomy and thoracotomy approach. Magnetic resonance imaging proved the most useful diagnostic technique for suspected dumbbell mediastinal tumors. In our experience, the extended thoracotomy proposed by Grillo and co-workers worked well for small tumors involving only one foramen in which the intraspinal extension was limited to 2 to 3 cm, and when no more than two laminectomies were required. On the other hand, thoracotomy and a longitudinal paravertebral incision are preferable for larger tumors (more than 4 cm) involving more than one foramen in which the intraspinal extension exceeds 2 to 3 cm, for tumors requiring multiple laminectomy, and when bony infiltration is present. 
5	Persistent segmental cutaneous anesthesia after a brown recluse spider bite. Patients with brown recluse spider bites commonly suffer from pain, muscular aching, and a variety of local dysesthesias during the acute and resolution phases of toxin-induced injury. This is our first well-documented observation of persistent cutaneous anesthesia caused by a spider bite. The anesthetic area conformed to the distribution of a specific nerve, the transverse cervical cutaneous nerve. The identification of the spider as a brown recluse and the location of the bite over the nerve's usual pathway strongly suggest that the venom was responsible for this complication. 
4	Vasculitis as a paraneoplastic syndrome. Report of 11 cases and review of the literature. In a study of 222 patients with vasculitis, we identified 11 who had an associated neoplasia. Seven had hematological neoplasia and 4 had solid malignant tumors. In 4 patients vasculitis gave the first evidence of the neoplasia or of its recurrence. Nine of our patients had cutaneous vasculitis. The other 2 had vasculitis involving the intestine and resulted in acute abdomens. These 2 patients needed prednisone treatment for the vasculitis. Neoplasia should be considered in patients with vasculitis without an apparent cause. 
1	Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guerin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value. 
4	Major clinical diagnoses found among patients with Raynaud phenomenon from the general population. This study of 62 individuals with Raynaud phenomenon (RP) drawn from the general population of South Carolina shows a profile of associated diseases that is different from the one reported from hospital based studies. We found that connective tissue diseases affect a much smaller fraction of patients with RP than previously reported. Compared to RP negative controls, our RP positive group was found to suffer more frequently from a variety of diseases, both RP related and not RP related. 
1	Pedunculated soft-tissue mass on the alveolar gingiva [clinical conference] A case of peripheral ameloblastoma, a rare intraoral neoplasm, has been presented. The lesion appears most commonly as a mass on the mandibular lingual gingiva of patients in their fifth and sixth decades of life. The peripheral ameloblastoma does not share the aggressive nature of the intraosseous variant. The lesion has been overtreated in the past and warrants only a local supraperiosteal excision. 
5	Stunned myocardium and myocardial collagen damage: differential effects of single and repeated occlusions. It has been suggested that collagen loss and damage is responsible for the dysfunction seen in stunned myocardium. To test this hypothesis we compared collagen in canine hearts stunned by repeated occlusion with collagen in hearts stunned by a single occlusion. Regional contractile function was equally depressed in both groups: segment shortening at 1 hour after reperfusion averaged 37% +/- 9% versus 32% +/- 9% of preocclusion values in repeated and single occlusion models, respectively. Midmyocardial collagen content was not different in either single occlusion (10.5% +/- 0.4%) or repeated occlusion models (9.5% +/- 0.7%) when compared with nonischemic hearts (8.5 +/- 0.8%). Collagen damage, which was revealed with polarized light microscopy, was seen in 5 of 6 dogs after repeated occlusion but was not apparent after a single occlusion. Thus although both models of stunned myocardium produce similar dysfunction, there was no apparent collagen loss. Furthermore, collagen damage was only seen after repeated occlusion. Therefore it appears unlikely that collagen damage is a primary mechanism of stunned myocardium. 
5	Mechanism of antitumor activity of tumor necrosis factor alpha with hyperthermia in a tumor necrosis factor alpha-resistant tumor. Cells from a radiation-induced fibrosarcoma (RIF-1) are exceedingly resistant to tumor necrosis factor alpha (TNF-alpha) in vitro. We tested whether the addition of mild hyperthermia (42.5 degrees C, 30 minutes) could enhance TNF-alpha activity against RIF-1 tumors growing in syngeneic hosts (C3H mice). TNF-alpha was administered intratumorally. Tumor cell killing essentially was not measurable following TNF-alpha, hyperthermia, or a combination of the two. Single-modality treatments also had no effect on tumor growth delay or on the x-ray dose (given 24 hours after the primary treatment) required to sterilize 50% of the tumors. The combination of TNF-alpha and hyperthermia, however, resulted in a marked increase in tumor doubling time and a highly significant reduction in the x-ray dose required to sterilize the tumors. Syngeneic lymph nodal lymphocytes and blood leukocytes did not appear to mediate the action of TNF-alpha on RIF-1 cells in vitro. Necrosis and hemorrhage were the most prominent histopathological alterations in the treated tumors. Electron microscopic studies 6 hours after therapy showed increased damage to capillary endothelial cells and accumulation of neutrophils in the capillaries of tumors treated with TNF-alpha with or without heat, suggesting that neutrophils may mediate the endothelial cell injury. These observations indicate a greater than additive tumoricidal effect of TNF-alpha with hyperthermia. Furthermore, they support the concept that the interaction between the two agents damages the vasculature, compromising the microcirculation and ultimately causing ischemic tumor necrosis. 
5	A prospective evaluation of the AO/ASIF universal femoral nail in the treatment of traumatic and reconstructive problems of the femur. Beginning in October 1986, we prospectively evaluated the AO/ASIF Universal Femoral Nail in the treatment of traumatic (89 nails) and reconstructive (11 nails) problems of the femur. For treatment of isolated femoral fractures, the mean time of patient positioning and nail insertion was 2.4 hours with a mean blood loss of 389 ml. Seventy-eight per cent of the patients were followed for a minimum of 12 months. There were no infections, one case of nail failure, two cases of screw fracture, and three nonunions. Sixteen nails have been uneventfully removed. The AO/ASIF femoral nail provides results comparable to other intramedullary interlocking devices. 
4	An unusual late complication following surgical repair of tetralogy of Fallot. A case is presented of extrusion of right ventricular outflow tract patch material through a mediastino-cutaneous fistula occurring five years after repair of tetralogy of Fallot. The focus of the mediastinal infection was an infected epicardial pacemaker electrode placed at the time of initial surgery. Subsequent echocardiographic studies showed minimal right ventricular outflow tract or pulmonary arterial dilatation, and, with no further surgery, the child is well after two and a half years follow-up. 
4	Sympathetic drive and vascular damage in hypertension and atherosclerosis. Current knowledge of the links between the sympathetic nervous system and vascular damage in hypertension and atherosclerosis is summarized. The main mechanisms leading to the structural changes of the arterial wall as a consequence of enhanced adrenergic drive are reported. Hemodynamic mechanisms, including increase in pressure leading to changes in the arterioles and alteration of flow pattern with impact mainly in the large arteries, respectively, account for the typical target organ damage observed in hypertension and is involved in the development of atherosclerotic lesions. Regarding the direct effect of catecholamines, the atherogenic effects of epinephrine and norepinephrine in the absence of changes in blood pressure and cholesterol levels have been demonstrated in vivo in monkeys and rabbits. In rats, catecholamine administration induces polyploidization of aortic smooth muscle cells in vivo and in vitro. Regarding the effects of lipid metabolism, adrenergic stimulation may induce free fatty acid transformation into triglycerides with secondary increase in very low density lipoprotein plasma levels and decrease of very low density lipoprotein transformation into high density lipoprotein through circulating lipoprotein lipase inhibition. Catecholamines may also increase cholesterol levels of the arterial wall, probably by triggering the acyl-cholesterol-acyl-transferase activity. Finally, indirect evidence of the pathogenetic role played by the sympathetic system in the development of vascular disease derives from the results of experiments showing that sympatholytic agents are capable of reducing both medial hypertrophy and atherogenesis. beta-Blockers, alpha- and beta-blockers, and centrally acting sympatholytic agents not only ameliorate hemodynamics but also appear to inhibit the direct effects of catecholamines on the arterial wall. 
3	Anton's syndrome in a patient with posttraumatic optic neuropathy and bifrontal contusions. We describe a patient who manifested Anton's syndrome after sustaining head trauma that resulted in optic nerve damage and bifrontal contusions. Denial of monocular blindness, generalized anosognosia, and confabulation were prominent neurobehavioral features. Anton's syndrome is most commonly encountered in patients with bilateral occipital cortex lesions. Patients previously described who demonstrated Anton's syndrome secondary to a peripheral lesion have had an associated delirium or profound dementia. Our case demonstrates that Anton's syndrome may occur in association with blindness from a peripheral lesion, even in the absence of a delirium or significant dementia. We suggest that the bifrontal dysfunction may have been a critical factor in the production of Anton's syndrome. Implications for the role of frontal lobe dysfunction in the genesis of anosognosia and confabulation are discussed. 
4	Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement. A prospective, randomized study of compression alone, compression and aspirin, and compression and low-dose warfarin. A prospective, randomized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression, alone or in combination with oral administration of either aspirin or low-dose warfarin, was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old. All patients began walking by the third postoperative day. One hundred and ninety-six patients who had 217 total hip arthroplasties were included. Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis, and the remainder were primary arthroplasties. Patients were randomized as to the type of prophylaxis that they received: intermittent pneumatic compression alone, seventy-six hips; intermittent pneumatic compression and aspirin, seventy-two hips; or intermittent pneumatic compression and low-dose warfarin, sixty-nine hips. Before discharge from the hospital, and at an average of seven days after the operation, all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography. The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups; the over-all relative frequency was 10 per cent. Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement. With the number of patients in our study, the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin. 
5	Endoscopic retrograde cholangiopancreatography in infantile cholestasis. The difficulty of distinguishing surgically correctable causes of conjugated hyperbilirubinaemia in infants from other causes means that some infants may undergo laparotomy and intraoperative cholangiography unnecessarily, and others may be referred for surgery too late. In an attempt to improve the diagnostic accuracy in infants with conjugated hyperbilirubinaemia when standard methods produced equivocal results, we have been using prototype paediatric duodenoscopes (PJF 7.5 and XPJF 8.0; Olympus) to perform endoscopic retrograde cholangiopancreatography (ERCP). From 159 infants with conjugated hyperbilirubinaemia, 11 were referred for ERCP, which was performed in nine. In four in whom bile ducts were definitely visualised laparotomy was avoided. Operative cholangiography confirmed patent bile ducts in one in whom visualisation had been uncertain. Three of four in whom bile ducts were not seen had extrahepatic biliary atresia. Visible bile drainage in the fourth excluded atresia. No major complications ensued but there was radiological evidence of gall bladder perforation in one (common hepatic duct block) and overinflation with air was a problem until finer cannulae (Wilson-Cook) were introduced. In appropriately selected patients with conjugated hyperbilirubinaemia, ERCP with paediatric duodenoscopes in experienced hands may provide useful diagnostic information. 
5	Physical examination and echo Doppler study in the assessment of femoral arterial complications following cardiac catheterization. Femoral arterial complications following cardiac catheterization have been well recognized. The development of an inguinal mass in these patients can represent a simple hematoma, a pseudoaneurysm, or an arteriovenous fistula. The utility of the physical examination in diagnosing these complications was assessed by using the echo Doppler study for comparison. This study shows that any single clinical sign should not be used in isolation, but a constellation of physical findings can suggest the correct diagnosis. 
3	Immunoassay of P2 protein in cerebrospinal fluid in neurological disorders. Cerebrospinal fluid samples were obtained at lumbar puncture from 53 patients with a wide variety of neurological disorders. Cerebrospinal fluid samples were tested for the presence of P2 protein, a constituent of myelin, with an enzyme linked immunosorbent assay technique using a specific polyclonal antibody. High concentrations of P2 in the cerebrospinal fluid paralleled a raised IgG index (clearance ratio), the presence of oligoclonal bands, as well as raised white cell counts or depressed albumin:IgG ratios. Twenty one patients had been diagnosed as having definite or probable multiple sclerosis and the remaining 32 had other conditions. Of the 13 patients with high positive P2, 12 (92%) were in the multiple sclerosis category; of the 40 patients with low (12) or undetectable (28) P2 concentrations, only nine (23%) were diagnosed as having multiple sclerosis. In this patient population the presence of high immunoreactive P2 concentrations in cerebrospinal fluid was closely associated with evidence of intrathecal immunoglobulin synthesis and with the clinical diagnosis of multiple sclerosis. On this basis it is suggested that immunoassay of P2 concentration in the cerebrospinal fluid may be of potential value in the investigation of patients with demyelinating disorders. 
5	Pulmonary malakoplakia in a patient with the acquired immunodeficiency syndrome. Differential diagnostic considerations. Malakoplakia is an unusual inflammatory condition characterized histopathologically by accumulations of benign macrophages, or von Hansemann's cells, that are associated with diagnostic intracellular and extracellular calcospherites, termed Michaelis-Gutmann bodies. Currently believed to represent an acquired defect of macrophage digestion, malakoplakia most commonly occurs in the urinary tract and is associated with a variety of infectious agents, notably gram-negative bacilli. We describe a patient with the acquired immunodeficiency syndrome who presented with a cavitating lingular mass. A transbronchial biopsy specimen revealed pulmonary malakoplakia, the seventh reported case of this condition and the second reported occurrence of pulmonary malakoplakia in a patient with acquired immunodeficiency syndrome. Microbiological cultures were positive for Rhodococcus equi. The significance of this finding, and the differential diagnosis of intra-alveolar histiocytic proliferations in patients with acquired immunodeficiency syndrome, is discussed. 
1	A clinical pilot study combining surgery with intraoperative pelvic hyperthermochemotherapy to prevent the local recurrence of rectal cancer. Intraoperative pelvic hyperthermochemotherapy (IOPHC) with mitomycin C (MMC) was prescribed for 14 patients with resectable advanced rectal cancer in an attempt to prevent a postoperative local recurrence. Immediately after rectal amputation and extended lymphadenectomy, IOPHC was performed using physiologic saline containing 40 micrograms/mL of MMC at 45.5 +/- 0.6 C for 90 minutes, with an apparatus devised for IOPHC. At the end of IOPHC, the esophageal temperature was 37.2 +/- 0.8 C and cooling was not required. Antitumor efficacy and complications in the IOPHC group were compared with findings in 12 rectal cancer patients who underwent surgery only within the same period of time. Operation time was not prolonged with IOPHC treatment. In cytologic examinations of the pelvic lavage just before IOPHC treatment, viable cancer cells were detected in 6 of the 14 patients but were never detected in the postoperative exudate drained from the pelvic cavity. Of the 12 patients in the control group, 2 had a local recurrence, while in the IOPHC group there was no local recurrence for 16.9 +/- 9.7 months at this writing. Postoperative complications did not differ between the groups. This IOPHC treatment is a favorable method in eradicating cancer cells for postoperative local recurrence of rectal cancer. 
5	Expressional potency of mRNAs encoding receptors and voltage-activated channels in the postmortem rat brain. The stability and integrity of mRNAs encoding neurotransmitter receptors and voltage-activated channels in the postmortem rat brain was investigated by isolating poly(A)+ mRNA, injecting it into Xenopus oocytes, and then examining the expression of functional neurotransmitter receptors and voltage-activated channels in the oocyte membrane by electrophysiological recording. This approach was also used to assess the stability of mRNAs in brains that were incubated in oxygenated mammalian Ringer's solution for various lengths of time and from brains that were freshly frozen and then thawed at room temperature. Oocytes injected with mRNA from up to 21-hr postmortem brains gave large agonist- and voltage-activated responses, indicating that mRNAs encoding neurotransmitter receptors and voltage-activated channels are relatively stable in postmortem brain tissue. In contrast, oocytes injected with mRNA from brains incubated in Ringer's solution exhibited smaller responses, and oocytes injected with mRNA from tissue that was frozen and then thawed displayed very small or undetectable responses. Northern blot analysis using a nucleic acid probe for rat brain Na(+)-channel mRNA indicated that the size of the Na+ currents in injected oocytes reflected the levels of mRNA for Na+ channels in the different mRNA preparations. Thus, the expressional potency of mRNAs encoding neurotransmitter receptors and voltage-activated channels is quite stable in postmortem brains in situ, but it is reduced if the brains are kept in oxygenated saline, and freezing and thawing of tissue results in rapid degeneration of mRNA. 
1	Cell cycling in bladder carcinoma determined by monoclonal antibody Ki67. Current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour. The monoclonal antibody Ki67 recognises an antigen present in actively dividing cells and Ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours. In this study, Ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder. The proportion of cells stained in muscle invasive tumours (12.3 +/- 5.4%) was significantly greater than in superficial tumours (4.3 +/- 1.9%) and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours. These results show that Ki67 reactivity correlates with high tumour stage and poor differentiation. Ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information. 
1	Expression of aminopeptidase N (CD13) in mesenchymal tumors. For a long time, CD13 molecules have been considered to be restricted to myeloid cells and related neoplasms. Meanwhile, however, expression of CD13 has also been detected in some hepatocellular, gallbladder, renal, and lung carcinomas, and even in some fibrosarcomas and malignant melanomas. In this study, expression of CD13 antigen was immunohistochemically examined in non-neoplastic mesenchymal cells, along with 33 benign and 83 malignant mesenchymal tumors (MET) using CD13 monoclonal antibodies (MAb) My7, U71, WM-15, and MoU48. In non-neoplastic mesenchymal cells, expression of CD13 was restricted to perivascular fibrocytes/blasts, tissue histiocytes, osteoclasts, and to the perineurium of peripheral nerve trunks. Under neoplastic conditions, CD13 was detectable in some tumors of smooth muscle, fibrous, fibrohistiocytic, synovial, osteogenic, and peripheral nerve sheath origin, and even in some tumors of adipose tissue. Tumors of striated muscle origin, of autonomic ganglia, and of cartilage-forming tissues were CD13-negative throughout. Thus in most but not all tumors studied the pattern of expression of CD13 mirrors the situation found in their cells of origin. These findings enrich the data on expression of leukocyte differentiation antigens in extra-hematopoietic tissues. Expression of CD13, which meanwhile is known to be identical to aminopeptidase N, an important peptide-cleaving enzyme, in only some MET might reflect a special functional state of these neoplasms. 
1	Role of systemic therapy in advanced non-small-cell lung cancer. Increasing evidence supports the investigation of chemotherapy in patients with non-small-cell lung cancer (NSCLC). Randomized studies in patients with stage IV disease have shown increased survival in chemotherapy-treated patients compared to best supportive care and indicate the ability of chemotherapy to alter the natural history of this disease. Randomized studies involving adjuvant and neoadjuvant chemotherapy have also shown encouraging results. These studies and results of recent pilot studies utilizing neoadjuvant chemotherapy and concomitant chemoradiotherapy indicate a potential benefit from the use of chemotherapy in patients with NSCLC and call for its continued intensive investigation in clinical trials. 
4	Captopril-stimulated renal vein renin in hypertensive patients with or without renal artery stenosis. To examine the efficacy and usefulness of captopril-enhanced renal vein renin (RVR) measurements in detecting the functional significance of renal artery stenosis found in hypertensives, we compared these values in 22 patients with arteriographically documented renovascular hypertension due to unilateral (URVH: 14 patients) or bilateral renal artery stenosis (BRVH: 8 patients) and 12 patients with high renin essential hypertension (EHT). Before captopril administration, RVR ratio was less than 1.5 in 8 patients (36.4%) with renovascular hypertension and all patients (100%) with EHT. Captopril enhanced the lateralization of renal vein renin in renovascular hypertension; the postcaptopril RVR ratio was greater than 2.0 in 18 patients (81.8%) and greater than 1.5 in all the patients (100%). On the other hand, RVR ratio remained unchanged in most patients with EHT. There was no significant difference in the postcaptopril RVR ratios between URVH and BRVH. However, the postcaptopril RVR ratio was higher in atherosclerosis (10 patients) than in fibromuscular dysplasia (11 patients) (P less than .05). Captopril also elucidated contralateral renin suppression as expressed by a contralateral/peripheral renin ratio of less than 1.0, which was associated with a favorable outcome of unilateral surgical intervention. Captopril-stimulated RVR indices were valuable in detecting the functionally significant renal artery stenosis and predicting surgical curability in renovascular hypertension. 
4	Effects of anxiety on family members of patients with cardiac disease learning cardiopulmonary resuscitation. The effects of anxiety on learning cardiopulmonary resuscitation (CPR) by family members of patients with cardiac disease was examined. Family members of hospitalized patients (n = 17), family members of nonhospitalized patients (n = 12), and a control group (n = 21) all took one of nine Heart Saver programs in which CPR was taught and performance evaluated. Subjects took the State Anxiety Inventory three times: immediately before the program, immediately after the performance test, and 2 months after completion of the program. Family members of hospitalized patients had significantly higher before-program anxiety scores than the other groups. This difference was not present immediately after the program or 2 months later. Family members of hospitalized patients showed a significant decline in anxiety over the three testing times. These outcomes support the benefit of teaching CPR to this group. 
3	Risks factors for cerebral infarction in good-grade patients after aneurysmal subarachnoid hemorrhage and surgery: a prospective study. A prospective series of 265 patients with aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) upon admission were evaluated as to neurological outcome and computerized tomography (CT) findings 1 to 3 years (mean 1.4 years) after the SAH and surgery. A total of 73 patients underwent acute surgery (within 72 hours after the bleed: Days 0 to 3), 86 were operated on subacutely (between Days 4 and 7), and 91 had late surgery (on Day 8 or later). Fifteen patients died before surgery was undertaken and another 20 patients died during the follow-up period. A total of 104 patients received nimodipine and the rest of the patients received either placebo (109 patients) or no medication (52 patients). A logistical regression analysis revealed the following prognostic factors for cerebral infarction, in order of importance: the amount of blood on the primary CT scan; postoperative angiographic vasospasm; the timing of the operation; and a history of hypertension. The use of nimodipine was associated with a significant reduction of cerebral infarcts visualized by CT scanning in patients who received intermediate or late surgery. In patients who underwent acute surgery no significant difference between the incidence of cerebral infarcts was observed. 
3	Experience with surgical treatment of Takayasu's disease. We reviewed 28 patients with Takayasu's disease to determine the incidence of stroke and its relationship to the involvement of the thoracic aortic arch and its branches. We describe surgical experiences with 10 of the 28 patients who required 21 vascular surgical procedures for critical thoracic aortic arch arterial stenoses, upper and lower extremity ischemia, and renal artery stenoses. Four of the 28 patients initially had a stroke caused by occlusion of one or more thoracic aortic arch arteries. Six of the 10 patients underwent 7 bypass procedures for critical thoracic arch stenoses. All have remained free of stroke for 5 or more years. Four patients had five anastomotic stenoses or graft occlusions in late follow-up; the development of these stenoses did not relate to disease activity at the time of the operative procedure. All bypass grafts originating from the subclavian axillary artery developed anastomotic stenoses; no anastomotic stenoses occurred in bypass grafts originating from the ascending aorta. In contrast to other reports, no anastomotic false aneurysms occurred. Occlusions of major aortic arch arteries in Takayasu's disease cause stroke. Bypass of critically stenoses aortic arch arteries protects against stroke and is best performed with grafts originating from the ascending aorta. Anastomotic stenoses but not anastomotic aneurysms are common. This study suggests that aggressive surgical treatment can be performed with good results. 
2	Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism. Our aim was to define mechanisms whereby conjugated estrogens (Premarin, exogenous estrogen; Ayerst Laboratories, New York) increase the risk of developing cholesterol gallstones and to determine the role, if any, of dietary cholesterol. We studied gallbladder motor function, biliary lipid composition and secretion, cholesterol absorption, cholesterol synthesis and esterification by peripheral blood mononuclear cells, the clearance of chylomicron remnants, and bile acid kinetics in 29 anovulatory women. 13 were studied on both a low (443 +/- 119 mumol/d) and high (2,021 +/- 262 mumol/d) cholesterol diet. Premarin increased the lithogenic index of bile (P less than 0.05), increased biliary cholesterol secretion (P less than 0.005), lowered chenodeoxycholate (CDCA) pool (P less than 0.001) and synthesis (P less than 0.05), altered biliary bile acid composition [( CA + DCA]/CDCA increases, P less than 0.005), stimulated cholesterol esterification (P less than 0.03), and enhanced the clearance of chylomicron remnants (P = 0.07). Increases in dietary cholesterol stimulated the biliary secretion of cholesterol (P = 0.07), bile acid (P less than 0.05), phospholipid (P = 0.07), and as a result, did not alter lithogenic index. The reduction in CDCA pool and synthesis by Premarin was reversed by increasing dietary cholesterol. Off Premarin, only 24% of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid. On Premarin, 68% of this increase in cholesterol was recovered as these biliary lipids. We conclude that Premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis. These actions of Premarin divert dietary cholesterol into bile. 
5	Anaplastic carcinoma presenting with cervical lymphadenopathy. We describe 50 patients with anaplastic carcinoma presenting with a mass in the neck. The diagnosis of anaplastic carcinoma was confirmed by immunocytochemistry to exclude very poorly differentiated squamous carcinomas, amelanotic melanoma, and non-Hodgkin's lymphoma. The primary site was established immediately in 26 patients (25 in the head and neck; 1 in the lung); a further 4 had radiological evidence of a primary tumour in the lung. The primary site was established later in 1 patient, in the ethmoid sinuses. In 20 patients the primary site was never established. The commonest primary site was the nasopharynx. The basic treatment policy was radiotherapy, although 20% of patients with a known primary tumour, and 50% of those without, were untreated. The 2-year survival was about 30% in both groups, and did not differ significantly. Prognostic factors for survival were age, performance status, and T status of the primary tumour. Sex, node status, node level, and laterality of nodes, were not. 
3	The South Karelia Air Pollution Study. The effects of malodorous sulfur compounds from pulp mills on respiratory and other symptoms. The paper mills in South Karelia, the southeast part of Finland, are responsible for releasing a substantial amount of malodorous sulfur compounds such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and methyl sulfides [(CH3)2S and (CH3)2S2], into ambient air. In the most polluted residential area the annual mean concentrations of hydrogen sulfide and methyl mercaptan are estimated to be 8 and 2 to 5 micrograms/m3 and the highest daily average concentration 100 and 50 micrograms/m3. The annual mean and highest daily concentrations of sulfur dioxide (SO2) are very low. We studied the effects of malodorous sulfur compounds on eye, nasal and respiratory symptoms, and headache in adults. A cross-sectional self-administered questionnaire was distributed in February 1987 and responded to by 488 adults living in a severely (n = 198), a moderately (n = 204), and a nonpolluted community (n = 86). This included questions about occurrence of the symptoms of interest during the previous 4 wk and 12 months and individual, behavioral, and other environmental determinants of the symptoms. The response rate was 83%. The odds ratios (OR) for symptoms experienced often or constantly in severely versus nonpolluted and moderately versus nonpolluted communities were estimated in logistic regression analysis controlling potential confounders. The odds ratios for eye (moderate exposure OR 11.70, Cl95% 2.33 to 58.65; severe exposure OR 11.78, Cl95% 2.35 to 59.09) and nasal symptoms (OR 2.01, Cl95% 0.97 to 4.15; OR 2.19, Cl95% 1.06 to 4.55) and cough (OR 1.89, Cl95% 0.61 to 5.86; OR 3.06, Cl95% 1.02 to 9.29) during the previous 12 months were increased, with a dose-response pattern. 
1	Systems used to study the nature of the leukemic cell and predict treatment outcome in patients with myeloproliferative disorders. Cell culture techniques have been used to study normal and leukemic hematopoiesis. Investigations provided data on the nature of the clonogenic leukemic cell, its patterns of in vitro growth, role of stimulating factors, and effects of chemotherapeutic agents. Assay systems developed to study leukemic progenitor cells or self-renewal capacity have been useful clinically as predictive indicators of success of remission-induction therapy and have allowed testing of drug sensitivity in vitro. Alternative approaches using short- and long-term suspension cultures have provided systems to evaluate leukemic cells, including nonclonogenic, biochemical, and kinetic events. In vitro systems have been introduced to measure cell cycle events accurately and to identify metabolic mechanisms of drug resistance. The information provided by all of these systems has allowed a more comprehensive and multifocal characterization of the nature of the leukemic process and has better directed our approach to treatment. 
1	Complications of stapled anastomoses in anterior resection for rectal carcinoma: colorectal anastomosis versus coloanal anastomosis. Postoperative results of 48 patients who underwent anterior resection using the EEA-stapler were evaluated. In all but 2 cases the indication for surgery was colorectal carcinoma. In 24 patients an anastomosis was created above the 5 cm level (above the anal verge: colorectal anastomosis) and in 24 at the 0-5 cm level (coloanal anastomosis). There was no perioperative mortality. The only complication observed in the colorectal anastomosis group was one case of late anastomotic stenosis. In the coloanal anastomosis group there were 4 cases with early anastomosis leaks, 3 cases with late stenosis and 5 cases with various degrees of late fecal incontinence, ultimately resulting in a permanent diverting stoma in 5 (10.4%) patients. We conclude that for rectal tumors the EEA-stapled anterior resection provides excellent functional results in most cases. Stapled coloanal anastomoses more often demonstrate various (early and late) complications. Nevertheless in spite of chronic discomfort, many patients still prefer their complaints to a permanent stoma. 
4	The Greenfield filter as the primary means of therapy in venous thromboembolic disease. During a five year period at Akron City Hospital, 165 Greenfield filters were placed in 165 patients. Of this group, 78 patients were available for long term analysis, and of these, 42 did not receive anticoagulation treatment for venous thromboembolic diseases, either acutely or on an outpatient basis. An analysis of the outcome for these 42 patients who had the Greenfield filter only as the primary mode of therapy for the disease included chart review and asking each person a standard set of questions. Leg swelling was the most common complaint, occurring in 33 per cent of patients. Venous stasis ulceration occurred in two patients and recurrent deep venous thrombosis occurred in one patient. When compared with a historical control group with venous thromboembolic disease that was treated with anticoagulation alone, the incidence of these sequelae in Greenfield-treated patients was not significantly different. Finally, in this review, the Greenfield filter is better than 95 per cent effective in the prevention of pulmonary embolism. This is no less effective than anticoagulation alone, the efficacy of which is 95 to 98 per cent. The placement of a Greenfield filter is a safe procedure that can usually be done after a local anesthetic was administered to the patient with a complication rate of less than 10 per cent. Unfortunately, major complications of anticoagulation (usually hemorrhage) are relatively common at a rate of 2 to 15 per cent, and occur more frequently in the older population. It is for reasons of safety of therapy and of an equal or better efficacy that the Greenfield filter is recommended in a broader range of clinical circumstances. In particular, it is concluded that the Greenfield filter should be used as a primary means of therapy in venous thromboembolic disease, particularly in those patients who are more than 65 years of age, when the risks of anticoagulation are most threatening. 
5	Intralaryngotracheal thyroid. A case of intralaryngotracheal thyroid in a 57-year-old man is presented. The treatment modalities are considered and the previous literature is reviewed. 
2	Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa. Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications. 
5	Elective diagnostic laparoscopy. Laparoscopy developed as a science at the turn of the century, and many scientists assisted in the evolution of this technique. However, it was many years before the multiple trocar system was developed that allowed internal organs to be moved and biopsies to be obtained. This has led to the development of numerous indications for elective diagnostic laparoscopy. Adequate preparation and attention to instrumentation ensure the safety of this operation. Elective diagnostic laparoscopy is a useful adjunct to many other diagnostic modalities such as, for instance, the assessment of abdominal pain, abdominal masses, fever of unknown origin, and gastrointestinal bleeding. In many other circumstances, such as the assessment of oncology cases, this modality is superior to conventional radiology because biopsy specimens may be obtained. If the procedure is correctly performed, the diagnostic yield is extremely high and the morbidity and mortality are low. The role of this important technique should not be underestimated by today's practicing surgeon. 
5	Long-term outcome following anterior cerebral artery ligation for ruptured anterior communicating artery aneurysms. The long-term prognosis (15 years) was determined for 17 patients who had undergone anterior cerebral artery (ACA) ligation as the sole treatment for an anterior communicating artery aneurysm. The number of early and late rebleeds was lower than expected from previously ruptured aneurysms. Late ischemia was not a major complication while late postoperative epilepsy occurred in 19% of survivors. In a review of previously published series, ACA ligation appears to have significantly reduced the rates of both early and late rebleeding. This study helps to define the late results of "conservative" operations for ruptured aneurysms. 
4	Prolongation of ventricular refractoriness by class Ia antiarrhythmic drugs in the prevention of ventricular tachycardia induction. The effects of class la antiarrhythmic drugs (procainamide, quinidine) on the right ventricular effective refractory period (VERP) and intraventricular conduction time were assessed during serial invasive electrophysiologic studies for sustained monomorphic ventricular tachycardia (VT). In 47 patients with remote myocardial infarction, sustained VT was inducible by up to two extrastimuli after the basic drive at one of two basic cycle lengths at the right ventricular apex. With oral drug administration, sustained VT was no longer inducible (group I) in 27 patients but remained inducible (group II) in 20 with the same protocol. Class la drugs prolonged the VERP in both groups, but there was greater lengthening when drugs were effective (e.g., +32 +/- 14 msec in group I vs +12 +/- 19 msec in group II; p less than 0.005, basic cycle length 600 to 700 msec). Prolongation of the VERP by greater than 30 msec had an 88% positive predictive value for prevention of sustained VT induction. In all except one patient in group I, drugs prolonged the VERP such that the coupling intervals that had resulted in sustained VT induction under control conditions were no longer attainable. In contrast, conduction time through the ventricle (surface QRS duration) in sinus rhythm and during right ventricular pacing was prolonged similarly regardless of efficacy (e.g., +33 +/- 21 msec vs +27 +/- 27 msec at a cycle length of 400 msec). The presence of similar plasma levels of drug did not imply equivalent prolongation of the VERP in the two groups. These results suggest that greater prolongation of the VERP by oral procainamide or quinidine correlates with drug efficacy against VT induction and is a better predictor of drug effect than achievement of a "therapeutic plasma level.". 
3	Ganglioglioma: a clinical study with long-term follow-up. Gangliogliomas are uncommon tumors of mixed neoplastic glial and neuronal elements. Because of their low incidence, few large series exist that fully describe the clinical characteristics of patients afflicted with this tumor. We have reviewed the medical records of 20 patients at Duke University Medical Center with histologically proven gangliogliomas. These patients typically presented within the first three decades of life and their most common presenting symptom was seizures. Therapies included surgical resection, either partial or total, radiation therapy, and/or chemotherapy. Long-term follow-up was achieved by chart review and by telephone interview. Patients who underwent gross total resection alone seemed to fare the best when comparing all treatment groups, and we therefore recommend this as the main form of treatment. 
4	Familial paroxysmal kinesigenic ataxia and continuous myokymia. A large family with paroxysmal ataxia and continuous myokymic discharges is described. The disorder is of autosomal dominant inheritance. During attacks coordination of movements and balance are disturbed; often a postural tremor of the head and the hands and fine twitching in some of the facial and hand muscles are present. The attacks usually last a few minutes and may occur several times per day. They first appear in childhood and tend to abate after early adulthood. The attacks are frequently precipitated by kinesigenic stimuli similar to those in paroxysmal kinesigenic choreoathetosis. Their occurrence can be reduced or prevented by carbonic anhydrase inhibitors. Between attacks a slight postural tremor and ataxia was found in a few of the elderly affected members. Fine rippling myokymia was obvious in a few and could be detected on close inspection in about half of the adults. Electromyography (EMG) showed myokymic discharges in all affected members. The characteristics and reactivity of this myokymic activity suggest multiple impulse generation in the peripheral nerves. 
3	Sensations during chest tube removal. Nurses prepare patients for chest tube removal, yet little has been written to indicate the sensations to be expected during this routine procedure. The sensations reported by patients and factors that could influence those sensations were examined in this study. The sample consisted of 36 patients after thoracic surgery (24 men and 12 women), all of whom were scheduled to have either a mediastinal or a pleural tube removed. They reported their sensations and the intensity of those sensations (using a 100 mm visual analog scale) within 15 minutes after tube removal. The most frequently reported sensation during chest tube removal was burning, followed by pain and pulling with mean intensities of 64, 62, and 45, respectively. Subjects reported having few sensations after the tube was removed with only five reporting soreness in the chest. The sensations and intensities did not differ for those who did and did not receive analgesia or for those having a pleural tube versus a mediastinal tube removed. The sensations were similar for the old and young subjects with younger subjects reporting higher intensities. Women reported pain more frequently than men, but the intensities of the sensations reported by men and women were not significantly different. The sensations reported during chest tube removal differ from those described in the literature and can be used to prepare patients more appropriately for chest tube removal. 
4	Placebo controlled trial of xamoterol versus digoxin in chronic atrial fibrillation. Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were randomised to treatment periods of two weeks on xamoterol (200 mg twice daily), low dose digoxin, or placebo, in a blind crossover study. The results (mean SEM) of symptom scores, a treadmill exercise test, and 24 hour ambulatory electrocardiographic monitoring were obtained. Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin. Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration. Xamoterol, by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate, significantly reduced the difference between the two compared with placebo. In contrast, digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night. Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin. Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity. These changes were translated into symptomatic benefit for the patients studied. 
4	Embolism during caesarean section. We investigated the occurrence of gas embolism during Caesarean section using a Doppler ultrasound probe and found that it occurs between uterine incision and delivery. Embolism is less common during general anaesthesia than has been reported during regional anaesthesia. Both ruptured membranes and a protracted uterine incision to delivery interval predispose to embolism. 
4	Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats. Smoking exacerbates the increase in arterial pressure in hypertension. The effect of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA]) after bolus injections of phenylephrine was compared in deoxycorticosterone acetate (DOCA)-salt sensitive and normotensive rats. Osmotic minipumps that dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and normotensive rats for 18 days. Anesthetized DOCA-nicotine, DOCA-saline, control-nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3, 110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively. Nicotine decreased the sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA-saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (-1.45 +/- 0.21) rats. The reflex decrease in respiratory activity (% delta MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (-24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats. The reflex decrease in heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17) and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14). 
2	Persistent rectal ulcer associated with human papillomavirus type 33 in a patient with AIDS: successful treatment with isotretinoin. Rectal dysplasia and carcinoma associated with human papillomavirus infection are increasing in prevalence among homosexual men, particularly those infected with the human immunodeficiency virus. We report a case involving a 39-year-old homosexual man with AIDS who developed a persistent rectal ulcer. A biopsy of the ulcer revealed severe squamous dysplasia, and human papillomavirus type 33 was detected in rectal tissue with use of in situ DNA hybridization. This genotype of virus has not been previously associated with anal or rectal dysplasia in homosexual men, including those infected with the human immunodeficiency virus. The rectal ulcer resolved after 2 months of oral therapy with 60 mg/d of isotretinoin, a retinoid. 
5	The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Retinoic acid is a vitamin A derivative with striking effects on development and cell differentiation. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized and indirect evidence suggests that they have distinct roles. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions. Because the RAR alpha gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21-q11-22) translocation specifically associated with APL, we analysed RAR alpha gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RAR alpha gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RAR alpha fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RAR alpha and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor alpha in leukaemogenesis. 
5	Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion. Massive transfusion may cause abnormalities of electrolytes, clotting factors, pH, and temperature and may occur in a scenario of refractory coagulopathy and irreversible shock. Identification of correctable variables to improve survival is complicated by the interplay of this pathophysiology. Temperature may be an under-appreciated problem in the genesis of coagulopathy. In vitro studies have demonstrated that platelet function and vascular response are critically temperature-dependent. We reviewed the records of 45 trauma patients without head injury or co-morbid medical illness who required massive transfusions. The mean Injury Severity Score was 55 +/- 6, a mean of 22.5 +/- 5 units of blood was transfused, and mortality was 33%. Nonsurvivors were more likely to have had penetrating injury (88% versus 55%), received more transfusions (26.5 +/- 9 versus 18.6 +/- 1, p less than 0.05), had lower pH (pH 7.04 +/- 0.06 versus 7.18 +/- 0.02, p less than 0.05), had lower core temperature (31 +/- 1 degree C versus 34 +/- 1 degree C, p less than 0.01), and had a higher incidence of clinical coagulopathy (73% versus 23%). Severe hypothermia (temperature less than 34 degrees C) occurred in 80% of the nonsurvivors and in 36% of survivors. Patients who were hypothermic and acidotic developed clinically significant bleeding despite adequate blood, plasma, and platelet replacement. Avoidance or correction of hypothermia may be critical in preventing or correcting coagulopathy in the patient receiving massive transfusion. 
1	The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. With the euglycemic clamp technique, we evaluated the effects of graded doses of insulin on glucose turnover rates and forearm lactate balance in five weight-losing patients with cancer before surgery and five age- and weight-matched healthy volunteers (control subjects). Insulin was infused sequentially at increasing rates of 0.5 (low physiologic), 1.0 (high physiologic), and 4.0 (supraphysiologic) mU/kg.min for 120 minutes each. Concurrently, rates of glucose appearance and disappearance were derived from [3-3H] glucose infusion. The mean postabsorptive rate of glucose appearance in patients (2.9 +/- 0.1 mg/kg.min) was significantly higher (p less than 0.02) than that of control subjects (1.98 +/- 0.16 mg/kg.min). Complete suppression of endogenous glucose production occurred at high physiologic insulin concentrations. With progressive insulin infusion, the rate of glucose disappearance increased to 3.6 +/- 1.2, 8.7 +/- 0.8, and 13.7 +/- 1.1 mg/kg/min in control subjects and 2.9 +/- 0.4, 5.3 +/- 0.3, and 10.9 +/- 0.9 mg/kg.min in patients, significantly different from that of control subjects (p less than 0.05) during the intermediate (high physiologic) insulin infusion. A comparable slight increase in arterial plasma lactate concentration was observed in both groups with progressive hyperinsulinemia. Baseline peripheral lactate flux was identical in patients (-272 +/- 56 nmol/100 gm.min) and in controls (-271 +/- 57 nmol/100 gm.min). Progressive physiologic hyperinsulinemia resulted in significantly (p less than 0.05) augmented peripheral lactate efflux in patients (-824 +/- 181 nmol/100 gm.min) compared with control subjects (-287 +/- 64 nmol/100 gm.min). Supraphysiologic insulin abolished this increased lactate efflux in patients. Postabsorptive rates of endogenous glucose appearance in weight-losing patients with cancer were elevated, but complete suppression was achieved with insulin concentrations in the physiologic range. Total body glucose use was diminished in these patients, consistent with a state of insulin resistance. This impaired insulin action on peripheral glucose use was associated with an increase in peripheral lactate release in patients. 
4	Dietary fats and oils in cardiac arrhythmia in rats. The effect of long-term feeding of various dietary fats and oils on cardiac arrhythmia was studied in an animal model of sudden cardiac death. After confirmation that a dietary supplement of saturated animal fat (SF) increased the animals' susceptibility to develop cardiac arrhythmia under ischemic stress whereas the polyunsaturated fatty acids of sunflower seed oil (SSO) reduced this susceptibility, we found that diets supplemented with either chemically refined palm oil (PO-I) or physically refined palm oil (PO-II) gave results that were generally intermediate in value between the SF and the SSO groups. However, during reperfusion of a previously ischemic heart, both PO-I- and PO-II-supplemented diets appeared to be as effective as SSO in reducing ventricular premature beats. In addition, the incidence of animals displaying severe ventricular fibrillation was much less after palm-oil feeding than it was after SF feeding. These preliminary results warrant further investigation of the potential antiarrhythmic effects of commercial palm oil. 
4	Holter monitoring of ventricular arrhythmias in a randomised, controlled study of intravenous streptokinase in acute myocardial infarction. The occurrence of ventricular arrhythmias attributed to streptokinase treatment in acute myocardial infarction is not well defined. Holter monitoring was performed for 24 hours in 81 patients with suspected acute myocardial infarction randomised in a ratio of 2:1 to intravenous streptokinase 1.5 x 10(6) IU (n = 55) or placebo infusion (n = 26) 6.7 hours (mean) after the onset of symptoms. No episodes of ventricular fibrillation were recorded. For the whole 24 hour period and during the first three hours after the start of treatment the incidence and frequency of ventricular arrhythmias were similar in the patients randomised to streptokinase and to placebo. But when the results in patients randomised "early" after the onset of symptoms of suspected acute myocardial infarction were analysed separately the frequency of abnormal complexes, pairs, runs, and repetitive arrhythmias seemed to be higher in patients allocated to streptokinase. This may reflect arrhythmias associated with reperfusion. 
5	Hypothalamic glucocorticoid implants prevent fetal ovine adrenocorticotropin secretion in response to stress. We evaluated the role of the hypothalamic paraventricular nucleus (PVN) in control of ACTH secretion in fetal sheep. Dexamethasone (DEX, 700 micrograms) (n = 6) or cholesterol (CHOL, 700 micrograms) (n = 5) implants were placed bilaterally 2 mm lateral to PVN of fetal sheep at 108 to 111 days of gestation (dga). After 5 days recovery, fetuses were challenged with: 1) hypotension (50% drop of blood pressure), 2) hypoxemia (fall of greater than 5 mm Hg in fetal PaO2), and 3) corticotropin-releasing hormone (CRH) (10 micrograms iv, single injection to fetus). Hypotension and hypoxemia were repeated after 125 dga. Compared with CHOL, DEX fetuses had lower average concentrations of ACTH in plasma after hypotension [23 +/- 0.5 vs. 149 +/- 83.8 and 31 +/- 13.1 vs. 101 +/- 31.3 pg ml-1 at less than 125 and more than 125 dga, respectively (mean +/- SEM, P less than 0.05)] and during hypoxemia [11 +/- 1.6 vs. 292 +/- 152.8 and 33 +/- 9.4 vs. 304 +/- 91.3 pg ml-1 at less than 125 and more than 125 dga, respectively (P less than 0.05)]. DEX and CHOL responses to CRH at 122 to 127 dga (10 micrograms iv) were not different (38 +/- 23.9 vs. 92 +/- 26.7 pg ml-1, respectively). Immunocytochemistry demonstrated that CRH was decreased in PVN and eliminated from median eminence in DEX, but not in CHOL fetuses. Arginine vasopressin (AVP) immunostaining of PVN of DEX and CHOL fetuses was similar; however, unlike CHOL, DEX fetuses showed no AVP immunostaining of the external zone of median eminence. These results show that, in fetal sheep, high concentrations of glucocorticoid near the fetal PVN prevent increases in plasma ACTH secretion seen in controls in response to hypotension and hypoxemia, and exert at least part of their effect at the level of the CRH- and AVP-producing neurons located in the PVN. 
2	Changes in the postenteropathic form of the hemolytic uremic syndrome in children. An analysis was made of clinical and laboratory findings in children with the diarrheal form of the hemolytic uremic syndrome (HUS) treated at The Children's Hospital, Birmingham between 1970 und 1987. From 1982 the rate of referral increased, the prodromal illness more often consisted of bloody diarrhea, and the mean age at presentation doubled from 2 to 4 years. For patients with a good outcome there was an excess of males in the period 1970-81, and females in the period 1982-87. Moreover, in the years 1982-87 the disorder was distinguished from that of the earlier time by a positive correlation between adverse outcome and both neutrophil leukocytosis and a higher hemoglobin concentration at presentation. Prognostic scores obtained by logistic regression analysis were specific for each period. From July 1983 stool samples were analyzed for verocytotoxin-producing Escherichia coli (VTEC) and neutralizable verotoxin. Positive results were obtained in 39% of cases. The nature of HUS has changed and the new form of the disorder is associated with VTEC infection. 
2	A nongastrin malignant ampullary tumor causing gastric acid and pepsin hypersecretion. A case report. We report a case of multiple duodenal ulcers with gastric hypersecretion due to a nongastrin secretagogue produced by a malignant tumor of the pancreas in a 78-year-old man. The case resembled a Zollinger-Ellison syndrome (ZES) with high acid output (basal acid output 27, sham meal-stimulated 37, maximum acid output 47 mEq/h), but with fasting gastrin 43 pg/ml, nonresponsive to secretin. As in ZES, pepsin output was comparatively low, and secretion was inhibitable by atropine (50% inhibited by 1 microM). The tumor removed at surgery contained less than 1 ng gastrin per gram, but was many times more potent than pentagastrin in stimulating acid from a lumen-perfused rat stomach. The tumor also contained cholecystokinin (CCK-8 and CCK-33), motilin, insulin, and somatostatin, which were also present in adjacent normal pancreas; in addition, the tumor contained pancreatic polypeptide and pancreatic cancer-associated antigen. This case represents a rare syndrome due to an as yet undefined peptide secreted by a (frequently malignant) pancreatic endocrine tumor and masquerading as ZES. This is the first report of studies of pepsin secretion and of the effect of atropine, suggesting that the physiologic effects of the secretagogue resemble that of gastrin. 
5	Simultaneous occurrence of mitral valve prolapse and systolic anterior motion in hypertrophic cardiomyopathy. This report describes the simultaneous occurrence of mitral valve prolapse (MVP) and systolic anterior motion (SAM) in hypertrophic cardiomyopathy (HC). In 25 patients (aged 7 to 62 years, mean 29), 15 (60%) of whom were male, distal portions of the anterior or posterior mitral leaflets approached or made midsystolic contact with the ventricular septum, whereas the proximal portion of the mitral leaflets showed marked cephalad excursion into the left atrium, 5 to 15 mm beyond the mitral annular plane. Three mitral valves that were available for gross visual inspection were not morphologically typical of patients with primary MVP. Clinical features and natural history (1 to 14 years [mean 6] of follow-up), cardiac dimensions, and distribution of left ventricular hypertrophy defined in the study patients did not appear to differ distinctly from those in the overall referral population of patients with HC evaluated at our institution. Hence, patients with HC may show a striking pattern of mitral valvular motion involving SAM into the left ventricular outflow tract, as well as MVP; this prolapse motion is probably due to anatomic disproportion between the mitral valve and the small left ventricular cavity rather than to the coexistence of 2 separate disease entities. Such patients further define the great diversity evident within the broad clinical spectrum of HC. 
5	Intrapleural tetracycline for the prevention of recurrent spontaneous pneumothorax. Results of a Department of Veterans Affairs cooperative study This prospective, multicenter, randomized, "unblinded," controlled clinical trial was designed to determine if the intrapleural instillation of 1500 mg of tetracycline hydrochloride would be effective in diminishing the ipsilateral rate of recurrence for spontaneous pneumothorax. During the 4-year enrollment period, 113 patients were assigned to the tetracycline group; 116 patients were assigned to the control group. During the 5-year study period, the recurrence rate in the tetracycline group (25%) was significantly less than that in the control group (41%). Use of tetracycline seemed to reduce the recurrence rates for patients with either primary or secondary spontaneous pneumothorax and for patients with either an initial or a recurrent pneumothorax. We conclude that the intrapleural administration of tetracycline in patients with spontaneous pneumothorax significantly reduces the rate of ipsilateral recurrence but is associated with intense chest pain. Intrapleural tetracycline therapy is indicated for patients with a spontaneous pneumothorax who are hospitalized and are treated with tube thoracostomy. 
2	Cytomegalovirus colitis in AIDS: presentation in 44 patients and a review of the literature. As part of a double-blind, placebo-controlled study of ganciclovir in cytomegalovirus (CMV) colitis, the clinical characteristics of 44 patients enrolled at one center were analyzed in detail. All were homosexual men who had CMV on colonic biopsy. CMV colitis was the index diagnosis for acquired immune deficiency syndrome (AIDS) in 11 (25%) of the 44 patients. All had diarrhea, but it was intermittent in 13 patients (30%). Bleeding was uncommon, but 35 patients (80%) were febrile (median temperature of 38.9 degrees C). Weight loss was reported by 39 patients (89%), among whom the median loss was 6.8 kg. Endoscopy revealed normal colonic mucosa but CMV on biopsy in 11 patients (25%). Colonoscopic biopsies positive for CMV were found only in the cecum in 7 (39%) of 18 patients. Most patients (54%) had received zidovudine before the diagnosis of CMV colitis. The median time to the development of CMV colitis after the diagnosis of AIDS was 16 months in those patients who had received zidovudine and 3 months in those who had not (p less than 0.02). We conclude that CMV colitis can present early in AIDS and often with such nonspecific signs as fever, intermittent diarrhea, weight loss, and hematochezia. Importantly, it can appear normal on colonoscopy and occurs frequently only in the right colon, necessitating full colonoscopy and multiple biopsies for accurate diagnosis. 
2	Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of variceal hemorrhage. Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were included in a prospective controlled trial to assess the efficacy and safety of portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of variceal hemorrhage. Forty-one patients were randomized to portacaval anastomosis and 41 to sclerotherapy. After excluding dropouts, 34 patients were treated with portacaval anastomosis and 35 with sclerotherapy. The incidence of variceal rebleeding during follow-up (mean +/- SD, 20.6 +/- 14.2 months) was significantly higher in the sclerotherapy than in the portacaval groups, either considering the overall treated group or only patients completing sclerotherapy (40% and 25% vs. 2.9%; P = 0.0002 and P = 0.01, respectively). The 2-year probability of suffering from at least one episode of hepatic encephalopathy was significantly higher in patients submitted to portacaval anastomosis than in those treated with endoscopic sclerotherapy (40% vs. 12%; P = 0.04). However, disabling encephalopathy only appeared in 3 of 34 patients who underwent surgery (8.8%). Early and long-term mortality did not differ between the therapeutic groups; 2-year survival rates were 83% for portacaval anastomosis and 79% for sclerotherapy. It is concluded that portacaval anastomosis is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in spite of the greater incidence of hepatic encephalopathy. The role of portacaval anastomosis in the elective treatment of variceal rebleeding should be reassessed. 
4	The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators BACKGROUND. Nonrheumatic atrial fibrillation increases the risk of stroke, presumably from atrial thromboemboli. There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke. METHODS. We conducted an unblinded, randomized, controlled trial of long-term, low-dose warfarin therapy (target prothrombin-time ratio, 1.2 to 1.5) in patients with nonrheumatic atrial fibrillation. The control group was not given warfarin but could choose to take aspirin. RESULTS. A total of 420 patients entered the trial (212 in the warfarin group and 208 in the control group) and were followed for an average of 2.2 years. Prothrombin times in the warfarin group were in the target range 83 percent of the time. Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently. There were 2 strokes in the warfarin group (incidence, 0.41 percent per year) as compared with 13 strokes in the control group (incidence, 2.98 percent per year), for a reduction of 86 percent in the risk of stroke (warfarin:control incidence ratio = 0.14; 95 percent confidence interval, 0.04 to 0.49; P = 0.0022). There were 37 deaths altogether. The death rate was markedly lower in the warfarin group than in the control group: 2.25 percent as compared with 5.97 percent per year, for an incidence ratio of 0.38 (95 percent confidence interval, 0.17 to 0.82; P = 0.005). There was one fatal hemorrhage in each group. The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups. The warfarin group had a higher rate of minor hemorrhage than the control group (38 vs. 21 patients). CONCLUSIONS. Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring. 
5	Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. A 39-year-old man and his 42-year-old sister, both vegetarians, had episodic confusion for many years, but their mental function was normal between those episodes. They were recently diagnosed with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hyperammonemia was documented during an episode of confusion in the male sibling but not in his sister. Both had elevated plasma ornithine, glutamine, and alanine levels and persistently low plasma lysine levels. Homocitrulline was present in their urine, and orotic aciduria and orotidinuria developed in the male sibling following ingestion of allopurinol. Studies on their cultured skin fibroblasts showed deficient metabolism of ornithine, indicating a defect in ornithine transport across the mitochondrial membrane. During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal. Since therapy started, their clinical conditions have also improved, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months. 
1	The epidemiology of cancer among Hispanic women. The experience in Florida. To explore cancer incidence among Hispanic women living in Dade County, Florida, data were analyzed from the statewide cancer registry. For all but three sites, Hispanics had lower rates of the 15 most prevalent cancers than non-Hispanics. However, higher rates of cancer among Hispanics were noted for cancers of the gallbladder, liver, and heart and soft tissue. Subgroups of women had significantly higher rates of cervical cancer and thyroid cancer. Lower rates among Hispanics were observed for cancers of the esophagus, vagina, breast, colon, buccal cavity and pharynx, and malignant melanoma. These data suggest that most cancer sites traditionally higher among US Latino women were not higher among Dade Hispanics, and that sites more common among non-Hispanics have not yet shown an increased incidence among Hispanic women in Dade County. 
1	Decreased mortality in users of estrogen replacement therapy In a prospective study of 8881 postmenopausal female residents of a retirement community in southern California, we evaluated in detail the relationship between estrogen use and overall mortality. After 7 1/2 years of follow-up, there had been 1447 deaths. Women with a history of estrogen use had 20% lower age-adjusted, all-cause mortality than lifetime nonusers (95% confidence interval, 0.70 to 0.87). Mortality decreased with increasing duration of use and was lower among current users than among women who used estrogens only in the distant past. Current users with more than 15 years of estrogen use had a 40% reduction in their overall mortality. Among oral estrogen users, relative risks of death could not be distinguished by specific dosages of the oral estrogen taken for the longest time. Women who had used estrogen replacement therapy had a reduced mortality from all categories of acute and chronic arteriosclerotic disease and cerebrovascular disease. This group of women had a reduced mortality from cancer, although this reduction was not statistically significant. The mortality from all remaining causes combined was the same in estrogen users and lifetime nonusers. 
5	Epidemiologic risk factors for children with acute lower respiratory tract infection in Buenos Aires, Argentina: a matched case-control study. The risk factors that predisposed 516 hospitalized and 154 ambulatory patients to acute lower respiratory tract infection (ALRI) are examined in a matched case-control study. The control group was selected from children attending immunization and well-baby clinics at the same institution that was treating the children with ALRI. Sex, age, nutritional status, socioeconomic level, as well as season and place of residence were used as matching criteria. Because of their distinct profiles, hospitalized and outpatient groups were analyzed separately. However, the four variables with the highest odds ratios (incidence ratios or relative risk) were found to be the same for both groups. These variables were related to the host's condition (bronchial hyperreactivity, presence of persistent symptoms of the upper respiratory tract), family (presence of acute respiratory tract disease in household members), and environment (indoor contaminants). 
3	Lateral deviation of the eyes on forced lid closure in patients with cerebral lesions. We examined 35 patients with unilateral cerebral lesions to determine the incidence of lateral deviation of the eyes under forcefully closed lids and the reliability of this sign in predicting the side of the lesion. Only patients with radiologically confirmed unilateral lesions were studied. Over 70% of patients had contralateral ocular deviation (Cogan's "spasticity of conjugate gaze"), 20% had ipsilateral deviation, and less than 9% of the patients had no deviation. Lateral ocular deviation was as sensitive, but not as specific, as a unilateral Babinski plantar response in determining the side with the lesion. Contralateral deviation was more common with parietotemporal localization, suggesting that the phenomenon reflects an underlying disturbance of attentional mechanisms. 
4	Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade. Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems. 
1	Changes in the relative frequency of gastric adenocarcinoma in southern California. The incidence of gastric cancer is decreasing in most counties of the developed world, but at the Los Angeles County-University of Southern California Medical Center, we diagnosed 99.8 cases of gastric adenocarcinoma per 10(5) discharges in the period 1982 to 1986 as opposed to 62.2 per 10(5) discharges in 1972 to 1976 (P less than .0001). This change involved primarily Hispanics younger than 30 years of age with 30 cases per 10(5) vs 4.2 cases per 10(5) (P less than .0001) and whites older than 30 years: 87 cases per 10(5) vs 54 cases per 10(5) (P less than .05) during 1982 to 1986 and 1972 to 1976, respectively. There was no change in the relative frequency rates of gastric adenocarcinoma among African Americans and Asians. Although these changes do not seem important enough to make the detection of gastric cancer a high-priority public health problem, they should alert physicians working in areas with high Hispanic populations of the relative possibility of the occurrence of gastric malignancy even in young patients. Also, we have found that gastric cancer is still prevalent in whites of low socioeconomic class. 
5	Medicinal leeches: once again at the forefront of medicine. Medical grade leeches have recently been used in the management of acute problems relative to venous congestion in patients with traumatic injuries and surgical problems. Specific cases, especially in the realm of reconstructive microsurgery, have demonstrated the effectiveness and application of leech therapy. Specific contraindications include arterial insufficiency from either anatomic or mechanical obstruction. We present five illustrative cases of successful therapeutic intervention. 
5	Behavioral management of psychogenic cough: alternative to the "bedsheet" and other aversive techniques. The treatment of persistent psychogenic cough, a potentially debilitating condition among pediatric patients, can pose diagnostic and treatment dilemmas. Its treatment by the use of a procedure called reinforced suggestion technique was described previously. The use of an alternative procedure relying upon parental and self-monitoring of coughing and either social or material rewards for decreasing rates of coughing is presented. 
5	Colonoscopy during an attack of severe ulcerative colitis is a safe procedure and of great value in clinical decision making. Thirty-four patients who had severe ulcerative colitis had a colonoscopic examination during the attack. The indications were resistance to therapy and/or differential diagnostic purposes. Total colonoscopy was performed in 25 cases and less extensive examination in nine. Biopsy was taken in 22 cases. No clinically significant complications occurred. The procedure helped us to postpone immediate surgical intervention in 19 cases. Fourteen of these patients have maintenance treatment and are still well after a follow-up median time of 5 yr (6 months to 10 yr). 
5	Intraoral-extramaxillary sinus approach for ligation of the maxillary artery: an anatomic study with clinical correlates. Surgical control of severe epistaxis is usually reserved for cases refractory to more conservative techniques. We present our experience with intraoral ligation of the maxillary artery as it courses through the buccal fat pad before it enters the pterygopalatine fossa and branches posterior to the maxilla. This technique has been found useful in the control of nasal hemorrhage as well as an adjunct to other surgical procedures, such as removal of benign and malignant neoplasms involving the maxilla and paranasal sinuses. This technique was used for ligation of the maxillary artery in 20 patients. The artery was readily identified in some cases, but required more extensive dissection in others; therefore, an anatomic study in 18 preserved and fresh cadaver specimens was undertaken to investigate the variability of the maxillary artery in the region of the buccal fat pad. There appeared to be significant variation in the distance from the buccal mucosal incision site, as well as variation in the relationship to the pterygoid muscles. This relationship to the pterygoids explains the occasional difficulty in locating the artery for ligation. This technique represents a reasonable alternative to the more traditional transantral approach to ligation of the maxillary artery, as long as the surgeon understands the anatomy of the region, its variations, and where the artery may be located if not immediately apparent. No major complications have been experienced. 
5	Excess purine degradation caused by an imbalance in the supply of adenosine triphosphate in patients with congestive heart failure. To evaluate purine degradation in patients with congestive heart failure concentrations of serum hypoxanthine, lactate, and noradrenaline were measured before and after submaximal treadmill exercise in 12 patients with chronic congestive heart failure and nine healthy volunteers. In four patients the concentration of hypoxanthine was significantly higher than in the controls or in the remaining eight patients with congestive heart failure. Venous lactate and noradrenaline in the four patients with high concentrations of hypoxanthine were also significantly higher than those in the eight patients with normal concentrations of hypoxanthine. Patients who responded normally were also more likely to have been treated with vasodilators and angiotensin converting enzyme inhibitors. Exercise induced arrhythmias were more common in the patients with high concentrations of hypoxanthine. These results suggest that the excess purine degradation in patients with congestive heart failure might be the result of a "relative" disturbance in the supply of adenosine triphosphate caused by the shift of cellular metabolism from aerobic glycolysis to anaerobic glycolysis during submaximal exercise and that hypoxanthine (a substrate for xanthine oxidase and a source of free radicals) was increased after submaximal exercise in some patients with congestive heart failure. 
5	Maxillary sinus hypoplasia masquerading as chronic sinusitis. Maxillary sinus hypoplasia is a common condition that may be misdiagnosed as chronic sinusitis. Although hypoplasia can usually be seen on conventional sinus films, computed tomography may be necessary, as in the cases described by the authors in this article. 
1	The clinical pharmacology of etoposide. Etoposide, a semisynthetic derivative of podophyllotoxin, is increasingly used to treat cancer. Etoposide is a phase-specific, cytotoxic drug acting in the late S and early G2 phases of the cell cycle. It appears to cause breaks in DNA by either an interaction with DNA-topoisomerase II or the formation of free radicals. Most studies show a biexponential decay after the intravenous (IV) administration of etoposide. The peak plasma concentrations of drug and the area under the concentration versus time curve (AUC) are linearly related to the IV dose. Considerable interpatient variability of pharmacokinetic variables exists after IV etoposide. Various metabolites of etoposide have been identified, but their detection and quantitation are disputed. Approximately 30% to 70% of an etoposide dose is excreted. The bioavailability of oral etoposide is approximately 50%, but its absorption is not linear with increasing doses within the range in clinical use. Considerable interpatient and intrapatient variability exists in the pharmacokinetics of oral etoposide. There is no evidence of etoposide accumulation after multiple consecutive doses by either the IV or oral route. The exact roles of the liver and kidney in metabolism and excretion of etoposide are uncertain. Etoposide has been shown to be a highly schedule-dependent drug in clinical studies. This, together with the phase-specific action of etoposide and its increasingly widespread use in treating cancer, makes the clinical pharmacology of this drug of great clinical importance. 
1	Immunohistochemical demonstration of the placental form of glutathione S-transferase, a detoxifying enzyme in human gliomas. Expression of the human placental form of glutathion S-transferase (GST-pi) in human gliomas was investigated by immunohistochemical methods, and the result was compared with that of normal human glial cells. The gliomas in this study were composed of five benign astrocytomas (Grade 2), ten anaplastic astrocytomas (Grade 3), and 16 glioblastomas (Grade 4). Normal human glial cells showed only a weak immunostaining response for GST-pi in the cytoplasm or some nuclear membranes. All of benign astrocytomas had diffusely weak GST-pi immunostaining, resembling that of normal glial cells. With increasing grade, gliomas showed a strongly positive reaction for GST-pi. The positive reactions were remarkable especially in the gemistocytes and giant cells in the high-grade gliomas. These results suggest that cells of gliomas have some detoxifying function and the expression of this detoxifying enzyme, GST-pi, is related to the degree of malignancy of the gliomas. 
2	Effect of endotoxin and a burn injury on lung and liver lipid peroxidation and catalase activity. Both endotoxin and a burn alone produce oxidant-induced tissue lipid peroxidation. The endotoxin response is due in large part to hydrogen peroxide. The combination of endotoxin after a burn results in an increased liver, but not lung, oxidant injury. Our purpose was to determine whether the burn oxidant injury inactivated endogenous liver tissue catalase, thereby amplifying a subsequent H2O2 insult. Twenty-six adult sheep were studied. Twelve sheep had a 15% TBS burn. Tissue catalase activity, measured in lung and liver 3 days postburn, was significantly decreased from a control of 3.58 +/- 1.8 and 193 +/- 63, respectively, to 1.72 +/- 0.63 and 148 +/- 33 k(sec-1)/0.5 gram tissue. The addition of endotoxin 3 days postburn resulted in an increase in liver malondialdehyde, MDA, a measure of lipid peroxidation, from a control of 110 +/- 80 to 450 +/- 54 nmol/gram tissue. This value was significantly greater than the 210 +/- 80 nmol/gram tissue seen after endotoxin alone. Lung tissue MDA with burn and endotoxin was 65 +/- 8 compared to 42 +/- 7 for control and 80 +/- 6 nmol/gram for endotoxin alone. We conclude that a decrease in liver catalase activity occurs after a burn. The decrease corresponds to an accentuated oxidant-induced lipid peroxidation after an added endotoxin insult where H2O2 is known to be an etiologic agent. The catalase activity also decreases in postburn lung, but accentuated lung damage was not seen, indicating a variable tissue response from the burn-induced decrease in antioxidant activity. 
4	Usefulness of the electrophysiology laboratory for evaluation of proarrhythmic drug response in coronary artery disease. Two potential manifestations of proarrhythmic responses to type IA antiarrhythmic agents in the electrophysiology laboratory were evaluated in 122 patients with chronic coronary artery disease and previous myocardial infarction: (1) conversion of uniform nonsustained ventricular tachycardia (VT) into sustained VT after drug administration, and (2) induction of sustained VT by fewer extrastimuli after drug administration. Forty-two patients were evaluated for nonsustained VT. Eighty patients were evaluated for sustained VT: 30 of these had spontaneous sustained VT only while receiving empiric therapy with quinidine or procainamide, whereas the remaining 50 developed spontaneous VT in the absence of antiarrhythmic drugs. All patients underwent programmed stimulation in the baseline state and after procainamide. Four patients had conversion of induced uniform nonsustained VT into the same morphology, but sustained VT after procainamide administration. These responses only occurred in patients evaluated for nonsustained VT. Over 90% of patients presenting with sustained VT had uniform sustained VT induced at the baseline study and after procainamide, regardless of whether the spontaneous arrhythmia occurred only in the presence or absence of antiarrhythmic drugs. There was no significant difference in the change in mode of induction from baseline to procainamide study, regardless of whether patients had developed spontaneous VT only in the presence or absence of antiarrhythmic drugs. One patient with no inducible VT at the baseline study had inducible uniform sustained VT after procainamide administration, and 1 patient with inducible VT at baseline developed spontaneous sustained uniform VT after procainamide administration. Both patients had developed spontaneous sustained VT only while receiving therapy with type IA agents. 
2	Islet cell carcinoma of the pancreas presenting as bleeding from isolated gastric varices. Report of a case and review of the literature. Gastrointestinal hemorrhage from left-sided portal hypertension and gastric varices is an unusual presentation for islet cell carcinoma of the pancreas. Islet cell tumors of the pancreas themselves are rare. They present in a variety of ways. Those that elaborate functional hormones cause specific neuroendocrine syndromes. Nonfunctional tumors characteristically present later with symptoms of metastatic disease or as a result of local enlargement. We present a case of islet cell carcinoma of the pancreas presenting with recurrent gastrointestinal bleeding from gastric varices and review the literature for this rare presentation. We emphasize the importance of a careful initial diagnostic work-up that may enable curative surgery. 
1	Oral contraceptives and breast cancer. Review and meta-analysis. To evaluate the relation between use of oral contraceptives and the incidence of breast cancer, the authors reviewed the epidemiologic literature and used quantitative methods to summarize the data. Study results for any use of oral contraceptives were pooled using a model that accounted for both interstudy and intrastudy variability. The authors also explored interstudy variability and modeled a duration-effect relation between oral contraceptive use and breast cancer. Case-control and follow-up studies were considered separately. Overall, the authors observed no increase in the risk of breast cancer for women who had ever used oral contraceptives, even after a long duration of use. These results were consistent across study design. However, data combined from case-control studies revealed a statistically significant positive trend (P = 0.001) in the risk of premenopausal breast cancer for women exposed to oral contraceptives for longer duration. This risk was predominant among women who used oral contraceptives for at least 4 years before their first term pregnancy (relative risk = 1.72; 95% confidence interval = 1.36 to 2.19). Additional study is required to determine whether this finding in a subgroup of exposed women is confirmed and whether the risk remains increased with advancing age. 
1	Local recurrence and survival following nerve-sparing radical cystoprostatectomy. From March 1982 through July 1988, 76 men underwent nerve-sparing radical cystoprostatectomy for carcinoma of the bladder at our hospital. Of the 76 patients 2 (2.6%) had positive surgical margins (dome of the bladder and left ureter) and neither had positive margins at the site of nerve-sparing modifications. Of 3 patients (3.9%) who had local recurrence none had positive surgical margins. The 5-year actuarial local recurrence rate is 7.5%. Thirteen of 76 patients (17%) died of transitional cell carcinoma and 7 (9%) died of other causes, while 53 (70%) are alive without evidence of disease with a mean followup of 38.4 months. The 5-year actuarial survival rates are 64% over-all, 68% without disease and 78% disease-specific. Of the 42 evaluable men who underwent cystoprostatectomy alone 27 (64%) are potent, compared to 2 of the 12 men (17%) who also underwent urethrectomy. We conclude that the nerve-sparing modifications do not compromise cancer control, that local recurrence and survival rates are at least comparable to those achieved with standard radical cystoprostatectomy, and that it is possible to preserve potency in most men undergoing this procedure. 
3	Osseointegration of titanium implants in total hip arthroplasty. Osseointegration is defined as direct contact on the light microscopic level between living bone tissue and the implant. Using titanium screw dental implants in the jaw, a lasting interface under loaded conditions extending over a 20-year follow-up period has been demonstrated. This demonstration brings up the question whether a similar interface can be achieved in total hip arthroplasty (THA) between living bone and a titanium alloy implant under necessitated conditions of immediate loading. Two series of cases are reported. The first series used a femoral, press-fit, titanium alloy component and the second used a press-fit titanium acetabular component and redesigned femoral, press-fit, titanium alloy component. Both demonstrated a high percentage of good to excellent results. Roentgenograms showed that the geometrical changes in the redesigned femoral component gave early indications of a better fixation with loading in valgus, less subsidence, and less evidence of distal stress transfer. A two-and-one-half-year postoperative anatomic specimen study confirmed osseointegration to the press-fit titanium alloy femoral component. Multiple areas of contact between bone and metal without fibrous interposition were seen. Examination by electron microscopy supported the light microscopic findings. These findings support further use of smooth, press-fit titanium components in THAs without the need for porous coating, mesh, or other surface modifications. 
1	Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy. This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity. 
1	Pulmonary metastases and bone sarcomas. Surgical removal of lesions appearing after adjuvant chemotherapy. Pulmonary metastasis is the leading cause of death in pediatric patients with bone tumors. Multiple thoracotomies for surgical removal of individual lesions are performed at many centers. To explore the efficacy of this procedure and establish guidelines for an appropriate choice of patients, the experience with 43 thoracotomies in 24 children was reviewed. The appearance of first metastasis later than one year after diagnosis, presence of fewer than five nodules, and completeness of surgical resection were favorable predictors of postthoractomy survival. Early or multiple metastases, unresectable disease, and hilar, nodal, or pleural lesions conferred an unfavorable prognosis. With careful patient selection, pulmonary metastecotomy is a safe procedure that has few operative or long-term complications. It must be emphasized that although surgical removal of pulmonary metastases prolongs survival with good quality of life, the majority of patients with bone sarcomas ultimately succumb to their disease after thoracotomy. Follow-up time of greater than eight years is necessary to adequately assess the effectiveness of pulmonary resection in eradicating all disease in these patients. 
3	Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery. A total of 213 patients with verified aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) were enrolled in a double-blind placebo-controlled trial to determine the effect of intravenous nimodipine on delayed ischemic deterioration and computerized tomography (CT)-visualized infarcts after SAH and surgery. The administration of the drug or matching placebo was started immediately after the radiological diagnosis of a ruptured aneurysm had been made. Of the 213 patients enrolled in the study, 58 were operated on early (within 72 hours after the bleed: Days 0 to 3), 69 were operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8 or later). Eleven patients died before surgery was undertaken and one was not operated on. A follow-up examination with CT scanning, performed 1 to 3 years after the SAH (mean 1.4 years), revealed no significant differences in the overall outcome between the groups. However, nimodipine treatment was associated with a significantly lower incidence of deaths caused by delayed cerebral ischemia (p = 0.01) and significantly lower occurrence of cerebral infarcts visualized by CT scanning in the whole population (p = 0.05), especially in patients without an associated intracerebral hemorrhage on admission CT scan (p = 0.03). 
4	Sclerotherapy of varicose and telangiectatic leg veins. Minimal sclerosant concentration of hypertonic saline and its relationship to vessel diameter The author reports the results of a double-blind, paired-comparison study using saline sclerosant plus or minus heparin additive. The study was designed to elucidate the effects of increasing concentrations of hypertonic saline with regard to vessel diameter, clinical efficacy, complications, and discomfort. Six hundred women with bilaterally symmetrical starburst telangiectasias or varicose veins were entered into the study. Sodium chloride 11.7% appeared to be the minimal sclerosant concentration of saline that produced the most effective vein sclerosis of vessels of less than 8 mm in diameter, while producing the least morbidity. The optimal concentration of the sclerosant may vary with the diameter of the vessels under therapeutic consideration. 
5	Selective breeding of dogs for segregation of limb edema from microfilaremia as clinical manifestations of Brugia infections. Three generations of beagles were monitored for microfilaremia (mf) and clinical disease during repeated infection with Brugia pahangi and were selectively bred for offspring manifesting limb edema and low or amicrofilaremia. A high microfilaremic female mated to a high microfilaremic male produced 7 pups, 6 of which maintained mf greater than 1,000/ml for greater than 2 years after 5 monthly infections of 10 infective larvae each. An uninfected female mated to another high mf male produced 5 pups, 4 of which did not exceed 1,000 mf/ml 7 months after initiation of the repeating infection regimen; 1 of these remained amicrofilaremic after 2 additional challenges. Neither the parents nor the offspring from these matings manifested chronic limb edema. Two matings were conducted with offspring from the microfilaremic female by breeding siblings with the lowest mf and breeding siblings with the highest mf. The high mf siblings produced 4/5 offspring manifesting chronic limb edema (greater than or equal to 7 months duration) and either no mf (in 2 dogs) or less than 100 mf/ml after the repeating infection regimen. The lower mf siblings produced 5 offspring, all with greater than 1,000 mf/ml 6 months after the initiation of the repeating infection regimen; none manifested edema. Comparisons of IgG antibody levels, specific for extracts of adult worms, showed no consistent differences between these 2 litters of dogs that could be associated with limb edema or mf when monitored for 16 months; however, the onset of lymph node enlargement was much earlier in the group of dogs manifesting limb edema than in the other litter. 
5	The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Fasting serum glucose, glycosylated hemoglobin, and fructosamine concentrations were determined in 304 consecutive subjects admitted with acute stroke, within 48 hours of ictus. Based on the medical history and these results, subjects were divided into known diabetics, newly diagnosed diabetics, subjects with stress hyperglycemia, and nondiabetics. The type of stroke was classified as lacunar infarct, cerebral infarct, or intracerebral hemorrhage, based on clinical examination by a neurologist and computed tomographic brain scan and/or autopsy. Immediate and 3-month outcomes were examined in relation to (1) fasting glucose, glycosylated hemoglobin, and fructosamine levels by stroke subtypes, and (2) glucose tolerance categories by stroke subtypes. A high fasting glucose level was associated with an increased mortality, but this was observed only among patients with intracerebral hemorrhage. Patients with stress hyperglycemia, but not diabetics, had increased mortality. In spite of having similar glucose concentrations to those patients with stress hyperglycemia, diabetics did not have a worse outcome compared with nondiabetics. It is concluded that the association between glucose concentration and outcome is a reflection of stress relating to stroke severity, rather than a direct harmful effect of glucose on damaged neurons. 
3	Stiffman syndrome: a rare paraneoplastic disorder? An unusual case of the stiffman syndrome, associated with an oat cell carcinoma of the bronchus, is reported. Pathological examination showed that it was due to an encephalomyelitis similar to that seen in paraneoplastic disorders. This suggests that atypical cases of the stiffman syndrome may occasionally be paraneoplastic. 
1	Characterization and significance of sulfonylurea receptors. This study describes and characterizes a putative sulfonylurea receptor. The radioligand used was [3H]glipizide (9 Ci/mmol). The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient. Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h. Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein. Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities. Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes. Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators. Sulfonylurea binding to the beta-cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel. 
2	Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease. 
1	Angiotropic B-cell lymphoma (malignant angioendotheliomatosis): failure of systemic chemotherapy. A 65-year-old female with angiotropic B-cell lymphoma is reported. Despite the absence of systemic involvement on formal staging and the favourable response of the cutaneous lesions to triple systemic chemotherapy with prednisolone, vincristine and cyclophosphamide, postmortem findings showed that death was due to widespread disease dissemination. 
3	Transcranial stab wounds: morbidity and medicolegal awareness. In this series of eight patients with transcranial stab wounds, the importance of classifications of such wounds as a separate traumatic entity is stressed. The mechanisms of neuronal and vascular damage in these wounds are discussed and are found to be specific from other head injuries. Cerebral injury by stabbing is largely restricted to the wound tract. Frontal stabs (two cases) are accompanied by the least morbidity and mortality, while temporal stabs (four cases) are more commonly fatal. In transorbital stabs (two cases) carotid-cavernous fistulae resulted. Early recognition, administration of antitetanus serum and antibiotics, and debridement may minimize complications. 
5	Reversed lateralization of cognitive functions in right handers. Exceptions to classical aphasiology. Most current and past research on the cerebral organization of cognitive functions has presupposed certain specialized hemisphere operations. At least for right handers, language and praxis are to be organized in the left hemisphere, while affective prosody, configurational spatial capacity, and global attention are lateralized in the right hemisphere. Deviations from these presuppositions, as in crossed aphasics and perhaps left handers, are generally considered to be 'exceptions' and either to disprove the rules or to be irrelevant to the rule. We report 4 very 'exceptional' cases, right handers with almost entirely reversed lateralization of functions. Analysis of the intrahemispheric relationships between functions suggests that there may be a specific neurobiology to the interrelationships between and among cognitive functions, handedness, and the intrahemisphere localization of the function. 
3	Development and reversal of contingent inefficacy and tolerance to the anticonvulsant effects of carbamazepine. The relationship of the timing of drug administration to anticonvulsant efficacy against amygdala kindled seizures was studied. During kindling development, rats received carbamazepine (CBZ, 15mg/kg) before (CBZ-before) or after each amygdala stimulation (CBZ-after). After kindling to full seizures, when all animals were given CBZ before the stimulation, only the CBZ-after group showed a good anticonvulsant response. The rats that had received CBZ before (during development of kindled seizures) remained unresponsive to CBZ treatment (contingent inefficacy). When drug-naive or CBZ-after animals repeatedly received CBZ before electrical stimulation, they developed tolerance to its anticonvulsant effects (contingent tolerance). The tolerance could be reversed by a period of treatment with CBZ-after or by kindling the animal drug-free, but not by CBZ administration alone or by time off from both drug and seizures. These findings suggest that inefficacy and tolerance to CBZ may be affected by the temporal contingencies of drug administration and that responsiveness can be reinstated by altering these contingencies. 
5	Cystic fibrosis mutations in North American populations of French ancestry: analysis of Quebec French-Canadian and Louisiana Acadian families. A 3-bp deletion (delta F508) in the cystic fibrosis (CF) gene is the mutation on the majority of CF chromosomes. We studied 112 CF families from North American populations of French ancestry: French-Canadian families referred from hospitals in three cities in Quebec and from the Saguenay-Lac St. Jean region of northeastern Quebec and Acadian families living in Louisiana. delta F508 was present on 71%, 55%, and 70% of the CF chromosomes from the major-urban Quebec, Saguenay-Lac St. Jean, and Louisiana Acadian families, respectively. A weighted estimate of the proportion of delta F508 in the French-Canadian patient population of Quebec was 70%. We found that 95% of the CF chromosomes with delta F508 had D7S23 haplotype B, the most frequent haplotype on CF chromosomes. In the Saguenay-Lac St. Jean families, 86% of the CF chromosomes without delta F508 had the B haplotype, compared with 31% for the major-urban Quebec and Louisiana Acadian families. The incidence of CF in the Saguenay-Lac St. Jean population was 1/895 live-born infants. 
5	Estimation of myocardial ischemic injury during ventricular fibrillation with total circulatory arrest using high-energy phosphates and lactate as metabolic markers. STUDY OBJECTIVE: To define the time course of myocardial ischemic injury using high-energy phosphate (HEP) depletion and the cessation of lactate production as metabolic markers. SETTING: Data were collected in a laboratory animal model. TYPE OF PARTICIPANTS: Ten immature mixed breed swine weighing 23.2 +/- 3.5 kg. DESIGN: After thoracotomy, transmural myocardial biopsies were taken in vivo during normal sinus rhythm and at designated times during ventricular fibrillation with total circulatory arrest (VF-TCA). MEASUREMENTS AND MAIN RESULTS: Frozen tissue samples were analyzed for adenine nucleotides, by high-performance liquid chromatography, and lactate by enzymatic assay. At five minutes of VF-TCA, myocardial adenosine triphosphate averaged 50% of control. At 15 minutes of VF-TCA, 89% of animals had myocardial adenosine triphosphate levels above 20% of control and adenylate charge ratio above 0.60. With more than 30 minutes of VF-TCA, all animals had adenosine triphosphate levels below 10% of control and adenylate charge ratio below 0.30. In addition, myocardial lactate levels plateaued after 30 minutes of VF-TCA, indicating the cessation of lactate production. CONCLUSION: These results suggest that the myocardium can tolerate VF-TCA for as long as 15 minutes without irreversible injury; however, post-ischemic myocardial dysfunction may occur after as little as five minutes of VF-TCA. With more than 30 minutes of VF-TCA, myocardial injury is likely to be irreversible. 
5	Changes in gastric mucosa that antedate gastric carcinoma. Endoscopic biopsy specimens of the gastric mucosa from 13 patients who were found at follow-up examination to have gastric carcinoma were compared for abnormal histologic features, type of intestinal metaplasia, and presence of immunoreactive carcinoembryonic antigen (CEA), with specimens from 40 tumor-free controls. Villus-like changes and angular infolding, cytologic nuclear pleomorphism, distinct nuclear border, irregular thickness of the nuclear membrane, irregular chromatin clumping, prominent nucleoli, and distinct nucleoli were manifestations of the carcinoma group. Angular infolding, distinct nuclear border, irregular thickness of the nuclear membrane, and distinct nucleoli were also observed in the latent stage before detection of carcinoma. The individual features, however, lacked specificity. Histochemically, a IIB subtype of intestinal metaplasia, and immunoreactive CEA in the cytoplasm of foveolar epithelium appeared exclusively in the patients with carcinoma. These findings indicate that the gastric epithelium of patients with gastric carcinoma tends to be morphologically and histochemically abnormal even before the recognition of classical dysplasia. This can be described as abnormal epithelium and is believed to provide the soil on which gastric carcinoma develops. 
4	Follow-up of patients with low output, low gradient hemodynamics after percutaneous balloon aortic valvuloplasty: the Mansfield Scientific Aortic Valvuloplasty Registry. Symptomatic patients with a low cardiac output and low aortic valve gradient have a poor prognosis but are at high risk for aortic valve surgery. The outcome of percutaneous balloon aortic valvuloplasty in this subgroup of patients is unclear. Therefore, 67 patients (group 1) underwent percutaneous balloon aortic valvuloplasty between December 1, 1986 and November 1, 1987 who had a low cardiac index (less than 2.5 liters/min per m2) and a low aortic valve gradient (less than or equal to 40 mm Hg) before the procedure. The results were compared with 200 patients (group 2) who had a low cardiac index but not a low aortic valve gradient (greater than 40 mm Hg) before the procedure and who had similar baseline presenting symptoms. After balloon aortic valvuloplasty, there was a greater decrease in aortic valve gradient in patients in group 2 than in patients in group 1 (mean +/- SD -33.0 +/- 16.7 mm Hg and -14.6 +/- 6.9 mm Hg, respectively; p less than 0.001) although there was no significant difference in improvement in estimated aortic valve area (0.31 +/- 0.21 and 0.31 +/- 0.22 cm2, respectively; p = NS). In-hospital mortality was 11.9% for patients in group 1 which was not significantly different from the 7.5% mortality for patients in group 2. However, the actuarial probability of survival at 12 months for patients who survived the initial hospitalization was 46% in group 1 and 64% in group 2 (p less than 0.05). Moreover, at follow-up (mean 8.8 months) 64% of surviving group 1 patients displayed clinical improvement, compared with 70% of surviving group 2 patients. 
4	Long-term minoxidil treatment in refractory hypertension and renal failure. Twenty-two patients with severe or accelerated hypertension refractory to conventional hypotensive therapy have been treated with minoxidil for an extended period. Patients were divided in three groups according to different degrees of renal function or the presence of accelerated hypertension. In the first group (8 patients with normal or slightly decreased renal function) BP fell from 197 +/- 11/118 +/- 3 before minoxidil therapy to 157 +/- 7/98 +/- 2 after six months (p less than 0.001), and remained steady during the following eighteen months. In the second group (9 patients with creatinine clearance of 30 +/- 3 ml/min.1.73 m2) BP decreased from 192 +/- 9/119 +/- 4 to 147 +/- 6/91 +/- 4 at six months (p less than 0.001); renal function did not show any significant modification during the eighteen months of the study. In the third group (5 patients with accelerated hypertension) BP fell from 243 +/- 14/137 +/- 6 to 166 +/- 13/99 +/- 7 at six months (p less than 0.01). Seven patients, four in the first and three in the second group, were followed for more than six years; these patients, with mild renal insufficiency (creatinine clearance 50 +/- 4 ml/min) before minoxidil therapy, were on a protein unrestricted diet for the entire length of the study. In this group of patients BP fell from 182 +/- 9/115 +/- 3 to 150 +/- 6/96 +/- 2 after one year (p less than 0.01) and remained well controlled for the following six years or more. Renal function did not show any significant worsening over the years (monthly decrement in creatinine clearance 0.08 ml/min). 
5	A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982 A unique opportunity to evaluate the method of chemical lymph node clearance for colorectal cancer exists at Ferguson Hospital. Lymph node clearance has been used at the institution since 1977, and this retrospective analysis was undertaken to ascertain its validity there. Furthermore, the node positive group was evaluated to ascertain if the current staging system (Turnbull, 1967) is prognostically accurate for the Dukes' C group. Specifically evaluated for possible prognostic variance was the survival of those patients whose tumors demonstrated partial bowel wall penetration and only one to four positive nodes, a "C1 subset," previously reported to have favorable prognosis. Eight hundred sixty-four cases of colon and rectal cancer treated surgically from 1977 to 1982 were analyzed. There was a mean of 27 lymph nodes retrieved per specimen and a mean of 4.5 positive nodes per Dukes' C specimen. There were 43 C1 and 201 C2 cases with five-year survival rates of 73 and 38 percent, respectively. The results of chemical clearance at Ferguson Hospital were found to be comparable with that of other centers using chemical clearance and superior to hand dissection. The C1 subset clearly is noted to have prognostic advantage and should occupy a separate designation in any staging system. 
2	The starved colon--diminished mucosal nutrition, diminished absorption, and colitis. Nutrition of colonic epithelial cells is mainly from short chain fatty acids (SCFAs) produced by bacterial fermentation in the colonic lumen. n-Butyrate contributes more carbon of oxidation to epithelial cells than glucose or glutamine from the vasculature. Incomplete starvation of colonic epithelial cells through lack of luminal SCFAs leads, in the short term, to mucosal hypoplasia with either diminished absorption or diarrhea. A chronic lack of SCFAs or complete organ starvation in conjunction with other factors leads to nutritional colitis, either "diversion colitis" or "starvation colitis." Whether predominantly diarrhea or colitis develops in mucosal malnutrition appears to depend upon the severity and duration of starvation. Ulcerative colitis may be classified as a nutritional colitis in that colonic epithelial cells are unable to utilize SCFAs reflecting epithelial starvation despite abundant SCFAs. 
1	Preventing cervical cancer by treating genital warts in men. Why male sex partners need androscopy. The increased incidence of cancer of the genitourinary and anorectal areas has been directly related to the coexistence of genital human papillomavirus infection. The diagnosis and treatment of condyloma acuminatum in men is important not only to prevent cancer but also to decrease the reservoir of virus that is being transferred to women. Screening with androscopy (examination of male genitals with a colposcope after a vinegar solution has been applied to the skin) is indicated for all men who are at risk for this infection. Treatment options include chemical application, cryosurgery, laser therapy, and interferon injections. To be effective, treatment must include both sexual partners. 
5	Practical aspects of pulsatile gonadotropin-releasing hormone administration. Pulsatile administration of gonadotropin-releasing hormone represents a major advance in the treatment of anovulation in women who fail to ovulate with clomiphene citrate and is an alternative for many women who currently receive human menopausal gonadotropin. Four issues must be addressed before administering pulsatile gonadotropin-releasing hormone: (1) safety, (2) efficacy, (3) convenience, and (4) cost. Each of these issues will be affected by the three major decisions a physician makes with gonadotropin-releasing hormone therapy: (1) patient selection, (2) route of administration, and (3) dose of gonadotropin-releasing hormone. The ideal candidate for gonadotropin-releasing hormone therapy is a patient with an absence of endogenous pulsatile gonadotropin-releasing hormone, as seen in hypothalamic amenorrhea. Although women with polycystic ovarian disease can be treated with pulsatile gonadotropin-releasing hormone, a decreased ovulation rate should be expected. The route of administration, intravenous or subcutaneous, and the degree of monitoring can be tailored by the physician to fit each patient's needs. Pulsatile gonadotropin-releasing hormone therapy is a safe, effective, convenient, and economical alternative to human menopausal gonadotropin for ovulation induction in women resistant to clomiphene. 
5	High-risk metastatic gestational trophoblastic disease. A new dose-intensive, multiagent chemotherapeutic regimen. Dose-intensive, multiagent chemotherapy for the treatment of high-risk gestational trophoblastic disease has evolved as the treatment of choice for these patients. High-dose methotrexate in combination with etoposide, dactinomycin, vincristine and cyclophosphamide (EMA-CO) has now been demonstrated to be superior to the traditional methotrexate, dactinomycin, cyclophosphamide chemotherapy in patients with prognostic scores of greater than or equal to 8. An attempt was made to improve upon the EMA-CO regimen by increasing the dose intensity of etoposide and adding cisplatin to the high-dose methotrexate, etoposide and dactinomycin. That regimen was used on four patients with ultra-high-risk gestational trophoblastic disease. 
1	The internal oblique-iliac crest free flap in composite defects of the oral cavity involving bone, skin, and mucosa. The reconstruction of oromandibular defects following ablative surgery is a challenging undertaking. When the defect involves skin as well as mucosa, the challenge becomes even greater. The internal oblique iliac crest osteomyocutaneous free flap is particularly useful for reconstruction of through-and-through composite defects due to the inclusion of two separate soft-tissue flaps on the same vascular pedicle. We report our experience with this flap in the reconstruction of 10 patients with such defects. The utility, and the limitations of this form of reconstruction are discussed in detail. 
5	Extradural implantation of sacral anterior root stimulators. A technique for extradural deafferentation of the S2 to S5 segments and extradural implantation of stimulating electrodes is described, and its application to twelve patients with spinal cord lesions is reported. Nine patients use their implants for micturition, and seven are fully continent. The advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed. 
1	The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases. 
3	Stroke rehabilitation: Australian patient profile and functional outcome. A prospective, multi-institutional, population based study identified 1274 non-surgical stroke admissions to all hospitals in a major Australian city during 1984. The demographic and diagnostic profile and the nature of functional recovery of all 258 first stroke survivors who were referred for inpatient rehabilitation are presented. The median duration of rehabilitation stay was 49 days. The mean functional independence score, as measured on a modified Barthel Index at admission was 44, compared with 78 on discharge, a mean improvement of 34. Stair climbing had the lowest mean value on admission (12), while bowel control had the lowest residual deficit on discharge (95). The stroke study group was representative of the unimpaired aged population in all respects except ethnicity, where differences are attributed to age. The variables identified as significant are; side and severity of paralysis, age and sex, marital status and ethnicity. Stroke rehabilitation outcome was not influenced by etiology, site of lesion, arterial distribution, occupation or education. 
4	Reversal of cardiac dysfunction secondary to type 1 primary hyperoxaluria after combined liver-kidney transplantation. A 23-year-old man with type 1 primary hyperoxaluria, renal failure, and oxalosis developed a severe cardiomyopathy while awaiting combined liver-kidney transplantation. This manifested as radiographic cardiomegaly, a dilated hypokinetic left ventricle with a decreased ejection fraction, ventricular arrhythmias, and cardiac uptake on bone scanning. On liver and kidney transplantation, these abnormalities markedly improved and/or reversed. The cardiac size almost normalized, the left ventricular ejection fraction increased from 20% to 34%, the ventricular arrhythmias resolved, and the cardiac uptake on bone scanning disappeared. This coincided with normalization of oxalate production and excretion. Severe cardiac involvement secondary to oxalosis in patients with primary hyperoxaluria may improve or reverse with combined liver-kidney transplantation. 
5	Surgical outcome in 435 patients who sustained missile head wounds during the Iran-Iraq War. Variables important in predicting the final postsurgical outcome of 435 patients who sustained missile head wounds during the Iran-Iraq War were evaluated over a 99-month period. The type of projectile, site of injury, and presence or absence of foreign material did not seem to have a significant effect on the final outcome. Of the patients with a perforating type of injury, 48.8% had a poor surgical outcome as compared with 19.9% with a penetrating type and 15.6% with a tangential type. This difference is statistically significant (chi 2 = 14.7 and 17.1, respectively; p less than 0.001). The most important factor in predicting overall outcome was the Glasgow Coma Scale (GCS) score at the time of admission. Mortality and morbidity contributing to a poor surgical outcome were noted in only 6% of patients with a GCS score at admission of 13 to 15, in 24.6% of those with a GCS score of 9 to 12, in 57% of those with a GCS score of 6 to 8, and in 65% of those with a GCS score of 3 to 5. Of the 71 patients who died, 75% had a score of 3 to 8. Perforating projectiles or those traversing two or more dural compartments were statistically significant in contributing to mortality and morbidity (chi 2 = 17.2; p less than 0.001). The incidence of focal neurological deficit was 100, 90.6, 88, and 52.2% in patients with GCS scores of 3 to 5, 6 to 8, 9 to 12, and 13 to 15, respectively. The two best predictors of mortality in this group of patients were a low GCS score and infection. 
1	Preoperative chemotherapy (cisplatin and fluorouracil) and radiation therapy in stage III non-small-cell lung cancer: a phase II study of the Lung Cancer Study Group. The Lung Cancer Study Group conducted a phase II pilot study of concurrent chemotherapy and radiation therapy (chemoradiotherapy) before surgery in 85 eligible patients with non-small-cell cancer limited to the chest but in whom attempted resection would have been likely to leave residual disease (advanced stage IIIA and minimal stage IIIB disease). Cisplatin, 75 mg/m2, was given on days 1 and 29; fluorouracil, 1 g/m2 per 24 hours, was administered as a continuous infusion on days 1 through 4 and on days 29 through 32; and thoracic radiation, 30 Gy in 15 fractions, was administered on days 1 through 19. Two patients achieved a complete response and 46 patients had a partial response for an overall response rate of 56%. Toxicity from chemoradiotherapy was moderate but acceptable. Eight weeks after therapy was initiated, 54 patients underwent thoracotomy and tumor resection was attempted: 29 (34%) had complete resection and 15 (18%) had incomplete resection. Although surgical dissection was generally more difficult than in patients not pretreated with chemoradiotherapy, there was no apparent increase in postoperative complications. In 8 patients (9%), no viable tumor was detected pathologically in the resection specimen. Of the 18 patients whose tumors were completely resected and had disease recurrence, none had recurrence only in the chest, 12 (67%) had recurrence only in distant sites, and 3 developed second primary tumors. Median survival of all patients was 13 months. The overall results do not indicate a major benefit from this preoperative chemoradiotherapy regimen in patients with advanced but potentially resectable non-small-cell lung cancer. These results suggest a need to define better the relative roles of preoperative radiotherapy and chemotherapy. 
4	Genetic data and natural history of Friedreich's disease: a study of 80 Italian patients. The clinical and genetic features of 80 patients with Friedreich's disease from 64 families are described. Diagnostic criteria were: no evidence of dominant inheritance, onset by the age of 20 years, progressive unremitting ataxia of limbs and gait, and absence of knee and ankle jerks. Furthermore, at least one of the following accessory signs was present: dysarthria, extensor plantar response and echocardiographic evidence of hypertrophic cardiomyopathy. Two peaks of onset age were evident at 6-9 and 12-15 years. Analysis of intra-family variation of onset age and absence of clustering of cardiomyopathy and diabetes did not suggest genetic heterogeneity. Peripheral nerve impairment was an early finding and showed slight further progression, whereas involvement of the cerebellar and corticospinal pathways appeared later and mainly accounted for the progressive worsening of the disease. 
4	Push-enteroscopy for diagnosis of patients with gastrointestinal bleeding of obscure origin. Push-enteroscopy using a disinfected colonoscope was performed on 39 patients with gastrointestinal bleeding of obscure origin. Our results show that: (1) A high percentage of patients (38%) have pathological lesions responsible for bleeding located in the distal duodenum and proximal jejunum, which are readily detected by push-enteroscopy. (2) Duodeno-jejunal arteriovenous malformations (AVMs) are the most common cause for bleeding, and these lesions can be conveniently cauterized through the endoscope. (3) An efficient sequence of steps for diagnosis of patients with this problem includes push-enteroscopy when the initial EGD and colonoscopy are normal followed by small bowel radiography. Mesenteric angiography and intraoperative enteroscopy can be reserved for patients with severe bleeding when push-enteroscopy and small bowel radiography are negative. We conclude that push-enteroscopy has an important role to play in the early assessment of patients with gastrointestinal bleeding of obscure origin. 
1	Epididymal metastasis from prostatic adenocarcinoma mimicking adenomatoid tumor. A case of epididymal metastasis from prostatic carcinoma is presented. The initial histologic findings were suggestive of adenomatoid tumor, but a diagnosis of metastatic adenocarcinoma of prostatic origin has been established by prostatic acid phosphatase and prostate-specific antigen immunoperoxidase staining. 
2	Sexually transmitted causes of gastrointestinal symptoms in homosexual men. The possible etiologic agents that may cause gastrointestinal complaints in homosexually active men are multiple, and their diagnosis is complex. This article presents a logical approach to the work-up and diagnosis of gastrointestinal complaints in homosexually active men and to discuss their treatment and disease intervention. 
3	Cerebrospinal fluid rhinorrhea following acoustic neurinoma surgery. Technical note. The authors describe a method of preventing cerebrospinal fluid (CSF) rhinorrhea following surgery for acoustic neurinoma. Mastoid air cells exposed during craniectomy are skeletonized and packed with bone dust, then covered with Surgicel soaked with Tisseel fibrin glue. The use of this technique has reduced the number of acoustic neurinoma cases requiring secondary mastoidectomy for CSF leakage from 16% to 5%. 
1	Prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma. BACKGROUND. Morphologic evaluation of bone marrow for neuroblastoma cells is a routine and important component of clinical staging. Specific immunostaining of malignant cells with monoclonal antibodies should be more sensitive, however, and may improve the detection of metastases and provide additional prognostic information. METHODS. We looked for tumor cells in bone marrow from 197 patients with newly diagnosed neuroblastoma, using immunoperoxidase staining with monoclonal antibodies (immunocytologic analysis) and examination of smears and specimens obtained by trephine biopsy (conventional analysis). RESULTS. Routine smears and trephine-biopsy specimens were positive for tumor cells in 46 percent of the patients, whereas 67 percent were positive on immunocytologic analysis (P less than 0.0001). Immunocytologic analysis detected bone marrow metastases in 34 percent of patients considered to have only localized or regional disease (Stage I, II, or III). It also identified tumor cells that were not detected by conventional analysis in patients with widespread disease (Stage IV or IVS). Tumor content, as determined by immunocytologic analysis, predicted clinical outcome in relation to the age of the patient at diagnosis. Patients with Stage II or III disease diagnosed after one year of age who did not have occult marrow metastases did well, whereas those with metastases did poorly (P = 0.006). Patients in whom Stage IV disease was diagnosed before they were one year of age did well if bone marrow metastases were few or absent, but had poor survival if the marrow contained more than 0.02 percent tumor cells (P = 0.03). CONCLUSIONS. Immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information. The relations among marrow metastases, age at diagnosis, and clinical outcome illustrate the biologic heterogeneity of neuroblastoma. 
5	Iliofemoral arterial complications of balloon angioplasty for systemic obstructions in infants and children The medical and radiological records of 64 consecutive infants and children who underwent transfemoral balloon dilation of the aorta or aortic valve were reviewed to determine the incidence, nature, and post-treatment outcome of acute iliofemoral complications. Balloon dilation angioplasty or balloon valvotomy was performed with 8F and 9F catheters without an arterial sheath. Patients ranged in age from 5 days to 15.4 years (mean, 6.4 years). Of 64 patients, 29 (45.3%) had an acute iliofemoral complication, including thrombosis (18 of 64), complete disruption (five of 64), incomplete disruption (three of 64), and arterial tear (three of 64). The arterial pathology was confirmed in 23 of 29 patients by one or a combination of surgical exploration and repair (18 of 29), angiography (six of 29), and magnetic resonance imaging (three of 29). Of eight patients, three with arterial disruption had acute hypotension requiring transfusion and immediate surgery; the other five had absent pedal pulses after the procedure. Of these five, three developed bleeding during thrombolytic therapy and underwent surgical exploration, and two were diagnosed by angiography after ineffective thrombolytic therapy. Angiography in three patients with iliac artery avulsion showed tapered occlusion in two and an aneurysm in one. In patients with iliofemoral thrombosis, angiography showed occlusion from the puncture site to the origin of the external iliac artery. Eleven patients (17% of the entire group and 38% of the group with acute iliofemoral complications) had reduced or absent pedal pulses at the time of discharge. A significant correlation was found between increased incidence of iliofemoral thrombosis and disruption (as well as abnormal pedal pulses at hospital discharge) and low patient weight. 
4	Prevalence of coronary heart disease in Scotland: Scottish Heart Health Study Data from 10,359 men and women aged 40-59 years from 22 districts in the Scottish Heart Health Study were used to describe the prevalence rates of coronary heart disease in Scotland in 1984-1986 and their relation to the geographical variation in mortality in these districts. Prevalence was measured by previous history, Rose chest pain questionnaire, and the Minnesota code of a 12 lead resting electrocardiogram. The prevalence of coronary heart disease in Scotland was high compared with studies from other countries that used the same standardised methods. A history of angina was more common in men (5.5%) than in women (3.9%), though in response to the Rose questionnaire 8.5% of women and 6.3% of men reported chest pain. A history of myocardial infarction was three times more common in men than women, as was a Q/QS pattern on the electrocardiogram. There were significant correlations between the different measures of coronary prevalence. District measures of angina correlated well with mortality from coronary heart disease, and these correlations tended to be stronger in women than in men. There was no significant correlation between mortality from coronary heart disease and measures of myocardial infarction. The study provides data on the prevalence of coronary heart disease in men and women that are valuable for the planning of cardiological services. 
4	The case against childhood cholesterol screening Because some authorities have proposed blood cholesterol screening for children to prevent coronary heart disease, we reviewed published studies to estimate the potential risks and benefits of such screening. Childhood cholesterol levels are a poor predictor of high cholesterol levels in young adulthood and will be an even poorer predictor of coronary heart disease later in life. There is no evidence that blood cholesterol levels can be lowered more easily in children than in adults, and it seems unlikely that cholesterol reduction in childhood will be much more effective at preventing coronary heart disease than cholesterol reduction begun in middle age. Screening and interventions to lower blood cholesterol levels for millions of children would be expensive, could lead to labeling and family conflicts, and may cause malnutrition and increased noncardiovascular mortality. Because the benefits of cholesterol screening are unlikely to exceed these risks, we conclude that children should not be screened for high blood cholesterol levels. 
5	Epidural anaesthesia for labour and caesarean section in a parturient with a single ventricle and transposition of the great arteries. We describe a case of a 29-year-old parturient with a single ventricle and transposition of the great arteries who had lumbar epidural analgesia/anaesthesia with a local anaesthetic for labour, emergency Caesarean section and postoperative pain. Her outcome and that of her baby was successful. The anaesthetic techniques used in other parturients with similar congenital cardiac anomalies are reviewed. 
1	Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival. From 1976 to 1989, 21 adult patients with previously untreated acute promyelocytic leukemia were seen at the University of Virginia Hospital. We reviewed their cases retrospectively to determine the impact of hemorrhagic complications and other factors on treatment outcome. We observed a complete remission rate of 35%; the median survival in complete responders was 15 months. Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis. Fatal intracranial hemorrhage was the leading cause of death, occurring in eight (40%) of the 20 patients evaluated. Initial leukocyte count greater than 4.0 x 10(9)/L and platelet count less than 20 x 10(9)/L were significantly associated with an increased risk of intracranial hemorrhage. In patients with disseminated intravascular coagulation, the rate of intracranial hemorrhage was reduced by treatment with heparin. The high mortality of 40% (8/20) due to intracranial hemorrhage during induction was a major contributor to the low complete remission rate of 35% (7/20) in this series of consecutive unselected patients with newly diagnosed acute promyelocytic leukemia. 
4	A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction. The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state. 
4	Ultrastructural changes in rat hearts following cold cardioplegic ischemia of differing duration and differing modes of reperfusion. Morphologic consequences of prolonged global hypothermic (15 degrees C), cardioplegic ischemia and two reperfusion techniques were studied in Langendorff-perfused rat hearts. A 'gentle' reperfusion technique, with gradual rise in perfusate temperature and pressure to physiologic levels over 30 min, was used for 12 hearts following 2-hour or 3 1/2-hour (6 in each group) ischemia. Abrupt reperfusion, with perfusate at 37 degrees C and 70 mmHg, was performed on 13 hearts (6 ischemic for 2 hours and 7 for 3 1/2 hours). Six nonischemic, perfused hearts served as controls. Randomly selected specimens from the left ventricle after 45-60 min reperfusion were prepared for transmission electron microscopy. Volume fractions of myocardial structural components were calculated from stereologic point-counting on the electron micrographs. Two-way analysis of variance revealed that interstitial edema developed with increasing ischemic time and was not influenced by reperfusion technique. The degree of endothelial damage was independent of ischemic time, but was lessened by 'gentle' reperfusion. Both mitochondrial injury and myocyte edema were less when perfusate temperature and pressure were slowly raised after 3 1/2-hour ischemia. 
5	The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration Three dominant mutations of mec-4, a gene needed for mechanosensation, cause the touch-receptor neurons of Caenorhabditis elegans to degenerate. With deg-1, another C. elegans gene that can mutate to induce neuronal degeneration and that is similar in sequence, mec-4 defines a new gene family. Cross-hybridizing sequences are detectable in other species, raising the possibility that degenerative conditions in other organisms may be caused by mutations in similar genes. All three dominant mec-4 mutations affect the same amino acid. Effects of amino-acid substitutions at this position suggest that steric hindrance may induce the degenerative state. 
2	Systemic and renal production of thromboxane A2 and prostacyclin in decompensated liver disease and hepatorenal syndrome. To assess the role of altered renal and systemic production of thromboxane A2 and prostacyclin in the hepatorenal syndrome, urinary excretion of their major renal and extrarenal metabolites was measured in patients with compensated and decompensated liver disease, chronic renal failure, and hepatorenal syndrome. Urinary excretion rates of all prostanoids (renal and extrarenal) were increased in subjects with liver disease compared with normal controls. Moreover, they were considerably higher in subjects with severe hepatic decompensation but good renal function compared with those with hepatorenal syndrome. In contrast, the excretion rate of all metabolites was reduced in patients with chronic renal failure. The excretion rate of all metabolites was markedly elevated during the early stages of hepatorenal syndrome and decreased in parallel with creatinine clearance. When corrected for creatinine clearance, there was a strong correlation between prostanoid excretion and serum bilirubin in subjects with liver disease; there was no difference, however, in the excretion of renal and extrarenal prostanoids between hepatorenal syndrome and severe hepatic decompensation. It is concluded that hepatic decompensation is associated with a progressive increase in prostanoid excretion but that changes in production of prostacyclin or thromboxane A2 are unlikely to be major factors in the pathogenesis of the hepatorenal syndrome. 
4	Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs. Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia. 
5	Heart weights of white men 20 to 39 years of age. An analysis of 218 autopsy cases. Review of autopsy data for 218 white men between 20 and 39 years of age who died of injuries or suddenly and unexpectedly indicated a mean heart weight of 371 g. The mean for those dying of external causes was 364 g whereas the mean for those dying of natural causes was 446 g. A coefficient for heart weight expressed as a percentage of body weight was lower in heavy individuals than lightweight individuals; it ranged between 0.38% and 0.55%, with a mean of 0.48%. Heart weight, including epicardial fat, increased with age and body weight. These data may be useful to those who are called upon to investigate sudden and unexpected deaths. 
1	Chest wall involvement by lung cancer: computed tomographic detection and results of operation. The aim of this prospective study was to evaluate: (1) the role of computed tomographic scanning in predicting chest wall invasion by peripheral lung cancer and (2) the results of operation according to the depth of chest wall involvement and other potential indicators of long-term survival. One hundred twelve patients with non-small cell lung cancer adjacent to the pleural surface who underwent computed tomographic scanning and subsequent thoracotomy were entered into this study. Tumor invasion was confined to the visceral pleura in 53 patients, to the parietal pleura in 18 patients, and to intercostal muscles in 25 patients; invasion extended beyond this layer in 16 patients. The computed tomographic criteria for chest wall invasion were (1) obliteration of the extrapleural fat plane, (2) the length of the tumor-pleura contact, (3) the ratio between the tumor-pleura contact and the tumor diameter, (4) the angle of the tumor with the pleura, (5) a mass involving the chest wall, and (6) rib destruction. The computed tomographic criteria 1 and 3 were significantly related to pathologic findings. Sensitivity was 85% for criterion 1 and 83% for criterion 3, specificity being 87% and 80%, respectively. Long-term survival of patients with T3 disease critically depended on the lymph node state and completeness of resection. The adenocarcinoma cell type and the T4 category were unfavorable prognostic factors. The depth of chest wall invasion did not affect survival, except for extensive rib and soft tissue infiltration. En bloc resection yielded better results than discontinuous resection. 
1	High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment. 
5	Bacteriology of the ethmoid bullae in children with chronic sinusitis. Cultures from 105 children with chronic sinusitis who had failed aggressive medical management were retrospectively studied. Patients with immunodeficiency and cystic fibrosis were excluded from the study. Because the most common sites of disease were the infundibula and anterior ethmoid sinuses, samples of mucosa removed from the anterior ethmoid bullae during endoscopic ethmoidectomy were routinely cultured for aerobic and anaerobic organisms. Fungal cultures were performed for 55 bullae. The principal organisms isolated were alpha-hemolytic Streptococcus, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae non-type B. Only 12 anaerobic organisms and four fungi were isolated. Of the 204 bullae cultured, multiple organisms were found in 61 bullae and 40 showed no growth. Isolates of other less common organisms were also found. These data are analyzed on the basis of age and duration of symptoms, and antibiotic treatment is described. 
2	Cereal-based oral rehydration therapy. II. Strategic issues for its implementation in national diarrheal disease control programs. Field studies in Bangladesh demonstrated that after proper training, village mothers were able to prepare and use rice-based, salt-enriched oral rehydration solutions containing safe concentrations of sodium, and were capable of achieving significantly fewer treatment failures and a reduction in the duration of diarrhea than with glucose-based oral rehydration solutions (ORS). An additional longitudinal study showed that improved growth and weight gain occurred with the consistent use of ORS; the effect was greater when rice-based ORS were used. In addition, the following possible limitations and benefits of cereal-based oral rehydration therapy, which are relevant to the strategies for its implementation in national diarrheal disease control programs, are discussed: safety, osmolarity, hypernatremia, spoiling, effectiveness, rehydration ability, reduction in diarrhea volume and duration, nutritional effects, effect on food intake, acceptance and usage by care givers, training of health workers, self-reliance of families, effect on other child survival activities, costs, potential problems in changing to cereal-based ORS, and the role of industrial production in packaged cereal-based ORS. 
3	Accidental death from a black-powder rifle breech plug. Authentic black-powder muzzle-loader weapons and replicas are used today primarily for hunting game such as deer and hogs. The following is a case presentation of accidental death from cerebral trauma caused by a .45-caliber black-powder-rifle breech plug implanting in the victim's brain. 
5	Effects of medical and surgical treatment on cerebral perfusion and cognition in patients with chronic cerebral ischemia. The effects of medical treatment with and without cerebral revascularization procedures on cognition and cerebral blood flow were compared among 36 patients with extracranial occlusive cerebrovascular disease and cognitive impairments. Three comparable groups were studied. The first group (N = 18) received only medical treatment by control of risk factors for stroke (including hypertension, diabetes, and hyperlipidemia) and antiplatelet aggregant medication. The second group (N = 10) had the same medical treatment plus superficial temporal-to-middle cerebral artery bypass, and the third group had the same medical treatment plus carotid endarterectomy. Regional cerebral blood flow and cognition were monitored in all three treatment groups over a 3-year interval. All groups showed stabilization without expected rates of decline for both cerebral blood flow and cognition, but no statistically significant differences emerged among the treatment groups. 
5	Spontaneous bacterial peritonitis due to Salmonella enteritidis in cirrhotic ascites. Spontaneous bacterial peritonitis due to Salmonella is uncommon. We report three patients with ascites infected by Salmonella. All three patients had advanced chronic liver disease, typically cirrhosis with portal hypertension. Salmonella enteritidis grew in the ascite fluid culture of the three patients. There was no clinical or microbiological evidence of Salmonella infection other than in the ascitic fluid. One patient died before antibiotic treatment was started, but the other two were treated with different combinations of antimicrobial drugs. One of them died on the fourteenth day of hospitalization, and the other survived. 
4	Randomized trials in the study of antihypertensive drugs. Heterogeneity in response to antihypertensive drugs can be addressed by randomized trials in individual subjects. In such a trial a patient receives pairs of treatment periods (one period of each pair active drug, one matched placebo, in random order); patient and clinician are blinded to allocation, and treatment targets are monitored. These trials can optimize antihypertensive therapy in clinical practice and facilitate the investigation of new drugs and the study of pathophysiology. Such trials also have potential in helping decide whether common, nonspecific symptoms reported by patients are really drug related. 
2	Acute cholangitis. Cholangitis is an infection of the biliary ductal system that results from the combination of bactibilia and biliary obstruction. Choledocholithiasis has been the leading cause of cholangitis. However, in recent years, especially at tertiary referral centers, nonoperative biliary manipulations, often in patients with unresectable malignancies, have become the most common cause of cholangitis. As a result, the complete triad of fever and chills, jaundice, and abdominal pain, as originally described by Charcot, is now seen less frequently. Most patients still have leukocytosis and abnormal liver function tests, but many patients with indwelling tubes may develop cholangitis without significant jaundice. E. coli, Klebsiella species, and the enterococci remain the most frequently isolated organisms, and anaerobes including Bacteroides fragilis are recovered in 15% to 30% of patients. However, Enterobacter and Pseudomonas species, as well as yeasts, are now being isolated more frequently from patients with indwelling tubes, who often have been treated previously with antibiotics. Computed cholangiography usually is necessary to determine the cause and site of biliary obstruction. In the majority of patients with cholangitis, cholangiography can be delayed until the patient has been afebrile for a minimum of 24 to 48 hours. Initial therapy includes bowel rest, intravenous fluids, and antibiotics. Many antibiotic regimens are now available to cover the gram-negative aerobes, the enterococcus, and the anaerobes that are likely to be causing the biliary infection. The combination of a penicillin and an aminoglycoside has been the gold standard. However, recent studies suggest that the newer broad-spectrum penicillins provide adequate therapy for these patients. Only a small percentage (5%-10%) of patients with toxic cholangitis require emergency biliary decompression. The choice of percutaneous or endoscopic drainage should be made on the basis of the presumed site and cause of obstruction as well as local expertise. The nature of the biliary obstruction may be the most important determinant of outcome. At present, patients with end-stage malignant obstruction account for most of the deaths, whereas approximately 95% of patients survive an episode of cholangitis. 
2	Management of the acute abdomen complicating oral anticoagulation therapy. Acute abdominal pain in the patient receiving oral anticoagulants poses a difficult diagnostic and therapeutic challenge. We describe two cases of peritonitis requiring laparotomy in anticoagulated patients, and review 49 similar case reports from the world literature. These patients were usually explored for signs of bowel obstruction. At operation, the intestine often appeared infarcted, but pathologic examination commonly revealed intramural hematomata. In contrast, we present microscopic evidence of hemorrhagic cecal infarction complicating oral anticoagulation therapy in one patient. Intramural intestinal hemorrhage is the most common cause of acute abdominal pain in the anticoagulated patient who undergoes laparotomy. In addition to intramural hemorrhage, 14 per cent of patients had coexistent volvulus, appendicitis, intestinal wall disruption or intestinal infarction. We conclude that anticoagulated patients with suspected intramural intestinal hemorrhage may have severe intraabdominal pathology requiring operation. Therefore, operation is mandatory for patients who fail to improve after a short course of expectant management. 
2	Cardiorespiratory effects of endoscopic esophageal variceal sclerotherapy. Endoscopic variceal sclerotherapy (EVS) is an effective means of controlling variceal hemorrhage, which develops as a consequence of portal hypertension. While esophageal perforation, ulceration, strictures, and mediastinitis are potential complications associated with this procedure, it is not clear whether isolated pleuropulmonary events such as pleuritis, pneumonitis, and adult respiratory distress syndrome are causally related to the EVS. Endoscopy and sedation with the attendant risk of aspiration, particularly in the background of hepatic encephalopathy, may account for some of these events. Recent controlled studies of respiratory function demonstrate that EVS as such results in minor changes in gas exchange, lung volumes, and pulmonary and systemic hemodynamics. Most pulmonary complications have been reported with the use of sodium morrhuate sclerosant. Comparative studies among different sclerosants are necessary to evaluate relative safety. Finally, there have been rare reports of myocardial ischemia and pericarditis reported in association with EVS, but these are of a transient nature. Chest symptoms, roentgenographic pleuropulmonary changes, pulmonary hemodynamics, and cardiac perturbations are transient and should not preclude offering EVS to patients with variceal hemorrhage. 
5	Vasopressin-related bullous disease of the legs. We report a 33-year-old man who developed cutaneous necrosis of the lower extremities with extensive bulla formation after i.v. administration of vasopressin for the treatment of bleeding esophageal varices. Due to its potent nonselective vasoconstrictive action, vasopressin not only may induce cardiac and gastrointestinal ischemia, but cutaneous ischemia as well. As in our patient, this may lead to extensive necrotic skin lesions at sites distant from the infusion. 
4	Long-term prognosis of myocardial ischemia detected by Holter monitoring in peripheral vascular disease. To assess the long-term prognostic significance of myocardial ischemia, as measured by ambulatory electrocardiographic monitoring, in patients with occlusive peripheral arterial disease, 176 eligible patients scheduled for elective peripheral arterial surgery at Brigham and Women's Hospital were prospectively studied. All patients were monitored preoperatively without alterations to baseline medications. Prospective follow-up was obtained during routine medical care as provided by blinded, independent physicians and by subsequent telephone contact with the patients. Thirty-two patients (18%) had a total of 75 episodes of myocardial ischemia, 73 (97%) of which were asymptomatic. During a mean follow-up period of 615 days, there were 9 cardiac deaths, 1 occurring in-hospital after peripheral vascular surgery, and 13 nonfatal myocardial infarctions, 4 occurring in-hospital after peripheral vascular surgery. Cardiac events occurred in 12 of 32 patients with ischemia (38%), including 6 cardiac deaths, and in 10 of 144 patients without ischemia (7%), including 3 cardiac deaths (risk ratio 5.4, 95% confidence interval 2.6 to 11.4). The sensitivity of ischemia was 55%, the specificity was 87%, the positive predictive value was 38%, and the negative predictive value was 93%. In a multivariate Cox proportional-hazards model controlling for age, gender, coronary risk factors, history of angina, myocardial infarction, coronary artery disease and antianginal medications, the presence of ischemia was the only independent predictor of outcome. In patients with peripheral arterial disease, who often are unable to perform adequate exercise testing, ambulatory monitoring for myocardial ischemia is a significant independent predictor of 1- to 2-year prognosis. 
4	An effective treatment protocol for intraarterial drug injection. Between 1972 and 1988, 48 patients with extremity ischemia after an intraarterial drug injection were treated with the following protocol: heparin, dextran 40, dexamethasone, elevation, and early mobilization of the extremity. A tissue ischemia score, derived by assessing the color, capillary refill, sensory function, and temperature of the extremity, was used to assess the ischemic injury. Each sign was scored either normal = 0 or abnormal = 1; then summed to provide the tissue ischemia score (range, 0 to 4). Twenty-four (50%) patients had an extremity tissue ischemia score less than or equal to 2. After treatment 22 of the 24 patients had a normal extremity, and 2 required limited digital amputations. In this group, outcome was comparable regardless of the time interval from intraarterial drug injection to treatment. Ten of 24 (50%) patients with an extremity tissue ischemia score greater than 2 had a normal extremity, 3 had a functional deficit, and 11 required digital amputations. Twelve of the 24 patients were treated within 24 hours and had a significantly superior outcome when compared to the 12 who were treated more than 24 hours after intraarterial drug injection (p less than 0.001, Fisher's exact test). The tissue ischemia score is a useful predictor of extremity outcome in patients with intraarterial drug injection. The outlined treatment protocol is effective in minimizing tissue injury caused by intraarterial drug injection. Institution of treatment within 24 hours of intraarterial drug injection is particularly important in patients who manifest severe ischemia. 
5	Hemodynamic effects of H2-receptor antagonists. Histamine H2-receptor antagonists (H2RAs) often are administered to intensive care unit patients in an attempt to reduce gastric acidity and to prevent stress-related mucosal damage. These agents have an extremely low overall incidence and severity of adverse reactions; however, hemodynamically significant hypotension has been noted. Clinical studies with rapidly administered intravenous cimetidine in critically ill patients have demonstrated a depression in blood pressure in up to 75 percent of patients. Ranitidine, also studied in this setting, does not appear to induce similar hemodynamic changes. The newer H2RAs, famotidine and nizatidine, have not been evaluated in critically ill patients. 
5	Multiplexing studies of effects of rapid atrial pacing on the area of slow conduction during atrial flutter in canine pericarditis model. BACKGROUND. We report that rapid atrial pacing interrupts atrial flutter when the orthodromic wave front from the pacing impulse is blocked in an area of slow conduction in the reentry circuit. To characterize the area of slow conduction during atrial flutter and rapid pacing, we studied 11 episodes of induced atrial flutter, mean cycle length 157 +/- 20 msec, in eight dogs with sterile pericarditis. METHODS AND RESULTS. Atrial electrograms were recorded simultaneously from 95 pairs of right atrial electrodes during the interruption of atrial flutter by rapid atrial pacing, mean cycle length 139 +/- 21 msec. Areas of slow conduction during atrial flutter were demonstrated at one to three sites in the reentry circuit. After rapid pacing captured the reentry circuit, one area of slow conduction either disappeared (10 episodes) or the degree of slow conduction in an area of slow conduction decreased (one episode). Both changes were in association with activation of the region by a wave front from the pacing impulse that arrived from a direction different than that during the induced atrial flutter. Interruption of atrial flutter during rapid pacing occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction that had either newly evolved during rapid pacing (seven episodes) or that was previously present (four episodes). CONCLUSIONS. Areas of slow conduction present during atrial flutter and rapid pacing of atrial flutter are functional and depend on both the atrial rate and the direction of the circulating wave fronts. Interruption of atrial flutter by rapid pacing results from block of the orthodromic wave front of the pacing impulse in an area of slow conduction in the reentry circuit. 
5	Risk factors for multiorgan failure: a case-control study. The aim of this study was to identify factors associated with Multiple Organ Failure (MOF), and assess possible interactions between the risk factors identified as such. We studied 40 MOF cases and 120 controls, out of all the surgery and trauma patients who needed intensive care at our institution in a 24-month period. The univariate analyses showed that age, hypovolemic shock, massive volume administration (MVA), sepsis, and time of evolution before arriving to the hospital (TE) were significantly associated with MOF. Logistic regression analysis showed that neither age nor MVA were independently associated with MOF after adjusting for all of the other variables. Interactions seemed to be present between age, sepsis, and shock. We conclude that in our surgery and trauma ICU adult patient population, hypovolemic shock, sepsis, and TE are independent risk factors for MOF. The importance of the association between shock and sepsis is discussed, as well as the possible relevance of TE as a risk factor. 
1	Localization and surgical treatment of occult insulinomas. Management of patients with biochemical evidence of insulinoma and negative preoperative imaging studies (occult) tumors is controversial, varying from primarily medical management to aggressive, blind nearly total pancreatectomy to extirpate the tumor. Since 1982, 12 consecutive patients with occult insulinoma underwent preoperative portal venous sampling (PVS) for insulin followed by surgical exploration with intraoperative ultrasound (IOUS). Eleven of twelve patients (92%) had insulinoma removed and were cured. Portal venous sampling correctly predicted the location of the insulinoma in 9 patients (75%) and that no tumor would be found in another patient. A fourfold insulin gradient in the pancreatic tail of one patient correctly predicted that a distal pancreatectomy would remove the insulinoma despite the fact that neither palpation nor IOUS identified any tumor. Intraoperative ultrasound was the single best method to identify occult tumors because it correctly identified 10 of 11 insulinomas that were found, including five pancreatic head tumors that were not palpable. Palpation identified five insulinomas. Of the 10 tumors that were identified during operation by palpation or ultrasound, IOUS identified significantly more (100% versus 50%, p = 0.03) and guided the successful enucleation of each. The results support the strategy of preoperative PVS and operation with IOUS to localize and remove insulinoma in patients with occult tumors. Most tumors (75%) will be correctly localized to a specific pancreatic region by preoperative PVS and identified by IOUS (83%), allowing simple enucleation and biochemical correction of hypoglycemia. Morbid blind pancreatic resections are no longer indicated and long-term medical management of hypoglycemia should be reserved for the occasional patient (8%) who fails preoperative PVS and operation guided by IOUS. 
5	Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta-glucosaminidase and beta 2-microglobulin excretion. Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated. 
5	Role of nasal allergy in chronic maxillary sinusitis--diagnostic value of nasal challenge with allergen. The role of nasal allergy in chronic maxillary sinusitis without an air-fluid level was studied in 37 patients. Seventy-three nasal provocation tests with various inhalant allergens were performed in 37 patients by means of rhinomanometry, and maxillary sinus radiographs were performed before and repeatedly after the allergen challenge. Forty-one positive nasal responses (NRs) occurred in 29 patients; 13 were immediate only, 18 were late only, and 10 NRs were dual responses. Of these responses, 32 demonstrated radiographic changes, primarily an increase in mucosal edema and/or opacification. These responses were accompanied by increased pressure in the maxillary sinuses, acute headache, and sometimes otalgia. Eight patients did not develop any NRs; however, increased thickening of the mucosal membrane of the maxillary sinuses, accompanied by subjective symptoms, was recorded in three of these nonresponders. These results demonstrate the role of nasal allergy in some patients with chronic maxillary sinusitis, which may affect the diagnostic and therapeutic approaches to this disorder. 
3	The use of obstetric analgesia in Sweden 1983-1986 The use of obstetric analgesia was investigated in a Swedish population-based prospective study of 335,207 births, which represents almost all women who had vaginal deliveries in Sweden between 1983 and 1986. Lumbar epidural analgesia (EDA) was used in 16%, paracervical block (PCB) in 12%, pethidine or morphine in 49% and pudendal block in 62%. All four types of analgesia were much more commonly used by nulliparae than multiparae. Variables such as maternal age, smoking, nationality, relationship with the infant's father and gestational age had only moderate influence on the rates of different types of analgesia. EDA and PCB were more frequently used in larger than in smaller hospitals and in the daytime than at night. No such differences were found for pethidine or morphine, or pudendal block, which were administered routinely by midwives. 
1	Surgical management of renal cell carcinoma with extensive intracaval involvement using a venous bypass system suitable for rapid conversion to total cardiopulmonary bypass. Renal cell carcinoma involves the vena cava in approximately 4% of the patients. Presently surgical extirpation is the only form of therapy that can result in cure. Recently management of extensive vena caval involvement has involved the use of cardiopulmonary bypass with circulatory arrest and hypothermia. We describe a technique using a venous bypass pump system (femoral vein to right atrium) for resection of renal cell carcinoma with suprahepatic vena caval extension (type II), which avoids the risks and complications of cardiac arrest and hypothermia but allows for rapid conversion to total cardiopulmonary bypass should the intraoperative need arise. 
5	Obstructive jaundice: use of expandable metal endoprosthesis for biliary drainage. Work in progress. Expandable metal endoprostheses were implanted transhepatically in 61 patients with obstructive jaundice. Fifty-three patients had malignant and eight had benign obstructions. Because of the small diameter of the compressed stent (7 F), primary implantation of the stent without a previous catheter drainage was preferred. Postprocedural complications occurred in three patients (5%) (biliary pleuritis, peritonitis, hepatic artery aneurysm). The 30-day mortality rate was 8.2%. Reocclusions were observed in six of the patients with malignant obstructions (11%) (observation period, 1-10 months; mean, 4.5 months) and in two of the patients with benign stenoses (25%) (observation period, 3-21 months; mean, 9 months). The higher reocclusion rate of benign obstructions must be interpreted with care because of the small number of patients. From their preliminary experience, the authors conclude that expandable metal endoprostheses offer patency rates equal to those of plastic stents. The implantation trauma is reduced due to the small 7-F introducing catheter system. 
1	Clinical and pathological findings in prostates following intravesical bacillus Calmette-Guerin instillations. The prostates of 36 patients who were treated with intravesical bacillus Calmette-Guerin were evaluated by digital rectal examination and transrectal ultrasonography. When abnormal palpatory and/or ultrasonographic findings were detected, core needle biopsies from the suspicious areas were performed. Of the 36 patients 20 underwent biopsies of the prostate. Pathological findings revealed typical granulomas in 8 patients (3 caseating and 5 noncaseating multifocal granulomas). Nonspecific chronic prostatitis was noted in 4 patients and benign prostatic hyperplasia was noted in 8. The number of bacillus Calmette-Guerin instillations ranged from 6 to 19. The interval from initiation of therapy to biopsy ranged from 1.5 to 14.5 months. Caseating granulomas were found during the early course of bacillus Calmette-Guerin instillations (1.5 to 3.0 months), whereas noncaseating granulomas were detected at later stages (4 to 14.5 months). These findings present a high incidence of granuloma formation in patients treated with intravesical bacillus Calmette-Guerin. The duration of therapy is a determinant factor in the induction of granuloma type. 
2	Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study. A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities. 
5	Recurrent peritonitis: evidence for possible viral etiology. A 45-year-old woman who was treated with continuous ambulatory peritoneal dialysis (CAPD) developed recurrent peritonitis characterized by cloudy effluents, elevated white blood cell (WBC) counts (predominantly lymphocytes), and negative culture results. This case report suggests that she may have had viral peritonitis as indicated by a positive viral culture, the presence of viral antibodies in serum and peritoneal dialysis effluent (PDE), hematological findings, and cell surface receptor studies. The possibility of a viral cause should be considered in patients with culture-negative peritonitis, especially if they do not respond to antibiotics. 
1	Rectus abdominis muscle flap with microvascular anastomoses for repair of recurrent sarcoma. After radical resection of a recurrent leiomyosarcoma, the thoracic wall was stabilized with a Gore-Tex graft. The skin and soft tissue defect was repaired with a large rectus abdominis flap in which the circulation was secured by end-to-end microvascular anastomosis of the inferior epigastric artery to the internal mammary artery, which had to be cut during tumor removal. 
3	Multiple cranial nerve deficits after ethylene glycol poisoning. We report the cases of two patients who developed cranial nerve palsies after drinking ethylene glycol. A 33-year-old man developed multiple cranial nerve deficits nine days after the ingestion of ethylene glycol in a suicide attempt. Clinical findings included profound bilateral cranial nerve VII palsies and severe dysfunction of cranial nerves IX and X. The neuropathy occurred despite treatment with hemodialysis. The dysphagia completely cleared within two weeks, but at six months a severe bilateral cranial nerve VII dysfunction persisted. A 22-year-old man undergoing hemodialysis for ethylene glycol-induced renal failure developed bilateral cranial nerve VII dysfunction 14 days after ingestion. At a three-month follow-up, the patient demonstrated only moderate functional recovery. The etiology of the cranial nerve deficits is unknown but may be related to oxalate crystal deposition of ethylene glycol-induced pyridoxine dysfunction. 
5	Intraabdominal hemorrhage as a result of segmental mediolytic arteritis of an omental artery: case report. This article describes the fifth reported case of segmental mediolytic arteritis and the second in a survivor. The patient had intraabdominal bleeding as a result of a ruptured omental artery. The pathologic and arteriographic findings are described. The pathology is characterized by segmental disruption of the medial smooth muscle cells and the initiation of mediolysis. Mediolysis is associated with marked segmental thinning of the vessel wall, often with only the adventitia intact. Fibrin is deposited at the adventitial and medial surfaces, and hemorrhage into the media may occur. As in this reported case, lysis of the adventitia leads to sudden, often catastrophic intraabdominal hemorrhage. Little associated adventitial inflammation occurred. Segmental mediolytic arteritis seems to involve the intra-abdominal muscular arteries in elderly patients with nonspecific abdominal symptoms. An angiogram showed patchy areas of narrowing involving ileal, gastroduodenal, and renal arteries that correlated with the pathologic findings observed in the excised omental arteries. 
4	Double-blind randomized trial of perioperative fibrinolytic enhancement for femoropopliteal bypass. Patients with rest pain or acute peripheral arterial thrombosis are known to have impaired endogenous fibrinolysis, which is associated with an increased risk of early vascular graft thrombosis. This risk is exacerbated by the fibrinolytic shutdown which is known to occur after major surgery. Stanozolol, which has been demonstrated to enhance endogenous fibrinolysis, was therefore used in an attempt to prevent this perioperative fibrinolytic shutdown and so enhance graft patency. Twenty-seven patients were randomized to receive either 50 mg stanozolol or placebo intramuscularly 24 h before operation, followed by a 6 week course of either 5 mg stanozolol or placebo orally, twice daily. On the second day after operation, 10-11 MBq of autologous 111indium-labelled platelets were injected, with scanning over the graft on the 3 following days. Despite using a large depot of stanozolol, significant effects, such as raised plasminogen (P less than 0.001), reduced fibrinogen (P less than 0.001) and reduced euglobulin lysis time (P less than 0.001), were not seen until the seventh day after operation, with maximum benefit at 6 weeks. This was reflected in the 111indium-labelled platelet deposition studies. The placebo group had a progressive increase in platelet deposition on all 3 days. In contrast, those receiving stanozolol showed a lower, static picture of deposition. However, these changes did not attain statistical significance. Three patients experienced early graft thrombosis, two in the placebo group and one in the stanozolol group. Only an incomplete inhibition of the perioperative fibrinolytic shutdown was achieved. Much longer preoperative courses are thus required to allow the maximum effect to be present at the most crucial time. At present, perioperative fibrinolytic enhancement does not appear to be a practical proposition, and we must await the development of new safer and more potent agents. 
4	Accelerated transmural gradients of energy compound metabolism resulting from left ventricular hypertrophy. Eighteen dogs underwent transmural left ventricular biopsies for adenosine triphosphate and suturing of the noncoronary cusp, creating valvular aortic stenosis. Three months after aortic stenosis and the subsequent development of left ventricular hypertrophy, animals underwent repeat transmural left ventricular biopsies followed by total myocardial ischemia at 37 degrees C. Left ventricular tissue samples for adenosine triphosphate and lactate levels were determined at 15-minute intervals and compared with 15 control animals. No significant difference between subendocardial and subepicardial adenosine triphosphate levels was found between left ventricular samples taken before left ventricular hypertrophy and 3 months after left ventricular hypertrophy. Significant differences in adenosine triphosphate utilization occurred between subendocardial and subepicardial layers in control and left ventricular hypertrophy myocardium, however. The gradient between the subendocardium and the subepicardium was significantly increased by left ventricular hypertrophy (p less than 0.05). Significant differences also occurred within the same layer when left ventricular hypertrophy and control groups were compared. During total ischemia, lactate concentration was significantly greater within the subendocardium than within the subepicardium in left ventricular hypertrophy. The onset of ischemic contracture was 48.2 +/- 2.1 minutes in left ventricular hypertrophy versus 62.3 +/- 1.8 minutes in control hearts (p less than 0.01). Subendocardial intramyocardial pressure increased significantly earlier than subepicardial in both left ventricular hypertrophy and control hearts. Adenosine triphosphate was used, and lactate accumulated more rapidly in animals with a more pronounced hemodynamic gradient. These data show that after left ventricular hypertrophy, adenosine triphosphate stores in the subendocardium and the subepicardium are unchanged from control values, yet the rates of adenosine triphosphate utilization and lactate accumulation during total ischemia are significantly increased. Furthermore, the subendocardial to subepicardial gradient of adenosine triphosphate utilization during ischemia found in normal hearts is markedly increased by left ventricular hypertrophy. 
4	Chest pain in teenagers. When is it significant? Chest pain in teenagers often has no obvious organic cause. Onset of symptoms with an emotionally stressful situation may indicate psychogenic chest pain. The differential diagnosis also includes cardiac, musculoskeletal, gastrointestinal, and respiratory disorders. Routine testing generally does not help to establish a diagnosis and may even do harm by reinforcing a patient's unspoken fear of serious illness. Most teenagers with chest pain have no such illness, and symptoms usually resolve without therapy. An important role for primary care physicians is to provide support during evaluation and follow-up. 
5	Desmopressin in nocturnal enuresis. The effect of intranasal desmopressin on primary nocturnal enuresis was investigated in a study divided into 2 parts in which the first part was a randomized, double-blind, placebo-controlled cross-over study of 52 Finnish school children 5 to 13 years old. A variety of approaches had previously been attempted in most children, including water deprivation, night awakenings, enuresis alarm and imipramine, without success. The patients were randomized to 4 periods of 3 weeks each: 2 periods on placebo and 2 periods on 20 micrograms. desmopressin spray. The entire 12-week treatment period was preceded and followed by control periods (without treatment). The number of dry nights, measured as calculated averages per week, increased significantly (p less than 0.01) from 0.6 dry nights during pre-treatment to 4.3 and 4.6 dry nights per week during the 2 desmopressin treatment periods, respectively. The placebo responses were 2.1 and 2.4 dry nights per week, respectively. The second part of the study was an open dose-finding and drug safety study of a further 3 months in duration. The aim was to evaluate the efficacy and tolerance of 20, 30 and 40 micrograms. doses. All 47 patients who relapsed during the post-treatment period in part 1 were included. During this period 53% of the patients responded fully, 19% were intermediate responders and 28% did not respond. As reported in other studies most patients suffered relapse after treatment. During continued treatment for 3 months at doses between 20 and 40 micrograms. desmopressin was well tolerated, had no effect on body weight or blood pressure and did not cause any adverse reactions. 
1	'High single-dose' European PUVA regimen also causes an excess of non-melanoma skin cancer. We report the results of a long-term (12.8 years) follow-up study of the detection of malignant and benign skin tumours in patients with psoriasis, who were treated with PUVA according to the European, 'high single-dose' regimen. A total of 13 squamous cell carcinomas (SCC) and 24 basal cell carcinomas (BCC) were diagnosed in 11 of 260 patients. The incidence of both SCC and BCC was increased in comparison with the general Dutch population. The ratio of SCC to BCC in the general population was 1:8 but was 1:2.5 in our study group. A positive correlation was observed between the development of SCC and the total UVA dosage, the age of the patient at the start of the PUVA treatment and a history of arsenic use. This dose-related increase in the incidence of SCC, reported in studies from the U.S.A., has not been found in earlier European studies. The average time period between the start of PUVA therapy and the diagnosis of the first malignant skin tumour was 6.0 years for SCC and 4.7 years for BCC. Among the 49 benign skin tumours were actinic keratoses, a keratoacanthoma and 'PUVA keratoses', a newly described hyperkeratotic lesion, especially found in PUVA-treated patients. 
5	Importance of sampling method in DNA analysis of lung cancer. Lung carcinomas are characterised by considerable histological variation within the tumour. The possible effects of this morphological heterogeneity on the estimation of tumour ploidy were investigated. Multiple tissue blocks were systematically taken from 20 lung tumours and analysed by flow cytometry. The routine, archival paraffin wax embedded diagnostic blocks from these cases were also analysed. Nineteen (95%) of the tumours were shown to contain aneuploid stemlines by systematic sampling, but if only one of these systematic tissue blocks had been taken from each case the incidence of DNA aneuploidy could have been as low as 45%. Only 15 (75%) tumours were aneuploid when all the routine archival blocks were analysed, but by specifically selecting tumour areas from the archival material the accuracy of this method was increased to 90%. It is concluded that tumour sampling methods are of primary importance in assessing the DNA content of lung tumours. Routine paraffin wax embedded archival tissue provides a suitable source of material for this purpose, provided that "turnover" selection is carried out. 
4	Medicare Peer Review Organization preprocedure review criteria. An analysis of criteria for three procedures The Medicare Peer Review Organization (PRO) program includes preprocedure review using explicit criteria to assess the appropriateness of specific procedures. This study evaluates the variability in the PRO preprocedure criteria for the three procedures most frequently reviewed by PROs: carotid endarterectomy, cataract removal, and cardiac pacemaker implants. In August 1989, the PRO review criteria were received from the Health Care Financing Administration. To provide a reference point for reviewing the PRO criteria, national practice guidelines for these three procedures were identified. Wide variability was demonstrated in the PRO procedure-specific carotid endarterectomy and cataract removal review criteria among PROs, and the criteria differed significantly from the identified practice guidelines. The criteria for cardiac pacemaker implants were somewhat less variable, and were based, to varying degrees, on practice guidelines developed by the American College of Cardiology (ACC). Greater attention is needed to improve the development of review criteria, including the use of relevant practice guidelines, to ensure that review criteria are optimal. 
1	Presentation of breast carcinoma as Volkmann's contracture due to skeletal muscle metastases. Metastases to the skeletal muscles are extremely rare. They usually occur during the course of a pulmonary or digestive carcinoma. We describe a case of breast carcinoma presenting with forearm muscle metastases and Volkmann's type contracture. 
5	Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism. Between 1982 and 1989, 145 patients underwent operations for persistent or recurrent primary hyperparathyroidism (HPT). At re-exploration, 15 patients (10.3%) were found to have locally recurrent parathyroid tumors (11 patients with adenoma and 4 with carcinoma). These 15 patients had 28 previous operations at outside institutions for HPT. Patients with locally recurrent HPT secondary to adenoma had a longer disease-free interval than patients with locally recurrent carcinoma. At the time of evaluation at the National Institutes of Health (NIH) for recurrent or persistent HPT, each patient was symptomatic and patients with carcinoma had significantly more symptoms and higher serum levels of calcium and parathyroid hormone than patients with adenoma. Locally recurrent parathyroid neoplasm was correctly localized by preoperative testing in 14 of 15 patients. These 15 patients underwent 18 reoperations at NIH for excision of locally recurrent parathyroid tumors. Following the final reoperation (two patients had more than one procedure), each patient had normal serum levels of calcium. In addition each patient remains biochemically cured (based on normal serum calcium level), with a median follow-up interval of 21 months. Local recurrence of parathyroid adenoma comprises a small but significant proportion of cases of recurrent or persistent HPT and can be indistinguishable from parathyroid carcinoma. Findings suggestive of carcinoma include shorter disease-free interval, higher serum levels of calcium and parathyroid hormone, and histologic appearance. Whether the locally recurrent parathyroid neoplasm is benign or malignant, aggressive surgery can control serum levels of calcium in these patients with acceptable rates of morbidity. 
3	Traumatic hyphaema: a retrospective study of 314 cases. A retrospective study was made of 314 consecutive cases of traumatic hyphaema in a mixed urban and rural Scottish population. Secondary haemorrhage occurred in 4.1% of cases and was not associated with a worsening of final visual acuity. There were no identifiable risk factors for secondary haemorrhage. Poor visual outcome was in most cases attributable to retinal pathology. The use of antifibrinolytic agents does not appear to be necessary in such a population, and the importance of detecting associated retinal detachment is emphasised. 
1	Human papillomavirus screening for women with atypical Papanicolaou smears. A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice. 
2	Intracatheter streptokinase for recurrent peritonitis in CAPD. Intracatheter streptokinase (SK) is advocated as effective treatment with minimal adverse effects in both recurrent bacterial peritonitis and catheter fibrin blockage in continuous ambulatory peritoneal dialysis (CAPD) patients. We reviewed 35 instillations in 20 patients noting a high (86%) side effect profile consisting of fever, onset of turbid dialysis effluent and/or abdominal pain. SK probably releases fibrin clot containing bacteria, leukocytes and debris from the colonized catheter into the peritoneal cavity causing a "peritonitis-like syndrome" of 1 to 3 days duration. Fungal peritonitis occurred after SK in 2 patients. Failure of SK therapy was encountered in Staphylococcus epidermidis infection (p less than 0.05 versus other organisms), which may be related to its protective capsular polysaccharide slime and ability to adhere to plastic prosthetic devices. SK, in this study, was useful treatment in relapsing bacterial peritonitis (50% overall cure) but failed to correct catheter malfunction. 
4	Coagulation factor abnormalities as possible thrombotic risk factors after Fontan operations. Severe thromboembolism occurred in 3 of 37 patients who had undergone Fontan-type operations for correction of congenital heart defects several months to years after the operation. The patients were screened for coagulation factor abnormalities to find out whether known prothrombotic risk factors could explain the high frequency of thromboembolism. 63 abnormalities were found in 24 of the 37 patients. The commonest and most pronounced abnormality was deficiency of protein C, a known risk factor. Concentrations of antithrombin III and factors II and X were significantly lower in protein-C-deficient patients than in those with normal protein C concentrations. These findings suggest that the high thrombotic risk in these patients is caused or at least associated with an imbalance between procoagulant and anticoagulant factors. 
2	Mortality and causes of death in Crohn's disease. Review of 50 years' experience in Leiden University Hospital. Six hundred and seventy one patients (52.5% women) with Crohn's disease seen at Leiden University Hospital between 1934 and 1984 were identified. Follow up was 98.2% complete. Sixty four (9.7%) of the 659 patients died. The cause of death was related to Crohn's disease in 34 patients, probably related to the disease in four, and unrelated, from incidental causes, in 25. The cause of death could not be identified in one patient. There was a significant decrease of deaths related to the disease after 1973. Causes of death such as amyloidosis and malnutrition have disappeared and postoperative deaths have decreased. The standardised mortality ratio showed an excess mortality of 2.23 for all patients. It was higher for women (3.30) than for men (1.76). A comparison of two recent 10 year periods showed a significant decrease in standardised mortality ratio in men but not in women. Patients whose disease started before the age of 20 years had an excess mortality compared with older patients. This study supports the view that the prognosis of Crohn's disease has improved in general but high quality medical and surgical management is important particularly for younger patients. 
4	Primary balloon dilatation of coarctation of the aorta in neonates. Primary balloon dilatation of coarctation of the aorta was attempted in 10 consecutive neonates (age range 2-23 days). The coarctation site was crossed and the balloon inflated in all but one patient. In two patients with associated severe isthmal hypoplasia there was no change in the gradient after dilatation. In the remainder, the residual gradients were trivial and angiography showed complete relief of coarctation. Severe recoarctation developed 5-12 weeks after dilatation in five patients, each considered to have had an excellent initial result. The coarctation was rapidly progressive in three patients in whom Doppler studies within two weeks of the development of recoarctation had shown no significant gradient. In the other two patients progressive restenosis was charted by Doppler examinations over the course of 6-8 weeks. Three patients had a second, initially successful, dilatation procedure. One patient remained well with no residual gradient 18 weeks later. Stenosis recurred within eight weeks in the other two, and both have undergone successful surgical repair. Balloon dilatation of a native coarctation of the aorta gave excellent immediate results in most neonates. Severe isthmal hypoplasia is, however, a contraindication to balloon dilatation and early restenosis is an important problem. These results do not support the continued use of primary balloon dilatation of coarctation of the aorta in neonates. 
5	Detailed examination of complete bioprosthetic heart valves. Six (3 control and 3 explanted) bioprostheses were examined histologically after embedding the complete valve in "plastic" and sectioning across the valve at 90 degree to the horizontal plane, and then horizontally across a stent post, with a low speed saw. The prostheses, porcine or pericardial, had been in place 52 to 121 months. In addition to cusp changes of degeneration and calcification that have been previously reported, the authors found extensive pannus deposition on the cloth covering the inflow surface of the prostheses, with some extension onto the biologic components; evidence of insudation of tissue fluid and ingrowth of fibroblasts; deposition of collagen; and infiltration of mononuclear cells in the interstices and interfaces. Non-biologic components showed changes which may have affected prosthesis function. The synthetic material covering the metal/plastic frame showed interstitial mononuclear cells. Two of the three explanted valves showed changes in the polymeric plastic, and one in the metal components, including accentuated notching along the surfaces when compared to unimplanted prostheses. A larger number of prostheses must be examined before definite conclusions can be drawn. 
5	Radiographic detection of recurrent carious lesions associated with composite restorations. The greatest potential problem associated with posterior composite restoration is secondary caries detection. It is essential that secondary caries is detected as early as possible to enhance the prognosis for a successful treatment outcome. This laboratory study evaluated the optimum level of radiopacity of composite materials for radiographic detection of secondary carious lesions associated with composite materials. Results indicated that for the radiologic detection of secondary caries, it is sufficient for composite materials to have the same level of radiopacity as enamel. 
4	Characterization of auscultatory gaps with wideband external pulse recording. Three types of auscultatory gaps, called G1, G2, and G3, that occur during blood pressure measurement have been identified by using wideband external pulse recording. We have previously shown that the wideband external pulse recorded during cuff deflation can be separated into three components (K1, K2, and K3), one of which (K2) is closely related to the Korotkoff sound. G1 occurs with cuff pressure just below systolic and is characterized by the presence of K1 and K2 with intermittent disappearance of K2. G1 gaps are related to a phasic decrease of arterial (systolic) pressure and were exhibited by 13 of 60 hypertensive patients. G2 gaps are related to a phasic increase of arterial (diastolic) pressure, occur when cuff pressure is just above diastolic, and are characterized by the presence of K1, K2, and K3 with intermittent disappearance of K2. Seven of 60 hypertensive patients exhibited a G2 gap. G3 gaps occur with cuff pressure between systolic and diastolic and are characterized by an underdeveloped or blunted K2 signal. Three of 60 hypertensive patients exhibited a G3 gap. The identification of auscultatory gaps in relation to the wideband external pulse provides a qualitative measure of their existence, can be of significant value in better understanding aspects of the auscultatory blood pressure measurement technique, and provides an objective basis with which to better understand the mechanisms that cause them. 
1	Synergism of ara-C-imuvert combination in aborting the development of transplanted chloroleukemia in the rat. The development of chloroleukemia in the rat after transplantation of C51 chloroma cells can be aborted by treatment with an exogenous source of differentiating activity (DA) or by stimulation of endogenous DA production by the administration of Imuvert, a biologic response modifier. Success or failure of treatment was determined by the ratio of DA to leukemic cell load. Accordingly, in the present study we examined the hypothesis that treatment with cytosine arabinoside (ARA-C) to reduce the leukemic cell load coupled with Imuvert would be more effective than either given alone. Treatment with ARA-C-Imuvert aborted the development of chloroleukemia in 79% of the animals in contrast to 0%, 9% and 45% in animals treated with buffer, ARA-C, or Imuvert respectively. These results suggest that stimulation of endogenous DA in combination with cytoreductive agents offers a potentially curative treatment for myelogenous leukemia. 
5	Choledochotomy for calculous disease in the elderly. To determine the risk of operations on the biliary tract in the elderly, we retrospectively examined 56 patients 80 years of age or older undergoing choledochotomy for calculous disease and compared their outcomes with those of a contemporary group of 257 patients undergoing similar surgery. Thirty of 56 elderly patients (54%) required urgent surgery for acute cholangitis, acute cholecystitis, or obstructive jaundice (serum bilirubin greater than 5 mg/dL), compared with 97 of 257 younger patients (38%) (p = 0.029). Mortality in elderly patients was significantly higher (5 of 56) than in younger (6 of 257) patients (p = 0.015). In three of the five patients who died, urgent surgery was performed for obstructive jaundice, reflecting the higher mortality experienced by jaundiced patients in the entire series (9.4%). Biliary cultures grew organisms in 25 of 27 elderly patients (93%). This is in contrast to findings of bactibilia in 62 of 118 patients (53%) under the age of 80 (p = 0.001). Similarly, preoperative blood cultures were positive more often in elderly (63%) than in younger patients (26%) (p = 0.007). Mean postoperative hospital recovery was longer in the elderly group (16.2 +/- 8.5 days) than in the younger group (12.2 +/- 9.3 days) (p = 0.002). In conclusion, elderly patients, particularly those with obstructive jaundice, are at higher risk for complicated biliary tract disease necessitating choledochotomy. They appear to be more susceptible to bactibilia and bacteremia, and require longer hospital recovery than younger patients. 
4	Clinical evaluation of high-frequency (ultrasonic) mechanical debridement in the surgical treatment of calcific aortic stenosis. Repair of aortic valve stenosis due to calcific degeneration may lead to hemodynamic and clinical improvement without the problems inherent with prosthetic valves. We have evaluated the use of a device capable of debriding calcium, the Cavitron ultrasonic aspirator (CUSA), as an adjunct to mechanical debridement in the repair of calcific aortic stenosis. Ten patients (five women), ages 63 to 83 years, were studied by M-mode, two-dimensional, and Doppler echocardiography before and an average of 26 (range 3 to 124) days after this procedure. The degree of calcification of the valve cusps was clearly reduced. The maximal cusp excursion increased from 0.7 +/- 0.1 cm preoperatively to 1.5 +/- 0.4 cm postoperatively (p = 0.006). The peak aortic gradient fell from 80 +/- 36 mm Hg to 28 +/- 10 mm Hg (p = 0.0007). The mean aortic gradient fell from 53 +/- 20 mm Hg to 16 +/- 5 mm Hg (p less than 0.0001). Aortic valve area calculated by the continuity equation increased from 0.6 + 0.2 cm2 to 1.6 +/- 0.6 cm2 (p = 0.0009). No patient had more than mild aortic insufficiency preoperatively. Postoperatively, color Doppler flow mapping revealed severe aortic insufficiency in two patients. Seven patients had further echocardiographic evaluation 99 (range 33 to 196) days after the procedure. These studies revealed the development of severe aortic insufficiency in an additional four patients. Four patients with severe symptomatic aortic insufficiency eventually underwent aortic valve replacement. Pathology revealed scarring and retraction of the aortic cusps. Widening of the commissures was responsible for the severe aortic insufficiency. 
1	Cisplatin, continuous-infusion 5-fluorouracil, and intermediate-dose methotrexate in the treatment of unresectable non-small cell carcinoma of the lung. Forty-one patients with unresectable non-small cell carcinoma of the lung (NSCCL) were treated with cisplatin 20 mg/m2/d for 5 days as a daily bolus injection, 5-fluorouracil 800 mg/m2/d by continuous infusion for 5 days, and intermediate-dose methotrexate 200 mg/m2 on days 15 and 22 of a 28-day cycle (PFM). One complete and 23 partial responses were observed, yielding an overall response rate of 60%. There was no significant difference in response rates based on histologic subtype or extent of disease (locally unresectable versus metastatic). Median duration of response was 6 months, and the median survival of all patients was 10 months. Two patients with unresectable disease at presentation became resectable after chemotherapy and remain disease-free at 46+ and 53+ months. Toxicity was modest, with oral mucositis the major adverse effect. Clinically important neutropenia was uncommon. PFM is an active regimen in NSCCL and deserves further study in the "neoadjuvant" setting. 
4	Transoesophageal echocardiography improves the diagnostic value of cardiac ultrasound in patients with carcinoid heart disease. Transthoracic and transoesophageal cardiac echocardiography and Doppler investigations were performed in 31 consecutive patients with malignant midgut carcinoid tumours. The transoesophageal images allowed measurement of the thickness of the atrioventricular valve leaflets and the superficial wall layers on the cavity side of both atria. The mean thickness of the anterior tricuspid leaflet was significantly greater than that of the mitral valve--a difference not seen in a control group of age-matched patients without carcinoid tumours and with normal cardiac ultrasound findings. In addition, the edges of the tricuspid leaflets were thickened giving them a clubbed appearance. Tricuspid incompetence was detected transoesophageally in 71% of the patients with carcinoid compared with 57% by transthoracic investigation. The inner layer of the right atrial wall in the carcinoid patients was significantly thicker than that of the left atrium and that of both atria in the controls. Furthermore, patients with other signs of severe carcinoid heart disease had significantly thicker mean right atrial luminal wall layer than those with less or no signs of right heart disease. Transoesophageal cardiac ultrasound investigation improved the diagnostic accuracy and seemed to show the structural changes typical of carcinoid heart disease established by histopathological investigations. 
5	Myocardial magnesium: relation to laboratory and clinical variables in patients undergoing cardiac surgery. Magnesium concentration was measured in the right atrial appendage of 100 patients undergoing cardiac surgery and associations with serum and mononuclear blood cell magnesium, other laboratory values and patient clinical variables were studied. In addition, magnesium was measured in the right atrial appendage and left ventricular free wall in 23 autopsy subjects to determine whether there was a proportional relation between right atrial appendage and left ventricular free wall magnesium. The mean left ventricular free wall/right atrial appendage magnesium ratio was 2.13 +/- 0.39 (r = 0.67, p = 0.0009). In the group with cardiac surgery, the right atrial appendage magnesium concentration correlated inversely with age (r = -0.54, p = 0.001). The mean right atrial appendage magnesium concentration (micrograms/g wet weight tissue) was lower in patients with postoperative cardiac arrhythmia than in those without arrhythmia (103 +/- 13 versus 111 +/- 10, p = 0.009) and in diabetic than in nondiabetic patients (103 +/- 13 versus 109 +/- 12, p = 0.02). The right atrial appendage magnesium concentration also tended to be lower in patients receiving potassium/magnesium-losing diuretics, although this difference did not achieve statistical significance (105 +/- 14 versus 109 +/- 11, p = 0.16). Right atrial appendage magnesium concentration correlated positively with serum creatinine concentration (r = 0.31, p = 0.002) and negatively with serum calcium concentration (r = -0.29, p = 0.013). Serum magnesium did not correlate with right atrial appendage or mononuclear blood cell magnesium concentration or clinical variables. There was a statistically significant correlation between mononuclear blood cell and right atrial appendage magnesium concentrations in some subgroups of patients. 
5	Morphological observations late (greater than 30 days) after clinically successful coronary balloon angioplasty. This report describes clinical, morphological, and histological findings late (1.6-24.1 months [average, 8.2 months]) after clinically successful coronary balloon angioplasty in 20 necropsied patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 (70%) of patients, including six patients with sudden coronary death. Of the 20 patients, 14 (70%) had cardiac causes of death and six (30%) had noncardiac causes of death. Two major subgroups of histological findings were observed: 1) intimal proliferation (60%) and 2) atherosclerotic plaques only. Of the eight sites with atherosclerotic plaques only, six were eccentric lesions and two were concentric lesions. No morphological evidence of previous angioplasty injury (cracks, breaks, or tears) was observed in the eight patients with atherosclerotic plaques only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphological findings at angioplasty restenosis sites, specific treatment strategies for coronary artery balloon angioplasty restenosis are proposed. 
4	Torsade de pointes: a critical care nurse's dilemma. Torsade de pointes is a polymorphous ventricular tachycardia characterized by a gradual change in the direction of the QRS complex. Because critical care nurses are the first to recognize arrhythmias, they require the knowledge and skill to intervene appropriately. This case report focuses on identification of the characteristics, contributing factors, therapeutic modalities, and relevant nursing diagnoses for the patient with torsade de pointes. 
5	The effect of intravenous fixed-dose heparin during total hip arthroplasty on the incidence of deep-vein thrombosis. A randomized, double-blind trial in patients operated on with epidural anesthesia and controlled hypotension. Heparin was given in fixed doses intravenously during unilateral primary total hip-replacement operations in a prospective, double-blind trial to assess the effect on the incidence of deep-vein thrombosis. One hundred and fifty patients were randomly assigned to one of two groups before the operation. Twenty-four patients were excluded from the study, leaving 126 patients. Group I consisted of sixty-six patients who received saline solution intravenously, and Group II comprised sixty patients who received heparin. All patients had epidural anesthesia with controlled hypotension. Fixed doses of heparin were administered five minutes before the operative incision was made and every thirty minutes throughout the operation. Mean arterial pressures were maintained at between fifty and sixty millimeters of mercury in all patients. Ascending venography was done on the seventh day after the operation. The incidence of deep-vein thrombosis was 24 per cent (sixteen of sixty-six patients) in Group I and 8 per cent (five of sixty patients) in Group II; the difference is significant (p = 0.03). The intraoperative loss of blood averaged 220 +/- 79 milliliters in Group I compared with 269 +/- 109 milliliters in Group II. An average of less than one unit of blood was transfused for each patient in each group. Postoperatively, there was no difference between the groups with regard to the amount of drainage that was collected in a Hemovac device or the values for hematocrit. 
4	The role of calcium channel blockers in the treatment of essential hypertension. Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk. 
4	Isolation of preferentially expressed genes in the kidneys of hypertensive rats. By differential hybridization, three complementary DNAs designated as S3, S2, and SA were isolated, and the corresponding messenger RNAs (mRNAs) were differentially expressed between the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. S3 is identical to cytochrome P450 IV A2. SA encoded a protein of 546 amino acid residues, and its carboxyl terminal region had a slight homology to luciferase. No homologous sequence has been reported in S2 sequences. S3 mRNA was about four times more abundantly expressed in the kidneys of 28-day-old SHR than in those of age-matched WKY rats, but there was no difference at age 16 weeks. A low NaCl diet positively modulated the expression of the S3 gene. S2 mRNA was almost undetectable in the kidneys of 28-day-old WKY rats but was clearly detected in those of age-matched SHR. The expression level of S2 mRNA in the livers of 16-week-old SHR was about five times higher than that of age-matched WKY rats. The expression of S2 mRNA in the livers was modulated by dietary NaCl and captopril. SA mRNA was more than 10 times more abundantly expressed in the kidneys of SHR than in those of WKY rats from age 4 weeks. With the administration of captopril, the expressions of SA mRNA in the livers of SHR were positively modulated. Because these three genes are not only differentially expressed between SHR and WKY rats but also related to sodium metabolism or blood pressure control, the identification of these genes may provide important probes to examine the mechanisms of hypertension. 
4	Coronary collateral circulation in coronary artery disease and systemic hypertension. The extent and functional capacity of coronary collateral circulation in patients with systemic hypertension has not been elucidated. In the present study, 313 patients with coronary artery disease were studied to evaluate coronary collateral circulation in relation to the presence of systemic hypertension and left ventricular hypertrophy. Patients had greater than or equal to 95% diameter luminal obstruction of either the left anterior descending or the right coronary artery. Patients were classified into 2 groups: The hypertensive group consisted of 61 patients, mean age 55 +/- 9 years, with systemic hypertension, and the normotensive group consisted of 252 patients, mean age 53 +/- 8 years, without hypertension. The hypertensive group had more severe angina pectoris and less history of healed myocardial infarction than the normotensive group (p less than 0.001). Left ventricular wall thickness was 1.26 +/- 0.1 cm in the hypertensive and 1.03 +/- 0.06 cm in the normotensive group (p less than 0.001). The hypertensive group had more extensive coronary collateral circulation than the normotensive group (p less than 0.01). There was a positive relation between coronary collateral circulation and left ventricular wall thickness (p less than 0.001). These results indicate that patients with systemic hypertension and coronary artery disease have an increase in coronary collateral circulation corresponding to the degree of left ventricular wall thickness. 
3	Substance abuse and cerebral blood flow. OBJECTIVE AND METHOD: This paper reviews acute and chronic effects of drugs of abuse on cerebral blood flow (CBF) and metabolism and their clinical significance. The most important source of information for the review is human research reports published in refereed journals. A few animal studies, book chapters, and abstracts that are especially relevant are also included. RESULTS: In humans, ethanol in small doses produces cerebral vasodilation; higher doses induce cerebral vasoconstriction. Chronic alcoholism is associated with reduced CBF and cerebral metabolism. Sedatives and antianxiety drugs lead to global reduction in CBF and cerebral metabolism. Caffeine, even in small doses, is a potent cerebral vasoconstrictor. Cerebral vasodilation is seen immediately after cigarette smoking, but chronic smokers show global reduction in CBF. Changes in CBF after marijuana smoking are variable; both increases and decreases are seen. Chronic marijuana smoking, however, seems to reduce CBF. Most inhalants and solvents are vasodilators; chronic abuse is accompanied by a decrease in CBF. A number of drugs of abuse, including ethanol, amphetamines, cocaine, nicotine, and caffeine-phenylpropanolamine combinations, increase the risk for stroke. Reduction in CBF associated with chronic use of ethanol, nicotine, inhalants, and solvents is at least partially reversible upon abstinence. CONCLUSIONS: Topics for future research include regional brain function, which mediates drug-induced mood changes (euphoria); CBF concomitants of psychological and physiological characteristics that increase addiction potential; changes in CBF that accompany withdrawal syndromes; mechanisms responsible for drug-induced stroke; and effects of functional and organic complications on CBF. 
4	Results and complications of angioplasty in aortoiliac disease Percutaneous transluminal angioplasty was used to treat 340 aortoiliac lesions in 200 patients who were followed for as long as 90 months (mean, 28.7 months; median, 23 months). The initial success rate was 94.7% for lesions and 93.0% for patients. The indications for percutaneous transluminal angioplasty included claudication in 117 patients (58.5%), rest pain or ischemic night pain in 47 (23.5%), limb salvage in 33 (16.5%), and aiding in wound healing in three (1.5%). In the series, 70% of the patients had two or more cardiovascular risk factors. Angioplasty was initially unsuccessful in 14 patients, and 10 patients were lost to follow-up. Follow-up was obtained in 176 patients. The long-term results were analyzed using the life table method to determine cumulative patency. Fourteen patients were considered failures because of recurrent disease or symptoms. The projected 7.5-year cumulative patency rate was 85%. When the response to redilatation was considered, the projected 7.5-year cumulative patency rate was 92%. The results indicate that percutaneous transluminal angioplasty can successfully correct aortoiliac lesions and provide a long-term benefit for as long as 7.5 years. 
1	Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma. Independent and interactive effects related to the development of hepatocellular carcinoma were assessed using a community-based case-control study for hepatitis B virus, habitual alcohol drinking, cigarette smoking, peanut consumption and history of hepatocellular carcinoma among the immediate family. All 200 male newly diagnosed hepatocellular carcinoma patients were recruited consecutively through the period of study as the case group from two teaching medical centers in northern and southern Taiwan. Healthy community residents matched one-to-one with cases on age, sex, ethnic group and residential area were selected as the control group. The carrier status of HBsAg and HBeAg was determined by blind radioimmunoassays, and other risk factors were obtained through standardized interviews according to a structured questionnaire. Conditional logistic regression analysis showed a significant association between hepatocellular carcinoma and the carrier status of HBsAg and HBeAg with an odds ratio of 16.7 and 56.5, respectively, for carriers of HBsAg alone and for carriers of both HBsAg and HBeAg. There was a dose-response relationship between cigarette smoking and hepatocellular carcinoma with an odds ratio of 1.1, 1.5 and 2.6, respectively, for those who smoked 1 to 10, 11 to 20 and more than 20 cigarettes a day. A significant association with hepatocellular carcinoma was also observed for the habitual alcohol consumer with an odds ratio of 3.4. Those whose immediate family had a history of hepatocellular carcinoma were more likely to have the disease develop, with an odds ratio of 4.6. However, the frequency of peanut consumption was not significantly associated with hepatocellular carcinoma. 
3	'Locked-in syndrome' for 27 years following a viral illness: clinical and pathologic findings. We describe a man who, after a presumed encephalitic illness, was "locked-in" for 27 years. His CT and autopsy findings showed atrophy of the brainstem and a cystic lesion at the base of the pons. He survived longer than most other patients in a similar state. 
5	Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem. 
4	Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. Acute lung injury characterized by increased microvascular permeability is one feature of multiple-organ system failure and the adult respiratory distress syndrome. Intestinal ischemia-reperfusion injury has been linked to this type of acute lung injury. The purpose of these experiments was to examine the pathogenic mediators that link the two processes, with particular emphasis on the roles of endotoxin and tumor necrosis factor alpha (TNF alpha). Previously described characteristics of the acute lung injury in this rat model of intestinal ischemia-reperfusion include pulmonary neutrophil sequestration, depletion of lung tissue ATP, alveolar endothelial cell disruption, and increased microvascular permeability. Plasma levels of TNF in the systemic circulation of sham-operated animals and those with intestinal ischemic injury less than 60 minutes in duration were very low or undetectable. Intestinal ischemia for 120 minutes was associated with TNF elevation to 1.19 +/- 0.50 U/mL. Reperfusion for periods of 15 and 30 minutes generated 5- to 10-fold increases in circulating TNF levels (6.61 +/- 3.11 U/mL, p greater than 0.05 and 10.41 +/- 5.41 U/mL, p = 0.004 compared to sham); however this increase in circulating TNF was transient and largely cleared within 60 minutes after initiating reperfusion. Portal vein endotoxin levels were found to increase significantly before the appearance of TNF in systemic plasma, suggesting that gut-derived endotoxin may induce TNF release from hepatic macrophages into the systemic circulation. Anti-TNF antibody attenuated the increase in pulmonary microvascular permeability in this preparation but did not prevent pulmonary neutrophil sequestration. These observations suggest that endotoxin and TNF have pathogenic roles in this acute lung injury, but that mechanisms of adherence of neutrophils to endothelial cells independent of TNF may be involved. The accumulation of neutrophils in the lung but the prevention of a vascular permeability increase in the presence of antibody to TNF may imply an in vivo role for TNF in the process of neutrophil activation. These studies provide additional evidence of the importance of the endogenous inflammatory mediators in the development of systemic injury in response to local tissue injury. 
5	Adenovirus colitis in the acquired immunodeficiency syndrome. Adenovirus was identified in colonic tissue by transmission electron microscopy or culture in 5 of 67 (7.4%) homosexual men seropositive for human immunodeficiency virus (51 with the acquired immunodeficiency syndrome) with diarrhea. Colonoscopy showed the mucosa to be normal in 3 cases and mildly inflamed in 2. Light microscopy showed foci of mucosal necrosis that contained chronic inflammatory cells and degenerating and necrotic epithelial cells with amphophilic nuclear inclusions. By transmission electron microscopy, hexagonal viral particles characteristic of adenovirus were identified within the inclusions. Only 1 patient was concomitantly infected by a second potential enteric pathogen. It was concluded that adenovirus, an uncommon enteric pathogen in immunocompetent adults, causes intestinal pathology and may be associated with diarrheal illness in persons with the acquired immunodeficiency syndrome. 
2	Towards a true prevalence of peptic ulcer: the Sorreisa gastrointestinal disorder study. This study, designed to overcome methodological problems inherent in earlier prevalence studies of peptic ulcer, was carried out in a municipality in northern Norway. It included the total population of 2027, aged 20-69 years, and comprised a questionnaire and search for previously diagnosed peptic ulcers in the local medical records for all subjects, and additional endoscopy of all subjects with dyspepsia and their matched healthy controls (n = 619). The overall prevalence was 10.5% in men and 9.5% in women, a sex ratio close to one and a higher duodenal:gastric ratio than previously reported from this region. A substantial 1% prevalence of asymptomatic ulcers was also observed. 
5	The clinical significance of fluid collections in acute pancreatitis. Computed tomography (CT) displays fluid collections in patients with acute pancreatitis as well defined intra- or extrapancreatic homogeneous areas with low attenuation numbers. We followed, prospectively, the clinical courses of 128 patients who had CT during an episode of acute pancreatitis, to determine the natural history and clinical significance of any fluid collections that developed. Fluid collections were found in 48 (37%) of the 128 patients with pancreatitis. Thirty-eight developed in the 86 (44%) patients with alcoholic pancreatitis, five in the 33 (15%) with biliary pancreatitis and five in the nine (55%) with other causes of pancreatitis (excluding chronic pancreatitis, trauma, or malignancy). On clinical follow-up of the 48 patients with fluid collections, 21 patients required operation; two died before an operation was done and 25 did not require operation. Operations were done to treat pseudocysts (14), abscess (5), and necrosis (3). One patient had an operation for a pseudocyst and an abscess. All 14 patients requiring operation for pseudocyst had collections greater than 7 cm and 13 of these patients had alcoholic pancreatitis. Of the 25 patients not requiring operation, five were lost to follow-up, and 19 of the 20 who had spontaneous resolution of their fluid collection(s) had collections less than 6 cm in diameter. The eight patients who required operative pancreatic debridement for abscess or necrosis had multiple small fluid collections. In summary, fluid collections were found in one-third of patients with acute pancreatitis and were often associated with the development of local complications. 
5	CD34 antigen expression in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. One characteristic of Philadelphia chromosome (Ph')-positive acute leukemia is the occasional presence of both lymphoid and myeloid features in the same leukemia. This phenomenon supports the theory that this subtype of acute leukemia arises from lymphoid-myeloid stem cell, pluripotent progenitors. Very few reports, however, describe the immunophenotype, especially CD34 antigen, of Ph'-positive acute lymphoblastic leukemia (ALL). It has been shown that CD34, the human progenitor cell antigen, is found on 1% or less of normal human bone marrow cells, approximately 30% of acute leukemias, and multipotent progenitor cells; CD34 is not found on normal peripheral blood cells. A high frequency of CD34 expression was found in children with Ph'-positive ALL: CD34 was positive for all six patients tested, and one had an acute mixed-lineage leukemia. These findings suggest the involvement of a pluripotent stem cell in Ph'-positive ALL. 
1	Dysplasia and DNA aneuploidy in a pelvic pouch. Report of a case. A patient with an 18-year history of ulcerative colitis was operated on with colectomy, mucosal proctectomy, ileoanal anastomosis, and an S-type pelvic pouch due to intractable chronic continuous disease. The patient was followed by endoscopic controls and biopsy sampling from the pouch at regular intervals. A gradual development of severe atrophy in the ileal mucosa was followed by the development of low grade dysplasia. At the most recent endoscopic control, 4 years after the construction of the pouch, biopsies were sampled also for flow cytometric DNA analyses. DNA aneuploidy was detected in a biopsy from the center of the pouch, and a biopsy taken immediately adjacent showed low grade dysplasia. These findings underline the importance of endoscopic follow-up after construction of a pelvic pouch and focus attention to the potential of malignant transformation of the mucosa. 
5	Round fingerpad sign: an early sign of scleroderma. We describe a clinical skin sign in scleroderma termed round fingerpad sign. This term refers to disappearance of the peaked contour on fingerpads and replacement with a hemisphere-like fingertip contour; this change is especially apparent on the ring fingers. A positive round fingerpad sign was found in 72 of 72 ring fingers in 36 patients with progressive systemic sclerosis in 69 of 72 ring fingers in patients with mixed connective tissue disease, and in 24 of 24 ring fingers of patients with Raynaud's phenomenon and sclerodactyly. In contrast, a negative round fingerpad sign was seen in 240 of 240 fingers in normal women (controls). The high sensitivity of this sign is noteworthy. A positive round fingerpad was seen in sign not only typical scleroderma patients but also in groups with less severe skin sclerosis (i.e., in those patients with mixed connective tissue disease or those with Raynaud's phenomenon and sclerodactyly). The sign is a new and useful clinical marker for the early diagnosis of scleroderma. 
4	Which drug prevents tachycardia and hypertension associated with tracheal intubation: lidocaine, fentanyl, or esmolol? Eighty patients, ASA physical status II-IV, scheduled for noncardiac surgery, were randomly assigned in a double-blind, placebo-controlled manner to receive a preintubation dose of either placebo, 200 mg lidocaine, 200 micrograms fentanyl, or 150 mg esmolol. Induction of anesthesia was accomplished with 4-6 mg/kg thiopental IV followed immediately by the study drug; 1-1.5 mg/kg succinylcholine was given at minute 1. Laryngoscopy and intubation were performed at minute 2 with anesthesia thereafter maintained with 1 MAC (+/- 10%) isoflurane in 60% nitrous oxide in oxygen at a 5 L/min flow for 10 min. Heart rate was recorded every 15 s and blood pressure every minute from induction until 10 min after intubation. Maximum percent increases in heart rate (mean +/- SE) during and after intubation were similar in the placebo (44% +/- 6%), lidocaine (51% +/- 10%), and fentanyl (37% +/- 5%) groups, but lower in the esmolol (18% +/- 5%) group (P less than 0.05). Maximum systolic blood pressure percent increases were lower in the lidocaine (20% +/- 6%), fentanyl (12% +/- 3%), and esmolol (19% +/- 4%) groups than in the placebo (36% +/- 5%) group (P less than 0.05), but not different from each other (P greater than 0.05). Only esmolol provided consistent and reliable protection against increases in both heart rate and systolic blood pressure accompanying laryngoscopy and intubation. 
5	Systemic pattern of free radical generation during coronary bypass surgery. Diffuse impairment of ventricular function after cardiac surgery may be related to the generation during reperfusion of the myocardium of free radicals derived from oxygen. Fifteen patients undergoing elective coronary bypass surgery were studied by previously described assays for peroxidised lipids and for isomerised lipids which were used as indices of free radical activity. Serial blood samples were obtained from systemic arterial, mixed venous, and coronary sinus catheters before, during, and after the ischaemic period. The patients underwent coronary artery surgery on cardiopulmonary bypass with a membrane oxygenator, relative hypothermia 30-34 degrees C, and intermittent cross-clamping of the aorta. During the ischaemic periods there were no significant changes in the indices of free radical activity. During the reperfusion phase there was a significant increase in free radical indices in arterial and mixed venous blood. A small rise in free radical indices in coronary venous blood was not statistically significant. These data indicate that free radical activity is increased in patients shortly after the cessation of cardiopulmonary bypass. The pattern of distribution between the different sampling sites suggests that much of the observed increase in isomerised and peroxidised lipids originates from tissues other than the myocardium. 
2	The human hepatic asialoglycoprotein receptor is a target antigen for liver-infiltrating T cells in autoimmune chronic active hepatitis and primary biliary cirrhosis. Autoantibodies to the human hepatic asialoglycoprotein receptor have been found in nearly 50% of the sera of patients with autoimmune chronic active hepatitis and in 15% of patients with primary biliary cirrhosis. In this study we demonstrate that the human hepatic asialoglycoprotein receptor is also a target antigen for T cell-mediated immune responses. Peripheral blood lymphocytes of 37% (7 of 19) of patients with autoimmune chronic active hepatitis and 33% (2 of 6) of patients with primary biliary cirrhosis showed a proliferative response to highly purified human hepatic asialoglycoprotein receptor, whereas no proliferation was found with peripheral blood lymphocytes of patients with chronic viral hepatitis (0 of 13) and healthy blood donors (0 of 4). Moreover, we isolated T-cell clones from liver biopsy samples of two patients with autoimmune chronic active hepatitis and two patients with peripheral blood lymphocytes. Between 2.8% and 14.3% of these clones showed a specific proliferative response to purified human hepatic asialoglycoprotein receptor. The response was restricted to autologous antigen-presenting cells and could be blocked by monoclonal antibodies against human leukocyte antigen-DR molecules. The response of T cells to the human hepatic asialoglycoprotein receptor did not require the lectinlike activity of the asialoglycoprotein receptor. Thus the human hepatic asialoglycoprotein receptor could be identified as a major target antigen of humoral and cellular immune reactions in autoimmune-mediated liver diseases. 
2	Elevated intracranial pressure and computed tomography of the brain in fulminant hepatocellular failure. Cerebral herniation is a leading cause of death in patients with fulminant hepatocellular failure. Classical signs of elevated intracranial pressure are often absent in these patients. A reliable noninvasive method by which the presence of cerebral edema could be determined is much needed. To assess the efficacy of computed tomography of the brain in this setting, we compared the radiographic findings to the intracranial pressure measured by an epidural monitor in patients with fulminant hepatic failure. Unfortunately, a considerable difference existed between the presence of cerebral edema diagnosed by computed tomography of the brain and elevation of the intracranial pressure. Our observations suggest that in patients with fulminant hepatic failure and advanced hepatic encephalopathy, computed tomography of the brain is of little value in detecting cerebral edema. Pressure monitoring is most important to establish the presence and guide the therapy of intracranial hypertension. 
5	Hemicorporectomy: a collective review. Hemicorporectomy or translumbar amputation has been described as the most revolutionary of all operative procedures. Frederick E. Kredel, who first voiced the concept of the operation in 1950, referred to it as halfectomy. Demonstration of his cadaver studies established the feasibility of the operation. Amputation is effected through the lower lumbar area of the body. Necessary life functions are preserved in the upper torso. Kredel envisioned hemicorporectomy as a curative operation for locally advanced cancer, limited to the pelvis, not encompassable by standard operative intervention. Additional indications are intractable decubitus ulcers with malignant change, particularly in paraplegics; pelvic organs, and bone infection with nonhealing fistulae; and crushing trauma to the pelvis. The first hemicorporectomy operation was reported in 1960. Thirty-four operations have been recorded in the world literature. Two heretofore unreported cases are added, raising the total to 36. Review of these 36 cases confirms the conviction that hemicorporectomy is a humane and ethical alternative to the suffering encumbered by advancing, painful, malodorous malignant disease not treatable by conventional means. While cure rates are not substantial, the best results are reported in paraplegics with intractable decubitus ulcers with or without malignancy. Rehabilitation is prolonged and costly. Most survivors have been restored to preoperative occupations or other gainful employment. 
3	Tay-Sachs disease in Moroccan Jews: deletion of a phenylalanine in the alpha-subunit of beta-hexosaminidase. Tay-Sachs disease is an inherited lysosomal storage disorder caused by defects in the beta-hexosaminidase alpha-subunit gene. The carrier frequency for Tay-Sachs disease is significantly elevated in both the Ashkenazi Jewish and Moroccan Jewish populations but not in other Jewish groups. We have found that the mutations underlying Tay-Sachs disease in Ashkenazi and Moroccan Jews are different. Analysis of a Moroccan Jewish Tay-Sachs patient had revealed an in-frame deletion (delta F) of one of the two adjacent phenylalanine codons that are present at positions 304 and 305 in the alpha-subunit sequence. The mutation impairs the subunit assembly of beta-hexosaminidase A, resulting in an absence of enzyme activity. The Moroccan patient was found also to carry, in the other alpha-subunit allele, a different, and as yet unidentified, mutation which causes a deficit of mRNA. Analysis of obligate carriers from six unrelated Moroccan Jewish families showed that three harbor the delta F mutation, raising the possibility that this defect may be a prevalent mutation in this ethnic group. 
5	Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia. To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed. 
2	Bronchial asthma and acid reflux into the distal and proximal oesophagus. The prevalence of pathological gastro-oesophageal reflux in children and adolescents with asthma was studied by 24 hour two level oesophageal pH monitoring in 42 subjects aged 9-20 years with moderate or severe bronchial asthma. The importance of oesophagobronchial nerve reflexes and of aspiration of gastric acid as triggers in asthma was assessed by studying whether episodes of reflux into the distal and into the proximal oesophagus were followed by asthma attacks. Twenty-one subjects (50%) had a pathological total reflux time in the distal oesophagus and six (16%) in the proximal oesophagus. Nine patients had pathological gastro-oesophageal reflux into the distal oesophagus together with symptoms of asthma during the day on which the recording took place. In three of them the episodes of asthma symptoms were significantly correlated with preceding episodes of reflux into the distal oesophagus, and in one subject to reflux into the proximal oesophagus. We conclude that pathological gastro-oesophageal reflux is common in children and adolescents with asthma, but it seems to provoke symptoms of asthma in only a few. Symptoms of asthma were more often elicited by exposure of the distal oesophagus to gastric acid, possibly by a vagal reflex, than by aspiration of gastric juice. 
3	Substantia nigra: a site of action of muscle relaxant drugs. Sites of action of centrally active muscle relaxant drugs are not well defined. Clinical experience with such drugs suggests that the spinal cord may be one of the important regions from which pathologically increased muscle tone may be relieved. Supraspinal centers that may also be involved in the expression of muscle relaxant action have not yet been defined. We report here that microinjections of therapeutically relevant muscle relaxants into the midbrain tegmentum of genetically spastic rats decrease muscle tone. The substantia nigra is the region from which midazolam, baclofen, and tizanidine (drugs used clinically in the treatment of spasticity), or gamma-vinyl-GABA, (-)-2-amino-7-phosphonoheptanoate, and [D-pro2-D-phe7-D-trp9]-substance P (experimental drugs active in animal models of spasticity), reduce muscle tone in genetically spastic rats and Hoffmann reflexes in normal rats. The effects of muscle relaxant drugs are topographically restricted to the substantia nigra pars reticulata and are receptor specific. These observations disclose a previously unknown function of the substantia nigra in mediating muscle relaxation. 
1	Cancer incidence among foundry workers in Denmark. Cancer incidence was studied among 6,144 male foundry workers who were invited to participate in either of two Danish national silicosis surveys conducted during 1967-1969 and 1972-1974. Cancer incidence was followed through to the end of 1985 by computerized linkage to the Danish Cancer Registry, and Standardized Morbidity Ratios (SMRs) were calculated based on incidence rates for the Danish population. For the entire cohort, significantly elevated SMRs were seen for all cancers (SMR, 1.09; 95% CI, 1.01-1.18) and lung cancer (SMR, 1.30; 95% CI, 1.12-1.51), and SMRs were at the borderline of statistical significance for bladder cancer (SMR, 1.24; 95% CI, 0.97-1.59). Excess lung and bladder cancer risk were confined to workers who had worked in foundries for at least 20 y. There was a positive correlation between silicosis prevalence in employees at the foundries at the time of the x-ray examinations and lung cancer incidence during the follow-up period. Squamous cell carcinomas, anaplastic carcinomas, and other lung cancers accounted for the excess lung cancer risk, whereas there was not excess risk among the foundry workers for adenocarcinomas of the lung. 
5	Comparison of pulse oximeters: accuracy at low arterial pressure in volunteers. A laboratory model was developed of limb hypoperfusion in volunteers, using parital occlusion of the brachial artery with consequent reduction in radial artery pulse pressure. This was used to compare the function of 13 pulse oximeters and the effect of reduced pulse pressure and mild hypoxia on these devices. With the exception of one device, all the pulse oximeters studied demonstrated similar accuracies at pulse pressures exceeding 20 mm Hg. There were however, significant differences between several of the pulse oximeters in both ability to display readings and accuracy of readings displayed when brachial artery occlusion reduced radial artery pulse pressures equal to or less than 20 mm Hg. 
1	Xeroderma pigmentosum: review and report of a case. Xeroderma pigmentosum is a rare inherited dermatosis that provides insight into the basic mechanism of carcinogenesis. It is a model disorder linking defective DNA repair with clinical abnormalities and neoplasia. UV light-induced damage to the skin begins early and results in multiple benign and malignant skin tumors, especially in sun-exposed areas of the head and neck. Oral cancers, primarily squamous cell carcinomas of the anterior third of the tongue, occur with greatly increased frequency. A patient with multiple facial neoplasia and oral manifestations of xeroderma pigmentosum is presented. The role of the dentist in surveillance of oral and perioral structures is emphasized. The dentist is advised against the use of UV light-curing units in these patients because UV-induced epithelial damage may cause dysplasia when DNA repair mechanisms are dysfunctional. 
4	Carotid-cavernous sinus fistula associated with a primitive trigeminal artery. Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery. 
1	LDH isoenzymes in cerebrospinal fluid in various brain tumours. This study examined the isoenzymatic pattern of LDH in the cerebrospinal fluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage. 
2	Radiation-induced proctosigmoiditis. Prospective, randomized, double-blind controlled trial of oral sulfasalazine plus rectal steroids versus rectal sucralfate. In a prospective study, 37 consecutive patients with radiation-induced proctosigmoiditis were randomized to receive a four-week course of either 3.0 g oral sulfasalazine plus 20 mg twice daily rectal prednisolone enemas (group I, N = 18) or 2.0 g twice daily rectal sucralfate enemas plus oral placebo (group II, N = 19). The two groups were comparable with respect to demographic features, duration of symptoms, and clinical and endoscopic staging of the disease. Fifteen patients in group I and 17 in group II completed the trial. At four weeks, both groups showed significant clinical improvement (P less than 0.01 for group I and P less than 0.001 for group II) and endoscopic healing (P less than 0.01 for group I and P less than 0.001 for group II). When the two groups were compared, sucralfate enemas showed a significantly better response as assessed clinically (P less than 0.05), although endoscopically the response was not statistically different (P greater than 0.05). We conclude that both treatment regimens are effective in the management of radiation proctitis. Sucralfate enemas give a better clinical response, are tolerated better, and because of the lower cost should be the preferred mode of short-term treatment. 
5	Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Follicular lymphoma, the most common human lymphoma, characteristically has a t(14; 18) interchromosomal translocation. It is typically an indolent disease comprised of small resting B cells, but frequently develops into a high-grade lymphoma. The t(14; 18) translocates the Bcl-2 gene, generating a deregulated Bcl-2-immunoglobulin fusion gene. Bcl-2 is a novel inner mitochondrial membrane protein that extends the survival of certain cells by blocking programmed cell death. To determine the oncogenic potential of the t(14; 18) translocation, we produced transgenic mice bearing a Bcl-2-immunoglobulin minigene that structurally mimicked the t(14; 18). An indolent follicular hyperplasia in these transgenic mice progressed to a malignant diffuse large-cell lymphoma. The long latency, progression from polyclonal to monoclonal disease, and histological conversion, are all suggestive of secondary changes. Half of the immunoblastic high-grade lymphomas had a rearranged c-myc gene. Our transgenic mice provide an animal model for tumour progression in t(14; 18) lymphoma and show that prolonged B-cell life increases tumour incidence. 
1	Cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The authors studied data of combination assays of tumor markers, because simultaneous elevation of different types of tumor markers in the serum was puzzling. They interpreted such phenomena regarding cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19-9 in ovarian tumors. The tissue expression of the antigens was compared with preoperative serum levels. Several different factors were found to cause the simultaneous elevation of two or three of these markers in the serum. Furthermore, even when the levels of some of the tumor markers were raised in the serum, the ovarian tumor did not always produce the marker by itself. This study indicates that immunohistochemical identification of a marker in tumor tissue is prerequisite to the use of that marker in the serum to monitor disease status. 
4	Thromboembolism. A complication of weekly chemotherapy in the treatment of non-Hodgkin's lymphoma. In a retrospective survey of 85 patients who received chemotherapy as treatment for non-Hodgkin's lymphomas, the authors found that clinically apparent thromboembolic disorders occurred in four of 11 patients receiving weekly chemotherapy, and in none of 74 patients who were treated on less intensive schedules, suggesting that intensive weekly chemotherapy is thrombogenic. The possible mechanisms of this effect are discussed. 
5	European experience with itraconazole in systemic mycoses. Since January 1985 more than 100 patients with deep fungal infections have been treated with itraconazole (200 to 400 mg/day) in Northern Italy. Evaluation of the drug efficacy and tolerance was possible in one patient with sporotrichosis, in 34 with aspergillosis, and in 36 with cryptococcosis (mainly patients positive for human immunodeficiency virus). Response to itraconazole alone was obtained in the case of sporotrichosis and in 24 of 34 patients with different forms of aspergillosis (of the 18 patients with invasive pulmonary aspergillosis, 15 were cured). Patients with cryptococcosis received itraconazole for active infection and/or for prevention of relapse. Active infection was treated successfully with itraconazole alone in 9 of 12 patients and with itraconazole plus flucytosine in 8 of 10 patients. Of the 31 patients who received itraconazole maintenance therapy for up to 27 months, 4 (13%) had relapses; 14 (45%) did not have relapses, and decline of serum antigen was detected in 12 of them; and 13 (42%) were completely cured (serum antigen titer dropped to zero). With the exception of hypokalemia in one patient, itraconazole was well tolerated even in patients who received the drug for several months or years. 
1	Study of preneoplastic changes of liver cells by immunohistochemical and molecular hybridization techniques. The status of hepatitis B virus DNA was investigated by in situ hybridization in multifocal areas of a noncancerous hepatitis B virus-associated cirrhosis. This liver exhibited a marked degree of dysplasia and adenomatous hyperplasia. The results of these studies were correlated with the histopathology and immunohistochemical stains for hepatitis B core and surface antigens. There was clear evidence of a marked reduction to absence of hepatitis B viral DNA by in situ hybridization and absence of HBc and HBsAg in the foci of liver cell dysplasia and adenomatous hyperplasia. These results support the hypothesis that liver cell dysplasia and adenomatous hyperplasia are preneoplastic in nature. 
5	Interpleural analgesia improves pulmonary function after cholecystectomy. The purpose of this study was to examine the effects of interpleural bupivacaine on analgesia and ventilatory capacity after cholecystectomy. Forty-two patients undergoing elective cholecystectomy were randomly assigned to two groups: one to receive interpleural administration of bupivacaine-adrenaline mixture (Group 1 = 22 patients) and the other standard administration of intramuscular meperidine (Group 2 = 20 patients) for postoperative pain relief. The intensity of pain was evaluated by a visual analogue scale (VAS) preoperatively as well as at 2, 8, 24 and 48 hr postoperatively. At the same time, FVC and FEV1.0 measurements were obtained for all patients. The group given interpleural bupivacaine had better pain relief with mean VAS of 0.6 +/- 0.9 (mean +/- SD) 1.1 +/- 1.4, 0.6 +/- 0.9 and 0.8 +/- 1.2 compared with 5.2 +/- 2.2, 5.8 +/- 2.7, 5.5 +/- 2.2 and 4.5 +/- 1.8 for patients receiving meperidine (P less than 0.001). The patients in Group 1 also had larger FVC and FEV than those in Group 2: FVC 22 +/- 14.5 per cent vs 32 +/- 15.2 per cent (P less than 0.005), FEV1.0 25 +/- 15.5 vs 38 +/- 14.8 per cent (P less than 0.001) (mean +/- SD). We conclude that the interpleural analgesia can achieve better pain relief with greater ventilatory capacity than a standard analgesic regimen in the first two days after cholecystectomy. 
5	Assessment of cataracts from photographs in the Beaver Dam Eye Study. Presence and severity of age-related cataract was determined in adults 43 to 84 years of age in Beaver Dam, Wisconsin. Duplicate photograph gradings for nuclear sclerosis (n = 1160), cortical opacities (n = 1159), and posterior subcapsular cataract (n = 1137) were performed. There are five levels of nuclear sclerosis. Exact agreement occurred in 64.7% of the cases; agreement within one category in 99.8%. For cortical opacities, graders estimate involved area in nine segments of the lens. When the continuous scale is divided into 12 categories of severity, exact agreement varied between 73.5 and 82.4%; for agreement within one category, rates varied between 84.6 and 89.9%. For posterior subcapsular cataracts, exact agreement for involvement of the central circle occurred in 95.0% and agreement within one category occurred in 97.7%. Intraobserver comparisons disclosed similar concordance. These grading schemes are semiquantitative, reproducible, and can be performed for the large numbers of photographs from population-based studies. 
5	Prognostic significance of conjugate eye deviation in stroke patients. We prospectively studied the prognostic significance of conjugate eye deviation in 80 patients with acute stroke and compared the 3-month mortality and disability of these patients to those of the Tilburg epidemiological study of stroke. Mortality of patients with conjugate eye deviation was higher (41%) than for the general stroke population (34%), but this difference was not statistically significant (p less than 0.179). Looking at mortality and disability together, we found the outcome of patients with conjugate eye deviation to be significantly worse (p less than 0.001). Deviation of the eyes occurred more frequently to the right (65%) than to the left (35%). In the patient group with eye deviation to the left, mortality was significantly higher (64%, p less than 0.001) than in the group with eye deviation to the right (25%); only two patients of the former group (n = 28) could return home. Compared to the Tilburg epidemiological study of stroke, the group with eye deviation to the left did significantly worse, both for mortality alone (p less than 0.001) and for mortality and disability together (p less than 0.001). The group with eye deviation to the right did significantly worse only for mortality and disability together (p less than 0.01). Our results indicate that conjugate eye deviation is a prognostic factor for poor short-term mortality and disability in stroke patients, especially when the eyes are deviated to the left. 
5	Pathophysiological insights into the cardiomyopathy of Chagas' disease. The evidence gained from both human and animal studies of chronic chagasic cardiomyopathy suggests that the disease occurs as a consequence of several discrete and progressive pathophysiological processes occurring after infection, the ultimate expression of which depends on a host of unidentified factors. Collectively, the infection-associated events compromise microvasculature function and result in hypoperfusion, with consequences indistinguishable from those observed in other, nonparasitological cardiomyopathic diseases secondary to hypoperfusion. Therefore, chronic chagasic cardiomyopathy may share similar pathophysiological abnormalities with other chronic congestive cardiomyopathic states. 
1	Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma. Preliminary results. Cryosurgery, the in situ freezing of cancer, has been proposed in the past as a possible treatment for unresectable hepatic tumors. Its advantage lies in the fact that it is a very focal treatment sacrificing less normal tissue than surgical resection, allowing treatment of multiple lobes. Because cryosurgery does not affect large vessels, tumors in difficult locations, such as adjacent to the inferior vena cava (IVC), can be treated. With the use of intraoperative ultrasound to place the cryoprobes and monitor the freezing process, 18 patients with unresectable metastatic colon carcinoma confined to the liver were treated. Of the 18 patients treated, 4 (22%) are in complete remission as determined by computed tomography (CT) scans and carcinoembryonic antigen (CEA) levels, with a mean follow-up of 28.8 months. Four patients (22%) were not adequately treated at the time of cryosurgery. The number of lesions frozen in each patient ranged from 1 to 12, with a mean of 6 lesions. Fourteen patients had bilobar disease; three patients had previous right lobectomies with recurrences in their remaining left lobes prior to cryosurgery, and one patient had unilobar disease. Mean survival of the 14 cases with recurrence was 21.4 months, with 2 of the 14 still alive. Ultrasound-guided hepatic cryosurgery appears to be an effective treatment for metastatic colon carcinoma to the liver that is unresectable (including patients with bilobar and multiple lesions). These preliminary results indicate that the procedure warrants further study. 
4	Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham Heart Study experience). The baseline electrocardiograms of 5,125 original subjects of the Framingham Heart Study were measured to examine the relation of the QT interval corrected for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43 and greater than or equal to 0.44 were studied in relation to these outcomes. There were no significant differences in the risk of total mortality, sudden cardiac death or death due to coronary artery disease according to QTc. A similar lack of significant association between QTc and these 3 outcomes was observed among all persons studied and in the 2 sexes after using a multiple regression analysis to control for several potentially confounding characteristics including age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood pressure and Framingham relative weight. The results of this study fail to demonstrate an association between baseline QTc and overall mortality, and deaths due to sudden cardiac events or coronary artery disease in a large population-based cohort of essentially healthy persons in whom pathologic forms of QTc prolongation are uncommon. 
3	Significance of magnetic resonance imaging in acute head injury. One hundred seventy-seven patients who had incurred head trauma were studied with magnetic resonance imaging (MRI). Patients varied from those with mild injury without any focal neurological deficit to those with severe injury with post-traumatic coma. Altogether, 177 lesions were demonstrated by MRI in 123 of 177 patients within 3 days of injury using T2-weighted (SE2000/40,2000/111) and T1-weighted (IR1500/500/40) multislice sequences. In contrast, computerized tomography (CT) demonstrated 103 lesions in 90 patients. MRI was superior to CT in the diagnosis of nonhemorrhagic contusions demonstrated as a high-intensity area on T2-weighted imaging. MRI provided some information to evaluate the severity of diffuse axonal injury or to predict delayed traumatic intracerebral hematoma (DTICH). 
5	Effects of hypertension on pregnancy monitoring and results. The effect of severity of hypertension on fetal heart rate tracing changes and neonatal outcomes was evaluated on all patients with hypertension seen in 1980 and 1981 (666 cases, 10% of the pregnant population) in the Chicago-Lying In Hospital. The patients were grouped according to severity of hypertension, and the fetal heart rate monitoring, drugs administered, mode of delivery, and neonatal outcome were analyzed. Half of the patients (326) had mild hypertension and 13% (87) had severe hypertension; the remainder (253) had moderate hypertension. There were 49% primiparous and 51% multiparous women. The diagnosis of preeclampsia was made in 76% of cases, and chronic hypertension in 19%. Only 12% of the total were premature by dates, but 47% of this group were among the severe group. Oxytocin was given to 50%, whereas delivery was spontaneous in 56% of cases, and by cesarean section in 22%. This was higher among the severe hypertension group (37%), and the prematurity rate was 47%. Nonstress testing was done in one third of cases and only nonreactivity was associated with neonatal death. Neonatal depression (Apgar score less than 6 at 5 minutes) was significantly associated with intrapartum fixed baseline and late decelerations; these were the best predictors of fetal outcome. The administration of magnesium sulfate, hydralazine, meperidine, or morphine did not predictably affect the fetal heart rate pattern. The perinatal mortality was 21% in the mild group and 36% and 138%, respectively, among moderate and severe cases of hypertension. Close antepartum and intrapartum surveillance, including proper fetal monitoring, should help to reduce risks for mother and fetus through timely intervention. 
3	Familial Creutzfeldt-Jakob disease without periodic EEG activity. Four members of a kindred with Creutzfeldt-Jakob disease are reported, in whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt-Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rare in familial forms of Creutzfeldt-Jakob disease, as it is in other slow transmissible encephalopathies. 
3	Occult, bilateral anterior sacral and intrasacral meningeal and perineurial cysts: case report and review of the literature. None of the more than 180 cases of anterior sacral meningocele reported in the past 150 years has been bilateral, and only two have been associated with occult intrasacral meningocele. We report a unique case of bilateral anterior sacral cysts, communicating with the subarachnoid space, associated with occult intrasacral meningeal and perineurial (Tarlov's) cysts, in an asymptomatic woman. The pertinent clinical and diagnostic imaging literature is reviewed. 
3	Intrathecal morphine 0.2 mg versus epidural bupivacaine 0.125% or their combination: effects on parturients. To compare the efficacy and side effects of 0.2 mg intrathecal (IT) morphine with 0.125% epidural bupivacaine, 62 women in labor were studied. They were randomly divided into three groups: group 1 (n = 20) received IT morphine; group 2 (n = 22) received epidural bupivacaine; and group 3 (n = 20) received a combination of both using a combined spinal-epidural (CSE) technique. According to a visual analogue scale for assessing analgesia, neither IT 0.2 mg morphine nor 10 ml 0.125% epidural bupivacaine was effective in producing adequate pain relief in labor, whereas the combination produced excellent analgesia. The use of IT morphine significantly reduced the dosage requirement of epidural bupivacaine. The incidence of nausea, vomiting, and pruritus was significantly higher when IT morphine had been administered, whereas that of urinary retention did not differ. No serious respiratory depression occurred in any of the patients. When the course of labor was studied, the prior use of IT morphine significantly prolonged the duration of the first stage of labor and the total duration of labor. We conclude that the administration of 0.2 mg IT morphine in combination with epidural administration of 0.125% bupivacaine provides better analgesia than the administration of either drug alone. 
4	Felodipine in the treatment of hypertensive type II diabetics: effect on glucose homeostasis. The effect of felodipine on glucose tolerance was evaluated in 18 male type II diabetic patients treated with diet alone, who were hypertensive despite beta-blocker treatment. The study was a double-bind cross-over comparison of placebo and felodipine in addition to beta-blockade. Oral glucose tolerance tests were performed at randomization and at the end of each 4-week double-blind treatment period. The doses of felodipine given were 5 mg b.i.d. for 2 weeks followed by 10 mg b.i.d. for a further 2 weeks. Blood pressure was significantly reduced during felodipine treatment, whereas heart rate remained unaltered. HbA1c and fasting insulin levels did not change during the treatment periods. Fasting and maximal blood glucose levels were not altered between any of the treatment periods. However, there was a small but statistically significant increase (median increase 4%) in the area under the glucose concentration vs. time curve after felodipine as compared to placebo treatment. This increase was not considered to be clinically significant in the short term, but the finding merits further investigation in a rigorous long-term study. 
5	A surgical approach to the cervicothoracic spine. We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care. 
5	CV 205-502--effectiveness, tolerability, and safety over 24-month study. Twenty hyperprolactinemic women (median prolactin [PRL] 2,989 mU/L, range 1,149 to 11,910 mU/L), previously unsuccessfully treated with bromocriptine, were treated in a prospective study, for 3 to 24 months with the new, nonergot, long-acting, dopamine agonist, CV 205-502. Treatment resulted in normalization of PRL in 14 patients, in one daily dose of 0.075 to 0.150 mg of the drug. Three patients were treated in doses above 0.150 mg up to 0.300 mg, but PRL was not normalized during the study. Menstrual function was restored in 15 of 18 amenorrheic patients. Galactorrhea, present in 7 patients, disappeared in 5. Four patients became pregnant and gave birth to healthy children. In conclusion, we found CV 205-502 effective in one daily dose, with good tolerability; it is safe and provides a valuable alternative to the dopamine agonist drugs in use today. 
5	Continuous electrocardiographic monitoring in hypertensive crises in pregnancy. Twenty-four patients first seen with hypertensive crises during pregnancy were studied by continuous electrocardiographic monitoring for a period of 24 hours to detect the presence of serious ventricular arrhythmias. Three patients were excluded from analysis because of low serum potassium levels. Thirteen of the remaining 21 patients had ventricular tachycardia on subsequent analysis of the electrocardiogram. These arrhythmias subsided after induction of anesthesia when blood pressure control was optimal. This finding may be implicated in the pathogenesis of pulmonary edema and sudden death in these patients. 
2	Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. OBJECTIVE: To evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. DESIGN: Nested case-control study. SETTING: Tennessee Medicaid program. PARTICIPANTS: Medicaid enrollees 65 years of age or older were included in the study. The 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986. The 7063 control persons represented a stratified random sample of other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs, compared with that among nonusers, was 4.1 (95% CI, 3.5 to 4.7). For current users, the risk increased with increasing dose, from a relative risk of 2.8 (CI, 1.8 to 4.3) for the lowest to a relative risk of 8.0 (CI, 4.4 to 14.8) for the highest dose category. The risk was greatest in the first month of use (relative risk, 7.2; CI, 4.9 to 10.5). If the association is fully causal, 29% of peptic ulcers in the study sample resulted from the use of these drugs, and the excess risk associated with such use was 17.4 hospitalizations for ulcer disease per 1000 person-years of exposure. CONCLUSIONS: These data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons. 
1	Oral contraceptives and breast cancer. Among women in general the risk of breast cancer through 59 years of age does not appear to be affected appreciably by the use of oral contraceptives. Nonetheless, concern continues to be expressed about the effects of early age at first use, long-term duration of use, formulation, and a variety of other factors thought to influence breast cancer risk in the presence of oral contraception. A number of recent studies restricted to young women suggest that long-term use may increase the risk of disease occurring very early, but the present lack of consistent findings in well-conducted epidemiologic studies prevents any certain conclusion with regard to cause-and-effect. However, if an increased risk were indeed present, the most plausible interpretation is that long-term oral contraception promotes earlier clinical manifestation of breast cancer in some women while having no net impact on their lifetime risk of the disease. 
4	Response of spinal cord blood flow and motor and sensory evoked potentials to aortic ligation. To produce spinal cord ischemia in the lamb, ligation of the thoracic aorta was performed for 15, 30, and 45 minutes in three animals each. Spinal cord blood flow and motor and sensory evoked potentials were measured before, during, and after aortic ligation. Ischemia with a blood flow of zero during ligation was encountered in the thoracic and lumbar cords, followed by hyperemia upon release of the ligature. Both somatosensory and motor evoked potentials were obliterated during aortic ligation and gradually recovered following resumption of flow. Motor and sensory evoked potentials behaved similarly to high aortic ligation. 
1	An inner city cancer prevention clinic. Design, methods, and early results. An American Cancer Society demonstration pilot project is underway that is designed to provide comprehensive cancer prevention-related services to the underserved community of West Oakland, California. An array of cancer prevention services are being made available through an inner-city clinic (West Oakland Health Center), including cancer risk assessments and education about cancer, physical examinations for cancer, teaching of self-examination procedures, smoking cessation, and nutrition counseling, appointments for Pap smears, sigmoidoscopy, mammography, and other more specialized screening procedures, case management for findings suspicious for cancer, and community education programs. Described is the process of implementing these services, their utilization, and their impact (after 6 months). 
5	Etiology of acute lower respiratory tract infections in Gambian children: I. Acute lower respiratory tract infections in infants presenting at the hospital. Ninety infants less than 1 year of age with pneumonia and 43 control infants were investigated for viral and chlamydial infection with the use of culture and serology and for bacterial infection with the use of blood cultures, lung aspirates, antibody assays and antigen detection procedures. One or more potential pathogens were identified in 62 (69%) cases with pneumonia and in 12 (28%) controls. Infection by respiratory viruses was identified in 42 (49%) cases and in 8 (19%) controls. Respiratory syncytial virus was the commonest pathogen identified and was found in 32 cases (37%). Bacterial infections were also common, being found in 27 (30%) cases and 3 (7%) controls, and predominantly involved Streptococcus pneumoniae (20%) or Haemophilus influenzae (11%). Bacterial infections were associated with raised white blood cell counts and were identified more often by antigen detection procedures (68%) than by culture of blood or lung aspirates (34%) or by serology (33%). Mixed viral-bacterial infections were identified in 13 cases (15%). Infection with Chlamydia trachomatis was diagnosed in 2 infants with acute lower respiratory tract infection and in 1 control infant. 
3	The electrodiagnostic findings in polyneuropathies associated with IgM monoclonal gammopathies. Electrodiagnostic studies were analyzed in patients with neuropathy associated with IgM monoclonal proteins, 7 with anti-myelin associated glycoprotein reactivity (MAG) and 7 nonreactive to MAG. The findings were distinctly different in the two groups. The electrodiagnostic studies of all the MAG-reactive patients had demyelinating features with slowing of conduction and prolonged distal latencies while only one of the MAG-nonreactive patients had a demyelinating pattern. In fact, the MAG-nonreactive patients were a heterogeneous group, both electrodiagnostically and clinically. This study supports the concept that MAG-reactive polyneuropathy is demyelinating in type, and is caused by the activity of the IgM M-protein directed at an antigen in the myelin sheath. 
5	Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Use of the protected specimen brush technique in 54 mechanically ventilated patients. To obtain accurate information on distal bronchial microflora during acute exacerbation in patients with chronic bronchitis, we prospectively studied 54 such patients who had been receiving mechanical ventilation because of hypercapnic respiratory failure. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient within the first 24 h after admission. Cultures of protected brush specimens demonstrated no growth in 27 patients (50%). With the exception of fever (38.2 +/- 0.8 versus 37.7 +/- 0.6 degrees C; p less than 0.05), the initial severity of the episode of exacerbation was similar in patients with and without infection. A total of 44 organisms were isolated in the 27 patients with positive cultures; the predominant pathogens were Hemophilus spp. and Streptococcus spp. (involved in 74% of cases), but other organisms were isolated in 12 of 27 patients. Mortality rates, duration of mechanical ventilation, and duration of hospitalization were not significantly different between patients with bronchial microflora treated with appropriate antimicrobial therapy (n = 27) and patients without bronchial microflora either receiving empirical antibiotic therapy (n = 18) or not (n = 9). These data suggest that distal bronchial infection due to the usual pathogens, as far as shown by protected specimen brush cultures, may not be the sole or even the predominant cause of acute exacerbation of chronic bronchitis in patients requiring mechanical ventilation. 
3	Role of diabetologist in evaluating diabetic retinopathy. OBJECTIVE: To evaluate the ability of diabetologists to screen diabetic patients for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Comparison of eye examination performed by diabetologists with direct ophthalmoscopy through an undilated pupil and by ophthalmologists through a dilated pupil with seven-field stereoscopic fundus photography (gold standard). The study consisted of 67 insulin-dependent and non-insulin-dependent diabetic outpatients attending a diabetes clinic. RESULTS: On the basis of fundus photography, patients were classified as having no or insignificant (30%), minimal (31%), moderate (24%), or severe (15%) retinopathy. The diabetologists and ophthalmologists performed similarly in their ability to classify severity of diabetic retinopathy accurately. When no or insignificant retinopathy (isolated microaneurysms only) was detected by examination, clinically significant retinopathy detected by fundus photography was highly unlikely (less than 5%). On the other hand, if more than isolated microaneurysms were seen on examination, all examiners missed more severe lesions detected by fundus photography. Patients with corrected visual acuity worse than 20/30 had a high likelihood (100%) of moderate or severe retinopathy. CONCLUSIONS: Motivated well-trained diabetologists can screen for diabetic retinopathy. The absence of detectable lesions by direct ophthalmoscopy indicates that automatic referral to an ophthalmologist is not necessary. However, if any level of retinopathy is detected or corrected acuity is worse than 20/30, referral to an ophthalmologist is required. In this setting, fundus photography is advised because it is the most sensitive means of detecting clinically significant retinopathy. If other nonophthalmologists can be trained to achieve similar results, current recommendations for ophthalmologic referral that require annual ophthalmologic examinations for most diabetic patients may need to be reconsidered. 
1	Vegetables, fruits, and carotenoids and the risk of cancer. Low intake of vegetables, fruits, and carotenoids is consistently associated with increased risk of lung cancer in both prospective and retrospective studies. In addition, low levels of beta-carotene in serum or plasma are consistently associated with the subsequent development of lung cancer. The simplest explanation is that beta-carotene is protective. Since retinol (preformed vitamin A) is not related in a similar manner to lung cancer risk, beta-carotene appears to function through a mechanism that does not require conversion into vitamin A. However, the importance of other carotenoids and other constituents of vegetables and fruit has not been adequately explored. Both prospective and retrospective studies suggest that vegetable and fruit intake may reduce the risk of cancers of the mouth, pharynx, larynx, esophagus, stomach, colon, rectum, bladder, and cervix. But because of fewer studies and less consistency among studies, the epidemiologic evidence is at present less persuasive than for lung cancer. 
2	Paf-acether synthesis by Helicobacter pylori. Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa. 
1	Transrectal ultrasonography in the evaluation of the infertile man: a report of 3 cases. The traditional evaluation of the infertile man with azoospermia or low ejaculate volume includes determination of serum testosterone and follicle-stimulating hormone levels, a seminal fructose test, post-ejaculate urinalysis and, sometimes, vasography. Transrectal ultrasonography, a technique currently familiar to most urologists, recently has been added to our diagnostic armamentarium. This office-based imaging procedure provides an accurate assessment of the prostate, ejaculatory ducts and seminal vesicles, which can be helpful in the evaluation of certain infertile patients. We describe 3 patients who presented with either azoospermia or decreased ejaculate volume in whom transrectal ultrasonography had a critical role in the fertility evaluation. The clinical indications for and interpretation of transrectal ultrasonography in the infertile population are described. Transrectal ultrasonography currently is the most accurate, inexpensive and readily available noninvasive imaging technique used to diagnose obstruction of the ejaculatory ducts in the infertile patient with either azoospermia or low ejaculate volume. 
5	Radiotherapy for palliation of locally advanced prostatic carcinoma. Some patients present with distressing symptoms due to locally advanced prostatic carcinoma which may be refractory to hormonal manipulation and/or surgical treatment. Over an 8-year period 26 patients received local palliative radiotherapy for recurrent bleeding and lower urinary outflow tract obstruction. All were treated with conventional external beam radiotherapy and all but 2 obtained useful palliation of symptoms, especially those with recurrent bleeding. We also found that radiotherapy could be given to the majority of patients on an out-patient basis in 2 or 3 fractions. This was well tolerated and there were few side effects. 
5	The Marinesco-Sjogren syndrome examined by computed tomography, magnetic resonance, and 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. The Marinesco-Sjogren syndrome is an autosomal recessive degenerative disorder characterized by congenital cataracts, cerebellar ataxia, spasticity, mental deficiency, and skeletal abnormalities. We studied two adult siblings with Marinesco-Sjogren syndrome using anatomic and metabolic brain imaging techniques to characterize the pattern and nature of abnormalities in the brain. Computed tomographic and magnetic resonance imaging showed diffuse brain atrophy of mild to moderate degree, involving primarily the white matter of the cerebrum, cerebellum, brain stem, and cervical spinal cord. The pattern of atrophy resembled that seen in diffuse leukoencephalopathies. Measurements of local cerebral glucose metabolic rates with positron emission tomography revealed no statistically significant differences from normal control subjects in most regions, but metabolic rate was decreased in the thalamus in one patient. The findings support a diffuse white matter disorder in Marinesco-Sjogren syndrome. 
5	Celiac disease, brain atrophy, and dementia. We report 5 patients who developed dementia before age 60 and were subsequently found to have celiac disease (CD). Intellectual deterioration ranged from moderate to severe, and diffuse cerebral or cerebellar atrophy was found on brain CT. Diagnosis of CD was confirmed by findings of subtotal villous atrophy in jejunal biopsy specimens and positive serum reticulin and gliadin antibodies. Conspicuously, gastrointestinal symptoms were mild. The gluten-free diet failed to improve the neurologic disability except in 1 patient. CD is a multisystem disorder and may play a role in some cases of presenile dementia. Although the pathogenetic mechanisms are obscure, immunologic mechanisms are implicated. 
3	Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled beta 2 agonist OBJECTIVE--To determine whether inhaled salmeterol, a new long acting inhaled beta adrenergic agonist, reduces nocturnal bronchoconstriction and improves sleep quality in patients with nocturnal asthma. DESIGN--Randomised, double blind, placebo controlled crossover study. SETTING--Hospital outpatient clinics in Edinburgh. SUBJECTS--Twenty clinically stable patients (13 women, seven men) with nocturnal asthma, median age 39 (range 18-60) years. INTERVENTIONS--Salmeterol 50 micrograms and 100 micrograms and placebo taken each morning and evening by metered dose inhaler. Rescue salbutamol inhalers were provided throughout the run in and study periods. MAIN OUTCOME MEASURES--Improvement in nocturnal asthma as measured by peak expiratory flow rates and change in sleep quality as measured by electroencephalography. RESULTS--Salmeterol improved the lowest overnight peak flow rate at both 50 micrograms (difference in median values (95% confidence interval for difference in medians) 69 (18 to 88) l/min) and 100 micrograms (72 (23 to 61) l/min) doses twice daily. While taking salmeterol 50 micrograms twice daily patients had an objective improvement in sleep quality, spending less time awake or in light sleep (-9 (-4 to -44) min) and more time in stage 4 sleep (26 (6-34) min). CONCLUSIONS--Salmeterol is an effective long acting inhaled bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms twice daily improves objective sleep quality. 
4	Vascular complications after orthotopic liver transplantation. Over a 57-month period, we performed 430 orthotopic liver transplants in 372 patients. A total of 38 vascular complications were identified including hepatic artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n = 5). A number of potential risk factors for the development of vascular thrombosis were evaluated with only children, weight less than 10 kg, and cold ischemia time found to be significant. The clinical presentation included fulminant hepatic failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex ultrasonography was diagnostic in nearly all cases. Therapeutic modalities included revascularization, revascularization followed by retransplantation, retransplantation alone, and observation. Five cases of hepatic artery rupture occurred in four patients. Infectious arteritis was present in four patients. The 6-month actuarial survival in patients with vascular complications was 70%. Early diagnosis is critical for graft salvage, with surgical intervention the mainstay of therapy. 
5	Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization. 
1	Modified Van Nes rotationplasty in the treatment of malignant neoplasms in the lower extremities of children. A technique of modified Van Nes rotationplasty has been used since 1981 for limb salvage surgery in children and adolescents with malignant sarcoma of the lower extremity. The original procedure for lesions of the distal femur was further modified and adopted for selected lesions of the proximal femur and tibia. Sixteen skeletally immature children form the base of this report. The tumors were located in the distal femur in ten children, the proximal tibia in five and the proximal femur in one. There were no intraoperative complications and postoperative complications included one infection requiring debridement and three minor healing delays. There were no local recurrences, neurovascular compromises, late derotations, or psychologic decompensations. One patient died of metastatic disease and another died of a second malignancy (leukemia). The remaining patients are good, functional, below-knee prosthesis users who participate in a number of sporting and athletic activities. The procedure is safe, has a relatively low complication rate, allows for the functional demands of an active, growing child, and accommodates for the future growth of extremities. 
1	Diagnosis of metastatic lesions to the stomach by salvage cytology. A report of three cases. Secondary neoplasms of the stomach are rare and are often clinical and diagnostic problems. Three patients with bleeding "volcano-like" ulcers were diagnosed by combined endoscopic "salvage" cytology and surgical biopsy as having metastatic submucosal lesions from hematologic spread. The combination of endoscopic appearance, clinical findings, and tissue and cytologic examination can lead to the correct diagnosis. The results from these cases support the utility of this cytologic technique in combination with biopsy in this clinical setting. 
5	Polymorphisms of GLUT2 and GLUT4 genes. Use in evaluation of genetic susceptibility to NIDDM in blacks. The liver/islet (GLUT2) and muscle/adipose tissue (GLUT4) glucose-transporter gene products, membrane proteins that facilitate glucose uptake into cells, are important molecules for normal carbohydrate metabolism. Recent isolation of the genes encoding these proteins provides a means to assess the role of possible defects that might contribute to impaired glucose-stimulated insulin secretion or impaired insulin-mediated glucose uptake, both prominent phenotypic features of non-insulin-dependent diabetes (NIDDM). A GLUT2 cDNA clone was isolated from a human liver cDNA library to search for polymorphisms at this locus in American Blacks. Three highly polymorphic sites were identified, one of which (EcoRI-Hae III) appears to be due to an insertion and/or deletion of 200 base pairs of DNA. Significant linkage disequilibrium between these sites over approximately 30 kilobases of genomic DNA suggested that these polymorphisms could be in linkage disequilibrium with mutations at this locus if they exist. A GLUT4 cDNA clone was also utilized to search for polymorphisms at this locus, but only one previously described polymorphism was observed. GLUT2 and GLUT4 cDNA probes were used to evaluate DNA polymorphisms in genomic DNA from American Blacks with NIDDM. The allelic, genotypic, and haplotypic frequencies of the DNA polymorphisms at these loci did not differ from the frequencies in nondiabetic subjects. Because no associations with NIDDM were found, it appears unlikely that mutations at these loci contribute in a major way to the genetic susceptibility to NIDDM observed in American Blacks. 
5	Urinary tract dilatation in constipated children. Abnormalities of the upper urinary tract were sought retrospectively in 180 children with constipation who had been investigated surgically over a 5-year period. Of those in whom an intravenous urogram had been performed, the incidence of dilatation of the upper renal tract was high, but only 12% of the patients with non-organic constipation had been so investigated. 
1	Practical aspects of pulsatile gonadotropin-releasing hormone administration. Pulsatile administration of gonadotropin-releasing hormone represents a major advance in the treatment of anovulation in women who fail to ovulate with clomiphene citrate and is an alternative for many women who currently receive human menopausal gonadotropin. Four issues must be addressed before administering pulsatile gonadotropin-releasing hormone: (1) safety, (2) efficacy, (3) convenience, and (4) cost. Each of these issues will be affected by the three major decisions a physician makes with gonadotropin-releasing hormone therapy: (1) patient selection, (2) route of administration, and (3) dose of gonadotropin-releasing hormone. The ideal candidate for gonadotropin-releasing hormone therapy is a patient with an absence of endogenous pulsatile gonadotropin-releasing hormone, as seen in hypothalamic amenorrhea. Although women with polycystic ovarian disease can be treated with pulsatile gonadotropin-releasing hormone, a decreased ovulation rate should be expected. The route of administration, intravenous or subcutaneous, and the degree of monitoring can be tailored by the physician to fit each patient's needs. Pulsatile gonadotropin-releasing hormone therapy is a safe, effective, convenient, and economical alternative to human menopausal gonadotropin for ovulation induction in women resistant to clomiphene. 
1	Selective uptake of toxic nucleoside (125IUdR) by resistant cancer. We report uptake of a thymidine analogue 125-Iodine-5-iodo-2'-deoxyuridine (125IUdR) by nude mice bearing human xenografts of choriocarcinoma or colonic cancer. When 125IUdR was given alone, uptake by intestinal tissues was 5-10 times greater than by the tumours as measured by tissue gamma counting. This ratio was reversed when hydroxyurea or cytosine arabinoside were used as inhibitors of ribonucleotide reductase and were given in combination with 5-fluorouracil or methotrexate to inhibit thymidine synthesis shortly before injecting 125IUdR. Counting the radioactivity in tissues removed 24 hours after 125IUdR gave tumour to highest normal tissue ratios of up to 15:1, but the corresponding nuclear grain counts, which is probably a more reliable indicator of selective uptake into DNA, were in excess of 100:1. The addition of unlabelled IUdR to the regimen only reduced the uptake of 125IUdR when given in relatively large amounts. For this approach to be exploited it is concluded that the tumour must be resistant at the cell level to the inhibitor of DNA synthesis either de novo or as a result of prior exposure to it. This inhibitor can then be used to block uptake of the potentially toxic nucleoside analogue by normal renewal tissues while it is taken up by the resistant cancer cells. By inhibiting synthesis of the corresponding normal nucleosides with inhibitors to which the cancer cells are not resistant, incorporation of the toxic analogues into tumour DNA was enhanced. Although 125IUdR is a convenient agent for exploring this approach and is highly cytotoxic when incorporated in DNA, the clinical potential of reverse role chemotherapy probably lies with the development of toxic non-radioactive nucleoside analogues. 
5	Management of low-risk metastatic gestational trophoblastic tumors. The clinical course of 48 patients with low-risk metastatic gestational trophoblastic tumors (GTTs) treated with primary single-agent chemotherapy was reviewed. All patients achieved sustained remission, although 25 (51%) required a second single-agent regimen, and 7 (14%) needed combination chemotherapy to achieve it. An average of 3.4 courses of chemotherapy were necessary to achieve remission, and 6 patients (12%) underwent resection of resistant tumor foci. Primary single-agent chemotherapy is a reasonable treatment option in patients with low-risk metastatic GTT. 
1	Malignant melanoma of the oral cavity. A case report. The oral cavity is a rare location for the development of primary malignant melanoma. Less than 2% of all malignant melanomas develop in the region. A case report is presented, illustrating the management in the site of the palate, together with a review of the relevant literature. 
4	Carotid artery disease in patients with head and neck carcinoma. Irradiation has been shown experimentally to cause accelerated development of atherosclerosis in exposed large arteries. However, occurrence of such an entity in carotid arteries of patients after treatment for head and neck carcinoma is unknown. Therefore, we reviewed 179 patient charts who had undergone head and neck operations with or without irradiation between 1979-1987. Of these 179 patients, 107 (59.8%) were dead at time of follow-up. Cause of death was unknown in 42 (40%) patients; in the remainder included: respiratory arrest--33; carcinoma-related--18; cardiac--6;pneumonia--7; and trauma--1. Average interval from treatment to death was 23.5 months. Of the 72 patients known to be alive, follow-up was obtained in 52 patients. Their average age was 64.9 years. Risk factors for atherosclerosis included: male gender--43; smoking--50; hypertension--9; diabetes--4; coronary artery disease--12; and peripheral vascular disease--4. Seventy-five per cent of these patients received postoperative irradiation. Average follow-up was 64.5 months. Duplex scans were performed on 34 patients. Three patients had common or internal carotid stenoses greater than 75 per cent. All of these patients had received irradiation and none of them were symptomatic. Seven patients had carotid stenoses between 50 to 75 per cent; five of these had received irradiation. Of these five patients, one had a stroke 60 months postoperatively, and one had a TIA 36 months postoperatively. The remaining 58 patients (of which 48 had irradiation) had carotid stenoses less than 50 per cent and none were symptomatic. 
1	Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR. 
5	The case for porous-coated hip implants. The femoral side. A series of 1163 total hip arthroplasties (THAs) using porous-coated femoral components were roentgenographically assessed for implant fixation. For 959 primary THAs followed from two to 12 years, the femoral revision rate was 1% and the ten-year survivorship rate was 96.4%; 150 young patients had a fixation failure incidence of only 1.3% at a mean follow-up period of 6.4 years; in 204 revision THAs, the femoral re-revision rate was 4% at a mean follow-up period of 53.4 months. Failures were largely related to inadequate femoral canal filling. Because of refinements in implant design and surgical techniques, a press fit of the implant is currently achieved in 94% of cases compared to 36% during the first five years. Porous-coated femoral components have yielded results equivalent to those with cement in primary THAs. Excellent results were observed in relatively young patients and patients with revisions. 
4	Pancreatic transplantation: radiologic evaluation of vascular complications. Transplantation of the pancreas is an increasingly common therapeutic option for preventing or delaying complications of type I diabetes mellitus. The authors studied the relative roles of various radiologic examinations in diagnosing vascular complications in these grafts including arterial and venous thrombosis, stenosis, and anastomotic leak (the most common vascular factors that necessitate pancreatectomy of the transplant), as defined with pathologic or arteriographic data. The results of 78 scintigraphic flow studies, 40 abdominal and pelvic computed tomographic (CT) scans, 27 sonograms, and eight color Doppler studies were evaluated in 52 patients who received a total of 27 cadaveric and 26 living-donor grafts over a 12-year period. These results were correlated with the data from 45 gross and microscopic pathologic studies and 37 arteriograms to determine their relative value in enabling detection of graft thrombosis and other vascular complications. Scintigraphy, CT, sonography, and color Doppler were all sensitive in detection of generalized graft abnormalities but lacked specificity in defining the underlying etiologic factors. 
3	Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls. Ninety percent of the IIH patients were women; the mean age was 33. Obesity and recent weight gain were much more common among patients than controls. Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%). Daily occurrence of these symptoms was much more common among patients than controls. Controls also reported these and other IIH symptoms, but at lower frequencies. Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives. We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications. The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily. 
1	Testicular sex cord stromal tumour with granulosa cell differentiation: detection of steroid hormone receptors as a possible basis for tumour development and therapeutic management. A testicular sex cord stromal tumour with granulosa cell differentiation, typical of granulosa cell tumours of the adult type, was investigated immunohistologically on snap frozen and paraffin wax embedded material. The predominance of vimentin and the additional expression of cytokeratin subtypes 8 and 18, as well as the negative staining for epithelial membrane antigen, accorded with results previously reported, for ovarian granulosa cell tumours; the lack of expression of desmoplakin, however, was a distinctive feature. Together with negative staining for leucocyte common antigen, the antigen pattern facilitates the differential diagnosis between granulosa cell tumour and undifferentiated carcinoma or gonadal lymphoma, although its suitability for differentiating within the group of gonadal stromal tumours seems to be limited. The small growth fraction, shown by the monoclonal antibody Ki-67, is typical of the clinical behaviour of granulosa cell tumours. The expression of oestrogen and progesterone receptors, also recently found in testicular Leydig cell tumours, may provoke new approaches to the management of testicular granulosa cell tumours, as well as a new hypothesis on the development of these tumours. 
1	Abnormal vitamin B6 status in childhood leukemia. Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status. 
5	Superficial esophageal carcinoma. Surgical treatment and the results. We report 92 patients treated with esophagectomy for superficial esophageal carcinoma (SEC; 9.1% of all resected esophageal cancers at our institution). The operative mortality rate was 5.4%. In 24 cases, cancer invasion was limited to the mucosa, and in 68 to the submucosa. Twenty-three patients in the former group had no lymph node involvement, whereas 24 patients (35.3%) of the latter group had lymph node metastases. The 5-year survival rate after surgery for patients with SEC limited to the mucosa was 83.5%, which was significantly better than that for carcinoma invading the submucosa (54.9%). No recurrent disease occurred in patients with lesions limited to the mucosa. In conclusion, an esophagectomy with wide lymphadenectomy is necessary to provide a better prognosis for SEC invading the submucosa, whereas a less extensive treatment may be considered for SEC limited to the mucosa. 
5	Long-term echocardiographic follow-up of patients with a tricuspid bioprosthesis. To clarify the long-term results of bioprosthetic valve function in the tricuspid position, 29 consecutive patients who underwent tricuspid valve replacement (TVR) were evaluated. There were 20 girls/women and 9 boys/men, with ages ranging from 6 to 61 years (mean 41.4 years). The bioprosthetic valves included Hancock in 2, and Carpentier-Edwards in 27. The follow-up period ranged from 32 to 145 months (mean 89 months). Regurgitant flow of the tricuspid bioprosthesis was studied by color Doppler echocardiography. Peak velocity (Vp) and pressure half time (PHT) were measured by continuous wave Doppler echocardiography. Operative mortality was 13.7% (4/29), with the actuarial survival rate, including operative deaths, 75% at 10 years. Valve thrombosis developed in one patient 4 years after TVR. Color Doppler showed regurgitation in 7 of the 20 patients who were completely followed up, but they were all asymptomatic and required no special intervention. Cusp tear or calcification requiring reoperation was not observed in this study, including 8 patients younger than 35 years of age. The Vp was significantly slower, and PHT was significantly prolonged, in the tricuspid rather than the mitral position. These data demonstrate that bioprosthetic valves in the tricuspid position can be used safely. Doppler examination should be performed taking these different flow dynamics into account. 
5	Human ehrlichiosis: a rickettsial disease associated with severe cholestasis and multisystemic disease. We report an unusual case of a typically canine rickettsial disease, ehrlichiosis, in a 56-year-old man. Although only occasionally affecting humans with a mild illness, exposure to a tick bite in our patient led to severe multisystemic disease with intense cholestasis. Coma, acute renal failure and respiratory failure requiring mechanical ventilation ensued. Imaging procedures showed no biliary obstruction. A liver biopsy demonstrated bile stasis and sinusoidal lymphoid infiltrates. The diagnosis was confirmed serologically. Only partial improvement occurred with tetracycline therapy, but total resolution of all abnormalities eventually followed therapy with chloramphenicol. 
4	Circus movement atrial flutter in the canine sterile pericarditis model. Differential effects of procainamide on the components of the reentrant pathway. To evaluate the mechanisms of action of procainamide on the components of the reentrant pathway, drug-induced changes in activation patterns, effective refractory periods (ERPs), and stimulation thresholds were analyzed in nine dogs with sterile pericarditis and sustained atrial flutter. Activation maps were based on 127 close bipolar recordings from a special "jacket" electrode. From the control map, 22 +/- 2 sites covering the slow zone and the normal zone of the reentrant circuit were selected to measure ERPs and thresholds. The excitable gap was estimated from the longest ERP during pacing at the tachycardia cycle length. During atrial flutter, epicardial activation proceeded as a single wave around an arc of functional conduction block in the proximity of the atrioventricular (AV) ring or around a combined functional/anatomic obstacle, with the arc being contiguous with one of the venae cavae. An area of slow conduction, which accounted for 53 +/- 15% of the revolution time within 35 +/- 15% of the total length of the reentrant pathway, was bordered by the arc of block and the AV ring or a caval vein and the AV ring, respectively. Procainamide (5-10 mg/kg i.v.) prolonged the cycle length of atrial flutter from 144 +/- 17 to 190 +/- 24 msec (p less than 0.05) and then terminated the arrhythmia in all studies. The increase in cycle length was due to an increase in conduction time in the slow zone by 37 +/- 11 msec (86 +/- 17% of the total cycle length increase). During the last reentrant beat, conduction failed in the slow zone, with the arc of block joining the AV ring. At termination, procainamide had prolonged conduction time, stimulation threshold, and ERP in the normal zone by 11 +/- 18%, 40 +/- 80%, and 5 +/- 15%, respectively, compared with 51 +/- 16%, 86 +/- 93%, and 14 +/- 21%, respectively, in the slow zone (p less than 0.05 for all three parameters). The duration of the excitable gap did not change significantly. We conclude that procainamide preferentially affected the slow zone of single loop reentrant circuits. The drug terminated circus movement atrial flutter without abolishing the excitable gap, and its effect on conduction seemed the major determinant of the antiarrhythmic action. 
4	Alcohol consumption and blood pressure: a comparison of native Japanese to American men. We compared the cross-sectional association of alcohol consumption with blood pressure in 810 Japanese men (JM) living in Tokyo and 946 white men (WM) living in New York. Mean systolic (JM and WM, p less than 0.001) and diastolic blood pressure (JM, p less than 0.002; WM, p less than 0.001) were associated with alcohol consumption in both groups. Compared to abstainers, the heaviest drinkers had the highest systolic (JM, p = 0.001; WM, p less than 0.01) and diastolic (JM, p less than 0.002; WM, p less than 0.05) blood pressures. The relation of blood pressure to alcohol intake was J-shaped in the Americans, but linear in the Japanese. Exploratory analyses revealed that the J-shape may have been due to under-reporting of heavy alcohol ingestion by American abstainers. When abstainers were excluded, the relationships were similar in both the American and Japanese. The positive association between blood pressure and alcohol consumption persisted after adjustment for age, cigarette smoking, use of antihypertensive medications, body mass index, heart rate, abdominal skinfold thickness, hematocrit, fasting blood glucose, serum uric acid levels and urinary sodium/potassium ratio. Alcohol use was also related to prevalence of hypertension. These findings confirm the presence of an independent association between alcohol intake and blood pressure in both JM and WM and suggest that, despite differences in the metabolism of alcohol, the relation of alcohol consumption to blood pressure is similar in both nationalities. 
2	Plasma thrombin-antithrombin III complexes in the diagnosis of primary hepatocellular carcinoma complicating liver cirrhosis. Detection of hypercoagulable state might be helpful in the diagnosis of primary hepatocellular carcinoma (HCC) complicating liver cirrhosis (LC). Plasma levels of thrombin-antithrombin III complex (TAT) were determined in 50 patients of LC with or without HCC. The levels were above 2 ng/ml in 80% of 25 HCC patients, but only in 12% of 25 non-HCC patients (P less than 0.01). The levels over 2 ng/ml occurred even in five of six HCC patients whose serum alpha-fetoprotein levels were below 20 ng/ml as well as in two of three patients with HCC less than 2 cm in diameter. Those levels in HCC patients were significantly decreased within 8 days after treatment with transcatheter arterial embolization or infusion of antitumor agents, without affecting plasma antithrombin III levels. These results suggest that plasma TAT levels may be useful in the diagnosis of HCC complicating LC. 
1	Effective destruction of cervical intraepithelial neoplasia (CIN) 3 at 100 degrees C using the Semm cold coagulator: 14 years experience A total of 1628 women with CIN 3 treated with the Semm cold coagulator between 1975 and 1989 was followed primarily by cytology. The standard suitability criteria for ablation were adhered to except that patients were treated at their first visit when the colposcopist expected that the diagnosis would be no worse than CIN 3. Overall 97% of the women were treated at their first visit. In 30 women (2%) the histology was glandular or worse than expected, but 22 of these showed no persistent cervical disease subsequently. Follow-up was achieved for 87% at 10 years. In actuarial terms the primary success rate was 95% at 1 year and 92% at 5 years, it was similar for all age groups. Repeat cold-coagulation for persistent/recurrent CIN 3 was less successful and is not advised. The outcome for 226 pregnancies established after treatment is known. The rates for miscarriage, preterm or operative delivery were not increased. Cold-coagulation of CIN 3 at 100 degrees C as performed by us is as effective as any other treatment and calls into question the need for more expensive practices. 
3	Common headaches: type, duration, frequency and implications. Questionnaires completed by 327 preclinical medical and dental students showed that 97.9% had experienced headaches, most frequently attributed to insufficient sleep (38.8%), mental stress (38.8%), alcohol (38.5%), excess heat (36.7%), reading (31.5%), excess noise (29.9%) or light (27.7%), and sleeping too long (23.5%). The frequency and duration of these and other headaches are listed. 8% of the headache group had consulted a doctor. Only 2.1% of all students had never experienced a headache. Two hypotheses are examined: (1) can headaches be normal?--delineated by their disappearing soon after the noxious stimulus has ceased; (2) can pain in the head, as elsewhere in the body, act as a warning and therefore have protective, even survival value?. 
1	Correlation between hyperthermoradiosensitivity and clinical effect in carcinoma of the esophagus. The correlation between hyperthermoradiosensitivity evaluated by an in vitro succinate dehydrogenase inhibition (SDI) test and the histopathologic effects of hyperthermochemoradiotherapy (HCR therapy) were investigated in 43 patients with carcinoma of the esophagus. The succinate dehydrogenase (SD) activity of tissue fragments taken at biopsy was assayed after exposure to heat (43 degrees C.) and radiation (6 grays) was done. The sensitivity to radiation plus heat treatment was estimated by the percentage of SD activity of the treated cells, compared with that of the control cells. The 43 patients were divided into three groups according to the degree of SD activity after exposure to radiation plus heat treatment. The SD activity was less than 50 per cent in group 1 (highly sensitive), between 50 and 70 per cent in group 2 (moderately sensitive), more than 70 per cent in group 3 (less sensitive). Eighteen of 20 in group 1, 11 of 17 in group 2 and two of six in group 3 were classified as being histopathologically "effective" for HCR therapy. The two year survival rate for groups 1, 2 and 3 were 55.5, 34.9 and zero per cent, respectively, while there were no statistical differences with regard to prognostic factors. These data suggest that in vitro activities of SD correlate well with the clinical effectiveness of HCR therapy. Therefore, it is recommended that a SD inhibition test be included among the guidelines for clinical management. 
1	Tyrosine kinase and control of cell proliferation. The usefulness of phosphotyrosine antibodies for the detection of physiologically regulated or deregulated tyrosine kinases is discussed in this report. This rather rare enzymatic activity is shared by receptors for some polypeptide growth factors and by the products of Class 1 oncogenes. The antibodies are able to detect proteins phosphorylated on tyrosine in fibroblasts stimulated with growth factors such as EGF and PDGF. The major phosphorylated protein species are the receptors themselves, which undergo phosphorylation only after the addition of the exogenous factor and only transiently. Phosphotyrosine antibodies were able to detect the products of the retroviral Class 1 oncogenes, which are endowed with deregulated tyrosine kinase activity. In fact, in these cases a constitutive phosphorylation of the relevant proteins was observed, which occurred continuously and independently of the presence or lack of exogenous ligands. A tyrosine kinase constitutively activated in human gastric carcinoma cells was detected by P-Tyr antibodies. This molecule has been characterized at the molecular level, and the mechanisms responsible for its enzymatic activation have been investigated. The question of whether the tyrosine kinase identified is responsible for the induction and the maintenance of the transformed phenotype in gastric carcinomas remains to be answered. It is reasonable to suggest that this might be the case by analogy with other situations such as Class 1 oncogenes activated by transduction by retroviruses, abnormal expression of EGF receptors, or deregulated activity of c-abl-encoded proteins in chronic myelogenous leukemia and acute lymphoblastic leukemia. Thus, the search for deregulated kinases by means of phosphotyrosine antibodies seems to be useful for identifying new activated oncogenes in clinical oncology. 
5	Secretion of a unique collagen by spontaneously transformed murine keratinocytes (PAM cells) in vitro. A spontaneously transformed murine keratinocyte cell line (PAM cell) was found to secrete two nondisulfide-linked collagenous polypeptides with apparent molecular weight (MW) 190-kd and 120-kd. Pulse-chase experiments indicated that the 190-kd polypeptide was secreted into the culture medium in 2 h and processed to the 120-kd collagen component within 4 h. This process was inhibited by EDTA. The 120-kd polypeptide was sensitive to pepsin, and a 50-kd fragment was produced by a mild pepsin treatment at 4 degrees C. A cyanogen bromide peptide map of the 120-kd polypeptide was distinct from that of types I, II, III, IV, and V collagens. These properties indicate similarities to the type VIII-related collagen produced by human astrocytoma cells. The secretion of the collagen rapidly reached a maximum level on the first day of culture and subsequently declined with cell proliferation. An accelerated processing to the 120-kd polypeptide was observed under culture conditions of high cell density. Similar collagens were also found to be produced by normal human keratinocytes. These results indicate that the 120-kd polypeptide is a potentially functional protein that may participate in the formation of the extracellular matrix of keratinocytes. 
1	11 beta-hydroxyandrostenedione: a marker of adrenal function in hirsutism. To assess the role of the adrenal glands in the development of hirsutism, levels of 11 beta-hydroxyandrostenedione (11 beta-OHA), 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), androstenedione (delta 4A), and free and total testosterone (T) were measured in 63 hirsute females and 30 control patients. Six of the hirsute patients had basal levels of 11 beta-OHA and 17-OHP and responses to adrenocorticotropic hormone that were significantly greater than these values in controls and the other hirsute women. These women were designated as having an adrenal source for their hirsutism. Women with polycystic ovarian syndrome and idiopathic hirsutism had normal values of 11 beta-OHA and 17-OHP. Levels of total and free T, DHEAS and delta 4A were significantly higher than control values in all of the hirsute women. This study demonstrates that 11 beta-OHA can be used as a marker to assess the adrenal contribution to hirsutism. 
5	Obstructive sleep apnea following topical oropharyngeal anesthesia in loud snorers. Previous studies support the presence of an upper airway reflex mechanism that contributes to the maintenance of upper airway patency during sleep. We investigated the possibility that interference with this reflex mechanism contributes to the development of obstructive sleep apnea. Eight otherwise asymptomatic snorers (seven male and one female), age 39 +/- 5.3 yr (mean +/- SEM), underwent overnight sleep studies on three successive nights. An acclimatization night was followed by two study nights randomly assigned to control (C) and oropharyngeal anesthesia (OPA). On the OPA night topical anesthesia was induced using 10% lidocaine spray and 0.25% bupivacaine gargle. A saline placebo was used on night C. All subjects slept well on both study nights (mean sleep duration was 6.2 h on both study nights), and sleep stage distribution was similar on both nights. Obstructive apneas and hypopneas (OAH) rose from 114 +/- 43 during C to 170 +/- 49 during OPA (p less than 0.02). Central apneas and hypopneas (CAH) were unchanged between the two nights (8 +/- 4.9 versus 7 +/- 3). The duration of OAH was similar on both study nights (20 +/- 1.9 s during C versus 20 +/- 1.5 s during OPA). The frequency of movement arousals terminating OAH tended to be higher during OPA (7 +/- 2.9/h) than during C (3 +/- 0.7); P = NS. The frequency of oxyhemoglobin desaturations was also higher during OPA (5 +/- 2.1/h) than during C (3 +/- 1.4), p less than 0.07. 
1	Pseudocyst of the auricle: successful treatment with intracartilaginous trichloroacetic acid and button bolsters. Pseudocyst of the auricle is an asymptomatic, noninflammatory cystic swelling that typically involves the anthelix of the ear and results from an accumulation of fluid within an unlined intracartilaginous cavity. We report a patient with a recurrent pseudocyst of the auricle and describe a new surgical technique for treating this condition by applying 50% trichloroacetic acid to the intracartilaginous cavity and utilizing external button bolsters for compressive therapy. This therapeutic approach is simple to perform in the office, results in permanent resolution of the pseudocyst, preserves the normal architecture of the external ear, and provides excellent postoperative and long-term cosmetic results. 
1	Expression of the MDR1 gene in human gastric and colorectal carcinomas. We measured expression of the MDR1 gene (also known as the PGY1 gene) in the human gastrointestinal tract. MDR1 messenger RNA (mRNA) levels were elevated in 13 of 15 colorectal carcinoma specimens and in six of 13 gastric carcinoma specimens. Well-differentiated colorectal carcinomas contained significantly higher concentrations of MDR1 mRNA than moderately differentiated colorectal carcinomas. Similarly, moderately differentiated gastric carcinomas contained higher concentrations of MDR1 mRNA than poorly differentiated gastric carcinomas. MDR1 gene expression in normal colorectal and gastric tissues adjacent to carcinomas was similar to that in the carcinomas. MDR1 gene expression in xenografts of colorectal and gastric carcinomas in nude mice was also investigated. Elevated expression of the MDR1 gene was seen in only four of 18 xenografts of colorectal carcinoma and was not seen in any xenografts of gastric carcinoma. P-glycoprotein was distributed over the luminal surface of the colorectal carcinoma. These results imply that the higher levels of MDR1 mRNA found in well-differentiated carcinomas derived from colorectal tissues are the results of increased expression of the MDR1 gene in the luminal surface cells. The level of expression of the MDR1 gene in colorectal and gastric carcinomas appears to correlate with the degree of differentiation and also appears to be affected by transplantation into nude mice. 
2	Prognostic factors in alcoholic liver disease. VA Cooperative Study Group. Two hundred eighty-one alcoholic patients were prospectively evaluated by clinical, biochemical, and histologic parameters during a 4-yr period to assess their prognosis. They were stratified into four categories of injury: 1) fatty liver (26 patients), 2) acute alcoholic hepatitis (106), 3) cirrhosis (39), and 4) cirrhosis with superimposed alcoholic hepatitis (111). The rate of survival and variables correlating with survival varied according to the group. At 48 months, 70% of the patients with fatty liver were alive, 58% in the alcoholic hepatitis group, 49% in cirrhosis, and 35% in alcoholic hepatitis superimposed upon cirrhosis. Within group one, deaths were due to causes unrelated to liver disease. In the alcoholic hepatitis group, factors significantly correlating with survival were ascites, alanine amino-transferase levels, grams of alcohol consumed, continuation of alcohol intake, and clinical severity of disease. Survival in patients of group three correlated significantly with prothrombin time and histologic severity score. Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis, with the most significant predictors of survival being age, grams of alcohol consumed, the ratio of serum aminotransferases (AST:ALT) and the histologic and clinical severity of the disease. Although a different pattern of correlates was observed for each pathologic level of injury, knowledge of the various correlates aids in prognostic assessment. 
3	Haemostatic changes in the loin pain and haematuria syndrome: secondary to renal vasospasm? Twenty-five patients (seven male, 18 female) were diagnosed as having the loin pain and haematuria syndrome. Presenting symptoms were either loin pain alone or pain associated with macroscopic or microscopic haematuria, and were longstanding, having been present for mean of 9.3 years in males, and 10 years in females. Ten patients described symptoms of passing gravel or renal stones but these were only demonstrated radiologically in two patients. Investigation of all patients showed anatomically normal renal tracts, normal renal function, and no significant proteinuria. Phase-contrast microscopy during episodes of haematuria revealed dysmorphic red cells in all 10 patients studied. Renal biopsies were performed in 20 patients and showed no glomerular pathology, but arteriolar and arterial hyalinosis was seen in 13 of 20 (65 per cent), fibro-elastosis in larger vessels in eight of 20 (40 per cent) and red blood cells in tubules in 13 of 20 (65 per cent) patients. The histological appearance in vessels was similar to that seen in cyclosporin A nephrotoxicity and would be consistent with the hypothesis that regional vasospasm occurs in the cortical circulation. Haematological studies in 22 patients, when compared with age and sex matched controls, showed the presence of circulating platelet aggregates, elevation of plasma beta-thromboglobulin (p less than 0.001), and increased platelet aggregation in response to serotonin and ADP (p less than 0.05 and p less than 0.03, respectively). Plasma concentrations of D dimer (p less than 0.02) and C-reactive protein (p less than 0.03) were also significantly elevated in the patient group. There was no deterioration of renal function during a mean observation period of 3.7 years and no patients developed proteinuria. Treatment was largely supportive; seven patients with intractable loin pain underwent surgical denervation with the relief of pain in four. 
5	Isolated erythroid hypoplasia and renal insufficiency induced by long-term griseofulvin therapy. We describe a patient with hematuria, pyuria, eosinophiluria, decreased renal function, and severe anemia that developed while she was receiving chronic therapy with griseofulvin for onychomycosis. We offer evidence that griseofulvin can cause an isolated erythroid hypoplasia and possibly an allergic interstitial nephritis. This is the first documented case of the above entities induced by the agent. We would recommend, based on our report, that otherwise healthy patients, when maintained on the drug for extended periods of time, have periodic determinations of renal function and hematologic status. As drug-induced erythroid hypoplasia typically occurs after a relatively long period of dosing, it may be prudent in certain individuals to monitor the CBC at approximately bimonthly intervals after initiation of therapy. Recommendations regarding monitoring of renal function are more difficult, as acute allergic interstitial nephritis can occur after either short- or long-term exposure to certain drugs. 
4	The mechanism of heart failure caused by cardiac allograft rejection. Rejection of the cardiac allograft is often associated with reversible myocardial failure, the mechanism of which is not understood. We have examined this phenomenon in a small animal model that provides the opportunity for multimodality study of the rejection process. Heterotopic cardiac transplantation was performed in the Lewis rat with Lewis X Brown-Norway (allografts) or Lewis (isografts) donors. Without immunosuppression, allografts are completely rejected in 6 to 8 days. At 3 days cardiac grafts were explanted and mounted on a modified Langendorff apparatus for functional measurements or submitted for pathologic examination and biochemical determination of high-energy phosphates. Three-day isografts (n = 9) had minimal histologic changes. Pathologic examination of 3-day allografts (n = 13) showed lymphocytic infiltrate and myocyte necrosis, histologic features for which antirejection treatment is usually given clinically. For grafts subjected to functional studies (n = 11), heart rate, cardiac output, coronary flow, and stroke work were determined at baseline and in response to isoproterenol (3 x 10(-8) mol/ml). Three-day allografts (n = 6) and isografts (n = 5) had similar baseline function. The chronotropic response to isoproterenol was similar in allografts and isografts, but allografts had diminished cardiac output and stroke work after isoproterenol. Adenosine triphosphate levels were normal (41.9 nmol/mg) in 3-day allografts (n = 4). We have evaluated functional, biochemical, and pathologic changes associated with myocardial dysfunction during heterotopic cardiac transplant rejection in a small animal. This model reproducibly demonstrates diminished contractile reserve in 3-day allografts with normal baseline function and high-energy stores but histologically significant rejection. 
4	Influence of Doppler sample volume location on the assessment of changes in mitral inflow velocity profiles. Previous studies that have validated Doppler indexes of mitral inflow have used pulsed wave sample volume locations either at the level of the mitral valve anulus or at the tips of the mitral valve leaflets. Although significant differences between absolute values for peak velocities and velocity time integrals at these sample volume locations have previously been reported, no information exists that has compared changes in inflow profiles after an intervention to improve left ventricular filling. To address this question, 13 patients with severe pulmonary hypertension (mean pulmonary artery pressure, 50 +/- 13 mm Hg) caused by chronic thromboembolic disease were studied with use of Doppler echocardiography immediately before and after surgical reduction of pulmonary hypertension (pulmonary vascular resistance decreased from 916 +/- 413 to 233 +/- 89 dynes.sec.cm5). This clinical model has been shown to have abnormal mitral inflow velocity profiles that improve markedly after surgery. Doppler measures of early and late peak velocities were significantly lower both before and after surgery when sampling at the mitral anulus compared with the leaflet tips, although late filling parameters and the deceleration of early flow velocity tended to differ little. With surgery, the significant increase in peak early velocity and the ratio of early to late velocity was present regardless of the sample volume location (peak E at leaflet tips, 47.1 +/- 16.0 to 68.9 +/- 15.4 [p less than 0.001], and at anulus, 40.7 +/- 11.3 to 56.2 +/- 14.6 cm/sec [p less than 0.001]; peak E/A at leaflet tips, 0.95 +/- 0.4 to 1.55 +/- 0.9, and at anulus, 0.78 +/- 0.3 to 1.32 +/- 0.7 [both p less than 0.02]). 
5	Oral labetalol in hypertensive urgencies. The response to incremental doses of oral labetalol in 16 patients with hypertensive urgencies is presented. After inadequate blood pressure control with 20 mg of intravenous furosemide, each patient received a 300 mg oral dose of labetalol. Subsequent oral doses of labetalol, 100 mg, were administered at 2-hour intervals, if the diastolic blood pressure remained greater than 100 mm Hg. The maximum dose of labetalol per patient was 500 mg. Five patients required only the initial 300 mg dose of labetalol. Two patients required further therapy for satisfactory blood pressure control. Mean arterial pressure fell from 156 +/- 12 mm Hg to 123 +/- 14 mm Hg. 
1	Bcr/abl recombinant DNA analysis versus karyotype in the diagnosis and therapeutic monitoring of chronic myeloid leukemia. Karyotype and bcr/abl recombinant DNA analyses are two means of detecting the chromosomal aberration in chronic myeloid leukemia. The authors compared these two methods in a retrospective study of 36 patients with CML in which they found the bcr/abl DNA recombinant event in 100% (29 of 29) of those patients who had the Philadelphia chromosome. To achieve this sensitivity, a battery of two bcr probes and three restriction enzymes is necessary. The authors propose a sequential algorithm for efficient use of these probes and enzymes. In 76% of the patients, bcr/abl rearrangement can be detected with a Bgl II digest and a 3' commercial probe. An additional 21% of patients can be detected by a second assay in which the same membrane is rehybridized to a 3' and 5' combination bcr probe. One patient (3%) required an additional restriction enzyme digest with BamH I to detect the recombinant event by the same 3' probe. Karyotype analysis is used to determine cytogenetic remission in patients with CML under therapy. The authors studied the use of DNA analysis by the Southern blot technique to detect a decrease in the relative number of leukemic cells. By dilution studies and densitometric scanning of autoradiographs, the authors were able to detect a 15% decrease in the relative number of cells having the bcr/abl recombinant event. The authors report the preliminary results of three patients in whom they compared the karyotype and recombinant DNA analysis at multiple time points in their clinical course. In conclusion, the bcr/abl recombinant DNA analysis is superior to karyotype for the diagnosis of CML and can be used for monitoring treated patients. 
1	Forces of change in the health care system. Implications for cancer care in the 1990s. Dramatic changes will occur in the health care system during the 1990s which will profoundly affect the delivery of care for cancer. Perhaps the most important factor is the aging of the population. As the proportion of people who achieve old age increases, the absolute prevalence and incidence of cancer will increase despite improved treatment techniques. This phenomenon will increase health care expenditures despite ongoing efforts to control costs. Second, there will be continuing efforts at cost control and increased emphasis on quality assurance and outcomes by third party payers. Providers will be scrutinized and compared with one another. The large payers of the nation's health care bills will demand proof of outcome and cost leading to bidding by providers and payment only to those who have the best outcome for the least money. Third, there will be an increasing emphasis on prevention and screening, in public health policy, an approach that may conflict with personal freedom. Fourth, there will be increasing deliberations and questions about the ethics of the health care system and treatment decisions. There will be continuing debate about the need for a rationing of health care and the right of individual privacy versus the states' right to preserve life. These changes will impact on all health care professionals whose practice includes patients with cancer. 
2	Pancreatic ascites: treatment by continuous somatostatin infusion. Two male patients with recurrent acute pancreatitis due to alcohol abuse were admitted with pancreatic ascites (high concentration of amylase, raised protein concentration, no specific cytologic features). Ultrasound (US) and computed tomography (CT) confirmed gross ascites and inflammation of the pancreas in both patients, and a pseudocyst in the head of the pancreas in one of them. Treatment with total parenteral nutrition (TPN) and a H2-blocking agent was instituted and continued for 4 and 2 wk, respectively. Due to lack of improvement, somatostatin infusion (250 micrograms/h) was started. During the next few days, there was a rapid improvement of the clinical status, and the production of ascites ceased. We conclude that somatostatin infusion should be tried before any invasive diagnostic or therapeutic intervention in patients with pancreatic ascites. 
3	Partial cytochrome b deficiency and generalized dystonia. An 18-year-old female had clinical features of idiopathic torsion dystonia with bilateral hypodense putaminal lesions on computed tomography. Mitochondrial encephalomyopathy was suspected because of persistent lactic acidemia and myopathy. Studies of oxidative metabolism on isolated skeletal muscle mitochondria revealed partial cytochrome b deficiency indicating a defect in the cytochrome b- c1 complex. This finding represents a unique, multisystem syndrome of progressive dystonia, putaminal degeneration, myopathy, and mitochondrial cytochrome b deficiency. Mitochondrial metabolic disorders may be a cause of torsion dystonia when other known associated factors are absent. 
1	Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial. Between October 1985 and March 1988, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase II trial of carboplatin 560 mg/m2 every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 21 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/microliters, and 37% had platelet count nadirs less than 25,000/microliters. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity. 
5	Efficacy of induction therapy in cadaveric renal transplantation comparing rabbit antithymocyte serum and Minnesota antilymphoblast globulin. From August 1986 to July 1989, 98 patients receiving primary cadaveric kidney transplants received either RATS (n = 50) or MALG (n = 48) during the induction phase of a quadruple immunosuppressive protocol. Patient groups were well matched. The duration of RATS and MALG treatment and the time of CyA induction were equivalent. Serum creatinine and rejection episodes up to 1 year were not statistically different. Hematologic side effects resulted in dose reduction of MALG in 42% of patients without adverse rejection results. In the RATS group, no dosage reductions were required. One-year patient survivals (96% to 100%), and 1-year graft survival (82% to 85%) were not significantly different in the 2 groups. Infectious complications were 30% higher in the MALG group and a significant factor in 2 deaths. Monitoring of lymphocyte subsets revealed insignificant differences in the percent of decrease of each cell population between MALG and RATS groups during induction. 
1	Prognostic factors and value of adjunctive nephrectomy in patients with stage IV renal cell carcinoma. We reviewed 57 cases of Stage IV renal cell carcinoma to clarify the factors influencing prognosis and to evaluate the value of nephrectomy. Cumulative survival from the initial diagnosis was analyzed with respect to the patients' age, sex, side of primary tumor, initial performance status (PS), site of metastasis, and nephrectomy. Overall survival for the patients was 51 percent at one year, 22 percent at three years, and 11 percent at five years. Age, sex, and side of primary tumor had no influence on survival. Improved survival was correlated with good PS, metastases limited to single organ, and removal of the primary tumor. With regard to histopathologic features in nephrectomized patients, low grade and stage were correlated with longer survival. These factors should be considered in the analysis of results of future clinical trials of metastatic renal cell carcinoma. 
1	Natural history of cardiac rhabdomyoma in infancy and childhood. Although spontaneous regression of cardiac rhabdomyoma has been reported, prognosis is still considered to be poor and surgery continues to be indicated. The experience with rhabdomyoma diagnosed in live infants over a 20-year period was reviewed. Diagnosis by angiography or echocardiography was accepted only if multiple tumors were present or if tuberous sclerosis was also diagnosed. Nine patients (3 diagnosed prenatally and the remaining 6 at age less than 8 months) were identified as having a total of 24 tumors. Measurements in 2 planes demonstrated at least some evidence of regression in 24 patients (100%), with 20 of 24 having complete resolution. One patient required delayed surgery for excision of a subaortic ridge that appeared at the site of a resolved tumor. Our findings suggest that pediatric cardiac rhabdomyoma is most often a benign condition in which spontaneous regression is the rule. Surgery is recommended only for patients with refractory dysrhythmias or severe hemodynamic compromise. 
4	Regurgitant jet size by transesophageal compared with transthoracic Doppler color flow imaging. Combined echocardiography and Doppler color flow mapping from transthoracic imaging windows has become the standard method for the noninvasive assessment of valvular regurgitation. This study compared regurgitant jet areas by Doppler color flow imaging derived from the newer transesophageal approach with measurements obtained from conventional transthoracic apical views. Maximal regurgitant jet area determinations and an overall visual estimate of lesion severity were obtained from 42 patients who underwent color flow examination by both techniques. Seventy-three regurgitant lesions were visualized by transesophageal flow imaging: 34 mitral, 22 aortic, and 17 tricuspid jets. Transthoracic studies in the same patients revealed fewer regurgitant lesions for each valve; 20 mitral, 16 aortic, and 12 tricuspid (p = 0.0009). A comparison of maximal jet areas determined by transesophageal and transthoracic studies showed a good overall correlation (r = 0.85, SEE = 2.8 cm2) and a systematic overestimation by the transesophageal technique (TEE = 0.96 TTX + 2.7). For the subgroup with mitral insufficiency, valve lesions visualized by both techniques were larger by the transesophageal approach (n = 18, 6.0 versus 3.6 cm2, p = 0.008). Semiquantitative visual grading of individual valve lesions by two independent observers revealed a higher grade of regurgitation with more jets classified as mild (38 versus 25), moderate (18 versus 13), and severe (17 versus 10) by esophageal imaging than by transthoracic imaging. Thus, transesophageal color flow mapping techniques yield a higher prevalence of valvular regurgitation than do transthoracic techniques in the same patients. Jet area and the overall estimate of regurgitant lesion severity were also greater by transesophageal color Doppler imaging compared with standard transthoracic imaging. 
4	Oral contraceptive therapy and the surgical management of ENT patients: a review of current clinical practice. The current policy of British Otolaryngologists with regard to the preoperative cessation of the oral contraceptive pill is reported. This is based on a confidential questionnaire sent to all members of the British Association of Otolaryngologists. The overall response rate was 66%, 91% of which were from practising otolaryngologists and forms the basis of this report, the remaining 9% being from respondents not engaged in active surgery. Although there is evidence to show an increased risk of developing thromboembolic complications after major abdominal, gynaecological and hip surgery in those patients taking the oestrogen-containing contraceptive pill, the risk following minor and intermediate surgery (which forms the bulk of the otolaryngologist's workload) is not known. Not surprisingly therefore the results of the survey show a varied policy across the country with 36.5% of respondents choosing to continue the pill and 25% always stopping the pill preoperatively. The remainder elect to stop the pill only in certain circumstances. 
1	The relationship of Papanicolaou testing and contacts with the medical care system to stage at diagnosis of cervical cancer. The relationship of Papanicolaou (Pap) testing and physician visits to stage at diagnosis of cervical cancer was assessed by interviews with 149 women with invasive cervical cancer and 214 women with in situ cervical cancer. A significantly smaller percent of study subjects with invasive disease than in situ disease had at least one Pap test in the 3 years prior to diagnosis (age- and race-adjusted odds ratio: 3.38). The two groups did not differ in visits to a physician for other reasons during this period. Pap testing decreased with increasing age for both groups, but not physician visits. While 65% percent of the subjects with invasive disease aged between 65 and 79 years had never had a Pap test until diagnosis, 88% had seen a physician in the preceding 3 years. Women with regional or distant invasive disease were least likely to have had Pap tests, and, within this group, those aged between 35 and 64 years were also least likely to have seen a physician. Strategies for early detection must reflect missed opportunities and the need to bring those not receiving care into the system. 
2	The hazards of surgical glove dusting powders. Surgical contaminants of many kinds, including glove powder, constitute a source of formation of granulomas. This is particularly well-documented in the peritoneal cavity ("starch peritonitis"), but has been documented in most anatomic sites. The production of starch-free gloves should remove this hazard, but the surgeon should remain aware that most particulate substances introduced into the body inevitably set up an inflammatory response. 
3	Diurnal fluctuations of arterial ketone body ratio in normal subjects and patients with liver dysfunction. To explore the metabolic aspects of chronic liver disease, diurnal changes of arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were investigated in normal subjects, patients with chronic liver disease (Child's class A or B), and patients with hepatic failure (Child's class C). Ketone body ratio in normal subjects increased after breakfast from 0.96 to 2.00, after lunch from 2.17 to 2.38, and after dinner from 1.23 to 2.55 with blood glucose level ranging from 103 to 141 mg/dL (5.7 to 7.8 mmol/L). By contrast, the ketone body ratio in the Child A or B group changed little and remained within a range of 0.70-1.35 despite a large change in blood glucose level from 102 to 176 mg/dL (5.7 to 9.8 mmol/L). Ketone body ratio in Child's class C remained near or below 0.4 with no response to glucose administration, despite a marked elevation in blood glucose level. These results indicate that hepatic mitochondrial redox potential undergoes diurnal changes in sharp response to meals in normal liver function but that these fluctuations are absent in patients with liver damage (Child's class A, B, and C). Furthermore, it remains at low levels in severe liver failure (Child's class C). It is also suggested that hepatic mitochondrial redox potential plays an important role in the regulation of blood glucose levels. 
1	Immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma. Epidermal growth factor receptor (EGF-R) expression was studied immunohistologically in 38 patients with esophageal squamous cell carcinoma. The EGF-R was faintly expressed in basal and parabasal layers of normal esophageal epithelia and in cancer nests of 20 patients; it was strongly expressed in all areas of dysplastic epithelia and in cancer nests of 18 patients. The patients with strongly expressed EGF-R had lymph node metastases more frequently, and their prognosis was poorer than those with faintly expressed EGF-R. The EGF-R expression showed a mosaic pattern in 17 patients and a diffuse pattern in 21 patients. The patients with a mosaic pattern had lymph node metastases more frequently and a worse prognosis than those with a diffuse pattern. Expression of EGF-R in metastatic lymph nodes was similar to that in strongly expressing areas of primary cancers with a mosaic pattern. Thus EGF-R expression may be an important indicator for malignancies of esophageal squamous cell carcinomas because primary cancer cells with strongly expressed EGF-R metastasize to lymph nodes more frequently. 
5	An effective treatment protocol for intraarterial drug injection. Between 1972 and 1988, 48 patients with extremity ischemia after an intraarterial drug injection were treated with the following protocol: heparin, dextran 40, dexamethasone, elevation, and early mobilization of the extremity. A tissue ischemia score, derived by assessing the color, capillary refill, sensory function, and temperature of the extremity, was used to assess the ischemic injury. Each sign was scored either normal = 0 or abnormal = 1; then summed to provide the tissue ischemia score (range, 0 to 4). Twenty-four (50%) patients had an extremity tissue ischemia score less than or equal to 2. After treatment 22 of the 24 patients had a normal extremity, and 2 required limited digital amputations. In this group, outcome was comparable regardless of the time interval from intraarterial drug injection to treatment. Ten of 24 (50%) patients with an extremity tissue ischemia score greater than 2 had a normal extremity, 3 had a functional deficit, and 11 required digital amputations. Twelve of the 24 patients were treated within 24 hours and had a significantly superior outcome when compared to the 12 who were treated more than 24 hours after intraarterial drug injection (p less than 0.001, Fisher's exact test). The tissue ischemia score is a useful predictor of extremity outcome in patients with intraarterial drug injection. The outlined treatment protocol is effective in minimizing tissue injury caused by intraarterial drug injection. Institution of treatment within 24 hours of intraarterial drug injection is particularly important in patients who manifest severe ischemia. 
4	Renal vascular disease in African-Americans and other racial minorities. Hypertensive end-stage renal disease is about 10-fold more common nationwide in African-Americans than in Caucasians and 17-fold higher in some sections of the United States. These figures are alarming and require a much greater effort in understanding the causes of this disparity and improving blood pressure control in this population to prevent catastrophic renal damage. More information is also needed about the renovascular status of other minorities. Financial obstacles to antihypertensive care appear to be an important contributing factor to the disparities of end-stage renal disease in African-Americans and perhaps other minorities. 
5	Species-dependent effects of adenosine on heart rate and atrioventricular nodal conduction. Mechanism and physiological implications. This study 1) compares the negative chronotropic and dromotropic actions of adenosine in guinea pig, rat, and rabbit hearts; 2) investigates the mechanism(s) for the different responses; and 3) determines the physiological implications. Isolated perfused hearts were instrumented for measurement of atrial rate and atrioventricular (AV) nodal conduction time. Differences in metabolism of adenosine were determined in the absence and presence of dipyridamole (nucleoside uptake blocker) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, adenosine deaminase inhibitor). Dipyridamole plus EHNA decreased adenosine's EC50 for the negative dromotropic effect by 14-fold in guinea pig heart and 1.6-fold in rat heart. This is consistent with the greater number of [3H]nitrobenzylthioinosine binding sites measured in membranes from guinea pig (1,231 +/- 68 fmol/mg protein) compared with rat (302 +/- 31 fmol/mg protein) and rabbit (260 +/- 28 fmol/mg protein) atria. The potency of adenosine to slow atrial rate and prolong AV nodal conduction time was greater in guinea pig than in rat or rabbit hearts. This rank order of potency correlated well with the number of binding sites for the specific adenosine receptor radioligand 125I-aminobenzyladenosine in guinea pig (102 +/- 13 fmol/mg protein), rat (11 +/- 0.5 fmol/mg protein), and rabbit (8 +/- 1 fmol/mg protein) atrial membranes. Hypoxia increased the rate of adenosine release by severalfold and caused slowing of heart rate and AV block. In spontaneously beating hearts, the main effect of hypoxia was a slowing of ventricular rate, which in the guinea pig heart was due to AV block and in the rat heart to atrial slowing. In atrial paced hearts, hypoxia caused a marked prolongation of AV nodal conduction time in guinea pig (39 +/- 4 msec) and rabbit (29 +/- 5 msec) hearts, but only small effect in rat hearts (10 +/- 2 msec). The differences in response to hypoxia could be accounted for by the species-dependent differences in the 1) amount of adenosine released and metabolized, 2) sensitivity of the hearts to adenosine, and 3) dependency of AV nodal conduction on atrial rate. The findings indicate that the results from physiological or pharmacological studies on adenosine in one species may not be applicable to others, and the ultimate effect of adenosine and hypoxia is to slow ventricular rate. 
5	Daytime reduction of gastro-oesophageal reflux after healing of oesophagitis and its value as an indicator of favourable response to maintenance treatment. In order to investigate the response of gastro-oesophageal reflux after medically induced healing of oesophagitis and its relation to the occurrence of relapse during prophylactic treatment, 20 patients with erosive/ulcerative oesophagitis underwent 24 hour oesophageal pH monitoring before and after healing achieved with 12 to 24 week treatment with ranitidine 150 or 300 mg twice daily. Compared with pretreatment values, after macroscopic healing, a significant reduction in daytime median percentage of reflux time (10.0 v 6.5; p less than 0.05) and median number of reflux episodes lasting more than 5 minutes (5-5 v 1.0; p less than 0.05) were observed, whereas during night time reflux frequency and severity did not change. During maintenance treatment with ranitidine 150 or 300 mg nocte, five of the six patients, who had shown no improvement in gastro-oesophageal reflux after acute healing, relapsed. These results suggest that, in contrast with previous work, a decrease in gastro-oesophageal reflux in patients with reflux oesophagitis can be achieved after macroscopic healing, and that the occurrence of such a reduction after acute healing is predictive of a good response to longterm treatment. 
4	Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model. A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap. The right common iliac artery was divided in 15 rabbits. In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group). In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group). After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals. The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005). Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb. The augmentation in perfusion provided by these connections can be quantified. 
3	Nonfearful panic disorder in neurology patients validated by lactate challenge. OBJECTIVE: Nonfearful panic disorder meets the DSM-III-R criteria for panic disorder but is not associated with subjective fear and anxiety. The authors determined its prevalence in a group of neurology patients and assessed its diagnostic validity as a panic disorder subtype by evaluating the response of the patients with nonfearful panic disorder to sodium lactate and antipanic pharmacotherapy. METHOD: The subjects were all neurology patients referred over 1 year to a university hospital's psychiatric consultation service because of negative medical workups for their symptoms (N = 48). Patients who met the DSM-III-R criteria for panic disorder but did not report subjective anxiety or fear during panic episodes were diagnosed as having nonfearful panic disorder. Afterward, each of those patients received a sodium lactate infusion and, 5 hours later, a sodium chloride infusion. They were then treated with antipanic medication and followed for at least 6 months. RESULTS: Of the 48 neurology patients referred for psychiatric evaluation, 11 (23%) met the criteria for panic disorder, and all 11 met the criteria for nonfearful panic disorder. All 11 responded positively to lactate but not to placebo, and they each experienced an at least 75% reduction in symptoms during the 6-month follow-up period. Detailed case reports of three of these patients are presented. CONCLUSIONS: These findings support the construct and predictive diagnostic validity of nonfearful panic disorder as a subtype of panic disorder and suggest that a lack of attention to this group leads to both the underestimation of the prevalence of panic disorder and to the withholding of potentially successful treatments for this group. 
1	Effects of site-directed mutagenesis at residues cysteine-31 and cysteine-184 on lecithin-cholesterol acyltransferase activity. Native lecithin-cholesterol acyltransferase (LCAT; phosphatidylcholine-sterol acyltransferase; phosphatidylcholine:sterol O-acyltransferase, EC 2.3.1.43) protein, and LCAT in which either or both of the enzyme free cysteines had been replaced with glycine residues by site-directed mutagenesis, has been expressed in cultured Chinese hamster ovary cells stably transfected with the human LCAT gene. The mass of LCAT secreted, determined by immunoassay, did not differ in the native and mutant species. LCAT specific activity was also unchanged in the mutant species. In particular, the cysteine-free double mutant, in which Cys-31 and Cys-184 had both been replaced, was fully active in the synthesis of cholesteryl esters. This result is not consistent with a catalytic role for LCAT free cysteine residues. The classical inhibitor of LCAT activity, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), which strongly (89%) inhibited the native enzyme, had partial (45%) inhibitory activity with mutant enzyme species containing a single -SH residue, while the double mutant was not significantly inhibited by DTNB. These data are interpreted to suggest that Cys-31 and Cys-184 are vicinal both to each other and to the "interfacial binding site" at residues 177-182, and that DTNB exerts its effect by steric inhibition. 
4	A novel mechanical cardiac assist device for reversing left ventricular failure. Diastolic augmentation of aortic pressure is an efficacious means of improving coronary perfusion in heart failure. A novel mechanical cardiac assist device (MCAD), that has advantages over a conventional intraaortic balloon pump and left ventricular assist devices, has been developed. It consists of a high efficiency rotary solenoid, coupled to a pair of actuator plates that clamp on a shunt aortic graft section, and operates in a diastolic counterpulsation mode. The system has been evaluated in six anesthetized, thoracotomized dogs with myocardial ischemia. The MCAD was activated 30-40 min after coronary artery occlusion and synchronized with the R-wave. As illustrated by a representative sample of the data obtained from one of several trials, the preliminary experimental results demonstrated that the MCAD worked effectively to fulfill the primary functions of a counterpulsation assist device, i.e., augmentation of coronary perfusion and reduction in the vascular impedance to ventricular ejection. 
5	Scintigraphic assessment of leukocyte infiltration in acute pancreatitis using technetium-99m-hexamethyl propylene amine oxine as leukocyte label. The infiltration of leukocytes has been linked to the pathophysiology of complicated or severe pancreatitis. We have tested the ability of leukocyte scintigraphy using technetium-99m-hexamethyl propylene amine oxine (HM-PAO) as label to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis. Twenty-eight patients with acute pancreatitis (eight with biliary, 13 with alcoholic, and seven with unknown origin) were studied with leukocyte scintigraphy using planar imaging and single photon emission computed tomography (SPECT). Fourteen patients had a mild (group I), II a severe (group II), and three a lethal outcome (group III) of pancreatitis. All patients of group III, six of group II, and two of group I had a positive leukocyte scan. Thus, the sensitivity of leukocyte scintigraphy for the detection of a lethal course of acute pancreatitis was 100%, of a severe course 54%, and of a severe or lethal course 64%. The specificity of a negative scan for a mild pancreatitis was 86%. Comparison of the results of leukocyte scintigraphy with those of contrast enhanced CT showed that six of eight patients with pancreatic necrosis in CT had a positive leukocyte scan, but only five of 20 patients without detectable pancreatic necrosis in CT. In summary, leukocyte infiltration into the pancreas during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy using technetium-99m-HM-PAO as label. A correlation between the severity of the disease and leukocyte infiltration exists. 
3	Clinical dysautonomia in patients with bronchial asthma. Study with seven autonomic function tests. Fifty asthmatic patients and 20 healthy control subjects, carefully age- and sex-matched, were subjected to seven standardized tests to evaluate their autonomic status. Due care was taken to remove factors which could interfere with results. Of the tests concerned with the parasympathetic system, the intravenous atropine test (p greater than 0.10) and heart rate response to standing (p greater than 0.01) which measured the basal parasympathetic tone, did not show a significant difference. Tests requiring stimulation of the parasympathetic system, ie, deep breathing test (p less than 0.001), Valsalva maneuver (p less than 0.001), and carotid sinus massage (p less than 0.001) showed significantly heightened response. Postural fall of blood pressure (p greater than 0.10) and sustained hand grip test (p greater than 0.10), chiefly concerned with the sympathetic system, did not show a significant difference. Of the 50 asthmatic patients, nine were atopic and 41 nonatopic. When the results were compared in the two groups separately, we found that there was no alteration in the measurements except the intravenous atropine test which showed heightened response with atopic subjects (p less than 0.05). These results suggest that hyperresponsiveness of the parasympathetic system is an important factor in producing bronchial spasm in asthmatic patients, and atopic and nonatopic subjects do not differ much in their autonomic status. 
4	Cardiovascular risk factor clustering and ratio of total cholesterol to high-density lipoprotein cholesterol in angiographically documented coronary artery disease. High levels of cardiac risk factors tend to cluster together and act synergistically. To develop a suitable and practical marker for clustering, we evaluated 380 consecutive patients at the time of coronary angiography. Analyses of lipid, rheologic, clinical and arteriographic profiles indicated a variety of interwoven relations. Because the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (total/HDL cholesterol) was closely related to both the presence and extent of greater than or equal to 50% diameter reduction of greater than or equal to 1 coronary arteries, it was used to divide patients into quartiles. Clustering of high- and low-level risk factors was demonstrated in the highest and lowest quartiles of total/HDL cholesterol, respectively (p less than 0.001). The highest quartile may be characterized by an only moderately elevated total cholesterol level but patients in this quartile may have a very low HDL cholesterol level, high triglycerides, a tendency toward high hemoglobin and fibrinogen levels, a history of smoking, previous myocardial infarction and multivessel disease. These results suggest that total/HDL cholesterol serves as a marker not only for obstructive coronary disease but also for a cluster of potentially modifiable risk factors. 
1	Distribution of immunoglobulins and secretory component in gastric cancer of the aged. The secretory immune system plays an important role in the local humoral immunity of the gastrointestinal tract. In order to evaluate humoral immunity in gastric cancer, distribution of immunoglobulins (Ig) and secretory component was immunohistochemically studied in 74 early and 15 advanced primary gastric cancers. In non-cancerous gastric mucosa, IgA and IgM, and secretory component were mainly identified in the cytoplasm of the intestinal metaplasia. In early gastric cancer of well-differentiated type, the localization of IgA and IgM, and secretory component was similar to that of intestinal metaplasia. In advanced gastric cancer, they were faintly observed and showed low positivity. The number of Ig-containing cells infiltrating cancerous stroma was enumerated. Immunoglobulin A-containing cells were dominant in the stroma of early gastric cancer. On the other hand, there were few Ig-containing cells in the stroma of advanced gastric cancer, and the number of IgA-containing and IgM-containing cells was also decreased. These results suggest that local humoral immunity is suppressed in gastric cancer, especially in advanced gastric cancer. 
5	Decalcification of a choroidal osteoma. A 56-year-old man presented with a clearly defined orange tumour in the posterior pole of his left eye. A choroidal osteoma was suspected, and ultrasonography confirmed the diagnosis. Fluorescein angiography demonstrated subretinal neovascularisation on the nasal edge of the tumour, which was treated with krypton laser photocoagulation twice. Recurrent subretinal neovascularisation occurred one year later and was not amenable to treatment. Three years after the patient first presented, thinning of the tumour was noted on follow-up examination. During the next 15 months the tumour completely disappeared, leaving an area of retinal pigment epithelial and choroidal atrophy. Total decalcification of the choroidal osteoma was demonstrated by ultrasonography. 
4	Hemodynamic basis of stasis ulceration--a hypothesis. Approximately 25% of patients with stasis ulceration have normal or below normal ambulatory venous pressures. A reflux index was calculated by multiplying postexercise pressures by Valsalva-induced foot venous pressure elevation. In patients with stasis ulceration, reflux index was found to have an excellent negative predictive value with a clear discriminant line between normal limbs and those with ulcers. Increasing incidence of stasis ulceration was demonstrated with increasing reflux index value. Even when ambulatory venous pressure was within the normal range, the index was found to be abnormal in ulcerated limbs because Valsalva-induced foot venous pressure was elevated in these limbs. Conversely, some patients with stasis ulceration and normal Valsalva foot venous pressure elevation were found to have abnormal ambulatory venous pressure values, yielding an elevated reflux index. Preliminary analysis indicates that reflux index may be a better predictor of surgical outcome after valve reconstruction procedures than either ambulatory venous pressure or Valsalva-induced foot venous pressure elevation. The concept of reflux index is a hypothesis that attempts to explain inconsistencies observed in implicating ambulatory venous hypertension as the sole determinant of venous reflux. 
4	Automatic implantable cardioverter-defibrillator implantation without thoracotomy using an endocardial and submuscular patch system. The automatic cardioverter-defibrillator lead system is implanted by a thoracotomy procedure that may result in atelectasis, pleural effusion, cardiac tamponade and lengthy convalescence. A new defibrillator lead system that allows selection of different defibrillating current pathways is implanted without a thoracotomy. Ten patients requiring a cardioverter-defibrillator for recurrent sustained ventricular tachycardia (five patients) or aborted sudden cardiac death (five patients) were evaluated for implantation of this lead system. A lead configuration with a bidirectional defibrillating current pathway was implanted in nine patients. The defibrillation threshold with this lead configuration was 15 J in five patients, 20 J in three and 30 to 35 J in one patient. In the remaining patient the lead system had a 40 J defibrillation threshold and was not implanted. No perioperative complications occurred. Induced ventricular fibrillation was successfully terminated at the predischarge and intermediate follow-up (8 to 12 weeks) electrophysiologic studies. During the follow-up period, there were three deaths (one sudden, two due to heart failure) and two lead system failures (oversensing with inappropriate shocks in one patient and patch lead fracture in another). Implantation of the cardioverter-defibrillator lead system by a nonthoracotomy approach is feasible, has no significant perioperative complications and is well tolerated by patients. Effective defibrillation was demonstrated immediately as well as at intermediate follow-up study. The occurrence of patch lead fracture and oversensing requires improvement in the present (nonthoracotomy) lead system technology. 
3	Physiologic and psychobehavioral research in oncology. A major thrust in research in psychosocial oncology is the study of the interaction of psychologic and physiologic variables. This discussion reviews the current status and future directions of such research. Areas addressed include pain, nausea and vomiting with chemotherapy, sexuality, effects of cancer on psychologic and neuropsychologic function, impact of psychologic factors on cancer and its treatment, and psychoneuroimmunology. In addition, specific recommendations for strategies to facilitate research in these areas of psychosocial oncology are proposed. 
5	Syncope of unknown origin: clinical, noninvasive, and electrophysiologic determinants of arrhythmia induction and symptom recurrence during long-term follow-up. Ninety-one consecutive patients with syncope of unknown origin underwent electrophysiologic studies (EPS). Univariate analysis identified the following variables: age, + signal-averaged ECG (SAECG), left ventricular ejection fraction (LVEF), history of myocardial infarction, coronary artery disease, left ventricular aneurysm, and history of sustained monomorphic ventricular tachycardia (SMVT) on Holter; multivariate analysis identified +SAECG, LVEF, and history of SMVT as risk factors for induction of SMVT at EPS. All patients were followed up for 19.0 +/- 8.3 months and 17 had recurrence of syncope. Patients were divided into empiric, EP-guided, and no therapy groups. The EP-guided therapy group included all patients with SMVT at EPS. Recurrence rates among all three groups were similar. We conclude that: (1) Patients who have inducible SMVT at EPS can be identified using certain clinical and noninvasive variables. When these patients undergo EP-guided therapy, their rate of recurrence of syncope becomes compatible with that of patients who had no arrhythmia induced at EPS. (2) Empiric therapy does not offer any benefit over no therapy in reducing the rate of recurrent of scope. 
4	Radiation-associated valvular disease. The prevalence of radiation-associated cardiac disease is increasing due to prolonged survival following mediastinal irradiation. Side effects of radiation include pericarditis, accelerated coronary artery disease, myocardial fibrosis and valvular injury. We evaluated the cases of three young patients with evidence of significant valvular disease following mediastinal irradiation. One patient underwent the first reported successful aortic and mitral valve replacement for radiation-associated valvular disease (RAVD) as well as concurrent coronary artery revascularization. A review of the literature revealed 35 reported cases of RAVD, with only one successful case of valve replacement that was limited to the aortic valve. Asymptomatic RAVD is diagnosed 11.5 years after mediastinal irradiation compared with 16.5 years for symptomatic patients, emphasizing that long-term follow-up is important for patients receiving mediastinal irradiation. This study defines a continuum of valvular disease following radiation that begins with mild asymptomatic valvular thickening and progresses to severe valvular fibrosis with hemodynamic compromise requiring surgical intervention. 
3	Immunological differentiation between neuroborreliosis and multiple sclerosis. Neuroborreliosis, a tick-borne spirochaetosis of the central nervous system, is diagnosed by the presence of intrathecally synthesized Borrelia burgdorferi-specific antibodies. Multiple sclerosis and neuroborreliosis can show similarities in clinical symptoms as well as lymphocytic cell reactions and oligoclonal bands in the isoelectric focusing of cerebrospinal fluid. To differentiate between multiple sclerosis and neuroborreliosis we tested intrathecally synthesized IgM and virus antibodies. The IgM indices were higher for most of the neuroborreliosis patients studied than for those with multiple sclerosis, and cell counts were also significantly higher in the acute stage of the disease. In 84% of multiple sclerosis patients we were able to demonstrate intrathecal antibody production against measles, rubella or mumps virus. Neuroborreliosis patients had no intrathecal virus antibody synthesis. The specification of oligoclonal bands resulting from isoelectric focusing of cerebrospinal fluid with an ELISA for B. burgdorferi can further substantiate the diagnosis of neuroborreliosis or help to rule it out in multiple sclerosis patients with positive borrelia-specific serology. 
2	Colonoscopy in critically ill patients. What conditions call for it? Indications for colonoscopy in the intensive care unit include acute lower intestinal bleeding, sigmoid volvulus, pseudo-obstruction of the colon, and suspicion of pseudomembranous colitis. Although the incidence of cardiorespiratory complications may be higher in these critically ill patients, the procedure can be done safely with proper attention to detail. Because of colonic dilatation, endoscopy can often be done without bowel preparation. 
4	Evaluation of metastatic cardiac calcification in a model of chronic primary hyperparathyroidism. Recent reports have fueled an interest in the prevalence and significance of metastatic calcium deposition in patients with chronic hyperparathyroidism. Experimental data are limited by the lack of suitable in vivo animal models. We have developed a model of marked hypercalcemia and overproduction of parathyroid hormone using somatic gene transfer. Briefly, the process involves infection of cultured rodent fibroblasts (RAT-1 cells) with a retroviral expression vector that contains the gene encoding human parathyroid hormone. Fibroblasts are grown to confluence on collagen-coated dextran microcarrier beads and are injected into the peritoneal cavities of syngeneic Fisher rats. Human parathyroid hormone production in rat serum is quantified by an immunoradiometric assay for human parathyroid hormone (1-84), which does not recognize rat parathyroid hormone. These rats consistently show production of human hormone within a week. Levels increase progressively, often to 1 ng/ml within 60 days of injection. Serum calcium showed a concomitant rise to an average of 15.5 mg/dl. In this study, 13 rats that had been transplanted with parathyroid hormone-producing fibroblasts were killed 80 days after injection. Examination of the skeleton revealed demineralization and histopathologic sequelae of parathyroid hormone excess with extensive osteoclastic bone resorption. Examination of the hearts revealed calcification in five of 13 hearts. There was no involvement of major coronary arteries or conducting systems, but there was calcification of cardiac myocytes, primarily in subepicardial region. This model may permit an understanding of the mechanisms for sudden cardiac death in severe hypercalcemia. 
5	Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with surgically treated congenital heart disease residing greater than or equal to 1,200 meters above sea level. Little data are available on the hemodynamic effects of premedications and anesthetic agents on infants and children. Ketamine is the most frequently used anesthetic agent for cardiac catheterization procedures in pediatric patients with congenital heart disease. Previous reports both suggest and deny ketamine's pulmonary vasoreactive effects. Since the advent of sophisticated noninvasive equipment, one of the few indications for cardiac catheterization is to obtain accurate pressure data. If ketamine alters pulmonary vascular resistance, it would negate the primary reason for the procedure. Because the patient population studied herein resides greater than or equal to 1,200 meters above sea level, concerns about pharmacologic effects on pulmonary vascular resistance are enhanced. Simultaneous pulmonary artery and aortic pressures, thermodilution cardiac outputs, and blood gases were measured in room air (16% oxygen) and with ketamine infusion in 14 patients at cardiac catheterization. Reaction to hypoxia identified 3 groups: normal, intermediate and hyperresponders. The normal responders had normal resistance ratios (0.11) in room air and had little resistance ratio response to hypoxia (+0.02), hyperoxia (-0.03) or ketamine (+0.01). The intermediate responders had a slightly higher but normal resistance ratio (0.20) in room air, and a moderate reaction to hypoxia (+0.13), hyperoxia (-0.08) and ketamine (+0.11). The hyperresponders had an elevated resistance ratio (0.42) in room air and a striking reaction to hypoxia (+0.65), hyperoxia (-0.17) and ketamine (+0.49). Hypoxia and ketamine have a greater effect on resistance ratio than hypoxia alone in patients with reactive pulmonary vascular beds. Ketamine should not be used in children undergoing procedures to establish operability based on pulmonary vascular resistance or pulmonary vascular reactivity. 
1	Liver fatty acid-binding protein: a marker for studying cellular differentiation in gut epithelial neoplasms. Human liver fatty acid binding protein is a 127 residue cytoplasmic protein synthesized in liver and in the intestinal epithelium. Previous studies of normal and transgenic mice indicated that the liver fatty acid-binding protein gene is a sensitive marker of enterocytic differentiation. This study shows the use of immunohistochemical methods to examine liver fatty acid-binding protein gene expression in normal human colonic epithelium, colonic villoglandular adenomas, nonmucinous and mucinous adenocarcinomas, and several types of noncolonic epithelial neoplasms. Cells containing liver fatty acid-binding protein were found in normal colonic epithelium, in two thirds of colorectal villoglandular adenomas and nonmucinous adenocarcinomas, and in one third of mucinous adenocarcinomas but not in noncolonic, nonhepatic carcinomas. All liver fatty acid-binding protein-positive colonic adenomas and adenocarcinomas contained patches of immunoreactive cells distributed among histologically identical patches of cells without liver fatty acid-binding protein immunoreactivity. This "mosaicism" was also found in metastases from liver fatty acid-binding protein-positive colonic adenocarcinomas. Immunostaining of these liver fatty acid-binding protein-positive tissues for carcinoembryonic antigen did not show a mosaic cellular pattern in its expression. These data suggest that within a given neoplasm, differences exist in the differentiation programs of monoclonally-derived, malignant colonic epithelial cells and that liver fatty acid-binding protein is a useful marker for operationally defining these subpopulations. Liver fatty acid-binding protein is also a potentially useful diagnostic marker for colorectal and hepatic carcinomas. 
4	Post-transplant hypertension. Post-transplant hypertension remains an important risk factor for cardiovascular mortality and graft function. There are multiple mechanisms responsible for post-transplant hypertension. The details of these mechanisms are poorly understood. Steroids, acute and chronic rejection, recurrent renal disease, native kidney disease, and renal artery stenosis have all been implicated in causing post-transplant hypertension. With the addition of cyclosporine, a known hypertensive agent, to the immunosuppressive armamentarium, the evaluation of post-transplantation hypertension has become difficult. Presently, medical therapy is initially directed toward the complications of cyclosporine nephrotoxicity. Empirically, converting enzyme inhibitors are added to the antihypertensive regimen. Further management is aimed at identification of specific causes of post-transplant hypertension. Unfortunately, because of the multifactorial etiology of post-transplant hypertension and a lack of detailed information about the mechanisms, medical and surgical therapy are often unrewarding. Further study is needed to clarify the mechanisms involved in post-transplant hypertension, and thus direct therapy. 
1	Oral diseases in older adults [clinical conference] In the case presented, a 65-year-old man with multiple dental, medical, and social problems benefited from interdisciplinary assessment and treatment. Despite his poor oral-health status and oral-health behaviors upon admission, patient education and dental therapy resulted in improved daily oral hygiene, elimination of oral diseases, and improved oral function. The overall quality of life of any individual, particularly an older one, can be enhanced through oral-disease prevention, health promotion, and, when indicated, dental therapy. This patient was treated in a hospital environment with a well-established team approach to geriatric care. However, regardless of the care setting, the physician can play a key role in improving the oral health status and quality of life of older adults by including an oral screening examination as part of the periodic comprehensive geriatric assessment, recognizing oral pathology, requesting dental consultations and encouraging appropriate dental service utilization. 
4	Traumatic rupture of aorta. Diagnosis by Doppler echocardiography. Traumatic rupture of aorta is a serious complication in accidents, mainly road accidents, with a high mortality unless an immediate diagnosis and surgical correction is made. A case of traumatic rupture of the aorta shown in the acute phase by Doppler-echocardiography is reported. This technique can be of great value in the study of patients with thoracic trauma who do not show clear signs of aortic rupture which require urgent aortography. 
5	Reciprocal inhibition between forearm muscles in spastic hemiplegia. We studied reciprocal inhibition of H-reflexes in the forearm flexor and extensor muscles in 14 patients with spastic hemiplegia secondary to a focal cerebral lesion and 14 normal volunteers. In the spastic limb, the Hmax/Mmax ratio was increased in both flexor and particularly extensor wrist muscles. The 3 normal inhibitory phases of reciprocal inhibition between extensor and flexor forearm muscles were markedly reduced on the spastic side of patients. The early disynaptic phase showed the greatest alteration. Reduced or absent inhibition between forearm muscles associated with increased spinal motoneuron excitability may be typical to spastic hemiplegia. 
1	Nonhomologous chromatid exchange in hereditary and sporadic renal cell carcinomas. For the development of renal cell carcinomas, it has been suggested that a germ-line or somatic mutation occurs on one of the homologous chromosomes 3p, and subsequently the other 3p segment is lost. We have examined the karyotype and/or the allelic combination on chromosomes 3 and 5 by restriction fragment length polymorphism analysis in normal kidney and tumor samples from 28 renal cell carcinomas that developed in two patients with von Hippel-Lindau disease; we then compared the results to those of sporadic tumors. An unbalanced translocation between chromosome 3p and 5q or other chromosomes was found to be the most common aberration. We developed a model of nonhomologous chromatid exchange involving breakpoint clusters at chromosomes 3p13, 3p11.2, 5q22, and 8q11.2. Subsequent chromatid segregation may result in net loss of the 3p segment either (i) in one step or (ii) after a nondisjunctional loss of the derivative chromosome carrying the 3p segment. This general mechanism could also be implicated to explain genetic changes occurring in other types of solid tumors. 
2	Spontaneous pneumoperitoneum. A surgical dilemma. Pneumoperitoneum is usually the result of hollow viscus perforation with associated peritonitis. Nonsurgical spontaneous pneumoperitoneum incidental to intrathoracic, intra-abdominal, gynecologic, iatrogenic, and other miscellaneous causes not associated with perforated viscus have been documented in the literature. Seven cases of spontaneous pneumoperitoneum admitted over 3-year period to Grady Memorial Hospital, Atlanta, Georgia are reported. Six patients with pneumoperitoneum underwent exploratory laparotomy when clinical examination suggested an acute abdomen; no intra-abdominal pathology was documented in any of these patients. A seventh patient, on ventilatory support, was managed conservatively after performing a diagnostic peritoneal lavage that was negative. There were no cases of radiographically misdiagnosed pneumoperitoneum. Pneumoperitoneum, preceded by a reasonable incidental cause in a patient with a adequate abdominal examination, may warrant continued observation thus avoiding an unnecessary laparotomy. 
4	Nisoldipine--effects on the renin-angiotensin-aldosterone system and catecholamines. Studies in normotensive and hypertensive subjects. We have studied the effects of nisoldipine, a new calcium channel antagonist, on the renin-angiotensin-aldosterone system and on plasma catecholamines in 10 healthy volunteers and in 29 patients with primary essential hypertension. Of these 29 patients, thirteen had normal renin hypertension (NRH), and sixteen had low renin hypertension (LRH). Eight healthy volunteers received placebo. Short-term (24 h) effects were measured in all subjects and long-term (up to 6 months) effects of 10-40 mg nisoldipine daily were monitored in the 29 hypertensive patients. Plasma renin activity (PRA) increased slightly, although this rise was not statistically significant, 1 h after the first dose of nisoldipine in both normotensive subjects and hypertensive patients. After 2 h PRA had returned to the pre-treatment level. No change in PRA was observed after administration of placebo. Plasma angiotensin II (AII) levels showed considerable variation after nisoldipine administration. Plasma aldosterone levels decreased despite the increase in PRA and AII concentrations. However, no concomitant reduction in urinary aldosterone excretion was observed. Plasma noradrenaline levels increased slightly 2-4 h after administration of nisoldipine, and decreased again thereafter, but no changes in plasma adrenaline levels were seen. Nisoldipine had no long-term effects on the renin-angiotensin-aldosterone system or on serum catecholamine levels. 
5	Increased sympathetic outflow in cirrhosis and ascites: direct evidence from intraneural recordings. OBJECTIVE: To determine if central sympathetic outflow is increased in patients with cirrhosis and ascites. PATIENTS: Eleven patients with cirrhosis and ascites, 8 patients with cirrhosis but without ascites, and 7 age-matched and 8 young healthy volunteers. METHODS: With subjects supine, direct microneurographic recordings of efferent post-ganglionic muscle sympathetic nerve activity were obtained from the peroneal nerve, and sympathetic burst frequency was compared with subjects' blood pressure, heart rate, sodium excretion, catecholamines, and plasma renin activity. All patients with cirrhosis were studied at least 5 days after withdrawal from all medications and after 7 days of a 20 mmol/d sodium, 1-L fluid-restricted diet. Age-matched volunteers were studied after 7 days of 20 mmol/d sodium intake and young healthy volunteers after 7 days of 150 mmol/d sodium intake. RESULTS: Sympathetic nerve activity in ascitic patients (65 +/- 15 bursts/min; mean +/- SD) was markedly increased, whether compared with patients with cirrhosis but without ascites (34 +/- 16 bursts/min; P less than 0.001), age-matched healthy volunteers on similar sodium intake (27 +/- 22 bursts/min; P less than 0.001), or young healthy subjects (21 +/- 10 bursts/min; P less than 0.001). The frequency of muscle sympathetic nerve discharge was directly related to plasma norepinephrine and epinephrine concentrations, plasma renin activity, and heart rate, all of which were increased in those patients with cirrhosis and ascites, and inversely related to 24-hour urinary sodium excretion, the fractional excretion of sodium, and subjects' pulse pressures. Sympathetic nerve activity fell from 78 to 6 bursts/min in one patient after liver transplantation. CONCLUSIONS: This study provides the first direct evidence that elevated plasma norepinephrine concentrations in patients with cirrhosis and ascites are due to increased central sympathetic outflow. Sympathetic nerve activity is not increased in patients with cirrhosis but without ascites. Because there were direct positive correlations of sympathetic nerve activity with plasma norepinephrine concentrations, plasma epinephrine concentrations, plasma renin activity, and heart rate, the increase in central sympathetic outflow in patients with cirrhosis and ascites appears generalized and not restricted to muscle nerves. The anti-natriuretic effects of parallel increases in renal and muscle sympathetic nerve activity could account for the inverse correlation between muscle sympathetic nerve activity and sodium excretion. 
4	Remodeling of the rat right and left ventricles in experimental hypertension. Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles. 
3	Prognostic significance of multimodality evoked response testing in high-risk newborns. Exposure to hypoxic-ischemic events in fetal or neonatal life may lead to permanent brain damage and subsequent neurodevelopmental deficits. Clinical and diagnostic tools have been somewhat helpful in identifying an at-risk group, particularly those patients sustaining significant neurologic sequelae. In this prospective study, the prognostic significance of multimodality evoked responses in high-risk newborns was examined. A group of 44 high-risk newborns, as well as 14 healthy newborns, were tested during the newborn period with auditory brainstem responses and somatosensory evoked responses; these tests were repeated at 2 and 6 months corrected age. A neonatal neurologic examination, the Einstein Neonatal Neurobehavioral Assessment Scale, was also conducted. At 1 year corrected age, both groups were assessed in a blind fashion by a pediatric neurologist and a psychologist to determine neurodevelopmental outcome. Results indicated that somatosensory evoked response abnormalities in particular predict an abnormal neurologic status at 1 year of age. Abnormalities that persisted or worsened correlated with severe neurologic impairment, whereas an abnormal somatosensory evoked response that improved or normalized in infancy was associated with mild to moderate neurologic sequelae. Increased brainstem conduction in the auditory brainstem responses was also associated with neurologic sequelae. Normal findings from auditory brainstem responses and somatosensory evoked responses predicted normal developmental scores in all areas, as well as a normal neurologic outcome at 1 year with negative predictive powers ranging from 85-100%. Evoked response testing appears to be an important adjunct to the neurologic investigation of high-risk newborns. 
4	Introduction: nutritional aspects of palm oil. The production, composition, and food uses of palm oil are outlined in this introduction to a detailed appraisal of the nutritional and health implications of the use of palm oil in the food supply. The putative role of dietary fats and oils in general, and of palm oil in particular, in the etiology of coronary heart disease and cancer is critically assessed. It is concluded that the evidence available is difficult to interpret unambiguously. Some evidence to suggest that the minor components of palm oil might have useful biological effects is also discussed. 
1	Squamous cell carcinoma-antigen for detection of squamous cell and mucoepidermoid carcinoma after primary treatment: a preliminary report. This study evaluated the efficacy of using the periodic measurement of the serum level of squamous cell carcinoma antigen (SCC-antigen) for determining the local recurrence and/or metastasis of squamous cell and mucoepidermoid carcinomas after primary treatment. It was found that at the time of clinical recognition of recurrence, the SCC-antigen level was normal, but metastasis to regional lymph nodes or to remote organs generally was accompanied by an increase of SCC-antigen. Changes in the SCC-antigen level with mucoepidermoid carcinoma seemed to be less sensitive than with squamous cell carcinoma. 
4	A controlled trial of community based coronary rehabilitation. Two hundred patients who had suffered an acute myocardial infarction 4-6 weeks before entered a randomised controlled trial of exercise treatment at a community sports centre supervised by a general practitioner. Eighty one per cent of the treatment group continued to exercise until they returned to work and 73% completed three months' exercise. There were no serious complications of the exercise course. The prevalence of angina pectoris fell by 10% in the treatment group but rose by 60% in the control group. The perceived energy level rose by significantly more in the treatment group than in the controls. The rise in predicted maximum oxygen uptake was significantly greater in the treatment group than in the control group as was the reduction in the double product (a reflection of myocardial workload) at peak exercise. Coronary rehabilitation in the community can be both safe and effective. 
4	Hyperhomocysteinemia: an independent risk factor for vascular disease. BACKGROUND. Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency. METHODS. We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 mumol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age. RESULTS. Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia. CONCLUSIONS. Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency. 
5	Polyarteritis nodosa presenting as a biliary stricture. Polyarteritis nodosa, a disease of the media of small and medium-sized arteries, has protean manifestations and many presenting signs and symptoms. Gastrointestinal involvement is common but involvement of the biliary tree is rare. We report a unique case of polyarteritis presenting as a biliary stricture. 
5	The use of Molteno implant and anterior chamber tube shunt to encircling band for the treatment of glaucoma in keratoplasty patients. This retrospective study reviews the results of 35 keratoplasty patients with complex corneal and glaucoma disease, who received Molteno-type (n = 25) or anterior chamber tube shunt to encircling band (ACTSEB)-type (n = 10) implant for the treatment of difficult glaucomas. The implant was placed before the keratoplasty in 14 eyes, during the keratoplasty procedure in 6 eyes, and subsequent to the corneal surgery in 15 eyes. Mean follow-up for the keratoplasty was 25.46 months (range, 6-58 months) and 24.74 months (range, 7-42 months) for the seton procedure. Graft rejection occurred in 12 (34%) of 35 eyes and was progressive in 9 eyes. Nonimmunologic failure was seen in 9 (26%) of 35 eyes. Grafts were repeated in ten eyes with eight of these (80%) remaining clear at a mean of 14.4 months. Considering the results of the repeat grafts, 25 (71%) of 35 eyes achieved clear transplants. Overall, 46% of patients had final visual acuities of 20/100 or better and 69% had final visual acuities of 20/400 or better. The mean preoperative intraocular pressure (IOP) of 34.54 mmHg (range, 14-68 mmHg; standard deviation [SD], 11.51) was lowered to a mean of 14.65 mmHg (range, 6-30 mmHg; SD, 4.49). In the final analysis, 30 (86%) of 35 eyes were judged successful from a glaucoma standpoint. We conclude that the Molteno- and ACTSEB-type implants are viable treatment alternatives in this difficult glaucoma group. 
5	Pneumonia complicating abdominal sepsis. An independent risk factor for mortality. Nosocomial pneumonia (NP) is associated with a significant mortality, 66% in a previous retrospective study of NP complicating intra-abdominal sepsis (IAS). We prospectively compared the outcome of NP complicating IAS with that of recurrent IAS (R-IAS) in the absence of NP. Data were collected prospectively on 300 patients with IAS; 34 patients who presented with pneumonia were excluded from the analysis (44% mortality). One hundred seventy-one patients with no NP and no R-IAS (group 1) had a hospital mortality of 20% (34 patients); 36 without NP in whom R-IAS developed (group 2) had a 17% mortality (six patients); and 47 with NP but no R-IAS (group 3) had a 53% mortality (25 patients). Finally, 12 patients who had both NP and R-IAS suffered a 75% mortality (nine patients). We examined the relationships among the following putative risk factors and mortality: APACHE (acute physiology and chronic health evaluation) II score (at initial presentation with IAS), the need for mechanical ventilatory assistance following initial treatment for peritonitis, steroid requirement, generalized peritonitis vs abscess, and the need for surgical as opposed to percutaneous treatment. Using mortality as the dependent variable, group 2 vs 3 as the explanatory variable, and the risk factors as confounders, logistic regression analysis indicated that the group difference was significant after controlling for confounders. We conclude that NP complicating IAS is an independent risk factor associated with a significant mortality compared with R-IAS. These data challenge the notion that death in IAS is usually due to recurrent or persistent intra-abdominal infection. 
5	Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome. Scleroderma developed in six women who were taking L-tryptophan. Fasciitis and morphea were most common, but one patient had pleural effusion, hypertension, and signs of cardiac and kidney failure. In five patients the biopsy findings were characteristic of scleroderma; the sixth patient had Crohn's disease and developed fasciitis; her biopsy specimen showed inflammatory arteritis. All patients' conditions improved after cessation of their L-tryptophan intake, initiation of corticosteroid therapy, or both. These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading. 
4	Recanalization of chronic total coronary arterial occlusions by percutaneous excimer-laser and laser-assisted angioplasty. A low primary success and high restenosis rate after recanalization of chronic total occlusions by conventional coronary angioplasty have encouraged the application of new interventional techniques like excimer-laser angioplasty. In 39 patients with a coronary occlusion for 1 to 12 months, recanalization was attempted by laser angioplasty through a multifiber-catheter coupled to a pulsed XeCl excimer laser. After successful passage of the occlusion by a standard guidewire in 27 patients (69%), the laser catheter was advanced over the central guidewire and crossed the occlusion in 25 patients (64%). In 2 patients with unsuccessful passage of the laser catheter, the subsequent attempt with a low profile balloon catheter also failed. In 19 of the 25 patients with successful laser recanalization, the residual stenosis exceeded 50% and was therefore followed by additional balloon angioplasty. The average residual stenosis after laser was 61 +/- 17% of the vessel diameter, and after balloon angioplasty 28 +/- 9% (n = 19), whereas after laser angioplasty alone it was 38 +/- 5% (n = 6). No complications associated with the laser application were observed. Angiographic control after 24 hours showed a reocclusion of 2 (8%) recanalized vessels. In this pilot study, laser angioplasty proved to be a safe and feasible method for the treatment of chronic total coronary occlusions. Because it was necessary to guide the catheter by a central wire, the primary success was limited by a successful passage of the wire of the occlusion. The rate of stand-alone laser angioplasty has to be increased by future improvements of the technique to enable a comparative evaluation of this method with conventional angioplasty. 
2	Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. This study was undertaken to determine whether routine use of a modified triple-lumen five French sphincter of Oddi manometry catheter would reduce the frequency and severity of post-manometry pancreatitis and pancreatic enzyme elevation. Seventy-six patients were alternately assigned to undergo sphincter of Oddi manometry (SOM) with a standard perfusion (infused group) catheter or the newly developed aspiration (aspirated group) catheter. After SOM, there were significantly more patients in the infused group with both amylase and lipase values elevated at least two times the upper limits of normal at 2 (p less than 0.001), 6 (p = 0.01), and 18 hours (p = 0.03) after the procedure. As compared with the standard perfusion system, the aspiration catheter was associated with a decreased frequency of clinical pancreatitis (23.5% vs. 3%, p = 0.01) reduced hospital stay (5 +/- 1.83 days, mean +/- SE, versus 1 day; p = 0.03) and milder pancreatitis. The aspiration manometry catheter should be considered for standard use for SOM, particularly if the pancreatic duct sphincter is being evaluated. 
3	Trial of brief intermittent neuroleptic prophylaxis for selected schizophrenic outpatients: clinical and social outcome at two years. OBJECTIVE--To evaluate a novel approach to the prophylaxis of schizophrenic relapse characterised by administration of brief courses of neuroleptic for the earliest non-psychotic signs of relapse (prodromal symptoms). DESIGN--Two year follow up of subjects randomised, double blind, to receive either active (control group) or placebo (intermittent group) depot neuroleptic medication. Both groups received brief courses of oral neuroleptic when prodromal symptoms or relapse occurred. SETTING--Psychiatric outpatient department, Charing Cross Hospital, London. SUBJECTS--54 Stable patients in remission who met the American Psychiatric Association's DSM-III criteria for schizophrenia on the basis of case notes. MAIN OUTCOME MEASURES--Survival without relapse, survival without hospitalisation, point prevalence of extrapyramidal side effects and tardive dyskinesia, structured assessment of social functioning (social adjustment scale II), and frequency of prodromal symptoms. RESULTS--Of 19 relapses recorded over two years, 10 (53%) were preceded by non-psychotic prodromal signs. Survival rates for both relapse and hospitalisation were worse with intermittent treatment than continuous treatment over the two year follow up: 92% of controls and only 54% of patients given intermittent treatment survived the two year period without hospitalisation. Prolonged or frequent relapses as well as episodes of prodromal symptoms were more frequent with intermittent treatment. Lower scores for extrapyramidal side effects were recorded in the intermittent treatment group, but periodic assessments of social functioning failed to show any social advantages from this. CONCLUSION--The findings are at variance with a previous report of one year follow up in this cohort and attest to the superiority of continuous depot neuroleptic prophylaxis in preventing both psychotic and neurotic or dysphoric morbidity in schizophrenia. 
4	Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy. We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed. 
4	Hypertrophy, fibrosis and diastolic dysfunction in early canine experimental hypertension. To examine the relations among hypertrophy, fibrosis and diastolic performance in early experimental hypertension, 18 control dogs and 12 dogs with experimental left ventricular hypertrophy were studied. Diastolic function was impaired in dogs with left ventricular hypertrophy, with decreased Doppler early to atrial inflow velocity ratio (E/A) (1.35 versus 1.72), increased atrial filling fraction (35% versus 29%), decreased sonomicrometric peak rates of wall thinning (-2.01 versus -3.37 liters/s) and filling (4.33 versus 6.64 liters/s) and prolonged time constant of isovolumetric relaxation (tau; 34.3 versus 28.1 ms). Neither chamber stiffness (k; P = AekV) nor passive elastic stiffness (E; E = k sigma, where sigma = stress) was increased. At postmortem examination, the hypertensive left ventricle weighed significantly more than normal (116 versus 80 g; p less than 0.01) and had greater muscle fiber diameter at endocardial and epicardial sampling sites in the apical free wall, basal free wall and septum (mean diameter 50 +/- 8 microns in hypertensive dogs, 37 +/- 8 microns in normal dogs; p less than 0.01). In contrast, neither percent fibrosis (1.2 +/- 0.8 versus 0.9 +/- 0.6 in normal dogs) nor fibrotic volume (1.21 +/- 0.63 versus 0.72 +/- 0.42%/g in normal dogs) was significantly increased. Peak volumetric filling rate was inversely related to fiber diameter (r = -0.74, p less than 0.001), although no variable of left ventricular function was significantly related to percent or volume fibrosis (all r less than 0.60, all p greater than 0.05). Thus, diastolic dysfunction may exist in the setting of hypertrophy without significant fibrosis. Increased myocyte size was associated with early diastolic filling abnormalities characteristic of the hypertensive left ventricle. Fibrosis appears to be a less important determinant of diastolic performance. 
3	Candida pyelonephritis complicating traumatic C5 quadriplegia: diagnosis and management. We present the first reported case of Candida pyelonephritis in a spinal cord injured patient. In addition to multiple courses of empiric antibiotics, the neurogenic bladder and alteration in cell-mediated immunity found in spinal cord injured patients may have increased this patient's susceptibility to fungal disease. A 50-year-old patient with C5 motor functional quadriplegia developed Candid albicans pyelonephritis while undergoing rehabilitation. The patient had several surgical procedures and multiple courses of antibiotic therapy during acute hospitalization. He continued to have a hectic fever curve, leukocytosis with increased band forms, lethargy, and progressive uremia during rehabilitation. Successful investigation of the patient's condition included assessment of serologic tests for Candida precipitin antigen; multiple blood and urine cultures; exclusion of other causes of hectic fever; abdominal computerized tomogram, which revealed a left kidney hypodensity with irregular margins; and a retrograde pyelogram, which demonstrated multiple renal pelvic-filling defects. Cystoscopically placed ureteral stents, which relieved the genitourinary obstruction, drained gross pus from which Candida albicans was cultured; the patient was treated with amphotericin B and showed clinical improvement. Pathogenesis, presentation, diagnosis, and treatment of Candida pyelonephritis are reviewed. 
2	Incisional parapubic hernias. A parapubic hernia, distinct from other lower abdominal wall hernias, is identified as a particular type of incisional hernia. This hernia results from the disruption of the musculotendinous elements of the abdominal wall as they insert into the pubis. This disruption is brought about by either the destruction of these musculotendinous tissues at their lower end or the resection of portions of the pubic bone as is sometimes done in suprapubic radical prostatectomies for easier access to the prostate. Seven cases have been identified and reported. Men and women were seen to make up a clinical picture that is suggestive of the diagnosis, namely, multiple previous operations through the lower abdominal wall, procedures of a gynecologic or urologic nature, a herniation that mimics an incisional or inguinal hernia, and a defect that cannot possibly be corrected without the use of a prosthesis. When the diagnosis is accurately established, the polypropylene mesh is inserted in the preperitoneal space and anchored laterally to the ligaments of Cooper and in between to the arcuate pubic ligament and the periosteum of the posterior aspect of the pubis. Excellent results have been obtained, and the success must be ascribed to the recognition of the parapubic hernia as a distinct entity. 
4	Inhibition of norepinephrine release from vascular adrenergic neurons by oral administration of beta-blocker in DOCA-salt hypertension. The ability of a beta-blocker to inhibit vascular sympathetic nerve activity associated with hypertension was studied in DOCA-salt hypertension in rats. A seven week treatment of DOCA and salt resulted in a significant increase in the systolic blood pressure of the uninephrectomized rats. The administration of propranolol (40 mg/L and 80 mg/L in drinking water) had little effect on the development of hypertension. After a three week administration of propranolol, perfused mesenteric vasculatures were prepared in vitro, and endogenous norepinephrine release as well as vascular responsiveness were examined. Endogenous norepinephrine and pressor responses during periarterial nerve stimulation were greater in the untreated DOCA-salt hypertensive rats than in the normotensive rats. In the DOCA-salt hypertensive rats treated with propranolol, the stimulation-evoked norepinephrine release and pressor responses were significantly attenuated, at both doses, compared with the untreated DOCA-salt hypertensive rats. These results demonstrate that propranolol inhibited the vascular sympathetic nerve activity in DOCA-salt hypertensive rats. This occurrence suggests a possible role of presynaptic beta-adrenoceptors in the regulation of sympathetic tone in DOCA-salt hypertension. 
2	Deceptive bizarre stromal cells in polyps and ulcers of the gastrointestinal tract. The clinical and pathologic features of 33 pseudomalignant lesions of the gastrointestinal tract with bizarre stromal cells are reported. Deceptive histologic changes were identified in ulcers of seven patients and in inflammatory polyps of 26. A misdiagnosis of malignant neoplasm was made in six of the 33 patients (three polyps and three ulcers). A history of gastrointestinal bleeding and/or inflammatory bowel disease was common. The bizarre stromal cells were usually distributed beneath the ulcerated mucosa or within granulation tissue. They stained strongly for vimentin in 20 of 23 cases. Some of the bizarre cells also stained for muscle specific actin (seven of 23 cases). The cells appear to be reactive fibroblasts or myofibroblasts. Follow-up information obtained on 24 of the 33 patients (including four of the six cases initially diagnosed as malignant) revealed 22 patients to be alive without evidence of a malignant neoplasm (average follow-up, 13 months). Two patients died of other causes. Correct recognition of these bizarre stromal cells in gastrointestinal ulcers and inflammatory polyps will prevent a potentially serious diagnostic pitfall. 
5	Increasing the yield of ventricular tachycardia induction: a prospective, randomized comparative study of the standard ventricular stimulation protocol to a short-to-long protocol and a new two-site protocol. Programmed ventricular stimulation with a standard protocol that used up to three extrastimuli was compared prospectively with a short-to-long protocol and a two-site protocol in 77 consecutive patients undergoing electrophysiologic study in an attempt to increase the yield of ventricular tachycardia (VT) induction. The short-to-long protocol uses a train of eight stimuli at a short cycle length and up to two extrastimuli. The two-site protocol is similar to the standard protocol but delivers the last extrastimulus via a second spatially separated right ventricular catheter. Patients were divided into two groups based on indications for study: group 1 included 45 patients with syncope, nonsustained VT, or both, and group 2 included 32 patients with a history of sustained VT, sudden cardiac death, or both. The yield of VT induction with the short-to-long protocol was less than that with the standard protocol. In none of the patients in group 1 in whom the standard protocol results were negative did the short-to-long protocol produce sustained VT. Only two patients, both in group 2, had sustained arrhythmias induced by the short-to-long protocol when the standard protocol results were negative: one had sustained VT induced and one with long QT syndrome had ventricular fibrillation (VF) induced with the short-to-long protocol. However, the short-to-long protocol failed to induce sustained VT in seven patients in whom the standard protocol produced sustained VT. All seven of these patients required three extrastimuli with the standard protocol for induction of VT. 
4	Systolic hypertension in the elderly: reasons not to treat. Isolated systolic hypertension in the elderly is associated with increased morbidity and mortality. Accurate measurement of blood pressure in older patients is difficult. Therapy can be associated with various complications, and the special problems of the elderly, such as orthostatic hypotension and hyperkalemia, should be carefully considered. Drugs should be used in low doses and changes in dosage should be made infrequently. Patients should be monitored frequently for untoward effects of therapy. The benefits of blood pressure reduction and the optimal degree of blood pressure reduction remain unknown. 
3	Motor unit discharge characteristics and short term synchrony in paraplegic humans. Frequency of firing and regularity of discharge of human motor units, and short term synchrony between pairs of motor units, have been assessed in extensor digitorum communis (EDC) and tibialis anterior (TA) muscles in control subjects and in clinically complete paraplegic subjects. The discharge pattern of TA motor units in paraplegia ranged from extremely regular to very irregular for different motor units whereas in the control population, and in EDC of both groups, there was a narrow, but intermediate, range of regularity. There was little difference in the incidence and degree of short term synchrony (STS) in EDC between paraplegic and normal subjects. In contrast, virtually no STS of motor units was observed in the TA muscles of the paraplegic group whereas control subjects exhibited approximately the same amount of STS in their TA and EDC muscles. It is concluded that the extra burden placed on arm muscles in paraplegia does not change the amount of synchronisation between motor units. Furthermore, section of the spinal cord does not increase STS as predicted from lesions of the reticulospinal tract in cats. This may reflect the coincidental removal of supraspinal synchronising inputs of motoneurons or the reorganisation of synaptic inputs in chronic paraplegia. 
5	Vigabatrin: rational treatment for chronic epilepsy. Vigabatrin is a selective, irreversible suicide inhibitor of GABA transaminase and thus increases brain and CSF GABA. In 33 adult patients with long standing refractory epilepsy on treatment with one or two standard anti-convulsant drugs, the addition of vigabatrin up to 3g daily for eight weeks was associated with a 48.2% reduction in seizure frequency. Twenty patients who had exhibited a 50% or more reduction in frequency of one or more seizure types entered an eight week double-blind placebo controlled phase. Patients on vigabatrin maintained a 54.7% reduction of seizure frequency, whereas those on placebo showed an 18.6% increase in seizure frequency, a highly significant difference between the two groups. In the open phase, seven patients were withdrawn due to unacceptable and reversible adverse events. The commonest side effects were drowsiness, depression and mood instability, and headaches. Vigabatrin is a potentially valuable new treatment for chronic epilepsy, especially partial seizures with or without secondary generalisation. 
5	Clinical and Doppler echocardiographic evaluation of bioprosthetic valve failure after 10 years. Four hundred thirteen consecutive patients underwent valve replacement with a bioprosthesis between 1976 and 1982. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132 patients, and multiple valve replacement in 41. The Carpentier-Edwards porcine (n = 336), Angell-Shiley porcine (n = 23), Hancock porcine (n = 11), and the Ionescu-Shiley pericardial valves (n = 43) were inserted. Follow-up between 5 and 12 years postoperatively was 98% complete. Freedom from structural valve deterioration was 72 +/- 7%, 59 +/- 9%, and 59 +/- 9%, respectively, after aortic, mitral, and double valve replacement. The risk of structural valve deterioration and reoperation for valve-related complications was significantly increased with the Ionescu-Shiley pericardial prosthesis. The risk for reoperation was inversely related to patient age. Postoperative Doppler echocardiographic studies in 87% of available patients revealed a subgroup of asymptomatic patients with evidence of structural valve deterioration. These patients (n = 61) had significantly reduced prosthetic valve areas (aortic less than 1 cm2, mitral less than 1.7 cm2), elevated resting transvalvular gradients (aortic greater than 40 mm Hg), or moderate-to-severe regurgitation. In summary, postoperative Doppler echocardiographic examination identified asymptomatic patients with structural valve dysfunction. These patients must be followed up carefully to determine the optimal timing of reoperation. 
5	Incidence of myocarditis. A 10-year autopsy study from Malmo, Sweden. Although myocarditis has been known for almost two centuries, data in regard to its incidence have varied widely. Autopsy studies have reported an incidence of 3.5% to as high as 10%. The main reason for such diversity of data appears to be the lack of unanimity as to what constitutes myocarditis. Recently, definitions of myocarditis have been proposed and precise criteria for the morphologic recognition of myocarditis have been published. In this study an analysis of 12,747 consecutive autopsies performed from 1975 to 1984 at Malmo (Sweden) General Hospital was carried out. Applying the newly proposed histologic criteria, the diagnosis of myocarditis was made in 136 cases, which constitute 1.06% of the autopsy population studied. This rate of myocarditis incidence at postmortem is lower by far than rates previously published. 
3	Maternal serum alpha-fetoprotein screening: further consideration of low-volume testing. Unrecognized assay drift that may occur during low-volume (fewer than 500 specimens per week) maternal serum alpha-fetoprotein testing could result in either underestimation or overestimation of the number of pregnant women who are at increased risk of fetal malformations and genetic anomalies. Quality control software programs that incorporate the use of a multirule Shewhart chart are designed to detect assay drift. Careful selection of quality control sera for inclusion in analytic assays and appropriate application of a multirule quality control procedure to values that are obtained on these control materials should detect assay drift, regardless of the volume of patients' specimens in the run. 
3	Visual dysfunction in Alzheimer's disease: relation to normal aging [published erratum appears in Ann Neurol 1991 Mar;29(3):271] In patients with Alzheimer's disease (AD), compared with age-matched and young healthy control subjects, visual deficits in the following functions were observed: color, stereoacuity, contrast sensitivity, and backward masking (homogeneous and pattern). Critical flicker fusion thresholds were normal, relative to age-matched healthy subjects. For color, the majority of the errors were tritanomalous (blue axis). Color and stereoacuity deficits were unrelated to severity of dementia, in accordance with models of vision that describe these functions as modular rather than diffuse for cortical localization. Although contrast sensitivity was depressed throughout the frequency range in AD, more patients were impaired at low than at high spatial frequencies, contrasting with the observed normal aging pattern of high-frequency loss. Healthy elderly subjects showed depressed critical flicker fusion thresholds and reduced contrast sensitivity at high frequencies, relative to the young group; differences between these groups were not found for the other vision tests. A subset of the AD group received detailed neuro-ophthalmological examination, and no abnormalities were found. This finding, taken together with normal thresholds for critical flicker fusion, suggests that the widespread visual dysfunction reported here is more likely to be related to known pathological changes in primary visual and association cortex in AD than to changes in the retina or optic nerve. 
1	Rationale for different chemotherapeutic and radiation therapy strategies in cancer management. The two primary therapeutic strategies in cancer have been to give either chemotherapy and radiation therapy together or give a complete course of one treatment modality before starting the second. Clinical studies show that toxicity has been one of the major deterrents to substantial improvements in cancer management when the two modalities are administered together. On the other hand, the prolonged time necessary to administer all of one modality followed by the other makes it likely that repopulation of the tumor during sequential treatment will diminish therapeutic effectiveness. A third strategy of giving chemotherapy and radiation therapy has been developed. This new regimen was designed to give chemotherapy initially, maintain the chemotherapy schedule to avoid any reduction in its effectiveness, and add radiation therapy as early as possible in between courses of chemotherapy to minimize the development of cross resistance. One of the primary objectives of alternating chemotherapy and radiation therapy is to increase the therapeutic index by reducing toxicity without a significant reduction in therapeutic effectiveness. Recent clinical, experimental, and theoretic results with radiation therapy and chemotherapy for cancer management emphasize the necessity of giving both modalities with the greatest intensity possible in the initial phase of induction therapy. Cancer treatment scheduling determines the toxicity and thereby limits the dose intensity that can be tolerated. Scheduling may also govern the antitumor effect directly; however, normal host tissue makes the determination of the direct effects on the tumor difficult, if not impossible, in clinical studies. Well-defined experimental solid-tumor systems provide the means for determining directly the relationship between toxicity and antitumor effects in relation to tumor burden and total therapeutic dose. In addition, its relationship to dose intensity and scheduling can be determined by the using more sophisticated research techniques, such as response surface methods. Well-defined clinical protocols to determine how to interact chemotherapy with radiation therapy more effectively hold considerable potential for rapid improvement in treatment of radiosensitive and chemosensitive cancers. 
2	Primary sclerosing cholangitis. Primary sclerosing cholangitis is a rare disease of unknown etiology. Sclerosis of the bile ducts may actually be the final result of multiple factors such as autoimmune, bacterial, congenital, drug, or viral injury. The most commonly associated diseases are ulcerative colitis and chronic pancreatitis. Except in the earliest stages of the disease, liver histologic findings are not specific. Most patients present with jaundice, pain, and pruritus, although an increasing number of asymptomatic patients with inflammatory bowel disease and abnormal liver function are being identified. Cholangiography is key to the diagnosis and is usually pathognomonic except in the unusual case where primary sclerosing cholangitis is confused with cholangiocarcinoma. Many forms of medical therapy have been tried, including antibiotics, azathioprine, cholestyramine, colchicine, cyclosporine, D-penicillamine, steroids, and ursodeoxycholic acid. To date, none of these medications has been proved to alter the course of this disease. Recent reports of ursodeoxycholic acid trials have been encouraging, but long-term results of ongoing randomized trials have yet to be published. In recent years, balloon dilatation of biliary strictures has been accomplished via endoscopic and percutaneous transhepatic approaches. However, in patients with primary sclerosing cholangitis, these nonoperative manipulations must be done repeatedly, may entail multiple general anesthetics, and are difficult to perform. We believe that a direct surgical approach to the biliary tree with long-term transhepatic stenting is indicated in selected patients with severe hilar or extrahepatic stricturing, persistent jaundice or recurrent cholangitis, and no evidence of cirrhosis. Hepatic transplantation should be reserved for patients with primary sclerosing cholangitis who have well-established cirrhosis and have not responded to other therapeutic measures. 
4	Severe hypertension after liver transplantation in alpha 1 antitrypsin deficiency. Five children with alpha 1 antitrypsin deficiency and terminal liver disease received liver grafts; all five became hypertensive and four developed hypertensive encephalopathy. There was evidence of renal disease preoperatively and renal biopsy specimens showed variable glomerulonephritic histology with IgA nephropathy in one, mesangial-proliferative changes in two, and mesangio-capillary glomerulonephritis type I in two. Four hypertensive episodes were preceded by a fall in creatinine clearance. The association of glomerulonephritis with alpha 1 antitrypsin deficiency in children is more common than has been recognised. Affected patients are prone to severe hypertension of probable renal origin after liver transplantation and the renal lesion may affect long term prognosis. 
5	Suicidal ligature strangulation with an elastic band. An unusual case of self-strangulation with an elastic band is described. The victim was a young Hispanic male with a complicated psychiatric history, including suicide attempts. Mechanisms of strangulation and mechanical asphyxial death are discussed briefly. 
5	PTCA of gastroepiploic bypass. A technique for percutaneous transluminal coronary angioplasty (PTCA) of gastroepiploic bypass is described using standard PTCA devices. Severe spasm of gastroepiploic bypass occurred. Modification of guide catheter position is suggested to avoid inducing gastroepiploic bypass spasm. 
5	Permanent external striated sphincter stents in patients with spinal injuries. Nine patients with complete quadriplegia underwent external striated sphincter stenting with the Wallstent in place of an external striated sphincterotomy. Although suprapubic catheters were placed to provide an outlet should problems develop with the stent, they were successfully removed within 6 weeks in all but 1 patient. Complete bladder emptying with reduced voiding pressures was achieved, together with a significant reduction in the duration of hyper-reflexic contractions. Epithelialisation of the stent was almost complete within 3 months and intermittent catheterisation or endoscopy (and resection) is possible through the stent. Although this is a preliminary report of this new technique, it is hoped that sphincter stenting will provide a rapid, safe and effective method of treating high pressure hyper-reflexia and detrusor sphincter dyssynergia in quadriplegic patients. 
3	Management of pseudarthrosis after arthrodesis of the spine for idiopathic scoliosis. Sixty-three first, second, or third-time repairs of one or more pseudarthroses were done in fifty-one patients who had had an arthrodesis for idiopathic scoliosis. Forty-five of the patients were female and six were male. The average age was 30.2 years. The indications for the sixty-three repairs were pain (twenty-five repairs), progression of the curve (sixteen), both pain and progression of the curve (twelve), and radiographic changes only (ten). Failure of the implant was identified before 27 per cent of the sixty-three procedures. The pseudarthroses were diagnosed an average of 2.8 years after the initial arthrodeses. Sixty-eight per cent of the defects were visible on plain radiographs preoperatively and 32 per cent were identified at operation. During the time between the original arthrodeses and the repairs of the pseudarthroses, the scolioses increased by a mean of 7 degrees and the kyphoses, by a mean of 10 degrees. Harrington distraction was the most commonly used instrumentation (twenty-six [41 per cent] of the sixty-three procedures), and autogenous iliac bone was the most commonly used material for the graft (thirty-three [52 per cent] of the procedures). 
1	Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas. Two hundred sixty-two invasive breast carcinomas dating from 1979 to 1984 were tested for vimentin and keratin on formaldehyde-fixed paraffin-embedded sections. None of 26 lobular carcinomas expressed vimentin. Vimentin expression in 10% or more of tumor cells was found in 78% of medullary (14 of 18), in 16% of ductal not otherwise specified (NOS) (35 of 214), and in two of four mucinous carcinomas. A further seven tumors showed vimentin expression in less than 1% to 10% of the cells. Vimentin was expressed in tumor cells of 30% (28 of 93) of grade III invasive ductal NOS carcinomas versus 7% (7 of 105) of grade II and 0% of grade I carcinomas (0 of 10). Vimentin was found to be preferentially expressed in tumors growing in broad, often anastomosing bands or sheets with extensive necrosis, scanty supportive stroma, high nuclear grade, and numerous mitoses. The authors conclude that vimentin is not detected in lobular carcinomas, but is preferentially expressed in medullary and in high-grade ductal NOS breast carcinomas. 
5	Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras. 
2	The vagus nerve, gastric secretions, and their relationship to peptic ulcer disease. Although peptic ulcer disease was known to the ancients, the process by which the disease was produced remained a mystery. As advances were made in medicine and science, so too were advances made in the understanding of digestion and gastrointestinal disease. The treatment of peptic ulcer disease improved as our understanding of the digestive process grew. The current surgical treatment for peptic ulcer disease follows the principals articulated by Lester R. Dragstedt, MD, PhD, which he based on his observations in the research laboratory. We present a historical perspective of the role of the vagus nerve in the control of gastric secretions and its relationship to peptic ulcer disease, placing particular emphasis on Dragstedt's contributions. 
5	The frequency, causes and timing of death within 30 days of a first stroke: the Oxfordshire Community Stroke Project. In a prospective, community-based study of 675 consecutive patients with a first-ever stroke, of whom over 90% had computed tomography (CT) and/or necropsy examinations, 129 deaths occurred within 30 days of the onset of symptoms, a case fatality rate (CFR) of 19%. The 30 day CFR for patients with cerebral infarction was 10% (57 of 545, for primary intracerebral haemorrhage 52% (34 of 66), for subarachnoid haemorrhage 45% (15 of 33) and for those of uncertain pathological type 74% (23 of 31). The CFR for patients who had been functionally dependent pre-stroke was 33% compared with 17% for those who had been independent pre-stroke. The age-adjusted relative risk of death for patients who had been functionally dependent pre-stroke was not significantly greater (1.8, 95% confidence interval 0 to 4.3). There was a significant trend for CFR to increase with age (Chi square for trend = 4.0, p less than 0.05). This relationship was found in those patients who had been functionally independent prestroke (Chi square for trend = 7.9, p less than 0.005) but not in those who had been dependent pre-stroke (Chi square for trend = 0.5, NS). The pattern of increasing CFR with increasing age amongst those who had been independent prestroke was seen particularly in patients with cerebral infarction (Chi square for trend = 8.6, p less than 0.005). The age-adjusted relative risk of death for patients with cerebral infarction who had been functionally dependent pre-stroke was 2.2 (95% confidence interval 1.2 to 4.1). Fifty three percent of all deaths within 30 days of stroke were due to the direct neurological sequelae of the stroke. 
1	Correlates of survival and the Daumas-Duport grading system for astrocytomas. In order to examine the correlation between prognosis and the histological features of nuclear atypia, mitosis, endothelial proliferation, and necrosis in supratentorial adult astrocytomas, the authors reviewed 251 such cases treated at the Massachusetts General Hospital between 1972 and 1980. One point was given for the presence of each feature. The total number of features was translated into a grade as follows: none of the four features = Grade 1 (one patient), one feature = Grade 2 (36 patients), two features = Grade 3 (33 patients), and three or four features = Grade 4 (181 patients). The period of survival was significantly associated with grade, the presence or absence of each of the four histological features, patient's age, type of operation, radiation therapy, and extent of tumor (log rank, p less than 0.05). The variables associated with grade were age (p less than 0.001) and radiation therapy (p less than 0.02). After adjustment for these variables using a Cox proportional-hazards model, the difference in overall survival time between patients in Grades 2 and 3 was not statistically significant. When comparable groups of patients were examined in terms of age or receipt of radiation therapy, the median survival times differed markedly. Patients 50 years of age or less had a median survival time of 68 months (Grade 2 tumors), 29 months (Grade 3 tumors), and 13 months (Grade 4 tumors). Patients over 50 years of age had a median survival time of 6 months (Grade 2 and 4 tumors) and 9 months (Grade 3 tumors). Those patients who had received radiation therapy had a median survival time of 68 months (Grade 2 tumors), 21 months (Grade 3 tumors), and 11 months (Grade 4 tumors). Those patients who did not receive radiation therapy had a median survival time of 1 month (Grade 2 tumors) and 2 months (Grade 3 and 4 tumors); over half of these patients died within 2 months of surgery. This grading system, originally proposed by Daumas-Duport, et al., is simple, objective, and reproducible, and correlates well with survival times. The authors recommend that astrocytomas be graded on a scale of 1 to 4, with Grade 1 reserved for the rare adult supratentorial astrocytoma with none of the four histological features. 
5	Chronic urticaria exacerbated by the antioxidant food preservatives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Two patients with chronic idiopathic urticaria in whom remissions were achieved with dye- and preservative-elimination diet had exacerbations of their urticaria when they were challenged under double-blind, placebo-controlled conditions with butylated hydroxyanisole and butylated hydroxytoluene. After elimination of butylated hydroxyanisole and butylated hydroxytoluene from their diets, there was marked abatement of the frequency, severity, and duration of their urticaria. These antioxidants appear capable of aggravating symptoms in certain patients with chronic urticaria. 
4	Echocardiographic evaluation of patients with clinically suspected arterial emboli. 153 patients (mean age 42 years, range 16-60) who had arterial embolic events were examined prospectively by transthoracic and transoesophageal echocardiography. Patients older than 60 years and those with evidence of extracranial carotid artery occlusive disease were excluded. 84 patients had a cerebral ischaemic event, 50 patients had embolic events in an abdominal organ or limb, and 19 patients had acute retinal ischaemia. The transthoracic echocardiographic examination was normal in 92 patients (60%), whereas only 65 patients (42%) had normal findings after both transthoracic and transoesophageal examination (p less than 0.005). Intracardiac masses, including valvular vegetations, were found in 39 patients (25%), including 27% of patients with cerebral embolism and 32% of these with peripheral embolism, but in none of the patients with retinal ischaemia (p less than 0.001). 47 patients (31%) had valvular disease, 10 (7%) had wall motion abnormalities, 23 (15%) had abnormalities of the interatrial septum, and 9 patients (6%) had diseases of the thoracic aorta. Cardiovascular abnormalities were frequently found by echocardiography in patients with arterial emboli. The transesophageal technique significantly increased the chance of detecting such abnormalities, especially intracardiac masses. 
5	Characteristics of natural antibody responses to the circumsporozoite protein of Plasmodium vivax. The antibody response to the prototype circumsporozoite (CS) protein of Plasmodium vivax (CSPV) was studied in Thai soldiers experiencing occupational malaria. Seventy-four (65%) of 114 men followed during assignment to a malaria transmission area developed blood-stage infection with P. vivax. IgG antibodies against the central repeat region of the CSPV protein were quantitated by ELISA using the recombinant protein, NS181V20, as the capture antigen. One quarter of the subjects had detectable anti-CSPV antibodies at the beginning of the study. CSPV antibody seroconversion was documented in 16 of 26 subjects assessed during their first observed episodes of vivax malaria. This antibody response was of moderate magnitude, fell off after the first week post-diagnosis and appeared, at the low levels observed, to be unassociated with protection. Continued assessment of anti-CSPV antibody after subjects left the transmission area found no increase associated with release of P. vivax. These findings indicate that CS antibody responses to P. vivax during occupational malaria share many characteristics with responses to P. falciparum. 
5	Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep. In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury. 
4	Air embolism of the brain in rabbits pretreated with mechlorethamine. Infusion of 400 microliters air into the left internal carotid artery of five anesthetized rabbits caused transient pial arteriole air embolism, an immediate 41.9 +/- 0.8% dilatation of the embolized vessels, suppression of the cortical somatosensory evoked response to 29.4 +/- 2.7% of baseline, and a progressive decline in ipsilateral cerebral blood flow (measured by hydrogen clearance) to 46 +/- 4.1% of baseline after 2 hours. These values were significantly different from those at baseline and from the responses of 10 control rabbits given equivalent intracarotid saline infusions. Twelve other rabbits were made leukopenic by treatment with 1.5 mg/kg i.v. mechlorethamine 72 hours prior to study. Mean +/- SEM leukocyte count decreased from 6,320 +/- 73/mm3 to 1,890 +/- 66/mm3 without any change in the leukocyte differential or erythrocyte and platelet counts. Intracarotid infusion of saline into seven of the leukopenic rabbits caused no changes. In the other five leukopenic rabbits, infusion of 400 microliters air caused air embolism but did not produce the anticipated declines in cerebral blood flow or the cortical somatosensory evoked response, both of which remained indistinguishable from baseline values and responses in the seven saline-treated leukopenic controls. Similarly, air-embolized arterioles showed nonsignificant dilatation in leukopenic rabbits. Our data suggest that the decreases in both cerebral blood flow and brain function seen after air embolism require the presence of leukocytes. 
5	Pharmacological versus non-pharmacological prophylaxis of recurrent migraine headache: a meta-analytic review of clinical trials. In order to generate information about the relative effectiveness of the most widely used pharmacological and non-pharmacological interventions for the prophylaxis of recurrent migraine (i.e., propranolol HCl and combined relaxation/thermal biofeedback training), meta-analysis was used to integrate results from 25 clinical trials evaluating the effectiveness of propranolol and 35 clinical trials evaluating the effectiveness of relaxation/biofeedback training (2445 patients, collectively). Meta-analysis revealed substantial, but very similar improvements have been obtained with propranolol and with relaxation/biofeedback training. When daily recordings have been used to assess treatment outcome, both propranolol and relaxation/biofeedback have yielded a 43% reduction in migraine headache activity in the average patient. When improvements have been assessed using other outcome measures (e.g., physician/therapist ratings), improvements observed with each treatment have been about 20% greater. In both cases, improvements observed with propranolol and relaxation/biofeedback have been significantly larger than improvement observed with placebo medication (14% reduction) or in untreated patients (no reduction). Meta-analysis thus revealed substantial empirical support for the effectiveness of both propranolol and relaxation/biofeedback training, but revealed no support for the contention that the two treatments differ in effectiveness. These results suggest that greater attention should be paid to determining the relative costs and benefits of widely used pharmacological and non-pharmacological treatments. 
5	cAMP mediates IL-1-induced lymphocyte penetration through endothelial monolayers. Endothelial cell incubated with IL-1 have been shown adhere more lymphocytes than nontreated endothelial cells. Here we demonstrate that IL-1 can also increase lymphocyte penetration through endothelial monolayers in vitro. IL-1 induced a transient increase in the number of lymphocytes penetrated through the endothelial monolayer into a filter in a time- and dose-dependent manner. This effect could be mimicked by increasing the cytosolic cAMP levels in the endothelial cells either by forskolin or dibutyryl-cAMP. Concomitantly we were able to show that IL-1 increased the cytosolic cAMP levels in endothelial cells. An inhibitor of adenylate cyclase, ddAdo, decreased both the IL-1-induced cAMP elevation and lymphocyte penetration. A protein kinase A inhibitor HA 1004 could inhibit the IL-1-induced lymphocyte penetration, where as protein kinase C (N-(2-guamidino-ethyl)-5-isoquinolinesyl foamide hydrocloride) and calcium-calmodulin (N-(6-aminohexyl)-5-chloro-1-naphthalensulfanamide) inhibitors had no effect. Adding dibutyryl-cGMP or calcium ionophore to the endothelial cells could not mimic IL-1-induced penetration and finally IL-1 did not induce PKC translocation in endothelial cells. These data support the view that IL-1 acts via cAMP as a second messenger in regard to lymphocyte penetration through endothelial cells. The above data demonstrate that IL-1-induced lymphocyte penetration through endothelial cells and that this IL-1-induced signal is transduced via cAMP in endothelial cells. 
4	Differentiation of ventricular tachyarrhythmias. Implantable devices capable of several modes of therapy will require differentiation of various ventricular tachyarrhythmias. Three methods of arrhythmia analysis, magnitude-squared coherence, ventricular rate, and irregularity of cycle length were performed for 45 episodes of induced ventricular tachyarrhythmia in 15 patients. Differentiation of monomorphic ventricular tachycardia from polymorphic ventricular tachycardia and ventricular fibrillation was possible by mean magnitude-squared coherence, less possible by rate, and not possible by beat-to-beat irregularity. Faster monomorphic ventricular tachycardia overlapped with rates of polymorphic ventricular tachycardia and ventricular fibrillation. Differentiation of polymorphic ventricular tachycardia and ventricular fibrillation was not possible by rate or irregularity. A progressive decrease in mean magnitude-squared coherence from monomorphic ventricular tachycardia to polymorphic ventricular tachycardia to ventricular fibrillation strengthens previous observations that coherence is a measure of rhythm "organization.". 
5	Muscle blood flow and muscle metabolism during exercise and heat stress. The effect of heat stress on blood flow and metabolism in an exercising leg was studied in seven subjects walking uphill (12-17%) at 5 km/h on a treadmill for 90 min or until exhaustion. The first 30 min of exercise were performed in a cool environment (18-21 degrees C); then subjects moved to an adjacent room at 40 degrees C and continued to exercise at the same speed and inclination for a further 60 min or to exhaustion, whichever occurred first. The rate of O2 consumption, 2.6 l/min (1.8-3.3) (average from cool and hot conditions), corresponded to 55-77% of their individual maximums. In the cool environment a steady state was reached at 30 min. When the subjects were shifted to the hot room, the core temperature and heart rate started to rise and reached values greater than 39 degrees C and near-maximal values, respectively, at the termination of the exercise. The leg blood flow (thermodilution method), femoral arteriovenous O2 difference, and consequently leg O2 consumption were unchanged in the hot compared with the cool condition. There was no increase in release of lactate and no reduction in glucose and free net fatty acid uptake in the exercising leg in the heat. Furthermore, the rate of glycogen utilization in the gastrocnemius muscle was not elevated in the hot environment. There was a tendency for cardiac output to increase in the heat (mean 15.2 to 18.4 l/min), which may have contributed to the increase in skin circulation, together with a possible further reduction in flow to other vascular beds, because muscle blood flow was not reduced. 
2	Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. By intrasplenic immunization we raised a rat mAb (mAb V1q; IgG2a, kappa) with a potent neutralizing activity against natural mouse TNF (1 microgram/ml mAb V1q/100 U/ml TNF). mAb V1q was used to study the role of endogenous TNF in experimental peritonitis induced by sublethal cecal ligation and puncture. mAb V1q persisted for over 5 days in the serum of mice injected with 100 micrograms of the antibody and, therefore, proved useful for in vivo experiments. As little as 20 micrograms mAb V1q/mouse prevented lethal shock of the animals by 400 micrograms LPS/mouse. In sublethal cecal ligation and puncture i.p. injection of mAb V1q directly and up to 8 h after induction of experimental peritonitis lead to death of the animals within 1 to 3 days. The lethal effect of mAb V1q was compensated by injection of recombinant mouse TNF. Similar mAb V1q effects as in immunocompetent mice were shown in severe combined immune deficiency mice deficient of mature functional B and T cells. Taken together, these data suggest that during the early phase of peritonitis endogenous TNF may stimulate nonlymphoid cells such as granulocytes, macrophages, platelets, and fibroblasts to ingest bacteria and to localize inflammation, respectively. These beneficial effects of TNF may determine survival. Thus, our data may have implications for the therapeutic management of a beginning peritonitis. 
4	Severe tricuspid regurgitation after mitral valve repair: diagnosis by intraoperative transesophageal echocardiography. Transesophageal echocardiography facilitates the evaluation of valvular repair in the operating room. The functional valvular morphology and degree of valvular regurgitation can be assessed before and after repair. This technique can also identify unsuspected findings--in this case, severe tricuspid regurgitation complicating cardiopulmonary bypass. We report a previously undescribed cause of traumatic tricuspid regurgitation. 
5	Near fatal subacute thallium poisoning necessitating prolonged mechanical ventilation. The authors describe a case of severe sensory-motor polyneuropathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weaning from the ventilator was possible. Further intensive physical rehabilitation required an additional 6 months hospital stay, and 18 months later, neurological recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of thallotoxicosis and the present treatment is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery. 
2	Isoenzyme profiles of four strains of Giardia lamblia and their infectivity to jirds. The infectivity to jirds (Meriones unguiculatus) and the cyst excretion pattern of a recently isolated strain of Giardia lamblia from Egypt, Strain CDC:1088:1 (EGY), were compared to those of three well-established strains. All five jirds inoculated orally with strain UNO:0487:1 (UNO) became infected and began excreting cysts 3-6 days post-infection (dpi); no cysts were detected between 8-12 dpi after which time cysts were produced through day 19. Four of the five jirds infected with Strain ATCC:30957 (WB) and three of the five jirds infected with strain CDC:0284:1 (VA) excreted cysts from 6-20 dpi and 6-22 dpi, respectively. One of five jirds inoculated with EGY excreted cysts on 8 dpi only. At necropsy, trophozoites were recovered from only three UNO-infected jirds but from all WB- and VA-infected jirds that excreted cysts. The one jird which excreted cysts of EGY was negative at necropsy, but EGY trophozoites were found in one non-patient jird. Isoelectric focusing indicated that these four strains of G. lamblia represented three zymodemes. WB and VA were assigned to one zymodeme, EGY to a second, and UNO, which shared common bands with both other zymodemes, to the third. Although the similarities and differences in infectivity and cyst excretion patterns appear to coincide with the zymodemes to which the strains can be assigned, further study is needed to examine the parasitologic behavior of these strains in relation to isoenzyme patterns. 
1	Localization of basic fibroblast growth factor mRNA in melanocytic lesions by in situ hybridization. Basic fibroblast growth factor (bFGF) is a mitogen for normal human melanocytes and keratinocytes in culture. Experiments in vitro suggest that keratinocytes supply bFGF to melanocytes through a paracrine mechanism and that the aberrant expression of bFGF in melanomas confers growth independence from bFGF-producing cells. To determine whether bFGF is expressed in vivo, we examined a series of benign and malignant melanocytic lesions in situ using bFGF riboprobes on tissue sections, and correlated bFGF expression with histologic phenotype. Seventeen melanocytic neoplasms were studied, including four common acquired nevi, four dysplastic nevi, four primary malignant melanomas, and five metastatic melanomas. Nevic cells in benign intradermal nevi showed low signal intensity (1+), whereas compound and dysplastic nevi showed 2+ to 3+ expression in the junctional nevic cell population and 1+ expression in the dermal nevic cell population. Melanocytes in primary melanomas had intermediate (2+) and those in metastatic melanomas had low (1+) levels of bFGF gene transcripts. Fibroblasts expressed high levels (3+) and epidermal and adnexal keratinocytes moderate (2+) levels of bFGF in all cases studied. Basic FGF expression in endothelial cells, known to produce and respond to this growth factor in vitro, was lower than that in the fibroblast and keratinocyte cell population and, in 10 of 17 cases, no bFGF mRNA was detectable. This study shows that bFGF is expressed in nevomelanocytes in vivo in all melanocytic lesions studied and thus cannot be used as a marker for transformation. The presence of bFGF gene transcripts in the various dermal cell types and in keratinocytes suggests that it may act as an autocrine and paracrine growth factor in regulating cellular proliferation in the skin. 
4	Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group 796 men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction [MI] ), were randomised to double-blind placebo-controlled treatment with oral aspirin 75 mg/day and/or 5 days of intermittent intravenous heparin. The risk of MI and death was reduced by aspirin. After 5 days the risk ratio was 0.43 (confidence intervals, 0.21-0.91), at 1 month 0.31 (0.18-0.53), and at 3 months 0.36 (0.23-0.57). Aspirin reduced event rate in non-Q-wave MI and unstable angina, independently of electrocardiographic abnormalities or concurrent drug therapy. Heparin had no significant influence on event rate, although the group treated with aspirin and heparin had the lowest number of events during the initial 5 days. Treatment had few side-effects and high patient compliance. 
4	Salt and hypertension. Lessons from animal models that relate to human hypertension. A high NaCl diet can raise blood pressure in both susceptible people and in susceptible animals, and the mechanisms are probably quite similar for both humans and animals. The possibly harmful effects of a high NaCl diet are not unexpected since both prehistoric man and mammals evolved in a low NaCl world. Evolutionary forces molded mammals to adapt well to a low sodium intake; the modern high NaCl intake goes "against the grain" of this adaptation. The high NaCl diet can cause premature mortality by raising blood pressure in susceptible people. We have new evidence that in a hypertensive setting, a high NaCl diet can increase mortality even though it does not cause a further rise of blood pressure. Multiple small cerebral infarcts are a partial cause of this excess mortality. Recent evidence also indicates that a high potassium diet reduces the rise of blood pressure caused by a high NaCl diet, whereas a low normal potassium intake encourages an NaCl-induced rise of blood pressure. It is the combination of kidneys that tends to retain NaCl together with a high NaCl intake that produces a rise in blood pressure. This combination tends to cause NaCl retention, which can trigger a rise in blood pressure in susceptible humans and animals. Such a rise in blood pressure can augment renal NaCl excretion and regain the previous NaCl balance. In the Dahl salt-sensitive (DS) rat, there are several renal abnormalities that would tend to encourage sodium retention. By analogy, renal "abnormalities" are probably present in people susceptible to hypertension. 
3	Increased MEPP frequency as an early sign of experimental immune-mediated motoneuron disease. Intracellular recordings of miniature end-plate potentials were performed in extensor digitorum longus muscles from guinea pigs with experimental immune-mediated motoneuron destruction. In the early stages of the disease, the miniature end-plate potential frequency was elevated compared to that in control and normal animals. The amplitude and time course of the miniature end-plate potentials as well as the resting potential of the muscle fibers were not altered, which implies integrity of the postjunctional membrane. The increase in frequency of miniature end-plate potential reflects an increase of basal acetylcholine release and documents dysfunction of the presynaptic terminal of the neuromuscular junction. The increased frequency was associated with high levels of antimotoneuronal IgG in the blood and the presence of IgG at motor end-plates. These data suggest that the presynaptic terminal of the neuromuscular junction may be involved in the immune attack in animal models of motoneuron degeneration. 
4	Thromboexclusion of the right ventricle in children with pulmonary atresia and intact ventricular septum. Twelve children with pulmonary atresia and intact ventricular septum underwent closure of the tricuspid valve as a part of a new surgical procedure. In two cases a concomitant Fontan operation was performed. In each patient the right ventricle was very small and right ventricular pressure was higher than systemic pressure. Ventricle-coronary connections provided flow of desaturated blood from the right ventricle into the coronary arteries in 11 of 12 cases. Five of the 12 children did not survive operation and postmortem examination of each revealed severe acute and chronic myocardial ischemic damage and high-grade obstruction or interruption of the proximal left anterior descending coronary artery. Preoperative angiography demonstrated occlusive changes in the coronary arteries, resulting in right ventricular dependent circulation, in all five children who died and in one child who survived operation. Seven children who survived operation are well 4 months to 3.5 years later. Two have undergone subsequent successful Fontan operation and two others are considered suitable candidates for this operation. Tricuspid valve closure is recommended for a carefully selected group of infants with pulmonary atresia and intact ventricular septum provided a right ventricular-dependent coronary circulation can be excluded on the basis of preoperative coronary cineangiography. 
4	Irrigation device for neuroangiographic procedures. A simple irrigation device for use in diagnostic and interventional neuroangiographic procedures is described. The device is used to flush bubbles and blood clots from catheter hubs. The authors also describe a technique in which this device can be used to prevent filling a catheter with air when a guide wire is removed. 
4	Lower extremity percutaneous transluminal angioplasty: multifactorial analysis of morbidity and mortality. We analyzed the outcome of 202 percutaneous transluminal angioplasty (PTA) procedures performed between 1983 and 1989 to quantitate procedural risks and define factors associated with suboptimal results or immediate clinical failure. Premorbid factors studied included age, sex, treatment of single versus multiple lesions, stenoses versus occlusions, premorbid status of the limb (claudication vs limb threat), and most distal level of PTA. Adverse outcomes included complications (hematoma, acute occlusion, or thrombosis of PTA site, distal embolization, failure to dilate or cross, arterial dissection, rupture, and significant systemic derangement), major amputations (below knee and above knee), and deaths. There were 66 complications (32.7%), 22 amputations (10.9%), and 12 deaths (5.9%) in our series. Logistic regression analysis revealed that the major predictive variable for the occurrence of a complication (p = 0.002), and the only predictive variable for the outcomes of amputation and death (p = 0.0001 and p = 0.0139, respectively), was the premorbid clinical status of the limb. Lower extremity PTA is not an intrinsically benign procedure and is associated with a significant risk of complication, amputation, and procedure-associated death. These adverse outcomes cluster in patients with limb threat. Therefore it may be reasonable to restrict the use of PTA to patients with claudication and strictly selected cases of limb threat. 
4	The population mean predicts the number of deviant individuals OBJECTIVE--To examine the relation between the prevalence of deviation and the mean for the whole population in characteristics such as blood pressure and consumption of alcohol. DESIGN--Re-examination of standardised data from the Intersalt study, an international, multicentre study on the determinants of blood pressure. SETTING AND SUBJECTS--Samples of adults representing 52 populations in 32 countries. MAIN OUTCOME MEASURES--The relations, expressed as correlation coefficients, between the mean population values for blood pressure, body mass index, alcohol consumption, and sodium intake and the prevalence of, respectively, hypertension (greater than or equal to 140 mm Hg), obesity (body mass index greater than or equal to 30 kg/m2), high alcohol intake (greater than or equal to 300 ml/week), and high sodium intake (greater than or equal to 250 mmol/day). RESULTS--There were close and independent associations between the population mean and the prevalence of deviance for each of the variables examined: correlation coefficients were 0.85 for blood pressure, 0.94 for body mass index, 0.97 for alcohol intake, and 0.78 for sodium intake. CONCLUSIONS--These findings imply that distributions of health related characteristics move up and down as a whole: the frequency of "cases" can be understood only in the context of a population's characteristics. The population thus carries a collective responsibility for its own health and well being, including that of its deviants. 
1	The effects of nonthyroid disease and drugs on thyroid function tests. Serious nonthyroid illness and caloric deprivation, which so often accompany systemic illness, have diverse and still incompletely understood effects on thyroid hormone economy. We have discussed the pathophysiologic basis for the most common pattern of alterations in routine thyroid function tests: a decreased serum T3 concentration; normal or, in critically ill patients, a low total serum T4 level; and a normal free T4 concentration. Another, less frequent pattern (high total and free T4 with a normal serum T3) can be encountered transiently in the acutely ill medical or psychiatric patient. With the recent advent of sensitive assays for TSH and better methods for serum free T4, it is now possible to define more quickly and accurately the thyroid-metabolic status of most of these sick patients; the vast majority are euthyroid. Certain drugs confound the picture. The most important of these include dopamine and high-dose glucocorticoids, both of which suppress TSH secretion from the pituitary and may actually cause a state of central hypothyroidism. Other drugs have multiple effects on thyroid hormone indices (e.g., amiodarone). Knowledge of all of the ways in which systemic illness, starvation, and certain drugs may influence thyroid function tests is crucial in assessing the thyroid status of patients with serious nonthyroid disease. 
2	Biliary cholesterol transport and precipitation: introduction and overview of conference. Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. The cholesterol and phospholipid are subsequently exposed to the bile salts contained in the bile, which leads to the process of micellation. Two situations may arise depending on whether there is enough bile salt in proportion to cholesterol to complete this "maturation" process. If the cholesterol saturation is low, at equilibrium the bile salts will have completely micellized the vesicles. On the other hand, if bile is saturated with cholesterol, the micellation process is incomplete and vesicles and micelles will be present at equilibrium. The residual vesicle in this latter situation may have a higher cholesterol/phospholipid ratio because of the greater propensity of phospholipid to be micellized. This situation may result in cholesterol nucleation. The mechanism of nucleation from vesicles and the possible role of nucleating and antinucleating proteins in this process have been discussed. 
5	Late arterial hemorrhage secondary to a Greenfield filter requiring operative intervention. Retroperitoneal hematomas associated with Greenfield filters have been described and are generally characterized as clinically insignificant. We report a retroperitoneal hematoma that was associated with a Greenfield filter and that required operative intervention because of hemodynamic instability. At operation a lumbar arterial laceration apparently caused by a protruding filter prong was identified and ligated. The implications of this occurrence for filter placement indications are discussed. The potential life-threatening severity of filter-associated hematomas is emphasized. 
1	A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982 A unique opportunity to evaluate the method of chemical lymph node clearance for colorectal cancer exists at Ferguson Hospital. Lymph node clearance has been used at the institution since 1977, and this retrospective analysis was undertaken to ascertain its validity there. Furthermore, the node positive group was evaluated to ascertain if the current staging system (Turnbull, 1967) is prognostically accurate for the Dukes' C group. Specifically evaluated for possible prognostic variance was the survival of those patients whose tumors demonstrated partial bowel wall penetration and only one to four positive nodes, a "C1 subset," previously reported to have favorable prognosis. Eight hundred sixty-four cases of colon and rectal cancer treated surgically from 1977 to 1982 were analyzed. There was a mean of 27 lymph nodes retrieved per specimen and a mean of 4.5 positive nodes per Dukes' C specimen. There were 43 C1 and 201 C2 cases with five-year survival rates of 73 and 38 percent, respectively. The results of chemical clearance at Ferguson Hospital were found to be comparable with that of other centers using chemical clearance and superior to hand dissection. The C1 subset clearly is noted to have prognostic advantage and should occupy a separate designation in any staging system. 
1	Systemic preoperative chemotherapy with cisplatin, methotrexate and vinblastine for locally advanced bladder cancer: local tumor response and early followup results. A total of 44 patients with infiltrating, locally advanced bladder cancer (stages T 3a-b, T 4a-b and N+/N0) were treated with the systemic chemotherapy regimen of cisplatin, methotrexate and vinblastine (CMV) in the neoadjuvant setting, of whom 39 were evaluable for response. After planned radical cystectomy and 2 to 3 cycles of chemotherapy no tumor was found on the pathological specimen of 4 patients (10%), the tumor was downstaged in 19 (49%) and no change was observed in 16 (41%). Toxicity included leukopenia in 29 patients (66%), 1 of whom died of granulocytopenic sepsis, nausea and vomiting in 39 (89%) and mild to moderate mucositis in 18 (41%). Median followup is 12 months with a range of 6 to 39 months. Of 32 patients followed for longer than 6 months 6 (19%) experienced progression or recurrence of disease. We conclude that preoperative CMV chemotherapy is effective in inducing downstaging of the tumor, although systemic toxicity limits its use to cautiously selected patients. 
4	What is the best method for assessing the long-term outcome of surgery for accessory pathways and atrioventricular junctional reentrant tachycardias? The success of surgery for supraventricular tachycardia (SVT) is evaluated by a variety of methods in different hospitals. Unfortunately, the predictive values of these methods are not known. We therefore compared the various methods in 261 patients undergoing surgery for SVT at Westmead Hospital since 1981. Surgical outcome was assessed by early tests during the first week after surgery (serial 12-lead electrocardiograms, telemetric monitoring of the electrocardiogram, and electrophysiological study performed using epicardial wires); later tests at 6 months after surgery (12-lead electrocardiograms and electrophysiological study); and symptomatic review done by telephone interview at a median of 34 months after surgery. Early tests were obtained in 97%, later tests were obtained in 76%, and symptomatic review was obtained in 98% of patients. All of the examined tests were inaccurate methods of surgical assessment compared with the late electrophysiological study. A large proportion of the patients proven to be surgical failures at the late electrophysiological study were not detected by early tests (83%), by later electrocardiograms (66%), or by symptomatic assessment (41%). Accurate assessment of surgical outcome requires a late electrophysiological study to permit comparison of surgical techniques. Late electrophysiological study also provides accurate information on the current risks and benefits of proposed surgery for communication to patients to enable them to make an informed decision on future treatment. Most patients are willing to have a late electrophysiological study and usually benefit from clarification of their true surgical outcome. 
5	Pyoderma gangrenosum complicating Felty's syndrome. The case of a 54-year-old woman with Felty's syndrome whose course was complicated by mucocutaneous lesions clinically typical of pyoderma gangrenosum is described. Necrotizing sinusitis and saddle nose deformity were distinctive clinical features. Lymphocytic vasculitis and rheumatoid nodule formation observed within panniculus at the base of a cutaneous lesion and in a nasal mucosal lesion were unexpected histopathologic findings. 
5	Pathogenesis of ischemic necrosis in random-pattern skin flaps induced by long-term low-dose nicotine treatment in the rat. The objectives of the present experiments were to study the effects of long-term low-dose nicotine treatment on skin hemodynamics, viability, and microvascular morphology in 4 x 10 cm dorsally based acute random-pattern skin flaps in the rat. In addition, the reversibility of the nicotine-induced detrimental effects on skin-flap viability following cessation of nicotine treatment also was investigated. Low-dose nicotine (0.6 mg/kg) administered twice daily and subcutaneously for 24 weeks significantly (p less than 0.05) decreased skin-flap capillary blood flow, distal perfusion, and length and area of skin viability compared with the saline-treated control (n = 15). However, these same parameters in rats (n = 15) whose nicotine treatment had been withheld for 2 weeks prior to skin-flap surgery were not significantly different from the control, thus indicating that the detrimental effects of this long-term, low-dose nicotine treatment were reversible. The mean plasma level of nicotine in the nicotine-treated rats was 8.1 +/- 0.4 micrograms/dl and was within the range of plasma nicotine levels reported for human heavy cigarette smokers. Light and electron microscopic studies did not show evidence of histologic damage to the cutaneous microvasculature in acute random-pattern skin flaps and samples of normal (nonoperated) skin in nicotine-treated rats. It is concluded that long-term plasma levels of nicotine similar to those of heavy cigarette smokers are detrimental to the capillary blood flow and viability of random-pattern skin flaps in the rat. These deleterious effects can be avoided if skin flaps are raised 2 weeks after cessation of nicotine treatment. This low-dose nicotine treatment does not cause histologic damage to the microvasculature. Other pathogenic mechanisms of nicotine-induced skin flap ischemia are discussed. 
2	Unsuspected syphilitic hepatitis in a patient with low-grade proteinuria and abnormal liver function A 25-year-old patient was found to have cholestatic liver enzyme abnormalities during assessment for asymptomatic low-grade proteinuria at the US Naval Hospital in Portsmouth, Virginia. These abnormalities persisted for a 6-month period, and an extensive workup, including viral serologic studies, rapid plasma reagin test, iron studies, ceruloplasmin, antimitochondrial, antinuclear, and anti-human immunodeficiency virus antibodies, endoscopic retrograde cholangiopancreatography, and liver biopsy, was unrevealing until serologic tests for syphilis were repeated to evaluate a new onset of urethral discharge. The patient had none of the more characteristic signs of secondary syphilis. The liver enzyme abnormalities rapidly resolved after treatment with penicillin. Syphilis remains the great impostor and still must be considered in the differential diagnosis of unexplained liver enzyme abnormalities, even in a patient with no symptoms or signs of early syphilis. 
5	Course of diabetic retinopathy following cataract surgery Five patients with mild to moderate retinopathy to both eyes underwent complication-free cataract surgery in one eye. Within three months of surgery deterioration of the retinopathy was observed in the operated eye only. In four patients there was an increase of intraretinal haemorrhages and hard exudates, accompanied by clinically significant macular oedema manifested as retinal thickening and extensive fluorescein leakage from both the macular and the peripapillary capillary networks. Of these four patients one also developed retinal ischaemia, evident ophthalmoscopically by flame-shaped haemorrhages and cotton-wool spots and angiographically by areas of capillary non-perfusion. The fifth patient showed proliferation of new blood vessels and vitreous haemorrhage. Diabetic patients scheduled for cataract surgery should undergo a thorough preoperative evaluation of any existing retinopathy. Postoperatively they should be followed up at close intervals so that any progression of retinopathy can be promptly detected and considered for laser treatment. 
5	L-tryptophan use and the eosinophilia-myalgia syndrome. We present a case of the eosinophilia-myalgia syndrome in a patient taking large doses of L-tryptophan for sedation. He developed the now-classic findings of myalgias, skin changes, and marked eosinophilia. This syndrome was first recognized in late 1989, and epidemiologic studies have demonstrated an association of the clinical syndrome with ingestion of L-tryptophan. The mechanism of toxicity remains unknown. Casual use of L-tryptophan has been diminished by its rapid removal from the nutrition counter of health food stores. 
3	Graves orbitopathy: correlation of CT and clinical findings. The clinical and high-resolution computed tomographic (CT) findings in 71 patients (142 orbits) with Graves orbitopathy and 20 healthy patients (40 orbits) were retrospectively reviewed. The orbits with orbitopathy were subgrouped at clinical examination into those with (n = 18) and those without (n = 124) optic neuropathy. Mean extraocular muscle diameters and the calculated muscle diameter index were significantly increased in all orbits with ophthalmopathy, particularly in those with optic neuropathy. Graves orbitopathy affected the superior muscle group (63.4%) more than the medial (61.3%) or inferior (57%) recti. The most common pattern of muscle involvement involved all five measured extraocular muscles. Solitary muscle involvement most frequently involved the superior muscle group (6.3%). Significant enlargements of the retrobulbar optic nerve sheath and superior ophthalmic vein were noted only in orbits with optic neuropathy. Anterior displacement of the lacrimal gland at CT correlated with clinical palpability and occurred more frequently in patients with optic neuropathy. Severe apical crowding was the most sensitive indication of optic neuropathy at CT. 
3	Response to suxamethonium in a myasthenic patient during remission. A cumulative dose followed by an infusion was used to determine the dose response to suxamethonium in a patient with diagnosed myasthenia gravis who was in true remission (asymptomatic while receiving no therapy). The ED50 and ED90 values for suxamethonium were 0.08 mg/kg and 0.20 mg/kg, and an infusion rate of 3.2 mg/kg/hour was required to maintain a 90-95% depression of the single twitch response as monitored by integrated electromyography. These values are within the range for normal patients, and we conclude that myasthenic patients during a true remission may not demonstrate resistance to suxamethonium. 
5	Intraoperative coronary angiography using fluorescein. Intraoperative coronary angiography using fluorescein was applied to evaluate the patency of saphenous vein grafts just after completion of the distal anastomosis. By this technique, the area of the revascularized myocardium was well estimated in real time. This intraoperative direct-vision examination gives us more timely and precise information during coronary artery bypass grafting. 
1	Osteosarcoma of the spermatic cord. Malignant tumors of the spermatic cord are rare but the vast majority of these tumors are sarcomas. We report on a patient with osteosarcoma arising in the spermatic cord. Left radical orchiectomy with high dissection of the spermatic cord was performed, and the patient remains free of recurrence 2 years postoperatively. We could find no previous discussion or report of this tumor. 
4	Myocardial uptake of indium-111-labeled antimyosin in acute subendocardial infarction: clinical, histochemical, and autoradiographic correlation of myocardial necrosis. Indium-111-labeled antimyosin has been utilized in the diagnosis and localization of acute transmural myocardial infarction. The present report describes a patient who presented with a massive subendocardial infarction. Two days after the injection of antimyosin, the patient's clinical status markedly deteriorated and he expired. Postmortem examination demonstrated severe three-vessel coronary artery disease with extensive myocyte death in the endocardium. Autoradiography and histochemical staining of the prosected heart demonstrated high correlation for myocardial necrosis and corresponded to clinical evidence for diffuse subendocardial infarction. 
3	Ultrasonography and magnetic resonance imaging in Leigh disease. An infant with Leigh disease, who was the younger sister of a similarly affected infant, had been examined before the onset of the disease. Ultrasonography revealed hyperechoic lesions in the putamen and caudate nucleus during the preclinical stage. At onset, these changes extended into the cerebral cortex and medulla. These lesions were also detected by T2-weighted magnetic resonance imaging (MRI) as areas of increased signal intensity. Her brother demonstrated the same ultrasonographic results; cranial computed tomography disclosed low-density areas in the basal ganglia which were detected as hyperechoic lesions by ultrasonography. These findings suggest that ultrasonography is useful in detecting early intracranial lesions in Leigh disease. 
2	Variants of intestinal metaplasia in the evolution of chronic atrophic gastritis and gastric ulcer. A follow up study. A follow up study with biopsy was initiated in 1982 to define the relations between variants of intestinal metaplasia and the evolution of chronic atrophic gastritis and gastric ulcer. All patients (58 with chronic atrophic gastritis and 66 with gastric ulcer) had intestinal metaplasia at the start of the study. In the six year period to 1988 a total of 241 biopsies were performed on the patients with chronic atrophic gastritis and 243 on the patients with gastric ulcer. Initially, 81% of the patients with chronic atrophic gastritis presented with type I intestinal metaplasia and 14% with type III intestinal metaplasia. During follow up type I was predominant, often associated with grades 2 and 3 active disease (81%) and 45% of these patients reverted to a non-intestinal metaplasia status by the third year of follow up. In contrast, type III metaplasia was more common in the absence of appreciable inflammation (78% of biopsy specimens), being persistent in five of seven patients in the third year of follow up, and was found to be associated with dysplasia in three of these patients. Similarly, the initial biopsy specimen showed type I metaplasia in most patients with gastric ulcer (82%) and type III in only 4%. Type I metaplasia was also predominant in these patients (80%), particularly in active disease (68%), gradually regressing with healing. In contrast, type III was associated with delayed ulcer healing and reactivation (75%; six of eight patients). 
4	Sudden cardiac death while wearing a Holter monitor. The Holter tapes of 61 patients (46 men, mean age +/- standard deviation 65 +/- 11 years) with sudden cardiac death while being monitored were analyzed. Thirty-eight patients were known to have coronary artery disease, 5 had cardiomyopathy, and 7 had aortic valve disease. Etiology remained unknown in 11 patients. Mean New York Heart Association functional class was 2.5 +/- 0.7. Thirty patients had received antiarrhythmic drugs and 32 had received digitalis. Sudden death occurred at rest in 73%. In the hours before death, repetitive ventricular arrhythmias were found in 50 patients (82%), with atrial fibrillation in 34%. Patients with bradyarrhythmic death (18%) had less complex ventricular activity compared to patients with tachyarrhythmic death (p less than 0.01). Lethal arrhythmias--monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, torsades de pointes, primary ventricular fibrillation, and 1:1 conducting atrial tachycardia--were found in 26 (43%), 15 (25%), 5 (8%), 3 (5%), and 1 patient, respectively. The coupling interval of the final ventricular tachycardia correlated inversely with the initial frequency of ventricular tachycardia (p less than 0.05). For patients with tachyarrhythmic death, an increase of heart rate within the last 3 hours was noted (83 vs 89 beats/min, p less than 0.05). Ventricular premature complexes and the proportion of patients with greater than 2 couplets and greater than 2 triplets increased significantly only within the last hour before death. 
4	Entrapment of a folded-over introducer sheath in the iliofemoral artery: an unusual complication of PTCA guiding catheter exchange An arterial introducer sheath became folded over in the iliac artery during PTCA. This probably resulted from withdrawal of a doubled over Judkins left coronary guiding catheter through the introducer sheath. Nonsurgical, atraumatic removal was accomplished after the acute bend of the introducer sheath had been withdrawn to the site of arterial entrance. 
3	Synchronous Hodgkin's disease and myelofibrosis terminating with granulocytic sarcoma and acute megakaryocytic leukemia. Our patient had stage IIIAI Hodgkin's disease with synchronous myelofibrosis and myeloid metaplasia. A slowly progressive myeloproliferative disease developed over 9 1/2 years and terminated in a painful osteolytic bone disease, spinal extradural granulocytic sarcoma and acute megakaryocytic leukemia. It is likely that this was a result of the myeloproliferative disease rather than a late complication from combination chemotherapy. Our case demonstrates the importance of a curative approach to Hodgkin's disease even in the face of a coexistent disease with a long or unknown natural history. 
5	An overview of intimal hyperplasia. Many hypotheses have been postulated for the development of intimal hyperplasia in vein and prosthetic grafts. In these hypotheses, the central theme seems to be endothelial injury, but not always denuding injury. As we progress into the biologic era with more sophisticated research tools, the study of the endothelial cell may give us the answers to the problem of intimal hyperplasia. In addition, the leukocyte is still a relatively unknown entity and further modification of their function may hold promise. 
3	Abdominal wall pain: an alternative diagnosis. The cause of abdominal pain need not necessarily reside in the viscera; the abdominal wall is another source of symptoms. Some causes of abdominal wall pain are obvious, e.g. hernias, but not so others such as nerve entrapment syndromes. This review is concerned with causes of abdominal wall pain which, although common, may be easily overlooked. 
3	Time of rehabilitation admission and severity of trauma: effect on brain injury outcome. Outcome after traumatic brain injury, defined by the Glasgow Outcome Scale (GOS) and length of stay in acute rehabilitation, was measured in 59 patients admitted to an intensive rehabilitation program to examine the effects of severity of the initial brain injury, severity of multiple trauma, and length of stay in the acute care hospital. Severity of initial brain injury, best measured by length of coma, was the most significant predictor of GOS outcome. Length of acute hospitalization was a small, but significant, predictor of GOS. Severity of initial brain injury, length of acute hospitalization, and gender emerged as predictors of length of rehabilitation hospital stay. Although length of acute hospitalization is apparently affected by severity of brain injury, it adds significantly--more than severity of brain injury--to the prediction of length of rehabilitation. 
4	Rapid baroreceptor resetting in Dahl salt-sensitive rats. Dahl salt-sensitive rats rapidly become hypertensive when exposed to a high salt diet, but Dahl salt-resistant rats maintain normal blood pressure on a high salt diet. A defect in baroreceptor afferents is thought to play a key role in the low sensitivity of baroreceptor reflexes in Dahl salt-sensitive rats even in the prehypertensive stage during low salt treatment. In the present study, we tested whether differences in rapid resetting ability might contribute to differences in baroreceptor function in Dahl rats. Four groups of rats were tested: salt-sensitive and salt-resistant rats on low salt and high salt diets (0.15% and 8.0% NaCl). We compared the rapidly resetting responses of baroreceptors from each group using an in vitro preparation. Rapid resetting was assessed for each aortic baroreceptor (n = 46) by linear fit of the relation of pressure threshold and conditioning mean arterial pressure. Each group had a wide range of resetting ratios (the slope of the resetting relation). Despite higher initial pressure thresholds in salt-sensitive rats on a high salt diet, resetting ratios among the four groups were similar. Thus, the ability of Dahl salt-sensitive baroreceptors to rapidly reset is preserved, despite high dietary salt and a genetic predisposition to dysfunction. The present findings in Dahl rats reinforce the results of recent studies of rapid resetting during spontaneous and renal hypertension, which suggests that the rapid resetting process is remarkably resistant to factors that compromise baroreceptor function. 
1	Expression of laminin and its receptor LBP-32 in human and rat hepatoma cells. Dramatic cellular changes that occur during hepatocarcinogenesis are associated with major alterations in extracellular matrix formation and in the relationships between cells and their microenvironment. We have studied the expression of laminin, the major noncollagenous glycoprotein of basement membrane, and the laminin receptor 32 kD laminin-binding protein in two rat (Faza 967 and HTC) and two human (HepG2 and HBGC2) hepatoma cell lines that express a variety of liver-specific functions. Laminin was found in the rough endoplasmic reticulum of these cells when the indirect immunoperoxidase method and electron microscopic examination were used. Radiolabeled laminin, immunoprecipitated from both media and cell extracts, was resolved by electrophoresis on sodium dodecyl sulfate gel in two major polypeptides that comigrated with the A and B subunits from Engelbreth-Holm-Swarm tumor laminin. Immunoblot analysis showed that the Mr = 400,000 polypeptide did not correspond to the A subunit of laminin. Northern blot analyses demonstrated large amounts of B1 and B2 mRNAs but no A chain mRNA. We conclude that the tumor cells produce the laminin B chains only. In contrast, normal adult hepatocytes from either man or rat lacked laminin mRNAs, whereas in 1-day primary culture, B chain mRNAs became detectable. The steady-state level of 32 kD laminin-binding protein mRNA was 10-fold and threefold higher in rat hepatoma cells than in freshly isolated and 1-day cultured normal rat hepatocytes, respectively. In human hepatocytes, the steady-state levels of 32 kD laminin-binding protein mRNAs varied depending on the donor and never reached the level of the human hepatoma cells. 
1	Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. Major increases have occurred in the incidence of basal cell carcinoma and squamous cell carcinoma of the skin, as well as in cutaneous malignant melanoma during the period 1973 through 1987 in British Columbia. The greatest increases in basal and squamous cell carcinomas are on the head and neck. This indicates that exposure to sunlight is the major causative factor. The greatest increase in melanoma is on the trunk in men and on the lower limbs in women. The dramatic increases in nonmelanoma skin cancers in British Columbia, a relatively low sunlight area, suggest that major prevention programs are needed in areas that are not considered "sunspots.". 
1	Malignant melanoma occurring during pregnancy: a report of the Northern Israel Oncology Center (1968-1988). Medical records of seven patients treated within a 20 year period for malignant melanoma during pregnancy were reviewed. No significant detrimental prognostic effects could be attributed to pregnancy. The current literature on melanoma and pregnancy is discussed. Based on this, pregnancy seems not to be contraindicated in melanoma patients. 
2	Caseating hepatic granulomas in Hodgkin's lymphoma. A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver. 
1	Motility factor produced by malignant glioma cells: role in tumor invasion. To better understand the cellular mechanism of tumor invasion, the production of a cell motility-stimulating factor by malignant glioma cells was studied in vitro. Serum-free conditioned media from cultures of rat C6 and human T98G cell lines contained a factor that stimulated the locomotion of the producer cells. This factor was termed the "glioma-derived motility factor." The glioma-derived motility factor is a heat-labile protein with a molecular weight greater than 10 kD and has relative stability to acid. The factor showed not only chemotactic activity but also chemokinetic (stimulated random locomotion) activity in the two types of glioma cells studied. Although glioma-derived motility factors in conditioned media obtained from two different cell origins are likely to be the same, chemokinetic migration of T98G cells to their conditioned medium was much stronger than that of C6 cells to theirs. Coincubation of cells with cytochalasin B, which disrupts the assembly of cellular actin microfilaments, almost completely inhibited the cell migration stimulated by glioma-derived motility factor. Cytochalasin B also induced marked alterations in cell morphology, including cell retraction and arborization, while the drug did not affect cell attachment to culture dishes. These results indicate that glioma cells produce a motility factor which may play a role particularly when tumor cells are detached and migrate away from the original tumor mass, thus promoting tumor invasion. Also, glioma cell migration stimulated by the motility factor requires the normal organization of cytoskeletons such as actin microfilaments. 
4	Usefulness of tomographic thallium-201 imaging for detection of restenosis after percutaneous transluminal coronary angioplasty. The role of tomographic thallium-201 exercise and redistribution imaging in the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 116 patients: 61 (53%) with 1- and 55 (47%) with multivessel PTCA, with a total of 185 dilated vessels. Complete revascularization was performed in 89 (77%) and partial revascularization in 27 (23%) of the patients. Restenosis was angiographically demonstrated in 69 (60%) of the patients and 85 (46%) of the vessels 6.4 +/- 3.1 months after PTCA. Disease progression in previously normal vessels was noted in 11 patients. The results were: (1) for detection of restenosis in the group of patients, single-photon emission computed tomographic (SPECT) versus exercise electrocardiographic sensitivity was 93 vs 52% (p less than 0.001), specificity 77 vs 64%, and accuracy 86 vs 57% (p less than 0.001). The results were similar in the complete and partial revascularization groups. (2) SPECT was 86% sensitive, specific and accurate for restenosis detection in specific vessels with comparable results for 1-versus multivessel PTCA and complete versus partial revascularization. Sensitivity, specificity and accuracy were: 89, 95 and 92% for the left anterior descending coronary artery; 88, 79 and 82% for the right coronary artery; and 76, 83 and 85% for the left circumflex coronary artery. Eighty-one percent of the diseased nondilated vessels were correctly identified. (3) Disease progression to greater than 50% stenosis was detected with 91% sensitivity, 84% specificity and 85% accuracy. SPECT thallium-201 imaging is an excellent tool for the detection of restenosis and disease progression after PTCA in the settings of 1- and multivessel angioplasty and complete and partial revascularization. 
4	Cardiovascular disease risk profiles. This article presents prediction equations for several cardiovascular disease endpoints, which are based on measurements of several known risk factors. Subjects (n = 5573) were original and offspring subjects in the Framingham Heart Study, aged 30 to 74 years, and initially free of cardiovascular disease. Equations to predict risk for the following were developed: myocardial infarction, coronary heart disease (CHD), death from CHD, stroke, cardiovascular disease, and death from cardiovascular disease. The equations demonstrated the potential importance of controlling multiple risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, glucose intolerance, and left ventricular hypertrophy) as opposed to focusing on one single risk factor. The parametric model used was seen to have several advantages over existing standard regression models. Unlike logistic regression, it can provide predictions for different lengths of time, and probabilities can be expressed in a more straightforward way than the Cox proportional hazards model. 
1	Synchronous diffuse well-differentiated lymphocytic lymphoma and gastric adenocarcinoma presenting as splenomegaly and iron deficiency anemia. Diffuse well-differentiated lymphocytic lymphoma (D-WDLL) and chronic lymphocytic lymphoma (CLL) represent closely related neoplasms which may have indolent courses. Dating back more than one century, reports of associated second primary malignancies continue to intrigue clinicians. A case of synchronous D-WDLL and gastric adenocarcinoma, presenting as splenomegaly and iron deficiency anemia, is presented. The case and literature are reviewed. 
3	Prevalence and characteristics of multiple analgesic drug use in an elderly study group. With few exceptions, use of multiple analgesic drugs achieves dubious increases in analgesia while placing elders at increased risk of the many potential adverse effects of analgesic drugs. The potential for duplication of analgesic therapy among the elderly is great due to prevalent painful chronic conditions and the variety of prescription and nonprescription analgesic remedies available. The prevalence of multiple analgesic product use and patterns of concurrent use of different analgesic categories was investigated in a geographically defined population of persons 65 years of age and older. The demographic characteristics of users of multiple analgesic drug products were examined, as were their smoking status, alcohol use, lifetime history rates of major illnesses, physical functioning, pain experiences, memory performance, and depressive symptoms. A substantial proportion of analgesic users reported taking multiple products in the preceding 2 weeks (14.4% of female and 10.5% of male analgesic users). Men who reported pain in the preceding year were more likely to use multiple analgesic products. Women who experienced pain or limited physical functioning, or who had higher depressive symptom scores or a life-time history of ulcers were most likely to use multiple analgesic products. Thus, although some users of multiple analgesic products reported significant pain, several other factors were shown to be related to the phenomenon of multiple use. 
4	Doxazosin effects on insulin and glucose in hypertensive patients. The Finnish Multicenter Study Group. This study investigates the effects of prolonged doxazosin treatment on serum lipids, glucose, serum insulin, and blood pressure in hypertensive patients. Following 26 weeks of treatment with doxazosin, supine and standing blood pressures were significantly decreased at a final mean daily dose of 6.4 mg. Blood glucose levels were significantly lower at 26 weeks than after the initial placebo period (p less than 0.05) or after 4 weeks' treatment with doxazosin (p less than 0.001). There was a significant (p less than 0.05) decrease in serum insulin levels following 4 weeks of treatment, and a highly significant (p less than 0.001) decrease after 26 weeks. In addition, doxazosin produced a significant reduction in total cholesterol (p less than 0.05) and low-density lipoprotein (LDL) cholesterol (p less than 0.01) after 26 weeks, although the levels of high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, and triglycerides showed no significant change. There was a tendency for the ratio of HDL: total cholesterol to increase. The combined changes in blood pressure, blood glucose levels, serum insulin, and serum lipids favorably affect the probability of developing coronary heart disease (CHD). 
4	Gynecologic vascular abnormalities: diagnosis with Doppler US. The authors describe the use of duplex and/or color Doppler ultrasonography of the pelvis in three women to demonstrate the presence of venous malformations. One patient with a pulsatile vaginal mass was shown to have an arteriovenous malformation of the vaginal wall. The second patient was shown to have an unsuspected venous angioma in the endometrial cavity. The third patient was shown to have adnexal varices that closely mimicked hydrosalpinx. In the latter two cases, the duplex and color flow capabilities of an endovaginal probe were especially important. 
1	Spontaneous perinephric hemorrhage: imaging and management. We report on 10 patients with spontaneous perinephric hemorrhage associated with underlying disease, including renal cell carcinoma (5), angiomyolipoma (2), malignant melanoma (1), periarteritis nodosa (1) and severe portal hypertension (1). The etiology could not be identified with computerized tomography (CT) in 5 cases (50%), including 2 renal cell carcinomas, 1 angiomyolipoma, 1 periarteritis nodosa and 1 portal hypertension. Arteriography demonstrated underlying lesions in 4 of these 5 cases (80%) including the case of vasculitis. CT combined with magnetic resonance imaging is accurate for the diagnosis of spontaneous perinephric hemorrhage but the underlying pathological condition is often undetectable in the acute phase due to the perinephric blood. CT should be the first study performed if this diagnosis is suspected. Arteriography is recommended if a renal mass is not detected. If a mass is not identified with these 2 imaging studies and the patient is clinically stable, followup thin slice CT should be performed. 
2	Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. After nearly 18 years of research, the association between human leukocyte antigens A1-B8-DR3 and autoimmune chronic active hepatitis still provokes debate. The principal reasons for this are disease heterogeneity and racial variation in the distribution of human leukocyte antigens between populations. The aim of the present study was to reexamine the relationship between these antigens and autoimmune chronic active hepatitis in a well-characterized series of patients. Ninety-six outpatients with autoimmune chronic active hepatitis and an additional 14 referred for liver transplantation with end-stage autoimmune chronic active hepatitis were studied. Human leukocyte antigen frequencies were compared with those of 100 racially and geographically matched controls. The A1-B8-DR3 haplotype was present in 38% of patients compared with 11% of controls (chi 2 = 20.6, p less than 0.0005). When all the DR3-positive patients were eliminated, there was a striking secondary association with DR4; 35 (80%) of 44 remaining patients were DR4 positive compared with 31 (39%) of 79 DR3-negative controls (Fisher's exact probability test p = 0.000031, pc = 0.0013). In addition patients with A1-B8-DR3 are seen at a significantly younger age than those without (39.75 yr vs. 48.21 yr, p less than 0.025), relapse more frequently (52% of patients with A1-B8-DR3 relapsed on one or more occasions compared with 34% of patients without this haplotype) and are more frequently referred for liver transplantation. These data indicate for the first time that two genes within the major histocompatibility complex closely linked to the DR3 and DR4 genes independently confer susceptibility to autoimmune chronic active hepatitis. 
5	Clinicopathological features of elevated lesions of the duodenal bulb. We present here our findings on patients with an elevated lesion of the duodenal bulb. All these patients were treated in our clinics between the years 1984 and 1988. These lesions were present in 36 of 8,802 patients who underwent upper gastrointestinal pan-endoscopy. Two patients had a duodenal carcinoma, 2 an adenoma, and 1 a Brunner's gland adenoma. There were 15 with a hyperplastic polyp, 3 with a heterogenic gastric mucosa, 3 with Brunner's gland hyperplasia, 6 with duodenitis, and 4 with regenerative mucosa. Among these 36 lesions, only 69% (25 lesions) were evident on the upper gastrointestinal X-ray series. Adenoma and Brunner's gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa. Both duodenal carcinomas were detected by endoscopic biopsy and were resected. Histologically, these lesions were limited to the submucosal layer and were of the non-pedunculated polypoid form, but there were no other characteristic endoscopic features, in comparison with other elevated lesions. Thus, upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion. 
4	Silent myocardial ischemia during rehabilitation for cerebrovascular disease. In asymptomatic patients the importance of silent ischemic ST-T wave changes on Holter monitoring is known to be a significant predictive variable for one-year mortality of postmyocardial infarction patients. This case report represents the uses of ambulatory ECG to detect ischemic ST changes in patients who have had recent strokes. The cases reported here of silent myocardiac ischemia in stroke patients reflect previous reports in which 70% of the ischemic episodes in patients with symptomatic coronary artery disease are not associated with angina and in which approximately 10% to 15% of acute myocardial infarctions are silent. We now believe that the incidence of "silent" ischemia may be precipitated in poststroke patients during their rehabilitation program. This belief is supported by two main factors. First, a high level of personally relevant mental stress exists which activates the sympathoadrenal system, which may lead to myocardial ischemia. Second, some stroke patients become aphasic and are unable to communicate adequately even if they experience angina symptoms. We have found that poststroke, most patients could not undergo exercise treadmill testing secondary to a variety of factors: inability to coordinate limbs, poor endurance, inability to follow directions, and/or lack of attention. We now propose that 24-hour monitoring for ST-T wave changes poststroke should be considered as part of a vigorous investigation for myocardial ischemia during the rehabilitation of these patients because they have an increased risk of cardiac morbidity. 
3	The painful shoulder: Part I. Extrinsic disorders. Shoulder disorders are most commonly manifested by pain and limited function. Careful history and examination help the physician localize the problem to the shoulder joint, the surrounding tissues or adjacent sites that can cause referred pain to the shoulder. Common extrinsic causes of shoulder pain include postural problems and cervical spine disorders. 
2	Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results. 
5	Biotype as determinant of natural immunising effect of cholera. To test the hypothesis that clinical Vibrio cholerae O1 infections protect against recurrent cholera, treated cholera episodes in a rural Bangladesh population of 188,153 people who were followed between 1985 and 1988 were analysed. Of the 2214 people with initial episodes of cholera, 7 had a second episode. The incidence of cholera was 61% lower in subjects who had had an earlier episode than in those without such an episode. Whereas initial episodes of classical cholera were associated with complete protection against subsequent cholera, initial episodes of El Tor cholera were associated with negligible protection. 
1	Analysis of antigen expression at multiple tumor sites in epithelial ovarian cancer. The question of whether the antigenic phenotype of human epithelial ovarian cancer varies in a given patient between the primary tumor and metastatic sites or among metastatic sites themselves is an important issue in planning potential therapeutic strategies for ovarian cancer. We have obtained tumor specimens from at least two separate sites during operations on 12 patients with epithelial ovarian cancer, and we have typed these specimens with a group of 18 monoclonal antibodies that react with cell-surface glycoprotein and carbohydrate antigens, including blood group antigens. Antibodies with relative specificity for malignant cells as well as those that detect more widely distributed epithelial antigens were used. A total of 31 specimens from 12 patients with advanced adenocarcinoma (8 serous, 3 undifferentiated, 1 endometrioid) of the ovary were studied, including fresh ascites cells in two patients. Frozen sections of tumor specimens were stained with the antibodies by the indirect immunoperoxidase technique and graded semiquantitatively. Little difference was seen in antigenic expression of tumors that were obtained from various sites in the same patient for either the epithelial cell markers or blood group markers. Intratumoral antigenic heterogeneity was seen, but this was generally quite consistent within a given patient's specimens. As anticipated, variations in antigen expression were seen among specimens from different patients. The antigenic phenotype of the tumor specimens in a given patient, as determined immunohistochemically by our group of antibodies, showed only minor variation among primary and metastatic sites. 
1	Validation of intermediate end points in cancer research. Investigations using intermediate end points as cancer surrogates are quicker, smaller, and less expensive than studies that use malignancy as the end point. We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer. Candidate intermediate end points may be selected from case series, ecologic studies, and animal experiments. Prospective cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association. The most appropriate measure of this association is the attributable proportion. The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0, but not if it is close to 0. Usually, the attributable proportion is close to neither 1.0 nor 0; in this case, valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation. This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point. We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points. This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer. 
1	Assessment of "squamous cell carcinoma antigen" (SCC) as a marker of epidermoid carcinoma of the anal canal. We measured squamous cell carcinoma antigen (SCC) in epidermoid carcinoma of the anal canal in 66 patients. Samples were taken at diagnosis, before treatment, and during follow-up; 353 samples were analyzed. The positive threshold was taken as 2 ng/ml. At diagnosis, the sensitivity of the marker was 44 percent and its specificity 92 percent. In our series, the pretherapeutic level of SCC does not correlate with T as in Papillons' Clinical Staging System, but it does correlate with nodal invasion (P less than 0.05). It is of no prognostic value at the time of diagnosis. During follow-up, at relapse the level of SCC is 20.3 +/- 43 ng/ml. This increase is significant (P less than 0.01): the sensitivity of the marker is 77 percent. In patients who have relapsed, development of the illness correlates with the level of SCC, which is of prognostic value (P less than 0.01). In conclusion, the level of SCC should be associated with the clinical follow-up of patients with epidermoid carcinoma of the anal canal. 
3	Effects of the calcium antagonist nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats. We studied the efficacy of preischemic and postischemic systemic treatment with a new calcium antagonist nilvadipine in a permanent focal cerebral ischemia model of spontaneously hypertensive rats. Rats that underwent microsurgical middle cerebral artery occlusion were blindly assigned to a single intraperitoneal injection of nilvadipine (0.32 mg/kg) or the same amount of polyethylene glycol either 15 minutes before, immediately after, 1 hour after, or 3 hours after occlusion of the left middle cerebral artery. Neurologic conditions of rats were closely examined, and rats were killed 24 hours later. Removed brains were sliced coronally, stained with triphenyltetrazolium chloride, and the size of infarct was determined. Although no neurologic improvements were observed in the treated rats, the area of infarcts was significantly reduced in the groups treated before, immediately after, and 1 hour after occlusion of the middle cerebral artery. Treatment started 3 hours after occlusion was ineffective. 
1	Bilateral malignant phyllodes tumours. We report a rare example of bilateral primary malignant phyllodes tumours. The diagnosis was supported by the identification of a benign epithelial element in each lesion. The case illustrates the typical dimorphic features of malignant phyllodes tumours. A contralateral tumour should not be regarded as metastatic without histological confirmation. 
1	Principles of treatment of pediatric solid tumors. Great strides have been made in the treatment of pediatric solid tumors over the last three decades. A multimodality approach involving a combination of surgery, radiation therapy, and chemotherapy is now used in the treatment of these diseases. This article reviews the principles that guide the use of these modalities and the multidisciplinary approach used to integrate them into a coordinated treatment plan. The role of each modality in the control of local and systemic disease is described. Radiation treatment planning, dose fractionation, and toxicity are also discussed. 
5	Effect of pentoxifylline on hemodynamics, alveolar fluid reabsorption, and pulmonary edema in a model of acute lung injury. We investigated the effect of pentoxifylline (PTX) on the development of pulmonary edema in a model of adult respiratory distress syndrome in rabbits. Lung injury was induced by repeated saline lavages in adult rabbits weighing 2.5 to 3.5 kg. Rabbits pretreated with PTX (20 mg/kg bolus followed by 20 mg/kg/h infusion) developed significantly lower amounts of lung edema 4 h after saline lavage (extravascular lung water to dry weight ratio [W/D], 6.9 +/- 0.6 SD versus 8.9 +/- 0.5 in control animals). PTX produced a 25% increase in cardiac output, but there were no differences between treated and untreated groups in calculated pulmonary vascular resistance or microvascular pressure. To determine whether PTX could have lowered pulmonary venous resistance and thus lowered effective microvascular pressure for fluid filtration, we directly measured pulmonary artery and left atrial pressures, and measured by micropuncture the pressure in 20 to 40 microns subpleural venules in four open-chested rabbits 3 to 4 h after lavage. Venous resistance was low (venous pressure drop 0.9 +/- 0.1 mm Hg) and was unchanged by PTX infusion. To determine if PTX decreased lung water by accelerating active alveolar fluid reabsorption, a single 60-ml aliquot of saline was instilled into the lungs of normal rabbits treated with saline or PTX. Both groups had a similar decrease in lung water content 1 and 4 h later. Our data indicate that PTX reduces edema formation in rabbits after saline lavage, not by lowering microvascular pressures for fluid filtration or by acceleration alveolar fluid reabsorption, but possibly by its anti-inflammatory effect on neutrophil function. 
1	Haemangiosarcoma of the maxillary antrum. Angiosarcomas are extremely rare in the head and neck and the histological diagnosis is often difficult. We present a case of a haemangiosarcoma of the maxillary antrum in a 33 year old male. The histological diagnosis and subsequent management are discussed. 
4	The hyperlipidemia of the nephrotic syndrome. Lipid abnormalities in patients with the nephrotic syndrome have long been recognized. However, the significance of these lipid abnormalities, the mechanisms producing them, and their potential treatment have all been a cause of debate. Recent data have helped clarify each of these areas of controversy. Studies of the lipoprotein abnormalities of patients with the uncomplicated nephrotic syndrome have shown that many will have elevated levels of total and low-density lipoprotein cholesterol, whereas only a few will have elevated levels of high-density lipoprotein cholesterol. If these lipid abnormalities have the same significance in this population as in other populations studied, then some patients with unremitting nephrotic syndrome will be at high risk for cardiovascular disease. The elevated cholesterol levels noted in the nephrotic syndrome are caused primarily by enhanced hepatic synthesis, with lesser contributions by decreased clearance and altered enzyme activities. The signal for enhanced hepatic lipogenesis may relate to changes in plasma albumin concentration, plasma oncotic pressure, a local effect of viscosity at the hepatic sinusoidal level, or a loss of urinary proteins or other liporegulatory substances. Recently, a number of short-term studies in nephrotic patients have documented the safety and efficacy of lipid-lowering drugs such as the bile acid-binding resins, probucol, and the HMGCoA (hydroxymethylglutaryl coenzyme A) reductase inhibitors. 
5	Patient factors predicting early alcohol-related readmissions for alcoholics: role of alcoholism severity and psychiatric co-morbidity. The current study was undertaken primarily to identify whether psychiatric co-morbidity was associated with the rate and time of alcohol-related inpatient readmissions for a group of 255 patients discharged from alcoholism treatment at a midwestern rural medical center. A structured interview obtained information regarding psychiatric disorders, including depression, antisocial personality disorders and polysubstance abuse, as well as alcohol history and sociodemographics. Ninety-eight subjects (38.4% of sample) were readmitted for alcoholism-related diagnoses within 15 months of discharge. Patients with a long history of heavy drinking, high daily alcohol consumption and history of previous alcoholism treatment were most likely to be readmitted with an alcoholism-related primary diagnosis. Once these variables were controlled for, other major psychiatric disorders, polysubstances abuse and sociodemographic variables did not appear to predict time to readmission. However, other potentially more sensitive outcome measures such as return to drinking were not evaluated in the present study. 
5	The "stuck twin" phenomenon: ultrasonographic findings, pregnancy outcome, and management with serial amniocenteses. Thirteen consecutive twin pregnancies affected by the "stuck twin" phenomenon were reviewed to determine the potential benefit of serial amniocenteses. The fetal survival rate for the eight pregnancies that underwent serial amniocenteses was 69% (11 of 16 fetuses). This is significantly improved compared with a fetal survival rate of 20% among the five preceding pregnancies managed without serial amniocenteses at the same institution (p = 0.01). It is also markedly improved compared with a combined fetal survival rate of 16% among 48 previously reported pregnancies with the stuck twin phenomenon managed without serial amniocenteses (p less than 0.0001). Survival correlated with the absence of concomitant pregnancy complications (i.e., maternal hypertension or intractable labor) and with the absence of severe fetal structural abnormalities. Procedural complications occurred in three of eight pregnancies (37.5%) managed with serial amniocenteses and was attributed as a cause of fetal death in one case. Two of 11 survivors (18%) had complications after serial amniocenteses including brain infarction and renal tubular necrosis. Serial amniocenteses may significantly improve the survival rate of twin gestations affected by the stuck twin phenomenon but may be associated with complications among survivors. 
1	Razor-blade surgery. The razor blade can be a valuable tool in the performance of many minor surgical procedures. It is extremely sharp, flexible, inexpensive, readily available, and easy to use. The technique and specific applications are reviewed and discussed. 
2	Cryptosporidium infection in acquired immunodeficiency syndrome: not always a poor prognosis. Chronic diarrhea and malabsorption accompanied by simultaneous infection with the protozoa Giardia lamblia and Cryptosporidium occurred in a 22-year-old homosexual man with antibody to human immunodeficiency virus (HIV). Small bowel biopsy demonstrated total villous atrophy and marked mononuclear infiltration in the lamina propria simulating celiac disease. Treatment with metronidazole resulted in resolution of diarrhea, clearance of parasites, and marked improvement in small bowel histology. Although diarrhea and malabsorption in immunocompromised patients with cryptosporidiosis are regarded as ominous, our patient remained disease free for the next 3 years. Thus, infection with Cryptosporidium in patients with HIV does not always lead to intractable diarrhea or death. 
1	Femoral mononeuropathy after radical prostatectomy. Femoral mononeuropathy is a recognized complication following abdominal and vaginal hysterectomy. Retractor injury and lithotomy position were postulated mechanisms. We report a femoral nerve lesion following a radical perineal prostatectomy. 
3	The effectiveness of different methods of defining traumatic brain injury in predicting postdischarge adjustment in a spinal cord injury population. Traumatic brain injury (TBI) can occur concomitantly with spinal cord injury (SCI). Much of the initial work in this area has focused on identifying coincidence rates and risk factors; less has focused on possible long-term implications of TBI when it occurs with SCI. In this study, SCI/TBI and neurologically matched SCI-only groups were formed on the basis of clinicians' ratings of neuropsychologic test scores. SCI/TBI and SCI-only groups were also formed using Halstead Category cutoff scores, presence/absence of loss of consciousness, and clinicians' ratings of severity of TBI. Dependent measures assessed an average of two years postinjury measured personal, social, and family adjustment of the individual with SCI and that of a significant other. Loss of consciousness and nonconsensus clinical ratings of presence/absence of TBI predicted postdischarge adjustment poorly. Severity ratings in the moderate to severe range, and Category cutoff scores did have some predictive value, with patients defined as impaired being more likely to report adjustment difficulties or being described as having adjustment difficulties by a significant other. The difficulty of making unequivocal diagnoses of TBI in this population is discussed and implications for future research delineated. 
1	Squamous cell carcinoma in situ arising in an ovarian mature cystic teratoma. Report of one case with histopathologic, cytogenetic, and flow cytometric DNA content analysis. A squamous cell carcinoma in situ arose in an ovarian mature teratoma (ie, dermoid cyst) in a 62-year-old woman. Flow cytometric DNA content analysis of paraffin-embedded in situ carcinoma showed a normal DNA content with moderate to high proliferative activity (S-phase fraction estimate, 16% to 18%). Cytogenetic analysis of the in situ cancer and the benign cystic portion of the tumor revealed a 46,XX karyotype. In addition, the benign cystic portion of the tumor revealed homozygous chromosomal heteromorphisms, compared with heterozygous markers found in peripheral blood lymphocytes. These results show that this squamous cell carcinoma in situ was euploid and suggest that the mature cystic teratoma was derived from a single germ cell after meiosis I. 
1	Steroid cell tumor of the ovary in a child. An 8-year-old girl exhibited severe, progressive virilization of 2 years' duration associated with markedly elevated circulating testosterone concentrations. Based on her initial clinical presentation and results of a chemical evaluation, she was originally thought to have non-classic 21-hydroxylase deficiency, but her condition did not respond to corticosteroid therapy. Further evaluation confirmed the presence of an ovarian neoplasm. The excised ovary contained an attached gray-brown mass. Light microscopic and ultrastructural examination revealed the mass to be a steroid cell tumor. Because Reinke's crystals were not present, it was designated to be a steroid cell tumor not otherwise specified. This case represents one of 22 reported cases of steroid cell tumor occurring in children described in the literature, most of which have been associated with heterosexual precocity. To our knowledge, steroid cell tumors are benign when they occur in prepubertal children. Although they are rare, steroid cell tumors of the ovary should be considered in cases of childhood virilization. 
5	Intussusception encephalopathy: an underrecognized cause of coma in children. Intestinal intussusception is a common cause of bowel obstruction in infancy and early childhood. Typically the presenting signs and symptoms are referable to the abdomen. On occasion the most prominent presenting feature is depressed level of consciousness. We describe 3 patients who presented with coma associated with intussusception. 
4	The prevalence of cardiac valvular pathosis in patients with systemic lupus erythematosus. The purpose of this study was to determine the prevalence of valvular pathosis in a population of patients with SLE, to assess the candidacy of such patients for antibiotic prophylaxis before dental treatment. The hospital records of 112 patients with SLE were reviewed and screened for endocarditis, heart murmurs, and other valvular pathosis. Two of the 112 patients had confirmed cases of bacterial endocarditis. This prevalence is comparable to endocarditis prevalence rates in patients with prosthetic valves and is also three times that in patients with rheumatic heart disease. The high prevalence of endocarditis in this population of patients with SLE suggests that according to present perspectives on patient management, patients with SLE should be considered for antibiotic prophylaxis before dental therapies associated with formation of a bacteremia. 
4	Angioscopy for intraoperative management of thromboembolectomy. Our experience with angioscopy suggests that direct visualization of the arterial lumen during thromboembolectomy procedures would provide a more reliable method of assessing luminal morphologic characteristics than angiography alone. We inspected 32 grafts (seven aortobifemoral, 18 infrainguinal bypass, and seven dialysis access fistula grafts) in 32 patients. Thirty-one patients had thrombotic events and one patient had an acute embolus. Angioscopy following standard catheter thrombectomy revealed significant amounts of retained thrombus or neointima in all thrombectomies. Angioscopic information from 18 patients with an infrainguinal bypass graft led to graft revision in six cases and placement of a new graft in 10 cases. One graft limb was replaced in seven aortobifemoral grafts, and multiple repeated thrombectomies were employed to extract debris in the remaining six cases. Repeated graft thrombectomy was also beneficial in dialysis access fistulas. Angioscopy allowed us to omit the completion angiogram and led to an improved technical result. We conclude that angioscopy is useful during thromboembolectomy procedures. 
2	Antibodies in anti-HBe-positive patient sera bind to an HBe protein expressed on the cell surface of human hepatoma cells: implications for virus clearance. The relevance of the recently described membrane-bound form of the HBe protein for the antiviral immune response was examined. The data show that antibodies in anti-HBe, but not in anti-HBc-positive human sera efficiently bind to the membrane expressed HBe. No evidence was obtained that the HBc can reach the cell surface in a form that can be detected with human antibodies. The findings suggest that the decline of virus titer that is usually observed after seroconversion from HBe to anti-HBe might be the result of an antibody-mediated elimination of infected cells. 
5	Follicular thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome We retrospectively analyzed the outcome of all patients who received their primary treatment for follicular thyroid cancer at the Mayo Clinic between 1946 and 1970. The diagnosis was confirmed by reexamination of preserved tissue specimens. The 57 female and 43 male patients (mean age, 53 years) underwent follow-up for a maximum of 32 years (mean, 17.4 years). All patients were treated surgically, and total removal of primary tumor was thought to have been accomplished in all but three. Only 2 of the 88 patients without distant metastatic lesions at the time of initial diagnosis underwent ablation of the thyroid remnant. At the conclusion of the study, 52 patients had died, thyroid cancer being the cause of death in 19. On the basis of univariate survival analysis, age more than 50 years, tumor size that exceeded 3.9 cm, higher tumor grade, presence of marked vascular invasion, adjacent tissue invasion, and distant metastatic involvement at the time of initial diagnosis were associated with increased cancer mortality. Multivariate analysis (by Cox proportional hazards model), however, identified only age greater than 50 years, marked vascular invasion, and metastatic disease at the time of diagnosis to be independent predictors of follicular thyroid cancer-related mortality. Patients with two or more of these predictors were classified as being high risk. These patients had 5- and 20-year survival rates of 47% and 8%, respectively; the corresponding survival data for the low-risk group were 99% at 5 years and 86% at 20 years. The identification of these risk groups may facilitate a more rational approach to treatment of follicular thyroid cancer. 
3	The nature and course of olfactory deficits in Alzheimer's disease. OBJECTIVE: The aim of this study was to determine the specific nature and course of olfactory deficits in Alzheimer's disease. Previous studies had noted impaired odor identification, but there was no unanimity about the presence of odor detection deficits. METHOD: Odor identification was tested in 55 patients with Alzheimer's disease and 57 elderly control subjects by using the University of Pennsylvania Smell Identification Test. Odor detection was assessed in 46 subjects with Alzheimer's disease and 40 control subjects by using a forced-choice threshold test with geraniol as the odorant. RESULTS: Significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment, and these deficits increased as Alzheimer's disease progressed. There was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects. On the other hand, odor detection deficits did not appear until Alzheimer's disease was relatively advanced. Smell identification test scores were correlated with Mini-Mental State scores, but geraniol detection was not. CONCLUSIONS: Odor identification is impaired early in Alzheimer's disease and may be more influenced by cognitive status than is acuity of odor detection, which is not altered until later in the disorder. The pattern of hyposmia in Alzheimer's disease suggests that the disorder may not "begin in the nose," as has been theorized previously. Further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia. 
5	Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly. To determine the prevalence of carcinoma in situ of the testis and other testicular histopathological abnormalities in the general male population, we examined gonads from 399 men 18 to 50 years old who died suddenly and unexpectedly. No sign of malignancy was found in any of these gonads. However, 3 of the 399 men had been previously treated for testicular tumor or carcinoma in situ. Thus, the over-all prevalence of testicular neoplasia in the population studied was 0.8% (95% confidence limits 0.2 to 2.2%). This frequency is of the same magnitude as the lifetime risk of testicular cancer in the Danish male population. The median weights of the left and right testes were 19.3 and 19.7 gm., respectively. This difference was statistically significant (p = 0.00003). Thus, our study confirmed that on average the left testis is smaller than the right testis. The median weight of the gonads collected in our study was 0.9 gm. lower than the weight of testes examined 40 years earlier at the same department of forensic medicine. However, this difference was not statistically significant (p = 0.17). Microscopic examination of the gonadal specimens revealed that 83% of the men exhibited complete spermatogenesis, including late spermatids in all tubules. In the age group studied we found no age-related changes in testicular weight or in the proportion of tubules with degenerative changes, such as spermatogenic arrest, the Sertoli-cell-only syndrome or hyalinization. 
2	Limitations in the evaluation of therapy in inflammatory bowel disease: suggestions for future research. The current treatment of inflammatory bowel disease (IBD), though improved over earlier therapies, remains variable rather than consistent and supportive rather than curative. The similar management of ulcerative colitis (UC) and Crohn's disease (CD), which are thought to be differing though related disorders, suggests that therapy is nonspecific. The variation in therapeutic practices results from the fact that the etiologies of the diseases are obscure, from limited knowledge of the biological and pharmacological actions of drugs commonly prescribed (sulfasalazine, 5-ASA compounds, steroids, 6-MP and azathioprine), from an inadequate understanding of genetic differences influencing drug metabolism, from insufficient awareness of the factors influencing drug efficiency (concurrent use of antimotility drugs, cigarette smoking, food combinations), from the variability of the patient groups studied (extent and severity of disease), and from incomplete documentation of the clinical status of patients at the time of therapeutic trial. Future advances in treatment will depend on gaining new information about the nature of IBD and of drug pharmacology and bioavailability, derived from collaborative studies by clinicians, clinical investigators, and basic scientists. Important areas for IBD research include the biology of intestinal epithelium, the nature of the IBD inflammatory reaction and of gut mucosal immune regulation (via the application of new biotechnologies) and more representative experimental animal models. Decisive multicenter therapeutic studies require agreement on definitions of ulcerative colitis and Crohn's disease, accurate characterization of patient groups, acceptable objective criteria of IBD severity and activity, and reliable indicators of therapeutic response. 
4	Sex differences in control of cutaneous blood flow. Women are far more likely than men to suffer from Raynaud's disease. The purpose of this study was to determine whether there are gender differences in local or central control of cutaneous blood flow that could account for the increased incidence of Raynaud's disease in women. To assess cutaneous blood flow, hand blood flow (HBF), finger blood flow (FBF), or skin perfusion (SP) was measured by fluid plethysmography, mercury strain-gauge plethysmography, or laser Doppler spectroscopy, respectively, in 47 volunteers. Basal HBF in men exceeded that of women (12.1 +/- 2.0 versus 6.2 +/- 1.5 ml/100 ml/min). Likewise, FBF in men surpassed that of women (19.5 +/- 4.1 versus 7.7 +/- 1.8 ml/100 ml/min). Similarly, SP in men was greater than that of women (270 +/- 42 versus 81 +/- 16 perfusion units). However, after total body warming (to induce a thermal sympatholysis), HBF in women exceeded that of men, suggesting that the lower basal HBF in women was due to increased sympathetic outflow to the extremities. Mental stress and deep inspiration reduced HBF and SP in men. Paradoxically, both of these maneuvers increased HBF and SP in women. To determine whether these paradoxical responses in women were due to the women's elevated basal sympathetic tone, these experiments were repeated after total body cooling in men to increase sympathetic tone and after total body warming in women to reduce sympathetic tone. Total body cooling reduced HBF and SP in men. Under these conditions, mental stress and deep inspiration induced vasodilation. In women, total body warming for 10 minutes increased HBF. 
4	Outcome of prophylactic therapy for idiopathic anaphylaxis. OBJECTIVE: To determine the efficacy of a prophylactic regimen (prednisone, H1 blockade, and sympathomimetic amine therapy) in patients with idiopathic anaphylaxis. DESIGN: Clinical trial before and after treatment. SETTING: Referral-based allergy clinic at a major medical center. PATIENTS: Fifty-three patients with a history compatible with idiopathic anaphylaxis for at least 6 months before presentation to the allergy service and with subsequent management by the service for at least 6 months. INTERVENTIONS: Patients with frequent life-threatening symptoms were treated with a prophylactic regimen. Patients with infrequent episodes of idiopathic anaphylaxis were only treated acutely for each episode of anaphylaxis. MEASUREMENTS AND MAIN RESULTS: The results favored prophylactic treatment with prednisone for patients who were classified as generalized-frequent in the clinical outcome measures of frequency (per patient per year) of episodes (mean before treatment, 7.31 +/- 6.46; after treatment, 3.61 +/- 4.73; P less than 0.02) and emergency room visits (mean before treatment, 1.94 +/- 3.42; after treatment, 0.21 +/- 0.44; P less than 0.005) and for patients classified as angioedema-frequent in the frequency of episodes (mean before treatment, 14.93 +/- 15.89; after treatment, 2.58 +/- 2.18; P less than 0.003) and emergency room visits (mean before treatment, 0.76 +/- 1.01; after treatment, 0.07 +/- 0.11; P less than 0.025). No statistically significant difference was found for patients classified as generalized-infrequent in the frequency of episodes (mean before treatment, 2.01 +/- 1.30; after treatment, 1.36 +/- 1.79) or of the emergency room visits (mean before treatment, 0.56 +/- 0.71; after treatment, 0.32 +/- 0.75) or for patients classified as angioedema-infrequent in the frequency of episodes (mean before treatment, 1.94 +/- 1.55; after treatment, 2.03 +/- 2.16) or of emergency room visits (mean before treatment, 0.27 +/- 0.44; after treatment, 0.37 +/- 0.59). CONCLUSIONS: Prophylactic treatment with prednisone and H1 antihistamines with or without sympathomimetic amines improves clinical outcome in patients who are classified as idiopathic anaphylaxis-angioedema frequent and idiopathic anaphylaxis-generalized frequent. 
5	Outpatient orthognathic surgery: criteria and a review of cases. Over a 9-year period, 87 orthognathic procedures were performed in an outpatient environment. Procedures performed included horizontal mandibular osteotomies, rapid palatal expansions, bilateral sagittal split osteotomies, posterior and anterior maxillary osteotomies, and Le Fort I osteotomies. Fourteen of these patients were subsequently admitted to a hospital for either observation or full inpatient care. The rates of admission varied for each of the procedures, with length of anesthesia statistically related to the frequency of admission. Patient selection criteria and facilities used are reviewed. 
5	Acute respiratory tract infection in children in Idikan Community, Ibadan, Nigeria: severity, risk factors, and frequency of occurrence. A longitudinal, community-based study of the epidemiology of acute respiratory tract infection (ARI) in children less than 5 years old was carried out in a community of low socioeconomic level in Ibadan, Nigeria. The annual incidence of ARI ranged from 6.1 to 8.1 episodes per child per year. The incidence was highest in the first 2 years of life and decreased with increasing age. The incidence was higher in boys than in girls. ARI occurred in all seasons of the year. The most common symptoms were cough, nasal discharge, and fever, while the most common signs referable to the respiratory tract were abnormal breathing sounds, tachypnea, and chest retraction. 
5	Polyglucosan body disease. Adult polyglucosan disease has been described in 15 cases. All had signs of peripheral neuropathy, upper motor neuron signs, and 12 of the 15 had sphincter problems. Dementia was prominent in 8 of 15 cases. We reported 2 cases that contained these clinical features. Electrophysiological studies showed axonal neuropathy. Somatosensory evoked potentials on the second patient were abnormal. Sural nerve biopsy showed clusters of polyglucosan bodies. Although the presence of polyglucosan bodies in biopsy is nonspecific, the number as well as the clinical features are necessary to make the diagnosis. Branching enzyme activity in muscle extracts of the muscles were normal. Hence, a specific enzyme abnormality is not yet known. 
5	Posthospital course and outcome in schizophrenia. To study the early course of schizophrenia, we assessed 79 early phase, young, DSM-III schizophrenic patients at two successive posthospital follow-ups, 2.5 and 5.0 years after index hospitalization. More than 50% of the sample had poor overall outcome, with either severe impairment in functioning and symptoms, or suicide, in the follow-up period. Rehospitalization rates decreased significantly during the course of the two posthospital assessments, despite the sample showing persisting psychosis. Only a small group of schizophrenic patients showed complete remission: 10% at the first follow-up and 17% at the second follow-up, when patients who suicided are excluded from consideration. While progressive deterioration is not common in schizophrenia, our relatively negative findings challenge the conclusions of some other longitudinal studies. Implications of our data on schizophrenic course are discussed. 
2	Incidence of gallstones in a Danish population. Five-year incidence of gallstone disease was assessed by ultrasonography in an age- and sex-stratified random population of Danish origin aged 30, 40, 50, and 60 years. The response rate was 82.8% (2987/3608). Nonrespondents did not differ from respondents regarding variables concerning gallstone disease. The 5-year incidence of gallstone disease in men aged 30, 40, 50, and 60 years was 0.3%, 2.9%, 2.5%, and 3.3%. Corresponding figures in women were 1.4%, 3.6%, 3.1%, and 3.7%. The incidence of gallstones was significantly higher in subjects aged 45 years or more compared with those aged 35 years. The sex difference in gallstone incidence decreased with increasing age. A significantly higher incidence of gallstone disease was found among subjects with former polyps in the gallbladder. Spontaneous disappearance of gallstones was seen in 4.5%. 
5	A randomized controlled evaluation of a psychosocial intervention in adults with chronic lung disease. The effect of a stress management program on morbidity and psychosocial and physical function in patients with chronic lung disease was assessed. Adults attending either a VA pulmonary clinic or university hospital pulmonary rehabilitation clinic who met criteria for obstructive or restrictive pulmonary disease were randomly assigned to receive the intervention or to a control group. The intervention was provided by a nurse and included one to three teaching sessions, reading material, audiotapes, and telephone follow-up. The program focused on stress management techniques such as cognitive restructuring, progressive relaxation, breathing exercises, and visual imagery. The 45 experimental subjects were similar to the 49 controls with respect to baseline characteristics. Experimental and control subjects had similar rates of mortality, hospital days, bed-disability days, restricted-activity days, and physician visits during the 12-month follow-up. There were no differences between the two groups in physical or psychosocial function at six months or in levels of stressful life changes, social supports, and self-esteem at six and 12 months. Intervention recipients had better function at 12 months, suggesting a possible benefit of the intervention. 
1	Experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model. A rodent bladder cancer model that is induced by intravesical instillation of N-methyl-N-nitrosourea (MNU) was characterized. Cohorts of four to five week old female Fisher 344 rats received four biweekly 1.5 mg. doses of intravesical MNU and were sacrificed at various intervals. By week 13 all animals had flat atypia and/or papillary transitional cell tumors, and 67% of the lesions were moderately (grade II) or poorly differentiated (grade III). By week 20, 83% had gross muscle invasive tumors that eventually killed the host. A cohort of 40 MNU treated animals was subsequently treated commencing at week 17 after initiation of MNU with one of three intravesical six week regimens: 1) saline; 2) BCG (Tice strain); or 3) recombinant human tumor necrosis factor (RTNF) plus adriamycin. There was no difference in animal survival or tumor growth in any group of animals commencing therapy at week 17. A second cohort of 107 animals commenced therapy at 13 weeks after initiation of MNU with one of five intravesical six week regimens: 1) intravesical BCG (Tice strain); 2) adriamycin; 3) recombinant human tumor necrosis factor (RTNF); 4) RTNF plus adriamycin; or 5) BCG plus adriamycin. BCG, RTNF or adriamycin alone had no effect on tumor growth; however, BCG plus adriamycin and RTNF plus adriamycin commencing at week 13 significantly inhibited tumor growth and progression. In conclusion, this autochthonous intravesical rodent transitional cell carcinoma model appears useful for the following reasons: 1) it closely resembles human transitional cell carcinoma histologically and biologically in that all animals develop neoplastic changes in-situ that progress to muscle invasion and kill the host; 2) as with human bladder cancer these tumors do not respond to intravesical therapy if treated when tumor burden is large; however, tumor growth is inhibited when treated early; and 3) this model appears appropriate for screening and developing new intravesical treatments for superficial bladder cancer. 
4	Antithrombotic efficacy of continuous extradural analgesia after knee replacement. We have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty. Forty-eight patients were allocated randomly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days. All patients wore compressive elastic stockings and no anticoagulant drugs were administered. Bilateral venography was performed 10 days after surgery. Continuous extradural analgesia did not impede mobilization of the patients. One case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia. The use of continuous extradural analgesia resulted in a significant difference in the total incidence of deep vein thrombosis (18% compared with 59% after general anaesthesia (P = 0.02]. The incidence of calf vein thrombosis was 12% compared with 45% after general anaesthesia (P = 0.05). 
1	Breast cancer: the military's experience at Wilford Hall USAF Medical Center. We reviewed the experience with breast cancer at Wilford Hall USAF Medical Center for the years 1978 through 1988. A total of 868 cases were identified in the Wilford Hall Tumor Registry; overall 5-year and 10-year survivals were 63% and 39%, respectively. Infiltrating ductal carcinoma represented the principal histologic category. The other predominant variants included invasive lobular carcinoma, lobular carcinoma in situ, and ductal carcinoma in situ. Until recently, most of these patients (90%) had modified radical mastectomy as their definitive surgical therapy, with chemotherapy reserved primarily for patients with advanced disease. 
5	1990 AcroMed Award in basic science. Cauda equina anatomy. II: Extrathecal nerve roots and dorsal root ganglia. Inconsistent data exist regarding the anatomy of the spinal nerve roots lateral to the thecal sac. A newly developed in situ technique was used to precisely define anatomic parameters on 20 fresh human cadavers. The take-off angle of the nerve roots from the thecal sac decreases from a mean of approximately 40 degrees from L1-L5 to 22 degrees at S1. The motor bundles are directly ventral to the sensory fibers within individual roots extrathecally. Dorsal root ganglia size varies with vertebral level. The majority of ganglia lie directly beneath the vertebral pedicles and one third overlie a portion of the lateral intervertebral disc. These previously undescribed relationships may aid in the understanding of lumbosacral neurocompressive disorders and are important to note during pedicle screw insertion, posterolateral decompression for spinal trauma, and paravertebral approaches for lateral disc herniations. 
1	Haemangiopericytoma of the temporal bone. Haemangiopericytoma is an uncommon vascular tumour with a widespread distribution. Although meningeal involvement is well recognized, only a few sporadic cases of temporal bone lesions have been documented, all with doubtful sites of origin. Late presentation together with the restrictive anatomy of this region often precludes its effective removal and even minimal residual disease may progress rapidly. A series of three such patients are presented in order to discuss the natural history, histological features and treatment of this disease. 
2	Putative mechanisms of cytoprotective effect of certain antacids and sucralfate. An investigation of cytoprotective activity of certain antacids and inert particles was carried out by treating ethanol-induced gastric mucosal damage in rats in order to clarify possible mechanisms by which aluminum-containing antacids act. Al(OH)3 inhibited gastric mucosal damage in a dose-related and time-dependent manner. Neither aluminum ions themselves nor the particle size of the Al(OH)3 complex were responsible for the observed cytoprotection, since neither AlCl3, chemically inert Al2O3*C, nor sea sand showed protective effects. Hyperosmolality in the gastric lumen was not a deciding factor in inducing cytoprotection. Silicic acid and titanium dioxide, with superficial charge similar to Al(OH)3 proved to be effective in inhibiting gastric hemorrhagic lesions and releasing PGE2, suggesting that the surface charge of Al(OH)3 may be important in its cytoprotective properties. The same may also be valid for sucralfate. Since antacid-induced cytoprotection was only partly reduced by pretreatment with indomethacin, it is likely that additional mechanisms and mediators other than prostaglandins, such as nonprotein sulfhydryls, also are involved in gastric cytoprotection arising from aluminum-containing antacids. 
4	Association of pneumothorax and hypotension with intraventricular haemorrhage. To test the hypothesis that acute hypotension resulting from pneumothorax would be associated with severe brain injury (grade 3 or 4 intraventricular haemorrhage), 67 very low birthweight (VLBW) infants of 32 weeks' gestation or less with respiratory distress syndrome and pneumothorax were studied. Thirty six had pneumothorax associated with systemic hypotension and 31 had pneumothorax with normal blood pressure. The groups were similar in gestational age and severity of their respiratory distress syndrome. Thirty two of 36 of infants with pneumothorax associated with hypotension (89%) had grade 3 or 4 intraventricular haemorrhage. This percentage was significantly greater than the percentage for infants with pneumothorax and normal blood pressure (three of 31, 10%). The risk ratio for grade 3 or 4 intraventricular haemorrhage for infants with pneumothorax associated with hypotension was 9.8 compared with neonates with pneumothorax and normal blood pressure. These observations are consistent with the hypothesis that systemic hypotension and cerebral hypoperfusion are important factors leading to intraventricular haemorrhage in VLBW infants. 
4	Efficacy of percutaneous mitral balloon valvuloplasty with the inoue balloon. Percutaneous mitral balloon valvuloplasty has become an accepted technique for use in selected patients with severe, symptomatic mitral stenosis. Recently, a new balloon catheter with an "hourglass" shape and specially designed guidewires and dilators has become available (Inoue balloon). The design of this balloon provides ease of manipulation and self-stabilization across the mitral valve during inflation. These features should decrease the incidence of complications associated with the procedure. Preliminary results in 12 consecutive patients who underwent percutaneous mitral balloon valvuloplasty with the Inoue balloon are presented. The mitral valve area increased from 0.92 +/- 0.21 cm2 before the procedure to 1.75 +/- 0.40 cm2 after the procedure. No complications occurred from the procedure, including no increase in severity of mitral regurgitation or creation of an atrial septal defect. Further follow-up is necessary to determine the long-term efficacy with this new balloon. Nonetheless, the preliminary results are encouraging. 
2	Cathepsins D and E in normal, metaplastic, dysplastic, and carcinomatous gastric tissue: an immunohistochemical study. Immunohistochemical distributions of cathepsins D and E were determined in normal mucosa, metaplastic, dysplastic, and cancerous lesions of the human stomach. Cathepsins D and E were localised in the foveolar epithelium and parietal cells of the normal gastric mucosa, but their intracytoplasmic distributions were different - cathepsin E distribution was even and diffuse in the cytoplasm while cathepsin D was found in coarse intracytoplasmic granules. Chronic inflammation and ulcer did not influence the distribution of these enzymes. No positive staining was obtained in the incomplete type of intestinal metaplasia, dysplasia, and well differentiated adenocarcinoma. Tumour cells of signet ring cell carcinoma and poorly differentiated adenocarcinoma cells, however, gave strong and diffuse stainings for cathepsins D and E in the cytoplasm. The results suggest that the distribution of cathepsins D and E is related to each specialised function of the foveolar epithelium and the parietal cells, and that their disappearance is associated with development of well differentiated adenocarcinoma from intestinal metaplasia. 
4	Parenteral illegal drug use and limb loss. The problem of illegal drug abuse and extremity loss was identified in 27 patients-22 men and 5 women, with a mean age of 26 years. Associated medical problems included: smoking in 27, cardiac disease in 2, diabetes in 3, and hypertension in 3. Six femoral pseudoaneurysms, 2 with distal emboli and all with sepsis and thrombosis, directly contributed to limb loss along with 2 patients with progressive phlegmasia dolens. There were 3 below-the-elbow, 7 above-the-knee, 11 below-the-knee, and 6 transmetatarsal amputations. Eight patients received prostheses; 8 patients subsequently died in follow-up. 
5	Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. Pearson's marrow-pancreas syndrome (McKusick No. 26056) is a fatal disorder of hitherto unknown etiology involving the hematopoietic system, exocrine pancreas, liver, and kidneys. The observation of high lactate/pyruvate molar ratios in plasma and abnormal oxidative phosphorylation in lymphocytes led us to postulate that Pearson's syndrome belongs to the group of mitochondrial cytopathies. Since rearrangements of the mitochondrial genome between direct DNA repeats were consistently found in all tissues tested, our results show that this disease is in fact a multisystem mitochondrial disorder, as suggested by the clinical course of the patients. Based on these observations, we would suggest giving consideration to the hypothesis of a defect of oxidative phosphorylation in elucidating the origin of other syndromes, especially those associated with an abnormal oxidoreduction status in plasma. 
4	Embolization of a giant renal arterial aneurysm. A 49-year-old man presented with right flank pain. Angiography revealed a giant right renal arterial aneurysm. Giant renal arterial aneurysms are typically treated by nephrectomy. In this patient the aneurysm was embolized successfully with multiple Gianturco-Wallace coils and polyvinyl alcohol. This case indicates that embolization may be a reasonable alternative to nephrectomy. 
2	Outpatient laparoscopic laser cholecystectomy. Laparoscopic laser cholecystectomy has been performed clinically in the United States since 1988. After refinement of the technique, the procedure was offered on an outpatient basis. Eighty-three patients underwent laparoscopic laser cholecystectomy during the study period. Thirty-seven (45%) had the procedure as an outpatient. Younger patients were more suited for the outpatient procedure and those without previous surgery were more likely to have the procedure done as an outpatient. Weight, operating time, and gallbladder pathology were similar, although patients with acute inflammation of the gallbladder were more likely to require hospitalization. The primary reason for patient admission was patient preference. 
5	Intrathecal immunoglobulin M synthesis in multiple sclerosis. Relationship with clinical and cerebrospinal fluid parameters. Intrathecal IgM synthesis was assessed through the detection of oligoclonal bands in cerebrospinal fluid (CSF) and through calculation of IgM index values and total CSF IgM amounts. Intrathecal production of IgM was then evaluated along with other CSF parameters and clinical variables in 150 patients with multiple sclerosis (MS). Intrathecal production of IgM was detected in 55% of patients and was found to correlate with disease activity, manifesting as a recent relapse, as well as the total number of relapses. An inverse correlation was found between CSF oligoclonal IgM and both the time interval between the last relapse and lumbar puncture, and duration of the disease process. It also correlated with the number of leucocytes, free kappa and lambda light chain bands in CSF. No correlation was found between intrathecal IgM synthesis and degree of disability (Kurtzke scale), disease progression index (Poser scale), or total cerebral plaque burden (detected by enhanced CT and MRI scans). Oligoclonal IgM bands were found to be more specific for active disease process than either IgM index or total CSF IgM amount. It is concluded that intrathecal synthesis of IgM, as detected by CSF oligoclonal bands, is a useful parameter in monitoring disease relapse activity in MS. 
2	Chylous ascites due to sarcoidosis. A 33-yr-old black female with systemic sarcoidosis developed chylous ascites. A CT scan showed extensive mesenteric lymphadenopathy. At laparotomy, the mesenteric and para-aortic lymph nodes were enlarged and diffusely matted. Histologically, normal lymph node morphology was virtually replaced with noncaseating granulomas. Corticosteroids and dietary manipulations were unsuccessful in managing the ascites, and repeated large-volume paracentesis was necessary to provide symptomatic treatment. This is the first reported case of chylous ascites caused by sarcoidosis. 
1	Defining the role of subtotal colectomy in the treatment of carcinoma of the colon. Seventy-two patients with colon cancer were treated by primary subtotal colectomy, including 23 patients with acute and subacute left colon obstruction. There were two operative deaths and no cases of disabling diarrhea. One death occurred in the group with colon obstruction. Other indications for subtotal colectomy included multiple polyps associated with the primary tumor (32), synchronous carcinomas (15), a previous transverse colostomy for obstruction (8), associated severe sigmoid diverticular disease (2), age less than 50 years with a positive family history (3), adherence of the sigmoid loop to a cecal tumor (2), and metachronous carcinoma (2). There were multiple indications in several patients. Subtotal colectomy has a defined role in a wide variety of clinical settings associated with colon cancer, including management of obstruction of the left and sigmoid colon, particularly if the proximal colon cannot be evaluated before operation by colonoscopy or barium enema. Segmental or regional colonic resections are appropriate if the entire colon can be evaluated before operation and no associated neoplasms are revealed. 
5	Long term follow-up of descending thoracic aorto-iliac/femoral bypass. A prospective study of 26 patients undergoing descending thoracic aorto-iliac/femoral (DTAI/F) bypass was conducted over a 13-year period with an average follow up of 53 months. Reasons for selecting the procedure were occluded aortic bifurcation grafts (9 patients), hostile abdomen (6), infected aortic graft (1), microaorta (10, and surgeons preference in 8 patients who had juxtarenal aortic occlusion. The operative mortality was 3.8% (1 patient). A late mortality of 36% was due to myocardial infarction (1), lung carcinoma (2), renal failure (4), stroke (1) and pulmonary insufficiency (1). Graft failure occurred in 4 patients at 23, 26, 54 and 109 months respectively. Primary cumulative patency was 86% statistically valid at 42 months. DTAI/F bypass is recommended in selected patients when conventional approaches to the aorta are considered unduly hazardous. 
4	In vitro and in vivo evaluation of a right ventricular assist device. A simple right ventricular assist device (RVAD) has been developed. This device will be useful in situations where biventricular failure has been partially treated by placement of a left ventricular assist device, or when right ventricular failure occurs in isolation. This pneumatically actuated, R-wave synchronized, sac type pump contains no valves, and is connected by a graft to the pulmonary artery. The RVAD was tested in a circulation simulator to verify its hemodynamic efficacy and then implanted in six calves for 2-4 weeks to evaluate its biocompatibility. In vitro testing of the RVAD demonstrated that it restored normal hemodynamics in the presence of severe simulated RVF. In six animal implantations, a small amount of thrombus was found in one pump. No anticoagulants were employed. Thrombus was present in the connecting graft in three animals; in two this was clearly related to technical implant errors. No evidence of significant hemolysis was found. This simple RVAD has been found to be hemodynamically effective, is simple to use, and is well tolerated. Refinements in the interconnection graft between the pulmonary artery and the device are necessary. 
1	Immunoscintigraphy of ovarian cancer with indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody. The safety and diagnostic accuracy of immunoscintigraphy with the indium-111-labeled monoclonal antibody OV-TL 3 F(ab')2(111In-OV-TL 3 F(ab')2) for diagnosis and follow-up of ovarian cancer was prospectively studied in 31 patients. Planar and SPECT scintigraphy were performed up to 4 days after i.v. injection of 140 MBq 111In-OV-TL 3 F(ab')2. Surgical evaluation was possible in 22 out of 31 patients. Imaging results were compared with X-ray computed tomography, ultrasound, and CA 125 serum level using the histologically confirmed surgical findings as a "gold standard." Apart from a transient rash observed in two patients, no other immediate or delayed adverse reactions were observed. Within the surgically evaluated group, ovarian cancer lesions were detected in 16 out of 17 patients (94%). Of 45 distinct tumor deposits found at operation, 67% were detected and localized with immunoscintigraphy while X-ray computed tomography and ultrasound visualized 53% and 23%, respectively. 
2	Obesity and colorectal adenomatous polyps. Obesity has been investigated as a risk factor for various malignancies, including colon cancer. A case-control study was conducted on patients in three colonoscopy practices in New York City to determine possible risk factors for colorectal adenomatous polyps, a known precursor lesion for most cases of colorectal cancer. Among 301 case subjects with incidence adenomatous polyps (174 men and 127 women) and 506 control subjects (223 men and 283 women), an increased risk was observed with increasing body mass index in women (odds ratio 2.1, 95% confidence interval 1.1-4.0; for highest versus lowest quartile, linear trend P = .02). A nonsignificant trend was observed for men. The increased risk seen in women is consistent with prior observations regarding reproductive hormonal and dietary risk factors for colorectal cancer. 
5	Endotoxemia in human septic shock. To evaluate the incidence, pattern and clinical importance of endotoxemia in septic shock, frequent, serial endotoxin determinations were made prospectively in patients with shock. Detectable endotoxin occurred in 43 of 100 patients with septic shock, but in only one of ten patients with shock due to nonseptic causes. During septic shock, endotoxemia frequently occurred in the absence of Gram-negative bacteremia. Using a logistic regression model, multiple organ failure occurred 10.3 times more frequently and depression of left ventricular ejection fraction (less than or equal to 45 percent) 4.8 times more frequently in endotoxemic patients. In patients with positive blood cultures, endotoxemia was associated with a high mortality. We conclude that endotoxemia occurs frequently in septic shock and is associated with severe manifestations of this syndrome, including cardiac depression and multiple organ failure. This study suggests that endotoxin is an important mediator of septic shock and supports efforts to develop anti-endotoxin therapies for treating patients with this disease. 
5	A clinical study of acute gastrointestinal hemorrhage associated with various shock states. Gastrointestinal hemorrhage from stress ulceration is a life-threatening complication in a critically ill patient. We retrospectively studied 471 patients admitted to the Department of Traumatology of our hospital who developed shock in their clinical course. Forty-two patients (8.9%) developed gastrointestinal hemorrhage, most within 1 wk (76.2%). The hemorrhage lesion usually was located in the corpus of the stomach. The mortality rate of the shock patients with gastrointestinal hemorrhage was 33.3% (14 of 42). Comparison of different types of shock showed that the incidence, severity, and mortality rates of gastrointestinal hemorrhage were significantly higher in septic shock patients than in hemorrhagic shock patients. These findings show the importance of preventive therapy against progression of early mucosal damage and development of gastrointestinal hemorrhage in shock patients, especially those with sepsis. 
5	Audit of results of operations for infantile pyloric stenosis in a district general hospital Because of the proposal that infants with hypertrophic pyloric stenosis should only be treated by surgeons with an interest in paediatric surgery, we carried out a retrospective study to audit our experience in a district general hospital. Forty six infants over a five year period underwent pyloromyotomy. There were no deaths, and 36 infants (78%) made uneventful recoveries. Perforation of the duodenal mucosa occurred during the operation in 11 patients, and eight complications developed in six of these infants. There were seven wound infections, and two patients had vomiting that lasted four days or longer after their operations. There were no long term feeding problems. The results of this study show that such patients can be successfully treated in district general hospitals, and three areas merit special attention: meticulous surgical technique, the use of prophylactic antibiotics, and early graduated feeding. 
3	A follow-up study of intractable seizures in childhood. One hundred forty-five children with seizures that were refractory to medical therapy for at least 2 years were followed 5 to 20 years after onset. The majority of children with uncontrollable seizures (61%) were mentally retarded, and most of these (73%) had onset of seizures at younger than 2 years of age. Age of onset was significantly later (mean 5.0 +/- 0.5 yr [SEM]) in the group of children with borderline to normal intelligence. Follow-up data showed remission of seizures in a significant proportion of children with borderline or normal intelligence, with a linear decrease of the percentage with persistent seizures at a rate of about 4% per year. Remission of seizures was much less frequent (1.5%/yr) in the group with mental retardation. Seizure type had some effects on outcome. Children with focal atrophic brain lesions did no worse than those without definable pathology on brain-imaging studies. 
3	Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent. 
1	The unique aspects of acute promyelocytic leukemia. Acute promyelocytic leukemia (APL) accounts for approximately 10% of cases of acute myeloid leukemia (AML). Distinctive features of this disorder at the time of diagnosis include leukopenia coexisting with a marrow replaced with granulated dysplastic promyelocytes, disseminated intravascular coagulopathy, lack of Ia (HLA-DR) antigen expression, and translocation between the long arms of chromosomes 15 and 17 (t[15;17]). Heparin is widely but not universally used to interfere with the coagulopathy during the initial phases of treatment. Serial bone marrow examinations during the induction period demonstrate the achievement of remission despite the persistence of malignant-appearing promyelocytes. Patients with APL are generally younger than those with other subtypes of AML, have a 70% to 80% likelihood of entering remission, and are thought to have a more favorable prognosis than other individuals with AML. Remission may be achieved with a conventional anthracycline-cytarabine combination, anthracycline alone, or, apparently, all-trans retinoic acid. Genes potentially important in myeloid differentiation such as granulocyte colony-stimulating factor (G-CSF) and myeloperoxidase are located close to the breakpoint in the t(15;17) but have not been conclusively shown to be rearranged in the translocation. A better understanding of the unique aspects of APL may well shed light on the pathogenetic processes of AML. 
4	Coronary artery bypass grafting in a patient with cryoglobulinemia. Coronary artery bypass grafting (CABG) was performed in a patient with cryoglobulinemia. In order to decrease the concentration of cryoglobulin, the patient underwent double filtration plasmapheresis (DFPP) pre- and postoperatively as well as during cardiopulmonary bypass. Bypass surgery was performed under total cardiopulmonary bypass, moderate systemic hypothermia, and ventricular fibrillation without aortic crossclamping. No adverse effects of cryoglobulin appeared during the peri- and postoperative course. Technical considerations for open heart surgery in patients with cryoglobulinemia are described. 
5	The tissue origin of low back pain and sciatica: a report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. In an effort to define the origin of low back pain and sciatica, 193 patients were carefully studied using progressive local anesthesia. These patients had surgery for herniated discs, spinal stenoses, or both. Various tissues were stimulated during the performance of these lumbar spinal operations. This article discusses our observations and the results of that study. 
5	Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome). The clinicopathologic and radiologic features of 12 children with complete and incomplete forms of Drash syndrome are reported. Their common denominator was a nephropathy. Four had the full triad, consisting of nephropathy, Wilms tumor, and genital abnormalities; five had nephropathy and genital abnormalities, and three had nephropathy and Wilms tumor. Of the 11 children who had proteinuria, eight had the nephrotic syndrome. Of the 10 whose condition progressed to end-stage renal failure, seven were less than 3 years of age. The histologic features of Wilms tumor were favorable in all seven children, and the tumor was bilateral in three. Of the nine patients who had genital abnormalities, eight had 46,XY karyotype and either ambiguous genitalia (six patients) or normal female phenotype (two). One other patient had a normal 46,XX female karyotype and phenotype but had both mullerian and wolffian structures and a streak ovary. Nine patients had a distinct pelvicaliceal abnormality not previously reported as a feature of this syndrome. Other congenital abnormalities were aniridia, mental retardation, deafness, nystagmus, and cleft palate. This syndrome must be considered in any infant with unexplained nephropathy, particularly in young phenotypic female infants and in those children with ambiguous genitalia or Wilms tumor with an early presentation. 
5	Reconstruction of patellar tendon rupture after total knee arthroplasty with an extensor mechanism allograft. Although patellar tendon rupture after total knee arthroplasty (TKA) is a rare complication, the consistently poor outcome of conventional tendon repair has convinced some to abandon such reconstruction in favor of a prospective protocol using an allograft distal extensor mechanism. The graft consists of a quadriceps tendon, a patella with a cemented prosthesis, a patellar tendon, and a tibial tubercle. Since December 1985, 13 knees in 12 patients were reconstructed using this method. Ten knees were followed for six to 51 months; five of these knees were followed for more than 24 months. Knee extension power and improved function were ultimately attained in all cases, although minimal extensor lags were present in three cases. Preoperative motion returned in all but one knee. Healing of the allograft to the host tissue was attained primarily at all of the tibial junctions. Two graft complications occurred, both in the first three months after surgery: one quadriceps junction treated by resuture failed at the one-month mark, and the other graft had to be revised for extensor weakness from rupture of the graft at the patella-patellar tendon junction, which was attributed to surgical damage to the tendon. After completion of healing to the host and rehabilitation of the knee joint, no grafts in the series failed during the course of normal daily activities. One patient fractured the allograft patella in a severe fall. The long-term durability of this construct needs to be studied further. 
4	Retrograde recanalization of an occluded posterior tibial artery by using a posterior tibial cutdown: two case reports. Recanalization of two occluded posterior tibial arteries was successfully achieved by utilizing a retrograde approach via a posterior tibial artery cutdown at the level of the ankle. Both cases were previously unsuccessfully attempted by using an antegrade approach. Thus, the choice of access vessel (arterial entry site) becomes a crucial determinant of angioplasty success. 
3	Chronic pain. Understanding of the etiology of chronic pain is growing rapidly as researchers seek to integrate physiologic and psychosocial mechanisms. When nurses assess clients with chronic pain, they should make their assessments using both verbal and nonverbal methods and realize that no one instrument is comprehensive enough to be used alone. The key to successful treatment of these difficult clients lies in the use of a comprehensive approach that takes the client seriously and integrates both physiologic and psychosocial approaches. 
4	Resistance to ischaemia of small afferent nerve fibres in diabetes mellitus. Thermal thresholds were measured in the left forearms of 26 healthy subjects and 10 patients with diabetes mellitus during ischaemic compression block. During the period when ischaemic block of large fibres caused paraesthesia and loss of touch sensation, the cold threshold rose in normals. The cold threshold was less clearly elevated and the warm perception remained unaltered by ischaemia in diabetics. These results show that not only large afferent and efferent nerve fibres but also thinly myelinated A delta and unmyelinated C fibres are resistant to ischaemia in the diabetic nerve. 
1	Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease. Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of "high-risk" proliferative fibrocystic change increased with age. 
4	Noninvasive assessment of cardiac output in children using impedance cardiography. This study evaluated the effect of intracardiac shunting on the accuracy of thoracic bioimpedance-derived cardiac output determinations. Twenty-six patients, ranging in age from 3 months to 17 years, underwent cardiac catheterization during which simultaneous Fick and impedance measurements of cardiac output were obtained. The subjects were divided into three groups: 10 children with no intracardiac shunts, nine children with predominant left-to-right intracardiac shunts, and seven children with predominant right-to-left intracardiac shunts. Positive correlations between impedance and Fick-derived cardiac output determinations were obtained in the non-shunt group (r = 0.84), with lower correlations in the left-to-right shunt group (r = 0.70). In the right-to-left shunt group, the impedance derived cardiac output correlated with Fick pulmonary flow (r = 0.82), but the variability was unacceptably large. Although further study is needed, impedance cardiography appears to have validity as a methodology in pediatric critical care and cardiovascular health research. 
4	Coarctation of the aorta and post-stenotic aneurysm formation. Despite earlier angiography, post-stenotic aneurysm of the aorta was an unexpected finding at operation in two patients with coarctation. One aneurysm was found in an intercostal artery in a 19 year old man and the other was a false aneurysm just distal to the coarctation site in a 7 year old boy. These aneurysms are fragile, apt to rupture, and difficult to diagnose preoperatively. Though local factors such as jet streams and bacterial endocarditis may influence their formation there must be an underlying generalised weakness in the arterial wall. A coarctation should not be regarded as an isolated arterial abnormality because it may be a feature of a more generalised disease. Because of the risk of rupture, which may not be prevented by antihypertensive treatment, operation should not be delayed in any age group. 
2	Volvulus of the colon. The charts of all patients with colonic volvulus at the University of Louisville Hospitals between 1983 and 1988 were reviewed. A total of 45 patients were identified, and there were 17 with cecal volvulus and 29 with sigmoid volvulus (1 had both). Two-thirds of the patients were either demented, bedridden, or used constipating drugs. Initial nonoperative decompression was achieved in 26 of 29 patients with sigmoid volvulus but in only three of nine patients in which it was attempted with cecal volvulus. Two of these recurred, and 16 of the 17 cecal volvulus patients underwent operation. One-third of the sigmoid volvulus patients had at least one recurrent episode on the index admission. Fourteen of the 29 had an operation, and half of these patients died following surgery. Fifteen sigmoid volvulus patients chosen to be treated with successive nonoperative treatment had no mortality. Mortality was higher following emergent (4 of 5) than elective (2 of 9) operation for sigmoid volvulus, and one of three died after operation for a successfully decompressed first episode. Mortality for nonoperative reduction of an early recurrence was zero of four patients, while operative mortality for recurrence was two of seven (all had successful preoperative deflation). There was no mortality or recurrence in four patients with cecal volvulus treated by cecopexy alone, but all three patients died in whom tube cecostomy was performed. Two of nine patients died following right hemicolectomy. These data suggest that if an elective operation is to be performed for sigmoid volvulus, it should be done following one or more recurrences and that nonoperative decompression can be safely performed on successive occasions. 
4	Multilevel occlusive vascular disease presenting with gangrene. The medical records of all patients subjected to lower extremity amputations during a 3-year period were reviewed. It was shown that advanced age and the presence of multiple medical problems do not predispose to higher levels of limb loss. Although diabetic patients more frequently undergo amputation because of sepsis than their nondiabetic counterparts, the diabetic state was not found to be associated with a greater likelihood of above knee (AK) procedures. Prior arterial surgery was not shown to make AK amputation more likely, but it was disconcerting to note that limb salvage was not achieved in many individuals despite patent proximal inflow revascularization procedures. This initial study showed that several presumed risk factors were not predictors of amputation level. Those patients requiring AK amputations had a greater frequency of combined segment (aortoiliac and femoropopliteal) occlusive disease than those who had successful amputations at more distal levels. A follow-up study of 41 consecutive patients presenting with tissue loss due to combined segment occlusive disease was performed. Eighteen (Group I) underwent inflow procedures only, while 23 (Group II) also underwent distal revascularization. The groups were similar with respect to age, risk factors, extent of tissue loss and sepsis. At 1 year 10 (56%) Group I and only 3 (13%) Group II patients required major amputation (P = 0.01). Distal bypass, in addition to an inflow procedure, is recommended for those who present with tissue loss due to multilevel arterial occlusion. 
2	Host response to mycobacterial infection in the alcoholic rat. Animals, chronically treated with alcohol, were inoculated with mycobacteria (bacillus Calmette-Guerin, 10.2 x 10(6) organisms) into the spleen to produce a granulomatous hepatitis. Before infection, chronic alcohol ingestion was associated with a depressed skin test response to phytohemagglutinin, 71.7% of baseline (P = 0.009). Mycobacterial (bacillus Calmette-Guerin) infection stimulated phytohemagglutinin skin test response to 417% of baseline in controls and 299% in alcoholics (P less than 0.001). The hepatic granuloma response was altered with smaller but more numerous granulomas (mean +/- SEM, 81.2 +/- 1.5 microns2 of area with a frequency of 1.8 granulomas per field in alcoholics vs. 129.8 +/- 5.71 microns2 and 1.2 granulomas per field in controls; P less than 0.001). These changes were associated with a 10-fold increase in colony-forming units per gram of liver (54.5 +/- 18.2 in alcoholics vs. 5.6 +/- 1.83 in controls; P = 0.0006). This model offers precise parameters for host response to infection and indicates that alcohol significantly impairs the clearing capacity for mycobacteria from the liver. 
1	Legislative influences on cancer care. Deficit reduction politics was a major force in policymaking in the 1980s and a pervasive fact of life in the development of health policy. The Medicare budget was habitually used to find savings for deficit reduction and reforms, such as how to address the problem of 31 to 37 million uninsured Americans, were postponed. The 101st Congress did produce major physician payment reforms and in the spring of 1990, the Pepper Commission issued its recommendations for access to care and long-term care. Less sweeping but significant proposals affecting cancer care were considered by Congress. For example, positive actions were taken on anti-smoking and food labeling proposals. Funding for the National Institutes of Health was increased, and there was a growing awareness of the threat to biomedical research presented by assaults on animal research facilities. 
5	A case of amnesia after excision of the septum pellucidum. Tumours of the septum pellucidum (SP) are rare and seldom associated with memory impairment either before or after operation. A patient is described who developed amnesia after transcallosal excision of a tumour of the SP. Radiology did not show any major lesion of the brain areas traditionally associated with amnesia. Because septal nuclei could have been damaged during surgery their possible role in memory functions is discussed. 
5	Cytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone. The hamster mAb 145-2C11 specific for the CD3 complex of murine T lymphocytes shares many properties with OKT3, including the induction of T cell activation. In vivo, the injection of 145-2C11 entails a variety of pathologic changes in relation to the systemic release of cytokines. We tested the effects on this cytokine release syndrome of different doses of methylprednisolone (m-PDS) given at various intervals of time before the 145-2C11 mAb. The administration of high doses of m-PDS (50 mg/kg) 2 to 3 h before the mAb resulted in an almost complete inhibition of the systemic release of TNF-alpha, IL-2, and IL-6. As far as the pathologic changes are concerned, the hypothermia, the acute renal tubular necrosis, and the fatty infiltration of the liver were completely prevented whereas the hypoglycemia was only partially attenuated. The protective effect of m-PDS on the toxicity of 145-2C11 was confirmed by the reduction of the mortality rate among galactosamine-sensitized mice. The inhibition of the release of cytokines by m-PDS did not affect the immunosuppression triggered by 145-2C11 as assessed by the CTL activity against alloantigens measured 48 h after the injection of the mAb. We conclude that the administration of very high doses of glucocorticoids 2 to 3 h before 145-2C11 prevents the release of cytokines and attenuates the acute toxicity of the mAb. Similar protocols could allow mitigation of the cytokine-release syndrome induced by the OKT3 mAb in man. 
4	High incidence of cardiopulmonary complications associated with implantation of adrenal medullary tissue into the caudate nucleus in patients with advanced neurologic disease. OBJECTIVE: The purpose of our study was to examine the cardiopulmonary complications of a group of patients who had undergone implantation of adrenal medullary tissue into the caudate nucleus for treatment of neurologic disease. DESIGN: Prospective study with partially matched historical controls. SETTING: Tertiary care community medical center. PATIENTS AND METHODS: Seven patients with advanced Parkinson's disease and three patients with progressive supranuclear palsy underwent implantation of adrenal medullary tissue into the caudate nucleus. These patients were compared with respect to their cardiopulmonary complications with a control group who had undergone craniotomy and then compared with a control group who had undergone only abdominal surgery. RESULTS: In the study group, six patients developed major postoperative complications including development of large pleural effusions, lobar atelectasis, pneumonia, upper airway obstruction, and cardiac arrest. Three patients had minor complications including development of small pleural effusions, subsegmental atelectasis, purulent bronchitis, mild congestive heart failure, and atrial flutter/fibrillation. One patient had an unremarkable postoperative course. The first control group, whose only surgery was a craniotomy, had only one major complication. The second control group, the abdominal surgery control group, had one major and five minor complications. CONCLUSION: The particular neurologic disease, its severity, and the type of surgery performed appear to be causative factors in the high incidence of complications in the study group. 
1	Local failure and related complications after definitive treatment of carcinoma of the prostate by irradiation or surgery. The authors review their institution's experience with the failure of definitive treatment to achieve local tumor control and with the distant dissemination and local morbidity associated with such failure. The causes of local failure are various: incomplete resection, implantation of spilled cells, and, possibly, selective implantation of circulating tumor cells in traumatized tissues after surgery and totally or partially resistant cells, new tumors, or radiologic misses after radiation. Treatment of local failure may be prophylactic or therapeutic and differs depending on the stage of the disease. Failure to control the tumor locally in the presence of distant metastases does not alter the length of survival, but it can profoundly affect the quality of survival. 
4	Right hemothorax: an unusual presentation of ruptured aortic dissection. This report presents the case of a 55-year-old male with rupture of a descending thoracic aortic dissection into the right hemithorax who successfully underwent prosthetic graft replacement of the involved segment of the aorta through left thoracotomy. 
4	Synthesis of IL-1 alpha and IL-1 beta by arterial cells in atherosclerosis. Interleukin-1 (IL-1) has been implicated as a regulatory protein in the development and clinical sequelae of atherosclerosis. To determine which cells in the atherosclerotic plaque synthesize IL-1 in situ, the authors evaluated histologic sections of iliac arteries from cynomolgus monkeys using probes for IL-1 alpha and beta. A polyclonal antibody to IL-1 alpha and beta was used to determine if proteins were concomitantly produced. The predominant cells expressing IL-1 alpha and beta mRNA were foam cells in the intima. Adherent leukocytes and vascular smooth muscle cells (VSMCs) expressed mRNA for IL-1 alpha. Microvascular endothelium expressed mRNA for both IL-1 alpha and beta. IL-1 proteins were located frequently in cells expressing IL-1 mRNA. These results indicate that endothelium and VSMCs, in conjunction with macrophages, serve as localized sources of IL-1 protein synthesis. These findings suggest that vascular cells may contribute directly to the pathogenesis of atherosclerotic vascular disease by actively secreting potent biologic mediators that modify vascular and immune cell function. 
5	Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparison of low-molecular-weight heparin and unfractionated heparin. In a prospective, randomized, double-blind study, the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin (standard heparin) in 136 patients who had elective total hip replacement. The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of standard heparin three times a day. Treatment with low-molecular-weight heparin began twelve hours before the operation, and treatment with standard heparin began two hours preoperatively; both regimens were continued for ten days. Twelve days postoperatively, bilateral ascending phlebography was performed in 122 patients, sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received standard heparin. Pulmonary scintigraphy was performed in 127 patients. Deep-vein thrombosis was diagnosed in forty-four patients: nineteen (30 per cent) of the sixty-three who received low-molecular-weight heparin and twenty-five (42 per cent) of the fifty-nine who received standard heparin. All but four patients, two from each treatment group, were asymptomatic. The difference in the total rate of thrombosis in the two groups was not significant (p = 0.189). However, thrombosis occurred in the thigh in only six (10 per cent) of the patients who received low-molecular-weight heparin but in eighteen (31 per cent) of those who received standard heparin, a significant difference (p = 0.011). Pulmonary embolism was detected in twenty-seven patients: eight (12.3 per cent) of those who received low-molecular-weight heparin and nineteen (30.6 per cent) of those who received standard heparin. Only three patients had clinical signs of embolism. Pulmonary embolism was significantly more frequent in the group that received standard heparin (p = 0.016). Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received standard heparin. Prophylaxis was not discontinued because of hemorrhage in any patient. The efficacy of low-molecular-weight heparin was superior to that of standard heparin in the prevention of femoral thrombosis and pulmonary embolism, although the over-all incidence of deep-vein thrombosis was not statistically different.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	DNA ploidy pattern in rectal carcinoid tumors. The nuclear DNA pattern of 22 rectal carcinoids was determined by cytophotometry of paraffin embedded tissues. The results were compared with clinical as well as histopathologic features of the tumor. Three of the carcinoids with synchronous or metachronous metastasis had aneuploid DNA pattern, whereas 19 tumors with no metastasis showed diploid DNA pattern. No other single clinical or pathologic feature of the tumor could predict more accurately the malignant potential and the subsequent course of the rectal carcinoid. It is concluded that DNA aneuploidy in rectal carcinoid tumors is not so rare as indicated by earlier studies and that it is a factor of significant prognostic value. 
1	Positive selection of candidate tumor-suppressor genes by subtractive hybridization. A positive selection system designed to identify and recover candidate tumor-suppressor genes is described. The system compares mRNA expression of genes from normal and tumor-derived human mammary epithelial cells grown in a special medium that supports similar growth rates of the two cell types. mRNAs uniquely expressed in normal cells are recovered as cDNAs after subtraction with mRNA from tumor cells. Seven different clones, from 0.6 to 4.8 kilobases in transcript size and including both rare and abundunt transcripts, were recovered in the first 23 clones analyzed. Among the isolated clones were genes encoding the gap-junction protein connexin 26, two different keratins, and glutathione-S-transferase pi, as well as an unknown gene in the S100 family of small calcium-binding proteins. In principle, tumor-suppressor genes include two classes: class I, in which loss of function results from mutation or deletion of DNA and class II, in which loss of function is from a regulatory block to expression. A class II suppressor gene is assumed to be regulated by a different suppressor gene that lost its function by mutation or deletion. Both classes of tumor-suppressor genes may provide valuable proteins with clinical applications in cancer diagnosis or therapy. Class II suppressors may be especially useful because the normal genes are present and their reexpression may be inducible by drugs or other treatments. 
3	Radical intracapsular removal of acoustic neurinomas. Long-term follow-up review of 11 patients. Historically, the neurosurgical treatment of large acoustic neurinomas has developed with two principal goals: complete tumor removal and preservation of facial nerve function. A recent goal for small tumors is the preservation of hearing. Out of a personal series of 124 acoustic neurinomas treated over the past 35 years, the senior author has undertaken a radical intracapsular approach in 12 patients with large tumors (greater than 3 cm in diameter). Surgical indications for intracapsular removal included advanced age (five cases), the patient's wish to avoid any risk of facial paralysis (six cases), contralateral facial palsy (one case), and contralateral deafness (one case). Eleven of these 12 patients were available for follow-up review. Tumor recurrence developed in two patients (18%) at 2 and 3 years postoperatively; there were no late recurrences. Four patients died of unrelated causes, 10 to 19 years after surgery. The remaining five patients have survived a mean of 12 years since surgery without recurrence (range 3 to 22 years). Facial function was preserved in nine patients (82%). The results suggest that radical intracapsular removal may be the procedure of choice under certain circumstances and may offer an alternative to focused high-energy radiation. 
1	Characterization of a factor-dependent acute leukemia cell line with translocation (3;3)(q21;q26). A strictly factor-dependent cell line (UCSD/AML1) was established from a patient with the syndrome of multilineage acute leukemia with high platelets. The patient's cells and the cell line karyotype were 45,XX,-7,t(3;3)(q21;q26), typical of the syndrome of acute leukemia with high platelets. The cell line expresses CD34, CD7, TdT, and myeloid (CD13, CD14, CD33) and megakaryocyte/platelet (CD36, CD41, CD42b, CDw49b) antigens. In short-term culture, UCSD/AML1 cells proliferate in response to interleukin-3 (IL-3), IL-4, IL-6, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage CSF (GM-CSF), but not IL-1, IL-2, IL-5, or G-CSF. In long-term culture, proliferation can be sustained by GM-CSF, IL-6, or M-CSF. When maintained in GM-CSF, a small percentage of cells form multinucleated megakaryocyte-like giant cells. Culture with GM-CSF combined with IL-6, but not with IL-6 alone, increased giant cell formation fourfold to sevenfold. IL-6 alone or in combination with GM-CSF increased expression of platelet-related antigens. In contrast, culture with phorbol ester induced formation of macrophage-like cells. UCSD/AML1 is the first human acute nonlymphocytic leukemia cell line established from a patient with an acute leukemia syndrome associated with a specific chromosome abnormality. 
5	Effects of glucose on hypoxic vasoconstriction in isolated ferret lungs. To characterize the effects of glucose on the pulmonary vascular response to anoxia and hypoxia, isolated ferret lungs were ventilated with 28% O2 and 5% CO2 and perfused at constant flow (100 ml.kg-1.min-1). Perfusate glucose concentrations were allowed to fall spontaneously to less than 1 mM (low glucose) or were controlled at 5-6 mM (normal glucose) or 12-17 mM (high glucose). At 60, 120, and 180 min of perfusion, the inspired O2 tension (PIO2) was reduced to 0, 10, or 30 Torr for 30 min, and vasomotor responses were quantified by continuous measurement of pulmonary arterial pressure. At PIO2 of 0 Torr, the response consisted of an early phase of transient intense vasoconstriction and a late phase of sustained slight vasoconstriction. High glucose markedly potentiated the magnitude of late-phase vasoconstriction with each successive anoxic exposure. This effect was not reproduced in normal glucose lungs and was not caused by a change in perfusate osmolarity, an action on blood cells, or an altered ability of pulmonary vascular smooth muscle to contract. At PIO2 of 10 Torr, high glucose not only potentiated late-phase vasoconstriction but also slowed the onset of early-phase vasoconstriction. At PIO2 of 30 Torr, high glucose had no effect on vasomotor responses, which were characterized by a slowly developing sustained vasoconstriction. Our results suggest that the vascular response of isolated ferret lungs to severe hypoxia consisted of separate early and late phases of vasoconstriction. This biphasic response may have resulted from two distinct vasoconstrictor mechanisms or from modulation of a single vasoconstrictor mechanism by a secondary vasodilator influence. 
3	Magnetic resonance imaging in neurological disorders. To investigate the role of magnetic resonance imaging (MRI) in neurological disorders, 115 children were studied in two groups. Group A (78 patients) was studied by paired computed tomography and MRI cranial scans. Group B (37 patients) was studied by paired computed tomography assisted myelography (CTM) and MRI spinal scans. In group A, the scans were generally equivalent for supratentorial tumours and for investigating fits, hydrocephalus, benign intracranial hypertension, and cerebral atrophies, but MRI scanning was superior for posterior fossa tumours and cysts. In group B, MRI scans were superior for intramedullary spinal tumours, spinal dysraphic problems with tethering or syrinx, and were complementary to CTM in diastematomyelia. 
1	Cancer in populations living near nuclear facilities. A survey of mortality nationwide and incidence in two states. Reports from the United Kingdom have described increases in leukemia and lymphoma among young persons living near certain nuclear installations. Because of concerns raised by these reports, a mortality survey was conducted in populations living near nuclear facilities in the United States. All facilities began service before 1982. Over 900,000 cancer deaths occurred from 1950 through 1984 in 107 counties with or near nuclear installations. Each study county was matched for comparison to three "control counties" in the same region. There were 1.8 million cancer deaths in the 292 control counties during the 35 years studied. Deaths due to leukemia or other cancers were not more frequent in the study counties than in the control counties. For childhood leukemia mortality, the relative risk comparing the study counties with their controls before plant start-up was 1.08, while after start-up it was 1.03. For leukemia mortality at all ages, the relative risks were 1.02 before start-up and 0.98 after. For counties in two states, cancer incidence data were also available. For one facility, the standardized registration ratio for childhood leukemia was increased significantly after start-up. However, the increase also antedated the operation of this facility. The study is limited by the correlational approach and the large size of the geographic areas (counties) used. It does not prove the absence of any effect. If, however, any excess cancer risk was present in US counties with nuclear facilities, it was too small to be detected with the methods employed. 
5	Buruli ulcer in Benin In a study of 28 patients with Mycobacterium ulcerans infection (Buruli ulcer) in Oinhi, Benin, it became clear that the disease can regress as well as progress, and that patients can have lesions of different stages simultaneously. A system of disease staging was introduced (I = subcutaneous nodule; II = cellulitis; III = ulceration; IV = scar formation). Research to find an effective treatment for this crippling disease is urgently needed. 
5	Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin. The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function. 
5	Transformation-associated alterations in interactions between pre-B cells and fibronectin. Marrow stromal elements produce as yet uncharacterized soluble growth factors that can stimulate the proliferation of murine pre-B cells, although close contact between these two cell types appears to ensure a better pre-B cell response. We have now shown that freshly isolated normal pre-B cells (ie, the B220+, surface mu- fraction of adult mouse bone marrow) adhere to fibronectin (FN) via an RGD cell-attachment site, as shown in a serum-free adherence assay, and they lose this functional ability on differentiation in vivo into B cells (ie, the B220+, surface mu+ fraction). Similarly, cells from an immortalized but stromal cell-dependent and nontumorigenic murine pre-B cell line originally derived from a Whitlock-Witte culture were also found to adhere to fibronectin (FN) via an RGD cell-attachment site. Moreover, in the presence of anti-FN receptor antibodies, the ability of this immortalized pre-B cell line to proliferate when co-cultured with a supportive stromal cell line (M2-10B4 cells) was markedly reduced (down to 30% of control). This suggests that pre-B cell attachment to FN on stromal cells may be an important component of the mechanism by which stromal cells stimulate normal pre-B cell proliferation and one that is no longer operative to control their more differentiated progeny. Two differently transformed pre-B cell lines, both of which are autocrine, stromal-independent, tumorigenic in vivo, and partially or completely differentiation-arrested at a very early stage of pre-B cell development, did not bind to FN. In addition, anti-FN receptor antibodies were much less effective in diminishing the ability of these tumorigenic pre-B cells to respond to M2-10B4 cell stimulation, which could still be demonstrated when the tumorigenic pre-B cells were co-cultured with M2-10B4 cells at a sufficiently low cell density. Analysis of cell surface molecules immunoprecipitated from both the nontumorigenic and tumorigenic pre-B cell lines by an anti-FN receptor antibody showed an increase in very late antigen (VLA) alpha chain(s) in both tumorigenic pre-B cell lines and a decrease in the beta 1 chain in one. Interestingly, all of the pre-B cell lines expressed similar amounts of messenger RNA for the beta 1 chain of the FN receptor. These results suggest that alteration of FN receptor expression on pre-B cells may represent a mechanism contributing to the outgrowth of leukemic pre-B cells with an autocrine phenotype and capable of stromal cell-independent, autonomous growth. 
2	Rectal examination in patients with pain in the right lower quadrant of the abdomen OBJECTIVE--To determine whether rectal examination provides any diagnostic information in patients admitted to hospital with pain in the right lower quadrant of the abdomen. DESIGN--Casualty officer or surgical registrar recorded symptoms and signs on admission on detailed forms. Final diagnosis was noted on discharge from hospital. SETTING--District general hospital. PATIENTS--1204 Consecutive patients admitted to hospital with pain in the right lower quadrant of the abdomen as their major complaint; 1028 had a rectal examination on admission. MAIN OUTCOME MEASURES--Odds ratio for each symptom and sign related to final diagnosis. Results of multiple logistic regression analysis for acute appendicitis. RESULTS--Right sided rectal tenderness, present in 309 of those examined, was more common in patients with acute appendicitis (odds ratio 1.34, p less than 0.05). This odds ratio was considerably less than that for other clinical signs--namely, tenderness in the right lower quadrant (odds ratio 5.09), rebound tenderness (3.34), guarding (3.07), and muscular rigidity in the abdomen (5.03). In the logistic regression analysis of patients with acute appendicitis, when allowance was made for the presence or absence of rebound tenderness, rectal tenderness on the right lost its significance. Six patients had masses palpable rectally, of which three were palpable on abdominal examination; the other three patients had acute appendicitis. No other unexpected diagnoses were established, and no useful additional diagnostic information was obtained by routine rectal examination. CONCLUSION--If patients presenting with pain in the right lower quadrant of the abdomen are tested for rebound tenderness then rectal examination does not give any further diagnostic information. 
1	Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy. 
5	Stress and sudden death. The case of the long QT syndrome. The idiopathic long QT syndrome (LQTS) represents a unique clinical example of stress-related sudden cardiac death. LQTS is characterized by the association of several distinctive electrocardiographic features, among which prolongation of the QT interval is the best known, with life-threatening arrhythmias that usually occur under conditions of physical or psychological stress. Effective therapies exist and are represented by antiadrenergic interventions; beta-adrenergic-blocking agents are the treatment of choice. When they fail, left cardiac sympathetic denervation has also proven to be very effective. The latter result suggests a role for alpha-adrenergic mechanisms in the arrhythmias of LQTS. The stressors more frequently associated with syncopal events in LQTS patients include fear, exercise fraught with emotions, swimming, and awakening because of a loud noise. Experimentally, life threatening arrhythmias have been induced during a highly emotional situation in conscious cats with normal hearts in which right stellate ganglia have been ablated, resulting in QT interval prolongation. This selective denervation creates a sympathetic imbalance of the type proposed by one of the pathogenetic hypotheses for LQTS. 
3	Cosmetic, functional, independent: self-help aids. Self-help orthotics have been developed to assist functional activities for high-level spinal cord injured patients. The goal of rehabilitation has been to do this with as little intrusion on independence and cosmesis as possible. This paper describes devices to help a patient with C6 quadriplegia independently place his own utensils and eat with an almost normal appearance. The new self-help aids are made from standard silverware, a rivet, and two one-eighth-inch Kydex loops. The loops are riveted centrally on the utensil, allowing for free rotation. The device was evaluated on a patient with C6, complete quadriplegia. The subject demonstrated independence in donning and doffing the device and in eating with an almost normal appearance. 
3	Pupillary and electroretinographic abnormalities in a family with neuronal intranuclear hyaline inclusion disease. Abnormal pupillary function and a severely depressed electroretinogram were found in four members of a family with neuronal intranuclear hyaline inclusion disease, an idiopathic degenerative disorder that involves the central and peripheral nervous systems. Symptoms were limited to the gastrointestinal system and consisted principally of abdominal pain, constipation, and severe weight loss. The discovery of light-fixed pupils in the propositus led to the first antemortem diagnosis by rectal biopsy in two generations of this family. Abnormalities of gastrointestinal motility and pupillary reactions constituted the only objective evidence of autonomic dysfunction; the abnormal electroretinogram was the only evidence of central nervous system dysfunction. 
1	Oxygen-exacerbated bleomycin pulmonary toxicity Bleomycin is an antineoplastic agent with potential for producing pulmonary toxicity, attributed in part to its free radical-promoting ability. Clinical and research experiences have suggested that the risk of bleomycin-induced pulmonary injury is increased with the administration of oxygen. We report a case in which the intraoperative administration of oxygen in the setting of previous bleomycin therapy contributed to postoperative ventilatory failure. Our patient recovered with corticosteroid therapy. Physician awareness of a potential interaction between oxygen and bleomycin may help reduce the morbidity and mortality related to bleomycin therapy. 
5	Severe preeclampsia presenting as dysphonia secondary to uvular edema. A case report. In addition to hypertension and proteinuria, generalized edema is seen commonly in women with severe preeclampsia. A patient presented to us at term with the complaint of dysphonia. Upon examination she appeared to be clearly preeclamptic and had a grossly edemetous uvula, which we think occurred secondary to generalized edema. This case might be the first reported one of preeclampsia presenting as dysphonia and of uvular edema in association with preeclampsia. 
5	Isotonic high-sodium oral rehydration solution for increasing sodium absorption in patients with short-bowel syndrome. We compared the effect of a standard oral rehydration solution and a high-sodium polymeric-glucose solution on sodium absorption in short-bowel syndrome. Six patients with high jejunostomy were tested in a random order with the standard solution or a solution containing maltodextrins (18 g Glucidex 12/L) enriched with 2.5 g NaCl/L. Solutions were administered via a nasogastric tube at a rate of 2 mL/min. Jejunal effluent was collected during an 8-h period. The net 8-h fluid absorption was not significantly different in the two periods. Glucose absorption was greater than 90% of the administered amount for both solutions. Net sodium absorption was greater for the maltodextrin solution than for the standard solution (56 +/- 12 vs 24 +/- 20 mmol, P less than 0.05). We conclude that replacement of glucose with maltodextrins and addition of sodium in the standard oral rehydration solution results in improved sodium absorption in short-bowel syndrome. 
5	Acute hypercalcemic crisis after an open heart operation. Acute hyperparathyroidism developed in a previously normocalcemic 64-year-old woman during the first week after a coronary operation. Prolonged QT interval in the electrocardiogram and hypercalcemia were documented on the fourth postoperative day. Neck exploration on the fifth postoperative day revealed a lower right parathyroid adenoma. Parathyroidectomy resulted in rapid and dramatic improvement of the clinical picture and normalization of laboratory values. 
3	Transient entrapment neuropathy of the posterior interosseous nerve in violin players. Eleven white male right handed violin players complained of transient muscular deficit of the extensor compartment of the left forearm during and after prolonged playing. This was associated with paraesthesiae and pain. Relief was achieved keeping the wrist and the elbow flexed, with the supinated forearm held by the contralateral hand. An anatomical study showed changes of the relationship of the posterior interosseous nerve with its surrounding structures with pronation and supination of the forearm. On the basis of the clinical features, the anatomical studies and the response to a simple physiotherapeutic regime, it is suggested that prolonged pronation of the forearm may cause transient entrapment of the nerve. 
1	Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla. We present a rare case of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the left maxilla that developed in a 63-year-old Japanese man. The tumor recurred repeatedly despite multiple surgical removals, radiotherapy, and chemotherapy and led to progressive cachexia; the patient died after 3.8 years of hospitalization. Histopathologic examination revealed that the recurrent tumor was carcinosarcoma, which had progressed from malignant ameloblastoma with fibroma. An autopsy confirmed the diagnosis of malignant mixed tumor with lung metastasis of malignant ameloblastoma and fibrosarcoma. 
5	Stroke in pediatric acquired immunodeficiency syndrome. In a 4 1/2-year period, 4 of 68 children in a longitudinal study of neurological complications of human immunodeficiency virus (HIV) infection had clinical and/or neuroradiological evidence of stroke, yielding a clinical incidence of stroke in this population of 1.3% per year. During this period, 32 subjects died, and permission for autopsy was granted in 18 of the patients, including 3 of 4 who had clinical evidence of stroke. The prevalence of cerebrovascular pathological features in our consecutive autopsy series was higher than the clinical incidence. At autopsy cerebrovascular disease was documented in 6 (24%) of 25 children with HIV infection, including all 3 children who had clinical evidence of stroke. Four patients had intracerebral hemorrhages, 6 patients had nonhemorrhagic infarcts, and 3 had both. Hemorrhage was catastrophic in 1 child and clinically silent in 3 children, all of whom had immune thrombocytopenia. One child had an arteriopathy that affected meningocerebral arteries. In another child, the arteries of the circle of Willis were aneurysmally dilated. Two children had coexisting cardiomyopathy and subacute necrotizing encephalomyelopathy with vascular proliferation. These results suggest that stroke should be considered when children with HIV infection develop focal neurological signs. 
4	Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats. It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the interleukin-2-treated group over an additional 38 days. Mean arterial pressure (+/- SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5 +/- 3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 170.3 +/- 3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukin-2-dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats. 
2	Immune complexes in the choroid plexus in liver cirrhosis. A histopathologic and immunofluorescence study of the choroid plexus was performed in 12 cases of liver cirrhosis (cirrhosis group) and in 20 patients who died of diseases with no evidence of liver or brain involvement, and in which renal disease and alcoholism were also excluded (control group). IgA, IgG, IgM, C3, and C1q were investigated by direct immunofluorescence technique. Positive immunofluorescence in the choroid plexus was found in 83.33% of the cirrhosis group. IgA and IgG were the immunoglobulins more frequently found. C3 was also commonly found. Histologic examination of the choroid plexus showed changes in 66.67% of the cirrhosis group characterized, mainly, by subepithelial deposition of a homogeneous, acidophilic, and periodic acid-Schiff-positive substance, with thickening of the epithelial basement membrane. In the control group, the immunofluorescence in the choroid plexus was negative in all cases and only two cases (10%) presented histopathologic changes of the choroid plexus with a pattern similar to that of the cirrhosis group. 
1	Brush cytology in the diagnosis of colonic neoplasms. During a three-year period (1986-1988), 234 colonic brush specimens were received in the authors' laboratory. Nine samples (4%) were deemed unsatisfactory for evaluation because of inadequate cellularity and/or poor fixation. In 11 cases concomitant or follow-up histologic specimens were not available. The remaining 214 specimens included 82 malignant neoplasms, 88 neoplastic polyps (adenomas), and 44 nonneoplastic lesions. Sixty-seven (82%) of malignant neoplasms were correctly diagnosed by brush cytology. Three cases of adenoma with severe dysplasia or in situ carcinoma were diagnosed as adenocarcinoma by cytology. No false-positive diagnoses were made of nonneoplastic lesions. Brush cytology was found to be a more sensitive technique in the diagnosis of colon cancer than endoscopic biopsy (82% and 74% sensitivity, respectively). The combination of the two techniques increased the sensitivity to 90% and improved the overall accuracy of the test. Seventy-one (82%) of the colonic adenomas were correctly diagnosed by cytology. Brush cytology is a convenient, safe, and accurate technique which should be used concurrently with endoscopic biopsy or polypectomy. 
1	Expression of intercellular adhesion molecule-1 (CD54) on hematopoietic progenitors. The distribution of intercellular adhesion molecule-1 (ICAM-1), a ligand for lymphocyte function antigen-1, on hematopoietic tissue was determined using the anti-ICAM-1 monoclonal antibody CL203.4 with flow cytometry and short-term semi-solid hematopoietic progenitor cultures. After timed incubation in media with fetal bovine serum, 29% of erythroid burst-forming units (BFU-E), 24% of erythroid colony-forming units (CFU-E), and 52% of granulocyte-macrophage colony-forming units (CFU-GM) bone marrow progenitors expressed ICAM-1. This finding, which is consistent with the detection of ICAM-1 on acute non-lymphoblastic leukemic blasts, is at variance with recent reports. ICAM-1 was also detected on bone marrow blasts, proerythroblasts, promyelocytes, and cells of monocyte/macrophage lineage, but was not detected on erythroblasts, normoblasts, neutrophilic myelocytes, metamyelocytes, bands, or on most lymphocytes. These results indicate that maturation of cells of the erythroid and myeloid lineage is associated with loss of ICAM-1. The distribution of ICAM-1 on bone marrow progenitors, early precursor cells, and accessory cells in conjunction with the function of this molecule in cell-cell interactions suggests that ICAM-1 may play a role in the cell-cell and cell-stromal interactions that regulate hematopoiesis. 
1	Characterization and histopathological correlation of cytosol proteins of benign and malignant breast tumors. Significant differences in cytosol protein level exist between normal/benign and cancerous breast tissues. There is a positive correlation between the cytosol protein level and histological grade of carcinoma. Well-differentiated carcinoma have a lower value of cytosol protein than poorly differentiated carcinoma. In slab gel electrophoregrams, the total numbers of bands are almost identical in normal, benign, and malignant conditions. In addition, 37 Kd protein band is consistently present in malignant cases and always absent in normal or benign cases. More extensive biophysical examination of this band may provide further insight into the protein alterations in cancer cells at the molecular level. 
5	Effective endothelialization of polyurethane surfaces. Response to shear stress and platelet adhesion. Biomer and Mitrathane are thromboresistant polyurethane ureas that are suitable for coating artificial valves. Degeneration of the surface coatings, however, does occur over time, and in experimental animal studies adherent thrombi have been observed as a complication. In this study, morphometric techniques applied to scanning electron microscopy were used to assess whether vascular endothelial cells harvested from jugular veins of fetal lambs could be grown to confluence on these polyurethane surfaces, whether the monolayer would remain intact under conditions of shear stress (104 dynes/cm2), and whether this would result in decreased platelet adherence of sheep platelets relative to nonendothelialized surfaces. The results have shown that both Biomer and Mitrathane could be endothelialized: 88.8 +/- 5.1% of the Biomer surface consisted of intact confluent endothelial cells, as did 95.45 +/- 1.7% of the Mitrathane surface. After 6 hr of shear stress, a significant reduction in this feature was observed (p = 0.02), but both materials still maintained a high percentage of confluent endothelial cells (78.65% for Biomer and 85.58% for Mitrathane). After 48 hr of shear stress, however, the percent confluence was similar to control values, which suggested new cell growth. Endothelialized Biomer compared with Mitrathane had fewer adherent single platelets, or small or large aggregates (p = 0.001, p = 0.01, and p = 0.05, respectively); this feature was not affected by shear stress. Whereas endothelialization of the surface clearly decreased platelet adherence on Mitrathane (p = 0.01), only a trend was seen with Biomer. These studies therefore show that endothelialization of these polyurethane surfaces is feasible. 
5	Spontaneous pneumothorax in AIDS patients with recurrent Pneumocystis carinii pneumonia despite aerosolized pentamidine prophylaxis. Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS) may predispose these patients to recurrent apical Pneumocystis infection. Bullous changes and pulmonary cysts develop in the lung apices due to repeated episodes of inflammation and cytotoxic effects of HIV on pulmonary macrophages. These changes progress despite prophylaxis against recurrent Pneumocystis infection with aerosolized pentamidine, increasing the risk of spontaneous pneumothorax. Two cases are presented of bilateral pneumothoraces in patients with AIDS and recurrent P carinii pneumonia despite aerosolized pentamidine prophylaxis. Patients receiving aerosolized pentamidine prophylaxis for Pneumocystis pneumonia appear to have an increased risk of pneumothorax due to recurrent apical infections with P carinii. 
1	Endoscopic placement of a Foley catheter across a stricture and rectovaginal fistula to perform a barium enema. Evaluation of enteric fistulas is often best performed with barium contrast studies. Clinical situations that preclude the satisfactory installation of barium decrease the yield of the study. A case is presented of a 59-yr-old female with stage III-B cervical carcinoma and a known rectovaginal fistula with an adjacent sigmoid colon stricture. An additional more proximal, enteric fistula was suspected. Definitive preoperative knowledge of the existence or absence of this fistula would have shortened the duration of a planned palliative intervention. The rectovaginal fistula and stricture precluded adequate barium and air installation for contrast study. Colonoscopy was unsuccessful. We have developed a combined technique in which the endoscopic placement of a semirigid guidewire allowed placement of a Foley catheter across the fistula and stricture. Successful barium study was performed. Intraoperative time and hospital stay were shortened. 
1	Differential diagnosis of sclerosing cholangiocarcinomas of the common hepatic duct (Klatskin tumors). Although it is recognized that some other lesion may be the cause, a presumptive diagnosis of Klatskin tumor is usually made when a focal stenotic lesion of the common hepatic duct is seen on a cholangiogram of a jaundiced patient. Biopsy is so often nondiagnostic that decisions about therapy are usually made on the basis of the imaging tests and lack of evidence for some other disease. Because the accuracy and consequences of this strategy have never been tested, we contrasted the preoperative diagnosis of Klatskin tumor with the final diagnosis in 98 consecutive patients treated from 1985 to 1990. Preoperative investigations included ultrasound and computed tomographic scans, percutaneous transhepatic cholangiography, endoscopic retrograde cholangiopancreatography, and angiography. Sclerosing cholangiocarcinomas of the bile duct were correctly diagnosed in 68 cases. The final diagnosis was other than a sclerosing adenocarcinoma in 30 (31%) cases. There were 5 papillary bile duct carcinomas, 12 gallbladder carcinomas invading the bile duct, 5 metastatic tumors to the bile duct, 2 cases of Mirizzi syndrome, 3 granulomas, and 3 cases of idiopathic benign focal stenosis. Patients with papillary adenocarcinomas had an extensive filling defect of the duct, which was often thought to be unresectable. However, four of these five lesions could be completely excised, and the tumor was confined to the duct wall in all four. The outcome of surgical treatment of the other eight patients with benign lesions was good in most cases. These findings demonstrate the pitfalls of assuming that a focal stenosis of the hepatic duct represents a sclerosing adenocarcinoma. The diagnosis is much less specific than is generally thought, so there is considerable opportunity for mismanaging such patients. 
5	Comparison of ambulatory left ventricular ejection fraction and blood pressure in systemic hypertension in patients with and without increased left ventricular mass. To evaluate the effects of long-standing systemic hypertension on left ventricular (LV) function during daily activities, ambulatory radionuclide monitoring of LV ejection fraction (EF) and blood pressure was performed during exercise and other structured activities in 31 hypertensive patients. Patients were divided into 3 groups based on the absence of LV hypertrophy (group 1 [n = 16], LV mass 107 +/- 12 g/m2), presence of LV hypertrophy without electrocardiographic changes (group 2 [n = 10], LV mass 141 +/- 8 g/m2) and LV hypertrophy with associated electrocardiographic changes (group 3 [n = 5], LV mass 158 +/- 9 g/m2). The groups were similar with respect to age, baseline medication, treated and untreated blood pressure, resting EF and treadmill exercise time. Patients in group 3 had the longest history of hypertension. Peak filling rate was normal in group 1 (2.9 +/- 0.4 end-diastolic volume/s), but reduced at rest in groups 2 (2.4 +/- 0.4) and 3 (2.1 +/- 0.3). Patients in group 1 had normal EF responses to exercise and mental stress testing, as well as during routine ambulatory activities. Patients in group 2 had a blunted EF response to exercise, and those in group 3 had a significantly abnormal response. Both group 2 and 3 patients demonstrated abnormal EF responses to mental stress, as well as cold pressor testing in association with significant increases in mean arterial pressure and marked reduction in diastolic filling rate. Decreases in EF were also observed during routine patient monitoring in 3 group 3 patients and 4 group 2 patients. These events were associated with significantly increased blood pressure. 
3	Paraplegia after a routine lumbar laminectomy: report of a rare complication and successful management. Arachnoid cysts of the spinal canal are relatively common lesions that may be either intra- or extradural. These cysts are usually asymptomatic but may produce symptoms by compressing the spinal cord or nerve roots. We report a case in which an intradural thoracic arachnoid cyst became symptomatic after a routine decompressive lumbar laminectomy for spinal stenosis. Myelography revealed no abnormality, although magnetic resonance imaging and computed tomography after myelography demonstrated a mass within the posterior aspect of the thoracic spinal canal associated with anterior displacement and compression of the spinal cord. A change in the flow dynamics of the cerebrospinal fluid probably allowed the development of spinal cord compression due to one of the following: expansion of the cyst, decreased cerebrospinal fluid buffer between the cord and the cyst, or epidural venous engorgement. A concomitant and more cephalad lesion such as an arachnoid cyst should be considered when myelopathic complications arise after lumbar surgery. Magnetic resonance imaging and computed tomography after myelography are useful to demonstrate the additional pathological processes. 
5	Methodological problems in evaluation of cardiovascular effects of stress in humans. Cardiovascular effects of stress in humans are often assessed by application of physical or emotional stimuli in a laboratory environment. Although this method provides important information, these procedures have several limitations. First, blood pressure and heart rate responses to laboratory stressors are characterized by a limited within-subject reproducibility. Second, there is poor correlation between blood pressure and heart rate responses to different stressors, which implies that individual reaction to stress may be estimated differently according to the test used. Finally, these responses bear only a limited relation to 24-hour or daytime blood pressure variability, that is, they reflect to only a limited extent the tendency of blood pressure to vary during daily activities. If assessed by techniques that allow blood pressure to be continuously recorded for 24 hours in ambulatory subjects, blood pressure variability represents a possible approach to observation of cardiovascular reactivity away from an artificial laboratory environment. However, whether blood pressure variability should be expressed as a percentage or in absolute values is controversial. Furthermore, although naturally occurring stress may markedly increase blood pressure, 24-hour blood pressure variations also depend on factors that are not related to emotional stimuli. Thus, the study of cardiovascular responses to stress in humans encounters several problems, regardless of the method used. 
2	Pleuropulmonary manifestations of hepatic amebiasis Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess. 
5	Penile implants in the treatment of Peyronie's disease. The treatment of Peyronie's disease remains controversial. Patients who fail conservative therapy may require surgical intervention to restore the ability to have sexual intercourse. Plaque excision and dermal grafting have not been universally successful, and alternate procedures that rely on the placement of a penile prosthesis have gained in popularity. We reviewed our experience with 35 patients with advanced Peyronie's disease treated with a penile prosthesis. Preoperatively, 55% of the patients were unable to engage in intercourse due to pain or angulation of the penis and 25% were unable to achieve any erection at all. Postoperatively, with a mean followup of 6.9 years, 88% of the patients were able to engage in intercourse and were satisfied with the results obtained. In selected patients with advanced disease the implantation of a penile prosthesis remains a highly successful and satisfying alternative for the treatment of Peyronie's disease. 
4	Long-term amiodarone administration protects against global myocardial ischemia. Reports on the effects of amiodarone on cardiac function have been variable. This study addresses the effect of long-term amiodarone administration on recovery of cardiac function after a period of global ischemia. Normotensive and spontaneously hypertensive rats were used. Normotensive rats (n = 6) received 240 mg/kg amiodarone for 4 weeks, for a total of 72 +/- 3 mg. Hypertensive rats (n = 6) received 500 mg/kg amiodarone for 4 weeks, for a total of 116 +/- 5 mg. Final myocardial concentrations of amiodarone and desethylamiodarone were 1.85 +/- 1.75 and 0.50 +/- 0.61 micrograms/g wet weight for the normotensive rats and 1.30 +/- 0.58 and 0.31 +/- 0.17 micrograms/g for the hypertensive rats (p = nonsignificant). Equal numbers of controls received sterile saline solution for 4 weeks. The hearts were excised and perfused in a Langendorff apparatus. The results indicate that, after 15 minutes of normothermic ischemia, hearts treated with this relatively low dose of amiodarone recovered a greater percentage of preischemic work (97% +/- 13%) as compared with the controls (76% +/- 17%) (p less than 0.005). 
5	MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration. This study reports on the specific expression of the MIC2 gene, a pseudoautosomal gene located on the short arms of the X and Y chromosomes, on Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET) cells. The gene product, a cell membrane protein, is recognized by the newly established monoclonal antibody (MoAb) HBA-71 and the previously described MoAb 12E7 and RFB-1. Furthermore, the reaction pattern of the MIC2 antibodies, especially HBA-71, with normal tissues and a great number of benign and malignant tumors (70 different tumors, 199 tumor samples), as well as the correlation between the specific chromosomal aberrations, i.e., the t(11;22) and the del(22) and the expression of this antigen, are demonstrated. Both ES and pPNET cells express the MIC2 gene in very high amounts, which represents a highly selective and almost unique feature of these cells, making an assignment of these tumors in one entity even more likely. The MIC2 antibodies are of great value for clinical and research purposes. 
1	Mammography and age: are we targeting the wrong women? A community survey of women and physicians. To determine mammography use among women with a broad range of ages, the authors surveyed women aged 30 to 74 years and physicians practicing primary care in two eastern North Carolina counties. Twenty-five percent of women in their 30s had ever had a mammogram, and 34% intended to have one in the coming year. From 45% to 52% of women in their 40s, 50s, and 60s had ever had a mammogram, and 55% to 57% intended to have one in the next year. Thirty-seven percent of women aged 70 to 74 years had ever had a mammogram, and 40% intended to have one in the following year. Nineteen percent of physicians reported screening nearly all women aged 30 to 39 years, and 14% screened few women aged 50 to 74 years. Younger women were more worried about breast cancer than older women and assessed their risk as higher, attitudes that were generally associated with higher mammography utilization. These community surveys suggest that mammography use may be excessive among younger women; older women continue to be underscreened. 
1	Subpleural mononuclear cell infiltration. Significance in the differential diagnosis of pleuritis showing nonspecific histologic findings. To determine if patients who had lymphocyte-rich pleural effusion and a pleural biopsy without any specific findings could be histopathologically differentiated between those with tuberculous and nontuberculous pleuritis, we histologically re-evaluated the pleural biopsies of all patients whose pleural effusion was predominant with lymphocytes and contained no malignant cells. A total of 40 patients with a nonspecific histologic findings of pleural biopsy specimen were categorized based on their ultimate diagnosis as having tuberculous (n = 15), carcinomatous (n = 10) or nontuberculous, benign pleuritis (n = 15). The pleural biopsy specimen of patients with nontuberculous, benign pleuritis frequently showed a band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate (10 out of 15 patients), while the same finding was infrequent in those with tuberculous pleuritis (0 out of 15, p = 0.0001) and pleuritis associated with carcinoma (three out of 10, p = 0.082). Based on these results, the presence of band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate in pleural biopsy specimens of patients with lymphocyte-rich pleural effusion suggests that the pleuritis is nontuberculous in its nature. 
5	Lung lobe torsion following lobectomy. Three cases of postoperative pulmonary lobe torsion were reported. Two of three showed hemorrhagic infarctions, and as a result underwent rethoracotomies and removal of the affected lobes. From these experiences, we consider that computed tomography (CT) and bronchofiberscopic examinations are useful for the diagnosis of advanced torsion. 
3	Lymphocytic hypophysitis with involvement of the cavernous sinus and hypothalamus. Two cases of lymphocytic hypophysitis are reported, in which hypothalamic involvement causing diabetes insipidus was a prominent clinical feature. In one case, a man had clinical and radiological evidence of the involvement of the cavernous sinus. This represents the second reported case of a man with lymphocytic hypophysitis. A transsphenoidal biopsy established the diagnosis in both cases. Neither the involvement of the cavernous sinus nor permanent diabetes insipidus has been reported previously. A review of the literature is provided. 
3	Headaches and multiple sclerosis: a clinical study and review of the literature. Whether multiple sclerosis (MS) can cause headaches is controversial. To clarify the association between headaches and MS we prospectively analyzed 104 consecutive MS patients using detailed headache evaluations. Fifty-four patients (52%) reported headaches, compared with 5 of 35 (14%) patients initially suspected to have MS but subsequently proven to have other disorders, and 18 of 100 (18%) matched general neurology patients. The MS patients had tension headaches or vascular headaches of the migraine type; there was no distinctive "MS headache." Seven of these patients had headaches with their first MS symptoms, but in only one did headaches recur with disease activity. Headaches did not correlate with any clinical features of MS. We conclude that an association between headaches and MS may exist. 
5	Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days. The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients (P less than .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance. 
4	Edgar J Poth lecture. Pathogenesis, diagnosis, and treatment of thrombosis. Thrombosis and its major sequela, embolism, continue to contribute significantly to morbidity and mortality, both as primary disorders and as complications of other systemic systems. The understanding of the etiology of thromboembolism and the role of platelets, endothelium, and the plasma proteins in the development of thrombotic disorders has recently improved. Other blood cells, in particular neutrophils, have been suggested as possible mediators of thrombosis in clinical disorders characterized by decreased capillary blood flow. Newer imaging techniques such as duplex scanning have improved the accuracy and ease of diagnosis. Thrombolytic therapy is a more physiologic approach to the management of thrombosis, but its role is limited by systemic fibrinolysis. The development of fibrin-specific agents and better delivery techniques in combination with thromboembolectomy and anticoagulation should improve the management of patients with thrombosis. 
1	A phase II multi-institutional trial of low-dose N-(phosphonacetyl)-L-aspartate and high-dose 5-fluorouracil as a short-term infusion in the treatment of adenocarcinoma of the pancreas. A Southwest Oncology Group study. Adenocarcinoma of the pancreas is a highly lethal malignancy and chemotherapy has had little impact on the natural history of this disease. PALA, used to potentiate 5-fluorouracil (5-FU), has been shown to have synergy in vivo and in vitro. Twenty-seven patients were treated with an intravenous push dose of PALA (250 mg/m2) followed 24 hours later with a 24-hour infusion of 5-FU (2600 mg/m2). This regimen was repeated weekly. There was one partial response of 21 eligible patients with an estimated response rate of 5%. Toxicity was severe with one toxic death and four patients experiencing Grade 4 toxicity. 5-Fluorouracil and PALA, given in the schedule described, do not appear to be effective against adenocarcinoma of the pancreas. 
1	A clinical triad to diagnose paraneoplastic retinopathy. Two elderly men developed photosensitivity and light-induced glare, transient visual symptoms, and progressive visual loss several months before small cell carcinoma of the lung was discovered. Both patients had impaired visual acuity and color vision, ring scotomas, and attenuated retinal arteriole caliber. Electroretinography demonstrated abnormal cone and rod-mediated responses. Antiretinal antibodies were identified in their serum. Their visual sensory function improved following therapy with immunosuppressive agents. The triad of photosensitivity, ring scotomatous visual field loss, and attenuated retinal arteriole caliber should alert one to a paraneoplastic disorder affecting the retina. 
4	Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial. Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage. 
1	Vitreous changes and macular edema in central retinal vein occlusion. The condition of the posterior vitreous was determined in 56 eyes with central retinal vein occlusion (CRVO). Using a life-table analysis, it was studied in 56 eyes. The incidence of posterior vitreous detachment (PVD) in the CRVO eyes at the first vitreous examination did not differ significantly from that in 64 age-matched control eyes. However, the incidence of PVD in CRVO eyes increased from 39.3% at the first vitreous examination to 58.5% after 6 months, and to 69.6% 1 year from the examination. The incidence of PVD in CRVO eyes during follow-up was statistically higher than that of the controls (P = .009). The incidence of PVD after the first vitreous examination was significantly higher in eyes with hemorrhagic retinopathy than in eyes with venous stasis retinopathy (P = .04). In the 34 eyes with macular edema, the edema lasted significantly longer in those with vitreomacular attachment (VMA) at the first examination than in those without VMA at this time (P = .02). VMA may play an important role in the pathogenesis and chronicity of macular edema in CRVO. 
4	Use of computed tomographic scanning and aortography in the diagnosis of acute dissection of the thoracic aorta. Before the introduction of computed tomographic (CT) scanning, aortography was the investigation of choice for acute aortic dissection. Between 1978 and 1982, 24 patients were referred to the Brompton Hospital with suspected acute thoracic aortic dissection; all had aortography with diagnosis confirmed at surgery (n = 12) or necropsy (n = 2) or supported by clinical outcome (n = 8). One patient in whom aortography was negative had type B dissection at necropsy and another patient was lost to follow up. CT scanning became available in this unit in 1983 and between 1983 and 1987 was used as the only imaging investigation in 32 patients with suspected acute dissection of the thoracic aorta while in a further 22 patients aortography was used alone. Results were confirmed at surgery (n = 18), necropsy (n = 3), or supported by clinical outcome (n = 31). Two patients were lost to follow up. In an additional 16 patients both aortography and CT scanning were performed with concordant findings in 10. In six in whom the results were discordant, aortography was normal in three in whom subsequent CT scanning showed type B dissection and CT scanning was normal in three patients in whom aortography showed type A dissection. Both CT scanning and aortography are reliable techniques for assessment of suspected acute dissection of the thoracic aorta. Both techniques misdiagnose occasionally and the frequency of misdiagnosis will be minimised by performing both investigations in patients where the level of clinical suspicion is high and the initial investigation negative. CT scanning tends to miss type A dissection and in view of the success of surgery in this condition this failing has the more serious clinical consequences. 
3	Stroke after heavy marijuana smoking. I examined two young men who developed cerebral infarction associated with heavy marijuana smoking. Both were light tobacco smokers, but they did not drink alcohol or use other street drugs. Diagnostic work-up for nonatherosclerotic causes of stroke was unremarkable. I postulate that marijuana-associated alterations in systemic blood pressure resulted in vasospasm, leading to strokes in these patients. 
5	Signs, complications, and platelet aggregation in familial exudative vitreoretinopathy. Between 1979 and 1989, I examined 106 patients (16 pedigrees) with signs of familial exudative vitreoretinopathy. Of these patients, 101 had familial exudative vitreoretinopathy, and five had a sporadic manifestation. The complications of familial exudative vitreoretinopathy, deformation of the posterior retina, vitreous hemorrhage, amblyopia, and retinal detachment, caused diminished visual acuity. Of 170 eyes, retinal neovascularization was observed in 18 eyes (11%), and retinal exudates were observed in 16 eyes (9%). Several forms of retinal detachment occurred in 37 of 180 eyes (21%), which often took an unfavorable course. A falciform retinal fold was observed in 14 eyes (8%). Retinal surgery was performed in 14 eyes; reattachment of the retina was successful in only seven eyes. Platelet aggregation studies disclosed no significant differences between seven patients with familial exudative vitreoretinopathy and ten control subjects. The pathogenesis of the disease is based on a premature arrest of the vascular development of the retina. 
1	Patient-controlled analgesic administration. A comparison of steady-state morphine infusions with bolus doses. The authors have shown previously that bone marrow transplant (BMT) patients who self-administered bolus doses of morphine gained equal oral mucositis pain relief while using less drug compared with similar patients receiving morphine by staff-controlled continuous infusion. In a follow-up study they compared the efficacy and side effects of morphine in two groups of marrow transplant patients who controlled their own analgesic administration either by conventional bolus-dose, patient-controlled analgesia (PCA) or by adjusting the rate of continuous morphine infusion to increase or decrease their plasma morphine concentration. Patients controlling their morphine infusion rates (pharmacokinetically based patient-controlled analgesia [PKPCA] group) obtained more relief from oral mucositis pain than did patients using conventional PCA. Patients in the PKPCA group used more morphine than PCA patients and achieved superior pain relief without significant increases in side effects (e.g., nausea, mood changes, sedation). The authors conclude that PKPCA improves the management of prolonged, severe pain in marrow transplant patients and that this approach to patient-controlled analgesia may be useful in other types of persistent pain. 
1	Prospective, randomized trial of palliative treatment for unresectable cancer of the esophagus. To evaluate the best method of palliation for obstructing nonresectable squamous cell carcinoma of the mid or distal esophagus, 27 patients were prospectively randomized to one of three treatment arms: (1) esophageal intubation with an Atkinson tube (AT, 10 patients), (2) esophageal intubation followed by radiation therapy (AT/RT, 8 patients), and (3) endoscopic laser therapy followed by irradiation (L/RT, 9 patients). Pretreatment characteristics were similar in the three groups. There was no procedure-related mortality. There were eight total complications related to the tube and none related to laser treatment (p = 0.02). Mean survival was 119 days in the AT group, 72 days in the AT/RT group, and 169 days in the L/RT arm (p = not significant). Quality of survival was most dependent on swallowing ability, and the swallowing score increased by 2.3 units in the AT group, 1.8 units in the AT/RT group, and 1.4 units in the L/RT group (p = not significant). Adding RT to laser therapy significantly increased time in treatment (mean, 38.7 days) when compared with the AT group (mean, 12.5 days) (p less than 0.001). However, only 1 patient required repeat laser ablation. It is concluded that AT and L/RT result in good palliation as measured by relief of dysphagia and survival time. However, morbidity of AT is significantly greater than that of L/RT. Laser and radiation therapy with a reduced total dosage of RT or with a change in fractionation schedule to limit treatment time is the preferred method of palliation. 
3	Spinal cord injuries. Clinical, functional, and emotional status. Ninety-eight patients with traumatic spinal cord injury, at a median age of 33.5 years (range, 16-72 years), with nonremarkable distributions of neurologic characteristics were investigated at a median of 2.3 years (range, 0.1-23 years) after injury. Functioning, mood disturbances, and overall quality of life were recorded with established self-assessment instruments. Physical dysfunction levels were moderate, being proportionate to neurologic impairment. Psychosocial functions, mood states, and quality-of-life perceptions did not differ from those of a control population sample. Psychosocial function and mood disturbances varied greatly during the first 4 years after injury, but patients' later recordings expressed predominantly a balanced emotional state and a rewarding social life. Progress in this direction consisted of clearly lessened physical dysfunction 1 year after injury and better psychosocial function and well-being after 2 years, whereas patterns of social activities and contacts became gradually less inhibited during a 4-year period after injury. Analysis of complications in patients' histories that affected function and mood showed severe pain to be the only complication that related to lower quality-of-life scores. Urinary incontinence and infection and autonomous dysreflexia related to inhibited self-care performance; spasticity related to impaired ambulation and feeding skills. Gainful employment was the only demographic factor linked to high quality-of-life scores. 
1	Hyperandrogenism in peripubertal girls. Androgens arise from either adrenal or ovarian secretion or by peripheral conversion of secreted precursors. The adrenals and ovaries normally contribute about equally to testosterone and AD production. DHAS is the major adrenal 17-KS. Testosterone is the major circulating form of androgen. More than 96% of plasma testosterone is bound to SHBG; the free testosterone seems to be the bioavailable fraction. Hyperandrogenism must be considered in any girl with premature or excessive development of public hair or acne, menstrual irregularity (whether it be oligo-amenorrhea or dysfunctional uterine bleeding), or obesity. The most common cause of premature public hair development (pubarche) is premature adrenarche. The most common cause of hyperandrogenism presenting in a teenage girl is polycystic ovary syndrome. However, the differential diagnosis includes "exaggerated adrenarche," late-onset congenital adrenal hyperplasia, virilizing tumors, Cushing's syndrome, hyperprolactinemia, acromegaly, and abnormalities of androgen action or of metabolism. The plasma free testosterone is a more sensitive indicator of hyperandrogenism than is the total testosterone concentration. The pattern of response of plasma free testosterone, DHAS, and cortisol to dex-suppression testing is diagnostic of the source of androgen excess. Most hyperandrogenic adolescents will be found to have PCOS. The treatment is chosen according to particular symptoms, such as menstrual irregularity, hirsutism, or obesity. 
4	The renin-angiotensin system and renal function in kidney transplantation. The use of converting enzyme inhibitors (CEI) has permitted us to assess the role of the renin-angiotensin system in the control of arterial pressure and renal function in various conditions. In renal transplant recipients treated by azathioprine and steroids, the occurrence of CEI-induced deterioration of renal function is highly suggestive of renal artery stenosis, whereas renal vasodilatation associated with unchanged glomerular filtration rate in response to CEI is indicative of a significant role of native kidneys. In hypertensive recipients without renal artery stenosis, the absence of renal hemodynamic changes after CEI may be predictive of subsequent chronic rejection. The information provided by CEI is rather different in cyclosporine treated subjects. In this setting, no acute effect of CEI on renal hemodynamics is detectable. Whether the renal response to CEI is similar in cyclosporine when compared to conventionally treated patients with renal artery stenosis remains to be demonstrated. 
4	Arterial protection: a neglected but crucial therapeutic goal. Hypertension is accompanied by 2 major types of arterial pathologic conditions: smooth muscle hypertrophy of arteriolar resistance vessels and atherosclerosis, primarily involving the larger arteries. Smooth muscle hypertrophy may develop either as a secondary defense against elevated intravascular pressure or as a primary defect responsible for the increased pressure. Insulin and a number of other trophic stimuli may play a pathogenetic role in vascular hypertrophy. Reducing blood pressure and trophic stimuli may cause hypertrophy to be reversed. Because atherosclerosis may be markedly accelerated by hypertension, especially in the presence of concomitant risk factors, such as hypercholesterolemia, cigarette smoking and diabetes mellitus, antihypertensive treatment may attenuate or even reverse the extent of atherosclerosis, but only when the causative factors are also corrected. Some commonly used antihypertensive agents, e.g., diuretics and beta blockers without intrinsic sympathomimetic activity, often aggravate hypercholesterolemia and glucose intolerance, thereby diminishing their potential protective value. Other types of drug therapy, such as alpha blockers, beta blockers with intrinsic sympathomimetic activity or other vasodilator activity, angiotensin-converting enzyme inhibitors and calcium entry blockers that may not induce biochemical changes, should provide better control of multiple risks and thereby better protection against atherosclerosis. With a better understanding of how hypertension induces arterial damage, clinicians will be able to provide more appropriate treatment and, it is hoped, alleviate such damage. 
3	Attenuation of suxamethonium myalgias. Effect of midazolam and vecuronium. We studied the incidence of fasciculations and postoperative myalgias in 100 female outpatients who had laparoscopy under thiopentone, N2O, isoflurane anaesthesia. Four groups of 20 patients each were pretreated with saline (group 1), tubocurarine 0.05 mg/kg (group 2), vecuronium 0.006 mg/kg (group 3), or midazolam 0.025 mg/kg (group 4), followed by suxamethonium 1.5 mg/kg. Group 5 received only vecuronium 0.1 mg/kg as relaxant (no suxamethonium). Fasciculations were graded, and postoperative myalgias rated on the first and third postoperative days. In groups 1-5 the incidence of fasciculations was 95, 15, 25, 95 and 0%; the incidence of myalgias on the first day after operation was 70, 45, 65, 75 and 60%, and on the third day after operation 20, 5, 20, 20, and 5%, respectively. We conclude that pretreatment with vecuronium, but not midazolam, decreases the incidence of fasciculations after suxamethonium (p less than 0.05) and that in this patient population, postoperative myalgias appear to be unrelated to the use of suxamethonium. 
2	New surgical approach to complicated gastroesophageal reflux disease: transthoracic parietal cell vagotomy. Surgical treatment of peptic stricture of the esophagus associated with columnar (Barrett) metaplasia can be a difficult problem. Collis-Nissen fundoplication restores an intraabdominal antireflux barrier for most cases of peptic stricture; however, 20% of patients may have persistence of pathological acid reflux. By reducing acidity of postoperative reflux, parietal cell vagotomy may complement nonresectional surgical results for Barrett stricture. 
1	Esophageal adenocarcinoma in a patient with surgically treated achalasia. Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastro-esophageal reflux disease. 
3	Fibromyalgia in human immunodeficiency virus infection. Tenderness was assessed by point count and by scored palpation in 51 patients with human immunodeficiency virus (HIV) infection as well as 51 patients with rheumatoid arthritis (RA) and 50 patients with psoriatic arthritis (PsA). Fifteen of 51 (29%) patients with HIV infection met criteria for fibromyalgia, based on the presence of 10 tender (of 14) "fibrositic" points. Similar results were observed among patients with PsA (24%). The prevalence of fibromyalgia was higher among patients with RA (57%). Patients with HIV and PsA were less tender than patients with RA. Fibromyalgia in patients with HIV was significantly associated with myalgia and arthralgia, but not with age, duration of HIV infection, stage of HIV disease, or zidovudine therapy. 
4	Perforin-mediated myocardial damage in acute myocarditis. Endomyocardial specimens were obtained from 7 patients with acute myocarditis. Immunohistochemical examination of the mononuclear infiltrate showed mainly cytotoxic T lymphocytes and natural killer cells. Perforin (a pore-forming protein found in cytotoxic lymphocytes) was identified in this myocardial lymphocytic infiltrate and electron microscopy showed myocardial cell damage that may have been associated with these perforin containing lymphocytes. The results indicate that in acute idiopathic and viral myocarditis, myocardial damage may be due to the action of perforin-secreting lymphocytes. 
5	Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results. Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab-England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period. 
4	Nephropathy in model combining genetic hypertension with experimental diabetes. Enalapril versus hydralazine and metoprolol therapy. We compared the effects of the angiotensin-converting enzyme inhibitor enalapril and a conventional antihypertensive regimen (hydralazine and metoprolol) on kidney function, albuminuria, and glomerular ultrastructure in hypertensive diabetic and nondiabetic rats. Diabetes was induced with streptozocin at 8 wk of age in spontaneously hypertensive (SHR) rats. Antihypertensive drugs were administered in drinking water from the time of induction of diabetes in all groups. Blood pressure reduction was equal in the diabetic and nondiabetic SHR rats receiving either enalapril or hydralazine plus metoprolol. In diabetic SHR rats, there was a rise in serum creatinine after 32 wk, which did not occur in diabetic rats treated with either antihypertensive regimen or in nondiabetic rats. Both drug regimens reduced albuminuria in diabetic and nondiabetic SHR rats to a similar degree. Enalapril and the combination of hydralazine and metoprolol were associated with decreased glomerular basement membrane thickness and glomerular volume in diabetic and nondiabetic SHR rats without significant effect on fractional mesangial volume. Thus, antihypertensive therapy retards the development of albuminuria, glomerular basement membrane thickening, and glomerular hypertrophy in the rat in the presence or absence of diabetes. No specific benefit of angiotensin-converting enzyme inhibition was observed in these hypertensive models of nephropathy. Human studies comparing the effects of different classes of antihypertensive drugs on kidney function, proteinuria, and glomerular morphology are warranted. 
4	Cor triatriatum dexter: antemortem diagnosis in an adult by cross sectional echocardiography. Cor triatriatum dexter is a rare cardiac abnormality in which the right atrium is subdivided into two distinct chambers. This anomaly is generally attributed to the persistence of the right sinus venosus valve and it is frequently associated with severe malformations of other right heart structures. The antemortem diagnosis of the membrane may be difficult and its presence is often only established at necropsy. In a woman of 56 with Ebstein's anomaly the echocardiographic features of cor triatriatum dexter were examined before and during cardiac catheterisation. These investigations showed the position of the membrane, that there was no gradient between the two atrial chambers, and that there were perforations in the centre of the membrane. 
2	Extracorporeal shock wave lithotripsy for biliary stones. Extracorporeal shock wave lithotripsy is a noninvasive technique for treatment of patients with gallbladder and bile duct stones. Selected patients with gallbladder stones can be treated on an outpatient basis without general anesthesia and may return to full activity within 1 or 2 days. Stone-free rates of 40% to 60% at 6 months have been achieved in most reported series with minimal morbidity. Bile duct stone lithotripsy has achieved stone clearance in 80% of patients in whom conventional methods were unsuccessful and therefore constitutes a valuable second-line treatment for these patients. 
5	Speech, velopharyngeal function, and hearing before and after orthognathic surgery. Articulation, voice, resonance, hearing sensitivity, and middle ear function were examined in 34 patients before and 3, 6, 9, and 12 months after orthognathic surgery. Thirty of the 34 patients had articulation errors before surgery. Errors on the sibilants /s/ and /z/ occurred most frequently, followed by those on /j,zh,ch/ and /sh/. Errors were predominantly distortions with both visual and acoustic components. After surgery, articulation improved spontaneously in the absence of intervention. Most of the preoperative articulation errors were eliminated by 3 months postoperative, but, thereafter, a gradual decline was noted so that by 12 months, errors occurred on /s/ and /z/. Voice, resonance, velopharyngeal port area, and hearing sensitivity were not altered by surgery. This study suggests that severe skeletal malocclusions requiring surgical correction have deleterious effects on the patients' articulation of consonants and that surgical alteration leads to the correction of most of these errors. 
5	The importance of the GHQ in general practice. The relationship between General Health Questionnaire (GHQ) score and complaints presented at the general practitioners office was examined, and showed that the correlation between them is not as high as might be expected. Many patients who present psychosocial problems to their GP appear to have a low GHQ score; many patients with a high GHQ score exclusively present somatic complaints, which are also assessed by the GP as being purely somatic. Implications of the results are discussed. 
1	Primary neoplasms of the central nervous system in children. Modern diagnostic imaging techniques are able to detect primary neoplasms of the central nervous system (CNS) in children safely and accurately but with less specificity as to cell type or degree of malignancy. These neoplasms, often peculiar in cell type and size, mediated by hydrocephalus in their clinical presentation, demand careful and often extensive imaging techniques best to evaluate their geography and character. Added to these basic observations, determination of the neoplasm from surrounding edema, detection of possible spread, and evaluation of residual or recurrent neoplasm are prime responsibilities of the pediatric neuroradiologist toward the child, neurosurgeon, and oncologist. 
3	Hematoma of the optic nerve sheath after penetrating trauma. We have presented a case involving the diagnosis and management of optic nerve sheath hematoma. Our patient's positive outcome demonstrates the usefulness of megadose steroid therapy for acute optic nerve injury. 
4	Coffee, caffeine, and cardiovascular disease in men BACKGROUND. For many years, an association between coffee consumption and the risk of coronary heart disease has been suspected. Although based on small numbers of end points, a prospective study has suggested a particularly strong association between recent coffee drinking and the incidence of cardiovascular disease. METHODS. We examined prospectively the relation of coffee consumption with the risk of myocardial infarction, need for coronary-artery bypass grafting or angioplasty, and risk of stroke in a cohort of 45,589 U.S. men who were 40 to 75 years old in 1986 and who had no history of cardiovascular disease. RESULTS. During two years of follow-up observation, 221 participants had a nonfatal myocardial infarction or died of coronary heart disease, 136 underwent coronary-artery surgery or angioplasty, and 54 had a stroke. Total coffee consumption was not associated with an increased risk of coronary heart disease or stroke. The age-adjusted relative risk for all cardiovascular disease among participants who drank four or more cups of coffee per day was 1.04 (95 percent confidence intervals, 0.74 to 1.46). Increasing levels of consumption of caffeinated coffee were not associated with higher risks of cardiovascular disease. Higher consumption of decaffeinated coffee, however, was associated with a marginally significant increase in the risk of coronary heart disease (relative risk, 1.63; 95 percent confidence interval, 1.02 to 2.60). Finally, we observed no pattern of increased risk across the subgroups of participants with increasing intakes of caffeine from all sources. Adjustment for major cardiovascular-risk indicators, dietary intake of fats, and cholesterol intake did not materially alter these associations. CONCLUSIONS. These findings do not support the hypothesis that coffee or caffeine consumption increases the risk of coronary heart disease or stroke. 
5	Effect on outcome of prolonged exposure of patients to nitrous oxide. Prolonged (several days or repeated) exposure to nitrous oxide (N2O) can cause injury or death. To assess whether relatively prolonged anesthesia with N2O in normal patients might similarly cause untoward effects, we investigated whether the addition of N2O to isoflurane anesthesia caused injury to patients having surgical resection of acoustic neuroma lasting approximately 10 h. Twenty-six patients undergoing surgical resection of acoustic neuroma were randomly assigned to a regimen that included or excluded N2O (50%-60%) during isoflurane anesthesia plus intravenous adjuvants. On average, slightly less isoflurane (0.24%) was used during anesthesia with N2O. We measured standard clinical variables (blood pressure, heart rate), oxygen saturation, neurologic status, pain, and the incidence and type of morbid outcomes. Exposure to N2O did not increase the incidence of morbid outcomes (including hepatic injury, infection, or hypoxemia), prolong hospitalization, or increase common postoperative complaints such as nausea, vomiting, coughing, or headache. Patients anesthetized with either regimen were equally satisfied with their anesthetic. 
4	Impact of the availability of a prior electrocardiogram on the triage of the patient with acute chest pain STUDY OBJECTIVE: To determine whether information from a prior electrocardiogram (ECG) improves diagnostic accuracy in the emergency department (ED) evaluation of patients with acute chest pain. DESIGN: Analysis of prospectively collected data from a cohort study. SETTING: Emergency departments of four community and three university hospitals. PATIENTS: 5,673 patients aged greater than or equal to 30 years who presented to the EDs of participating hospitals for evaluation of acute chest pain, including 772 (14%) with acute myocardial infarction (AMI). MEASUREMENTS AND MAIN RESULTS: After adjusting for clinical characteristics, no significant difference was found in the sensitivities of admission to the hospital or to the coronary care unit (CCU) between AMI patients with and without prior ECGs available for review. However, non-AMI patients with prior ECGs available for review were more likely to avoid CCU admission than were non-AMI patients without prior ECGs. This improvement in specificity was most marked in the 2,024 patients whose current ED ECGs had changes consistent with ischemia or infarction: when a prior ECG was available, non-AMI patients were more than twice as likely to be discharged (26% vs. 12%) and about 1.5 times as likely to avoid CCU admission (39% vs. 27%) (both p less than 0.0001). Admission rates of AMI patients with and without prior ECGs were similar. CONCLUSION: When the current ECG is consistent with ischemia or infarction, the availability of a prior ECG for comparison to determine whether the ECG changes are old or new improves diagnostic accuracy and triage decisions by reducing the admission of patients without AMI or acute ischemic heart disease (increased specificity) without reducing the admission of patients with these diagnoses (unchanged sensitivity). 
3	Gaze-evoked visual seizures in nonketotic hyperglycemia. Focal motor seizures are commonly a symptom of nonketotic hyperglycemia (NKH). Posture-induced motor seizures are less common but have been reported in some patients with this disorder. We report the first case of gaze-evoked sensory (visual) seizures in nonketotic hyperglycemia. Both seizures and ictal EEG findings disappeared shortly after hyperglycemia was corrected. 
2	Nausea, vomiting, and retching. Although nausea, vomiting, and retching have plagued mankind since antiquity, limited attention has been given to the three symptoms as separate entities. Although knowledge of symptom occurrence is essential to practice, nurses must focus on patients' response or distress to the occurrence of symptoms. The differentiation of symptom occurrence and symptom distress of nausea, vomiting, and retching is critical to the management and self-care demands of patients and the enhancement of their quality of life. Basic research on patterns of these individual symptoms and their components promises to provide a more progressive and fruitful approach to the patient response to these symptoms. 
1	Causes of death in hospitalized intravenous drug abusers. The authors reviewed at autopsy the causes of death of 274 patients with evidence of intravenous drug abuse who had been admitted to a large public hospital. There were 127 who died from diseases unrelated to intravenous drug abuse, and in 41% of these, chronic alcoholism was implicated. Deaths from overdose syndromes and drug-related organ pathology comprised only 11% of all cases. The mean age at death was 39 years. There was a male/female ratio of 3.6:1. Half of all patients died from infection--72 from acquired immunodeficiency syndrome (AIDS) alone. These findings indicate that persons hospitalized with a history of intravenous drug abuse usually die from causes other than overdose and that AIDS and chronic alcoholism are significant problems. Emphasis should be placed upon detecting "hidden" intravenous drug deaths to provide more accurate statistical information. 
4	Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery. Low cardiac output syndrome frequently follows cardiopulmonary bypass (CPB) surgery. In the present study, we used dobutamine to increase cardiac index (CI) and oxygen delivery (DO2) in 18 patients after open heart surgery. Using increasing doses of dobutamine up to 10 micrograms/kg.min-1, we observed statistically significant (p less than .01) increases in mean CI (2.50 +/- 0.10 to 3.56 +/- 0.18 L/min.m2) and in mean heart rate (HR) (83 +/- 3 to 105 +/- 3 beat/min). Mean systemic vascular resistance index decreased significantly (p less than .01) in all patients (2271 +/- 101 to 1648 +/- 83 dyne.sec/cm5.m2). Pulmonary vascular resistance index did not change in the ten coronary artery bypass graft patients, but decreased significantly (p less than .01) in the eight valve replacement patients (561 +/- 98 to 421 +/- 79 dyne.sec/cm5.m2). Mean DO2 increased in all patients, although there was no concomitant increase in oxygen consumption (VO2) in four patients. We observed a significant (p less than .01) increase in mean VO2 in the remaining 14 patients (110 +/- 6 to 148 +/- 12 ml/min.m2), in spite of significant decreases in PaO2 and increases in right-to-left intrapulmonary shunting. Although increases in HR and ventricular arrhythmias may limit its use, dobutamine increases CI and DO2 in patients after CPB. In the present study, dobutamine's varying metabolic effect exemplifies the need for close monitoring of hemodynamic and metabolic variables when using vasoactive drugs in the postoperative period. 
1	Perinatal transmission of human papillomavirus. Human papillomavirus infection is probably the most prevalent sexually transmitted disease in the United States. In adults, it is associated with condylomata acuminata and with neoplastic changes ranging from dysplasia to carcinoma. Infected mothers may transmit human papillomavirus during the perinatal period; affected children face prolonged, difficult treatment for respiratory papillomatosis. Prevention of infection remains the best approach, since diagnostic and therapeutic methods are suboptimal. 
3	An evaluation of sensory changes and pain relief in trigeminal neuralgia following intracranial microvascular decompression and/or trigeminal glycerol rhizotomy. Nineteen patients with trigeminal neuralgia were treated with either trigeminal ganglion glycerolysis or glycerolysis and intracranial microvascular decompression. All had a good degree of pain relief. Of those receiving glycerol alone (group A), 50% subjectively reported a mild reduction of fine tactile sensation. A similar response was reported by those treated with both glycerol and decompression (group B). The degree of sensory loss was so mild that thermal testing was useless as a discriminatory tool. The degree of sensory loss was not greater when both surgical procedures were performed than when the less-invasive trigeminal ganglion glycerolysis alone was used. 
5	Alterations of adrenoceptors in the nasal mucosa of allergic patients in comparison with nonallergic individuals. Nasal hyperreactivity in nasal allergy may be due to changes of the characteristics in adrenergic receptors. Radioligand receptor-binding studies with the antagonists, 3H-prazosin (alpha 1-adrenoceptor), 3H-rauwolscine (alpha 2-adrenoceptor), and 125I-(-)-Cyanopindolol (beta-adrenoceptor) were performed in homogenates of nasal mucosa of allergic and nonallergic (NA) patients to investigate this hypothesis. The heterogeneous NA group was subdivided into control individuals and patients with chronic sinusitis and vasomotor rhinitis. No significant differences in affinities or densities of alpha 1- and alpha 2-adrenoceptors could be demonstrated in allergic patients in comparison with NA and control individuals. The beta-adrenoceptor density was significantly reduced in allergic patients in comparison with that of control individuals. Neither changes in agonist binding or in the effect of Gpp(NH)p on the agonist binding to beta-adrenoceptors could be observed in allergic patients. The subtype selective antagonist, LK203-030, demonstrated the presence of a homogeneous population of beta 2-adrenoceptors in human nasal mucosa of both NA and allergic patients. In vitro, autoradiography demonstrated specific 125I-(-)-Cyanopindolol labeling of the epithelium in NA and allergic patients. In conclusion, no changes in characteristics of alpha 1- or alpha 2-adrenoceptors in the nasal mucosa could be demonstrated in nasal allergy. However, a decreased number of beta-adrenoceptors may reflect a beta-adrenergic abnormality in nasal allergy. 
4	Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study. Plasma fibrinogen was measured in a sample of 8824 men and women aged 40-59 years participating in the Scottish Heart Health Study, and related to cardiovascular risk factors. Women had higher fibrinogen levels than men. In both sexes, multivariate analysis showed that fibrinogen was positively associated with age, smoking, total cholesterol and body mass index and negatively associated with alcohol consumption. Among women, early menopause and systolic blood pressure were also associated with fibrinogen levels. Univariate analyses showed weak positive associations with fish consumption for both sexes although only male white fish consumption entered the final model. Women with a history of contraceptive pill usage had significantly lower fibrinogen levels. The relationship between fibrinogen and physical activity was complex, and could largely be explained by smoking. These findings support the hypothesis that raised fibrinogen is one mechanism by which several major risk factors may promote coronary heart disease. However, known risk factors explained, at most, 10% of the total variance in fibrinogen levels among the general population. 
4	Early and late results after isolated coronary artery bypass surgery in 159 patients aged 80 years and older. We have studied 159 patients 80 years of age or older who have had isolated coronary artery bypass grafting (CABG) since 1977. Eighty-seven percent have had surgery since 1984. Two thirds of the patients were male, and the mean age was 82 years. Most patients (97%) were in New York Heart Association (NYHA) functional class III or IV, 89% had unstable/postinfarction angina pectoris, and 67% had rest pain. Almost half (47%) required preoperative admission to the coronary care unit, 6% required preoperative use of an intra-aortic balloon pump, and 20% were operated on emergently. Significant left main coronary artery disease (greater than or equal to 50% stenosis) was present in 41%. Ten patients (6.3%) died within 30 days of surgery, with seven more patients dying during the same hospital admission or soon after transfer to another institution. This resulted in an overall hospital mortality of 10.7%. The median hospital stay was 10 days. On univariate analysis, the significant predictors of hospital mortality were NYHA IV, angina at rest, preoperative admission to the coronary care unit, emergency operation, ejection fraction less than 0.50, and the presence of mitral regurgitation. On multivariate analysis, ejection fraction less than 0.50 was the only significant risk factor (p less than 0.01). Of hospital survivors, 98% have been followed for a mean of 29 months. The estimated 5-year survival (+/- SEM) of all patients was 71 +/- 4.5%, and for hospital survivors, 80 +/- 4.5%. The most important predictor of adverse survival was an ejection fraction less than 0.50. Seventy-nine percent are angina-free, and 89% are in NYHA classes I and II. The majority of patients felt that they were improved by surgery. We conclude that CABG in patients 80 years or older, although associated with increased operative risk, gives excellent relief of symptoms and good 5-year survival. Patients should not be denied CABG because of age alone. 
1	Diagnosis and localization of prostate carcinoma by fine-needle aspiration cytology and correlation with histologic whole-organ sections after radical prostatectomy. Twenty-nine patients with clinical stage T1-2, NO, MO prostate carcinoma were treated by retropubic radical prostatectomy. Diagnosis was made by fine-needle aspiration biopsy from six to eight separate sectors of the prostate. At the time of biopsy, diagrams of the palpated organ were drawn, depicting the location of the lesion and the site of each biopsy. Without the examiners' knowledge of cytologic data, extirpated prostate glands were examined with whole organ histologic sections, and carcinomas were scored according to the method of Gleason. The location and extent of all typical and malignant foci were mapped on a standard diagram. The results of preoperative cytologic examination were compared with postoperative histopathologic findings, showing a tendency toward underestimation of both the extent and degree of differentiation of the carcinomas during cytologic examination. In no case were these parameters overestimated during cytologic examination. The Gleason score correlated well with the presence of capsular and seminal vesicle invasion. 
4	Natural history of progressive ischemic stroke in a population treated with heparin Data on the acute natural history of progressive stroke with or without heparin treatment are limited. To define the acute course of patients treated with heparin for progressive stroke, we examined the charts of 69 such patients identified through the Cornell Neurology Database from October 1979 to June 1985. Analysis included determining whether further clinical deterioration or hemorrhagic complications were associated with readily identifiable clinical or laboratory variables. Twenty-five patients (36%) continued to deteriorate while receiving heparin, another two (3%) worsened due to intracerebral hemorrhage, and a total of 10 patients (14%) had bleeding complications. No clinical features or heparin dosing regimens distinguished the patients likely to benefit from heparin. Clinical progression or hemorrhage did not correlate with the level of anticoagulation as measured by the average heparin dose per day or the mean partial thromboplastin time. Without unequivocal evidence demonstrating heparin's ineffectiveness for progressive stroke, many clinicians managing such patients will continue to use heparin. Our results suggest that this decision should not be governed by such clinical features as a patient's age or sex or by the vascular distribution of the stroke. Furthermore, frequent measurement of and overzealous efforts to adjust the partial thromboplastin time may be unnecessary since it does not correlate with outcome. 
5	Characterization of a factor-dependent acute leukemia cell line with translocation (3;3)(q21;q26). A strictly factor-dependent cell line (UCSD/AML1) was established from a patient with the syndrome of multilineage acute leukemia with high platelets. The patient's cells and the cell line karyotype were 45,XX,-7,t(3;3)(q21;q26), typical of the syndrome of acute leukemia with high platelets. The cell line expresses CD34, CD7, TdT, and myeloid (CD13, CD14, CD33) and megakaryocyte/platelet (CD36, CD41, CD42b, CDw49b) antigens. In short-term culture, UCSD/AML1 cells proliferate in response to interleukin-3 (IL-3), IL-4, IL-6, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage CSF (GM-CSF), but not IL-1, IL-2, IL-5, or G-CSF. In long-term culture, proliferation can be sustained by GM-CSF, IL-6, or M-CSF. When maintained in GM-CSF, a small percentage of cells form multinucleated megakaryocyte-like giant cells. Culture with GM-CSF combined with IL-6, but not with IL-6 alone, increased giant cell formation fourfold to sevenfold. IL-6 alone or in combination with GM-CSF increased expression of platelet-related antigens. In contrast, culture with phorbol ester induced formation of macrophage-like cells. UCSD/AML1 is the first human acute nonlymphocytic leukemia cell line established from a patient with an acute leukemia syndrome associated with a specific chromosome abnormality. 
4	Disproportionate septal hypertrophy associated with erythroblastosis fetalis. We retrospectively reviewed clinical and echocardiographic data on 10 newborns with erythroblastosis fetalis who were admitted to our nurseries between 1984 and 1988 and who required a double-volume exchange transfusion and neonatal intensive care. Echocardiograms were performed in the first 48 hours of life. In 5 patients, disproportionate septal hypertrophy was demonstrated; 1 additional patient had biventricular hypertrophy with a thickened septum but not disproportionate septal hypertrophy. The mean septal: left ventricular free-wall ratio for the group (n = 10) was 1.37. No correlation was apparent between the occurrence of disproportionate septal hypertrophy and newborn glucose, bilirubin, or hematocrit values. When analyzed separately, the 4 patients who did not receive intrauterine blood transfusions had a ratio of 1.73 +/- 0.21 (mean +/- SEM); this was significantly greater than the ratio in the 6 patients who were transfused in utero (1.13 +/- 0.24). In patients who underwent transfusions, there was no correlation between the number of transfusions and the septal:left ventricular ratio. This study reports a significant but previously unrecognized cardiac hypertrophy with disproportionate septal hypertrophy in patients with erythroblastosis fetalis. Our data suggest a sparing effect of intrauterine fetal transfusions. The mechanism by which these transfusions may affect the hypertrophic development of the myocardium remains to be determined. 
5	Pyogenic hepatic abscess. Presented is a case of spontaneous pyogenic hepatic abscess in a previously healthy young man without associated risk factors. This disease entity has a low incidence, however, it is associated with significant morbidity and mortality if diagnosis and treatment are delayed. 
1	Magnetic resonance imaging of small hepatocellular carcinoma. Thirty-eight patients with small hepatocellular carcinomas (HCCs), size less than 20 mm, initially detected by ultrasound (US) and histologically confirmed, were examined by magnetic resonance (MR) imaging, computed tomographic (CT) scan, and angiography. MR imaging demonstrated HCC nodules in nine (75.0%) of 12 patients with tumors less than 10 mm in diameter and in 22 (84.6%) of 26 patients with tumors 10-20 mm in diameter. In total, HCC nodules were detected in 31 of 38 patients (81.6%) by MR imaging. On the other hand, HCC lesions were found on CT scan in 14 of 26 patients (53.8%) and in 27 of 35 patients (77.1%) by angiography. With MR imaging, HCC nodules were demonstrated in 21 of 31 patients on both T1 and T2 weighted images, and 13 of 21 patients (61.9%) were shown to have low intensity areas or iso intensity areas on T1 weighted image, whereas the other eight patients (38.1%) were shown to have high intensity areas. All 21 patients were shown to have high intensity areas on T2 weighted image. Among 15 resected cases, four patients had a high intensity area on T1 weighted image, and a significant fatty change was noted in HCC nodules by histological study of the resected specimen. We suggest that MR imaging is a useful diagnostic imaging modality, even in small HCC of less than 20 mm. 
1	Aqueductal (pencil) glioma presenting as neurogenic pulmonary edema: a case report. A case of neurogenic pulmonary edema due to hydrocephalus, without initial neurological deficit, is described. Computed tomography demonstrated a ring enhancing lesion in the tectum of the mesencephalon obstructing the aqueduct of Sylvius. The lesion, on autopsy, was a rare mesencephalic glioma described in the literature as a "pencil glioma" of the aqueduct. 
1	Second cancer after radiation therapy for cancer of the uterine cervix. Radiation-induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11,855 patients including 5725 patients treated with radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery alone. The observed-to-expected ratios of the second primary cancer was 0.933 for the patients with radiation therapy alone and 1.074 for the patients with postoperative radiation therapy, respectively. No significant increase was observed in the risk of second primary cancers when all sites were combined. However, assessing on site by site basis, significant excess was noted for the rectum cancer, leukemia, and bladder cancer for the radiation therapy group but not for the surgery group. A significant excess of lung cancer was observed in both radiation therapy and surgery groups, which was attributed to some other causative factors. Radiation-induced cancers were suggested to develop apparently in organs involved in the irradiated field. 
5	Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients. The distribution of the immunoglobulin Km(1) and Gm phenotypes was examined in patients with connective tissue diseases, including systemic lupus erythematosus, mixed connective tissue disease, and scleroderma, whose sera were characterized for antibodies against nuclear antigens and polypeptides of U small nuclear ribonucleoproteins. We found a strong association between Km(1) phenotype and susceptibility to systemic lupus erythematosus (P less than 0.00001, relative risk = 17). We also found a positive association between the Km(1) phenotype and the presence of anti-double-stranded DNA antibodies. The presence of certain immunoglobulin genes or gene families may have a role in susceptibility to the development of autoantibodies and/or of connective tissue disease. 
5	The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma. One hundred fifty-one patients with colorectal polyps containing invasive adenocarcinoma treated by resection were studied to determine the incidence of lymph node metastasis and whether lymph node metastasis was related to the depth of invasion. Other variables evaluated included size and configuration of the polyp, grade of adenocarcinoma, presence or absence of lymphovascular invasion, and degree of differentiation. In patients with sessile polyps, the incidence of lymph node metastasis was 10 percent. Eighty percent of these lesions had lymphovascular invasion. For pedunculated polyps, the overall incidence of lymph node metastasis was 6 percent. However, there was no incidence of lymph node metastasis when the depth of invasion was limited to the head, neck, and stalk of the polyp (Levels 1, 2, and 3). Only when the depth of invasion reached to the base of the stalk (Level 4) was the risk of lymph node metastasis high (27 percent). The other risk factors were not associated with lymph node metastasis. We concluded that the most significant risk factor for lymph node metastasis in patients with invasive carcinoma in a polyp was invasion into the submucosa of the bowel wall (Level 4). 
1	Vertebral hemangiomas: fat content as a sign of aggressiveness. Thirty-two vertebral hemangiomas (VHs) were evaluated with nonenhanced computed tomography (CT), T1-weighted magnetic resonance (MR) imaging, CT enhanced with contrast material, and selective spinal arteriography. The stroma between the osseous trabeculae was found to correspond to either fatty tissue or soft tissue or both. All 11 asymptomatic VHs showed complete fatty stroma at CT and increased signal intensity at MR imaging. In contrast, all four compressive VHs had soft-tissue attenuation at CT. Three compressive VHs showed low signal intensity on MR images. Predominantly fatty stroma at CT and increased signal intensity at MR imaging were associated with normal or only slightly increased vascularization at selective spinal arteriography or contrast-enhanced CT, while soft-tissue stroma at CT and low signal intensity at MR imaging were associated with distinct hypervascularization. The authors' experience suggests that fatty VHs may represent inactive forms of VH, while soft-tissue content at CT and low signal intensity at MR imaging may indicate a more active vascular lesion with potential to compress the spinal cord. CT and MR imaging may be especially valuable for evaluating patients with clinical signs or symptoms of uncertain origin and findings compatible with VH at plain radiography. 
3	The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation. To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV. 
1	Mammographic follow-up of low-suspicion lesions: compliance rate and diagnostic yield. All recommendations for mammographic follow-up of low-suspicion lesions seen at mammography during a 6-month period were reviewed to establish compliance rate and eventual outcome. One hundred forty-four of 2,650 mammograms (5%) showed minimal abnormalities that warranted short-term and periodic mammographic follow-up. Rates of compliance at 4 months and at 1, 2, and 3 years were 88%, 71%, 60%, and 47%, respectively. Progressive mammographic change was found in 10 patients, only one of whom had a carcinoma. It was concluded that mammographic follow-up of low-suspicion lesions is a reasonable alternative to surgical biopsy, although patient compliance remains a significant problem. 
4	Comparison of coronary angiographic features and oral dipyridamole thallium 201 tomography. Coronary angiography and left ventriculography is commonly used to identify those patients with incomplete infarctions and therefore, a need for revascularization. The authors compared coronary angiography and left ventriculography with thallium 201 tomography using oral dipyridamole to identify patients with potential ischemia in the infarct zone indicating viable tissue. Forty-five patients (37 men, 8 women) with acute myocardial infarctions (29 anterior, 16 inferior) who received intravenous thrombolytic therapy were studied. On the basis of the left ventriculograms, only 16 patients were judged to have residual function in the infarct zone. Six of these patients had no thallium redistribution in the infarct zone, indicating lack of residual ischemia. Of the 29 patients with no residual function in the infarct zone, 18 had redistribution in the infarct zone, suggesting residual ischemic myocardium and thus viable tissue. Among the 32 patients with open infarct vessels, 15 had no redistribution in the infarct zone, but of the remaining 13 patients with occluded infarct vessels, 9 had redistribution in the infarct zone indicating residual ischemia and thus viable tissue. The authors' data suggest that neither wall motion analysis by left ventriculography nor the angiographic status of the infarct vessel identifies those patients with residual ischemia as evidenced by thallium tomography using oral dipyridamole. 
3	Experimental alcoholic skeletal muscle myopathy is characterised by a rapid and sustained decrease in muscle RNA content. An investigation was made into the effects of ethanol feeding (36% of total calories) on skeletal muscle. From 7 to 42 days, muscle weights and protein and DNA contents of alcohol-treated rats were significantly lower (10-23%) than pair-fed controls (with glucose as 36% of total calories). Ethanol feeding markedly reduced muscle RNA content by 22-34%, when compared to controls. Muscle RNA content of ethanol-fed rats at 7, 14, 28 and 42 days of treatment was significantly lower than initial values (i.e. at 3 days) by 22-38%. Thus, ethanol feeding caused an initial net loss and thereafter a reduction in the rate of accretion of RNA. The marked and sustained loss in the muscle protein synthetic apparatus may be a precipitating event in the development of experimental skeletal muscle myopathy. 
3	Enveloping the bladder with displacement of flap of the rectus abdominis muscle for the treatment of neurogenic bladder. Neurogenic bladder is a frequent occurrence. A new surgical technique has been designed and was used successfully in 18 patients with ideal results. The key point of the operation is to turn over a flap of rectus abdominis muscle to envelop the bladder. Contraction of the muscle flap and the abdominal muscles would enhance voiding ability. In the meantime, the bladder is displaced forward and the resultant change in the bladder-posterior urethral angle also favors voiding. Since the bladder is near the anterior abdominal wall manual compression during voiding is made easier. All of these advantages greatly facilitate voiding. 
3	Poisoning with equine phenylbutazone in a racetrack worker. Phenylbutazone is a potent nonsteroidal, anti-inflammatory drug often used by veterinarians to treat racetrack animals. Its use in human beings is limited because of significant adverse effects and the availability of newer, safer drugs. We report the case of a 24-year-old man who ingested 17 g of equine phenylbutazone over a 24-hour period to treat the pain of a toothache. He developed grand mal seizures, coma, hypotension, respiratory and renal failure, and hepatic injury. Serum phenylbutazone concentration obtained approximately eight hours after presentation was 900 micrograms/mL. The patient recovered during six weeks of intensive supportive care and repeated hemodialysis. 
4	Lung injury in a surfactant-deficient lung is modified by indomethacin. Repetitive total lung lavage in adult rabbits leads to a reproducible severe surfactant-deficient lung injury. Hypoxemia requiring mechanical ventilation occurs, accompanied by a substantial pulmonary hypertension, a large intra-alveolar protein leak, peripheral neutropenia, and pathological features of marked neutrophil infiltration with extensive hyaline membrane formation. Pretreatment with indomethacin abolishes postlavage pulmonary hypertension, preserves a slightly better lung function with higher arterial PO2, and prevents the postlavage peripheral neutropenia found in untreated animals. Pretreatment with a thromboxane A2 receptor blocker (L 655,240, Merck Frosst, Canada) also completely attenuated pulmonary hypertension, providing evidence that thromboxane A2 mediates pulmonary arterial hypertension after lung lavage. However, specific thromboxane receptor blockade had no other long-lasting beneficial effects on the ongoing injury in this model. 
1	Glomus tumours of the skin: an immunohistochemical investigation of the expression of marker proteins. Immunohistochemical studies were carried out on cutaneous glomus tumours from 10 patients. The glomus areas in these tumours reacted strongly with anti-smooth muscle (CGA-7), anti-muscle (HHF-35) and anti-vimentin antibodies. Their neural supply was analysed using several nervous tissue markers (anti-neurone specific enolase, anti-S 100, anti-Leu 7, anti-neurofilaments). The results indicate a sprouting and proliferation rather than entrapment of pre-existing nerve fibres. 
5	Management of chronic middle ear effusion with prednisone combined with trimethoprim-sulfamethoxazole. Fifty-three patients were enrolled and evaluable in a randomized, double-blinded controlled clinical trial comparing prednisone for 7 days plus trimethoprim-sulfamethoxazole (TMP/SMZ) for 30 days vs. TMP/SMZ alone in treating chronic middle ear effusion (MEE). Clearing of the effusion in both ears or in one when only one was involved was called complete resolution; clearing in one of two affected ears was called partial resolution. The outcomes 2 weeks after initiation of therapy of 26 patients initially treated with prednisone plus TMP/SMZ were complete resolution in 20, partial resolution in three, and unchanged in three. The outcomes in 27 patients initially treated with TMP/SMZ alone were complete resolution in eight, partial resolution in three, unchanged in 13 and development of acute otitis media in three (P less than 0.01 for complete resolution). Two weeks after initiation of therapy, patients with a MEE that failed to clear were crossed over to the alternative regimen. Overall 29 of 41 patients (71%) who received oral prednisone plus TMP/SMZ initially or after the crossover had complete resolution of their middle ear effusion at 2 weeks after starting prednisone and TMP/SMZ. Five of 35 (14%) patients treated with prednisone plus TMP/SMZ and one of six (17%) patients treated with TMP/SMZ alone who had complete resolution at 4 weeks required subsequent referrals for tympanostomy tubes. A course of prednisone for 7 days plus TMP/SMZ for 30 days with monthly follow-up should be considered in children with MEE persisting beyond 6-8 weeks before referral for tympanostomy tube placement. 
5	Oral contraceptive therapy and the surgical management of ENT patients: a review of current clinical practice. The current policy of British Otolaryngologists with regard to the preoperative cessation of the oral contraceptive pill is reported. This is based on a confidential questionnaire sent to all members of the British Association of Otolaryngologists. The overall response rate was 66%, 91% of which were from practising otolaryngologists and forms the basis of this report, the remaining 9% being from respondents not engaged in active surgery. Although there is evidence to show an increased risk of developing thromboembolic complications after major abdominal, gynaecological and hip surgery in those patients taking the oestrogen-containing contraceptive pill, the risk following minor and intermediate surgery (which forms the bulk of the otolaryngologist's workload) is not known. Not surprisingly therefore the results of the survey show a varied policy across the country with 36.5% of respondents choosing to continue the pill and 25% always stopping the pill preoperatively. The remainder elect to stop the pill only in certain circumstances. 
5	Dexamethasone as an adjunct in oropharyngeal obstruction in a patient with leukemia. Incipient airway obstruction due to fulminating bacterial infection of pharyngeal tissues requires prompt and definitive intervention. A case is presented in which dexamethasone was a key adjunct to antibiotic therapy in averting this problem in a severely neutropenic patient with acute leukemia. 
1	Increasing the cancer screening of the medically underserved in south Florida. Diagnosis and treatment of cancers at advanced stages have contributed to a significantly lower survival rate among individuals of low socioeconomic status compared with those in higher brackets. In an effort to increase the accessibility and acceptability of cancer screening among such individuals in Dade County, Florida, the Cancer Control Division of the Sylvester Comprehensive Cancer Center at the University of Miami School of Medicine initiated a pilot early detection program in 1987. The program initially provided breast cancer screening for women, aged 40 and older, who attended ten community health care centers located in low-income neighborhoods. With the selection of Miami by the American Cancer Society as one of three sites for conducting a screening demonstration project for the socioeconomically disadvantaged, this program has recently been expanded to include pelvic screening for women, aged 40 and older, and prostate screening for men, aged 65 and older. 
2	Complete jejunoileal necrosis due to torsion of the superior mesenteric artery. We have reported a case of small-bowel volvulus in which complete jejunoileal necrosis resulted from torsion of the superior mesenteric artery. This case was unusual not only because of the extent of necrosis but also because primary small-bowel volvulus is rare in adults. Despite nearly total small-bowel resection, the patient continues to do well 6 months postoperatively. 
5	Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity. Natural killer (NK) cells are an important defense against intravascular tumor dissemination. Tumor embolization can occur at surgery, so we tested whether surgical stress decreased perioperative NK cell cytotoxicity, and examined the underlying mechanism of suppression. Patients with solid tumors underwent NK cell cytotoxicity assay just before and 24 hours after surgery in a 3-hour chromium 51 release assay. The NK cell cytotoxicity was significantly decreased postoperatively. We considered that surgical NK cell impairment might be due to (1) NK cell redistribution, (2) presence of suppressor cells, or (3) direct "toxic" effects on NK cells. Impaired NK cell cytotoxicity was not due to NK cell redistribution, because differential counts showed no significant changes in the percentage of large granular lymphocyte NK morphology. To isolate possible suppressor cells, postoperative cells from patients were selectively depleted of NK cells using anti-Leu-11b monoclonal antibody plus complement; these cells were then mixed with autologous preoperative cells. Postoperative NK cell cytotoxicity was markedly impaired, but the postoperative NK depleted cells did not suppress preoperative NK cells. We conclude that NK cell functional impairment from surgical stress is due to direct "toxic" effects on NK cells rather than either NK cell redistribution or the generation of NK-directed suppressor cells. 
1	Radiotherapy. The mainstay in the treatment of early glottic carcinoma. Early squamous cell carcinoma of the glottis may be effectively treated with surgery or radiation therapy. Controversy exists as to whether radiation therapy effects survival at the expense of vocal function by ultimately requiring more total laryngectomies for salvage of local tumor recurrence. This study reviewed the medical records of 185 patients with T1 or T2, NO invasive squamous cell carcinoma of the glottis treated with primary radiation therapy between 1969 and 1984. All patients were followed up for a minimum of 5 years after completion of therapy. One hundred sixty-one patients met the criteria for local control analysis. Radiation therapy controlled disease in 93% (105 of 113) of patients with T1 lesions and 73% (38 of 48) of those with T2 tumors. Ultimate control of disease for T1 and T2 lesions, including surgical salvage, was 111 (98%) of 113 and 44 (92%) of 48 patients, respectively. The rate of successful surgical salvage was 75% (T1) and 70% (T2). The T2 lesions with impaired vocal cord mobility or anterior commissure disease were identified as being at increased risk for recurrence after primary radiation therapy. Overall voice preservation was 90%. Our data demonstrate that radiation therapy effects disease-free survival rates that are comparable to those produced by surgery, without sacrificing voice. Although a small percentage of patients with selected early glottic lesions may be more effectively treated with primary conservation surgery, these data do not support a change in philosophy concerning primary treatment of early glottic cancer with radiation therapy. 
1	Pathologic characteristics of human T-cell lymphotropic virus (HTLV)-related extranodal orofacial lymphomas. Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of four HTLV-related and seven HTLV-unrelated EOFL, were investigated with respect to the immunohistochemical and clinical features. HTLV-related EOFL were of T-cell phenotype and were associated with a poorer prognosis than HTLV-unrelated EOFL, most of which were of B-cell origin. The appearance of giant cells with cerebriform nuclei was helpful in identifying HTLV-related EOFL. The relatively high incidence of T-cell type EOFL in our series was considered to be related to the high percentage of HTLV carriers in our district, an area endemic for adult T-cell leukemia-lymphoma. 
5	Clinical experience with the Nimbus pump. The Nimbus pump is an indwelling, electromagnetic powered left ventricular (LV) assist device inserted transfemorally. The inflow cannula (7 mm) is positioned across the aortic valve and the pump in the descending aorta. Indications for insertion include cardiogenic shock despite maximal medical support and PCWP greater than 18 mmHg, MAP less than 90 mmHg, and Cl less than 2 L/min/m2. Twelve patients underwent the attempt at surgical insertion of the Nimbus pump. Diagnoses included eight acute myocardial infarctions (AMI), two ischemic cardiomyopathy, one postpartum cardiomyopathy, and one transplanted heart rejection. Eight (67%) of twelve patients had successful insertion. One patient had peripheral vascular disease preventing passage, and three had femoral vessels too small for insertion (less than 7.5 Hagar dilator). Five patients with the diagnosis of AMI had successful insertion and three (60%) underwent sufficient LV recovery for removal of the device; the other two patients died of stroke and ventricular arrhythmias, respectively. Three patients with the diagnosis of cardiomyopathy had progression of the disease process, and their needs exceeded the capabilities of the pump and they died of multiorgan failure. The Nimbus pump is an attractive LV assist device because of its pumping capacity (3.5 L/min) and minor surgical procedure for insertion. However, its application is limited because of access route and size. The device appears to work well for patients in cardiogenic shock after AMI (60% recovery) but does not appear indicated for patients with cadiomyopathy. 
5	Patients with mental disorders who work. Mental illness can devastate persons intellectually and emotionally; with maintenance therapy, however, certain patients with chronic mental illnesses are capable of holding a variety of jobs. From the total population of psychiatric patients in our VA outpatient clinic, the 87 who were gainfully employed were identified to determine common factors among them. Affective disorders were the predominant diagnoses among patients who worked, while schizophrenia was more common among those who did not. Alcoholism was diagnosed in approximately 25% of working and nonworking groups. 
4	Hepatic resection for advanced hepatocellular carcinoma with removal of portal vein tumor thrombi. In 13 of 398 patients who underwent hepatectomy, tumor thrombi of the remnant portal vein was concomitantly removed by the balloon catheter method in 8, an open method under hepatic vascular exclusion in 1, and resection of the occlusive portal segment followed by portal reconstruction in 4. In 8 of these patients the liver was cirrhotic. The mode of hepatectomy consisted of bisegmetectomy or trisegmentectomy in 11, segmentectomy in one, and partial resection in one patient. Two patients died of portal thrombosis or hepatic failure in the hospital. The mean survival in four patients was 12 months. Seven are still alive (mean, 16 months). In the corresponding period, nine patients with occlusive tumor thrombi of the portal confluence were hospitalized without operation and survived up to 4 months (mean, 64 days) after detection of the tumoral occlusion. The causes of death of the nine patients were bleeding esophageal varices, rupture of the tumor, or hepatic failure. It was revealed that removal of tumor thrombi in the remnant portal vein contributes to (1) portal decompression, (2) feasibility of arterial embolization, and (3) increase in resectability of the main tumor. At present, this procedure might be regarded as an emergency procedure for the avoidance of the above lethal impendence, but it may open the door to an adjuvant therapy. 
1	Congenital angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type. The autopsy of a stillborn infant showed an extensive intravascular proliferation of atypical cells throughout the body. There was no infiltration by these cells of the parenchyma of the bone marrow, lymph nodes, or thymus. By histochemistry, these cells were negative for naphthol-ASD-chloroacetate esterase, a marker of granulocytes. By immunohistochemistry, they were reactive with MT-1 and anti-Leu-22, but unreactive with MB-1, L26, anti-Leu-M1, Tu-9, and antihemoglobin antibodies. A few cells reacted with antileukocyte common antigen and UCHL-1. Based on these findings, the lesion was diagnosed as angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type, which occurred congenitally. Most angiotropic lymphomas in the literature are of the B-cell type, and no leukemia virus type I antibody was negative in the mother. 
1	Adverse impact of fibrin clot inhibitors on intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors. Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model. To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors. 
5	Tuberculous psoas muscle abscess following chemoprophylaxis with isoniazid in a patient with human immunodeficiency virus infection. A 34-year-old man with human immunodeficiency virus infection and disseminated Mycobacterium avium and Mycobacterium intracellulare infection developed a right psoas muscle abscess due to Mycobacterium tuberculosis. The abscess occurred 18 months after completion of a 12-month course of chemoprophylaxis with isoniazid that was given because of a positive reaction with purified protein derivative of tuberculin. The adjacent vertebrae did not appear to be involved. The abscess was drained with a percutaneously inserted catheter, and he received standard antituberculous chemotherapy. Three weeks into therapy, a second drainage with a catheter was required. The isolation of two mycobacteria in this patient and the apparent failure of chemoprophylaxis with isoniazid are noted. 
5	Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin. 
4	Catastrophic thrombosis of porcine aortic bioprostheses. Hemodynamically critical thrombotic stenosis of porcine bioprosthetic valves in the aortic position without thrombotic predisposition is rare. Two patients at our institution abruptly manifested thrombotic stenosis of porcine bioprosthetic valves in the aortic position within 3 months of implantation without apparent predisposing factors. Clinicians should consider this rare but catastrophic complication in the appropriate setting. 
5	Unsupervised children in vehicles: a risk for pediatric trauma. In this study, a series of instances of children injured by a motor vehicle set in motion by an unsupervised child are reviewed. During a 24-month period, nine such children were identified through a multihospital and coroner's office monitoring system in a single urban county. Injuries ranged from multiple abrasions and contusions to serious leg and head injuries. Three children died. The typical circumstance involved a child releasing the brake or placing the vehicle in gear in a private driveway which resulted in the vehicle striking or rolling over the victim. In four of the nine cases, the child who set the vehicle in motion fell or jumped from the vehicle and then became the injured victim. The extent of these unusual motor vehicle-related injuries is unknown because they are unlikely to be reported in official police statistics. According to the study findings, there is a need to educate the public and health professionals about the risks associated with leaving a child unattended in a motor vehicle and the hazardous environment of the private driveway. Preventive measures would include not leaving a child unattended in a vehicle, locking unattended vehicles to prevent access, and redesigning of private driveways. 
1	Cadherin cell adhesion receptors as a morphogenetic regulator. Cadherins are a family of cell adhesion receptors that are crucial for the mutual association of vertebrate cells. Through their homophilic binding interactions, cadherins play a role in cell-sorting mechanisms, conferring adhesion specificities on cells. The regulated expression of cadherins also controls cell polarity and tissue morphology. Cadherins are thus considered to be important regulators of morphogenesis. Moreover, pathological examinations suggest that the down-regulation of cadherin expression is associated with the invasiveness of tumor cells. 
1	Pathologic fracture through a solitary enchondroma of the radial diaphysis: case report. Solitary enchondromata are rare but well recognised benign bone tumours. They are extremely rare in the radius. We report the case of a pathologic fracture through a solitary enchondroma in the radial diaphysis and its successful treatment. 
5	Interlocking intramedullary nailing for supracondylar and intercondylar fractures of the distal part of the femur. Thirty-seven fractures of the distal part of the femur in thirty-five patients were treated with interlocking intramedullary nailing. All fractures were nailed by a closed technique after any intercondylar extension of the fracture had been managed by reduction and stabilization with percutaneous lag-screws. Patients who had an isolated condylar fracture or a severely comminuted intercondylar fracture were treated with other types of implants. There were thirty extra-articular (type-A) fractures and seven intra-articular (type-C1 and type-C2) fractures. Postoperatively, early mobilization exercises and weight-bearing were begun. At an average duration of follow-up of 20.5 months (range, fifteen to twenty-six months), all thirty-seven fractures had healed. There were no malunions of either the supracondylar or the intercondylar fractures. Complications were infrequent and included chronic irritation from the distal screws in three patients and delayed union in one; the latter healed with two centimeters of shortening after bone-grafting. There were no infections. The functional results were assessed with the modified knee-rating system of The Hospital for Special Surgery. Thirteen knees (35 per cent) had an excellent result; twenty-two (59 per cent), a good result; and two (5 per cent), a fair result. The results correlated with the age of the patient and the presence of an intra-articular fracture. We concluded that closed interlocking intramedullary nailing is an excellent technique for both supracondylar and simple intercondylar fractures in which closed reduction and percutaneous fixation of the articular fracture is possible. 
4	Preservation of regional myocardial function during coronary angioplasty with an autoperfusion balloon catheter: a case report. Echocardiographic assessment of regional myocardial function was performed during standard balloon coronary angioplasty followed by autoperfusion balloon angioplasty of a proximal left anterior descending artery stenosis. Septal and apical akinesis occurred within 60 seconds of standard balloon inflation, but regional function was well preserved during prolonged autoperfusion balloon inflation. 
4	Successful direct PTCA on LAD after first episode of acute myocardial infarction: does it improve cardiac function? Patients who received direct percutaneous transluminal coronary angioplasty (PTCA) after acute mycardial infarction and maintained potency but with unimproved cardiac function were studied. In 15 patients, the first episode of acute myocardial infarction was caused by a left anterior descending branch lesion; 11 had an ejection fraction of 50% or more in the left ventriculogram in the follow-up period (improved group), and 4 patients had ejection fraction of less than 50% (unimproved group). There was so significant difference between the groups in the mean time between the onset of infarction and revascularization (improved group, 259.3 +/- 76.9 min; unimproved group, 168.0 +/- 101.6 min) or in the sigma Q. which was the sum of the Q wave depth of V2, V3, and V4 at the time of admission (improved group, 12.1 +/- 15.6 mm; unimproved group 29.8 +/- 13.4 mm). The maximum creatine kinase concentration was significantly higher in the unimproved group (improved group 2670 +/- 893 IU/L; unimproved group, 7243 +/- 1928 IU/L, p less than 0.05), and the time taken from the onset to reach its peak was significantly shorter in the unimproved group (improved group, 13.0 +/- 5.1 hr; unimproved group, 6.8 +/- 1.3 hr, p less than 0.05.) These results suggest the probability of sudden deterioration of myocardium, and factors other than microcirculatory thromboembolism should be considered as the cause of unimproved cardiac function after successful direct PTCA. 
4	Traumatic rupture of the thoracic aorta presenting as transient paraplegia. A patient involved in a high-speed motor vehicle accident presented paraplegic to the emergency department. He was noted to have an abnormal chest x-ray and, subsequently, underwent aortography which revealed aortic transection. The patient's paraplegia resolved spontaneously prior to definitive aortic repair hours later. Aortic rupture presenting as paraplegia is a rare association, but one an emergency physician should be cognizant of, especially in the case of blunt or decelerating trauma. 
5	Neurohormonal factors in functional dyspepsia: insights on pathophysiological mechanisms. Neurohormonal factors were investigated in 10 patients with functional dyspepsia who had normal or slow upper gut transit and 10 age- and sex-matched healthy controls. Gastric and small bowel motility and transit, jejunal responses to luminal distention and IM neostigmine, gut hormones, and vagal and sympathetic functions were studied. Slow upper gut transit was defined by a gastric emptying slope less than 0.3%/min or 10% small bowel transit time greater than 300 minutes. Four patients with slow transit had reduced postprandial antral motility and gut hormone responses. Two of the four patients had vagal and sympathetic dysfunction. In 6 patients with normal transit, balloon distention in the jejunum was perceived at a lower volume (32.7 +/- 5.9 mL) than in controls (46.6 +/- 3.0 mL). Pressure responses to balloon distention were reduced in 5 and exaggerated in 1 patient; abnormal efferent vagal (2 patients) and sympathetic (1 patient) function were also documented. In view of the normal transit, motility, and jejunal pressure responses to neostigmine in all 6 patients, the abnormal response to distention suggests afferent dysfunction. Functional dyspepsia is a heterogenous disorder. Abnormal transit is sometimes associated with disorders of extrinsic neural control, but the latter are also found in patients with normal transit. Increased perception of intraluminal stimuli in those with normal transit suggests a disturbance in afferent function. 
2	Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus infection in twins. Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed. 
3	Distinguishable types of dyspnea in patients with shortness of breath. Dyspnea frequently accompanies a variety of cardiopulmonary abnormalities. Although dyspnea is often considered a single sensation, alternatively it may encompass multiple sensations that are not well explained by a single physiologic mechanism. To investigate whether breathlessness experienced by patients represents more than one sensation, we studied 53 patients with one of the following seven conditions: pulmonary vascular disease, neuromuscular and chest wall disease, congestive heart failure, pregnancy, interstitial lung disease, asthma, and chronic obstructive pulmonary disease. Patients were asked to choose descriptions of their sensation(s) of breathlessness from a dyspnea questionnaire listing 19 descriptors. Cluster analysis was used to identify natural groupings among the chosen descriptors. We found that patients could distinguish different sensations of breathlessness. In addition, we found an association between certain groups of descriptors and specific conditions producing dyspnea. These findings concur with those in an earlier study in normal volunteers in whom dyspnea was induced by various stimuli. We conclude that different types of dyspnea exist in patients with a variety of cardiopulmonary abnormalities. Furthermore, different mechanisms may mediate these various sensations. 
1	Comparison of STIR and spin-echo MR imaging at 1.5 T in 45 suspected extremity tumors: lesion conspicuity and extent. Short inversion time inversion recovery (STIR) imaging and a double-echo spin-echo (SE) sequence at 1.5 T in 45 sequential patients with suspected extremity tumors were compared to assess the number of lesions detected, subjective conspicuity of lesions, approximate volume of abnormality detected in each lesion, and identification of peritumoral brightening in tissues adjacent to each lesion. STIR sequences enabled detection of all 45 lesions; 44 were detected with the SE sequence. Tumor appeared most conspicuous on STIR images in 35 patients (78%) and was most conspicuous on SE images in 10 patients (22%). Peritumoral brightening, which indicated either peritumoral edema or microscopic tumor infiltration, was detected in 20 patients but was detected only with STIR sequences in nine patients. It is concluded that, although STIR and SE sequences are comparable for lesion detection in the extremities, most lesions appear more conspicuous with STIR. STIR may enable detection of a greater volume of abnormality than SE sequences and may therefore have important implications for local staging and surgical and radiation therapy planning. 
5	Surgical management of islet cell dysmaturation syndrome in young children. Islet cell dysmaturation syndrome (ICDS) encompasses the causes of infantile hyperinsulinemic hypoglycemia histologically described as islet cell hyperplasia, pancreatic adenomatosis and nesidioblastosis. Eleven infants underwent 14 pancreatic resections for ICDS from 1965 to 1990 at the University of California at Los Angeles Medical Center for severe hypoglycemia unresponsive to medical therapy. Seizures were the presenting symptoms of hypoglycemia in eight infants. Six patients had nesidioblastosis, four had islet cell hyperplasia and one patient had an adenoma with histologically normal pancreatic islet cells. Four neonates underwent 80 per cent pancreatic resection; three with nesidioblastosis required reoperation (90 to 95 per cent resection). Four older infants underwent 80 per cent pancreatic resection but required diazoxide for less than six months postoperatively. Three infants underwent 90 to 95 per cent pancreatic resection. None have required reoperation or postoperative medications. All infants are normoglycemic without pancreatic exocrine insufficiency and none had postoperative complications. Five infants had preoperative neurologic impairment, with three having severe retardation; all showed some improvement postoperatively, but only one infant now has normal findings on neurologic examination. Early diagnosis and aggressive surgical resection should minimize neurologic complications of the ICDS. 
3	Midazolam-induced benzodiazepine withdrawal syndrome A case history of a patient who developed severe anxiety and agitation on two occasions after discontinuation of a midazolam infusion is presented. The withdrawal symptoms interfered with effective mechanical ventilation and the patient required the reintroduction of a long-acting benzodiazepine to treat the withdrawal state and to facilitate weaning from mechanical ventilation. 
4	Transesophageal echocardiography is superior to transthoracic echocardiography in the diagnosis of sinus venosus atrial septal defect. The purpose of this study was to compare transthoracic and transesophageal echocardiography in the diagnosis of various types of atrial septal defects. Forty-one adult patients with the clinical diagnosis of atrial septal defect were studied by transthoracic and transesophageal echocardiography (30 women, 11 men; 18 to 81 years of age). Transthoracic echocardiography demonstrated the atrial septal defect in 33 patients (secundum type in 28, primum type in 3 and sinus venosus type in 2). Transesophageal echocardiography demonstrated the defect in all 41 patients. Thus, in 8 (20%) of 41 patients the atrial septal defect was demonstrated by transesophageal and not by transthoracic echocardiography. Six of the eight had a sinus venosus type atrial septal defect; the other two patients had a secundum atrial septal defect (one of these two had a technically poor transthoracic echocardiogram and the other had a small atrial septal defect). Transthoracic echocardiography, therefore, failed to demonstrate the sinus venosus defect in six (75%) of eight patients. An anomalous venous connection associated with the sinus venosus defect was visualized by transesophageal echocardiography in seven of the eight patients but was not seen on transthoracic echocardiography in any patient. Sinus venosus type atrial septal defects are frequently not visualized in adults by conventional transthoracic echocardiography. Transesophageal echocardiography is recommended when an atrial septal defect is clinically suspected but cannot be visualized by transthoracic echocardiography. 
5	The epithelial changes associated with squamous cell carcinoma of the vulva: a review of the clinical, histological and viral findings in 78 women. Seventy-eight excised specimens of squamous cell carcinoma of the vulva were reviewed retrospectively for the presence of lichen sclerosus or vulvar intraepithelial neoplasia (VIN) at sites proximal to the tumour or more distant. Lichen sclerosus was evident in 61% and VIN alone in 31%. VIN III (differentiated) was associated with over 50% of the specimens with lichen sclerosus. HPV 16 was found in six of the 11 VIN lesions, investigated but in none of the six with lichen sclerosus. 
3	Vascular abnormalities in epidermal nevus syndrome. We report a patient with epidermal nevus syndrome and right hemispheric infarct and review 3 others with neurologic manifestations best explained by ischemia or hemorrhage. Each had a significant vascular abnormality such as occlusion or blood vessel dysplasia. None had hemimegalencephaly. We hypothesize that underlying vascular dysplasia is the cause of the neurologic lesions in these patients. 
1	Is DNA ploidy of prognostic significance in stage I cutaneous melanoma? Recent studies have suggested that the presence of DNA aneuploidy in stage I cutaneous melanoma carries a poor prognosis. To see if our experience correlated with these reports, we used DNA analysis by flow cytometry of propidium iodide-stained nuclei disaggregated from formalin-fixed paraffin-embedded tissue of biopsy specimens to retrospectively study 55 patients who had cutaneous stage I melanomas. The patients had been treated from 1977 to 1987 with a mean follow-up of 5.4 years. Thirty-nine (71%) of the 55 histograms were diploid, and 16 (29%) of the histograms were aneuploid. DNA content was significantly associated with other conventional prognostic factors, including growth pattern, ulceration, pathologic stage, tumor thickness, and Clark's level. DNA aneuploidy was significantly related to disease-free survival and predicted a poorer prognosis (p less than 0.05), but when stratified for tumor thickness it lost significance. A multivariate discriminant function analysis of 12 factors in melanoma showed six factors to be independently significant in determining prognosis. DNA content (p = 0.034) ranked fifth in importance behind growth pattern (p less than 0.001), ulceration (p less than 0.001), thickness (p = 0.001), and pathologic stage (p less than 0.005). DNA content, although significantly associated with conventional prognostic factors and disease-free survival, is not the best indicator of biologic behavior of melanomas in this study. Further investigation into its usefulness is necessary before DNA content can become a routine diagnostic modality in the work-up of stage I cutaneous melanomas. 
1	Diffusion and binding of monoclonal antibody TNT-1 in multicellular tumor spheroids. Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets necrotic cells of tumors. Our data reveal that there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment bound poorly to the spheroids. Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids. These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micrometastases. 
5	Translumbar arch aortography: a retrospective controlled study of usefulness, technique, and safety. Subclavian and axillary artery stenoses may lead to axillofemoral bypass graft failure. These arteries were assessed preoperatively with arch aortography performed after conventional high translumbar peripheral aortography by exchanging the initial 16-gauge sheath for a 5-F pigtail catheter. Thirty-two diagnostic translumbar runoff and arch (TLR-arch) aortograms were obtained in 30 patients with advanced lower extremity ischemia. In six patients (20%), the results of the arch study influenced the choice of an inflow site. These patients were compared with 70 control subjects who underwent conventional translumbar aortography without arch studies. In the TLR-arch group, two major complications occurred in one patient, while in the control group 11 major complications occurred in 10 patients. One retroperitoneal hematoma occurred in the TLR-arch group; two occurred in the control group. The mean change in hematocrit for the TLR-arch group was -3.81% (-0.0381), and for the control group it was -4.17% (-0.0417). This difference was not statistically significant. Arch aortography is a valuable adjunct to the translumbar aortofemoral study. It can be simply performed without increasing the morbidity of the peripheral study. 
3	Carotid endarterectomy for elderly patients: predicting complications OBJECTIVE: To determine whether the complication or death rate from carotid endarterectomy can be predicted from hospital and physician structural variables, such as the hospital's teaching status or the number of endarterectomies done by the surgeon per year. DESIGN: Survey of medical records. After controlling for the severity of the patient's condition on the basis of data in the medical record at the time of the endarterectomy, regression analyses were used to predict the postoperative stroke, heart attack, and 30-day death rate as a function of patient, physician, and hospital characteristics. SETTING: Three geographic areas (states or large parts of states; average population, 3 million) in the United States. PATIENTS: Random sample of 1302 patients 65 years of age or older having carotid endarterectomy in 1981. INTERVENTION: Carotid endarterectomy. MEASUREMENTS AND MAIN RESULTS: Of 1302 patients, 11.3% had a postoperative stroke or heart attack or died within 30 days of the operation. Patient age, race, income, and gender; physician volume, board certification status, and age; and hospital size, for-profit status, ownership, and teaching status were not significantly related to the postoperative complication or death rate. If the surgeon was a graduate of a foreign, but not a Western European or Canadian, medical school, however, the average complication or death rate rose from 10.4% to 19.6% (P less than 0.05). CONCLUSIONS: The effectiveness of carotid endarterectomy depends heavily on its complication rate. Because complications after surgery cannot, in general, be predicted from structural variables, referring physicians cannot rely solely on the surgeon's experience and qualifications when recommending a carotid endarterectomy. The surgeon's and the hospital's actual postoperative complication and death rate should be considered. 
5	Clinical and molecular diagnosis of Miller-Dieker syndrome. We report results of clinical, cytogenetic, and molecular studies in 27 patients with Miller-Dieker syndrome (MDS) from 25 families. All had severe type I lissencephaly with grossly normal cerebellum and a distinctive facial appearance consisting of prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip, thin vermilion border, and small jaw. Several other abnormalities, especially growth deficiency, were frequent but not constant. Chromosome analysis showed deletion of band 17p13 in 14 of 25 MDS probands. RFLP and somatic cell hybrid studies using probes from the 17p13.3 region including pYNZ22 (D17S5), pYNH37 (D17S28), and p144-D6 (D17S34) detected deletions in 19 of 25 probands tested including seven in whom chromosome analysis was normal. When the cytogenetic and molecular data are combined, deletions were detected in 21 of 25 probands. Parental origin of de novo deletions was determined in 11 patients. Paternal origin occurred in seven and maternal origin in four. Our demonstration of cytogenetic or molecular deletions in 21 of 25 MDS probands proves that deletion of a "critical region" comprising two or more genetic loci within band 17p13.3 is the cause of the MDS phenotype. We suspect that the remaining patients have smaller deletions involving the proposed critical region which are not detected with currently available probes. 
5	Successful treatment of severe premenstrual syndrome by combined use of gonadotropin-releasing hormone agonist and estrogen/progestin Although abolishment of ovarian cyclicity by the use of a long-acting GnRH agonist (GnRH-a) provides effective treatment for premenstrual syndrome (PMS), its use is limited by sequellae of the resultant hypoestrogenism. In this study the effects of estrogen/progestin replacement on the symptomatic improvement afforded by GnRH-a were evaluated in eight women with severe PMS. The 8-month study design included 2 months of control, 2 months of GnRH-a alone, and 4 further months in which the exogenous steroids were replaced in randomized, double blind, placebo-controlled cross-over fashion using 1 month each of 1) conjugated equine estrogen (CEE) on days 1-25, 2) 10 mg medroxyprogesterone acetate (MPA) on days 16-25, 3) CEE (days 1-25) plus MPA (days 16-25), and 4) placebo alone. Mood and physical symptoms were measured daily on a valid and reliable instrument, the Calendar of Premenstrual Experiences. As expected, administration of GnRH-a alone resulted in a 75% improvement in luteal phase symptom scores (17.8 +/- 4.8 vs. 4.2 +/- 1.6; P less than 0.01). Combined sequential administration of CEE and MPA in addition to GnRH-a was effective in maintaining the reduced symptom scores seen after GnRH-a alone and was superior to the addition of CEE alone, MPA alone, or placebo. This combination of CEE and MPA resulted in a 60% improvement (P less than 0.05) compared to the luteal phase of control months in both behavioral (14.1 +/- 3.9 vs. 4.2 +/- 0.8) and total (17.8 +/- 4.8 vs. 6.5 +/- 1.8) symptoms. We conclude that the undesirable consequence of ovarian steroid deficiency in the treatment of PMS by GnRH-a can be overcome by the addition of sequential estrogen and progestogen replacements without significantly reducing the effectiveness of GnRH-a in this disorder. 
1	Carcinoma of the vulva. Clinicopathologic factors involved in inguinal and pelvic lymph node metastasis. Eighty-five women with vulvar squamous cell carcinoma were subjected to radical vulvectomy with bilateral inguinal and femoral node dissection or to radical vulvectomy with bilateral inguinofemoral and deep pelvic node dissection. The association between lymph node status (metastatic or not) and several parameters was analyzed: tumor location, size and clinical stage; tumor thickness, histologic grade and mitotic index; blood vessel, lymphatic and perineural infiltration; and lymphocytic and plasma cell infiltrates. There were no metastases to the pelvic lymph nodes without previous inguinal lymph node involvement. Unilateral vulvar carcinomas did not have contralateral metastatic nodes when there was no ipsilateral nodal involvement. Lymphatic vessel infiltration showed a statistically significant correlation with inguinal node metastases (P less than .05). No correlation was found between lymph node metastasis and tumor size, clitoral invasion, tumor thickness, histologic grade, blood vessel and perineural infiltration, lymphocytic and plasma cell infiltrates, and mitotic index. 
2	Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom. To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome. 
4	A rare case of renovascular hypertension due to iatrogenic thoracoabdominal aortic dissection. A report of successful surgical treatment in childhood. Renovascular hypertension due to iatrogenic thoracoabdominal aortic dissection in an 8-year-old girl with aortic valvular stenosis is presented. A splenorenal arterial anastomosis without splenectomy was successfully performed. This procedure is considered best suited for children with thoracoabdominal aortic dissection as the autogenous graft is expected to grow and provide long-term patency. The spleen left in situ was expected to be advantageous, from the immunological aspect, at the time of open heart surgery for aortic valvular stenosis, which was anticipated in the near future in this child. 
4	Reentrant ventricular arrhythmias in the late myocardial infarction period: mechanism by which a short-long-short cardiac sequence facilitates the induction of reentry. The electrophysiological mechanism by which a short-long-short stimulated cardiac sequence facilitates the induction of ventricular tachyarrhythmia was investigated in dogs 4 days after ligation of the left anterior descending coronary artery. In these dogs, reentry develops in the surviving electrophysiologically abnormal epicardial layer that overlies the infarct zone when premature stimulation results in a critically long arc of functional conduction block. The activation wavefront circulates around both ends of the arc, coalesces, and conducts slowly distal to the arc before reactivating sites proximal to the arc to initiate a figure-eight reentrant circuit. Epicardial isochronal activation maps and effective refractory periods (ERPs) were determined during three different stimulation protocols: A, a basic train of eight beats at a cycle length of 300 msec followed by a single premature stimulus (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt lengthening of the last cycle of the train before S2 to 600 msec; C, a basic train of eight beats at a cycle length of 600 msec followed by S2. Protocol B was found to result in a differential lengthening of ERP at adjacent sites within the border of the epicardial ischemic zone, whereas protocols A and C induced, respectively, comparable shortening and lengthening of ERPs at the same sites. The differential lengthening of ERPs at adjacent sites resulted in an increased dispersion of refractoriness so that a premature stimulus induced functional conduction block between those sites. The development of a longer arc of conduction block and, hence, a longer reentrant pathway as well as slower conduction of the circulating wavefront during protocol B allowed more time for refractoriness to expire proximal to the arc and for the circulating wavefront to reexcite those sites to initiate reentry. The lengthening of ERP, associated with a single long cycle (protocol B), ranged from 44% to 79% of the total increase in ERP after a series of eight long cycles (protocol C). Epicardial sites with longer ERPs located close to the center of the ischemic zone showed more lengthening of refractoriness during protocol B compared with more normal sites near the border of the ischemic zone. This strongly suggests that the increased dispersion of refractoriness during protocol B is caused by the shorter memory of ischemic myocardium to the cumulative effects of preceding cycle lengths. 
1	Ultrastructural demonstration of peroxidase expression in acute unclassified leukemias: correlation to immunophenotype and treatment outcome. The lineage affinity of 57 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping and analysis of immunoglobulin gene configuration. Twenty-three cases of myeloid and three cases of megakaryocytic differentiation were identified by detection of ultrastructural myeloperoxidase (UMPO) and platelet peroxidase (UPPO). No significant correlation was noted between myeloid marker expression and POEM positivity, whereas presence of CD 19 or CD 24 antigen significantly correlated with POEM negativity (P = .001 and .023, respectively). Ig gene rearrangements including oligoclonal patterns were also recorded in 8 of 14 UMPO+ patients tested. Fourteen UMPO+ patients responded poorly to an ALL/AUL chemotherapy regimen with a low complete remission (CR) rate of 29% and a short median remission duration (MRD) of 5 months. The POEM- patients proved very heterogenous with respect to immunophenotype and Ig gene rearrangement. Seventeen of 21 patients tested had Ig gene rearrangements, including oligoclonal patterns. Combined data suggest that a proportion of these cases probably derive from a very immature lymphoid progenitor cell, particularly because 15 POEM- AUL patients showed a response to ALL/AUL chemotherapy comparable to that observed in patients with definitive acute lymphoblastic leukemia (ALL) (CR rate 80%, MRD 20 months). Thus, ultrastructural analysis of peroxidase expression can provide decisive prognostic information in AUL patients. 
5	Short-term variability of ventricular arrhythmia and rapid assessment of drug efficacy. Statistical criteria for suppression and aggravation of ventricular arrhythmia were defined by means of 50 short-term drug tests performed in 24 patients. Each patient's spontaneous variability (SV) was evaluated by linear regression analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter monitoring. The response to a single oral dose of disopyramide, 300 mg, flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting 4 hours. Lidocaine was administered intravenously in incremental doses of up to 4 mg/min and was evaluated over 3 hours. Threshold values of ventricular arrhythmia corresponding to 95% confidence limits were calculated from baseline recordings and were used to ascertain the likelihood of a true drug effect. The minimum decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while an increase of at least 947% was required for a proarrhythmic effect. When these efficacy criteria were applied, 16 of 50 short-term tests revealed no drug effect. In contrast, when a 70% threshold derived from studies of daily variability was employed, only 7 of 50 trials were negative. Thus individual determination of hourly arrhythmia variability yields more stringent criteria than extrapolation from day-to-day spontaneous variation. 
3	Rehabilitation in brain disorders. 1. Basic sciences. This learning module highlights the basic sciences of brain disorders and their relevance to the rehabilitation process. It is part of the chapter on rehabilitation in brain disorders for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. The chapter is composed of four articles, and each builds on principles established in the others. This article contains essential information on the hierarchy and integration of cerebral neural processes, functional anatomy, and neurochemistry. It also highlights newer advances in brain plasticity and response to injury, at a cellular level and with reference to acute and secondary processes, which will likely be at the forefront of medical management and functional "damage control" in the near future. The learner is directed to articles 2, 3, and 4 in this chapter for supporting information. 
1	Implementation of cancer prevention guidelines in clinical practice. Data from several sources, including consumer surveys, physician surveys, and medical record audits, indicate that consumers do not receive cancer screening tests as recommended by the National Cancer Institute, the American Cancer Society, and the U.S. Preventive Services Task Force. Performance rates are consistently below published standards for all tests except Pap tests. Major reasons physicians do not perform the recommended tests include physician forgetfulness, disagreement with recommendations, lack of time, and patient refusal. Physicians also tend to overestimate their own performance rates. Barriers to screening test performance can be categorized into patient factors, physician factors, test factors, and health care delivery system factors. Interventions, such as computerized reminder systems, physician audits with feedback, and patient education and reminders, can be effective in promoting performance of such screening. Interventions that target both physician and patient may be particularly effective. 
4	Vascular abnormalities in epidermal nevus syndrome. We report a patient with epidermal nevus syndrome and right hemispheric infarct and review 3 others with neurologic manifestations best explained by ischemia or hemorrhage. Each had a significant vascular abnormality such as occlusion or blood vessel dysplasia. None had hemimegalencephaly. We hypothesize that underlying vascular dysplasia is the cause of the neurologic lesions in these patients. 
1	Epitope mapping of human thyroglobulin. Heterogeneous recognition by thyroid pathologic sera. Thyroglobulin is the major Ag of the thyroid gland involved in autoimmune pathologies. Epitope mapping was carried out with a rabbit polyclonal immune serum against fusion proteins expressed in prokaryotic cells. After screening of an initial human thyroglobulin cDNA library and subcloning of immunoreactive clones, seven epitopes were characterized and localized on the human thyroglobulin monomeric molecule. One was close to each extremity of the molecule, and five others were concentrated in the middle, covering a sixth of this 2748-amino-acid chain. The immunoreactivities of 18 autoimmune sera from different thyroid pathologies were tested against the seven previously characterized epitopes. Those from Hashimoto's thyroiditis were the most immunoreactive. Immune responses were heterogeneous for sera from different pathologies as well as for those from the same pathology. The central epitopes and the near-C-terminal epitope, however, were the epitopes most often recognized by the immune sera. These findings show that some autoepitopes overlap accurately with some heteroepitopes characterized by a polyclonal immune serum directed against the mature protein. 
2	Esophageal contribution to chest pain in patients with coronary artery disease. We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients. 
3	Use of intravenous stilbestrol diphosphate in patients with prostatic carcinoma refractory to conventional hormonal manipulation. The patient presenting with severe bone pain after primary hormonal therapy, with vertebral collapse, or with uremia resulting from ureteric obstruction should be considered for intravenous stilbestrol diphosphate therapy. The urologist can expect early marked improvement in the patients' mobility and pain, with a reduction in analgesic requirements, from a single 7-day course of treatment. In addition, the drug is inexpensive and free of the side effects commonly associated with cytotoxic therapy. Accurate monitoring of the response is possible with serum prostate-specific antigen measurements, which also enable further therapy to be planned efficiently. 
4	Calcium channel blockers in geriatric hypertension. Though the calcium channel blockers have been used to treat angina pectoris for almost a decade, the long-acting forms of these agents that have become available in the last few years have made them practical for use as antihypertensive agents as well. They are becoming increasingly popular in this role, especially to treat elderly hypertensive patients. Because they are vasodilators with a mild diuretic action, they are logical treatment choices for the majority of hypertensive patients who have increased peripheral vascular resistance. They offer the advantage of a dual benefit for hypertensive patients with angina, and they have no effect on carbohydrate or lipid metabolism. Disadvantages include cost and a side effect profile that includes headaches, palpitations, ankle edema, and constipation. 
3	Selected neurologic complications of pregnancy. Many neurologic disorders, such as eclampsia, pseudotumor cerebri, stroke, obstetric nerve palsies, subarachnoid hemorrhage, pituitary tumors, and choriocarcinoma, can develop in the pregnant patient. Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion. Pseudotumor cerebri can be associated with serious visual complications; thus, the therapeutic goal is to prevent loss of vision. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The major causes of stroke in pregnant patients are arterial occlusion and cerebral venous thrombosis. Lumbar disk prolapse is common in pregnant patients, and lumbosacral plexus injuries can occur during labor or delivery. In addition, peripheral nerve compression or entrapment syndromes are thought to be caused by the retention of fluid during pregnancy. The incidence of subarachnoid hemorrhage during pregnancy is 1 in every 10,000 patients, a rate 5 times higher than in nonpregnant women. Because of a proliferation of prolactin-secreting cells, the pituitary gland can enlarge dramatically during pregnancy, a change that can disclose a previously unknown tumor or cause a known pituitary tumor to become symptomatic. The incidence of choriocarcinoma is 1 in 50,000 full-term pregnancies but 1 in 30 molar pregnancies. This malignant tumor has a high rate of cerebral metastatic lesions. In addition to these disorders that develop during pregnancy, the pregnant state can affect numerous preexisting neurologic conditions, including epilepsy, headaches, multiple sclerosis, myasthenia gravis, spinal cord injury, and brain tumors. We discuss advice for patients with such conditions who wish to become pregnant, recommendations for medical and surgical management, and surgical considerations for neurologic complications during pregnancy. 
3	The role of pain in the last year of life of older persons. A random sample of 200 decreased older community residents was studied with a focus on the role of pain in the last year of life. Interviews with a surviving close person elicited retrospective reports. Pain increased over the final year; one month before death 66% felt pain frequently or all of the time, substantially higher than a matched comparison group of living persons (24%). For both groups across the year, pain was associated with most measures of behavioral competence, perceived quality of life, and psychological well-being. Hierarchical multiple regressions indicated that background and health variables explained 28% to 32% of the variance of pain over the year. Controlling for background variables and health, pain contributed significantly to lowered happiness and to depression, but had no independent impact on hope and interest in the world. After controlling for physical health, the older old were judged to have less pain than the younger old. 
5	Localization of malignant melanoma using monoclonal antibodies. Finding a screening test to evaluate patients with cancer for occult metastatic disease, as well as imaging all known disease, is a goal of research efforts. Twenty-nine evaluable patients with deeply invasive (stage I), regional nodal (stage II), or systemic (stage III) melanoma underwent imaging by administration of a preparation of the antimelanoma antibody labeled with technetium 99m. Scan results indicated that 28 of 32 confirmed metastatic sites were imaged with this technique (88% sensitivity). Analysis of the individual positive sites revealed that nodal basins and visceral metastases accounted for the highest percentage of metastatic sites imaged, with 14 (88%) of 16 nodal basin metastases and all four visceral metastases being detected through imaging. Occult nodal disease was detected in the iliac nodal chain in two of the 29 patients. The imaging of benign tumors and nodal basins not containing disease accounted for a confirmed false-positive rate of 21%. Three (10%) of the 29 scan results were confirmed to be false-negative. In vivo tumor localization with monoclonal antibodies showed a sensitivity similar to that of other roentgenographic procedures for identifying metastatic disease and was useful in two of three patients in identifying occult iliac nodal disease, a region that is difficult to evaluate with physical examination and other imaging modalities. 
1	Biologic aggressiveness of palpable and nonpalpable prostate cancer: assessment with endosonography. The biologic aggressiveness of palpable versus nonpalpable prostate cancer was evaluated in 666 patients studied with endosonography over a 24-month period. Biologic aggressiveness was defined by a combined histologic and grade-stage category score. In 314 patients suspected of having prostate cancer 328 biopsies were performed. Carcinoma was detected in 99 patients, by means of both palpation and endosonography (n = 80), endosonography alone (n = 9), and palpation alone (n = 8); two cancers were not detected with either palpation or endosonography. All patients with normal results of digital examination had a combined grade-stage category score lower than 9. Fifty-five of 69 patients (80%) with abnormal results of digital examination and available histologic data had a histologic score of 6 or higher; 38 of these patients (69%) had a combined grade-stage category score of 9 or higher. Although the number of patients is small, these data suggest that nonpalpable cancers are biologically less aggressive than palpable ones and that the advantage of endosonography over palpation in detection of clinically significant cancers is limited. 
3	Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice. The lysosomal storage disorder glycogenosis type II is caused by acid alpha-glucosidase deficiency. In this study we have investigated the possible applicability of mannose 6-phosphate receptor-mediated enzyme replacement therapy to correct the enzyme deficiency in the most affected tissues. Bovine testes acid alpha-glucosidase containing phosphorylated mannose residues was intravenously administered to mice and found to be taken up by heart (70% increase of activity) and skeletal muscle (43% increase); the major target organs. The uptake of nonphosphorylated human placenta acid alpha-glucosidase by heart and skeletal muscle appeared to be significantly less efficient, whereas uptake of dephosphorylated bovine testes enzyme was not detectable. The phosphorylated bovine testes acid alpha-glucosidase remained present in mouse skeletal muscle up to 9-15 d after administration, with a half-life of 2-4 d. Besides being measured in skeletal muscle and heart, uptake of phosphorylated bovine testes and nonphosphorylated human placenta acid alpha-glucosidase was measured in several other organs, but not in brain. The increase of acid alpha-glucosidase activity was highest in liver and spleen. We concluded that application of mannose 6-phosphate receptor-mediated enzyme replacement therapy may offer new perspectives for treatment of glycogenesis type II. 
3	Epidermoid tumors of the 4th ventricle: report of seven cases. Epidermoid tumors occur very rarely in the 4th ventricle. We discuss the history, clinical course, and the surgical results for seven patients. One patient had a remittal of symptoms, probably due to the emergence of the tumor from the 4th ventricle into the cisterna magna. Total removal of the capsule was possible only in the youngest patient. At present, four patients (mean follow-up, 6 years) enjoy good general and neurological health. 
5	Fluorometric determination of pseudocholinesterase activity in postmortem blood samples. A fluorometric assay using 3-(p-hydroxyphenyl) propionic acid (HPPA) was conducted to determine the activity of pseudocholinesterase (ChE) [Enzyme Commission (EC) No. 3.1.1.8] in postmortem blood samples so as to test for organophosphate poisoning. By the enzymatic reaction of ChE, its substrate, benzoylcholine, produces choline, which is oxidized by choline oxidase to generate hydrogen peroxide. HPPA is oxidized by hydrogen peroxide and peroxidase to become the fluorogenic dimer whose concentration is measured fluorometrically at an excitation emission wavelength of 320 nm and an elimination emission wavelength of 404 nm. The selectivity and sensitivity of the present method were found to be superior to those of conventional pH and spectrophotometric methods. 
4	Deep vein obstruction and leg swelling caused by femoral ganglion. We present a case of a rare ganglion cyst originating from the hip joint and compressing the common femoral vein producing signs and symptoms that mimicked a deep vein thrombosis. Excision of the mass promptly restored normal venous return. This condition has not been previously reported in the English-language medical literature. 
5	The long-term effectiveness of hysteroscopic treatment of menorrhagia and leiomyomas. One hundred fifty-six of 177 patients admitted to the St. Luke's/Roosevelt Hospital Center between November 1973 and November 1988 for hysteroscopic treatment of menorrhagia and/or uterine leiomyomas were followed for long-term complications and necessity for repeat surgery. Ninety-four patients underwent submucous resection alone and 62 patients underwent endometrial ablation with or without submucous resection. Among the submucous-resection group, 24.5% reported late postoperative problems and 15.9% underwent further surgery. After 9 years of followup, 83.9% of the patients had not required further surgery. Among the ablation group, 22.5% experienced recurrence of increased bleeding and 8.1% had another surgical procedure. After 6 years of follow-up, 91.3% of the patients had not required further surgery. Twenty-one patients became pregnant after submucous resection, with 18 infants delivered. No patients who underwent endometrial ablation became pregnant. This modality of treatment appears to be effective over the long term, although effectiveness appears to diminish with time. 
4	Neonatal calves develop airflow limitation due to chronic hypobaric hypoxia. Neonates and infants presenting with pulmonary hypertension and chronic hypoxia often exhibit airway obstruction. To investigate this association, we utilized a system in which neonatal calves are exposed to chronic hypobaric hypoxia and develop severe pulmonary hypertension. For the present study, one of each pair of six age-matched pairs of neonatal calves was continuously exposed to hypobaric hypoxia at 4,500 m (CH); the other remained at 1,500 m. At 2 wk of age, mean pulmonary arterial pressure (MPAP), dynamic lung compliance (Cdyn), resistance (RL), and static respiratory system compliance (Crs) were measured at 4,500 m in both CH and control calves exposed acutely to hypoxia (C). These measurements were repeated after cumulative administrations of nebulized methacholine (MCh). Tissues were removed for histological examination and assessment of bronchial ring contractility to MCh and KCl. After 2 wk of hypobaric hypoxia, MPAP (C 35 +/- 1.7 vs. CH 120 +/- 7 mmHg, P less than 0.001) and RL (C 2.64 +/- 0.16 vs CH 4.99 +/- 0.47 cmH2O.l-1s, P less than 0.001) increased. Cdyn (C 0.100 +/- 0.01 vs. CH 0.082 +/- 0.007 l/cmH2O) and Crs (CH 0.46 +/- 0.003 vs. C 0.59 +/- 0.009 l/cmH2O) were not significantly different. Compared with airways of C calves, airways of CH animals did not exhibit in vivo or in vitro MCh hyperresponsiveness; however, in vitro contractility to KCl of airways from CH animals was significantly increased. Histologically, airways from the CH calves showed increases in airway fibrous tissue and smooth muscle. 
2	Neonatal diarrhea at a maternity hospital in Rangoon Between 1981 and 1986, 1,540 infants born at the Central Women's Hospital in Rangoon were transferred to the Sick Baby Unit because of diarrhea (15.4 per 1,000 live births). Rates among cesarean infants were five times as high as those of infants born vaginally (51.0 and 10.3 per 1000 live births, respectively). One hundred eighty-four of the infants with diarrhea died (case fatality rate = 12 percent). We conclude that neonatal diarrhea is endemic in this large maternity hospital in Burma, and that control efforts should be targeted especially to cesarean and low birthweight infants. 
5	Puppet-like syndrome of Angelman: a pathologic and neurochemical study. We present the first pathologic descriptions of the puppet-like syndrome of Angelman based on autopsy studies of a 21-year-old woman. The noteworthy findings were a small brain with mild cerebral atrophy but normal gyral development. There was marked cerebellar atrophy with loss of Purkinje and granule cells and extensive Bergmann's gliosis. Study of dendrite morphology using Golgi impregnations of the visual cortex revealed a prominent decrease in dendritic arborization of layer 3 and layer 5 pyramidal neurons. Quantitative Golgi analysis also revealed a significant decrease in the numbers of dendritic spines in apical layer 3 dendrites and both apical and basal layer 5 dendrites. Neurochemical studies of frozen brain tissue demonstrated markedly reduced gamma-aminobutyric acid content in the cerebellar cortex, as well as elevated glutamate content in the frontal and occipital cortices. Although there are no definite morphologic correlates of many of the clinical signs, the pronounced dendritic pathology and neurochemical abnormalities in cerebral cortex may provide a physiologic basis for mental retardation. 
4	Rash after treatment with anistreplase. A palpable purpura developed on the legs and lower abdomen of a woman of 54 five days after she was treated with anistreplase anisoylated plasminogen streptokinase activator complex (APSAC) for an acute myocardial infarction. Histological examination of a skin biopsy specimen taken 6 days after treatment showed leucocytoclastic vasculitis. The rash resolved within two weeks and there were no other complications. 
5	Effects of indomethacin on hepatogenic pulmonary angiodysplasia. A patient had liver cirrhosis associated with marked hypoxemia. With administration of indomethacin (75 mg/day for six days), PaO2 was elevated up to 50 mm Hg from 44 mm Hg. At that time, dynamic pulmonary perfusion imaging revealed a plateau time course curve of MAA uptake in the lungs, as compared with findings obtained during the state of severe hypoxemia without indomethacin. These observations suggest that part of hepatogenic pulmonary angiodysplasia is a functional vasodilatation that is presumably modulated by vasoactive substances, such as prostaglandins and/or other eicosanoids. 
4	Detection of Coxsackievirus B3 RNA in myocardial tissues by the polymerase chain reaction. Coxsackievirus B3 is a possible etiologic agent in some forms of myocarditis and idiopathic dilated cardiomyopathy. A method for the detection of coxsackievirus B3 RNA was developed using the polymerase chain reaction based on the amplification of a cDNA copy of the positive-strand viral RNA. The fidelity of the method was established in two murine models for coxsackie B3 myocarditis. All cardiac specimens with adequate RNA for study from coxsackie B3-infected mice contained detectable viral RNA, in contrast to none of control specimens from noninfected mice. The sensitivity of the technique was established at approximately 1 to 100 plaque-forming units of virus per gram of tissue, and the specificity was established as limited to the coxsackievirus B3 serotype among nine viruses tested. In patients with myocarditis, one of five specimens contained detectable viral RNA, whereas none of 11 specimens from patients with idiopathic dilated cardiomyopathy or 21 myocardial specimens from patients with a wide variety of other cardiac disorders contained detectable coxsackie B3 viral RNA. The results show that the polymerase chain reaction is a useful means for detecting coxsackie viral RNA and its application should help in the evaluation of hypotheses concerning the infectious etiology of human myocarditis and idiopathic dilated cardiomyopathy. 
4	A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo. In vivo correlations of action potential duration measured by a monophasic action potential catheter and effective refractory period measured by a separate pacing catheter have been poor, probably because of the known variability of both action potential duration and effective refractory period between different ventricular sites. In this study, a new quadripolar contact electrode catheter designed for simultaneous pacing and monophasic action potential recording at closely adjacent sites (2 mm separation between recording electrodes and pacing electrodes) was tested in five closed chest dogs and four patients. Dog studies: Pacing thresholds were extremely low, ranging from 0.02 to 0.25 mA (mean +/- SD 0.099 +/- 0.051, n = 36) and were stable over time (less than 20% increase during 1 h of continuous pacing). Because of the close proximity of pacing and recording electrodes, the pacing artifact nearly coincided with the monophasic action potential upstroke. Because of the low pacing threshold, however, pacing artifacts were small (33 +/- 17% of the monophasic action potential amplitude at twice diastolic threshold strength) and did not affect the duration or configuration of the simultaneously recorded monophasic action potential. The short stimulus response time and the undisturbed monophasic action potential signal fidelity during pacing allowed precise simultaneous measurements of action potential duration and effective refractory period at the same endocardial site. 
4	Oscillometric finger blood pressure versus brachial auscultative blood pressure recording. In this study, a recently marketed proprietary finger blood pressure monitor, the Marshall, Astro F-88, was compared with the standard auscultative brachial mercury sphygmomanometer on 125 subjects. Measurements were undertaken according to the standards set by the American Heart Association. Sensitivity of the finger blood pressure measurement was 76% for systolic and 75% for diastolic blood pressure in diagnosis of high blood pressure (systolic greater than 140 mm Hg and diastolic greater than 90 mm Hg). Specificity was 86% for systolic and 82% for diastolic blood pressure. Positive predictive values were 58% for systolic and 38% for diastolic blood pressure in the study population in which prevalence of hypertension was 12%. The correlation coefficient (Pearson) for systolic values between devices was 0.76 (P less than .0001) and 0.57 (P less than .0001) for diastolic pressure. Values obtained by the finger monitor were found to be higher than those obtained by the mercury sphygmomanometer. Mean differences and standard deviations (paired t test) for systolic and diastolic pressures between the two devices were 2.3 +/- 14.9 mm Hg (P less than .08) and 2.9 +/- 14.5 mm Hg (P less than .02), respectively. These values are not in accordance with the proposed national standards because only 48% of the systolic and 37% of the diastolic blood pressure measurements were within 5 mm Hg of the mercury sphygmomanometer measurements. Therefore, although these differences may well be due to different techniques of monitoring employed by the devices, this device is not recommended for evaluation of blood pressure. 
5	Necrotizing tracheobronchitis: complication of mechanical ventilation in an adult. A 51-year-old woman had localized interstitial pneumonia that rapidly progressed to involve all lung fields. After 9 days of conventional mechanical ventilation, pneumothorax developed in the presence of an obstruction of the right main bronchus. Bronchoscopy and endobronchial biopsies revealed NTB involving the tracheobronchial tree distal to the tip of the endotracheal tube, with complete obstruction of the right main bronchus by hard, eschar-like material. Tracheal mucosa proximal to the tip of the endotracheal tube was normal. Subsequent bronchoscopy, 20 days later, showed marked resolution of NTB. Though a frequent complication of mechanical ventilation in the neonate, NTB as a complication of conventional mechanical ventilation has not previously been recognized in an adult. Necrotizing tracheobronchitis should be suspected in adults who have had mechanical ventilation and who are experiencing ventilatory difficulties, after routine problems have been treated or excluded. 
1	Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone. The effect of dexamethasone (DEX) (9 alpha-Fluro-16 alpha-methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program. Patients were treated with DEX 0.5 mg/d until the day of human chorionic gonadotropin administration. The cells were cultured for 24 hours in the presence of androstenedione (10(-7)M). After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours. The medium was then harvested and assayed for estradiol (E2) and progesterone (P). Results were compared with those of a control group who was not treated with DEX. Estradiol production by cells was significantly lower in the study group treated with DEX. Progesterone production was not influenced by DEX. Follicular fluid levels, E2, and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment. These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function. 
1	Appendectomy in primary and secondary staging operations for ovarian malignancy. Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures. 
3	Electrophysiology and colour perimetry in dominant infantile optic atrophy. A typical finding in dominant infantile optic atrophy (DIOA) is the variation of the phenotypic expression of the DIOA gene even within one family. It is of special interest for genetic consultation to evaluate an examination method for detecting subclinically involved patients. Seven patients of two families were examined. Three of them had the typical symptoms of DIOA: reduced visual acuity, tritan defect, temporal pallor of both optic discs, and a relative central scotoma for white test spots. In visual evoked cortical potentials (VECP) the amplitudes were reduced, and in one patient the latencies were slightly delayed and two patients considerably so. The amplitude of the negative component of the PERG was markedly reduced, while the positive component was normal. In the remaining four family members normal retinal and cortical responses were recorded under standard conditions and visual fields and colour vision (FM 100 hue) were also normal. However, static perimetry with blue test spots showed in two family members enlarged central scotomas, thus proving that they had subclinical DIOA. 
1	Distinguishing malignant mesothelioma from pulmonary adenocarcinoma: an immuno-histochemical approach using a panel of monoclonal antibodies. A panel of six monoclonal antibodies (MAbs) was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas. Monoclonal anti-human milk fat globulin (HMFG-2), anti-carcinoembryonic antigen (NP-2), anti-epithelial membrane antigen (EMA), anti-cytokeratin (PKK-1), anti-tumor-associated antigen 72 (B72.3), and anti-human myelomonocytic antigen (Leu M-1) antibodies were used to localize their respective antigens in formalin-fixed, paraffin-embedded tumors by using the avidin-biotin-complex immunoperoxidase technique. In all, 28 mesotheliomas obtained from Ohio State University Anatomic Pathology files and from a Southwest Oncology Group (SWOG) protocol were compared to 22 pulmonary adenocarcinomas by using this MAb panel. None of the mesotheliomas demonstrated positive staining with MAbs NP-2 (anti-CEA) or Leu M-1. However, 95% (21/22) of adenocarcinomas stained with one of these two antibodies. Although neither of these two MAbs stained all adenocarcinomas, each antibody demonstrated positive immunostaining in more than 90% of the adenocarcinomas studied. Therefore, MABs NP-2 and Leu M-1 are, individually, quite useful for distinguishing mesothelioma from adenocarcinoma. However, in our study, no single MAb could be used to distinguish these two tumor types in every case. MAb B72.3 stained 91% (20/21) adenocarcinomas but also stained 7% (2/28) of mesotheliomas. MAb HMFG-2 reacted positively with 95% of adenocarcinomas, but also stained 39% of the mesotheliomas, usually in a membranous pattern. MAbs EMA and PKK-1 were not found useful in distinguishing mesothelioma from adenocarcinoma. We conclude that MAbs Leu M-1 and NP-2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas. 
3	One-year outcome after cerebral infarction in whites, blacks, and Hispanics. Little is known about outcome after cerebral infarction for different ethnic groups. Of 590 stroke patients hospitalized from 1983 to 1986 at the Neurological Institute, cerebral infarction over age 39 years occurred in 135 whites, 177 blacks, and 82 Hispanics. Outcome after cerebral infarction differed by ethnicity. The 1-month mortality rate was similar in whites and blacks and least in Hispanics. Whites had a slightly greater risk of recurrent stroke or death than blacks or Hispanics until 6 months after infarction, when their risk stabilized, while the risk in blacks and Hispanics continued to rise for the entire year of follow-up. By 1 year, the rate of recurrent stroke or death was 34.8 +/- 4.2% in whites, 31.1 +/- 3.6% in blacks, and 21.4 +/- 4.8% in Hispanics (p = 0.04). Differences were found in the distribution of various stroke risk factors in the three ethnic groups. A Cox proportional hazards model demonstrated that the ethnic differences in stroke risk factors and infarct subtype were responsible for the ethnic differences in outcome. An abnormal first electrocardiogram was a risk factor for stroke recurrence or death in all three ethnic groups, while a nonlacunar infarct subtype and a history of diabetes were significant only in Hispanics. Understanding the associations of stroke determinants with ethnicity may lead to more focused secondary prevention of recurrent stroke. 
3	Fine surface structure of an intraspinal neurenteric cyst: a scanning and transmission electron microscopy study. The case of an 11-year-old boy with an intraspinal neurenteric cyst, which recurred 8 years and 3 months after surgery, is presented. Scanning and transmission electron microscopy of the cyst epithelium revealed marked resemblance to that of the respiratory tract, despite the presence of numerous goblet cells mimicking intestine on light microscopy study. Detailed ultrastructural findings are described. 
2	Endoscopic cholangiopancreatography in hepatic clonorchiasis--a follow-up study. Cholangiographic changes of the biliary system in 16 patients with proven hepatic clonorchiasis, diagnosed by positive stool or bile ova isolates, were studied. All patients presented with epigastric pain. Other symptoms included jaundice in 31% (5 of 16) and fever in 12.5% (2 of 16). Praziquantel given at 25 mg/kg for three doses in 1 day were administered. Three consecutive stool tests were performed 3 months after treatment and were negative in 87.5% (14 of 16). ERCP studies were repeated at a mean interval of 31.6 months (range, 8 to 69 months). Measurements of the bile ducts on retrograde cholangiograms before and after treatment were compared using the paired Student's t test. Filling defects and blunting of the terminal bile ducts seen on the initial cholangiogram, interpreted as the presence of adult worms, disappeared after treatment. However, there was no significant change between pre- and post-treatment measurement of bile duct caliber. Bile duct dilation, irregularities, and ductal proliferation persisted despite eradication of the parasite. 
1	The technicon H6000 analyzer discriminates chronic lymphocytic leukemia from other B-cell leukemias through automatic assessment of large unstained cells. The separation of chronic lymphocytic leukemia of B-cell origin from other chronic B-cell leukemias is subjective, being largely based on the morphologic features of the lymphoid cells in the peripheral blood. The percentage of large unstained cells determined with a Technicon H6000 analyzer (an automated blood cell differential analyzer, Technicon Instruments Corp, Tarrytown, NY) was used as a cell volume variable in an investigation of 70 cases of chronic lymphocytic leukemia of B-cell origin and of other chronic B-cell leukemias. The significant degree of correlation between the percentage of large unstained cells and morphoimmunophenotypic diagnosis, although obtained for a relatively small number of cases, suggests that this method of cell volume analysis can be used to improve diagnostic reproducibility in chronic B-cell leukemia. 
5	Altered expression of the retinoblastoma gene product in human sarcomas. BACKGROUND. The retinoblastoma-susceptibility (Rb) gene is a prototype tumor-suppressor gene originally isolated from patients with heritable retinoblastoma. This gene encodes a nuclear phosphoprotein whose expression is altered in several types of human tumors. METHODS. We studied the expression of the Rb protein in 44 primary and 12 metastatic high-grade human sarcomas by means of immunohistochemical methods and Western blotting. Computerized image analysis was used to quantify the level of Rb gene product in individual tumor cells. The expression of the Rb gene was then correlated with clinical outcome in the patients with primary tumors. RESULTS. Of the 44 patients with primary sarcomas, 13 (30 percent) had tumors with normal, homogeneous expression of the Rb protein in essentially all tumor cells. Thirty-one patients with primary tumors (70 percent) had altered Rb expression; in 18 (40 percent) the Rb protein was heterogeneously expressed, and in 13 (30 percent) it was detected in fewer than 20 percent of the tumor cells. All 12 of the patients with metastatic sarcomas had altered expression of the Rb protein. When the findings in the patients with primary tumors were correlated with clinical outcome, survival was found to be significantly increased in the patients whose tumors had homogeneous Rb expression, as compared with those with either heterogeneous expression (P = 0.026) or no expression (P = 0.012). CONCLUSIONS. Tumors in which the expression of Rb gene product was decreased were more aggressive than tumors in which this protein was expressed by nearly all cells. The Rb gene product may be an important prognostic variable in patients with these tumors. 
3	A comparison of midazolam with and without nalbuphine for intravenous sedation. The introduction of nalbuphine to intravenous sedation with midazolam added little to the quality of sedation for short operative procedures. There was a greater tendency for patients who received nalbuphine and midazolam to sleep in the afternoon after treatment compared with those who received only midazolam. Significantly more patients had nausea and vomiting in the midazolam/nalbuphine group than did patients in the midazolam-only group. 
1	The tall cell variant of papillary carcinoma of the thyroid gland. Comparison with the common form of papillary carcinoma by DNA and morphometric analysis. The tall cell variant of papillary carcinoma of the thyroid manifests a more aggressive behavior than the usual form of papillary carcinoma of the thyroid. Morphometric analysis of nuclear features and DNA analysis may yield information predictive of aggressive behavior. Accordingly, the DNA content and morphometric features of the neoplastic cells of the tall cell variant were measured and compared with measurements obtained from neoplastic cells of the usual form of papillary carcinoma. Six of the 11 tall cell neoplasms were aneuploid, as were four of the eight usual papillary neoplasms. Although benign cells were separated from malignant cells in each case, differences between tall and usual papillary carcinoma cells were not observed regarding DNA content, chromatin texture, or nuclear size and shape. Differences in the clinical behavior of these neoplasms will likely need to be explained on the basis of other characteristics. 
2	The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma. One hundred fifty-one patients with colorectal polyps containing invasive adenocarcinoma treated by resection were studied to determine the incidence of lymph node metastasis and whether lymph node metastasis was related to the depth of invasion. Other variables evaluated included size and configuration of the polyp, grade of adenocarcinoma, presence or absence of lymphovascular invasion, and degree of differentiation. In patients with sessile polyps, the incidence of lymph node metastasis was 10 percent. Eighty percent of these lesions had lymphovascular invasion. For pedunculated polyps, the overall incidence of lymph node metastasis was 6 percent. However, there was no incidence of lymph node metastasis when the depth of invasion was limited to the head, neck, and stalk of the polyp (Levels 1, 2, and 3). Only when the depth of invasion reached to the base of the stalk (Level 4) was the risk of lymph node metastasis high (27 percent). The other risk factors were not associated with lymph node metastasis. We concluded that the most significant risk factor for lymph node metastasis in patients with invasive carcinoma in a polyp was invasion into the submucosa of the bowel wall (Level 4). 
1	Anaplastic large cell (Ki-1) lymphoma with histiocytic phenotype simulating carcinoma. Histiocytic and epithelial cell types share many cytomorphologic and functional characteristics; it is predictable, therefore, that corresponding malignancies might be difficult to distinguish. Described is the case of a 52-year-old woman in whom disseminated anaplastic large-cell lymphoma simulated carcinomatosis by conventional morphologic criteria. Evidence of histiocytic differentiation was derived from immunocytochemical, fine structural, and genetic probe analyses. The diagnosis of histiocytic neoplasia is discussed in relation to categories previously termed malignant histiocytosis, "Ki-1" lymphoma, and regressing atypical histiocytosis, and comparisons are made with animal tumor models. 
3	Evoked potentials in assessment and follow-up of patients with Wilson's disease. Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy. 
1	A new DNA marker (D10S94) very tightly linked to the multiple endocrine neoplasia type 2A (MEN2A) locus. Combined somatic cell hybrid and linkage studies between D10S94 and five pericentromeric loci (FNRB, D10Z1, MEN2A, RBP3, and D10S15) have localized the new DNA sequence pcl1/A1S-6-c23 at D10S94 to 10q11.2. No recombinants were observed between D10S94 and D10Z1 or MEN2A. D10S94 maps in proximal 10q11.2 very near to MEN2A. There are three possible orders for the six loci that we investigated from the centromeric region of chromosome 10. At present the genetic data do not allow us to order MEN2A with respect to D10Z1 and D10S94. The three possible orders are FNRB-D10Z1-D10S94-MEN2A-RBP3-D10S15, FNRB-D10Z1-MEN2A-D10S94-RBP3-D10S15, and FNRB-MEN2A-D10Z1-D10S94-RBP3-D10S15. In view of the fact that no recombinants between D10S94 and MEN2A or between D10S94 and D10Z1 were observed, the combined haplotypes formed from RFLPs and D10Z1 and D10S94 will increase the informativeness and accuracy of genotype prediction for at-risk members of the families having the MEN 2A syndrome, particularly when the affected parent is female. The localization of D10S94 with respect to MEN2A will prove valuable in experiments directed toward cloning the MEN2A locus. 
5	Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. We performed a 10-year retrospective analysis of the frequency of local postoperative infectious complications in methotrexate (MTX)-treated rheumatoid arthritis patients who underwent total joint arthroplasty. Sixty patients, who had a total of 92 joint arthroplasties, were receiving MTX. A comparison group of 61 patients with a combined total of 110 total joint arthroplasties were not receiving MTX. The 2 groups were compared for the occurrence of local postoperative infectious complications and poor wound healing. Eight patients in the MTX group experienced a total of 8 complications (8.7% of procedures). In comparison, 5 patients in the non-MTX group experienced a total of 6 complications (5.5% of procedures), a difference that was not statistically significant (chi 2 = 0.816, P = 0.366). Statistical analysis of many other variables revealed none that could be identified as risk factors for postoperative complications. These results suggest that treatment in the perioperative period with weekly low-dose pulse MTX does not increase the risk of local postoperative infectious complications or poor wound healing in rheumatoid arthritis patients who undergo total joint arthroplasty. 
5	The safety of low-dose prednisone before and immediately after heart-lung transplantation. Preoperative steroid use has been considered a contraindication to heart-lung as well as lung transplantation. Moreover, most centers delay prednisone administration until 2 to 3 weeks postoperatively until airway healing is secure. We have performed 19 heart-lung transplantations and four single-lung transplantations since 1983. Five recipients (4 heart-lung, 1 single lung) had received prednisone, 5 to 40 mg daily, for 2 to 10 years preoperatively. All recipients were administered prednisone, 0.5 mg/kg daily, starting on postoperative day 1, with a taper to 0.2 mg/kg daily by 4 weeks. Minnesota antilymphocyte globulin (for 10 days), cyclosporine, and azathioprine were also employed. Bronchoscopy, lavage, and transbronchial biopsies were performed every 2 weeks for 3 months postoperatively. No patient had a serious airway complication; 2 heart-lung recipients, not on prednisone preoperatively, had a minor tracheal slough detected on bronchoscopy that resolved spontaneously. Actuarial survival after heart-lung transplantation is 84% +/- 8% and 69% +/- 16% at 1 year and 2 years, respectively. We conclude that prednisone commencing at a dose of 0.5 mg/kg daily from the first postoperative day is a safe practice after heart-lung transplantation. The long-term use of low-dose prednisone before heart-lung transplantation does not preclude normal tracheal healing. The safety of prednisone before and immediately after single-lung transplantation awaits confirmation by further experience. 
1	Parental age in sporadic hereditary retinoblastoma. Of 104 children with sporadic hereditary retinoblastoma born between 1945 and 1970, we studied the age of their parents at the birth and compared this age with the mean age of parents at the birth of their children during the same period in The Netherlands. The mean age of fathers at the birth of their children with sporadic hereditary retinoblastoma (33.7 years) was significantly higher than the mean age of fathers at the birth of their children in the general population (32.5 years) (P less than .05, one sided). Similarly, the mean age of mothers at the birth of their children with sporadic hereditary retinoblastoma (31.2 years) was significantly higher than the mean age of mothers at the birth of their children in the general population (29.5 years) (P less than .05, one sided). We further analyzed this parental age factor by measuring the relative risk of age groups and comparing the incidence of sporadic hereditary retinoblastoma in the various parental age groups with the incidence of sporadic hereditary retinoblastoma in the total population. Mothers 35 years of age or older had a relative risk of 1.7 to have a child with sporadic hereditary retinoblastoma compared with mothers in the population in general (P = .006, one sided). Similarly, fathers 50 years of age or older had a relative risk of 5.0 to have a child with sporadic hereditary retinoblastoma compared with fathers in the population in general (P = .04, one sided). No parental age effect was found in children with nonhereditary retinoblastoma. We conclude that a high paternal and a high maternal age are significant risk factors for sporadic hereditary retinoblastoma. 
4	Hemodynamic consequences of carotid-carotid bypass for innominate artery stenosis. The carotid-carotid cervical bypass is one surgical option for symptomatic atherosclerotic lesions of the innominate artery. Controversy exists regarding the necessity of surgically excluding the innominate plaque from the cerebral circuit. A canine study was instituted to characterize the hemodynamic alterations that occur in the right common carotid artery proximal to the bypass graft, termed the critical segment. The direction of flow in the critical segment determines whether emboli originating in the innominate may be propelled cranially despite a patent bypass graft. Six mongrel dogs underwent placement of an autogenous arterial crossover graft as a carotid-carotid bypass. A stenosis of the innominate artery was quantitatively altered, and an electromagnetic flowmeter measured the magnitude and direction of flow in the critical segment at three levels of diameter reduction in the innominate artery. For low-grade stenoses, flow in the critical segment was always prograde. For high-grade stenoses, the flow was always reversed. Stenoses between 57% and 67% yielded flow values of 10 +/- 24 ml/min, and it was in this range that mean flow reversal was found to occur. Even when the mean flow was near zero in the critical segment, flow was not stagnant but oscillated in antegrade and retrograde directions throughout the cardiac cycle. These data indicate that a carotid-carotid bypass causes complete flow reversal in the critical segment when there is high-grade stenosis in the innominate artery. Theoretical analysis of the hemodynamic circuit indicated that arm exercise would augment retrograde flow in the critical segment. 
4	The "all-autogenous" tissue policy for infrainguinal reconstruction questioned. In 33% of patients referred for infrainguinal reconstruction for limb-threatening ischemia (mean preoperative ankle-arm index [AAI] = 0.26), no suitable autogenous reconstruction was possible. In 40% of cases, intraoperative pre-bypass contrast arteriography was necessary to identify a graftable tibial or pedal artery. The results of polytetrafluoroethylene (PTFE) and autogenous bypasses were compared after 1 to 3 years. After 1 year, patency was 85% and 67% for autogenous and PTFE bypasses, respectively. Limb salvage was 90% for autogenous bypass and 70% for PTFE bypass. Cumulative patency rates at 3 years were 80% for autogenous and 57% for PTFE grafts. Graft surveillance with duplex scanning and AAI was valuable in detecting failing grafts. For both types of reconstruction, secondary procedures were required to maintain patency. We attribute the excellent results with PTFE in part to long-term aspirin and warfarin therapy. In cases of combined superficial femoral and severe infra-popliteal occlusive disease, PTFE bypass is an excellent alternative when no autogenous conduit is available. 
1	Drug response of head and neck tumors in native-state histoculture. We describe a chemosensitivity testing of head and neck tumors, in which a native-state histoculture, ie, a three-dimensional culture system that maintains important in vivo properties, including tissue architecture, was used. Fifteen specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatin (DDP) at concentrations of 1.5, 15, and 37.5 micrograms/mL; fluorouracil at concentrations of 4.0, 40, and 100 micrograms/mL; and combinations of cisplatin and fluorouracil in corresponding doses. Growth and measurement of drug responses were successfully completed in 10 specimens (five others were contaminated, four of them prior to instituting rigorous antibiotic washes). The results indicated cisplatin sensitivity in five of 10 patients; fluorouracil sensitivity in four of 10 patients; and fluorouracil-cisplatin sensitivity in seven of eight patients. Our preliminary results indicate that the native-state histoculture technique is feasible to test chemosensitivity of head and neck tumors. 
5	Spinal accessory nerve palsy: an unusual complication of coronary artery bypass The neurologic complications of coronary artery bypass surgery have been well documented, with a reported incidence of 61% in one large study. Most injuries to the peripheral nervous system involve the brachial plexus. We report the first case of a spinal accessory nerve lesion after coronary bypass surgery. The patient presented with progressive right shoulder weakness. Electrodiagnostic studies revealed a partial lesion of the right spinal accessory nerve. Physical therapy, including strengthening, range of motion, and electric stimulation to the right shoulder, was prescribed to assist recovery of strength and function. Repeat electrodiagnostic studies confirmed nerve regeneration. Prompt recognition of spinal accessory nerve damage after coronary bypass surgery is essential. Early rehabilitation will improve the chances of a better functional outcome. 
2	Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy. The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had greater than 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders. 
5	Penetrating aortic ulcers: diagnosis with MR imaging. The authors studied seven patients with penetrating aortic ulcers with use of magnetic resonance (MR) imaging. All patients were evaluated for acute chest symptoms, and the presence of aortic ulcers was confirmed by means of angiography in all seven patients. Five patients also underwent computed tomography (CT). Three patients underwent surgical repair of the thoracic aorta. MR findings included intramural hematoma and focal aortic wall ulceration in four patients, focal ulceration in one, focal intramural hematoma in one, and focal intramural hematoma with rupture in one. The diagnosis of intramural hematoma was made by the detection of increased signal intensity on T1- and T2-weighted MR images. MR imaging was superior to angiography in depicting the extent of intramural thrombus, although one ulceration diagnosed at angiography was missed at MR imaging. MR imaging was superior to CT in differentiating acute intramural hematoma from atherosclerotic plaque and chronic intraluminal thrombus, although it did not depict displaced intimal calcification in one patient with extensive intramural hematoma. 
2	Interventional gallbladder procedures. Interventional radiologic procedures in the gallbladder are influencing both the diagnosis and therapy of many gallbladder disorders. Current diagnostic and therapeutic percutaneous techniques offer important alternatives for their management. This article highlights the spectrum of interventional radiologic techniques available for gallbladder diseases. 
2	Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum. The spatial relations between bacteria and the affected tissues can indicate pathogenic mechanisms. This study was undertaken to define the spatial relation of Helicobacter pylori to the human gastric mucosa. Antibodies against gastric mucus and ruthenium red were used to stabilise the glycoprotein structure of the mucus and glycocalyces in antral biopsy specimens from eight patients infected with H pylori. The location of organisms and ultrastructural features were assessed using systematic scanning and transmission electron microscopy: 92 (2)% (mean (SE] of H pylori were in the pit mucus, and 7 (3)% were in the surface mucus; 60 (12)% of H pylori were close to epithelial cells, with only 5 (2)% located near the epithelial intercellular junctions. Fine filamentous strands extended between organisms and nearby epithelial cells, with few organisms in membrane to membrane contact. H pylori were not observed between, beneath, or within cells of the gastric mucosa. The preferred location of H pylori in the gastric antrum is within the pit mucus close to the epithelial cell surface, with no evidence that they have a direct toxic effect on the mucosa. 
1	Role of upper gastrointestinal investigations in a screening study for colorectal neoplasia. Should patients with positive faecal occult blood screening tests who are free of colorectal neoplasia undergo upper gastrointestinal investigation? Altogether 16,985 faecal occult blood tests were completed in a group of 18,818 asymptomatic patients (45-75 years) offered screening at two yearly intervals. A total of 447 (2.6%) were positive and underwent large bowel investigations. No neoplastic disease was identified in 283 (63%) of them. Fourteen (5%) also underwent gastroscopy for upper gastrointestinal symptoms, benign conditions were identified in five and a gastric carcinoma in one. No further investigations were instituted in the remaining 269 subjects who have now been followed up for a median period of 5 years (2-8 years). Five have been referred for benign upper gastrointestinal conditions, but none for upper gastrointestinal malignancy. Thirty one subjects have died - one from gastric cancer (a patient who had undergone a previous partial gastrectomy for a duodenal ulcer and who had persistent upper gastrointestinal symptoms). The remaining deaths were unrelated to the upper gastrointestinal tract. Nineteen people who have left the trial area have been monitored for the development of malignant disease; none have presented with upper gastrointestinal malignancy. These data support the view that upper gastrointestinal investigations need not be performed routinely in this group of subjects, but may be reserved for those with relevant symptoms. 
1	Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. The records of 2,673 patients randomized according to seven consecutive Eastern Cooperative Oncology Group (ECOG) studies of adjuvant therapy for breast cancer were reviewed for the occurrence of vascular complications. All protocols opened and closed between June 1977 and July 1987. The objectives of the present study were (1) to compare the frequency of vascular complications among patients who received adjuvant therapy for breast cancer with patients on observation, and (2) to estimate the contribution of chemotherapy and hormonal therapy to the occurrence of venous and arterial thrombi. The frequency of thrombosis, both venous and arterial combined, was 5.4% among patients who received adjuvant therapy and was 1.6% among patients on observation (P = .0002). Premenopausal patients who received chemotherapy and tamoxifen had significantly more venous complications than those who received chemotherapy without tamoxifen (2.8% v 0.8%, P = .03). Postmenopausal patients who received tamoxifen and chemotherapy had significantly more venous thrombi than those who received tamoxifen alone (8.0% v 2.3%, P = .03) or those who were observed (8.0% v 0.4%, P less than .0001). Premenopausal patients who received tamoxifen and chemotherapy had a 1.6% frequency of arterial thrombosis, significantly more than patients who received chemotherapy alone (1.6% v 0.0%, P = .004). The frequency of arterial thrombosis among postmenopausal patients was not significantly correlated with adjuvant therapy. In conclusion, patients who received adjuvant therapy for breast cancer had a 5.4% frequency of thromboembolic complications, significantly more than those who were observed. The combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with more venous thrombi than tamoxifen alone among postmenopausal patients. 
5	Nerve growth factor binding domain of the nerve growth factor receptor. A structural analysis of the rat low-affinity nerve growth factor (NGF) receptor was undertaken to define the NGF binding domain. Mutant NGF receptor DNA constructs were expressed in mouse fibroblasts or COS cells, and the ability of the mutant receptor to bind NGF was assayed. In the first mutant, all but 16 amino acid residues of the intracellular domain of the receptor were removed. This receptor bound NGF with a Kd comparable to that of the wild-type receptor. A second mutant contained only the four cysteine-rich sequences from the extracellular portion of the protein. This mutant was expressed in COS cells and the resultant protein was a secreted soluble form of the receptor that was able to bind NGF. Two N-terminal deletions, in which either the first cysteine-rich sequence of the first and part of the second cysteine-rich sequences were removed, bound NGF. However, a mutant lacking all four cysteine-rich sequences was unable to bind NGF. These results show that the four cysteine-rich sequences of the NGF receptor contain the NGF binding domain. 
1	Late recurrence of a hepatocellular carcinoma in a patient with incomplete Alagille syndrome. In this study, the case of a patient presenting a second hepatocellular carcinoma 13 years after resection of a first tumor of the same type is reported. In this case, etiological investigations remained negative, but an incomplete form of syndromatic Alagille syndrome with paucity of bile ducts in the nontumoral tissue was detected and associated with nodular regenerative hyperplasia and foci of dysplasia. Malignant transformation in Alagille syndrome seems to be extremely rare. The fact that such tumors evolve very slowly could be an argument for partial hepatectomy and, if necessary, liver transplantation. 
5	Effect of alcohols and other hypnotics in mice selected for differential sensitivity to hypothermic actions of ethanol. Mice selectively bred for resistance (HOT) and sensitivity (COLD) to the hypothermic effect of an acute dose of ethanol were tested twice during the course of genetic selection for their hypothermic response to other alcohols and sedative hypnotics. The drugs administered were ethanol, propanol, n-butanol, t-butanol, pentanol, diazepam, phenobarbital, pentobarbital, methyprylon and ethchlorvynol, all of which have sedative effects on the central nervous system, and hydralazine, a peripheral vasodilator. All drugs decreased body temperature of both HOT and COLD mice. In mice selected for seven to nine generations, COLD mice were more sensitive than HOT mice to all sedative drugs. The longer-chain alcohols were more potent than ethanol in inducing hypothermia, but the magnitude of the response difference between HOT and COLD mice appeared to be smaller. The difference between HOT and COLD mice in hypothermic sensitivity to an acute dose of ethanol was greater after 11-15 generations of selection than after seven generations. Similarly, the differential effect of the other alcohols, phenobarbital, pentobarbital, and methyprylon, on HOT and COLD mice increased with more generations of selection but to a lesser extent than ethanol. These data demonstrate that selecting for sensitivity to acute ethanol hypothermia has produced mice that are also differentially sensitive to other sedative hypnotic agents. They also support the hypothesis that the drugs used in the present study share a common mechanism of action for inducing hypothermia, which may be regulated by a common set of genes. 
4	Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery. Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent. 
4	Repair of supravalvar aortic stenosis: cardiovascular morphometric and hemodynamic results. Supravalvar aortic stenosis is associated with normal systolic pressure in the aorta and its branches with the singular exception of the coronary arteries, which are hypertensive. This uncommon lesion has been treated by patch aortoplasty of several types. We examined hemodynamics and morphometrics in 13 patients who underwent operation for supravalvar aortic stenosis from 1979 through 1988. They ranged in age from 2 to 43 years (mean age, 14.5 +/- 3.8 years [+/- standard error of the mean]). There were no operative deaths. Preoperative and postoperative (1 to 5 years) catheterization or echocardiography or a combination of these was done in all but 3 patients (1 died late suddenly without a postmortem examination; 1 was lost to follow-up; and 1 has not yet been restudied). Pressure gradients across the stenosis in patients treated with a single-sinus patch (n = 4) were 65 +/- 18 mm Hg preoperatively and 5 +/- 3 mm Hg postoperatively (p less than 0.05) and in patients with a bisinus patch (n = 6), 83 +/- 15 mm Hg preoperatively and 6 +/- 2 mm Hg postoperatively (p less than 0.05); the two groups were not significantly different. Measurements of the diameters of the coronary arteries, aortic annulus, and descending aorta were made, and calculation of the ratio of the coronary artery and annulus diameters to the descending aortic diameters both preoperatively and postoperatively was possible in 5 patients. The left coronary artery was larger than normal before and after operation. Preoperatively there was a disproportionate increase in left coronary artery and annulus size during systole. Left ventricular wall thickness decreased significantly postoperatively (p less than 0.05). Repair of supravalvar aortic stenosis (localized and diffuse) by both single sinus and bisinus patch repair is safe and hemodynamic results are good. 
5	The Senegal DNA haplotype is associated with the amelioration of anemia in African-American sickle cell anemia patients. We have previously determined that in African sickle cell anemia (SS) patients three different beta-like globin gene cluster haplotypes are associated with different percent G gamma (one of the two types of non-alpha chains comprising hemoglobin F [HbF]), mean percent HbF, and percent dense cells. We report now that in adult New York SS patients, the presence of at least one chromosome with the Senegal haplotype is associated with higher Hb levels (1.2 g/dL higher) than is found for any other non-Senegal haplotype (P less than .004). The percent reticulocytes and the serum bilirubin levels were lower in these patients. When the effect of alpha-gene number was analyzed by examining a sample of SS patients with concomitant alpha-thalassemia, the same results were obtained. Because the HbF level is significantly higher among the Senegal haplotype carriers in this sample, the inhibitory effect on sickling of this Hb variant may be one of the reasons for the haplotype effect. We conclude that the Senegal beta-like globin gene cluster haplotype is associated with an amelioration of the hemolytic anemia that characterizes sickle cell disease. 
3	Central nervous system involvement in patients with facial palsy due to borrelial infection. Patients with a peripheral facial palsy due to an underlying Ixodes-borne borreliosis often have cerebrospinal fluid findings indicating meningeal involvement. The aim of the present study was to identify signs of CNS involvement by means of brain-stem evoked response audiometry (BSER) in patients with a facial palsy due to borreliosis, as well as in patients with a facial palsy of unknown aetiology. Bell's palsy. Abnormalities in BSER were found to be significantly more common along the borrelial patients. Furthermore, a reversal of these abnormalities following treatment with benzyl-penicillin was found in the majority of patients with borreliosis. The results of the present study emphasize the importance of diagnosing and treating an underlying borreliosis in patients with a peripheral facial palsy. 
2	The effectiveness of double-gloving in otolaryngology. Thirty-four sets of consecutively used double gloves (68 pairs) used by otolaryngologists and their assistants in operations known to have a high risk of glove punctures were studied. The perforation rates for the outer and inner layers were 35.3 and 8.8% respectively, indicating that a second set of gloves substantially improves the likelihood of maintaining an intact barrier between medical staff and patient. 
4	A 47-kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation. Several autoimmune sera from patients with Raynaud phenomenon decorated mammalian kinetochores and bound to a 47-kDa protein on immunoblots of nuclear lysates. Antibody affinity-purified from immunoblots of the 47-kDa band recognized kinetochores, but due to crossreaction with an 18-kDa protein, localization remains elusive. We used one of these sera to purify the antigen from HeLa cells synchronized in mitosis as a noncovalent complex with a 25-kDa protein. The antigen was released from DNA by intercalation with 25 mM chloroquine. Ion-exchange chromatography yielded the pure complex with an apparent molecular size of 68 kDa, which was separated into its components by gel filtration in 6 M guanidinium chloride. Upon two-dimensional gel electrophoresis the 47-kDa protein gave two main spots of pI 6.6 and 6.7, respectively. Posttranslational modification is indicated by additional antigenic spots, by lack of a free alpha-amino group, and by chromatographic behavior of peptides on reversed-phase chromatography. The amino acid sequence for 205 residues of the 47-kDa protein has been established. This sequence is highly homologous with the translated reading frame of RCC1, a gene reportedly involved in regulating onset of mammalian chromosome condensation. 
4	Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. The literature on arterial aneurysms is subject to potential misinterpretation because of inconsistencies in reporting standards. The joint councils of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery appointed an ad hoc committee to address this issue. This communication, prepared in response to the need for standardized reporting, defines and classifies arterial aneurysms and recommends standards for describing the causes, manifestations, treatment, and outcome criteria that are important when publishing data on aneurysmal disease. 
1	Follicular neoplasms of the thyroid in men older than 50 years of age. A DNA flow cytometric study The clinical behavior of follicular neoplasms of the thyroid in elderly men can be difficult to predict on histologic grounds alone. To assess the usefulness of DNA flow cytometry in predicting the metastatic potential of these tumors, the authors studied 44 primary and metastatic follicular neoplasms of the thyroid by DNA flow cytometry of paraffin-embedded tissue. The neoplasms were obtained from 44 men ranging in age from 50 to 79 years (mean, 60). There were 29 follicular adenomas, 11 primary follicular carcinomas (neoplasms with capsular and/or vascular invasion), and 4 metastatic follicular carcinomas. Follow-up information was available on 40 of the 44 patients. The mean follow-up was 114 months. Twenty-five of the 29 follicular adenomas had a diploid DNA content, 2 (7%) were tetraploid, and the DNA histograms on 2 were not interpretable. All patients with follicular adenomas had no evidence of disease (NED) at last follow-up. Eight of the 11 primary follicular carcinomas were diploid. Six of these patients had NED, one died with carcinoma at 82 months, and no follow-up was available on one. Three (27%) of the primary follicular carcinomas were aneuploid or tetraploid. Two of these patients had NED, and the third died with carcinoma 84 months after diagnosis. Two of the four metastatic follicular carcinomas were diploid and two (50%) were aneuploid or tetraploid. One of the two patients with diploid metastatic follicular carcinomas died with carcinoma, as did one of the two patients with aneuploid metastatic follicular carcinomas. These results suggest the following: (1) follicular carcinomas are more likely to be aneuploid or tetraploid than are follicular adenomas; (2) follicular neoplasms without capsular or vascular invasion may include a small number of aneuploid or tetraploid tumors; and (3) DNA ploidy does not add to the prognostic value of histologic studies alone. 
1	Different mRNAs code for dopa decarboxylase in tissues of neuronal and nonneuronal origin. A cDNA clone for dopa decarboxylase (EC 4.1.1.28) has been isolated from a rat pheochromocytoma cDNA library and the cDNA sequence has been determined. It corresponds to an mRNA of 2094 nucleotides. The length of the mRNA was measured by primer-extension of rat pheochromocytoma RNA and the 5' end of the sequence of the mRNA was confirmed by the PCR. A probe spanning the translation initiation site of the mRNA was used to hybridize with mRNAs from various organs of the rat. S1 nuclease digestion of the mRNAs annealed with this probe revealed two classes of mRNAs. The comparison of the cDNA sequence and published sequences for rat liver, human pheochromocytoma, and Drosophila dopa decarboxylase supported the conclusion that two mRNAs are produced: one is specific for tissue of neuronal origin and the other is specific for tissues of nonneuronal (mesodermal or endodermal) origin. The neuronal mRNA contains a 5' untranslated sequence that is highly conserved between human and rat pheochromocytoma including a GA stretch. The coding sequence and the 3' untranslated sequence of mRNAs from rat liver and pheochromocytoma are identical. The rat mRNA differs only in the 5' untranslated region. Thus a unique gene codes for dopa decarboxylase and this gene gives rise to at least two transcripts presumably in response to different signals during development. 
5	Ketamine as analgesic for total intravenous anaesthesia with propofol. A prospective study of 18 patients who underwent noncardiac surgery was performed to study the use of ketamine as an analgesic during total intravenous anaesthesia with propofol. A comparison was made with the combination propofol/fentanyl. The propofol/ketamine combination resulted in haemodynamically stable anaesthesia without the need for additional analgesics. Postoperative behaviour was normal in all patients and none of the patients reported dreaming during or after the operation. Propofol seems to be effective in eliminating side effects of a subanaesthetic dose of ketamine in humans. We recommend the propofol/ketamine combination for total intravenous anaesthesia for surgery when stable haemodynamics are required. 
5	Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice. Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor. 
2	Randomized, double-blind, placebo-controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding. A randomized, double-blind, placebo-controlled trial of somatostatin was conducted among 120 patients admitted for bleeding esophageal varices (59 placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin followed by a 5-day continuous infusion of 250 micrograms/h and an identical administration of placebo were evaluated for both the control of bleeding and prevention of early rebleeding from varices. Failure to control bleeding occurred in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to failure occurring earlier with placebo (P = 0.036). blood and plasma transfused per hour during drug infusion of trial drug was reduced in the somatostatin group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was halved in somatostatin-treated patients. The average effect of somatostatin was a 41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P = 0.0545) after adjustment for the severity of liver disease, which was the only other variable having a significant influence on time to failure. There was no difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or complications. It is concluded that somatostatin is safe and more effective than placebo for the control of variceal bleeding. 
4	Mortality in hereditary antithrombin-III deficiency--1830 to 1989 To determine whether antithrombin-III (AT-III) deficiency leads to an excess mortality, we studied 171 individuals from ten families with a proven hereditary deficiency. 73 were classified as certainly deficient either by direct measurement of AT-III concentration or by mendelian inheritance patterns. 98 individuals had a high probability (0.5) of deficiency. The 64 deaths recorded did not exceed those expected for the general population adjusted for age, sex, and calendar period. We suggest that a policy of prophylactic anticoagulation for patients with AT-III deficiency cannot be recommended. 
3	Spectral electroretinography in thioridazine toxicity. In three patients with thioridazine toxicity, the electroretinogram (ERG) to red light was found to be below the average normal range. A significant increase in its amplitude appeared with cessation of therapy in two cases. A further deterioration of the ERG amplitude to all stimulus conditions (white, blue, and red lights) occurred when the dose of the medication was increased in the third patient. 
5	Endothelium-derived relaxing factor inhibits hypoxic pulmonary vasoconstriction in rats. The hypothesis that endothelium-derived relaxing factor (EDRF) modulates hypoxic pulmonary vasoconstriction (HPV) was tested in isolated, blood-perfused rat lungs ventilated with gas mixtures of 21% O2-5% CO2-74% N2 (normoxia) or of 3% O2-5% CO2-92% N2 (hypoxia); 30 microM NG-monomethyl-L-arginine (L-NMMA), an inhibitor of EDRF production, caused a reduction in the endothelium-dependent relaxant response to acetylcholine (ACh) from 62 +/- 7, 88 +/- 4, and 100 +/- 4% to 26 +/- 8, 49 +/- 12, and 75 +/- 7% at ACh concentrations of 1, 10, and 100 microM, respectively (p less than 0.05 at all concentrations), indicating that L-NMMA acts via the inhibition of EDRF production. L-NMMA induced a concentration-related augmentation in HPV of 20 +/- 5, 32 +/- 8, and 34 +/- 8% at concentrations of 30, 300, and 1,000 microM (p less than 0.05, compared with a vehicle control group at all concentrations). The pressor response to a dose of angiotensin II (A-II), which produced the same increase in pulmonary artery pressure as that induced by hypoxia, was also significantly augmented (2 +/- 0.6%), but to a lesser extent. The augmentation of HPV by 30 microM L-NMMA was completely reversed by 1 mM L-arginine (a precursor of EDRF), but not by D-arginine (an isomer of L-arginine). One and 6 mM L-arginine, but not 6 mM D-arginine caused a significant inhibition of HPV by 20 +/- 2 and 47 +/- 12% (p less than 0.05, compared with the vehicle control group) and a small but not significant reduction in A-II-mediated contraction. 
2	Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon. 
3	Functional evaluation of quadriplegic patients using a hand neuroprosthesis. The objective of this retrospective study was to compare the abilities of quadriplegic patients to complete activities of daily living with and without the use of a portable hand neuroprosthesis. The neuroprosthesis provided synthetic hand grasp through functional neuromuscular stimulation of paralyzed forearm and hand muscles. Data were obtained from telephone interviews, patient records, and videotapes. Twenty-two quadriplegic patients were included in the study; 15 were functional at a C5 spinal cord injury level and seven at a C6 level. The median success rate (ie, the percentage of patients who could complete each activity) across the ten activities was 89% with the hand neuroprosthesis but was only 49% without the hand neuroprosthesis. All patients could perform more tasks when the neuroprosthesis was used, although the relative improvement of C5 patients was larger than that of C6 patients. 
5	Fatal embolization of intestinal contents through a duodenocaval fistula. Embolization of intestinal contents to the lung is an exceedingly rare event, which to our knowledge, has never been reported as a cause of death. Equally rare is duodenocaval fistula resulting from a penetrating duodenal peptic ulcer. We present the case of a 51-year-old man whose duodenal ulcer led to a fistulous tract with the inferior vena cava and subsequently to progressive pulmonary embolization of intestinal contents, ultimately resulting in death from respiratory failure. 
2	Ehlers-Danlos syndrome type IV: diagnosis and therapy of associated bowel perforation. Ehlers-Danlos syndrome type IV is a heritable disease of type III collagen metabolism. This diagnosis is suspected in a patient with a combination of clinical manifestations and family history, but it is confirmed only by culture of the patient's skin fibroblasts and demonstration of a defect in type III collagen metabolism. The disease may rarely present with spontaneous colonic perforation, a complication traditionally treated by primary closure of the perforated segment and creation of an end colostomy. Attempts at bowel reanastomosis have often resulted in repeated colon perforations. We present the first patient with Ehlers-Danlos type IV syndrome to develop a colon perforation proximal to an end colostomy, and discuss the surgical strategy to prevent recurrences of this and other postoperative complications associated with the syndrome. 
1	Deceptive bizarre stromal cells in polyps and ulcers of the gastrointestinal tract. The clinical and pathologic features of 33 pseudomalignant lesions of the gastrointestinal tract with bizarre stromal cells are reported. Deceptive histologic changes were identified in ulcers of seven patients and in inflammatory polyps of 26. A misdiagnosis of malignant neoplasm was made in six of the 33 patients (three polyps and three ulcers). A history of gastrointestinal bleeding and/or inflammatory bowel disease was common. The bizarre stromal cells were usually distributed beneath the ulcerated mucosa or within granulation tissue. They stained strongly for vimentin in 20 of 23 cases. Some of the bizarre cells also stained for muscle specific actin (seven of 23 cases). The cells appear to be reactive fibroblasts or myofibroblasts. Follow-up information obtained on 24 of the 33 patients (including four of the six cases initially diagnosed as malignant) revealed 22 patients to be alive without evidence of a malignant neoplasm (average follow-up, 13 months). Two patients died of other causes. Correct recognition of these bizarre stromal cells in gastrointestinal ulcers and inflammatory polyps will prevent a potentially serious diagnostic pitfall. 
1	Morbidity, mortality, and quality of life for patients treated with levothyroxine In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy. 
2	Prochlorperazine and transdermal scopolamine added to a metoclopramide antiemetic regimen. A controlled comparison. Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed. 
1	Small cell carcinoma of the pancreas and biliary tract. Four cases of anaplastic carcinoma of the pancreas or biliary tract were studied clinicopathologically and immunohistochemically. All four cases were intermediate cell type and contained a minimum amount of microscopic foci of differentiated glandular adenocarcinoma. Argyrophilic tumor cells were not seen in any of the four tumors. Immunohistochemically, no tumor was positive for hormonal products, but all tumors were positive for epithelial markers. These findings suggest that the anaplastic carcinoma are not derived from argyrophilic cells, but rather from adenocarcinomas which have the potential for anaplastic metaplasia. The long-term survival of one patient emphasized the importance of chemotherapy in the treatment of small cell carcinoma of the pancreas and biliary tract. 
1	Biphasic reduction and concanavalin A binding properties of serum alpha-fetoprotein in preterm and term infants. Reference values for postnatal serum alpha-fetoprotein (AFP) and concanavalin A (ConA) binding subfractions of AFP in preterm and term infants are presented. Preterm infants had 10-fold higher serum concentrations of AFP than did term infants at birth. The reduction of serum values of AFP was biphasic in both groups and differed significantly between the two groups. The first declining phase continued for approximately 4 months in preterm and for 2 months in term infants, and was related to the degree of prematurity. The AFP values reached adult levels by 12 months in preterm and by 9 months in term infants. The developmental pattern of the carbohydrate moiety of AFP was determined by ConA fractioning. The proportion of the ConA nonreactive subfraction of AFP in preterm and term infants at birth was 6% and 13%, respectively; it increased more rapidly in term than in preterm infants but reached 85% to 95% by the age of 6 months in both infant groups. Our results indicate that the postnatal maturation of AFP synthesis is dependent on gestational age. Malignant recurrences of neonatal sacrococcygeal teratomas were associated with an increase in serum concentration of AFP and a decrease in the proportion of the ConA nonreactive subfraction of AFP. 
2	The acutely affected abdomen in paraplegic spinal cord injury patients. The records of 145 paraplegic or quadriplegic patients were reviewed to identify those factors useful in the correct diagnosis of the acute abdomen in this population. Twenty-one patients had 22 episodes of acute or subacute abdominal problems. Presenting complaints, physical findings, and laboratory results were useful in various ways. However appropriate radiographic studies led to the correct diagnosis in 77% of patients. Although paraplegic and quadriplegic patients are predisposed to a distinct constellation of medical problems, including urinary tract infection and calculi, they also may present with other abdominal conditions that cause significant morbidity and mortality if not promptly recognized. 
3	Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals. Twenty hogs were administered the following procedures before, during, and after overdistraction of the spinal column at T5-T6: somatosensory (SEP) and neurogenic-motor evoked potentials (NMEPs), hydrogen clearance procedures, Stagnara wake-up tests, and aortic-injection of silastic plastic. To ensure that overdistraction was possible, a nonosseous, circumferential osteotomy was made at T5-T6 and distraction applied in one-ratchet increments using Harrington instrumentation. Overdistraction was maintained for 3, 5, 6, 10, 15, 20, 25, or 30 minutes. Results indicated that the duration of overdistraction, as represented by lost NMEPs, was always correlated with the animal's clinical status on wake-up test. If overdistraction was maintained more than 6 minutes, 100% of the animals demonstrated positive wake-up results; if maintained between 5 and 6 minutes, 75% demonstrated positive wake-up results; and if maintained less than 5 minutes, only 25% demonstrated positive wake-up results. Time-to-loss of the NMEPs and SEPs, after onset of overdistraction, fell within two groups: slow and fast. In the slow group, it required slightly more than 20 minutes (mean = 20.6) for the potentials to be lost, while in the fast-loss group data were lost in slightly less than 4 minutes (mean = 3.6). Blood flow studies and inspection of the spinal cord revealed that the mechanism of action for the slow group appeared to be ischemia of the spinal cord that extended several centimeters above and below the site of maximum distraction. In the fast-loss group, it appeared that gross structural damage, with some very localized ischemia, were the mechanisms of actions influencing the integrity of the spinal cord. 
5	Disseminated zygomycosis associated with systemic lupus erythematosus. We describe a 36-year-old patient who had systemic lupus erythematosus (SLE) and died of disseminated zygomycosis. There was rapid progression of his SLE, leading to suspicion of superimposed infectious disease, but the actual cause of his multiorgan failure was not recognized until after death. The manner in which systemic fungal infection may mimic SLE is discussed. 
1	Hepatic tumors: signal enhancement at Doppler US after intravenous injection of a contrast agent. Experiments were carried out to detect and establish the origin of Doppler and echo signal enhancement in small vessels of the systemic circulation and of tumors after intravenous injection of a contrast agent. Eight woodchucks (Marmota monax) were studied; each woodchuck had naturally occurring hepatocellular carcinoma. Injections of 0.1-4.0 mL of air-filled human serum albumin microspheres were administered into a hind limb or jugular vein. Ultrasound (US) examination included transabdominal duplex scanning, color Doppler imaging, placement of a Doppler transducer on the exposed tumor, and surgical implantation of pulsed Doppler cuffs. Doppler signals were assessed by recording color Doppler images and results of spectral analysis. While subjective echo level was unaffected within the tumors, dramatic Doppler signal enhancement was recorded in both normal and tumor vessels. At optimum dose levels, a signal gain of approximately 10 dB was recorded from the tumor. Analysis showed that the echo enhancement was due to the presence of the contrast agent in branches of the hepatic artery. These results suggest that tumor detection may be enhanced by intravenous administration of a US contrast agent. 
4	A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients. Patients were stratified according to whether or not there were bone metastases only. Four hundred twelve patients entered this trial; 378 were assessable for tolerability and 365 for efficacy. The overall response rates were comparable between FEC 50 (44.6%) and FEC 75 (44.7%), but both were better than the epirubicin alone (30.6%) (P = .04 and P = .0006, respectively). The complete response rate was better in FEC 75 (15.5%) than in FEC 50 (7%) (P = .025) or epirubicin (4%) (P = .002). Similar results were obtained in the group of patients without bone-only metastases. No difference in the three treatments was observed in the patients with bone metastases only. Mean durations of response were similar in the three groups, being 412 days, 440 days, and 350 days for FEC 50, FEC 75, and epirubicin, respectively. Patients without previous adjuvant chemotherapy fared better than those with previous treatment (without anthracyclines). Tolerability was fair in the three groups. Overall, the epirubicin-alone group showed better tolerance than the two other groups, which did not differ significantly. Time to progression and survival were not different among the three groups, but more early relapses occurred in the epirubicin and FEC 50 groups; survival seemed to be better during the first 8 months in the FEC 75 group, and the survival difference between the epirubicin group and the FEC 75 group was of borderline significance. No difference in survival was observed between epirubicin- and FEC 50-group patients, even though the response rate was significantly worse in the monochemotherapy group. 
2	Raised urinary secretory IgA in chronic diarrhoea. Secretory IgA outputs in urine have been measured in 24 malnourished Gambian children who had been admitted to hospital with chronic diarrhoea and in 43 children from a rural Gambian village. Village children of poor nutritional state (less than or equal to 74% weight for age compared with the National Center for Health Statistics reference curve) had secretory IgA outputs that were only one third of those of better nourished individuals. In contrast, the patients with chronic diarrhoea had secretory IgA outputs that were significantly raised compared with village children, regardless of nutritional state. These results demonstrate that secretory IgA production in the urinary tract can be stimulated by intestinal disease, suggesting that malnourished children are able to mount a response to mucosal infection and supporting the hypothesis of a common secretory immune system. 
2	Endoscopic sclerotherapy in extrahepatic portal hypertension in pregnancy. Extrahepatic portal hypertension usually occurs during childhood, but a substantial number of patients may reach adult life. There is a general agreement that pregnancy may become hazardous to these patients, and some authors even consider this condition as a contraindication to conceiving. A case of endoscopic sclerotherapy in such a patient is herein presented, and the approach to such patients is discussed. 
4	Microalbuminuria in essential hypertension. Clinically apparent proteinuria in essential hypertension is associated with increased cardiovascular and total mortality and is an independent risk factor for cardiovascular and cerebrovascular disease. Subclinical elevation of urinary albumin excretion is seen more frequently than clinical proteinuria in essential hypertension and the levels of microalbuminuria (excretions of 30 to 300 mg/24 h) correlate with blood pressure. The increased urinary albumin excretion in hypertension may be explained by several factors such as renal hemodynamic changes, permselectivity changes of the glomerular filter, and structural arteriolar and glomerular changes due to nephrosclerosis. It has been clearly demonstrated that microalbuminuria is a risk factor for the development of clinical proteinuria, renal failure and increased cardiovascular mortality in insulin-dependent diabetes mellitus. It is still not known whether microalbuminuria also predicts development of proteinuria and decline in renal function in hypertension but there is some evidence indicating that microalbuminuria may be a marker of increased cardiovascular risk in hypertensives. 
3	Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study. This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients. 
5	Eosinophil activation in systemic sclerosis. Circulating levels of eosinophil cationic protein (ECP) were increased 4-fold in patients with systemic sclerosis (SSc) compared with those in healthy control subjects. There was no correlation between the ECP concentrations and laboratory indices of inflammatory activity or visceral involvement. Mean ECP levels were higher in patients with a history of occupational exposure to silica, even though patients who had no such history also had ECP levels higher than normal. The patients had increased bronchoalveolar levels of ECP, which correlated with impaired lung functioning. Skin infiltration with activated eosinophils and extracellular deposits of ECP were present in skin biopsy samples from the SSc patients. We conclude that eosinophil activation is part of the inflammatory process in SSc. 
1	Characterization of the effect of two 4-methyl piperidine derivatives of hemicholinium-3, A-4 and A-5, on choline transport. A-4 and A-5 are tertiary and N-methyl quaternary 4-methylpiperidine analogs of hemicholinium-3 (HC-3). Previous work in this laboratory has shown A-4 and A-5 to be inhibitors of the sodium-dependent, high affinity choline uptake system (SDHACU). Their effects on choline transport were characterized further using neuroblastoma 41A3 cells. These cells rapidly take up choline through two separate mechanisms: a SDHACU system and a sodium-independent, low affinity uptake system (SILACU). A-4, A-5 and HC-3 decreased 5 microM choline transport in a dose-dependent fashion. The compounds were unable to decrease choline transport at 250 microM choline suggesting that they are inactive with respect to SILACU. All three compounds significantly increased the Km but not the Vmax for the SDHACU system, suggesting a competitive mechanism of inhibition. Ki values ranged from 18 to 25 microM for A-4, 20 to 26 microM for A-5 and 68 to 75 microM for HC-3. Dose-response curves for inhibition of choline transport by A-5 and HC-3 were not changed by a 24-hr pre-exposure of the cells to each inhibitor. However, after a 24-hr pre-exposure to A-4, a significantly different dose-response curve was obtained compared to the dose-response curve for A-4 in untreated cells. After a 24-hr pre-exposure, a 4-hr recovery period was sufficient to remove the effect of each compound. These data suggest that A-4 and A-5, like HC-3, inhibit the SDHACU, competitively and reversibly. 
4	Longitudinal dissociation of atrioventricular accessory pathways. Unusual properties of atrioventricular (AV) accessory pathways were found during electrophysiologic investigations in four patients (three men and one woman). Anterograde longitudinal dissociation of the accessory pathway was observed in two patients and retrograde longitudinal dissociation in two others. Two patients had an accessory pathway with a slow conduction time, one in anterograde direction and one in retrograde direction. These observations further expand our knowledge of the spectrum of electrophysiologic properties of accessory AV pathways. 
3	Learning disabilities in epilepsy: neurophysiological aspects. Subclinical generalized spike-wave discharges are often accompanied by transitory cognitive impairment, demonstrable by psychological testing during EEG recording. Transitory cognitive impairment is demonstrated most readily by difficult tasks and during generalized regular spike-wave bursts lasting for more than 3 s, but can also be found during briefer and even focal discharges. That this is not simply a consequence of global inattention is shown by the fact that focal discharges exhibit some specificity: left-sided focal spiking is more likely to produce errors on verbal tasks, for instance, whereas right-sided discharges are more often accompanied by impairment in handling nonverbal material. Both learning difficulties in general and specific abnormal patterns of cognitive functioning are well documented in children with epilepsy and are most pronounced in those with frequent interictal discharges. However, there is now evidence that intermittent cognitive impairment due to the discharges themselves contributes significantly to such neurophysiological abnormalities. The significance of transitory cognitive impairment accompanying subclinical EEG discharges for everyday functioning is uncertain, but there is experimental evidence that subclinical discharges may be accompanied by disruption of educational skills in children or by impairment of driving performance in motorists. In some individuals, suppression of discharges by antiepileptic drugs has demonstrably improved psychological function, but further work is required to determine the indications for such treatment. 
2	Ascites increases the resting energy expenditure in liver cirrhosis. The purpose of this study was to investigate the effect of ascites on the energy metabolism of patients with liver cirrhosis. The resting energy expenditure was determined in 10 patients with liver cirrhosis and ascites of moderate or large volume. The resting energy expenditure measurement was performed using indirect calorimetry and the resting energy expenditure predictive value was calculated with the Harris-Benedict equation, both before and after removal of ascitic fluid by paracentesis. Metabolic stress factors were absent in all cases. After an interval of 11.2 +/- 7.7 days between measurements, a weight loss of 16.6 +/- 10.3 kg was observed with paracentesis. The resting energy expenditure measured by indirect calorimetry showed a statistically significant decrease from 1682 +/- 291 to 1523 +/- 240 kcal/day (P less than 0.005) after removal of ascites. The repeatability of our indirect calorimetry method only allowed for the analysis of the results in 4 of 10 patients in whom ascites removal produced a consistent decrease in resting energy expenditure. There were no statistically significant differences between the measurements obtained by indirect calorimetry and those provided by the Harris-Benedict equation, but the latter had a moderate reliability in predicting the real resting energy expenditure of every patient. Our results suggest that, far from being an inert volume, ascites may be associated, at least in some patients, with an increased resting energy expenditure and therefore accelerate the appearance of protein energy malnutrition with corresponding complications. 
1	Syringomatous squamous tumors of the breast. Four cases are reported of syringomatous squamous tumors of the breast occurring in women aged 37 to 70 years. The lesions were characterized histologically by relatively well-circumscribed tumor-like nodules composed of a proliferation of teardrop or comma-shaped islands of squamous epithelium. The squamous epithelial islands contained central lumens lined by eosinophilic cuticles and were surrounded by a densely cellular fibrous matrix, thus closely resembling the growth pattern of dermal eccrine syringomas. The lesions appeared to arise de novo from breast parenchyma without evidence of transitions with the surrounding normal or hyperplastic mammary epithelium and were not associated with the overlying skin or nipple epidermis. In all cases, the surrounding breast tissue showed fibrocystic and benign proliferative changes, and in one case, the lesion was found in the vicinity of a large cyst surrounded by microcalcifications. All patients were treated by local surgical excision and have shown no evidence of recurrence over a follow-up period of 1 to 6 years. The histologic differential diagnosis and the possible pathogenesis of these lesions are discussed. 
1	Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient. 
1	Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Between 1983 and 1986, the National Institute for Cancer Research in Genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy (CT) and radiation therapy (RT). One hundred sixteen patients were randomized to receive neoadjuvant CT followed by definitive RT (treatment arm A) or alternating CT and RT. In treatment arm A, RT consisted of 70 Gy to the involved areas and 50 Gy to the uninvolved neck at 2 Gy/fraction, five fractions per week. In treatment arm B, RT consisted of 60 Gy to involved areas and 50 Gy to the uninvolved neck in three courses of 20 Gy each, 2 Gy/fraction, ten fractions/2 weeks alternated with four courses of CT. CT consisted of vinblastine 6 mg/m2 intravenously followed 6 hours later by bleomycin 30 IU intramuscularly, day 1; methotrexate 200 mg intravenously, day 2; leucovorin rescue, day 3. CT was repeated every 2 weeks up to four courses. The same CT was used in both treatment arms of the study. Fifty-five patients were entered in treatment arm A and 61 in treatment arm B. Complete responses were 7/48 and 19/57 in treatment arms A and B, respectively (P less than 0.03). Four-year progression-free survival was 4% in treatment arm A and 12% in treatment arm B (P less than 0.02), and four-year survival was 10% in A and 22% in B (P less than 0.02). Mucosal tolerance was significantly worse in treatment arm B (P less than 0.00004). The subgroup analysis shows the major improvement of alternating CT and RT in patients with the worst prognostic characteristics. 
4	Hemopump ventricular support for patients undergoing high risk coronary angioplasty. Prophylactic implantation of a Hemopump (Johnson and Johnson, Skillman, NJ) has been evaluated in nine patients selected for high risk coronary angioplasty. They were unstable patients, refractory to maximal pharmacology, with indications for revascularization, but contraindications for surgery such as low ejection fraction and lack of material for bypass. In all, the target lesion was located on the last patent vessel. The pump was inserted under local anesthesia, without any graft. A specially designed occluder permitted avoidance of retrograde bleeding during implantation. The bypass flow ranged from 2.5 to 3.2 L/min, and permitted a rise in cardiac index from 2.05 to 2.55 L/min/m2, with a drop in capillary wedge pressure from 13 (7-18) to 10 (7-13) mmHg. During balloon inflation, no electrocardiographic changes were observed, because only minor ventricular arrhythmias occurred. No significant hemolysis was seen (plasma free hemoglobin less than 10 mg/dl in all) after 2 hr of pumping. The only limitation of the technique appears to be difficulty at the time of implantation from narrow, stenosed, or tortuous iliofemoral arteries (3 patients). This experience strongly supports the benefit of temporary left ventricular Hemopump support in high-risk situations and clearly shows the need for a smaller pump. 
2	Spontaneous rupture of the stomach in an adult. We have reported a case of spontaneous rupture of the stomach in an adult. Immediate onset of severe upper abdominal pain after overindulgence in food and drink along with radiographic evidence of pneumoperitoneum and the clinical findings of massive abdominal distention, epigastric tenderness, shock, and occasionally subcutaneous emphysema should suggest the possibility of gastric rupture. The treatment is simple, but mortality is high when surgical intervention is not rapid. 
4	Regression of infundibular pulmonary stenosis after successful balloon pulmonary valvuloplasty in adults. Between July 1985 and March 1988, 22 adult patients with congenital pulmonary stenosis underwent balloon pulmonary valvuloplasty. There were 10 males and 12 females aged 16-45 (average 25 +/- 9.9) years. All patients had additional mild to severe infundibular stenosis; 16 were restudied 6-36 (mean 12.6) months later by repeat catheterization. Student's t-test was used for comparison of data. Right ventricular (RV) systolic pressure before dilatation was 84-196 (mean 129 +/- 32.3) mm Hg, and the peak pulmonary gradient (PPG) was 60-176 (mean 111 +/- 33.2) mm Hg immediately after dilatation. The RV systolic pressure dropped to 32-140 (mean 59.2 +/- 27) (P less than 0.001); and PPG dropped to 10-113 (mean 37.8 +/- 26.4) (P less than 0.001), and the infundibular gradient ranged from 8 to 113 (mean 35.1 +/- 25.8) mm Hg. The infundibular diameter, before dilatation, ranged from 2 to 15 (mean 9.5 +/- 4) mm Hg. At repeat catheterization, the RV systolic pressure dropped further to 33-66 (mean 42.8 +/- 9.7) mm Hg and the PPG was reduced to 0-48 (mean 18.4 +/- 10.9) mm Hg (P less than 0.001). The infundibular gradient regressed to 0-34 (mean 15 +/- 8.8) mm Hg (P less than 0.001). The infundibular diameter increased to 8-25 (mean 15.8 +/- 5.4) (P less than 0.001). It is concluded that moderate to severe infundibular stenosis, in adults, can regress after successful pulmonary valvuloplasty. 
1	Changing demographics in the United States. Implications for health professionals. The coming decade will bring dramatic changes in the composition of the American population. Changes in immigration laws, illegal and legal immigration into this country, and the aging of the "baby boomers" will all result in profound changes in the demographics of this country. These demographic changes will necessitate alterations in all aspects of the health care system. This article focuses on the projected changes that will occur in relation to the elderly, Hispanics, Asian Americans, and the economically disadvantaged, and on the related implications for health care professionals. The cancer incidence and mortality rates for each discussed minority group differ from the rates presently reported for white Americans. Thus, health professionals will have to be aware of the differences among these groups and tailor their primary and secondary prevention efforts accordingly. The future task for all health care providers serving minorities and the elderly will be to familiarize themselves with the special health problems of the population with whom they work and with the ethnocultural barriers that deter proper use and delivery of health services. 
3	Obstructive sleep apnea following topical oropharyngeal anesthesia in loud snorers. Previous studies support the presence of an upper airway reflex mechanism that contributes to the maintenance of upper airway patency during sleep. We investigated the possibility that interference with this reflex mechanism contributes to the development of obstructive sleep apnea. Eight otherwise asymptomatic snorers (seven male and one female), age 39 +/- 5.3 yr (mean +/- SEM), underwent overnight sleep studies on three successive nights. An acclimatization night was followed by two study nights randomly assigned to control (C) and oropharyngeal anesthesia (OPA). On the OPA night topical anesthesia was induced using 10% lidocaine spray and 0.25% bupivacaine gargle. A saline placebo was used on night C. All subjects slept well on both study nights (mean sleep duration was 6.2 h on both study nights), and sleep stage distribution was similar on both nights. Obstructive apneas and hypopneas (OAH) rose from 114 +/- 43 during C to 170 +/- 49 during OPA (p less than 0.02). Central apneas and hypopneas (CAH) were unchanged between the two nights (8 +/- 4.9 versus 7 +/- 3). The duration of OAH was similar on both study nights (20 +/- 1.9 s during C versus 20 +/- 1.5 s during OPA). The frequency of movement arousals terminating OAH tended to be higher during OPA (7 +/- 2.9/h) than during C (3 +/- 0.7); P = NS. The frequency of oxyhemoglobin desaturations was also higher during OPA (5 +/- 2.1/h) than during C (3 +/- 1.4), p less than 0.07. 
4	Erythrocyte fatty acids, plasma lipids, and cardiovascular disease in rural China. Cardiovascular disease (CVD) mortality (coronary heart disease, hypertensive heart disease, and stroke), plasma lipids, and red blood cell fatty acid composition were examined in an ecologic study in 65 rural counties in the People's Republic of China. Means of plasma total cholesterol, triglyceride, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations were substantially lower and the ratio of HDL cholesterol to total cholesterol was higher in this Chinese population than in Western populations. Mortality rates for CVD in China were well below Western values. Within China neither plasma total cholesterol nor LDL cholesterol was associated with CVD. A strong inverse correlation between red blood cell oleate concentrations and CVD was observed. However, red blood cell oleate concentrations were not associated with plasma cholesterol but were strongly negatively associated with arachidonate concentrations, suggesting potential diminution of CVD by oleate through reduced platelet aggregability. The results indicate that geographical differences in CVD mortality within China are caused primarily by factors other than dietary or plasma cholesterol. 
5	Rectal strictures: treatment with fluoroscopically guided balloon dilation. The authors performed 25 fluoroscopically guided balloon dilation procedures in nine patients with rectal strictures. In all cases, the stricture developed after rectal surgery. Four patients underwent ileoanal anastomosis after total colectomy for various conditions; five patients underwent rectosigmoid end-to-end anastomosis after resection of a tumor or as treatment for diverticulitis. Maximal stricture dilatation was attained in 20 instances with a single 15-30-mm balloon. In five procedures, two balloons (20 or 15 mm) were inflated simultaneously ("kissing balloons" technique) to dilate the strictures. In five patients, only one dilation procedure was required for effective treatment of the strictures, with no clinical evidence of strictures after follow-up of 1.5-56 months (mean, 29.5 months). In the other four patients, multiple procedures were performed: nine in one patient, five in one patient, and three in two patients. In these patients, no recurrent symptoms developed during follow-up of 1.25-18 months (mean, 8.1 months) after the last dilation. Complicating leaks, infection, or hemorrhage did not occur after any of the procedures. Fluoroscopically guided balloon dilation is a safe and effective procedure for the treatment of rectal strictures. 
5	Cystic medionecrosis of the coronary arteries and fatal coronary vasospasm. The histopathological basis of coronary vasospasm is not well defined. We report a patient with directly observed coronary artery spasm in whom cystic medionecrosis of the coronary arteries and great vessels and myxomatous degeneration of the mitral valve were evident. We suggest that myxoid connective tissue lesions of the heart may be linked to coronary vasospasm. 
1	Rectourethral fistula caused by Kaposi's sarcoma. A 35-year-old man with the acquired immunodeficiency syndrome-related complex was evaluated for a persistent urethral discharge, pneumaturia and watery diarrhea. Radiographic and endoscopic procedures established the diagnosis of a rectourethral fistula. Perineal exploration and excision of the fistula revealed the pathological diagnosis of Kaposi's sarcoma. The differential diagnosis of an acquired rectourethral fistula and the significance of Kaposi's sarcoma are discussed. 
4	Effect of propranolol on endothelin-induced increase in cytosolic free calcium. This study was designed to investigate the effect of propranolol on endothelin (ET)-1-induced increase in cytosolic Ca2+ [( CA2+]i) in cultured vascular smooth muscle cells (VSMCs) obtained from rat aorta. Propranolol (0.01 to 1 mmol/L) reduced the changes in the initial transient and the later sustained phase of [Ca2+]i induced by 100 nmol/L ET-1 as well as 10 mmol/L procaine. The inhibitory action of propranolol on the change in [Ca2+]i induced by ET-1 may be involved in one of the mechanisms of propranolol-induced reduction of vasospasms. 
4	Acute posterior multifocal placoid pigment epitheliopathy with cerebral involvement. In a patient with angiographically proven cerebral vasculitis five months after acute posterior multifocal placoid pigment epitheliopathy (APMPPE) neurological symptoms promptly responded to steroid treatment. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis. Magnetic resonance imaging (MRI) revealed multifocal white matter lesions in the hemispheres and the brain stem suggesting a diffuse subcortical vasculitis. 
3	Functional results of facial nerve suture after removal of acoustic neurinoma: analysis of 25 cases. The facial nerve is sometimes severed during the removal of acoustic neurinomas, either intentionally to ensure complete removal, or unintentionally because of difficulties in identification. In such cases we have, if possible, sutured the nerve stumps microsurgically, either end to end or by use of an intervening nerve graft. We analyzed the outcome of 25 instances of facial nerve suturing in a series of 219 patients operated on for acoustic neurinoma from 1979 to 1987. The first signs of recovery appeared at an average of 12 months, and there was continued improvement for several years. Recovery was graded from 1 to 6. The anastomosis was successful in 24 of the 25 sutured nerves, in that at least some facial movement and tone were restored (Grade 5 or higher). In 11 of the 25 cases, facial appearance at rest and with movement was moderately good (Grade 2 or 3). A Grade 1 result, with no perceivable facial dysfunction, was never achieved. Typically, oral muscles showed the most improvement and frontal muscles the least. Facial appearance was better at rest than with movement, which was always complicated by some degree of synkinesis. Closure of the eye was so good in 13 of the 25 cases that neither tarsorrhaphy nor an eyelid spring was necessary. When the facial nerve is severed, intraoperative suture is recommended, because it provides a chance for moderately good restoration of facial appearance. 
3	Motor units in incomplete spinal cord injury: electrical activity, contractile properties and the effects of biofeedback. The electrical and contractile properties of hand muscles in a selected population of quadriplegic subjects were studied intensively before and after EMG biofeedback. Spontaneously active motor units and units that could only be slowly and weakly activated were observed in these subjects, in addition to units that were voluntarily activated normally. This suggests a considerable overlap of surviving motor neurons to a single muscle that are below, near or above the level of a lesion. Despite the common occurrence of polyphasic potentials and other signs of neuromuscular reinnervation, the average twitch tension of single motor units in hand muscles of quadriplegic subjects was not significantly different from that in control subjects. Nor did it increase after biofeedback training that typically increased the peak surface EMG by a factor of 2-5 times. The percentage of spontaneously active units was also constant. The surface EMG may be increased during biofeedback by using higher firing rates in motor units that can already be activated, rather than by recruiting previously unavailable motor units. 
5	Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. BACKGROUND. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS. Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS. Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS. The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy. 
1	Photodynamic therapy in the treatment of squamous cell carcinoma of the head and neck. Photodynamic therapy is an experimental modality for tumor treatment based on the combined action of the tumor-localizing agent, ie, hematoporphyrin derivative, and red light. From 1985 through 1989, 26 patients were treated using hematoporphyrin-derived drugs and 630-nm light delivered by a tunable dye laser. All patients had biopsy-proved squamous cell carcinoma of the head and neck, and they had either failed the traditional treatment modalities or refused conventional therapies. Histological complete responses were achieved in 20 (77%) of 26 patients and partial responses in 5 (19%) of 26 patients for periods up to 48 months. Only minimal toxic reaction was noted in the group. As a guide to treatment planning for a patient group with large tumors, we used an optical dosimetry model based on tissue optics. The rate of complete responses to this treatment was 8 (73%) of 11. Our data indicate that photodynamic therapy is capable of inducing significant clinical and histological responses in the majority of those treated, and in some patients a prolonged response is produced. In certain select head and neck malignancies, photodynamic therapy has an important role as a treatment modality. 
5	Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. The clinical and laboratory features of 29 patients who had one of three anti-aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports. These autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis (24 patients) and pulmonary fibrosis (23 of 29), but also including inflammatory arthritis (26/29), keratoconjunctivitis sicca (17/29), sclerodactyly (21/29), Raynaud's phenomenon (27/29), hepatitis (8/29) and subcutaneous calcinosis (7/29). The most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease. No patient fulfilled the classification criteria for systemic lupus erythematosus, although 10 had autoantibodies to extractable nuclear antigens including Ro, La, RNP, and Sm, and two patients had anti-dsDNA antibodies. Although it seems unlikely that anti-aminoacyl-tRNA synthetase antibodies are directly responsible for causing disease, they may provide an important clue to the aetiology of this unusual syndrome. 
5	Pathologic bronchial vasculature in a case of massive hemoptysis due to chronic bronchitis. The cause of bleeding in a patient with recurrent massive hemoptysis was not apparent after bronchoscopy and gross examination of the lobectomy specimen. Histologic submission of all major bronchi uncovered dilated, tortuous bronchial arteries just below the bronchial mucosa with sites of both current and healing arterial rupture. This bronchial arterial abnormality is common to several chronic pulmonary diseases, but is rarely diagnosed as a cause of massive hemoptysis. Careful pathologic examination of major bronchi in the setting of hemoptysis of unknown causation is recommended. 
5	Endoscopic laser arytenoidectomy revisited. Arytenoidectomy is currently the most reliable method of treating patients with bilateral vocal cord paralysis. Although both endoscopic and external approaches have been described, the endoscopic laser technique is more desirable because it requires no incision and allows for the immediate assessment of airway size. Eleven patients with bilateral vocal cord paralysis treated by endoscopic laser arytenoidectomy were presented in 1984. At that time, 10 of the 11 patients had been successfully decannulated. Follow-up on that group of patients revealed that 7 of the 10 successfully treated patients remain decannulated with a good airway, although 2 of these patients required a revision procedure to excise a granuloma. One patient failed at 15 months and has failed two subsequent revision operations, and 2 patients have been lost to follow-up. Since 1984, 17 additional patients with bilateral vocal cord paralysis have been treated by the authors using the same endoscopic laser arytenoidectomy technique; all have been successfully managed, with a minimum follow-up of 3 years. The technique of this operation will be reviewed. This study demonstrates the clinical usefulness of endoscopic laser arytenoidectomy in the treatment of bilateral vocal cord paralysis. 
5	Unknown primary squamous cell carcinoma metastatic to the neck. We analyzed retrospectively 157 cases of metastatic neck squamous cell carcinoma from unknown primary sites, treated with surgery, radiotherapy, excisional biopsy, and combined modalities. Median follow-up was 74 months, and overall actuarial survival was 55% at 5 years. The surgery-treated group, despite a higher rate of manifesting primary tumors, had significantly better survival at 5 years compared with those receiving radiation therapy, of whom 23% had residual disease after treatment. Primary tumors were discovered during follow-up in 16% overall. Different treatments yielded comparable results in lower-staged neck disease (NX, N1, N2a), while surgery appeared more effective in controlling advanced disease (N2b, N3a). Factors that affected survival include neck stage, connective tissue invasion, and presence of recurrent or residual disease after treatment. 
2	Gallbladder perforation and bile leakage: percutaneous treatment. Three patients with spontaneous gallbladder perforation and one with an iatrogenic bile leak causing bile peritonitis were treated successfully by means of percutaneous catheter drainage. Three patients had cholelithiasis as the cause of perforation; the fourth patient had previously undergone gallstone dissolution with methyl tert-butyl ether lavage and developed bile peritonitis a few hours after removal of the catheter. In three patients, a percutaneous cholecystostomy catheter provided successful decompression; in the fourth patient, drainage was performed with a percutaneous sump catheter in the subhepatic space adjacent to the gallbladder. No specific complications occurred. Follow-up was performed at 1, 12, 22, and 59 months, respectively. To date, one of the four patients has undergone elective cholecystectomy (1 month after drainage). The remainder of the patients are asymptomatic. This preliminary experience suggests that the severe complication of gallbladder perforation and bile leakage may be treated, at least temporarily, by means of percutaneous drainage. 
1	Primary adenocarcinoma of the bladder: favorable prognostic significance of deoxyribonucleic acid diploidy measured by flow cytometry. Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy. 
2	Endocrine consequences of alcohol abuse. The recognized endocrine consequences of alcohol abuse are reviewed on an organ by organ basis. The organ systems for which the most information is available (liver, heart, brain) are presented first followed by those where the information base is less. 
5	Characteristics of an elderly driving population referred to a geriatric assessment center. A retrospective, case-control study was performed to determine the characteristics of elderly drivers referred to an outpatient geriatric assessment center. It was hypothesized that the driving population was operating at a higher cognitive and functional level than nondrivers. One hundred eighty-two subjects meeting the entry criteria were studied. Twenty-three percent of the subjects were driving at the time of their assessment. Compared to nondrivers, drivers were younger (P = .0001), were more likely to be male (P = .003), scored higher on a mental status examination (P = .0001), and were more independent in Physical and Instrumental Activities of Daily Living (P less than .0001). Despite these findings, the mean Folstein Mini-Mental score for drivers (23.7) was below normal; 40% of drivers were diagnosed as having Alzheimer's dementia at the time of their evaluation, and over 26% of the drivers needed help with either dressing or bathing. The frequency of impaired elderly drivers in this referral setting was high. The authors conclude that conditions that affect the driving task are common in geriatric assessment centers. Prospective studies of elderly drivers are needed to answer the difficult question of who among the elderly should drive. 
4	Correction of metabolic acidosis in experimental CPR: a comparative study of sodium bicarbonate, carbicarb, and dextrose. STUDY OBJECTIVE: Carbicarb, sodium bicarbonate, and 5% dextrose were compared for effects on resuscitability in a canine model of electromechanical dissociation after ventricular fibrillation. DESIGN/INTERVENTIONS: 21 healthy mongrel dogs were anesthetized with pentobarbital, intubated, and mechanically supported. They were instrumented to measure heart rate, arterial pressure, pulmonary artery pressure, right atrial pressure, cardiac output, and arterial and mixed venous blood gases. The dogs were then subjected to a protocol that consisted of three successive CPR episodes. During each episode they were treated with repeated injections of one of the three substances, randomly chosen. After two minutes of ventricular fibrillation and four minutes of electromechanical dissociation, CPR was started with a thumper (rate, 60; duty cycle, 50%). If recovery was not obtained after five minutes of CPR, 1 mEq/kg carbicarb or sodium bicarbonate or 5 mL D5W was injected in the right atrium. Half the dose of the same substance was injected every five minutes thereafter; 1 mg epinephrine was also injected every five minutes until recovery. Hemodynamic and gasometric evaluations were performed five and 20 minutes after recovery. This later evaluation served as baseline for the next CPR episode. MEASUREMENTS AND MAIN RESULTS: The duration and success rates of CPR are similar in the three CPR groups. Hemodynamic parameters were also similar during recovery. Bicarbicarb and sodium bicarbonate increased bicarbonate levels and corrected pH in the arterial and mixed venous blood. There was no difference in the blood gas values after carbicarb and sodium bicarbonate. CONCLUSION: In this model of cardiac arrest, carbicarb was not superior to sodium bicarbonate in the correction of metabolic acidosis during CPR. 
5	Differential effects of continuous versus intermittent suction on tracheal tissue. The purpose of this study was to determine the differential effect of continuous versus intermittent application of negative pressure on tracheal tissue during endotracheal suctioning. The sample consisted of 12 mongrel dogs, randomly assigned to group 1 (N = 5), continuous suction, or group 2 (N = 5), intermittent suction. All animals were orally intubated (40F endotracheal tube). Two control animals were intubated and not suctioned. Animals in group 1 and 2 were suctioned every 15 minutes for 4 hours for a total of 16 suction passes. Endotracheal suctioning was performed by using a 14F suction catheter either continuously (10 seconds) or intermittently (2 seconds with, 1 second without for a total of 10 seconds) at a suction pressure of 200 mm Hg and a suction flow rate of 16 L/min. Tracheal tissue samples were examined for simplified and major simplified damage, ulceration, and ulceration with necrosis. Results indicated that all forms of damage were present with both suctioning techniques. No significant differences were found between group 1 and group 2 (Wilcoxon rank sum) for any of the alterations. Results indicate that both continuous and intermittent application of negative pressure with endotracheal suction produces significant damage to tracheal tissue. 
4	Future directions in vasodilator therapy for heart failure. Vasodilator therapy has become a major pharmacologic approach for improving left ventricular function, and consequently, vasodilator drugs are being used increasingly in the treatment of heart failure. Ideally, vasodilator drugs used in the long-term management of heart failure should show clearly defined pharmacodynamic effects. These include reduced impedance to left ventricular ejection, increased venous capacitance, increased left ventricular ejection fraction and reduced heart size, absence of neurohormonal stimulation, and slowed progression of left ventricular dysfunction. The mechanisms of action and sites of activity of the various vasodilator drugs currently available vary considerably, and none as yet has proved ideal for the treatment of heart failure or hypertension. The complexity surrounding the multiple vasoconstrictor mechanisms involved in heart failure has led to a rationale for combined vasodilator therapy and certain combinations are discussed. From a therapeutic standpoint, the development of drugs with multiple mechanisms of action is particularly attractive. Flosequinan is a new vasodilator agent whose cellular mechanism of action remains uncertain. Flosequinan has the advantage of being able to relax both arterial and venous beds and as such may be particularly beneficial in the treatment of heart failure. 
2	Vaccination against hepatitis B and protection against chronic viral carriage in The Gambia. 358 children in the Gambian villages of Keneba and Manduar, where hepatitis B virus (HBV) infection is endemic, were vaccinated with plasma-derived vaccine against HBV according to one of four regimens and followed for up to 4 years. Two regimens by which vaccine was injected intradermally into children between 0 and 4 years old led to peak geometric mean (95% CI) concentrations of antibody against HBV surface antigen of 270 (202-358) and 555 (418-748) mlU/ml. The third regimen--intramuscular vaccination of children aged between 0 and 4 years--gave geometric mean peak antibody concentrations of 926 (765-1122) mlU/ml. A fourth regimen was intramuscular vaccination of children between 1 and 9 months old, which gave geometric mean antibody concentrations of 5431 (3903-75,456) mlU/ml. Despite these widely divergent responses and a 89% decay in antibody over the first 2 years, vaccination against HBV was 97% effective in preventing chronic infection. Vaccination was less effective in preventing uncomplicated infection: 5.3% of 264 vaccinees in Keneba and 19.1% of 94 vaccinees in Manduar tested positive for antibody to HBV core antigen. These "breakthrough infections" did not differ in frequency between regimens, and were associated with low initial antibody responses and chronic maternal carriage of HBV. 
1	The interferon system in carcinoma of the cervix. Effect of radiation and chemotherapy. Thirteen patients with advanced carcinoma of the cervix were studied for parameters of the interferon system compared with 40 age-matched and sex-matched controls. All patients had measurable serum interferon levels; controls did not. All patients had non-antibody-type interferon-inhibitory activity, and controls had none. Interferon-synthesizing potential was higher in controls than in patients. After successful radiation and chemotherapy, these parameters normalized in the patients. No change was seen in one patient who did not respond to therapy. 
4	Left ventricular asynchrony: an indicator of regional myocardial dysfunction. There is a marked heterogeneity of myocardial wall thickening within the left ventricle and among different individuals. It is therefore difficult to detect regional myocardial dysfunction from absolute values of systolic wall thickening. We tested whether the extent of left ventricular asynchrony during ischemia and reperfusion can be used to quantify the severity of regional myocardial dysfunction when nonischemic baseline function is not known. In six anesthetized, open-chest dogs regional myocardial wall thickness was measured by means of sonomicrometry under control conditions, at three degrees of ischemic dysfunction (mild, moderate, and severe), and after release of a 15-minute occlusion of the left circumflex coronary artery, when degrees of moderate and mild reperfusion dysfunction similar to the preceding ischemic dysfunction were present. Two indexes of left ventricular asynchrony were calculated: (1) postejection thickening (PET) and (2) the phase difference of the first Fourier harmonic of posterior versus anterior myocardial wall motion (PD). Systolic myocardial wall thickening was decreased from 15.3 +/- 3.1 (standard deviation) % (control value) to 9.7 +/- 1.4% (mild ischemia), 4.2 +/- 1.6% (moderate ischemia), and -3.7 +/- 3.1% (severe ischemia). Conversely PET increased from 0.02 +/- 0.04 mm (control value) to 0.15 +/- 0.22 mm (mild ischemia), 0.19 +/- 0.15 mm (moderate ischemia), and 0.50 +/- 0.26 mm (severe ischemia). PD increased from 9 +/- 28 degrees (control value) to 22 +/- 19 degrees (mild ischemia), 54 +/- 18 degrees (moderate ischemia), and 107 +/- 21 degrees (severe ischemia). After release of the 15-minute left circumflex coronary artery occlusion, PET and PD recovered to 0.34 +/- 0.19 mm and 36 +/- 24 degrees (moderate dysfunction) and 0.25 +/- 0.31 mm and 29 +/- 8 degrees (mild dysfunction), respectively. There were inverse linear relationships between systolic wall thickening and PET (r = -0.86, p less than 0.001) and between systolic wall thickening and PD (r = -0.87, p less than 0.001). Inotropic stimulation by postextrasystolic potentiation increased regional systolic myocardial posterior and anterior wall thickening but did not alter the extent of left ventricular asynchrony. Thus, when normal baseline function is not known, the severity of regional myocardial dysfunction at a given inotropic state can be determined by analysis of left ventricular asynchrony. There was no significant correlation between the extent of PET and PD during ischemia and at early reperfusion and the recovery of contractile function at late reperfusion. Thus PET does not provide a prospective marker for the functional outcome of reperfusion. 
5	Reoperative versus conservative management for gastrointestinal fistulas. Development of a fistula is a serious complication. It is necessary to identify its anatomic and pathologic features, as these can influence the outcome of treatment independent of the primary disease. Electrolyte abnormalities should be addressed as volume deficits are being restored. Sepsis, the most common cause of death in patients with fistulas, must be controlled, and the skin must be protected. Reoperation and conservative management are not opposing forms of therapy but rather are complementary. 
5	Lack of effect of induced menses on symptoms in women with premenstrual syndrome BACKGROUND. No physiologic abnormality of the luteal phase has been consistently demonstrated in women with premenstrual syndrome (PMS). Using the progesterone antagonist mifepristone, we truncated the late luteal phase of the menstrual cycle in a blinded fashion to evaluate the relation of the events of the late luteal phase to the symptoms of PMS. METHODS. Fourteen women with PMS were given mifepristone (12.5 or 25 mg per kilogram of body weight) by mouth on the seventh day after the surge of luteinizing hormone. On the sixth through the eighth days after the surge, they also received injections of either placebo or human chorionic gonadotropin (2000 IU). Seven women with PMS received placebo instead of both mifepristone and human chorionic gonadotropin. All the women completed daily questionnaires measuring a variety of mood-related and somatic symptoms. RESULTS. Mifepristone consistently induced menses. The women receiving only mifepristone had plasma progesterone levels like those of the follicular phase (less than 3 nmol per liter) within four days, whereas all the other women had plasma progesterone levels characteristic of the luteal phase (greater than 8 nmol per liter) for at least seven days after treatment. In all three groups, the severity of symptoms was significantly higher after treatment than before, according to an analysis of variance with repeated measures. The level and pattern of the ratings of symptom severity were similar in all treatment groups. CONCLUSIONS. Neither the timing nor the severity of PMS symptoms was altered by mifepristone-induced menses or luteolysis. The temporal association of typical PMS symptoms with an artificially induced follicular phase suggests that endocrine events during the late luteal phase do not directly generate the symptoms of PMS. 
1	Magnetic resonance imaging contrast agents: theory and application to the central nervous system. The theoretical aspects of magnetic resonance (MR) imaging contrast agents are reviewed, and their current applications to the central nervous system (CNS) and their future applications are discussed. Profound differences exist between contrast agents used for MR imaging and computerized tomography (CT). In MR imaging, the contrast agents are not imaged directly but rather act on adjacent protons to shorten T1 and T2 relaxation times. This in turn results in signal intensity changes. The lanthanide metal, gadolinium, in the form of gadopentetate dimeglumine, has been found to be both safe and efficacious as the only currently approved contrast agent for MR imaging. Magnetic resonance imaging revolutionized the detection and treatment of disease affecting the brain and spine. Initially, it was thought that signal characteristics on MR imaging would allow differentiation of specific pathology. It was soon found that MR studies were able to detect more abnormalities but were less able to characterize them. The recent development of contrast agents for MR imaging has allowed this modality to surpass CT for the evaluation of most CNS lesions. At present, contrast-enhanced MR imaging is generally accepted as the study of choice for evaluating acoustic neurinomas, pituitary lesions, meningeal disease, primary and secondary brain tumors, active multiple sclerosis, intradural spinal neoplasms, intramedullary spinal disease, and postoperative states in both the spine and brain. Even when contrast-enhanced CT can detect the same abnormalities, evaluation of the lesions in multiple planes on MR imaging can sometimes yield invaluable information, especially prior to surgery. Future developments of contrast material for MR imaging include non-gadolinium compounds, intrathecal contrast media, cerebral blood flow and volume evaluation, and, possibly, antibody-labeled contrast agents. 
4	Postcardiotomy mechanical circulatory support in the elderly. The role of mechanical circulatory support after cardiac operations in elderly patients is not clearly established. Between November 1985 and July 1989, 18 patients 65 years of age or older (mean age, 71 years; range, 65 to 82 years) were treated after cardiotomy with a centrifugal vortex or pneumatic mechanical ventricular assist device. This group comprised 1.9% of the 926 patients 65 years of age or older undergoing cardiac surgical procedures and 69% of the 26 patients requiring postcardiotomy support during this interval. Before institution of mechanical support, all patients were receiving maximal inotropic support and 16 patients had intraaortic balloon pumps inserted. Univentricular support was used in 9 patients (6 left, 3 right) and biventricular support in 9 patients. The mean duration of support was 45 hours (range, 8 to 118 hours). Twelve patients (67%) were successfully weaned, 8 (44%) were discharged from the hospital, and 6 (33%) remain alive 11 to 31 months postoperatively. Four of the 6 survivors are in New York Heart Association class I, 1 is in class II, and 1 is in class IV. The Combined Registry for ventricular assist device support has recently reported an overall survival rate of 12% in patients 65 to 70 years of age and 6% in those older than 70 years. Our results are comparable with those reported for younger patients and justify the use of postcardiotomy ventricular assist device support in the elderly. 
2	Increased sympathetic outflow in cirrhosis and ascites: direct evidence from intraneural recordings. OBJECTIVE: To determine if central sympathetic outflow is increased in patients with cirrhosis and ascites. PATIENTS: Eleven patients with cirrhosis and ascites, 8 patients with cirrhosis but without ascites, and 7 age-matched and 8 young healthy volunteers. METHODS: With subjects supine, direct microneurographic recordings of efferent post-ganglionic muscle sympathetic nerve activity were obtained from the peroneal nerve, and sympathetic burst frequency was compared with subjects' blood pressure, heart rate, sodium excretion, catecholamines, and plasma renin activity. All patients with cirrhosis were studied at least 5 days after withdrawal from all medications and after 7 days of a 20 mmol/d sodium, 1-L fluid-restricted diet. Age-matched volunteers were studied after 7 days of 20 mmol/d sodium intake and young healthy volunteers after 7 days of 150 mmol/d sodium intake. RESULTS: Sympathetic nerve activity in ascitic patients (65 +/- 15 bursts/min; mean +/- SD) was markedly increased, whether compared with patients with cirrhosis but without ascites (34 +/- 16 bursts/min; P less than 0.001), age-matched healthy volunteers on similar sodium intake (27 +/- 22 bursts/min; P less than 0.001), or young healthy subjects (21 +/- 10 bursts/min; P less than 0.001). The frequency of muscle sympathetic nerve discharge was directly related to plasma norepinephrine and epinephrine concentrations, plasma renin activity, and heart rate, all of which were increased in those patients with cirrhosis and ascites, and inversely related to 24-hour urinary sodium excretion, the fractional excretion of sodium, and subjects' pulse pressures. Sympathetic nerve activity fell from 78 to 6 bursts/min in one patient after liver transplantation. CONCLUSIONS: This study provides the first direct evidence that elevated plasma norepinephrine concentrations in patients with cirrhosis and ascites are due to increased central sympathetic outflow. Sympathetic nerve activity is not increased in patients with cirrhosis but without ascites. Because there were direct positive correlations of sympathetic nerve activity with plasma norepinephrine concentrations, plasma epinephrine concentrations, plasma renin activity, and heart rate, the increase in central sympathetic outflow in patients with cirrhosis and ascites appears generalized and not restricted to muscle nerves. The anti-natriuretic effects of parallel increases in renal and muscle sympathetic nerve activity could account for the inverse correlation between muscle sympathetic nerve activity and sodium excretion. 
5	Rib infarcts and acute chest syndrome in sickle cell diseases. In the absence of evidence for pneumonia or pulmonary embolus, primary pulmonary infarction has been assumed to be the cause of the syndrome of chest pain, fever, and pulmonary infiltrate on chest X-ray that commonly complicates sickle cell anaemia. To find out whether the syndrome might be due to rib infarction, 99mTc-diphosphonate bone scans were done. In the eleven episodes thus investigated (10 patients) the scans showed segmental areas of increased radionuclide uptake in ribs, indicative of bone infarction. A possible sequence of events is that the rib infarcts are primary and cause bone pain, followed by soft tissue reaction, pleuritis, and splinting. The resultant hypoventilation leads to atelectasis and subsequent development of the radiographic changes of the acute chest syndrome. Prevention of hypoventilation and treatment of bone pain are important therapeutic goals. 
4	Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. The prevalence of pulmonary hypertension in 507 patients hospitalized with portal hypertension but without known pulmonary hypertension who underwent cardiac catheterization was prospectively studied. Ten (2%) of these patients, 6 of whom were clinically asymptomatic, had primary pulmonary hypertension. Second, 26 patients with symptomatic pulmonary hypertension complicating portal hypertension were reviewed. Pulmonary hypertension occurred later after diagnosis of portal hypertension in patients with a surgical shunt (10 patients) than in those without a shunt (147 +/- 49 vs. 44 +/- 27 months; P less than 0.0001). Cardiac index correlated inversely with pulmonary arterial pressure (r = -0.45; P less than 0.01) and was lower in the 5 patients who died of pulmonary hypertension than in the 5 who died of liver failure (1.52 +/- 0.14 vs. 3.69 +/- 1.88 L/min.m2; P less than 0.05). Third, systemic and splanchnic hemodynamics were compared in 285 patients with alcoholic cirrhosis and 29 controls. No significant relation was found between elevated pulmonary vascular resistance and increased portal pressure, zzygos blood flow, or cardiac index. Pulmonary hypertension is considerably more frequent than was previously estimated in patients with portal hypertension. The risk of developing pulmonary hypertension could increase with the duration of portal hypertension without any clear relation to the degree of portal hypertension, hepatic failure, or amount of blood shunted. 
5	Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study. A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease. 
4	Surgical experience with cerebral amyloid angiopathy. Cerebral amyloid angiopathy can present as lobar intracerebral hemorrhage in an elderly person, presumably due to increased fragility of the vessels affected by amyloid deposition. For this reason, patients presenting with intracerebral hemorrhage and suspected of having cerebral amyloid angiopathy have often been treated nonsurgically. Since 1983 we have evaluated 11 patients with cerebral amyloid angiopathy (nine women and two men, mean age 73 years) who have undergone either intracerebral hematoma evacuation or brain biopsy. Nine of the 11 patients presented with intracerebral hemorrhage, which was unilobar in three patients and multilobar in six and involved the parietal lobes seven times, the frontal lobes four times, the temporal lobes four times, and the occipital lobes twice. These nine patients underwent hematoma removal, with no cases of abnormal intraoperative bleeding or recurrent hemorrhage. Six patients improved neurologically, and two were unchanged after hematoma evacuation; the remaining patient had a fatal cardiopulmonary arrest during the immediate postoperative period. During follow-up in seven patients (median 11 months, range 1 week to 74 months) none experienced a recurrent intracerebral hemorrhage and four continued to improve. Two of the 11 patients had cerebral amyloid angiopathy diagnosed by brain biopsy as part of an evaluation for dementia, also without surgical complications. This series suggests that patients with cerebral amyloid angiopathy may safely undergo operative procedures, and patients presenting with intracerebral hemorrhage may show neurologic improvement following evacuation of the hematoma. 
4	Intestinal ischemia complicating abdominal aortic surgery. A 9-year experience with 2137 patients undergoing infrarenal abdominal aortic reconstruction was reviewed to determine both the incidence of intestinal ischemia and the clinical, anatomic, and technical factors associated with this complication of aortic surgery. A total of 24 (1.1%) patients had overt intestinal ischemia, documented by reoperation or endoscopic findings. Of these, colon ischemia occurred in 19 (0.9%) and small bowel ischemia developed in 5 (0.2%) patients. The incidence after elective operation for aneurysmal or occlusive disease did not differ, but patients with ruptured aneurysms and those undergoing reoperative procedures for total graft replacement were at higher risk. Preoperative angiography was most helpful in ascertaining risk. Ligation of a patent inferior mesenteric artery was the most common (74%) feature in patients with colon ischemia. With preexisting inferior mesenteric artery occlusion, impairment of collateral circulation was attributable to superior mesenteric artery disease, dissection or retractor injury, prior colon resection, or exclusion of hypogastric perfusion. Bloody diarrhea was the most frequent postoperative symptom and colonoscopy the most reliable means of diagnosis. One half of patients with colon ischemia required resection after late recognition of perforation. All cases of small bowel ischemia were related to superior mesenteric artery disease or injury or use of suprarenal clamping. The overall mortality rate was 25% but rose to 50% if bowel resection was required. Intestinal ischemia remains an infrequent but serious complication of aortic surgery. Despite a multifactorial cause, identification of patients at increased risk can lead to operative strategies to reduce its occurrence. 
4	Left atrial bacterial mural endocarditis. An unusual case of Staphylococcus aureus endocarditis confined to the mural left atrium is presented. Echocardiographic studies revealed a 1.5 x 2.0-cm vegetation mimicking a myxoma situated in the path of a mitral regurgitant jet on a color Doppler test. Emboli to upper and lower extremities and brain complicated the patient's preoperative course. Surgical excision and pathologic examination confirmed this rare occurrence. 
5	Preperitoneal herniorrhaphy for the acutely incarcerated groin hernia. Elective preperitoneal or posterior repair for recurrent groin hernias and primary femoral hernias has been shown to be a technically advantageous approach. In addition to the ease of inguinal floor and femoral canal assessment, scar tissue from prior anterior herniorrhaphy can be avoided. The emergency management of the acutely incarcerated or strangulated hernia of the groin using this approach has not been addressed. During a 30-month period, all patients with a diagnosis of acute incarceration of a groin hernia (n = 28) were surgically managed using either the anterior approach (AA) (n = 14) or the preperitoneal approach (PA) (n = 14). Two patients with strangulated intestine in the AA group required an additional midline incision for bowel evaluation and resection. Intestinal evaluation was easily accomplished through the same incision in four patients in the PA group. The preperitoneal approach also allowed proximal control of incarcerated or strangulated viscera, thus avoiding excessive manipulation of gangrenous or necrotic intestine, potential spillage of infected contents into the peritoneal cavity, and entry of bacteria, toxins, potassium, and the metabolic waste products of anaerobic metabolism into the systemic circulation during hernia reduction. There have been no recurrences in either group, and minor complications, such as wound infection and cellulitis, in the two groups are not statistically different. 
5	Antisocial alcoholics: are there clinically significant diagnostic subtypes? Of 360 alcoholic male inpatients assessed with a diagnostic interview, 106 (29%) were found to have a co-occurring diagnosis of antisocial personality. Of these ASP alcoholics, 86 were further subdivided into those with only ASP and alcoholism (n = 38), those with ASP, alcoholism and drug dependence (n = 30) and those with ASP, alcoholism and depression (n = 18; 9 of whom also had drug abuse). Comparisons among the three antisocial groups indicated that they differed in measures of psychopathology and course and severity of alcoholism. When the ASP groups were compared to an alcoholism only group, an earlier onset, more rapid course and increased percentage of many alcoholism symptoms were found in the ASP groups, confirming the findings of other studies. 
4	An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For every 1% reduction in cholesterol, an estimated 2.5% reduction in CHD incidence is indicated (95% CL: 1.1, 3.9). With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials. With regard to total mortality, this efficiency was higher in secondary than in primary preventive trials. The efficiency was also somewhat dependent on the baseline cholesterol level. This study shows that cholesterol reduction is effective in lowering CHD incidence, but cholesterol reduction must be at least 8-9% to be effective in lowering total mortality. 
2	Hyperplastic gastric polyps associated with persistent Helicobacter pylori infection and active gastritis. We report two cases of patients with 3-yr histories of upper gastrointestinal symptoms, hyperplastic gastric polyps, and active chronic gastritis. Biopsies retrospectively stained with Giemsa revealed the persistent presence of Helicobacter pylori (HP) in gastric biopsies of both patients throughout the 3 yr. After treatment with amoxicillin and bismuth subsalicylate, both became asymptomatic, one demonstrating disappearance and recurrence of the gastric polyps in conjunction with the HP. These cases demonstrate 3 yr of hyperplastic gastric polyps associated with HP and active gastritis. 
4	Elderly patients with congestive heart failure under prepaid care. PURPOSE: Because of concern about the quality of care received by Medicare patients in health maintenance organizations (HMOs), the care of patients with congestive heart failure (CHF) in eight HMOs was compared with the care of fee-for-service (FFS) Medicare cases. PATIENTS AND METHODS: We compared the care of 170 patients with CHF enrolled in one of eight Medicare HMOs with the care of 191 similar FFS patients. Panels of expert physicians developed criteria for evaluating quality of care, and specially trained nurse clinicians abstracted medical records. RESULTS: Outpatient evaluation and management were similar in both settings, although HMO patients were significantly more likely to be advised to restrict salt intake. However, FFS patients with uncontrolled hypertension were more likely to have their medication regimens changed (62% versus 36%, p less than 0.01). Ejection fractions were obtained equally as often, and inpatient management was similar for both groups. Nonetheless, HMO providers scheduled follow-up visits within 1 week of hospital discharge more often (42% versus 27%, p less than 0.01). CONCLUSIONS: This study suggests that financial incentives of prepaid care are not detrimental to most aspects of care for CHF patients. More rapid follow-up after hospital discharge for patients with CHF suggests that HMOs may be more effective in delivering continuity of care for patients with chronic illness. 
5	Renal transplants: can acute rejection and acute tubular necrosis be differentiated with MR imaging? Magnetic resonance (MR) imaging was used in 40 renal transplant recipients to determine whether this modality can enable distinction of acute tubular necrosis (ATN) and acute rejection by means of corticomedullary differentiation (CMD). Each patient underwent initial MR imaging after allograft renal transplantation. Twenty-nine of these 40 patients (72%) also underwent subsequent follow-up MR imaging. Seventeen studies were obtained during episodes of ATN; 12 of these studies (71%) showed poor CMD. Eleven studies were obtained during episodes of acute rejection; eight of these studies (73%) showed poor CMD. In addition, six of seven studies (86%) showing various combinations of renal disease (ATN, acute rejection, chronic rejection, and cyclosporine toxicity) also showed poor CMD. Loss of CMD is reversible after improvement of ATN and acute rejection. Because loss of CMD is a nonspecific though sensitive sign reflecting renal transplant dysfunction, MR imaging is of limited value in the differentiation of ATN from acute rejection. 
2	Helicobacter pylori infection: a simplified diagnostic approach. We evaluated the diagnostic accuracy of endoscopic finding of nodular antritis and rapid urease test (RUT) in order to simplify the approach to the diagnosis of Helicobacter pylori (H. pylori) infection. Forty-four consecutive patients (mean age 7.9 yr, range 6-13 yr) referred because of recurrent abdominal pain as the main symptom, were prospectively investigated for the presence of H. pylori. H. pylori positivity or negativity was defined as the concordance of two of the following tests: RUT, microbiologic culture, and histologic examination on bioptic samples. RUT sensitivity was 100%, whereas specificity was 87.5%. The presence of nodular antritis had a sensitivity of 96.4% and specificity of 87.5% in H. pylori infection diagnosis. The predictivity value of combined RUT and nodular antritis, whether positive or negative, was 100%. Only in case of discordance do we suggest the utilization of other expensive tools for diagnosis of H. pylori infection. 
5	Esophageal and gastric endoscopy in critically ill patients. How can it help you? Bleeding from the upper gastrointestinal tract in a critically ill patient is a tough diagnostic situation. Endoscopy can help physicians determine the cause of bleeding and can also provide several therapeutic options. The authors discuss these applications of the current technology. 
5	Induction of mixed erythroid-megakaryocyte colonies and bipotential blast cell colonies by recombinant human erythropoietin in serum-free culture. The effects of recombinant human erythropoietin (rEp) on murine hematopoietic progenitors were studied using a serum-free culture. A high concentration of rEp stimulated the formation of mixed erythroid-megakaryocyte colonies (EM colonies) and blast cell colonies, as well as erythroid colonies, erythroid bursts, and megakaryocyte colonies from normal mouse bone marrow cells. Direct effects of rEp on EM colony, megakaryocyte colony, and erythroid burst formation were confirmed by depletion of accessory cells such as T cells, B cells, and macrophages from crude bone marrow cells, and inhibition of the colonies by the addition of rabbit anti-rEp antibody to the culture in a dose-dependent fashion. Replating experiments were performed to confirm the differentiating ability of blast cell colonies grown in the presence of rEp. Most of the blast cell colonies yielded not only secondary erythroid colonies but also megakaryocyte colonies in the presence of 2 IU/mL rEp. Some of the blast cell colonies produced secondary EM colonies in the presence of 16 IU/ml rEp of 2 IU/mL rEp plus interleukin-3, although no granulocyte-macrophage colonies were found in the secondary culture. These results suggest that Ep acts not only as a late-acting factor that is specific for erythroid progenitors, but also as a bipotential EM-stimulating factor for murine hematopoietic cells. 
1	Surgical management of 552 carcinomas of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded). Results of the French Surgical Association Survey. Five hundred fifty-two cases of primary carcinoma of the extrahepatic bile ducts (gallbladder and periampullary tumors excluded) collected from 55 surgical centers were reviewed retrospectively. Three hundred seven patients (56%) had upper-third lesions (proximal carcinoma), whereas 71 (13%) and 101 (18%), respectively, had middle-third and lower-third bile duct carcinomas. The remaining patients had diffuse lesions. Resectability rates were 32% for upper-third localization compared to 47% and 51% for middle-third and lower-third localization, respectively. The operative mortality rate for proximal carcinomas was significantly lower with resection (16%) compared with palliative surgery (31%) (p less than 0.05). Overall 1-year survival (operative deaths excluded) was 68% after tumor resection compared to 31% after palliative surgery (p less than 0.001). Long-term results after surgical resection correlated with local and regional extension of the disease. The results of this study show that resection of extrahepatic bile duct carcinomas, particularly in an upper-third localization, often is associated with worthwhile long-term survival. 
1	Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma. 
4	Phenobarbital and cerebral blood flow during hypertension in the newborn beagle. Phenobarbital sodium has been used in anticonvulsant concentrations (15 to 40 micrograms/mL serum) in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages. Although its clinical usefulness in this regard is controversial, phenobarbital treatment has been shown to reduce periventricular and intraventricular hemorrhages after hypertensive insult in newborn beagles. In this study cerebral blood flow values in steady state and during phenylephrine-induced hypertension with and without phenobarbital pretreatment were measured in newborn beagles. At anticonvulsant dosage, phenobarbital sodium decreased mean arterial blood pressure transiently during steady state and significantly reduced total cerebral blood flow during phenylephrine-induced hypertension without reducing mean arterial blood pressure. This phenobarbital sodium effect on cerebral blood flow was not as great in the presence of acidosis, and the initial hypotensive effect of phenobarbital sodium was sustained for a longer period of time during acidosis. Phenobarbital sodium may reduce the incidence of hemorrhages in the newborn brain by providing protection against isolated hemodynamic stresses characterized by acute increases in cerebral blood flow, with or without increased mean arterial blood pressure. 
1	Expression of murine renin genes in subcutaneous connective tissue. A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of transgenic fetuses from several independent lines revealed scattered T-antigen-containing mesenchymal cells and fibroblasts in the subcutaneous layer of the skin between the panniculus carnosus muscle of the skin and the skeletal muscle of the body wall. This localization is consistent with the location of overt tumorigenesis in adult mice. This pattern was specific for the renin-T antigen fusion gene as no immunohistochemical staining was observed in transgenic fetuses containing a heterologous promoter-T antigen fusion gene. Northern blot analysis of tumor RNA indicated that most of the tumors expressed both T antigen and the endogenous renin gene Ren-1c. In addition, when multiple renin genes were introduced by crossing transgenic mice with nontransgenic DBA/2J mice, which contain another allele of the Ren-1 locus as well as the duplicated locus Ren-2, the resultant tumors expressed the Ren-2 gene. Northern blots were then used to analyze renin expression in the subcutaneous tissue of normal mice. Fully processed renin mRNA was detected in eviscerated 15.5-day postcoitus fetal and newborn carcasses and in newborn skin. Our data indicate that there is a renin-expressing cell population in fetal and newborn subcutaneous tissue. 
4	Dissection of the aorta associated with congenital malformation of the aortic valve. The association of congenital aortic valve malformation and aortic dissection is analyzed. Over a 30 year period, 186 patients with non-iatrogenic aortic dissection were studied at necropsy. The aortic valve was tricuspid in 170 (91.4%), bicuspid in 14 (7.5%) and unicuspid in 2 (1.1%). Among the 16 patients with aortic dissection and a congenitally malformed valve, the age at death ranged from 17 to 82 years (mean 52) and 13 (81%) were men. The entrance tear of the aortic dissection was located in the ascending aorta in all 16 patients with a malformed valve but in only 68% of those with a tricuspid aortic valve. The aortic valve was stenotic in 6 of the 16 patients with a congenitally malformed valve. Fatal rupture of the false channel occurred after acute ascending aortic dissection in each of the 11 patients (none with healed dissection) who did not have operative therapy for the dissection. Two of the 16 patients with a malformed valve compared with no patient with a tricuspid aortic valve had aortic isthmic coarctation. Histologic sections of aorta from 10 patients disclosed severe degeneration of the elastic fibers of the media in 9 patients. Thus, a congenitally malformed aortic valve appears to be present at least 5 times more frequently in adults with than in those without aortic dissection, and in our patients the entrance tear was always in the ascending aorta, which usually had severe loss of elastic fibers in its media. 
5	Aggressive blood conservation in coronary artery surgery: impact on patient care. Data on 100 consecutive non-emergency coronary artery bypass (CABG) patients were analyzed retrospectively. Sixty-nine patients received no homologous blood (Group I). Thirty-one patients received a total of 118 units of blood products averaging 2.23 units of red cells (Group II). The average red cell transfusion rate for all patients was 0.7 units per patient. The median age for Group I was 61 and Group II was 68 years (p less than 0.05). The average number of grafts was the same for both (3 per patient) with 75% of Group I and 58% of Group II receiving internal mammary artery (IMA) grafts (p less than 0.05). Twelve of the Group II patients who received intraoperative transfusions on cardiopulmonary bypass to maintain adequate hemoglobin levels were older and had lower admission hematocrits: 36 +/- 0.8% compared to 41 +/- 0.5% for all other patients (p less than 0.05). Average postoperative blood loss was 889 +/- 38 ml for Group I and 1077 +/- 104 ml for Group II (p less than 0.05). Increased hemorrhage was correlated with bypass time and IMA use but not with preoperative heparin administration, pre-existing risk factors (diabetes, hypertension, etc.), bleeding time, post-bypass clotting time, age or number of grafts. Two patients in Group II and none in Group I required exploration for excessive postoperative hemorrhage. Mortality rate was 2% (both in Group II, neither transfusion related). Discharge hematocrits were the same for all at 29.4 +/- 0.4%. Among anemia-related postoperative symptoms, only sinus tachycardia was significantly higher in Group I (20%) compared to Group II (6.5%). 
1	Survival in patients with large-bowel cancer. A population-based investigation from the Melbourne Colorectal Cancer Study. Five-year survival data were obtained in 97 percent or 1105 of 1140 new patients with histologically confirmed colorectal adenocarcinoma during a 12-month period in 1981 and 1982, as part of a large comprehensive population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Fifteen percent of patients were Dukes' A stage, 32 percent were Dukes' B, 25 percent were Dukes' C, and 29 percent were Dukes' D. At five years after diagnosis, the observed survival rate was 36 percent and the adjusted rate was 42 percent. Dukes' staging was a highly discriminating factor in survival (P less than 0.001). Survival rates were better in women than in men and better for patients with colon cancer than for patients with rectal cancer. Survival by Dukes' staging was not affected by colon subsite or by the tumor being the first and single tumor, metachronous tumor, or synchronous tumor. The survival of younger patients was better for Dukes' stages A, B, and C, and worse for Dukes' D. Survival was worse in the presence of bowel perforation in Dukes' C and D stages. Within Dukes' D (incurable cases), survival was best in the absence of hepatic metastases, slightly worse when only hepatic metastases were present, and poorest in the presence of both hepatic and extrahepatic metastases. Statistical modeling of survival determinants other than staging indicated that cell differentiation had the largest effect (survival decreasing with poor cell differentiation), followed by site (survival worse for rectal cancer than colon cancer), then age (survival better for younger patients), while bowel perforation had the smallest effect on survival. 
5	Ventilatory effect of acute pulmonary hypothermia. The isolated effect of cooling the pulmonary circulation on ventilation was quantified in nine anesthetized dogs. The right pulmonary artery (RPA) was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the RPA between, but not during, periods of cooling. Cooled blood boluses were injected into the RPA under conditions in which either bolus temperature (5-35 degrees C) or volume (0-1.5 ml/kg body wt) varied. Inspiratory time (TI), expiratory time (TE), breath duration (TT), and peak integrated activity (PEAK) were determined from diaphragm EMG. Results for five postinjection breaths were converted to a percent of the values from five preinjection breaths. There was a linear relationship between bolus temperature and TI [r = 0.61, slope (x) = 0.59%/degrees C, P less than 0.001), TE (r = 0.73, x = 1.43%/degrees C, P less than 0.001] as well as TT (r = 0.74, x = 1.10%/degrees C, P less than 0.001), whereas PEAK was unaffected (n = 9). When injection temperature was 5 degrees C, an inverse linear relationship existed between bolus volume and TI (r = 0.75, x = -15.2%.ml-1.kg-1, P less than 0.001) and TE (r = 0.78, x = -23.4%.ml-1.kg-1, P less than 0.001) (n = 4). In two dogs tested the effect of bolus injection was minimal at residual volume and progressively increased with lung volume. The effect of cold bolus injection was eliminated after right vagotomy in three dogs. Results indicate that cooling of some vagal receptor in the lung increases breathing frequency primarily by shortening TE. 
5	Simultaneous or staged bilateral total knee replacements in rheumatoid arthritis. A prospective study. In a prospective study of 100 knee arthroplasties in patients with rheumatoid arthritis, simultaneous bilateral surgery was compared with staged bilateral replacements. All patients had improved function following their operations but those who had staged surgery only achieved maximum benefit after the second knee had been replaced. The complication rate was no greater for simultaneous surgery and we therefore advocate the method for those patients who require bilateral replacements. 
4	Long-term follow-up of medical versus surgical therapy for hypertrophic cardiomyopathy: a retrospective study In a retrospective analysis 139 patients with hypertrophic cardiomyopathy were followed up for 8.9 years (range 1 to 28 years). Patients were divided into two groups: Group 1 consisted of 60 patients with medical therapy and Group 2 of 79 patients with surgical therapy (septal myectomy). Groups 1 and 2 were subdivided according to the medical treatment. Group 1a received propranolol, 160 mg/day (n = 20); Group 1b verapamil, 360 mg/day (n = 18); and Group 1c, no therapy (n = 22). Group 2a received verapamil, 120 to 360 mg/day, after septal myectomy (n = 17) and Group 2b had no medical therapy after surgery (n = 62). In Group 1, 19 patients died (annual mortality rate 3.6%) and in Group 2, 17 patients died (mortality rate 2.4%, p = NS). Of the patients who died, approximately one half to two thirds in both Groups 1 and 2 died suddenly and the other one half to one third died because of congestive heart failure. The 10 year cumulative survival rate was 67% in Group 1, significantly smaller than that in Group 2 (84%, p less than 0.05). In the subgroups, the 10 year survival rate was 67% in Group 1a, 80% in 1b (p less than 0.05 versus 1a) and 65% in 1c (p less than 0.05 versus 1b). The 10 year survival rate was 100% in Group 2a (p less than 0.05 versus 1a, 1b, 1c) and 78% in Group 2b (p less than 0.05 versus 2a). It is concluded that cumulative survival rate is significantly better in surgically than in medically treated patients. 
5	Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. We compared T-cell proliferative responses to acetylcholine receptor (AChR) and to purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, and blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus cells gave significantly higher and more consistent responses to AChR than parallel cultures of autologous blood cells, whereas responses to PPD showed an opposite trend. Thus there was a preferential localization of AChR-reactive T cells in the hyperplastic MG thymus. Furthermore, there was a strong correlation between blood and thymus cell responses to PPD (but not to AChR), arguing that the hyperplastic MG thymus contains a sample of sensitized peripheral T cells. By contrast, both AChR- and PPD-responsive T cells were almost undetectable in thymus from nonmyasthenic patients, which is evidently much less receptive to circulating T cells. Cells from MG thymomas showed the highest stimulations by AChR but did not consistently react to PPD. However, the uninvolved thymus adjacent to these thymomas behaved almost identically to the hyperplastic samples described above. Our interpretation is that AChR-specific T cells are initially sensitized in the MG thymoma but are selectively trapped in the hyperplastic thymus after being primed elsewhere. 
5	Delayed endolymphatic hydrops and its relationship to Meniere's disease. Delayed endolymphatic hydrops (EH) can be characterized as having ipsilateral and contralateral types. They are similar in that both have early and late phases of otologic symptoms and that the early phase is a profound hearing loss in one ear. The late phases differ, however, in that the ipsilateral type develops the symptoms of EH (episodic vertigo) in the deaf ear and the contralateral type develops the symptoms of EH (fluctuating hearing loss and/or episodic vertigo) in the hearing ear. In more than half the cases of both types of delayed EH, the profound hearing losses in the early phase are simply discovered to be present in early childhood without a known time of onset. The temporal bones of two patients with contralateral delayed EH show pathologic changes in the deaf ears that are similar to those known to occur in mumps and measles labyrinthitis, whereas the pathologic changes in the hearing ears are similar to those known to occur in Meniere's disease. These observations support the proposition that Meniere's disease may occur as a delayed sequela of inner ear damage sustained during an attack of subclinical viral labyrinthitis occurring in childhood. 
5	Direct measurement of skeletal muscle fatigue in patients with chronic heart failure. Skeletal muscle function was measured as force production and fatigue in both the quadriceps (a large locomotive muscle) and adductor pollicis (a small intrinsic hand muscle) in five healthy volunteers, five patients with mild chronic heart failure, and five patients with severe chronic heart failure. The quadriceps of patients with chronic heart failure had a reduced muscle cross sectional area, a reduced maximum isometric force production, and an increased tendency to fatigue. Isometric force production and fatigue of the adductor pollicis, however, were not significantly different between the three groups under control conditions. But during circulatory occlusion fatigue in the adductor pollicis increased more in the patients with severe chronic heart failure. These differing findings in quadriceps and adductor pollicis suggest that skeletal muscle atrophy and reduced isometric force production are not a necessary consequence of chronic heart failure per se, because they were only present in the large locomotive muscle. The normal values for muscle fatigue observed in adductor pollicis in patients with chronic heart failure imply that skeletal muscle blood flow must increase normally during muscle activation when only a small muscle mass is used. These results are not compatible with the concept of a generalised impairment of normal vasodilatation within active skeletal muscle. In contrast, activation of a large muscle, such as quadriceps, results in the rapid onset of fatigue in patients with severe chronic heart failure. This fatigue may be related to the inability of the cardiovascular system to provide the required blood flow for the activation of a large muscle mass. 
5	Exocrine pancreatic function in chronic liver diseases. To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity. 
1	The use of probenecid as a chemoprotector against cisplatin nephrotoxicity. Probenecid inhibits cisplatin (CP) secretion in humans and protects against CP-induced nephrotoxicity in rats. The authors conducted a Phase I trial of escalating doses of CP using probenecid as a chemoprotector. Fifty-four courses of CP at doses ranging from 100 to 160 mg/m2 were given by 24-hour infusion to 36 patients. There was no renal impairment at any dose. Ototoxicity, however, became the dose-limiting toxicity; 14 patients experienced a 20 or greater decibel (dB) loss. Seven percent of courses were associated with a leukocyte count of less than 1.5 x 10/microliters, and 19% with a platelet count of less than 50 x 10(3)/microliters. Only three patients developed neurotoxicity. Correlating pharmacokinetic data and toxicity, the authors found that high cumulative dose, area under the curve (AUC) for unbound platinum, and cumulative AUC were associated with ototoxicity and peripheral neuropathy. It was concluded that probenecid may protect against CP nephrotoxicity and warrants further investigation. Its unique mechanism of action and lack of toxicity make it ideal to combine with other chemoprotectors. 
1	Adenocarcinoma of the appendiceal stump. We have reported the case of a 58-year-old woman with nonspecific abdominal complaints in whom barium enema and subsequent colonoscopy showed a 3 cm lobulated adenocarcinoma within a villous adenoma arising from the appendiceal stump. Because such appendiceal malignancies have no specific clinical signs, symptoms, or radiologic features, preoperative diagnosis is extremely difficult, and colonoscopy may be required to clarify radiologically demonstrated irregularities. 
4	Effect of diltiazem and thromboxane A2 synthetase inhibitor (OKY-046) on vessels following experimental subarachnoid hemorrhage. In order to examine the functional changes in the vascular smooth muscle, the effects of a thromboxane A2 synthetase inhibitor (OKY-046) and a calcium channel blocker (diltiazem) on vessels following subarachnoid hemorrhage, and the contractile activity of cerebral vessels with various vasoactive agents, were investigated by studying isometric tension recordings in rings of cat basilar artery. The maximum contractile activities of the vessels in response to noradrenalin and adrenaline during the course of subarachnoid hemorrhage were significantly less than those in the control group. On the other hand, the maximum contractile activity of the vessels in response to prostaglandin F2 alpha on the seventh day following subarachnoid hemorrhage was significantly augmented compared with that in the control group. A significant decline in the relaxation of responsiveness to diltiazem during the course of subarachnoid hemorrhage was observed compared with that of diltiazem in the control group. This responsiveness to vasoactive agents was not influenced by the application of OKY-046. The present study reveals functional changes in vascular smooth muscle exposed to subarachnoid hemorrhage in response to vasoactive agents and a calcium entry blocker. Thromboxane A2 may not be a significantly influential factor in the present results. It is suggested that cerebral vasospasm may well be related to functional changes of the arterial wall, which appear to be associated with derangement of the mechanisms of smooth muscle constriction and dilatation based on organic changes. 
4	Nonuniform regional deformation of the pericardium during the cardiac cycle in dogs. We hypothesized that local contact forces between the pericardium and the heart cause regional variation in pericardial deformation during the cardiac cycle, reflecting volume changes of the underlying cardiac chambers. To test this, we measured regional pericardial area over the right atrium (RA) and right ventricle (RV) with orthogonal pairs of sonomicrometers in six open-chest dogs. At a left ventricular end-diastolic pressure of 5 mm Hg, RV pericardial area paralleled RV volume, that is, shrinkage during ejection by 10 +/- 8% and expansion during filling. RA pericardial area was reciprocally related to RV pericardial area, with average expansion during ventricular ejection of 2 +/- 2%, thus paralleling RA volume during RV ejection. With volume loading, RV pericardial shrinkage during ejection increased to 14 +/- 6%, but the RA pericardial area change was no longer reciprocal (0 +/- 3% change during RV ejection). Elimination of contact forces by cardiac tamponade resulted in both marked attenuation of RV pericardial area changes and synchronization of the RV and RA pericardial area pattern; that is, both shrank during RV ejection. In two additional dogs, measurement of pericardial area over left ventricle and atrium showed similar results. We conclude that dynamic pericardial contact forces cause regional variation in pericardial deformation, which reflects volume changes of the underlying chambers. These findings imply that the influence of the pericardium on filling and ejection may be more complex than previously recognized, varying both by chamber and dynamically over the course of the cardiac cycle. 
1	Primary bone tumours of the thoracic skeleton: an audit of the Leeds regional bone tumour registry. An audit of the Leeds regional bone tumour registry found that primary bone tumours of the thoracic skeleton constituted 90 of the 2004 cases (4.5%). Thirty seven per cent occurred in the ribs, 32% in the scapulae, 11% in the thoracic vertebrae, 11% in the sternum, and 9% in the clavicles. Malignant tumours were more common than benign (54 v 36) and occurred in an older population (mean ages 47 and 31 years). The scapula was the most common site for malignant lesions and the ribs the most common site for benign tumours. Chondrosarcoma was the commonest tumour in older patients, fibrous dysplasia and plasmacytoma in the middle age group, and eosinophilic granuloma in children. Presenting symptoms were a poor guide to whether the lesion was malignant or not. This and the small proportion of correct preoperative diagnoses indicate the need for early biopsy. Bone tumour registries provide a valuable source of cumulative information about uncommon tumours and facilitate accurate diagnosis, teaching, and research. 
5	In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Cloned integrin alpha 2 subunit complementary DNA was expressed on human rhabdomyosarcoma (RD) cells to give a functional VLA-2 (alpha 2 beta 1) adhesion receptor. The VLA-2-positive RDA2 cells not only showed increased adhesion to collagen and laminin in vitro, but also formed substantially more metastatic tumor colonies in nude mice after either intravenous or subcutaneous injection. These results show that a specific adhesion receptor (VLA-2) can markedly enhance both experimental and spontaneous metastasis. In contrast to the metastasis results, there was no difference in either the in vitro growth rate or apparent in vivo tumorigenicity of RD and RDA2 cells. 
5	Differential alpha-fetoprotein lectin binding in hepatocellular carcinoma. Diagnostic utility at low serum levels. The reactivity of serum alpha-fetoprotein (AFP) from 20 patients with hepatocellular carcinoma (HCC) with immobilized lentil lectin was examined and found to be significantly greater (39% +/- 18%) than that of the same protein from seven patients with chronic liver disease (CLD, 11.2% +/- 3.3%), seven with fulminant hepatic failure (FHF, 10% +/- 8.4%), and eight normal pregnant women (4.1% +/- 2.7%). The reactivity with Concanavalin A (Con A) was also significantly greater for AFP from HCC patients (44.5% +/- 12.5%) than that from FHF patients (7.7% +/- 4%) and normal pregnant women (5.3% +/- 3.3%), but not from patients with CLD. The reactivity with lentil lectin permitted distinction between those with HCC (31.3% +/- 14.1%) and those with uncomplicated CLD (11.2% +/- 8.4%) even when the absolute levels of serum AFP were in the same range (80-400 ng/ml). Evaluation of the alterations by lectin binding methodology may be useful in overcoming problems associated with distinguishing between malignant and CLD, particularly at moderate serum AFP elevations. 
5	En bloc transplantation of kidneys from donors weighing less than 15 kg. into adult recipients. En bloc transplantation of kidneys from donors who weighed less than 15 kg. into 20 adult patients is described. Intraperitonealization of the medial kidney allowed adequate renal positioning and growth. Graft venous thrombosis occurred in 1 patient and irreversible graft rejection occurred in 4 patients. Graft survival was 65% with excellent function at a mean followup of 8.8 months. En bloc transplantation of pediatric cadaver kidney grafts in adults is an acceptable procedure. 
5	Epstein-Barr virus associated oesophageal ulcers in AIDS. Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration. 
4	Sympathovagal interaction during mental stress. A study using spectral analysis of heart rate variability in healthy control subjects and patients with a prior myocardial infarction. We tested the hypothesis that psychological stress testing in the clinical laboratory provokes changes in the sympathetic and vagal activities regulating heart rate that can be assessed noninvasively using spectral analysis of RR variability. To account for the effects on respiration produced by talking, this study was performed with two different procedures: the I.K.T. (i.e., a computer-controlled mental task that is performed in silence and does not entail human confrontation) and a stressful interview. Finally, we assessed whether ischemic heart disease modifies the spectral changes induced by psychological stress by comparing a group of healthy subjects (age, 38 +/- 2 years) with a group of patients (age, 52 +/- 3 years) recovering from 1-month-old myocardial infarctions. The findings indicate that psychological stress induced marked changes in the sympathovagal balance, which moved toward sympathetic predominance. The low-frequency component of RR variability, a marker of sympathetic activity, increased from 58 +/- 5 normalized units (NU) to 68 +/- 3 NU with the I.K.T. and to 76 +/- 3 NU with the interview. This increase was absent in the group of post-myocardial infarction patients. However, arterial pressure increased significantly in both groups of subjects. The possibility of age playing an important role in determining the differences observed was disproved by the findings of a marked increase in low frequency with mental stimuli in an additional group of borderline hypertensive subjects with ages (55 +/- 2 years) comparable to those of post-myocardial infarction patients. 
2	Ileal pouch-anal anastomosis. Reoperation for pouch-related complications. The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients. 
4	Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study. An observational surveillance study was conducted to monitor the safety and effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients with digitalis intoxication. Before April 1986, a relatively limited number of patients received treatment with digoxin-specific Fab fragments through a multicenter clinical trial. Beginning with commercial availability in July 1986, this study sought additional, voluntarily reported clinical data pertaining to treatment through a 3 week follow-up. The study included 717 adults who received Digoxin Immune Fab (Ovine). Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin. Fifty percent of patients were reported to have a complete response to treatment, 24% a partial response and 12% no response. The response for 14% of patients was not reported or reported as uncertain. Six patients (0.8%, 95% confidence interval 0.3% to 1.8%) had an allergic reaction to digoxin-specific antibody fragments. Three of the six had a history of allergy to antibiotic drugs. Twenty patients (2.8%, 95% confidence interval 1.7% to 4.3%) developed recrudescent toxicity. Risk of recrudescent toxicity increased sixfold when less than 50% of the estimated dose of antibody was administered. A total of 215 patients experienced posttreatment adverse events. The events for 163 patients (76%) were judged to result from manifestations of underlying disease and thus considered unrelated to Fab treatment. Digoxin-specific antibody fragments were generally well tolerated and clinically effective in patients judged by treating physicians to have potentially life-threatening digitalis intoxication. 
4	The effect of intravenous fixed-dose heparin during total hip arthroplasty on the incidence of deep-vein thrombosis. A randomized, double-blind trial in patients operated on with epidural anesthesia and controlled hypotension. Heparin was given in fixed doses intravenously during unilateral primary total hip-replacement operations in a prospective, double-blind trial to assess the effect on the incidence of deep-vein thrombosis. One hundred and fifty patients were randomly assigned to one of two groups before the operation. Twenty-four patients were excluded from the study, leaving 126 patients. Group I consisted of sixty-six patients who received saline solution intravenously, and Group II comprised sixty patients who received heparin. All patients had epidural anesthesia with controlled hypotension. Fixed doses of heparin were administered five minutes before the operative incision was made and every thirty minutes throughout the operation. Mean arterial pressures were maintained at between fifty and sixty millimeters of mercury in all patients. Ascending venography was done on the seventh day after the operation. The incidence of deep-vein thrombosis was 24 per cent (sixteen of sixty-six patients) in Group I and 8 per cent (five of sixty patients) in Group II; the difference is significant (p = 0.03). The intraoperative loss of blood averaged 220 +/- 79 milliliters in Group I compared with 269 +/- 109 milliliters in Group II. An average of less than one unit of blood was transfused for each patient in each group. Postoperatively, there was no difference between the groups with regard to the amount of drainage that was collected in a Hemovac device or the values for hematocrit. 
1	Squamous cell carcinoma arising in a sternotomy scar. The case of a 73-year-old man in whom squamous cell carcinoma developed in a median sternotomy scar 12 months after coronary artery bypass grafting is presented. A brief review of the literature is included. The etiology of scar carcinoma is discussed and an outline of management given. 
1	Fallopian tube cancer. The Roswell Park experience. Sixty-four patients with primary fallopian tube cancer treated at Roswell Park Memorial Institute from 1964 to 1987 underwent retrospective clinicopathologic review. In 40 patients fallopian tube cancer was the only primary, but in 24 patients primary fallopian tube cancer was part of a multifocal upper genital tract malignancy. Of the 40 patients with unifocal fallopian disease, the median survival was 28 months. Only 15% of patients were alive and disease free with follow-up ranging from 22 to 141 months (median, 90.5 months). Survival was not associated with stage of disease, tumor histology, grade, or depth of invasion in this series. Fourteen patients who received cisplatin-based chemotherapy were evaluable for response. Three patients (21%) responded; two complete and one partial. Twelve patients without clinical evidence of disease underwent second-look procedures, ten laparotomy and two laparoscopy. Four of ten second-look laparotomies were negative. Secondary debulking was done in three of four patients with gross disease, one of which had a negative third-look laparotomy. Negative laparotomy, second-look or third-look, was associated with improved survival (P = 0.016). One of the two laparoscopies was negative, but the patient recurred. In the remaining 24 patients cancer of the fallopian tube was part of a multifocal upper genital tract malignancy. In 12 patients tubal disease was invasive, and in 12, it was in situ. Separate primaries occurred in the ovaries (n = 20); uterus (n = 7); and cervix (n = 2). This represents 1.3% of ovarian malignancies treated at Roswell Park Memorial Institute during the study period. Fallopian tube cancer seems as virulent as ovarian cancer with few long-term survivors. It is frequently associated with other sites of upper genital tract malignancy. Second-look laparotomy is an important predictor of survival. Second-look laparoscopy may be useful if positive. 
2	Endoscopic assessment of chloroquine phosphate-induced damage to esophageal, gastric, and duodenal mucosa. Eighteen patients with Plasmodium vivax malaria were prospectively evaluated to assess the time of onset and extent of upper gastrointestinal mucosal injury caused by oral administration of four tablets (600-mg base) of chloroquine. Endoscopy was performed in the group of three separate patients. Each patient underwent endoscopy, both before the drug was given, and at intervals of 1, 2, 4, 12, 24, and 36 h. Before the drug was given, endoscopy was normal in all of the patients. However, mucosal erosions developed in four of 18 patients who were endoscoped 24 and 36 h after chloroquine ingestion (gastric, four; duodenal, two; esophageal, one). The same doses of chloroquine failed to produce any mucosal lesions when given to these four patients while they were afebrile and when given to 11 healthy individuals who served as controls. Poor correlation was noted between subjective symptoms and endoscopic findings. In conclusion, neither malaria alone nor chloroquine alone causes mucosal lesions. However, chloroquine administered during malarial fever causes mucosal damage in susceptible individuals. 
5	Different tumor-derived p53 mutants exhibit distinct biological activities. In its wild-type form, the protein p53 can interfere with neoplastic processes. Tumor-derived cells often express mutant p53. Full-length mutant forms of p53 isolated so far from transformed mouse cells exhibit three common properties in vitro: loss of transformation-suppressing activity, gain of pronounced transforming potential, and ability to bind the heat shock protein cognate hsc70. A tumor-derived mouse p53 variant is now described, whose site of mutation corresponds to a hot spot for p53 in human tumors. While absolutely nonsuppressing, it is only weakly transforming and exhibits no detectable hsc70 binding. The data suggest that the ability of a p53 mutant to bind endogenous p53 is not the sole determinant of its oncogenic potential. The data also support the existence of gain-of-function p53 mutants. 
2	Late volume changes in retrosternal colon bypass. Esophageal obstruction by malignancy, chemical burns, or other less common entities presents a challenge for the surgeon. Either for esophageal substitution after esophageal resection or as a bypass for the obstructed esophagus, colon interposition is often the best available option. Massive colonic enlargement requiring resection of the interposed dilated colon developed recently in 2 of our patients who had a colon bypass 22 and 10 years earlier, respectively. 
5	Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide. We have identified a region of the human tumor necrosis factor alpha (TNF-alpha) gene promoter that is necessary for maximal constitutive, virus-induced, and lipopolysaccharide (LPS)-induced transcription. This region contains three sites that match an NF-kappa B binding-site consensus sequence. We show that these three sites specifically bind NF-kappa B in vitro, yet each of these sites can be deleted from the TNF-alpha promoter with little effect on the induction of the gene by virus or LPS. Moreover, when multimers of these three sites are placed upstream from a truncated TNF-alpha promoter, or a heterologous promoter, an increase in the basal level of transcription is observed that is influenced by sequence context and cell type. However, these multimers are not sufficient for virus or LPS induction of either promoter. Thus, unlike other virus- and LPS-inducible promoters that contain NF-kappa B binding sites, these sites from the TNF-alpha promoter are neither required nor sufficient for virus or LPS induction. Comparison of the sequence requirements of virus induction of the human TNF-alpha gene in mouse L929 and P388D1 cells reveals significant differences, indicating that the sequence requirements for virus induction of the gene are cell type-specific. However, the sequences required for virus and LPS induction of the gene in a single cell type, P388D1, overlap. 
1	Boron neutron capture therapy of intracerebral rat gliosarcomas. The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation. 
5	Coronary angioplasty in symptomatic patients after bypass surgery. With the availability of percutaneous transluminal coronary angioplasty (PTCA), the management of patients who present with recurrent angina following coronary artery bypass surgery (CABG) has changed. From January 1987 to December 1988, 149 symptomatic post CABG patients underwent coronary angiography at our institution. Ninety were treated with medical antianginal therapy, 14 had repeat surgery, and 45 underwent PTCA. Complications of repeat CABG included one death, two perioperative myocardial infarctions, and four patients with postoperative supraventricular arrhythmia. PTCA was performed on 42 lesions in 37 native vessels (88% success rate), and on 24 lesions in 23 vein grafts (91.7% success rate). Complications included acute reocclusion (one patient), peripheral artery occlusion (one patient), hematoma formation (one patient), and periprocedure myocardial infarction (one patient). No deaths occurred. At a mean follow-up of 5.9 +/- 3.8 months, 10 patients had recurrent symptoms, six of whom were found to have restenosis. Repeat PTCA was successfully accomplished in four patients; the other two were treated medically. It is concluded that PTCA is a feasible alternative to repeat CABG in selected patients and can be achieved with a high success rate and minimal complications. 
1	Fetal choroid plexus cysts: a prospective study and review of the literature. To determine the incidence and significance of fetal choroid plexus cysts, a prospective study was carried out at Queen's Medical Centre, Nottingham. The incidence of cysts was found to be 0.42% and the size of cysts varied from 3 to 13 mm with a mean diameter of 6.2 mm. Choroid plexus cysts were associated with other fetal abnormalities in three cases, two of which were subsequently found to have a chromosomal abnormality, one Trisomy 18 and one Trisomy 21. A review of the reported cases of choroid plexus cysts reveals an overall incidence of 5.8% for Trisomy 18. We therefore recommend that in patients with choroid plexus cysts a detailed scan should be carried out to look for the ultrasound markers of Trisomy 18. If there is an associated abnormality or cysts are large (13 mm or greater in diameter) and bilateral then a karyotyping should be carried out. 
1	Epidermotropic eccrine porocarcinoma. Three cases of epidermotropic eccrine porocarcinoma are summarized and compared with reported cases. All patients had a long-standing tumor on a lower extremity that rapidly metastasized to the skin and proximal lymph nodes. The histologic picture was consistent with an intraepidermal eccrine sweat gland carcinoma. 
3	Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis. An autoimmune response to myelin basic protein (MBP) has been proposed to participate in the development of the chronic neurologic manifestations that may accompany Borrelia burgdorferi-induced Lyme disease. Using an immunospot assay, we counted cells secreting antibodies to MBP. Anti-MBP IgG antibody-secreting cells were detected in CSF from eight of 13 consecutive patients with Lyme neuroborreliosis irrespective of stage of disease. The numbers were between 1/370 and 1/5,000 CSF cells (mean, 1/1,250 in the 13 patients). The highest numbers were encountered in two patients with severe signs of CNS involvement. The numbers decreased in parallel with clinical improvement after treatment. Anti-MBP IgG antibody-secreting cells were also observed in the CSF from patients with a variety of other inflammatory diseases of the nervous system, and their role in the development of tissue damage remains unsettled. Anti-MBP IgG antibody-secreting cells were not detected in the patients' blood, reflecting accumulation of this autoantibody response to CSF. 
4	Salt and hypertension--future directions. The comments that follow reflect the personal views of this author regarding some useful directions of research in the field of salt and hypertension. From a physiological perspective, salt sensitivity is defined, and the merits and limitations of certain animal models of hypertension used to study this issue are discussed. The need to more clearly define the mechanisms that detect sodium intake and control the renal excretion of sodium is discussed. Additionally, the need to better understand the relation between sodium homeostasis, volume regulation, and the consequences of dysfunction in these regulatory system on the arterial vasculature and interstitial matrix is emphasized. The necessity for the application of new tools and approaches in a number of investigative areas is discussed. Finally, the necessity of equally imaginative whole animal and cell/molecular research and efforts to merge and integrate the data obtained at the cellular level with that of intact systems is emphasized. 
5	Learning a unimanual motor skill by partial commissurotomy patients. A series of motor tests on four Chinese partial commissurotomy patients is reported. The single-stage commissurotomy in all four patients included the anterior commissures and two-thirds or four-fifths section of the corpus callosum with sparing of the splenium. There was no demonstrable ability to transfer hand posture in these patients. This was the major evidence for functional deconnexion. A newly learned task of one-hand knotting revealed right hand impairment in all four patients. There was no dyspraxia in the right hand for over-learned object-handling tasks in these patients. It is suggested that there might be right hemisphere specialisation for the initial acquisition of unimanual object-handling skills and that the spared callosal fibres in the splenium alone are insufficient to mediate task control under these conditions. This is supported by the finding that one of these patients, who was the only one who had a right parietal lesion, was unable to perform the newly learned task with either hand. 
5	Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenicity. The receptors for erythropoietin and other cytokines constitute a new superfamily. They have no tyrosine-kinase or other enzyme motif and their signal-transducing mechanism is unclear. Here we describe two classes of activating mutations in the erythropoietin receptor (EPOR). A single point mutation in the exoplasmic domain enables it to induce hormone-independent cell growth and tumorigenesis after expression in nontumorigenic, interleukin-3-dependent haematopoietic cells. A C-terminal truncation in the cytoplasmic domain of the EPOR renders the receptor hyperresponsive to erythropoietin, but is insufficient to induce hormone-independent growth or tumorigenicity. The activating point mutation retards intracellular transport and turnover of the receptor. These alterations in metabolism and tumorigenicity caused by the EPOR with activating point mutations are similar to those observed in erythropoietin-independent activation of the wild type EPOR by association with gp55, the Friend spleen focus-forming virus glycoprotein. 
3	Wrist flexion as an adjunct to the diagnosis of carpal tunnel syndrome. The effects of five minutes of wrist flexion on median motor and sensory evoked potential latencies in 87 individuals were studied. Nineteen subjects had carpal tunnel syndrome (CTS) as diagnosed by increased median nerve latencies across the wrist, and 68 had values in the normal range and were assigned to the control group. A slight prolongation of up to 0.5m sec of evoked potential latencies was observed in both groups after flexion, but the differences between the two groups were not significant to establish the value of adding wrist flexion to conventional screening methods. 
1	Clinicopathologic features of hepatocellular carcinoma in young patients. To investigate clinicopathologic characteristics of hepatocellular carcinoma (HCC) in young adults, excised tumors from 21 patients younger than 45 years (young group) were compared with findings in tumors from 204 patients older than 45 (old group). In the young group HCC showed (1) a high incidence of positive hepatitis B virus surface antigen (HBsAg) (young 71.4% versus old 20.1%); (2) relatively well-preserved hepatocellular function (indocyanine green test; young 10.7 +/- 8.8% versus old 20.6 +/- 10.8%); (3) low incidence of histologically verified concomitant cirrhosis (young 52.4% versus old 78.4%); and (4) a more advanced stage of the disease in TNM classification (Stage III; young 52.4% versus old 18.1%). With respect to survival rates achieved by surgery, there was no statistically significant difference between the two groups. Thus, hepatitis B virus may relate to the occurrence of HCC in the young patients. Despite the advanced stage in the young group, survival rate after surgery was comparable with that achieved in the old group. These observations mean that a close periodic surveillance of young adults with a positive HBsAg is required to detect HCC at an early stage. Treatment of patients with HBsAg using interferon or vidarabine and hepatitis B vaccine should be made to convert HBsAg to negative in these individuals. 
4	Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group. 
4	Traumatic rupture of the aorta--critical decisions for trauma surgeons. The diagnosis and initial stabilization of patients with traumatic rupture of the aorta (TRA) is performed by trauma surgeons. The resuscitations of 54 TRA patients at a Level I trauma center are reviewed. Although the survival of patients who underwent attempted repair was good (75%), 21/27 (78%) deaths occurred during phases of treatment controlled by a trauma surgeon. The techniques and sequencing of resuscitation can affect outcome. Pneumatic antishock garments were not beneficial in the prehospital setting for patients with TRA. In fact, PASG were on and inflated in all patients who presented in cardiac arrest. Awake, unanesthetized intubation caused fatal aortic rupture in three patients. Pharmacologic control of blood pressure during intubation is necessary. The amount of fluid, blood transfusion, and changes in blood pressure secondary to therapy did not statistically affect outcome. The average time from arrival in the ER to angiogram was 64.7 minutes. The average time ER to operating room was 159.7 minutes. Seven cases of TRA had delayed diagnosis usually for a misinterpreted CXR (5/7). Delay in diagnosis did not directly contribute to any deaths. Associated abdominal injuries are a common cause of preventable deaths. Fourteen patients with combined abdominal injuries and TRA were identified. Four of six deaths occurred with potentially reparable injuries. Operative and diagnostic sequences must be adjusted to allow rapid control of all potentially fatal injuries. 
5	Saltpeter ingestion. A 37-year-old man presented to the emergency department after an attempt to self-treat his priapism with saltpeter (K+NO3). Initially he had a potassium of 7.6 with electrocardiographic changes and a markedly elevated CO2. The potassium and carbon dioxide normalized in less than 24 hours with standard treatment for hyperkalemia. Hyperkalemia is expected with large oral potassium ingestion; and the elevated CO2 was spurious, caused by the misreading of serum nitrates by the Ektachrom 700 system. Ingestion of K+NO3 should be added to the differential of hyperkalemia with a markedly elevated CO2. 
4	No effect of experimental noise exposure on human pregnancy. The effect of experimental noise exposure (15 minutes of 90-dB white noise via headphones) was examined on systolic, diastolic, and mean arterial pressures; heart rate; and stress hormones (ACTH, cortisol, prolactin, epinephrine, and norepinephrine) in normotensive and hypertensive pregnant women. No significant effects induced by noise exposure could be registered in these variables. Fetal and uterine blood circulation was also examined with a duplex pulsed Doppler system. No changes were seen on the fetal side as measured from the descending aorta in blood flow velocity (cm/second) or pulsatility or resistance indexes in either normotensive or hypertensive pregnancy. The only change observed was an increase in fetal heart rate in normotensive pregnancy. However, this increase could not be confirmed by cardiotocographic registration and is not clinically important. Uterine blood circulation was recorded from the proximal uterine artery on the placental side, and no effect of exposure was seen on pulsatility or resistance indexes. 
5	Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial. A total of 536 infants and children with acute otitis media were randomly assigned to one of six consistent year-long regimens involving the treatment of nonsevere episodes with either amoxicillin or placebo, and severe episodes with either amoxicillin, amoxicillin and myringotomy, or, in children aged 2 years or older, placebo and myringotomy. Nonsevere episodes had more favorable outcomes in subjects assigned to treatment with amoxicillin than with placebo, as measured by the proportions that resulted in initial treatment failure (3.9% vs 7.7%, P = .009) and the proportions in which middle-ear effusion was present at 2 and 6 weeks after onset (46.9% vs 62.5%, P less than .001; and 45.9% vs 51.5%, P = .09, respectively). In subjects whose entry episode was non-severe, those assigned to amoxicillin treatment had less average time with effusion during the succeeding year than those assigned to placebo treatment (36.0% vs 44.4%, P = .004), but recurrence rates of acute otitis media in the two groups were similar. In the 2-year-and-older age group, severe episodes resulted in more initial treatment failures in subjects assigned to receive myringotomy alone than in subjects assigned to receive amoxicillin with, or without, myringotomy (23.5% vs 3.1% vs 4.1%, P = .006). In the study population as a whole, severe episodes in subjects assigned to receive amoxicillin alone, and amoxicillin with myringotomy, had comparable outcomes. It is concluded that children with acute otitis media should routinely be treated with amoxicillin (or an equivalent antimicrobial drug). The data provide no support for the routine use of myringotomy either alone or adjunctively. 
4	Prolonged extracorporeal life support of pediatric and adolescent cardiac transplant patients. Options for mechanical support of pediatric patients with severe heart failure who are awaiting transplantation or have undergone transplantation are limited. This report examines 3 patients placed on extracorporeal life support (ECLS) while awaiting transplantation and 3 patients who underwent transplantation and suffered subsequent heart failure due to rejection or postoperative myocardial dysfunction. The overall survival rate was 2 of 6. The 2 surviving patients had a failing transplanted heart. There were no survivors among the patients placed on ECLS as a bridge to transplantation. In each case a contraindication to transplantation developed before a donor heart could be obtained. The mean time of ECLS support was 147.5 hours (range, 70 to 370 hours). The ECLS circuit did not affect cyclosporin levels or antirejection therapy. Extracorporeal life support can be used to support pediatric cardiac transplant patients with biventricular failure due to acute rejection or postoperative dysfunction. Although the results have been discouraging, ECLS may still have a role as a bridge to transplantation. However, complications can develop during ECLS that may preclude transplantation. 
1	Value of four models for selecting patients for local excision of invasive squamous cell carcinoma of the vulva. For 75 women with squamous cell carcinoma of the vulva who underwent radical vulvectomy and inguinofemoral lymphadenectomy, the authors assessed the efficacy of four models for selecting patients who could have been treated adequately with local excision of the tumor. Each of the three models proposed by Andreasson and Nyboe covered 25% of the patients, none of whom had groin metastases or died of cancer. Local recurrence in the vulva occurred in 10%. A model suggested by the International Society for the Study of Vulvar Disease covered almost 10% of the patients. One of seven patients had groin metastases, none died of cancer, and one of seven developed local recurrence in the vulva. The criteria of the clinically best suited model are tumor not situated on the clitoris and less than 4 cm in diameter, with only slight hyperchromasia. This model ought to be tested in a randomized study. 
1	The origin of epidermal melanocytes. Implications for the histogenesis of nevi and melanomas. Among the most venerable concepts in dermatopathology is Unna's 19th century notion of Abtropfung, ie, that melanocytes drop off from the epidermis to the dermis during the histogenesis of melanocytic tumors. Paradoxically, however, Unna's basic premise of an epidermal origin for melanocytes has been seriously questioned for over 40 years, based on experimental evidence favoring a neural crest origin for melanocytes. Recent work has strengthened the evidence for a neural crest origin of epidermal melanocytes, and it has been suggested that the concept of Abtropfung be replaced by the concept of Hochsteigerung. The concept of Hochsteigerung holds that melanocytes migrate up from the dermis into the epidermis-not only in normal development, but also during normal tissue maintenance. It now seems likely that the precursor of melanocytes, in both normal and abnormal differentiation, may not be a melanoblast (a primitive cell committed to melanocytic differentiation) but rather a pluripotential cell. Although axon-investing Schwann cells have been the traditional focus as the closest relative of the epidermal melanocyte, recent studies suggest that another nerve sheath cell, the perineural cell, might be a better candidate. These concepts have profound implications for the histogenesis of melanocytic nevi and melanomas. 
3	Emergency department approach to managing seizures in pregnancy. Seizures in pregnancy pose risks for both the mother and the fetus and must be managed aggressively. Antiepileptic drugs have some teratogenic potential, but the risks are not as profound as reported in earlier literature. There is definitely less risk to the fetus from anticonvulsant exposure than from uncontrolled seizures. The evaluation of a pregnant woman with new-onset seizures is the same as for the nonpregnant patient, including head computed tomography with appropriate abdominal shielding. Status epilepticus management is based on IV benzodiazepines, phenytoin, or phenobarbital. Good fetal outcome is dependent on rapid seizure control. Management of eclampsia is controversial. There is little evidence that magnesium sulfate has anticonvulsant properties, and its use as such will probably decline steadily in the future. At present, it is reasonable to manage eclamptic seizures in the same way that status epilepticus is managed. 
1	Historical review of pancreaticoduodenectomy. The performance of pancreaticoduodenectomy by Whipple in 1935 demonstrated that the operation was feasible technically and compatible with reasonable function after recovery. From the mid- to late 1940s until the last 10 years, the procedure was condemned by many because of its associated mortality and morbidity. For reasons that are not clear, the risk of pancreaticoduodenectomy in the last 10 years has fallen to less than 10% and in several centers, less than 5%. Postoperative complications have been reduced and blood transfusions are unnecessary in an increasing number of patients. Furthermore, a normal productive life without the need for medication and with no digestive disorder is expected. Seventy-one percent of patients are able to return to their preoperative occupation. 
5	Monocortical miniplate fixation of mandibular angle fractures. Noncompression monocortical miniplate fixation of mandibular fractures has become a reliable method of providing rigid fixation and eliminating the need for intermaxillary fixation. Recent studies, using a variety of internal fixation techniques, have described high complication rates at the mandibular angle. This article compares the use of one miniplate vs two miniplates in treatment of angle fractures. Since September 1985, 61 patients with 63 mandibular angle fractures have been treated with miniplates. Forty-four fractures were fixed with two miniplates. Six complications (3.1%) occurred, five of which were in the one-miniplate group. The complication rate in the double-miniplate group is the lowest reported of any plating technique. The use of two miniplates has proved to be an effective method of treating mandibular angle fractures. 
1	Cystic dilatation of the cystic duct: a new type of biliary cyst. A case of a patient with a congenital cyst that was localized solely to the cystic duct is presented. We propose including this anomaly in the biliary cyst classifications, which currently include choledochal and intrahepatic and extrahepatic biliary cysts. The diagnosis and management of this new type of cyst in addition to other types of biliary cysts are discussed. 
5	Isolated calf venous thrombosis: diagnosis with compression US. Compression ultrasound (US) is an excellent means of evaluating the femoral and popliteal veins but is generally regarded as inadequate for the diagnosis of calf vein thrombosis. This prospective study evaluated compression sonography of the calf veins in 45 symptomatic patients with normal femoral and popliteal veins. All patients underwent correlative venography. Compression US enabled identification of 15 of 17 patients with calf vein thrombosis (sensitivity, 88%). The two false-negative results were in patients with small isolated thrombi. Compression US results were true-negative in 26 of 27 patients with normal venograms (specificity, 96%). If these results can be duplicated by other investigators in larger series of patients, compression US will be an adequate screening modality for calf vein thrombosis. 
1	Serum tumor markers and patient allocation to good-risk and poor-risk clinical trials in patients with germ cell tumors. The allocation of patients with advanced germ cell tumors (GCT) to different treatment programs based on clinical characteristics is standard in the design of clinical trials today. Studies have shown that substantial differences exist between entry criteria and that these differences could influence the outcome of clinical trials. The factors contributing to these differences are not clear due to patient selection biases. Two hundred five unselected and consecutive patients allocated to and treated in good-risk and poor-risk treatment programs at Memorial Sloan-Kettering Cancer Center (MSKCC) were reassigned risk status by the Indiana University (IU) Classification. The results were compared with those of the Southeastern Cancer Study Group (SECSG). The results using both criteria indicated substantial agreement in total end results and the identification of good-risk patients. The results in poor-risk patients differed substantially, with 39 patients (19%) classified as poor-risk by MSKCC criteria and 66 (32%) by Indiana criteria. The major discrepancy occurred in IU Stage 7, in which 26 of 32 patients (81%) achieved a complete response. The major factor contributing to this difference in risk assignment was the use of serum tumor markers. Serum tumor markers must be incorporated into risk assignment criteria for GCT clinical trials to minimize the number of good-risk GCT patients in poor-risk trials. 
1	Melanocytic hyperplasia of the oral mucosa. Lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa. They are even more rare than the various morphologic types of nevomelanocytic lesions. This article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex, junctional lentigo ("jentigo"), atypical melanocytic hyperplasia (melanoma in situ), and melanocanthoma. The proper terminology for these lesions is also discussed. 
5	Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Bismuth subsalicylate (BSS) and placebo were evaluated in a double-blind, placebo-controlled study as adjunct to rehydration therapy in 123 children, aged 4 to 28 months, hospitalized with acute diarrhea. The dosing regimen was 20 mg/kg five times daily for 5 days. Significant benefits were noted in the BSS group compared with placebo as manifested by decreases in stool frequency and stool weights and an improvement in stool consistency, significant improvement in clinical well-being, and shortening of the disease duration. Patients treated with BSS had a significant reduction in duration of hospital stay (6.9 days) compared with placebo-treated patients (8.5 days). Also, intravenous fluid requirements decreased significantly more rapidly and to a greater degree in the BSS-treated group. Bismuth subsalicylate was associated with clearance of pathogenic Escherichia coli from the stools in 100% of cases but was not different from placebo in rotavirus elimination. Bismuth subsalicylate was well tolerated with no reported adverse effects. Blood bismuth and serum salicylate levels were well below levels considered toxic. In this study, BSS provided effective adjunctive therapy for acute diarrhea, allowing children to get well sooner with less demand on the nursing and hospital staff. 
3	Flow cytometric DNA content of adenoid cystic carcinoma of submandibular gland. Correlation of histologic features and prognosis. Flow cytometric analysis of nuclear DNA content was performed in 26 adenoid cystic carcinomas of the submandibular gland using archived, paraffin-embedded tissues. The DNA content was compared with multiple histologic parameters and clinical course. Ten carcinomas (38%) were aneuploid and 16 (62%) diploid. Aneuploid carcinomas demonstrated a higher frequency of solid cytoarchitecture, lymph node metastases, and advanced clinical stage, as compared with diploid carcinomas. Other histologic features predicting aggressive clinical behavior also correlated with abnormal DNA content and included invasion of nerves larger than 0.25 mm and intravascular extension. Our data suggest that DNA content analysis can be an effective objective parameter in the clinicopathologic assessment of adenoid cystic carcinoma. 
5	Blood conservation in cardiac surgery. We reviewed current blood conservation techniques and their use in cardiac surgery. Avoidance of aspirin preoperatively is an important blood conservation measure. Patients scheduled for an elective operation should participate in autologous predonation programs. With careful monitoring, patients with major coronary artery disease can safely donate blood preoperatively. Intraoperative processing of blood withdrawn before cardiopulmonary bypass provides autologous platelet-rich plasma for infusion after reversal of heparin sodium. Blood collected from the field during operation and blood remaining in the oxygenator after bypass can also be processed to yield washed and concentrated red blood cells for reinfusion. Randomized, prospective studies document that postoperative autotransfusion is both safe and effective in reducing homologous blood use. Aprotinin reduces plasma protein activation and platelet damage during bypass. The integration of available blood conservation techniques into a comprehensive program combined with careful consideration of the indications for transfusion may allow more patients to avoid transfusion entirely. 
3	A videofluoroscopy chair for the evaluation of dysphagia in patients with severe neuromotor disease. Due to the difficulties encountered in positioning severely neurologically impaired individuals for videofluoroscopic studies, the Rehab Tech Video FluoroChair was developed. The purpose of the chair is to provide the severely disabled patient with safe, stable postural support in an upright position for videofluoroscopic studies, with anterior-posterior, lateral, and rotational views easily performed. The chair features a removable headrest, a full back support, armrests, lateral truncal supports, and a patented base which is clamped to the footboard of the radiology table and allows for 200 degrees rotation of the patient. Two case studies illustrate the practical use and versatility of the Rehab Tech Video FluoroChair. 
5	Infectious mononucleosis in older adults. Infectious mononucleosis as a manifestation of primary Epstein-Barr virus infection occurs uncommonly in adults over age 40. While fever is almost universal, older patients with the disease often present without lymphadenopathy, pharyngitis, splenomegaly, lymphocytosis or atypical lymphocytes. Jaundice and hepatomegaly occur more commonly in older patients than in adolescents and create diagnostic confusion. Often, infectious mononucleosis in this age group is confused with lymphoma, leukemia or biliary obstruction, or is classified as "fever of unknown origin.". 
2	Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis. We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6-3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues. 
1	Amplification of oncogenes in mammary carcinoma shown by fine-needle biopsy. A procedure that measures the amplification of oncogenes in human cancer cells is described. The cells were obtained by fine-needle biopsy to allow repeated sampling from individual metastases. A drawback was the low number of cells obtained, but this could be overcome by using a slot-blot hybridization technique to measure gene amplification. Two patients with mammary cancer (primary tumors or metastases), analyzed for the levels of amplification of the oncogene erb-B2, are described in detail. This technique is suitable for analyzing alterations occurring during cancer progression and for identifying subgroups of mammary cancer with different characteristics. 
5	Delta sleep ratio. A biological correlate of early recurrence in unipolar affective disorder. Slow wave sleep abnormalities have long been described in depression but were considered to be nonspecific indicators of psychopathology. Computerized techniques, including amplitude frequency measures and spectral analyses, are permitting new approaches to the examination of delta sleep. Early studies suggested that many depressed patients demonstrate lower delta wave intensity during the first non-rapid eye movement period than the second one. This finding, prominent in middle-aged depressed patients, has led to an examination of the ratio between the first and second non-rapid eye movement periods. This delta sleep measure seems to be a more robust predictor of recurrence than rapid eye movement latency. Analysis of data on 74 patients in a long-term maintenance treatment study for a minimum of 24 months demonstrates that the delta sleep ratio can predict survival time following discontinuation of drug treatment. Individuals with a high delta sleep ratio remain clinically remitted five times longer than those with a low delta sleep ratio. 
4	The frequency-dependent behavior of cerebral autoregulation. Cerebral autoregulation is a complex physiological process composed of both fast and slow components that may respond differently to different rates and patterns of blood pressure variation. To assess the temporal nature of autoregulation, transcranial Doppler velocity recordings of the middle cerebral artery obtained over prolonged periods were compared with blood pressure recordings in 5 patients without cerebral disease and in 13 patients with intracranial pathological changes. Correlations between the velocity and pressure wave forms at various frequencies of variation were measured with systems analysis techniques. Patients with aneurysmal subarachnoid hemorrhage had high correlations indicating pressure-dependent flow and impaired autoregulation. Patients without cerebral disease had significantly lower correlations (P less than 0.01), indicating intact autoregulation. Examples of increasing correlations and correlations at new frequencies emerging as the clinical condition worsened are given. These preliminary examples suggest that the application of systems analysis techniques to velocity and pressure data allow measurement of the temporal nature of cerebral autoregulation. 
5	Neurologic complications of cardiac transplantation. Between 1984 and 1989, orthotopic cardiac transplantations were done in 90 patients from 10 to 65 years of age for end-stage, refractory congestive cardiomyopathy. Two patients had had ischemic strokes 5 months and 18 years, respectively, before transplantation. Six patients (7%) suffered acute neurologic events perioperatively. Three patients suffered cerebral infarctions. In 1 case this occurred 10 days before transplantation--probably as a result of systemic hypoperfusion--with the placement of ventricular assist devices. Two others suffered infarctions 5 and 21 days, respectively, after transplantation, each of probable embolic origin. Two patients had an acute intracerebral hemorrhage 21 and 36 days, respectively, after transplantation; both were located within the basal ganglia and subcortical regions. Both patients had moderate to severe hypertension, and in 1, renal failure and a coagulopathy developed before hemorrhage. Tremor, seizures, and an altered level of consciousness developed in 1 patient as an apparent toxic reaction to cyclosporine treatment. Only 1 patient died as a result of the neurologic complication--of an acute intracerebral hemorrhage. Three patients recovered fully, 2 partially. Only the case of drug toxicity could be directly attributed to the transplantation procedure itself. We conclude that the risk of an acute neurologic insult with orthotopic cardiac transplantation is low but may result from drug toxicity, cerebral ischemia, or hemorrhagic mechanisms. 
2	Primary solid neoplasms of the greater omentum. Primary solid tumors of the greater omentum are rare, with only 42 reported cases. Malignant hemangiopericytomas constitute only three of these cases. The 40-year-old patient described in this report had abdominal pain, a palpable abdominal mass, early satiety, and weight loss. At laparotomy a large omental hemangiopericytoma was excised, and no other evidence of disease was grossly evident. Eighteen months after initial laparotomy, the patient had widespread progression of the tumor and, despite chemotherapy, died 2 months later. A review of reported cases shows that abdominal discomfort (56%) and mass (35%) are the most common clinical characteristics of a primary omental tumor. Weight loss, ascites, and peritoneal implants usually indicate malignancy. Rare long-term follow-up prevents definitive conclusions regarding therapy and prognosis. At present, surgical excision alone appears to be the treatment of choice, with no demonstrable benefit from either chemotherapy or radiation. 
5	Acute limb ischaemia: the place of intravenous streptokinase. Intravenous streptokinase infusions (100,000 units/h) have been used to treat 48 patients, with 50 episodes of acute limb ischaemia who were unlikely to benefit from a surgical approach. These included 17 acute thromboses, 14 late or distal emboli and 19 bypass graft occlusions. Overall, 17 (34 per cent) instances had complete lysis with reappearance of distal pulses and a further 28 per cent had clinical improvement without change in pulse status. Final outcome after 30 days was limb salvage in 60 per cent, amputation in 24 per cent and death in 16 per cent, but this was achieved after eight patients without lysis had vascular reconstructive surgery. Serious complications were infrequent, but included a fatal stroke, a haematemesis and two episodes of distal embolization. The outcome was not related to the duration of ischaemia or the site of occlusion. Lysis was more frequent with emboli (50 per cent) and graft occlusions (47 per cent) than arterial thromboses (6 per cent). Limb salvage was more likely in patients with no neurological deficit in the limb (70 per cent) than if a deficit was present (37 per cent). In conclusion, intravenous streptokinase produced a moderate benefit with low morbidity and has a role in acute limb ischaemia if surgery is inappropriate and intra-arterial lysis unavailable. In particular, selected patients with emboli or graft occlusions without a neurological deficit may be most suitable. 
5	Simultaneous operative repair of multilevel lower extremity occlusive disease. Sixty-two patients (39 men (63%), 23 women (27%), mean age 68 years) with multilevel lower extremity arterial occlusive disease underwent simultaneous inflow and outflow operative arterial repair consisting of aortofemoral bypass in 22 (35%), axillofemoral bypass in 17 (28%), femorofemoral bypass in 15 (24%), iliac endarterectomy in 7 (11%), and unilateral aortoiliac bypass in 1 (2%), combined with 69 outflow procedures (unilateral in 55 patients, 89%), including above-knee femoropopliteal in 12 (17%), below-knee femoropopliteal in 35 (51%), femoroinfrapopliteal in 20 (29%), popliteal tibial in 1 (1%), and femoropedal bypass in 1 (1%). Multiple criteria were used to identify patients with multilevel disease likely to benefit from multilevel procedures. The operations were performed by two operating teams in a median time of 240 minutes. Prosthetic grafts were used for eight (13%) distal bypasses, the remainder were autogenous vein. There was one operative death (1.8%). The mortality rate, morbidity rate, and operative time were not significantly different from a group of patients who underwent concurrent, isolated inflow operations (aortofemoral, axillobifemoral, femorofemoral bypass or iliac endarterectomy). Mean follow-up was 14.9 months (range, 0 to 120). The life-table primary patency for the inflow procedures was 92.6% at 24 months, the outflow was 94.9% at 24 months. Cumulative limb salvage was 90.9% at 48-month follow-up. All patients with claudication were relieved of their symptoms. We conclude that complete correction of multilevel disease can be accomplished with operative time, morbidity rate, and patency equal to that of single level repair. Multilevel procedures provide complete relief of symptoms in a higher percentage of patients than has been reported after single level repair. 
4	Results of coronary surgery after failed elective coronary angioplasty in patients with prior coronary surgery The results of coronary artery bypass surgery after failed elective coronary angioplasty in patients who have undergone prior coronary surgery are unknown. Coronary angioplasty may be performed to relieve angina after surgery either to the native coronary vessels or to grafts. Failure of attempted coronary angioplasty may mandate repeat coronary surgery, often in the setting of acute ischemia. From 1980 to 1989, 1,263 patients with prior coronary bypass surgery underwent angioplasty; of these patients, 46 (3.6%) underwent reoperation for failed angioplasty during the same hospital stay. Of the 46 patients who underwent reoperation, 33 had and 13 did not have acute ischemia. In the group with ischemia, 3 patients (9.1%) died and 14 (42.4%) died or had a Q wave myocardial infarction in the hospital compared with no deaths (p = NS) and no deaths or Q wave myocardial infarction (p = 0.005) in the group without ischemia. At 3 years, the actuarial survival rate was 88 +/- 6% in the group with ischemia, whereas there were no deaths in the group without ischemia (p = NS), and freedom from death or myocardial infarction was 51 +/- 10% in the group with ischemia, versus no events in the group without ischemia (p = 0.006). In most patients with prior coronary bypass surgery, coronary angioplasty was performed without the need for repeat coronary bypass surgery. Should coronary angioplasty fail, reoperation in patients without acute ischemia can be performed with overall patient survival comparable to that of elective reoperative coronary bypass without coronary angioplasty. 
2	Human hepatic regenerative stimulator substance: partial purification and biological characterization of hepatic stimulator substance from human fetal liver cells. Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substance--a liver-specific growth factor--was partially purified from human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heat-stable, protease-sensitive, organ-specific and species-nonspecific. Human hepatic stimulator substance produced a two- to threefold increase of 3H-thymidine incorporation into hepatic DNA when injected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosamine (1.6 gm/kg body weight)-induced hepatic necrosis in rats were further evaluated. A survival rate of 4% (n = 24), 41% (n = 12, p less than 0.05), 33% (n = 12, p less than 0.05), 31% (n = 13, p less than 0.05) and 18% (n = 11, p greater than 0.05) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 x 10(8] intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning. 
5	HLA-D locus associations in alopecia areata. DRw52a may confer disease resistance. Because predisposition to autoimmunity has been associated with HLA-D alleles and alopecia areata is hypothesized to be a T-cell mediated autoimmune hair loss, we determined DR and DQ alleles in 88 white and 10 American black patients with alopecia areata as well as controls with the use of restriction fragment length polymorphism typing with cDNA probes. White patients with alopecia areata have an increase in the phenotype frequencies of DR4 and DQw8 and an increase in genotype frequencies of DR4 and DR5 (now DRw11[5]). These associations are in agreement with those reported in two other studies but are not significant when corrected by the number of HLA antigens tested. Sixty-one percent of all patients with AA have DR4 and/or DRw11(5) specificities vs 40% of controls, with more DR4,DRw11(5) and DQw7(w3), DQw8(w3) heterozygotes among patients. DQw6(w1) phenotype frequencies and DRw52a phenotype and genotype frequencies are significantly decreased in patients with alopecia areata relative to controls. This highly significant negative association with the HLA DRB3 allele DRw52a in whites persisted even when DR4- or DRw11(5)-positive individuals were excluded from the patient and control groups. These data suggest that HLA-DR4 and DRw11(5) with their associated DQw7(w3) and DQw8(w3) specificities may confer susceptibility to alopecia areata, while DRw52a may confer resistance. 
5	Outcome of patients with chronic affective disorder: a five-year follow-up. Patients with major depression, mania, or schizo-affective disorder that had been present without remission for 2 years or more at intake (N = 129) were followed prospectively for 5 years, as were 580 patients who had been ill for shorter periods at intake. Despite very substantial durations of episode, three-quarters of the chronic patients recovered, although recovery occurred much later in the follow-up period than it did among the nonchronic patients. Factors associated with recovery were less severe illness at intake, lack of psychotic features, good friendship patterns in adolescence, and, most important, a relatively high maximum level of functioning in the 5 years preceding intake. 
1	Primary invasive carcinoma of the vagina. A retrospective review was conducted of 53 women with invasive carcinoma of the vagina and without documented exposure to diethylstilbestrol who were seen at the University of California Irvine Medical Center, Long Beach Memorial Medical Center, and Saddleback Memorial Medical Center from 1976-1988. Forty-seven (89%) had squamous cell carcinoma and six (11%) adenocarcinoma. Thirty-seven (70%) were treated with whole-pelvis irradiation and brachytherapy, nine with surgery alone, and the other seven with a combination of treatments. The crude and corrected 2-year survival rates for the entire group were 47 and 69%, respectively. Those with previous pelvic surgery were more likely to develop serious treatment-related complications. There was a statistically significant correlation between previous hysterectomy and the diagnosis of primary invasive carcinoma of the vagina after the onset of symptoms. Women diagnosed during routine examination, before symptom onset, tended to have a survival advantage. All women, including those who have had hysterectomy, should be counseled to continue gynecologic cancer surveillance regardless of age. 
1	Frequent mutation of the p53 gene in human esophageal cancer. Sequence alterations in the p53 gene have been detected in human tumors of the brain, breast, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene. To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors. We examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carcinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5, 6, 7, 8, and 9. Two cell lines and five of the tumor specimens contained a mutated allele (one frameshift and six missense mutations). All missense mutations detected occurred at G.C base pairs in codons at or adjacent to mutations previously reported in other cancers. The identification of aberrant p53 gene alleles in one-third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus. 
1	Adenocarcinoma arising in a foregut cyst of the mediastinum. A case of malignant transformation in a mediastinal cyst of the esophageal reduplication type is presented. The cyst had been recognized 39 years previously, but remained asymptomatic until sudden growth occurred. It was resected totally from the esophagus and the patient recovered well. A review of the literature showed that malignancy in mediastinal foregut cysts is extremely rare. 
5	Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. The function of the c-Myc oncoprotein and its role in cell growth control is unclear. A basic region of c-Myc is structurally related to the basic motifs of helix-loop-helix (HLH) and leucine zipper proteins, which provide sequence-specific DNA binding function. The c-Myc basic region was tested for its ability to bind DNA by attaching it to the HLH dimerization interface of the E12 enhancer binding factor. Dimers of the chimeric protein, termed E6, specifically bound an E box element (GGCCACGTGACC) recognized by other HLH proteins in a manner dependent on the integrity of the c-Myc basic motif. Methylation of the core CpG in the E box recognition site specifically inhibited binding by E6, but not by two other HLH proteins. Expression of E6 (but not an E6 DNA binding mutant) suppressed the ability of c-myc to cooperate with H-ras in a rat embryo fibroblast transformation assay, suggesting that the DNA recognition specificity of E6 is related to that of c-Myc in vivo. 
4	Atrial activation sequence during atrial flutter in the canine pericarditis model and its effects on the polarity of the flutter wave in the electrocardiogram. Stable atrial flutter induced in both conscious and open chest states was studied in 30 mongrel dogs after production of sterile pericarditis. During the conscious state studies, induced atrial flutter (mean cycle length 128 +/- 15 ms) was always sustained greater than 15 min and was stable. Three types of flutter wave polarity were noted in electrocardiogram (ECG) lead II: positive in 16 dogs, negative in 3 and flat or slightly positive in 11. Sequential site atrial mapping during atrial flutter (mean cycle length 133 +/- 18 ms) in the open chest state showed either clockwise (18 dogs) or counterclockwise (12 dogs) circus movement in the right atrium. In 19 of 30 dogs, the circus movement clearly did not require any naturally existing anatomic obstacle; in 11, the orifice of the superior vena cava probably was also involved. Double potentials were recorded from the center of the reentrant circuit during atrial flutter, and fractionated electrograms were recorded from a pivot point of the reentrant wave front. A positive flutter wave in ECG lead II (12 dogs with counterclockwise circus movement) was associated with early activation of the Bachmann's bundle region compared with the posteroinferior left atrium and activation of the left atrium mainly in a superoinferior direction. A negative flutter was associated with the early activation of the posteroinferior left atrium compared with Bachmann's bundle and activation of a considerable portion of the left atrium in an inferosuperior direction. A flat or slightly positive flutter wave (14 of 18 with clockwise circus movement) was associated with activation of the left atrium almost simultaneously by two wave fronts coming from both these sites. In conclusion, atrial flutter in this dog model is due to circus movement in the right atrium, the center of which does not necessarily require an anatomic obstacle. Although atrial flutter is generated by circus movement in the right atrium, the flutter wave polarity in the ECG is determined primarily by the activation sequence of the left atrium. 
4	Epidemiologic studies demonstrating increased morning incidence of sudden cardiac death. To determine if sudden cardiac death shows a circadian variation, the mortality records of the Massachusetts population and the Framingham Heart Study were analyzed. The Massachusetts mortality data analysis revealed an increased morning incidence for out-of-hospital cardiac deaths similar to that previously described for nonfatal myocardial infarction. The records of the Framingham Heart Study allowed more comprehensive analysis of the time of sudden cardiac death. In this study, a prominent circadian variation was also identified in which frequency of sudden cardiac death increased sharply between 6 A.M. and 9 P.M.; distribution was fairly even throughout the rest of the day. This circadian pattern may be explained in part by physiologic changes that increase the likelihood of ventricular fibrillation or increase the risk of thrombosis in the morning hours. The possible role of the morning increase in physical and mental activity as a trigger of sudden cardiac death requires further investigation. 
2	Prune belly syndrome in females: a triad of abdominal musculature deficiency and anomalies of the urinary and genital systems. We describe seven female patients with deficient abdominal wall musculature and urinary tract and genital anomalies that represent the female equivalent of the prune belly syndrome. Urethral atresia, uterine duplication, and anorectal anomalies occurred frequently. The perinatal mortality rate was high; of the four surviving patients, renal failure developed in two and renal transplantation was required. The analysis of these cases suggests that urethral obstruction is an important factor contributing to the development of the prune belly syndrome in females. 
1	Marijuana smoking as a possible cause of tongue carcinoma in young patients. A case of T1N0M0 carcinoma of the tongue in a male 23-year-old 'regular' marijuana smoker is described. Hemiglossectomy and complete bilateral neck dissection were carried out. No post-operative radiotherapy was given as the resection margins were histologically negative. The tumour recurred one year later in the left cervical region involving the mandible and surgery was again performed, but after three months, neck disease was still evident. The case described case implies the introduction of marijuana as a possible new risk factor in the development of oral cavity tumours. Resection of the primary lesion has to be as wide as possible even in T1 cases, due to the aggressive biological behaviour of such tumours in young subjects. 
1	Oral zidovudine, continuous-infusion fluorouracil, and oral leucovorin calcium: a phase I study. A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day X 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose-limiting toxicity are warranted. 
5	Ultrasonographic detection of the second-trimester fetus with trisomy 18 and trisomy 21. Biparietal diameter/femur length ratio and nuchal thickness were found to be sensitive indicators for the prenatal detection of trisomy 18 and trisomy 21. A biparietal diameter/femur length ratio greater than 1.5 SD above the control mean correctly identified 5 of 11 (46%) fetuses with trisomy 21 and 3 of 4 (75%) fetuses with trisomy 18. Nuchal thickening (6 mm or more) correctly identified 5 of 12 (41%) fetuses with trisomy 21 and 2 of 4 (50%) fetuses with trisomy 18. The sensitivity and specificity of the biparietal diameter/femur length ratio in detecting either aneuploidy was 53% and 93%, respectively, whereas a thickened nuchal fold had a sensitivity of 44% and a specificity of 100%. The combined use of the two ultrasonographic measurements had an overall sensitivity of 81% and a specificity of 93%. Prospective ascertainment of these two trisomies appears warranted in low-risk populations. 
2	Esophageal adenocarcinoma in a patient with surgically treated achalasia. Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastro-esophageal reflux disease. 
5	Rupture of atheromatous plaque as a cause of thrombotic occlusion of stenotic internal carotid artery. We analyzed the clinical profiles and autopsy findings of five patients who died shortly after developing cerebral infarction following thrombotic occlusion of the internal carotid artery. In all five cases, thrombotic occlusion was caused by rupture of the fibrous lining over the gruel of atheroma at the origin of the internal carotid artery showing tight stenosis of the lumen. The mean +/- SD shorter diameter of the lumen at the site of occlusion was 1.5 +/- 0.4 mm. Our results show that an internal carotid artery with tight stenosis of the lumen by atheroma containing gruel harbors a risk of thrombotic occlusion, which may give rise to cerebral infarction by artery-to-artery embolism or by reduced cerebral perfusion. 
1	Psychoneuroimmunology. Implications for oncology? Accumulating evidence indicates that the central nervous system (CNS) may regulate the activity of the immune system. Although the overall significance of the immune system in cancer remains controversial, psychosocial influences on immune function could potentially provide a mechanism to account for some of the reports of an association between psychosocial factors and cancer prognosis. 
4	Coronary collateral recruitment: functional significance and relation to rate of vessel closure. Studies in animals and humans have demonstrated the anatomic presence and functional significance of coronary collaterals. The extent of collateralization varies among species and among individuals. Collateral vessels are usually adequate for preserving resting regional and global ventricular function in the face of coronary obstruction. During stress, however, collateral supply may be inadequate. Collateral development is a time-dependent process during both the initial occlusion and following transient reflow and reclosure. Therefore when a previously collateralized coronary occlusion is recanalized and then recloses, the extent of the resulting collateral recruitment will depend, at least in part, upon the period of reflow between the two occlusions. The longer the reflow period, the less enhanced will be the collateralization. This is illustrated in the cases presented and has also been demonstrated in animal studies. The exact mechanisms for this recurrent collateral recruitment need further study. 
2	Immunochemical studies of ferrochelatase protein: characterization of the normal and mutant protein in bovine and human protoporphyria. Protoporphyria is a hereditary disorder characterized by a marked decrease in the activity of ferrochelatase, the terminal enzyme in the heme biosynthetic pathway. We have prepared specific polyvalent antibodies against bovine ferrochelatase in rabbits. The specificity of the antibody preparation against ferrochelatase was demonstrated by western blot analysis and immunoprecipitation of ferrochelatase activity. The antibody also cross-reacted weakly with ferrochelatase from human mitochondria. To quantify immunoreactive ferrochelatase in tissue samples, a kinetic-based enzyme-linked immunosorbent assay (k-ELISA) was developed. Ferrochelatase activity and the level of immunoreactive protein were measured in hepatic mitochondria isolated from six normal and nine protoporphyric (homozygous) cattle. Ferrochelatase activity was less than 10% of normal in mitochondria from protoporphyric animals; the amount of immunoreactive material was equivalent to that from normal animals. Similar studies were performed with samples from three normal and two protoporphyric (heterozygous) humans. Ferrochelatase activity was decreased in protoporphyric samples (about 17% of normal, but there was no concomitant decrease in immunoreactive material. These data demonstrate that a normal amount of ferrochelatase protein is present and suggest that bovine and human protoporphyria result from point mutations in the gene encoding ferrochelatase. 
4	Physiology and pharmacology of cardiovascular catecholamine receptors: implications for treatment of chronic heart failure. In the sympathetic nervous system the physiologic effects of the endogenous catecholamines noradrenaline (NA) and adrenaline (A) are mediated by alpha- and beta-adrenoreceptors (ARs). Both AR-types can be subdivided into two major subtypes: alpha-ARs into alpha-1 (predominant effect: vasoconstriction) and alpha-2 (presynaptic: inhibition of NA-release; postsynaptic: vasoconstriction), beta-ARs into beta-1 (cardiac effects, renal renin release, and lipolysis) and beta-2 (presynaptic: facilitation of NA-release; postsynaptic: vascular, bronchial, and uterine smooth muscle relaxation, glycogenolysis and possibly part of the A-mediated cardiac effects). During the last 30 years growing evidence has accumulated that dopamine (DA), the third endogenous catecholamine and the immediate precursor of NA, may also cause peripheral effects through stimulation of specific DA-receptors, in addition to its known action at alpha- and beta-ARs. It is now well accepted that at least two different DA-receptors are present in many peripheral tissues (DA1 and DA2), including those of the cardiovascular and autonomic nervous system. They seem to be involved in dilation of certain vascular beds, inhibition of NA-release during nerve stimulation, natriuresis, and aldosterone release. In chronic heart failure cardiac beta-AR function decreases (presumably due to endogenous "down-regulation" by the elevated catecholamines), and this decrease is related to the severity of heart failure (judged clinically by New York Heart Association functional class). The human heart contains both functional beta-1 and beta-2 ARs; cardiac beta-1 and beta-2 ARs seem to be differentially affected by different kinds of heart failure; in end-stage dilated cardiomyopathy beta-1 ARs are selectively reduced, whereas beta-2 ARs are nearly normal. 
2	Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Catalan Countries Study on Upper Gastrointestinal Bleeding To assess the risk of upper gastrointestinal bleeding associated with the use of individual non-narcotic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), a multicentre study of 875 cases of upper gastrointestinal bleeding and 2682 hospital controls was done. With control for confounding factors, the overall odds ratio estimate for aspirin taken at least once during the week before the first symptom was 7.2 (95% confidence interval 5.4-9.6). Non-aspirin NSAIDs associated with upper gastrointestinal bleeding were diclofenac (7.9 [4.3-14.6]), indomethacin (4.9 [2.0-12.2]), naproxen (6.5 [2.2-19.6]), and piroxicam (19.1 [8.2-44.3]). Paracetamol, propyphenazone, and dipyrone did not increase the risk. A previous history of gastrointestinal bleeding or peptic ulcer did not greatly affect odds ratio estimates, which differed according to sex and were higher for younger than for older patients. However, the incidence of upper gastrointestinal bleeding was higher among the elderly. 
4	Catheterization of coronary artery bypass graft from the descending aorta. The increasing frequency of reoperation for coronary artery disease has led to the use of a variety of grafts. This report describes the catheter technique for selective opacification of a saphenous vein graft from the descending thoracic aorta to the posterior coronary circulation. 
5	Percutaneous coronary excimer laser-assisted balloon angioplasty: initial clinical and quantitative angiographic results in 50 patients. The initial clinical experience and quantitative angiographic results of percutaneous coronary excimer laser-assisted balloon angioplasty are described for 55 lesions in 50 patients. With use of a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% reduction in absolute percent diameter stenosis) was achieved in 41 (75%) of 55 lesions, with 100% subsequent balloon angioplasty success (less than 50% residual stenosis). By quantitative digital caliper technique, the percent diameter stenosis (mean +/- SE) was reduced from 81 +/- 1% to 50 +/- 3% after excimer laser angioplasty (p less than 0.001) and to 20 +/- 1% after balloon angioplasty (p less than 0.001); minimal luminal diameter increased from 0.56 +/- 0.04 to 1.46 +/- 0.08 mm (p less than 0.001) and 2.03 +/- 0.07 mm (p less than 0.001), respectively. By videodensitometric techniques, the percent area stenosis decreased from 86 +/- 2% to 54 +/- 3% after excimer angioplasty (p less than 0.001) and to 26 +/- 3% after balloon angioplasty (p less than 0.001). There were no perforations, need for emergency bypass surgery or deaths. The overall incidence of abrupt closure (3.6%), dissection (1.8%), embolization (1.8%), filling defect (6%), myocardial infarction (5.5%), side branch occlusion (3.6%) or spasm (3.6%) was infrequent and more related to subsequent balloon angioplasty than to the laser procedure. 
1	Immediate postoperative mammogram for failed surgical excision of breast lesions In a series of 200 consecutive preoperative needle localizations of non-palpable breast lesions, 128 lesions (64%) were calcified and 72 lesions (36%) were noncalcified on preoperative mammograms. Radiographs of the surgical specimen failed to confirm excision of 11 lesions (5.5%), seven calcified and four noncalcified. These 11 patients were taken directly from the surgical suite to the radiology suite, where an immediate postoperative mammogram was obtained. In five patients (2.5%), immediate postoperative mammograms showed surgical failure with the lesion still present. In six patients (3.0%), immediate postoperative mammograms showed that the lesion had been removed, even though the lesion had not been identified on surgical-specimen radiographs. No errors occurred in the interpretation of immediate postoperative mammograms, a fact corroborated by examination of surgical specimens obtained at repeat surgery in three patients and identification of skin calcifications in two patients, and with follow-up mammograms in six patients. Whenever a discrepancy between preoperative localization radiographs and surgical-specimen radiographs exists, the authors suggest immediate postoperative mammography to improve the diagnostic process. 
2	Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study. OBJECTIVE--To find out whether a 10-14 days' course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics. DESIGN--Prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics. Patients were seen at three and six weeks and three, six, nine, 12, and 18 months after their first visit. SETTING--Departments of infectious diseases in three hospitals in Linkoping, Malmo, and Stockholm, Sweden. PATIENTS--40 Consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks. INTERVENTIONS--20 Patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics. All patients received non-steroidal anti-inflammatory drugs, and four also received intra-articular steroid injections after at least six weeks' observation. MAIN OUTCOME MEASURES--Arthritic symptoms assessed clinically and by using Ritchies' index; blood measurements reflecting inflammatory activity; serum IgG, IgM, and IgA antibody titres; HLA tissue type. RESULTS--No difference was observed concerning duration of arthritis, grade of inflammation, and number of joints affected between patients treated and those not treated with antibiotics. Furthermore, there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin, IgG, and IgA concentrations. All values had returned to normal within three months. No patient developed chronic arthritis, but sustained slight arthralgia occurred in three patients. The HLA-B27 antigen was found in 23 (58%) of the patients, and its presence did not affect clinical outcome. The IgG, IgM, and IgA antibody responses were similar in patients treated with antibiotics and those not treated. CONCLUSION--Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection. 
4	Sensitivity of a set of myocardial infarction screening criteria in patients with anatomically documented single and multiple infarcts. A subset of 3 screening criteria (Q wave greater than or equal to 30 ms in lead aVF, any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV in lead V2, and R wave greater than or equal to 40 ms in V1) has been proposed to identify single nonacute myocardial infarcts. Cumulatively, these 3 criteria achieved 95% specificity, and 84 and 77% sensitivities for inferior and anterior myocardial infarcts, respectively, among patients identified by coronary angiography and left ventriculography. This study establishes the true sensitivities of the set of screening criteria in 71 patients with anatomically proven single myocardial infarcts and 32 patients with multiple myocardial infarcts. In the single inferior infarct group, the aVF criterion was 90% sensitive. The V2 criterion (any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV) was 67% sensitive in the single anterior infarct group. No single criterion proved sensitive in identifying a posterolateral infarct. The set of screening criteria performed just as well for multiple infarcts as it did for single infarcts, with a cumulative sensitivity of 72%. The overall sensitivity of the screening set in the 103 patients in all groups was 71%. 
4	Computed tomography in the evaluation of the aorta in patients sustaining blunt chest trauma. Computed tomography is used with increasing frequency to evaluate blunt chest trauma. Since traumatic aortic rupture (TAR) is a rapidly lethal condition, unnecessary CT scanning may not be justified. To determine the accuracy of chest CT scanning for TAR, we reviewed 17 patients who underwent both chest CT scanning and aortography. Five patients had TAR by aortography. CT scanning yielded three true positives and two false negatives. In 12 patients with a negative aortogram, CT scanning recorded four false positives and eight true negatives. The specificity was 23% and the sensitivity was 83% compared with aortography. The overall accuracy for CT scanning was 53%. From these data we conclude that in the presence of an unstable patient or where there is a strong clinical suspicion of TAR the patient should proceed directly to aortography. 
4	Lung thallium-201 uptake during exercise emission computed tomography. To test whether the analysis of lung uptake is worth adding to the interpretation of exercise thallium-201 (201TI) emission computed tomography (ECT), a lung/heart ratio of 201TI uptake was measured from an anterior image during ECT in 25 clinically normal (Group 1), 91 angiographically normal (Group 2), and 265 subjects with coronary artery disease (Group 3). The mean +2 s.d. of ratios in Groups 1 and 2 were the same (0.37). In Group 3, 80 subjects (30%) with increased ratios (greater than 0.37) had higher frequencies of prior infarction and multi-vessel disease, more severe left ventricular dysfunction, and 201TI defects than 185 subjects with normal ratios. Subjects with markedly increased ratios (greater than 0.45) had three-vessel disease more frequently than those with slightly or moderately increased ratios (67% versus 14% or 35%). Thus the measurement of lung/heart ratios may provide information regarding the severity of coronary artery disease and should be added to the routine interpretation of exercise ECT. 
1	Transferrin receptor activity as a marker in transitional cell carcinoma of the bladder. An immunohistochemical staining method was used to study transferrin receptors (TFR) in bladder tissue from 10 patients with benign conditions and 33 with bladder cancer. All patients with bladder cancer were followed up by cystoscopy at intervals of 3 months (mean follow-up period 11 months). The relationship between TFR activity and recurrence rates was investigated. It was not possible to demonstrate TFR in normal bladder mucosa except for the proliferating cells of the basal layer. TFR activity in malignant tissue correlated well with the histological grade and pathological stage of the tumour. Patients with low grade superficial tumours showing TFR activity had a higher recurrence rate than those with no TFR activity. It was concluded that TFR activity in low grade superficial bladder tumours is a useful marker for predicting the recurrence rate. 
5	Plasma neurotransmitters and cortisol in duodenal ulcer patients. Role of stress. Levels of noradrenaline, adrenaline, dopamine, free serotonin, platelet serotonin, and cortisol were measured in the plasma of duodenal ulcer patients and controls. All subjects received antacids, and these substances were also measured. During relapse, all patients showed raised noradrenaline, adrenaline, dopamine, free serotonin, and cortisol values. In contrast, platelet serotonin showed very low values, which correlated negatively with all the former, except free serotonin. No correlations were found in parameters of the controls. After healing, significant reductions of noradrenaline, adrenaline, dopamine, free serotonin, and cortisol and significant increases of platelet serotonin values were observed. However, only dopamine, free serotonin, and cortisol reached normal values. Noradrenaline and adrenaline remained higher and platelet serotonin lower, both significantly more so than normals. These still-altered parameters showed similar correlations to those found during relapses. The present results demonstrate that some baseline autonomic system imbalance exists in patients, amplified and accentuated during relapse. We discuss the possibility that stress plays some role in triggering duodenal ulcer relapse. 
1	Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects. 
5	The painful shoulder: Part II. Intrinsic disorders and impingement syndrome. Intrinsic disorders that can cause shoulder pain include arthritis, gout, pseudogout and osteonecrosis. In its mildest form, impingement syndrome may cause only minimal discomfort. At its worst, impingement syndrome may lead to rotator cuff tear. Bicipital tendinitis and rupture of the biceps tendon may also be associated with impingement. Early rehabilitative intervention is important. Physical therapy is directed toward restoring range of motion and muscle strength. 
5	Ultrasound for the detection of foreign bodies. STUDY OBJECTIVE: To determine the ability of an emergency physician to detect a variety of foreign bodies in an experimental model using a portable ultrasound device. DESIGN: Ten pieces of beef were sliced into cubes approximately 6 cm on each side. Six different groups of foreign bodies were examined: gravel, cactus spine, glass, metal, wood, and plastic. An independent observer placed the objects in a random fashion into the beef cubes. One hundred twenty observations were made using sets of ten beef cubes at a time. Five foreign bodies were placed into each set of ten beef cubes. INTERVENTIONS: A blinded emergency physician used a portable ultrasound with a 7.5-MHz transducer to determine the presence or absence of a foreign body in each cube. MEASUREMENTS AND MAIN RESULTS: Ultrasound detected 59 of 60 foreign bodies, including all cubes of meat embedded with gravel, cactus spine, plastic, metal, and wood. Glass was detected nine of ten times. Of the 60 cubes of meat with no foreign bodies, one false-positive was recorded. This yielded sensitivity, specificity, positive predictive value, and negative predictive value of 98%. Positive determinations by ultrasound were significantly greater in the meat cubes with foreign bodies compared with the control group with no foreign bodies (P less than .001 by chi 2). Although the subset of glass foreign bodies had one false-positive and one false-negative, it was not significantly different in comparison with the other groups (P greater than .05 by chi 2). CONCLUSION: Ultrasound has promise as a diagnostic tool for the detection of a variety of foreign bodies. Further clinical studies using ultrasound for the detection of foreign bodies are warranted. 
2	Computed tomographic and ultrasonographic findings in women with acute fatty liver of pregnancy. Acute fatty liver of pregnancy is associated with complications that can influence antepartum management and necessitate delivery. To date, liver biopsy has been regarded as the "gold standard" for diagnosis. Radiologic evaluation of the liver has been suggested as a less invasive means of diagnosing this entity. Five patients with acute fatty liver of pregnancy underwent ultrasonography; three underwent concomitant computed tomography (CT) of the liver. The liver appeared to be normal in all the patients undergoing CT evaluation and all undergoing ultrasonography except one. Normal liver examinations are not unusual findings in patients with acute fatty liver of pregnancy. 
4	Histologic investigation of vascular malformations of the face after transarterial embolization with ethibloc and other agents. Twenty-one vascular malformations located in the facial area, 11 high-flow arteriovenous malformations and 10 slow-flow malformations, underwent combined treatment by embolization and later surgery. Embolization was performed simultaneously with superselective angiography of the branches of the external carotid artery. The new biodegradable fibrosing agent Ethibloc was used in 16 cases. Histologic examination of the surgical specimens confirmed the good target orientation by the transarterial injection of Ethibloc. Limitations of this technique are discussed. The agent proved to have thrombogenic and fibrogenic properties. Some of the vascular walls degenerated and ruptured following the embolization, but there were no instances of necrosis of interstitial tissue or skin. Embolization treatment of vascular malformations of the face was not curative, but it facilitated subsequent surgery in all examined cases. 
5	Malnutrition and acute respiratory tract infections in Filipino children. The impact of malnutrition on morbidity and mortality associated with acute respiratory tract infection (ARI) was studied in Filipino children less than 5 years old. Malnutrition measured by weight-for-age Z-scores of less than -3 SD and less than -2 SD from the National Center for Health Statistics median reference population was associated with the following significant relative risks of morbidity: 1.24 (95% confidence interval [CI] = 1.14, 1.34) and 1.14 (95% CI = 1.08, 1.19), respectively, for ARI; and 1.9 (95% CI = 1.46, 2.39) and 1.2 (95% CI = 1.03, 1.47), respectively, for acute lower respiratory tract infection (ALRI). These risk ratios remained significant when adjusted for age, crowding, and parental smoking. Malnourished children with severe ALRI also had a mortality risk two to three times higher than that of healthy children. This risk remained significant even when adjusted for significant predictors of mortality, including clinical complications, concurrent measles, severe infections, and female gender; and for clinical factors, including extent of pneumonic infiltrates, dehydration, and hepatic enlargement. These findings underscore the importance of nutritional intervention in the control of morbidity and mortality among patients with ARI. 
3	Modifying the translabyrinthine approach to preserve hearing during acoustic tumour surgery. Removing an acoustic schwannoma using the translabyrinthine approach has previously been considered incompatible with hearing preservation. By modifying the approach and preventing the loss of endolymph, we have successfully removed an intracanalicular acoustic schwannoma, which originated from the inferior vestibular nerve, and preserved hearing in the operated ear. This report represents the preliminary findings using this particular technique in the management of an intracanalicular acoustic tumour. 
4	The fat embolism syndrome. A review. While fat embolism occurs in most (more than 90%) patients with traumatic injury, the fat embolism syndrome (FES) occurs in only 3%-4% of patients with long-bone fractures. FES involves multiple organ systems and can cause a devastating clinical deterioration within hours. The major clinical features of FES include hypoxia, pulmonary edema, central nervous system depression, and axillary or subconjunctive petechiae. Improvements have been made in supporting the respiratory compromise and adult respiratory distress syndrome that these patients develop. Aggressive measures to improve the pulmonary function, i.e., positive pressure ventilation and effective fluid management, are important and expedite fixation of bone fractures. 
5	Management of urinary tract infections in children. Urinary tract infection is common in children. The presentation varies with age. Younger children exhibit protean signs. Diagnosis is dependent on the demonstration of significant bacteriuria in a properly collected and handled urine sample. The approach to treatment depends on the degree of illness at presentation, the presence of structural urinary tract abnormalities, and the age of the patient. Pathophysiology of urinary tract infection is dependent on interactive factors of the host and of the invading microorganism. Urinary tract abnormalities have significant impact on the management of children with urinary tract infections, both medically and surgically. Of particular importance is the observation that renal damage usually occurs within the first 5 years of life, and treatment delay in some young patients may have significant consequences. The overall prognosis in children with urinary tract infection is favorable. 
4	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (the CASCADE study). This randomized study evaluates survivors of out-of-hospital ventricular fibrillation (VF) not associated with a Q-wave acute myocardial infarction who are deemed to be at a high risk of recurrence of VF. It compares the outcome of treatment with empirically administered amiodarone with the outcome of treatment with other antiarrhythmic agents guided by electrophysiologic testing or Holter recording, or both. The goal of therapy guided by electrophysiologic testing is to suppress inducible ventricular tachycardia (VT) or VF. Holter recording is used as the primary means of adjusting therapy only if patients are noninducible at the baseline electrophysiologic study. Patients are stratified according to cardiac diagnosis, ejection fraction, and whether they had previously received an antiarrhythmic agent that failed to suppress their arrhythmias. The primary end point of the study is total cardiac mortality. The first patient was enrolled in a pilot study on April 26, 1984. By October 1988, 142 patients had been enrolled in the full study and, as of May 1990, 199 patients have been enrolled. Compliance with therapy has been good, with no patients lost to follow-up and 8% of patients, equal in both drug groups, crossing over to alternate therapy. Baseline clinical characteristics remain similar in amiodarone and conventional drug groups. Pulmonary toxicity with amiodarone is 7% at 1 year, with no patients dying of pulmonary toxicity. In the first 142 patients, the overall 1-year cardiac mortality was 19%, with a 17% arrhythmic mortality (either VF or presumed arrhythmic death). 
4	Sports-related and non-sports-related sudden cardiac death in young adults. Sports-related sudden cardiac deaths were compared with non-sports-related sudden cardiac death in individuals (14 to 40 years old) who were autopsied from 1981 to 1988 at the Maryland Medical Examiner's Office. Thirty-four of 690 total cases of sudden cardiac death were sports-related, which represents 5% of sudden cardiac death in this age group. Causes of death were severe atherosclerosis (nine), hypertrophic cardiomyopathy with asymmetry (eight), coronary artery anomalies (four), idiopathic concentric left ventricular hypertrophy (three), myocarditis (two), arrhythmogenic right ventricle (one), Kawasaki disease (one), and unknown (six); two of the cases with unknown causes had tunnel arteries. Exercise-related deaths were more likely due to hypertrophic cardiomyopathy (p = 0.0007) compared with 102 age-, sex-, and race-matched controls in the non-exercise group; there was no difference in the incidence of severe atherosclerosis (p = 0.4). The mean age of individuals with hypertrophic cardiomyopathy with asymmetry was less than that of those with severe atherosclerosis (24 vs 32 years, p = 0.03). Thus exercise precipitates sudden cardiac death in younger individuals with hypertrophic cardiomyopathy. 
4	Thyrotoxicosis induced by topical iodine application. We describe an elderly man who was admitted with congestive cardiac failure and found to have thyrotoxicosis. He did not have goiter, and he had normal radioiodine uptake in his neck. Serum iodine levels were elevated, explaining the lack of increase in radioiodine uptake in the thyroid gland. He had multiple pressure sores, which were treated with povidone-iodine (Betadine) soaks. Biochemical data were consistent with Graves' disease unmasked by topical iodine application. Povidone-iodine soaks are commonly used in decubitus ulcer care and warrant special attention in patients with preexisting thyroid disorders. We have reviewed the literature on this unusual complication. 
4	Recovery of retrograde fast pathway excitability in the atrioventricular node reentrant circuit after concealed anterograde impulse penetration. The recovery of the retrograde fast pathway excitability in atrioventricular (AV) node reentry has been difficult to assess with ventricular extrastimulation because of difficulty in achieving sufficiently short intranodal coupling intervals and the potential interposition of "lower common pathway" nodal tissue. To circumvent these methodologic obstacles in 10 patients with inducible AV node reentrant tachycardia, a fixed atrial extrastimulus (A2) coupled to a basic atrial drive (A1) at a cycle length of 500 ms was utilized to reproducibly initiate AV node reentrant echoes. A ventricular extrastimulus (V3) was then introduced after A2 at progressively shorter coupling intervals (A2V3) in an attempt to pre-excite the retrograde fast pathway after concealed anterograde penetration by A2. In six patients, retrograde fast pathway pre-excitation was achieved at critical A2V3 intervals, as evidenced by the appearance of A3 by up to 28 +/- 6 ms in advance of the expected first AV node reentrant echo. In five of the six cases, the V3A3 interval was virtually unaltered (less than or equal to 5 ms decrease) when A2 was omitted. In seven patients, at a critically short A2V3 coupling interval (195 +/- 27 ms ), V3 abruptly failed to elicit A3 and concomitantly abolished all AV node echoes; yet when A2 was omitted, an A3 response returned, with V3A3 identical to previous values. 
2	Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis. Long-term follow-up of 27 patients with hepatitis B virus-related chronic liver disease treated by transplantation showed that 23 had hepatitis B virus recurrence. In 13 patients late changes in the grafts were similar to those described in other series: minor abnormalities in five cases, chronic active hepatitis in five cases and non-hepatitis B virus-related graft dysfunction in three cases. Three patients had incomplete histological follow-up. Analysis of the histological changes and viral antigen expression in six cases revealed a distinct and novel pattern termed fibrosing cholestatic hepatitis. Development of fibrosing cholestatic hepatitis was associated with rapidly progressive graft dysfunction. It is postulated that this pattern of fibrosing cholestatic hepatitis develops because of a high cytoplasmic expression of viral antigens, including HBsAg. The remaining case had some features of fibrosing cholestatic hepatitis. The main histological features of this unique syndrome include thin, perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular-type epithelium; prominent cholestasis; ground-glass transformation; and ballooning of hepatocytes with cell loss and mild mixed inflammatory reaction. 
1	Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines. Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant. Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed. Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors. Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole. Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes. The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole. The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas. 
2	Acquired benign esophagorespiratory fistula: report of 16 consecutive cases. Sixteen cases of acquired benign esophagorespiratory fistula were treated in a 20-year period. A delay in diagnosis was usual, and most patients were first seen with a pulmonary infection already developed. Contrast esophageal x-ray studies established the diagnosis in all patients. There were seven esophagotracheal and nine esophagobronchial fistulas. A fistula between the esophageal diverticulum and a bronchus considered to be of inflammatory origin developed in 7 patients. A fistula as the consequence of trauma developed in 9 patients, and these fistulas were situated at a higher level of the respiratory tree. All patients underwent surgical treatment; in 12 it was definitive, and in 4 temporary gastrostomy was performed to improve nutrition before definite repair. The definitive repair consisted of eventual diverticulectomy, division of the fistula, and suture of both esophageal and respiratory defects. Two patients required esophageal resection and later reconstruction with colon interposition. One patient died, creating an operative mortality of 8.3% in the definitive-repair group. The remaining 11 patients had a gratifying long-term result. There were two deaths in the gastrostomy group due to an extremely poor condition of patients and debilitating pulmonary infection. Early diagnosis of this rare condition is necessary if severe pulmonary complications are to be avoided. Early direct repair gives excellent results. 
2	Epidural morphine for analgesia after caesarean section: a report of 4880 patients This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated. 
1	Castanospermine vs. its 6-O-butanoyl analog: a comparison of toxicity and antiviral activity in vitro and in vivo. Inhibitors of glycoprotein processing, such as castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), have been shown previously to inhibit human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured human cells. In prior experiments, we have tested the toxicity and antiviral efficacy of castanospermine in mice infected with the Rauscher murine leukemia virus (RLV). When compared with 3'-azido-3'-deoxythymidine (AZT, zidovudine), castanospermine was less effective and more toxic. Since the 6-O-butanoyl analog of castanospermine was previously found to have a more favorable activity profile than the parent compound against HIV-1 in cultured cells, we compared the antiviral efficacy of both compounds in parallel in vitro and in vivo in the RLV system. Plaque formation in the XC assay was inhibited with a 50% inhibitory concentration (IC50) of 2.4 microM for the 6-O-butanoyl analog of castanospermine, as compared to 9 microM for castanospermine. For both compounds, concentrations resulting in significant cytotoxicity were about ten times higher. Both compounds significantly decreased HIV-1 env-induced syncytium formation in a novel in vitro assay. In RLV-exposed mice, the 6-O-butanoyl analog showed no advantage over the parent compound: both curves for toxicity as well as antiviral efficacy were super-imposable. We conclude that the 6-O-butanoyl analog of castanospermine as well as castanospermine itself are active antiviral agents in mice and that prolonged oral administration is tolerable. However, in comparison to AZT, their antiviral activity profiles are less favorable. 
5	The effects of tartar-control toothpaste on the oral soft tissues. Ninety-two dental and dental hygiene students completed a double-blind, controlled clinical trial. The purpose of the trial was to evaluate the effects of toothpastes, in varying concentrations of flavor and tartar-control agents. Four formulations of toothpastes were assessed: (A) control-low flavor with no tartar control; (B) medium flavoring with medium tartar control; (C) high flavoring with medium tartar control; and (D) medium flavoring with no tartar control. Soft tissue reactions were assessed objectively and independently by three examiners. Subjective perceptions about each toothpaste were gathered by a structured, open-ended questionnaire. The "tartar control" toothpastes, B and C, resulted in statistically significant (p less than 0.005) higher rates of mucosal reactions (e.g., ulceration, sloughing, erythema, migratory glossitis) than the "non-tartar control" toothpastes A and D. When the oral mucosal reaction rates were adjusted for multiple clinical observations within each subject at the same point in time there was no statistically significant (p greater than 0.05) difference between male (0.25) and female (0.28) subjects. In this study population, the order of preference was observed as toothpaste A greater than D greater than B greater than C. The major reasons for disfavor were burning sensation in toothpastes C (2.4%) and B (4%). 
1	Rupture of a benign mediastinal teratoma into the right pleural cavity. A 27-year-old woman with a ruptured mediastinal cystic teratoma had high levels of amylase and carcinoembryonic antigen in cystic fluid. The activity of the amylase is thought to be the most likely cause of the rupture. High levels of carcinoembryonic antigen in pleural fluid are not necessarily indicative of a malignant lesion but may suggest the presence of a ruptured teratoma in patients with mediastinal tumors. 
4	Coronary artery dissection--a case report. Coronary artery dissection, both spontaneous and catheter-induced, is associated with a significant morbidity and mortality. The authors present a case of a middle-aged woman with spontaneous right coronary artery dissection causing inferior wall myocardial infarction and left coronary artery dissection at the time of coronary arteriography. It is suggested that emergency aortocoronary bypass surgery be performed preceded by insertion of an intra-aortic balloon in acute evolving cases where coronary anatomy is favorable to limit infarction and avert loss of life. 
1	Adenocarcinomas of the colon and rectum in persons under 40 years old. A population-based study. Data collected by nine population-based tumor registries participating in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute were analyzed to characterize the epidemiology of noncarcinoid adenocarcinomas of the colon and rectum in young adults. Tumors diagnosed in persons under 40 years old between 1973 and 1984 (n = 1736) were compared with those in persons 40 years and older (n = 106,760). This first large U.S. population-based study of colorectal adenocarcinomas in the young shows a higher incidence in blacks than whites and later detection in black males. It also shows a higher proportion of tumors of mucinous and signet ring histological type than in older age groups. Among the younger group, the average annual age-adjusted incidence rate was 34% higher in black males than in white males (12.6 vs. 9.4 per million persons) and 46% higher in black females than in white females (13.0 vs 8.9 per million persons). The proportion of tumors that were right-sided varied by age: 0-29 years, 30%; 30-39 years, 26%; 40-49 years, 22%; 50-59 years, 21%; 60-69 years, 24%; 70-79 years, 30%; and 80+ years, 35%. Males under age 40 were less likely to present with localized disease (whites, 27%; blacks, 21%) than were those aged 40 and older (whites, 39%; blacks, 36%). The proportion of tumors classified as mucinous decreased with age, from 28% among those aged 0-19 years to 5% among those 40 years and older. A similar trend was observed for signet ring tumors. Although this latter type accounted for 10% of large-bowel tumors among subjects aged 0-19 years, this proportion decreased with age to 0.2% in those 40 years and older. 
5	Botulinum toxin therapy. Botulinum toxin therapy has emerged as a treatment modality for a variety of spastic- or contracture-related muscle diseases. Its safety has been proven for long-term use in the treatment of benign essential blepharospasm, hemifacial spasm, and certain types of strabismus. Recent approval from the Federal Drug Administration should make botulinum toxin available for use in a greater number of patients. 
5	Diffuse axonal injury: analysis of 100 patients with radiological signs. One hundred patients with head injuries who showed diffuse axonal injury on computed tomographic scans are reported. Evaluation of the Glasgow Coma Score, pupillary signs, and computed tomographic findings on admission led to an improved ability to forecast outcomes. Our relatively good results as compared with other series, can be explained by the high proportion of children and by the liberal use of computed tomography to evaluate head injuries, thus revealing that concussion may sometimes be regarded as an early form of diffuse axonal injury. 
3	Hospital admissions from the Surgical Day Care Centre of Vancouver General Hospital 1977-1987. The admissions to Vancouver General Hospital from its Surgical Day Care Centre were reviewed for the period 1977 to 1987. The overall mean rate of admission for the period was 0.28 per cent, for surgically-related admissions 0.22 per cent and for anaesthesia-related admissions 0.07 per cent. The principal reasons for surgery-related admissions were postoperative bleeding, complications, the need for further surgery, the requirement for prolonged postoperative care, and pain. Urology had a particularly high percentage of admissions compared with its workload, because of the diagnostic nature of much of the work. Anaesthesia-related admissions included "syncope," lack of an accompanying adult, aspiration pneumonitis and coincident acute disease. Twelve of the 14 patients admitted with syncope had surgery in the afternoon and had received less than ideal amounts of intravenous fluid. Seven of the 12 ASA physical status II patients admitted had an admission diagnosis related to the coincident disease. 
4	Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot. Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important. 
4	A clinically applicable method for long-term salvage of postischemic skeletal muscle. The clinical significance and applicability of interventions aimed at reducing reperfusion injury in postischemic skeletal muscle remain unproven, since long-term muscle salvage has not been demonstrated by most treatment protocols that attenuate early reperfusion injury. We have shown that reperfusion of ischemic skeletal muscle results in an early and prolonged sequestration of white blood cells and activation of the alternative complement cascade. The purpose of this study was to determine if 40 minutes of reperfusion with blood depleted of white blood cells and complement proteins, followed by 2 days of normal perfusion, would reduce muscle necrosis after 5 hours of ischemia. The isolated paired canine gracilis muscle model was used. The treatment muscle was initially reperfused with arterial blood that had been spun, washed, passed through a leukocyte removal filter, and resuspended in hydroxyethyl starch (greater than 99.9% removal of white blood cells and the complement proteins factor B and C4). The contralateral control muscle was subjected to unaltered reperfusion. Blood flow (ml/min/100 gm) was measured by timed collection of gracilis venous blood. Myeloperoxidase activity (absorbance at 655 nm/min/mg tissue protein) in muscle biopsies was used to monitor white blood cell sequestration. After 48 hours of reperfusion in vivo, necrosis was quantified by nitroblue tetrazolium staining. Initial reperfusion with white blood cell and complement depleted blood significantly reduced muscle necrosis (53% +/- 3% vs 29% +/- 8%, p less than 0.0025, paired t test). Early blood flow was improved, (p = 0.0025, repeated measure-ANOVA), but subsequent white blood cell sequestration was not altered (p = 0.33, repeated measure-ANOVA). This suggests that a significant amount of white blood cell mediated injury occurs during the first 40 minutes of reperfusion. Preventing early complement activation and white blood cell mediated reperfusion injury is an intervention that is feasible during surgery and may result in clinically significant salvage of postischemic skeletal muscle. 
3	Radiation-induced optic neuropathy: a magnetic resonance imaging study. Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain. 
3	Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans. The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region. 
4	Morphological and histopathological aspects of aneurysms after patch aortoplasty for coarctation. Repair of coarctation of the aorta by synthetic patch grafting has been complicated by late aneurysm formation. These aneurysms differ macroscopically from atherosclerotic thoracic aortic dilatations. Specimens for microscopic examination were taken from 14 of 20 patients undergoing aneurysm resection. Histological analysis of the specimens showed medionecrosis in 13 patients of the specimens showed medionecrosis in 13 patients (93%), foreign body reaction in 11 patients (78%), and intimal thickening in 3 patients (21%). The three layers of the aortic wall could be identified in the aneurysms. On the basis of these results, we discuss the etiologic factors and pathogenetic mechanisms involved in the development of these aneurysms. 
4	Effects of prolonged infusion of human alpha calcitonin gene-related peptide on hemodynamics, renal blood flow and hormone levels in congestive heart failure. We have previously demonstrated that short-term infusion of calcitonin gene-related peptide (CGRP) has beneficial effects in congestive heart failure. The effects of prolonged infusion of CGRP on hemodynamic functions, plasma hormones and renal blood flow were studied in 9 patients with congestive heart failure (New York Heart Association class III or IV, ejection fraction less than 35%). Hemodynamic variables were measured at 30-minute intervals for 8 hours during CGRP infusion (8 ng/kg/min) and for 2 hours after discontinuation. CGRP caused a decrease in right atrial (28%, p less than 0.05), pulmonary artery (22%, p less than 0.02), pulmonary artery wedge (37%, p less than 0.001) and systemic arterial (18%, p less than 0.05) pressures. Systemic vascular resistance decreased more than pulmonary vascular resistance. Cardiac output (72%, p less than 0.001) and stroke volume (60%, p less than 0.02) increased. Heart rate did not change. There was no evidence of tolerance throughout the infusion. The hemodynamic effects were lost within 30 minutes of stopping CGRP. Renal blood flow (34%, p less than 0.01) and glomerular filtration rate (43%, p less than 0.01) increased. Atrial natriuretic peptide decreased (p less than 0.05), while plasma cortisol (p less than 0.02) increased. Plasma epinephrine, norepinephrine, renin activity, aldosterone and growth hormone were unchanged. It is concluded that in patients with severe congestive heart failure, CGRP has sustained beneficial effects on hemodynamic functions and has no adverse effects on hormones. Unlike many other vasodilators, CGRP also increases renal blood flow and glomerular filtration. 
5	Parascapular free flaps for head and neck reconstruction. We report our experience with single-stage, primary reconstruction of the head and neck in 29 consecutive patients using parascapular free flaps. The commonest indications were for craniofacial defects (9), oropharyngeal soft tissue defects (10), and combined mandibular and soft tissue losses (4). Ablative surgery was performed for squamous carcinoma (22), melanoma (2), and malignant fibrous histiocytoma (2). Seven patients died of recurrent disease during a 3 1/2 year follow-up. Seven patients are alive with recurrence. Flap complications included total loss (2) due to unsalvageable microvascular thrombosis, wound breakdown with oropharyngeal fistula (2), mandibular osteomyelitis (1), trismus (2), neck contracture (1), and donor site wound dehiscence (1). The overall success of this reconstruction was 93%. Primary wound healing was the general rule with lower morbidity than with other reconstructive techniques. The flap is thin, pliable, and conforms well to three-dimensional defects. The lateral border of the scapula can be incorporated on the same vascular pedicle for single-stage mandibular reconstruction. No muscle is sacrificed, and the posterior donor defect is an added advantage. The parascapular flap is our first choice for reconstruction of major defects in the head and neck. 
2	Supportive evidence for the validity of the epidemiologic necropsy for gallstones OBJECTIVE: The epidemiologic necropsy measures the occurrence of unsuspected disease through the examination of necropsy records of patients who died for other reasons. The estimates of unsuspected disease derived from the epidemiologic necropsy should approximate what actually occurs in the living population. DESIGN/SETTING: To test this hypothesis, all necropsy records of adult patients at the University of Kansas Medical Center from 1950 to 1984 were examined for the presence of gallstones. Patients with previous cholecystectomy or whose gallstones were diagnosed during life were excluded. The data were stratified by age and race and compared with those of a screening survey from Canada, a surgical series from New York, two screening surveys from Italy, and one from Denmark. The crude necropsy detection rates and the rates from the screening surveys were standardized to the 1970 federal census for Kansas City. RESULTS/CONCLUSIONS: The standardized occurrence rates were similar and suggest that the epidemiologic necropsy accurately assesses the occurrence of asymptomatic gallstones in the living population, thus strengthening its validity as a research tool. 
5	The value of indium 111 leukocyte scanning in the evaluation of painful or infected total knee arthroplasties. Evaluation of painful total knee arthroplasties (TKAs) for infection can be difficult. Indium 111 (111In) leukocyte bone scanning provides a minimally invasive technique for evaluation of possible infection. Thirty-eight patients with a painful TKA who had surgical exploration after 111In leukocyte scanning were reviewed. The scan had an accuracy of 84%, a sensitivity of 83%, and a specificity of 85%. The 111In leukocyte scans must be interpreted in conjunction with the clinical evaluation of the patient because they are less accurate for study of TKAs than of total hip arthroplasties. 
1	Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas. Polyamine content (putrescine, spermidine, and spermine) or ornithine decarboxylase (ODC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonoscopy. Comparisons were made between those with and those without adenomatous polyps. Colonic mucosal polyamine content was measured in 44 persons. Mean putrescine content was 1.25 +/- 0.26 (SE) nmol/mg protein in 22 patients with adenomatous polyps compared with 0.53 +/- 0.12 nmol/mg protein in patients without polyps (P less than 0.02). Tissue content of spermidine and spermine did not differ between these two groups. Ornithine decarboxylase activity was measured in tissue from 45 patients. Mean ODC activity was 2.84 +/- 0.73 pmol/hr/mg protein in 23 persons with adenomatous polyps compared with 1.15 +/- 0.18 pmol/hr/mg protein in persons without polyps (P less than 0.05). Mucosal putrescine and ODC activity are elevated in patients with adenomatous polyps compared with patients without polyps. These biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps. 
4	Azathioprine. An effective, corticosteroid-sparing therapy for patients with recalcitrant cutaneous lupus erythematosus or with recalcitrant cutaneous leukocytoclastic vasculitis. Azathioprine sodium has been reported to be effective therapy for chronic cutaneous lupus erythematosus (LE) but rarely for chronic cutaneous leukocytoclastic vasculitis (LV). We used azathioprine in the treatment of six patients with cutaneous LE, four of whom had subacute cutaneous (nonscarring) LE and two of whom had chronic cutaneous (scarring, discoid) LE, and six patients with chronic cutaneous LV. The conditions of all patients had been resistant to conventional therapy, and they required long-term oral corticosteroid therapy for control of their disease. Two of the patients with LE had prominent palmar and/or plantar involvement. Three patients with LE had an excellent response to azathioprine, with near complete clearing of the skin lesions, allowing a decrease in prednisone dosage. One patient with LE initially demonstrated significant improvement, but azathioprine therapy had to be discontinued because of pancreatitis. The treatment failed in two patients with LE; one had nausea and the other repeatedly developed a drug-induced fever. Five of the six patients with LV had improved conditions, with complete control of the disease occurring in two patients and partial control in three patients. Azathioprine is effective for some patients with cutaneous LE and chronic cutaneous LV, but it should be reserved for patients with severe disease in whom more conventional treatment fails. 
2	Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen. We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality. 
2	Evaluation of the pre-S (pre-S(1)Ag/pre-S(2)Ab) system in hepatitis B virus infection. The diagnostic and prognostic value of pre-S(1)Ag and pre-S(2)Ab was investigated in 69 HBsAg surface antigen positive patients--14 with acute hepatitis B, 30 with chronic liver disease (six chronic persistent hepatitis, 14 chronic active hepatitis, 10 with cirrhosis) and in 25 asymptomatic carriers. Pre-S(1)Ag was found in all patients with chronic hepatitis B virus (HBV) infection regardless of viral replication. In contrast, pre-S(2)Ab was not detected in any patients. Acute hepatitis was studied sequentially with periodic controls at 20 day intervals. Pre-S(1)Ag cleared before HBsAg in six of 14 (43%) patients who progressed favourably, and the two antigens cleared simultaneously in eight of 14 (57%) cases. Patients with early clearance of pre-S(1)Ag progressed favourably, thus indicating the prognostic value of this test, which, however, is still of limited practical application given the small temporal difference between the moment of clearance of the two antigens. The first markers to clear, however, were HBeAg and DNA-HBV, which showed significant differences with respect to the clearance of HBsAg. Moreover, pre-S(2)Ab appeared before HBsAb in 57.1% of our patients and was found in some patients before pre-S(1)Ag and HBsAg had cleared (42.8%), thus allowing complete viral clearance and acute HBV infection to be predicted earlier. 
4	Everted cervical vein for carotid patch angioplasty. Because of the theoretic benefits of autologous vein we undertook an investigation to evaluate cervical veins (facial, external jugular) as patch material after carotid endarterectomy. A device that stimulated both circumferential fixation by sutures and radial tension exerted on in vivo patches was constructed to measure burst strength of tissue. Mean bursting pressure for groin saphenous vein (n = 10) was 94.5 +/- 15.1 pounds per square inch (psi), 75.5 +/- 8.9 psi for ankle saphenous vein (n = 10), 83.3 +/- 14.5 psi for everted (double layer) cervical vein (n = 5) and 10 +/- 3.3 psi for single layer cervical vein (n = 5). No significant differences between saphenous vein at any level and everted (double layer) cervical vein, but all were significantly different from single layer cervical vein (p less than 0.05). From June 1987 through November 1989, 19 patients underwent 21 carotid endarterectomies complemented with adjunctive everted cervical vein patch angioplasty. Indications for surgery were asymptomatic stenosis (53%), transient ischemic attack (29%), and cerebrovascular accident with recovery (18%). All patients were studied after surgery with duplex scanning. Asymptomatic recurrent stenosis was observed in one patient. Transient hypoglossal nerve dysfunction occurred in one other patient. One postoperative death occurred as a result of massive aspiration. These results indicate that everted cervical vein is comparable to the saphenous vein in resistance to bursting and can yield similar results as patch material after carotid endarterectomy. Accordingly, saphenous vein can be spared and lower extremity incisions avoided. 
5	Treatment of chronic liver disease caused by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. Deficiency of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, the second enzyme in the sequence that catalyses the synthesis of bile acids from cholesterol, leads to chronic liver disease in childhood as well as to malabsorption of fat and fat soluble vitamins. A 4 year old boy with this condition has been successfully treated by oral administration of a bile acid--chenodeoxycholic acid. He had been jaundiced since birth, grew poorly because of rickets, and had severe pruritus. Plasma transaminase activities were persistently raised. Chenodeoxycholic acid 125 mg twice daily for two months, and then 125 mg daily, cured his jaundice and pruritus, returned his transaminase activities to normal, and eliminated the need for calcitriol for prevention of rickets. On this treatment he has so far remained well for two years. A diagnosis of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency should be considered in any child with unexplained chronic hepatitis or cirrhosis, especially if the liver disease is accompanied by a clinically obvious malabsorption of fat soluble vitamins. A simple colorimetric test of the urine confirms the diagnosis and effective treatment can be started. 
5	Influence of hypoxia on adrenergic modulation of triggered activity in isolated adult canine myocytes. Although findings from several reports suggest that nonreentrant or focal mechanisms contribute to the genesis of arrhythmias during early ischemia, the contribution of triggered activity arising from early or delayed afterdepolarizations has not been resolved. We have previously demonstrated that beta- but not alpha-adrenergic stimulation induces afterdepolarizations and triggered activity in isolated normoxic myocytes. In the present study, the influence of the extent of cellular derangements as well as increases in [K+]o on alpha- and beta-adrenergic-mediated afterdepolarizations and triggered activity was evaluated. Adult canine myocytes were exposed to one of the following experimental conditions with simultaneous intracellular transmembrane action potential recordings: 1) low PO2 (less than 10 mm Hg, obtained using a specially designed hypoxic chamber) and low (6.8) pH; 2) low PO2, low pH, and high extracellular potassium ([K+]o) (10 mM); or 3) severe metabolic inhibition with cyanide (10(-6) M). Cells from each group were superfused with either the alpha-agonist phenylephrine (10(-5) or 10(-7) M, with 10(-5) M nadolol) or the beta-agonist isoproterenol (10(-6) M). Moderate changes in the action potentials were observed under conditions 1 and 2 (moderate hypoxia), whereas marked but reversible changes were observed with cyanide (severe metabolic inhibition). During moderate hypoxia in normal [K+]o, delayed afterdepolarizations or triggered activity were elicited by both alpha- (12 of 13 cells) and beta-adrenergic (five of five cells) stimulation. Increasing [K+]o during moderate hypoxia completely abolished the afterdepolarizations induced by alpha-adrenergic stimulation and prevented the occurrence of triggered activity. In contrast, the influence of beta-adrenergic stimulation was only attenuated by an increase in [K+]o. Exposure to cyanide completely prevented the induction of afterdepolarizations and triggered activity by both alpha- and beta-adrenergic stimulation. Our findings indicate that moderate hypoxia in normal [K+]o is associated with the development of adrenergic-mediated afterdepolarizations and triggered activity. In contrast, accumulation of [K+]o or severe impairment of cellular metabolism is accompanied by inhibition of adrenergic-mediated afterdepolarizations and triggered activity. 
2	Gallbladder wall thickening (congestive cholecystopathy) in chronic liver disease: a sign of portal hypertension. A thickened gallbladder wall is often seen with ultrasound in alcoholic cirrhosis. Hypoalbuminaemia is thought to be the cause since there is a strong association between bowel wall thickening and low serum albumin. To determine the role of portal hypertension in producing gallbladder wall thickening we studied 40 consecutive stable patients-37 with cirrhosis and three with portal hypertension due to primary biliary cirrhosis. Ultrasound assessment of the gallbladder wall was made after an overnight fast using a Technicare autosector. Wall thickness 4 mm or greater was considered abnormal. Twenty-seven patients had a thickened gallbladder wall and all had evidence of portal hypertension. Hypoalbuminaemia was not an important factor since it was only present in six cases with thickened walls. In two cases reduction in portal pressure with oral propranolol was associated with a decrease in gallbladder wall thickness. These results suggest that portal hypertension, not hypoalbuminaemia, is the dominant factor causing gallbladder wall thickening in cirrhosis. Ultrasound demonstration of gallbladder wall thickening in chronic liver disease should suggest the presence of portal hypertension. 
5	Patients in a persistent vegetative state attitudes and reactions of family members. Patients in a persistent vegetative state (PVS) constituted approximately 3% of the population in four Milwaukee nursing homes. In order to understand family members' attitudes and reactions toward such patients, 33 (92%) of 36 family members of patients in PVS contacted were studied. The age of the patients ranged from 19 to 95 with a mean age of 73.4 +/- 17.2 years, and family members' ages ranged from 41 to 89 with a mean age of 61.8 +/- 3.3 years. The etiology of the PVS varied from dementia to cerebral trauma. The mean duration of the PVS was 54 +/- 8.4 months (range 12 to 204). Family members reported that they visited patients 260 times during the first year following the onset of the PVS and were still visiting at a rate of 209 visits yearly at the time of the interview. There was no significant correlation between the frequency of the family members visits and the duration of the PVS, the patient's or family member's age, or the family member's relationship to the patient. Ninety percent of patients were considered by family members to have some awareness of pain, light or darkness, environment, taste, verbal conversation, or the family member's presence. Most family members thought they understood the patient's medical condition, and the majority did not expect the patient to improve. Nevertheless, the majority of family members wanted the patient to undergo therapeutic interventions, including transfer to the acute hospital and surgery. 
1	Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas. Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24). However, there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors. 
5	Hemodynamic and electrophysiologic evaluation of patients with hypertrophic cardiomyopathy surviving cardiac arrest. Hemodynamic and electrophysiologic studies were performed in 30 survivors of sudden cardiac arrest with hypertrophic cardiomyopathy (HC) to determine responsible factors. Electrophysiologic abnormalities alone were present in 27 patients (90%): sinus node dysfunction in 14 (47%), delayed atrio-ventricular nodal conduction in 1 (3%), abnormal His-Purkinje conduction in 7 (23%), an inducible atrial tachycardia in 7 (23%), and inducible sustained ventricular arrhythmia in 21 (70%). Sustained ventricular arrhythmia was polymorphic ventricular tachycardia (VT) in 18 patients (86%), monomorphic VT in 2 patients (7%) and ventricular fibrillation in 1 patient (3%). In 1 patient the arrhythmia recorded during an episode of cardiac arrest and induced at electrophysiologic study was polymorphic VT. VT was induced with less than or equal to 2 extra-stimuli in only 1 patient (3%) but with less than or equal to 3 extra-stimuli in 20 patients (97%). Potential causes of sudden cardiac arrest were found in all patients and were multiple in 13 patients (43%). These were (1) ventricular electrical instability in 21 patients (70%), (2) severe left ventricular outflow tract obstruction in 8 patients (27%), (3) bradycardia in 5 patients (17%), (4) myocardial ischemia associated with hypotension in 5 patients (17%), and (5) atrial tachycardia resulting in hypotension in 4 patients (13%). Of the 21 patients with inducible sustained ventricular arrhythmia, 17 received an implantable defibrillator device and 4 were treated with antiarrhythmic drugs. Seven patients underwent left ventricular septal myectomy. 
1	Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast. Complete axillary dissection was performed in 287 patients undergoing modified radical mastectomy between 1984 and 1987 to identify patterns of axillary node metastases, as well as discontinuous axillary node ("skip") metastases. Positive pathologic findings were compared with preoperative clinical examinations in 266 patients and showed only 60 cases (22.6%) clinically suspicious for tumor, in contrast to 131 (45.6%) with pathologically confirmed positive lymph nodes. Axillary contents were classified level I, II, or III based on their relationship to the pectoralis minor muscle. An average of 24.2 nodes was resected per patient (level I, 10; level II, 8.1; and level III, 5.3). Tumors ranged in size from 0.5 to 12.0 cm (mean, 2.6 cm), and increasing tumor size was associated with an increased likelihood of positive nodes. The data on 204 patients with complete clinical and pathologic data show that of 119 patients with negative level I nodes a limited axillary dissection (level I only) would fail to identify 6 with positive level II and 2 with positive level III nodes, whereas of 85 patients with positive level I nodes limited axillary dissection would fail to identify 17 with positive level II nodes, 7 with positive level III nodes, and 27 with positive levels II and III nodes. Complete axillary dissection (levels I, II, and III) should be performed to stage patients accurately, as well as to remove tumor-involved nodes and diminish local axillary recurrences. Clinical examination of the axilla appears to be a poor means of identifying axillary metastatic cancer. 
2	Emergency center ultrasonography in the evaluation of hemoperitoneum: a prospective study. The reliability of ultrasonographic detection (US) of hemoperitoneum in blunt abdominal trauma was evaluated in a prospective study of 72 patients. Independent of the examiner, sensitivity, specificity, and accuracy were, respectively, 86.7%, 100%, and 97.2%. Laparotomy was indicated in 76.9% of US hemoperitoneum-positive cases. No negative laparotomies were performed in this study group. If hemoperitoneum is revealed in US and vital signs are unstable, we think laparotomy is indicated. We believe that US in an emergency center is a quick, safe screening method in the evaluation of blunt abdominal trauma. US might take over a great part of the role of diagnostic peritoneal lavage. 
2	Relative frequencies of portosystemic pathways and renal shunt formation through the "posterior" gastric vein: portographic study in 460 patients. Percutaneous transhepatic portography was carried out in 460 patients with portal hypertension to study various collateral routes. Besides the left gastric vein, which was the most frequent collateral route and feeder of esophageal varices, a distinct vein located between the left gastric vein and the short gastric vein constituted a major collateral route in 191 patients (42%). In terms of frequency, this vein was more significant than the short gastric (34%) and the paraumbilical vein (24%) as a collateral route. We propose that this previously anonymous vein be called the "posterior gastric" vein because it runs posterior to the stomach. This vein also formed a renal shunt, a common cause of encephalopathy, in 43 (23%) of the 191 patients; the relative frequency of renal shunt formation by this vein was significantly greater than that by the left gastric vein (12%) and the short gastric vein (18%). 
5	Myocardial epinephrine sensitization with subanesthetic concentrations of halothane in dogs. The authors investigated myocardial epinephrine sensitization by subanesthetic concentrations of halothane. The dose-response relationship for the action of halothane was examined with etomidate plus varying subanesthetic concentrations of halothane in dogs. The arrhythmogenic threshold of epinephrine was decreased in a dose-dependent manner at end-tidal concentrations of halothane between 0.1 and 0.3%. At end-tidal halothane is greater than 0.3%, and no further reduction of arrhythmogenic threshold of epinephrine occurred. The plasma concentrations of epinephrine producing four or more premature ventricular contractions in 15 s were 201.3 +/- 34.3, 98.1 +/- 13.9, 60.3 +/- 8.63, 57.9 +/- 12.8, 54.5 +/- 8.61, and 53.9 +/- 4.86 ng/ml (mean +/- SEM), at 0, 0.1, 0.3, 0.5, 1.0, and 1.5% of halothane at end-tidal concentrations, respectively. The results suggest that in the presence of etomidate, halothane produces myocardial sensitization to epinephrine at subanesthetic concentrations as low as 0.1%. Increasing halothane to 0.3% produces a further reduction in the arrhythmogenic dose of epinephrine. 
2	Duodenogastric reflux and gastric histology after cholecystectomy with or without sphincteroplasty. Sixteen patients who had undergone cholecystectomy plus sphincteroplasty, 14 cholecystectomized patients and ten control patients were studied to evaluate whether differences existed in duodenogastric reflux and whether these were related to morphological damage of the gastric mucosa. Duodenogastric bile reflux during fasting was evaluated by measuring the concentration of total bile acids (by an enzymatic method) and single bile acids in the gastric juice by high performance liquid chromatography. The damage was evaluated histologically by systematic endoscopic biopsy of the antrum and body of the stomach. There was a statistically significant difference in fasting bile reflux between the three groups (Kruskal-Wallis test, P less than 0.001), and the group that underwent cholecystectomy plus sphincteroplasty had a significantly higher median value than the cholecystectomized group (P less than 0.05) and the control group (P less than 0.01). The distribution of chronic antral atrophic and superficial gastritis was different in the three groups (chi 2 test, P less than 0.005). Chronic atrophic gastritis was associated with cholecystectomy plus sphincteroplasty (P less than 0.01), while chronic superficial gastritis was more frequent in cholecystectomized patients. These results suggest that there may be more duodenogastric reflux after cholecystectomy plus sphincteroplasty than after cholecystectomy alone, and that there may be a correlation between the amount of duodenogastric reflux and the severity of mucosal damage. 
5	A randomized trial of cisplatin, vinblastine, and bleomycin versus vinblastine, cisplatin, and etoposide in the treatment of advanced germ cell tumors of the testis: a Southwest Oncology Group study This is a Southwest Oncology Group (SWOG) prospective randomized trial of cisplatin, vinblastine, and bleomycin (PVB) versus vinblastine, cisplatin, and etoposide (VP-16) (VPV) in the treatment of advanced germ cell tumors of the testis. The study objective was to determine what effect the replacement of bleomycin with VP-16 has on complete response (CR), survival, and drug toxicity. One hundred sixty-nine patients were registered and randomized. Of these patients, 160 were assessable for response. All had histologically confirmed disseminated germ cell neoplasms of testicular origin. Forty-six had minimal metastatic disease, and 114 had maximal disease. Seventy-seven were randomized to PVB and 83 to VPV chemotherapy. There was no significant difference in pretreatment characteristics between the two arms with regard to tumor burden, histologic type, and overall performance status. Patients received four courses of induction chemotherapy, either PVB (cisplatin 120 mg/m2 day 3, vinblastine 12 mg/m2 day 1, bleomycin 15 U/m2 twice per week) or VPV (vinblastine 8 mg/m2 day 1, cisplatin 120 mg/m2 day 3, VP-16 50 mg/m2 days 2 to 5). Chemotherapy was given every 3 weeks. Cytoreductive surgery was done postinduction if a chemotherapy CR was not achieved. There was no difference in the percentage of patients achieving a disease-free status between PVB (77%) and VPV (73%). The mean leukocyte nadir was similar for both treatments, but the mean platelet nadir was significantly lower (P = .003) in the VPV arm. All bleomycin-related toxicities (pulmonary, mucositis, skin) were avoided in the VPV arm. We conclude that bleomycin can be replaced in first-line therapy for advanced germ cell tumors without sacrificing efficacy and with the advantage of avoiding unnecessary drug toxicity. 
1	Response rates in relapsed Wilms' tumor. A need for new effective agents. Three hundred eighty-one children with Wilms' tumor were treated in the United Kingdom Children's Cancer Study Group WT1 Study (1982 to 1986). Seventy-one patients had relapses during or after treatment with surgery and chemotherapy, and radiation therapy, depending on stage and histologic characteristics. Forty-nine patients were evaluable for disease response to second-line chemotherapy alone. Evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse. With second-line combination chemotherapy (which included ifosfamide, etoposide/VM26, cisplatin/carboplatin, bleomycin, melphalan, and Thiotepa [Lederle Laboratories, Pearl River, NY]), there were five complete responses and 12 partial responses. In patients with favorable histologic findings, six of nine with Stage I, five of ten with Stage II, none of 11 with Stage III, three of 16 with Stage IV, and one of five with Stage V disease survived. Two survivors were treated with chemotherapy alone; the others received combined treatment with chemotherapy, radiation therapy, and/or surgery. For those with unfavorable histologic findings of any stage, only two of 20 survived. The authors conclude that, even for patients with localized disease with favorable histologic findings, the "salvage" rate is little more than 50%, and for all other stages and histologic findings the likelihood of cure after relapse is remote. There is clearly a need for additional effective chemotherapeutic agents for these patients. 
2	Portal venous gas in a patient with Crohn's disease. Portal venous gas usually occurs in the setting of an acute abdomen. Several causes for benign portal venous gas (PVG) have been reported. We describe the finding of PVG by computed tomography in a febrile patient with Crohn's disease and discuss the clinical implications of such a finding. 
5	Treatment of cervical spondylotic myelopathy by enlargement of the spinal canal anteriorly, followed by arthrodesis. Thirty-seven patients who had enlargement of the spinal canal anteriorly and stabilization of the spine for cervical spondylotic myelopathy were followed for an average of forty-nine months (range, twenty-eight to seventy months). Myelography and computed tomographic myelography were performed preoperatively on all patients to determine the location and features of the areas of decompression. The canal was enlarged by discectomy; by subtotal corpectomy and removal of the anteromedial parts of the pedicles; or by removal of osteophytes or of the posterior longitudinal ligament, or both. Partial corpectomy and interbody arthrodesis was performed in nine patients; subtotal corpectomy, including removal of the posterior parts of the vertebral bodies and of the posterior longitudinal ligament, and strut bone-grafting, in fifteen patients; and subtotal corpectomy, with detachment of the remaining thin posterior parts of the vertebral bodies and of the posterior longitudinal ligament, and strut bone-grafting, in thirteen patients. Postoperatively, radiographic examinations, including myelography and computed tomographic myelography, were performed for thirty-six patients and magnetic resonance imaging, for twenty-eight. A satisfactory neurological result was obtained in twenty-nine patients. Atrophy of the spinal cord, as seen on preoperative computed-tomographic myelograms, was predictive of an unsatisfactory result of the decompression, as was weakness of the peroneal muscles. All but one of the thirty-seven patients had improved walking ability at the most recent follow-up examination: seventeen patients improved by 1 point; fourteen, by 2 points; four, by 3 points; and one, by 4 points. The remaining patient reverted to the preoperative status after an initial improvement. The ability to walk at the interim examinations was compared with that at the most recent examination; three patients had continuing improvement, while three others had deterioration. The main cause of deterioration was new spondylotic changes associated with stenosis of the spinal canal, occurring at the level of the disc just cephalad to the fused levels. We concluded that anterior decompression followed by a secure arthrodesis should be an extensive procedure for patients who have cervical spondylotic myelopathy, as determined preoperatively from a myelogram or computed tomographic myelogram. Excision of the vertebral bodies should also be wide and should include the anteromedial parts of the pedicles. The third or fourth cervical vertebra should be included in the arthrodesis prophylactically in patients who have stenosis of the spinal canal when either of these vertebrae is adjacent to the level of fusion. 
5	Cup containment and orientation in cemented total hip arthroplasties. We reviewed the radiographs of 864 Charnley and STH (Zimmer) cemented total hip arthroplasties with a mean follow-up of seven years (maximum 16 years). Survivorship analysis was used to assess the correlation between radiographic performance and the bony containment or the coronal orientation of the acetabular cup. The cup orientation and containment were interrelated; all vertically oriented cups were completely contained, whereas 25% of more horizontal cups were only partially contained. Completely contained cups had significantly lower incidences of complete cement-bone radiolucency (p = 0.02) and of wear (p = 0.09). Vertically oriented cups had a lower incidence of continuous radiolucency than neutrally oriented cups, but this was not statistically significant (p = 0.25). Our results confirm the importance of complete bony containment, and also indicate that it is better to accept vertical orientation and obtain full bony coverage than to have a more horizontal orientation with partial containment. 
1	Evidence of a local immune activation in cystic brain tumors. The fluid of cystic brain tumors was characterized with regard to the protein content. In most malignant tumors, the concentrations of immunoglobulins G and M (IgG and IgM) were higher relative to other proteins in the cyst fluid than in the serum of the same patient. A markedly elevated ratio of monomeric to pentameric IgM was detected in the cyst fluid of two patients with glioblastomas. The results indicate a local immunoglobulin synthesis in malignant cystic brain tumors. It is hypothesized that higher-than-expected concentrations of IgG and IgM in cyst fluid as compared to plasma are a sign of an ongoing immune response triggered by the tumor. 
3	Epithelial cyst of the fourth ventricle. Case report. A case of epithelial cyst in the fourth ventricle of a 4-year-old child is described. A single epithelial layer with a clear basement membrane lining the cyst wall was observed. There were no prominent histological findings to suggest a pathogenesis for this cyst based on immunohistochemical or ultrastructural studies; however, the cyst fluid contained significant amounts of carcinoembryonic antigen. It is considered that the epithelial layer lining the cyst wall was possibly of endodermal origin. 
4	Caffeine and ventricular arrhythmias. An electrophysiological approach. Little information is known regarding caffeine's effect on the substrate supporting sustained ventricular arrhythmias. This prospective study evaluated the effect of coffee (275 mg of caffeine) on this substrate with programmed ventricular stimulation in 22 patients with a history of symptomatic nonsustained ventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Patients underwent electrophysiological testing before and 1 hour after coffee ingestion. Mean (+/- SEM) plasma caffeine level achieved after coffee consumption was 6.2 +/- 0.5 mg/L. Mean plasma catecholamine and potassium values were not altered significantly 1 hour following caffeine ingestion. The number of extrastimuli required to induce an arrhythmia was unchanged in 10 patients (46%), increased in six (27%), and decreased in six (27%). Rhythm severity was unchanged in 17 patients (77%), more severe in two (9%), and less severe in three (14%). In those patients with clinical ventricular arrhythmias, caffeine did not significantly alter inducibility or severity of arrhythmias, suggesting little effect on the substrate supporting ventricular arrhythmias. 
1	von Willebrand factor in head and neck cancer. Laboratory abnormalities in blood coagulation factors are common in patients with cancer but the significance is unknown. Twenty-eight patients with head and neck cancer were studied at the time of diagnosis. Twenty-five were advanced-stage (III or IV) patients. Levels of clotting factors, antithrombin III, and plasminogen were normal. Levels of von Willebrand factor (vWF), both antigenic and functional (ristocetin cofactor), were elevated. This group of patients were followed for a minimum of 41 months (median, 48 months). Fifteen patients died within the follow-up period. von Willebrand factor levels were significantly higher in these 15 than the 13 survivors. Extreme elevation of ristocetin cofactor (greater than 300 U/dl) was seen in six of the 15 patients who died and in none of the survivors. Plasma vWF is elevated in head and neck cancer and the level measured at the time of diagnosis may have prognostic and potentially therapeutic implications. 
5	Neurological phenomena during emergence from enflurane or isoflurane anaesthesia. During emergence from anaesthesia, transient neurological signs that would usually be considered pathological may appear. The objective of this randomized, patient (n = 30) and observer-blinded study was to compare prospectively the incidence and duration of post-anaesthetic neurological abnormalities in healthy patients undergoing minor elective procedures following thiopentone and succinylcholine induction, and enflurane-N2O or isoflurane-N2O anaesthesia. Patients were studied for 60 min after anaesthesia. Arousal state, muscle tone, deep tendon reflexes, plantar reflex, sustained clonus, shivering, intense muscular spasticity and temperature were assessed. Results of neurological examination were correlated with the patient's state of arousal. Transient emergent neurological abnormalities occurred more frequently following enflurane-N2O anaesthesia than isoflurane N2O anaesthesia. This was statistically significant (P less than 0.05) for quadriceps hyperreflexia, upgoing toes (positive Babinski reflex) and intense muscular spasticity. Neurological abnormalities occurred most commonly 5-20 min after anaesthesia and all abnormalities resolved within 60 min. Following enflurane anaesthesia, as patients became more alert the incidence of abnormalities declined, while the arousal state did not affect the incidence of abnormalities after isoflurane. There was no significant difference between axillary temperatures of those patients who shivered and those who did not. In conclusion, temporary emergent neurological abnormalities occurred more often following enflurane-N2O than after isoflurane-N2O anaesthesia. 
1	Vagal schwannoma. A patient with a benign encapsulated intrathoracic vagal schwannoma is presented and the literature is reviewed. The right paratracheal tumor was identified incidentally on a chest film and excised using a right thoracotomy. Although rare, vagal schwannomas should be considered for any mediastinal mass along the vagus nerves especially when the paratracheal tumor produces minimal or no respiratory symptoms suggesting a slow-growing, encapsulated process. 
1	Leucine kinetics in patients with benign disease, non-weight-losing cancer, and cancer cachexia: studies at the whole-body and tissue level and the response to nutritional support. We have performed intraoperative isotopic infusions of carbon 14-labeled leucine in 65 patients to define the abnormalities in protein metabolism at both the whole-body and tissue level in patients with weight-losing and non-weight-losing cancer. Eighteen patients had benign disease, 26 had non-weight-losing cancer, and 21 had cancer cachexia. Samples of plasma and expired breath were taken to determine rates of whole-body protein synthesis (WBPS), whole-body protein catabolism (WBPC), net protein catabolism, and albumin fractional synthetic rates. Tissue samples were taken to determine the fractional synthetic rates (FSR) of protein in muscle, liver, cancer, and the tissue in which the cancer arose. In addition, in 14 patients the effect of nutritional support on protein metabolism was assessed. In all parameters examined we were unable to detect any significant differences between patients with no cancer and the patients with non-weight-losing cancer. In contrast, patients with cancer cachexia had a significant elevation (p less than 0.005) in WBPC compared with the other two groups. WBPS was also elevated (to a lesser extent) in the patients with cancer cachexia, and the rate of net protein catabolism was increased significantly (p less than 0.05). Patients with cancer cachexia also had significantly higher values of FSR of protein in muscle (p less than 0.05), liver (p less than 0.05), and albumin (p less than 0.01) compared with the other two groups. In addition, the protein FSR in the cancer rose progressively when the values for the primary cancer were compared with those for nodal and systemic metastases. Further, although nutritional support resulted in an increase in host muscle protein synthesis (p less than 0.04), there was no promotion of FSR of protein in cancer. We conclude that patients with cancer cachexia are actively losing protein as a result of an increase in WBPC that is only partially compensated for by an increase in WBPS. There are compensatory increases in protein synthesis in muscle and liver, but these increases in host protein synthesis are insufficient to keep pace with the combined effect of the accelerated rate of protein synthesis in the cancer per se and the accelerated rate of net protein catabolism at the whole-body level. In response to nutritional support, there is a significant increase in the muscle protein synthesis, but we could not demonstrate any increase in cancer protein synthesis. 
3	Diagnostic imaging and surgical treatment of dumbbell tumors of the mediastinum. We describe the diagnostic procedures and surgical approaches employed in 5 patients with dumbbell tumors of the mediastinum. Magnetic resonance imaging accurately described the existence and longitudinal extension of the intraspinal component of the tumor and assisted in choosing the appropriate surgical approach. Both the intrathoracic and intraspinal components of the tumor were resected at one time by a thoracic and neurosurgical team. We employed the Grillo technique three times and a separate laminectomy and thoracotomy approach. Magnetic resonance imaging proved the most useful diagnostic technique for suspected dumbbell mediastinal tumors. In our experience, the extended thoracotomy proposed by Grillo and co-workers worked well for small tumors involving only one foramen in which the intraspinal extension was limited to 2 to 3 cm, and when no more than two laminectomies were required. On the other hand, thoracotomy and a longitudinal paravertebral incision are preferable for larger tumors (more than 4 cm) involving more than one foramen in which the intraspinal extension exceeds 2 to 3 cm, for tumors requiring multiple laminectomy, and when bony infiltration is present. 
4	Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery. A total of 213 patients with verified aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) were enrolled in a double-blind placebo-controlled trial to determine the effect of intravenous nimodipine on delayed ischemic deterioration and computerized tomography (CT)-visualized infarcts after SAH and surgery. The administration of the drug or matching placebo was started immediately after the radiological diagnosis of a ruptured aneurysm had been made. Of the 213 patients enrolled in the study, 58 were operated on early (within 72 hours after the bleed: Days 0 to 3), 69 were operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8 or later). Eleven patients died before surgery was undertaken and one was not operated on. A follow-up examination with CT scanning, performed 1 to 3 years after the SAH (mean 1.4 years), revealed no significant differences in the overall outcome between the groups. However, nimodipine treatment was associated with a significantly lower incidence of deaths caused by delayed cerebral ischemia (p = 0.01) and significantly lower occurrence of cerebral infarcts visualized by CT scanning in the whole population (p = 0.05), especially in patients without an associated intracerebral hemorrhage on admission CT scan (p = 0.03). 
4	The real impact of mechanical bridge strategy in patients with severe acute infarction. Results obtained in the past 3 years in patients referred with acute myocardial infarction (AMI) and cardiogenic shock for a mechanical bridge to urgent transplantation permit one to assess the real impact of the present strategy in clinical practice. Ten patients (mean age = 49) were admitted in serious condition (CI = 1.8 +/- 0.2 L/min/m2, PCWP = 28 +/- 6 mmHg, systolic aortic pressure = 88 +/- 20 mmHg, urine output 11 +/- 20 ml/hr) and were treated by maximal sympathomimetic support and i.v. enoximone. Two had to be implanted with a total artificial heart (TAH) and one with a left ventricular assist device (LVAD) for recurrent fibrillation despite hemodynamic improvement, within 8 hr. Two have received transplants and are living well after 20 months. Seven who initially improved markedly have been listed as urgent transplant candidates: two of these have been successfully transplanted, and three died suddenly after 6, 25, and 45 days, respectively. One has undergone successful coronary surgery. One patient (age 62, diabetic) was secondarily rejected for a transplant and died. This experience clearly shows that despite initial spectacular hemodynamic improvement, which was due to optimized medical management, death rate before transplant because of sudden ventricular fibrillation remains unacceptably high. This should prompt early mechanical support, with less invasive systems, in patients with AMI. 
5	Percutaneous angioscopy during coronary angioplasty using a steerable microangioscope. The feasibility of using a flexible, steerable angioscope to perform coronary angioscopy before and after percutaneous coronary angioplasty was tested. The microangioscope fits through an 8F coronary angioplasty guiding catheter and contains a multifiber viewing bundle incorporated into the body of a 4.3F balloon catheter with a central lumen for distal flushing and guide-wire passage. Angioscopy was performed without complications 45 times in 24 patients, including 6 patients with stable and 18 with unstable angina. Circumferential visualization of the target lesion was successful in 20 (83%) of the 24 patients and improved with operator experience. Excellent visualization of the target lesion was achieved in 16 (94%) of the last 17 patients. Plaque, thrombus and dissection were among the abnormal findings in the 20 patients (4 with stable, 16 with unstable angina) in whom circumferential viewing of the target lesion was achieved. In four patients with restenosis after angioplasty, the lesion morphology was distinctly different from that of lesions in arteries without prior angioplasty. In patients with stable angina, no thrombus or dissection was seen by angiography or angioscopy before angioplasty. In patients with unstable angina, thrombus was detected more frequently by angioscopy than by angiography before angioplasty (8 versus 2 of 16) and after (15 versus 2 of 16) angioplasty. Intimal dissection was also seen much more frequently by angioscopy than by angiography before angioplasty (7 versus 0 of 16) and after angioplasty (16 versus 7 of 16). It is concluded that high resolution percutaneous coronary angioscopy can be performed safely in conjunction with balloon angioplasty. Further investigation is needed before this diagnostic tool can be applied clinically. 
1	Gamma-detecting probe and autoradiographic studies of radiolabeled antibody B72.3 in CX-1 colon xenografts. Nude mice bearing CX-1 colon tumors were injected with 50 microCi 125I-labeled monoclonal antibody (MAb) B72.3. Radioactivity in tumors was studied with the gamma detecting probe (GDP) on days 1, 3, 7, and 10 after MAb injection. On each day, two mice were sacrificed and sections were examined with autoradiography (ARG), immunoperoxidase methods (IMP), and routine stains. Mean probe counts showed increasing tumor to background ratios and ARG demonstrated a progressive increase in radionuclide in the tumors. The distribution of 125I was primarily around the vascular spaces on day 1, but by day 3 and progressively it appeared in tumor gland lumina and necrotic areas. A regional correlation was shown between radionuclide in vascular spaces and its sequestration in tumor elements. 
5	Caffeine and cardiac arrhythmias. PURPOSE: To review the evidence supporting the belief that caffeine causes cardiac arrhythmias. DATA SOURCES: Studies published since 1982 identified through computerized searches of MEDLINE, TOXLINE, and Chemical Abstracts and a review of bibliographies of relevant articles on the subject of caffeine and cardiac arrhythmias. STUDY SELECTION: All clinical studies examining caffeine as a cause of cardiac arrhythmias and a selection of basic science experiments to illustrate caffeine's effects in vitro. DATA EXTRACTION: Study quality was assessed and all available clinical data pertaining to caffeine as a cause of arrhythmias were summarized. RESULTS OF DATA ANALYSIS: In one electrophysiologic study, caffeine was associated with an increased susceptibility to provoked cardiac arrhythmias. In five placebo-controlled trials, caffeine in doses up to 500 mg daily (equivalent to 5 to 6 cups of coffee) did not increase the frequency or severity of ventricular arrhythmias. One large epidemiologic study reported an increase in the frequency of ventricular extrasystoles in persons consuming 9 or more cups of coffee daily. CONCLUSION: Moderate ingestion of caffeine does not increase the frequency or severity of cardiac arrhythmias in normal persons, patients with ischemic heart disease, or those with pre-existing serious ventricular ectopy. 
5	Muscle fibre type and habitual snoring. Although anatomical abnormalities of the upper airway have been recorded in some patients with obstructive sleep apnoea (OSA), a muscle tone dysregulation also seems to have an important role in this disorder. Since habitual snoring is the initial stage of OSA, the structural characteristics of upper airway muscles (medium pharyngeal constrictor muscle [MPCM]) from 13 men (9 non-snorers and 4 habitual snorers) were studied. MPCM fibre structure in non-snorers was broadly similar to that in normal limb muscles, with the exception that fibre diameters were smaller for all fibre types. Compared with limb muscles, MPCM had a smaller proportion of type IIb fibres and a higher proportion of types I and IIa fibres. MPCM in habitual snorers had an abnormal distribution of fibre types (low percentage of type I and type IIb fibres and high percentage of type IIa fibres) compared with non-snorers (p less than 0.001) and the type IIa fibres were hypertrophic. No myopathic or neurogenic changes were seen. Two possible hypotheses explain the abnormal distribution of fibre types in snorers. First, a constitutionally determined reduction of slow alpha-motor neurons induces an adaptive transformation of type IIb to type IIa fibres and a hypertrophy of type IIa fibres; or, second, motor neurons change their patterns of discharge and, hence, of activation, and modify fibre-type distribution of MPCM as an adaptation to the anatomical characteristic of upper airway and habitual snoring. 
4	Glomerular hyperfiltration indicates early target organ damage in essential hypertension In 111 patients with essential hypertension (World Health Organization stage I or II), we examined the relationship between renal hemodynamics and left ventricular hypertrophy. Left ventricular structure was determined by two-dimensional guided M-mode echocardiography, renal blood flow by iodine I 131 aminohippuric acid clearance, and glomerular filtration rate by creatinine clearance. The glomerular filtration rate correlated with left ventricular mass (r = .52) and left ventricular cross-sectional area (r = .21). Conversely, at a similar age, body mass index, body surface area, and arterial pressure, hypertensive patients with left ventricular hypertrophy disclosed a higher glomerular filtration rate and filtration fraction than those without left ventricular hypertrophy, whereas renal blood flow and renal vascular resistance measurements were not significantly different. Thus, at similar levels of arterial pressure and renal blood flow, glomerular hyperfiltration was linked to early cardiac structural changes in essential hypertension. We conclude that, in a hypertensive patient with normal renal function, a high glomerular filtration rate may be an indicator for early target organ damage in essential hypertension. 
2	A controlled trial of beclomethasone versus betamethasone enemas in distal ulcerative colitis. Steroid enemas are widely used in distal inflammatory bowel disease (IBD). They are partly absorbed and suppress adrenocortical function. Beclomethasone dipropionate (BD) is a topically active steroid that undergoes rapid first-pass inactivation in the liver and is practically devoid of systemic side effects. We treated 32 consecutive patients with active distal ulcerative colitis (40 attacks) with 0.5 mg BD and/or 5 mg betamethasone phosphate (BP) enemas for 28 days. Clinical, laboratory, sigmoidoscopic, and histologic data were recorded before, during, and after the trial. The clinical efficacy of both treatments was similar. Betamethasone was slightly more effective in relation to the histologic improvement and disappearance of blood from the stools. Clinical signs of steroid overdosage were noted in patients on BP but not in patients on BD. Mean fasting plasma cortisol at the end of the trial was 2.9 micrograms/dl in the BP group and 15.3 micrograms/dl in the BD group. The adrenocorticotropin test was markedly suppressed in the BP group but not in the BD group. The absence of systemic steroid side effects makes BD enemas a useful addition in the therapy of IBD. Its oral administration should also be considered. 
3	Eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan: muscle biopsy findings in 4 patients. Muscle biopsies of 4 patients with the eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan showed lymphocytic infiltrates with occasional eosinophils largely restricted to interstitial fibrous tissue and perivascular areas. There was inflammation and fibrosis of muscle spindle capsules in 3 patients. In the 2 sickest patients, there was profound muscle atrophy, affecting both muscle fiber types. 
2	Acute urinary retention in a child with appendiceal abscess: diagnostic dilemma. Rarely do children with appendiceal abscess present with acute urinary retention as the only sign or symptom. This presentation may delay diagnosis and definitive therapy, thereby causing additional morbidity and possible mortality. We report the eighth case of acute urinary retention in a child associated with an appendiceal abscess. 
5	Secondary damage to the knee after isolated injury of the anterior cruciate ligament. Between 1978 and 1984, we examined and performed arthroscopy on 1000 consecutive patients. Ninety-eight of the 1000 had isolated ACL damage. These cases do not include patients with initial ACL injuries combined with other intraarticular damage. Diagnosis was by physical and arthroscopic examination. Examination took place an average 13.6 months after injury. Of the 98 isolated ACL injuries, 56 were complete ruptures and 42 were partial ruptures. In most cases of partial rupture, the clinical diagnosis was wrong. "Meniscal damage" was the usual diagnosis in these cases; the true diagnosis was made only by arthroscopic examination. Thirty-four of the 98 patients with isolated ACL injuries (30 men and 4 women) developed further intraarticular damage. Of these 34, 20 had complete ACL rupture and 14 had partial ACL rupture. Treatment after primary injury included physiotherapy in all patients and bracing in those whose knee was unstable during daily activities. Reconstructive surgical procedures were not performed in those patients. The time lapse from the primary to the secondary injury varied from 1 month to 20 years, with an average of 28 months. The secondary damage was caused by a secondary injury that was mild (22 cases) or developed insidiously (12 cases). Five types of secondary damage were observed: partial ACL tears that became complete--11 cases; meniscal tear--8 cases; loosening and subluxation of the anterior horn of the medial meniscus--14 cases; and fracture or damage to the articular condylar cartilage, with or without bone involvement--11 cases. It should be emphasized that the secondary damages were at times combined. 
5	Further evaluation of radical surgery following radiotherapy for advanced parotid carcinoma. A series of 30 patients who have been treated for advanced carcinoma of the parotid gland using radiotherapy followed by radical surgery is presented. Three patients deteriorated during preoperative radiotherapy and remained unfit for surgery; the remaining 27 underwent radical parotidectomy with block dissection of the neck. Twelve patients received additional radiotherapy after operation. Of those patients undergoing surgery, three have been lost to follow-up, 17 have died and seven remain alive; the period of follow-up ranges from 3 to 133 months. Fourteen patients remained free of recurrent disease at death or when last seen, and six patients developed a local recurrence at a medium period of 10.5 (range 3-36) months after surgery. For all 30 patients, the cumulative proportion surviving for 5 years was 30 per cent. 
5	Percutaneous balloon dilatation of benign biliary strictures. Percutaneous biliary dilatation is an effective alternative to surgical management of benign biliary strictures that has low morbidity and no reported mortality. Reported success rates for this procedure range from 40% to 90% depending on the size of the series, the type of patient being treated, and the length of follow-up period. The procedure is done in the fluoroscopy suite with an angioplasty balloon catheter. Transhepatic access is most common, but the procedure may be done via existing T-tube tracts or specially created jejunal loops. As the frequency of radical liver surgery such as liver transplant and radical trisegmentectomy rises, so too, the rate of biliary stricture is likely to rise, making percutaneous balloon dilatation an increasingly important tool in the interventional radiologist's armamentarium. 
4	Possible triggering of paroxysmal atrial fibrillation in normal hearts by psychological stressors: a report of two cases. Paroxysmal atrial fibrillation was triggered by psychological stress in two patients, both of whom had normal echocardiograms and coronary angiography. Neither patient was alcoholic or had ingested ethanol in relation to the onset of atrial fibrillation and both were free of metabolic derangements. Possible mechanisms involved in the triggering of atrial fibrillation are discussed. 
2	Mechanical sutures in perforation of the thoracic esophagus as a safe procedure in patients seen late. Between 1976 and 1988, we treated 13 perforations of the thoracic esophagus, excluding ruptured carcinoma and intraoperative wounds, by mechanical sutures without exclusion. The delay between perforation and treatment ranged from eight to 168 hours, more than 24 hours in 11. The length of perforation was 0.5 to 15.0 centimeters. Suture was covered with a flap in ten instances; an antireflux procedure was associated with five instances. No digestive ostomies were performed. There was one death; a patient who was comatose upon arrival. The results of this small series suggest that myotomy exposing the mucosa and a flap are two essential elements of the technique; perforations of less than 6 centimeters, even when seen late, may be treated by primary surgical closure. 
5	Computed tomography in the assessment of the postenucleation socket syndrome. To gain a deeper insight into the cause of the postenucleation socket syndrome, high-resolution computed tomography (CT) was performed in 22 anophthalmic patients before insertion of an intraorbital implant. The anatomy of the normal and the anophthalmic orbits was compared. Computed tomographic scans were made either in the sagittal and the coronal plane or in the sagittal and transverse plane. The authors discovered a sagging and retraction of the superior muscle complex and a downward and forward redistribution of orbital fat. Finally, an upward displacement of the distal end together with a retraction of the inferior rectus muscle was found. These phenomena were measured and appear to cause a rotatory displacement of orbital contents from superior to posterior and from posterior to inferior which is best demonstrated in the sagittal plane. This redistribution of orbital contents can explain the sequelae of the anophthalmic orbit. No signs of orbital fat atrophy could be demonstrated. With this knowledge, the proper treatment of patients with a postenucleation socket syndrome is ascertained. 
3	Continuous papaveretum infusion for the control of pain in painful sickling crisis. We describe our experience of using continuous papaveretum infusions to control pain in 24 children admitted on 45 occasions with painful sickling crisis. The children were aged from 1.7 to 14.3 years. Infusion duration ranged from one to nine days (median three days), total dose from 0.3 to 21 mg/kg (median 2.4 mg/kg), with a pronounced tendency for dosage to increase with increasing age. No respiratory depression was observed. One infusion was discontinued because of cerebral toxicity. 
4	Valvular and coronary surgery in renal transplant patients. The Authors report aortic valvular replacement (AVR) and coronary artery bypass graft surgery (CABG) successfully performed in two renal transplant patients. The postoperative blood urea and creatinine levels were comparable to the preoperative values. The first patient underwent isolated AVR. The second patient had an initial AVR combined with CABG followed two years later by a further AVR for prosthetic dysfunction. For many reasons, coronary artery (CAD) and valvular diseases are not uncommon in renal transplant patients. Cardiac surgery is feasible without impairment of the renal function provided some precautions are taken, ie good mean perfusion pressure during cardiopulmonary bypass (CPB), adequate volume replacement, and selected use of mannitol and dopamine. 
3	Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy. Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission. 
2	Adult and pediatric peritonitis rates in a home dialysis program: comparison of continuous ambulatory and continuous cycling peritoneal dialysis. We reviewed our 115-month experience with continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) in adult and pediatric patients to determine whether there is a difference in the incidence of peritonitis between patients performing CAPD or CCPD. Peritonitis rates were similar in patients performing CAPD or CCPD in both the adult and pediatric age groups. The overall CAPD peritonitis rate was significantly lower in adult patients when compared with pediatric patients. There was no difference in peritonitis rates for CCPD between adult and pediatric patients. When the data are divided into 3-year subgroups, the incidence of peritonitis is significantly lower in adult patients undergoing either CAPD or CCPD when compared with pediatric patients during the years 1986 to 1988. There is significant improvement over time in the incidence of peritonitis in both adult and pediatric patients performing CCPD; similarly, there is a trend toward improvement in patients performing CAPD. Staphylococcus species organisms remain the most common bacterial cause of peritonitis, except in pediatric patients under the age of 2 years or with nephrostomies, where gram-negative rod infections were more common. Peritonitis resulted in discontinuation of peritoneal dialysis in a greater number of adult patients. These results suggest that the number of catheter manipulations is not important in determining the incidence of peritonitis. Pediatric patients are more likely than adult patients to develop peritonitis with either CAPD or CCPD. Adult patients are more likely than pediatric patients to discontinue peritoneal dialysis secondary to peritonitis. 
4	Family history fails to identify many children with severe hypercholesterolemia. Optimal strategies for identifying children with hypercholesterolemia have not been established. Several groups have advocated that testing of serum cholesterol levels be limited to those children who have family histories of hyperlipidemia or premature coronary heart disease. We studied the ability of comprehensive family histories to identify children with hyperlipidemia in a group of 114 children (mean age, 8 +/- 4 years) who were referred for treatment of hypercholesterolemia. A positive family history was defined according to guidelines of the American Academy of Pediatrics. The mean fasting total cholesterol in the children was 5.74 +/- 1.42 mmol/L (222 mg/dL). Family history was negative for hypercholesterolemia or premature coronary heart disease in 22 (22%) of 100 children with total cholesterol levels greater than the 75th percentile for their ages, in 13 (18.3%) of 71 children with total cholesterol levels greater than the 95th percentile for their ages, and in four (11.8%) of 34 children with presumed heterozygous familial hypercholesterolemia. Of the 78 children who had both hypercholesterolemia and positive family histories, hyperlipidemia was reported in 72 families, whereas premature heart disease was reported in only 27. We conclude that in a population of children referred because of known hypercholesterolemia, a detailed family history not only fails to identify many children with mild hypercholesterolemia, but also fails to identify a significant proportion of children with markedly elevated cholesterol levels. Additionally, in families of children with hypercholesterolemia, a history of hyperlipidemia is more common than a history of premature heart disease. 
1	Retroviral transduction of protein kinase C-gamma into cytotoxic T lymphocyte clones leads to immortalization with retention of specific function. The molecular pathways that are responsible for delivering the proliferative signals from the cell surface to the nucleus in T lymphocytes are still unresolved, but recent data implicates protein kinase C (PKC) involvement in the TCR signaling pathway. To further address the role of PKC in T cell activation, the effects of high level expression of the PKC-gamma isoenzyme in murine CTL clones were examined. Unlike the parental cells that required periodic Ag stimulation for cell activation and growth, cells expressing a retrovirally transduced PKC-gamma gene propagated in culture independent of the need for Ag stimulation, although maintaining identical functional specificity to the parental CTL. Constitutive PKC-gamma expression may therefore mimic physiologic PKC activation, thereby abrogating the requirement for TCR-Ag interaction in T cell activation. 
5	Synergistic effects of INTERCEED(TC7) and heparin in reducing adhesion formation in the rabbit uterine horn model. Surgical adjuvants are commonly employed to reduce the frequency of postoperative adhesion development after reproductive pelvic surgery. The ability of indomethacin, promethazine dexamethasone, Intralipid, progesterone, and heparin to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone reduces adhesion formation, was examined in a rabbit uterine horn model. A significant reduction in adhesion formation was only observed with the combination of INTERCEED(TC7) plus heparin. In addition studies, heparin delivery by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal instillation failed to demonstrate efficacy. Similarly, heparin delivery with other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70) failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be efficaciously utilized as a carrier to deliver heparin to traumatized surfaces, thereby reducing adhesion formation. 
5	Marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas. To investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies, a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as granulosa cell tumor. Using monoclonal antibodies against different keratin subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4 and 13 were not found in mesothelial cells, but positive groups of cells were identified in several cystomas, adenomas, and carcinomas. While mesothelial cells did not react with the pan-epithelial marker BW495/36, invaginating metaplastic mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an increasing reactivity with BW495/36, with an increasing degree of malignancy. The reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC 125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50% of the ovarian cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or disappeared in granulosa cells of mature follicles (Graafian follicles), whereas granulosa cell tumors did not react with anti-keratin antibodies. The reactivity of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian carcinoma-associated antigens were not expressed in granulosa cells or granulosa cell tumors. The data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production of ovarian carcinoma associated antigens, in addition to focal production of keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200-kd glycoprotein and the ovarian carcinoma-associated antigens. 
5	Screening of nineteen unrelated families with generalized resistance to thyroid hormone for known point mutations in the thyroid hormone receptor beta gene and the detection of a new mutation. Generalized resistance to thyroid hormone (GRTH) is a syndrome characterized by impaired tissue responsiveness to thyroid hormone. Two distinct point mutations in the hormone binding domain of the thyroid hormone receptor (TR) beta have recently been identified in two unrelated families with GRTH. One, Mf, involves a replacement of the normal glycine-345 for arginine in exon 7 and another, Mh, replaces the normal proline-453 for histidine in exon 8. To probe for the presence of the Mf and Mh defect in 19 unrelated families with GRTH, we applied separate polymerase chain reactions using allele-specific oligonucleotide primers containing the normal and each of the two mutant nucleotides at the 3'-position. A total of 24 affected subjects and 13 normal family members were studied. The mode of inheritance was dominant in 13 families, was unknown in 5 families, and was clearly recessive in 1 family in which only the consanguineous subjects were affected. Primers containing the substitutions specific for Mf and Mh amplified exons 7 and 8, respectively, only in affected members of each of the two index families. Primers containing the normal sequences amplified exons 7 and 8 of the TR beta gene in all subjects except affected members of one family. In this family with recessively inherited GRTH, neither exon could be amplified using any combinations of primers and DNA blot revealed absence of all coding exons. These results indicate a major deletion of the TR beta gene, including both DNA and hormone binding domains. Since heterozygous members of this family are not affected, the presence of a single normal allele is sufficient for normal function of the TR beta. These data also support the hypothesis that in the dominant mode of GRTH inheritance the presence of an abnormal TR beta interferes with the function of the normal TR beta. Distinct mutations are probably responsible for GRTH in unrelated families. 
1	Detection of Epstein-Barr virus DNA in formalin-fixed paraffin-embedded tissue of nasopharyngeal carcinoma using polymerase chain reaction and in situ hybridization. The polymerase chain reaction method for amplification of DNA in formalin-fixed, paraffin-embedded tissue sections was used to detect Epstein-Barr virus DNA in nasopharyngeal carcinomas from Japanese patients. Thirty-one cases of nasopharyngeal carcinoma and 8 cases of lymph node metastasis of nasopharyngeal carcinoma were studied. Detection rates of Epstein-Barr virus in various types of nasopharyngeal carcinoma according to the World Health Organization classification were as follows: 10 of 10 undifferentiated carcinomas, 8 of 13 nonkeratinizing carcinomas, and 5 of 7 keratinizing carcinomas. Eight lymph node metastases, for which the primary was positive for Epstein-Barr virus, also contained Epstein-Barr virus DNA. By in situ hybridization using a biotinylated Epstein-Barr virus probe, it was clearly demonstrated that Epstein-Barr virus DNA was localized in the nuclei of the neoplastic cells. The clinical features of nasopharyngeal carcinoma with or without Epstein-Barr virus were not different. These results demonstrate that nasopharyngeal carcinoma in Japanese patients is closely associated with Epstein-Barr virus infection, similar to nasopharyngeal carcinoma of other endemic and nonendemic areas. 
2	Spontaneous rupture of hepatocellular carcinoma: a review of 172 Japanese cases. The spontaneous rupture of a primary hepatocellular carcinoma (HCC) accounts for 10% mortality of HCC patients in Japan. Because this problem occurs much less frequently in western countries, it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a HCC. In an effort to advance the general knowledge of this disease and clarify a selection for its treatment, we review 172 cases of spontaneous rupture of a HCC reported in the Japanese literature. The chief complaint of the patients was sudden epigastralgia or right hypochondriac pain. Abdominal paracentesis was positive in 86% of the patients. Liver failure was the cause of death in 42% of the patients. Therefore, it is important to evaluate liver reserve quickly. In addition, emergency hemostatic procedures must be implemented to avoid hemorrhagic shock. Although two-stage hepatectomy was performed in only 12% of the cases, these had the highest survival rates. Consequently, this is the procedure of choice for the treatment of spontaneous rupture of a HCC. 
1	Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities. Ninety-seven children who were diagnosed with acute lymphoblastic leukemia before 10 years of age and treated with chemotherapy alone, chemotherapy plus 1800-cGy cranial irradiation (RT), or chemotherapy plus 2400-cGy RT were evaluated for effects of therapy on dentofacial development. All patients were seen at least 5 years postdiagnosis. Dental abnormalities were determined from panoramic radiographs, and craniofacial evaluations were made from lateral cephalometric radiographs. Ninety-one (94%) of all patients and 41 (100%) of patients younger than 5 years of age at diagnosis had abnormal dental development. The severity of these abnormalities was greater in children who received treatment before 5 years of age and in those who received RT. Observed dental abnormalities included tooth agenesis, arrested root development, microdontia, and enamel dysplasias. Craniofacial abnormalities occurred in 18 of 20 (90%) of those patients who received chemotherapy plus 2400-cGy RT before 5 years of age. Mean cephalometric values of this group showed significant deficient mandibular development. The results of this study suggest that the severity of dentofacial-developmental abnormalities secondary to antileukemia therapy are related to the age of the patient at the initiation of treatment and the use of cranial RT. 
4	Vitreous changes and macular edema in central retinal vein occlusion. The condition of the posterior vitreous was determined in 56 eyes with central retinal vein occlusion (CRVO). Using a life-table analysis, it was studied in 56 eyes. The incidence of posterior vitreous detachment (PVD) in the CRVO eyes at the first vitreous examination did not differ significantly from that in 64 age-matched control eyes. However, the incidence of PVD in CRVO eyes increased from 39.3% at the first vitreous examination to 58.5% after 6 months, and to 69.6% 1 year from the examination. The incidence of PVD in CRVO eyes during follow-up was statistically higher than that of the controls (P = .009). The incidence of PVD after the first vitreous examination was significantly higher in eyes with hemorrhagic retinopathy than in eyes with venous stasis retinopathy (P = .04). In the 34 eyes with macular edema, the edema lasted significantly longer in those with vitreomacular attachment (VMA) at the first examination than in those without VMA at this time (P = .02). VMA may play an important role in the pathogenesis and chronicity of macular edema in CRVO. 
2	Rotavirus-specific antibody response in saliva of infants with rotavirus diarrhea. The reliability of saliva as an indicator of rotavirus infection was assessed among 15 infants (3-12 months) with rotaviral and 15 with nonrotaviral diarrhea. Paired salivary samples collected during acute and convalescent phases were tested for rotavirus-specific IgA and IgM by an ELISA. The sensitivity of IgA or IgM alone to predict infection was 53.3% and 46.6%, respectively; used in conjunction, the sensitivity rose to 80%. It seems that infants with rotaviral diarrhea mount mucosal antibody responses as reflected in their saliva; possibly salivary antibodies could be used to evaluate vaccine "take" in rotavirus vaccine trials. 
4	Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine. We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year-old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect. 
5	Standard v lightweight wheelchair propulsion in spinal cord injured patients. Twenty-six male SCI subjects (six quadriplegics, eight "high paraplegics," and 12 "low paraplegics") propelled both standard and lightweight wheelchairs at a "sprint pace" (Sp) for 400 feet, and at a "duration pace" (Du) for four continuous minutes. Pulse, blood pressure and respirations were measured before and after each trial, and V was calculated. Appropriate training and rest periods were given; order of wheelchair testing was randomized. A questionnaire was later administered. Variations in pulse, systolic blood pressure, and respirations were significant between myelopathic levels (P less than 0.01), but were not affected by the type of wheelchair used. Quadriplegic V was less (P less than 0.01) than that of either paraplegic group for Sp and Du trials; for Sp, lightweight wheelchair V is faster (P less than 0.01) than standard wheelchair V for all groups. 
2	Methotrexate therapy for persistent ectopic pregnancy after conservative laparoscopic management. Persistent ectopic pregnancy is a recognized complication of conservative laparoscopic surgery. Three such cases were treated successfully with methotrexate and citrovorum factor rescue. All three patients experienced mild lower abdominal pain for a maximum of 36 hours; no other adverse effects were noted. More experience with this therapy will be necessary before subsequent fertility rates can be determined. 
5	Gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model. Pseudomonas otitis externa is one of the most common infections treated by otolaryngologists. Infections induced in 30 guinea pigs appeared similar to that seen in humans. The ears were then placed into four treatment groups: group A, which received a single cleaning; group B, which received a single cleaning followed by gentamicin drops 4 times daily; group C, which received a single cleaning followed by a single gentamicin iontophoresis treatment; and group D, the control group, which received no treatment. Infections were analyzed by grading edema, purulence, and erythema. An average of 10.2 days was required for control group to return to normal appearance. Groups A, B, and C had mean resolution times of 5.9, 4.7, and 4.3 days, respectively. Gentamicin iontophoresis appears to be promising, with results as good as drop therapy in otitis externa in the guinea pig model. 
1	Granular cell tumors of the vulva. Granular cell tumor (GCT), although nearly ubiquitous, is seen infrequently in the vulva. A review of the surgical pathology files from Grady Memorial Hospital, Atlanta, Georgia, from 1983 through 1987 identified eight cases of vulvar GCT. Five of the eight patients had more than one skin and soft tissue lesion. Two of the five had biopsy-proven multicentric GCT with a unique clinical course. One of the patients was a 32-year-old woman with multiple vulvar, lingual, laryngeal, bronchial and pulmonary GCT, necessitating multiple excisions and ultimately pneumonectomy. The second patient had multiple GCTs in the vulva and inguinal area and finally in both lungs, resulting in her death at age 39. No dependable microscopic features could be identified to distinguish benign GCT from its more aggressive variant. However, Feulgen DNA histomorphometry demonstrated aneuploidy in the patient with apparent lung metastases, whereas the tumors from patients with a benign course as well as from the patient with multiorgan involvement were diploid. In three of five patients who could be interviewed there was a history of soft tissue tumors in members of the family. The multifocal nature and possible familial component of GCT need to be explored further. 
5	The automatic implantable cardioverter-defibrillator in young patients. An international survey identified 40 patients less than 20 years old who underwent surgical implantation of an automatic implantable cardioverter-defibrillator (AICD). There was a history of aborted sudden cardiac death or sustained ventricular tachycardia in 92.5% of these patients. Twenty-two patients (55%) had structural heart disease; dilated and hypertrophic cardiomyopathy were the most common diagnoses. Eighteen patients (45%) had primary electrical abnormalities including seven with the congenital long QT syndrome. There were no perioperative deaths associated with device implantation. Concomitant drug therapy was administered to 75% of the patients. Defibrillator discharge occurred in 70% of the patients, with 17 patients (42.5%) receiving at least one appropriate shock. There were two sudden and two nonsudden deaths at 28.2 months' median follow-up. Sudden death-free survival rates by life table analysis at 12 and 33 months were 0.94 and 0.88, respectively. Total survival rates at 12 and 33 months were 0.94 and 0.82, respectively. The AICD represents an effective treatment approach for young patients with life-threatening ventricular tachyarrhythmias. 
1	Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol history with obstetrical records. The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma. Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records. Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur. 
1	A self-assembling protein kinase C inhibitor. Previous studies have described a dicationic anticarcinoma agent that can chemically assemble in situ from monocationic phosphonium salts. The chemical combination of these monocationic precursors in the micromolar concentration range, occurring after their uptake by cells, was probably responsible for their synergistic inhibition of cell growth and for their selective cytotoxicity to Ehrlich ascites murine carcinoma cells relative to untransformed epithelial cells. Here, we report that the dicationic product that forms in this assembly reaction is an in vitro inhibitor of protein kinase C (PKC) alpha and beta 1 isoforms, exhibiting IC50 values of 20.4 microM and 35 microM, respectively. The monocationic precursors proved to be much weaker inhibitors of PKC (IC50 values greater than 200 microM). When PKC is exposed to combinations of the two precursors, the enzymatic activity decreases steadily as a function of time. Using dose-response data and HPLC kinetic studies, we show that when the two precursor compounds are added as a combination to PKC under these conditions, the rate of formation of the inhibitory product follows the observed time course of decline in PKC activity under identical conditions. We discuss the possibility that antiproliferative effects against carcinoma cells of the preformed dication and of the combined monocationic precursors involve inhibition of PKC. 
1	Lymphoproliferative disorders associated with carbamazepine. Carbamazepine-induced lymphoproliferative disorders are relatively rare. A 32-year-old woman developed cervical lymphadenopathy while taking carbamazepine. Histologic evaluation of the lymph node biopsy specimen demonstrated near-total effacement of the nodal architecture by a population of pleomorphic immunoblasts. The predominant cell population expressed CD3, CD2, CD5, and CD4, while results of testing for CD8 were negative. On the basis of the morphologic and immunohistologic features, a diagnosis of high-grade, non-Hodgkin's lymphoma, T-cell immunoblastic type, was made. Despite the fact that aggressive behavior is usually associated with immunoblastic lymphomas, the patient has done well for 33 months after cessation of carbamazepine in the absence of chemotherapeutic treatment. The clinical features of this patient's illness, therefore, suggest that it is best regarded as a so-called pseudolymphoma. 
4	Clinical outcome of emergency repeat coronary artery bypass surgery. To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time. 
5	Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic alpha-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done in random order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P greater than 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that alpha-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP. 
2	Alternate-day prednisone treatment and treatment maintenance in Crohn's disease. We have reviewed our data from 55 patients with Crohn's disease (CD) treated with alternate-day prednisone (average dose: 25 mg every other morning) between 1966 and 1989 for a mean duration of 6.6 yr. Daily divided corticosteroid doses were given to all patients with active disease that had not been responsive to supportive measures and, in almost all cases, not responsive to sulfasalazine alone. After initial remission was achieved, patients were switched to alternate-day doses. Treatment evaluations utilized global assessment and the CD activity index of Harvey and Bradshaw (CDAI-HB) shown to correlate closely with the National Cooperative Crohn's Disease Study (NCCDS) activity index (CDAI). CDAI-HB scores of 0-1 indicated no or minimal activity, whereas scores of 2-15 indicated progressive activity. With the CDAI-HB and global assessments, in agreement in all cases, 33 patients (60%) showed favorable responses with 95% confidence intervals (CI) of 46.8 to 73.2. Comparing the results with a literature-based 20% spontaneous long-term remission rate, the data are significant at p less than 0.01. Serious complications were gratifyingly low, with no observed instances of osteonecrosis. It is concluded that alternate-day prednisone treatment and treatment maintenance, with or without concomitant sulfasalazine, after conventional induction of remission with daily steroid doses, is a reasonable treatment option for patients with CD not responsive to sulfasalazine alone. 
1	Paraneoplastic brachial plexopathy in a patient with Hodgkin's disease. We describe a case of inflammatory brachial plexopathy that occurred in the context of a mild, diffuse sensorimotor peripheral neuropathy associated with Hodgkin's disease. Clinical, electrophysiologic, and pathologic studies helped distinguish this disorder from other causes of brachial plexopathy in patients with cancer. Treatment with corticosteroids seemed beneficial in this patient. We suggest that this may be another type of paraneoplastic condition associated with Hodgkin's disease. 
4	Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome. Moderate hypothermia (30 degrees C) induced before circulatory arrest is known to improve neurologic outcome. We explored, for the first time in a reproducible dog outcome model, moderate hypothermia induced during reperfusion after cardiac arrest (resuscitation). In three groups of six dogs each (N = 18), normothermic ventricular fibrillation cardiac arrest (no blood flow) of 17 minutes was reversed by cardiopulmonary bypass--normothermic in control group I (37.5 degrees C) and hypothermic to 3 hours in groups II (32 degrees C) and III (28 degrees C). Defibrillation was achieved in less than or equal to 5 minutes and partial bypass was continued to 4 hours, controlled ventilation to 20 hours, and intensive care to 96 hours. All 18 dogs survived. Electroencephalographic activity returned significantly earlier in groups II and III. Mean +/- SD best neurologic deficit between 48 and 96 hours was 44 +/- 8% in group I, 38 +/- 12% in group II, and 35 +/- 7% in group III (differences not significant). Best overall performance category 2 (good outcome) between 48 and 96 hours was achieved in none of the six dogs in group I and in four of the 12 dogs in the combined hypothermic groups II and III (difference not significant). Mean +/- SD brain total histologic damage score was 130 +/- 22 in group I, 93 +/- 28 in group II (p = 0.05), and 80 +/- 26 in group III (p = 0.03). Gross myocardial damage was greater in groups II and III than in group I--numerically higher overall and significantly higher in group III for the right ventricle alone (p = 0.02). Moderate hypothermia after prolonged cardiac arrest may or may not improve cerebral outcome slightly and can worsen myocardial damage. 
1	Local control of auricular, periauricular, and external canal cutaneous malignancies with Mohs surgery. Three hundred ninety-seven patients with 407 cutaneous malignancies of the auricle, periauricular region, and cartilaginous external ear canal were reviewed. Tumors were most commonly located in the preauricular and postauricular regions, followed by the helix, concha, antihelix, and ear canal. All lesions were excised with Mohs microscopic control of margins. For lesions requiring lateral temporal bone resection, an adaptation of fresh-tissue microscopic control was used to analyze deep and anterior margins suspected of harboring residual tumor. Two-year minimum follow-up of 229 patients with periauricular and auricular tumors (N = 231 tumors) and 14 patients with cartilaginous ear canal tumors (N = 14 tumors) revealed recurrence rates of 6.9% and 14.3%, respectively. Recurrences were most common in cases of large tumors (greater than 2.5 cm), basal cell carcinomas with morphea elements, and multiply recurrent lesions. We conclude that Mohs surgery is comparatively effective, though not uniformly curative, and can be adapted to supplement excision of large tumors in these regions. 
4	Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs. Experimental retinal branch vein occlusion using argon laser photocoagulation in miniature pigs induced the development of ischemic retinal territories associated with preretinal neovascularization. Preretinal partial pressure of oxygen (PO2) measurements on the ischemic territories, using O2-sensitive microelectrodes, established that the ischemic retinal areas were hypoxic. Scatter photocoagulation of these ischemic hypoxic territories restores the local PO2 to the normal values within 2 weeks. Hence, the reported inhibitory effect of photocoagulation on the development of retinal neovascularization could be due to a reversal effect on tissue hypoxia. 
3	Tongue atrophy in mixed connective tissue disease. A case is reported of tongue atrophy in a patient with mixed connective tissue disease (MCTD) and major myositic involvement. The case highlights oropharyngeal aspects of MCTD, including inability to wear dentures, dysarthria, and dysphagia. To our knowledge this is the first report of major tongue involvement in myositis as part of MCTD. 
5	Discontinuation of neuroleptic medication in older, outpatient schizophrenics. A placebo-controlled, double-blind trial. Thirty-five schizophrenic outpatients over the age of 52 who had been stable on neuroleptic medication were all switched to haloperidol. Ten patients were unable to tolerate the haloperidol and two dropped out of the study. The remaining 23 patients were randomly and blindly assigned to haloperidol or placebo and then followed for 6 months. Five patients did not complete the study due to medical or administrative reasons. Among the patients who completed the study, five of 10 randomized to placebo relapsed compared with only one of eight randomized to haloperidol. However, three of 10 patients randomized to placebo have remained stable without medication for 2.5 years. 
4	Outcome probabilities and life history after surgical mitral commissurotomy: implications for balloon commissurotomy. From 1967 to 1988, 339 patients with mitral stenosis underwent surgical commissurotomy, 103 with a closed and 236 with an open technique. The 1 month and 1, 5, 10 and 20 year overall survival rate was 99.7%, 99%, 95%, 87% and 59%, respectively, and the technique (open versus closed) was not a risk factor. Technique was also not a risk factor for a second mitral commissurotomy, subsequent mitral valve replacement, thromboembolism or poor functional status. Risk factors were older age at commissurotomy, black race, higher pulmonary vascular resistance, mitral leaflet calcification, left ventricular enlargement and postcommissurotomy mitral incompetence. The closed technique was a risk factor for mitral incompetence immediately after commissurotomy, but important incompetence developed in only 2 of the 103 patients undergoing closed commissurotomy. Mitral valve replacement was not required within 10 years in 78% of patients and within 20 years in 47%. Despite some increased prevalence of postcommissurotomy mitral incompetence and particularly in view of the considerable long-term likelihood of mitral valve replacement, initial therapy for most patients with mitral stenosis should probably be surgical closed (or percutaneous balloon) mitral commissurotomy. The equations developed in the present study can be used to predict and compare outcome probability after percutaneous balloon commissurotomy with that after surgical commissurotomy and to compare these with outcome probability after mitral valve replacement. 
5	Molecular characterization of beta-thalassemia intermedia in patients of Italian descent and identification of three novel beta-thalassemia mutations. In this study, we have defined by dot-blot analysis with allelic specific oligonucleotide probes or direct sequencing on amplified DNA the beta-thalassemia mutations in a large group of patients (23) of Italian descent with thalassemia intermedia. These patients had one parent with either the silent beta-thalassemia carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to 3.5%). Nearly all were genetic compounds for a severe beta-thalassemia mutation and a beta-thalassemia mutation associated with high residual output of beta-globin chains (beta + intervening sequence [IVS]-I-nt6, beta -87, beta -101), indicating that inheritance of a mild beta-thalassemia allele, even in a single dose, is the most common molecular mechanism producing thalassemia intermedia in the Italian population. In three cases, in whom we failed to define by dot-blot analysis the mutations, we sequenced the beta + globin gene and found three novel beta-thalassemia mutations, which are certainly very rare because they have been hitherto detected solely in a single patient. These mutations consist of: (1) a T-A substitution at position 2 of IVS-I, in a patient compound heterozygote for this mutation and the -87 promoter mutation; (2) a G-C substitution at position 844 of IVS-II, in a patient heterozygous for this mutation who showed normal sequences at the in trans beta-globin gene (The reason for the presence of clinical manifestations in a beta-thalassemia heterozygote has not been defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a frameshift and readthrough of the 5' untranslated region and most likely producing an elongated Hb molecule of 156 amino acid residues, in a patient heterozygous for this mutation with normal beta-globin gene sequences at the other locus. 
3	Postoperative complications in patients with disabling psychiatric illnesses or intellectual handicaps. A case-controlled, retrospective analysis. The purpose of this study was to quantitate the operative risk and costs encountered in the surgical treatment of institutionalized patients. Operative complications and duration of hospitalization for 200 institutionalized patients were compared with those in a control group of patients matched for age, sex, and type of operation drawn from the general hospital population. Postoperative complications occurred in 53 (26.5%) of the patients in the study group compared with 15 (7.5%) of the patients in the control group. Elective laparotomy was followed by a complication in 48% of institutionalized patients compared with 11.6% of matched controls. Emergency celiotomy carried a 75% complication rate in the study group. Atelectasis and pneumonia accounted for 50% of the postoperative complications and occurred with greatest frequency following intra-abdominal procedures. The median hospital stay for all institutionalized patients was 3 days more than for matched controls. A strategy for postoperative treatment is presented, with particular emphasis on prevention of pulmonary complications. 
4	Persistent uptake of indium-111-antimyosin monoclonal antibody in patients with myocardial infarction. Indium-111(111In)-antimyosin scintigraphy was investigated in 27 patients with myocardial infarction. 111In-antimyosin Fab was administered intravenously, and planar and single photon emission computed tomographic images were obtained 48 hours later. Uptake of 111In-antimyosin was present in 9 of 10 patients (90%) studied within 6 days of infarction. During the second week positive scans were seen in 16 of 16 patients (100%) including 13 (81%) who had normal creatine kinase levels. The mechanism of persistent positive antimyosin images in the subacute stage of myocardial infarction remains to be clarified. 111In-antimyosin scintigraphy may be useful as a noninvasive method for the detection of myocardial injury late and early after a suspected acute myocardial infarction. 
4	Transvascular intracardiac applications of a miniaturized phased-array ultrasonic endoscope. Initial experience with intracardiac imaging in piglets. BACKGROUND. Recent advances in miniaturization of phased-array and mechanical ultrasound devices have resulted in exploration of alternative approaches to cardiac and vascular imaging in the form of transesophageal or intravascular imaging. Preliminary efforts in adapting phased-array endoscopes designed for transesophageal use to a transvascular approach have used full-sized phased-array devices introduced directly into the right atrium in open-chested animals. The purpose of this study was to assess the feasibility of using a custom-made, very small phased-array endoscope for intracardiac imaging introduced intravascularly through a jugular venous approach in young piglets. METHODS AND RESULTS. Experimental atrial septal defects created in four piglets (3-4 weeks old) had been closed with a buttoned atrial septal defect closure device consisting of an occluder in the left atrium and a counteroccluder in the right atrium. Five to 15 days after atrial septal defect closure, the piglets were returned to the experimental laboratory, where a 6.3-mm, 17-element, 5-MHz phased-array probe mounted on a 4-mm endoscope was introduced through a cutdown incision of the external jugular vein and advanced to the right atrium. From the right atrium all four cardiac chambers, their inflows and outflows, and all four valves were well imaged with minimal superior and inferior rotation. High-resolution imaging of the atrial septum defined with anatomical accuracy, later verified by autopsy, the exact placement of both the occluder and counteroccluder in the left and right sides of the atrial septal defects and the absence of any shunting across the atrial septum in any of the four animals. CONCLUSIONS. Our efforts indicate that transvascular passage of small phased-array probes can be easily accomplished and is a promising technique for detailed visualization of cardiac structures. This approach may provide an alternative to transesophageal echocardiography, particularly for guiding interventional procedures such as placement of transcatheter closure devices in pediatric patients. 
2	Emergency surgical treatment for nonvariceal bleeding of the upper part of the gastrointestinal tract. Endoscopic and biochemical data were collected prospectively from 1,530 patients admitted with nonvariceal bleeding of the upper part of the gastrointestinal tract between September 1985 and June 1989. Therapeutic endoscopy was done for 93 patients who underwent emergency surgical treatment for bleeding, subsequently required in 29 patients with seven postoperative fatalities. In contrast, 31 (15.7 per cent) of 198 patients (mortality rate of 9.6 per cent at 30 days) died in the hospital who had undergone emergency operation in whom therapeutic endoscopy had not been performed; data for this latter group is now presented. At admission, a greater likelihood of emergency operation was associated with a systolic blood pressure of 100 millimeters of mercury and endoscopic stigmatas of recent hemorrhage (ESRH) (p less than 0.001). Rebleeding rates for the presence of fresh blood, active spurting and oozing hemorrhage or visible vessel in an ulcer base were 26.5, 28.9 and 35.9 per cent, respectively. Endoscopic stigmatas were thus associated with an increased risk of bleeding (p less than 0.0001) and rebleeding led to a sixfold increase in the mortality rate. Congestive cardiac failure, chronic obstructive airway disease, chronic renal failure and a history of previous malignant disease were each associated with postoperative mortality rates of more than 50 per cent. An increased risk of mortality after emergency operation was related to age (p less than 0.0001), preoperative (p less than 0.002) and total (p less than 0.0001) blood transfusion requirement. Immediate operation after resuscitation and endoscopy was required in 87 patients; 11 deaths (hospital mortality rate of 12.7 per cent and 9.2 per cent at 30 days) occurred in this group compared with 20 fatalities (18.0 per cent) documented in 111 patients (9.9 per cent at 30 days) who underwent surgical treatment for rebleeding. We conclude that age, concomitant medical illness and preoperative and total transfusion requirements are each related to outcome after emergency operations. Such urgent intervention is best avoided if at all possible in patients with severe concomitant medical illness. 
5	Premenstrual syndromes defined by symptom-sets. An analysis is made of the pattern of presenting premenstrual symptoms in randomly selected general practice patients from the Wellington region, New Zealand. Participants, 1826 healthy women 16-54 years old whose characteristics were reasonably representative of the adult female population, were asked about their general, obstetrical and gynaecological health. For the 1456 women who had menstruated within the last month or so, detailed questions were asked about the last menstrual cycle. Each woman was assigned to one of seven premenstrual symptom sets. Three groups had 'pure' symptoms, ie a predominant single symptom (breast tenderness, bloating or irritability). Three groups had 'mixed' symptom-sets. The largest of the 'mixed' groups was formed by the women who reported breast tenderness, bloating and irritability together with tension and depression. Women in this group were most likely to rate their symptomatology as severe. The last group contains a large number of women with miscellaneous symptoms. Characteristics of these groups are outlined. The study highlights the importance of distinguishing among premenstrual syndromes as this can foster more effective clinical management. 
4	Short- and long-term results of catheter balloon percutaneous transvenous mitral commissurotomy. Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 219 patients with symptomatic, severe rheumatic mitral stenosis. There were 59 men and 160 women, aged 19 to 76 years (mean 43). Pliable, noncalcified valves were present in 139 (group 1), and calcified valves or severe mitral subvalvular lesions, or both, in 80 patients (group 2). Atrial fibrillation was present in 133 patients (61%) and 1+ or 2+ mitral regurgitation in 59 (27%). Technical failure occurred with 3 patients in our early experience. There was no cardiac tamponade or emergency surgery. The only in-hospital death occurred 3 days after the procedure in a group 2 premoribund patient in whom last-resort PTMC created 3+ mitral regurgitation. Mitral regurgitation appeared or increased in 72 patients (33%); 3+ mitral regurgitation resulted in 12 patients (6%). There were 3 systemic embolisms. Atrial left-to-right shunts measured by oximetry developed in 33 patients (15%). Immediately after PTMC, there were significantly reduced (p = 0.0001) left atrial pressure (24.2 +/- 5.6 to 15.1 +/- 5.1 mm Hg), mean pulmonary artery pressure (39.7 +/- 13.0 to 30.6 +/- 10.9 mm Hg) and mitral valve gradient (13.0 +/- 5.1 to 5.7 +/- 2.6 mm Hg). Mitral valve area increased from 1.0 +/- 0.3 to 2.0 +/- 0.7 cm2 (p = 0.0001) and cardiac output from 4.4 +/- 1.4 to 4.7 +/- 1.2 liters/min (p less than 0.01). The results mirrored clinical improvements in 209 patients (97%). Multivariate analysis showed an echo score greater than 8, and valvular calcification and severe subvalvular lesions as independent predictors for suboptimal hemodynamic results. 
2	Tuberculous peritonitis: a study comparing cirrhotic and noncirrhotic patients. Tuberculous peritonitis is a rare disease, which often goes unrecognized because of the subtle clinical clues and its insidous onset. We retrospectively analyzed the records of 37 cases of tuberculous peritonitis diagnosed over a 15-year period, and compared the clinical and diagnostic features of cirrhotic and noncirrhotic patients. In cirrhotic patients, tuberculous peritonitis can simulate ascites from liver disease or spontaneous bacterial peritonitis. The diagnosis is difficult in these patients because the ascitic fluid may not be of the exudative type as a result of the low albumin level in serum, and lymphocytes do not predominate in all cases. Adenosine deaminase (ADA) activity in ascitic fluid was elevated (higher than 40 U/L) in all 11 patients (four patients with hepatic cirrhosis). The time required to achieve a correct diagnosis was significantly longer in cirrhotic than in noncirrhotic patients. The overall mortality was 13%, with deaths occurring exclusively among cirrhotic patients. We emphasize that tuberculous peritonitis in cirrhotic patients can present an atypical picture. A considerable element of suspicion is necessary. 
2	Refeeding of infants with acute diarrheal disease. The purpose of this study was to determine which infant formula among five would be the most efficacious for the refeeding of infants during an acute episode of diarrhea. Fifty male infants less than 12 months of age with severe diarrhea and at least 5% dehydration were admitted to a metabolic unit and studied in a prospective, single-blind protocol. Ten infants randomly received one of five types of formula: two-thirds diluted cow milk, cow milk formula (Nanon, Nestle, Inc., Sao Paulo, Brazil), Portagen, Pregestimil, or Prosobee (Mead Johnson & Co. Division, Evansville, Ind.). They continued to receive the same formula for 72 hours unless dehydration occurred. There were no associated infections, and they received no prior antibiotic treatment. Oral hydration together with intravenous fluid therapy was given to all patients during the initial treatment. During the first 72 hours of refeeding, patients fed Portagen excreted the least amount of stool and required reduced quantities of intravenous fluids or oral hydration. In contrast, patients fed diluted cow milk or any other formula had more severe diarrhea. Nine of the 10 patients fed Portagen completed the 72-hour treatment, whereas only 2 of 10 fed diluted cow milk tolerated it. Similarly, the cumulative proportions for high purging rate, dehydration, carbohydrate intolerance, and vomiting were more favorable for Portagen and least acceptable for diluted cow milk. No differences were found among the remaining three formulas tested. These data show that diluted cow milk is poorly tolerated by infants with severe diarrhea, whereas Portagen is more effective. 
4	Early diagnosis and survival of ruptured abdominal aortic aneurysms. The hospital records of patients treated with ruptured abdominal aortic aneurysm in a recent 5-year period were reviewed to collect data on factors which may be associated with mortality. Overall mortality was 62%. Patients with intraperitoneal rupture had a higher mortality (97%) than patients with retroperitoneal rupture (25%). Patients at increased risk were older than 80 years, presented with syncope, experienced a short duration of symptoms prior to emergency department (ED) arrival, had initial systolic blood pressure less than 90 mm Hg, and/or initial hemoglobin level less than eight on arrival at the ED and delay in beginning surgery. Multivariate analysis demonstrated preoperative blood pressure, preoperative hemoglobin, presence of syncope, and the amount of blood transfused were largely reflections of the type of rupture and had only slight independent relationship to mortality. The authors concluded that treating emergency physicians and surgeons have little control over the most important risk factors for mortality after aneurysm rupture, but may improve the prognosis by expediting diagnosis in the ED and surgical therapy. 
2	Chilaiditi's syndrome. A diagnostic challenge. Chilaiditi's syndrome should be considered in the differential diagnosis of abdominal and chest pain. Although interposition of the right colon is a relatively common radiologic finding, there is a distinct paucity of information in the medical literature. Chilaiditi's syndrome is usually asymptomatic, but when symptoms occur, conservative treatment is usually effective. Recognition is important because this syndrome can be mistaken for more serious abnormalities, which may lead to unnecessary surgical intervention. 
4	Long term follow-up of descending thoracic aorto-iliac/femoral bypass. A prospective study of 26 patients undergoing descending thoracic aorto-iliac/femoral (DTAI/F) bypass was conducted over a 13-year period with an average follow up of 53 months. Reasons for selecting the procedure were occluded aortic bifurcation grafts (9 patients), hostile abdomen (6), infected aortic graft (1), microaorta (10, and surgeons preference in 8 patients who had juxtarenal aortic occlusion. The operative mortality was 3.8% (1 patient). A late mortality of 36% was due to myocardial infarction (1), lung carcinoma (2), renal failure (4), stroke (1) and pulmonary insufficiency (1). Graft failure occurred in 4 patients at 23, 26, 54 and 109 months respectively. Primary cumulative patency was 86% statistically valid at 42 months. DTAI/F bypass is recommended in selected patients when conventional approaches to the aorta are considered unduly hazardous. 
4	Left ventricular mid-cavitary obstruction after balloon dilation in isolated aortic valve stenosis in children. A hyperdynamic left ventricle can lead to post-dilation mid-cavitary obstruction in the absence of any preballoon mid-cavitary obstruction in children with aortic valve stenosis. The purpose of this study was to define the incidence and course of post-dilation mid-cavitary obstruction. We reviewed the catheterization and echocardiographic data of 35 patients, ages 3 days to 18 years (mean = 7.9 years), with isolated aortic valve stenosis who underwent balloon dilation with a fall in aortic valve gradient to less than 20 mm Hg. Post-dilation mid-cavitary obstruction was suspected from post-dilation left ventricular angiogram and was quantitated by echocardiographic and Doppler examinations performed immediately after dilation and in a 1-3 month follow-up period. Continuous wave Doppler directed by color flow Doppler was used for evaluation and differentiation of post-dilation mid-cavitary obstruction and residual aortic valve stenosis. Three children (3/35 [9%]) all under 2 years of age developed post-dilation mid-cavitary obstruction immediately after dilation. The obstruction within the cavity resolved spontaneously in all three patients. Conclusions: 1) Post-dilation left ventricular mid-cavitary obstruction can occur in children under 2 years of age after balloon dilation of severe aortic valve stenosis, and 2) total regression of post-dilation mid-cavitary obstruction occurs spontaneously in all patients. 
1	Pituitary hemorrhage into a Rathke's cleft cyst This report describes a case of symptomatic pituitary hemorrhage into a Rathke's cleft cyst in a 25-year-old woman. The literature on pituitary hemorrhage in nonadenomatous sellar tumors is reviewed. 
1	Spontaneous necrosis in osteosarcoma. The percentage of necrosis in a primary osteosarcoma after the patient has received preoperative chemotherapy is prognostic and is usually used to select subsequent chemotherapy. However, the percentage of necrosis that occurs spontaneously, without preoperative chemotherapy, has not been adequately studied. The examination of histologic macrosections of 76 osteosarcomas from patients who had not received preoperative treatment and of 20 patients who had received preoperative chemotherapy revealed a significant difference in the percentage of necrosis. There was minimal spontaneous necrosis, but necrosis after preoperative chemotherapy was usually extensive. The larger the tumor, the greater the percentage of spontaneous necrosis; however, size did not correlate with the percentage of necrosis with preoperative chemotherapy. Survival among those patients who did not receive preoperative treatment correlated with the size and percentage of necrosis. Necrosis in an osteosarcoma in a patient who has received preoperative chemotherapy can be considered the result of chemotherapy and not a spontaneous event. 
1	Chemotherapy for medulloblastoma/primitive neuroectodermal tumors of the posterior fossa. Chemotherapy has only marginal efficacy in adult malignant brain tumors. In contrast, drug therapy is considerably more effective in medulloblastoma/primitive neuroectodermal tumors (MB/PNET) of the posterior fossa, the most common childhood primary central nervous system tumor. At the time of disease recurrence, a variety of different single agents and drug combinations result in tumor shrinkage and increased survival. The addition of chemotherapy to standard radiotherapy improves the rate and length of disease-free survival for those children with MB/PNET who have the most extensive tumors at diagnosis. It remains to be determined which drug or drug combinations are the most effective in MB/PNET, and which patients are most likely to benefit from chemotherapy. Chemotherapy may be useful to reduce or, in selected cases, obviate the need for radiotherapy and reduce treatment-related sequelae. 
3	Carbamazepine dose requirements during stiripentol therapy: influence of cytochrome P-450 inhibition by stiripentol. The inhibitory effect of stiripentol (STP) on disposition of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZE) was quantitated to establish CBZ dosage reduction guidelines for future clinical add-on efficacy trials of STP. In seven epileptic patients, STP (1,500-3,000 mg/day for 2 weeks) inhibited CBZ clearance by 50 +/- 16% (p = 0.001) and reduced the CBZE/CBZ plasma ratio by 45 +/- 14% (p = 0.0005). The inhibitory effect was gradually manifested over a period of 7-10 days after initiation of STP therapy. In contrast to inhibition of CBZE formation, STP had no effect (p greater than 0.05) on elimination clearance or half-life (t1/2) of CBZE in six healthy volunteers. STP most likely exerts inhibitory effects through inhibition of cytochrome P-450. This hypothesis was confirmed in the present study by the finding that a therapeutic concentration of STP (7 micrograms/mL) inhibited 10,11-epoxidation of CBZ in human liver microsomes by 40-50%. On the basis of results from this study, we propose that (a) CBZ dosage should be reduced in steps over a period of 7-10 days after initiation of STP, and (b) a CBZ dosage of 4.3 to 8.7 mg/kg/day will maintain therapeutic CBZ plasma levels of 5-10 micrograms/mL. 
3	Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic alpha-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done in random order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P greater than 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that alpha-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP. 
5	Postoperative complications in patients with disabling psychiatric illnesses or intellectual handicaps. A case-controlled, retrospective analysis. The purpose of this study was to quantitate the operative risk and costs encountered in the surgical treatment of institutionalized patients. Operative complications and duration of hospitalization for 200 institutionalized patients were compared with those in a control group of patients matched for age, sex, and type of operation drawn from the general hospital population. Postoperative complications occurred in 53 (26.5%) of the patients in the study group compared with 15 (7.5%) of the patients in the control group. Elective laparotomy was followed by a complication in 48% of institutionalized patients compared with 11.6% of matched controls. Emergency celiotomy carried a 75% complication rate in the study group. Atelectasis and pneumonia accounted for 50% of the postoperative complications and occurred with greatest frequency following intra-abdominal procedures. The median hospital stay for all institutionalized patients was 3 days more than for matched controls. A strategy for postoperative treatment is presented, with particular emphasis on prevention of pulmonary complications. 
1	Nuclear medicine in otolaryngology. Nuclear medicine has a distinct role to play in otolaryngological practice. Accurate diagnosis of endocrine conditions is now possible using precise in-vitro hormone measurement. Specific clinical questions can be answered using in-vivo investigations. 99mTcO-4/123I scintigraphy is used to evaluate thyrotoxicosis and solitary thyroid nodules. 99mTc/201T1 subtraction scanning is of value in the preoperative localization of parathyroid adenomas and 99mTcO-4 is particularly useful in assessing salivary and lachrymal gland function and drainage. 99mTc-MDP bone scanning is useful in the evaluation of osteomyelitis, temporomandibular joint dysfunction, bone graft viability and some facial fractures. The role of radioisotopes in the management of differentiated and medullary carcinoma of the thyroid is now well established. Although there are many other agents available to image head and neck cancer, few can actually achieve the required diagnostic sensitivity and specificity. The introduction of monoclonal antibodies into routine imaging has been hampered by distinct practical problems and the search is now on for more sensitive non-specific diagnostic agents. It is now possible to evaluate new 99mTc labelled tumour-imaging agents using animal tumour model systems and the use of radioactivity in all aspects of otolaryngological research adds an extra quantitive dimension. Together with SPECT, and the introduction of positron emission tomography (PET) to image the physiology of normal tissues and tumours, the use of radionuclide investigations can lead only to an increase in ENT diagnostic sensitivity and specificity and, subsequently, to an overall improvement in the way we diagnose, stage and treat head and neck cancer. 
5	Acute naming deficits following dominant temporal lobectomy: prediction by age at 1st risk for seizures. Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (less than or equal to 5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (greater than or equal to 25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks. 
3	Anorectal function in incontinent patients with cerebrospinal disease. Anorectal manometry and the electrical activity of the external anal sphincter were measured in 20 patients with well-defined, incomplete spinal lesions who were referred because of fecal incontinence and in 30 normal subjects. Six patients had a high spinal lesion, 11 had a low spinal lesion, and 3 had mixed high and low spinal lesions. Patients with high spinal lesions had normal basal pressures but abnormally low squeeze pressures and impaired rectal sensation. Unlike normal subjects, there was no relationship between the depth of sphincter relaxation and the distention volumes. The external sphincter responses to rectal distention and increases in intraabdominal pressure were enhanced, and leakage of perfusion fluid was uncommon. Patients with low spinal lesions had abnormally low basal and squeeze pressures, blunted rectal sensation, and showed impaired external anal sphincter responses to rectal distention or increases in intraabdominal pressures. Most of these patients leaked the infused fluid during these maneuvers. Sphincter function in patients with mixed lesions was more severely impaired than in patients with low and high spinal lesions. Patients with mixed lesions showed abnormally low basal and squeeze pressures, impaired rectal sensation, and no external anal sphincter responses to either rectal distention or increases in intraabdominal pressure. Leakage occurred during these maneuvers in all patients with mixed lesions. 
1	Photochemotherapy alone or combined with interferon alpha-2a in the treatment of cutaneous T-cell lymphoma. Eighty-two patients with either mycosis fungoides (MF) or parapsoriasis en plaques were treated with psoralens ultraviolet A light (PUVA). Clinical and histologic parameters were followed for a period from 6 months to 10 years. Complete clinical clearing of lesions was observed in 51 patients (62%) and most of them were in limited-plaque MF group or parapsoriasis en plaque. The mean total dose of PUVA for complete clearing was less for early MF. Thirty-one patients (38%) relapsed and responded to additional PUVA. Patients in early stages of the disease remained clear for up to 68 months after the first course of PUVA. Post-treatment skin biopsies with early MF showed histologic clearing. A new combination therapy for MF is presented in 15 patients. Recombinant interferon alpha-2a (Roferon-A), administered intramuscularly combined with PUVA were tested in a phase I trial. Interferon doses were from 6-30 million units three times weekly. Disease stages ranged from I-B to IV-B. Complete responses were obtained in 12 of 15 patients, and partial responses seen in 2 of 15 patients, for an overall response rate of 93%. The median duration of response exceeded 23 months (range, 3 to 25 months). All responding patients have been maintained on therapy. The dose-limiting toxicities were constitutional symptoms such as fevers and malaise (93.3%), leukopenias (40.0%), mental status changes consisting of depression and confusion (33.3%), and photosensitivity (26.6%). Interferon plus PUVA appear to be highly effective regimens for the treatment of patients with cutaneous T-cell lymphomas. 
5	Haematuria frequency syndrome in patients with positive HIV serology: observations in Zambia. Observations are presented on 9 patients recently treated in the University Teaching Hospital, Lusaka, Zambia, for painful urinary frequency, suprapubic pain and microscopic and/or macroscopic haematuria without any demonstrable urinary tract infection. At cystoscopy the bladder mucosa of all patients depicted a highly characteristic, uniformly congested appearance with no demonstrable ulcers; there was no significant reduction in bladder capacity. The histological appearance was essentially non-specific in type with an apparent resemblance to that of interstitial cystitis; mast cells were, however, absent in all specimens. An important feature common to all patients was an associated HIV infection; cytochemistry of the bladder tissue did not reveal an associated cytomegalovirus cystitis. No such case was observed in Zambia prior to the advent of HIV infection and the phenomenon was observed only in seropositive patients. It has been suggested that the virus is likely to be associated with the genesis of the bladder symptoms. The natural history of the disorder, its incidence among the seropositive individuals and its pathogenesis remain unclear. 
1	The ras oncogenes in human lung cancer. The three well-characterized genes of the ras gene family H-ras, K-ras, and N-ras, code for closely related 21-kD proteins that have a role in the transduction of growth signals. The ras proteins acquire transforming potential when a point mutation in the gene leads to replacement of an amino acid in one of the critical positions 12, 13, or 61. Overexpression of the normal protein, usually associated with gene amplification, can have similar effects. The detection of mutationally activated ras genes has been facilitated by the development of oligonucleotide hybridization assays that allow the identification of each possible mutation at the critical sites. Employment of the polymerase chain reaction has greatly increased the sensitivity of these assays. Studies of human lung cancer have shown that adenocarcinoma is the only subtype associated with ras mutations. These occur in about 30% of primary tumors. In almost all cases, the mutation is present in codon 12 of the K-ras gene. No mutations have been observed to date in tumors of nonsmokers, suggesting that the mutation may result from exposure to carcinogenic ingredients of tobacco smoke. Amplifications of ras genes were shown to be very uncommon in clinically early stages of lung cancer. Analysis of the clinical data of patients who were operated on for adenocarcinoma of the lung shows that K-ras mutations are not associated with particular histologic characteristics of the tumors or with specific presenting features. Patients with K-ras mutations, however, had significantly worse survival than did those without an activation. 
3	Characteristics of an elderly driving population referred to a geriatric assessment center. A retrospective, case-control study was performed to determine the characteristics of elderly drivers referred to an outpatient geriatric assessment center. It was hypothesized that the driving population was operating at a higher cognitive and functional level than nondrivers. One hundred eighty-two subjects meeting the entry criteria were studied. Twenty-three percent of the subjects were driving at the time of their assessment. Compared to nondrivers, drivers were younger (P = .0001), were more likely to be male (P = .003), scored higher on a mental status examination (P = .0001), and were more independent in Physical and Instrumental Activities of Daily Living (P less than .0001). Despite these findings, the mean Folstein Mini-Mental score for drivers (23.7) was below normal; 40% of drivers were diagnosed as having Alzheimer's dementia at the time of their evaluation, and over 26% of the drivers needed help with either dressing or bathing. The frequency of impaired elderly drivers in this referral setting was high. The authors conclude that conditions that affect the driving task are common in geriatric assessment centers. Prospective studies of elderly drivers are needed to answer the difficult question of who among the elderly should drive. 
5	Hiccups and breathing in human fetuses. Serial recording in 45 low risk fetuses throughout the second and third trimesters showed that hiccups were the predominant diaphragmatic movement before 26 weeks' gestational age and that there was a significant negative correlation with gestational age. There was a pronounced reduction between 24 and 26 weeks, which was the result of a decrease in the number of episodes of hiccups rather than a change in the duration of episodes. In contrast, fetal breathing was positively correlated with gestational age, the greatest increase in breathing occurring between 26 and 32 weeks' gestation. This was the result of both an increase in the number and duration of episodes. From the time that rest-activity cycles of behaviour could be determined in recordings, both breathing and hiccups were dependent on behavioural state or cycle, occurring predominantly during active episodes. This association between quiet and active behaviour and breathing did not alter with increasing gestational age, and the variables in fetal behavioural state became increasingly closely linked. The importance of prolonged and repeated recording, and also the need to take account of other variables in fetal behaviour, before any sinister conclusions can be drawn about the absence of fetal breathing is emphasised. 
5	Locked intramedullary nailing of femoral shaft fractures. One hundred twenty-three femoral shaft fractures were treated with Grosse-Kempf slotted, locked nails and followed for a median 20 (range, 12-60) months. There were eight intraoperative and 11 postoperative complications, among them two superficial and two deep infections. Most of the intraoperative complications and some postoperatively lost reductions could have been prevented by a better operative technique and judgment of stability. Seventy-eight results were graded as excellent, 24 as good, 19 as fair, and two as poor (one 9-cm shortening and one 40 degrees external malrotation). All fractures united without further procedures during the first year. 
1	A case of massive true thymic hyperplasia with non-Hodgkin's lymphoma. A case of massive true thymic hyperplasia with non-Hodgkin's lymphoma of the mediastinum is reported in a 14-year-old boy. Computed tomographic scan of the chest showed a mass of the anterior mediastinum and conspicuous swelling of the lymph nodes in the upper and lower mediastinum. They were grossly resected. The tumor of the anterior mediastinum was histologically diagnosed as true thymic hyperplasia. All of the mediastinal lymph nodes were diagnosed as non-Hodgkin's lymphoma, diffuse, mixed small and large cell type. 
1	Effect of dietary alpha-linolenic acid on growth, metastasis, fatty acid profile and prostaglandin production of two murine mammary adenocarcinomas. The purpose of this study was to determine whether dietary (n-3) fatty acids would affect mammary tumor growth and metastasis. Weanling female BALB/c mice were fed diets that contained 10% corn oil (CO), linseed oil (LO) or a fish oil-corn oil mix (FO) for 3-8 wk prior to receiving subcutaneous injections of one of two syngeneic mammary tumor cell types (410 and 410.4). Tumor growth was assessed by monitoring mean tumor diameter and tumor weight upon removal. Feeding LO, but not FO, reduced the growth (p less than 0.05) of 410.4 mammary tumors compared with growth in those fed CO. Metastasis data paralleled the tumor growth rate. Feeding LO and FO enhanced (p less than 0.005) incorporation of (n-3) fatty acids into tumors. Tumor prostaglandin E (PGE) production was reduced (p less than 0.005) by LO and FO, compared with CO. FO feeding reduced 410.4 tumor PGE synthesis more (p less than 0.05) than LO feeding, yet tumor growth was only inhibited by LO. These data suggest an inhibitory effect of dietary linolenic acid [i.e., 18:3 (n-3)] on mammary tumor growth and metastasis. However, this effect did not directly correlate with diet-induced changes in PGE synthesis. 
5	A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies. Angioplasty causes substantial injury to the coronary artery intima and media that is unrecognizable by angiography. On the basis of a substantial body of research in oncology and wound healing, it is hypothesized that restenosis is a manifestation of the general wound healing response expressed specifically in vascular tissue. The temporal response to injury occurs in three characteristic phases: inflammation, granulation and extracellular matrix remodeling. The specific expression of these phases in the coronary artery leads to intimal hyperplasia at 1 to 4 months. The major milestones in the temporal sequence of restenosis are platelet aggregation, inflammatory cell infiltration, release of growth factors, medial smooth muscle cell modulation and proliferation, proteoglycan deposition and extracellular matrix remodeling. Each step has potential inhibitors that could be used for preventive therapy. Resolution of restenosis, however, probably requires both creation of the largest possible residual lumen and substantial inhibition of intimal hyperplasia. 
1	Oral cancer: a survey of 566 cases from the University of Connecticut Oral Pathology Biopsy Service, 1975-1986. A survey of the University of Connecticut Oral Pathology Biopsy Service was undertaken to analyze cases of oral cancer accessioned during the 12-year period, 1975 through 1986 inclusive. Of 33,429 total specimens accessioned, there were 546 malignant oral neoplasms diagnosed and reported. Sixty-five (11.5%) originated from out of state. Invasive intraoral squamous cell carcinoma was the predominant tumor (69.7% of total), whereas lip cancer constituted only 2.8% of all malignancies. Minor salivary gland adenocarcinomas accounted for 11% of total malignancies whereas verrucous carcinoma, carcinoma in situ, and miscellaneous other forms of oral cancer accounted for the remainder (4.6%, 5.3%, and 6.6%, respectively). Cases of invasive squamous cell carcinoma were further analyzed by year, sex distribution, location subsite, age at diagnosis, and histologic grade. With the exception of histologic grading, we found that the characterization of cases of squamous cell carcinoma within the biopsy service tended to parallel results from a separate but related statewide analysis of both oral cancer and intraoral squamous cell carcinoma from Connecticut over a much longer time span. We concluded that the picture of oral cancer as characterized by cases within the University of Connecticut Oral Pathology Biopsy Service is generally reflective of the disease on a statewide level. 
5	Coronary flow and mental stress. Experimental findings. The hemodynamic, electrocardiographic, and coronary flow responses to a psychological test were studied in 13 pigs both in the absence (group 1, n = 8) and the presence (group 2, n = 5) of a transient occlusion of the left anterior descending coronary artery. The psychological test consisted of presenting food to a fasting but restrained animal for 3 minutes. In group 1, stress increased the heart rate from 128 +/- 5 to 176 +/- 8 beats/min (mean +/- SEM) and arterial pressure from 93 +/- 4 to 112 mm Hg. Comparing the individual increase in rate-pressure product with the increase in coronary conductance during the test, a parallel response was found in only two animals, whereas a relatively lower coronary conductance was observed in the remainder, suggesting vasoconstriction. Clinical signs of ischemia or life-threatening arrhythmias were never observed in this group of animals. Each group 2 animal underwent two occlusions of the left anterior descending coronary artery, randomly performed on separate days both in the presence and the absence of the food deprivation stress. When the latter was applied in the presence of occlusion, all animals developed ventricular fibrillation in less than 2 minutes (mean, 81.4 seconds). Conversely, only one animal had ventricular fibrillation when a 3-minute occlusion was performed without exposure to stress. This occurred despite the fact that more severe ischemia (as detected by an increase in left ventricular end-diastolic pressure and decreases in dP/dt and systolic pressure) was recorded at 3 minutes of occlusion. 
2	Does auxiliary heterotopic liver transplantation reverse hypersplenism and portal hypertension? In this study, performed to assess the effect of auxiliary heterotopic liver transplantation on portal hypertension and hypersplenism, eight patients with chronic liver disease who underwent the procedure and had functioning grafts for at least 6 months were analyzed. The transplantation resulted in (a) normalization of platelet and leukocyte counts, (b) reduction of splenomegaly by 20% +/- 3% (P less than 0.02), (c) disappearance of ascites, and (d) diminution of esophageal varices in all patients. Intraoperatively, the mean portacaval pressure gradient decreased with 54% +/- 7% after recirculation of the graft (P less than 0.05). In conclusion, a functioning auxiliary heterotopic liver graft decompresses portal hypertension and reverses hypersplenism. 
3	Traumatic subarachnoid-pleural fistula in a child. A case report. A seven-year-old girl sustained a gunshot wound to the chest and spine. Evaluation of a persistent pleural effusion demonstrated a subarachnoid-pleural fistula. Surgical closure of the dural defect resulted in resolution of the fistula. Traumatic subarachnoid-pleural fistulae are rare. The diagnosis is reached by an awareness of fistula formation from penetrating or blunt trauma to the chest. 
3	Spatial dispersion of magnetic stimulation in peripheral nerves. To assess the longitudinal dispersion of the stimulus induced by the magnetic coil, collision experiments were performed in seven normal ulnar nerves. A supramaximal electrical stimulus S1 was delivered at the wrist, and followed by a supramaximal stimulus S2 in the upper arm, which was either electrical (electrical collision studies), or magnetic (magnetic collision studies). The interstimulus interval was varied by 0.2 msec increments from the time of complete cancellation of the S2 evoked motor response onwards, to include the entire span of recovery of that compound motor action potential. Collision curves were obtained for both magnetic and electrical stimuli by plotting the amplitude of the motor response elicited by S2 as a function of the interstimulus interval. In all seven normal ulnar nerves, comparison of the collision curves showed that the S2 evoked motor response is restored significantly more slowly when magnetic stimulation is used. This finding is best explained by longitudinal dispersion of the stimulus induced by the magnetic coil relative to conventional electrical stimulation, the large fibers being stimulated further away from the coil than the small ones. This interpretation is confirmed by the findings obtained with the same method in two cases of ulnar neuropathy, and by comparison of different intensities of magnetic stimulation. 
1	Growth of group A rotaviruses in a human liver cell line. Recent observations in children with rotavirus gastroenteritis and in infant mice given rotavirus vaccine by oral administration suggest that this well-known gastrointestinal pathogen may infect the liver. To examine this possibility, the susceptibility of Hep G2 cells to infection with a variety of rotavirus strains was tested. These cells were used because they are considered to be well differentiated and exhibit many liver-specific functions. The Hep G2 cells supported the growth of the simian strain rhesus rotavirus (MMU 18006), a strain currently being used in vaccine trails, but did not support the growth of any human strain (D, DS1, Price or ST3). The rhesus rotavirus infection was cytopathic and resulted in release of lactate dehydrogenase. Rhesus rotavirus growth in Hep G2 cells displayed trypsin-enhanced infectivity and was inhibited by pretreatment of cells with Arthrobacter ureafaciens neuraminidase but not with neuraminidase from Clostridium perfringens. Hep G2 cells were also permissive for another simian strain (SA11), a bovine strain (UK) and single gene substitution reassortants containing VP7 (the major outer capsid neutralization protein) from a human rotavirus strain and the remaining 10 genes from either rhesus rotavirus or UK. In general, UK and its reassortants produced lower levels of antigen than did rhesus rotavirus and its reassortants. Hep G2 cells and other hepatic cell lines may prove to be useful tools to explore the hepatotropic potential of wild-type rotaviruses and candidate vaccine strains. 
4	Transesophageal echocardiography in acute aortic transection. Confirming the diagnosis of acute transection of the descending aorta can be problematic. Unnecessary patient movement and time delay are often associated with conventional investigations. We describe a patient in whom such an injury was clearly and quickly defined at the bedside by transesophageal echocardiography. 
2	Current concepts of cholesterol transport and crystal formation in human bile. The presence of vesicles in human bile probably accounts almost entirely for the frequently observed, but hitherto unexplained, phenomenon of metastable cholesterol supersaturation. This, in turn, largely explains the prolonged stability of cholesterol solubilized in supersaturated human bile. Under certain overall compositional conditions for a supersaturated native bile, the vesicular phase in its contribution to total cholesterol transport also becomes supersaturated in cholesterol. Because of this, the vesicles also become unstable, leading to formation of cholesterol crystals. A simple but common example of one factor affecting composition in this way is concentration of total solutes, especially the biliary lipids. Conversely, dilution of bile (e.g., hepatic bile) markedly reduces the cholesterol saturation level in biliary vesicles. The result is that such vesicles become much more stable. Under these conditions, cholesterol crystal formation becomes unlikely and rarely, if ever, occurs. 
5	Synergism of herpes simplex virus and tobacco-specific N'-nitrosamines in cell transformation. Previous studies indicate that herpes simplex virus (HSV) enhances the carcinogenic activity of smokeless tobacco and tobacco-related chemical carcinogens in animals. Since tobacco-specific N'-nitrosamines (TSNAs) such as N'-nitrosonornicotine (NNN) and 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users, the combined effects of TSNAs and HSV in cell transformation were investigated. Exposure of cells to NNN or NNK followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone. This study suggests that TSNAs and HSV can interact together and show synergism in cell transformation. 
1	Intratumoral oxygen pressure in malignant brain tumor. Oxygen pressure (pO2) in brain tumors, pO2 in brain cortex surrounding the tumors, and PaO2 were measured simultaneously during total resection in 16 patients with previously untreated brain tumors in order to detect hypoxic regions within the tumors. When the inhaled O2:N2O ratio was 1:3 under enflurane anesthesia, mean PaO2 was 109.2 +/- 5.8 mm Hg, a rather high value when compared with that obtained when air is inhaled under atmospheric pressure. The simultaneously measured intratumoral pO2 and pO2 in brain cortex surrounding the tumor were 15.3 +/- 2.3 and 59.8 +/- 6.5 mm Hg, respectively. Each intratumoral pO2 value was significantly lower than that of pO2 in brain cortex surrounding the tumor (mean less than 30 mm Hg, Wilcoxon signed rank test, p less than 0.005) and influenced the oxygen effects on radiation. These results appear to confirm that there are hypoxic regions within human brain tumors. A comparison between intratumoral pO2 and either the angiographic or contrast-enhanced computerized tomography scans of the tumor vasculature disclosed no correlation. 
1	Idiopathic and glucocorticoid-induced spinal epidural lipomatosis. Pathological overgrowth of the epidural fat in the spine has been described and reported nearly exclusively in patients either with Cushing's syndrome or on chronic intake of glucocorticoids for a variety of clinical disorders. The authors report four patients with documented spinal lipomatosis (three pathologically and one radiologically). Only one of these patients received corticosteroids, and none had an underlying endocrinological abnormality. All four patients were adult males with a mean age at onset of symptoms of 43 years (range from 18 to 60 years). The symptoms ranged from simple neurogenic claudication and radicular pain to frank myelopathy. Myelography followed by computerized tomography were instrumental in the diagnosis of the first three patients; the fourth was diagnosed by magnetic resonance imaging. The thoracic spine was involved in two cases and the lumbosacral area in the other two. The different treatment modalities were tailored according to the symptomatology of the patients. These included weight reduction of an overweight patient with minimal neurological findings in one case and decompressive laminectomy and fat debulking to achieve adequate cord decompression in the remaining three cases. Two patients improved significantly, the condition of one stabilized, and the fourth required a second decompression at other spinal levels. The various modalities of treatment and their potential complications are discussed. 
5	Langerhans cell histiocytosis in monozygotic twins. Langerhans cells histiocytosis, one of a group of histiocytosis syndromes characterized by Langerhans cell infiltration, has many clinical manifestations. In the past 30 years, numerous cases of presumed Letterer-Siwe disease, the acute multiorgan variant, have been reported in twins and siblings. Only recently has the Histiocyte Society established a criterion for a "definitive diagnosis" of Langerhans cell histiocytosis--the presence of Birbeck granules within the cells of the histiocytic infiltrate. We report the fatal outcome of Langerhans cell histiocytosis in monozygotic twin infants. There is no satisfactory explanation why Langerhans cell histiocytosis occurs concurrently in twins. We suggest that cytokines may provide an endogenous signal that triggers the pathologic proliferation of Langerhans cells. 
4	Increasing the yield of ventricular tachycardia induction: a prospective, randomized comparative study of the standard ventricular stimulation protocol to a short-to-long protocol and a new two-site protocol. Programmed ventricular stimulation with a standard protocol that used up to three extrastimuli was compared prospectively with a short-to-long protocol and a two-site protocol in 77 consecutive patients undergoing electrophysiologic study in an attempt to increase the yield of ventricular tachycardia (VT) induction. The short-to-long protocol uses a train of eight stimuli at a short cycle length and up to two extrastimuli. The two-site protocol is similar to the standard protocol but delivers the last extrastimulus via a second spatially separated right ventricular catheter. Patients were divided into two groups based on indications for study: group 1 included 45 patients with syncope, nonsustained VT, or both, and group 2 included 32 patients with a history of sustained VT, sudden cardiac death, or both. The yield of VT induction with the short-to-long protocol was less than that with the standard protocol. In none of the patients in group 1 in whom the standard protocol results were negative did the short-to-long protocol produce sustained VT. Only two patients, both in group 2, had sustained arrhythmias induced by the short-to-long protocol when the standard protocol results were negative: one had sustained VT induced and one with long QT syndrome had ventricular fibrillation (VF) induced with the short-to-long protocol. However, the short-to-long protocol failed to induce sustained VT in seven patients in whom the standard protocol produced sustained VT. All seven of these patients required three extrastimuli with the standard protocol for induction of VT. 
3	Effects of vagal stimulation on experimentally induced seizures in rats. Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded. 
3	Percutaneous thecoperitoneal shunt for syringomyelia. Report of three cases. Between January and April, 1990, three consecutive cases of syringomyelia were treated by percutaneous placement of thecoperitoneal shunts. Two of these patients had undergone craniovertebral decompression earlier at other centers and the third was treated primarily by a thecoperitoneal shunt. In each case, the syrinx was associated with Chiari I malformation, although the clinical presentation was due to a myelopathy. All three patients obtained unequivocal benefit from this simple procedure. Postoperative magnetic resonance images showed considerable shrinkage of the cysts corresponding with clinical improvement. 
5	Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody? Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and hyperkalemia. The bradyarrhythmias, which consist of disturbances in conduction and block at the level of the atrioventricular and sinus nodes, are mediated by a direct and vagotonic effect. The vagotonic effect of excess digoxin may also result in a marked slowing of the sinus rate in the setting of severe toxicity. Digoxin increases automatic and triggered electrical activity in atrial muscle, His-Purkinje system, and ventricular muscle, which predisposes to tachycardias. Many of the tachyarrhythmias are relatively specific for the toxic effects of digoxin. Atrial tachycardias with variable atrioventricular block, accelerated junctional rhythms (especially in the setting of atrial fibrillation), and fascicular tachycardias are characteristic digoxin toxic rhythms. Digoxin-specific antibody fragments should be considered the treatment of choice for any digoxin toxic arrhythmia associated with hemodynamic compromise or the threat of hemodynamic compromise. Hyperkalemia, when due to acute severe digoxin toxicity, is also an appropriate indication for digoxin-specific Fab fragment therapy. When assessing the risk:benefit ratio for using digoxin-specific Fab fragment therapy, one needs to determine, in addition to the electrocardiographic manifestations and patient's hemodynamic status (1) the severity of toxicity, as indexed by the amount ingested and/or the serum digoxin concentration; (2) the expected time course for reversal of toxicity, which is usually determined by the status of renal function; (3) the need for digoxin to provide ventricular rate control or improved ventricular contractility and therapeutic alternatives to digoxin; (4) the presence of a strong allergy history; (5) the presence of such factors as increased age and severity of heart disease that may predispose to digoxin toxicity. 
4	Morbidity, mortality, and quality of life for patients treated with levothyroxine In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy. 
2	Peritoneal dialysis in the geriatric patient. Elderly patients on chronic peritoneal dialysis (CPD) from two large chronic peritoneal dialysis programs were compared with younger patients in regard to peritonitis rates, catheter problems, hospital days, transfers to other forms of therapy, and mortality. Peritonitis rates and organisms were similar in younger and older patients. Catheter replacements were less common in the elderly. Differences in hospital days were attributable to hospitalization for vascular disease. The elderly were more likely to have the first episode of peritonitis, to die and to change dialysis modalities at all times after the first year of continuous ambulatory peritoneal dialysis (CAPD) treatment, although other than increased mortality, differences between the two groups were small. CPD appears to be an acceptable form of renal replacement therapy in the elderly. 
1	Peptic ulcer perforation as the presentation of Zollinger-Ellison syndrome. We examined the characteristics of patients with Zollinger-Ellison syndrome who developed a perforation prior to diagnosis to determine whether any clinical features were useful markers of the syndrome. Of 160 patients with Zollinger-Ellison syndrome, perforation occurred prior to the diagnosis being made in 11 (7%). At surgery, perforations were found in the duodenum in six cases and in the jejunum in five. In no case was tumor identified at emergency surgery, and the diagnosis of Zollinger-Ellison syndrome was made only in the postoperative period when excessive gastric secretions were noted. Neither acid output nor serum gastrin concentration were useful predictors for perforation. The patients, six men and five women, were 27-61 years old (median 48) and one had MEN-1. Three patients had no symptoms prior to the perforation. The other eight had symptoms for 1-15 years, with diarrhea occurring in 45% of the cases. Following the diagnosis of Zollinger-Ellison syndrome, patients were given medication to control gastric acid hypersecretion. Eight patients remained well, but the three patients who had had a partial gastrectomy had a complicated course despite medical therapy. Although features of perforation in Zollinger-Ellison syndrome are not specific, jejunal perforation or perforation associated with a history of diarrhea is suggestive of the diagnosis. Serum gastrin should be measured in every case and a partial gastrectomy avoided. 
5	Carotid-esophageal fistula following a penetrating neck injury: case report. Carotid arterial injuries frequently are associated with injuries to adjacent structure of the neck, particularly the esophagus and trachea. Complications from these repairs are common and fistula formation is herein described between the carotid artery and esophageal repair. 
5	Pressure-curve variations after trabeculectomy for chronic primary open-angle glaucoma. We report the results of a 5-year study of the influence of trabeculectomy on the maximum intraocular pressure (IOP) and the amplitude of its diurnal oscillation in 26 eyes (14 patients) with open-angle glaucoma. Pressure-curves were recorded before surgery and at 1 year and 5 years after surgery. The latter two pressure-curves demonstrated that trabeculectomy significantly reduced both the maximum IOP and the amplitude of the oscillations below preoperative values. 
5	Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the gamma nail and the dynamic hip screw. We have prospectively compared the fixation of 100 intertrochanteric fractures of the proximal femur in elderly patients with random use of either a Dynamic Hip Screw (DHS) or a new intramedullary device, the Gamma nail. We found no difference in operating time, blood loss, wound complications, stay in hospital, place of eventual discharge, or the patients' mobility at final review. There was no difference in failure of proximal fixation: cut-out occurred in three cases with the DHS, and twice with the Gamma nail. However, in four cases fracture of the femur occurred close to the Gamma nail, requiring further major surgery. In the absence of these complications, union was seen by six months in both groups. 
3	Strapless oral-nasal interface for positive-pressure ventilation. A custom-fabricated strapless oral-nasal interface (SONI) is described. It was used in the long-term administration of intermittent positive-pressure ventilation (IPPV) by 18 patients with paralytic or restrictive pulmonary insufficiency. This interface is an acrylic shell which is firmly fixed to an orthodontic bite plate; it is designed to form a seal over the nose and mouth for the entry of IPPV. Eight patients were ventilator dependent 24 hours a day. The ten patients who required only nocturnal aid had improvement in daytime arterial blood gases. Although nine of these patients could manage less than 15 minutes of unassisted breathing (free time) supine, all slept supine on SONI IPPV. The 13 patients who underwent sleep monitoring maintained a mean oxygen saturation of 95.3% +/- 1.7% and acceptable end-tidal pCO2 (30 to 45 mmHg). These 13 patients have used SONI IPPV for an average of 22 months (range = 3 to 63 months). Impediments to successful long-term use of a SONI include the presence of a hyperactive gag reflex or stimulation of excessive oral secretions. When combined with mouth IPPV, glossopharyngeal breathing, the intermittent abdominal pressure ventilator, or the cuirass ventilator for daytime use, SONI IPPV is an option for the patient who prefers total ventilatory support by noninvasive means. 
3	Acquired childhood aphasia. Outcome 1 year after onset. The effects of the variables age at onset, cause, severity and bilaterality of lesion, and type of aphasia on course and outcome were investigated in a group of 28 aphasic children. Analysis of spontaneous speech and tests of auditory verbal comprehension were used to determine the presence of aphasia. The severity of the cerebral lesion was assessed using a rating scale for computed tomographic scans. Most of the children had not recovered completely 1 year after onset. Recovery was significantly different according to etiological categories. Complete recovery was seen in the majority of traumatic cases. 
4	Interpreting results of exercise studies after acute myocardial infarction altered by thrombolytic therapy, coronary angioplasty or bypass. Numerous studies have assessed the ability of exercise modalities to predict patient outcome after acute myocardial infarction (AMI). Implicit in the use of these prior data to assess the prognosis of patients currently undergoing exercise studies is the assumption that patients selected for exercise assessment are similar over time and that the data generated in the past are therefore applicable to the current patient populations. This study retrospectively assessed the clinical, exercise, and rest and exercise radionuclide angiographic data in 791 consecutive patients referred for exercise radionuclide angiography within 1 month after AMI during a 5-year period to determine if the clinical and exercise characteristics of patients referred for exercise evaluation after infarction have changed significantly over time. Most parameters examined demonstrated significant increasing trends, including thrombolytic therapy at the time of AMI, revascularization procedure between AMI and exercise assessment, age, beta-blocker usage, Q-wave AMI, inferior infarction, exercise double product, exercise capacity, significant ST-segment depression with exercise, peak ejection fraction, and change in ejection fraction with exercise. These data indicate that the characteristics of patients selected to undergo exercise after AMI in a large referral center have changed significantly over time. If these data are applicable to other referral centers and to other exercise testing modalities, previously published results regarding exercise assessment after AMI will need to be reconfirmed in patients currently selected for testing, since these results may no longer be applicable in this current era of aggressive medical and interventional management. 
5	Massive splenomegaly. Superior results with a combined endovascular and operative approach. Splenectomy for massive splenomegaly (drained splenic weight, greater than 1000 g) has an uncommonly high morbidity and mortality because of technical challenges and problems of hemostasis. In a group of 10 patients with massive splenomegaly due to myeloproliferative disorders (average splenic weight, 4193 g), we developed a management algorithm based on preoperative angiographic embolization of the splenic artery. Average operating time was 1.7 hours (range, 1 to 2.5 hours). Average blood loss was 528 mL; six of the 10 patients had blood loss less than 250 mL. There were four minor complications and one major complication (gastric ulcer requiring reoperation). There were no deaths in the perioperative period, and no patients required reoperation for hemorrhage. 
5	Septic arthritis of the C1-C2 lateral facet joint and torticollis: pseudo-Grisel's syndrome. We present the case of a 76-year-old man who experienced the sudden development of fever, rightsided neck pain and stiffness, and torticollis. A soft tissue mass was noted on the right side of his neck, but his head was tilted to the left. Computed tomography scans (with reformatted sagittal and coronal images) of the patient's cervical spine revealed destructive changes of the right lateral masses of C1 and C2 and the clivus, and a well-delineated peridontoid soft tissue mass (confirmed by magnetic resonance imaging). After the second episode of right-sided hemiparesis, he underwent transoral surgical exploration, with anterior decompression and odontoidectomy. Histologic examination of the surgical material revealed granulation tissue, fibrosis, and chronic inflammation, consistent with abscess formation with invasion and compression of the spinal cord and bone. This case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection. 
4	Segmented turboFLASH: method for breath-hold MR imaging of the liver with flexible contrast. A method called segmented turboFLASH imaging allows high-resolution, multisection, short-inversion-time (TI) inversion-recovery (STIR), T1- or T2-weighted magnetic resonance (MR) studies of the liver to be completed within a breath-hold interval. The method was applied in a phantom and in 19 patients with hepatic lesions. Sequence comparisons were performed among segmented turboFLASH, single-shot turboFLASH, T1-weighted gradient-echo with ultrashort echo time, and T2-weighted spin-echo (SE) techniques. Signal from fat and liver could be nulled with the segmented turboFLASH method, with TIs of 10 and 300 msec, respectively; signal from these tissues could not be eliminated with the single-shot approach. Signal-difference-to-noise ratios and contrast for the best segmented sequences were comparable with those of the best T2-weighted SE and T1-weighted gradient-echo techniques. It is concluded that it is feasible to obtain breath-hold images with arbitrary tissue contrast by means of segmented turboFLASH imaging. The method may prove helpful for the detection and characterization of hepatic lesions and will likely have applications to other anatomic regions such as the chest and pelvis. 
5	Anterior lingual mandibular salivary gland defect. Evaluation of twenty-four cases. Lingual mandibular salivary gland defects in the posterior part of the mandible are not uncommon. Analogous defects in the anterior region, however, are rare, and the four new cases presented in this report bring the total number of reported cases up to 24. The purpose of the present study was to review and analyze the clinical, radiographic, and histologic features of the previously reported cases together with those of the present study. The majority of these defects were located in the cuspid and/or premolar area and were diagnosed in men in their fifth and sixth decades of life. Almost all defects contained normal salivary gland tissue. The differential diagnosis, treatment, and pathogenesis of these defects are discussed. 
1	Improved silver staining of nucleolar organiser regions in paraffin wax sections using an inverted incubation technique [published erratum appears in J Clin Pathol 1991 Jun;44(6):528] A new simple modification to the silver staining of nucleolar organiser regions (AgNORs) was devised which, by performing the incubation with the slide inverted, results in minimal undesirable background staining, a persistent problem. Inverted incubation is facilitated by the use of a commercially available plastic coverplate. This technique has several additional advantages over other published staining protocols. In particular, the method is straightforward, fast, and maintains a high degree of contrast between the background and the AgNORs. 
1	Intra-abdominal "angiosarcomatosis" report of two cases after pelvic irradiation. Angiosarcomas account for only 1% to 2% of all soft tissue sarcomas with the most common site of origin being skin and subcutaneous tissue particularly on the face and scalp of elderly patients. These neoplasms rarely arise in the small or large bowel with presentation as diffuse abdominal "angiosarcomatosis." Two patients are reported who were treated with adjuvant pelvic irradiation for gynecologic malignancies (squamous cell carcinoma of the cervix and adenocarcinoma of the endometrium) in whom diffuse abdominal angiosarcoma of intestinal origin developed 7 and 18 years later. Both patients were treated with standard megavoltage irradiation. The clinical course was rapid in both cases with death due to intra-abdominal hemorrhage and bowel obstruction. The pertinent literature relating to the association between radiation therapy and subsequent development of angiosarcomas of soft tissues and other sites is briefly reviewed. 
4	Effects of two chest tube clearance protocols on drainage in patients after myocardial revascularization surgery. The purpose of the study was to determine the effects of two methods of clot clearance on chest tube drainage in patients undergoing myocardial revascularization. Two hundred adult patients immediately after myocardial revascularization were randomly assigned to a specific chest tube manipulation group. The dependent variables were drainage, incidence of cardiac tamponade, incidence of surgical reentry, hemodynamic values, and number of manipulation episodes. Statistical analyses revealed no difference in any of the dependent variables when milking and stripping were used. Of the 200 patients, 78 did not require any manipulation of the chest tubes in the first 8 hours after surgery. One patient had signs of cardiac tamponade and six other patients required surgical reentry. Positioning of the connecting tube in a nondependent position assisted with the removal of drainage from the chest cavity. In conclusion, patients having myocardial revascularization did not need their chest tubes manipulated the first 8 hours after surgery. Visible drainage in the chest tube did not cause a lack of patency. 
5	Thalidomide: treatment of severe recurrent aphthous stomatitis in patients with AIDS. An increasing number of AIDS patients have been noted to suffer severe recurrent aphthous stomatitis (RAS), a condition often associated with high morbidity that remains unresponsive to conventional therapeutic interventions. In two cases thalidomide was administered to successfully treat AIDS patients with RAS. Both patients experienced complete abatement of pain shortly after therapy was initiated. Ulcerations that were present for months resolved after three or four weeks of thalidomide therapy without any adverse effects. Thalidomide appears to be an effective agent for the treatment of severe RAS unresponsive to traditional therapies. 
4	Interaction of 1,25-dihydroxyvitamin D and plasma renin activity in high renin essential hypertension. Renin secretion by the kidney is inhibited by an increase in free intracellular calcium concentration. This increase in free intracellular calcium content may be augmented by serum 1,25-dihydroxyvitamin D. In 10 subjects with high renin hypertension, an increase in dietary sodium intake resulted in an increase in urinary calcium excretion (2.5 to 3.4 mmol/L, P = .011) and an increase in serum 1,25-dihydroxyvitamin D (51.2 to 61.0 pmol/L, P = .045). An inverse correlation existed between the change in vitamin D and the change in plasma renin activity (r = -0.765, P = .01). An inverse correlation also existed between the change in plasma renin activity and the change in mean arterial blood pressure (r = -0.757, P = .011). It is postulated that the increase in dietary sodium led to an increase in serum 1,25-dihydroxyvitamin D concentration, which may have contributed to an increase in intracellular calcium concentration, a decrease in renal secretion of renin, and a fall in plasma renin activity. The resultant fall in PRA in part effected the change in blood pressure to the increased sodium intake. Therefore, 1,25-dihydroxyvitamin D may be a mediator in the response of high renin hypertension to increased sodium intake. 
5	A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. The role of leukocyte adherence in the mechanism of gastropathy induced by nonsteroidal antiinflammatory drugs was investigated using a rabbit model. Gastric damage was induced by intragastric instillation of indomethacin [5 mg/mL] for a period of 30 minutes. Histologically, this treatment resulted in extensive vascular congestion and leukocyte margination within the mucosa. Pretreatment with a monoclonal antibody [IB-4] directed against the common beta subunit of the CD11/CD18 adhesion glycoprotein complex significantly (P less than 0.05) reduced both the vasocongestion and the prevalence of leukocyte margination. Macroscopically, indomethacin treatment resulted in the formation of numerous hemorrhagic lesions in the corpus region of the stomach. Pretreatment with IB-4 reduced the extent of gastric hemorrhagic damage by approximately 85% (P less than 0.001). Damage in the group pretreated with IB-4 did not differ significantly from that in rabbits that did not receive indomethacin. In separate experiments, the dose of IB-4 used was shown to completely suppress the recruitment of granulocytes in response to two different agonists. These results support the hypothesis that leukocyte adherence to the vascular endothelium is an important event in the pathogenesis of ulceration induced by nonsteroidal antiinflammatory drugs. Leukocytes might contribute to ulceration by occluding microvessels, thereby reducing mucosal blood flow, and by releasing various mediators, proteases, and free radicals that can produce tissue necrosis. 
3	Cervico-ocular function in patients with spasmodic torticollis. The cervico-ocular (COR) and active and passive vestibulo-ocular reflexes (VOR) were measured in seven patients with spasmodic torticollis (ST) and six normal controls. The COR was found to be weak or absent in both groups. The VOR gain was similar in the two groups but five patients had a significant asymmetry of the response. There was no evidence of abnormal cervico-vestibular interaction during active head rotation. The study suggests that the VOR asymmetry frequently found in ST cannot be explained on the basis of an abnormal cervical input. 
1	All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. All-trans retinoic acid induces leukemic cells from patients with acute promyelocytic leukemia (M3) to differentiate in vitro to mature granulocytes which express the CD15 antigen and are capable of respiratory burst function. Of 35 M3 samples, only one failed to respond. In eight cases, we compared the efficacy of two naturally occurring isomers of retinoic acid, all-trans RA and 13-cis RA. Both isomers induce maximal differentiation at 10(-6) mol/L. The maximal response was maintained at 10(-7) mol/L for the all-trans but not for the 13-cis RA. We also observed that the metabolites 4-oxo-all-trans and 4-oxo-13-cis were effective at 10(-6) mol/L. This 1 order of magnitude difference in the in vitro differentiating potencies of all-trans RA and 13-cis RA in the blasts of promyelocytic leukemias predicts a difference in the clinical efficacy of the two drugs. 
4	Ponderal index as a predictor of postoperative complications. Four hundred sixty-eight patients undergoing elective surgery were prospectively followed for the development of postoperative complications. There was a trend toward increasing complication rate with a lower ponderal index. However, lower ponderal indices were associated with increasing rates of diabetes mellitus and hypertension. Of these patients, forty cases with postoperative complications were matched to 40 control cases for sex, age, concomitant illness and operation performed. The cases of postoperative complications had a statistically significantly lower ponderal index than the controls (11.98 versus 12.43). The increased risk of postoperative complications in those patients with a ponderal index of less than 11 was 3.36, and less than 13 was 3.44. Surgeons who treated patients with lower ponderal indices need to have a high index of suspicion for the development of postoperative complications in these patients. 
1	Prognostic factors in yolk sac tumors of the ovary. A clinicopathologic analysis of 29 cases. Twenty-nine ovarian cancer patients with yolk sac tumors and germ cell tumors with yolk sac tissue as a component of their disease (16 endodermal sinus tumor, 11 mixed germ cell tumors, one embryonal carcinoma, and one polyembryoma) were treated with cytoreductive surgery and combination chemotherapy. Prognostic factors were investigated in this group. Patients with Stage I disease had a more favorable prognosis (P less than 0.003) than those with Stages II and IV disease. The difference in prognosis was significant in cases where residual tumor was absent (P less than 0.003) and in cases where ascites was either absent or less than 100 ml in volume (P less than 0.05). Endodermal sinus tumor with either an intestinal (P less than 0.05) or microcystic pattern (P less than 0.01) was more common in survivors than in those who died. The age, preoperative serum alpha-fetoprotein level, maximum tumor size, and tumor weight had no significant correlation with prognosis. In advanced cases, chemotherapy regimens including cisplatin gave better results than those containing vincristine, dactinomycin, and cyclophosphamide (P less than 0.05). The optimal treatment of yolk sac tumors or tumors with yolk sac tissue as a component of the ovary is discussed in light of these results. 
5	Preoperative piroxicam for postoperative analgesia in dental surgery. Fifty patients were allocated randomly to receive placebo or piroxicam 40 mg, 2.5 h before surgical removal of lower third molars under general anaesthesia. A significantly greater number of patients in the piroxicam group did not require opioid analgesia after operation (P less than 0.05). The piroxicam group also required fewer doses of paracetamol in the first 24 h after recovery from anaesthesia (P less than 0.05), and the time from recovery to first postoperative analgesia was longer in those patients who had received piroxicam (P less than 0.05). Piroxicam did not significantly prolong the duration of recovery from anaesthesia. 
3	The headache-specific locus of control scale: adaptation to recurrent headaches. This paper describes the development, psychometric properties, and construct and incremental validity of a Headache-Specific Locus of Control Scale (HSLC). The HSLC is a 33 item scale designed specifically for recurrent headache sufferers. It assesses the individual's perceptions that headache problems and headache relief are determined primarily by: the individual's behavior (Internal factors), Health Care Professionals, or Chance factors. The psychometric properties of the HSLC were satisfactory. Among our findings were that: (1) the belief that headache problems and relief are determined by chance factors was associated with higher levels of depression, physical complaints, reliance on maladaptive pain coping strategies (p less than .001), and greater headache-related disability (p less than .01); (2) the belief that headache problems and relief are influenced primarily by the ministrations of health care professionals was associated with higher levels of medication use (p less than .01) and preference for medical treatment (p less than .001); and (3) the belief that headache problems are determined by the individual's responses and behaviors was associated with a preference for self-regulation treatment (p less than .01). These findings suggest adaptation to headache problems is influenced not only by the frequency and severity of the headache episodes, but by locus of control beliefs. The assessment of locus of control beliefs may provide useful information not typically obtained from standard medical evaluations. 
4	Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery. Comparatively little attention has been paid to the conjunctival toxicity of antibiotics administered at the time of cataract surgery. We have observed the effect of subconjunctival gentamicin and cefuroxime injection, using colour photography in a randomised single blind trial of 121 patients undergoing routine cataract surgery. Our results suggest that a hyperaemic eye is likely to occur about twice as often in patients injected with gentamicin (p less than 0.001). Gentamicin is associated with more pain postoperatively (p less than 0.05). Significant manifestations of gentamicin toxicity are conjunctival oedema and capillary closure. Cefuroxime has some theoretical advantages over gentamicin in its antibacterial spectrum. 
1	Prognosis and treatment of advanced squamous cell carcinoma secondary to epidermodysplasia verruciformis: a worldwide analysis of 11 patients. Data were collected from three medical centers in the USA, Poland, and Japan regarding 11 patients with advanced squamous cell carcinoma (SCC) secondary to epidermodysplasia verruciformis (EV). Analysis was conducted regarding primary tumor location, age at onset of EV, age at diagnosis of SCC, treatment of SCC, history of local tumor recurrence, presence of metastases, and age at death. Three of 11 patients developed both lymph node and visceral metastases and the mean patient age at death was 44 years (N = 6) with no patient to date living past 54 years. Mean patient survival time following metastases was 1.7 years (N = 2). Human papilloma virus typing of nine patients was performed. Current controversies regarding the treatment of patients with advanced SCC in the setting of EV are reviewed. 
3	Endoscopic coagulation of the choroid plexus using the Nd:YAG laser: initial experience and proposal for management. Although most patients with hydrocephalus are treated effectively with ventriculoperitoneal shunts, a small group fails to respond to diversion procedures. In some patients within this group, hydrocephalus may be caused in part by the overproduction of the cerebrospinal fluid (CSF). In other patients, previous shunt infections may limit the ability of the peritoneum to absorb fluid, and patient response to a ventriculoperitoneal shunt may be improved by reducing CSF production. We discuss a case of a 29-month-old hydrocephalic infant with a ventriculoperitoneal shunt who had ascites. Computed tomography showed bilateral symmetrical enlargement of the choroid plexus. Repeated cultures of the CSF and shunt tubing were sterile, and the daily production of the CSF exceeded 1000 ml. Therapy with acetazolamide decreased the CSF output temporarily, but it was discontinued after serious electrolyte abnormalities occurred. The endoscopic coagulation of the choroid plexus with a neodymium:YAG laser transmitted through a flexible quartz fiber decreased CSF production effectively. This procedure may be useful in a variety of clinical conditions associated with hydrocephalus or with other intraventricular lesions. 
2	Ileocolic nipple valve anastomosis for preventing recurrence of surgically treated Crohn's disease. Long-term follow-up of six patients. To prevent coloileal reflux after ileocecal resection, an ileocolic nipple valve anastomosis was constructed in six patients with Crohn's disease. The patients were observed for more than 7 years and were compared with 21 Crohn patients in whom conventional end-to-end ileocolic anastomosis was performed during the same period. The outcome was more favorable in the group with nipple valve anastomosis, i.e., longer interval between surgery and symptomatic relapse, and tendency to less frequent recurrence and re-resection. An association was found between radiologically preserved nipple valve and remission, and two patients with intact valve at long-term follow-up remained symptom-free. The observations implied that protection of the terminal ileum from coloileal reflux after ileocecal resection for Crohn's disease may favorably influence the prognosis. 
1	An immunohistochemical evaluation of progesterone receptor in frozen sections, paraffin sections, and cytologic imprints of breast carcinomas. Two monoclonal antibodies to progesterone receptor (PR), JZB39 and KD68, were used for the immunocytochemical visualization of PR in different kinds of breast cancer specimens including (1) cryostat sections of tumors frozen at -80 degrees C; (2) paraffin sections of tumors fixed in formalin or in Bouin's fixative for varying periods of time at room temperature or at 4 degrees C; and (3) imprints and cryostat sections prepared from the tissue used for frozen section diagnosis and stored at -80 degrees C after fixation in Zamboni's solution. Sections of conventionally frozen specimens as well as imprints and cryostat sections stored for varying periods of time were stained with the peroxidase-antiperoxidase technique, whereas the avidin-biotin technique was used for paraffin sections. In all types of specimens the PR immunostaining was localized to the nuclei of carcinoma cells and displayed considerable heterogeneity both in intensity and in distribution of positive cells. Close correspondence was found between the different immunohistochemical techniques as well as between immunostaining and steroid-binding assays. PR staining was more frequently positive in well-differentiated than in moderately or poorly differentiated carcinomas, whereas no meaningful correlation was found between PR staining and extent of the disease. Similar results were obtained with the immunostaining of estrogen receptor in the same material using monoclonal antibodies H222 and D75P3 gamma. Thus, by choosing the technique that best suits the type of specimen available, it is possible to obtain valid information on the receptor status of any breast carcinoma, regardless of its size and clinical presentation. 
5	Open-heart surgery in Jehovah's Witnesses. During a 7-year period, 11 adult members of the religious sect Jehovah's Witnesses underwent cardiac surgery with extracorporeal circulation. No homologous blood transfusions were given. Blood-conserving procedures were employed, viz. initial collection of autologous blood, haemofiltration or processing (Cell Saver) of blood collected during extracorporeal circulation and reinfusion of shed mediastinal blood. The total perioperative blood loss averaged 1080 ml (15 ml/kg body weight), equalling 19% of total body blood volume. The mean haemoglobin on discharge from hospital was 11.0 g/100 ml. There was no perioperative mortality. Postoperative pulmonary function was good and there was no serious morbidity. Jehovah's witnesses with serious, surgery-necessitating heart disease can be offered operation comprising recognized blood-conserving procedures. 
3	Task-dependent variations in parkinsonian motor impairments. Studies of visually-guided arm movements in patients with Parkinson's disease (PD) have suggested a relationship between slowness of movement and a reduction in the ratio of movement amplitude and peak velocity. Recent studies indicate, however, that PD impairments may be different for well-learned, natural movements performed without visual guidance, or movements associated with sequential motor behaviours such as speech. To address this issue, PD subjects and age/sex-matched controls were compared on the performance of three tasks, all of which required lowering the jaw: (1) single, rapid, visually-guided movements; (2) equivalent movements associated with a single speech syllable (inherently without visual guidance), and (3) well-learned speech movements produced in a natural sequence. PD subjects manifested similar deficits for visually-guided jaw lowering as those previously reported for arm movements, namely reduced velocity/amplitude ratios and increased movement durations. By contrast, analogous jaw movements during the sequential speech tasks were unimpaired on these measures. These results suggest that PD motor impairments are influenced by a variety of factors, including the degree to which tasks are familiar and natural, and the availability of visual information. 
2	Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat. 
3	Diurnal differences in response to oral levodopa. Diurnal differences in duration and quality of motor response to levodopa are frequently described by patients. The quality and duration of motor responses were objectively assessed to morning and afternoon oral levodopa doses in five patients with Parkinsonian motor fluctuations who complained of diurnal variation in response to their normal levodopa medication. Results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to levodopa remained unchanged throughout the day, and that the duration of response could be predicted by plasma levodopa levels. 
3	Rehabilitation in brain disorders. 2. Clinical manifestations and medical issues. This self-directed learning module highlights advances in clinical manifestations of brain disorders. It is part of the chapter on rehabilitation in brain disorders for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. This chapter is composed of four articles, and each builds on principles established in the others. This article covers medical complications, neurobehavioral aspects, and cognitive deficits seen in patients with brain disorders, specifically seizures, hydrocephalus, heterotopic ossification, and cardiovascular/pulmonary, neuroendocrine, gastrointestinal, genitourinary, communication, motoric, and visual/spatial/sensory disorders. Advances that are covered in this section are neuroendocrine complications, seizure prophylaxis, and coma treatment. The learner is directed to articles 1, 3, and 4 in this chapter for supporting information. 
3	Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma. The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors. Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p less than 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p less than 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p less than 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression. Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve. 
5	Severe gastrointestinal hemorrhage in Crohn's disease. Twenty-one of fifteen hundred twenty-six patients with Crohn's disease (CD) treated at The Mount Sinai Hospital between 1960 and 1986 developed severe gastrointestinal hemorrhage. There were 26 separate episodes of severe hemorrhage: 17 patients bled only once, three bled twice and one bled three times. The frequency of bleeding was significantly higher among patients with colonic involvement (17 of 929; 1.9%) than among those with small bowel disease alone (4 of 597; 0.7%) (p less than 0.001). Twelve patients required surgery on 13 occasions, which involved colon resection in all but one case. Eleven of these patients underwent surgery during their first hemorrhagic episodes, and 1 of 11 had a second operation for recurrent bleeding; the 12th patient, whose first hemorrhage had been treated medically, had surgery during a repeated episode of hemorrhage. The precise bleeding points could be located in only 2 of the 26 bleeding episodes, both at the ileocecal area. Three patients died, of whom two had not undergone surgery when they had bled a few weeks earlier. Primary bleeding episodes subsided without surgery in 10 of 21 cases, but 3 of these 10 patients (30%) rebled massively. By contrast primary excisional surgery was followed by recurrent hemorrhage in only 1 of 11 cases (9%). These differences in mortality and in recurrent bleeding rates, although not statistically significant, seem to favor removal of diseased bowel at the time of the first episode of massive hemorrhage. 
2	Appendiceal carcinoma masquerading as primary bladder carcinoma. We report 2 cases of appendiceal adenocarcinoma invading the bladder. Both tumors masqueraded as primary bladder carcinomas. Cystoscopic biopsies obtained adenocarcinomatous tissue and the secondary nature of the bladder lesion became apparent at laparotomy in both cases. One patient was treated with surgical resection of the appendix, the adjacent cecal wall and the bladder wall, and postoperative irradiation. She was well 10 years later. The other patient was treated with right colectomy and segmental bladder resection. She died of diffuse peritoneal recurrence 6 years later. 
3	Natural death as viewed by the medical examiner: a review of 1000 consecutive autopsies of individuals dying of natural disease. A study of 1000 consecutive autopsies of individuals dying of natural disease was conducted. Cardiovascular disease was responsible for 60.9% of all deaths with coronary artery disease--not only the main cause of cardiovascular death but also the main cause of all natural deaths--accounting for 45.1% of such cases. Diseases of the central nervous and respiratory systems accounted for 8.7 and 8.6%, respectively, of the natural deaths. Seizure disorders and pneumonia were the main causes of death in these organ systems. There were 124 deaths of children less than one year in age, 91 of which were due to sudden infant death syndrome (SIDS). All of the SIDS deaths were in children less than 10 months old. 
2	Closure of refractory perineal Crohn's lesion. Integration of hyperbaric oxygen into case management. A case is reported in which a comprehensive program of hyperbaric oxygen (HBO), surgical debridement and reconstruction, and continuing medical management resulted in complete and sustained closure of an extensive perineal Crohn's lesion refractory to conventional medical and surgical management. It is emphasized that in this case healing occurred in the setting of previous removal of all diseased intestinal tissue and only with the combined use of all three treatment modalities. HBO may be a useful adjunct in the therapy of large nonhealing perineal lesions post-proctocolectomy in patients who are unresponsive to metronidazole or to immunosuppressant therapy or who experience limiting side effects from continued medical therapy. 
1	Comparisons of diet and biochemical characteristics of stool and urine between Chinese populations with low and high colorectal cancer rates. In an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of China (low risk), and Chinese-Americans of similar ages in San Francisco County, Calif, in the United States (high risk). The findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high-fat, high-protein, and low-carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and malonaldehyde in urine. However, risk does not increase with low stool bulk and low total stool fibers. 
1	Acral melanoma: a review of 185 patients with identification of prognostic variables. One hundred eight-five patients with acral melanoma treated since 1972 were reviewed. These included 53 subungual lesions, 123 plantar lesions, and 9 palmar lesions. Eighty percent presented with stage I disease. Mean age was 57 years. Males outnumbered females 1.1:1. Seventeen percent (17%) were blacks. Actuarial 10-year survival was 58% for stage I patients and 35% for stage II patients. Univariate Cox regression analyses identified 5 prognostic variables affecting survival: stage at diagnosis (P less than 0.001), race (P less than 0.001), ulceration (P = 0.012), Clark's level (P = 0.014), and thickness of the primary lesion (P = 0.013). Factors unrelated to survival included sex of the patient, site (volar vs. subungual), histology, and treatment with amputation. Multivariate analysis for patients with stage I lesions identified race (P = 0.001) and ulceration (P = 0.018) as significant variables, with thickness approaching significance (P = 0.094). In an additional series of 71 patients with melanomas arising from extremity sites near the junction of glabrous and non-glabrous skin, survival was significantly poorer for those arising from glabrous skin (P = 0.024), and reflects a higher incidence of metastatic disease at diagnosis. Specific active immunotherapy was the principal adjuvant used for these patients, and survival was comparable to that reported with regional perfusion therapy. Acral melanoma a) has a strong racial predilection, b) carries a grave prognosis, and c) arises from glabrous skin. It is a clinical entity distinct from other extremity melanomas. Surgical management with either wide excision or amputation is appropriate for the primary lesion. 
5	Long-term morphology of spastic or flaccid muscles in spinal cord-transected rabbits. Despite difficulty in long-term maintenance of spinalized rabbits, muscular pathologic changes in chronic spinalized rabbits could be observed for a period of four weeks. Rabbits were prepared by spinal cord transection at T10 (spastic paralysis) or by spinal cord removal below L7 (flaccid paralysis). Spastic preparations showed hind-limb spasticity and reflex incontinence one to two days after operation. Hypertrophic fibers began to appear in spastic muscles after two weeks. This hypertrophy, thought to be caused by phasic repetitive contraction, was verified by electron microscopy to be different from normal exercise hypertrophy. Flaccid preparations maintained hind-limb flaccidity and overflow incontinence. In flaccid muscle, marked muscle fiber necrosis indicated rapid atrophy. Spinal deformity and joint contracture inactivate spinalized rabbits, and cause pressure sores. However, feeding assistance and avoidance of complications make long-term maintenance possible. 
5	Skeletal muscle as an alternative specimen for alcohol and drug analysis. In a random group of medical examiner cases, muscle tissue, as well as blood and vitreous humor, was analyzed for ethyl alcohol, and the results were compared. When the blood concentration was greater than 0.10 g/dL, the muscle to blood ratio was 1.00 or less (average 0.94), and when the blood concentration was less than 0.10 g/dL, this ratio was greater than 1.00 (average 1.48). The author proposes that this ratio is dependent upon the time course of absorption and distribution, as has been observed for vitreous humor, but with a more rapid equilibration. Muscle tissue was also analyzed in another group of cases found to be positive for one or more drugs in blood. The concentrations of the drugs in muscle varied from none detected to 6.5 times those in blood and seemed to be dependent on the time course between ingestion and death, as well as on the nature of the drug. For most common basic drugs, the ratios were often near unity. Muscle is proposed as a useful alternative specimen to postmortem blood. 
4	Left ventricular diastolic dysfunction presenting as ascites: the importance of clinically assessing central venous pressure. A 66-year-old man without history of heart disease or symptoms of left ventricular (LV) failure was admitted with transudative ascites. Echocardiography showed no valvular or pericardial disease and normal LV function. Gated pool scintigraphy confirmed normal LV systolic function but demonstrated severe right ventricular systolic dysfunction. Catheterization revealed left ventricular diastolic dysfunction as the cause of right-sided failure. The clinician evaluating transudative ascites cannot exclude LV failure on the basis of noninvasive assessment of systolic function alone. Appreciation of an elevated central venous pressure remains the most important evidence of a cardiac source of ascites. 
3	Magnetic resonance imaging contrast agents: theory and application to the central nervous system. The theoretical aspects of magnetic resonance (MR) imaging contrast agents are reviewed, and their current applications to the central nervous system (CNS) and their future applications are discussed. Profound differences exist between contrast agents used for MR imaging and computerized tomography (CT). In MR imaging, the contrast agents are not imaged directly but rather act on adjacent protons to shorten T1 and T2 relaxation times. This in turn results in signal intensity changes. The lanthanide metal, gadolinium, in the form of gadopentetate dimeglumine, has been found to be both safe and efficacious as the only currently approved contrast agent for MR imaging. Magnetic resonance imaging revolutionized the detection and treatment of disease affecting the brain and spine. Initially, it was thought that signal characteristics on MR imaging would allow differentiation of specific pathology. It was soon found that MR studies were able to detect more abnormalities but were less able to characterize them. The recent development of contrast agents for MR imaging has allowed this modality to surpass CT for the evaluation of most CNS lesions. At present, contrast-enhanced MR imaging is generally accepted as the study of choice for evaluating acoustic neurinomas, pituitary lesions, meningeal disease, primary and secondary brain tumors, active multiple sclerosis, intradural spinal neoplasms, intramedullary spinal disease, and postoperative states in both the spine and brain. Even when contrast-enhanced CT can detect the same abnormalities, evaluation of the lesions in multiple planes on MR imaging can sometimes yield invaluable information, especially prior to surgery. Future developments of contrast material for MR imaging include non-gadolinium compounds, intrathecal contrast media, cerebral blood flow and volume evaluation, and, possibly, antibody-labeled contrast agents. 
2	Colonoscopy during an attack of severe ulcerative colitis is a safe procedure and of great value in clinical decision making. Thirty-four patients who had severe ulcerative colitis had a colonoscopic examination during the attack. The indications were resistance to therapy and/or differential diagnostic purposes. Total colonoscopy was performed in 25 cases and less extensive examination in nine. Biopsy was taken in 22 cases. No clinically significant complications occurred. The procedure helped us to postpone immediate surgical intervention in 19 cases. Fourteen of these patients have maintenance treatment and are still well after a follow-up median time of 5 yr (6 months to 10 yr). 
5	Chronic pain in primary care. Identification and management of psychosocial factors. Chronic pain is a problem of great public health importance that is frequently seen in the primary care setting. Pain chronicity shows a strong association with psychosocial factors. Assessment of these factors should be composed of two parts: (1) psychological factors and (2) psychiatric illness. Psychological factors include all those pain-associated alterations in the patient's environment that reinforce illness behavior. Psychiatric illness includes those syndromes that retard recovery from illness or injury, such as depression, anxiety, substance abuse, and dementia. Psychiatric and psychological interventions can be successfully introduced in the context of a comprehensive rehabilitation effort. Usually these interventions can be accomplished by the family physician in concert with a consultant psychiatrist or psychologist. In severely disabled or resistant patients, referral to a multidisciplinary pain clinic will be necessary. 
5	Spreading depression-like depolarization and selective vulnerability of neurons. A brief review. If oxygen is withdrawn from rat hippocampal slices, a spreading depression-like response occurs earlier and is of larger amplitude in the CA1 area than in the dentate gyrus. After reoxygenation, recovery of synaptic transmission correlates inversely with the time spent in spreading depression. Recovery occurs more frequently in dentate gyrus than in CA1. Chlorpromazine and the gangliosides GM1 and AGF2 promote recovery from hypoxic depression of synaptic transmission in CA1. Prevention of irreversible loss of function correlates closely with a shortening of the time spent in spreading depression. If Ca2+ is withdrawn before hypoxia, then synaptic function recovers upon restoration of oxygen and [Ca2+]o, despite prolonged spreading depression. When spreading depression lasting more than 6-9 minutes is induced in fully oxygenated slices by superfusion with high-K+ solution, then transient recovery is followed by long-lasting loss of synaptic function. In intact brain of anesthetized rats, synaptic transmission in CA1 recovers after spreading depression-like depolarization lasting more than 30 minutes, but is lost irreversibly after 60 minutes. We conclude that entry of Ca2+ into neurons caused by spreading depression-like depolarization is important in the selective vulnerability of neurons; the duration of depolarization is critical to cell survival; and in the presence of a normal blood supply, neurons resist protracted spreading depression-like depolarization. 
1	Laparoscopic pelvic lymphadenectomy in the staging of early carcinoma of the cervix. Laparoscopic pelvic lymphadenectomy was performed in 39 patients. An incision of the peritoneum between the round and infundibulo-pelvic ligament on each side gave access to the retroperitoneal space. Subsequently, laparoscopic surgery allowed precise dissection of external and internal iliac vessels, umbilical artery, and obturator nerve. The peritoneum was left open, and the lymph was drained into the peritoneal cavity. No lymphocele was observed. Three to 22 (mean, 8.7) nodes were removed, and there was no significant morbidity. Sensitivity and specificity were 100% in this preliminary experience. It is thus possible to remove the first-line regional lymph nodes of the cervix for pathologic examination. Because "skip" metastases are quite rare in early cervical carcinoma, the risk of missing a positive node is low. Brachytherapy alone, vaginal surgery, or, in microinvasive carcinoma, conization alone can be applied safely without the need of a staging laparotomy in cases with negative nodes. 
3	Methsuximide for intractable childhood seizures. Methsuximide was added to the therapeutic regimens of 25 children with intractable epilepsy. In 15 patients the drug was well tolerated and resulted in a 50% or greater reduction in seizure frequency. No serious or irreversible adverse effects were seen. Methsuximide is frequently overlooked and may be an effective adjunctive antiepileptic for children with intractable seizures. 
3	Diagnosis of obstructive sleep apnea. The diagnosis of obstructive sleep apnea is frequently made by taking a meticulous history coupled with a high index of suspicion. Snoring and hypersomnolence are clinical features common to individuals with sleep apnea. Since snoring is said to be a "disease of listeners," it is not uncommon that bed partners reported an increased incidence of depression and marital displeasure. It is for this reason that the spouse or bed partner should be interviewed, since the patient may not be aware of any sleeping problems. Physicians should also be alert to complaints of excessive daytime somnolence, because studies have shown that patients with obstructive sleep apnea are at increased risk for automobile crashes. It has been estimated that approx 58,000 motor vehicle accidents involving people with sleep apnea will occur in the US each yr. By proper diagnosis and treatment, the physician is in a unique position to prevent at least some of the automobile accidents that result from falling asleep while driving. Polysomnography is the only definitive way to obtain a diagnosis of sleep apnea. This allows the physician not only to diagnosis the disorder, but also helps in the evaluation of the severity of the syndrome and selection of therapy. An ENT evaluation is also important in ruling out anatomic disorders that can cause upper airway obstruction. Certain factors, such as alcohol and sedative ingestion, may aggravate the condition in a person predisposed to sleep apnea, and subtle changes, such as unexplained hypertension, polycythemia, and cor pulmonale, should lead one to investigate the possibility of sleep apnea as the etiology. 
3	The large striatocapsular infarct. A clinical and pathophysiological entity. We examined 29 patients with strictly subcortical large striatocapsular infarctions. Eight of them had aphasia or neglect. All patients underwent transcranial Doppler ultrasonography or selective carotid angiography, magnetic resonance imaging, and single photon emission tomography for assessment of cerebral blood flow, blood volume, and cerebral perfusion reserve. The signs were compatible with cortical territorial infarctions rather than lacunes. On both magnetic resonance imaging and computed tomographic scans, the lesions corresponded to the territories of the medial and lateral group of the lenticulostriate arteries, Heubner's artery, or the anterior choroidal artery. The infarctions were either due to cerebral embolization into the M1 segment of the middle cerebral artery or due to stenosis at the same site, ie, lesions that acutely and simultaneously occluded the orifices of the lenticulostriate or neighboring arteries. Persistent occlusion of the middle cerebral arteries and a decrease of cortical regional cerebral blood flow were only found in patients with aphasia or neglect. All patients without aphasia or neglect showed a rapid recanalization of the middle cerebral artery occlusion or a stenosis of the M1 segment and no cortical regional cerebral blood flow decrease. Large striatocapsular infarctions occur due to occlusive disease of the middle cerebral artery (large-vessel disease) and not due to a disseminated in situ occlusion of the long penetrating arteries (small-vessel disease), as in lacunes. Neuropsychological deficits can be explained by decreased cortical blood flow due to a persistent occlusive lesion of the middle cerebral artery. 
5	Acute pulmonary embolism triggered by the act of defecation. Pulmonary embolism associated with the act of defecation has not been previously well described. Recently, we reported our experience with four patients who presented to us over a 12-month period with syncope, near syncope, or sudden death following the act of defecation. In all four cases, acute pulmonary embolism was shown to be the etiology of the defecation-associated events. A retrospective chart review of all patients with the diagnosis of pulmonary embolism at our institution over a three-year period yielded five additional patients with the diagnosis of defecation-associated pulmonary embolism. These nine patients accounted for 6.8 percent of all patients with a discharge diagnosis of pulmonary embolism seen at our institution during the three-year study period. Six of the nine patients died from their defecation-associated pulmonary embolism. These six deaths accounted for 25 percent of all deaths from pulmonary embolism seen at our institution during the study period. Based on our experience, we suggest that the act of defecation may trigger the development of acute pulmonary embolism in some patients with deep vein thrombosis. 
2	Use and misuse of oral therapy for diarrhea: comparison of US practices with American Academy of Pediatrics recommendations. To determine how closely US pediatricians follow the 1985 American Academy of Pediatrics Committee on Nutrition's recommendations on oral therapy for acute diarrhea, a questionnaire was administered to four groups: New England private practitioners, pediatricians from 27 states attending a postgraduate course, representatives of departments of pediatrics at US schools of medicine, and housestaff at Boston Children's and Massachusetts General hospitals. The responses from departments of pediatrics and housestaff were not significantly different from those of community practitioners in most categories. The reported rate of use of glucose-electrolyte solutions recommended by the American Academy of Pediatrics was not different from the use of nonphysiologic, high-osmolar, low-salt solutions such as sodas and juices. The usage rate for glucose-electrolyte solutions meeting the American Academy of Pediatrics-recommended carbohydrate-to-sodium ratio of less than 2:1 was less than 30%. Other findings included the general lack of agreement on the use of a single type of therapy and the common use of oral therapy only for mild or no dehydration. Although the American Academy of Pediatrics recommends that feeding be reintroduced in the first 24 hours of a diarrheal episode, the majority of respondents withhold feeding until the second day or later. These findings indicate that educational programs on oral therapy during acute diarrhea are needed in the United States. 
1	An electron and optical microscopic study of juxtaposed odontogenic keratocyst and carcinoma. Odontogenic keratocyst and squamous cell carcinoma commonly occur within the oral cavity; however, the juxtaposition of these lesions is rare. The light microscopic and ultrastructural features of such an event are reported. Although some morphologic similarities between the cyst and tumor were observed, definitive evidence of a common origin was not obtained. 
1	Bolus versus infusion regimens of etoposide and cisplatin in treatment of non-small cell lung cancer: a study of the North Central Cancer Treatment group In an effort to test clinically the hypothesis that the duration of cellular exposure to etoposide (VP-16) and cisplatin (CDDP) is an important determinant of cytotoxicity, we performed a phase III randomized trial comparing an outpatient bolus regimen of combined VP-16 and CDDP with a sequential infusion over 72 hours of these same two drugs. All patients had stage IV non-small cell lung cancer, and survival was the primary end point. Of 113 patients randomly allocated to the study, 108 were assessable for response, survival, and toxicity. A major response was observed in 20 (37%) of 54 patients on the bolus regimen and in 16 (30%) of 54 patients receiving infusion therapy. The median time to progression was 61 and 88 days for bolus and infusion therapy, respectively. The median survival time was 148 and 157 days, respectively (P = .71). Study results were not consistent with the possibility that infusion therapy could be associated with a 50% improvement in median survival, i.e. from 5 months to 7 1/2 months. Toxicity was primarily myelosuppression and was significantly greater with the infusion regimen. We conclude that infusion therapy as tested in this protocol with VP-16 and CDDP does not offer any advantage in response rate, time to disease progression, or survival as compared with bolus therapy. In addition, infusion therapy is associated with a greater degree of neutropenia and more treatment-related deaths. 
4	One hundred percent oxygen reverses muscle hypoxia in a rat hindlimb model of acute arterial occlusion. Significant morbidity results from extremity ischemia after acute arterial occlusion. Reestablishment of arterial flow is considered to be the ideal treatment, yet substantial tissue loss can occur before this is accomplished. Using a rat hindlimb model we investigated whether the administration of 100% oxygen would decrease tissue hypoxia from acute arterial occlusion. Adult male Sprague-Dawley rats were used, and Po2 recordings were taken from the gastrocnemius muscle by use of an oxygen electrode. Baseline muscle Po2 was recorded, and then the femoral artery was occluded. Repeat recordings were made after 20 minutes of ventilation with room air and after an additional 20 minutes of ventilation with 100% oxygen (N = 10). Control groups consisted of animals undergoing occlusion but continued on room air (N = 3) and animals undergoing sham occlusion but receiving the period of 100% oxygen ventilation (N = 3). Femoral artery occlusion produced a reduction in muscle Po2 from 28.0 +/- 1.4 to 6.1 +/- 2.0 (mean +/- SEM, p less than 0.001). Ventilation with 100% oxygen reversed the tissue hypoxia produced by occlusion (27.3 +/- 2.0, p less than 0.001). The administration of 100% oxygen without femoral artery occlusion resulted in a higher tissue Po2 than the occluded + oxygen group (94 +/- 12 vs 27.3 +/- 2.0, p less than 0.001). Mean arterial blood pressure increased in the experimental group concomitant with the administration of 100% oxygen, but there was no correlation between final blood pressure and final tissue oxygen tension. 
5	Hepatomuscular failure in septic catabolism: altered muscular response to plasma proteolytic factor in decreased hepatic mitochondrial redox potential. To estimate the contribution of muscle protein in whole-body protein catabolism, the muscular contribution index (MCI; urine 3-methylhistidine/urine total nitrogen) was determined in 49 cases of elective laparotomy, together with the arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential. MCI increased after operation and the occurrence of severe infection, provided KBR was maintained above 0.7. In patients with sepsis, however, MCI decreased dependently with KBR (n = 33; p less than 0.01). In these patients, plasma proteolysis-inducing activity determined by in vitro bioassay increased in inverse proportion to KBR (n = 20, p less than 0.01). Moreover, plasma concentrations of not only aromatic but also branched-chain amino acids markedly increased when KBR decreased to below 0.4 (n = 23; p less than 0.05). Thus the role of muscle protein in septic catabolism is diminished under reduced hepatic mitochondrial redox potential, despite the rapid increase of proteolysis-inducing activity. This finally leads to the failure of amino acid uptake by muscles, as well as liver. These results suggest that the deteriorated substrate exchange may form the metabolic background for multiple systems organ failure, which is often preceded by reduced KBR. 
4	Dural spinal cord arteriovenous malformation. After multiple hospital admissions and an inpatient rehabilitation stay, a 68-year-old woman was transferred to our rehabilitation facility with a paraparesis of unknown etiology. Previous studies included four CT scans and three MRIs which did not demonstrate the lesion. A myelogram was noncharacteristic. The correct diagnosis, confirmed by selective angiography, was ultimately contingent upon recognition of the clinical features and natural history of dural spinal cord arteriovenous malformations (SCAVM). The unusual combination of this multitude of nondiagnostic imaging studies in the uncommon dural SCAVM served to delay diagnosis and treatment. Such delay may have great functional consequences. This report illustrates the importance of suspecting SCAVM and recognizing its features. Emphasis is placed on the physiatrist's role in assuring proper diagnosis to expedite a timely treatment and to obtain the best functional outcome. A brief review of the classification, clinical features, pathophysiology, diagnosis, and prognosis of SCAVM is presented. 
5	Chilaiditi's syndrome. A diagnostic challenge. Chilaiditi's syndrome should be considered in the differential diagnosis of abdominal and chest pain. Although interposition of the right colon is a relatively common radiologic finding, there is a distinct paucity of information in the medical literature. Chilaiditi's syndrome is usually asymptomatic, but when symptoms occur, conservative treatment is usually effective. Recognition is important because this syndrome can be mistaken for more serious abnormalities, which may lead to unnecessary surgical intervention. 
1	Nd:YAG-laser in the microsurgery of frontobasal meningiomas. Forty-three patients with big frontobasal meningiomas underwent a microsurgical removal of the tumor. The 1.32 microns Nd:YAG-laser has proved useful in this prospective series particularly with the contactless shrinkage of the tumors and the necrotization of the dural and bony attachments. Tumor shrinkage was achieved by radiating the tumor surface with the Nd:YAG-laser. This technique facilitated the microsurgical dissection and reduced the blood loss by half. The Nd:YAG-laser necrotization of the dural and bony attachments reduced the recurrence rate following grade two resections from 20% to zero. The postoperative quality of life was excellent with a complete rehabilitation in 76% of the patients. The use of the 1.32 microns Nd:YAG-laser improved significantly the results of microsurgery for frontobasal meningioma. 
5	Colon carcinoma associated with ureterosigmoidostomy. A patient developing a colonic adenoma 38 years following ureterosigmoidostomy is presented. The mechanisms of neoplastic transformation associated with ureterosigmoidostomy is now better understood. This knowledge is being applied to develop modifications both of the surgical technique and the management of patients with this form of urinary diversion, and is a subject of discussion. 
4	Clinical cardiovascular magnetic resonance imaging. Magnetic resonance imaging (MRI) is a powerful tool providing high-resolution images of the heart and great vessels without the use of ionizing radiation or contrast agents. MRI systems currently in use at many hospitals can be used effectively in the routine, clinical evaluation of many forms of cardiovascular disease, including great vessel disease, ischemic cardiac disease and congenital cardiac disease. Moreover, quantitative and cine MRI techniques are now available, which provide highly accurate measures of chamber size, wall motion and wall thickening. Recent developments in the areas of myocardial tagging, high-speed imaging and MR assessments of flow and perfusion suggest potential for an increasing role of MRI in the clinical evaluation of the cardiovascular system. 
2	Nonoperative management of bile duct stones. The treatment of choice for most retained bile duct stones is by nonoperative means. If a T-tube is in place, percutaneous techniques via the T-tract are indicated. Percutaneous access via puncture of a Roux-en-Y loop is also practical. In the absence of a T-tube, retrograde endoscopic techniques should be used. Both techniques are very effective and safe. Stones in the intrahepatic and extrahepatic ducts also can be treated nonoperatively. Endoscopic sphincterotomy has a role in the treatment of selected patients with gallstone pancreatitis, acute cholangitis, and choledocholithiasis with in situ gallbladders. In difficult cases, endoscopic and percutaneous techniques are employed in combination. 
1	Gross cystic disease fluid protein-15 in salivary gland tumors. Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves. 
5	Modification of atrioventricular node transmission properties by intraoperative neodymium-YAG laser photocoagulation in dogs. The purpose of this study was to test the feasibility of neodymium-yttrium-aluminum-garnet (Nd-YAG) laser photocoagulation of the atrioventricular (AV) node to control the ventricular rate during rapid atrial rhythms without creating AV block. In 12 dogs on normothermic cardiopulmonary bypass, short laser pulses were delivered to an area between the coronary sinus orifice and the site of the most proximally recorded His deflection until second degree AV block occurred at a paced atrial rate of 200 beats/min. Long-term effects on AV node function were followed up for 3 months. Three animals developed chronic high grade AV block. In nine animals with preserved 1:1 conduction, the mean (+/- SEM) critical atrial cycle length resulting in AV node Wenckebach periodicity increased from 183 +/- 6 to 261 +/- 24 ms (+43%), the mean RR interval during induced atrial fibrillation increased from 248 +/- 14 to 330 +/- 27 ms (+32%) and the shortest RR interval during atrial fibrillation increased from 215 +/- 11 to 275 +/- 20 ms (+28%). Laser effects were not reversed by isoproterenol infusion. Histologic examination of the irradiated area showed fibrotic changes in the AV node and fatty metamorphosis. This study suggests that 1) graded Nd-YAG laser photocoagulation of the AV node region in dogs results in long-term modification of anterograde AV node transmission properties; 2) 1:1 conduction during sinus rhythm usually remains preserved, but ventricular rate during rapid atrial rhythms is chronically reduced; and 3) progression to high grade AV block occurs in a minority of animals. 
4	Probe angioplasty of total coronary occlusion using the Probing Catheter technique. Coronary angioplasty (PTCA) of total coronary occlusion is limited by the inability of guidewires and conventional dilating catheters to cross all such lesions. A new technique was therefore prospectively evaluated for PTCA of these lesions using the ultra-low-profile Probe "balloon on a wire" device. An intracoronary Probing Catheter was used to facilitate crossing the stenosis with a guidewire and then to deliver a Probe into the obstruction for balloon dilatation. This technique was utilized in 64 consecutive patients with "absolute" coronary occlusions demonstrating no angiographically detectable antegrade coronary flow. Successful dilatation was achieved in 47 (73%). Among 33 occlusions of less than 3 mo duration 31 (94%) were successfully dilated whereas only 16 of 31 more chronic occlusions were dilated (P less than .01). Chronic occlusions with a tapered morphology and those located more than 1 cm from a branch point were more frequently dilatable. There were no serious complications including no vessel perforations with this technique. The Probing Catheter technique offers a safe and effective method for the dilatation of recent coronary occlusions by using balloon on a wire technology. 
3	7th nerve palsy after extradural blood patch. We describe a patient who developed a 7th cranial nerve palsy following an extradural blood patch; full recovery followed. The likely aetiology is discussed. 
2	Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Susceptible rat strains develop hepatobiliary injury following the surgical creation of self-filling blind loops that cause small bowel bacterial overgrowth. Luminal bacteria or their cell wall polymers were implicated in the pathogenesis of the lesions because sham-operated rats and rats with self-emptying blind loops, having only slightly increased bacterial counts, did not develop hepatic injury. In this study, antibiotics with different spectra of activities were continuously administered starting 1 day or 22 days after surgery to determine which intestinal flora may be responsible for the development of hepatic injury in rats with small bowel bacterial overgrowth. Four weeks following surgery, Lewis rats with self-filling blind loops receiving no antibiotics had elevated liver histology scores (8.2 +/- 1.3 vs. 0.7 +/- 0.4) and plasma aspartate aminotransferase levels (269 +/- 171 vs. 84 +/- 24) compared with sham-operated rats, P less than 0.001. Oral gentamicin as well as oral and intraperitoneal polymyxin B, which binds endotoxin, did not prevent hepatic injury in rats with self-filling blind loops. However, oral metronidazole and tetracycline therapy continuously administered beginning 1 day after surgery diminished hepatic injury (histology score 3.0 +/- 1.8, 2.9 +/- 1.1; aspartate aminotransferase 87 +/- 25, 98 +/- 34; respectively P less than 0.001 compared with self-filling blind loops receiving no antibiotics). Metronidazole also protected Wistar rats that require 12 weeks to develop hepatic injury following experimentally induced small bowel bacterial overgrowth compared with rats with self-filling blind loops that received no antibiotic treatment (histology score 10.4 +/- 1.3 vs. 0.7 +/- 1.1, and aspartate aminotransferase 273 +/- 239 vs. 76 +/- 20, P less than 0.001). When rats started metronidazole therapy 22 days after self-filling blind loop surgery, elevated aspartate aminotransferase values decreased to normal during the next 77 days and final histology scores were normal. All rats with self-filling blind loops had negative peritoneal, liver, spleen, and blood cultures but approximately 75% of mesenteric lymph node cultures were positive irrespective of antibiotic treatment. Because Bacteroides species have been implicated in causing vitamin B12 and disaccharidase deficiencies in rats with self-filling blind loops, we documented the presence or absence of these organisms from blind loops using selective culture techniques. Metronidazole and tetracycline eliminated Bacteroides sp. from blind loops, but polymyxin B and gentamicin did not.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk. 
3	Brain magnetic resonance imaging and neuropsychologic evaluation of patients with idiopathic dilated cardiomyopathy. We compared brain magnetic resonance imaging and neuropsychologic performance in 20 neurologically asymptomatic patients suffering from idiopathic dilated cardiomyopathy (mean age 41 [range 18-49] years) and 20 age-matched controls (mean age 38 [range 28-49] years). Patients exhibited a significantly higher rate of cerebral infarcts (20% versus 0%, p less than 0.05) and cortical (50% versus 5%, p less than 0.01) and ventricular (55% versus 15%, p less than 0.02) atrophy than controls. Accordingly, semiquantitative volumetric measurements yielded a significantly increased ventricular-to-intracranial cavity ratio in the patients (6.2 +/- 2.9% versus 4.1 +/- 1.3%, p less than 0.01). This ratio and the cortical atrophy ratings correlated positively with disease duration (r = 0.63 and 0.54, p less than 0.05). Cognitive test performance was significantly worse in patients than in controls and was most impaired in those patients with morphologic cerebral abnormalities. 
2	Chronic functional gastrointestinal symptoms in Holocaust survivors. In Nazi-occupied Europe (1939-1945), Jews were submitted to extreme mental and physical hardships (the Holocaust). This study was designed to investigate the impact of the severe protracted suffering on the development of chronic functional gastrointestinal symptoms. Thus, we studied 623 consecutive patients of Eastern European origin who had been admitted for nongastrointestinal complaints. They filled out detailed questionnaires, and were divided into the following two groups: A) Holocaust survivors [237 subjects who had been for at least 6 months in either German concentration/extermination camps (95 subjects), ghetto and/or underground movements (65 subjects), labor camps not directly supervised by Germans (79 subjects)], and B) a control group (384 subjects from the same demographic background, who had not been exposed to Nazi persecutions). The symptoms investigated were the following: abdominal pain, irregular bowel habits, diarrhea, constipation, abdominal distension, heartburn, flatulence, anorexia, nausea, vomiting, mucus in stool, tenesmus, and aerophagia. Patients were defined as having functional symptoms after these had been present for at least 5 yr and relevant organic disease had been excluded. The prevalence, duration of suffering, and frequency of appearance of most symptoms were significantly higher in the group of Holocaust survivors. This study supports the clinical observations that severe and protracted suffering contributes to the development of chronic functional gastrointestinal symptomatology. 
1	Time to recovery of the hypothalamic-pituitary-adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome. The recovery time of the hypothalamic-pituitary-adrenal (HPA) axis after curative resection of adrenal tumors in patients with Cushing's syndrome is poorly documented. Eight consecutive patients were treated with a standardized hydrocortisone replacement strategy after curative resection of a cortisol-secreting tumor and the time to recovery of the HPA axis was determined. Hypercortisolism was documented by elevated 24-hour urinary free cortisol levels. Cure was documented by undetectable postoperative morning serum cortisol levels. Each patient received replacement hydrocortisone after surgery and was reevaluated every 3 to 6 months with an adrenocorticotrophic hormone (ACTH) stimulation test. Each patient was also monitored carefully for symptoms and signs of adrenal insufficiency, which was defined as symptoms consistent with this diagnosis that responded to increases in hydrocortisone levels. After surgical resection, each patient was cured of hypercortisolism. Subsequently, despite replacement hydrocortisone, each patient had symptoms of hypocortisolism, and in four of eight patients the dose of hydrocortisone was increased to relieve the symptoms. Patients required a median time of 15 months (range, 9 to 22 months) to recover a normal ACTH stimulation test and 19 months (range, 12 to 24 months) to allow discontinuation of replacement doses of hydrocortisone. The results suggest that surgical resection of a cortisol-secreting adrenal tumor will result in rapid cure of hypercortisolism, but complete recovery of the HPA axis and discontinuation of replacement steroids will require between 1 and 2 years. Normal adrenal function, as assessed by the cortisol response to ACTH, returns despite replacement doses of hydrocortisone, and replacement doses of hydrocortisone can be tapered rapidly or discontinued after a normal ACTH stimulation test. 
5	Thermographic findings in cranio-facial pain. This work assesses the differences in the thermographic findings in the craniofacial and neck areas between normal individuals and patients with craniofacial pain or headache, and investigates the influence of muscle contraction on such findings. Thermographic records were taken in 10 healthy subjects and 47 patients suffering from craniofacial pain or headache of different kinds. In the patients with painful episodes the record was taken between attacks. In all the normal subjects and in 19 patients lateral thermograms were also taken during and after maximal tooth clenching for three minutes. The majority of the patients, as compared to the normal group, showed some thermal alterations and asymmetry. Such alterations seem to be due both to vascular instability and muscle contraction: these two factors may be variably superimposed in the different conditions. In patients with cluster headache or chronic paroxysmal hemicrania the presence on the symptomatic side of a cold spot along the supraorbital area and/or the inner orbital canthus, was a constant finding. We conclude that thermography is useful as an additional diagnostic means in patients with head and face pain, and that the clenching test may increase the amount of information provided. 
5	Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Acute promyelocytic leukemia (APL; FAB M3) is characterized by a predominance of malignant promyelocytes that carry a reciprocal translocation between the long arms of chromosomes 15 and 17, t(15;17) (q22;q11.2-q12). This translocation has become diagnostic for APL, as it is present in almost 100 percent of cases. A Not I linking clone was used to detect this translocation initially on pulsed-field gel electrophoresis and subsequently with conventional Southern (DNA) analysis. The breakpoints in ten APL cases examined were shown to cluster in a 12-kb region of chromosome 17, containing two CpG-rich islands. The region is the first intron of the retinoic acid receptor alpha gene (RARA). 
1	Management of superficial G2 (pTa and pT1) bladder cancer. A total of 143 patients with superficial G2 (pTa, pT1) bladder cancer (48 G2pTa; 95 G2pT1) presenting between 1970 through 1987 were reviewed. Of 48 patients with G2pTa followed for up to eighteen years, G3 recurrence developed only in 1 (2.0%), and invasive cancer (greater than pT2) developed only in 2 (4.2%). They both received radiotherapy and have responded completely. There have been no cancer-related deaths. In contrast, in the 95 patients in whom the basement membrane had been breached (pT1), higher grade tumor (G3) developed in 11 (11.5%), and 15 (16%) had recurrences with invasion of muscle (greater than pT2). Among these there were 7 (7.3%) cancer-related deaths. 
1	Contiguous enlarged dental follicles with histologic features resembling the WHO type of odontogenic fibroma Defective odontogenesis and/or retarded eruption of teeth can be associated with histologic features akin to odontogenic fibroma in the dental follicles. Unerupted mandibular premolar and molar teeth of a 24-year-old man were surgically exposed, yet the teeth failed to erupt. About a year and a half later, radiographs indicated further enlargement of the follicle of the premolar, and both teeth were subsequently surgically removed. Histologically, the follicles were composed of mature collagenous tissue among which epithelial islands and numerous clusters of calcified bodies were present. Indirect immunofluorescence showed positive staining for type I and type III collagen, which exhibited a sparse distribution, but not for the aminoterminal propeptide of type III procollagen. The hamartomatous nature of the lesions is discussed with emphasis on their histologic resemblance to the WHO type of odontogenic fibroma. 
2	Association of hepatitis B surface antigen and core antibody with acquisition and manifestations of human immunodeficiency virus type 1 (HIV-1) infection. We examined the associations between seropositivity for hepatitis B virus (HBV) with the presence or development of antibodies to human immunodeficiency virus (HIV-1) and with HIV-1 induced T-helper lymphocyte deficiency or acquired immunodeficiency syndrome (AIDS). Serologic data on HBV and HIV-1, cytometric enumeration of CD4+ lymphocytes, clinical events (AIDS by Centers for Disease Control criteria) and hepatitis B vaccination histories were available on 4,498 homosexual participants in the Multicenter AIDS Cohort Study, Men were classified as to previous infection with HBV and prevalent or incident infection with HIV-1. Although there was an association between seropositivity for HBV infection and HIV-1 infection at enrollment (odds ratios anti-HBc 2.6; HBsAg 4.2), the relation between HBV seropositivity and subsequent seroconversion to HIV-1 was weaker (odds ratios 1.3 and 1.6). HIV-1 seroconversion was also associated with a history of certain other sexually transmitted diseases, but predisposing sexual practices did not account for the association between HBV and HIV-1 infection. Seropositivity for HBV infection at entry was not related to initially low or more rapid subsequent decline in T-helper lymphocyte counts and was not associated with an increased incidence of AIDS during 2.5 years of follow-up. History of vaccination against HBV did not appear to decrease susceptibility to HIV-1 infection or to subsequent progression of immunodeficiency. We conclude that prior HBV infection is unlikely to be specifically associated with acquisition of HIV-1 infection and is unrelated to more rapid progression of HIV-1-induced immunodeficiency. 
5	Prognostic factors in craniofacial surgery. From 1979 to 1989, 21 patients underwent craniofacial resection for malignancies involving the anterior skull base. Histologic types included 8 squamous cell carcinomas, 3 chondrosarcomas, 2 melanomas, 2 basal cell carcinomas, 2 adenocarcinomas, 2 poorly differentiated carcinomas, 1 malignant schwannoma, and 1 malignant hemangiopericytoma. Survival was 57%, with follow-up of 41 months. A 50% complication rate included osteomyelitis, cerebrospinal fluid rhinorrhea, meningitis, brain abscess, epidural abscess, and syndrome of inappropriate antidiuretic hormone. Recurrent disease occurred in 9 patients (41%), the most reliable predictor being dural invasion indicated preoperatively by CT scan or at operation. Patients demonstrating dural involvement (N = 9) had a 22% survival rate, while patients without (N = 12) had a survival rate of 83%. The impact of dural invasion on long-term survival is emphasized. Though complications were frequent, long-term results were favorable. 
1	Introduction: nutritional aspects of palm oil. The production, composition, and food uses of palm oil are outlined in this introduction to a detailed appraisal of the nutritional and health implications of the use of palm oil in the food supply. The putative role of dietary fats and oils in general, and of palm oil in particular, in the etiology of coronary heart disease and cancer is critically assessed. It is concluded that the evidence available is difficult to interpret unambiguously. Some evidence to suggest that the minor components of palm oil might have useful biological effects is also discussed. 
1	NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Acute promyelocytic leukemia (APL) is a well-defined entity among acute leukemia, cytogenetically characterized by a t(15;17) (q22;q11-12) translocation. In vitro and in vivo studies suggest that all-trans retinoic acid (RA) treatment restores cell maturation. We have isolated the first permanent cell line with t(15;17), derived from the marrow of a patient with APL in relapse. The establishment of the cell line, its morphologic, karyotypic, and immunohistochemical features are reported. RA induced cell line maturation. Cells strongly expressed myeloid markers, but also some T-cell markers. Additional karyotypic abnormalities, a 12p rearrangement and the possible presence of a homogeneous staining region (HSR) on 19q+ are discussed both in relation to T-cell (CD2, CD4) and monocyte (CD9) markers, and to the acquired cell growth autonomy. The cell line represents a remarkable tool for biomolecular studies. 
2	Chemical peritonitis secondary to intraperitoneal vancomycin. Although previously reported in the literature, the existence of chemical peritonitis due to vancomycin in patients on peritoneal dialysis remains controversial. We report four similar episodes of sterile peritonitis in three patients receiving intraperitoneal (IP) vancomycin. The prior report implicated a change in the brand of vancomycin preparation, from Vancocin to Vancoled, as a contributing factor. We noted the occurrence of such episodes following a switch from Vancocin to a generic preparation from Abbott Laboratories. High-performance liquid chromatographic (HPLC) profiles of the three preparations show Vancocin to have a lower level of impurities than the other two; the presence of certain contaminants in the other brands may be contributing to the clinical difference observed. We conclude that chemical peritonitis due to IP vancomycin administration does occur, and that increased awareness of this entity could allow other cases to be identified. 
1	Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. OBJECTIVES: To evaluate the frequency and the course of complete cytogenetic responses in interferon-alpha (IFN-alpha)-treated patients with chronic myelogenous leukemia. DESIGN: Two prospective trials in consecutive patients. SETTING: A major tertiary cancer center. PATIENTS: Ninety-six consecutive patients with chronic myelogenous leukemia with disease duration of less than 1 year. INTERVENTION: Patients received partially pure IFN-alpha intramuscularly, from 3 to 9 million U/d (51 patients) or recombinant IFN-alpha 2a (Roferon, Hoffmann-LaRoche, Inc., Nutley, New Jersey), 5 million U/m2 body surface area daily (45 patients). MEASUREMENTS: Hematologic and cytogenetic tests were administered. MAIN RESULTS: Seventy of the patients (73%) achieved hematologic remission (95% CI, 63% to 81%), and 18 (19%) had complete suppression of the Philadelphia chromosome on at least one cytogenetic test. A complete cytogenetic response was induced in 7 of 51 or 14% (CI, 6% to 26%) of the patients treated with the partially pure IFN-alpha and in 11 of 45 or 24% (CI, 13% to 40%) of the patients treated with recombinant IFN-alpha 2a. The difference in complete cytogenetic response between the two groups was 10.7% (CI, - 5% to 26%; P greater than 0.2). Eleven patients had durable, ongoing, complete cytogenetic responses from 6 to more than 45 months (median, more than 30 months). CONCLUSION: This study was the first to show sustained, complete cytogenetic responses in a subset of patients with chronic myelogenous leukemia treated with single-agent therapy. The nature of this remission, that is, whether it depends on continuous therapy, requires further study. 
3	Impact of day care on dementia patients--costs, well-being and relatives' views. Forty-seven patients in psychogeriatric day centre were analysed regarding use of resources, costs and well-being. The level of well-being was based on interviews with staff and relatives and related to the economic outcome--a cost utility analysis. A 6 month period prior to day care was compared with the first 6 months in such care. The use of resources at home increased by 20% while the use of institutional care was reduced by 22%. Fifty-three percent of the patients improved in their well-being after participation in day care. When the cost of utility analysis was applied, the cost for a well-year was 4293 pounds. 
1	Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion. Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been effective in treating some advanced malignancies in animals and humans. One complication of this treatment is a reversible, oliguric, acute renal failure, which has been ascribed to renal hypoperfusion and resultant prerenal azotemia. We serially studied renal function in 10 patients receiving high-dose regimens of recombinant interleukin-2 (rIL-2) to attempt to delineate further the nature of the renal dysfunction caused by IL-2 treatment. Renal plasma flow was computed from iodine 131 (I-131 Hippuran; Mediphysics, Paramus, NJ) orthoiodohippurate, excretion curves, and glomerular filtration rate (GFR) was determined by creatinine clearance. Studies done prior to and on day 4 of treatment showed that GFR fell in nine of 10 patients, with a mean decrease of 43% +/- 8%, and renal plasma flow fell in five of the 10 patients with a mean decrease of 5% +/- 10%. The average pretherapy filtration fraction was calculated to be 23% +/- 1% and after 4 days of treatment, decreased to a mean value of 15 +/- 2%. The BUN to creatinine ratio also declined in all patients. These findings collectively suggest that IL-2 nephrotoxicity may result from an intrarenal defect in addition to the previously described prerenal azotemia. Additionally, radionuclide studies of renal function are a reliable and reproducible noninvasive method of assessing these changes in renal function. 
5	Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death. 
5	Multiple organ failure: inflammatory priming and activation sequences promote autologous tissue injury. Systemic inflammation promotes multiple organ failure through the induction of diffuse microvascular leak. Inflammatory cells such as neutrophils propagate this process. Tissue injury by neutrophils may be viewed as a normal process, inflammation, that has become uncontrolled and generalized. Multiple inflammatory stimuli synergistically promote neutrophil-mediated tissue injury in priming and activation sequences. In some settings, cellular priming is mediated by platelet-activating factor and can be prevented by platelet-activating factor antagonists. Inhibiting cellular priming could be efficacious in the therapy of multiple organ failure. 
5	Endoscopic management of postoperative biliary leaks: review of 77 cases and report of two cases with biloma formation. Biliary leaks are uncommon complications of abdominal surgery. Left untreated, they may result in significant morbidity and mortality. The traditional treatment has been surgical, but several authors have reported successful endoscopic management. We review 77 cases of endoscopically managed postoperative biliary leaks reported in the literature over the past 15 yr. Endoscopic treatment was technically successful in 95% of cases, and resulted in biliary leak healing in 82%. Cystic stump leaks had a better prognosis for healing compared with common bile duct or hepatic duct leaks. We also present two additional cases of postoperative biliary leaks with biloma formation successfully treated with endoscopic stent placement. Our experience lends additional support to endoscopic management as the preferred approach to postoperative biliary leaks. 
1	The association of selected cancers with service in the US military in Vietnam. III. Hodgkin's disease, nasal cancer, nasopharyngeal cancer, and primary liver cancer. The Selected Cancers Cooperative Study Group As part of a series of investigations into the health of Vietnam veterans, we conducted case-control studies involving 310 men with Hodgkin's disease, 48 with nasal carcinoma, 80 with nasopharyngeal carcinoma, 130 with primary liver cancer, and 1776 controls between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible as cases; controls were recruited by random-digit dialing. Whereas the study had excellent power (96%) to detect a twofold increase in risk for Hodgkin's disease among Vietnam veterans, its ability to detect a similarly elevated risk in the other cancers was limited, ranging from 38% (nasal carcinoma) to 75% (primary liver cancer). Analyses showed that risks among Vietnam veterans relative to other men were 1.1 (Hodgkin's disease), 0.7 (nasal carcinoma), 0.5 (nasopharyngeal carcinoma), and 1.2 (primary liver cancer). None of these relative risks was significantly different from 1.0. Similar results were obtained if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. An examination of several attributes of military service in Vietnam (eg, branch, duration of service, and other characteristics that may have been associated with the use of Agent Orange) failed to identify any groups of veterans who were at increased risk for Hodgkin's disease. Small numbers limited further analyses of nasal, nasopharyngeal, and liver cancer. These results provide no evidence that, 15 to 25 years following service in Vietnam, the risk of these malignant neoplasms is higher among veterans. 
1	Elevated serum bromide concentrations following repeated halothane anaesthesia in a child. A 20-month-old child received 25 brief halothane general anaesthetics over a five-week period to allow cranial irradiation treatments for a posterior fossa ependymoma. Personality change during the last week of the treatment protocol raised the question of possible bromide intoxication. Serum bromide concentrations, using a gold chloride assay technique, were monitored at that time, and at four- and six-week intervals thereafter. Serum bromide concentrations demonstrated a four-fold change during this period ranging from peak levels of 2.2 mEq.L-1 (176 micrograms.kg-1) during the fifth week of treatment decreasing to less than 0.5 mEq.L-1 (less than 40 micrograms.ml-1) six weeks following the end of treatments. This demonstrates the possibility for repetitive, short halothane exposures to result in elevations of serum bromide and the potential of bromide intoxication in paediatric neuro-oncology patients. 
5	Acute psychosis. Functional versus organic. Acute psychosis is a true emergency and is a manifestation of multiple organic and functional disorders. The emergency medicine physician's role in dealing with the acutely psychotic patient is to control the patient's behavior, to delineate the etiology of the psychosis, and to provide appropriate initial treatment and disposition. When making initial contact with the psychotic patient, behavioral control can be accomplished through supportive, physical, or pharmacologic interventions. Judicious use of rapid tranquilization permits rapid control of these patients when supportive and other nonpharmacologic therapies fail. Initial examination is directed at identifying immediate life-threatening organic disorders and promptly treating them. Historical data, mental status examination, physical examination, and appropriate radiologic and laboratory investigations give information that assist in delineating functional from organic psychosis. Most acute organic psychoses, with the exception of some drug intoxications that clear in the Emergency Department, require medical or surgical admission. Acute functional psychotic patients who are a danger to themselves or others, who are without a reliable social support system, or who present with their first psychotic episode require admission to the psychiatric service for further evaluation and treatment. 
2	Rectal mucosal dysplasia in Crohn's disease. Serial sections of 812 rectal biopsy specimens from 356 Crohn's disease patients were analysed for mucosal epithelial dysplasia. Dysplasia was found in 18 patients (5%), with four showing dysplasia on repeat biopsy specimen. In these 22 biopsy specimens the dysplasia was mild in 13, moderate in nine, and severe in none. Subsequently, three patients (17%) developed neoplasms including carcinoma in two and an adenomatous polyp in one. In colectomy specimens which showed dysplasia, significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia (p less than 0.001). Thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer. Four carcinomas developed in patients with Crohn's disease who did not have dysplasia on rectal biopsy specimen. 
1	Cisplatin-fluorouracil interaction in a squamous cell carcinoma xenograft. Patients with squamous cell carcinoma of the head and neck are treated with cisplatin and fluorouracil according to a schedule based on the findings of clinical studies. A similar schedule showed a supra-additive effect in the treatment of xenografted human squamous cell carcinoma of the head and neck. We sought to ascertain whether this schedule was optimal. A single intraperitoneal injection of cisplatin (7.5 mg/kg) was combined with three injections of fluorouracil given during a 24-hour period (total dose, 150 or 80 mg/kg) before, during, or after cisplatin administration. The combined effect of cisplatin and fluorouracil on tumor growth and toxic effects was schedule dependent. Consideration of both toxic effects and tumor growth inhibition, as assessed by reduction of the area under the growth curve, the optimal administration interval was found to be fluorouracil given 3 days after cisplatin administration. 
5	Rounded atelectasis complicated by obstructive pneumonia and pulmonary arterial thrombosis [published erratum appears in Chest 1991 Jun;99(6):1556] A patient with a history of asbestos exposure developed rounded atelectasis. The mass was associated with local bronchial obstruction, obstructive pneumonia and arterial thrombosis. Autopsy demonstrated marked pleural thickening and radiographically inapparent asbestosis. This is the first reported case in which seemingly benign rounded atelectasis not only increased morbidity, but also contributed to mortality through airway obstruction and local arterial thrombosis. 
3	Treatment of patients with aortic dissection presenting with peripheral vascular complications. The incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% +/- 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (+/- 70% confidence limits) were high: 44% +/- 17% (4 of 9 patients), 50% +/- 11% (11 of 22 patients), and 43% +/- 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% +/- 14% [1 of 7 patients]) or loss of peripheral pulse (27% +/- 6% [18 of 66 patients]). Multivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditious diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral infarction develops the prognosis is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may improve the survival rate for these patients in the future. The initial surgical procedure should include repair of the thoracic aorta in most patients. 
5	Diagnostic value of DNA analysis in effusions by flow cytometry and image analysis. A prospective study on 102 patients as compared with cytologic examination One hundred twenty-six effusion samples from 102 patients were examined by cytology and flow cytometry (FCM). Overall, there was an 84% correlation between cytologic and FCM results. Of the 36 malignant cases determined by cytologic examination, FCM revealed an aneuploid peak in 20 (56%). Image analysis (IA) performed on the malignant cytologic cases with a diploid flow pattern detected two additional aneuploid peaks. In addition, FCM indicated three aneuploid cases in which cytologic characteristics were initially interpreted as benign (false negative). Aneuploidy was therefore detected in 64% of the malignant effusion specimens by FCM and IA. Twenty-three of the total of 24 aneuploid cases detected by FCM were associated with malignancy (predictive value = 96%). The one nonmalignant case was that of hemorrhagic pancreatitis with infected pseudocyst. FCM is an excellent tool when moderate to large numbers of tumor cells are present, whereas use of IA is advantageous for specimens containing smaller numbers of malignant cells because these can be directly analyzed. When an aneuploid peak is present, a diagnosis of malignancy must be suspected, and, if the initial cytologic screen is negative, a critical review of the cytology slides is justified. In those cases with an equivocal atypical cytology report and an abnormal cytometric histogram, additional investigation is warranted. In some malignancies the tumor cells will be diploid (in this study 36%) and neither FCM nor IA will add to tumor detection, leaving cytologic examination as the definitive technique. 
1	Staging and follow-up of breast cancer patients. Staging systems for breast cancer, unlike those of neoplasms in distant or recessed sites, allowed for the early development of clinical staging evaluation. It was established that clinical assessment of the breast lesion was often wrong compared with the pathologic examination (benign vs. malignant); clinical measurement of the tumor in centimeters was often larger than histologic size; and clinical assessment of axillary nodes (clear or metastatic) was incorrect in about 30% of cases. Although both clinical and pathologic staging provide effective discriminants for prognosis of treated patients, prognosis is more accurately determined by the pathologic stage. The single most important prognostic indicator is the axillary nodal status, and when positive, the number of positive nodes. The American Joint Committee on Cancer and the Union International Contra Cancer have agreed on a TNM staging for breast carcinoma, and this is the preferable staging system. Follow-up of treated patients is of most value in detecting local recurrence on the chest wall (after mastectomy) or in the irradiated breast (after lumpectomy), and also in early detection of contralateral breast cancer. Physical examination and periodic mammography are most useful. There is a tendency to overinvestigate asymptomatic patients (with bone scans, blood tests, etc.), but this has been correctly criticized in recent years. 
2	Isolated lipase and colipase deficiency in two brothers. Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described. Both were normally developed with a history of passing greasy stools since early infancy. Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations. After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal. No other aetiology for exocrine pancreatic insufficiency was found. This is the first report of congenital combined lipase and colipase deficiency in two brothers. 
3	Anaesthetic management of the brain dead for organ donation. An increasing number of anaesthetists is being called upon to manage organ donors during organ retrieval procedures. We briefly describe the technical aspects of the surgical procedure together with a guide to the anaesthetic management. The aims of the latter may be summarized as the "Rule of 100": systolic blood pressure greater than 100 mmHg, urine output greater than 100 ml.hr-1, PaO2 greater than 100 mmHg, haemoglobin concentration greater than 100 g.L-1. Common management problems (hypotension, arrhythmias, diabetes insipidus, oliguria, and coagulopathy) are discussed in detail. The intraoperative management of the brain-dead organ donor provides the anaesthetist with the challenge of a major surgical procedure in a subject with important physiological derangements. 
5	Relationship between histologic features, DNA flow cytometry, and clinical behavior of squamous cell carcinomas of the larynx. Flow cytometric analysis of DNA content was done on 133 primary squamous cell carcinomas of the larynx. Overall, 76 tumors (57.1%) were not diploid (aneuploid or tetraploid). The DNA index (DI) was calculated and grouped into three levels. Fifty-seven cases had a DI in a range of 1.85 to 2.15 (44 diploid and 13 tetraploid). The cases were grouped in relation to ploidy, proliferative index, and the tumor-node-metastasis (TNM) system. Every group was analyzed with respect to survival rate. Ploidy was related to histocytologic grade. In well-differentiated tumors (G1) survival rates at 48 months were 41.7% in diploid cases and 27.7% in nondiploid ones (relative risk [RR], 2.01; 95% confidence interval [CI], 0.89, 4.52). In NO cases that underwent surgery, survival rates at 48 months were, respectively, 81.8% and 49.2% (RR, 5.07; 95% CI, 0.76, 33.93). These results suggest that ploidy may be a new independent parameter of prognosis in squamous cell carcinoma of the larynx. This is useful in clinical practice because it allows the clinician to recognize those cases with poorer prognosis among the early tumors at a stage where other prognostic parameters are not yet available. 
1	Reconstitution of high-affinity opioid agonist binding in brain membranes. In synaptosomal membranes from rat brain cortex, the mu selective agonist [3H]dihydromorphine in the absence of sodium, and the nonselective antagonist [3H]naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with Kd values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 microM guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP[gamma-35S] binding sites by 90% and low Km, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP[gamma S] was diminished. High-affinity (Kd, 0.72 nM), guanine nucleotide-sensitive agonist binding was reconstituted by polyethylene glycol-induced fusion of the alkali-treated membranes with (opioid receptor devoid) C6 glioma cell membranes. Also restored was opioid agonist-stimulated, naltrexone-inhibited GTPase activity. In contrast, antagonist binding in the fused membranes was unaltered. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low Km GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor-guanine nucleotide binding protein complex. 
4	Transient myocardial ischemia and its relation to determinants of myocardial oxygen demand. Because of conflicting data and a clear need to establish the relative role of increase in myocardial oxygen demand versus reduction in coronary blood flow in the causation of transient ischemia, the role of heart rate and blood pressure changes immediately preceding and during the transient ischemic events observed during daily life were evaluated in 25 patients with coronary artery disease. Elevations in heart rate before onset of ischemia were observed in 61% of the episodes. Similarly, 73% of the ischemic events were preceded by an increase in arterial pressure. These data provide evidence for a significant role of increased myocardial oxygen demand in the genesis of transient myocardial ischemia. 
5	Denervation in hemiplegic muscles. This study examined the frequency of denervation activity in hemiplegic muscles in relation to the size and location of the central lesion. We studied 20 patients, 14 with major unilateral cerebral infarctions in the middle cerebral or internal carotid territories; four with a single lacune in the pons, internal capsule, or thalamus; and two with precentral infarcts. Using somatosensory evoked potentials, motor conduction studies, and assessments of conduction across the plexus and roots, we detected no conduction abnormalities on the affected side. Fibrillation was common in both groups, especially in distal and intermediate muscles. The distribution of the fibrillation and the normal conduction studies suggested that trauma of peripheral nerves was not a factor. Although the normal conduction studies and pattern of fibrillation activity do not exclude peripheral nerve trauma as the cause of the fibrillation, we suggest that transsynaptic degeneration is a reasonable alternative explanation. 
1	Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses. Nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma. To determine the etiological role of human papillomavirus in inverted papilloma, and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor, we retrospectively analyzed inverted papillomas from 26 patients, 7 of whom had squamous cell carcinoma. We used an immunohistochemical method and molecular pathologic techniques, or dot-blot hybridization of DNA extracted from paraffin-embedded tissues, in situ hybridization, and polymerase chain reaction. Human papillomavirus was detected in 5 of 26 patients (19%), 3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16. The latter 2 patients had inverted papillomas associated with squamous cell carcinoma. We speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas. 
3	Neuroleptic malignant syndrome: life-threatening complication of neuroleptic treatment in adolescents with affective disorder. Neuroleptic malignant syndrome (NMS) is an uncommon, potentially fatal side effect of neuroleptic treatment characterized by hyperthermia, rigidity, rhabdomyolysis, and delirium. In recent clinical studies of adults it was suggested that affective disorder is a risk factor for the development of neuroleptic malignant syndrome. The cases of two adolescents with neuroleptic malignant syndrome who were treated with neuroleptic therapy because of psychotic symptoms in association with primary affective disorders are reported. The occurrence of these cases, as well as the observations in adults, suggests that attention to the primary psychiatric diagnosis is important in neuroleptic usage and that physicians should be vigilant to the occurrence of neuroleptic malignant syndrome in the pediatric population. 
4	Essential thrombocythemia in young adults. Essential thrombocythemia is typically a disorder of adults in the sixth or seventh decade of life and is characterized by frequent thrombohemorrhagic complications. In young patients, the optimal management of complications is controversial. We studied 56 young adults (33 female and 23 male patients) with a diagnosis of essential thrombocythemia. The mean duration of follow-up was 4.68 years. The mean platelet count at diagnosis was 1,328,000/mm3. Platelet aggregation studies in 21 patients demonstrated hypoaggregation to epinephrine; spontaneous platelet aggregation was present in 4. At diagnosis, 39 patients were asymptomatic, and thrombocytosis was discovered incidentally. Throughout follow-up (up to 20 years), 24 patients remained asymptomatic. Thrombotic complications developed in 24 patients; they were life-threatening in only 3. The most common vaso-occlusive symptoms were migraine headache (in 12 patients) and erythromelalgia (in 3). Minor hemorrhagic complications occurred in six patients, and none was life-threatening. Serious complications (one cerebral and two myocardial infarctions) occurred in three patients, all of whom recovered. Two deaths occurred, neither of which was attributable to essential thrombocythemia. The treatment regimens used were chemotherapy in 9 patients, antiaggregating agents in 7, radioactive phosphorus in 1, the newer platelet-lowering agent anagrelide in 10, and only observation in 29. No treatment-related acute leukemias developed. This series of young patients with essential thrombocythemia, the largest to date, demonstrates a low incidence of life-threatening complications and a favorable long-term prognosis. Therapeutic recommendations should remain conservative, and potential leukemogens should be avoided unless serious complications develop. Anagrelide may be useful in young patients with thrombocythemia who are symptomatic. 
2	Hepatic portal venous gas: an unusual presentation of Crohn's disease. Hepatic portal venous gas is associated with numerous conditions and traditionally has been regarded as an ominous prognostic sign. There are several reports of hepatic portal venous gas occurring in patients with inflammatory bowel disease after or during the performance of colonic diagnostic studies. We report an unusual case of Crohn's disease whose initial presentation included hepatic portal venous gas. The literature of hepatic portal venous gas associated with inflammatory bowel disease is reviewed. 
5	Acute renal failure in obstructive jaundice in cholangiocarcinoma. This study was aimed at defining the natural history of renal failure in obstructive jaundice due to cholangiocarcinoma, which is an important health problem in northeastern Thailand. Sixty-four patients among a total of 130 patients with obstructive jaundice secondary to cholangiocarcinoma who developed acute renal failure were studied retrospectively. Analysis was made with respect to clinical features, laboratory findings, and outcome. The development of renal failure before surgery was observed in all patients. It was nonoliguric in 80% and was associated with severe jaundice, gram-negative infection (42%), hypotension (31%), hypoproteinemia (30%), hyponatremia (56%), and hypokalemia (63%). The mean duration of renal failure was 2 weeks. All patients underwent surgery for the relief of jaundice. Seventy-seven percent of the patients survived and had recovery of renal function after the relief of jaundice. Twenty-three percent of the patients died of infection. Clinical data highlight the higher serum bilirubin levels and the frequent occurrence of hyponatremia, hypokalemia, and hypotension in renal failure. Their possible roles in contributing to the development of renal failure are discussed. 
5	A biphasic pattern of anti-pre-S responses in acute hepatitis B virus infection. The clinical relevance of the immune response to the translation products of the pre-S1 and pre-S2 regions of hepatitis B virus was examined by testing sequential serum samples from 17 patients with acute self-limited hepatitis B and from two patients in whom chronic liver disease developed. Anti-pre-S antibodies were determined by enzyme immunoassays based on the inhibition of binding of monoclonal antibodies to epitopes in the pre-S1 and pre-S2 sequence. In acute, self-limited infection, anti-pre-S antibodies appeared in a biphasic pattern. The early antibodies were detected at the time of clinical signs of acute disease when HBsAg and often HBeAg were present, but hepatitis B virus DNA was no longer detectable in serum. Anti-pre-S levels then fell, but subsequently reappeared as the late antibody during the recovery phase, after development of anti-HBe, but before anti-HBs. Anti-pre-S responses were detected in 15 of 17 patients who recovered (88.2%) and in both patients with acute hepatitis B virus infection evolving to chronic liver disease. Although the early antibodies to pre-S1 and pre-S2 proteins appeared at the time of decreasing levels of infectious virus in serum in cases of self-limited infection, these antibodies also were transiently or continuously present with high levels of serum hepatitis B virus DNA in patients in whom chronic hepatitis B infection developed. Thus the anti-pre-S response in acute hepatitis is not a prognostic marker for clinical resolution. 
1	Chemotherapy for children with aggressive fibromatosis and Langerhans' cell histiocytosis. Two disorders involving histologically benign proliferations of fibrous tissue or of histiocytes occur preferentially in children and often require combined management by an orthopedic surgeon and a pediatric oncologist. Treatment of young people with aggressive fibromatosis usually begins with wide local excision of the lesion. However, some tumors cannot be completely removed either because of their location or because of the risk of subsequent serious dysfunction. Not infrequently, local recurrence supervenes despite previous wide local excision, and sometimes multiple tumors are present. In these situations a trial of multiple-agent chemotherapy incorporating vincristine, actinomycin D, and cyclophosphamide may be indicated in an attempt to control the disease. Radiation therapy may also be useful, but the relatively high dose (5000 cGy or more) needed in a growing child is at times a less attractive alternative. Biopsy of a lytic bone lesion in young patients with Langerhans' cell histiocytosis, formerly known as histiocytosis X, is also indicated for initial diagnosis. Biopsy and curettage are usually curative in the patient with an isolated lesion. Patients with multiple simultaneous or recurrent lesions need chemotherapy if dysfunction of the liver, spleen, or lungs is present. Drug therapy may also be beneficial for children with systemic symptoms. This article outlines suggestions for chemotherapeutic treatment in both diseases. 
2	Esophageal 24-h pH monitoring: is prior manometry necessary for correct positioning of the electrode? In 24-h esophageal pH monitoring, the electrode is usually positioned 5 cm above the manometrically localized esophagogastric junction. In order to replace esophageal manometry for this purpose, we tested whether the esophagogastric junction can be identified correctly by fluoroscopy or the determination of the pH-step between stomach and esophagus, compared with esophageal manometry. The distance from the nares to the esophagogastric junction was determined three times with each of the three methods in 46 patients and 14 volunteers. Fluoroscopy assumed the esophagogastric junction 1.23 +/- 0.23 cm (mean +/- SE) lower than the peak pressure point determined at manometry, pH-step only 0.45 +/- 0.16 cm. With pH-step, only one subject had a difference of more than 3 cm to the manometrically defined esophagogastric junction, whether gastroesophageal reflux disease (as proven by pH monitoring) was present or not. We conclude that the esophagogastric junction can usually be identified with sufficient accuracy by the measurement of the pH-step between stomach and esophagus. Fluoroscopy is far less accurate than pH-step, and should not be used. 
1	A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas. On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix. The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies. 
4	Cutaneous manifestations of multiple myeloma. We report the cutaneous manifestations of multiple myeloma, using a retrospective review of 115 patients' records obtained from tumor registry files. Five patients were found to have biopsy-proved extramedullary plasmacytomas without extension from an underlying bony focus. Twelve patients had ecchymoses without thrombocytopenia; two of them had biopsy-proved amyloidosis. One patient presented with pyoderma gangrenosum and was subsequently diagnosed with multiple myeloma. The last patient initially presented with what clinically appeared to be leukocytoclastic vasculitis, and, in the course of a standard workup, he was diagnosed with multiple myeloma. These findings are discussed with regard to the current literature on the cutaneous manifestations of multiple myeloma. 
5	Kupffer cell activation and endothelial cell damage after storage of rat livers: effects of reperfusion. Reperfusion injury characterized by loss of endothelial cell viability occurs after cold ischemic storage of livers for transplantation surgery. Here, ultrastructural changes in stored rat livers were examined by scanning and transmission electron microscopy. With increasing times of storage in Euro-Collins solution (4 to 24 hr) followed by 15 min of reperfusion at 37 degrees C, a sequence of structural alterations was observed involving endothelial and Kupffer cells. Widening of endothelial fenestrations occurred after 4 hr and progressed over 8 to 24 hr to retraction of cellular processes, ball-like rounding, sinusoidal denudation and ultrastructural derangements consistent with loss of cell viability. Kupffer cells exhibited progressive rounding, ruffling of the cell surface, polarization, appearance of wormlike densities, vacuolization and degranulation over a similar time course. By contrast, the structures of parenchymal and fat-storing cells were relatively undisturbed by cold storage and reperfusion. Alterations to endothelial and Kupffer cells were also studied as a function of time of reperfusion. After 24 hr of storage, endothelial cells showed retraction of cytoplasm before reperfusion that progressed quickly to loss of viability and denudation during reperfusion. Kupffer cell activation (ruffling, degranulation) during reperfusion was slower and occurred after deterioration of endothelial cells. Livers stored in Euro-Collins solution were also compared with livers stored in University of Wisconsin cold storage solution, an improved preservation medium for transplantation. University of Wisconsin solution provided better preservation of endothelial structure and markedly reduced parenchymal cell blebbing and swelling before reperfusion. University of Wisconsin solution also reduced Kupffer cell activation and release of lysosomal enzymes. In conclusion, endothelial cell deterioration followed by Kupffer cell activation occurred after increasing times of cold ischemic storage and reperfusion of rat livers. Both changes may contribute to the pathophysiology of graft failure caused by reperfusion-mediated storage injury. 
5	Infections of the clavicle in children. Of 23 children with infections of the clavicle, 11 had pyogenic osteomyelitis, four had tuberculosis, and eight (infants) had congenital syphilis. Acute pyogenic infections were treated by drainage. Resection of the clavicle was performed in chronic cases. Curettage and antituberculosis drugs were effective for children with tuberculous infection of the clavicle. Procaine penicillin was used for the treatment of congenital syphilis. Biopsy is generally necessary to differentiate chronic infection from neoplasm. 
5	Anterior femoral cutaneous nerve injury following femoral artery reconstructive surgery. Two cases are presented exhibiting symptoms and signs of bilateral anterior femoral cutaneous nerve injury, clinically sparing femoral nerve branches to the saphenous nerve and quadriceps muscles. This occurred following surgical dissection in the femoral triangles associated with femoral artery reconstructive surgery. Anterior femoral cutaneous nerve injury should be considered when anterior medial thigh pain and numbness occur following aortofemoral bypass graft surgery and other types of femoral artery reconstructive surgery. 
4	New technologies for the treatment of obstructive arterial disease. The well-known limitations of balloon angioplasty include unpredictable abrupt closure, chronic total occlusion, diffuse disease, and restenosis, among other factors. These limitations have prompted the development of new technologic approaches to angioplasty including laser applications for plaque ablation, mechanical device applications for plaque removal/debridement, and stent devices for structural maintenance of vascular lumen patency. Devices which directly apply laser energy for ablation of plaque material include a balloon-centered laser angioplasty system, excimer laser ablation catheter systems, and a fluorescence-guided spectral feedback laser system. Experience with these devices indicates that plaque can be successfully ablated by using laser energy. Vessel perforation and dissection are complications reported with these devices and the effects of laser angioplasty on restenosis remain unclear. Indirect application of laser energy has been tested by using a "hot tip" catheter and a laser balloon angioplasty system. Although the hot tip device has received FDA approval for use in peripheral arteries, it appears to have very limited applications in the coronary arteries. Laser balloon angioplasty appears to be beneficial in the setting of threatened acute closure; the device continues to be evaluated for potential beneficial impact on restenosis. Mechanical atherectomy catheters are designed to remove atherosclerotic plaque from the arterial system and include the AtheroCath, the Transluminal Extraction Catheter (TEC), and the Pullback Atherectomy Catheter (PAC). The Rotablator is an atheroablation device which debrides the obstructing plaque material with distal embolization of the particulate debris. Successful removal/debridement of atherosclerotic plaque has been demonstrated with the AtheroCath, Rotablator, and the TEC device. Pre-clinical studies demonstrate successful removal of plaque material with the PAC device. Despite the theoretic advantage of removing plaque material when performing angioplasty with these devices, there has been little or no reduction in restenosis rates based on a significant experience with the AtheroCath and the Rotablator. Intravascular stent devices including one self-expanding device design and two balloon-expandable device designs have been employed successfully in the elective setting to treat recurrent restenosis lesions. Two of the devices have been successfully tested in the setting of threatened acute closure. Early follow-up studies suggest some improvement in restenosis rates in certain clinical settings following intravascular stenting. Acute and subacute thrombosis remain substantial problems for stent devices and very aggressive anticoagulation regimens are necessary to minimize the adverse events. In summary, a number of a new technologic approaches for treatment of atherosclerotic lesions have been developed and are undergoing significant clinical evaluation.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study. This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients. 
2	Hilar malignancy: treatment with an expandable metallic transhepatic biliary stent. An expandable metallic transhepatic biliary endoprosthesis was used to treat 20 patients with hilar malignancy and isolated right and left intrahepatic ducts. In 12 patients, only one intrahepatic ductal system was drained; in eight patients, both systems were drained. In five patients, both systems were drained through a single transhepatic track by arrangement of two stents in a T configuration. The initial technical success rate in placing the stents and achieving internal drainage was 100%. Complications necessitating further intervention occurred in two of the 20 patients. Short-term clinical follow-up was available for 19 of the 20 patients. Two months after stent insertion, two patients complained of persistent jaundice, two patients died without jaundice, and 15 patients were free of symptoms of biliary obstruction. A variety of geometric configurations are possible with this endoprosthesis. The relative merits of these stent arrangements are discussed, and a new technique for placing the stents in a T configuration is described. 
1	Beta-carotene and cancer prevention: the Basel Study. In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk. 
3	Environmental risk factors in siblings with Parkinson's disease. To investigate possible risk factors in Parkinson's disease, we conducted a case-controlled study of 19 families having two or more siblings with Parkinson's disease. Demographic data were collected, including lifetime histories of places of residence; sources of drinking water; occupations, such as farming; and exposure to herbicides and pesticides. Rural living and drinking well water, but not farming and herbicide exposure, were significantly increased in 38 parkinsonians compared with 38 normal control subjects. A comparison of parkinsonian siblings with siblings with essential tremor revealed no differences in any risk factors for the years of shared environment. These data suggest that living in a rural environment and drinking well water are risk factors for Parkinson's disease and that the total life exposure to an environmental toxin may be more important than exposure in early life. 
4	Effects of salt, race, and hypertension on reactivity to stressors. Blood pressure and heart rate reactivity to a psychological stressor and to a cold pressor test were examined in a group of 51 normotensive and 37 unmedicated hypertensive men. All were studied twice, once while the participants were maintained on a moderately high salt (200 meq sodium/day) diet and once while the participants were maintained on an extremely low salt (10 meq sodium/day) diet. Dietary salt had no effect on blood pressure or heart rate responses to the two stressors. The systolic and diastolic responses of the white participants to the psychological stressor were greater than those of the black participants (both p less than 0.05); however, there was no difference between blacks and whites in reactivity to the cold pressor challenge. As compared with the normotensive group, the hypertensive group reacted to the psychological stressor with increased responses in systolic blood pressure, diastolic blood pressure, and heart rate (all p less than 0.05). The hypertensive group also hyperresponded in terms of the systolic pressure response to the cold pressor task (p less than 0.05). Plasma norepinephrine and epinephrine responses were not significantly different across the two diets, races, or diagnoses. 
2	Mucocele of the cystic duct remnant in eight liver transplant recipients: findings at cholangiography, CT, and US. The case histories and radiologic studies of eight liver transplant recipients who developed a mucocele of the allograft cystic duct remnant were retrospectively evaluated. All patients had clinical and/or laboratory evidence of biliary obstruction or cholangitis from 2 weeks to 3.3 years following transplantation. Cholangiographic, ultrasound (US), and computed tomography (CT) images were available for review in eight, five, and four patients, respectively. Cholangiograms demonstrated an extrinsic mass compressing the common hepatic duct in seven of eight patients. US and CT showed fairly well- to well-defined round fluid collections adjacent to the common hepatic duct in three and two patients, respectively. The findings of this study suggest that the detection at cholangiography of an extrinsic mass compressing the common hepatic duct appears to be specific for a mucocele of the allograft cystic duct remnant. CT and US images may offer confirmatory evidence. 
5	Growth in children from the Wosera subdistrict, Papua New Guinea, in relation to energy and protein intakes and zinc status. In a cross-sectional study of 123 children aged 24-120 mo from the Wosera subdistrict of Papua New Guinea, height, weight, hematocrit, hemoglobin, hair zinc, and presence of malaria were measured. Two 24-h recalls were undertaken in 67 of the children aged 72-120 mo; 52%, 73%, and 76% had energy, protein, and zinc intakes, respectively, less than two-thirds of the FAO/WHO/UNU recommendations. Stunting was prevalent (29%); 16% were moderately wasted. The prevalence of stunting and hair zinc concentrations less than 1.68 mumol/g was gender related; 38% of males vs 20% of females had Z scores for height-for-age (HAZ scores) less than -2 (P = 0.04); 26% of males vs 11% of females had hair zinc less than 1.68 mumol/g (P less than 0.05). Analysis of variance showed that age, sex, hemoglobin, and log hair zinc influenced HAZ scores, depending on the age group; both sex and the log of the hair zinc values were significant factors in the older children. Stunting in Worsera children was related to chronic deficits in energy and protein and was excerbated in the older male children by suboptimal zinc status. 
4	Simulated left ventricular aneurysm and aneurysm repair in swine. Patch reconstruction of left ventricular aneurysm may be superior to linear closure, but this hypothesis has not been tested experimentally. Accordingly, six anesthetized domestic pigs were instrumented to measure regional left ventricular wall thickening, stroke volume, systolic left ventricular pressure, and myocardial oxygen consumption. With total bypass and cardioplegia, a 6 by 8 cm Dacron patch was inserted into the anteroapical left ventricle. Simulations were as follows: left ventricular aneurysm, patch open; patch reconstruction, 50% patch plication; standard repair, ventriculotomy edges approximated. Global function, from stroke work (stroke volume x integral of left ventricular pressure)-left ventricular end-diastolic pressure curves, was depressed in all three simulations compared with control. A tendency for stroke work to be greater for standard repair than for left ventricular aneurysm and patch reconstruction at higher preloads was not statistically significant. Mechanical efficiency, from stroke work/myocardial oxygen consumption (joules per milliliter oxygen per beat), was 2.43 +/- 0.52 (mean +/- standard error of the mean) (control), 2.22 +/- 0.94 (standard repair), 1.27 +/- 0.39 (patch reconstruction), and 1.09 +/- 0.37 (left ventricular aneurysm) (no significant differences). Regional work was calculated as regional left ventricular wall thickening x integral of left ventricular pressure. The slope of the regional work-end-diastolic wall thickness relation decreased in the posterior wall 14.0 +/- 2.9 (control) versus 8.4 +/- 2.0 (left ventricular aneurysm), 6.9 +/- 1.4 (patch reconstruction), and 7.4 +/- 1.4 (standard repair) (p less than 0.05). In the anterior wall, contractility did not change significantly (7.4 +/- 1.2, control; 7.8 +/- 2.7, left ventricular aneurysm; 5.0 +/- 0.4, patch reconstruction; and 5.3 +/- 0.4, standard repair). Decreased end-diastolic wall thinning anteriorly suggested tethering. These results in the normal left ventricle suggest that patch ventriculoplasty is of no greater benefit than linear repair. Either repair may impede function of adjacent myocardium through restriction of regional diastolic lengthening. 
5	Hyperplastic gastric polyps associated with persistent Helicobacter pylori infection and active gastritis. We report two cases of patients with 3-yr histories of upper gastrointestinal symptoms, hyperplastic gastric polyps, and active chronic gastritis. Biopsies retrospectively stained with Giemsa revealed the persistent presence of Helicobacter pylori (HP) in gastric biopsies of both patients throughout the 3 yr. After treatment with amoxicillin and bismuth subsalicylate, both became asymptomatic, one demonstrating disappearance and recurrence of the gastric polyps in conjunction with the HP. These cases demonstrate 3 yr of hyperplastic gastric polyps associated with HP and active gastritis. 
5	Penetrating keratoplasty after ocular trauma. We reviewed the records of 41 patients who underwent penetrating keratoplasty for a corneal opacity caused by trauma between Jan. 1, 1983, and Dec. 31, 1988. Most of the patients were young males whose average age was 35 years. Common tools accounted for many injuries (14 of 41, 34%). Sixteen injuries (39%) were work-related. Thirty-six patients (88%) had corneal scars from a perforating injury, four patients (10%) had corneal edema, and one patient (2%) required emergency penetrating keratoplasty for extensive tissue loss. Of the 39 patients with one year of follow-up, 31 (82%) maintained clear corneal grafts. Rejection occurred in nine of 39 patients (23%) and only three (33%) of the rejections resolved. Visual outcome was favorable with 20 patients (51%) attaining best-corrected postoperative visual acuity of 20/20 to 20/40, nine patients (23%) attaining visual acuity of 20/50 to 20/100, and ten patients (26%) attaining visual acuity of 20/200 or worse. Preoperative retinal disease (six of 39, 15%), astigmatic errors (five of 39, 13%), graft failures (four of 39, 10%), and postoperative glaucoma (12 of 39, 31%) adversely influenced the outcome. Although the prevalence of postoperative complications is relatively high, good visual results can be obtained in patients who undergo penetrating keratoplasty after ocular trauma. 
4	Normalization of increased sodium sensitivity by maintenance hemodialysis. Blood pressure (BP) becomes more sodium and body fluid sensitive as renal function deteriorates. Thus, hypertension in chronic renal failure is mostly of the sodium sensitive type. We studied whether the increased sodium sensitivity (SS) can be restored to normal on the maintenance phase of hemodialysis (HD) therapy. Body weight (BW) and BP (specifically, mean arterial pressure [MAP]) were measured after HD and before the next HD, and the body fluid sensitivity (BFS) was calculated as the ratio of changes in these factors on both introduction and maintenance phases in HD patients (n = 56) who were not taking any antihypertensive drugs (BFS = delta MAP/delta BW). In a preliminary study, the amount of interdialytic sodium intake (QNa+) was measured (n = 30), and SS was calculated as the ratio of the change in MAP to QNa+ (SS = delta MAP/QNa+). Interdialytic BW gain (3.1 +/- 0.1 kg) was correlated with the amount of sodium intake (136 +/- 17 mEq), resulting in a positive relationship between BFS and SS (r = 0.79, P less than .0001). Therefore, BFS was used as an index of SS. As a whole, BFS decreased from the introduction to the maintenance phase (6.5 +/- 1.0 to 3.5 +/- 0.6 mm Hg/L, P less than .01). This decrease was marked (6.2 +/- 1.1 to 2.9 +/- 0.6 mm Hg/L, P less than .01) in patients (n = 46) whose BP was normalized in the maintenance phase, while not significant (7.9 +/- 1.9 to 6.3 +/- 1.3 mm Hg/L) in patients (n = 10) whose BP was still high. 
1	Occult vascular malformations of the optic chiasm: magnetic resonance imaging diagnosis and surgical laser resection. Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function. 
5	"Cloggology" revisited: endoscopic or surgical decompression of malignant biliary obstruction. In this study, 50 consecutive patients over age 60 with obstructive jaundice secondary to malignant stricture of the distal common bile duct were identified by endoscopic cholangiography. The patients were then randomized to palliative therapy with either endoscopic endoprosthesis or bypass surgery. Prospective indices of survival time, complication rates, hospitalization requirements, and quality of life were followed. All 25 patients randomized to endoprosthesis were treated by this procedure, whereas only 19 of 25 patients randomized to bypass surgery underwent operative biliary-digestive anastomosis. No difference in the above indices were found between the two groups. The authors concluded that palliation of obstructive jaundice due to a malignant bile duct stricture with endoscopically placed biliary stent is as effective as operative bypass. 
5	Effects of inflammation and copper intake on rat liver and erythrocyte Cu-Zn superoxide dismutase activity levels. Stress such as inflammation produces an acute phase response that includes elevated levels of ceruloplasmin, the main copper component of plasma. Inflammatory effects on cellular copper enzyme activity levels are largely unknown. Cu-Zn superoxide dismutase (SOD) activities in liver, the main site of ceruloplasmin secretion, decreased with turpentine-induced inflammation (0.1 mL, intramuscular, leg) in rats fed any of three copper levels (adequate = 6 mg/kg, marginal = 2.5 mg/kg and deficient less than 0.5 mg/kg). Ceruloplasmin activities rose significantly with inflammation in the adequate and marginal groups but not in the deficient animals. Hepatic Cu-Zn SOD immunoreactive protein levels were unaffected by copper status or inflammatory state. Erythrocyte Cu-Zn SOD activities were influenced by dietary copper but not inflammation. An additional group of rats fed 15 mg copper/kg did not show a turpentine-induced decrease in liver Cu-Zn activity levels. Inflammatory effects on other copper enzyme activities did occur as evidenced by increases in ceruloplasmin and decreases in serum extracellular SOD. In conclusion, an acute phase response in rats increased the amount of dietary copper required to maintain hepatic Cu-Zn SOD activity at levels equal to those of nonstressed, copper-adequate rats. Rat erythrocyte Cu-Zn SOD activities provided a blood measurement reflective of copper intake with or without stress, but these values did not reflect decreases in liver Cu-Zn SOD activities after 3 d of inflammation. 
5	Comparison of symptom characteristics of indwelling ureteral catheters. The signs and symptoms produced by 4 different types of 7F double pigtail catheters, including Cook polyurethane pigtail stent, Surgitek Silitek Uropass, Cook C-Flex and Van-Tec Soft stent, were analyzed prospectively. The stents were placed in 45 men and 28 women ranging in age from 23 to 72 years old. A total of 44 catheters had a suture attached to the bladder end of the catheter, which exited from the urethral meatus to facilitate removal. The remaining 29 catheters had no suture attached. Symptoms were evaluated at 2 and 6 days after insertion and 1 week following removal of the catheter, and included urinary frequency, nocturia, hematuria, flank pain, suprapubic pain, dysuria and pain on removal of the catheter. Frequency and nocturia were evaluated in minutes, pain was graded on a subjective scale of 0 (no pain) to 10 (severe pain), and dysuria and hematuria were assessed qualitatively. There were no significant differences among the 4 types of catheters in terms of frequency, nocturia, hematuria, flank pain, suprapubic pain and dysuria. In addition, there was no significant difference in urinary symptoms between catheters with and without a suture at either 2 or 6 days after insertion nor was there any difference in pain on removal of catheters with (mean 3.9) and without (mean 5.0) suture. We found that catheter composition and use of suture to facilitate removal did not significantly affect patient morbidity. 
5	Touch and surgical division of the anterior quadrant of the spinal cord. An investigation was carried out to determine whether tactile sensibility was affected by anterolateral cordotomy. There were 65 patients who had cordotomies for painful forms of cancer. Thirty eight had necropsy examination with histological investigation of the spinal cord. No form of mechanoreception was removed in any of the 65 patients and in the majority no forms of tactile sensibility were altered by division of the pathways in the anterolateral and anterior columns. In no case was graphaesthesia affected. Knowledge of joint position and movement and awareness of vibration was normal in 62 of the 65 patients. But information carried by these anterolateral pathways does reach neural levels of consciousness, for with total lesions of the posterior columns, previously reported, touch and pressure are still felt. Itch was removed by division of the anterolateral pathways. Although the posterior columns are essential for discrimination in mechanoreception, discrimination may be disturbed by lesions of the anterolateral pathways, notably two-point discrimination. The evidence on the pathways essential for conveying impulses giving rise to tickle was inconclusive. 
3	Haemophilus influenzae meningitis with prolonged hospital course. A retrospective evaluation of Haemophilus influenzae type b meningitis observed over a 2-year period documented 86 cases. Eight of these patients demonstrated an unusual clinical course characterized by persistent fever (duration: greater than 10 days), cerebrospinal fluid pleocytosis, profound meningeal enhancement on computed tomography, significant morbidity, and a prolonged hospital course. The mean age of these 8 patients was 6 months, in contrast to a mean age of 14 months for the entire group. Two patients had clinical evidence of relapse. Four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days. All patients received antimicrobial therapy until they were afebrile for a minimum of 5 days. Subsequent neurologic examination revealed a persistent seizure disorder in 5 patients (62.5%), moderate-to-profound hearing loss in 2 (25%), mild ataxia in 1 (12.5%), and developmental delay with hydrocephalus which required shunting in 1 (12.5%). One patient had no sequelae. 
1	Carcinoma of the thyroglossal duct. A review of 39 instances of excision of a cyst of the thyroglossal duct performed at St. Paul Medical Center, Dallas, Texas, revealed two patients with carcinoma of the thyroglossal duct. A review of the English literature yielded 146 instances of this uncommon tumor. Eighty-four per cent were papillary adenocarcinoma of thyroid type and 5 per cent were squamous cell carcinoma. The patients were from six to 81 years old with a 2:1 female to male ratio. Metastatic disease to lymph nodes was noted in 11 per cent and invasion of overlying strap muscles was found in 4 per cent. Carcinoma of the thyroid gland occurred in 14 per cent. Preoperative diagnosis was rare. The Sistrunk procedure is recommended for initial surgical therapy with further surgical or adjuvant therapy dependent on associated clinical findings. Prognosis for carcinoma of the thyroglossal duct of thyroid type parallels that of carcinoma of the thyroid gland. 
3	Quantitative assessment of extradural bupivacaine analgesia. Bupivacaine (0.5%) 20 ml was administered extradurally to six healthy volunteers. It was found that simultaneous application of 10 needles to the skin could evoke pain when analgesia was obtained to one needle stimulation. In addition, a laser beam was used as a quantitative technique to activate simultaneously many cutaneous nociceptors. For 7 h, thresholds (sensory and pain) and pain-evoked brain potentials (amplitude and latency) to laser stimulation were monitored and used for quantitative assessment of onset, efficacy and duration of analgesia at various dermatomes (C7, T8, T10, T12, L1, L3, S1). The onset time of analgesia was shortest and conduction delay longest at the dermatome related to the site of injection (L3). Full analgesia was obtained at L1, L3 and S1, although the peak efficacy at S1 was delayed for 120-180 min after injection. A minor effect was found at dermatome C7 approximately 60 min after injection. 
3	Chiari pelvic osteotomy for osteoarthritis. The influence of the torn and detached acetabular labrum. We assessed the results of Chiari pelvic osteotomy in 64 hips with early osteoarthritis in terms of acetabular labral detachment detected pre-operatively by arthrography. At an average follow-up of four years, assessment by the Merle d'Aubigne score showed 83% excellent or good results. These satisfactory results were achieved in only half the cases with a detached labrum, but in nearly all cases with normal or torn acetabular labra. Other factors such as the acetabular index, the level and angle of osteotomy, and the displacement following osteotomy did not affect the results. Chiari pelvic osteotomy is a worthwhile procedure for early osteoarthritis in selected cases, but a detached acetabular labrum increases the risk of clinical failure. 
1	Ureteral stump carcinoma incidentally found at cystectomy for bladder cancer. We report on a sixty-five-year-old man with hematuria secondary to superficial bladder cancer. Because of previous urethral trauma, a complete transurethral resection of his bladder tumor could not be done. He, therefore, underwent cystectomy, at which time we incidentally found a transitional cell carcinoma of the left ureteral stump that had been left from a previous left nephrectomy for a World War II-related injury. This case underscores the importance of a thorough investigation of the complete urinary tract in a patient with hematuria or other urinary tract symptoms even if an obvious cause is found for his symptoms. 
2	Polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction: POLIP syndrome. We describe 5 individuals (from three separate families) with a progressive neurological disorder characterized by sensorimotor peripheral polyneuropathy, cranial neuropathies (external ophthalmoplegia, deafness), and the syndrome of chronic intestinal pseudo-obstruction. Magnetic resonance imaging showed widespread abnormality of the cerebral and cerebellar white matter in the 2 patients studied. Autopsy examination in 3 revealed widespread endoneurial fibrosis and demyelination in the peripheral nervous system, possibly secondary to axonal atrophy, and poorly defined changes in cerebral white matter (leukoencephalopathy). The cranial nerves and spinal roots were less severely involved and the neurons in the brainstem and spinal cord were intact. The fatal gastrointestinal dysmotility was due to a severe visceral neuropathy. We suggest that these patients manifested a hereditary disorder with distinctive clinical, radiological, and neuropathological features, and propose the acronym POLIP to emphasize the distinctive tetrad of polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction. 
2	Sulphasalazine and prednisone compared with sulphasalazine for treating active Crohn disease. A double-blind, randomized, multicenter trial. OBJECTIVE: To determine whether sulphasalazine plus prednisone is more effective than sulphasalazine alone in treating active Crohn disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Multicenter trial in one university hospital and nine general hospitals. PATIENTS: Patients with active Crohn disease and a Van Hees Activity Index of 140 or more. Of 71 patients who were randomly assigned, 60 completed treatment and were analyzed. INTERVENTIONS: For 16 weeks, 30 patients received sulphasalazine, 6 g/d (or 4 g/d if adverse effects occurred) and prednisone, 30 mg/d initially. Prednisone therapy was tapered in increments of 5 mg/2 wk to 10 mg/d after 8 weeks. Thirty other patients received sulphasalazine and a placebo. MEASUREMENTS AND MAIN RESULTS: In the first 6 weeks of treatment, the Van Hees Activity Index decreased to a median of 70% (interquartile range, 57% to 81%) of the initial value in patients treated with sulphasalazine and prednisone and to a median of 87% (interquartile range, 70% to 94%) in patients treated with sulphasalazine alone (P = 0.001). In the last 4 weeks of treatment, the corresponding figures were 63% (interquartile range, 40% to 75%) and 70% (interquartile range, 54% to 90%) (P = 0.10). The Crohn's Disease Activity Index decreased in the first 6 weeks to a median of 65% (interquartile range, 57% to 86%) in patients receiving sulphasalazine and prednisone and to a median of 75% (interquartile range, 58% to 101%) in patients receiving sulphasalazine alone (P = 0.13). In the last 4 weeks of treatment, the corresponding figures were 65% (interquartile range, 42% to 90%) and 76% (interquartile range, 49% to 110%) (P = 0.19). CONCLUSIONS: The use of prednisone in addition to sulphasalazine in patients with active Crohn disease results in a significantly faster initial improvement, but not in a significantly better result after 16 weeks of treatment, when disease activity is measured by the Van Hees Activity Index. 
1	Restriction fragment length polymorphism analysis to study the genetic origin of complete hydatidiform mole. To determine the genetic origin of the complete hydatidiform mole, 20 abnormal pregnancies were studied with restriction fragment length polymorphism with five genomic probes: EJ 6.6, beta-globin gene, 3'alpha-hypervariable region, J-Bir, and St14. In the 12 cases of molar pregnancy, pure paternal origin was proved in 11 cases, but both maternal and paternal inheritance were shown in only one case. In the cases with pure paternal origin, all of the restriction fragment length polymorphisms were homozygous, although those of the fathers were heterozygous at 15 loci. In the four cases that mimicked hydatidiform mole but were diagnosed as hydropic change of villi, both paternal and maternal inheritance were noted. In the four pregnancies with blighted ovum, both paternal and maternal inheritance were shown in three cases; and in one case with a balanced translocation between chromosomes 13 and 14, only paternal inheritance was noted. This study showed that most of the complete hydatidiform moles were caused by fertilization of an empty egg by a duplicated haploid sperm, but rare exceptions may exist. 
2	(A)typical symptoms during single needle dialysis. In 5 elderly patients, an abnormally high occurrence of some symptoms was noted during dialysis. All patients were dialyzed with biocompatible membranes, bicarbonate dialysate, and a blood flow of 250 to 300 ml/min by a single needle system, on a fistula 14 Gauge catheter-needle. These symptoms were: 1) "angina," resistant to O2 and nitrates, with biochemical stigmata of infarction, but without electrocardiogram (ECG) localization; 2) intractable persistent hypotension, not hypovolemic, lasting 1 or 2 days; 3) esophagal spasms, with inability to swallow solid food. Because we knew that these symptoms were compatible with hemolysis (biochemically proven by the increase in serum LDH during dialysis and by a fall in haptoglobin) due to red cell fragmentation (RCF), we switched these patients from fistula dialysis (A) to central catheter dialysis (B), with the same apperture, blood flow, etc. The total number of sessions of A versus B were 512 and 891; the mean LDH ratios (serum LDH postdialysis divided by predialysis) were 1.8 and 1.0 (= no RCF); angina events were 132 (26%) for A, and 25 (3%) for B; persistent hypotension was seen 37 (7%) times in A and 5 (0.6%) times in B; esophagal spasms were noted 65 (13%) times for A, and 0 times for B. This clinical improvement was so overwhelming that 3 patients refused to be dialyzed again using their well functioning fistulae. This study also proved the need for a better designed and manufactured peripheral dialysis catheter-needle. 
3	Cerebrospinal norepinephrine concentrations and the duration of epidural analgesia This study was performed to determine whether the addition of norepinephrine to local anaesthetics prolongs epidural analgesia in man. In addition, cerebrospinal fluid norepinephrine (NE) concentrations were measured. In the first part of the study, epidural catheters were inserted in 14 patients before herniotomy. Mepivacaine, 1.5 per cent (0.35 ml.kg-1), was administered and norepinephrine (5 micrograms.ml-1) was added in seven patients. The duration of anaesthesia was prolonged from 54 +/- 11 min to 83 +/- 12 min (P less than 0.05) and CSF NE concentrations increased from 68 +/- 12 pg.ml-1 to 336 +/- 85 pg.ml-1 in the NE group (P less than 0.01). In the second part, eight patients with herpetic neuralgia received epidural analgesia at the fourth to eighth thoracic interspace, using bupivacaine 0.25 per cent, with and without NE. The CSF NE concentrations in this group were greater than in the surgical patients before operation and increased from 254 +/- 58 to 406 +/- 58 pg.ml-1 30 min after administration of bupivacaine with NE. The duration of pain relief was prolonged with NE. These results suggest that adding NE to local anaesthetics prolongs epidural analgesia. Moreover, NE concentrations in surgical patients increased to levels similar to those found in patients suffering from herpetic analgesia. This suggests that the increase of CSF NE in chronic pain states has an antinociceptive effect. 
5	Putative mechanisms of cytoprotective effect of certain antacids and sucralfate. An investigation of cytoprotective activity of certain antacids and inert particles was carried out by treating ethanol-induced gastric mucosal damage in rats in order to clarify possible mechanisms by which aluminum-containing antacids act. Al(OH)3 inhibited gastric mucosal damage in a dose-related and time-dependent manner. Neither aluminum ions themselves nor the particle size of the Al(OH)3 complex were responsible for the observed cytoprotection, since neither AlCl3, chemically inert Al2O3*C, nor sea sand showed protective effects. Hyperosmolality in the gastric lumen was not a deciding factor in inducing cytoprotection. Silicic acid and titanium dioxide, with superficial charge similar to Al(OH)3 proved to be effective in inhibiting gastric hemorrhagic lesions and releasing PGE2, suggesting that the surface charge of Al(OH)3 may be important in its cytoprotective properties. The same may also be valid for sucralfate. Since antacid-induced cytoprotection was only partly reduced by pretreatment with indomethacin, it is likely that additional mechanisms and mediators other than prostaglandins, such as nonprotein sulfhydryls, also are involved in gastric cytoprotection arising from aluminum-containing antacids. 
3	Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results. Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab-England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period. 
4	Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis. The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis. 
3	Epidemiology of epilepsy in Guaymi Indians from Bocas del Toro Province, Republic of Panama. This cross-sectional study was conducted to describe the epidemiology of epilepsy in Guaymi Indians residing in Changuinola, a small town on Panama's Caribbean coast near Costa Rica. We randomly selected households and attempted to enroll all residents aged less than or equal to 1 year; 337 eligible subjects agreed to participate (93% response rate). We administered a standard neurologic disease screening examination to all subjects and, if any abnormality was found, we administered a standard neurologic evaluation. We detected 19 cases of active epilepsy; the mean age at onset was 12 years, and generalized tonic-clonic seizures were the most common diagnosis (10 of 19, 53%). The prevalence of active epilepsy among Caribbean coastal Guaymi (57/1000) is considerably greater than that in lower class Panama City populations (22/1000) or in other parts of the world. To identify risk factors for epilepsy, we collected epidemiologic data and serum (for Cysticercus antibody) from subjects with active epilepsy and from 44 age/sex-matched controls. Significantly more cases (47%) than controls (6%) had other family members with epilepsy (relative risk, RR = 14); 44% of cases and 13% of controls reported a history of febrile seizures during childhood (RR = 6). 
3	Practical aspects of pulsatile gonadotropin-releasing hormone administration. Pulsatile administration of gonadotropin-releasing hormone represents a major advance in the treatment of anovulation in women who fail to ovulate with clomiphene citrate and is an alternative for many women who currently receive human menopausal gonadotropin. Four issues must be addressed before administering pulsatile gonadotropin-releasing hormone: (1) safety, (2) efficacy, (3) convenience, and (4) cost. Each of these issues will be affected by the three major decisions a physician makes with gonadotropin-releasing hormone therapy: (1) patient selection, (2) route of administration, and (3) dose of gonadotropin-releasing hormone. The ideal candidate for gonadotropin-releasing hormone therapy is a patient with an absence of endogenous pulsatile gonadotropin-releasing hormone, as seen in hypothalamic amenorrhea. Although women with polycystic ovarian disease can be treated with pulsatile gonadotropin-releasing hormone, a decreased ovulation rate should be expected. The route of administration, intravenous or subcutaneous, and the degree of monitoring can be tailored by the physician to fit each patient's needs. Pulsatile gonadotropin-releasing hormone therapy is a safe, effective, convenient, and economical alternative to human menopausal gonadotropin for ovulation induction in women resistant to clomiphene. 
4	Use of the metabolic tracer carbon-11-acetate for evaluation of regional myocardial perfusion. The high first-pass myocardial extraction fraction of carbon-11-acetate suggests that its initial uptake depends on blood flow. Accordingly, regional uptake of 11C-acetate at 4 min was compared to regional perfusion determined with nitrogen-13-ammonia in 119 segments in 15 patients with stable coronary artery disease by two methods. A close correlation was observed between initial relative myocardial concentrations (segmental activity normalized to maximal activity) of both tracers (11C-acetate = 0.88; 13N-ammonia + 0.079; s.e.e. = 0.064, r = 0.94, p less than 0.001). Furthermore, segmental net extractions (E.F), as calculated from the input function and segmental activities, of the two tracers correlated closely by E.FC-11 = 0.55E.FN-13 + 0.080 (s.e.e. = 0.045, r = 0.87, p less than 0.001). These relationships indicate that initial regional myocardial uptake of 11C-acetate reflects perfusion and that 11C-acetate permits near simultaneous evaluation of regional oxidative metabolism and of regional myocardial perfusion. 
3	Cerebral malaria in children Cerebral malaria is a rapidly progressive encephalopathy with up to 50% mortality. A cardinal feature is the massing of red cells containing mature Plasmodium falciparum within the cerebral capillaries. Adhesion of these parasitised red cells to endothelium, an event which may initiate cerebral malaria, is being studied at the molecular level. However, the relevance of these studies to the pathophysiology and treatment of human cerebral malaria is uncertain. Although chloroquine is still widely used to treat falciparum malaria, resistance has spread to most of the endemic zone. Quinine is emerging as the only effective treatment for cerebral malaria, though resistance to this drug threatens to become a problem. Alternative drugs are urgently needed. 
5	Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport. The p53 protein is rendered temperature-sensitive by a point mutation. Rat cells transformed by this mutant p53 and an activated ras oncogene grow well at 37 degrees C but cease DNA synthesis and cell division when shifted to 32 degrees C. Immunostaining demonstrates that the mutant p53 protein is in the nucleus of the arrested cells at 32 degrees C but in the cytoplasm of the growing cells at 37 degrees C. This is the first example of a protein which is temperature-sensitive for nuclear transport. The translocation from cytoplasm to nucleus and vice versa occurs 6 h after temperature shift and is coincident with the inhibition of DNA synthesis; transport from cytoplasm to nucleus does not require protein synthesis. Remarkably, inhibition of protein synthesis at 37 degrees C also results in the rapid appearance of mutant p53 in the cell nucleus. These results suggest the presence of a short-lived protein responsible for holding p53 in the cytoplasm at 37 degrees C but not at 32 degrees C. Analysis of a non-temperature-sensitive mutant p53 protein shows that its cytoplasmic location is sensitive to protein synthesis inhibitors but not to temperature. 
5	Progression through the cell cycle: an overview. Tissues in adults can be maintained at constant mass or they can increase or decrease in size because of imbalances of synthetic and degradative processes acting at the cellular and molecular levels. Some size changes are caused by physiologic conditions to which the tissue must adjust. Alternatively, the balance may be distorted in favor of net tissue increase in pathologic situations such as cancer. Strict regulatory mechanisms are required to keep proliferation responsive to the organism's needs; these mechanisms may be defective in disease. Net tissue proliferation requires repeated rounds of cell duplication in excess of that necessary to counterbalance cell death. Duplication of a cell requires a net doubling of its every molecule and structure. The myriad of molecular events required for cell proliferation such as DNA duplication and its partitioning at mitosis are tightly regulated in normal cells. One may conceive of two classes of molecules: those required for "housekeeping," which constitute the cell's structural and functional machinery, and those such as growth factors, their receptors, and second messengers involved in signal transduction responsible for regulating the activities of the housekeeping molecules. These molecular events and the cascade of processes that control them can be organized within the sequence of the cell cycle. In this brief overview, we illustrate these issues with a few examples taken from very recent discoveries of novel proteins that appear to have major regulatory roles. Most of these results have been obtained with mammalian fibroblasts, but some have originated with discoveries made using two very different yeasts. 
1	Contemporary management of a potentially lethal fetal anomaly: a successful perinatal approach to epignathus. Prenatal diagnosis of epignathus (a teratoma originating in the oropharynx) has been reported previously. However, in many of these cases the neonates succumbed to acute respiratory distress secondary to airway obstruction at the time of birth. We describe a case of antepartum diagnosis of epignathus using ultrasonography and magnetic resonance imaging as complementary techniques. The ability to accurately define the fetal anomaly permitted us to plan a unique strategy for peripartum management. After cesarean delivery of the infant from the uterus, the umbilical cord was not clamped and the fetoplacental circulation was left undisturbed. A tracheostomy was then performed, after which the umbilical cord was clamped and the infant was stabilized. Several hours later, a debulking procedure was performed in the operating room to remove the tumor from its attachment to the bony palate. Both mother and infant did well postoperatively. The ability to plan and perform a controlled tracheostomy while the infant remained oxygenated and ventilated proved to be lifesaving in this case. 
4	Progress in cardioprotection: the role of calcium antagonists. Calcium antagonists are now widely used for the treatment of clinical hypertension and angina pectoris. They are efficacious for the treatment of vasospastic, fixed atherosclerotic and mixed angina; they reduce the incidence of silent ischemia; and they have been shown to reduce postmyocardial infarct angina. Experimental data suggest that they may have certain cardioprotective properties in cases of acute myocardial ischemia and infarction, stunned myocardium, diastolic dysfunction, left ventricular hypertrophy and atherosclerosis. Moreover, they have been shown to improve exercise performance, as well as the diastolic abnormalities in patients with hypertrophic cardiomyopathy. In animals, they may delay or reduce the extent of myocardial necrosis after coronary occlusion or coronary occlusion followed by reperfusion, and in low doses that do not alter the hemodynamic profile, they have been shown to enhance the return of ventricular function in animals with stunned myocardium. However, the early first-generation calcium antagonists (nifedipine, verapamil, diltiazem) have not been shown to reduce myocardial infarct size or to enhance survival in patients with acute myocardial infarction. There now are clinical studies that suggest that, unlike beta blockers or nitrates, nifedipine may slow the development of atherosclerotic progression in humans over a 2-year period, and it seems likely that in the 1990s there will be further expansion of the use of calcium antagonists for not only angina and hypertension but also for aspects of cardioprotection. That calcium antagonists may delay, prevent or possibly regress atherosclerotic lesions is an exciting possibility. 
3	Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. Follow-up studies of psychiatric patients with panic disorder have shown an abnormally high mortality rate in men due to cardiovascular and cerebrovascular events. The authors report that in the New Haven portion of the Epidemiologic Catchment Area program the risk for stroke in persons with lifetime diagnoses of panic disorder was over twice that in persons with other psychiatric disorders or no psychiatric disorder. After adjustments for demographic differences between groups, the risk was even higher. While the results should be interpreted cautiously because of the small sample and absence of medical examinations, these findings are consistent with clinical studies showing an association between panic disorder and cardiovascular/cerebrovascular events. 
4	Prognosis and prognostic factors of retinal infarction: a prospective cohort study. OBJECTIVE--To determine the prognosis and adverse prognostic factors in patients with retinal infarction due to presumed atheromatous thromboembolism or cardiogenic embolism. DESIGN--Prospective cohort study. SETTING--University hospital departments of clinical neurology. PATIENTS--99 patients with retinal infarction, without prior stroke, referred to a single neurologist between 1976 and 1986 and evaluated and followed up prospectively until death or the end of 1986 (mean follow up 4.2 years). INTERVENTIONS--Cerebral angiography (55 patients), aspirin treatment (37), oral anticoagulant treatment (eight), carotid endarterectomy (13), cardiac surgery (six), and peripheral vascular surgery (two). MAIN OUTCOME MEASURES--Death, stroke, coronary events, contralateral retinal infarction; survival analysis confined to 98 patients with retinal infarction due to presumed artheromatous thromboembolism or cardiogenic embolism (one patient with giant cell arteries excluded), and Cox's proportional hazards regression analysis, including age as a prognostic factor. RESULTS--During follow up 29 patients died (21 of vascular causes and eight of non-vascular or unknown causes), 10 had a first ever stroke, 19 had a coronary event, and only one developed contralateral retinal infarction. A coronary event accounted for more than half (59%) of the deaths whereas stroke was the cause of only one death (3%). Over the first five years after retinal infarction the actuarial average absolute risk of death was 8% per year; of stroke 2.5% per year (7.4% in the first year); of coronary events 5.3% per year, exceeding that of stroke; and of stroke, myocardial infarction, or vascular death 7.4% per year. Prognostic factors associated with an increased risk of death were increasing age, peripheral vascular disease, cardiomegaly, and carotid bruit. Adverse prognostic factors for serious vascular events were increasing age and carotid bruit for stroke, and increasing age, cardiomegaly, and carotid bruit both for coronary events and for stroke, myocardial infarction, or vascular death. CONCLUSIONS--Patients who present with retinal infarction due to presumed atherothromboembolism or cardiogenic embolism are at considerable risk of a coronary event. The risk of stroke, although high, is not so great. Not all strokes occurring after retinal infarction relate directly to disease of the ipsilateral carotid system, although this is probably the most common cause. Few patients experience contralateral retinal infarction. Non-arteritic retinal infarction should be diagnosed or confirmed by an ophthalmologist, and the long term care of patients with the condition should involve a physician who has an active interest in managing vascular disease. 
1	Primary central nervous system lymphoma in a pediatric patient with acquired immune deficiency syndrome. Treatment with radiation therapy. Primary central nervous system (CNS) lymphoma, an otherwise rare pediatric tumor, has been reported with increasing frequency in children with acquired immune deficiency syndrome (AIDS). With current therapy, the outcome of this disease is invariably fatal. The authors present a case of primary CNS lymphoma in a 3.5-year-old girl with AIDS who received treatment with total brain irradiation. After treatment, the patient's mental status improved, the seizures resolved, and she had no further progression of her neurologic symptoms until she died of pneumonia 6 months later. The autopsy revealed a necrotic mass at the site of the original tumor. The brain stem and spinal cord, unirradiated, contained lymphomatous lesions. The patient had extensive fibrinoid necrosis and leukoencephalopathy that were consistent with radiation-induced CNS damage. Coexisting AIDS encephalopathy also contributed to the patient's CNS injury. Effective palliation of CNS lymphoma in children with AIDS may be obtained with cranial irradiation. Pediatric AIDS patients may show more severe tissue effects from irradiation than unaffected children. 
5	Radionuclide imaging of asymptomatic versus symptomatic total knee arthroplasties. Ninety-eight total knee prostheses were evaluated by roentgenograms and bone scans. Fifty-three were asymptomatic, and 45 were symptomatic. Thirteen prostheses required revision surgery. At a mean of 54 months, asymptomatic knee replacements generally showed only mild uptake in one or more zones. Only one knee had uptake equal to surrounding bone. However, symptomatic knee replacements showed significantly greater uptake in the patella, femur, and medial and lateral tibial plateau regions (Mann-Whitney two-sample rank test). Bone scans in the symptomatic group were obtained at a mean of 44 months. Excluding those patients who had revision surgery, the differences remained significant. Furthermore, symptomatic knee replacements with normal roentgenograms also had significantly greater uptake. Radiolucent lines were noted in 30% of asymptomatic patients, whereas 29% of symptomatic knees had radiolucencies. Radiolucencies were not generally associated with significantly greater uptake. Lateral release had no effect on the patellar score. 
4	Cardiac contractility and conduction: a comparison of antihypertensives. The four classes of first-line antihypertensive agents recommended in the 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure are reviewed here. Particular consideration is given to the effects of these agents on heart rate, atrioventricular nodal conduction, and myocardial contractility in patients with other cardiovascular diseases. Diuretics and angiotensin-converting enzyme inhibitors have no significant direct effects on cardiac function. beta-Blockers inhibit catecholamine stimulation of the heart and may be particularly beneficial in treating patients with a history of myocardial infarction. Calcium channel blockers reduce blood pressure by dilating arterial resistance vessels. They are structurally heterogeneous and highly selective in their sites of action. As a consequence, cardiac effects can be minimized by selecting a calcium channel blocker with more potent peripheral vasodilatory effects. A new calcium channel blocker, isradipine, currently undergoing clinical trials, is highly selective for arterial smooth muscle and appears to be a safe and effective antihypertensive agent. 
3	Lyme disease: recommendations for diagnosis and treatment The incidence and the endemic range of Lyme disease in the United States have increased steadily since the disease was originally recognized in Lyme, Connecticut, in 1975. Because of the varied clinical manifestations of this illness and the use of unstandardized serologic testing methods, diagnosis is often uncertain and treatment outcomes are often difficult to evaluate. The antibiotic regimens that are commonly used in clinical practice have changed rapidly. They show much regional variation with little critical comparison of treatment results. The clinical diagnosis and the literature on the treatment of the various stages of Lyme disease are reviewed. The reported data are supplemented with recommendations based on 15 years of clinical experience with this illness. 
1	A comparative analysis of three different techniques for the detection of breast cancer cells in bone marrow. Three different methods, morphologic, immunocytochemic, and fluorescence activated cell sorter (FC) analysis, were compared with respect to their efficiency in detecting breast cancer cells in bone marrow. In the first series of experiments, the three techniques were compared using bone marrow cells artificially mixed with a known amount of breast cancer cells, whereas in a second series bone marrow from breast cancer patients with bone metastases were used. The following results were obtained: When mixtures of the first series were analyzed, FC analysis detected from 1% to 10% of breast cancer cells in bone marrow (0.2% was a border line value), the morphologic method detected from 0.05% to 10%, and the immunocytochemic method, which was clearly superior, detected breast cancer cells in all mixtures (from 0.00025% to 10%). It was noted that, with both the morphologic and immunocytochemic methods, the percentage of breast cancer cells detected was 2 to 360 times higher than the percentage of added cells, and enrichment was inversely proportional to the percentage of added cells. This result could be a result of different separation of cells during centrifugation due to the different density of breast cancer cells. The superiority of the immunocytochemic method was confirmed in the second series of experiments. 
4	Indapamide: a diuretic of choice for the treatment of hypertension? In recent years, the therapeutic approach to mild hypertension has evolved from a stepped care approach to one including varied, initial monotherapies, with the selection of drug based on factors present in an individual patient, followed by combination therapy. The greatest cumulative experience of the value of antihypertensive therapy has been obtained with diuretics. The reduction in risk of cardiovascular disease with successful antihypertensive therapy using conventional agents, including diuretics, is not as great as might have been anticipated by the magnitude of change in blood pressure. This could be due to antecedent cardiovascular injury prior to therapy or to risk factors induced by therapy. The recent introduction of a new generation of drugs with combined diuretic and hypotensive effects that reduce blood pressure without inducing the biochemical changes associated with thiazides, offers an opportunity to evaluate this question. Indapamide is the first of this new generation to be released. Its pharmacologic characteristics show that it has the prerequisites to be considered a first-line drug for use in hypertension. It meets the requirements of a Phase II or second generation drug in that it has similar efficacy, but less short term toxicity than first generation drugs. It has been introduced at a cost that is competitive with thiazides and potassium-sparing combination drugs and is cheaper than many other classes of antihypertensive drugs. The major caution in promoting its use is that its long term effect on morbidity and mortality in hypertensive disease has not yet been evaluated. In summary, this is a promising new drug that has the potential to replace first generation thiazides in the routine management of hypertension. 
5	The role of the iliolumbar ligament in the lumbosacral junction. The biomechanical function of the iliolumbar ligament in the human lumbosacral junction was investigated by analyzing the three-dimensional movements of the whole lumbar and lumbo-sacral-ilium specimens. The experiment was repeated in the following three conditions: 1) intact iliolumbar ligament, 2) right iliolumbar ligament transected, and 3) bilateral iliolumbar ligaments transected. The representative values of the increased motions, compared with intact, after transection of the bilateral iliolumbar ligaments were 1.7 degrees (23%) in flexion, 1.1 degrees (20%) in extension, 0.3 degrees (18%) in axial rotation, and 1.2 degrees (29%) in lateral bending. The most restricted motion governed by the iliolumbar ligament in the lumbosacral junction was lateral bending. The bilateral iliolumbar ligament specimen could restrict flexion and extension of the lumbosacral junction, but the unilateral iliolumbar ligament preparation alone could not restrict these motions. The iliolumbar ligament also had the function of restricting the rotational movement of the lumbosacral junction. 
2	Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression. Primary biliary cirrhosis is characterized by the presence of antimitochondrial antibodies. Recently, six of the autoantigens have been identified as components of the 2-oxo acid dehydrogenase multienzyme complexes located within mammalian mitochondria. Immunoblotting studies have shown that two of these components, namely E2 and protein X of pyruvate dehydrogenase complex, are the major antigenic polypeptides recognized by autoantibodies. This study shows the development of an enzyme-linked immunosorbent assay to detect and quantitate antibodies to these two purified antigens. Coded serum samples from 166 patients with primary biliary cirrhosis, 140 patients with other liver and/or autoimmune disease, and 52 normal women were analyzed for reactivity using this immunoassay. These results indicate that this rapid, simple method has a 93% sensitivity and 96% specificity in the diagnosis of primary biliary cirrhosis. The titer of immunoglobulin G autoantibodies correlated not only with antimitochondrial antibody titer measured by indirect immunofluorescence (P less than 0.0001) but also with histological stage of disease (P less than 0.04) and prognostic biochemical variables such as higher serum bilirubin and lower serum albumin levels (P = 0.038 and 0.028, respectively). There was no significant correlation between titer of autoantibodies and serum globulin or immunoglobulin G levels, indicating that the positive correlation with disease progression was not secondary to hypergammaglobulinemia. 
1	Point mutation, allelic loss and increased methylation of c-Ha-ras gene in human hepatocellular carcinoma. Somatic alterations of the c-Ha-ras gene were examined in 21 Japanese patients with hepatocellular carcinoma. Restriction endonuclease analysis by double digestion with MspI and HpaII revealed that DNAs from two of 21 hepatocellular carcinoma tissues were affected by nucleotide substitution at the twelfth amino acid coding sequence of the c-Ha-ras gene. DNAs from cirrhotic noncancerous liver tissue, but not leukocytes, of one of these patients possessed the mutation, whereas DNAs from noncirrhotic liver tissue and leukocytes of the other patient did not. In one of the nine patients harboring heterozygosity for c-Ha-ras-related BamHI-fragments, the loss of one allele was demonstrated as a somatic change not only in DNA from the tumor tissue but also in DNA from the cirrhotic nontumorous tissue. In two of the 19 patients comparatively examined for digestion patterns of c-Ha-ras locus with HpaII and MspI, extensive methylation was observed as a somatic modification in both DNAs from the tumor and the cirrhotic nontumorous tissues. These results thus indicate that the genetic lesions affecting the c-Ha-ras gene do occur in human hepatocellular carcinoma and probably serve as one of the multiple steps in the process of hepatic carcinogenesis. 
1	Basal cell-specific and hyperproliferation-related keratins in human breast cancer. In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating. 
4	Ventricular responses to mental stress testing in patients with coronary artery disease. Pathophysiological implications. Recent research examining the effects of mental stress on left ventricular wall motion and/or ejection fraction has used four techniques to measure contractile function: radionuclide ventriculography, a stationary nuclear probe, two-dimensional echocardiography, and an ambulatory radionuclide left ventricular function monitor. This research has consistently revealed that mental stress-induced myocardial ischemia occurs frequently during laboratory stress testing, particularly among patients with exercise-induced ischemia. This ischemia is usually silent, occurs at low heart rate elevations but with significant blood pressure increases compared with exercise-induced ischemia, and is frequently not detected when electrocardiographic markers are used alone. Exploration of factors underlying differences between mental stress- and exercise-induced ischemia has provided a means for studying the complex pathophysiology of myocardial ischemia. 
3	Persistent segmental cutaneous anesthesia after a brown recluse spider bite. Patients with brown recluse spider bites commonly suffer from pain, muscular aching, and a variety of local dysesthesias during the acute and resolution phases of toxin-induced injury. This is our first well-documented observation of persistent cutaneous anesthesia caused by a spider bite. The anesthetic area conformed to the distribution of a specific nerve, the transverse cervical cutaneous nerve. The identification of the spider as a brown recluse and the location of the bite over the nerve's usual pathway strongly suggest that the venom was responsible for this complication. 
2	On-table pancreatography: importance in planning operative strategy. We describe our experience with 124 on-table pancreatograms performed during 117 operative procedures on 112 patients in a wide variety of clinical settings. Endoscopic retrograde cholangiopancreatography (ERCP) was performed on 84 occasions with a 73 per cent success rate for visualization of the main pancreatic duct. On-table pancreatography (OTP) was performed by one of five different techniques: retrograde, prograde or ambigrade ductography, cystography and ascending loopography after pancreaticojejunostomy. OTP provided important information about the main pancreatic duct when endoscopic visualization was unsuccessful (n = 23), incomplete (n = 17) or not performed (n = 33); there was a failure rate of 4 per cent. In 35 patients either the additional information or discrepancies between ERCP and OTP findings resulted in a change of operative plan (19 extra procedures, 16 altered procedures). Complete ductography was especially helpful in the 63 patients with chronic pancreatitis. OTP is technically simple, free from complications and invaluable for planning operative strategy. 
3	Sudden death and sleeping history among Finnish men. An autopsy was performed in 460 consecutive cases of sudden death among 35- to 76-year-old men. The closest cohabiting individual known to each decreased subject was interviewed. Snoring history was obtained in 321 of the 371 interviews. In 86 cases there was a history of 'habitual' (almost always or always) snoring, and 88 men snored 'often'. The mean age of subjects was 55.4 years. The mean body mass index (BMI) was 26.3 kg m-2. Among the obese snorers (n = 82), apnoeas had been observed 'occasionally', 'often', or 'habitually' in 49 cases. Death was classified as cardiovascular in 186 (40.4%) cases. Cardiovascular cause of death was more common among those who snored habitually or often than among those who snored occasionally or never (P less than 0.05). 'Habitual' snorers died more often while sleeping (P less than 0.05). Habitual snoring was found to be a risk factor for morning death (P less than 0.01). The possibility of obstructive sleep apnoea as a cause of sudden death should at least be considered if the decreased is known to have been a habitual snorer. 
2	Strongyloides stercoralis associated with a bleeding gastric ulcer. Infection with the helminthic parasite, Strongyloides stercoralis, is usually acquired by skin invasion (or occasionally via ingestion of larvae). After transformation to the adult form, the parasite preferentially localises in the small intestine, especially in the duodenal and jejunal part. A remarkable feature of Strongyloides is its property of endogenous reinfection. In the case of an immunocompromised host a massive infection, called hyperinfections Strongyloides, may occur. Numerous gastrointestinal complications of strongyloides infections, sometimes with a lethal outcome, have been reported. The intestinal manifestations are usually limited to the small bowel, and rarely involve the stomach. We report a patient with complicated strongyloides infection of the stomach. 
5	Transoesophageal pacing for perioperative control of neonatal paroxysmal supraventricular tachycardia. The perioperative management of a 16-day-old infant with recurrent supraventricular tachycardia (SVT) is discussed. Vagal manoeuvres and medication were not adequate in controlling the SVT. Since the patient was scheduled for extensive surgery in the prone position, it was decided to use transoesophageal pacing as the method of choice for conversion of SVT. Transoesophageal pacing succeeded several times in overriding the SVT and restoring normal heart rate and haemodynamic variables. The advantages and disadvantages of various methods of treating SVT in the newborn are discussed. 
4	Cardiovascular sequelae of therapeutic thoracic radiation. Mediastinal radiation damages endothelial cells, with resulting loss of capillaries and ischemia at the level of the microcirculation. These changes lead to increases in collagen and proliferation of fibrous tissue throughout the heart. Cardiac dysfunction following radiotherapy is surprisingly common and may be due to pericardial, myocardial, valvular, conduction system, or coronary artery disease. Greater awareness of cardiotoxicity has prompted changes in radiation techniques that appear to reduce clinical cardiovascular complications. 
3	Platelet monoamine oxidase activity in female migraine patients. Platelet monoamine oxidase activity (MAO) in a group (n = 17) of white, female migraineurs during an acute migraine attack was similar to both the values obtained for the same group of patients two to three weeks after the headache episode (pain-free period) and to the results obtained for a group (n = 18) of sex and race-matched, age-comparable, drug-free healthy volunteers (blind study; substrate p-tyramine, 38.7 +/- 5.7, 41.9 +/- 8.8 and 43.0 +/- 3.4 or p-methoxybenzylamine, 178.9 +/- 11.3, 177.2 +/- 6.9 and 181.0 +/- 9.7 nmole/hr/10(9) platelets +/- SD respectively). With each patient serving as its own control, MAO activity during the migraine episode and when pain-free failed to show a significant trend. Neither a number of other medical conditions nor the use of several medications appeared to significantly influence our results. The present work, while dealing only with a small but well defined patient population, argues against the possible usefulness of platelet MAO activity as a biological marker for migraine headaches. 
4	Linking in accessory pathways. Functional loss of antegrade preexcitation. BACKGROUND. Concealed retrograde activation has been proposed as a mechanism for antegrade conduction block in the bundle branches and atrioventricular accessory pathways. We studied this hypothesis (linking) in 10 patients with the Wolff-Parkinson-White syndrome in whom antegrade preexcitation could be persistently blocked by overdrive atrial pacing. METHODS AND RESULTS. An atrial pacing protocol, with a decremental ramp followed by an incremental ramp, defined a range of atrial paced cycle lengths (linking window) associated with both persistent conduction and block in the accessory pathway. Within the limits of the linking window, the ability of an atrial impulse to conduct over the accessory pathway was dependent on the preceding state (i.e., conduction or block). The observed linking window ranged from 70 to 290 msec (mean, 185 +/- 68 msec) and closely approximated the measured delay in retrograde activation of the accessory pathway during persistent antegrade block. The mean antegrade effective refractory period of the accessory pathways was long (486 +/- 156 msec), and in each case, it exceeded the antegrade refractory period of the normal atrioventricular pathway. Critically timed premature ventricular extrastimuli, delivered while linking was maintained in the accessory pathway, were able to interrupt the linking and restore antegrade accessory pathway conduction. CONCLUSIONS. These observations suggest that accessory pathway linking is associated with bidirectional block in the accessory pathway. The ability to initiate linking (and the stability of the phenomenon) depends on a critical relation between antegrade accessory pathway refractoriness and the magnitude of retrograde accessory pathway activation delay. 
1	Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location PURPOSE: To examine studies of normal colon and colorectal cancer for evidence that the location of the primary tumor proximal or distal to the splenic flexure of the colon may determine distinct genetic categories of this disease. DATA IDENTIFICATION: Studies were identified through a manual search of journals, through MEDLINE, and through review of bibliographies in identified articles. STUDY SELECTION: Approximately 300 articles were examined. About 150 articles were excluded because tumor location was not reported or was reported in a way that did not permit correlation with results or conclusions. DATA EXTRACTION: Articles were selected either because the presentation of data permitted correlation of results with anatomic regions of the colon or because they were relevant to inherited colorectal cancer. RESULTS OF THE ANALYSIS: Differences were noted in biologic properties of proximal and distal segments of normal fetal and adult colonic epithelium and in the epidemiologic, pathologic, cytogenetic, and molecular features of proximal and distal colorectal cancer. Some differences correlated with the features of inherited colorectal cancer (proximal, nonpolyposis or distal, and polyposis forms). CONCLUSIONS: Developmental and biologic differences in proximal and distal colon may reflect differing susceptibilities to neoplastic transformation. Differences in proximal and distal colorectal cancer suggest that each may arise through different pathogenetic mechanisms. Proximal tumors appear to represent a genetically more stable form of the disease and may arise through the same mechanisms that underlie inherited nonpolyposis colon cancer. Distal tumors show evidence of greater genetic instability and may develop through the same mechanisms that underlie polyposis-associated colorectal cancer syndromes. 
1	A comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood: results of a Pediatric Oncology Group study. Two hundred fifty-six children with previously untreated acute nonlymphocytic leukemia (ANLL) were evaluated on a Pediatric Oncology Group (POG) phase III randomized trial of both induction and continuation chemotherapies. Induction therapy compared vincristine, cytarabine, and dexamethasone (VADx) with daunorubicin, cytarabine, and thioguanine (DAT). The complete remission (CR) rate using DAT was superior (82% v 61%, P = .02). Postremission therapy consisted of either "standard" two-cycle therapy or a more intensive four-cycle regimen given for 2 years. Overall, there was no difference in outcome for patients randomized to either continuation regimen. The overall complete continuous remission rate (CCR) for the "best" induction/continuation therapy combination at 2 years was .50 (SE = .06), at 3 years was .35 (.04), and at 4 years was .34 (.05). Analysis of selected clinical and laboratory parameters demonstrated differences in induction responses favoring DAT induction but did not impact eventual disease-free survival. There were two subgroups of patients who responded better to four-cycle continuation therapy. These were patients with French-American-British (FAB) M1/M2 (2-year CCR was .20 v .44, P = .01) and patients older than 10 years at diagnosis (.32 v .62, P = .004). 
5	Pain relief achieved by transcutaneous electrical nerve stimulation and/or vibratory stimulation in a case of painful legs and moving toes. A patient is described with painful legs and moving toes. The pain had been occurring for more than 15 years, and a variety of therapies had been attempted with only partial, if any, success. Only morphine had succeeded in relieving the pain, but it had to be discontinued to avoid tolerance and dependence. We devised a treatment consisting of transcutaneous electrical nerve stimulation (TENS), vibratory stimulation (VS), and a combination of the two methods (TENS + VS). TENS brought about partial pain relief, but was less effective than VS; dual stimulation (TENS + VS) led to complete alleviation of the pain. Four months later, the patient was applying dual stimulation himself at home and was thus able to maintain complete relief with 3 or 4 weekly sessions. We suggest that dual stimulation results in a large-scale recruitment of large-diameter afferent fibres and may thus set up a powerful inhibitory control of nociception in our patient. 
3	Seizure outcome from anterior and complete corpus callosotomy. Eighty patients underwent anterior corpus callosotomy for treatment of generalized seizures. The patients' mean age was 18.3 years (range 4 to 53 years); the mean age at seizure onset was 5.27 years (range 0.1 to 27 years). The mean intelligence quotient (IQ) of 41 testable patients was 71.12 (range less than 30 to 114). The seizure outcome was as follows: 13% were seizure-free, 65% were significantly improved, and 22% were unchanged. Ten patients subsequently underwent a second operation to complete the callosal sectioning which resulted in additional seizure improvement in only five of them. Five complications resulted from 90 operations: two epidural hematomas, one delayed subdural hematoma, one bone-flap infection, and one postcallosotomy disconnection syndrome; two patients died. A younger age at onset of seizures, a higher IQ, and generalized tonic-clonic, atonic, complex-partial, and mixed seizure types were associated with improved seizure outcome. 
5	Immune functions during treatment of growth hormone-deficient children with biosynthetic human growth hormone. Immune functions, including cell surface markers, interleukin-2 receptor levels and responses of lymphocytes to mitogenic stimulation were evaluated in seven growth hormone deficient children ages 4-15 years, during treatment with biosynthetically derived human growth hormone. Treatment resulted in a decrease in % B cells and in % T total cells and also decreases in most individual patients' mitogen responses and interleukin-2 receptor levels. Most of the changes noted were transient and similar to those previously demonstrated during pituitary-derived human growth hormone treatment. Although not resulting in overt clinical manifestations in our patients, we think that potential interactions between growth hormone and immune functions need to be considered by physicians treating children with growth hormone. 
4	An assault on old friends: thiazide diuretics under siege. The adverse biochemical effects of thiazide use are of uncertain clinical significance. Thiazides raise LDL cholesterol only slightly in long-term studies and do not decrease HDL cholesterol. The evidence linking thiazide-induced hypokalemia with arrhythmias and sudden death is tenuous at best. Thiazide diuretics cause glucose intolerance, but no strong evidence has been advanced to suggest that this is dangerous. Because these effects are probably related to hypokalemia, a randomized trial comparing the effects of thiazides with thiazides plus a potassium-sparing diuretic on LDL cholesterol, ectopy on 48 hour ambulatory cardiac monitoring, fasting glucose and insulin, and post-glucose tolerance glucose and insulin would be of interest. The most compelling reason for continuing to use thiazides is that they have been shown in long-term randomized studies to reduce cardiovascular risk. Beta-blockers are the only other class of anti-hypertensive agent for which this claim can be made. The importance of long-term clinical trials in assessing the efficacy and toxicity of therapeutic agents is illustrated by the study that found clofibrate reduced cholesterol levels and coronary disease but increased total mortality. This finding remained undetected until a large randomized long-term trial was completed. Thiazide diuretics have not reduced the rate of coronary disease to the degree expected from epidemiologic studies, but the short length of the randomized trials may be responsible. It is not clear that other anti-hypertensive agents will be superior. Thiazides are less expensive than other anti-hypertensive agents being touted as metabolically safer; the cost issue is not a trivial matter. 
5	Use of a management plan for treating asthma in an emergency department. A standardised management protocol has been developed for the assessment and treatment of adults with acute asthma attending an emergency department. The management protocol consists of an assessment sheet for recording essential features of the history and examination findings and a flow diagram with guidelines for initial management that were based on spirometric recordings. The protocol was introduced at Wellington Hospital in 1986. The effect of this intervention was assessed by analysing emergency department records during the three months before and one year after the introduction of the protocol. The use of the assessment sheet improved history taking and led to the increased use of serial measures of airflow obstruction and improved documentation of follow up arrangements. The provision of management guidelines influenced the emphasis of management, including an increased use of corticosteroids intravenously and more frequent use of an additional dose of nebulised bronchodilator. In the light of the initial experience the protocol has been modified and its use either in an emergency department or in general practice is recommended. 
5	Landau-Kleffner syndrome: a pharmacologic study of five cases. Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae. 
3	Antivenom therapy in Russell's viper bite. Bleeding and renal failure are the two main manifestations responsible for the high morbidity and mortality in untreated Russell's viper bite victims. This study was an effort to find prognostic factors and a practical therapeutic approach for the care of such patients. Early detection of abnormalities in the clot quality test and/or evidence of systemic bleeding followed by immediate correction of the clotting defects using specific antivenom can reduce morbidity in Russell's viper envenomation. 
5	Emergency portosystemic shunt in patients with variceal bleeding. Thirty-five patients for whom emergency sclerotherapy or conservative treatment, or both, failed to arrest variceal bleeding, or who had early rebleeding and required emergency portosystemic shunts (EPSS) were studied. EPSS permanently controlled the variceal bleeding in all but one patient. In this patient, the shunt was patent as demonstrated by angiography. Esophageal varices disappeared in 18 patients and were reduced in 14. Three patients died before the endoscopic examination could be performed. The causes of death were hepatic failure in two and bleeding ulcerations of the gastric fundus in the other patient. One patient was classified in Child's category B and two in Child's category C. Thirty-two patients submitted to EPSS and were discharged alive. Twelve of these patients subsequently died, at an average of 11.2 months after undergoing the shunt procedure. Four of 12 patients died of hepatic failure; two patients died of hepatomas; two, other neoplasia; three, hemorrhaging duodenal ulcers, and one patient, renal failure. Analysis of actuarial survival rates showed that the five year survival rate was 43 per cent. The long term survival rates were fewer for patients with Child's category C than for those with combined Child's categories A and B (five year survival rates were 21 versus 55 per cent; p less than 0.05). During the follow-up period, none of the patients had variceal bleeding. Chronic encephalopathy developed in six, which was mild in three, moderate in one instance and severe in two. It developed soon after EPSS, with onset in the first month after discharge in three. Thus, when conservative treatment fails to arrest variceal bleeding, EPSS should be performed to guarantee definitive control of hemorrhage and prolong the survival period. 
1	Pneumocystis carinii pneumonia complicating somatostatin therapy of Cushing's syndrome in a patient with metastatic pancreatic islet cell carcinoma and Zollinger-Ellison syndrome. Described is the case of a 73-yr-old woman with metastatic pancreatic islet carcinoma that manifested initially as Zollinger-Ellison syndrome followed by onset of endogenous Cushing's syndrome, who developed Pneumocystis carinii pneumonia while on therapy with a long-acting somatostatin analog. Although P. carinii pneumonia has been observed in patients with Cushing's syndrome associated with other conditions, this is the first reported case in a patient with Zollinger-Ellison syndrome. Heightened awareness of the possibility of opportunistic infections in patients receiving somatostatin therapy for Cushing's syndrome of any cause, particularly Zollinger-Ellison syndrome, may be warranted. 
2	Sexual and physical abuse in women with functional or organic gastrointestinal disorders. STUDY OBJECTIVES: To determine the prevalence of a history of sexual and physical abuse in women seen in a referral-based gastroenterology practice, to determine whether patients with functional gastrointestinal disorders report greater frequencies of abuse than do patients with organic gastrointestinal diseases, and to determine whether a history of abuse is associated with more symptom reporting and health care utilization. DESIGN: A consecutive sample of women seen in a university-based gastroenterology practice over a 2-month period was asked to complete a brief questionnaire. MEASUREMENTS: The self-administered questionnaire requested information about demographics, symptoms, health care utilization, and history of abuse. Physicians indicated the primary diagnosis for each patient and whether she had ever discussed having been sexually or physically abused. RESULTS: Of 206 patients, 89 (44%) reported a history of sexual or physical abuse in childhood or later in life; all but 1 of the physically abused patients had been sexually abused. Almost one third of the abused patients had never discussed their experiences with anyone; only 17% had informed their doctors. Patients with functional disorders were more likely than those with organic disease diagnoses to report a history of forced intercourse (odds ratio, 2.08; 95% CI, 1.03 to 4.21) and frequent physical abuse (odds ratio, 11.39; CI, 2.22 to 58.48), chronic or recurrent abdominal pain (odds ratio, 2.06; CI, 1.03 to 4.12), and more lifetime surgeries (2.7 compared with 2.0 surgeries; P less than 0.03). Abused patients were more likely than nonabused patients to report pelvic pain (odds ratio, 4.05; CI, 1.41 to 11.69), multiple somatic symptoms (7.1 compared with 5.8 symptoms; P less than 0.001), and more lifetime surgeries (2.8 compared with 2.0 surgeries; P less than 0.01). CONCLUSIONS: We found that a history of sexual and physical abuse is a frequent, yet hidden, experience in women seen in referral-based gastroenterology practice and is particularly common in those with functional gastrointestinal disorders. A history of abuse, regardless of diagnosis, is associated with greater risk for symptom reporting and lifetime surgeries. 
4	Low-dose aspirin does not influence the clinical course of women with mild pregnancy-induced hypertension. The effect of low doses of aspirin on women with mild pregnancy-induced hypertension was investigated by means of a prospective, randomized, double-blind trial. Forty-seven women hospitalized at 30-36 weeks' gestation because of mild pregnancy-induced hypertension were treated by a daily dose of either 100 mg aspirin or placebo. The mean blood pressure values, rates of development of severe preeclampsia, gestational ages at delivery, newborn weights, and 5-minute Apgar scores were similar in the aspirin-treated and the placebo-treated groups. We conclude that low-dose aspirin is not curative but is essentially a preventive treatment which, in order to be effective, should be started weeks before clinical signs of preeclampsia are present. 
5	Healing of experimental intestinal anastomoses. Parameters for repair. Anastomotic dehiscence remains a major complication in surgery of the large bowel, and studies on the healing sequence of experimental anastomoses are necessary to define underlying mechanisms and find ways to improve surgical outcome, particularly in high-risk situations. For the quantitative description of anastomotic repair, both mechanical and biochemical parameters are employed, each with their own limitations. Mechanical parameters, either bursting pressure or breaking strength, only reflect growing anastomotic strength as long as disruption occurs within the anastomotic area, which is less than one week after surgery for the bursting pressure and probably up to two weeks for the breaking strength. The biochemical description of anastomotic repair has been limited to behavior of collagen, as represented by its rather unique constituent amino acid hydroxyproline. Conclusions based on collagen concentrations--per unit weight--should be considered with caution since they may change as a consequence of changes in noncollagenous substances. In this respect, collagen content, per unit length, is probably a better parameter to describe anastomotic collagen levels. Few investigations have addressed the quality of collagen (e.g., crosslinking or type). Since, at this time, no distinct correlations have been demonstrated between development of mechanical strength or occurrence of leakage and collagen levels in the healing anastomosis, attention should not be restricted to a description of the quantity of collagen present: the quality of anastomotic collagen should be investigated, perhaps even more so. 
1	Papillary cystic neoplasm of the pancreas: radiological and pathological characteristics in 11 cases. Clinical charts, radiological features, macroscopic and microscopic findings, and clinical follow-up data were retrospectively reviewed in 11 patients with papillary cystic neoplasm of the pancreas (PCNP). The patients were nine women and two men, aged from 13 to 51 years with a mean age of 25 years. The greatest diameter of the PCNPs ranged from 2.5 cm to 14.0 cm with a mean size of 7.5 cm. Six tumours were located in the tail of the pancreas, two in the body and three in the head. Most patients complained of abdominal pain or a mass. Ultrasonographic and/or computed tomography findings showed five solid, four mixed (solid and cystic) and two cystic types of tumour. Angiographically, PCNP was either a hypovascular or mild hypervascular mass with a displacement of the surrounding vessels. No vascular encasement was seen. Macroscopically all 11 tumours consisted of a well defined solid mass with degenerative change of various widths, including haemorrhage, necrosis or dystrophic calcification, and were represented by three radiological types of PCNP. The 11 patients with PCNP survived for from 3 to 253 months after curative resection without any signs of local recurrence or remote metastasis. PCNP usually affects the distal portion of the pancreas of young women. Despite its huge size, PCNP should be explored with aggressive surgical intent because of the inherently good prognosis. 
3	Alteration of platelet serotonin in patients with chronic tension-type headache during cold pressor test. Change of 5-hydroxytryptamine (5-HT) concentrations in platelets from patients with chronic tension-type headache (TH) and controls were observed during cold pressor test (CPT). Before cold stimulation, 5-HT concentrations in platelets from patients with TH were significantly lower than those found in controls. One minute after the start of cold stimulation, 5-HT levels in platelets from patients with TH were significantly much lower than in the controls, as control levels rose and TH levels fell. The results show that, under stress, the absorbance of 5-HT into the platelets in patients with TH is reduced. It is suggested that, in patients with TH, there are abnormalities of 5-HT uptake into platelets and factors which cause release of 5-HT from platelets. 
4	Treatment of congenital coronary arteriovenous malformations with micro-particle embolization. The successful treatment of a symptomatic coronary arteriovenous malformation (CAVM) by a percutaneous embolization technique with micro-particles is described. Objective evidence of ischemia and its subsequent disappearance after embolization is presented. The embolization technique and possible indications and contraindications are discussed. 
4	The dynamics of antegrade cardioplegia with simultaneous coronary sinus occlusion. Effects on aortic root infusion pressure, coronary sinus pressure, and myocardial cooling. It has been suggested that antegrade cardioplegia with coronary sinus occlusion improves homogeneous myocardial cooling and reduces myocardial injury in the presence of coronary artery occlusion. Little data are available on the exact relationships among the basic elements or this intervention, including antegrade infusion rate, aortic root pressure, the degree of coronary sinus occlusion, coronary sinus pressure, and myocardial cooling. The purpose of this study was to determine these relationships and to provide some basic guidelines for better understanding of this intervention. Twenty-two sheep were placed on cardiopulmonary bypass, the distal left anterior descending artery was occluded, and the proximal coronary sinus was snared. Sixteen combinations of infusion rate (3, 5, 7, or 9 ml/kg/min) and coronary sinus occlusion (total, subtotal, or moderate occlusion or no occlusion) were adopted for each 2 minutes of antegrade cardioplegia, yielding 96 measurements. Myocardial temperatures in the occluded and nonoccluded regions, aortic root infusion pressure, and coronary sinus pressure were measured during each infusion of cardioplegic solution. Coronary sinus occlusion was then released, and the whole heart was reperfused for 30 minutes for another infusion of cardioplegic solution and measurements. Results showed good degrees of linearity between infusion rate and aortic root infusion pressure for all coronary sinus occlusion and noninfusion groups (p less than 0.01). A positive effect of coronary sinus occlusion on aortic root infusion pressure was observed. The graded increases in infusion rate with various degrees of coronary sinus occlusion were constantly associated with elevation of coronary sinus pressure (p less than 0.01). It was also noted that myocardial temperatures in the region of the occluded left anterior descending artery were significantly lower in coronary sinus occlusion groups than in nonocclusion groups (p less than 0.01 or 0.05). Myocardial temperature in the nonoccluded region decreased significantly with the stepwise increases in infusion rate (p less than 0.01), but not with the increases in coronary sinus occlusion (not significant). Based on this and previous studies, we recommend that the induced coronary sinus pressure be safely maintained in the range of 25 to 35 mm Hg and that further studies be focused on the infusion rate of 5 ml/kg/min with subtotal or total coronary sinus occlusion for the intervention of antegrade cardioplegia plus coronary sinus occlusion. 
3	Risk factors for metastases in patients with retinoblastoma. The study is based upon a review of data from 583 consecutive patients with retinoblastoma over the years 1956 to 1986. Mean follow-up was 8 years, and median was 5.5 years. In 41 patients, metastases developed within 5 years. The influence of clinical and histopathologic risk factors on the occurrence of metastases was first analyzed by univariate tests. Significant variables were then reevaluated using the Cox proportional hazards method. Four factors were found to be independently associated with the development of metastases: optic nerve invasion with and without involvement of the resection line, choroidal invasion and enucleation of an affected eye more than 120 days after initial diagnosis. The 5-year metastatic risks associated with these factors were 67%, 13%, 8%, and 4%, respectively. The relative risk estimate, calculated from the Cox model, was used for a score classification with groups of low, medium, and high metastatic risk. The 5-year incidence of metastases was 4%, 43%, and 68%, respectively. 
4	Digital cutaneous vascular responses to histamine and neuropeptides in Raynaud's phenomenon. The pathophysiology of Raynaud's phenomenon is not well defined, but active cutaneous microvascular vasoconstriction and emptying must occur to account for the pallor and are reasons for studying the microvasculature. It has been proposed that there may be a defect in a local histamine vasodilator mechanism. The role of the peptidergic nervous system in Raynaud's phenomenon has not been previously investigated. To study the histaminergic and peptidergic axes in Raynaud's phenomenon, we measured the cutaneous microvascular responses of patients with Raynaud's phenomenon to digital intradermal injections of saline, histamine, the histamine-releasing agent, compound 48/80, substance P, and calcitonin gene-related peptide. We compared these results with those obtained in normal subjects. Intradermal cutaneous microvascular blood flow responses were quantified by planimetry and laser Doppler flowmetry. The results show: a) that in primary Raynaud's phenomenon there is no evidence of local deficiency in histamine release or insensitivity to histamine in the cutaneous microvasculature; and b) that patients with Raynaud's phenomenon react normally to the neuropeptides calcitonin gene-related peptide and substance P, providing a rationale for treating Raynaud's phenomenon with vasoactive peptides. 
5	A comparison of host responses of the Mongolian jird to infections of Brugia malayi and B. pahangi. Host responses of jirds receiving a single subcutaneous inoculation of subperiodic Brugia malayi were compared with those of jirds similarly infected with B. pahangi. Parasite burdens, lymphatic lesion severity, granulomatous reactivity, antibody responses to parasite antigens, and complete blood cell counts were assessed at 60 and 150 days post-inoculation. At 60 days post-inoculation, percentages of adults recovered at necropsy and lymphatic lesion severity were greater in B. pahangi-infected jirds. At 150 days post-inoculation, lesion severity and percentages of worms recovered were similar in both infections. No significant differences were noted in either infection in reactivity to homologous or heterologous parasite antigens in any parameter measured. Similarities in the kinetics of the inflammatory reactivities of the 2 infections suggest that previous observations made in the jird-B. pahangi model could be utilized in designing studies using B. malayi. Further, the more marked lesion severity observed in B. pahangi-infected jirds and the relative ease of maintaining B. pahangi in the laboratory support the continued use of this system as a conceptual model for the study of lymphatic lesion pathogenesis. 
5	Electron-microscopic identification of pseudoexfoliation material in extrabulbar tissue. The structure and distribution of pseudoexfoliation material in extrabulbar tissues from five eyes with typical unilateral intraocular pseudoexfoliation syndrome and two intraocularly unaffected fellow eyes were examined by transmission electron microscopy. In all seven eyes, unevenly distributed pseudoexfoliation aggregates were found in limbal conjunctivae, extraocular rectus and oblique muscles, orbital connective-tissue septa, and the walls of the posterior ciliary arteries, vortex veins, and central retinal vessels passing through the optic nerve sheaths. Typical pseudoexfoliation fibers occurred in close association with connective-tissue components, especially elastic fibers; a moderate predisposition of pseudoexfoliation clumps to accumulate around blood vessels was observed. The findings of pseudoexfoliation material in similar extrabulbar locations in intraocularly uninvolved fellow eyes indicates that pseudoexfoliation fiber formation outside the globe precedes its intraocular manifestation. The intermingling of pseudoexfoliation fibers, microfibrils, and elastic and collagen fibers suggests that pseudoexfoliation fiber formation might result from a disordered synthesis and/or assembly of connective-tissue microfibrils. 
5	Retroperitoneal fibrosis after surgery for aortic aneurysm in a patient with periarteritis nodosa: successful treatment with corticosteroids. A 54-year-old man with hepatitis B virus-related periarteritis nodosa developed retroperitoneal fibrosis with bilateral hydronephrosis 2.5 months after placement of an aortobifemoral prosthesis for abdominal aortic aneurysm. Retroperitoneal fibrosis disappeared after treatment with corticosteroids. This observation is interesting in the light of the hypothesis that retroperitoneal fibrosis is caused by vasculitis. 
5	Injuries of the external ear. Ear injuries occur in people of all ages but predominate in active people such as wrestlers, boxers, and bike riders. The types and extent of injury are a function of the force causing the injury. Shearing forces of moderate intensity cause hematoma formation, whereas greater force causes lacerations or even amputation. Sharp objects cause lacerations determined by the force, direction, and point of impact. The high ratio of surface area to mass makes the auricle vulnerable to extremes of temperature. People participating in high-risk activities should wear protective headgear. The goal of treatment is to restore the normal contours while preventing infection. Hematoma results in disfigurement by organization or chondritis. Evacuation and pressure dressings using sterile technique correct the condition. Second-degree burns are treated by regular cleansing and application of topical antimicrobials. Deeper burns require debridement, biologic dressings, or burying the cartilage subcutaneously for later reconstruction. Simple lacerations are closed under aseptic technique using either skin-to-skin sutures only or sutures of the skin combined with intercartilage sutures. Extensive and complex lacerations require meticulous care to match all fragments and prevent infection or loss of tissue. Bare cartilage must be covered with vascularized tissue. The treatment of total amputation is controversial. Some advocate reattachment as a composite graft using intravenous low molecular weight dextrans and heparin as adjuvants. Mladick dermabrades the amputated pinna, reattaches it with sutures, and then slips it into a pocket of elevated postauricular skin for 2 weeks. Others urge microvascular reanastomosis of the small nutrient vessels. Brent and Byrd separate the cartilage from its overlying skin and envelope it first with vascularized temporoparietal fascia and then a split-thickness skin graft. Chondritis is the most feared complication of injury or surgery of the pinna. It is an aggressive process, and prompt removal of pus and necrotic cartilage is required. Exteriorization and removal of all cartilage is effective but disfiguring. Removal of only affected cartilage and constant irrigation with antibiotic solutions is effective but requires prolonged hospitalization. Iontophoresis of antibiotics into the auricle may be effective and conserve tissue. Traumatic deformities are corrected with composite grafts from the opposite ear, costal cartilage, and local pedicled flaps.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	DNA and RNA flow cytometric study in multiple myeloma. Clinical correlations. Flow cytometric studies of cellular DNA and RNA content using the acridine-orange technique were conducted in 81 patients with multiple myeloma (MM). All patients were treated with the M-2 protocol and clinical response was evaluated according to the criteria of the Chronic Leukemia-Myeloma Task Force. Aneuploid DNA stemlines were found in 38.2% of untreated patients with a median DNA index (DNA-I) of 1.15 in marrow aspirates and 1.22 in biopsy specimens. The median percentage of cells with abnormal DNA content was 31.5 (aspirates) and 35 (biopsy specimens) and a positive correlation with the percentage of bone marrow plasma cells was observed. Significantly higher proliferation (S-phase) was found in marrow biopsy specimens as compared with marrow aspirates. Significantly higher RNA content (RNA index [RNA-I]) was observed in aneuploid versus diploid patients in biopsy material. There was no difference in response to the Memorial Hospital M-2 protocol between diploid and aneuploid patients. In patients with DNA-I greater than 1.15 remission duration was shorter as compared with DNA-I less than or equal to 1.15. Furthermore, no difference in cellular RNA content was noted between responders and nonresponders. This study demonstrates no correlation between cellular RNA content and response, as previously described for patients treated with vincristine, Adriamycin, and dexamethasone (VAD), but DNA aneuploidy appears to be an adverse prognostic factor in MM patients treated with the M-2 protocol. It also demonstrates that prognostic models for MM are not universal but depend on the chemotherapeutic regimen used. 
2	Treatment of duodenitis with cimetidine: a clinical, endoscopic, and histologic study. We studied the effectiveness of cimetidine in the treatment of endoscopically diagnosed duodenitis. Sixty-nine patients with the solitary endoscopic finding of duodenitis (6% of 1,200 patients who underwent fiberoptic endoscopy of the upper gastrointestinal tract in our unit over 3 years) were studied retrospectively: a good clinical response was apparent in 45 of 69 patients treated with cimetidine (65%), and a fair response in another four (6%). In a controlled, randomized prospective study, we evaluated the effectiveness of cimetidine in duodenitis. Statistically significant improvement for the clinical and endoscopic scores was found in 10 patients treated with cimetidine (p less than 0.01). Improvement in the histologic score did not reach statistical significance. No such improvement was demonstrated in seven placebo-treated patients. We believe that duodenitis is a "peptic syndrome," has a good response to cimetidine treatment, and behaves much like duodenal ulcer disease. 
5	The effects of tumor necrosis factor on intestinal structure and metabolism. Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study. 
5	Intravascular stents. General principles and status of lower-extremity arterial applications. The two major types of intravascular stents are balloon expandable and self-expanding. Many animal and, more recently, clinical studies have begun to delineate the real and potential roles of stents. Although the ideal intravascular stent does not exist, it is possible to identify characteristics of the hypothetical ideal stent. Iliac and femoropopliteal arterial applications of metallic stents are reviewed. Stents have proved useful in postangioplasty elastic recoil, in some cases of postangioplasty restenosis, and in angioplasty-induced dissection. Their role in primary angioplasty procedures is still uncertain, although in iliac angioplasty the immediate hemodynamic effects of angioplasty plus stenting are superior to those of angioplasty alone. It is clear that metallic stents have not solved the problem of postangioplasty restenosis, as restenosis still occurs in a significant number of cases. This problem is particularly evident in the femoropopliteal stent procedures, in which angiographic restenosis (more than 50% single diameter stenosis) at 6 months after treatment has occurred in approximately 30% of cases. The existence of poststenting restenosis, which often involves the stented segment, underscores the need for better drug regimens in angioplasty and for better understanding of the intimal fibrocellular proliferative response of the vessel wall to injury. Although potentially very useful, biodegradable stents are still a dream whose realization will demand the development of better materials. 
5	Tympano-cartilago-stapediopexy: a method to improve hearing in open technique tympanoplasty. Canal wall-down technique tympanoplasty was indicated in about 41 per cent of our cases with chronic suppurative otitis media. In this series done during the last four years, of 576 tympanoplasties, 240 cases needed type III tympanoplasty. In 145 cases, myringostapediopexy was carried out using temporalis fascia grafting over the head of the stapes. Tympano-cartilago-stapediopexy was performed in the other 95 cases by using tragal cartilage and perichondrium over the stapes. A comparison between the results of both methods of grafting is discussed. Improvement in hearing was achieved after tympano-cartilago-stapediopexy. This method proved to be suitable for those cases which need open technique tympanoplasty. 
1	The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta. Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. Other synthetic progestins had no effect, indicating that this induction is mediated by the novel Gestodene binding site and not by the conventional progesterone receptor. Furthermore, in four breast cancer cell lines, the extent of induction of TGF-beta correlated with intracellular levels of Gestodene binding site. No induction of TGF-beta was observed with the endometrial cancer line, HECl-B, which lacks the Gestodene binding site, but which expresses high levels of progesterone receptor. The inhibition of growth of T47D cells by Gestodene is partly reversible by a polyclonal antiserum to TGF-beta. These data indicate that the growth-inhibitory action of Gestodene may be mediated in part by an autocrine induction of TGF-beta. 
4	Tetralogy of Fallot with anomalous pulmonary venous connections: a rare but clinically important association. Anomalous pulmonary venous connections were found in seven (0.6%) of 1183 patients with tetralogy of Fallot. Three patients had totally anomalous connections (one supracardiac, one direct to coronary sinus, and one mixed supracardiac and infracardiac) and four patients had partially anomalous pulmonary venous connections. All patients presented with the clinical features of tetralogy of Fallot. Anomalous pulmonary venous drainage was suspected clinically in only one patient in whom there was a scimitar sign on the chest radiograph. The exact diagnosis was established by cross sectional echocardiography (one), preoperative or postoperative angiography (five), or at necropsy (one). Surgery was performed in six patients. Total correction without re-routing of the anomalously draining veins was successful in all those with partially anomalous connections, with no significant long term sequelae (follow up median 17 years). Of those with totally anomalous connections, the full diagnosis was made only at necropsy in one patient, successful one-stage correction was performed in one, and the other patient, who had partially obstructed mixed drainage, died shortly after one-stage correction. Histological examination of the lung biopsy specimen in this patient showed grade 2 pulmonary vascular disease. Tetralogy of Fallot with anomalous pulmonary venous connections is a rare association. Careful preoperative assessment is required in those with totally anomalous connections. 
1	New findings in treatment of colon cancer. Patients with colon cancer involving regional lymph nodes (stage C disease) have a 5-year survival rate of only 30% to 40%, and the majority die of recurrent disease. Recent trials have shown increased survival rates with postoperative use of fluorouracil plus levamisole. The authors discuss these findings and the implications on treatment recommendations for stage C colon cancer. 
5	Chronic postoperative endophthalmitis associated with Actinomyces species. Actinomyces species, gram-positive, non-spore-forming anaerobic bacilli were isolated from intraocular fluid obtained from four otherwise healthy patients with a delayed onset of postoperative endophthalmitis. One patient had a mixed anaerobic infection with recovery of both Actinomyces israelii and Propionibacterium acnes. In all four patients, early postoperative visual acuity was good but was eventually markedly reduced by intraocular inflammation that was first observed between 21 days and 4 months following uneventful extracapsular cataract extraction and posterior chamber intraocular lens implantation. Inflammation was characterized by anterior segment and vitreous cellular debris in all cases. All eyes responded to therapy that included intraocular, topical, and systemic antibiotics as well as pars plana vitrectomy and partial iridectomy. These cases further illustrate the need for microbiologic investigation, including anaerobic cultures, in all cases of chronic postoperative inflammation following extracapsular cataract extraction, regardless of the time of onset. 
4	Cavernous hemangioma of the spinal cord: report of 2 unusual cases. We present 2 cases of spinal cord intramedullary cavernous hemangioma; 1 patient is the 1st reported case of multiple spinal cord lesions. Diagnosis is greatly enhanced by the use of MRI. 
4	Home blood pressure readings in borderline hypertensive patients. Home blood pressure monitoring can provide valuable information for physicians managing borderline hypertensive patients. This study was conducted to compare office and home blood pressures in 36 borderline hypertensive subjects, and to determine the accuracy of the home monitoring unit used. The patients were very willing to record their home blood pressures for an extended period of time. The home blood pressure monitors were found to be quite accurate, and blood pressures measured at home were significantly lower than readings obtained in the office. In 39% (14 of 36) of the subjects studied, the average home blood pressures were more than 10 mmHg lower than their office readings. These findings support the hypothesis that home blood pressure monitoring can be useful in the management of borderline hypertensive patients. 
3	Correlation of abnormalities of interictal n-isopropyl-p-iodoamphetamine single-photon emission tomography with focus of seizure onset in complex partial seizure disorders. Single-photon emission tomography (SPECT) scanning with n-isopropyl-p-iodoamphetamine (IMP) was performed on 23 patients with complex partial seizures undergoing long-term video electroencephalographic (EEG) seizure monitoring. Twenty-one of the 23 patients had abnormalities on SPECT scanning consisting of areas of decreased activity reflecting diminished cerebral blood flow. In 15 of these 21 patients, there was good correlation between the site of the abnormality on SPECT scan and the site of origin of seizures monitored by EEG. Of the six remaining patients, four had multifocal SPECT abnormalities, with one of the abnormal areas corresponding with an ictal site. The two remaining patients had SPECT abnormalities and major ictal EEG foci in entirely different areas. In contrast to the high proportion of abnormal SPECT scans, only 10 of 23 focal abnormalities were discovered on magnetic resonance imaging (MRI) scans. Three patients who had seizures within 2 h of an initial scan were rescanned 4-5 h after injection. Focal areas of increased blood flow were noted on all three scans, although not always at the ictal site. The SPECT scan appears to be useful in interictal localization of seizure foci. Postictal scans may also be useful, although our numbers are too small to draw conclusions. 
3	Study of verbal description in neuropathic pain. The aim of this paper is to study the quality of verbal description and its diagnostic value in neuropathic pain. The verbal description of pain as assessed by a French adjective list questionnaire (QDSA) is compared between a group of 100 patients with neuropathic pain and a mixed group of 97 chronic benign and cancer non-neuropathic pain patients. Seventeen descriptors of the 61 QDSA descriptors have a significant intergroup frequency difference. By principal component analysis and Varimax rotation of the intercorrelation matrix of descriptors in the neuropathic group. 7 factors accounting for 66.0% of the total variance are derived. Six factors reflect purely sensory or affective aspects of the pain experience. Seven descriptors from the discriminant analysis function correctly assign 77% of neuropathic pain patients and 81% of the non-neuropathic pain patients. In a second neuropathic pain group of 32 patients, the discriminant function coefficient permits correct diagnostic categorization in 66% of the cases. Implications for clinical practice and trials are discussed. 
3	Feasibility and safety of vagal stimulation in monkey model. The feasibility, safety, and preliminary effects of chronic vagal stimulation were studied in an aluminagel monkey model. Pilot studies to perfect the equipment, determine stimulation thresholds, and insure the comfort and safety of the animals preceded this study. Four monkeys were equipped with an indwelling, 2-electrode cuff (titanium bands spaced 7 mm apart; silicone encased; 1.5 cm total length) in contact around the right vagus nerve; avoidance of the cardiac branch was confirmed by electrocardiograms. After postsurgical recovery, the intact and awake animals received constant-current stimulation (5 mA; 83 Hz, 143 Hz, or 50-250 Hz randomly; 0.5-ms pulse width) at the onset of every spontaneous seizure for the duration of the seizure or every 3 h for 40 s if stimulation had not occurred in the preceding hour. Stimulation periods of 2-6 weeks, with differing levels of stimulation, were preceded and followed by at least a 2-week baseline period of no stimulation. During the stimulation periods, the seizure rate decreased to zero in two monkeys and the interseizure intervals became invariable in the remaining two monkeys. These effects carried over temporarily into the poststimulation baseline periods. Vagal stimulation had no consistent effects on seizure severity or EEG interictal spikes. Histological studies of six vagus nerves were unable to separate electrode cuff damage from any direct effects stimulation may have had on the nerves. Although it appears that chronic vagal stimulation is feasible and that epileptogenic processes are influenced, the safety and efficacy of the procedure are still in question. 
4	Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance. The effect of ischemia reperfusion or hypoxia reoxygenation on pulmonary vascular permeability and resistance was studied in 25 isolated blood-perfused dog lungs. Vascular permeability, assessed by determining filtration coefficient (Kf), and vascular resistances were measured at the beginning and end of the experiment. Ischemia reperfusion was produced by occluding blood flow to the lung for 3 h and reperfusing for 1 h, whereas hypoxia reoxygenation was obtained by ventilating the lung with 95% N2-5% CO2 for 3 h and then ventilating with 95% O2-5% CO2 for 1 h with no interruption of perfusion. There was a significant increase in Kf in both ischemia reperfusion and hypoxia reoxygenation groups (51 and 85%, respectively), and total vascular resistance increased greatly in both groups (386 and 532%, respectively). Two additional groups were also studied in which the ischemia reperfusion or hypoxia reoxygenation lungs were pretreated with allopurinol (20 micrograms/ml). The Kf did not significantly increase in either the allopurinol ischemia reperfusion or the allopurinol hypoxia reoxygenation groups (22 and 6%, respectively). However, total vascular resistance significantly increased in both groups (239 and 224%, respectively). Although vascular permeability is modestly increased by both ischemia reperfusion and hypoxia reoxygenation, the predominant change in these conditions is the increased vascular resistance, which predominantly affects the postcapillary resistance and would result in a greater tendency for edema to develop in these slightly damaged lungs. Allopurinol, which inhibits xanthine oxidase, attenuated the permeability changes in both groups and may be useful in preventing ischemia reperfusion injury in certain conditions. 
1	A hepatocellular carcinoma of massive arterioportal shunts without tumor stain treated with CDDP two-route chemotherapy--a case report. Massive arterioportal shunts without tumor vessels or tumor stain are sometimes encountered in advanced cases of liver cirrhosis. Massive arterioportal shunts without tumor stain that responded well to intensive chemotherapy with cis-diamminedichloroplatinum II are reported. 
3	Differentiation in embryonal neuroepithelial tumors of the central nervous system. Ninety-six embryonal neuroectodermal tumors were studied histologically and immunohistologically with a panel of antibodies including glial, neuronal, epithelial, mesodermal, and myelin markers. In 71 tumors there was glial and neuronal differentiation and expression both of an S (photoreceptor) antigen and vimentin. In five tumors there was only glial differentiation and in 20 tumors only neuronal differentiation. No reactivity for myelin and epithelial markers was found. Histologic and immunohistologic findings identified various degrees of differentiation in different tumors, which was bipolar (glial and neuronal) in most tumors and unipolar in the remainder. The authors suggest that their findings may be the result of normal or aberrant oncogenic differentiation, agreeing with the nomenclature of the World Health Organization classification for these tumors with and the inclusion of a category for ependymoblastoma. 
5	Association of acute colonic pseudo-obstruction (Ogilvie's syndrome) with herpes zoster. Ogilvie's syndrome, or acute pseudo-obstruction of the colon is characterized by massive distension of the colon in the absence of organic distal obstruction. The syndrome is associated with various unrelated and, most often, extra-abdominal causes. An association between Ogilvie's syndrome and herpes zoster has been reported only once, by Ceccese et al. in 1985. We present a second such case. This patient did not show evidence of any active illness other than the involvement of the T10 dermatome by herpes zoster. The patient's symptoms of colonic obstruction subsided with resolution of the zosteriform rash. 
5	Heparin skin necrosis: delayed occurrence in a patient on hemodialysis. A case of skin necrosis in a patient receiving intravenous (IV) heparin during routine intermittent hemodialysis is reported. Multiple erythematous, tender lesions developed over the abdomen and thighs and rapidly became necrotic. Biopsies showed fibrin thrombi in the dermal venules and capillaries, but no cellular infiltrate. The patient was in her third month of regular hemodialysis. Skin necrosis associated with the use of heparin usually occurs within 2 weeks of beginning heparin therapy and has not been reported in patients receiving heparin with hemodialysis. Possible mechanisms, including acquired antithrombin III deficiency leading to heparin-induced skin necrosis, are discussed. 
5	Nimodipine after resuscitation from out-of-hospital ventricular fibrillation. A placebo-controlled, double-blind, randomized trial. One hundred fifty-five consecutive patients resuscitated after out-of-hospital ventricular fibrillation by a physician-manned advanced life support unit were randomly assigned to receive nimodipine or placebo at a dosage of 10 micrograms/kg as an intravenous injection immediately after restoration of spontaneous circulation, followed by an infusion of 0.5 micrograms/kg per minute for 24 hours. No significant difference was found in the 1-year survival rate of nimodipine-treated (30 [40%] of 75 patients) and placebo-treated patients (29 [36%] of 80 patients). Recurrent ventricular fibrillation during the treatment occurred in one patient in the nimodipine group compared with 12 patients in the placebo group. In a post hoc analysis of patients with very long delays in advanced life support (more than 10 minutes), the 1-year survival rate was higher with nimodipine (eight [47%] of 17 patients) than with placebo (two [8%] of 26 patients). Nimodipine may be of benefit in patients with delayed resuscitation. 
4	Cardiac arrhythmias from a malpositioned Greenfield filter in a traumatic quadriplegic. A case study is presented of premature Greenfield filter discharge with intracardiac migration and resulting life-threatening arrhythmias. These arrhythmias also interfered with the patient's transition from ventilatory support via orotracheal intubation to noninvasive positive airway pressure ventilatory support methods. The patient's arrhythmias were controlled by a demand cardiac pacemaker and cardiac glycoside therapy. No anticoagulants were used. She had no further filter migration nor significant complications for 16 months after hospital discharge. 
1	Secreted or nonsecreted forms of acidic fibroblast growth factor produced by transfected epithelial cells influence cell morphology, motility, and invasive potential. Addition of exogenous acidic fibroblast growth factor (aFGF) to NBT-II epithelial carcinoma cells results in fibroblastic transformation and cell motility. We have generated aFGF-producing NBT-II cells by transfection with recombinant expression vectors containing human aFGF cDNA, or the human aFGF cDNA coupled to a signal peptide (SP) sequence. The effects of the nonsecreted and the secreted 16-kDa growth factor on the morphology, motility, and cell invasive potential (gelatinase activity) were compared. aFGF coupled to a SP was actively secreted out of the producing cells. The secretion of aFGF was not necessary for induction of gelatinase activity, as this was observed in NBT-II cells producing aFGF with or without SP. Production of aFGF, whether secreted or not secreted, resulted in increased in vitro motility of most isolated clones; however, there was no correlation between aFGF level and motility rate. The data suggest that expression of aFGF in NBT-II cells induces metastatic potential through an autocrine or intracrine mechanism. 
4	Pneumococcal anticapsular antibodies in patients with chronic cardiovascular and obstructive lung disease in The Netherlands. Differences in pneumococcal anticapsular antibody concentrations were assessed among patients with various chronic disorders and among young (25-35 years of age) and older adults (55-65 years). Antibody concentrations were determined by ELISA, using the whole 23-valent pneumococcal polysaccharide vaccine as antigen. No differences in mean or distribution of serum antibody concentrations were found among young adults (either healthy or asthmatic) or among older adults (healthy or with chronic obstructive pulmonary or chronic cardiovascular disease). Each group included individuals with low antibody levels. Therefore, the enhanced susceptibility to pneumococcal infections reported for some groups at risk, that is, elderly individuals and patients with chronic obstructive pulmonary or chronic cardiovascular disease, cannot be attributed solely to low anticapsular antibody concentrations. 
5	The iris in Williams syndrome. Forty three children with Williams syndrome and 124 control subjects had their eyes photographed. The photographs were examined by three ophthalmologists and four geneticists of varying experience. A stellate pattern was noted more often in the irides of patients with Williams syndrome (51%) than in those of the control subjects (12%), and was more difficult to detect, or was absent, in heavily pigmented irides. We conclude that the stellate pattern is of diagnostic importance, particularly if the pattern is carefully defined and the clinician is experienced. 
1	Breast self-examination in relation to the occurrence of advanced breast cancer. Two hundred nine female enrollees of the Group Health Cooperative of Puget Sound who developed advanced-stage breast cancer during the period 1982-1988 were interviewed about their practice of breast self-examination (BSE), use of other breast cancer screening modalities, and medical and reproductive histories. Each subject's description of how she performed the examination was scored according to her mention of up to 10 recommended BSE techniques. A random sample of 433 women without advanced-stage breast cancer from the same population was interviewed for comparison. Relative to women not practicing BSE, the risk of advanced-stage breast cancer among BSE users was 1.15 (95% confidence interval, 0.73-1.81). Frequency of BSE did not differ between women with advanced-stage breast cancer and control subjects, whether in all subjects or in subgroups defined by age, use of mammography, or frequency of clinical breast examinations. While self-described proficiency in BSE was generally low in both case and control subjects, the small percentage of women reporting more thorough self-examinations, regardless of frequency, had about a 35% decrease in the occurrence of advanced-stage breast cancer compared to women who did not perform BSE. These results suggest that, while carefully performed BSE may avoid the development of some advanced-stage breast cancers, BSE as practiced by most Seattle-area women is of little or no benefit. 
4	A consensus approach to electrolytes and blood pressure. Could we all be right? This commentary sets forth the hypothesis that the putative beneficial or detrimental effects of specific electrolytes on blood pressure regulation in fact reflect highly integrated responses to interactions among these cationic and anionic species. In this paradigm, the impact of any given intake of an electrolyte on arterial pressure will be influenced by the concurrent consumption of other electrolytes. Thus, the heterogeneous blood pressure response in humans to isolated manipulations of nutrients such as sodium, calcium, and potassium may be determined, in part, by the adequacy of the dietary intake of other mineral elements. If this hypothesis is validated by continued research in this area, we would have new strategies available to improve blood pressure control in humans. For example, treatment of "NaCl sensitivity" in some humans might be more effectively approached by correcting dietary deficiencies of either potassium or calcium than by restricting dietary NaCl. 
5	Parathyroidectomy in chronic renal failure: a nine-year follow-up study. Seventy-three patients with chronic renal failure who underwent parathyroidectomy between March 1978 and April 1987 were reviewed. Thirty-four patients had undergone sub-total parathyroidectomy, and 39 patients had undergone total parathyroidectomy with parathyroid autograft into the forearm. Eight patients showed persistent hyperparathyroidism requiring a second surgical procedure. In all other patients there was highly statistical improvement in parathyroid hormone, total calcium, ionized calcium, alkaline phosphatase and a significant reduction in calcium x phosphate product. Histological evidence of osteitis fibrosa was present in 21 of 22 patients before surgery. Postoperatively, four showed complete resolution and improvement. Three patients developed histological evidence of osteomalacia during the study period. Only four of the 39 patients who underwent total parathyroidectomy with autograft had true recurrent hyperparathyroidism and only two of the 34 patients who underwent sub-total parathyroidectomy had recurrent disease, indicating that there is little to choose between the two techniques in the control of secondary hyperparathyroidism and its subsequent recurrence. In one patient with recurrence of hyperparathyroidism from a forearm parathyroid graft the histological picture was different from that of normal hyperplastic parathyroid tissue. Although it is probable that abnormal parathyroid tissue had been implanted there was no evidence of invasive growth into the forearm muscle. The most striking feature of long term follow-up was the difference in calcium x phosphate product in patients in whom vascular calcification increased compared to those patients with no change or regression of calcification. Mean calcium phosphate product in those patients with progressive vascular calcification was 4.93 for small and medium size vessels and 5.38 for large vessels compared to 4.10 for small and medium vessels and 4.09 for large vessels. In the former case the serum phosphate was 2.00 and 2.17 as compared to 1.75 or 1.73, suggesting that the aim in patients with end stage renal failure maintained by dialysis should be to control the serum phosphate concentration to 1.8 mmol or less and the calcium x phosphate product to less than 4.2. 
5	Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions. The c-myb protooncogene codes for a sequence-specific DNA-binding protein that appears to act as a transcriptional regulator and is highly conserved through evolution. The DNA-binding domain of Myb has been shown to contain three imperfectly conserved repeats of 52 amino acids that constitute the amino-terminal end. Within each repeat, there are three tryptophans that are separated by 18 or 19 amino acids and are flanked by basic amino acids. To determine the role of tryptophans and the flanking basic amino acids in the DNA-binding activity of Myb proteins, we have selectively mutagenized individual tryptophans as well as some of the amino acid residues that flank these tryptophans. Replacement of these tryptophans with glycine, proline, or arginine abolished the DNA-binding activity whereas replacement with other aromatic amino acids or leucine or alanine did not appreciably affect this activity. On the other hand the replacement of two amino acids, asparagine and lysine, that flank the last tryptophan with acidic amino acids completely abolished their DNA-binding activity. These results are consistent with a model we present in which the tryptophans form a hydrophobic scaffold that plays a crucial role in maintaining the helix-turn-helix structure of the DNA binding domain. Basic and polar amino acids adjacent to these tryptophans seem to participate directly in DNA binding. 
1	Management of local and regional recurrence after mastectomy or breast-conserving treatment. Locoregional failures after primary treatment for breast cancer include a diverse group of lesions that represent different categories of failures with various prognoses. Although patients with chest wall recurrences and regional nodal failures after traditional radical surgery have a poor prognosis, many patients can still achieve a significant degree of palliation and even long-term survival or cure with carefully orchestrated multimodal treatment. In patients who have breast failures after breast-conservation surgery and radiation, long-term salvage and cure can be achieved for the majority with prompt detection and appropriate treatment, which, like treatment for primary breast cancer, includes a consideration not only of local control but also of the risk of subsequent systemic failure and its need for treatment. 
1	Giant cell tumor of bone. Giant cell tumor is the second most common benign tumor of bone. Plain radiographs may demonstrate distinctive features but can also be misleading. The diagnosis may be aided by the use of other imaging modalities, such as bone scan, computed tomography and angiography. The recurrence rate is high, but some of the newer treatments seem to be associated with better outcomes. 
3	Ataxia in myxoedema: a neurophysiological reassessment. In a long-standing case of myxoedema with ataxia and dysarthria, neurophysiological investigations were carried out to assess how much of the ataxic dysbasic syndrome depended on the slowness of mechanical contraction and how much resulted from primary cerebellar involvement. It was observed that the Achilles reflexogram showed a marked prolongation of contraction and relaxation time and that in both quadriceps and triceps surae mechanical percussion induced a marked myxoedema and prolonged relaxation time. The EMG of these muscles during voluntary contraction and stopping reaction detected an excessive recruitment of the antagonistic muscles, starting without any abnormal delay, a finding at variance with a typical cerebellar pattern. Post-urographic analysis gave a pattern of oscillations still within the normal range. These findings suggest that the gait alterations of our patient depended on the increase in muscle contraction time and the consequent excessive recruitment of the antagonists. 
5	Reevaluation of the periodic acid-Schiff stain in acute leukemia with immunophenotypic analyses. To determine the sensitivity and specificity of the periodic acid-Schiff (PAS) stain in the diagnosis of acute leukemia in light of the finer characterization of this disorder now available through immunophenotyping, we examined the blasts from 51 patients with newly diagnosed acute leukemia by morphological, cytochemical, and immunophenotypic analyses. The 51 patients represented every new case of acute leukemia subjected to cytochemical stains and flow cytometry between July 1987 and February 1989. By cell-surface marker analysis, 29 exhibited lymphocytic lineage, while 21 were myelocytic. One was mixed lineage. The PAS positivity, defined by the presence of blocks or coarse granules in 5% or more of the blasts, was found in 15 of 29 lymphoblastic leukemias and in four of the myeloblastic leukemias. However, PAS-positive lymphoblastic leukemias were negative with the other cytochemical stains: myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase. The PAS-positive myeloblastic leukemias were positive with at least one other stain. Three cases of myeloblastic leukemia exhibited greater than 10% PAS-positive blasts, with all three being acute monoblastic leukemia. Thus, the sensitivity and specificity of the PAS stain alone for lymphoblastic leukemia was 52% (15 true positives of 29) and 81% (four false positives), respectively. The sensitivity of a cytochemical-staining combination of PAS positivity and myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase negativity in defining cases of lymphoblastic leukemia remained at 52%; however, the specificity of this combination for lymphoblastic leukemia was 100% (no false positives). Thus, a positive PAS stain, in combination with negative myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase stains, continues to have a diagnostic role in the distinction between lymphoblastic and myeloblastic leukemia, and greater immunologic sophistication serves to support this position. 
5	Understanding dizziness. How to decipher this nonspecific symptom. Dizziness is a common but often nonspecific symptom. Through careful history taking and physical examination, primary care physicians can usually determine the type of sensation (vertigo or light-headedness) and its source. Although most causes of dizziness are benign, disorders of the central nervous system tend to be ominous and require immediate referral to a specialist. 
4	Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: importance of atrial fibrillatory cycle length. The effects of intravenous procainamide (n = 30) or propafenone (n = 25) were evaluated in 55 patients with acute atrial fibrillation and the Wolff-Parkinson-White syndrome. All patients received either procainamide (12 to 15 mg/kg body weight) or propafenone (1 to 2 mg/kg) during sustained (greater than 10 min) atrial fibrillation or after termination of nonsustained atrial fibrillation. Termination of atrial fibrillation was attributed to a drug if it occurred less than or equal to 15 min after infusion. Measurements included mean cycle length of fibrillatory electrograms (mean AA interval) as measured at the high right atrium and shortest RR interval between pre-excited cycles during atrial fibrillation. Atrial fibrillation terminated more frequently after procainamide administration (65%) than after propafenone (46%), although this difference was not significant. Procainamide prolonged the shortest pre-excited RR interval (228 +/- 41 to 339 +/- 23 ms, p = 0.0001) as did propafenone (215 +/- 40 to 415 +/- 198 ms, p = 0.0001) and the magnitude of increase was greater for propafenone (p = 0.048). Patients with sustained atrial fibrillation had shorter mean AA intervals than did their counterparts with nonsustained atrial fibrillation (123 +/- 25 versus 186 +/- 35 ms, p = 0.0001). Termination of sustained atrial fibrillation by either drug was accompanied by prolongation of the mean AA interval but not necessarily by the shortest pre-excited RR interval. Termination of atrial fibrillation was heralded by a 68% increase in the mean AA interval after procainamide administration compared with a 30% increase when the arrhythmia persisted. For propafenone the increases were 90% and 68%, respectively. 
1	Indwelling epidural catheters for pain control in gynecologic cancer patients. Seven patients with severe pain caused by an advanced, incurable gynecologic malignancy were treated with an indwelling epidural catheter connected to an implantable subcutaneous port through which morphine was infused. There were few major complications associated with insertion or maintenance of the system. The average usage was 60 days, although the system functioned continuously for 6 months in one patient. Pain distribution in these women ranged from the upper abdomen to the lower extremities. All patients, including one with liver metastases, reported good to excellent pain control with the epidural narcotics. Two subjects with upper abdominal pain occasionally required supplemental oral oxycodone, but the other five patients had adequate pain relief with the epidural system alone. The indwelling epidural system provides excellent analgesia for patients with advanced, incurable gynecologic cancer. 
1	Pretreatment neuropsychological status and associated factors in children with primary brain tumors. We report on the neuropsychological status of 31 children with primary brain tumors who underwent assessment before receiving therapy. Overall, the children performed within normal limits in all test areas. The exception was the group with anterior hemispheric tumors who demonstrated deficits in executive cognitive functions. Also, when compared according to tumor type, children with midline tumors and hydrocephalus performed more poorly than others on measures of intelligence, executive abilities, visual-motor skills, and fine-motor functions. Although one-half to two-thirds of the children with supratentorial midline and infratentorial tumors had cranial nerve, oculomotor, or cerebellar deficits, only the latter were associated with specific neuropsychological deficits (poorer performance on fine-motor and visual-motor tests). Age did not appear to be a factor in these children's neuropsychological test performances. 
4	Hemifacial spasm caused by a spontaneous dissecting aneurysm of the vertebral artery. Case report. The authors describe the first reported case of dissecting aneurysm presenting with hemifacial spasm. The patient was a 58-year-old woman with left hemifacial spasm of 2 years' duration. Cranial nerve examination was otherwise normal and no other clinical symptoms were observed. Vertebral angiography revealed a fusiform enlargement of the left vertebral artery and contrast medium remaining in the intramural false lumen in the venous phase. Microvascular decompression of the facial nerve with wrapping of the aneurysm resulted in complete relief of the hemifacial spasm. 
1	Hemangiopericytoma of the sternum. Hemangiopericytoma of the chest wall is a rare tumor. We describe a patient with malignant hemangiopericytoma of the sternum who was treated with primary surgical resection and discuss the clinical, radiographic, and histologic features of the case. Surgical resection is the primary mode of therapy. High-dose radiotherapy and chemotherapy with a doxorubicin hydrochloride-containing combination may be warranted in certain cases. 
4	Insulin resistance and compensatory hyperinsulinemia: role in hypertension, dyslipidemia, and coronary heart disease. Resistance to insulin-stimulated glucose uptake and hyperinsulinemia may play a central role in the cause and clinical course of patients with non-insulin-dependent diabetes mellitus, high blood pressure, abnormalities of lipoprotein metabolism, and coronary heart disease. This article summarizes the evidence in support of this general hypothesis. 
3	Functional outcomes following selective posterior rhizotomy in children with cerebral palsy. The recent increase in popularity of selective posterior rhizotomy demands objective documentation of surgical outcome. For this reason, the authors have analyzed the status of 25 children with spastic cerebral palsy before and after rhizotomy to determine the effects of this therapy on muscle tone, range of movement, and motor function. Postoperative tests showed a reduction in muscle tone compared with preoperative assessments. Range of motion in the lower extremities was significantly increased and improvements in functional gross motor skills were noted. An increase in range of motion in the knees and thighs during gait was detected in 18 ambulatory patients studied with computerized two-dimensional motion analysis. Preliminary findings indicate that selective posterior rhizotomy reduced spasticity, thereby increasing range of motion and contributing to improvements in active functional mobility. 
5	Klinefelter's syndrome with anomalous origin of left main coronary artery Klinefelter's syndrome is a rare entity. Even rarer is an anomalous origin of the Left Main Coronary Artery. For both conditions to occur in the same patient is hence exceedingly rare. Reported here is a never previously reported case of a coronary congenital anomaly in a patient with Klinefelter's syndrome together with the proper angiographic approach. 
3	High incidence of cardiopulmonary complications associated with implantation of adrenal medullary tissue into the caudate nucleus in patients with advanced neurologic disease. OBJECTIVE: The purpose of our study was to examine the cardiopulmonary complications of a group of patients who had undergone implantation of adrenal medullary tissue into the caudate nucleus for treatment of neurologic disease. DESIGN: Prospective study with partially matched historical controls. SETTING: Tertiary care community medical center. PATIENTS AND METHODS: Seven patients with advanced Parkinson's disease and three patients with progressive supranuclear palsy underwent implantation of adrenal medullary tissue into the caudate nucleus. These patients were compared with respect to their cardiopulmonary complications with a control group who had undergone craniotomy and then compared with a control group who had undergone only abdominal surgery. RESULTS: In the study group, six patients developed major postoperative complications including development of large pleural effusions, lobar atelectasis, pneumonia, upper airway obstruction, and cardiac arrest. Three patients had minor complications including development of small pleural effusions, subsegmental atelectasis, purulent bronchitis, mild congestive heart failure, and atrial flutter/fibrillation. One patient had an unremarkable postoperative course. The first control group, whose only surgery was a craniotomy, had only one major complication. The second control group, the abdominal surgery control group, had one major and five minor complications. CONCLUSION: The particular neurologic disease, its severity, and the type of surgery performed appear to be causative factors in the high incidence of complications in the study group. 
5	Treatment of pyoderma gangrenosum with cyclosporine: results in seven patients. The mainstay of therapy for pyoderma gangrenosum has been corticosteroids, but many patients respond poorly. During the past 2 years we have treated seven patients who had pyoderma gangrenosum with cyclosporine after their condition proved resistant to conventional therapy. No evidence of permanent toxicity from cyclosporine was detected and treatment with other immunosuppressive agents was discontinued in five of seven cases. Tuberculosis was reactivated in one patient. Three patients had a remission, three had an intermediate response, and one did not respond. These results indicate that cyclosporine is useful in the treatment of patients with refractory pyoderma gangrenosum and suggest an immune mechanism in the pathogenesis of this disorder. 
5	Necrotizing angiopathy presenting with multifocal conduction blocks. We describe conduction block as an unusual electrophysiologic manifestation in a patient with necrotizing angiopathy. The patient developed subacute symptoms over a 1-month period consisting of progressive pain, tingling, and weakness of the lower extremities. Physical examination revealed a pattern consistent with a polyneuropathy. Electrodiagnostic studies provided evidence of a conduction block in the left ulnar nerve. Pathologic studies confirmed the process to be a necrotizing angiopathy. This report establishes the role of conduction block in human nerve ischemia. 
4	Prediction of pregnancy-induced hypertensive disorders by angiotensin II sensitivity and supine pressor test. An angiotensin II sensitivity test and a supine pressor test were done consecutively at 28 weeks gestation in 90 healthy, normotensive nulliparous women. None of the supine pressor tests was positive, applying the predefined threshold of a rise of 20 mmHg in diastolic blood pressure after rolling over; nine tests were positive using a corrected 9 mmHg cut-off level. Ten women had a positive angiotensin sensitivity test using a threshold of the effective pressor dose of 8 ng/kg/min; 22 women were positive using an effective pressor dose of less than or equal to 10 ng/kg/min. Later in pregnancy 12 women (13%) developed pregnancy-induced hypertensive disease (PIH). The specificity of both tests of predicting the development of PIH was about 90%. The sensitivity of the angiotensin sensitivity test at the 10 ng/kg/min level was 92%. Because of its low sensitivity of 25% the supine pressor test appears to have no value for the prediction of PIH. There was a significant positive association between angiotensin II refractoriness and birthweight. 
1	Management of macular puckers associated with retinal angiomas. Monocular visual loss in four patients was caused by epiretinal macular membranes associated with peripheral retinal capillary angiomas or angioma-like lesions. Three patients had solitary vascular lesions and one had two discrete vascular lesions. All patients were in good health, with no evidence of the von Hippel-Lindau syndrome. In three patients, spontaneous peeling of the macular membranes and visual improvement occurred 2 to 6 months after obliteration of the angioma-like lesions with cryotherapy (two patients), or cryotherapy combined with argon laser (one patient). The fourth patient underwent a vitrectomy 8 months after the macular pucker had failed to respond to treatment of the vascular lesion. 
3	Effects of anticonvulsant treatment and low levels of folate and thiamine on amine metabolites in cerebrospinal fluid. A total of 157 epileptic patients were studied with respect to (1) biogenic amine precursors and metabolites in the CSF, (2) levels of folate and thiamine in the blood and CSF, (3) length of treatment with phenytoin (PHT), (4) PHT intoxication, (5) CNS atrophy. Alterations in CSF amine metabolite levels were related primarily to PHT intoxication, and low CSF folate and thiamine levels, but not to length of treatment or CNS atrophy. PHT intoxication increased CSF 5-hydroxyindoleacetic acid (5HIAA). Low folate levels were associated with decreased CSF 5HIAA and homovanillic acid, while low thiamine levels were associated with decreased CSF 5HIAA and 3-methyoxy-4-hydroxyphenylethylene glycol. It remains to be seen to what extent these alterations in biogenic amine metabolism, mediated by low CNS vitamin levels, also lead to deficits in cerebral function. 
5	Asymptomatic and neurologically symptomatic HIV-seropositive individuals: prospective evaluation with cranial MR imaging. As part of a prospective multidisciplinary study of individuals seropositive for the human immunodeficiency virus (HIV), cranial magnetic resonance (MR) imaging was performed on 119 HIV-seropositive subjects (95 asymptomatic, 24 symptomatic) and the results were correlated with clinical data. MR images regarded as positive included those showing atrophy and/or white matter lesions. On the basis of these criteria, 96 subjects had normal MR images and 23 had abnormal images. Results of chi 2 analysis revealed a statistically significant difference between the asymptomatic group (12 of 95 [13%] with abnormal scans) and the symptomatic group (11 of 24 [46%] with abnormal scans) (P = .001). In the asymptomatic group, positive MR images showed fewer, smaller, and/or less extensive abnormalities. The researchers conclude that (a) MR imaging can show indirect evidence of HIV infection early in the disease, but abnormalities will be minor and seen only in a small minority of neurologically asymptomatic subjects; (b) the appearance of clinically recognizable neurologic disease correlates with the MR imaging findings of increasingly severe brain atrophy and white matter lesions; and (c) in some HIV-seropositive subjects, despite neurologic disease, MR images can remain normal. Results indicate that routine screening with cranial MR imaging of neurologically asymptomatic HIV-seropositive individuals would likely result in a low yield of positive findings. 
3	The Woolley and Roe case. A reassessment. In 1953, two patients, Cecil Roe and Albert Woolley, sued their anaesthetist for alleged negligence because they had developed painful spastic paraparesis after spinal anaesthesia. The court found that phenol, which was used to sterilise the outside of the ampoules of local anaesthetic, had percolated the glass through invisible cracks, contaminating the solution, but that the anaesthetist could not have been aware of this risk. The case was important, despite the fact that judgement was in favour of the anaesthetist, because of the fears that it generated over the incidence of paralysis after spinal anaesthesia. The 'invisible crack' theory has been the subject of much scepticism. New information has been obtained, and the case re-examined objectively. The most probable source of contamination, which led to paralysis in the two patients, and in a third who received spinal anaesthesia on the same day, has been identified. A similar explanation may lie behind a number of other episodes of paralysis associated with spinal anaesthesia. 
5	The ventilator-dependent child: issues in diagnosis and management. Infants, children, and adolescents with chronic respiratory failure are surviving in increasing numbers and, thereby, producing a significant population of ventilator-dependent pediatric patients. Chronic respiratory failure can occur as a complication of a wide variety of disease states; in pathophysiologic terms, it generally results from either decreased central nervous system output or inadequate force generated by the respiratory pump. Its laboratory hallmark is hypercapnia with or without hypoxemia. Stabilization of the patient with mechanical ventilatory support may permit long-term survival. Management of the ventilator-dependent pediatric patient is a complex task that must begin with an accurate prognostication of each patient's survival and quality of life. Once a decision is made concerning the practicality and appropriateness of long-term ventilatory support, informed choices must be made with respect to need for an artificial airway, mode of ventilation, and location of care. Many younger patients, especially those with intrinsic lung disease (like bronchopulmonary dysplasia), may require a hospital setting for long-term care, whereas others with neuromuscular or central disorders may benefit from being discharged to home. The patient's family must be thoroughly educated in the child's care, and they must be involved in decision-making. A multidisciplinary team of physicians, therapists, nurses, and other professionals is required to deliver optimal care. Outcome is good for most patients who are carefully selected. 
5	High-resolution linkage mapping for susceptibility genes in human polygenic disease: insulin-dependent diabetes mellitus and chromosome 11q. Insulin-dependent diabetes mellitus (IDDM) has a complex pattern of genetic inheritance. In addition to genes mapping to the major histocompatibility complex (MHC), several lines of evidence point to the existence of other genetic susceptibility factors. Recent studies of the nonobese diabetic mouse (NOD) model of IDDM have suggested the presence, on mouse chromosome 9, of a susceptibility gene linked to the locus encoding the T-cell antigen, Thy-1. A region on human chromosome 11q is syntenic to this region on mouse chromosome 9. We have used a set of polymorphic DNA markers from chromosome 11q to investigate this region for linkage to a susceptibility gene in 81 multiplex diabetic pedigrees. The data were investigated by maximization of lod scores over genetic models and by multiple-locus affected-sib-pair analysis. We were able to exclude the presence of a susceptibility gene (location scores less than -2) throughout greater than 90% of the chromosome 11q homology region, under the assumption that the susceptibility factor would cause greater than 50% of affected sib pairs to share two alleles identical by descent. Theoretical estimates of the power to map susceptibility genes with a high-resolution map of linked markers in a candidate region were made, using HLA as a model locus. This result illustrates the feasibility that IDDM linkage studies using mapped sets of polymorphic DNA markers have, both for other areas of the genome in IDDM and for other polygenic diseases. The analytic approaches introduced here will be useful for affected-sib-pair studies of other complex phenotypes. 
5	Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas. Two hundred sixty-two invasive breast carcinomas dating from 1979 to 1984 were tested for vimentin and keratin on formaldehyde-fixed paraffin-embedded sections. None of 26 lobular carcinomas expressed vimentin. Vimentin expression in 10% or more of tumor cells was found in 78% of medullary (14 of 18), in 16% of ductal not otherwise specified (NOS) (35 of 214), and in two of four mucinous carcinomas. A further seven tumors showed vimentin expression in less than 1% to 10% of the cells. Vimentin was expressed in tumor cells of 30% (28 of 93) of grade III invasive ductal NOS carcinomas versus 7% (7 of 105) of grade II and 0% of grade I carcinomas (0 of 10). Vimentin was found to be preferentially expressed in tumors growing in broad, often anastomosing bands or sheets with extensive necrosis, scanty supportive stroma, high nuclear grade, and numerous mitoses. The authors conclude that vimentin is not detected in lobular carcinomas, but is preferentially expressed in medullary and in high-grade ductal NOS breast carcinomas. 
1	Granulocytic sarcoma presenting as an epidural mass with acute paraparesis in an aleukemic patient. Granulocytic sarcomas are rare tumors composed of granulocytic precursor cells. They are most commonly encountered in patients with acute myelogenous leukemias and myeloproliferative disorders in blast crisis. Rarely, patients presenting with granulocytic sarcoma show no evidence of acute leukemia. The authors report an aleukemic patient with acute paraparesis from an epidural granulocytic sarcoma. Only five such cases have been reported previously. Immunoperoxidase stain for lysozyme and chloroacetate esterase stain were used to prove the myeloid origin of the tumor cells. 
4	Association between primary pulmonary hypertension and portal hypertension: analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations. To determine the clinical, laboratory and hemodynamic profile in patients with primary pulmonary hypertension and associated portal hypertension, 7 new cases and 71 previously reported cases were analyzed. There was no gender predilection and the average age at diagnosis was 41 years. Liver cirrhosis was the most frequent cause of hypertension (82%) and a surgical portosystemic shunt was present in 29%. Almost invariably, portal hypertension either preceded or was diagnosed concurrently with pulmonary hypertension, favoring the hypothesis that in portal hypertension, the pulmonary vasculature may be exposed to vasoactive substances normally metabolized or produced by the diseased liver, possibly inducing vasoconstriction or direct toxic damage to the pulmonary arteries. Clinically, exertional dyspnea was the most frequent presenting symptom (81%); other symptoms, such as syncope, chest pain and fatigue, were present in less than 33%. An accentuated pulmonary component of the second heart sound (82%) and a systolic murmur (69%) were the most common physical findings. At least 75% of these patients had evidence of pulmonary hypertension on electrocardiography (right ventricular hypertrophy) or roentgenography (cardiomegaly or dilated main pulmonary arteries, or both). Hemodynamic findings included severe pulmonary hypertension (mean pulmonary artery pressure 59 +/- 19 mm Hg) with normal pulmonary capillary wedge pressure and cardiac output. Treatment was basically palliative and the mean and median survival times were 15 and 6 months, respectively. In brief, on the basis of clinical presentation and laboratory features, patients with combined primary pulmonary hypertension and portal hypertension seldom represent a diagnostic challenge. Further research is needed on treatment, which remains palliative. The survival rate is poor and worse than that seen in isolated primary pulmonary hypertension. 
5	Mental activity, adrenergic modulation, and cardiac arrhythmias in patients with heart disease. All of the electrophysiological mechanisms of arrhythmias are sensitive to the influences of the autonomic nervous system, particularly to its adrenergic limb. Arrhythmogenic areas may also be dependent on the inhomogeneity of these influences because of their pathophysiological structure and/or the neurogenic or humoral nature of the vector of modulation. The complexity of the various possible scenarios, combined with the role of the rate dependence, explains why standardized protocols exploring the autonomic nervous system in clinical arrhythmias are difficult to define. Invasive electrophysiology is not adapted to address the problem. Isoprenaline infusion only reproduces the humoral adrenergic stimulation to which only a few types of arrhythmias are sensitive. The exercise test is a very complex investigation if the multiple parameters involved are considered. Only a part of its limitations are obviated by the mental stress. Under natural conditions, the neurogenic origin, the intensity of the sympathetic stimulation, and its suddenness are all critical factors responsible for severe tachyarrhythmias. Arrhythmias of the long QT syndrome are particularly demonstrative of the importance of the autonomic nervous system, but this evidence can also be documented in more trivial circumstances of diseased or apparently undiseased hearts. Exploring the autonomic nervous system behavior through heart rate variability in ambulatory recordings is the most recent and fruitful method of investigation. This nonprovocative approach has technical obstacles and practical and theoretical limitations related to the fundamental nature of the autonomic nervous system, which is both a marker of the cardiac status and a determinant of arrhythmias. 
5	Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism The potential of plasma measurement of D-dimer (DD), a specific derivative of crosslinked fibrin, for diagnosis or exclusion of pulmonary embolism was investigated in a prospective series of 171 consecutive patients who attended an emergency department with suspected pulmonary embolism. The diagnosis was made or excluded by means of a clinical decision-making process which included clinical evaluation, ventilation-perfusion (VQ) lung scan, and, as indicated, pulmonary angiography, venography, or non-invasive examination of the leg veins. Pulmonary embolism was diagnosed by this process in 55 (32%) of 170 patients with sufficient data. All but 1 of these 55 patients had a DD concentration of 500 micrograms/l or above. The sensitivity and specificity of this cutoff concentration for the presence of pulmonary embolism were 98% and 39%, respectively, which give positive and negative predictive values of 44% and 98%. Among the 115 patients (68%) who had inconclusive VQ scans, 31 were diagnosed as having pulmonary embolism. 29 of the remaining 84 patients without pulmonary embolism had DD concentrations below 500 micrograms/l, which means that further diagnostic procedures could have been avoided in a quarter of the patients with inconclusive VQ scans. The sensitivity of the plasma measurement of DD remained high even 3 and 7 days after presentation (96% and 93%). Plasma measurement of DD therefore has a definite place in the diagnostic procedure for suspected acute pulmonary embolism in attenders at emergency departments: a concentration below 500 micrograms/l rules out the diagnosis. 
1	Primary intratemporal tumours of the facial nerve: diagnosis and treatment. Benign primary tumours of the facial nerve are uncommon. A slowly progressive facial palsy should be considered the result of a nerve tumour until proven otherwise. Improvements in diagnostic imaging techniques of the temporal bone have increased the possibility of a correct pre-operative diagnosis but facial nerve tumours remain a frequently ignored or misdiagnosed entity as a consequence of their subtle and protean clinical manifestations. A series of 12 cases of primary facial nerve tumours is presented. The clinical features, diagnostic modalities and treatment are discussed in relation to a review of the literature. 
1	Structural and functional integrity of ovarian tumor tissue obtained by ultrasonic aspiration. For patients with ovarian epithelial cancer, survival increases when residual disease approaches zero after surgical removal of the tumor. A previous study using the Cavitron Ultrasonic Surgical Aspirator (CUSA) (Cavitron Lasersonic Corp., Stamford, CT) showed the successful removal of ovarian tumors from areas often considered unresectable: the diaphragm, spleen, stomach, and small bowel. However, the CUSA has not yet been approved by the Food and Drug Administration for gynecologic surgery except on an experimental basis. This study was designed to test whether ultrasonic irradiation produced by the CUSA caused alterations in cell structure or physiology of gynecologic tissue in adjacent areas. Paired tumor samples, unirradiated and irradiated, were obtained from ten patients, and portions were sent for pathologic structural evaluation and physiologic tissue culture evaluation. Histologic sections, stained with hematoxylin and eosin, showed that CUSA irradiation produced only minor tissue distortion as observed under the light microscope. A correct diagnosis would have been made in all cases had only tissue fragments obtained from the CUSA specimen trap been stained. For nine of ten patients, initial tumor cell viability was similar in the two specimen types. Flow cytometric DNA analysis confirmed that surgical methods produced matched samples. Cells that survived high-frequency ultrasound appeared functionally intact. For five of eight patients, the cells from the CUSA specimen traps survived and/or divided to a greater extent than those from the knife-dissected tumors. Cells from both surgical routes attained a similar number of passages in culture. It seems reasonable to extrapolate these in vitro observations with pelvic tumor tissues to normal surrounding tissue left in situ. Thus pelvic tissue is believed to be uninjured by CUSA ultrasonic irradiation. 
5	Management of hypertension and cardiovascular risk. Blood pressure reduction in hypertensive patients is a surrogate for the real therapeutic goal of reducing the risks consequent to hypertension. This surrogate is convenient but its use may have important therapeutic implications. Results of treatment with new antihypertensive agents, data from clinical trials, and insights into underlying mechanisms are reviewed. The overall success of antihypertensive therapy has been undeniable, but has reduced minimally the frequency of atherosclerosis and coronary events; metabolic disarray resulting from the agents used, especially thiazides and beta blockers, may have contributed to this. Electrolyte abnormalities predispose to malignant arrhythmias and sudden death during myocardial infarction. Left ventricular hypertrophy, a chief risk factor for coronary events, arrhythmias, and heart failure, responds selectively to antihypertensive agents. Similarly, progression of renal injury may be sensitive to the agents used. Obesity and hypertension frequently coexist. Evidence is growing that atherogenic abnormalities common in obese patients, such as insulin resistance, also occur in the nonobese patient and are sensitive to the antihypertensive agent selected. 
1	A new phantom for mammography. A new mammography phantom from Du Pont is described. It has a wider range of types of detail than in previous phantoms, including some which closely simulate breast tissues. Experience of its use, and comparisons with an earlier ("Barts") phantom, are reported. The Du Pont phantom appears to have greater sensitivity to changes in tube kV and focal spot size, and better discrimination between different film-screen combinations and between films from different breast screening centres. 
4	Life-threatening complications during anaesthesia in a patient with a ventriculo-atrial shunt and pulmonary hypertension [published erratum appears in Anaesthesia 1991 Mar;46(3):241] A 6-year-old patient with hydrocephalus who underwent revision of a ventriculo-atrial shunt is described. Anaesthesia was complicated by the occurrence of systemic hypertension and arterial hypoxaemia. The patient was subsequently found to have pulmonary hypertension secondary to recurrent pulmonary thromboembolism. The pathophysiological mechanisms for the patient's deterioration are discussed and the anaesthetic management of children with pulmonary hypertension is outlined. It is concluded that patients with a ventriculo-atrial shunt who present for surgery should be screened carefully for the presence of pulmonary hypertension. 
2	Gastro-oesophageal reflux during elective laparoscopy. An oesophageal pH electrode was used to record gastro-oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures. No refluxes were recorded during the 63 procedures from which results could be analysed; the upper 95% confidence limit from this observation is 3 in 63 (4.8%). Two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia. Tracheal intubation may be required during laparoscopy, although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless, with the same logic, it is suggested that all patients who hiccough should be intubated. 
3	Anti-GM1 IgM antibodies in motor neuron disease and neuropathy. We found anti-GM1 IgM antibodies in 23% of 56 patients with motor neuron disease (MND), in 19% of 69 patients with neuropathy, and in 7% of 107 controls with other neurologic and nonneurologic diseases. Most of these patients had anti-GM1 IgM antibody titers of 1:80 or less; slightly higher antibody titers (up to 1:640) were found in 3 patients, 1 with MND and 2 with neuropathy, and very high titers (1:20,480) in a patient with MND and an IgM kappa M protein that reacted with GM1, GD1b, and asialo GM1. Six other patients with anti-GM1 IgM that also bound to GD1b. Reactivity with GD1b did not correlate with anti-GM1 titers but was only present in patients with MND or neuropathy. Anti-GM1 IgM antibodies may be a normal constituent of the human antibody repertoire but their frequency and, in some cases, their levels are higher in patients with MND and neuropathy. The origin and the pathogenetic role of these antibodies in neural impairment remain to be established. 
3	An open trial of high-dosage antioxidants in early Parkinson's disease. High dosages of tocopherol and ascorbate were administered to patients with early Parkinson's disease as a preliminary open-labeled trial for the eventual controlled double-blind study evaluating antioxidants as a test of the endogenous toxin hypothesis of the etiology of Parkinson's disease. The primary endpoint of the trial was the need to treat patients with levodopa. The time when levodopa became necessary in the treated patients was compared with another group of patients followed elsewhere and not taking antioxidants. The time when levodopa became necessary was extended by 2.5 y in the group taking antioxidants. The results of this pilot study suggest that the progression of Parkinson's disease may be slowed by the administration of these antioxidants. A large multicenter, controlled clinical trial currently underway in North America evaluating tocopherol and deprenyl has the potential to confirm these results. 
4	Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term Our study examines the long-term cardiovascular effects after a brief period of angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR). SHR were treated with perindopril (3 mg/kg/day) by gavage from 2 to 6, from 6 to 10, or from 2 to 10 weeks of age. Systolic blood pressure was measured in the tail weekly until 25 weeks of age. Corresponding control groups received distilled water for the same periods. In each treatment group blood pressure was reduced significantly during treatment, rose when treatment stopped, but plateaued significantly below control SHR thereafter. This difference in blood pressure at 25 weeks of age was due to reduced total peripheral resistance as determined by microsphere methods, but plasma renin activity and angiotensin II concentrations were not different. Cardiac hypertrophy was also reduced in treated SHR. In a separate experiment, perindopril treatment from 6 to 10 weeks of age resulted in a significant reduction in the media/lumen ratios of mesenteric resistance vessels at 32 weeks of age. Concomitant administration of angiotensin II with perindopril from 6 to 10 weeks of age not only prevented the long-term effects on blood pressure seen with perindopril treatment alone but was associated with cardiovascular hypertrophy in excess of untreated control SHR. Finally, perindopril given for a shorter period (6 to 7 weeks) or later in life (20 to 24 weeks) had no significant long-term effects on blood pressure. These results demonstrate that a 4-week period of ACE inhibitor treatment in young SHR is sufficient to prevent the full expression of genetic hypertension and cardiovascular hypertrophy and that angiotensin II might be important in the development of hypertension in this model, its role in later life being less important. 
1	Regulation of pancreastatin release from a human pancreatic carcinoid cell line in vitro. The objective of these experiments was to investigate the influence of activation of three second messenger systems (protein kinase-C, adenylate cyclase-cAMP, and calcium mobilization) on the secretion of pancreastatin (PST) and chromogranin-A (CGA) by a human pancreatic carcinoid cell line (BON) in tissue culture. Stimulation of protein kinase-C by a phorbol ester (0.025-7.5 microM) caused a significant dose-related release of PST (186 +/- 22-4271 +/- 228% over controls). Treatment of BON cells with graded doses of 8-bromo-cAMP (0.14-3.0 mM) and isobutylmethylxanthine (IBMX; 0.01-1.0 mM) also stimulated a dose-related release of PST (107 +/- 22-284 +/- 28 and 16 +/- 12-1076 +/- 100% over controls, respectively). Incubation of BON cells with ionomycin (0.134-13.4 microM) increased the release of PST (102 +/- 15-554 +/- 21% over controls) in a dose-related manner. A combination of IBMX and ionomycin resulted in an additive effect, whereas treatment with a phorbol ester plus IBMX resulted in a synergistic effect on PST release. Pretreatment of BON cells with monensin, an agent that prevents processing of precursors to smaller peptides, significantly decreased PST, but not CGA, secretion in response to phorbol ester or ionomycin. These findings indicate that protein kinase-C, cAMP, and Ca2+ mobilization participate in CGA and PST secretion. Although the observation that secretions of PST and CGA in response to theophylline are quantitatively associated, the absence of a quantitative relationship in the release patterns of PST and CGA in response to phorbol ester and ionomycin do not support a simple precursor-product relationship between CGA and PST. The monensin experiments are consistent with the notion that PST is derived from CGA in BON cells. 
1	Genetic strategies of tumor suppression. The evaluation of the cancer cell is a complex multigene process. Tumor suppressor genes that are lost or inactivated, as well as genes that are overexpressed, play key roles in tumor progression. The identification of overexpressed genes has been expedited by the presence of transforming genes in some animal retroviruses. However, tumor suppressor genes have been difficult to identify and isolate because of their loss or inactivation during tumorigenesis. By a variety of methods, summarized in this review, a few tumor suppressors have been cloned and characterized, and many more have been recognized indirectly. The general finding at this time is that the same tumor suppressors (and oncogenes) are found associated with many different tumors, that several different altered genes are found typically in the same tumors, and that other oncogenes and tumor suppressor genes seem to be characteristically altered in particular tumor types as well. Functions of tumor suppressor genes include the control of normal cell activities such as proliferation and differentiation as well as senescence, which is a special kind of differentiation in which cells lose their ability to divide. The genetic basis of senescence and identification of genes involved in overcoming senescence, leading to immortalization (i.e., indefinite growth potential), are important areas of current investigation. Our laboratory is engaged in senescence/immortalization studies as a result of our discovery that normal human mammary epithelial cells can be immortalized by DNA of the human papilloma virus. These new studies are summarized here. 
5	Conservative management or closed nailing for tibial shaft fractures. A randomised prospective trial. We performed a prospective randomised trial on matched groups of patients with displaced tibial shaft fractures to compare conservative treatment with closed intramedullary nailing. The results showed conclusively that intramedullary nailing gave more rapid union with less malunion and shortening. Nailed patients had less time off work with a more predictable and rapid return to full function. We therefore consider that closed intramedullary nailing is the most efficient treatment for displaced fractures of the tibial shaft. 
5	Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in an acute-care hospital. Use of ciprofloxacin as an alternative to vancomycin for treatment of methicillin-resistant Staphylococcus aureus infection has been paralleled by the emergence of resistant strains. This phenomenon has also been noticed in our hospital. To confirm our observation, methicillin and ciprofloxacin susceptibilities were tested by disk diffusion and broth microdilution techniques. We studied 83 methicillin-resistant Staphylococcus aureus isolates obtained from various sources over a 4-month period. Ciprofloxacin resistance (MIC, greater than 2 micrograms/ml) was detected in 69 isolates (83%). Prior use of ciprofloxacin was reported for 24 of 69 patients with ciprofloxacin-resistant strains and 0 of 14 patients with ciprofloxacin-susceptible strains. The day of detection during the hospital stay and the location of the source patient were not significantly different between resistant and susceptible strains. Bacteriophage typing showed a higher occurrence of nontypeable strains among ciprofloxacin-resistant strains (54%). Review of our microbiology register showed a progressive increase in the rate of resistance to ciprofloxacin during the first year of use, with initial rates being about 10% and recent rates being higher than 80%. On the other hand, methicillin-susceptible S. aureus remained uniformly susceptible to ciprofloxacin (98.4%). We conclude that prior use of ciprofloxacin is an important factor for the selection of ciprofloxacin-resistant strains and that ciprofloxacin has limited usefulness against methicillin-resistant S. aureus. 
3	The effect of omental pedicle graft transfer on spinal microcirculation and laminectomy membrane formation. The properties of the omentum and its effect on spinal neurologic disease was investigated. Omental pedicle grafts were transferred to the laminectomized lumbar spines of nine neurologically normal dogs. Grafts were placed on either the dura or the spinal cord. Interruption of the graft's circulation was examined. To study the effect, the artery of the graft was injected with contrast and the graft-dura interface studied histologically. All injected specimens demonstrated vascular connections from the graft to the neural elements. The graft was found to decrease postoperative perineural scarring. The omentum appears to possess properties that could be applied to improve outcomes in spinal surgery. 
5	Internal capsule plaque and tonic spasms in multiple sclerosis. A patient developed hemilateral tonic spasms associated with a relapse of multiple sclerosis. An area of demyelination in the right internal capsule was observed on a magnetic resonance imaging scan. This lesion was not detectable on a second magnetic resonance imaging scan 10 months after the spasms had ceased. Paroxysmal symptoms in multiple sclerosis may represent transient phenomena related to inflammation in acute plaques. 
2	Treatment of hepatolithiasis: improvement of result by a systematic approach. In previous decades the result of treatment of hepatolithiasis has been unsatisfactory. The incidence of residual stones after surgery might reach 77%. In the past 6 years we adopted a systematic approach comprised of accurate delineation of disease in the liver and biliary tract by direct cholangiography, ultrasonography, and computed tomography; tailored surgical treatment according to the extent of involvement of the liver and biliary tract; access to the intrahepatic ducts through the left duct or round ligament approach when there was difficulty with common bile duct exposure; routine use of flexible choledochoscopy; and application of electrohydraulic lithotripsy for large and impacted stones. Complete stone clearance was achieved in 114 of 127 patients (89.8%). Of those patients who had incomplete stone clearance, only six cases (4.7%) were related to technical failure of postoperative choledochoscopy. The incidence of stone recurrence was 15.8%, the lowest rate so far reported. It was the same regardless of whether a biliary drainage procedure had been performed, but the treatment for recurrent stones was facilitated by previous hepaticocutaneous jejunostomy. Overall the surgical treatment required for stone recurrence was of a lesser magnitude than that in the past. 
5	Penetrating keratoplasty for keratoconus: complications and long-term success. A series of 100 penetrating keratoplasties for keratoconus performed between 1968 abd 1986 were reviewed for long-term results. The mean follow-up was 6.1 years with a range of 4-16 years. The systemic associations and the postoperative complications were analysed. Grafting in cases associated with Down's syndrome had a higher incidence of complications. 93% of grafts remained clear and 81% achieved a final corrected visual acuity of 6/12 or better. 21% of eyes developed a homograft reaction, with 50% of rejection episodes occurring in the first year after operation. Factors associated with higher incidence of rejection included loose sutures, traumatic wound dehiscence, and grafts larger than 8.5 mm. Only three grafts with rejection episodes lost graft clarity, while rejection in the rest was successfully reversed with topical steroid therapy. No relationship was found between donor age and long-term graft clarity. 
4	Low rate of treatment of hypercholesterolemia by cardiologists in patients with suspected and proven coronary artery disease. BACKGROUND. Although specific guidelines for the treatment of hypercholesterolemia have been published, it is not known whether physicians treating patients likely to have lipid disorders have adopted the recommendations. METHODS AND RESULTS. The approach of cardiologists to the treatment of hypercholesterolemia in a metropolitan teaching hospital was assessed by interviewing patients with chest pain who were admitted for coronary angiography in 1988-1989 and by measuring fasting blood lipid profiles. At 1 month and again 12-24 months later, patients were contacted by telephone to determine if there had been any changes in treatment. Of 95 patients evaluated, 81 had coronary artery disease. Only 17% of those with high levels of total cholesterol and/or low density lipoprotein cholesterol were being actively treated with diet and/or drugs. In the remaining patients, either lipid studies had not been done or abnormal results had not been addressed. There was little change in treatment approach during the month after the diagnostic procedure. Furthermore, the experience was similar in those patients subjected to coronary revascularization. One to 2 years after the initial intervention, 69 of the original study group could be contacted again. Although active dietary or pharmacological therapy was initiated in some individuals during this interval, it was stopped in others. Thirty-five percent of hypercholesterolemic patients were receiving targeted therapy. CONCLUSIONS. Thus, only a small proportion of patients with documented coronary artery disease and hypercholesterolemia were being actively treated for their lipid disorder, suggesting that the published treatment guidelines have not yet been fully accepted. However, an encouraging improvement in frequency of treatment of hypercholesterolemia was documented during the 1-2-year observation period. 
4	Primary prevention of coronary artery disease through a family-oriented cardiac risk factor clinic. Primary prevention of coronary artery disease in children and young adults is important and can be instituted through a family-oriented cardiac risk factor clinic. Such a clinic was initiated at the Medical College of Georgia in March 1988. Children whose total cholesterol level (TC) exceeded 200 mg/dL when screened by their primary care physician were referred with their siblings and parents for fasting lipid profile and further evaluation. Data are available for the initial 21 families, including 30 children and 36 adults. The mean TC level was 258 mg/dL for index cases, 195 mg/dL for siblings, and 233 mg/dL for parents. Follow-up data obtained after therapy at a mean of 6 months are available for 12 families, including 14 children and 14 adults. The mean change in TC was from 265 to 246 mg/dL; 82% of the patients had a decrease in TC. Only one index case was documented as having neither a sibling nor a parent with an elevated cholesterol level. Family-oriented cardiac risk factor clinics are important for the identification and treatment of hypercholesterolemia in asymptomatic young people when primary prevention is possible. 
3	Night waking during infancy: role of parental presence at bedtime. Night waking occurs commonly in infants and young children. The goal of this study is to determine whether parents who report being present when their infant falls asleep at bedtime are more likely to report increased frequency of night waking by the infant. Mothers were consecutively recruited when they brought their infants to the clinic for their 9-month well-child visit. A total of 122 mothers agreed to participate and completed a questionnaire consisting of closed-ended, forced choice questions about their infant's feeding and sleeping behavior, and demographic and psychosocial characteristics. For 33% of the mothers, a parent was routinely present when the infant went to sleep. The entire sample of infants averaged 4.1 night wakings during the week prior to questionnaire completion. Infants whose parents were present at bedtime were significantly more likely to wake at night than infants whose parents were not present (6.2 vs 3.1, P = .01). Frequent night waking (seven or more wakings in the prior week) occurred in 28% of the sample. More of the infants whose parents were present experienced frequent night waking compared with infants whose parents were not present (40% vs 22%, P less than .04). When potential confounding variables were controlled by multivariate analysis, parents being present when the child went to sleep was independently associated with night waking (P less than .03). The association of parental presence at bedtime and night waking has implications for preventing and managing disruptive night waking in infancy. 
1	Management of the pregnant patient with carcinoma of the breast. The diagnosis of carcinoma of the breast during pregnancy poses a challenging dilemma. Although once regarded as incurable, recent reports reveal similar long term survival rates for pregnant and nonpregnant patients who have carcinoma of the breast. When referred to a surgeon, a pregnant woman with a suspicious mammary mass deserves an expedient histologic diagnosis; delay may jeopardize the chances of survival. Once the diagnosis is established, pregnant patients should be treated in a manner similar to nonpregnant patients because there is no evidence that carcinoma of the breast in pregnant women is biologically different than carcinoma of the breast in other premenopausal women. Fears of fetal exposure to radiation should not deter a physician from ordering appropriate preoperative diagnostic tests to stage the patients. Operation may be performed safely when general anesthesia is administered and postoperative adjuvant therapy should be administered when necessary. The involvement of multiple subspecialties in the management of these patients is highly recommended. 
3	Glucosephosphate isomerase as a CSF marker for leptomeningeal metastasis. Glucosephosphate isomerase (GPI), also known as phosphohexoisomerase, is a glycolytic enzyme whose activity is elevated in serum and CSF of patients with primary and metastatic CNS tumors. To improve the diagnostic accuracy of leptomeningeal metastasis (LM), we measured GPI levels in CSF of 66 patients with CNS or systemic malignancies with suspected LM. We determined GPI kinetically using a coupled enzyme reaction assay. There were 31 males and 35 females, aged 1 to seventy-six. Thirty-one had primary brain tumors, and 35 had systemic cancer with suspected CNS metastasis. We analyzed 95 samples; GPI values ranged from 0.85 to 329.0 U/l (normal, less than 20 U/l). Compared with positive CSF cytology and myelography, GPI sensitivity was 53.5% and specificity 92.1% for the group as a whole. There was a highly significant association between elevated CSF GPI (greater than 20 U/l) and LM. The results were similar for both primary CNS and systemic malignancies. Although not very sensitive, an elevated CSF GPI strongly suggests LM and may aid in early diagnosis of this serious complication of cancer. 
5	Biochemical evaluation of calcium stone patients: how soon can it be done after stone surgery/passage? Biochemical evaluations were done two times for 29 outpatients with calcium stone disease, the first time within one month after surgical extraction or passage of stones and the second time two months or more later. Classification of the etiologic basis for the stone disease was the same after both tests in 27 patients. In the other 2 patients the diagnosis was changed from renal to absorptive hypercalciuria. Both of these patients had creatinine clearance rates less than 60 percent of normal during the first test. One also had multiple residual stones during both evaluations, and the second had a urinary tract infection during the first test that resolved with a normal creatinine clearance by the second test period. When nephrogenous cyclic adenosine monophosphate (cAMPn) assays were done on fasting specimens in these patients, the results were consistent with absorptive hypercalciuria. Almost all patients can be evaluated and placed in management programs within a few weeks after surgery. If cAMPn assays are not done, patients with decreased renal function secondary to residual stones or infection can be tested at a later time. 
5	Cytomegalovirus infections in pediatric liver transplantation. From 1986 to 1989, 26 consecutive pediatric liver transplant recipients were followed up at The Hospital for Sick Children, Toronto, Canada. The patients were reviewed to assess the incidence of infection with cytomegalovirus, the severity of disease, and the relationship of recipient and donor serostatus to cytomegalovirus disease. Overall, the incidence of infection was 54% (14/26). Over 90% of patients who were seropositive or whose donors were seropositive developed evidence of cytomegalovirus infection after transplantation. Forty-three percent (6/14) of those with cytomegalovirus infections developed severe, fatal cytomegalovirus disease, despite treatment with immunoglobulins and ganciclovir (Syntex Laboratories Inc, Palo Alto, Calif) or foscarnet sodium (Astra, Pharmaceutical Products Inc, Westborough, Mass). Of all posttransplant deaths, two thirds were associated with severe cytomegalovirus infection. Cytomegalovirus-related deaths occurred in three of four seronegative patients with seropositive donors and three of six seropositive patients with seropositive donors. Therefore, a seropositive donor appeared to be a major risk factor for severe cytomegalovirus disease. 
4	Electroencephalography laboratory diagnosis of prolonged QT interval. Patients with prolongation of the QT interval are at risk for significant neurological morbidity and mortality secondary to ventricular tachyarrhythmias. These patients frequently undergo electroencephalographic (EEG) examination to evaluate episodes of loss of consciousness, which may be associated with convulsions. Electrocardiogram recording as a part of the EEG is a simple and common practice, but analysis for possible QT prolongation is not routinely performed by electroencephalographers. This is, in part, due to the fact that while calculation of the corrected QT interval is straight forward, a calculator is generally required. A nomogram that is presented simplifies determination of the corrected QT interval, facilitating diagnosis of prolongation of the QT interval in the EEG laboratory. 
5	An evolutionary perspective on salt, hypertension, and human genetic variability. Natural selection for electrolyte conservation has likely been the norm throughout human evolutionary history. However, the current patterns of excessive dietary salt intake create the potential for salt overload. Under these conditions, hypertension may be considered an expected pathological response to an evolutionarily new constraint. The transatlantic Middle Passage may have created a genetic bottleneck for salt conservation in African-Americans. Although the initial consequences of this important historical event probably constricted genetic variability and further magnified the potential for salt-sensitive hypertension, the Middle Passage undoubtedly also served as a more generalized major source of environmental stress and may have stimulated subsequent hereditary diversity in the survivors of this holocaust and their descendants. Accelerated rates of mutation, genetic recombination, and transposable genetic elements in conjunction with enhanced opportunities for gene flow, new selective pressures, and drift have all contributed to the tremendous heterogeneity of contemporary African-Americans. It is unlikely that a single genetic event, even of the severity of the Middle Passage, can account comprehensively for the apparent susceptibility of this macroethnic group to high blood pressure and hypertension. 
5	Total knee arthroplasty in patients after patellectomy. Twenty-six total knee arthroplasties (TKAs) were evaluated in 22 patients who had had a patellectomy. Fourteen knees (12 patients) had a primary TKA, and 12 patients had a revision TKA. Two patients in the revision group, whose prostheses failed, were from the primary TKA group. The mean follow-up time was 8.5 years in the primary TKA group and 7.6 years in the revision TKA group. A group of 14 control knees with patellae was randomly generated but matched for prosthesis, diagnosis, surgeon, age, and time of surgery. This group was similarly evaluated with an average follow-up time of 6.9 years. The primary TKA group had seven knees that were rated as good or excellent, two as fair, and three as poor. The control group had a significantly higher average rating than the primary TKA group. In this group, there were 12 good or excellent knees, three fair, and none poor. Postoperative pain, flexion contracture, extension lag, and range of motion all contributed significant information to the final score, whereas other variables (walking, function, strength, and instability) did not contribute any additional information. Although higher overall scores may have been expected if the patients had patellae, the results during the follow-up examination were satisfactory and justified TKA in these patients. In general, however, patients without patellae may be at a higher risk for failure of the prosthesis, as seen in five patients having primary TKA and another ten patients with failed TKA requiring revision. 
5	Pre-discharge immunization among hospitalized Filipino children. Identifying opportunities to vaccinate eligible children is one way to boost rates of immunization especially in countries with low immunization coverage and where convalescence from infectious illness is a contraindication to vaccination. To determine the safety and immunogenicity of diphtheria-tetanus toxoid-pertussis and oral polio immunization, 210 convalescing infants and children and community controls, comparable image and nutritional status, were studied. Using the pertussis agglutination and poliovirus neutralization tests, quantitative serologic responses were compared in the two study groups. No significant differences in the incidence rates of febrile reactions (23% in controls; 28% in convalescents) of local reactions (92% in controls; 87% in convalescents) and of seroconversion (P greater than 0.05) were noted between the two groups. Our investigation suggests that infants and children convalescing from infectious illnesses can be safely and effectively vaccinated. This study further suggests that hospitalization provides an opportunity to vaccinate such children. 
5	Strapless oral-nasal interface for positive-pressure ventilation. A custom-fabricated strapless oral-nasal interface (SONI) is described. It was used in the long-term administration of intermittent positive-pressure ventilation (IPPV) by 18 patients with paralytic or restrictive pulmonary insufficiency. This interface is an acrylic shell which is firmly fixed to an orthodontic bite plate; it is designed to form a seal over the nose and mouth for the entry of IPPV. Eight patients were ventilator dependent 24 hours a day. The ten patients who required only nocturnal aid had improvement in daytime arterial blood gases. Although nine of these patients could manage less than 15 minutes of unassisted breathing (free time) supine, all slept supine on SONI IPPV. The 13 patients who underwent sleep monitoring maintained a mean oxygen saturation of 95.3% +/- 1.7% and acceptable end-tidal pCO2 (30 to 45 mmHg). These 13 patients have used SONI IPPV for an average of 22 months (range = 3 to 63 months). Impediments to successful long-term use of a SONI include the presence of a hyperactive gag reflex or stimulation of excessive oral secretions. When combined with mouth IPPV, glossopharyngeal breathing, the intermittent abdominal pressure ventilator, or the cuirass ventilator for daytime use, SONI IPPV is an option for the patient who prefers total ventilatory support by noninvasive means. 
1	Weight gain with breast cancer adjuvant treatment. Available information suggests that individuals with breast cancer gain weight during adjuvant treatment and that this weight gain may be associated with poor prognosis. Exploration of the factors which affect weight gain may aid in developing weight control interventions for these patients. To determine the factors which are associated with weight gain, 32 women undergoing adjuvant chemotherapy were followed over 2 years from the beginning of adjuvant treatment. Measures of psychologic functioning and self-reports of exercise levels and eating were assessed every 2 months during the course of treatment. Sixty-nine percent of the women gained weight over treatment, resulting in a significant weight gain for the group as a whole. Weight gain was correlated positively with several psychologic measures but not with assessed biologic measures. A multiple-regression equation using psychologic/behavioural measures of emotional discharge, logical analysis, affective regulation, interpersonal sensitivity, average number of symptoms, and obsessive compulsiveness accounted for 58% of the variance in overall weight gain. At 2 years of follow-up, 27 women had gained weight for an average of 6.03 kg. The coping style of logical analysis emerged as a significant predictor of disease recurrence, accounting for 28% of the variance in weight gain at 2 years. The results are discussed in terms of identification of women likely to gain weight during adjuvant treatment, directions for future research, and development of interventions to control weight gain. 
5	Intercostal arteriovenous fistula due to pleural biopsy A 32 year old woman had a pleural biopsy for a left pleural effusion, which showed caseating granuloma typical of tuberculosis. When the fourth biopsy specimen was removed considerable bleeding occurred from the puncture site. Four days later a bruit was audible over the punctured area, radiating to the back. Eight days after the procedure the patient had a massive bleed into the left pleural space. Selective aortic angiography showed an arteriovenous fistula between the 9th intercostal artery and vein and a pseudoaneurysm in the intercostal punctured area. Thoracotomy showed bleeding from the site of the pleural biopsy. The intercostal vessels were ligated and pleural decortication was performed, and the patient recovered uneventfully. 
1	Soft-tissue tumor with abnormal amianthoid collagen fibers. Electron microscopic examination of a solitary soft-tissue tumor from the face demonstrated large areas with abnormal amianthoid collagen fibers in the neoplasm. The lesion was classified as a benign neoplasm of myofibroblasts and tentatively named a myofibroblastoma. The significance of the amianthoid collagen fibers is unknown. Normal native collagen fibers were found in some parts of the neoplasm. 
3	Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. An increase in extracellular K+ concentration ([K+]c) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]c increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]c, the extracellular concentration of glutamate ([Glu]c) was measured along with [K+]c. The results indicate that a relatively specific increase in [Glu]c (as compared with other amino acids) was induced concomitantly with the increase in [K+]c. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]c. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury. 
1	Squamous carcinoma of the posterior pharyngeal wall. We have reviewed a 12-year experience with 295 patients treated for squamous carcinoma of the pharynx in order to focus on 78 patients whose lesions arose in the posterior wall. Surgery was the definitive therapy for the primary tumor in 57 (73%), including 3 treatment groups. Thirty-two patients had limited resections that preserved the larynx, involving local excision (7 patients), anterior pharyngotomy (7 patients), lateral pharyngotomy (6 patients), median labiomandibular glossotomy (6 patients), or median mandibulotomy with paralingual extension (6 patients). The second group consisted of 21 patients with more extensive tumors who required a laryngectomy and complex reconstruction, often with postoperative radiotherapy. Finally, there were four patients who developed metachronous second primaries in the pharynx subsequent to a laryngectomy. All required flap reconstruction. Of the 21 patients whose primary treatment was radiotherapy, 5 had lesions that were implanted after access was provided by a mandibulotomy. Cumulative 5-year survival was 32% and ranged from 44% in those with favorable lesions to 15% in those with extensive tumors. Our experience highlights the variety of treatment approaches available in patients with pharyngeal carcinomas confined to the posterior wall. Surgery in this setting carries acceptable morbidity and yields survival rates that compare favorably with those achieved by external radiation therapy alone. Results in patients with extensive lesions still leave much to be desired, despite radical surgery and aggressive radiotherapy. Innovative brachytherapy techniques using surgery for access deserve further investigation. 
1	Prognostic factors in stage IB squamous cervical cancer patients with low risk for recurrence. About one-half of cervical cancer patients whose tumors recur after radical surgery have negative lymph nodes and clear resection margins. We evaluated 95 patients with squamous cell tumors who underwent radical hysterectomy and pelvic lymphadenectomy between January 1975 and December 1985 and who were thought to be at low risk for recurrence to see whether other clinical or histopathologic factors were predictive of tumor recurrence. Detailed retrospective record review and complete pathology review were accomplished for each case. The 5-year actuarial survival rate was 89%. Nine patients developed recurrent disease (9.5%), of whom eight died. Several clinical features were evaluated as possible prognostic factors: patient age (P = .26), patient race (P = .60), cervical diameter (P = .24), extent of gross cervical involvement (P = .36), and presence of contact bleeding (P = .82). Histopathologic features were examined: depth of invasion (P = .31), number of mitoses (P = .42), character of the tumor-stromal border (P = .15), histologic differentiation (P = .02), lymph-vascular space invasion (P = .56), and width of tumor (P = .23). Depth of invasion did correlate with increasing tumor width (P less than .001). Once node- and margin-positive patients are excluded, differentiation may be the only feature useful in identifying patients at risk for recurrence. Because almost one-half of our patients had poorly differentiated tumors, sole use of this feature as a criterion for adjuvant therapy would have resulted in overtreatment of low-risk patients. 
1	The recalcitrant perineal wound after rectal extirpation. Applications of muscle flap closure. Perineal wounds developing after abdominoperineal resection result in chronic purulent drainage and intermittent episodes of sepsis and are generally unresponsive to conservative medical and surgical treatment. Thirteen consecutive patients (aged 27 to 74 years; mean, 48 years) who underwent debridement and immediate muscle flap closure of these wounds were analyzed to identify risk factors for delayed healing and to evaluate the effectiveness of muscle flap coverage. Three risk factors were identified: preoperative or postoperative radiation therapy, resection for recurrent carcinoma, and inflammatory bowel disease. A total of 19 muscle flaps (11 gracilis, five gluteal thigh, two gluteus maximus, and one rectus abdominis) were used to close these wounds. During an average 3.5-year follow-up, four (31%) minor complications and one (8%) recurrence were noted to occur. Muscle flaps provide safe, effective, single-stage procedures for the closure of chronic perineal wounds. 
3	Effects of vigabatrin (gamma-vinyl GABA) on neurotransmission-related amino acids and on GABA and benzodiazepine receptor binding in rats. The effect of 12-day intraperitoneal i.p. administration of vigabatrin (GVG, gamma-vinyl GABA) to rats on the neurotransmission-related amino acids in various brain regions (cortex, hippocampus, cerebellum, and spinal cord), cisternal fluid (CSF) and blood was studied. Results showed that GVG administration increased the levels of GABA in cortical and subcortical regions of the brain and CSF without affecting GABA and benzodiazepine receptors in the cortex. In addition, a dose-dependent decrease was noted in the concentration of glutamate in the hippocampus and in the concentrations of aspartate and glutamine in the cortex, hippocampus, and cerebellum. The changes in the levels of amino acids in the brain, except for that of GABA, were not reflected in the CSF, however, and the levels of amino acids in discrete brain regions did not show any correlation with those in the serum or in the CSF. The results suggest that GVG administration might suppress development and spread of seizures not only by elevating the level of the inhibitory amino acid GABA, but also by decreasing the levels of excitatory amino acids in the brain. 
1	Effects of treatment on long-term survivors with malignant astrocytomas. We reviewed the records of 160 consecutive patients with glioblastoma and anaplastic astrocytoma to evaluate the long-term consequences of radiation therapy and chemotherapy. We defined long-term survivors as those patients with glioblastoma or anaplastic astrocytoma who lived at least 100% longer than median survival of historical controls, for example, 2 years for patients with glioblastoma and 4 years for patients with anaplastic astrocytoma. There were 9 (5.6%) long-term survivors. Three (30%) became demented and died without evidence of tumor recurrence. One, after survival of 10 years, died of tumor recurrence. Of the remaining survivors, 2 (22%) have significantly impaired short-term memory function and other neurological deficits such as gait apraxia. Three (30%) can function independently. It is likely but cannot be proved that it is radiotherapy and not chemotherapy that is the causal factor of this dismal therapeutic outcome. Our study suggests restraint in the use of radiotherapy for patients with brain tumors that have more favorable prognoses than glioblastomas and anaplastic astrocytomas, such as low-grade astrocytomas and oligodendrogliomas. 
5	Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning. Biliary tract obstruction or anastomotic leakage are common problems following liver transplantation. In a sequential study, 31 patients with a liver transplant were investigated by 99mTc-IODIDA (IODIDA) scanning and T tube cholangiography (TTC) and the results were compared with clinical outcome. Seven patients had an extrahepatic biliary obstruction and one patient had a biliary leak. In the detection of biliary complications TTC and IODIDA scanning were similar in terms of sensitivity (63 per cent for both) but TTC had a better specificity (79 per cent versus 60 per cent) and accuracy (74 per cent versus 60 per cent) than IODIDA scanning. When liver function was taken into account, the diagnostic efficacy of both tests in patients with bilirubin levels of less than 200 mumol/l was similar. With levels greater than 200 mumol/l there was a greater number of false positive results with IODIDA scanning (12 per cent versus 54 per cent). The only significant biliary leak was clearly detected by TTC but not IODIDA scanning. TTC remains the more effective way of evaluating the biliary tract after transplantation. IODIDA scanning has limited value when bilirubin levels are elevated, but may provide additional information about blood supply, hepatocyte function and intrahepatic cholestasis. 
1	Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity. Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease. 
3	Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance. Evaluation of the sellar area was performed with magnetic resonance imaging in 101 patients (age range 0.8-27 years) with hypopituitarism, isolated diabetes insipidus, hypogonadotrophic hypogonadism, and central precocious puberty. The hypopituitary patients (n = 70) included multiple pituitary deficiency (n = 23), pituitary deficiency with diabetes insipidus (n = 5), and isolated growth hormone deficiency (n = 42). The patients with multiple pituitary deficiency showed pathological morphological findings in all cases, with stalk and posterior lobe always involved. The group with associated diabetes insipidus had abnormal stalk in four of five cases and posterior lobe not visible in all cases. Only five of 42 (12%) patients with isolated growth hormone deficiency had abnormalities of the sellar area. In two out of four patients with isolated diabetes insipidus posterior lobe was not seen. All patients with hypogonadotrophic hypogonadism (three with Kallmann's syndrome, one Prader-Willi syndrome, and two idiopathic hypogonadism) appeared normal. In precocious puberty (n = 21) the three patients with onset of symptoms before age 2 years exhibited a hypothalamic hamartoma, whereas in the others with onset of puberty between age 2 and 7 the magnetic resonance image was normal in 17 of 18 patients. The probability of finding a pathological magnetic resonance image was considerably high in our patients with multiple pituitary deficiency, isolated diabetes insipidus, and precocious puberty with very early onset of symptoms. On the contrary, purely functional abnormality is suggested in most patients with isolated growth hormone deficiency, hypogonadotrophic hypogonadism, and precocious puberty with later onset of symptoms. 
5	Antibodies to nuclear lamin C in chronic hepatitis delta virus infection. Sera of patients with chronic hepatitis delta virus infection stained the nuclear periphery in indirect immunofluorescence. Using proteins of isolated nuclei, isolated nuclear matrices, the nuclear pore complex-lamina fraction and purified lamins A and C as antigen source in immunoblotting experiments, nuclear lamin C was identified as the reactive antigen. Most sera tested (8 of 10) recognized nuclear lamin C exclusively, but not the nuclear lamins A and B. Antibodies reacting with both nuclear lamins A and C, which share extensive sequence homologies, have been reported to occur in autoimmune hepatitis and primary biliary cirrhosis. The present findings suggest that the novel autoantibody associated with chronic hepatitis delta virus infection recognizes an epitope localized in the short carboxyterminal region of nuclear lamin C. 
5	Hyperkalaemia during rapid blood transfusion and hypovolaemic cardiac arrest in children. A morbidity and mortality review documented a high occurrence of hyperkalaemia in cardiac arrests associated with rapid blood transfusion, which resulted in further study. In order to stimulate events during rapid blood transfusion and cardiac arrest, the central circulation was modeled as a linear one compartment, and used to stimulate a child who suffered a hypovolaemic cardiac arrest and was resuscitated with rapid blood transfusion (RBT). The simulation suggested that the combination of RBT and a low cardiac output state could be associated with hyperkalaemia, if the potassium concentration in the plasma fraction of the transfused blood was greater than or equal to 10 mmol.L-1. In an associated clinical study the plasma potassium concentration during cardiac arrest was documented from a retrospective review of 138 cardiac arrests in a paediatric population. Patients were divided into two groups. The RBT-group received a rapid blood transfusion during resuscitation. The non-RBT group did not receive blood during resuscitation. During cardiac arrest the plasma [K] in the non-RBT group was 5.63 +/- 2.39 mmol.L-1 compared with 8.23 +/- 1.99 mmol.L-1 in the RBT-group (P less than 0.05). The hyperkalaemia during cardiac arrest in the RBT-group could be explained as a consequence of RBT to a hypovolaemic child with a low cardiac output. 
4	Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: serial CK-MB sampling in the emergency department [published erratum appears in Ann Emerg Med 1991 Apr;20(4):420] STUDY OBJECTIVES: Patients presenting to the emergency department with chest discomfort are a difficult problem for emergency physicians. Nearly 50% of patients with acute myocardial infarction (AMI) will initially have nondiagnostic ECGs on ED presentation. The purpose of this study was to determine if patients with AMI having nondiagnostic ECGs could be identified using new immunochemical assays for serial CK-MB sampling in the ED. DESIGN: Chest pain patients, more than 30 years old, with pain not caused by trauma or explained by radiographic findings, were eligible for the study. Serial serum samples were drawn on ED presentation (zero hours) and three hours after presentation, then analyzed for CK-MB using four immunochemical methods and electrophoresis. Standard World Health Organization criteria were used to establish the diagnosis of AMI, including new Q-wave formation or elevation of standard in-hospital serum cardiac enzyme markers. SETTING: A tertiary cardiac care community hospital. MEASUREMENTS AND MAIN RESULTS: The serum from 183 patients hospitalized for possible ischemic chest pain was collected and analyzed. Thirty-one of 183 patients (17%) were found to have AMI by standard in-hospital criteria. Sixteen of the 31 patients (52%) with AMI had nondiagnostic ECGs on presentation. Immunochemical determination of serial CK-MB levels provided a sensitive and specific method for detecting AMI in patients within three hours after ED presentation compared with standard electrophoresis. The four immunochemical methods demonstrated a range in sensitivity from 50% to 62.1% on ED presentation versus 92% to 96.7% three hours later. The immunochemical tests demonstrated specificities ranging from 83.0% to 96.4% at three hours, with three of the four tests having specificities of 92% or greater. Electrophoresis had a sensitivity of 34.5% on ED presentation, increasing to 76.9% at three hours, with a specificity of 98.6%. CONCLUSIONS: Immunochemical CK-MB methods allowed rapid, sensitive detection of AMI in the ED. Early detection of AMI offers many potential advantages to the emergency physician. Early detection of AMI, while the patient is in the ED, could direct disposition of this potentially unstable patient to an intensive care setting. Such information may prevent the ED discharge of patients with AMI having nondiagnostic ECGs. The diagnosis of AMI within a six-hour period after symptom onset may allow thrombolytic therapy to be given to patients with AMI not having diagnostic ECGs. This study served as a pilot trial for a multicenter study of the Emergency Medicine Cardiac Research Group, which is currently ongoing. 
1	Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors. Ribonucleic acid was isolated from a wide spectrum of central nervous system tumors to examine the expression of platelet-derived growth factors (PDGF) A and B, tumor growth factors (TGF-beta) 1 and 2, and ros messenger ribonucleic acid. Eight glioblastoma cell lines were examined as well as cell cultures from 22 tumor explants. The explants included 6 glioblastomas, 4 anaplastic astrocytomas, 5 astrocytomas, 3 ependymal tumors, 2 meningiomas, 1 medulloblastoma. and 1 ganglioglioma. For comparison, 2 nontumor glial cell cultures were included. The PDGF B-chain was expressed in 5 of 8 glioblastoma cell lines, 2 of 6 glioblastomas, and in 3 of 4 anaplastic astrocytoma explants. There was no PDGF B expression in 4 astrocytomas, 3 ependymomas of varying malignancy, in the remainder of the tumors, or in the nontumor glial cells. The PDGF A-chain was expressed in all of the tumors, with the exception of the malignant ependymoma and in both nontumor glial cell cultures. TGF-beta 1 was expressed in all of the tumors and in nontumor glial cells. The expression of TGF-beta 2 was expressed in many of the benign and malignant tumors and also in both nontumor glial cell cultures. The ros messenger ribonucleic acid was expressed in 1 of 5 glioblastoma cell lines and in 2 of 6 glioblastoma cell explants, but in none of the other tumors or in the nontumor glial cells. 
4	Splenic septic emboli in endocarditis. The significance of septic emboli to the spleen is inferred by the frequency of septic emboli in general seen in patients with left-sided infective endocarditis who are referred for valve replacement. To determine the proper management of splenic infarcts and abscess due to septic emboli, we retrospectively reviewed the records of 108 patients with left-sided endocarditis who underwent valvular surgery at the University of Illinois Hospital from 1980 through 1988. Intravenous drug abuse was the etiology in 68% (n = 73). The incidence of splenic infarcts and abscess was 19% (n = 20), but an incidental finding of splenic infarcts was found in 38% (n = 11) of 29 asymptomatic patients who had computed tomograms. Streptococci and staphylococci were the causative organisms in 85% (n = 17). Localized findings were absent in 90% of splenic infarcts and abscesses. Abdominal computed tomograms were diagnostic of the sequelae of splenic septic emboli in 100%. No patient had intra-abdominal bleeding complications associated with cardiopulmonary bypass. Splenectomy was performed in 50% (n = 10) of patients 3-24 days (mean, 11.2 days) after valve replacement. Indications for splenectomy included persistent sepsis in 60% (n = 6), large (greater than 2 cm) and peripheral lesions in 30% (n = 3), and splenic rupture in 10% (n = 1). Perioperative mortality of patients who underwent splenectomy was 30% (n = 3). The following conclusions can be drawn: 1) Splenic septic embolus is common in endocarditis. 2) Abdominal computed tomography should be performed for all patients. 
4	Body fluid spaces and blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. Blood pressure (BP) may increase in hemodialysis patients during treatment of anemia with recombinant human erythropoietin (r-HuEPO). Since fluid volume is a determinant of BP in dialysis patients, changes in body fluid spaces during r-HuEPO therapy could affect BP. Thus, 51Cr-labeled red blood cell (RBC) volume, inulin extracellular fluid (ECF) volume, and urea total body water (TBW), as well as cardiac output, plasma renin activity (PRA), and plasma aldosterone concentration were determined postdialysis before and after r-HuEPO therapy in patients in whom changes in BP could be managed by ultrafiltration alone. Eleven patients entered the study: one had a renal transplant and two required addition of antihypertensive drug therapy and were excluded; eight, of whom two required antihypertensive drug therapy following the study, were included in the analyses. Results revealed an increase in predialysis hemoglobin from 67 to 113 g/L (6.7 to 11.3 g/dL) (P = 0.001) during 18 +/- 6 weeks of therapy. Predialysis diastolic BP increased from 80 to 85 mm Hg (P = 0.07), while postdialysis diastolic BP was unchanged at 73 mm Hg. 51Cr-RBC volume increased, from 0.7 to 1.3 L (P = 0.004). ECF tended to decrease, from 13.7 to 10.8 L (P = 0.064), while TBW decreased to a similar extent, but not significantly, 34.3 to 31.2 L (P = 0.16). Postdialysis ECF volume was positively correlated with mean arterial BP at baseline (r = 0.89, P = 0.007) and after therapy (r = 0.74, P = 0.035). However, the regression lines for this relationship were different (P = 0.022) before and after therapy. 
1	Ultrastructural evidence for differentiation in a human glioblastoma cell line treated with inhibitors of eicosanoid metabolism. Human glioblastoma cells incubated in the presence of inhibitors of eicosanoid biosynthesis show decreased cellular proliferation without cytotoxicity. We studied the ultrastructural morphology of a human glioblastoma cell line cultured with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or 5,8,11,14-eicosatetraynoic acid, a cyclooxygenase and lipoxygenase inhibitor. When glioblastoma cells were treated for 3 days with antiproliferative concentrations of either agent, they shared many morphological characteristics, including evidence for increased astrocytic differentiation with only limited signs of toxicity. The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes. The glioblastoma cell shape also became more elongated, losing the usual nuclear lobularity and nuclear inclusions, especially in NDGA-treated cells. Many cytoplasmic organelles packed the cytosol of the inhibited glioma cells, including prominent Golgi apparatus, dilated smooth endoplasmic reticulum evolving into dilated vesicles, cytoplasmic vacuoles, and numerous concentric laminations. There was limited evidence for toxicity, however, as the mitochondria were more pleomorphic with some mitochondrial distention and disruption of the cristae along with an increase in cytoplasmic vacuolization. We conclude that the inhibitors of eicosanoid biosynthesis, NDGA and 5,8,11,14-eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also induce increased astrocytic differentiation. 
5	Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis. Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor. 
1	The role of chemotherapy for node-negative breast cancer. Approximately 25% of women with early stage breast cancer and negative axillary nodes will eventually die of metastatic disease. Some studies have shown a recurrence rate of 40% or more at 10 years in this relatively good prognostic group. The incidence of breast cancer continues to increase approximately 1% per year with a great increase in the frequency of early stage disease (particularly in situ carcinoma). The increased use of mammography and physical examination with appropriate follow-up will increase the frequency of diagnosis of node-negative patients compared with those with more advanced stages. Women with positive axillary nodes who are premenopausal benefit from adjuvant chemotherapy, whereas those who are postmenopausal have shown a clear reduction in mortality when treated with tamoxifen. It is even more reasonable to speculate that women with node-negative disease could have an even greater benefit from adjuvant therapy because they have a lower tumor burden at the time of diagnosis. Compared with earlier clinical adjuvant trials, more recent studies (1981-89) have shown a disease-free survival advantage for node-negative breast cancer patients treated with adjuvant chemotherapy. Hopefully, the differences noticed in disease-free survival will show a similar survival advantage with further observations. The results of these clinical trials suggest that adjuvant chemotherapy may be of benefit to patients with node-negative disease but do not support the contention that all node-negative patients with breast cancer should receive adjuvant chemotherapy. Some prognostic subgroups (tumor size greater than 2 cm) have shown an overall 10-year survival rate of 92% for women who have not received adjuvant therapy. The benefits versus toxicities of adjuvant therapy should be carefully evaluated before the initiation of adjuvant therapy. 
5	Cauda equina anatomy. I: Intrathecal nerve root organization. The three-dimensional organization of the human cauda equina has not been described previously. This is partly due to the difficulties of dissecting individual, unfixed nerve roots. By the use of a newly developed in situ fixation and embedding technique on 15 fresh human cadavers, the cross-sectional anatomy of the cauda equina was defined from L2-L3 to L5-S1. A highly consistent cross-sectional pattern was observed in all specimens. The lower sacral (S2-S5) and coccygeal roots were located in the dorsal aspect of the thecal sac, whereas the lumbar and first sacral roots exhibited an oblique, layered pattern as they ascended. The motor bundle was situated anteromedial to its respective sensory bundle within each layer, Invaginations of arachnoid held the nerve roots in a fixed relationship to one another. This previously undescribed three-dimensional anatomy within the thecal sac may aid in the understanding and treatment of trauma, neurocompressive syndromes, and tumors of the cauda equina. 
5	Comparison of ventricular arrhythmia induction with use of an indwelling electrode catheter and a newly inserted catheter. Two methods of serial electrophysiologic testing are in widespread use. Most commonly, the electrode catheter is removed after each study and a new catheter reinserted through the femoral vein for every subsequent test. An alternative method employs an electrode catheter that remains in place during several days of serial testing. Little is known about differences between these two methods with respect to the likelihood of induction of arrhythmia or the frequency of complications. To determine whether inducibility of sustained arrhythmia is altered or if the frequency of complications is unacceptably high with use of an indwelling catheter, a prospective randomized study was conducted in 78 patients. Each patient underwent baseline testing, several days of electropharmacologic testing with an indwelling catheter, a 24 h drug elimination period and placement of a new electrode catheter. Ventricular stimulation studies were then performed in each patient with both the indwelling and new electrode catheters. No differences were found between the indwelling and new catheter tests with respect to induction of arrhythmia, number of extrastimuli required to induce arrhythmia, rate of arrhythmia or requirement for cardioversion. Ventricular pacing thresholds were higher and effective refractory periods were slightly longer when measured with the indwelling catheter. Complications related to the 156 catheter insertions included two that may have been related to the indwelling catheter (one episode of staphylococcal sepsis and one presumed pulmonary embolism) and four that were related to invasive procedures (pneumothorax in all). There were no long-term adverse sequelae of these complications. 
4	The natural history of left ventricular spontaneous contrast. Spontaneous contrast in the left ventricle is an unusual entity. We retrospectively studied 16 patients who were found to have spontaneous contrast present on two-dimensional echocardiograms, specifically noting their clinical characteristics, the reproducibility of this phenomenon, the presence of thrombi and embolic events, and prognostic implications. Diagnoses included ischemic heart disease in nine patients, dilated cardiomyopathy in six patients, and hypertensive cardiomyopathy in one patient. The mean ejection fraction was 17.6%. There were six thromboembolic events in four patients. The spontaneous contrast was reproducible for periods of time up to 39 months. Patients who had improvement in their left ventricular dysfunction or who underwent aneurysmectomy had disappearance of the spontaneous contrast. Those patients who had spontaneous contrast reproduced on subsequent echocardiograms did not seem to have a worse prognosis than patients with similarly depressed ventricular function, but a larger study is necessary to verify this. 
3	Catecholaminergic systems in the medulla oblongata in parkinsonian syndromes: a quantitative immunohistochemical study in Parkinson's disease, progressive supranuclear palsy, and striatonigral degeneration. We investigated tyrosine-hydroxylase (TH)-immunoreactive neurons in the medulla oblongata corresponding to the A1 and A2 cell groups in autopsy tissue of patients with Parkinson's disease (PD) (n = 3), progressive supranuclear palsy (PSP) (n = 3), striatonigral degeneration (SND) (n = 2), and in controls (n = 4). The estimated total number of TH-positive neurons in the A1 and the A2 regions was normal in PD and PSP patients. The sparing of medullary catecholaminergic cells in PD and PSP may be related to their minor degree of melanization and the possibility that intermediate compounds associated with the oxidative catabolism of norepinephrine and epinephrine may be less cytotoxic than those generated by degradation of dopamine. Patients with SND showed a marked loss of TH-immunoreactive cells in the A1 and the A2 groups, which may contribute to the impairment of vasomotor control characteristic of the disease. 
5	A clinically applicable method for long-term salvage of postischemic skeletal muscle. The clinical significance and applicability of interventions aimed at reducing reperfusion injury in postischemic skeletal muscle remain unproven, since long-term muscle salvage has not been demonstrated by most treatment protocols that attenuate early reperfusion injury. We have shown that reperfusion of ischemic skeletal muscle results in an early and prolonged sequestration of white blood cells and activation of the alternative complement cascade. The purpose of this study was to determine if 40 minutes of reperfusion with blood depleted of white blood cells and complement proteins, followed by 2 days of normal perfusion, would reduce muscle necrosis after 5 hours of ischemia. The isolated paired canine gracilis muscle model was used. The treatment muscle was initially reperfused with arterial blood that had been spun, washed, passed through a leukocyte removal filter, and resuspended in hydroxyethyl starch (greater than 99.9% removal of white blood cells and the complement proteins factor B and C4). The contralateral control muscle was subjected to unaltered reperfusion. Blood flow (ml/min/100 gm) was measured by timed collection of gracilis venous blood. Myeloperoxidase activity (absorbance at 655 nm/min/mg tissue protein) in muscle biopsies was used to monitor white blood cell sequestration. After 48 hours of reperfusion in vivo, necrosis was quantified by nitroblue tetrazolium staining. Initial reperfusion with white blood cell and complement depleted blood significantly reduced muscle necrosis (53% +/- 3% vs 29% +/- 8%, p less than 0.0025, paired t test). Early blood flow was improved, (p = 0.0025, repeated measure-ANOVA), but subsequent white blood cell sequestration was not altered (p = 0.33, repeated measure-ANOVA). This suggests that a significant amount of white blood cell mediated injury occurs during the first 40 minutes of reperfusion. Preventing early complement activation and white blood cell mediated reperfusion injury is an intervention that is feasible during surgery and may result in clinically significant salvage of postischemic skeletal muscle. 
1	Non-Hodgkins lymphoma of the head and neck: experience in the Grampian area. The records of 44 cases of non-Hodgkins lymphoma (NHL) presenting to the ear, nose and throat department in the Grampian area from 1980-1988 were examined in relation to site of occurrence, histology, age at presentation, clinical stage, treatment and survival. The median age was 67 years and there was a preponderance of high grade histology, especially in disease affecting the tonsil. Most deaths occurred in the first year; patients with high grade disease and those in stages three and four had a significantly poorer survival during the first year. The site of disease had no influence on survival. 
4	Role of angiotensin-converting enzyme inhibitors in congestive heart failure. Conventional therapy for congestive heart failure (CHF) includes sodium-restricted diet, diuretics, digitalis, vasodilators, and short-term intravenous administration of beta-adrenergic agonists during episodes of decompensation. A specific class of vasodilators, the angiotensin-converting enzyme inhibitors, has recently gained predominance in the treatment of congestive heart failure. The primary mechanism of action is to reduce production of angiotensin II by competitive inhibition of the enzyme that converts angiotensin I into angiotensin II. Reduced levels of angiotensin II, in turn, promote vasodilation and lower aldosterone production. The benefits of angiotensin-converting enzyme inhibitor therapy in chronic congestive heart failure have been demonstrated by improvement in left ventricular performance, exercise capacity, functional status (using New York Heart Association classification), and survival. 
2	Extracorporeal shock wave lithotripsy of gallstones: results and 6-month follow-up in 141 patients. A study of biliary shock wave lithotripsy of gallstones sponsored by Dornier Medical Systems, Munich, began in the United States in May 1988 to evaluate the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) and the need for adjunctive therapy with ursodeoxycholic acid (UDCA). One hundred forty-one symptomatic patients with one to three gallstones 5-30 mm in diameter were randomized to treatment. One week before ESWL, patients were given either UDCA or placebo. This treatment was continued for 6 months. All patients underwent follow-up at predetermined intervals. According to the protocol, re-treatment for fragments larger than 5 mm in diameter could be performed only at 6 weeks; 26 (18%) of the 141 patients were retreated. At 6 months, the stone-free rates for single stones were as follows: patients with noncalcified stones receiving UDCA, 29%; patients with noncalcified stones receiving placebo, 24%; and patients with partially calcified stones receiving either UDCA or placebo, 6%. No significant difference was noted between the UDCA and placebo groups. At 6 months, the stone-free rates in patients with single, noncalcified stones 20 mm or less in diameter were 40% (UDCA) and 32% (placebo), which is superior to rates for those with solitary, noncalcified gallstones 21-30 mm in diameter and those with two or three stones. 
5	The perception of life events and daily stress in nonulcer dyspepsia. Previous studies on the association of nonulcer dyspepsia with major life events were performed without emphasis on the perception of these events, and have yielded conflicting results. The present study examined the perception of life events and, in addition, the role of daily "hassles" (stressful events) in patients with nonulcer dyspepsia. Thirty-three dyspeptic patients as defined by normal endoscopy and ultrasonogram and 33 controls of comparable sex, age, and social class were recruited for study. Both groups were asked to select from 56 major life events those they had experienced and to give a rating on how they perceived them. They were further asked to select similarly from 117 items of daily stress and to rate the severity of each item. The results demonstrated that the number of positive and negative events and the positive score were similar in both dyspeptic patients and controls, but dyspeptic patients had a higher perceived magnitude of negative events and a higher score of total life change as given by the summation of magnitude of positive and negative events (both p less than 0.05). The "hassles" scores were not significantly different between dyspeptic patients and controls. Analysis of individual life events revealed that dyspeptic patients had significantly (p less than 0.05) higher scores than controls in items of minor law violations, major change in closeness of family members, and major personal illness or injury. We conclude that patients with nonulcer dyspepsia have higher negative perception of major life events, which indicates that psychological factors may play a role in the pathogenesis of nonulcer dyspepsia. 
5	Nodular regenerative hyperplasia: a cause of ascites and hepatomegaly after chemotherapy for leukemia. Tender hepatomegaly and ascites occurred in a young woman receiving cytosine arabinoside and daunorubicin for acute myelogenous leukemia. Whereas veno-occlusive disease was suspected clinically, liver biopsy showed nodular regenerative hyperplasia with no evidence of hepatic vein abnormalities. It is postulated that nodular regenerative hyperplasia can be initiated by hepatotoxicity of chemotherapy agents used to treat leukemia and/or that these agents exacerbate clinical manifestations of this histological abnormality. Nodular regenerative hyperplasia should be added to the list of liver problems occurring in patients with leukemia. 
5	Risks of intestinal anastomoses in Crohn's disease. Six hundred fifty-eight intestinal anastomoses in 429 operations for Crohn's disease were studied prospectively during an 8-year period to detect variables connected with perioperative morbidity. Postoperative complications occurred in 9.7% of the patients, 4% had to be reoperated on, and the overall mortality rate was 0.5%. In multivariate analysis by stepwise logistic regression, the only variable significantly (p = 0.03) associated with overall rate of complications was long-term corticosteroid therapy. Serious complications were more common in cases of intra-abdominal abscesses (p = 0.01) and preoperative steroid medication (p = 0.03). The combination of both of these risk factors increased the rate of reoperations from 0.6% (no steroids, no abscess) to 16% (steroids and abscess). No significant association with postoperative complications could be found for age, sex, duration of disease, previous operations, nutritional status, emergency surgery, extent of disease, type, number, and localization of anastomoses, presence of proximal ileo-/colostomy, or histologically inflamed margins of resection. 
5	Emergency surgical treatment for nonvariceal bleeding of the upper part of the gastrointestinal tract. Endoscopic and biochemical data were collected prospectively from 1,530 patients admitted with nonvariceal bleeding of the upper part of the gastrointestinal tract between September 1985 and June 1989. Therapeutic endoscopy was done for 93 patients who underwent emergency surgical treatment for bleeding, subsequently required in 29 patients with seven postoperative fatalities. In contrast, 31 (15.7 per cent) of 198 patients (mortality rate of 9.6 per cent at 30 days) died in the hospital who had undergone emergency operation in whom therapeutic endoscopy had not been performed; data for this latter group is now presented. At admission, a greater likelihood of emergency operation was associated with a systolic blood pressure of 100 millimeters of mercury and endoscopic stigmatas of recent hemorrhage (ESRH) (p less than 0.001). Rebleeding rates for the presence of fresh blood, active spurting and oozing hemorrhage or visible vessel in an ulcer base were 26.5, 28.9 and 35.9 per cent, respectively. Endoscopic stigmatas were thus associated with an increased risk of bleeding (p less than 0.0001) and rebleeding led to a sixfold increase in the mortality rate. Congestive cardiac failure, chronic obstructive airway disease, chronic renal failure and a history of previous malignant disease were each associated with postoperative mortality rates of more than 50 per cent. An increased risk of mortality after emergency operation was related to age (p less than 0.0001), preoperative (p less than 0.002) and total (p less than 0.0001) blood transfusion requirement. Immediate operation after resuscitation and endoscopy was required in 87 patients; 11 deaths (hospital mortality rate of 12.7 per cent and 9.2 per cent at 30 days) occurred in this group compared with 20 fatalities (18.0 per cent) documented in 111 patients (9.9 per cent at 30 days) who underwent surgical treatment for rebleeding. We conclude that age, concomitant medical illness and preoperative and total transfusion requirements are each related to outcome after emergency operations. Such urgent intervention is best avoided if at all possible in patients with severe concomitant medical illness. 
5	The Hastings bipolar hemiarthroplasty for subcapital fractures of the femoral neck. A 10-year prospective study. In a 10-year prospective study, 561 displaced subcapital fractures of the femoral neck in 546 patients were treated with the Hastings bipolar hemiarthroplasty. Within six months of their operations, 148 patients had died. In 322 hips followed up, 243 with adequate serial radiographs separated by more than one year, only 14 (5.6%) showed acetabular erosion. A group of 91 had been reviewed for between three and nine years (mean, 4 years 10 months) and of these, 95% had no pain or slight pain only. Comparison with an earlier series of conventional hemiarthroplasties reported from this institution showed that the clinical results were similar, but that the erosion rate had been halved. 
4	Comparison of coronary angiography and early oral dipyridamole thallium-201 scintigraphy in patients receiving thrombolytic therapy for acute myocardial infarction. We evaluated 50 consecutive patients who received thrombolytic therapy for acute myocardial infarction using thallium-201 single photon emission computed tomography in combination with oral dipyridamole (300 mg) to assess the frequency of residual myocardial ischemia. Thallium studies were performed early after myocardial infarction at a mean of 4.6 days (range 3 to 11) in 50 patients. The time from the onset of chest pain to the administration of thrombolytic therapy was 2.6 hours (range 0.5 to 5.5). Q wave myocardial infarction was evident in 46 patients; four patients had a non-Q wave infarction (anterior infarction in 31 patients and inferior infarction in 19 patients). The serum mean peak creatinine kinase was 1503 IU/L (range 127 to 6500). Coronary angiography was performed in all patients at a mean of 3.1 days (range 2 to 10) and revealed the infarct-related vessel to be patent in 36 patients (72%). The ejection fraction was 48% (range 26% to 67%). After dipyridamole administration, 13 patients (26%) developed angina that was easily reversed with the administration of intravenous aminophylline. Systolic blood pressure decreased from 122 to 115 mm Hg (p less than 0.05) and the heart rate increased from 76 to 85 beats/min (p less than 0.05). None of the patients had significant hypotension, arrhythmias, or evidence of infarct extension. Perfusion abnormalities were present on the initial thallium images in 48 patients. Redistribution suggestive of ischemia was present in 36 patients (72%). Ischemia confined to the vascular distribution of the infarct vessel was evident in 22 patients. Seven patients had ischemia in the infarct zone as well as in a remote myocardial segment. Thus 29 patients (58%) had ischemia in the distribution of the infarct vessel. Ischemia in the infarct zone was evident in 19 of 36 patients (53%) with open infarct vessels and in 10 of 14 patients (71%) with occluded infarct vessels. In conclusion, thallium-201 single photon emission computed tomography using oral dipyridamole was safely performed in patients with recent myocardial infarctions who receive thrombolytic therapy. 
5	Myotonic dystrophy: quantification of muscle weakness and myotonia and the effect of amitriptyline and exercise. The purpose of this study was to quantify the degree of muscle weakness and myotonia in 12 patients with myotonic dystrophy (MD), and to quantitatively determine the effects of a four- to six-month therapeutic trial of amitriptyline. Patients had exercised with weights for one or more years. Some had shown initial improvement in muscle strength, but had reached a plateau; others had not improved when the study began. Muscle weakness was quantified by comparing the five-second maximum voluntary contraction (MVC) in newtons (N) per kg (body weight) of 12 patients and 20 healthy subjects. Knee extensor, elbow flexor, and first dorsal interosseous (FDI) muscles were compared. Myotonia was quantified by measuring relaxation times (RTs) at the end of the five-second MVC produced by FDI, as the time taken for the MVC to decrease by 50% and 75% (referred to as 1/2 and 3/4RT). The results were as follows: (1) the mean muscle strength of each of the three muscles of the patients was significantly (p less than .001) reduced compared with healthy subjects; and (2) 1/2 and 3/4RT means of the patients (vs healthy subjects) were significantly prolonged (p less than .01). Eight of the patients participated in a therapeutic trial of amitriptyline. Therapeutic effects were quantified by measuring muscle strength, 1/2 and 3/4RT, and percent change in evoked muscle action potential (MAP) from the FDI muscle after a ten-second MVC, to determine change in excitability. Mean muscle strength of FDI improved from .27 to .33N/kg, (p less than .05). 
1	Microstaging of squamous cell carcinomas. The clinical classification of squamous cell carcinoma, which was established primarily by the International Union Against Cancer (UICC), does not permit optimal estimation of expected metastasis. The authors' results indicate that metastasis can be more accurately estimated on the basis of invasion depth, histopathologic grading, and especially tumor thickness. One essential advantage of these criteria is that they can be established by a histopathologist. It is interesting to note that in the authors' collective no carcinoma less than 2 mm thick metastasized, that is, a relatively high percentage of carcinomas (48%) can be graded as no-risk carcinomas. The risk of metastasis for undifferentiated carcinomas greater than 6 mm thick that have infiltrated the musculature, the perichondrium, or the periosteum, however, is quite high. Tumors between 2 and 6 mm thick with moderate differentiation and a depth of invasion that does not extend beyond the subcutis can be classified as low-risk carcinomas. 
5	Giant hemangioma of the liver with pain, fever, and abnormal liver tests. Report of two cases. In conclusion, we report the cases of two patients with large hemangiomas of the liver, abdominal pain, increased ESR and fibrinogen, increased serum alkaline phosphatase and gamma-glutamyltransferase activity, and normal white blood cell counts. Clinical and biochemical abnormalities disappeared after surgical resection. Increased ESR and fibrinogen are probably related to thrombosis within the tumor. This mode of presentation may suggest a diagnosis of hepatocellular carcinoma. 
3	The treatment of Gilles de la Tourette syndrome by limbic leucotomy. A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy. 
5	Area of lateral ventricles measured on cranial ultrasonography in preterm infants: association with outcome. The association between measurements of lateral ventricle area (determined by serial ultrasound scans) and outcome was studied in 70 preterm neonates of 33 weeks' gestation or less. The study group was subdivided into four groups according to cranial ultrasonographic findings at 2 weeks postnatal age: group A (n = 15) had isolated periventricular/intraventricular haemorrhage; group B (n = 20) had periventricular/intraventricular haemorrhage and dilated ventricles; group C (n = 24) had periventricular/intraventricular haemorrhage and periventricular leukomalacia with or without dilated ventricles; and group D (n = 11) had isolated periventricular leukomalacia. Eighty seven preterm infants with no evidence of intracranial disease and good neurodevelopmental outcomes at 2 years formed the control group. A poor outcome was observed in infants in group B, C, and D, particularly in those who had persistent dilated ventricles at 6 weeks postnatal age and extensive periventricular leukomalacia. There was no difference in outcome between group A and controls. During the first six weeks of life ventricular area growth velocities were significantly higher in groups B, C, D, compared with normal controls and group A. We suggest that persistent ventricular dilatation at this early stage carries a bad prognosis, which is the result of atrophy of the brain. 
4	Transtelephonic defibrillation. STUDY OBJECTIVES: This study was undertaken to assess the safety and reliability of a device for transtelephonic defibrillation. DESIGN: The transtelephonic system consists of a patient unit and a base station. The patient unit contains a monitor-defibrillator, electrode pads, microphone, microprocessor, and DC defibrillator. The base station comprises a control panel, computer, and ECG display. SETTING: Fifteen patients who were treated in our emergency department for cardiac arrest were placed on patient units that activated our base station in a remote location within the ED. TYPE OF PARTICIPANTS: Thirteen patients were treated for ventricular fibrillation, and two patients were treated for ventricular tachycardia. INTERVENTIONS: Thirty-one shocks were delivered transtelephonically. MEASUREMENTS AND MAIN RESULTS: In all cases, voice and ECG transmission were established without difficulty. CONCLUSIONS: We conclude that this system represents a safe and reliable method for the treatment of ventricular fibrillation, and we advocate additional use to study the prehospital applications of transtelephonic defibrillation. 
5	Experience with in situ saphenous vein bypasses during 1981 to 1989: determinant factors of long-term patency. From 1981 to 1989, 361 consecutive in situ saphenous vein bypasses were performed. Indications for revascularization were critical limb ischemia (n = 335, 93%), popliteal aneurysm (n = 15, 4%), and claudication (n = 11, 3%). Outflow tract was the popliteal artery in 116 (32%) and tibial artery in 245 (68%) of bypasses. At 6 years primary patency was 63% and secondary patency was 81%. During the performance of the in situ bypass procedure, 86 (24%) venous conduits were modified because of a technical failure (n = 49, 13%) or an inadequate vein segment (n = 37, 10%). Secondary patency at 4 years for bypasses requiring modification was 72% compared to 84% for bypasses not modified (p less than 0.05). Atherosclerotic disease of the inflow artery necessitating endarterectomy, patch angioplasty, or replacement lowered primary patency at 3 years (69%) compared to the inflow artery not requiring reconstruction (46%, p less than 0.02). In the follow-up period, 95 (26%) bypasses were revised because of thrombosis or hemodynamic failure. Bypasses requiring revision had a 4-year secondary patency of 68% compared to 88% for bypasses not revised (p less than 0.02). The first 179 cases (1981 to 1985) were compared to the subsequent 182 cases (1986 to 1989). The secondary patency at 3 years for the latter half (92%) compared to the first half (80%) of the experience was significantly improved (p less than 0.02). The secondary patency for bypasses not requiring revision was significantly improved (p less than 0.02) for the latter half (n = 142, 97%) compared to the first half (n = 124, 83%) of the series. Long-term patency with the in situ saphenous vein bypass is dependent on surgical experience, quality of the venous conduit, and atherosclerotic disease of the inflow artery that necessitates reconstruction. Meticulous surgical technique and compulsive bypass surveillance results in superior long-term patency. 
5	Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities. To determine whether untreated mild coagulopathy in patients with no evidence of clinical bleeding is associated with an increased risk of hemorrhage after paracentesis or thoracentesis, retrospective examination was conducted of 608 consecutive procedures for which prothrombin time (PT), partial thromboplastin time (PTT), platelet (Plt) counts, and preprocedure and postprocedure hemoglobin concentrations were available. There was no increased bleeding in patients with mild to moderate coagulopathy (defined as PT or PTT up to twice the midpoint normal range or pit count of 50 to 99 x 10(3) per microL [50-99 x 10(9)/L]). However, patients with markedly elevated serum creatinine levels (6.0 to 14.0 mg/dL [530-1240 mumol/L]) had a significantly greater average hemoglobin loss (-0.82 +/- 1.3 g/dL [-8 +/- 13 g/L], n = 11) than patients with normal serum creatinine levels (-0.12 +/- 0.88 g/dL [-1 +/- 9 g/L], n = 450) (p = 0.011). Overall, the frequency of bleeding complications requiring red cell transfusions was very low: 0.2 percent of events. The most common diagnosis for patients who had paracentesis was alcoholic liver disease (72%); for those having thoracentesis, it was infection (37%). It can be concluded that, for these patients, prophylactic plasma or platelet transfusions are not necessary. Patients with markedly elevated serum creatinine deserve close postprocedure observation. 
5	Benign missense variations in the cystic fibrosis gene. The common mutation causing cystic fibrosis is a deletion of phenylalanine 508 (delta F508), which occurs in a putative nucleotide-binding fold of the gene product. We report two additional mutations, substitution of cysteine for phenylalanine 508 (F508C) and substitution of valine for isoleucine 506 (I506V). Three compound heterozygous persons, two delta F508/F508C and one delta F508/I506V, had normal clinical and epithelial physiological studies indicating that the F508C and I506V mutations are benign. This opportunity to study the in vivo function of these mutations suggests that amino acid substitutions are more benign than changes in the length of this portion of the putative nucleotide-binding fold. These mutations must be taken into account when performing molecular diagnosis and carrier detection for cystic fibrosis. 
5	Hyperfunctioning metastatic follicular thyroid carcinoma in Pendred's syndrome. A 66-year-old woman with Pendred's syndrome underwent a partial thyroidectomy when she was 17 years old. At the age of 52 years, she had a second thyroid operation because of hyperthyroidism due to a toxic multinodular goiter with a mediastinal extension consisting of several separate nodules. Five years later a hyperfunctioning metastatic follicular carcinoma was diagnosed histologically. After treatment with radioactive iodine, the patient was well. To the authors' knowledge, this is the first description of a metastatic follicular thyroid carcinoma in Pendred's syndrome and the first report of hyperthyroidism occurring after malignant degeneration of a dyshormonogenetic goiter. 
2	Reversal of chronic hepatic encephalopathy by colonic exclusion: poor correlation with blood GABA levels. Previous studies have suggested that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is a key factor in the syndrome of portasystemic encephalopathy. We report the case of a patient with medically intractable portasytemic encephalopathy after portacaval shunt who had marked clinical improvement after creation of an end ileostomy. Plasma GABA and serum ammonia levels were measured before and after ileostomy. Although the clinical syndrome and the EEG improved markedly after the ileostomy, the plasma GABA levels remained markedly elevated. Preoperative and postoperative GABA levels were 865 and 633 pmol/ml, respectively (nl = 100-180 pmol/ml). Our findings confirm previous reports of the efficacy of colonic exclusion in patients with intractable portasystemic encephalopathy. However, our results conflict with the hypothesis that GABA itself is the key mediator of the syndrome. 
1	DNA sequences 3' of the Ig H chain cluster rearrange in mouse B cell lines. A mouse myeloma cell line MPC11 (IgG2b, kappa) and variants derived from it have been used to study DNA rearrangements that occur at the Ig H chain locus. One variant, F5.5, has acquired both VH gene and C epsilon gene rearrangements. Through genomic Southern blot analysis initially directed to mapping the C epsilon gene rearrangement, we observed that the VH region rearrangement was linked, through an inversion event, to sequences that originate 3' of the CH cluster, i.e., 3' of the C alpha gene. Subsequent studies have shown that DNA rearrangements within the region 3' of the C alpha gene are detected in several other mouse myeloma and hybridoma cell lines and are not associated with the expression of specific isotypes. 
3	Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy. We report the cases of four patients who were taking the anticonvulsant drugs phenytoin or carbamazepine and in whom skin lesions developed that showed histologic features suggestive of mycosis fungoides. Two patients had a solitary lesion on the trunk, whereas the other two patients had multiple plaques. In all four patients systemic signs were absent. 
5	MYC rearrangement and translocations involving band 8q24 in diffuse large cell lymphomas. The configuration of the MYC gene in diffuse large cell lymphomas (DLCL) with translocations involving band 8q24 [t(8q24)] has not been systematically studied. We collected cytogenetic and clinical data on 171 consecutive cases of DLCL, including cleaved, noncleaved, and immunoblastic types, of which 96 had DNA available and 124 had abnormal karyotypes. The cases with DNA available were evaluated for MYC rearrangement (MYC-R) by Southern hybridization of EcoRI-digested tumor DNA using an exon-1 probe, a combination of probe and enzyme known to detect over 85% of breaks in sporadic Burkitt's lymphoma. In cases studied at diagnosis, MYC-R, t(8;14)(q24;q32), or other t(8q24) were not prognostically significant. Among the 124 cases with karyotypic abnormalities, seropositivity for human immunodeficiency virus was significantly more common in cases with a t(8q24) (72%) than in cases without it (9%) (P less than .05). Of the four cases with an MYC -R, two had a t(8;14), one had a t(7;8;14)(p15;q24;q32), and one had a t(8;?)(q24;?) and a del(8)(q24). In the three previous cases with translocations involving 8q24 and 14q32, comigration of the rearranged MYC band with either the J region or the switch-mu region of the Ig heavy chain gene could not be demonstrated, leaving the 14q32 breakpoint undefined at the molecular level. Among the remaining 72 cases where both an abnormal karyotype and molecular data were available, 11 had a t(8q24), either t(8;14) or t(8;22)(q24;q11), in the absence of an MYC-R. In these cases, the 8q24 break was presumably located outside of the EcoRI MYC fragment. All 15 cases with a t(8q24) were also screened for point mutations in the PvuII site in the first exon of MYC; two cases that were not MYC-R showed loss of this restriction site. These results indicate that in most DLCL with t(8;14) or other t(8q24), the 8q24 breakpoint lies away from the MYC gene; in a minority of these cases, point mutations in regulatory noncoding regions were detected. 
5	Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts. Uric acid stone formation ordinarily is prevented by increases in the urinary pH after meals. This postprandial alkaline tide is lost in patients who make such calculi. Single dose, alternate day administration of an alkaline potassium salt will increase urinary pH and simulate this normal physiological mechanism. An important part of the regimen is patient self-monitoring to verify that the urinary pH increases to greater than 6.8, 1 1/2 to 2 hours after the medication is taken. In contrast to multiple dose daily regimens, this mode of base administration is tolerated better and easier to follow. In 17 patients, 7 with the recurrent gravel/colic syndrome and 10 with prior stones, this regimen abolished calculus formation during an average followup of 2 1/2 years. However, further studies are needed before this regimen can be recommended as standard therapy for uric acid stone prophylaxis. 
5	Utility of upright tilt-table testing in the evaluation and management of syncope of unknown origin PURPOSE: Vasovagally mediated hypotension and bradycardia are believed to be common, but difficult to diagnose, causes of syncope. Upright tilt-table testing has been proposed as a possible way to test for vasovagal episodes. This study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin. PATIENTS AND METHODS: Twenty-five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/minute given intravenously), in an attempt to provoke bradycardia, hypotension, or both. Of the 25 patients, there were 14 males and 11 females, with a mean age of 50 +/- 16 years. Six control patients with no history of syncope were also studied. All tilt-positive patients received therapy with either beta-blockers, disopyramide, transdermal scopolamine, or hydroflurocortisone, the efficacy of which was evaluated by another tilt-table test. RESULTS: Syncope occurred in six patients (24%) during the baseline tilt and in nine patients (36%) during isoproterenol infusion (total positives, 60%). None of the controls had syncope during the test. All patients who had positive test results eventually became tilt-table-negative by therapy, and over a mean follow-up period of 16 +/- 2 months no further episodes have occurred. CONCLUSION: From this study we conclude that upright tilt-table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy. 
3	Oxidation reactions in Parkinson's disease. Free radicals generated from oxidation reactions may contribute to the pathogenesis of Parkinson's disease (PD). Free radicals are capable of reacting almost instantaneously with membrane lipids and causing lipid peroxidation, membrane injury, and cell death. Dopamine is metabolized by oxidation reactions capable of generating free radicals. Recent evidence indicates that the substantia nigra of patients with PD contains increased iron, which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals. Further, the end products of lipid peroxidation are increased in the substantia nigra of patients with PD, supporting the notions that free radicals are being generated and may contribute to dopamine neuronal death. This hypothesis suggests that antioxidant therapies may slow the rate of progression of PD and raises concern that metabolites of levodopa therapy may accelerate the rate of neuronal degeneration. 
1	Cholecystectomy and right colon cancer in Puerto Rico. A case-control study was undertaken to evaluate the possible relationship between cholecystectomy and right colon cancer. Two hundred patients with adenocarcinoma of the cecum or ascending colon (diagnosed between 1984 and 1989) were compared with 200 matched neighborhood controls. Cholecystectomy history was obtained through interviews using structured questionnaires and subsequently validated from hospital records. A statistically significant association (odds ratio = 2.14) was found between right colon cancer and a history of prior cholecystectomy. The altered bile metabolism which occurs after removal of the gallbladder may have a carcinogenic effect on the right colon. Dietary habits of the colon cancer patients in our study were consistent with prior reports in the literature, showing that this group has a lower intake of vegetables and cereal fiber than the control population. 
4	A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats. Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003). 
5	Esophageal adenocarcinoma in a patient with surgically treated achalasia. Although squamous cell carcinoma of the esophagus occurs with increased incidence in primary achalasia, esophageal adenocarcinoma has been considered rare in this condition. We report a patient with long-standing achalasia in whom adenocarcinoma of the esophagus occurred many years after Heller esophagomyotomy, presumably related to Barrett's esophagus complicating gastro-esophageal reflux disease. 
5	Childhood traumas: an outline and overview Childhood psychic trauma appears to be a crucial etiological factor in the development of a number of serious disorders both in childhood and in adulthood. Like childhood rheumatic fever, psychic trauma sets a number of different problems into motion, any of which may lead to a definable mental condition. The author suggests four characteristics related to childhood trauma that appear to last for long periods of life, no matter what diagnosis the patient eventually receives. These are visualized or otherwise repeatedly perceived memories of the traumatic event, repetitive behaviors, trauma-specific fears, and changed attitudes about people, life, and the future. She divides childhood trauma into two basic types and defines the findings that can be used to characterize each of these types. Type I trauma includes full, detailed memories, "omens," and misperceptions. Type II trauma includes denial and numbing, self-hypnosis and dissociation, and rage. Crossover conditions often occur after sudden, shocking deaths or accidents that leave children handicapped. In these instances, characteristics of both type I and type II childhood traumas exist side by side. There may be considerable sadness. Each finding of childhood trauma discussed by the author is illustrated with one or two case examples. 
1	Vascularized full-thickness parietal bone grafts in maxillofacial reconstruction: the role of the galea and superficial temporal vessels. Reconstruction of bony structures of the face is always a problem as big as the defect and the function that must be replaced. Everything from simple grafts to sophisticated distant bone flaps has been used. Based on the studies of Cutting et al., Psillakis et al., and Casanova et al., we have developed the full-thickness galeoparietal bone flap, initially for mandibular reconstruction, but of great use for all maxillofacial reconstructions. From July of 1987 to December of 1988, 14 patients have been operated on. The experience with this flap is shown in four patients as follows: primary reconstruction of a mandible as a result of ameloblastoma, secondary reconstruction of a mandible with associated old fractures and malalignment of segments, bilateral malar reconstruction in a patient with Treacher Collins syndrome, and severe sequelae of an already treated Romberg case. Small variations could be made to best accommodate the technique used to the defect we were treating. Some technical details, the experience, the results, and possible sequelae or complications are also discussed. 
1	Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma. A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy. 
5	Severe hypertension after liver transplantation in alpha 1 antitrypsin deficiency. Five children with alpha 1 antitrypsin deficiency and terminal liver disease received liver grafts; all five became hypertensive and four developed hypertensive encephalopathy. There was evidence of renal disease preoperatively and renal biopsy specimens showed variable glomerulonephritic histology with IgA nephropathy in one, mesangial-proliferative changes in two, and mesangio-capillary glomerulonephritis type I in two. Four hypertensive episodes were preceded by a fall in creatinine clearance. The association of glomerulonephritis with alpha 1 antitrypsin deficiency in children is more common than has been recognised. Affected patients are prone to severe hypertension of probable renal origin after liver transplantation and the renal lesion may affect long term prognosis. 
3	Left alien hand sign and mirror writing after left anterior cerebral artery infarction. A 43-year-old, right-handed man was admitted complaining of peculiar movements of his left hand. Computed tomography scan and magnetic resonance imaging showed an infarct area in the territory of the left anterior cerebral artery. The abnormal movements of the left hand were diagnosed as so-called alien hand sign. This patient also exhibited mirror writing with his left hand. The clinical manifestations and neuroradiological findings of this case are described in detail, and the possible mechanisms of these extremely rare combinations of alien hand sign and mirror writing are discussed. 
5	Massive hemorrhage from an arterioureteral fistula associated with chronic renal transplant failure. A case of arterioureteral fistula from the graft artery stump of a failed transplant and the native ureter is reported. This case illustrates one of the possible complications of graft anastomosis. The etiological factors involved in the formation of the aneurysm and eventually the fistula are discussed. 
1	Systematic computer-aided search of optimal staging system for colorectal cancer. Two hundred and ninety-eight patients with curatively resected colorectal cancer were classified into 12 categories according to the depth of tumour penetration (T1-T4), and lymph node status (N0-N2). Using a computer, these categories were grouped into 2-12 stages in every possible combination, so a total of 146,975 logical classifications were generated. The optimal model was selected for each group of classifications with equal stage number, thus giving the greatest prognostic information on 5-year survival according to the Akaike criterion. The results showed that (1) 13% of the total classifications, including 85% of the 3-stage classifications, were better than the Dukes system in predicting our patients' outcomes; (2) the T-level was a stage-determinant even more important than the N-level; and (3) major changes in prognosis occurred at more advanced stages than the classical "turning points". We conclude that in order to find an optimal staging of cancer, systematic computer-aided search through all the possible classifications is necessary, using the appropriate database. 
4	Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation. To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations. 
1	Efficacy of interferons on bowenoid papulosis and other precancerous lesions. Preliminary results of an open randomized trial of recombinant interferon gamma in patients suffering from bowenoid papulosis are described. Recombinant interferon gamma was given subcutaneously to 12 patients at a daily dose of 4 X 10(6) I.U. by injection. Four patients each were assigned to one of three treatment groups consisting of continuous therapy (group A) with three subcutaneous injections per week for 13 weeks; intermittent block therapy (group B) with four six-week cycles consisting of five injections on days 1, 3, 5, 7, and 9 of each cycle; and intermittent single-dose therapy (group C) with six four-week cycles consisting of only one subcutaneous injection on day one of each cycle. At the twenty-sixth week after onset of therapy, complete responses were seen in three of four patients of treatment group A, whereas in the treatment groups B and C only one patient, respectively, responded partially. These results suggest that in contrast to condylomata acuminata bowenoid papulosis lesions respond better to continuous than to intermittent interferon gamma injections. 
5	Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model. The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood. We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period. Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was started on day 8. Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated. The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively. 
3	99TCm-HMPAO SPECT studies in traumatic intracerebral haematoma. Traumatic intracerebral haematomas are a common neurosurgical emergency. Their management, particularly the role of surgical removal, is controversial. Deterioration often occurs late, and is unpredictable. Eight patients with traumatic intracerebral haematomas were admitted to the neurosurgical unit to monitor their clinical state. All were studied within 48 hours of admission with single photon emission computerised tomography (SPECT), using the recently introduced radionuclide 99Technetiumm-Hexamethyl propylene amine oxime (99Tcm-HMPAO). At the time of the SPECT study, all the patients had been clinically stable. Three patients remained so; in the other five, the conscious level deteriorated, necessitating craniotomy and evacuation of the haematoma. In all the patients, the SPECT studies demonstrated perfusion defects that corresponded to the location of the haematoma, as demonstrated by computerised tomography (CT). However, in the five patients who subsequently deteriorated, the perfusion defects seen on the SPECT scan appeared larger than the haematoma, as seen on the CT scan. In addition, there was widespread poor retention of 99Tcm-HMPAO in the ipsilateral hemisphere. These differences were quantifiable. Interestingly, these differences were present at a time when the patients were clinically stable, before their deterioration. It is concluded that SPECT studies with 99Tcm-HMPAO are of possible use as predictors of late deterioration in the management of traumatic intracerebral haematomas. 
2	Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. A patient is described who has features of Pearson syndrome and who presented in the neonatal period with a hypoplastic anemia. He later developed hepatic, renal, and exocrine pancreatic dysfunction. At the age of 5 years he developed visual impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia, and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 4.9 kb. The deleted region was bridged by a 13-nucleotide sequence occurring as a direct repeat in normal mtDNA. Both Pearson syndrome and Kearns-Sayre syndrome have been noted to be associated with deletions of mtDNA; they have not previously been described in the same patient. These observations indicate that the two disorders have the same molecular basis; the different phenotypes are probably determined by the initial proportion of deleted mtDNAs and modified by selection against them in different tissues. 
4	Close correlation of intra-abdominal fat accumulation to hypertension in obese women. The relation between intra-abdominal visceral fat accumulation and blood pressure was investigated in 67 obese women (mean body mass index, 33.6 +/- 3.1; average age, 50 +/- 11 years). As an index of intra-abdominal fat accumulation, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area was determined using a computed tomographic section at the level of the umbilicus. When the obese subjects were divided into a hypertensive group and a normotensive group, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area in the hypertensive group was significantly higher (0.53 +/- 0.33 versus 0.29 +/- 0.12, p less than 0.01). Significant correlations between the ratio of intra-abdominal visceral fat area to subcutaneous fat area and systolic blood pressure (r = 0.62, p less than 0.001) and diastolic blood pressure (r = 0.53, p less than 0.001) also were found. However, no significant difference existed in either the body mass index or the waist-to-hip circumference ratio between the hypertensive and normotensive groups. Plasma renin activity, aldosterone, epinephrine, and norepinephrine levels were not significantly different between the two groups. Moreover, the correlation between the ratio of the intra-abdominal visceral fat area to subcutaneous fat area ratio and blood pressure was found independent of age and body mass index by multiple regression analyses. We conclude that intra-abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity. 
5	A composite driving system for LVAS and IABP: practical and effective driving and weaning. We have devised a new method, termed alternate synchronous driving (ASD), to wean patients from a left ventricular assist system (LVAS) to a pressure assist intraaortic balloon pump (IABP). We have built a new drive unit, VCT200, to apply ASD easily and automatically. After IABP insertion in the final weaning stage, this method drives the LVAS and IABP alternately, with electrocardiogram (ECG) synchronization. The pumping ratio of IABP increases while that of LVAS decreases according to recovery of natural heart function. In in vitro studies, ASD was effective when bypass flow (BF) was less than 50% of total flow (TF) (TF:BF + cardiac output [CO]), and its advantages increased under lower BF conditions. Mean aortic pressure (mAP) and CO increased 10 mmHg and 15%, respectively, with this method (IABP:LVAS = 1:1) when BF was 30% of TF. During in vivo studies, mAP increased 75.7 +/- 6.7 mmHg to 80.1 +/- 3.6 mmHg (p less than 0.001), and the CO increased from 3.1 +/- 0.5 L/min to 3.3 +/- 0.5 L/min (p less than 0.001), while the endocardial viability ratio (DPTI/TTI) increased 20-30%. This method was used in a 62-year-old man in which LVAS was applied after ventricular aneurysmectomy, BF was reduced from 2.2 L/min to 1.1 L/min by using ASD without any change in systemic perfusion. This reduction of BF could not be achieved with LVAS alone. From these data, this system could wean patients from LVAS and then switch to IABP smoothly, easily, and automatically, without hemodynamic instability. 
1	Ductal carcinoma in situ with microinvasion. A curable entity using surgery alone without need for adjuvant therapy. Of 408 negative axillary node (NAN) patients surgically treated at Roswell Park Cancer Institute (Buffalo, NY, 1976 through 1987), 36 (8.8%) presented with ductal carcinoma in situ with microinvasion (DCISM). In more than 50% of the patients (20/36) the disease was detected solely by mammography (microcalcifications and/or radiological density less than 1.5 cm). Thirty-three patients underwent modified radical mastectomy; three had wide excision +/- axillary dissection. Residual disease after excisional biopsy was found in 22 of 33 mastectomy specimens (67%): 11 (33%) pure ductal carcinoma in situ, five (15%) DCISM, and six (18%) frankly invasive. Of the 22 incidents of residual disease, 50% (11) were multicentric (one third of all specimens). These findings imply a high likelihood of residual cancer after excisional biopsy in these patients. All patients were free of disease for a mean follow-up of 57 months (range, 16 to 137). These findings indicate that DCISM is an entirely curable disease when treated by mastectomy alone, without the need for adjuvant therapy, regardless of the status of other prognostic factors such as tumor size, histologic differentiation, age, or steroid receptor status. 
4	Successful liver transplantation in a patient with a thrombosed portomesenteric system after multiple failed shunts. Combined portal and mesenteric vein thrombosis preventing restoration of adequate portal venous flow has been considered a contraindication to liver transplantation. We report a patient with failed splenorenal (SR), portocaval (PC), and mesocaval (MC) shunts, who despite the absence of any obvious means for supplying portal venous inflow to a hepatic graft, successfully underwent orthotopic liver transplantation. A method of reconstruction of the portal vein with the use of vein grafts anastomosed to a large splanchnic venous collateral is described. This technique can be used in selected patients in whom orthotopic liver transplantation might otherwise be considered technically impossible. 
5	Mitral valve disruption following percutaneous balloon valvuloplasty. Two cases of massive mitral regurgitation due to mitral valve disruption following percutaneous balloon valvuloplasty are reported. This severe complication occurred in two elderly women with recurrent mitral stenosis after previous surgical commissurotomy. Due to their unstable hemodynamic and clinical condition, both patients underwent emergency valve replacement. At surgery, the commissures appeared fused and heavily calcified; the chordae tendineae thickened, shortened, and fused; and the leaflets presented a large tear with sheared edges. Because the technical aspects of both procedures were unremarkable, the anatomic features of the mitral valve seemed to affect the occurrence of severe mitral regurgitation. Percutaneous balloon valvuloplasty should be therefore applied carefully to patients with prior surgical valvotomy, in whom the structural alterations of the mitral apparatus may predispose to severe valvular damage. 
5	Late complications in pediatric cardiac transplant recipients. Late complications occurring more than 3 months after cardiac transplantation were analyzed in 29 pediatric patients in whom 31 cardiac transplantations were performed. Age at transplantation ranged from 3 months to 18 years (mean, 11.3 years) with follow-up ranging from 3.5 to 54 months (mean, 21.6 months). There were seven late deaths and two patients with retransplantations. Of nine grafts lost, eight were due to acute rejection, and one was due to coronary disease. Four of the grafts lost were secondary to patient noncompliance with prescribed immunosuppression. The mean rejection frequency more than 1 year after cardiac transplantation was significantly higher in those patients who eventually lost their grafts; however, these patients could not be distinguished by their rejection frequency in the first year. Eight patients had coronary disease, with five diagnosed at autopsy, two at cardiac retransplantation, and one by angiography. All eight patients were on double immunosuppression; none of the 19 patients on triple therapy had coronary disease with similar follow-up. There were 12 serious infections in eight patients (four associated with OKT3) with no deaths. Five patients had arrhythmias requiring treatment including two pacemakers; four of the five were associated with rejection episodes. Twelve of 29 patients developed early hypertension, and five developed late hypertension (greater than 1 year). There were two malignancies; one patient with Hodgkin's lymphoma was cured with chemotherapy, and one patient with histiocytic lymphoma was discovered at autopsy. Two patients had cholecystectomies, and five patients required laser gingivectomies. 
4	Effects of long-term verapamil therapy on serum lipids and other metabolic parameters. Calcium antagonists have been used successfully in the management of hypertension for more than a decade, but less is known about their long-term metabolic effects. To define the impact of one calcium antagonist, verapamil, on serum lipids and other metabolic parameters, we placed 45 hypertensive patients on verapamil monotherapy and followed them for 4 to 8 years. After a mean treatment period of 5.3 years, total cholesterol and triglyceride levels were not significantly different from baseline, whereas the mean high-density lipoprotein cholesterol value increased significantly from 1.17 +/- 0.41 mmol/L at the initiation of treatment to 1.39 +/- 0.36 mmol/L at 5.3 years (p less than 0.05). Other important biochemical parameters, including serum glucose, potassium and uric acid levels were unaffected by verapamil therapy. No serious side effects or adverse cardiovascular events occurred during verapamil therapy, and there were no study dropouts. It therefore seems likely that this agent will become increasingly useful in the long-term management of essential hypertension. 
5	Tropical neuromyelopathies and retroviruses: a review. Debilitating disorders of the nervous system have a relatively high prevalence in the tropics, a geographic region that is often deficient in specialists in the fields of neurology and epidemiology. During World War II, attention was called to a possible nutritional origin for most of these diseases. Recently, however, human T lymphotropic virus type I (HTLV-I), formerly linked only to a rare form of leukemia (adult T cell leukemia), has been associated with a spastic paraplegia observed mostly in tropical areas and referred to as tropical spastic paraparesis. This entity is also observed in nontropical areas endemic for HTLV-I, including Japan, South America, and the southern United States. Viruses of the HTLV family are being associated increasingly with pathology in humans. The pathogenesis of HTLV-I-associated tropical spastic paraparesis remains to be understood. However, future research is expected to favor a multidisciplinary approach, with exciting potential insights derived from the fields of neurology, immunology, and infectious diseases. The aim of this review is to summarize contemporary research related to the viral etiology of this clinical entity. 
5	Defining the role of subtotal colectomy in the treatment of carcinoma of the colon. Seventy-two patients with colon cancer were treated by primary subtotal colectomy, including 23 patients with acute and subacute left colon obstruction. There were two operative deaths and no cases of disabling diarrhea. One death occurred in the group with colon obstruction. Other indications for subtotal colectomy included multiple polyps associated with the primary tumor (32), synchronous carcinomas (15), a previous transverse colostomy for obstruction (8), associated severe sigmoid diverticular disease (2), age less than 50 years with a positive family history (3), adherence of the sigmoid loop to a cecal tumor (2), and metachronous carcinoma (2). There were multiple indications in several patients. Subtotal colectomy has a defined role in a wide variety of clinical settings associated with colon cancer, including management of obstruction of the left and sigmoid colon, particularly if the proximal colon cannot be evaluated before operation by colonoscopy or barium enema. Segmental or regional colonic resections are appropriate if the entire colon can be evaluated before operation and no associated neoplasms are revealed. 
5	A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant. 
3	Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. The diversity of infectious agents capable of inducing meningitis and blood-brain barrier (BBB) injury suggests the potential for a common host mediator. The inflammatory polypeptides, IL-1 and TNF, were tested in an experimental rat model as candidate mediators for induction of meningitis and BBB injury. Intracisternal challenge of rIL-1 beta into rats induced neutrophil emigration into cerebrospinal fluid (CSF) and significantly increased BBB permeability to systemically administered 125I-BSA as early as 3 h later (P less than 0.05). This injury was reversible, dose dependent and significantly inhibited by prior induction of systemic neutropenia (via intraperitoneal cyclophosphamide) or preincubation of the rIL-1 beta inoculum (50 U) with an IgG monoclonal antibody to rIL-1 beta. Similar kinetics and reversibility of CSF inflammation and BSA permeability were observed using equivalent dose inocula of rIL-1 alpha. rTNF-alpha was less effective as an independent inducer of meningitis or BBB injury over an inoculum range of 10(1) U (0.0016 micrograms/kg)-10(6) U (160 micrograms/kg) when injected intracisternally, but inoculum combinations of low concentrations of rTNF alpha (10(3) U) and rIL-1 beta (0.0005-5.0 U) were synergistic in inducing both meningitis and BBB permeability to systemic 125I-BSA. These data suggest that in situ generation of interleukin-1 within CSF (with or without TNF) is capable of mediating both meningeal inflammation and BBB injury seen in various central nervous system infections. 
4	Epidural anaesthesia for labour and caesarean section in a parturient with a single ventricle and transposition of the great arteries. We describe a case of a 29-year-old parturient with a single ventricle and transposition of the great arteries who had lumbar epidural analgesia/anaesthesia with a local anaesthetic for labour, emergency Caesarean section and postoperative pain. Her outcome and that of her baby was successful. The anaesthetic techniques used in other parturients with similar congenital cardiac anomalies are reviewed. 
2	Endoscopic laser surgery. A single-center comprehensive experience. A retrospective review of endoscopic procedures using the Nd:YAG laser was carried out for patients treated between October 1985 and March 1989. During this 42-month period 165 procedures were performed on 100 patients. The study encompasses a unique period of time in this center, as it includes the initial application, and finally, the time when its use became routine. Indications for laser surgery included the treatment of tumors, bleeding, benign strictures, arterial occlusions, and hemorrhoids. Nd:YAG laser was found to be effective in the treatment of these lesions. The overall success rate was 81 per cent. Patients who are poor surgical candidates would especially benefit from this therapeutic alternative. 
5	Iatrogenic saphenous neuralgia: successful therapy with neuroma resection. We report the case of a patient with saphenous neuralgia secondary to iatrogenic trauma resulting from bypass surgery in the femoral-popliteal region. Early symptoms of this condition were medial calf and ankle pain, with no findings of motor and reflex abnormalities. Exploration of the thigh 2 years later revealed a neuroma of the nerve in the distal dissection site, medial to the knee. Resection of the neuroma alleviated this condition. It is noted that saphenous neuropathy is seen as a spontaneous entrapment syndrome as well as a complication of orthopedic and vascular procedures performed on the medial area of the knee. Saphenous neuralgia is often not recognized by neurosurgeons. If the condition is intractable, it does respond to surgical therapy. 
5	Automatic implantable cardioverter-defibrillator implantation without thoracotomy using an endocardial and submuscular patch system. The automatic cardioverter-defibrillator lead system is implanted by a thoracotomy procedure that may result in atelectasis, pleural effusion, cardiac tamponade and lengthy convalescence. A new defibrillator lead system that allows selection of different defibrillating current pathways is implanted without a thoracotomy. Ten patients requiring a cardioverter-defibrillator for recurrent sustained ventricular tachycardia (five patients) or aborted sudden cardiac death (five patients) were evaluated for implantation of this lead system. A lead configuration with a bidirectional defibrillating current pathway was implanted in nine patients. The defibrillation threshold with this lead configuration was 15 J in five patients, 20 J in three and 30 to 35 J in one patient. In the remaining patient the lead system had a 40 J defibrillation threshold and was not implanted. No perioperative complications occurred. Induced ventricular fibrillation was successfully terminated at the predischarge and intermediate follow-up (8 to 12 weeks) electrophysiologic studies. During the follow-up period, there were three deaths (one sudden, two due to heart failure) and two lead system failures (oversensing with inappropriate shocks in one patient and patch lead fracture in another). Implantation of the cardioverter-defibrillator lead system by a nonthoracotomy approach is feasible, has no significant perioperative complications and is well tolerated by patients. Effective defibrillation was demonstrated immediately as well as at intermediate follow-up study. The occurrence of patch lead fracture and oversensing requires improvement in the present (nonthoracotomy) lead system technology. 
4	A double-blind comparative study of doxazosin and prazosin when administered with beta-blockers or diuretics. The antihypertensive efficacy and safety of doxazosin (once daily) and prazosin (twice daily) were compared in patients with mild or moderate essential hypertension (diastolic blood pressure [DBP] 95 to 114 mm Hg) not adequately controlled by diuretics and beta-blockers. Doxazosin produced significantly greater mean reductions in standing (p = 0.01) and supine (p = 0.04) DBP than did prazosin; there were no significant between-group differences in either mean systolic blood pressure or heart rate. The overall mean daily doses for efficacy-evaluable patients were 4.7 mg of doxazosin and 6.7 mg of prazosin. Sixteen patients (84.2%) treated with doxazosin and 13 patients (56.5%) treated with prazosin were considered therapeutic successes (decrease in standing DBP greater than or equal to 10 mm Hg or to less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline). Of the 19 efficacy-evaluable patients treated with doxazosin, 15 (78.9%) showed improvement in the severity category of hypertension; an improvement in severity was reported in 14 patients (60.9%) treated with prazosin. Doxazosin produced a more favorable effect on serum lipid levels than did prazosin, although no statistically significant within- or between-group differences were observed. Most side effects experienced with either doxazosin or prazosin were mild or moderate and were tolerated or disappeared with continued treatment. The overall evaluation of toleration was excellent or good for 18 (90%) doxazosin- and 21 (91%) prazosin-treated patients. Clinical efficacy was rated as excellent or good for 16 patients (80%) treated with doxazosin and 15 patients (68%) treated with prazosin. 
3	Non-vesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake. Glutamate uptake into nerve and glial cells usually functions to keep the extracellular glutamate concentration low in the central nervous system. But one component of glutamate release from neurons is calcium-independent, suggesting a non-vesicular release that may be due to a reversal of glutamate uptake. The activity of the electrogenic glutamate uptake carrier can be monitored by measuring the membrane current it produces, and uptake is activated by intracellular potassium ions. Here we report that raising the potassium concentration around glial cells evokes an outward current component produced by reversed glutamate uptake. This current is activated by intracellular glutamate and sodium, inhibited by extracellular glutamate and sodium, and increased by membrane depolarization. These results demonstrate a non-vesicular mechanism for the release of glutamate from glial cells and neurons. This mechanism may contribute to the neurotoxic rise in extracellular glutamate concentration during brain anoxia. 
1	Thyroid and parathyroid cancer. The epidemiology, etiology, pathology, and management of thyroid and parathyroid carcinoma are discussed. Emphasis is placed on the clinical differences in the management and treatment of the various histologic subtypes of thyroid cancer. The biologic and prognostic differences among the various histologic types of thyroid cancer and their relationship to age are stressed. 
1	Vaginal removal of the pedunculated submucous myoma. Historical observations and development of a new procedure. A new method of vaginal removal of submucous fibroids was attempted on 151 patients. The procedure involves dilation of the cervix with Laminaria tents and removal of the submucous fibroid by grasping with appropriate instruments. Myomas were removed successfully in 92% of the patients; hysterectomy and abdominal myomectomy were avoided in all but four of them. Perforation occurred in two patients. Morbidity was minimal. The four patients who desired pregnancy conceived. 
1	The utility of circulating levels of human pancreatic polypeptide as a marker for islet cell tumors. The measurement of plasma levels of human pancreatic polypeptide (hPP) has been reported to be clinically useful in predicting the existence of pancreatic islet cell neoplasms in patients with familial multiple endocrine neoplasia type 1 (FMEN-I) and the possible presence of metastatic disease in patients with islet cell tumors. However, these studies have not been prospective and involve small numbers of patients. In this study, fasting plasma samples from 36 patients with biopsy-proved islet cell tumors were analyzed for hPP by radioimmunoassay and compared with age-matched control subjects. Of 13 patients with FMEN-I who had islet cell tumors, 7 (54%) had elevated plasma hPP levels before surgery. After resection of all islet cell tumors, 4 of 12 patients evaluated after surgery still had elevated levels. Fifteen patients had islet cell tumors that were localized (seven insulinomas and eight gastrinomas), but none of these patients had elevated hPP levels, either before or after surgery. Nine patients, including one with FMEN-I, with metastatic islet cell tumors to the liver were studied; three with more advanced disease had elevated hPP levels before surgery. Each of the nine patients underwent resection of all gross disease and the three patients with elevated preoperative levels had normal postoperative hPP levels. Our results indicate that basal plasma levels of hPP were not clinically useful. The hPP levels did not reliably predict the presence of islet cell tumors in patients with FMEN-I, because 46% of patients with tumors did not have elevated plasma levels, and in those with elevated values hPP levels did not reliably predict the resection of all tumor. Plasma levels of hPP have no utility in patients with localized sporadically occurring islet cell tumors and limited utility (33%) in predicting the presence of metastatic islet cell tumors to the liver. 
4	Unilateral diffuse pulmonary artery involvement in Takayasu's arteritis associated with coronary-pulmonary artery fistula and bronchial-pulmonary artery fistula: a case report. Diffuse involvement of the right pulmonary artery associated with fistulas between the pulmonary artery and systemic artery is reported in a woman with Takayasu's arteritis. The most proximal portion of the abdominal aorta was pronouncedly narrowed and the aortic wall was markedly calcified. Both the celiac artery and the superior mesenteric artery were totally occluded and drained by the meandering artery arising from the inferior mesenteric artery. The proximal right pulmonary artery was focally narrowed and the middle lobe artery was occluded. All other branches of the right pulmonary artery were diffusely narrowed with sparse distributions of their distal branches. Fistulas were identified between the right coronary artery and the right pulmonary artery and between the right bronchial artery and the right pulmonary artery. This is the first English report of Takayasu's arteritis presenting with a coronary-pulmonary artery fistula that is secondary to a diffuse unilateral involvement of the pulmonary artery. 
1	A newly established human osteosarcoma cell line with osteoblastic properties. A human osteosarcoma cell line, HuO9, was established from a tumor that was heterotransplanted into athymic nude mice. Antiserum against nude mouse spleen cells was added to the early passage cultures to eliminate the host fibroblastic cells. The cell line retained a high activity of liver/bone/kidney-type alkaline phosphatase (ALP) and secreted osteocalcin, i.e., bone gamma-carboxyglutamic acid-containing protein (BGP), into the medium. The addition of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the ALP activity as well as the level of BGP secreted into the medium. The ALP of 1,25(OH)2D3-treated cells has the same inhibition characteristics to heat and amino acids as that of untreated cells. Synthetic human parathyroid hormone stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) approximately 100-fold within five minutes. However, the stimulation was not observed with a synthetic human thyrocalcitonin. When HuO9 cells were transplanted into the back of a nude mouse, a tumor with an abundant osteoid formation and mineralization was produced. The results indicate that the HuO9 cell line expresses well-differentiated osteoblastic phenotypes. HuO9 is the first established human cell line to produce BGP, and it provides a useful model for the studies of osteoblasts and the regulatory mechanisms of BGP production. 
4	Calciotropic hormones in human and experimental hypertension. Although altered cellular calcium handling plays a critical role in the pathophysiology of hypertension, little attention has been focused on the impact of calcium regulating hormones on this process. Recent research provides evidence that parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D, as well as newly described factors such as calcitonin gene-related peptide (CGRP), exert target-organ-specific actions in cardiac and peripheral vascular tissues, are linked to the renin-aldosterone system, and thus to the control of sodium metabolism, and may directly participate in the hypertensive process, especially in low renin and salt sensitive forms of hypertensive disease. The metabolic set-point of these linked renin and calcium hormone systems, which serve to transduce environmental dietary mineral signals at the cellular level, determines the blood pressure consequences of sodium and calcium loading and/or restriction, and helps to explain the heterogeneous and seemingly inconsistent effects of these dietary maneuvers on blood pressure. Measurement of renin and calcium factors in hypertension thus provides a physiological basis for individualized therapeutic recommendations in human hypertension. 
2	Sexually transmitted parasitic diseases. Sexual activity is the primary method of transmission for several important parasitic diseases and has resulted in a significant prevalence of enteric parasitic infection among male homosexuals. The majority of parasitic sexually transmitted diseases involve protozoan pathogens; however, nematode and arthropod illnesses are also included in this group. Trichomoniasis, caused by Trichomonas vaginalis, is the most common parasitic STD. Infection with this organism typically results in the signs and symptoms of vaginitis. Trichomoniasis can be diagnosed in the office setting by performing a microscopic evaluation of infected vaginal secretions and can be successfully treated with metronidazole. Both pediculosis pubis, caused by the crab louse Pthirus pubis, and scabies, caused by the itch mite Sarcoptes scabiei, present with severe pruritus. A papular or vesicular rash and linear burrows seen in the finger webs and genital area are characteristic of scabies. Pediculosis pubis is diagnosed by observing adult lice or their nits in areas that bear coarse hair. The diagnosis of scabies is confirmed by scraping suspicious burrows and viewing the mite or its byproducts under the microscope. Lindane, 1% used in treating scabies, is also very effective for treating pediculosis pubis. Synthetic pyrethrins, also applied as a cream or lotion, are less toxic alternatives for the treatment of either condition. Oral-anal and oral-genital sexual practices predispose male homosexuals to infection with many enteric pathogens, including parasitic protozoans and helminths. The most common of these parasitic infections are amebiasis, caused by Entamoeba histolytica, and giardiasis caused by Giardia lamblia. Both entities may cause acute or chronic diarrhea, as well as other abdominal symptoms. Most gay men with amebiasis are asymptomatic, and invasive disease in this group is extremely rare. Both amebiasis and giardiasis can be diagnosed on the basis of microscopic examination of stool specimens, although duodenal aspiration is occasionally necessary to confirm a diagnosis of giardiasis. Multiple treatment regimens exist for amebiasis. Iodoquinol is a good choice for asymptomatic cyst carriers, whereas the combination of metronidazole plus iodoquinol is used for symptomatic patients. Quinacrine and metronidazole are both efficacious in the treatment of giardiasis. 
5	Orbital compartment syndrome. Direct measurement of orbital tissue pressure: 1. Technique. Many disorders of the orbit produce an increase in intraorbital pressure, which may result in the development of an orbital compartment syndrome and visual loss. Traditionally, orbital tension is assessed clinically by indirect means based on retrodisplacement of the globe. The authors describe their experience with the "slit-catheter" technique for direct tissue pressure measurement as applied to the orbit. The preliminary results indicate that normal orbital pressure ranges from 3.0 to 6.0 mm Hg. In patients with Graves' orbitopathy the values ranged from 7.0 to 15.0 mm Hg. The results suggest that the technique may have many exciting possibilities as a clinical research tool in orbital disease, and its use will result in better understanding of orbital compartment syndromes. 
3	Meta-analysis of sulfasalazine in ankylosing spondylitis. At present there is no widely accepted therapy for ankylosing spondylitis (AS), a progressive debilitating disease. The effectiveness of sulfasalazine in AS still lacks strong evidence, as well, the magnitude of its benefit is unknown. A meta-analysis was carried out to assess the effectiveness of sulfasalazine in AS. A search of the literature was done using Medline, Index Medicus, the reference lists of articles located and contacting content experts to reveal unpublished studies. Five randomized controlled trials (RCT) comparing sulfasalazine to placebo were located and assessed methodologically. The methodologic quality of all 5 RCT was considered satisfactory and consequently these studies were included in the meta-analysis. The pooled estimate of clinical benefit (and its 95% confidence interval) favoring sulfasalazine, over and above that observed in the placebo group was as follows: Duration of morning stiffness -28.2% (-54.6 to -1.8%); severity of morning stiffness -30.6% (-52.5 to -8.7%); severity of pain -26.7% (-44.3 to -9.1%); general well being -7.1% (-24.3 to 10.0%); erythrocyte sedimentation rate -9.2% (-24.8 to 6.4%); and IgA -11.7% (-18.8 to -4.7%). Adverse effects, mostly mild, were more frequently observed in the sulfasalazine group (odds ratio [OR] = 1.5746, p = 0.1082). The occurrence of dropouts (OR = 1.1554, p = 0.6119) was similar in both groups. Sulfasalazine is a safe and effective drug in the short term treatment of AS. 
4	Clinical experience with the Nimbus pump. The Nimbus pump is an indwelling, electromagnetic powered left ventricular (LV) assist device inserted transfemorally. The inflow cannula (7 mm) is positioned across the aortic valve and the pump in the descending aorta. Indications for insertion include cardiogenic shock despite maximal medical support and PCWP greater than 18 mmHg, MAP less than 90 mmHg, and Cl less than 2 L/min/m2. Twelve patients underwent the attempt at surgical insertion of the Nimbus pump. Diagnoses included eight acute myocardial infarctions (AMI), two ischemic cardiomyopathy, one postpartum cardiomyopathy, and one transplanted heart rejection. Eight (67%) of twelve patients had successful insertion. One patient had peripheral vascular disease preventing passage, and three had femoral vessels too small for insertion (less than 7.5 Hagar dilator). Five patients with the diagnosis of AMI had successful insertion and three (60%) underwent sufficient LV recovery for removal of the device; the other two patients died of stroke and ventricular arrhythmias, respectively. Three patients with the diagnosis of cardiomyopathy had progression of the disease process, and their needs exceeded the capabilities of the pump and they died of multiorgan failure. The Nimbus pump is an attractive LV assist device because of its pumping capacity (3.5 L/min) and minor surgical procedure for insertion. However, its application is limited because of access route and size. The device appears to work well for patients in cardiogenic shock after AMI (60% recovery) but does not appear indicated for patients with cadiomyopathy. 
4	Transesophageal echocardiography to detect atrial clots in candidates for percutaneous transseptal mitral balloon valvuloplasty. Left atrial thrombi are common in patients with mitral stenosis. When percutaneous balloon mitral valvuloplasty is performed on such patients, there is a potential risk of thrombus dislodgment and embolization. In this study conventional transthoracic echocardiography and transesophageal echocardiography were performed for percutaneous balloon mitral valvuloplasty on 19 consecutive candidates (6 men, 13 women, 23 to 81 years old). In five patients (26%), transesophageal echocardiography revealed a left atrial thrombus; in only one of these was there a suspicion of left atrial thrombus on transthoracic echocardiography. Balloon mitral valvuloplasty was canceled in four of the five patients. Three underwent mitral valve surgery that confirmed the echocardiographic findings. Transesophageal echocardiography is better than conventional transthoracic echocardiography in detecting left atrial clots in candidates for balloon mitral valvuloplasty. Because of the potential risk of embolization, transesophageal echocardiography is recommended in all candidates for balloon mitral valvuloplasty. 
1	Application of the monoclonal antibody Ki-67 on prostate biopsies to assess the fraction of human prostatic carcinoma. The feasibility of using the monoclonal antibody Ki-67 as a proliferation marker in human prostatic carcinoma was studied on aspiration and core biopsy specimens obtained from 50 patients suspected of having prostate cancer. In 32 prostatic adenocarcinomas the Ki-67 index varied from 0.3 to 13.3% (mean 4.3) in cytological smears and from 0.8 to 17.8% (mean 5.1) in frozen sections from histological core biopsies. No significant correlation between the percentage of cells positive for Ki-67 and the histological tumor differentiation could be established. In 18 patients with benign prostatic hyperplasia the Ki-67 index varied from 0 to 3.0% (mean 1.2) and from 0 to 3.8% (mean 1.4) in cytological and histological material, respectively. The differences in the observed Ki-67 index between benign and malignant prostatic tissues are of statistical (p less than 0.001) and of clinical significance. Nine patients who underwent endocrine treatment or radiotherapy entered a followup protocol in which the Ki-67 staining procedure was applied to periodically obtained cytological aspiration biopsies. During month 1 after the start of therapy a statistically significant (p less than 0.05) decrease in the Ki-67 index to 58% of the initial values was found, while at 2 and 3 months the proliferative fraction showed a further decrease to 27 and 7%, respectively. As a marker, the monoclonal antibody Ki-67 was shown to provide a reliable method to estimate the proliferative cell fraction of human prostate cancer. 
5	A prospective study of acute central retinal artery obstruction. The incidence of secondary ocular neovascularization. We conducted a prospective study to determine the incidence of ocular neo-vascularization following acute central retinal artery obstruction. Only patients initially evaluated within 7 days of visual loss were eligible. Any patient with pre-existing ocular neovascularization or clinical evidence of the ocular ischemic syndrome noted at the initial evaluation was excluded. During the 18-month study, 33 consecutive patients were enrolled. Six patients subsequently developed neovascularization of the iris, an incidence of 18.2%. In these six patients, neovascularization of the iris appeared as early as 12 days to as late as 15 weeks following the artery obstructions. Five of the six patients (15.2% of the total) later developed neovascular glaucoma. Another patient in this series developed neovascularization of the optic disc without neovascularization of the iris, an incidence of 3.0%. Only two of the seven patients with ocular neovascularization had ipsilateral hemodynamically significant carotid artery disease as determined by noninvasive carotid artery testing. This study confirms results of previous retrospective studies that the incidence of ocular neovascularization after central retinal artery obstruction is higher than commonly thought. It also shows that, in the majority of cases, carotid artery disease is not responsible for the neovascularization seen after central retinal artery obstruction. 
5	Factors associated with binocular single vision in microtropia/monofixation syndrome. We reviewed the charts of 398 patients with microtropia/monofixation syndrome to determine what factors influence the level of binocularity attained. Most patients (82%) exhibited some degree of stereoacuity. Patients with a later age at presentation of the initial deviation were more likely to exhibit stereoacuity (p less than 0.001). Patients with smaller initial deviations were also more likely to exhibit stereoacuity (p = 0.016), as were those with smaller manifest deviations on final testing (p less than 0.001). Patients with amblyopia on final testing were less likely to demonstrate stereoacuity (p = 0.0001). Generally, the more intervention required in the form of optical or surgical correction, the poorer the level of binocularity. 
1	The role of the physician in the late diagnosis of primary malignant tumors of the small intestine. Survival from primary malignancies of the small intestine has not improved during the last four decades. One reason for this is the advanced stage of disease at the time of surgery. In order to determine why diagnosis is made late, we reviewed the records of all patients with small bowel malignancy diagnosed between 1967 and 1988. The time from the onset of symptoms to the first medical contact and the time from medical contact until diagnosis were evaluated in 77 patients. The average delay in diagnosis attributable 1) to the patient failing to report symptoms was less than 2 months, 2) to the physician not ordering the appropriate diagnostic test was 8.2 months, and 3) to the radiologist failing to make the diagnosis was 12 months. Thus, the major delay in diagnosis was after medical help was sought and not from the onset of symptoms to first medical consultation. Physicians must increase their sensitivity to the subtle but persistent symptoms that necessitate a small bowel evaluation. 
3	Genetic mapping of new DNA probes at Xq27 defines a strategy for DNA studies in the fragile X syndrome. The fragile X syndrome is the most common cause of familial mental retardation and is characterized by a fragile site at the end of the long arm of the X chromosome. The unusual genetics and cytogenetics of this X-linked condition make genetic counseling difficult. DNA studies were of limited value in genetic counseling, because the nearest polymorphic DNA loci had recombination fractions of 12% or more with the fragile X mutation, FRAXA. Five polymorphic loci have recently been described in this region of the X chromosome. The positions of these loci in relation to FRAXA were defined in a genetic linkage study of 112 affected families. The five loci--DXS369, DXS297, DXS296, IDS, and DXS304--had recombination fractions of 4% or less with FRAXA. The closest locus, DXS296, was distal to FRAXA and had a recombination fraction of 2%. The polymorphisms at these loci can be detected in DNA enzymatically digested with a limited number of restriction endonucleases. A strategy for DNA studies which is based on three restriction endonucleases and on five probes will detect one or more of these polymorphisms in 94% of women. This strategy greatly increases the utility of DNA studies in providing genetic advice to families with the fragile X syndrome. 
5	Babinski-Nageotte syndrome on magnetic resonance imaging. A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis sparing the face, and a typical left Wallenberg's syndrome. These symptoms resulted from a lesion in the left half of the medulla oblongata, suggesting Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first case of ischemic infarction in the territory of the left vertebral artery and posterior inferior cerebellar artery demonstrated on magnetic resonance imaging. Severe bilateral lesions of the distal vertebral arteries demonstrated on digital subtraction angiography may have contributed to the development of this syndrome. 
5	Risk for postoperative congestive heart failure. To identify predictors of postoperative congestive heart failure (CHF), a high-risk population, mainly hypertensive and diabetic patients undergoing elective general operations, was studied. Of the 254 patients, 6 per cent had postoperative CHF. Among patients with preoperative cardiac disease (that is, previous myocardial infarction, valvular disease or CHF), 17 per cent had postoperative CHF; in contrast with less than 1 per cent of those without cardiac disease (p less than 0.001). Patients with diabetes were also at high risk (12 versus 2 per cent, p less than 0.005), particularly those with cardiac disease. Patients who had equal to or greater than 40 millimeters of mercury increases or decreases intraoperatively in mean arterial pressure in relation to preoperative baseline had increased postoperative failure rates (p less than 0.02). Of note, postoperative failure rates were highest among patients with less than 500 milliliters per hour of net intake (input and output) (p less than 0.03). Risk for postoperative CHF was restricted to patients with preoperative symptomatic cardiac disease and was especially high if patients also had diabetes. Intraoperative fluctuations in mean arterial pressure increased the probability of postoperative failure, while the intraoperative administration of higher net volumes of fluid was associated with decreased risk. 
3	Concurrent and construct validity of the Pediatric Evaluation of Disability Inventory. The purpose of this study was to determine the validity of the Development Edition (pilot version) of the Pediatric Evaluation of Disability Inventory (PEDI) in groups of disabled and nondisabled children. The PEDI is a new functional assessment instrument for the evaluation of disabled children aged 6 months to 7 years. The PEDI has been developed to identify functional status and change along three dimensions: 1) functional skill level, 2) caregiver assistance, and 3) modifications or adaptive equipment used. The PEDIs were administered as a parental-report questionnaire, and the results were compared with data obtained by the Battelle Developmental Inventory Screening Test (BDIST). The BDIST is a standardized assessment with developmental and adaptive content. Subjects were 20 children between the ages of 2 and 8 years with arthritic conditions and spina bifida and 20 nondisabled children matched for age and sex. All subjects' scores on the BDIST cognitive domain were no greater than 1.50 standard deviations below the mean for their age group. Concurrent validity was supported by moderately high Pearson product-moment correlations between BDIST and PEDI summary scores (r = .70-.80). Construct validity was supported by significant differences between the disabled and nondisabled groups' PEDI scores and by discriminant analysis identifying the PEDI scores as better group discriminators than the BDIST scores. Results validate the Developmental Edition of the PEDI and support the further development and standardization of the final version. Use of the PEDI in clinical pediatric physical therapy practice is discussed. 
5	Effects of prostaglandin E1 on collagen diseases with high levels of circulating immune complexes. Prostaglandin E1 (PGE1) was administered to 4 patients with collagen diseases presenting with high levels of circulating immune complexes (CIC) in sera. Our study patients had progressive systemic sclerosis, systemic lupus erythematosus, polyarteritis nodosa, and rheumatoid arthritis. In all 4 patients, CIC levels significantly decreased after administration of PGE1 by continuous infusion at 10/ng/kg/min via central venous catheter for 72 h. In addition, the skin ulcer in a patient with PSS healed completely, and the finger necrosis in a patient with RA improved. These results suggest that PGE1 given by continuous venous infusion is effective in reducing CIC, in addition to improving peripheral vascular disorders. 
3	Drug-induced headache. Headache induced by medications used for nonheadache conditions, and more importantly, headache perpetuated by symptomatic medications used for primary headache disorders are discussed in detail in this article. The clinical features and mechanisms of drug-induced headaches are reviewed. Ergotamine and analgesic rebound phenomena are described. Management strategies for drug-induced headaches are outlined. 
1	Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens The authors investigated the humoral and tissue expression of six antigens associated with medullary thyroid cancer (MTC): calcitonin (CT), calcitonin gene-related peptide (CGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), somatostatin (SRIF), and thyroglobulin (TG). The antigens were studied in the neoplastic C cells using immunohistochemistry with specific antisera and in the plasma using specific radioimmunoassay. Eighteen patients (8 male and 10 female patients, aged 12-72 years) were studied. Mean follow-up was 70.7 months (range, 2-179 months). Nine patients (50%) died of their disease after a mean follow-up of 47.2 months (range, 2-116 months). By immunostaining, primary tumors expressed CT and CEA in all cases and NSE was positive in 90%, CGRP in 66%, SRIF in 63%, and TG in 58%. Metastatic tissues were positive in all cases of CT staining, 92.8% of CEA, 71.4% of NSE, 73.3% of CGRP, 38.5% of SRIF, and only 13.3% of TG staining. In positive cases the percentage of positive cells and the degree of staining were variable among the different antigens. The expression of an antigen in the neoplastic cells was associated with the hypersecretion of the corresponding antigen in the circulation in the case of CT and CEA. The levels of these antigens were elevated in all patients with metastases and could accurately predict the appearance of new metastases or indicate the effective treatment of previous metastases by surgery. In the case of NSE, CGRP, and SRIF, few patients had increased plasma concentrations of the antigens and these usually occurred during very advanced phases of the disease. Detectable levels of serum TG were never observed. When the outcome of the disease was compared with the expression of CT, CEA, NSE, CGRP, and TG, no correlation could be found. On the contrary, SRIF expression in the primary tumor could differentiate two groups of patients with different survival rates. SRIF-positive patients had survival rates of 100% and 50% at five and seven years, respectively, whereas SRIF-negative patients had survival rates of 40% at five years and 25% at seven years. 
5	Small intestinal fatty acid synthesis is increased in diabetic rats. Several studies have demonstrated that intestinal triglyceride production and secretion are increased in diabetic animals and may contribute to the hypertriglyceridemia that accompanies diabetes. There are three potential sources of fatty acids for intestinally derived triglycerides; de novo fatty acid synthesis, circulating free fatty acids, or dietarily derived fatty acids. Prior data have demonstrated that de novo cholesterol synthesis is increased in the small intestine of diabetic animals. The primary aim of the present study was to determine the effect of diabetes on small intestinal de novo fatty acid synthesis. We found that de novo fatty acid synthesis in the small intestine is increased approximately 2-fold in streptozotocin-induced diabetic rats. In contrast, hepatic fatty acid synthesis is decreased in the diabetic animals. The increase in intestinal fatty acid synthesis is observed in both the fed and fasting states. Limiting food intake by pair feeding prevents the diabetic-induced increase in small intestinal fatty acid synthesis, a finding similar to previous data on cholesterol synthesis. Thus, the increase in both small intestinal cholesterol and fatty acid synthesis is dependent on the increased food intake that accompanies poorly controlled diabetes. The present study indicates that increases in small intestinal de novo fatty acid synthesis in diabetic animals could play an important role in providing fatty acids for increased small intestinal triglyceride synthesis and secretion. 
4	Neonatal repair of tetralogy of Fallot with and without pulmonary atresia. Our experience with the arterial switch operation for transposition of the great arteries has confirmed the attainability of excellent results with elective neonatal surgery. Up to this time, we have repaired tetralogy of Fallot during the neonatal period only when symptoms, either severe persistent cyanosis or cyanotic spells, have been present. This review assesses the results of such nonelective neonatal correction of tetralogy between 1973 and 1988. Twenty-seven neonates with either symptomatic tetralogy of Fallot or symptomatic tetralogy of Fallot with valvar pulmonary atresia underwent repair. Mean age at repair was 8 +/- 8.4 days and mean weight was 3.0 +/- 0.7 kg. Unsatisfactory palliative shunts had previously been placed elsewhere in four patients. Twenty-five transannular patches and two conduits were used for reconstruction of the right ventricular outflow tract. There were five deaths in the hospital, three of which were due to avoidable technical problems. All deaths occurred in patients with pulmonary artery (Nakata) index less than 150 mm2/m2. One premature child weighing 2.3 kg displayed an absent pulmonary valve-like syndrome after repair and died late of respiratory complications caused by aneurysmal branch pulmonary arteries. Actuarial survival at 5 years was 74%. There was a single rapidly declining hazard phase for death, with the hazard approaching zero at 1 1/2 years after repair. Actuarial freedom from need for reoperation was 76% at 5 years. Postoperative catheterization of 15 long-term survivors showed right ventricular pressure less than 70% systemic in 13 cases. All patients are symptomatically well and functioning in sinus rhythm 1 to 15 years after repair (mean, 5 +/- 4 years). This experience with neonates with symptoms suggests that, if mortality is lower in the absence of symptoms, elective repair of tetralogy of Fallot could be reasonably undertaken during the first months of life. 
4	Femoral saphenous vein bypass in a newborn. This is believed to be the youngest patient to undergo a saphenous vein bypass for iatrogenic trauma of the right superficial femoral artery. The infant had emergency right heart catheterisation and Rashkind septostomy for severe desaturation due to transposition of the great arteries. During the exposure of the saphenous vein, the superficial femoral artery was accidentally severed at it's origin. An attempt to restore the circulation by end-to-end anastomosis failed and resulted in persistent limb ischemia for over 4 hours. The baby was reoperated upon, the damaged part of the superficial femoral artery was resected and a saphenous vein graft interposed between the common and the distal superficial femoral artery. 
2	Significance of natural polymerized albumin and its receptor in hepatitis B infection of hepatocytes. Lack of information regarding the presence of native albumin polymer in serum and its structural similarity to the one produced by glutaraldehyde treatment casts doubt on the postulate that hepatitis B virus attachment to hepatocytes is mediated through polymerized albumin. We used a sandwich enzyme-linked immunosorbent assay with murine monoclonal antibodies raised against glutaraldehyde-polymerized albumin to detect native albumin polymer in human serum and its cross-reactivity with other albumin polymers. Presence of polymerized albumin receptor on the HepG2 cell was studied by radioreceptor assay. Purified hepatitis B virus and synthetic peptide analogous to part of pre-S2 sequence (120-145) were used to study polymerized albumin-dependent attachment of the virus to HepG2 cells. Antibodies raised against pre-S2 peptide were used to inhibit the pre-S2 and hepatitis B virus attachment to HepG2 cells. Glutaraldehyde-treated polymerized albumin was found to be immunologically cross-reactive with native albumin polymer. Its levels were found to be significantly raised in sera of patients with liver diseases. Polymerized albumin has specific saturable receptor on HepG2 cells with two classes of binding sites of different equilibrium dissociation constant (Kd1 = (16 +/- 9.6)pmol/L and Kd2 = (1,019 +/- 172)pmol/L. Albumin monomer was unable to compete for the polymerized albumin receptor sites on HepG2 cells. Anti-pre-S2 antibodies inhibit hepatitis B virus and pre-S2 binding to hepatocyte by 40% and 70%, respectively. Added extraneous polymerized albumin and the antibody against it did not interfere with virus attachment to HepG2 cells. 
5	Estrogen deficiency in adolescents and young adults: impact on bone mineral content and effects of estrogen replacement therapy. Because the long-term effects of estrogen replacement in adolescents with ovarian failure and hypothalamic amenorrhea have not been previously studied, we conducted a 2-year study of 35 patients to determine factors contributing to baseline bone density measures (bone density, bone mineral content, and bone width) and the response to estrogen therapy. Estrogen-deficient patients were often profoundly osteopenic by single-photon absorptiometry of the radius and dual-photon absorptiometry of the spine, despite estrogen replacement. Variables that were significant predictors of better initial single-photon absorptiometry measurements included increased age, increased body mass index, spontaneous pubertal development, lack of radiation therapy, and lower serum osteocalcin. Patients treated with estrogen/progestin had stable cortical bone mineral content and bone density at the distal one-third of the radius, a slight improvement in bone density at the distal one-tenth of the radius, and on encouraging, but marginal, improvement in the z score (standard deviation from the mean) of bone mineral content at the distal one-tenth. The z scores for cortical bone width and bone density decreased, suggesting a possible relative worsening over time. In untreated estrogen-deficient girls, bone mineral content and bone density decreased (but not significantly); the z score of cortical bone width showed a significant decrease. Using dual-photon absorptiometry, a history of radiation therapy was found to be a predictor of lower bone density compared with age-matched controls. Estrogen progestin therapy did not result in changes in serum levels of lipids and antithrombin III, weight, or blood pressure. 
5	Growth velocity before sudden infant death. Weight velocities of 136 infants who died from sudden infant death syndrome (SIDS) were compared with those of 136 controls matched for sex, birth weight, and type of feeding. It was found that the SIDS infants gained weight more slowly overall and that the differences were significantly different for infants who were not breast fed in the last two weeks in which it was possible to estimate their growth velocity. Breast fed infants had more periods of growth below the 25th centile than expected. These differences are unlikely to be useful in the prediction of which babies are likely to die from SIDS as there are frequent episodes of poor growth in infants who do not die. 
5	Incidence of cocaine-associated rhabdomyolysis. STUDY HYPOTHESIS: Rhabdomyolysis is a common complication of cocaine use, and muscle symptoms fail to predict its development. STUDY POPULATION: A prospective, convenience sample of patients presenting to the emergency department of a large inner-city hospital with complaints related to cocaine use were eligible for inclusion. Patients were excluded if they had other potential causes of elevated creatine kinase (CK) levels or rhabdomyolysis. A control group comprised patients who were not cocaine users and satisfied the exclusion criteria. Sixty-eight patients were studied. METHODS: Initial evaluation included determination of the presence of muscle pain or swelling and total CK levels. Patients with a CK level of more than 800 U/L had additional tests, including a urine myoglobin, urine drug screen, and serum phosphorus. Rhabdomyolysis was defined by a serum CK level of more than 1,000 U/L (more than fivefold that of normal). CK levels were compared by two-tailed Student's t test. Muscle symptoms were compared with the development of rhabdomyolysis by Fisher's exact test. RESULTS: The CK level in the cocaine group was 931 +/- 1,785 U/L (mean +/- 1 SD). The CK level in the control group was 242 +/- 168 U/L (P = .028). Of the cocaine users, 24% (eight of 34) had rhabdomyolysis; one developed multiorgan failure and died. No patient in the control group had a CK level of more than 1,000 U/L. Only one cocaine user who developed rhabdomyolysis had muscle symptoms. Three cocaine users had muscle symptoms but did not develop rhabdomyolysis. No patient in the control group had muscle symptoms or developed rhabdomyolysis. Muscle symptoms did not predict the CK level (P = .55). CONCLUSION: This study revealed that 24% of the cocaine users had rhabdomyolysis. Many of the cases of rhabdomyolysis were not predictable from history or physical examination, making laboratory evaluation essential. 
4	Hypertension in African-Americans. A considerable disparity exists between African-Americans and US Caucasians in the incidence, severity, and management of hypertension. As a consequence, overall hypertension-related morbidity and mortality rates are at least threefold to fivefold higher in African-Americans than in Caucasians. Alarmingly high frequencies of stroke, end-stage renal disease, congestive heart failure, and left ventricular hypertrophy occur in African-Americans. To bring this crisis under control will require a renewed commitment to expanded research, improved public health measures, and more effective clinical intervention. Current hypertension control programs must be expanded and adequately funded. In addition, primary prevention of hypertension should be strongly recommended for the US population, especially African-Americans. 
5	Synchronous diffuse well-differentiated lymphocytic lymphoma and gastric adenocarcinoma presenting as splenomegaly and iron deficiency anemia. Diffuse well-differentiated lymphocytic lymphoma (D-WDLL) and chronic lymphocytic lymphoma (CLL) represent closely related neoplasms which may have indolent courses. Dating back more than one century, reports of associated second primary malignancies continue to intrigue clinicians. A case of synchronous D-WDLL and gastric adenocarcinoma, presenting as splenomegaly and iron deficiency anemia, is presented. The case and literature are reviewed. 
2	Rapid induction of hepatic fibrosis in the gerbil after the parenteral administration of iron-dextran complex. The parenteral administration of iron-dextran complex to gerbils caused hepatic hemosiderosis and fibrosis after 6 wk. Type I and III collagen synthesis in the liver developed from perisinusoidal stellate cells that are often referred to as myofibroblasts. Immunohistologically these cells were shown to have large intracellular deposits of ferritin. The hepatic fibrosis appeared to be associated with aggregates of these cells rather than the aggregates of Kupffer cells, which also occur in hemosiderosis in the liver. No appreciable necrosis of hepatocytes to trigger the fibrotic response was found, so that the fibrosis appeared to be related to the accumulation of ferritin in the perisinusoidal stellate cells. In contrast, rats and mice did not accumulate ferritin in their perisinusoidal cells or develop hepatic fibrosis in response to parenterally administered iron, although they accumulated similar or greater amounts of total iron in their livers. The rapid induction of hepatic fibrosis in gerbils in response to parenterally administered iron will provide a model to investigate the mechanism of induction of collagen deposition in response to iron overload and a means of quickly evaluating therapeutic treatments for iron overload-induced fibrosis in vivo using iron-chelating drugs. 
3	Hypoglycemia, hypotonia, and cardiomyopathy: the evolving clinical picture of long-chain acyl-CoA dehydrogenase deficiency. Inherited defects in fatty acid oxidation, which have been described and diagnosed with increasing frequency in the last decade, are most commonly attributed to a deficiency in the activity of medium-chain acyl-CoA dehydrogenase. Few cases of the related enzyme defect of long-chain acyl-CoA dehydrogenase activity have been reported. An infant with documented long-chain acyl-CoA dehydrogenase deficiency is described with a detailed metabolic profile, long-term clinical follow-up, and response to treatment. This patient is compared with the seven previously published cases of this disorder in order to stress the unique features of the initial presentation, more subtle late manifestations of the disease, and clinical and biochemical differentiation from the more common medium-chain acyl-CoA dehydrogenase deficiency. This report stresses the enlarging spectrum of the clinical presentation and natural history of this defect in fatty acid oxidation. 
1	"Moustache" appearance in craniopharyngiomas: unique magnetic resonance imaging and computed tomographic findings of perifocal edema. This report describes two cases of craniopharyngioma with perifocal edema. In both patients, computed tomography and magnetic resonance imaging (MRI) revealed that the tumors occupied the suprasellar cistern, invaginated the floor of the 3rd ventricle and were tightly adherent to the ventricular walls. The intraventricular portions of the tumors were cystic, containing protein-rich fluid as suggested by MRI and confirmed by operative findings. There was perifocal edema in the hypothalamus adjacent to the intraventricular tumor, the optic tracts, and the posterior limbs of the internal capsules, resembling the shape of a moustache on axial computed tomographic and MRI scans. The perifocal edema subsided after treatment of the intraventricular tumor by surgical resection or radiation therapy. The "moustache" appearance seems a unique, characteristic feature of perifocal edema, which is observed infrequently with certain craniopharyngiomas. 
5	Traumatic rupture of the aorta--critical decisions for trauma surgeons. The diagnosis and initial stabilization of patients with traumatic rupture of the aorta (TRA) is performed by trauma surgeons. The resuscitations of 54 TRA patients at a Level I trauma center are reviewed. Although the survival of patients who underwent attempted repair was good (75%), 21/27 (78%) deaths occurred during phases of treatment controlled by a trauma surgeon. The techniques and sequencing of resuscitation can affect outcome. Pneumatic antishock garments were not beneficial in the prehospital setting for patients with TRA. In fact, PASG were on and inflated in all patients who presented in cardiac arrest. Awake, unanesthetized intubation caused fatal aortic rupture in three patients. Pharmacologic control of blood pressure during intubation is necessary. The amount of fluid, blood transfusion, and changes in blood pressure secondary to therapy did not statistically affect outcome. The average time from arrival in the ER to angiogram was 64.7 minutes. The average time ER to operating room was 159.7 minutes. Seven cases of TRA had delayed diagnosis usually for a misinterpreted CXR (5/7). Delay in diagnosis did not directly contribute to any deaths. Associated abdominal injuries are a common cause of preventable deaths. Fourteen patients with combined abdominal injuries and TRA were identified. Four of six deaths occurred with potentially reparable injuries. Operative and diagnostic sequences must be adjusted to allow rapid control of all potentially fatal injuries. 
5	The value of routine preoperative laboratory testing in predicting postoperative complications: a multivariate analysis. The purpose of this study was to evaluate the ability of preoperative laboratory testing to predict postoperative complications. Five hundred twenty patients undergoing elective surgery had their American Society of Anesthesiologists' classification, ponderal index, electrolyte values, glucose levels, blood urea nitrogen/creatinine values, complete blood counts, coagulation studies, total protein/albumin/lymphocyte count, electrocardiogram, chest radiograph, urinalysis, pulmonary function tests, type of anesthesia, and type of operation recorded preoperatively. Patients were followed prospectively after surgery for the development of complications. The data were analyzed by univariate and multivariate methods. Postoperative complications were strongly associated with American Society of Anesthesiologists' classification, type of anesthesia, and type of operation. However, only a few laboratory tests, such as electrocardiogram, chest radiograph, and nutritional status, were associated with postoperative complications. Therefore, in general, preoperative laboratory testing should only be undertaken for specific indications. Recommendations for routine tests are made depending on the age of the patient. 
1	Serologic determinants of survival in patients with squamous cell carcinoma of the head and neck. Specific circulating serum proteins may reflect unique properties governing the growth and progression of head and neck cancers. One hundred three previously untreated patients with squamous cell carcinoma of the head and neck were prospectively evaluated for serum IgA, IgG, and IgM and C1q-binding macromolecules. Immunoglobulins were assessed by the immunoturbidimetric technique. C1q-binding macromolecules (C1qBM) were measured utilizing the iodine-125 assay of Zubler et al (J Immunol 1976; 116: 232-5). Neither the level of serum immunoglobulins nor C1qBM values were correlated with the primary site, AJC (American Joint Committee on Cancer) stage of disease, or size of primary lesion. Likewise, comparison of serum IgA with C1qBM values demonstrated that these laboratory parameters were independent variables (r = 0.15 by Pearson linear regression). Univariate statistical analysis, utilizing the Cox proportional hazard model, showed serum IgA and C1qBM values to each contribute significantly to the ability to predict survival in patients with advanced squamous cell carcinoma of the head and neck (p = 0.01 and 0.003, respectively). Furthermore, multivariate analysis reveals that both C1qBM and serum IgA levels contribute significantly to the hazards model beyond staging in predicting survival (p less than 0.001). Predictive results were most apparent in patients with stage IV disease and related to the probability of both regional and distant metastatic recurrences. Conversely, serologic analysis provided no information in patients who were staged early. These results support pretreatment multiparametric serologic analysis of patients with squamous cell carcinoma of the head and neck. 
5	Penetrating injuries to the stomach. The charts of 298 consecutive patients with penetrating gastric injuries were reviewed. Mechanisms of injury were gunshot wounds in 167, stab wounds in 107 and shotgun wounds in 24. Twenty-eight patients died within 24 hours and 27 patients had serosal injuries. These patients were excluded from the study. The morbidity of gastric injury was defined in 243 patients. The probability of morbidity from the gastric wound was assessed by a multivariate analysis of 11 factors, including number of associated injuries, amount of contamination, age, mechanism of injury, shock, thoracostomy tube, injury to operation time, operative time, blood replacement and injury to the diaphragm or colon. Extensive complications developed in 65 patients. Eleven patients died. The gastric injury was directly associated with 15 extensive complications: ten instances of empyema after gastric and diaphragmatic injuries, two instances of gastric repair breakdown, gastric repair bleeding requiring exploration, a missed gastric injury and one instance of gastric outlet obstruction. One patient died of sepsis after breakdown of the gastric repair. Complications were statistically associated with age, gunshot wounds and the use of 2 or more units of blood. Other factors did not statistically increase complications. The 12.5 per cent empyema rate (ten of 81 patients) with gastric and diaphragmatic wounds was unexpected, but not statistically significant. Morbidity from penetrating gastric injuries is secondary to technical and infectious complications. Age, mechanism of injury and blood transfusion correlated with morbidity. The increased incidence of empyema suggests consideration of pleural lavage in combined gastric and diaphragmatic injuries. 
4	Hydatid cyst of the interatrial and interventricular septum of the heart. To our knowledge this report describes the first case of a large hydatid cyst involving the full thickness of both the interatrial and interventricular septum of the heart, which was detected at autopsy. The cyst was intact. Clinically, there was complete heart block. 
1	Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues. PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well as nonneoplastic tissues and several endocrine glands and tumors. To characterize the distribution of PLP in human endocrine tissues and tumors, we localized PLP in formalin-fixed paraffin-embedded material using the avidin-biotin-peroxidase technique with polyclonal antisera. Among peptide hormone-producing tissues, PLP was identified in nontumorous adenohypophysis and pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, and adenomatous parathyroids; adrenal medulla and pheochromocytomas; normal pancreatic islets; and endocrine tumors of pancreas, gut, and lung, including small cell carcinomas. In other endocrine tissues PLP was identified in nontumorous thyroid follicular epithelium, colloid nodules, and follicular neoplasms; normal adrenal cortex, adrenocortical adenomas, and carcinomas; nontumorous testicular Leydig cells; normal ovarian granulosa and thecal cells; an ovarian thecoma and a granulosa cell tumor; placental trophoblast; and decidua. These results demonstrate that PLP is localized in many normal and neoplastic endocrine cells, including those not known to influence extracellular calcium homeostasis. The presence of PLP in a variety of endocrine tissues suggests that it may play a local physiological role in the growth or function of endocrine cells. 
3	Tumor-associated neurological dysfunction prevented by lazaroids in rats. The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier permeability and tumor-associated neurological dysfunction was evaluated in a brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2-methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on Days 6 through 10 following implantation. Neurological function and vascular permeability were assessed on Day 10. Methylprednisolone and U-74006F were equally effective at preventing neurological dysfunction compared to the control group (p less than 0.01); U-78517F was slightly less effective than U-74006F and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction. Delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability (p less than 0.006) while U-74006F and U-78517F had no effect on permeability. This suggests that U-74006F and U-78517F prevented tumor-associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries, and that U-74006F or U-78517F could prove useful in the treatment of brain tumors. 
1	Computed tomography-guided fine-needle aspiration of retroperitoneal lymph nodes in gynecologic oncology. Computed tomography-guided fine-needle aspiration was performed on 30 retroperitoneal lymph nodes in 29 patients with gynecologic cancer. There were no serious complications. Review of the cytologic material demonstrated malignant cells in 83% of the aspirates. Because the predictive value of a positive aspirate approaches 100%, therapy for metastatic disease can be initiated in these patients with the need for an open biopsy. Among five aspirates in which malignant cells were not seen, the cellularity of the specimen appeared to be the critical factor determining the predictive value of the aspirate. Whereas neither of two patients with negative aspirates of adequate cellularity has developed recurrent disease, two of three patients with hypocellular negative aspirates have. Because a hypocellular negative aspirate from a retroperitoneal lymph node may not be a true reflection of disease status, either repeat aspiration or open biopsy is advisable. 
4	The role of beta-blockade therapy for ventricular tachycardia induced with isoproterenol: a prospective analysis. Isoproterenol is sometimes required for ventricular tachycardia (VT) induction. However, the role of beta-blockade for treatment of such VT has not been critically assessed. The use of beta-blockade was evaluated prospectively in 14 consecutive patients who required isoproterenol 2.4 +/- 1.3 (+/- S.D.) micrograms/min to induce sustained monomorphic VT (greater than 30 seconds, or requiring termination due to hemodynamic collapse) after a negative baseline study. The VT mechanisms were enhanced automaticity (group A, six patients), triggered automaticity (group B, three patients), and reentry (group C, five patients). Groups A and B had serial intravenous electropharmacologic tests with propranolol alone (0.2 mg/kg), verapamil alone (0.15 mg/kg), and propranolol plus verapamil, and group C had serial tests with propranolol alone, procainamide or quinidine (class Ia drug) alone, and propranolol plus a class Ia drug until VT could no longer be induced. All six patients in group A responded to propranolol alone. In group B, one patient responded to verapamil alone, and two patients responded to propranolol plus verapamil. In group C, three patients responded to propranolol alone, one patient responded to a class Ia drug alone, and one patient responded to propranolol plus a class Ia drug. During a follow-up of 7 to 37 (17.9 +/- 10.7) (+/- S.D.) months, VT has not recurred in any patient. Three patients treated initially with propranolol alone have required substitution of amiodarone due to refractory congestive heart failure. In patients requiring isoproterenol for VT induction, beta-blockade alone appears to be effective in preventing reinduction of VT caused by enhanced automaticity. A heterogeneous response occurs when the VT mechanisms are triggered automaticity or reentry. 
4	Endogenous vasopressin supports blood pressure and prevents severe hypotension during epidural anesthesia in conscious dogs. To evaluate whether, and to what extent, release of endogenous vasopressin supports blood pressure when efferent sympathetic drive is blocked by epidural anesthesia, the authors studied the effects of high epidural anesthesia alone and when vasopressin was prevented from acting at its vascular (V1)-receptor in six awake, trained, unsedated dogs. On different days, the same dose of 0.5% bupivacaine (8-13 ml) was injected epidurally in a randomized fashion either in the presence or absence of (V1)-vasopressin receptor blockade, and the effects were evaluated on cardiovascular (arterial blood pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, and on plasma concentrations of vasopressin and renin. Results were also contrasted to those obtained after epidural injection of saline alone (placebo) in the same dogs. When endogenous vasopressin was prevented from acting by intravenous pretreatment with a specific V1-receptor antagonist (beta-mercapto-beta, beta-cyclopenta-methylene-propionyl-O-Me-Tyr-Arg-Vasopressin), epidural anesthesia resulted in a rapid and sustained 35% decrease in mean arterial blood pressure from 92 mmHg +/- 5 SE to 60 mmHg +/- 4. In contrast, only a 14% decrease in mean blood pressure from 92 mmHg +/- 5 to 79 mm Hg +/- 6 was noted after epidural anesthesia alone. This difference between groups was statistically significant (P = 0.0001). The V1-receptor blockade alone had no detectable effect. Vasopressin plasma concentrations significantly increased from 3.4 +/- 0.3 pg.ml-1 to 16.2 +/- 3.2 pg.ml-1 after epidural anesthesia but did not change after epidural saline. 
3	Nerve growth factor prevents toxic neuropathy in mice. Taxol is a promising new antitumor drug with therapeutic use that is limited by a toxic sensory neuropathy. Taxol is also cytotoxic to dorsal root ganglion neurons in vitro, but this effect is prevented by cotreatment with the trophic protein, nerve growth factor. We sought to develop an animal model and then to determine whether nerve growth factor can prevent taxol neuropathy in vivo. Administration of taxol to mice resulted in a profound sensory neuropathy characterized by decreases in dorsal root ganglion content of the peptide neurotransmitter, substance P, elevated threshold to thermally induced pain, and diminished amplitude of the compound action potential in the caudal nerve. Coadministration of nerve growth factor prevented all of these signs of neurotoxicity. These findings suggest that administration of nerve growth factor may prevent certain toxic sensory neuropathies. 
2	Gastric antral vascular ectasia ("watermelon stomach"): radiologic findings. Radiologic findings in a patient with gastric antral vascular ectasia are described on computed tomographic scans, upper gastrointestinal series, and specimen radiographs. Findings include prominent, scalloped antral folds radiating to the pylorus and thickening of the gastric antrum. Pathognomonic red vascular folds, likened to stripes on a watermelon, can be seen endoscopically. 
3	The relationship of antibody levels to the clinical spectrum of human neurocysticercosis. One hundred proven cases of cerebral cysticercosis were studied with an enzyme linked immunoassay (ELISA) employing cyst fluid as antigen, with a view to detecting specific antibodies in serum and cerebrospinal fluid (CSF). Antibody levels were correlated with the clinical presentation of the patients, the type and number of cysts detected on their brain scans, the anatomical position of these cysts and the presence of lymphocytes in the CSF. Patients could be divided into two distinct categories, one with low levels of antibody in the serum and absent antibody in the CSF, and the other with high levels in both the serum and the CSF. This differentiation matched the clinical presentation of a benign and a malignant group. Antibody levels could not be related to the type of cysts as observed on the brain scan, but depended on the anatomical position of the cyst, being lower if the cysts were confined to the cerebral cortex. A correlation of antibody levels with the number of cysts was only found in the benign group. 
2	Etiology and mechanisms of acute infectious diarrhea in infants in the United States. Infectious diarrhea, caused by a wide variety of viral, bacterial and parasitic pathogens, is a common reason for morbidity and hospitalization for children in the United States. Overall, rotavirus is the most common cause of acute diarrheal disease in infants. Salmonella, Shigella, and Campylobacter are the most frequently isolated bacterial pathogens, and Giardia and Cryptosporidium are the parasites that most commonly produce acute infectious diarrhea. The mechanisms by which these enteropathogens cause diarrhea are highly variable, and include crypt cell proliferation, cellular invasion, elaboration of enterotoxins or cytotoxins, and enteroadhesion. In infants the incidence of diarrheal disease is higher and the severity of the illness is greater than in older children and adults. An increased rate of exposure to enteropathogens, as a result of fecal-oral contamination, may explain some of the increased incidence of diarrhea in infants. However, age-specific differences in host defense mechanisms may also account for the increased susceptibility to and severity of certain enteric infections in infants. 
4	Use of technetium-99m sestamibi to determine the size of the myocardial area perfused by a coronary artery. The value of the new radionuclide tracer, technetium-99m (Tc-99m) sestamibi, to demonstrate myocardial perfusion in areas supplied by specific coronary arteries was evaluated in patients injected with the agent during cardiac catheterization. Tc-99m sestamibi differs from thallium-201 in its physical characteristics (photon energy 140 keV), half-life (6 hours) and lack of significant redistribution, allowing its administration during an episode of chest pain or ischemia occurring outside the nuclear medicine laboratory with later imaging to visualize the distribution. In 13 patients Tc-99m sestamibi was administered intravenously during balloon-occlusion angioplasty. In 11 of 13 patients, defects of the single photon emission computed tomography images corresponded to the area made ischemic during angioplasty. In the remaining 2 patients, abundant collateral flow was present and no defects were seen. In a second study, 15 patients had Tc-99m sestamibi selectively injected into a coronary artery during angiography. Later imaging identified the area supplied by the artery injected. Tc-99m sestamibi imaging can detect perfusion defects associated with short episodes of ischemia, and the area supplied by the different coronary arteries. 
3	Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients To explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system (CNS) lesions associated with acquired immunodeficiency syndrome (AIDS), the authors retrospectively examined the radiographic studies of 149 AIDS patients who presented with signs and symptoms of the three most common focal CNS lesions. Of these patients, 74 (50%) had Toxoplasma abscesses, 45 (30%) had primary CNS lymphoma, and 30 patients (20%) had progressive multifocal leukoencephalopathy (PML). Magnetic resonance (MR) imaging was more sensitive than computerized tomography (CT) in detecting lesions, especially in cases of PML. Whereas CT was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma, 71% of the solitary lesions seen on MR images were lymphomas. These results indicate that empirical treatment for toxoplasmosis, the most common initial treatment for AIDS patients with neurological symptoms stemming from mass lesions, is not likely to be successful for patients with solitary lesions on MR images. Rather, early biopsy is advisable. If the presence of lymphoma is confirmed, the rapid initiation of treatment can allow prolonged high-quality survival. 
4	Intraabdominal hemorrhage as a result of segmental mediolytic arteritis of an omental artery: case report. This article describes the fifth reported case of segmental mediolytic arteritis and the second in a survivor. The patient had intraabdominal bleeding as a result of a ruptured omental artery. The pathologic and arteriographic findings are described. The pathology is characterized by segmental disruption of the medial smooth muscle cells and the initiation of mediolysis. Mediolysis is associated with marked segmental thinning of the vessel wall, often with only the adventitia intact. Fibrin is deposited at the adventitial and medial surfaces, and hemorrhage into the media may occur. As in this reported case, lysis of the adventitia leads to sudden, often catastrophic intraabdominal hemorrhage. Little associated adventitial inflammation occurred. Segmental mediolytic arteritis seems to involve the intra-abdominal muscular arteries in elderly patients with nonspecific abdominal symptoms. An angiogram showed patchy areas of narrowing involving ileal, gastroduodenal, and renal arteries that correlated with the pathologic findings observed in the excised omental arteries. 
5	Raf-1 protein kinase is required for growth of induced NIH/3T3 cells. Many growth factors regulate the cytoplasmic Raf-1 protein kinase, consistent with its having a central role in transduction of growth signals. The kinase is ubiquitously expressed and can promote proliferation, presumably in a manner dependent on growth-factor receptors and membrane-associated oncogenes. We have now examined the dependence of serum- and TPA (12-O-tetradecanoylphorbol-13-acetate)-regulated NIH/3T3 cell growth on RAF-1 kinase to determine whether Raf-1 is essential for receptor signalling. We inhibited Raf-1 function by expressing c-raf-1 antisense RNA or kinase-defective c-raf-1 mutants. Antisense RNA for c-raf-1 interferes with proliferation of normal NIH/3T3 cells and reverts raf-transformed cells. In revertant cells, DNA replication induced by serum or TPA was eliminated or reduced proportionately to the reduction in Raf protein levels. Expression of a kinase-defective Raf-1 mutant (craf301) or a regulatory domain fragment (HCR) inhibited serum-induced NIH/3T3-cell proliferation and raf transformation even more efficiently. Inhibition by antisense RNA or craf301 blocked proliferation and transformation by Ki- and Ha-ras oncogenes. We conclude that raf functions as an essential signal transducer downstream of serum growth factor receptors, protein kinase C and ras. 
2	Glucose polymers as an alternative to glucose in oral rehydration solutions. Several issues involving glucose-based oral rehydration therapy may limit its acceptability and sustained use. Our studies suggest that defined short-chain glucose polymers (2 to 9 glucose units) are hydrolyzed and absorbed faster than isocaloric solutions of D-glucose in the small intestine of the rat. Glucose polymers, primarily from rice-based solutions, have been shown to be as effective as glucose-based solutions. They offer additional advantages in reducing the amount and duration of diarrhea with lesser volumes of solution, thereby reducing the costs of treatment. Rice-based solutions provide high caloric density and increase the absorption of sodium without an osmotic overload. The result is increased net absorption of glucose, sodium, and water. Glucose polymers from rice or other starches in oral rehydration solutions may be effective, inexpensive, easily used, and safe treatments for acute diarrhea. 
4	Value and limitations of proximal jet dimensions for the quantitation of valvular regurgitation: an in vitro study using Doppler flow imaging. To evaluate usefulness and limitations of proximal jet dimensions for the quantitation of valvular regurgitation, fluid jets were created in a pulsatile flow model, and proximal jet width and cross-sectional area were measured by means of color Doppler flow imaging. When circular orifices with diameters from 1 to 6 mm were studied, jet width and cross-sectional jet area measured as close as possible to the orifice were directly related to the orifice diameter (r = 0.97; standard error of the estimate, 0.4 mm; y = 0.5 + 0.97x) and the orifice area (r = 0.97; standard error of the estimate, 5.7 mm2; y = 0.22 + 2.47x), respectively. No significant dependence on flow rate or pressure gradient was found for these measurements. Jet width was measured with color M-mode Doppler by use of the smallest sample volume size (1 mm) and was slightly greater than the orifice diameter (4.2 +/- 1.7 mm versus 3.8 +/- 1.7 mm). However, cross-sectional areas were approximately fourfold the orifice areas, on average (52.5 +/- 24.6 mm2 versus 12.3 +/- 9.7 mm2), with a range of twelvefold (smallest orifice) to threefold (largest orifice). When the sample volume size was reduced from 2.4 to 1.0 mm, color areas decreased by 25.6 +/- 6.0%. Slit-shaped orifices were studied with two different orientations of the slit-parallel and perpendicular to the ultrasound beam: Color M-mode measurements were again slightly greater than length and width of the slit, but cross-sectional areas were substantially larger than the orifice areas and increased between 44% and 115% when changing the orientation of the slit from perpendicular to parallel. This, again, reflected problems with lateral resolution. When cross-sectional areas were measured at increasing distances from the orifice, the cross-sectional jet area increased significantly within a few millimeters. This increase was greater with higher gradients and smaller orifice sizes. In case of a small orifice (2 mm) and a high gradient (130 to 160 mm Hg), increase in area was as great as 122% within a distance of only 5 mm. Thus, proximal jet width and cross-sectional area were directly related to the orifice size, which could be a valuable parameter for the evaluation of valvular regurgitation. Measurements of jet width by color M-mode seemed to be most accurate but are limited by the fact that in vivo valvular defects may be irregular rather than of circular shape.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. Coronary artery anomalies were found in 1,686 patients (1.3% incidence) undergoing coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988. Of the 1,686 patients, 1,461 (87%) had anomalies of origin and distribution, and 225 (13%) had coronary artery fistulae. Most coronary anomalies did not result in signs, symptoms, or complications, and usually were discovered as incidental findings at the time of catheterization. Eighty-one percent were "benign" anomalies: 1) separate origin of the left anterior descending and circumflex from the left sinus of Valsalva; 2) ectopic origin of the circumflex from the right sinus of Valsalva; 3) ectopic coronary origin from the posterior sinus of Valsalva; 4) anomalous coronary origin from the ascending aorta; 5) absent circumflex; 6) intercoronary communications; and 7) small coronary artery fistulae. Other anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias, congestive heart failure, or sudden death. Potentially serious anomalies include: 1) ectopic coronary origin from the pulmonary artery; 2) ectopic coronary origin from the opposite aortic sinus; 3) single coronary artery; and 4) large coronary fistulae. Coronary artery anomalies require accurate recognition, and at times, surgical correction. 
3	Interstitial cystitis: successful management by increasing urinary voiding intervals. A variant of the interstitial cystitis (IC) syndrome, minimal or no pain or significant pain that has been lessened by another therapy, can be clinically improved by retraining of the individual's voiding pattern. Patients with greater pain but capable of completing this protocol also may be helped. While this group of patients fills the diagnostic criteria of IC and has many of the classic changes, many differ in that they have minimal or no pain, while simultaneously they have a dysfunctional bladder as expected from long-term low-volume voiding. All patients were placed on a protocol which focused on progressively increasing intervals between voids. Fifteen to thirty minutes initially were added to their present voiding time. The same increase was added to the voiding pattern every three or four weeks until an interval of three to four hours between voids was achieved. Twenty-one patients fit the criteria to be entered into this study. Overall 71 percent (15/21) had successful management of their symptoms and reported a 50 percent decrease in their symptoms of urinary urgency, frequency, and nocturia. Nineteen percent (4/21) reported 25 percent decrease in symptoms and 10 percent had no change. Presence of significant pain adversely affects outcome, 3/7 (with pain) improvements versus 12/14 (without pain). For all patients there was a significant increase in bladder capacity (92 mL average before study and 179 mL after) and average daily voids (13.2/day prestudy and 7.4 post-therapy). These differences in voided profiles were statistically significant (p value less than 0.01). 
5	A prospective analysis of intramuscular meperidine, promethazine, and chlorpromazine in pediatric emergency department patients. STUDY OBJECTIVE: To examine physiologic responses and efficacy of 2, 1, and 1 mg/kg IM meperidine, promethazine, and chlorpromazine (MPC), respectively, in children. DESIGN: Prospective, unblinded trial. SETTING: A university and community emergency department. PATIENTS: Sixty-three hemodynamically and neurologically stable children. INTERVENTION: Single dose of IM MPC. MEASUREMENTS AND MAIN RESULTS: Serial respirations, heart rate, arterial systolic blood pressure, oxygen saturation, and Glasgow Coma Scale were measured at 30-minute intervals. Effectiveness was assessed by two independent observers using separate visual analog scales for cooperation and sedation. Times to sleep (27 +/- 24 minutes), sitting upright (103 +/- 87 minutes), ED discharge (4.7 +/- 2.4 hours), eating (11 +/- 7.9 hours), and normal behavior (19 +/- 15 hours) were acceptable. Minor, but statistically significant, changes in respiration rate (-1.9 +/- 0.4), heart rate (+4.5 +/- 1.8), oxygen saturation (-0.7 +/- 0.3%), and Glasgow Coma Scale (-2.5 +/- 0.6) occurred for 120 minutes after MPC. No serious complications or resuscitation were required. Mean visual analog scale scores were 5.0/10.4 or more in 71% of cases, with interobserver agreement very good (cooperation, r = .79; effectiveness, r = .80). Twenty-nine percent of children were judged insufficiently sedated. CONCLUSION: IM MPC is a safe and generally effective agent for ED procedures in selected children. 
2	Efficacy of octreotide acetate in treatment of severe postgastrectomy dumping syndrome. The present study evaluates the acute and chronic use of a long-acting somatostatin analog, octreotide acetate, in the treatment of patients with severe postgastrectomy dumping syndrome. In the acute phase, 10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a 'dumping breakfast' in a randomized double-blind fashion. On one day octreotide (100 micrograms) was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected. An additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls. During placebo treatment the test meal resulted in an immediate increase (p less than 0.01) in the pulse rate and in plasma levels of glucose, glucagon, pancreatic polypeptide, neurotensin, and insulin. Similar changes were seen in the control group with respect to placebo; however glucagon and neurotensin (p less than 0.05) did not show the same magnitude of increase as seen with placebo. Treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides. These changes were associated with complete ablation of diarrhea (p less than 0.001). Pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping. Treatment with octreotide acetate resulted in delayed gastric emptying and transit time (578 +/- 244 minutes) versus 76 +/- 23 minutes with placebo and 125 +/- 36 minutes in controls (p less than 0.05). Chronic daily treatment with octreotide acetate resulted in minimal side effects. These patients demonstrated a stable fasting plasma glucose, normal liver function tests, and an average weight gain of 11% during a 12-month period. In addition most patients were able to resume employment. The long-acting somatostatin analog, octreotide acetate, is highly effective in preventing the development of symptoms of severe dumping syndrome, both vasomotor and gastrointestinal. 
5	Organ hypertrophy and responses of colon microbial populations of growing swine to high dietary protein. Thirty-two castrated male crossbred growing pigs (average initial wt 26.9 kg) were used to determine the effect of a high level of dietary protein (37%) compared with a normal level of protein (15%) on enterobacteria and Campylobacter sp. inhabitation in the large intestine and on visceral organ hypertrophy and the interrelationships between these two factors. Pigs were kept in pairs (eight pens of two pigs/diet) and fed their respective diets and libitum. Eight pigs (two pens of two pigs fed each diet) were killed at wk 4, 8, 12 and 16 without fasting. Fecal samples were obtained every 2 wk from animals scheduled for necropsy at 16 wk, and colon contents were obtained from all pigs at necropsy; samples were enumerated individually for enterobacteria and Campylobacter sp. Weights of heart, lungs, liver, kidneys, perirenal fat and empty stomach, small intestine and large intestine were recorded at necropsy. Stomach, cecum and proximal colon were sectioned for histopathologic examination. Daily body weight gain was depressed by high dietary protein, but liver and kidneys were heavier in the high protein group than in controls at each time interval. Mild lymphoid hyperplasia of Peyer's patches in the small intestine in some pigs in both groups was indicative of antigenic stimulation but not of pathologic significance. There was no effect of diet on counts of enterobacteria or Campylobacter sp. in feces or colon contents during the 16-wk experiment. We conclude that the hypertrophic response of the tissues of growing pigs to high dietary protein is not the result of the presence of Campylobacter sp. or enterobacteria in the colon contents. 
5	Effects of local reduction in pressure on distensibility and composition of cerebral arterioles. This study examined effects of local reductions in mean and pulse pressures on cerebral arterioles in normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). WKY and SHRSP underwent clipping of one carotid artery at 1 month of age. At 10-12 months of age, mechanics of pial arterioles were examined in vivo in anesthetized rats. Bilateral craniotomies were performed to expose pial arterioles in the sham and clipped cerebral hemispheres. Stress-strain relations were calculated from measurements of pial arteriolar pressure (servo null), diameter, and cross-sectional area of the arteriolar wall. Point counting stereology was used to quantitate individual components in the arteriolar wall. Before deactivation of smooth muscle with EDTA, mean (Pm) and pulse (Pp) pressures were significantly less (p less than 0.05) in clipped than in sham arterioles in WKY (Pm, 63 +/- 2 versus 73 +/- 2 mm Hg; Pp, 23 +/- 3 versus 30 +/- 3 mm Hg) and SHRSP (Pm, 94 +/- 4 versus 110 +/- 4 mm Hg; Pp, 27 +/- 2 versus 38 +/- 3 mm Hg). Cross-sectional area of the arteriolar wall was less (p less than 0.05) in clipped than in sham arterioles in both groups of rats (1,403 +/- 125 versus 1,683 +/- 125 microns2 in WKY; 1,436 +/- 72 versus 1,926 +/- 134 microns2 in SHRSP). There was a correlation between cross-sectional area of the vessel wall and pulse pressure (r2 = 0.66), but not mean pressure (r2 = 0.09). During maximal dilatation with EDTA, the stress-strain curve was shifted to the left in clipped arterioles of SHRSP, but not of WKY, which indicates that carotid clipping in SHRSP reduces passive distensibility of cerebral arterioles. The proportion of distensible components in the vessel wall (smooth muscle, elastin, and endothelium) was reduced in clipped arterioles in SHRSP, but not in WKY. These findings suggest that 1) vascular hypertrophy of cerebral arterioles is related more closely to pulse pressure than to mean pressure, and 2) reduction of pial arteriolar pressure completely prevents cerebral vascular hypertrophy and attenuates increases in passive distensibility of cerebral arterioles in SHRSP. 
1	Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience with 42 cases. Before surgery, 12 patients with suspected leiomyoma and 12 patients with suspected leiomyosarcoma were studied by endoscopic ultrasonography (EUS), computed tomography (CT), endoscopy, and barium swallow. The results were correlated with surgery and histology. Ten leiomyomas, one benign gastric ulcer, one carcinoid metastasis, eight leiomyosarcomas, two leiomyoblastomas, one mucus secreting adenocarcinoma, and one bronchial carcinoma were diagnosed. Eighteen additional patients suspected to have benign submucosal lesions by endoscopy and barium meal were treated non-surgically, and studied by EUS and CT. EUS was superior to other imaging techniques in the detection, staging, and follow-up of submucosal smooth muscle tumors because of clear imaging of the intramural abnormality and adjacent lymph nodes. 
5	Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram. 
4	The determination of aortic valve area by the Gorlin formula: what the cardiac sonographer should know. The application of the Gorlin formula in the cardiac catheterization laboratory is the standard of reference for the determination of aortic valve area. The continuity equation now enables the cardiac sonographer to determine aortic valve area noninvasively in the echocardiography laboratory. The comparison of the results obtained by the two methods is inevitable. The cardiac sonographer should have a basic understanding of the theory and pitfalls of the Gorlin formula so that when conflicting results are obtained, the possible reasons why will be clear. 
5	Otological manifestations of a new familial polyostotic bone disorder. Fifty members of a family with a unique autosomal dominant bone disease were investigated. Nineteen of the family members were either known to have, or were strongly suspected of having the disease. All but one of these had a hearing loss which was conductive in the younger age group and mixed in the older members. The common finding in those who had middle ear surgery was replacement of the long process of incus by a fibrous band. The histological features were similar to those found in Paget's disease. The age of onset, distribution of lesions and radiographic findings, however, were not typical of this disorder. 
1	Homeobox gene expression plus autocrine growth factor production elicits myeloid leukemia. In the murine myelomonocytic leukemia WEHI-3B, proviral insertions have induced expression of the Hox-2.4 homeobox gene and the gene for the myeloid growth factor interleukin 3 (IL-3). To assess their potential oncogenic role, normal bone marrow cells were infected with retroviruses bearing the genes for IL-3 or IL-3 plus Hox-2.4. Unlike the IL-3 virus, the IL-3/Hox-2.4 virus was highly leukemogenic. Infected cells expressing both genes exhibited retarded differentiation in vitro, generated myelomonocytic cell lines, and provoked a rapid, transplantable myeloid leukemia in vivo. The oncogenic action of Hox-2.4 appears to derive from its ability to impede the IL-3-driven terminal differentiation of myeloid cells. The results suggest that homeobox genes can regulate key differentiation processes such as self-renewal capacity and that their inappropriate expression can be oncogenic. 
4	Skewflap versus long posterior flap in below-knee amputations: multicenter trial. A multicenter trial of alternative techniques for below-knee amputation is described in which surgeons in 11 centers randomized 191 patients with end-stage occlusive vascular disease to two different methods of stump construction. The skewflap technique was performed in 98 and the long posterior flap was performed in 93. The two groups were well matched in respect to age, sex, smoking, diabetes, and indications for amputation. Early outcome was compared in terms of 30-day mortality rate: skew 11 (11%) deaths versus long posterior flap 16 (17%); the state of the wound at 1 week (primary healing 60% in both groups); the need for surgical revision at the same level 7 (7%) versus 7 (8%), and revision to a higher level 10 (10%) versus 7 (8%). Follow-up information at 6 months was available from records or by mailed questionnaire in 188 (98%) at 6 months, 20 died during that interval. It showed that a prosthetic limb was fitted to 64 (84%) of skew flaps and 50 (77%) of long posterior flaps. Walking, alone or with support, was achieved in 59 (78%) and 46 (71%), respectively. None of these differences reached statistical significance. It is concluded that the skew flap is just as effective as the long posterior flap and is an excellent option for below-knee amputation. 
5	Mycobacterial infection after renal transplantation--report of 14 cases and review of the literature. During a nine-year period, 14 cases of mycobacterial infection (tuberculosis) developed in 403 renal transplant recipients at the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, an incidence of 3.5 per cent. The annual incidence of tuberculosis was about 50 times higher than that in the general population. Infection was disseminated in nine (64.3 per cent), pulmonary in four (28.6 per cent), and genitourinary in 1 (7.1 per cent). In one patient tuberculosis was transmitted by the donor's kidney. The clinical manifestations were often ill-defined and not different from that in the normal host. Cultures from all patients grew Mycobacterium tuberculosis; concomitant infection with other organisms was present in five patients (35.7 per cent). Two of 18 patients (group 1) with positive pretransplant tuberculin skin test developed tuberculosis after transplantation (11 per cent), and neither received isoniazid prophylaxis; three of 70 patients (group 2) with negative skin tests developed tuberculosis after transplantation (4.3 per cent). The difference between the two groups was not statistically significant. Review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases. Tuberculosis was disseminated in 38.7 per cent, pulmonary in 40.2 per cent, cutaneous in 12 per cent, and miscellaneous in 9.4 per cent. Atypical mycobacteria were responsible for 29 per cent of disseminated infections, 8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis. Invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis (p less than 0.0001). The mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent (p less than 0.005). These findings (1) confirm the higher incidence of tuberculosis in renal transplant recipients, compared to the general population; (2) suggest that pretransplant skin testing probably has little value in identifying patients at risk; (3) show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis; (4) confirm that the donor kidney may be an important source of infection; and (5) indicate that concomitant infection with other organisms is common. 
5	Diagnosis of acute rupture of the quadriceps tendon by magnetic resonance imaging. A case report. Quadriceps tendon rupture occurred in a 56-year-old man receiving anticoagulant therapy. The diagnosis was inconclusive until magnetic resonance imaging (MRI) was used to delineate the rupture site clearly. MRI is a useful adjunct to diagnosis of soft-tissue injuries in cases in which swelling or other soft-tissue abnormalities obscure examination or preclude the use of more routine diagnostic modalities. 
3	A new challenge--robotics in the rehabilitation of the neurologically motor impaired. Rehabilitation robotics is a research area, originating in engineering, that has emerged in the last decade. Its broad aim is to use robot technology to assist people with movement dysfunction. The neurologically impaired population might gain considerably from the provision of robots as "assistants" or "therapy aides," but the interface with the machine must match both the physical and intellectual abilities of the user. We therefore consider a multidisciplinary approach, encompassing both behavioral and engineering perspectives, to be essential in achieving this aim. However, to date, published reports have been largely restricted to engineering journals or conference reports, and relatively little has appeared in the therapy literature. This article seeks to introduce physical therapists to robotics, describe possible applications to the rehabilitation of neurologically impaired patients, and suggest issues deserving further investigation. 
4	Clinical and hemodynamic assessment of the hepatojugular reflux. The hepatojugular reflux (HJR) test was studied to assess the ability to clinically predict response during cardiac catheterization and to determine its significance in patients without heart failure and correlate it to their baseline hemodynamic parameters. Sixty-five patients considered to be free of heart failure undergoing routine cardiac catheterization were enrolled. The HJR test, defined as the venous pressure response to sustained abdominal compression, was performed in a standardized manner at the bedside assessing change in internal jugular venous pressure and during right-sided cardiac catheterization measuring change in right atrial pressure. For comparison a sustained increase greater than or equal to 1 cm was considered positive. In 62 of 65 patients the HJR test stabilized by 15 seconds. The results during examination at the bedside agreed with those at catheterization (K = 0.74, p less than 0.001). The HJR test result correlated best with baseline mean right atrial pressure (r = 0.59) and right ventricular end-diastolic pressure (r = 0.51), and in bivariate regression analysis predicted right atrial (F(1,63) = 32.8, R2 = 0.34, p less than 0.0001) and right ventricular end-diastolic (F(1,63) = 22, R2 = 0.26, p less than 0.0001) pressures. A positive test had high sensitivity and specificity for predicting right atrial pressure greater than 9 mm Hg (1.0, 0.85) and right ventricular end-diastolic pressure greater than 12 mm Hg (0.90, 0.89). It is concluded that 15 seconds is adequate for interpretation, and bedside observation predicts the response during right-sided cardiac catheterization. 
1	Elective radical neck dissection in epidermoid cancer of the head and neck. A retrospective analysis of 853 cases of mouth, pharynx, and larynx cancer. A retrospective analysis of 853 patients with cancer of the mouth, pharynx, and larynx operated on over a 30-year period was performed. Four hundred fifty-seven of them had a radical neck dissection (RND) at some point. Five hundred ninety patients had no clinically positive nodes (N-o) necks at the time of primary treatment; 99 of these had elective neck dissection, whereas 95 others had a delayed RND when nodes became clinically involved. Twenty-three percent of all N-o patients had microscopically involved nodes and less than half of these were among those patients selected for elective RND. Furthermore, 58% of those patients who had elective RND did not have positive nodes. Comparative analysis of elective RND, delayed therapeutic RND after clinical appearance of nodes, and composite operations for patients with N1-N3 disease indicates little difference in disease-free survival when the nodes in the elective RND were positive microscopically for tumors (56%, 49% and 47% respectively). It thus seems that elective RND offers no real advantage over a careful watchful waiting approach in most patients. 
4	Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial The Multiple Risk Factor Intervention Trial (MRFIT) is a randomized primary prevention trial that tested the effect of a multifactor intervention program on coronary heart disease (CHD) mortality in 12,866 high-risk men aged 35-57 years. Men were randomly assigned to either a special intervention (SI) program, which consisted of dietary advice for lowering blood cholesterol levels, counseling aimed at cessation for cigarette smokers, and stepped-care treatment for hypertension for those with elevated blood pressure, or to their usual sources of health care within the community (UC). Among the 12,866 randomized men, 8,012 (62%) were hypertensive at baseline. For this subgroup, mortality rates with 10.5 years of follow-up were lower for the SI than for the UC group by 15% (p = 0.19) for CHD and 11% (p = 0.13) for all causes. These results reflected more favorable outcomes for SI compared with UC hypertensive men during the 3.8 posttrial years (March 1982 through December 1985) than during the preceding 6-8 years (through February 1982). During the posttrial years, death rates were lower for SI than for UC men by 26% (p = 0.09) for CHD and 23% (p = 0.02) for all causes. For those with diastolic blood pressure equal to or more than 100 mm Hg, this posttrial trend was a continuation of a trend during the trial; therefore, with 10.5 years of follow-up, death rates were markedly lower for SI than for UC by 36% (p = 0.07) for CHD and 50% (p = 0.0001) for all causes. Similarly, for those without baseline resting electrocardiographic abnormalities, the favorable posttrial outcome for the SI group was a continuation of a trend during the trial. In contrast, for those with baseline diastolic blood pressure of 90-99 mm Hg and for those with baseline resting electrocardiographic abnormalities, the favorable posttrial mortality findings for the SI group were a reversal of unfavorable trends recorded during the trial. Two factors appear to have contributed to this more favorable mortality trend for the SI group: 1) a change in the diuretic treatment protocol for SI men about 5 years after randomization, which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50 mg; and 2) a favorable effect of intervention on nonfatal cardiovascular events during the trial years. In addition, delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed.(ABSTRACT TRUNCATED AT 400 WORDS). 
2	Anorectal function in incontinent patients with cerebrospinal disease. Anorectal manometry and the electrical activity of the external anal sphincter were measured in 20 patients with well-defined, incomplete spinal lesions who were referred because of fecal incontinence and in 30 normal subjects. Six patients had a high spinal lesion, 11 had a low spinal lesion, and 3 had mixed high and low spinal lesions. Patients with high spinal lesions had normal basal pressures but abnormally low squeeze pressures and impaired rectal sensation. Unlike normal subjects, there was no relationship between the depth of sphincter relaxation and the distention volumes. The external sphincter responses to rectal distention and increases in intraabdominal pressure were enhanced, and leakage of perfusion fluid was uncommon. Patients with low spinal lesions had abnormally low basal and squeeze pressures, blunted rectal sensation, and showed impaired external anal sphincter responses to rectal distention or increases in intraabdominal pressures. Most of these patients leaked the infused fluid during these maneuvers. Sphincter function in patients with mixed lesions was more severely impaired than in patients with low and high spinal lesions. Patients with mixed lesions showed abnormally low basal and squeeze pressures, impaired rectal sensation, and no external anal sphincter responses to either rectal distention or increases in intraabdominal pressure. Leakage occurred during these maneuvers in all patients with mixed lesions. 
4	Neurologic complications in chronic renal failure: a retrospective study. We have retrospectively examined 324 patients with chronic renal failure and evaluated the probable underlying causes of neurologic complications, laboratory data and therapeutic interventions. The common neurologic problems in our patients were alterations in consciousness (40.7%) and convulsions (35.1%). When BUN concentration was above 135 mg/dl and creatinine clearance was below 8 m/min/1.73 m2, alteration of consciousness was observed and when BUN concentration was 200 mg/dl and creatinine clearance was below 7 m/min/1.73 m2, abnormal convulsives appeared. Changes in deep tendon reflexes and pathologic reflexes were associated with hypertension. All of the patients with cortical atrophy using computerized cranial tomography aluminum hydroxide at least for 18 months, and six of them had hemodialysis. Fourteen patients who underwent dialysis developed convulsions and were thought to have disequilibrium syndrome. These findings are consistent with the suggestion that the metabolic and biochemical derangements associated with CRF may be particularly detrimental to the still developing CNS of the child. 
3	Occult vascular malformations of the optic chiasm: magnetic resonance imaging diagnosis and surgical laser resection. Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function. 
2	Hepatopathy-thrombocytopenia syndrome--a complication of dactinomycin therapy for Wilms' tumor: a report from the United Kingdom Childrens Cancer Study Group. We have observed hepatopathy, associated with thrombocytopenia, in children receiving chemotherapy for Wilms' tumor. We have studied this hepatopathy-thrombocytopenia syndrome (HTS) in patients enrolled in the United Kingdom Childrens' Cancer Study Group (UKCCSG) Wilms' tumor trials (UKW1 and UKW2). At the time of this study, 501 patients had completed therapy. Treatment flow sheets were examined for evidence of hepatopathy (hepatomegaly with abnormal liver function tests) and severe thrombocytopenia (platelet count less than 25 x 10(9)/L). No child who developed the syndrome had received irradiation. HTS was seen in five of 355 (1.4%) of patients treated with combination chemotherapy but in none of the 146 patients treated with vincristine alone. In each instance, the onset was less than 10 weeks after diagnosis. In two children, hepatopathy was severe with jaundice, ascites, transaminases greater than 1,000 IU/L, and prolongation of prothrombin time. On average, HTS lasted 12 days, and resolved with supportive treatment. After recovery, the children tolerated chemotherapy, mostly at reduced dosage, without recurrence. There was no evident long-term morbidity. Dactinomycin is the probable cause of this syndrome. We conclude that the HTS is a rare but important complication of dactinomycin-containing combination chemotherapy for Wilms' tumor. Children developing "isolated" thrombocytopenia following dactinomycin are "at risk" of developing the full-blown syndrome and should have their treatment modified accordingly. 
1	Brief intensive chemotherapy for metastatic non-small-cell lung cancer: a phase II study of the weekly CODE regimen. Fifty-three patients, 17 with stage IIIB and 36 with stage IV non-small-cell lung cancer, were given CODE (cisplatin, vincristine, doxorubicin, and etoposide) plus antibiotic prophylaxis and an antiemetic regimen in an intensive chemotherapy program emphasizing weekly treatment and a planned brief duration (9-12 weeks); for 45 of these patients, the CODE program also included antifungal prophylaxis and supportive corticosteroids. Of the total study population, 33 patients (62%) responded to treatment, including five (9%) with complete response. The median survival for the entire group was 42 weeks (55 weeks for those with stage IIIB and 39 weeks for those with stage IV). More than 40% were alive at 1 year. Comparison of granulocyte counts of patients receiving prednisone with those of the subgroup to whom no corticosteroids were given showed less granulocytopenia for those receiving prednisone. Use of prednisone thus allowed improved delivery of myelosuppressive drugs. CODE was halted in nine patients because of disease progression. Although more constitutional side effects are associated with weekly chemotherapy than with standard chemotherapy, only 12 of the remaining 44 patients (27%) failed to receive at least 9 weeks of treatment. Serious toxicity was uncommon: There were no treatment-related deaths and only three episodes of neutropenia with fever. CODE is a novel treatment for non-small-cell lung cancer that this pilot study provided entirely in an outpatient setting over a 9-12 week period with an acceptable incidence of toxicity and a promising level of efficacy. Additional testing and comparison with other regimens or supportive care alone are warranted. 
5	Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification. The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both-sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms. 
5	Coagulation factor abnormalities as possible thrombotic risk factors after Fontan operations. Severe thromboembolism occurred in 3 of 37 patients who had undergone Fontan-type operations for correction of congenital heart defects several months to years after the operation. The patients were screened for coagulation factor abnormalities to find out whether known prothrombotic risk factors could explain the high frequency of thromboembolism. 63 abnormalities were found in 24 of the 37 patients. The commonest and most pronounced abnormality was deficiency of protein C, a known risk factor. Concentrations of antithrombin III and factors II and X were significantly lower in protein-C-deficient patients than in those with normal protein C concentrations. These findings suggest that the high thrombotic risk in these patients is caused or at least associated with an imbalance between procoagulant and anticoagulant factors. 
1	Progression of stage T1 bladder tumors after intravesical bacillus Calmette-Guerin [published erratum appears in J Urol 1991 Apr;145(4):840] Of 221 patients with superficial bladder tumors (stages Ta, Tis and T1) treated by transurethral resection and an initial 6-week course of intravesical bacillus Calmette-Guerin (BCG) 195 were evaluated after 3 months for local response. Of these patients 17 (8.7%) had a stage T1 tumor, of whom 14 (82%) subsequently had muscle invasion (7), uncontrolled local disease (6) or metastasis (1). The median interval to progression was 8.4 months, which was significantly (p = 0.0001) less than among the other 178 patients with a nonstage T1 lesion or no tumor found at 3 months, of whom 44 (25%) had progression (median more than 5 years). These data suggest that patients with stage T1 tumor 3 months after BCG therapy require additional therapy other than simple tumor resection and meticulous followup. 
5	Full-thickness skin graft vaginoplasty for treatment of the stenotic or foreshortened vagina. Vaginal stenosis or foreshortening following surgery or radiation therapy can lead to dyspareunia. This report concerns the successful use of full-thickness skin grafts taken from the flank overlying the iliac crest to treat vaginal stenosis or foreshortening. The operation consists of incising the involved area and creating a space which will become the recipient site. An elliptical piece of full-thickness skin harvested from the area overlying the iliac crest is cleared of underlying fat, trimmed to fit the recipient site, and sutured in place. Vaginal packing is used to keep the graft against the recipient bed. Ten patients have been treated successfully with this technique, without significant complications or sequelae. Follow-up from 6 weeks to 42 months showed excellent postsurgical vaginal capacity in all patients. Similarly, excellent functional results were achieved in eight patients, with distinct improvement in the remaining two. This procedure is a useful addition to the gynecologic surgeon's armamentarium. 
4	Acute dissection of the internal mammary artery: a fatal complication of coronary artery bypass grafting. A case of acute traumatic dissection of the right internal mammary artery is presented in a patient who had both IMAs grafted for recurrent angina 10 years after initial vein coronary revascularisation. The event was mistaken for spasm, but because of severe circulatory collapse no time was available to treat the patient appropriately. The purpose of this report is to facilitate the early recognition and avoidance of this potentially fatal complication. 
2	Expression of leukocyte adhesion molecules in the liver of patients with chronic hepatitis B virus infection. Virus-specific T-cell responses are believed to be involved in the pathogenesis of liver cell injury secondary to hepatitis B virus infection. In this study, liver biopsy specimens from patients with chronic hepatitis B virus infection were analyzed for expression of two major pathways of adhesion used by cytotoxic T cells to interact with target cells. The lymphocyte function-associated antigen 3 was found preferentially expressed on hepatocytes of patients with active hepatitis B virus replication, whereas the expression of the intercellular adhesion molecule 1 on hepatocytes seemed more closely related with inflammatory activity. Adhesion molecules were also highly expressed on T lymphocytes found in areas of piecemeal and spotty necrosis, indicating the presence of antigen-specific "memory" T cells at the site of hepatocellular injury. This study suggests that the expression of the lymphocyte function-associated antigen 3 on hepatocytes may be important for viral elimination. The coordinate expression of the intercellular adhesion molecule 1 may regulate inflammatory response and enhance viral antigen presentation to T cells. Conversely, the absence of hepatocyte adhesion molecules might be a favorable factor for viral persistence. 
5	Islet cell carcinoma of the pancreas presenting as bleeding from isolated gastric varices. Report of a case and review of the literature. Gastrointestinal hemorrhage from left-sided portal hypertension and gastric varices is an unusual presentation for islet cell carcinoma of the pancreas. Islet cell tumors of the pancreas themselves are rare. They present in a variety of ways. Those that elaborate functional hormones cause specific neuroendocrine syndromes. Nonfunctional tumors characteristically present later with symptoms of metastatic disease or as a result of local enlargement. We present a case of islet cell carcinoma of the pancreas presenting with recurrent gastrointestinal bleeding from gastric varices and review the literature for this rare presentation. We emphasize the importance of a careful initial diagnostic work-up that may enable curative surgery. 
5	Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Eighteen patients with active pancreatic ductal disruptions, including 14 with definable fluid collections, were treated with transpapillary pancreatic duct drains or stents. Twelve of these patients had undergone a previous percutaneous or surgical pancreatic drainage procedure or both, and 8 had long-term drainage tubes in chronic fistulous tracts. Transpapillary catheters could be placed across the ductal disruption or directly into the fluid collection in each case, and 16 of 18 patients had resolution of the disrupted pancreatic duct. Twelve of 14 fluid collections resolved. Complications were limited to mild exacerbation of pancreatitis symptoms in 2 patients and 2 patients who developed subsequent stent occlusion leading to recurrent pancreatitis (1 patient) or recurrent duct blowout with pseudocyst (1 patient). Nine patients had variably significant ductal changes attributable to pancreatic duct stents. At a median follow-up of 16 months, 7 patients ultimately required surgery for ongoing pancreatic pain or residual/recurrent fluid collection. The transpapillary treatment of ongoing pancreatic ductal disruption with or without fluid collection has the potential to obviate surgery in some patients, change an urgent surgical procedure into an elective one, or even assist the surgeon in the performance of intraoperative pancreatography. Further study of this technique appears warranted and must be placed into the perspective of current therapies. 
5	Would you recognize celiac axis syndrome? Since its original description, celiac axis syndrome has been a topic of debate. Clinical findings include postprandial abdominal pain, weight loss, and an epigastric bruit. Diagnosis is often made by exclusion and is confirmed by lateral aortography. The role of surgery in treating celiac axis syndrome is controversial. 
4	Modification of stroke susceptibility by genotype-dependent maternal influences. The influence of the prenatal and postnatal maternal environment on stroke susceptibility was evaluated by reciprocally crossing the spontaneously hypertensive (SHR) and the Dahl salt-sensitive (SS/Jr) inbred rat strains to produce reciprocal F1 hybrids that were nurtured, respectively, during prenatal and postnatal life by SHR or SS/Jr mothers. Following placement on a high-salt diet containing 8% NaCl at 35 days of age, F1 rats reared by SHR mothers had shorter survival times and were more likely to die with cerebral hemorrhage than F1s reared by SS/Jrs. Across reciprocal F1 female groups, enhanced susceptibility to stroke was associated with greater elevations of systolic blood pressure, but this association was not seen across reciprocal F1 male groups. There was also an association between blood pressure and stroke within each F1/gender subgroup: Rats eventually suffering strokes developed higher blood pressure after placement on the high-salt diet than rats that did not suffer stroke. Lower day 35 body weights (before exposure to the high-salt diet) were associated with greater likelihood of stroke both across the reciprocal F1 groups, and within three of the four F1/gender subgroups. The differences in stroke susceptibility between the reciprocal F1 groupings may be due to systematic differences in the prenatal and/or postnatal environments of SHR and SS/Jr mothers and may be mediated by variations in the nutritive capacity of the two inbred mothers. 
5	Ligamentous laxity across C0-C1-C2 complex. Axial torque-rotation characteristics until failure. The axial torque until failure of the ligamentous occipito-atlanto-axial complex (C0-C1-C2) subjected to axial angular rotation (theta) was characterized using a biaxial MTS system. A special fixture and gearbox that permitted right axial rotation of the specimen until failure without imposing any additional constraints were designed to obtain the data. The average values for the axial rotation and torque at the point of maximum resistance were, respectively, 68.1 degrees and 13.6 N-m. The specimens offered minimal resistance (approximately 0.5 N-m), up to an average axial rotation of 21 degrees across the complex. The torque-angular rotation (T-theta) curve can be divided into four regions: regions of least and steadily increasing resistances, a transition zone that connects these two regions, and the increasing resistance region to the point of maximum resistance. The regions of least and steadily increasing resistances may be represented by two straight lines with average slopes of 0.028 and 0.383 N-m/degree, respectively. Post-test dissection of the specimens disclosed the following. The point of maximum resistance corresponded roughly to the value of axial rotation at which complete bilateral rotary dislocation of the C1-C2 facets occurred. The types of injuries observed were related to the magnitude of axial rotation imposed on a specimen during testing. Soft-tissue injuries alone (like stretch/rupture of the capsular ligaments, subluxation of the C1-C2 facets, etc.) were confined to specimens rotated up to or close to the point of maximum resistance. The specimens that were subjected to rotations up to the point of maximum resistance of the curve spontaneously reduced completely on removal from the testing apparatus. Spontaneous reduction was not possible for specimens tested slightly beyond their points of maximum resistance. 
4	Immunohistochemical study of fibronectin in experimental myocardial infarction. Light microscopic immunohistochemical studies were performed to evaluate the distribution of fibronectin in paraffin sections of p-formaldehyde-fixed normal rat hearts and the hearts of rats that had undergone ligation of the left coronary artery. A peroxidase-labeled antibody technique was used, together with appropriate immunohistochemical control procedures, for the localization of fibronectin in normal hearts and in the hearts of sham-operated animals. Fibronectin was localized in the interstitial space between myocytes, and beneath arterial, venous, and capillary endothelium. At 4 hours after coronary ligation, fibronectin was localized in a patchy fashion in the cytoplasm and interstitial space of some of the myocytes in the area supplied by the ligated vessel. At 24 hours, there was more intense, homogeneous staining in necrotic myocytes in the infarcted area and in the capillary endothelium in the border zone. At 48 hours, the intensity of staining for fibronectin was maximal in and between the necrotic myocytes in the center of the infarct and in proliferating and migrating capillaries and fibroblasts in the border zone. Similar patterns of localization were observed at 3 and 7 days after coronary ligation, but with progressive decreases in the intensity of staining. Two sources of fibronectin appeared to have contributed to these changes: plasma fibronectin diffusing through damaged blood vessels would account for the early staining observed in necrotic myocytes in the center of the infarct, whereas de novo synthesis of fibronectin by connective tissue cells and endothelial cells in sprouting capillaries would be responsible for the subsequent staining observed in viable capillaries in the border zone of the infarct. Known properties of fibronectin in vitro, combined with these in vivo observations, indicate that fibronectin may influence the thrombotic, inflammatory, angiogenic, and fibrotic processes involved in infarct healing. 
2	Benign and malignant nodules in cirrhotic livers: distinction based on blood supply. The blood supplies of nodular lesions associated with liver cirrhosis were analyzed in vivo with various imaging modalities. The portal blood supply was evaluated with computed tomography (CT) during arterial portography (CTAP); the arterial blood supply was evaluated with hepatic angiography, CT angiography, CT following intraarterial injection of iodized oil, or ultrasound following intraarterial injection of carbon dioxide microbubbles. A total of 84 surgically confirmed hepatocellular carcinomas (HCCs) (less than or equal to 3 cm) and 25 areas of adenomatous hyperplasia (AH) were included in the study. At CTAP, a portal blood supply was seen in 96% of cases of AH and only 6% of HCCs (chi 2, P less than .005). In contrast, an arterial supply greater than that of the surrounding liver was verified in 94% of the HCCs and only 4% of the cases of AH (chi 2, P less than .005). The blood supply of areas of AH with atypical hepatocytes and the blood supply of well-differentiated HCCs (Edmondson grade 1) tended to be intermediate between that of AH without atypia and that of HCC that was Edmondson and Steiner grade 2 or greater. Evaluation of the blood supply of the nodular lesions associated with liver cirrhosis is considered to be useful in the differential diagnosis and treatment of early-stage HCC. 
1	Advances in medical imaging for cancer diagnosis and treatment. Over the last several decades, significant "new eyes" have been developed that improve the diagnosis, treatment, planning, and monitoring of human cancer: computer tomography (CT), magnetic resonance imaging (MRI) and spectroscopy (MRS), single photon emission computed tomography (SPECT), and positron emission tomography (PET). Innovative advances in both morphologic and functional imaging have led to a dramatic improvement in our ability to diagnose and monitor human cancer. Frequently, anatomic detail can be demonstrated in ways that exceed views at surgery, and functional biochemical imaging is being used to show the metabolic activity and receptor status of normal and pathologic states. In vivo functional and biochemical studies differentiate normal from neoplastic or nonviable tissue, and make it possible to measure progression or regression of the disease. Because physiologic changes often precede morphologic findings in many disease processes, the use of in vivo biochemical probes can demonstrate disease before anatomic abnormalities become evident. Gross changes in anatomy are no longer adequate endpoints for therapy protocols. Today, using physiologic imaging, we can evaluate the response to treatment within hours of administration of therapy. Adjuvant metabolic tumor imaging studies provide complimentary information to morphologic evaluation of human cancers that will ultimately lead to better patient care. 
3	Analysis of prognostic factors and clinicopathological staging of thymoma The prognostic value of four clinical variables (age and sex of patients, association with myasthenia gravis, and clinical stage) and histological type was analyzed in 83 consecutive patients with thymoma, histologically classified as cortical, medullary, and mixed. Age, sex, and association with myasthenia gravis did not prove to represent significant prognostic factors; clinical stage and histological type, on the contrary, had a highly significant prognostic value (p less than 0.001). A model of clinicopathological staging, based on both clinical stage and histological type, in which three major prognostic groups are considered is proposed. The degree of significance of this model is higher (p less than 0.0001) than that of clinical stage and histological type considered individually; its validity is further supported by the results of multivariate analysis according to the Cox regression model (p = 0.0001). We think it represents a prognostically valuable approach to the problem of management of thymoma. 
2	Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity. Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease. 
5	Risk factors for transmission of hepatitis B virus to Gambian children [published erratum appears in Lancet 1990 Dec 22-29;336(8730):1596] Risk factors for hepatitis B virus transmission were examined in 973 Gambian children aged 6 months to 5 years. 33% had evidence of infection with hepatitis B virus and a third of these were carriers. A significant association was found between infection and tropical ulcer scars, and between e antigenaemia and the presence of bedbugs in each child's bed. There was no association between infection and traditional scarring, circumcision, or injections. Skin disease and arthropods are the two most likely modes of transmission of hepatitis B virus between children in West Africa. 
2	Disseminated Pneumocystis carinii infection with hepatic involvement in a patient with the acquired immune deficiency syndrome. Extrapulmonary infection with Pneumocystis carinii (P. carinii) in AIDS patients is uncommon, and is often described only at postmortem examination. Although most antemortem cases involve spread to the bone marrow or spleen, P. carinii involvement of other organs has only recently been described. Despite the frequency of liver enzyme abnormalities in AIDS patients with a history of P. carinii pneumonia, P. carinii has been observed only rarely in the liver. We present a well-documented case of P. carinii involving the liver in an AIDS patient with P. carinii pneumonia and progressive liver enzyme abnormalities. We suggest that P. carinii infection should be considered in the differential diagnosis of AIDS-related liver disease. 
5	Intradural herniation of a thoracic disc presenting as flaccid paraplegia: case report. A case of intradural herniation of a thoracic disc in a patient with a flaccid paraplegia is described. Intradural herniation of a thoracic disc is considered a rare event. A review of the relevant patient literature revealed 14 other reports involving 28 patients. No other report has described a patient with an intradural thoracic disc herniation who developed a flaccid paraplegia. 
3	Movement analysis--an aid to early diagnosis of cerebral palsy. The purpose of this article is to review research related to the use of clinical analysis of movement as an aid to the early diagnosis of cerebral palsy. A historical perspective of clinical techniques used by physicians and physical therapists in the early diagnosis of cerebral palsy will be presented first, including recent research findings on clinical signs that were most predictive of this movement disorder. Predictive neuromotor behaviors common across several recent studies will be highlighted. Future trends in the use of movement analysis, including digitized kinematic analysis of term and preterm infants and fetal ultrasound techniques, will be discussed as well. 
5	Complications of Tenckhoff catheters post removal. Complications due to Tenckhoff catheters can occur at prolonged intervals after their removal. From January 1979 to October 1989, 431 patients at our center began continuous ambulatory peritoneal dialysis (CAPD), 278 of whom subsequently transferred to another form of renal replacement therapy. We identified 12 patients (4.3% or 12/278) with post removal catheter complications. There were 14 post removal complications, two each in two patients, and one in each of 12 others. The mean time to complication was 541 +/- 143 days (27-2,040). In 71% (10/14) of the complications, an abscess was found at the site of the previously removed Tenckhoff catheter. In 29% (4/14) of the complications, foreign body material consistent with a retained cuff was recovered. Documentation at the time of Tenckhoff catheter removal should include a statement regarding the presence of the Tenckhoff catheter cuffs, and patients with retained cuffs should be monitored closely for the development of abscesses or other complications. Immunocompromised patients are at high risk for these complications. 
5	Effects of retrovenous myocardial drug delivery after coronary artery occlusion in sheep. Retrovenous (RV) myocardial delivery of blood and drugs into the coronary sinus (CS) through a 3 lumen balloon catheter was evaluated in sheep (no coronary collaterals) for protection from ventricular fibrillation (VF) during coronary artery occlusion. The balloon was asynchronously inflated (CS occlusion) for 5 sec and then deflated for 5 sec with 1 cc/sec of flow. The left anterior descending coronary artery was occluded with inflation of a percutaneous transluminal coronary angiography balloon and therapy started immediately. In a control group (no therapy, n = 4) all developed VF by 30 min after coronary artery occlusion. The drugs lidocaine (L), esmolol (E), adenosine (A), and deferoxamine (D) were evaluated for effects on eliminating developing VF with intravenous (i.v.) administration compared with RV administration with venous blood (VB) or arterial blood (AB). The percent survival after CA occlusion (no VF) was: L i.v., 0%; L RV with VB, 43%; L RV with AB, 17%; E i.v., 50%; E RV with VB, 70%; A. i.v., 29%; A RV with VB, 88%; D i.v., 17%; and D RV with AB, 80%. There was a trend toward lower myocardial necrosis (seen by tetrazolium stain and/or light microscopy) in the RV survivors (especially with VB) compared with the group i.v. survivors. These data suggest that RV antiarrhythmic drug delivery is a feasible alternative to i.v. administration during CA occlusion. 
1	Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. Between 1975 and 1989, 108 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor (MB/PNET) of the posterior fossa were treated at the authors' institution. The patients were managed uniformly, and treatment included aggressive surgical resections, postoperative staging evaluations for extent of disease, and craniospinal radiation therapy with a local boost. Beginning in 1983, children with MB/PNET were prospectively assigned to risk groups; those with "standard-risk" MB/PNET were treated with radiation therapy alone, while those in the "poor-risk" group received similar radiation therapy plus adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vincristine, and cisplatin. The 5-year actuarial disease-free survival rate for all patients treated between 1975 and 1982 was 68%, and 73% when patients who died within 2 weeks after operation were excluded. This survival rate was statistically better for patients treated after 1982 (82%) compared to those treated between 1975 and 1982 (49%) (p less than 0.004). There was no difference in disease-free survival rates over time for children with standard-risk factors; however, there was a significant difference in the 5-year survival rate for poor-risk patients treated prior to 1982 (35%) compared to those treated later (87%) (p less than 0.001). For the group as a whole, a younger age at diagnosis correlated with a poorer survival rate; however, this relationship between age and outcome was significant only for children treated before 1983 (p less than 0.001). These results demonstrated an encouraging survival rate for children with MB/PNET, especially those treated with aggressive surgical resection followed by both radiation therapy and chemotherapy. The results strongly suggest that chemotherapy has a role for some, and possibly all, children with MB/PNET. 
5	Early assessment of coronary artery bypass graft patency by high-dose dipyridamole echocardiography. To assess the role of high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiographic testing in the evaluation of coronary artery bypass graft patency early after surgery, 18 consecutive patients with angina underwent dipyridamole echocardiography and coronary angiography before and 7 to 10 days after bypass surgery. Coronary angiography showed 2- or 3-vessel disease in 7 and 11 patients, respectively. A total of 53 bypass grafts were performed. Before bypass surgery 14 patients had a positive and 4 a negative test result. No complication occurred during the test performed early after surgery. Of the 14 patients with positive dipyridamole echocardiographic results before surgery, 10 had negative and 4 had positive results after surgery. All 4 patients had negative results before and after surgery. In the 4 patients with positive results after dipyridamole echocardiographic testing before and after bypass surgery, dipyridamole time increased from 5.8 +/- 5 to 9.3 +/- 0.9 minutes (p = 0.3) after the procedure and wall motion score index at peak dipyridamole changed from 1.55 +/- 0.2 to 1.28 +/- 0.3 (p = 0.05). Forty-nine of 53 grafts were patent as seen on angiography. Dipyridamole echocardiographic results were positive in 4 of 5 patients who had at least 1 obstructed graft or native vessel obstructed distal to bypass graft insertion. The remaining patient had diagnostic electrocardiographic changes during dipyridamole infusion without wall motion abnormalities. Dipyridamole echocardiographic results were negative in all 13 patients who had complete revascularization. In the 4 patients with positive test results, the procedure correctly identified the localization of the diseased bypass graft. 
3	Double-blind, placebo-controlled, cross-over trial of progabide as add-on therapy in epileptic patients. In a double-blind, cross-over trial, progabide (PGB) and placebo were compared as add-on therapy in 59 patients with moderate to severe epilepsy. Eight patients did not complete the study, 4 because of adverse drug reactions (elevation of liver transaminases, 2; gastritis, 1; and acute psychosis, 1) and 4 because of administrative reasons. Among the remaining 51 patients, seizure frequency was reduced greater than 50% in 18 patients with PGB treatment and in 8 patients with placebo (p less than 0.05). The number of days with seizures was significantly (p = 0.034) reduced during PGB treatment. Both patients' and physicians' preferences at the end of the trial were in favor (p less than 0.01) of PGB. Mild clinical side effects were present in 54.7% of the patients treated with PGB and in 37.7% with placebo. Increase in liver transaminases was observed in 2 patients during the double-blind study and in 1 during the follow-up period. Our data show that PGB, as previously reported, is useful in 30-40% of patients who are not responding completely to other antiepileptic drugs (AEDs). The compound is well tolerated, but liver function must be monitored. 
5	Biliobiliary fistula: preoperative diagnosis and management implications. Experience with cholecystohepaticodochal and cholecystocholedochal fistulas as a result of an erosion of gallstones from the gallbladder into the adjacent common duct in five patients is presented. The incidence was 1.4% in a population of 350 patients undergoing cholecystectomy. The condition was indicated clinically on the basis of a symptom triad of jaundice, fever, and pain with cholelithiasis in a small contracted gallbladder. In addition, proximal intra- and extrahepatic ductal dilatation, calculus in the common duct, and normal-caliber (or unprofiled) distal common duct on ultrasound scan were present in all the patients. Endoscopic retrograde cholangiopancreatography proved to be the most useful means of investigation, and it confirmed the diagnosis in four patients before surgery. A modified antegrade cholecystectomy was performed with the gallbladder opened inferiorly at the fundus, and the stones were evacuated. A partial cholecystectomy and choledochoplasty were accomplished with gallbladder flaps whenever feasible. Other useful operative procedures are side-to-side hepaticodochojejunostomy and hepaticodochoduodenostomy. In the presence of high benign bile duct stricture, an approach to the left hepatic duct is now preferred for biliary bypass. 
1	Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues. Monoclonal and polyclonal antibodies recognizing human parathyroid hormone-like protein (PTHLP) have been produced using a series of recombinant and synthetic PTHLP peptides. These antibodies have been used to develop a two-site immunometric enzyme immunoassay which detects PTHLP[1-87] and PTHLP[1-141] but not PTH. The immunoassay detected PTHLP in extracts of squamous carcinomas and normal tissues at concentrations from 7-515 ng PTHLP[1-87]/mg protein. Immunoblotting of the extract which showed the highest immunoreactivity, a squamous carcinoma of the lung from a patient with hypercalcemia, revealed a major band having an apparent mol wt of 26,500 and several other higher mol wt bands. Similar polypeptides were observed by immunoblotting cell extracts from a cell line, SCaBER, which secretes immunoreactive PTHLP into its medium and also from tumors in nude mice derived from this cell line. Chaotropic agents did not alter the immunoblotting pattern, and antibodies to three different epitopes of PTHLP recognized these bands, indicating PTHLP expression in the extracts. Immunohistochemical staining of normal human tissue with these antibodies revealed several PTHLP-containing tissues and confirmed the results of the immunoassay, suggesting a paracrine role for PTHLP. Staining was observed in several neoplastic tissues including squamous cell carcinomas, lung carcinoma, bladder carcinoma, osteogenic sarcoma, and adenocarcinoma of the colon. 
3	Neuropsychological deficits in fetal alcohol syndrome and fetal alcohol effects. A clinical sample of 19 school-aged native children diagnosed with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) was compared with age- and sex-matched normal controls. Results on a battery of intellectual and neuropsychological tests indicated large and significant differences between alcohol-affected children and controls. FAS differed significantly from controls on measures of intellectual abilities, while FAE did not; FAS mean scores on these measures were significantly lower than FAE means. For neuropsychological measures, FAS were significantly poorer than controls on most measures, while FAE showed deficits compared with controls only on grip strength. The results suggest that neuropsychological measures would be a valuable supplement to intellectual measures for the purpose of assessing alcohol effects because they are less vulnerable than intellectual measures to the influence of cultural and educational experiences. 
4	Fractured and retained guide-wire fragment during coronary angioplasty--unforeseen late sequelae. During a difficult coronary angioplasty, the tip of the guide wire became inadvertently wedged in a distal vessel, fractured, and retained in situ. Because of the otherwise successful nature of the angioplasty and the patient's great risk for cardiac surgery, it was elected to leave the wire fragment in place. Recurrence of symptoms led to recatheterization, which in addition to restenosis of the original angioplasty site showed diffuse narrowing of the arterial segment that contained the retained wire fragment. This occurred despite systemic anticoagulation with Coumadin in the interval between procedures. Thus retained guide wire fragments in patent coronary arteries may cause arterial narrowing despite systemic anticoagulation. 
5	Ossified chronic subdural hematoma: case report. A case of ossified chronic subdural hematoma is presented in a 13-year-old male in whom the mass was surgically removed. His neurological deficits continued afterward but were less severe. 
1	Treatment of port-wine stains during childhood with the flashlamp-pumped pulsed dye laser. Seventy-three patients between the ages of 3 months to 14 years (average age 6 years 2 months) with port-wine stains were treated with the flashlamp-pumped pulsed dye laser. More than 75% lightening was achieved with an average of 2.5 treatments in 33 patients (45%), 50% to 74% lightening after an average of 1.7 treatments in 31 (42%), 26% to 49% lightening after 2 treatments in 5 (7%), and less than 25% lightening after 1 treatment in 4 (5%). The overall average lightening after one treatment was 53%. The percentage of lightening increased as the number of treatments increased. Three patients had 100% clearance of the port-wine stain. Patients aged between 3 months and 6 years (44 patients) had a better response after the first treatment (55% lightening) than did patients aged between 7 and 14 years (29 patients with a 48% lightening; p = 0.027). Complications included cutaneous depressions in four patients, hyperpigmentation in 16 patients, and hypopigmentation in three patients. All complications were transient and disappeared completely. 
5	A randomized double-blind crossover comparison of four rate-responsive pacing modes. The aim of this study was to compare, both subjectively and objectively, four modern rate-responsive pacing modes in a double-blind crossover design. Twenty-two patients, aged 18 to 81 years, had an activity-sensing dual chamber universal rate-responsive (DDDR) pacemaker implanted for treatment of high grade atrioventricular block and chronotropic incompetence. They were randomly programmed to VVIR (ventricular demand rate-responsive), DDIR (dual chamber demand rate-responsive), DDD (dual chamber universal) or DDDR (dual chamber universal rate-responsive) mode and assessed after 4 weeks of out-of-hospital activity. Five patients, all with VVIR pacing, requested early reprogramming. The DDDR mode was preferred by 59% of patients; the VVIR mode was the least acceptable mode in 73%. Perceived "general well-being," exercise capacity, functional status and symptoms were significantly worse in the VVIR than in dual rate-responsive modes. Exercise treadmill time was longer in DDDR mode (p less than 0.01), but similar in all other modes. During standardized daily activities, heart rate in VVIR and DDIR modes underresponded to mental stress. All rate-augmented modes overresponded to staircase descent, whereas the DDD mode significantly underresponded to staircase ascent. Echocardiography revealed no difference in chamber dimensions, left ventricular fractional shortening or pulmonary artery pressure in any mode. Cardiac output was greater at rest in the dual modes than in the VVIR mode (p = 0.006) but was similar at 120 beats/min. Beat to beat variability of cardiac output was greatest in VVIR mode (p less than 0.0001), with DDIR showing greater variability than DDD or DDDR modes (p less than 0.05). Mitral regurgitation estimated by Doppler color flow imaging was similar in all modes, but tricuspid regurgitation was significantly greater in VVIR than in dual modes (p less than 0.03). Subjects who preferred the DDDR mode and those who found the VVIR mode least acceptable had significantly greater increases in stroke volume when paced in the DDD mode than in the ventricular-inhibited (VVI) mode at rest (22%) when compared with subjects who preferred other modes (2%, p = 0.03). No other objective variable was predictive of subjective benefit from any rate-responsive pacing mode. Thus, dual sensor rate-responsive pacing (DDDR) is superior objectively and subjectively to single sensor (VVIR, DDIR and DDD) pacing and subjective benefit from dual chamber rate-augmented pacing is predictable echocardiographically. 
5	Congenital heart defects in malformation syndromes. This article presents a comprehensive review of the type and frequency of congenital heart defects found in malformation syndromes which have been categorized by etiology. Certain cardiac phenotypes can be as helpful in identifying certain syndromes as can be seen with the more familiar facial, body, and behavioral phenotypes. An awareness of syndromes with a higher risk of congenital heart defect, and knowledge concerning heart defects which are distinctive for certain syndromes, focuses prenatal diagnosis efforts and fetal echocardiography. By using a mechanistic classification in which congenital heart defects are regarded as families of related defects rather than individual lesions, patterns can be recognized among different syndromes. 
2	A combined electromyographic and cineradiologic investigation in patients with defecation disorders. Records from 20 patients on whom defecography and electromyography were performed simultaneously because of defecation disorders were analyzed. According to the electromyographic investigation, the patients could be divided into three main groups: 1) normal sphincter reaction; 2) paradoxical sphincter reaction; and 3) combined reaction. Group A was characterized by a marked reduction of muscular activity during emptying and a pronounced closing reflex after emptying. This was followed by return of normal tonic activity. Patients in group B had no relaxation of the sphincters during emptying but a pronounced increased activity in the external sphincter and the puborectalis muscle. They also had severe emptying difficulties at defecography. No closing reflex was seen. In group C the electrical activity in the sphincters increased during moderate straining and when emptying was complete a clear closing reflex was seen. In this study, a dynamic visualization of the defecation together with a registration of electromyographic activity in the striated anal sphincters was performed. It was shown that patients with paradoxical sphincter reaction were lacking a closing reflex after emptying was complete. This has not been reported previously and is important evidence for the paradoxical defecation pattern. It was also shown that the patients with rectoceles had paradoxical sphincter reaction. 
2	Serum pepsinogen I and gastrin concentrations in children positive for Helicobacter pylori. Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information. 
5	Genetics of asthma and hay fever in Australian twins. The occurrence of self-reported asthma/wheezing and hay fever among 3,808 pairs of twins from the Australian National Health and Medical Research Council Twin Registry was examined for evidence of genetic transmission by path analytic methods. The cumulative prevalence of asthma or wheezing was 13.2% and of hay fever, 32%. There were significant correlations in liability to reported disease among twins, and these were higher in monozygotic twins (MZ) (r = 0.65) than in dizygotic twins (DZ) (r = 0.25), and in male MZ twins (r = 0.75) compared with female MZ twins (r = 0.60). Analysis under the assumptions of the classic twin model suggested that there were genetic factors common to asthma and hay fever, with a correlation in genetic liability to the traits of 0.52 for men and 0.65 for women. These genes acted substantially in a nonadditive fashion in men but not in women. As the genetic correlation was significantly less than unity, this implied additional genetic factors influencing either or both diseases individually. The estimated heritability of these diseases was 60 to 70% in this population. Environmental causes of both diseases also were correlated (r = 0.53 for men and 0.33 for women). Cigarette smoking was only weakly associated with wheezing. 
1	Increased survival of patients with massive lymphadenopathy and prostate cancer: evidence of heterogeneous tumour behaviour. The survival of patients with prostate cancer and radiologically detectable lymph node enlargement has been studied prospectively over an 8-year period. Computed tomography in 108 patients presenting with symptoms, signs or biochemical results suggesting lymphatic spread revealed pelvic or abdominal node masses in 60 patients; in 29 (48%), the masses measured more than 4 cm and the maximum node diameter was 15 cm. Two-thirds of patients had advanced (T3/T4) tumour stage. Following treatment, actuarial survival in all 60 patients with nodal enlargement was 40% at 5 years. Within this group, survival in 22 patients with lymphadenopathy but negative bone scans at diagnosis was significantly better than that of 38 patients with both node and bone disease (70% vs 20% at 5 years). This improvement was related both to an apparent inability of certain tumours initially to progress and seed within bone and to a marked sensitivity of the node masses to subsequent hormonal manipulation. Primary tumour grade was proportionally similar in both groups. Unexpectedly, 6 of the 38 patients with combined disease obtained a complete remission after treatment. The reason for this heterogeneous biological behaviour remains unclear; but these observations underscore the importance of vigorous treatment in all patients with advanced lymph node disease. 
4	Deleterious effects of testicular venous occlusion in young rats. To determine the differences between testicular arterial and venous obstruction, the spermatic artery or vein, or both, were occluded for varying periods of time in young rats. Two months later, at the conclusion of the study, the testes were examined. Histologic degeneration after vascular obstruction was graded by a modified Johnsen's tubular biopsy score (TBS). The testicular concentrations of enzymes (lactic dehydrogenase and sorbitol dehydrogenase), known to decrease with testicular injury, were measured. TBS and seminiferous tubule diameter (STD) were found to decrease significantly after two hours of vascular occlusion and were similar regardless of whether the obstruction was produced by occlusion of arterial inflow or venous drainage, or both. Testicular concentration of enzymes decreased significantly after permanent ligation of the spermatic artery and vein, but decreased minimally when the vascular obstruction lasted less than 120 minutes. Testicular injury produced by venous occlusion was equally severe and occurred as rapidly as injury produced by arterial or combined arteriovenous occlusion. No significant injury was noted in the contralateral testes in any group. 
1	N-[18F]fluoroacetyl-D-glucosamine: a potential agent for cancer diagnosis Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-[18F]fluoroacetyl-D-glucosamine (18F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that 18F-FAG has potential as a new agent for tumor imaging. 
5	Laryngeal oedema from a neck haematoma. A complication of internal jugular vein cannulation. Laryngeal oedema occurred after formation of a neck haematoma after attempted internal jugular vein cannulation. This resulted in complete respiratory obstruction and respiratory arrest and it was impossible to ventilate her lungs manually or intubate her trachea. Oxygenation of the patient was only possible using transtracheal ventilation. 
1	Whole-body lipolysis and triglyceride-fatty acid cycling in cachectic patients with esophageal cancer. Whole-body lipolytic rates and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were measured with stable isotopic tracers in the basal state and during beta-adrenergic blockade with propranolol infusion in five cachectic patients with squamous cell carcinoma of the esophagus, five cachectic cancer-free, nutritionally-matched control patients, and 10 healthy volunteers. Resting energy expenditure and plasma catecholamines were normal in all three groups. The basal rate of glycerol appearance in blood in the patients with cancer (2.96 +/- 0.45 mumol.kg-1.min-1) was similar to that in the nutritionally matched controls (3.07 +/- 0.28 mumol.kg-1.min-1), but 48% greater than in the normal-weight volunteers (2.00 +/- 0.16 mumol.kg-1.min-1) (P = 0.028). The antilipolytic effect of propranolol and the rate of triglyceride-fatty acid cycling in the patients with cancer were also similar in the cachectic control group and approximately 50% greater than in the normal-weight volunteers, but the differences were not statistically significant because of the variability in the data. We conclude that the increase in lipolysis and triglyceride-fatty acid cycling in "unstressed" cachectic patients with esophageal cancer is due to alterations in their nutritional status rather than the presence of tumor itself. Increased beta-adrenergic activity may be an important contributor to the stimulation of lipolysis. 
5	Unusual lymphoproliferative oropharyngeal lesions in heart and heart-lung transplant recipients. Three unusual cases of oropharyngeal lympho-proliferative lesions were seen in recipients of heart and heart-lung transplants. Two caused acute upper respiratory obstruction necessitating urgent ENT intervention. All patients were receiving immunosuppressive drugs including cyclosporin. The two obstructive cases were adenotonsillar enlargement in a 6-year-old, and a tumour of the tonsil and tongue base with cervical lymph node enlargement in a 32-year-old male. Both were caused by Epstein-Barr Virus-associated lymphoproliferative disorder. The third patient, a 32-year-old female, had a presumed low grade T-cell lymphoma that regressed spontaneously. Histopathological diagnosis of these lympho-proliferative disorders after transplantation usually requires immunocytochemistry to distinguish polyclonal proliferative disorders from true lymphoma. Polyclonal lymphoproliferative disorders after transplantation do not usually require aggressive cytoreductive therapy, but respond to simple measures such as the reduction of immunosuppression. 
5	A case-control study of the effectiveness of bicycle safety helmets in preventing facial injury. In a case-control study we sought to assess the potential effectiveness of helmets in preventing facial injuries. Our study included 212 bicyclists with facial injuries and 319 controls with injuries to other body areas, who were treated in emergency rooms of five Seattle area hospitals over a one-year period. Using regression analyses to control for age, sex, education and income, accident severity, and cycling experience we found no definite effect of helmets on the risk of serious facial injury (odds ratio 0.81; 95 percent confidence interval = 0.45, 1.5), but protection against serious injuries to the upper face (odds ratio 0.27; 95% CI = 0.1, 0.8). No protection was found against serious injuries to the lower face. The independent effect of helmet use on facial injury was difficult to isolate due to the association of head and facial injuries. Our results suggest that bicycle helmets as presently designed may have some protective effect against serious upper facial injuries. 
5	National General Practice Study of Epilepsy: newly diagnosed epileptic seizures in a general population. The National General Practice Study of Epilepsy is a prospective population-based cohort study of 1195 patients with newly diagnosed or suspected epileptic seizures. At the time of initial classification (6 months after notification), 104 patients were excluded. Of the remaining 1091 patients, 220 (20% [95% confidence interval 18-23%]) had febrile seizures, 564 (52% [49-55%]) definite epileptic seizures, and 228 (21% [19-23%]) possible epilepsy. In the definite epilepsy group the proportions of males and females were similar, 25% (21-28%) were younger than 15 years and 24% (21-28%) were 60 years or older. The definite seizures were classified as cryptogenic in 62% (58-66%), remote symptomatic in 21% (18-25%), and acute symptomatic in 15% (12-18%). The aetiology of epilepsy was vascular disease in 15% (12-18%) and tumour in 6% (4-8%). Among older subjects the proportion with an identifiable cause was much higher: 49% (41-58%) were due to vascular disease and 11% (6-16%) to tumour. Only 252 (45% [41-49%]) of the 564 patients with definite epileptic seizures were registered at the time of their first seizure. 52% (48-56%) of the patients had partial or secondarily generalised seizures, and only 39% (35-43%) seizures generalised from the outset. 
1	Recent advances in etoposide therapy for non-small cell lung cancer. Non-small cell lung cancer (NSCLC) continues to be a major health problem in the US. In 1990, approximately 120,000 new cases will be diagnosed, and the majority of these patients will have either unresectable disease or resected disease that has a relatively low chance of being cured. A variety of chemotherapy treatments have been evaluated in patients with advanced NSCLC. The objective of this review is to summarize the results of the chemotherapy trials in Stage III and IV NSCLC patients. 
5	Temporal movement control in patients with Parkinson's disease. Patients with Parkinson's disease (PD) have been reported to be unable to modify their movement velocity to adapt to changing environmental demands. For example, when movement amplitude is varied, PD patients usually exhibit a nearly constant peak velocity, whereas elderly subjects show an increase of their peak velocity with increased amplitude. The experiment examined the ability of PD patients to vary the duration of their movement (four different percentages of their maximum) under conditions where temporal, but not spatial, control was emphasised. PD patients had longer movement times than control subjects, but were able to vary the duration of their movement with comparable temporal accuracy to that of elderly subjects. For both groups, the agonist EMG activity increased with decreased movement duration. For the PD patients, the number of agonist bursts increased with increased movement duration. 
4	The antihypertensive mechanism of delapril, a newly developed converting enzyme inhibitor, is related to the suppression of vascular angiotensin II release in the spontaneously hypertensive rat. Accumulating evidence suggests an important role of vascular renin-angiotensin system (RAS) in the local control of arterial tone. To further gain insight into the significance of vascular RAS in hypertension, we investigated the relationship between the antihypertensive action of delapril, a newly developed converting enzyme inhibitor (CEI), and its effects on vascular angiotensin II (Ang II) release in spontaneously hypertensive rats (SHR). Male SHRs were given delapril or its active metabolite (5-hydroxydelapril diacid; 5-hydroxy-DPD) orally (10 mg/kg/day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was directly determined by extraction with Sep-Pak C18 cartridges connected to the perfusion system. Both delapril and 5-hydroxy-DPD produced a sustained antihypertensive action. The spontaneous release of Ang II from isolated perfused hind legs of control SHRs was about 50 to 110 pg during the first 30 min of perfusion, and it remained stable up to 3 h. Another active metabolite, delapril diacid (DPD), when added to the perfusion medium (10(-9) to 5 x 10(-5) mol/L), suppressed the Ang II release in a dose-dependent manner. The maximal percent inhibition of Ang II released evoked by DPD (5 x 10(-6) mol/L) was approximately 51%. Oral pretreatment of either delapril or 5-hydroxy-DPD for 2 weeks suppressed the Ang II release by 61% and 73% for delapril and 5-hydroxy-DPD, respectively. These results suggest the presence of a functional RAS in vascular tissues, and that delapril exerts its antihypertensive effect through inhibition of vascular Ang II release in SHRs. 
5	A comparison of parallel versus perpendicular placement of retention sutures in abdominal wound closure. A new technique for placement of retention sutures is described. Twenty-five rats underwent midline laparotomy incision. The control group was closed with traditional placement of through-and-through retention sutures placed in a perpendicular direction to the wound. The experimental group was closed with retention sutures placed in a parallel direction to the wound as described below. Wound bursting strength was significantly (P less than 0.001) greater at one to five days in the experimental group compared with the control animals. In addition, inflammatory reaction and pressure necrosis were greater in the control group. It appears that parallel placement of sutures has less of a tendency to cut through tissue when subjected to the distracting forces on a midline wound. 
5	Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer. A cytologic method for sampling the normal breast by fine-needle aspiration (FNA) was used to determine the frequency of clinically inapparent proliferative breast disease (PBD) in women with family histories of breast cancer. The authors attempted to obtain specimens from each quadrant of both breasts in 51 female first-degree relatives of breast cancer patients. The study group had no detectable masses by physical examination or mammography. Samples were prepared on membrane filters, Papanicolaou stained, and evaluated cytomorphologically. Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled; cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in 20 of the 51 women (39.2%). When epithelium was obtained, nuclear area, perimeter, and diameter were measured with the use of computerized image analysis. Nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia. The authors' findings indicate that FNA sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent PBD. 
5	Molecular characterization of erythrocyte glycophorin C variants. Human erythrocyte glycophorin C plays a functionally important role in maintaining erythrocyte shape and regulating membrane mechanical stability. Immunochemical and serologic studies have identified a number of glycophorin C variants that include the Yus, Gerbich, and Webb phenotypes. We report here the molecular characterization of these variants. Amplification of glycophorin C mRNA from the Yus phenotype, using two oligonucleotide primers that span the coding domain, generated a 338-bp fragment compared with a 395-bp fragment generated by amplification of normal glycophorin C mRNA. Sequencing of the mutant 338-bp fragment identified a 57-bp deletion that corresponds to exon 2 of the glycophorin C gene. Similar analysis showed deletion of 84-bp exon 3 in the Gerbich phenotype. In contrast to the generation of shorter than normal DNA fragments from mRNA amplification in the Yus and Gerbich phenotypes, amplification of mRNA from the Webb phenotype generated a normal-sized fragment. Sequencing of this DNA fragment showed an A----G substitution at nucleotide 23 of the coding sequence, resulting in the substitution of asparagine by serine. This modification accounts for the altered glycosylation of glycophorin C seen in this phenotype. These results have enabled us to characterize glycophorin C variants in three different phenotypes that involve deletions of exons 2 and 3 of the glycophorin C gene, as well as a point mutation in exon 1 that results in altered glycosylation of this protein. 
5	Human immunodeficiency virus-associated Hodgkin's disease. Clinicopathologic studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells. Hodgkin's disease (HD) was diagnosed in 24 patients who were either seropositive for human immunodeficiency virus (HIV) (21) or members of a high-risk group (three), but had not developed acquired immune deficiency syndrome (AIDS). Clinical presentation of the disease was characterized by constitutional symptoms in all, especially fever (23/24) and disseminated disease (22/24) at diagnosis. Mediastinal adenopathy was rare. Bone marrow involvement was particularly frequent (12/24), and a positive bone marrow biopsy preceded lymph node biopsy in 5 of the 12. Histopathologic features of these tumors included an increased number of nonlymphoid stromal cells, i.e., histiocytic and/or fibroblastoid. In some tumors these fibrohistiocytoid stromal cells were arranged in bundles, but distinct nodule with birefringent collagen band formation was not observed. Twenty-two patients were treated, most with combination chemotherapy; one was untreated; one, unknown. Sixteen, including the one untreated, died with disease at 3 to 25 months; one died of an unrelated cause; four were alive at 3 to 24 months; three were lost to follow-up. Frequent bone marrow involvement at presentation suggests the usefulness of the bone marrow biopsy for diagnosis in subjects at risk, especially when they present with spiking fever of unknown origin. Contrary to most previous series, virtually all of our cases were of mixed cellularity type, characterized by increased fibrohistiocytoid stromal cells in place of depleting lymphocytes. The classic nodular sclerosing feature with birefringent collagen band formation was not observed. In conclusion, HIV-associated HD was characterized by advanced stage with fever at presentation, preponderance of mixed cellularity histologic type with increased fibrohistiocytoid stromal cells, and poor outcome. Hodgkin's disease in AIDS patients presents an intriguing biological model to study the role of stromal histiocytes in immunodeficient patients. 
5	Intraoperative scintigraphy for active small intestinal bleeding. Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, "blind" resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine. 
1	T-lymphocytic leukemia expresses complex, branched O-linked oligosaccharides on a major sialoglycoprotein, leukosialin. Leukocytes express a major sialoglycoprotein, leukosialin, of which the apparent molecular weight (mol wt) can be variable according to the differences in O-glycans attached to this molecule. In the present study, we analyzed the structures of O-glycans attached to leukosialin present in various T-lymphocytic leukemia cells. T-lymphoid cells from patients with acute T-lymphocytic leukemia express a large amount of the branched hexasaccharides, NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6)GalNAc, which are also expressed in activated normal T lymphocytes, but that are almost absent in resting normal T lymphocytes. T-lymphoid cells from patients with chronic T-lymphocytic leukemia, on the other hand, mainly express the tetrasaccharides NeuNAc alpha 2----3Gal beta 1----3(NeuNAc alpha 2----6)GalNAc on leukosialin, but they also express a small significant amount of the hexasaccharides. The same hexasaccharides can be detected in thymocytes. The increased amount of the hexasaccharides in acute leukemia is associated with increased activity of beta 1----6 GlcNAc-transferase, a key enzyme in forming the hexasaccharides. Immunoblot analysis of cell lysates showed that monoclonal antibody (MoAb) T-305 reacts preferentially with leukosialin of high mol wt containing the hexasaccharides. These findings indicate that T-lymphocytic leukemia cells reexpress the oligosaccharides present in immature cells. 
3	Magnetic resonance imaging of fourth ventricular epidermoid tumors. Two pathologically proved cases of epidermoid tumor of the fourth ventricle are presented; clinical history and computed tomographic, magnetic resonance imaging, and histopathologic findings are included. 
4	Dissecting aneurysm of the pulmonary artery with pulmonary hypertension. Pulmonary artery dissection was observed in a 64-yr-old female patient with severe pulmonary hypertension, which was probably primary (pulmonary vascular resistance, 817 dyn.s.cm-5; normal range less than or equal to 200 dyn.s.cm-5). The patient was admitted to the hospital because of severe dyspnea on exertion. Echocardiography demonstrated a dissecting aneurysm of the pulmonary artery. Right heart catheterization revealed severe pulmonary hypertension (mean pulmonary artery pressure, 64 mm Hg; normal range, 10 to 22 mm Hg); dissection of the pulmonary artery was confirmed by pulmonary arteriography. One-year follow-up was uneventful. In the literature, 28 patients with dissecting aneurysm of the pulmonary artery are reviewed. The dissection has only been diagnosed in life in one patient (by echocardiography). 
4	Pineal hyperactivity in spontaneously hypertensive rats: muscarinic regulation of indole metabolism. 1. Choline acetyltransferase activity and [3H]quinuclidinyl benzylate-binding sites were detected in the pineal gland of normotensive Wistar-Kyoto rats and of spontaneously hypertensive rats. 2. In vitro, muscarinic activation by pilocarpine increased the pineal metabolic production of hydroxyindole derivatives up to 5-hydroxytryptamine and produced a less marked stimulation of melatonin biosynthesis. 3. Electrical field stimulation of pineal gland slices caused similar metabolic effects. 4. Muscarinic blockade with atropine inhibited the effects on hydroxyindole metabolism. 5. [3H]Quinuclidinyl benzylate-binding sites, indicative of muscarinic receptors, were more numerous, and basal 5-hydroxytryptamine and melatonin levels were higher, in the pineal gland of spontaneously hypertensive rats compared with Wistar-Kyoto rats. 6. The atropine-sensitive metabolic effects of pilocarpine and electrical field stimulation on the pineal gland were increased in spontaneously hypertensive rats compared with Wistar-Kyoto rats. 
2	Isoperistaltic intestinal lengthening for short bowel syndrome. Because of improvements in supportive care, many infants now survive massive intestinal loss and have short bowel syndrome. Unfortunately, some survivors are left with an insufficient amount of intestine and cannot be weaned from total parenteral nutrition. An isoperistaltic intestinal lengthening procedure was used to treat surgically two such infants with 25 centimeters of remaining small intestine and absent ileocecal valves. This surgical technique longitudinally divides the short, dilated small intestine into two smaller, parallel lumens that are anastomosed end to end. This procedure preserves all mucosa, prolongs transit time by doubling intestinal length and corrects the ineffective peristalsis by tapering the dilated intestine. The lengthening technique can be performed because of the anatomic division of the intestinal vasculature within two leaves of the mesentery. Longitudinal division between the two leaves maintains vasculature to each side of the intestine. The isoperistaltic intestinal lengthening procedure, as it was successfully applied to two infants, is described in detail. 
3	Crico-tracheal disruption and common carotid artery occlusion: a case of blunt trauma. A case of blunt trauma to the neck is presented. While driving an all terrain vehicle (ATV), a 20-yr-old male was struck across the anterior neck by a cord suspended between two poles. Initial findings were suggestive of an isolated laryngeal injury; 48 hours later, however, a dense left hemiplegia became manifest. A CT scan demonstrated a large right frontoparietal cerebral infarct, and an angiogram confirmed occlusion of the right common carotid artery. Intractable cerebral oedema developed, and the patient died five days after the initial insult. Such injuries should alert the clinician to the possibility of major vascular injury, and if suspected, angiography is warranted. 
4	Sudden death due to right ventricular cardiomyopathy. A 21-year-old man died suddenly at a small party. He had had no clinical signs of cardiac disease except for a slightly abnormal electrocardiogram (occasional premature ventricular contractions) since he was 15 years of age. Autopsy examination revealed cardiomegaly (469 g), with right atrial and ventricular dilatation. The right ventricular myocardium was massively replaced with adipose tissue, and there was one isolated fatty lesion in the right side of the ventricular septum. There were no congenital malformations such as a septal defect or valvular deformity. Histologically, muscular fibers remaining in the right ventricular wall showed neither degenerative nor inflammatory changes. An isolated lesion of the ventricular septum consisted of almost complete replacement of the muscle bundles with adipose tissue. Such a pathologic condition has recently been termed right ventricular cardiomyopathy. Postmortem examination is necessary to make a definite diagnosis of the disease, because in most adult cases of the disease, sudden death occurs before there have been any critical signs. 
5	Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy. To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 +/- 3.0 to 16.1 +/- 2.5 ml/kg/min, p less than 0.05) as did the oxygen pulse (9.0 +/- 2.2 to 12.6 +/- 1.8 ml/beat, p less than 0.02). Resting heart rate (87 +/- 18 to 62 +/- 9 beats/min, p less than 0.05) and peak exercise heart rate (133 +/- 13 to 105 +/- 30 beats/min, p less than 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 +/- 0.06 to 0.25 +/- 0.11 and peak exercise ejection fraction also tended to increase (0.19 +/- 0.11 to 0.28 +/- 0.15, difference not significant). Both resting plasma norepinephrine (613 +/- 706 to 303 +/- 142 pg/ml, p less than 0.05) and epinephrine (71 +/- 50 to 40 +/- 21 pg/ml, p less than 0.05) were reduced. Circulating lymphocyte beta-adrenergic receptor number was unchanged (1,334 +/- 292 to 1,344 +/- 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity. 
4	Abdominal aortic aneurysm with perianeurysmal fibrosis: experience from 11 Swedish vascular centers. Case records of 2026 patients operated on because of abdominal aortic aneurysms from 11 Swedish Vascular Centers were reviewed and revealed 98 cases (4.8%) of inflammatory abdominal aortic aneurysm. Also included in this case-control study was an analysis of a randomized group of 82 patients from the same centers who had noninflammatory abdominal aortic aneurysms. Four inflammatory aneurysms were ruptured, compared with 16 in the noninflammatory group (p less than 0.01). A higher proportion of patients with inflammatory abdominal aortic aneurysms had symptoms that led to radiographic investigations. The median erythrocyte sedimentation rate was 39 mm versus 19 mm (26% of patients with inflammatory abdominal aortic aneurysms had erythrocyte sedimentation rates greater than 50 mm; p less than 0.001), and the serum creatinine level was increased in 27 and 8 patients (p less than 0.01) in the inflammatory and noninflammatory groups, respectively. Preoperative investigations revealed ureteral obstruction in 19 patients with inflammatory abdominal aortic aneurysms, of whom 12 had preoperative nephrostomy or ureteral catheter placement. At operation, 20 additional patients exhibited fibrosis around one or both ureters. Although ureterolysis was performed in 19 patients, preoperative and postoperative creatinine levels did not differ between these patients and the conservatively treated ones. Duration of surgery (215 vs 218 minutes), intraoperative blood loss (2085 vs 2400 ml) and complications did not differ significantly between the groups. Overall operative (30-day) mortality was equal (11% vs 12%) but was increased for patients undergoing elective surgery for inflammatory abdominal aortic aneurysms (9% vs 0%; p = 0.03). 
2	Swallowing disorders in patients with prolonged orotracheal intubation or tracheostomy tubes. Eleven patients were tested for swallowing dysfunction after prolonged orotracheal intubation. Ten had a tracheostomy tube. Mean duration of orotracheal intubation was 19.9 days, mean age 65 yr, and no patient had a concomitant neurologic deficit. All patients had a modified barium swallow with videofluoroscopy. All patients had at least one defect of 11 defects characterized. There was a mean of six defects/patient. The most common defects were delayed triggering of the swallow response (present in all patients) and pharyngeal pooling of contrast material (n = 9). Follow-up videofluoroscopy was performed in five patients (all had improved) with mean defects decreasing from 6.1 to 2.8/patient. With one exception, no patient had any defect that was worse than mild in severity. We concluded that prolonged orotracheal intubation with or without tracheostomy may cause prolonged and severe swallowing dysfunction. The deficits improve with time. The presence of a gag reflex does not confer protection against aspiration of pharyngeal contrast. 
5	Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Inducible cell adhesion molecule 110 (INCAM-110), is a 110-kd adhesion receptor for lymphocytes and monocytes identified on cytokine-activated endothelium. Using immunoperoxidase techniques, little or no INCAM-110 was detected on endothelium in normal human tissues. In contrast, INCAM-110 was expressed in postcapillary venules in a variety of active inflammatory processes. In acute appendicitis, INCAM-110 was found coincident with strong expression of endothelial leukocyte adhesion molecule 1 (ELAM-1), a cytokine-inducible molecule that functions in neutrophil adhesion. However, in certain chronic inflammatory processes (eg, sarcoidosis), INCAM-110 was observed without simultaneous ELAM-1 expression. Anti-INCAM-110 antibody E1/6 also marked several extravascular cell types, including lymphoid dendritic cells, some tissue macrophages, synovial lining cells, and reactive mesothelial cells. These data suggest a role for endothelial INCAM-110 in the pathophysiology of both acute and chronic inflammatory reactions. Furthermore INCAM-110 may function as an adhesion molecule for mononuclear leukocytes in a variety of extravascular sites. 
1	Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. 
5	Management of Brucella endocarditis with aortic root abscess. Three cases of Brucella endocarditis with aortic root abscess are reported. Two patients were successfully managed by a combination of medical therapy and surgery. The third patient died suddenly 36 hours after admission to hospital. 
2	Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus. The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg. We have investigated whether this antigen is a target structure for human T-lymphocytes. Using recombinant HBxAg protein, we found HBxAg-specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals. With HBxAg-specific synthetic polypeptides, several T-cell epitopes were identified. Most were located in the carboxyterminal half of the HBxAg protein. Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CD8-negative subtype. These data establish for the first time HBxAg as an antigen in the cellular immune response. 
2	Preexposure of the peritoneum to live bacteria increases later mixed intraabdominal abscess formation and delays mortality. Intraabdominal infections are a major source of morbidity and mortality for the trauma and postoperative patient. Transient peritoneal contamination with bacteria after either intentional or unintentional violation of the gut are common. The effect of this intermittent antigen exposure upon later formation of intraabdominal abscesses is unclear. Previous experiments by others have demonstrated that repeated exposure to Bacteroides fragilis capsular polysaccharide can induce a T lymphocyte-mediated immunity to subsequent induction of pure B. fragilis abscess formation. In a murine mixed intraabdominal abscess model, preexposure to live Escherichia coli, B. fragilis, or both increased the number of later abscesses and in some cases their bacterial composition. Further, immunization with E. coli alone increased late mortality without altering overall mortality. These data suggest that the alterations of immune function produced by live, transient bacteria upon subsequent mixed intraabdominal abscess induction result in fundamentally different consequences from those observed after specific polysaccharide antigen exposure and subsequent monomicrobial abscess induction. 
5	Isolated muscular sarcoidosis causing fever of unknown origin: the value of gallium-67 imaging. An unusual case of a patient with a long-standing fever of unknown origin (FUO) is presented whose gallium-67 (67Ga) images revealed increased activity only in the calf muscles bilaterally. Other imaging modalities also failed to show chest or other abnormal findings. Subsequent biopsy of the right gastrocnemius muscle revealed noncaseating granulomas consistent with the diagnosis of sarcoidosis. When using 67Ga to evaluate a patient with a FUO, imaging of the extremities should always be included. Also, when abnormal Ga-67 uptake is present in the extremities, sarcoidosis should be included in the differential diagnosis. 
3	Dexamethasone increases plasma levels of albendazole. Therapy of neurocysticercosis with cysticidal drugs is frequently complicated by the exacerbation of symptoms that follows the inflammation triggered by the acute destruction of cysticerci. Treatment of such adverse reactions with dexamethasone is highly effective. However, it has been shown that dexamethasone lowers the plasma levels of praziquantel, thus reducing its cysticidal efficacy. We measured plasma levels of albendazole, another strong cysticidal drug, when dexamethasone was given simultaneously. We found that dexamethasone increased the plasma levels of albendazole by about 50% (P less than 0.002); hence, it seems that cysticercosis and the ensuing inflammation can be treated simultaneously with albendazole and dexamethasone without diminishing the efficacy of the cysticidal drug. 
5	Arrhythmias in patients with CHF. Should they be treated? Ventricular arrhythmias are a major cause of death in patients with congestive heart failure. Dr Ellenbogen and his associates discuss the current thinking, based on recent studies, concerning use of antiarrhythmic agents to prevent sudden cardiac death in these patients. As they point out, the proper antiarrhythmic therapy may be crucial to long-term survival. 
4	Nifedipine gastrointestinal therapeutic system in the treatment of hypertension. Results of a multicenter trial. The Modern Approach to the Treatment of Hypertension (MATH) Study Group. Nifedipine, in the gastrointestinal therapeutic system (GITS) formulation, a controlled-release formulation for once-a-day administration, was evaluated in the Modern Approach to the Treatment of Hypertension (MATH) trial. In this study conducted at 127 centers, 1155 patients with mild-to-moderate hypertension representative of the spectrum seen in practice were included in the analyses of effectiveness. After a 2 week placebo period, nifedipine GITS therapy was started at 30 mg/day and was titrated to a maximum dose of 180 mg/day over 6 weeks. Response criteria were a sitting diastolic blood pressure less than 90 mm Hg and a decrease of greater than or equal to 10 mm Hg. After titration, patients were observed for 12 weeks during treatment. At the final visit, nifedipine GITS significantly (P less than .0001) reduced sitting systolic blood pressure 17 +/- 14 mm Hg (mean +/- SD), and sitting diastolic blood pressure 14 +/- 8 mm Hg. Similar highly significant reductions in standing blood pressure were observed. For all subjects, 76% achieved goal blood pressure response during titration. More than 50% were controlled on doses of 30 to 60 mg/day. At the final visit blood pressure reductions in men and women were similar, except for a significantly greater decrease in sitting systolic pressure for women. A similar proportion of blacks responded compared with whites, and reductions in sitting systolic and diastolic blood pressure were also similar in the 2 groups. Nifedipine GITS had no effect on renal function, serum potassium, or total, HDL, or LDL cholesterol. Uric acid was reduced by 0.5 mg/dL (P less than .001). 
4	Low-dose heparin. A cause of hematoma of rectus abdominis. Although hematomas of the rectus abdominis muscle are commonly reported complications of systemic anticoagulation treatment, they are a rare complication of prophylactic administration of low-dose heparin. The occurrence of a massive hematoma of the rectus sheath is reported in a woman with chronic obstructive pulmonary disease and acute respiratory failure who was receiving low doses of heparin for the prevention of deep venous thrombosis. Three other cases of hematoma of the rectus sheath resulting from prophylactic use of heparin are reviewed. The development of hematoma in these patients may have resulted from intramuscular abdominal injection of heparin and from strain of the rectus abdominis muscle caused by coughing. When prophylactic administration of heparin is necessary in patients with a tendency to paroxysmal cough, subcutaneous injections of heparin in the thigh may be preferable to subcutaneous injections in the abdomen. 
4	Multiple arterial fenestrations, multiple aneurysms, and an arteriovenous malformation in a patient with subarachnoid hemorrhage. We report the case of a 49-year-old, right-handed man with multiple vascular pathologies, including a fenestrated anterior communicating artery and middle cerebral artery, an aneurysm of the anterior communicating artery, multiple aneurysms of the middle cerebral artery, and an arteriovenous malformation. Diagnoses were made through computed tomography, cerebral angiography, magnetic resonance imaging, and intraoperative dissection. The lesions were managed surgically in stages with satisfactory results. Congenital and hemodynamic factors may have combined to manifest in the anomalies present in this unique case. We believe that no similar combination of vascular pathology has been reported previously. 
1	Radiographic manifestations of anomalies of the brain. Congenital brain anomalies are classified as developmental anomalies, effects of teratogens, errors of histogenesis, or sequelae of infections. The imaging options for delineation of these anomalies are many; a basic understanding of the disorder is central to the effective choice of imaging modality. This review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants. 
1	Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. In an effort to critically define the incidence and clinical characteristics of secondary responses to cisplatin-based therapy in patients with ovarian cancer previously treated with a cisplatin-based program, a retrospective review was undertaken of patients at the Memorial Sloan-Kettering Cancer Center who received greater than or equal to two cisplatin/carboplatin-based programs. Eighty-two patients were identified who met the entry criteria of having had a cisplatin-free interval (CFI) of more than 4 months between the completion of their first regimen and the institution of a second cisplatin/carboplatin program. Of the 72 assessable patients (10 had no measurable disease, and a laparotomy was not performed to assess response), 31 (43%) responded, including 10 surgically defined complete responses (S-CRs). The overall response rates (and S-CR rate), based on duration of CFI, were 5 to 12 months, 27% (5%); 13 to 24 months, 33% (11%); and more than 24 months, 59% (22%). Twenty-nine patients (35%) received noncisplatin/carboplatin-containing treatments between the cisplatin programs. Patients without any treatment for more than 24 months from the completion of their initial therapy experienced a 77% (17 of 22) response rate and a 32% (seven of 22) S-CR rate. In conclusion, secondary responses to cisplatin/carboplatin-based treatment are common in patients with ovarian cancer who have previously responded to the agents and increase in frequency with greater distance from the initial therapy. 
5	Catabolic effects of high-dose corticosteroids persist despite therapeutic benefit in rheumatoid arthritis. Although corticosteroids (CS) cause nitrogen wasting in healthy humans, it is not known whether the salutary antiinflammatory and appetite-stimulating effects of CS in inflammatory diseases mitigate this effect. We measured nitrogen balance before, during, and after 3 d of high-dose methylprednisolone therapy in nine patients with flare-ups of rheumatoid arthritis. There was evidence of preexisting somatic protein and fat depletion in seven of nine subjects. Patients were allowed to eat freely on a metabolic ward. Nitrogen balances were -0.89 +/- 1.38 g/d (means +/- SEM) before CS therapy, -5.77 +/- 1.30 g/d during therapy (P less than 0.001), and -3.54 +/- 1.38 g/d after therapy (P less than 0.01) despite increased energy and nitrogen intake and clinical resolution of inflammation during and after the pulse therapy. We conclude that patients with rheumatoid arthritis are often cachectic and high-dose CS cause nitrogen wasting in these patients despite an antiinflammatory and appetite-stimulatory benefit. 
3	Headaches in dementia. We investigated 288 elderly subjects with various degree of dementia, focusing on headaches. Seventy-three of 288 elderly subjects (25.3%) complained of some headaches. The most common type was the tension-type headache, from which 43 of the 73 subjects with headaches (58.9%) suffered. The degree of cognitive disturbances, evaluated by Hasegawa's intelligence scale, significantly correlated to the prevalence of headaches, and indicated that patients with dementia appeared to have less headaches. The methodological issues and views on headache research in dementia were assessed, and it is concluded that the field is a difficult one, with potential for error. 
5	Swimmer's migraine. Three cases of sudden, severe headache occurring during swimming are described. A 51-year-old female had been engaging in a swimming exercise for about 20 minutes when she suddenly experienced a pulsating headache in the parietotemporal region, accompanied by nausea. A few days later, she experienced a similar episode, again during swimming practice. A 45-year-old male developed a pulsating headache with nausea immediately after diving into a swimming pool, and had a similar attack during diving practice 1 week later. A 32-year-old male developed a pulsating headache accompanied by nausea while swimming in the sea. In all three cases, blood pressure, pulse rate, neurological findings, cervical spinal x-rays, brain CT scans, and hematological findings were normal and the outcome was good. Although these patients' headaches were diagnosed as benign exertional headache, pathophysiologically they appeared to resemble the headache associated with sexual activity. 
5	Does somatostatin analogue prevent experimental acute pancreatitis? Because somatostatin is a potent inhibitor of pancreatic secretion, we hypothesized that pretreatment with somatostatin analogue octreotide (SMS 201-995) might prevent cerulein-induced edematous pancreatitis. We studied 18 rats prepared with jugular vein catheters. The following agents were administered intravenously to groups of four rats for 6 hours: 1 mL/h (control) crystalloid solution; 1-microgram/kg bolus then 1 microgram/kg per hour of octreotide; and 5 micrograms/kg per hour of cerulein; also, in a fourth group of six rats, octreotide and cerulein were administered simultaneously. At the end of experiments, blood was drawn for plasma amylase determinations; rats were killed and pancreata were examined. Supramaximal cerulein administration to conscious rats induced hyperamylasemia and edematous pancreatitis, confirming previous observations; in both groups of rats receiving cerulein, there was prominent interstitial edema, acinar vacuolization, and mild-to-moderate acute inflammation. While octreotide pretreatment of rats with cerulein-induced acute pancreatitis was associated with a lesser increase of wet pancreas weight and plasma amylase concentration, there was little overall benefit of octreotide pretreatment in this form of experimental acute pancreatitis. 
1	Angiocentric immunoproliferative lesion/T-cell non-Hodgkin's lymphoma and the acquired immune deficiency syndrome: a case report and review of the literature. The lesions known as lymphocytic vasculitis, polymorphic reticulosis (midline malignant reticulosis, lethal midline granuloma), lymphomatoid granulomatosis, and angiocentric lymphoma form what have been collectively termed the angiocentric immunoproliferative lesions (AIL). Because of recent reports demonstrating clonal rearrangements of the T-cell receptor in these lesions, the AIL are now thought to represent a continuous spectrum of post-thymic T-cell non-Hodgkin's lymphoma (NHL). NHL associated with the acquired immune deficiency syndrome (AIDS) represents intermediate or high-grade B-cell malignancies in HIV-infected patients that may be etiologically related to the Epstein-Barr virus (EBV). There have been reports of EBV-associated T-cell NHL, AIL, and large granular lymphocyte (LGL) proliferations, as well as HIV-associated T-cell neoplasia, LGL/T-cell proliferations, and AIL. We describe a case of polymorphic reticulosis (lethal midline granuloma) arising in an HIV-infected individual, who later progressed to AIDS, and review the literature on HIV-associated and EBV-associated T-cell neoplasia, LGL/T-cell proliferations, and AIL. The etiology of this AIL/T-cell NHL, especially in relation to EBV and HIV, is discussed. 
1	Acute tumor lysis syndrome after intrathecal methotrexate administration. A 44-year-old man had acute tumor lysis syndrome after a single dose of intrathecal methotrexate was administered for lymphomatous meningitis (high-grade, small noncleaved B-cell) in the setting of untreated systemic disease. The metabolic derangements reversed completely with conservative therapy and did not recur with subsequent treatment. Intrathecal methotrexate administration results in potentially toxic systemic methotrexate levels which persist longer than an equivalent systemic dose. Active central nervous system lymphoma may increase the duration of toxic levels in the circulation and contribute to the peripheral effects of the drug. The pathogenesis of tumor lysis syndrome in this patient and the mechanisms of systemic toxicity of intrathecal methotrexate are discussed. 
1	Repetitive conservative surgery for recurrence of endometriosis. We evaluated the recovery of fertility and the relief of pain symptoms in a long-term follow-up of 42 women undergoing repetitive conservative surgery for recurrent endometriosis. The mean age of the patients was 31.1 +/- 4.3 years. At the time of their second operation the disease was stage IV in 14 women, stage III in 25, and stage I in three. After reoperation, the patients were followed for a mean period of 41.8 +/- 30.3 months. Pain symptoms returned in eight women, dysmenorrhea and deep dyspareunia in eight, and pelvic pain in seven. Eight of the 28 women (28.6%) who attempted to conceive achieved a total of 13 pregnancies. The corrected pregnancy rate was 35%, and the cumulative rate at 27 months was 30.7%. A third operation was necessary in six women after a mean period of 35 months. Conservative surgery is an effective therapeutic option for infertile patients with recurrent endometriosis. 
4	Proximal tubular alpha 2-adrenoceptor density in the spontaneously hypertensive rat. In the kidney of the spontaneously hypertensive rat (SHR), alpha 2-adrenoceptors are increased and may be related to hypertension. We measured alpha 2-adrenoceptor density and characteristics in a proximal tubule suspension with the alpha 2-adrenoceptor antagonist, 3H-rauwolscine. SHR had a significantly greater density of alpha 2-adrenoceptors when compared to their normotensive controls, the Wistar-Kyoto (WKY) rats (146 +/- 13 v 58 +/- 7 fmol/mg protein; P less than .001). Competition experiments determined the alpha 2-adrenoceptor to be an alpha 2B-subtype. Agonist competition curves were shallow and exhibited pseudo-Hill slopes of less than 1, indicating that they bind to both high and low affinity receptor sites. In summary, alpha 2-adrenoceptors are increased in the proximal tubule of SHR and appear to be of the alpha 2B-subtype. An increase in alpha 2-adrenoceptors may be related to abnormalities in hypertension. 
5	Babies born before arrival at hospital. OBJECTIVE--To establish the prevalence of babies born before arrival at two local hospitals. To identify women at risk of giving birth before arrival, and the morbidity and mortality associated with such births. DESIGN--A case control study. Each baby born before arrival and its mother were compared with the next born in the hospital (random control), and one matched for gestation and birthweight, together with their mothers. SETTING--Two maternity units serving East Birmingham and Solihull. SUBJECTS--All babies (and their mothers) born before arrival at these hospitals from January 1983 to December 1987. MAIN OUTCOME MEASURES--Perinatal mortality rates, patterns of perinatal morbidity, demographic, social and obstetric features of the mothers. RESULTS--137 (0.44%) of 31,140 consecutive births were before arrival at hospital (BBA group). The perinatal mortality rate in the BBA group was 58.4/1000 (8 deaths) compared with 10.1/1000 for all inborn babies (relative risk 5.8, 95% confidence interval 2.9-11.4). In the BBA group the mean birthweight of 3008 g was 212 g (95% CI 50-374 g) less than that in the random control group; the mean gestation of 266 days was 10 days less (95% CI 5.9-14.1 days) than in the random control group. Hypothermia was the commonest morbidity. Women delivered before arrival tended to be either multigravid inner city Asians living a long way from the hospital or unmarried unbooked younger white Europeans. CONCLUSIONS--The high perinatal mortality was related to immaturity and low birthweight, rather than to birth before arrival itself. Although groups of mothers at risk of delivery before arrival can be identified more information is needed to establish whether additional antenatal care would be beneficial for these women and their babies. 
4	Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries. Pertussis toxin, an irreversible inhibitor of some G proteins, inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. In the present study, the effects of the toxin were examined on endothelium-dependent and -independent relaxations of hypercholesterolemic and atherosclerotic porcine coronary arteries to assess the functional state of the endothelial pertussis toxin-sensitive G protein. Male Yorkshire pigs were maintained on either a regular diet (control group, n = 7) or a 2% high-cholesterol diet (cholesterol-fed group, n = 7) for 10 weeks. After the initial 2 weeks of maintenance, animals in both groups underwent balloon catheter removal of the endothelium of the left anterior descending or left circumflex coronary arteries. Endothelium-dependent responses were examined in vitro after 10 weeks of maintenance; at this time, a full lining of endothelial cells in both left coronary arteries was confirmed histologically. In arteries with endothelium of the control group (normal responses), pertussis toxin significantly inhibited the endothelium-dependent relaxations to serotonin, UK14304 (a selective alpha 2-adrenergic receptor agonist), and thrombin but not those to ADP, bradykinin, or the calcium ionophore A23187. In previously denuded arteries of the control group (effects of endothelial regeneration alone) or intact arteries of the cholesterol-fed group (effects of hypercholesterolemia alone), the relaxations to serotonin, UK14304, and thrombin were impaired significantly; those relaxations were impaired further in previously denuded arteries of the cholesterol-fed group (effects of atherosclerosis). The inhibitory effects of pertussis toxin were significantly reduced after endothelial regeneration and in hypercholesterolemia and were almost absent in atherosclerosis. 
3	Development of language in six hemispherectomized patients. The development of language skills in the isolated right hemisphere was investigated by comparing the performance of 3 left hemispherectomized with that of the 3 right hemispherectomized patients and three groups of control subjects on baseline clinical measures of language and on production and judgement of morphological markers. The initial brain insult in the hemispherectomy patients of each group had occurred either during early, middle or late childhood. The left hemispherectomy patients were severely impaired in language processing across all three stages of language development. The consequences of a right hemisphere insult on language development were more restricted, with deleterious effects being apparent only in the case in which the lesion was acquired during early childhood. 
1	Mandibular reconstruction with composite microvascular tissue transfer. Microvascular free tissue transfer has provided a variety of methods of restoring vascularized bone and soft tissue to difficult defects created by tumor resection and trauma. Over 7 years, 26 patients have undergone 28 free flaps for mandibular reconstruction, 15 for primary squamous cell carcinoma of the floor of the mouth or tongue, 7 for recurrent tumor, and 6 for other reasons [lymphangioma (1), infection (1), gunshot wound (1), and osteoradionecrosis (3)]. Primary reconstruction was performed in 19 cases and secondary in 9. All repairs were composite flaps including 12 scapula, 5 radial forearm, 3 fibula, 2 serratus, and 6 deep circumflex iliac artery. Mandibular defects included the symphysis alone (7), symphysis and body (5), symphysis-body-ramus condyle (2), body or ramus (13), and bilateral body (1). Fourteen patients had received prior radiotherapy to adjuvant or curative doses. Eight received postoperative radiotherapy. All patients had initially successful vascularized reconstruction by clinical examination (28) and positive radionuclide scan (22 of 22). Bony stability was achieved in 25 of 26 patients and oral continence in 24 of 26. One complete flap loss occurred at 14 days. Complications of some degree developed in 22 patients including partial skin necrosis (3), orocutaneous fistula (3), plate exposure (1), donor site infection (3), fracture of reconstruction (1), and fracture of the radius (1). Microvascular transfer of bone and soft tissue allows a reliable reconstruction--despite previous radiotherapy, infection, foreign body, or surgery--in almost every situation in which mandible and soft tissue are absent. Bony union, a healed wound, and reasonable function and appearance are likely despite early fistula, skin loss, or metal plate or bone exposure. 
5	Nitrous oxide antagonizes CNS stimulation by laudanosine in mice. We have investigated whether nitrous oxide antagonizes or augments the CNS stimulant action of laudanosine in mice by comparing the mean convulsive doses (CD50 (SE] of a control group and those following pretreatment with 65% nitrous oxide in oxygen for 20 and 180 min. Nitrous oxide significantly increased CD50 from 46.8 (1.4) mg kg-1 of control to 57.3 (1.3) mg kg-1 at 20 min and 53.5 (1.7) mg kg-1 at 180 min. The attenuation of the effect of nitrous oxide at 180 min, suggestive of possible partial drug tolerance, was not statistically significant. These findings indicate that nitrous oxide antagonizes the CNS stimulating action of laudanosine. 
5	Observations on the haemopoietic response to critical illness. Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM-CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis. 
1	Reconstructions after resections of tumors involving the proximal femur. Advances in prosthesis design, the use of allografts, and a systematic approach to the staging and surgical treatment of musculoskeletal tumors have made limb salvage possible in the proximal femoral region. With the use of effective adjuvant therapy, limb salvage is now an option for the majority of patients presenting with locally invasive neoplasms in this area. The increase in functional outcome is sufficient to warrant serious consideration of limb salvage over the corresponding amputation. Preoperative planning is discussed along with surgical techniques. 
2	The effects of synthetic human secretin on calcium carbonate solubility in human bile This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 micrograms.kg-1.h-1 for 45 minutes followed by 0.5 micrograms.kg-1.h-1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and PCO2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ion-specific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 +/- 3 mmol/L to 41 +/- 3 mmol/L (P less than 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 +/- 2 mmol/L to 4.7 +/- 1 mmol/L (P less than 0.05). Ionized calcium concentrations decreased from 0.7 +/- 0.005 mmol/L to 0.5 +/- 0.02 mmol/L (P less than 0.05) while pH increased significantly from 7.44 +/- 0.06 to 7.6 +/- 0.04 (P less than 0.05). Carbonate concentrations increased significantly from 0.15 +/- 0.02 mmol/L to 0.26 +/- 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 +/- 0.002 (mmol/L)2 to 0.135 +/- 0.015 (mmol/L)2 (P less than 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for calcium carbonate precipitation. 
1	Radiation therapy for intraductal carcinoma. Is it an equal alternative? Of 213 consecutive patients with intraductal carcinoma, 109 were selectively treated with mastectomy and 104 with radiation therapy. There were eight local recurrences, seven in patients treated with radiation therapy and one in a patient treated with mastectomy. Histologically, there were 110 comedocarcinomas and 103 noncomedocarcinomas. Seven local recurrences occurred in patients with comedocarcinomas and one in a patient with a noncomedo tumor. Three (38%) of eight local recurrences (all comedo) were invasive. The 5-year actuarial survival for all subgroups was 100%. The median follow-up was 51 months. Intraductal carcinoma is unlikely to metastasize to axillary lymph nodes, and routine dissection is unnecessary. Ductal carcinoma in situ of the comedo variety is more aggressive and more likely to recur than its noncomedo counterpart. We currently view conservative therapy for patients with intraductal comedocarcinoma with caution. 
5	Colorectal adenocarcinoma in patients less than 40 years of age. From 1973 to 1985, 105 patients under 40 years of age were treated for colorectal adenocarcinoma at Roswell Park Cancer Institute. There were 51 males and 54 females. The mean age was 32 years. The majority of patients were treated for left colon or rectal carcinomas. Ninety-seven of 105 patients underwent surgical resection of their primary cancer, 70 (67 percent) of which were potentially curative. Twenty-seven patients underwent palliative resections. Dukes' A or B lesions were not seen in patients less than 20 years old, whereas these early lesions were seen in 11 percent of patients 20 to 29 years old and in 26 percent of patients greater than 30 years of age. The mean survival for patients between 20 and 29 years was 39 months and 46 months for patients 30 years and older. 
3	Autonomic dysfunction and Guillain-Barre syndrome. The use of esmolol in its management. A 17-year-old girl with Guillain-Barre syndrome and autonomic dysfunction was treated successfully with esmolol. Esmolol may be an appropriate drug for the rapid assessment and control of tachyarrhythmias in critically ill patients. 
5	Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: a randomized, placebo-controlled, crossover trial. Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05). 
5	Neonatal calves develop airflow limitation due to chronic hypobaric hypoxia. Neonates and infants presenting with pulmonary hypertension and chronic hypoxia often exhibit airway obstruction. To investigate this association, we utilized a system in which neonatal calves are exposed to chronic hypobaric hypoxia and develop severe pulmonary hypertension. For the present study, one of each pair of six age-matched pairs of neonatal calves was continuously exposed to hypobaric hypoxia at 4,500 m (CH); the other remained at 1,500 m. At 2 wk of age, mean pulmonary arterial pressure (MPAP), dynamic lung compliance (Cdyn), resistance (RL), and static respiratory system compliance (Crs) were measured at 4,500 m in both CH and control calves exposed acutely to hypoxia (C). These measurements were repeated after cumulative administrations of nebulized methacholine (MCh). Tissues were removed for histological examination and assessment of bronchial ring contractility to MCh and KCl. After 2 wk of hypobaric hypoxia, MPAP (C 35 +/- 1.7 vs. CH 120 +/- 7 mmHg, P less than 0.001) and RL (C 2.64 +/- 0.16 vs CH 4.99 +/- 0.47 cmH2O.l-1s, P less than 0.001) increased. Cdyn (C 0.100 +/- 0.01 vs. CH 0.082 +/- 0.007 l/cmH2O) and Crs (CH 0.46 +/- 0.003 vs. C 0.59 +/- 0.009 l/cmH2O) were not significantly different. Compared with airways of C calves, airways of CH animals did not exhibit in vivo or in vitro MCh hyperresponsiveness; however, in vitro contractility to KCl of airways from CH animals was significantly increased. Histologically, airways from the CH calves showed increases in airway fibrous tissue and smooth muscle. 
1	Imaging modalities in recurrent head and neck tumors. Patients with recurrent neoplasms of the head and neck present perplexing management problems, and accurate preoperative assessment of their disease is crucial. Thirty-eight patients with suspected recurrent neoplasms comprise this study: 30 had computed tomography scans, 4 had magnetic resonance images, and 4 patients underwent both computed tomography and magnetic resonance imaging to assess the anatomical extent of pathology in 34 malignant and 4 benign tumors. Contrast enhancement was essential for detecting disease on computed tomography scan. Differentiation of recurrent tumor was more difficult when the patient had undergone radiation. Magnetic resonance imaging demonstrated superior visibility in recurrent parotid and paranasal sinus neoplasm, but was less helpful in laryngeal and pharyngeal recurrences. Computed tomography demonstration of a mass with infiltration of normal fat or tissue planes or lymphadenopathy correlated highly with recurrent disease. Imaging techniques and fine points for determining recurrent neoplasms are presented. 
5	Advantages of beta blockers versus antiarrhythmic agents and calcium antagonists in secondary prevention after myocardial infarction. Patients who have sustained greater than or equal to 1 myocardial infarcts are at high risk for sudden death or reinfarction; the risk is highest for those with lowest ventricular ejection fraction, continuing myocardial ischemia and asymptomatic high-density and complex premature ventricular contractions. At present, beta blockers when given prophylactically are the only agents that reduce the incidence of sudden death and reinfarction in survivors of myocardial infarction (MI) in the first 2 years. The beneficial effect was shown to correlate with a reduction in heart rate, the effect being absent or deleterious with beta blockers with marked sympathomimetic activity. The effects of beta blockers on ventricular fibrillation appeared to be dissociated from those on premature ventricular contractions. Trials with calcium antagonists indicate that these drugs had no effect or increased the mortality rate. The divergent effect of beta blockers and calcium antagonists is unexplained but may be due in part to a lack of bradycardiac effect of calcium antagonists; there were no differences in effect among different calcium antagonists. Data from trials involving class I antiarrhythmic agents indicate that agents acting by depression of cardiac conduction are either devoid of effect or produce a modest increase in mortality. Results of the Cardiac Arrhythmia Suppression Trial, employing the newer class I agents flecainide and encainide, were used to determine whether the suppression of premature ventricular contractions in the survivors of acute MI reduces mortality. Flecainide and encainide suppressed premature ventricular contractions greater than 80%, but resulted in an increased mortality rate undoubtedly due to a marked proarrhythmic effect. Whether these data can be extrapolated to all class I agents is uncertain. Preliminary data with class III antiarrhythmic agents suggest that these agents, especially amiodarone, similarly to beta blockers, have the potential to reduce mortality in survivors of MI. Evolving data suggest that in the secondary prevention of morbid events in the survivors of acute MI, the focus must shift away from antiarrhythmic agents that delay conduction and toward beta blockers and antifibrillatory actions resulting from a prolongation of refractoriness. 
5	Development of a soft, pliable, slow heparin release venous graft. To prevent their collapse, a certain amount of stiffness is generally required for prosthetic venous grafts, so EPTFE grafts have been used. However, the native vein is pliable without any stiffness. We developed a soft and pliable graft that can maintain patency of the lumen because of its compliance. Fresh porcine ureter was incubated in a ficin solution to remove cell components and noncollagenous proteins. One percent protamine sulfate solution was injected into the ureter lumen to impregnate the inner surface. The ureter was then crosslinked with a 1% glutaraldehyde solution, dipped into a 1% heparin solution for 5 hours, and rinsed with distilled water. This procedure made the ureter very soft and pliable, and also conferred antithrombogenicity to the graft by heparinization. The grafts were implanted into the posterior vena cavae of 20 dogs and were removed from 1 to 878 days after implantation. Eighteen grafts were patent, but two grafts were occluded at the anastomotic site at 218 and 107 days, respectively. As a control experiment, nonheparinized grafts were implanted into 15 dogs; all were occluded with fresh thrombi. All the patent grafts kept their original elasticity, which allowed them to heave in unison with the heartbeat, and were similar in appearance to the native vena cava. Heparinization was effective in preventing thrombus formation. These results indicate that this type of graft is an ideal prosthesis as a venous graft, having physiologic properties such as compliance and antithrombogenicity. 
4	Rate-related left bundle branch block as a cause of non-ischemic chest pain. A case is presented of rate-dependent left bundle branch block associated with chest pain in a patient with angiographically normal coronary arteries. Lactate extraction showed no evidence of myocardial ischemia. It appears that in this case, chest pain was associated with sudden ventricular asynergy rather than myocardial ischemia. 
5	Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage. Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe. 
3	The role of methanethiol in the pathogenesis of hepatic encephalopathy. Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant. In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy. 
4	Acute myocarditis simulating myocardial infarction in a child. Pediatric chest pain usually occurs in benign conditions. However, this case portrays the dramatic electrocardiographic appearance of acute myocardial ischemia in a boy with biopsy-proven myocarditis who had only mild chest pain. This underscores the need for eliciting a detailed history when evaluating a patient with chest pain. If the pain cannot be clearly attributed to chest wall phenomena, or if there are historical or physical findings suggestive of an arrhythmia or angina, then further investigation with a chest radiograph and a 12-lead electrocardiogram is recommended. Myocarditis must be considered in the differential diagnosis of any child whose electrocardiogram is indistinguishable from an acute myocardial infarction. Finally, endomyocardial biopsy allows early diagnosis and institution of therapy, which may have beneficial effect on decreasing morbidity and mortality. Further follow-up and research is still needed to evaluate the effect of early treatment of myocarditis on long-term myocardial function and the development of chronic cardiomyopathy. 
2	Measles-associated diarrhea in hospitalized children in Lima, Peru: pathogenic agents and impact on growth. Because the causes of measles-associated diarrhea are not well known, 0- to 5-year-old children presenting to the hospital with measles-associated diarrhea (cases, n = 77) or acute diarrhea only (controls, n = 77) were compared. Growth and diarrheal morbidity were evaluated for 1 month after acute illness. Campylobacter jejuni was more frequently isolated from cases (31%) than controls (16%; P = .03). Rotavirus was absent in all cases versus 28% of controls (P less than .001). Incidence density for new episodes of diarrhea was significantly greater in cases (6.5 vs. 4.1; odds ratio, 1.6; confidence intervals, 1.09-2.34; P = .01), as was duration of episodes (3 vs. 2 days, P = .02). Both groups showed similar positive cumulative percentage weight gains throughout follow-up. These data support the theory of measles as a risk factor for developing diarrhea. The bacteriologic and virologic findings may reflect the immunologic response of the host to measles infection. 
1	A clinical and flow cytometric analysis of patients with nasopharyngeal cancer. Abnormal cellular DNA content, a hallmark of malignancy, is known to be an important prognostic factor in many human solid tumors; however, no data have been published on whether cellular DNA content carries prognostic significance for patients with nasopharyngeal cancer (NPC). Archival, formalin-fixed, paraffin-embedded pathology specimens representing pretreatment tissue biopsies from 55 patients (41 men and 14 women) with NPC were analyzed for cellular DNA content in a retrospective fashion from 1968 to 1988. Individual tumors were classified as either lymphoepithelioma, squamous cell, or anaplastic carcinoma, and were staged according to International Union Against Cancer (UICC) criteria. All patients were treated with curative intent using a 4 to 6 MeV linear accelerator to total doses ranging from 50 to 60 Gy in 4 to 6 weeks. The overall 5-year actuarial survival for all 55 patients was 44.4% (men, 41%; women, 52%). Survival by T stage was as follows: T1, 65%; T2, 51%; T3, 36%; and T4, 27%. Similarly, the 5-year survival rate declined as the bulk of nodal metastases increased: N0, 62%; N2, 50%; N3, 37%; and N1, 25%. Patients who had anaplastic carcinoma had a 5-year survival of 73%, those with lymphoepithelioma had a 60% survival, and those with squamous cell cancer (SCC) had a 30% survival. There was a statistically significant difference in 5-year survival between patients with SCC and those with nonkeratinizing histologies (P less than 0.05). In addition, there was a significant association between patients older than 40 years of age with SCC and patients younger than 40 years of age with nonkeratinizing malignancies (P less than 0.01). Of the 55 tumors successfully analyzed, 22 (40%) were diploid and 33 (60%) were aneuploid. The mean coefficient of variation (CV) of all 55 samples was 6.17%. There was no significant difference in 5-year survival between patients with diploid and those with aneuploid tumors (48% versus 42%). Furthermore, there was no statistically significant survival difference between aneuploid and diploid tumors within any one histologic subgroup. There was also no significant survival difference related to the DNA index. The results indicate that the extent of local tumor spread is still the most important prognostic factor for patients treated with radiotherapy for NPC. The data support the conclusion that patients with lymphoepithelioma and anaplastic carcinomas have a superior survival to patients with squamous cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	Hybridization protection assay: a rapid, sensitive, and specific method for detection of Philadelphia chromosome-positive leukemias. The Philadelphia (Ph1) chromosome is present in greater than 90% of patients with chronic myelogenous leukemia (CML) and in 2% to 20% of those with acute leukemias, for which it is an important prognostic marker too. The chimeric BCR-ABL mRNAs resulting from the translocation encode either a 210-Kd or a 190-Kd protein. The techniques used to detect Ph1 chromosome include karyotyping, Southern analysis to demonstrate bcr rearrangement, and polymerase chain reaction to amplify the BCR-ABL transcripts. However, the routine performance of these methods by clinical laboratories is cumbersome, time consuming, and exposes laboratory personnel to radioisotopes. We describe here the clinical application of a new method, the hybridization protection assay (HPA), which uses chemiluminescent acridinium-ester-labeled probes in conjunction with PCR for detection of the amplified BCR-ABL sequences. The method is sensitive, specific, and can reliably distinguish between the transcripts for P190BCR-ABL and P210BCR-ABL. In contrast to the 2 days or longer required for conventional hybridization, HPA analysis can be completed in less than 30 minutes. We have successfully used this method to analyze 60 leukemia samples (34 from Ph1-negative acute leukemias; 6 from Ph1-positive acute leukemias; and 20 from CML) with complete correlation (of BCR-ABL positivity or negativity) with the results of karyotype or Southern Blot analysis of genomic DNA for bcr rearrangement. Therefore, the HPA, in conjunction with PCR, appears to provide a rapid and reliable test for the diagnosis of Ph1-positivity. 
1	Association between DNA ploidy pattern and cellular atypia in colorectal carcinomas. A new clinical application of DNA flow cytometric study? Fresh tissue specimens from 406 colorectal carcinomas were analyzed by DNA flow cytometric study, and the DNA ploidy pattern was compared with Dukes' stage, histologic grade, and degree of cellular atypia. Sixty-one percent of the carcinomas had a distinct aneuploid DNA pattern. The proportion of aneuploid carcinomas was significantly higher in the advanced Dukes' stages than in the localized ones. A highly significant association was found between DNA ploidy pattern and degree of cellular atypia, whereas no association was demonstrated between DNA ploidy pattern and histologic grade. This finding might indicate that cellular atypia has a stronger prognostic impact than the growth pattern of the tumor. The authors suggest that flow cytometric DNA quantification may replace assessment of cellular atypia in the histologic evaluation. Furthermore, together with earlier findings by others, these results indicate that the degree of cellular atypia may be conserved during the development from adenomas to carcinomas. 
3	A self-administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome. Noninvasive tests for carpal tunnel syndrome (CTS) are of limited diagnostic value. A self-administered hand symptom diagram has been developed for use in the diagnosis and epidemiologic study of CTS. Diagrams are rated classic CTS, probable, possible or unlikely. Diagram ratings were compared with nerve conduction diagnoses in 110 patients with upper extremity complaints. A hand diagram rating of classic or probable CTS had sensitivity of 0.64, specificity of 0.73 and positive predictive value of 0.58. The negative predictive value of an unlikely diagram was 0.91. We conclude that the diagram is a useful diagnostic tool and may be valuable for occupational and population screening. 
5	Eosinophilic meningitis: cause of a chronic pain syndrome. Three tourists developed eosinophilic meningitis after visiting the Fijian Islands. Two had a severe and long lasting illness with chronic intractable pain. In one patient electrophysiological studies and MRI scan of the brain were abnormal and provided evidence of both radicular and cerebral parenchymal involvement by the most likely causative agent, Angiostrongylus cantonensis. 
3	Stroke in pediatric acquired immunodeficiency syndrome. In a 4 1/2-year period, 4 of 68 children in a longitudinal study of neurological complications of human immunodeficiency virus (HIV) infection had clinical and/or neuroradiological evidence of stroke, yielding a clinical incidence of stroke in this population of 1.3% per year. During this period, 32 subjects died, and permission for autopsy was granted in 18 of the patients, including 3 of 4 who had clinical evidence of stroke. The prevalence of cerebrovascular pathological features in our consecutive autopsy series was higher than the clinical incidence. At autopsy cerebrovascular disease was documented in 6 (24%) of 25 children with HIV infection, including all 3 children who had clinical evidence of stroke. Four patients had intracerebral hemorrhages, 6 patients had nonhemorrhagic infarcts, and 3 had both. Hemorrhage was catastrophic in 1 child and clinically silent in 3 children, all of whom had immune thrombocytopenia. One child had an arteriopathy that affected meningocerebral arteries. In another child, the arteries of the circle of Willis were aneurysmally dilated. Two children had coexisting cardiomyopathy and subacute necrotizing encephalomyelopathy with vascular proliferation. These results suggest that stroke should be considered when children with HIV infection develop focal neurological signs. 
5	Nurse-monitored cardiac recovery: a description of the first 8 weeks. Health problems and related patient management during early recovery after cardiac surgery are not well documented. As part of a larger study of recovery from cardiac surgery 75 patient-care giver pairs received telephone calls from nurses at 1, 2, 3, 4, 6, and 8 weeks after discharge for the purpose of intervening to facilitate early recovery at home. After each call, nurses recorded detailed notes on the patients' progress and concerns. Content analysis of detailed nurses' recordings revealed the following predominant nursing actions: assessment, provision of support, reinforcement of predischarge teaching, referrals, and teaching. The five nursing diagnoses that occurred most frequently across the 8-week recovery period were altered comfort: pain; ineffective coping, individual; activity intolerance; sleep pattern disturbance; and altered nutrition. In response to these problems, patients managed and prevented health-related problems and engaged in health promotional and normalizing activities. By anticipating common problems in recovery, patients and care givers can be better prepared for going home. Similarly nurses can be better prepared to anticipate and respond to common recovery problems. 
5	Acupuncture and chronic pain: a criteria-based meta-analysis. A literature search revealed 51 controlled clinical studies on the effectiveness of acupuncture in chronic pain. These studies were reviewed using a list of 18 predefined methodological criteria. A maximum of 100 points for study design could be earned in four main categories: (a) comparability of prognosis, (b) adequate intervention, (c) adequate effect measurement and (d) data presentation. The quality of even the better studies proved to be mediocre. No study earned more than 62% of the maximum score. The results from the better studies (greater than or equal to 50% of the maximum score) are highly contradictory. The efficacy of acupuncture in the treatment of chronic pain remains doubtful. 
2	Mucosal characteristics of pelvic ileal pouches. This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all eight with pouchitis) had subtotal or total villous atrophy and crypt hyperplasia. In this group, nine had colorectal type sulphomucin and the 40kD colonic protein was detected in two. These changes were not observed in patients with less severe villous abnormalities. Sucrase-isomaltase activity was, however, present in all 25 pouch specimens. We conclude that although some ileal pouches acquire certain colonic characteristics, complete colonic metaplasia does not occur. 
1	Insulin-like growth factor-I receptors in nonfunctioning thyroid nodules. We have recently demonstrated the production of insulin-like growth factor-I (IGF-I) as well as the presence of type I IGF receptors in human thyroid cells in primary culture. The role of IGF-I in the control of thyroid cell growth has been well established. In order to investigate the involvement of IGF-I in abnormal thyroid growth, the density of IGF-I receptors in solitary, cold, micro- and macro-follicular thyroid adenomas, and in extranodular histological normal tissue was studied. Forty-three euthyroid patients with isolated cold nodules were selected for the study. In 30 patients the presence of IGF-I receptors was evaluated by using quantitative immunohistochemistry; in 10 patients by using radioligand binding studies, and in 3 patients by using affinity labeling. Cross-linking and binding studies clearly demonstrated the presence of a homogeneous class of binding sites for type I IGF receptors. Furthermore, radioligand studies did not show any significant differences in receptor density between the 2 types of thyroidal tissues. Conversely, the computerized analysis of 900 fields of nodular and normal thyroid tissues immunostained with the monoclonal antibody alpha-IR3, strongly indicated that higher concentrations of IGF-I receptors were present in the epithelial cells of non-functioning thyroid nodules than in the adjacent extranodular thyroid tissues. These studies strongly suggest that the same type I IGF receptor is present in thyroid follicular adenomas as in histological normal thyroid tissue removed from the same patient. The higher concentration of IGF-I receptors as documented by immunostaining in the adenomas suggests that IGF-I may contribute to the abnormal growth of the neoplasms. 
2	Duodenal ulcer and refined carbohydrate intake: a case-control study assessing dietary fibre and refined sugar intake An association between duodenal ulceration and a low fibre intake and a high refined carbohydrate diet has been reported. We therefore compared the current diet, smoking habits, social class, and possible other risk factors of 78 patients with duodenal ulcer and a community control group matched for age and sex. Logistic regression for matched sets was used to calculate the relative risks for successive quintiles of dietary fibre and sugar intake before and after adjustment for total calorie intake and for the possible confounding effect of other known risk factors. Relative risks did not differ materially or consistently for total dietary fibre or for the cereal moiety whether adjusted or not for calorie intake. By contrast, relative risks tended to be reduced with high vegetable fibre intake and with low refined sugar intake. After controlling for smoking and social class, both of which were associated with ulcer disease, and for relative weight (Quetelet's index), the relation between ulcer disease and low refined sugar intake persisted, while that with high vegetable fibre intake was reduced. The results of this study indicate that a lack of cereal or total fibre intake plays no part in duodenal ulcer development but that a low refined sugar intake may be a protective factor. 
5	Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. Forty-seven patients with metastatic malignant melanoma were treated with two 5-day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2. 
5	Possible platelet contribution to pathogenesis of transient neonatal hyperammonaemia syndrome. The pathogenesis of the transient neonatal hyperammonaemia syndrome is largely unknown. The role of platelet activation was investigated in three preterm infants with this syndrome by non-invasive methods. In all three infants, urinary concentrations of beta-thromboglobulin and 11-dehydrothromboxane B2 levels were much higher during the hyperammonaemia than those in ten control preterm infants. It is possible that transient platelet activation occurs in the portal system of these infants, thereby causing the hyperammonaemia. 
5	Acute bronchitis: general practitioners' views regarding diagnosis and treatment. A survey was conducted among 800 Dutch general practitioners to establish their views on the diagnosis and treatment of bronchitis and related disorders with reference to 12 theoretical patients. The answers of the 467 respondents (response rate 60%) showed no clear relationship between signs and symptoms of the patients and the diagnosis made. In the authors' opinion the diagnosis of pneumonia was made too often. The decision whether or not to prescribe an antibiotic for a coughing patient was based in part on the diagnosis made, but in part it was also made on the basis of the signs and symptoms, irrespective of the diagnosis. The authors have the impression that general practitioners tend to prescribe antibiotics too quickly to coughing patients. There is a need for guidelines for diagnosis and treatment of patients with acute bronchitis and related conditions. 
5	All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. All-trans retinoic acid induces leukemic cells from patients with acute promyelocytic leukemia (M3) to differentiate in vitro to mature granulocytes which express the CD15 antigen and are capable of respiratory burst function. Of 35 M3 samples, only one failed to respond. In eight cases, we compared the efficacy of two naturally occurring isomers of retinoic acid, all-trans RA and 13-cis RA. Both isomers induce maximal differentiation at 10(-6) mol/L. The maximal response was maintained at 10(-7) mol/L for the all-trans but not for the 13-cis RA. We also observed that the metabolites 4-oxo-all-trans and 4-oxo-13-cis were effective at 10(-6) mol/L. This 1 order of magnitude difference in the in vitro differentiating potencies of all-trans RA and 13-cis RA in the blasts of promyelocytic leukemias predicts a difference in the clinical efficacy of the two drugs. 
4	Clinical and anatomical considerations for nonoperative therapy in tibial disease and the results of angioplasty. For a 6-year period, 96 patients had 146 below-knee angioplasties. There were 31 total occlusions and 95 multiple stenoses. All patients had distal ischemia, and 40% had gangrene. The primary success rate was 97%, and the 2-year limb salvage rate was 83%. The ankle/brachial index increased from a mean of 0.25 before the procedure to 0.62 afterward. At 2 years (35 patients), the mean ankle/brachial index was 0.55. For the same period, 320 femorodistal bypasses were performed. The results of angioplasty are comparable to those of surgery, but angioplasty is only suitable in about 20-30% of patients presenting with isolated tibial disease. Suitable lesions are five or fewer stenoses and occlusions 5 cm or less in length. 
3	Urinary retention due to sacral myeloradiculitis: a clinical and neurophysiological study. We report 5 cases of sacral myeloradiculitis presenting with transient urinary retention. Neurophysiological testing, including bulbocavernosus reflex, pudendal evoked response and external anal sphincter electromyography, was performed. Parasympathetic pelvic nerves, pudendal nerves as well as the spinal cord seem to be involved to various degrees in this infrequent disorder. 
1	Predictors of physician nonadherence to chemotherapy regimens. Physician nonadherence to cancer treatment regimens may diminish treatment efficacy and compromise clinical research. The influence of clinical, demographic, and psychosocial patient characteristics on physician adherence to breast cancer chemotherapy was investigated, as was the role of the clinician's attitudes concerning the chemotherapy. One hundred seven women recently diagnosed with breast cancer were followed for 26 weeks of treatment. Fifty-six (52%) of the patients experienced unjustified modification for at least one chemotherapeutic agent. Stepwise multiple regression revealed independent contributions of increased patient age, treatment setting (clinic versus academic or community private practice), and stage of disease to physician nonadherence. Regimen complexity, delay in seeking treatment, and presence of psychiatric disorder did not contribute, in general, to unjustified regimen modifications. Patient psychological and psychiatric factors, however, did influence prescribing behavior for vincristine. Physician awareness of factors contributing to unnecessary treatment modifications may reduce the frequency of such behaviors. 
5	Decreased toxicity of polymorphonuclear neutrophils toward hepatocytes isolated from rats with acute inflammatory reaction. We have recently demonstrated that polymorphonuclear neutrophils were toxic to hepatocytes through a protease-mediated mechanism. Since synthesis of antiproteases is markedly increased during acute inflammatory reaction, the aim of this work was to investigate the toxicity of neutrophils against normal vs. inflammatory rat hepatocytes. Acute inflammatory reaction was induced by subcutaneous injection of turpentine 24 hr before the experiments. Hepatocytes from normal and turpentine-treated rats were isolated by collagenase digestion. They were incubated with human neutrophils stimulated by 1 mg/ml opsonized zymosan. Cytotoxicity was quantified by the percentage of alanine aminotransferase activity released by hepatocytes in culture medium after an 18-hr incubation period. By comparison to normal hepatocytes, inflammatory hepatocytes were more resistant to the toxicity of neutrophils. At a neutrophil/hepatocyte ratio of 20:1, the alanine aminotransferase activity releases were 53.7% +/- 5.4% (mean +/- 1 S.E.) and 27.4% +/- 4.8% for normal and inflammatory hepatocytes, respectively. Similarly, inflammatory hepatocytes were found to be less sensitive than normal hepatocytes to the toxic effect of purified neutrophil cathepsin G. In contrast, both types of hepatocytes exhibited the same sensitivity to H2O2 generated by a system consisting of glucose and glucose oxidase. Two arguments suggested that the resistance of inflammatory hepatocytes to protease toxicity was explained by an increased production of antiproteases by these cells: (a) when tested against cathepsin G and porcine pancreatic elastase activities, the protease inhibitory capacity of conditioned medium from inflammatory hepatocytes was higher than that of conditioned medium from normal hepatocytes; (b) conditioned medium from inflammatory hepatocytes markedly reduced the toxicity of stimulated neutrophils as that of cathepsin G. 
3	Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. To assess the magnitude of Creutzfeldt-Jakob disease (CJD) occurrence among recipients of pituitary-derived human growth hormone (HGH), we conducted an epidemiologic follow-up of 6284 recipients of HGH distributed through the National Hormone and Pituitary Program. Seven neuropathologically confirmed cases of CJD have occurred in this population to date: six patients with clinical CJD presented with ataxia and imbalance, rather than with altered mentation, which is the most common initial manifestation in sporadic CJD, and one patient died in the preclinical incubation state of the disease. All seven cases occurred among the nearly 700 HGH recipients who started therapy before 1970. Since only 10% of the cohort has been followed up for the 15-year average incubation interval from midpoint of HGH treatment to onset of symptoms, the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of CJD. The median duration of HGH therapy of 100 months in the CJD cases was significantly longer than 41 months for all patients starting treatment before 1970; thus, the duration of pituitary HGH therapy is a major risk factor for CJD. 
5	Effect of motion artefact on pulse oximeters: evaluation of four instruments and finger probes. The ability of the Ohmeda 3700, Nellcor N200, Datex Satlite Plus and Simed S100 pulse oximeters to detect induced hypoxaemia in the presence of motion artefact was assessed, under conditions of controlled vibration using an industrial vibration facility. Vibration at 4 Hz and 8 Hz induced increases in detection time for hypoxaemia and spurious decreases in the displayed SaO2 in some of the oximeters tested. Finger-dependent differences in oximeter performance and pulse rate registration were noted especially in those oximeters without ECG linkage (Ohmeda 3700 and Simed S100). Subsequently, eight different pulse oximeter finger probes were assessed for those characteristics that may predispose to motion artefact. There were marked differences in the mass of the probes, the forces exerted on the test finger and in the force required to displace the probes from the subject's finger. Differences in both the microprocessor programmes and the physical characteristics of the finger probes may explain the observed differences in function. Similar studies should form part of the standard evaluation of new pulse oximeters. 
4	Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions. Myocardial areas distal to complete coronary artery occlusions are poorly protected by antegrade cardioplegia. We assessed the effects of coronary sinus cardioplegia in 30 patients undergoing bypass operations and at high risk of cardioplegic maldistribution because of the following anatomical patterns of coronary artery disease: critical (greater than or equal to 50%) stenosis of the left main trunk with total occlusion of the right coronary artery (16 patients) or critical (greater than or equal to 70%) stenosis of the right coronary artery with total occlusion of the left anterior descending (11 patients) or circumflex artery (3 patients). After induction of arrest through the aorta, coronary sinus cardioplegia was given intermittently during the cross-clamp period at a flow rate of 100 mL/min. Intraoperatively, occluded arteries were consistently found to be filled with the retrogradely infused solution. One patient died early postoperatively of low cardiac output and a second patient died later during his hospital stay, presumably of an arrhythmia. At autopsy, none of them had pathological evidence of inadequate myocardial protection. One patient sustained a myocardial infarction and 3 others required inotropes for more than 24 hours postoperatively. Postoperative values for right and left stroke volume indices were not significantly different from prebypass levels. Overall, these results are consistent with the occurrence of limited intraoperative ischemic damage and, by inference, suggest the efficacy of the coronary sinus route in preserving myocardial areas supplied by completely occluded coronary arteries and, hence, in jeopardy of inadequate cardioplegia delivery. 
4	Ability of calcium-entry blockade by felodipine to disclose different pathogenetic mechanisms behind hyperventilation-induced myocardial ischemia in men. To verify that myocardial ischemia occurring during either the overbreathing or recovery phase of the hyperventilation test is based on different pathogenetic mechanisms, 2 consecutive series of patients, selected on the basis of their response to a run-in hyperventilation test, were studied. Group I comprised 15 patients who developed ST-segment depression early during overbreathing, whereas group II consisted of 12 patients showing ST-segment depression late during the recovery phase. A single oral dose of felodipine 10 mg or of placebo was administered on 2 consecutive days according to a randomized, double-blind, crossover design, and the hyperventilation test was repeated, on both days of the study, 3 to 5 hours after drug intake. In group I, ST-segment depression occurred after placebo in all patients during overbreathing, with an increase in rate pressure product (from 112 +/- 31 at baseline to 168 +/- 55 mm Hg x beats/min/100 at the onset of ST-segment depression; p less than 0.01). After felodipine, 13 patients continued to show ST-segment depression during overbreathing, together with an increase in rate pressure product (from 107 +/- 24 at baseline to 158 +/- 46 mm Hg x beats/min/100 at the onset of electrocardiographic changes; p less than 0.01). In group II, all 12 patients showed ST-segment depression during recovery after placebo, with a rate pressure product comparable to baseline conditions (112 +/- 35 at baseline vs 102 +/- 27 mm Hg x beats/min/100 at the onset of ST-segment depression; difference not significant). After felodipine, no patient developed ST-segment depression or chest pain. 
1	Pleomorphic (anaplastic) neuroblastoma in nude mice. Two pleomorphic (anaplastic) neuroblastomas, from two children aged 1 and 6 years, were transplanted into nude mice. Two noteworthy observations were made. In one case, the transplanted tumor gave rise to a soft-tissue sarcoma. Moreover, in both cases hepatic metastases were associated with a striking modification of murine hepatocytes, resulting in hyperchromatic and dysplastic nuclei. The latter finding was particularly evident in the hepatic areas surrounding all metastases of pleomorphic (anaplastic) neuroblastoma cells. 
5	Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas. Cutaneous sarcoidosis often responds poorly to topical and intralesional corticosteroids but may respond to moderate to high doses of oral corticosteroids. To avoid the use of systemic corticosteroids, we treated 17 patients with cutaneous sarcoidal granulomas with hydroxychloroquine (2 to 3 mg/kg/day) in an open clinical trial. If response occurred, other medications were first tapered and then the hydroxychloroquine dosage was reduced or stopped. The cutaneous lesions of 12 patients regressed within 4 to 12 weeks, and they were able to stop other therapies; three patients had a partial response, and two patients had no regression. Two of eight patients with pulmonary sarcoidosis improved. No ocular toxicity was noted. 
5	Long term survival and severe rebleeding after variceal sclerotherapy. Of 197 consecutive patients with cirrhosis admitted because of bleeding from esophageal varices, 133 were included in a prospective study of elective sclerotherapy. We evaluated the incidence of extensive rebleeding and mortality rate. The period of study was 54 months and the mean follow-up period was 21 months. Forty-one patients had severe rebleeding and a majority of the episodes occurred during the first year. Only four patients had more than five sessions of sclerosis when rebleeding occurred. The probability rate for patients to be free of severe rebleeding after 48 months, according to Pugh's classification, was 88 per cent for those with grade A, 50 percent for grade B and 43 percent for grade C. The over-all mortality rate was 38.8 per cent (53 patients), with the highest rate noted during the first year. The mortality rate of patients with severe rebleeding was much higher than that of those who did not rebleed. Kaplan-Meier survival analysis at four years was 52 per cent, and survival rates in relation to Pugh's classification were 73 per cent for A, 53 per cent for B and 34 per cent for C. Differences between the three groups were statistically significant. Therefore, because of the high mortality rate associated with patients with cirrhosis and extensive rebleeding during the first year, it is important to achieve, as soon as possible, eradication of esophageal varices. 
1	The role of aspiration cytologic examination in the diagnosis of carcinoma of the breast. A study of 2,000 patients who had undergone fine needle aspiration of a solid lump of the breast was conducted to determine the accuracy of this technique. During the period 1982 to 1989, all patients with a solid mammary mass, presenting to a specialized breast unit were initially investigated by fine needle aspiration cytologic examination (FNAC). To date, we present data on 2,000 consecutive aspirations with matching histologic diagnosis on the excised pathologic specimens. In particular, the relationship between tumor histologic factors and the accuracy of cytologic diagnosis was examined. The sensitivity of FNAC in the diagnosis of a malignant growth was 84 per cent; this represents first aspiration results only. The specificity was more than 99 per cent. The rate of acellular or unsatisfactory aspirations was 12 per cent. We had a positive predictive rate for diagnosis in carcinoma of the breast of almost 95 per cent. The diagnosis of lobular and in situ patterns of disease was questioned, with three of three in situ lesions and ten of 23 lobular lesions missed by FNAC. We do not recommend that FNAC replace excision biopsy and frozen section in the diagnosis of carcinoma of the breast. 
5	Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections. We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen. 
5	Protamine transcript sharing among postmeiotic spermatids. Sharing of cytoplasmic constituents through intercellular bridges connecting postmeiotic spermatids can allow for functional equivalence of genetically nonequivalent spermatids. The technique of in situ hybridization was used to study postmeiotic distribution of transcripts from the mouse protamine 1 (Prm-1) gene among spermatids of mice with chromosomally unbalanced gametes. The Prm-1 gene is located on chromosome 16 and is expressed exclusively in haploid spermatids. Mice doubly heterozygous for two Robertsonian translocations involving chromosome 16 were used for the study of postmeiotic accumulation of transcripts of the Prm-1 gene in spermatogenic cells. The meiotic segregation pattern of chromosomal homologues in these mice produces some spermatids that are chromosomally unbalanced; some spermatids lack chromosome 16 while others have two. In situ hybridization with a cDNA probe for the Prm-1 gene transcript performed on both whole testis sections and spermatogenic cell suspensions showed that there was no statistical difference in distribution of grains over step-5 to step-10 spermatids from Robertsonian-translocation heterozygous mice and from control mice of normal karyotype. These results are consistent with sharing of transcripts of the Prm-1 gene among spermatids within a syncytium. 
1	Image cytophotometric DNA analysis of atypical hyperplasias and intraductal carcinomas of the breast. With the use of image analysis, DNA content was quantified on paraffin-embedded tissue sections of 25 atypical hyperplasias and 35 intraductal carcinomas of the breast by comparison of integrated gray levels of Feulgen-stained control and ductal cell nuclei. The mean full-peak (G0/G1) control cell DNA histogram coefficient of variation was 5.5%. DNA aneuploidy was more common in intraductal carcinomas compared with atypical hyperplasias (71% of intraductal carcinomas vs 36% of atypical hyperplasias) and correlated with a lack of cytologic (nuclear) and architectural differentiation (63% moderate vs 93% poor and 38% cribriform vs 82% solid). In addition, multiple DNA stemlines were observed in 40% of intraductal carcinomas. We conclude that (1) some atypical hyperplasias demonstrate abnormal DNA content consistent with neoplastic transformation, (2) aggressive forms of intraductal carcinoma are more frequently associated with DNA content abnormalities, and (3) frequent DNA stemline heterogeneity in intraductal carcinoma supports the hypothesis that multiple genetic events occur in the development of mammary intraepithelial neoplasia. 
1	Late development of a squamous carcinoma in a reconstructed pharynx. We report a case in which a squamous cell carcinoma was found to have arisen from a delto-pectoral skin flap used in pharyngeal reconstruction. The flap had been forming a neo-pharynx for 24 years. No other signs of recurrent disease had developed in this period. This raises the possibility of tumour induction in heterotopic skin used for oropharyngeal reconstruction. 
4	Extracorporeal membrane oxygenation for the circulatory support of children after repair of congenital heart disease. We have treated 39 infants and children with congenital heart disease with extracorporeal membrane oxygenation during the past 5 years. Thirty-six were treated for low cardiac output or pulmonary vasoreactive crisis after repair of congenital heart defects. Twenty-two (61%) survived. Most patients were cannulated from the neck via the right internal jugular vein and the right common carotid artery. Six patients were cannulated from the chest, including three who had separate drainage of the left side of the heart with a left atrial cannula. Two of these patients survived and were the only survivors of the nine patients cannulated in the operating room because they could not be weaned from cardiopulmonary bypass after open cardiac operations. We also reviewed 312 patients (the predictor study series) having open cardiac operations before the availability of extracorporeal membrane oxygenation; 27 of these patients died. Data were collected at 1 and 8 hours postoperatively to determine if any parameters might predict early mortality. With these parameters used as criteria, patients who went on extracorporeal membrane oxygenation were as sick as those who died before extracorporeal membrane oxygenation was available. The most common complication was bleeding related to heparinization. The mean transfusion requirement in survivors was 1.50 +/- 1.13 ml/kg/hr, 5.63 +/- 7.0 ml/kg/hr in the nonsurvivors, and 7.46 +/- 8.29 ml/kg/hr in those cannulated in the operating room because they could not be weaned from bypass. Four children had intracranial hemorrhage, and two of them died. There was one late death. Nine of the 22 survivors are entirely normal. All survivors who do not have Down's syndrome are considered to have normal central nervous system function. We conclude that extracorporeal membrane oxygenation can improve survival in patients with both pulmonary artery hypertension and low cardiac output after operations for congenital heart disease. 
5	Diagnostic value of ventricular stimulation in patients with idiopathic dilated cardiomyopathy. To assess the response to programmed ventricular stimulation and the clinical outcome, we performed a prospective study in 103 patients with idiopathic dilated cardiomyopathy. The protocol used up to three extrastimuli delivered at two right ventricular sites during sinus rhythm and ventricular pacing at 100 and 150 beats/min and was repeated during infusion of 1 to 4 micrograms/min of isoproterenol. Sustained monomorphic ventricular tachycardia (VT) was induced in 8 of 11 patients with spontaneous sustained VT, in none of 35 patients without significant ventricular arrhythmias during Holter monitoring, and in 9 of 56 patients with salvos of ventricular premature beats. Isoproterenol infusion facilitated the induction of two episodes of sustained VT in patients with spontaneous sustained VT; however, in all but one of the remaining patients, induction of ventricular tachyarrhythmias was not impaired. During the follow-up period there were eight sudden deaths among patients who initially had syncope, inducible sustained VT, or both and three episodes of sustained VT in patients who initially had nonsustained VT but inducible sustained VT. Isoproterenol infusion can be used to safely facilitate induction of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. The induction of sustained VT was associated with a poor prognosis. 
1	Melanoma and soft tissue sarcoma in seven patients. Seven patients with both melanoma and sarcoma were seen at the Dana Farber Cancer Institute (Boston, MA) over a 4-year period. Three had additional malignant neoplasms; one of these patients also had the hereditary cutaneous malignant melanoma, dysplastic nevus syndrome. These observations suggest the possibility of a biologic relationship between melanoma and sarcoma, the nature of which remains unknown. 
5	Can the blood urea nitrogen/creatinine ratio distinguish upper from lower gastrointestinal bleeding? We wanted to know if the blood urea nitrogen to creatinine (BUN/Cr) ratio could help distinguish upper from lower gastrointestinal bleeding. We analyzed retrospectively patients admitted to our hospital for gastrointestinal bleeding over the past 5 years. A total of 126 patients represented 74 upper bleeds and 52 lower bleeds. The mean BUN/Cr ratio was significantly higher in upper than lower bleeders, 34.8 and 17.8 respectively (p less than 0.001). No lower bleeder had a ratio of greater than or equal to 36, whereas 38% of upper bleeders had a ratio of greater than or equal to 36. The BUN/Cr ratio may be an easy, cheap method of distinguishing upper from lower gastrointestinal bleeding in some cases. A BUN/Cr ratio of greater than or equal to 36 suggests upper gastrointestinal bleeding, whereas a ratio of less than 36 is not helpful in locating the source of bleeding. 
1	Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer. Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival. 
5	Acceleration of scrapie in trisomy 16----diploid aggregation chimeras. We studied the susceptibility to prion infection of the trisomy 16----diploid chimeric mouse, a putative model of Down syndrome. When weanling chimeras were inoculated intracerebrally with scrapie prions, the time until appearance of the first symptoms of scrapie was reduced by 17 days (from a mean control time of 153 days) and the time to death was reduced by 30 days (from control time of 170 days). Our results with trisomy 16 chimeras argue that the susceptibility to central nervous system degeneration caused by prions can be modulated by chromosome imbalance. 
5	Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. The prevalence of spontaneous reversal of flow in the portal venous system was non invasively evaluated by Doppler ultrasound in 228 patients with liver cirrhosis and portal hypertension. Reversed flow was detected in the portal vein in 7 patients (3.1%), in the splenic vein in 7 patients (3.1%), and in the superior mesenteric vein in 5 patients (2.1%), with an overall prevalence of 8.3% (19/228). This prevalence did not differ in relation to the etiology of liver cirrhosis, whereas hepatofugal flow was found in more patients classified as Child's C (15.4%) and B (12.5%) than those classified as Child's A (2.7%) (P less than 0.02) and was associated with a higher frequency of hepatic encephalopathy (21% vs. 7.2%; P less than 0.05). Endoscopic evaluation of esophageal varices did not reveal any correlation between the presence and size of varices and hepatofugal flow, whereas red signs were detected more frequently in patients with this hemodynamic pattern (42.1% vs. 24.4%; NS). The rate of previous variceal bleeding was not significantly different in patients with and without hepatofugal flow (30.8% vs. 24.4%; NS). Conversely, the prospective evaluation of 15 patients with hepatofugal flow and 29 matched patients with hepatopetal flow, derived from the group of 228 patients, followed up for a period of 12-18 months, showed that variceal bleeding occurred in 9 of 29 patients with hepatopetal flow and in none of the 15 patients with hepatofugal flow (P less than 0.02). However, no statistical difference was found in the survival rates. This study indicates that the actual prevalence of reversed flow in the portal, splenic, and superior mesenteric veins in a nonselected cirrhotic population is 8.3%. From a clinical point of view, the data suggest that this finding might be considered an important prognostic factor because, while occurring in cirrhotic patients with more severe functional impairment, it might play a protective role against the risk of bleeding. 
1	Human macrophage colony-stimulating factor induces macrophage colonies after L-phenylalanine methylester treatment of human marrow. Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L-phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose-dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment. 
5	Nonorganizational religious participation among elderly black adults. This study investigated rates of participation in nonorganizational religious activities of elderly Black adults. Four indicators of participation were examined: reading religious materials, watching or listening to religious programs, prayer, and requests for prayer. Demographic, religious denomination, and health disability factors influenced participation in these behaviors. The findings were discussed for their implications for the development of a multidimensional conceptualization of religiosity. 
5	Effect of antiplatelet and anticoagulant therapy on patency of femorotibial bypass grafts. In a retrospective study, 210 autogenous femorotibial saphenous vein grafts inserted during the 15 years from 1967 to 1982 were followed-up for a mean period of 62.3 +/- 5.7 months. Seven patients, who had had eight grafts died in hospital. The remaining 202 grafts fell into three groups: (1) Sixty grafts in patients who received 325 mg of dipyridamole and 1.0 g of acetylsalicylic acid daily, starting on the second postoperative day and continuing for six months. (2) One hundred and two grafts in patients on no antithrombotic therapy. (3) Forty grafts in patients on warfarin therapy to maintain the prothrombin time (prothrombin-proconvertin method) within the therapeutic range (0.10 to 0.20). Medication was continued for six months. This group included more high-risk patients than the other two groups. The mean ages and the incidence of risk factors did not vary significantly between the groups. The patency rates in three groups at five years were 62.5%, 44.0% and 26.0% and at ten years 48.5%, 25.0% and 21.5% for the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups, respectively. The limb salvage rates were 100%, 96% and 85% in the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups respectively. Thus, the best results were seen in the aspirin/dipyridamole group. 
2	Efficacy of ephedrine in the prevention of postoperative nausea and vomiting. Although reported in the aerospace literature and anecdotally by anesthesiologists, the putative antiemetic effect of ephedrine remains unquantitated. We therefore prospectively studied ephedrine as an antiemetic agent in the perioperative setting in 97 patients undergoing general anesthesia for outpatient gynecologic laparoscopy. Patients were assigned in a double-blind randomized fashion to receive a standardized general anesthetic followed by an intramuscular dose of either ephedrine (0.5 mg/kg), droperidol (0.04 mg/kg), or saline before the conclusion of surgery. Nausea, retching, or vomiting, as well as the degree of sedation and discharge times, were assessed in the recovery room and for 24 h postoperatively. Ephedrine was found to have a significantly antiemetic effect (P less than 0.05) when compared with placebo and an antiemetic effect similar to that of droperidol. Sedation scores were also significantly less in the ephedrine group than in both placebo and droperidol groups. Finally, variations in mean arterial blood pressure among the three groups were not statistically significant. We conclude that ephedrine is an effective antiemetic agent with minimal sedative side effects in patients undergoing outpatient laparoscopy. 
2	Early and frequent detection of HBxAg and/or anti-HBx in hepatitis B virus infection. To clarify the significance of the X gene of hepatitis B virus, we have tested for anti-HBx in the serum and HBxAg in the liver at different stages of the natural history of hepatitis B virus infection. Sera were screened by enzyme-linked immunosorbent assay and positive results confirmed by immunoblot. Purified recombinant MS2 Pol-HBx fusion protein was used as target for both assays. Among serial sera of patients with nonfulminant acute hepatitis, 24 of 64 patients (37.5%) were positive for anti-HBx. In fulminant cases, 15 of 36 patients (42%) had anti-HBx. In chronic hepatitis patients with high rates of hepatitis B virus replication, we found a significantly (p less than 0.01) higher prevalence of anti-HBx, 14 of 25 patients (56%), than in those with low replication, 14 of 66 patients (21%), or among asymptomatic HBsAg carrier blood donors (20 of 126 = 16%) without detectable hepatitis B virus replication (p less than 0.0001). The highest prevalence of anti-HBx was found in HBsAg carriers with cirrhosis (41 of 54 patients = 76%) and/or with hepatocellular carcinoma (18 of 33 patients = 54%). The findings suggest that anti-HBx appears as a common and early marker of hepatitis B virus infection, transient in self-limited hepatitis but persisting with progression to chronicity. In chronic hepatitis, the prevalence of anti-HBx correlated with the intensity and duration of hepatitis B virus replication but neither with the severity of the liver disease nor with malignant transformation per se. 
1	Hemangioma of the temporalis muscle. A rare case of an intramuscular hemangioma of the temporalis muscle is reported. The clinical examination, carotid arteriogram, computed tomographic scan, and aspiration cytology suggested the vascular nature of the tumor, but an exact diagnosis could only be made after histopathologic examination. Temporary occlusion of the ipsilateral external carotid artery and subperiosteal dissection permitted complete, wide excision without much bleeding. 
1	Different patterns of gene expression in ras-resistant and ras-sensitive cells. We have shown previously that nontumorigenic NIH 3T3 cells can be made tumorigenic and metastatic by transfection and expression of activated ras, whereas in LTA cells, which are tumorigenic but nonmetastatic, the degree of malignancy is not altered by ras. To investigate possible mechanisms of natural ras resistance, we compared the expression patterns of several genes thought to be involved in ras-induced metastatic progression in LTA (ras-resistant) and NIH 3T3 (ras-sensitive) cells, before and after constitutive expression of transfected T24-H-ras. We examined the expression of the nuclear "early-response" genes jun and fos and the "tumor-suppressor" retinoblastoma (Rb) gene, as well as genes involved in invasion (major excreted protein [MEP], tissue inhibitor of metalloproteinases [TIMP]), and cell adhesion (secreted phosphoprotein 1 [SPP1; also known as osteopontin]). We found distinct differences in both the basal and ras-induced levels of expression of most of these genes in LTA versus NIH 3T3 cells. High levels of MEP and low levels of TIMP were induced in ras-transfected NIH 3T3 cells, whereas LTA cells showed intermediate levels of MEP and high levels of TIMP that were only marginally affected by the expression of transfected ras. Similarly, SPP1 expression was strongly induced by ras in NIH 3T3 cells but was repressed by ras in LTA cells. Enzymogram assays for functional gelatinase activity showed an increase in 67-kd and 62-kd bands in NIH 3T3 cells in the presence of ras. LTA cells showed no gelatinolytic activity in the presence or absence of ras. Data from an in vitro assay for chemoinvasiveness showed a pattern as predicted from the expression of invasion-related genes; chemoinvasiveness in ras-transfected NIH 3T3 was greater than in LTA and ras-transfected LTA cells, which was greater than in NIH 3T3 cells. Differences in expression of the genes examined are believed to contribute to the ras responsiveness of NIH 3T3 cells and the ras resistance of LTA cells. 
3	Open depressed skull fracture missed on computed tomography: a case report. A case of an open depressed skull fracture that was missed on standard computed tomographic (CT) scan is presented. The fracture was seen on a CT generated lateral scout film, and after repositioning the gantry, further CT images clearly showed the fracture and underlying brain injury. The authors recommend that all patients with head trauma undergoing head CT have either a CT generated lateral scout film or a lateral skull radiograph to assess the vertex of the skull, an area poorly visualized on standard axial images. 
5	Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease. Facioscapulohumeral disease (FSHD), an inherited neuromuscular disorder, is characterized by progressive wasting of specific muscle groups, particularly the proximal musculature of the upper limbs; the primary defect in this disorder is unknown. We studied a patient with FSHD to determine whether the mitochondrial respiratory chain was functionally abnormal. Muscle biopsy revealed fiber atrophy with patchy staining for oxidative enzymes. Electron microscopy of a liver section showed many enlarged mitochondria with paracrystalline inclusions. Decreased oxidation of the respiratory substrates-alanine and succinate-in skin fibroblasts suggested a deficiency of complex III of the electron-transport chain; cytochrome c oxidase activity (complex IV) was in the normal range. Biochemical analysis of liver supported the fibroblast data, since succinate oxidase activity (electron-transport activity through complexes II-IV) was reduced, whereas complex IV activity was normal. Furthermore, analysis of the cytochrome spectrum in liver revealed typical peaks for cytochromes cc1 and aa3, whereas cytochrome b (a component of complex III) was undetectable. Southern blot analysis of fibroblast mtDNA revealed no major deletions or rearrangements. Our study provides the first documentation of a specific enzyme-complex deficiency associated with FSHD. 
3	Anticardiolipin antibodies: a study of frequency in TIA and stroke. We undertook a prospective study of consecutive patients to determine the frequency of elevated IgG and IgM anticardiolipin antibodies in transient ischemic attack and ischemic stroke and found elevated IgG antibodies in 8.2% (9 of 110) and IgM in 9.1% (10 of 110), only the former being significantly greater than in a healthy control population. We suggest that anticardiolipin screening be concentrated on the young. 
4	New angiotensin converting enzyme inhibitors. Their role in the management of hypertension. The introduction of orally active angiotensin converting enzyme (ACE) inhibitors has revolutionized the treatment of hypertensive disorders and provided an effective alternative for the management of congestive heart failure (CHF). By interfering with the formation of angiotensin II, the active agent of the renin system, ACE inhibitors block the system's vasoconstrictive and sodium-retaining effects, with a consequent reduction in systemic blood pressure. The net effect is improved blood flow and reduced cardiac work. Thus, ACE inhibitors are likely to improve cardiac work capacity and quality of life. Their mechanism of action differs markedly from that of traditional antihypertensive agents which lower blood pressure while reducing cardiac output and blood flow. Since the primary action of ACE inhibitors is to block the renin system, a dramatic response to monotherapy suggests a large renin factor while the lack of a response suggests a low-renin state more amenable to treatment with a diuretic or calcium antagonist. Because of their many attributes, ACE inhibitors are increasingly used as first-line therapy for the treatment of hypertension or CHF. The prototype orally active ACE inhibitor, captopril, is a sulfhydryl compound with a good safety profile at the recommended dosages but reported toxicity at higher dosages. Second-generation ACE inhibitors (eg, enalapril and quinapril) are more potent sulfhydryl-free esters with a greater affinity for the converting enzyme. These newer agents are pro-drugs requiring ester hydrolysis to form the active free acid compound. 
4	Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: results of a prospective, placebo-controlled study. The antiarrhythmic efficacy of intravenously administered amiodarone was examined in a prospective, randomized, placebo-controlled study that involved 77 patients after coronary artery bypass surgery. Amiodarone was given after surgery in a loading bolus of 300 mg for 2 hours followed by 1200 mg every 24 hours for 2 days and 900 mg every 24 hours for the next 2 days. Amiodarone suppressed both supraventricular and ventricular arrhythmias within 12 hours after the start of therapy. Particularly, the incidence of atrial fibrillation (5% vs 21% in the control group; p less than 0.05) and of nonsustained ventricular tachycardia (3% vs 16%; p less than 0.05) was reduced by amiodarone. Heart rate was slowed (p less than 0.001) and repolarization--as judged by JTc interval--was prolonged compared with the control group (p less than 0.01). In two patients, amiodarone infusion was stopped because of excessive QTc prolongation. No detrimental hemodynamic effects of the drug were observed. Thus the intravenous administration of amiodarone appears to be suitable for patients in whom rapid suppression of symptomatic supraventricular and ventricular arrhythmias is warranted in the presence of left ventricular dysfunction. 
5	Is it correct to correct? Developmental milestones in 555 "normal" preterm infants compared with term infants. To determine whether correction for preterm birth should be applied during developmental assessment, we conducted a prospective national survey of very premature infants (born at less than 32 weeks of gestation); neurodevelopment in the first 2 years was studied with the Dutch child health care developmental assessment. In 555 preterm children who had no evidence of handicap at 2 years of age, the age at which developmental milestones were reached was established. The results were compared with the results of the same assessment in Dutch children born at term. During the first year, the development of the very premature children equaled the development of normal children when full correction was applied. At 2 years of age, development was equal to or better than normal children's development without correction. We conclude that full correction for prematurity should be applied in the first year to avoid overreferral for developmental stimulation, whereas at 2 years of age correction is not necessary. 
4	The effect of Ca and Mg supplementation and the role of the opioidergic system on the development of DOCA-salt hypertension. The effect of calcium and magnesium supplementation and the role of opioidergic system was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were divided into four groups receiving standard laboratory rat diet (control group; n = 9); a calcium-rich diet with 2% CaCl2 added (Ca-group; n = 12); a magnesium-rich diet with 0.5% MgO added (Mg-group; n = 11); and a calcium and magnesium-rich diet with 2% CaCl2 and 0.5% MgO added (Ca/Mg-group; n = 11); each diet contained 7% NaCl. After four weeks on these diets, the rats were decapitated and blood was obtained for the measurement of plasma electrolytes, intraerythrocyte sodium, potassium and magnesium content (RBC-Na, -K, in mEq/L cells and RBC-Mg, in mg/dL cells) and plasma beta-endorphin concentration (beta-END, in pg/mL). In the control group, systolic blood pressure and RBC-Na were obviously higher than in the other groups. Plasma beta-endorphin concentration was 45.1 +/- 13.4 in the control group, 70.7 +/- 17.4 in the Ca-group (P less than .05 v control group), 58.0 +/- 20.1 in the Mg-group and 83.8 +/- 24.8 in the Ca/Mg-group (P less than .01 v control group). The blood pressure correlated significantly with both RBC-Na (r = 0.416, P less than .01) and beta-END (r = 0.436, P less than .005). A negative correlation was also observed between RBC-Na and beta-END (r = 0.437, P less than .005). 
1	Remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of beta-carotene or vitamin A. Participants in the intervention trials were fishermen (Kerala, India), who chewed tobacco-containing betel quids daily before and throughout the study period. Frequency of oral leukoplakia, micronuclei in oral mucosal cells, and alterations in nuclear textures were used as endpoints. Administration of vitamin A (60 mg/wk) for 6-mo resulted in complete remission of leukoplakias in 57% and a reduction of micronucleated cells in 96% of tobacco-chewers. beta-carotene (2.2 mmol/wk) induced remission of leukoplakia in 14.8% and reduction of micronucleated cells in 98%. Vitamin A completely suppressed and beta-carotene suppressed by 50% formation of new leukoplakia within the 6-mo trial period. After withdrawal of vitamin A or beta-carotene treatment, oral leukoplakias reappeared, frequency of micronuclei in oral mucosa increased, and nuclear textures reverted to those present before the administration of chemo-preventive agents. The protective effect of the original treatment could be maintained for at least 8 additional months by administration of lower doses of vitamin A or beta-carotene. 
1	Colonic stenoses: use of oral barium when retrograde flow is completely obstructed on barium enema studies. Forty patients with complete obstruction to retrograde barium flow on barium enema examinations, without clinical or radiographic evidence of obstruction, were studied further with orally administered barium in the same session. All patients had undergone aborted double-contrast barium enema studies and had received antispasmodics intramuscularly before the examination. The authors describe the technique, as well as the clinical and radiologic findings, that allows the safe ingestion of oral barium in patients with stenotic lesions of the colon. In all patients, oral barium passed through the small bowel and the stenotic site in an average of 148 minutes, with no complications. In seven patients, there were synchronous lesions in the colon and small bowel, and the findings were determined better with oral barium studies in 19 patients. If a barium enema study is done and retrograde passage of barium is obstructed by a lesion in the left side of the colon, additional diagnostic information can be obtained by giving the patients oral barium. This practice is safe if precise criteria are applied. 
5	Iliac versus cranial bone for secondary grafting of residual alveolar clefts. Secondary bone grafting of the maxilla in the mixed transitional dentition stage has become a well-accepted procedure in the surgical protocol for rehabilitation of patients with residual alveolar clefts. This retrospective study was undertaken to evaluate and compare the long-term results obtained with iliac or cranial cancellous bone graft material in the area of alveolar clefts and was based on the independent experience of two plastic surgeons from the same center using exclusively cranial or iliac cancellous bone, respectively. The criteria for surgery were similar. The surgical technique, with the exception of the bone-grafting material, also was similar, and all patients were treated by the same group of orthodontists. Fifteen patients from each group, from a total of over 100 patients, were randomly selected and included in the study. All patients were followed up from 18 to 60 months. Operative and perioperative parameters, donor-site morbidity, and long-term results were evaluated, compared, and analyzed. There were no significant differences between the two groups, and equally good results in terms of bone incorporation, tooth eruption, and appearance were obtained with both iliac and cranial bone grafts. We conclude from our study that successful bone grafting is primarily achieved by adherence to meticulous surgical technique, simultaneous closure of coexisting oronasal or palatal fistulae, use of cancellous bone particles only, and coverage of the grafts with well-vascularized flaps. The source of bone graft does not seem to primarily influence the success of the outcome. 
1	Ureterosigmoidostomy: long-term results, risk of carcinoma and etiological factors for carcinogenesis. We followed postoperatively 75 patients who underwent ureterosigmoidostomy between 1942 and 1987. Of the patients 30 were asked to undergo routine examination, including fiberoptic sigmoidoscopy with biopsy and analysis of a urine-feces slurry for nitrate, nitrite and nitrosamines in comparison to 20 control volunteers. After a mean observation of 14 years 7 months (1 to 46 years) 64.5% of the patients had bilaterally normal kidneys without any previous complications, 77.5% of the renal units being normal. Sigmoidoscopic biopsy revealed 3 carcinomas at the ureterocolonic junction resulting in an 8.5 to 10.5-fold increased risk of colon carcinoma compared to the general population. The excretion of nitrite and N-nitrosamines was increased, and nitrate excretion was decreased compared to healthy control volunteers, suggesting endogenous formation of nitrosamines by bacterially reduced nitrate and endogenous amines. The urological long-term results of ureterosigmoidostomy are similar to those of conduits. However, the increased incidence of colon carcinoma is not yet proved to be higher than in conduits. 
5	Adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung. Two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma. No other known precipitants were evident. The adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors. Tumour related blood borne factors may have contributed to lung injury in these cases. 
1	Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors. The authors investigated the presence of epidermal growth factor (EGF-R), estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were expressed in all tumor specimens analyzed, with significantly higher levels in tumor samples compared with normal mucosa (P less than 0.05). The immunohistochemical study demonstrated the presence of EGF-R in basal and parabasal cells of normal mucosa and in most of the cancer cells. There was no correlation between EGF-R and tumor localization or T classification. On the other hand, the authors did find an interesting correlation between EGF-R levels and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors. Moreover, the three patients whose tumors expressed the highest EGF-R levels had disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5% expressed very low but detectable ER, PR, and AR levels, respectively. No statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens, and neither was there any correlation of ER, PR, and AR with the pathologic findings. The authors' results suggest that the EGF-R system may play a role in regulating the growth of laryngeal cancer. Additional studies should demonstrate whether, as in other tumor types, EGF-R expression may have prognostic significance in human laryngeal cancer. 
5	Ligation of the superficial femoral vein in prevention of pulmonary embolism: an old fashion procedure? From 1974 to 1988, interruption of the superficial femoral vein (SFV) was performed to prevent pulmonary embolism (PE) in 73 patients. The mean age of the patients was 62 years. Phlebography showed thrombi in the following localizations: calf veins (67.3%), superficial femoral or popliteal veins (56.6%), common femoral veins (19.5%) and iliac veins (2.7%). A floating thrombus in the popliteal or femoral vein was the main indication for surgery in 97.3% of patients. Pulmonary embolism had occurred in 76.7% and was associated with neoplasm in 13.7%. Ligation of the SFV was performed in 93 limbs and completed iliac or femoral thrombectomy in 32.3%. The procedure was performed under locoregional anesthesia in 82.9% of the cases. Hospital mortality was 1.4% and 3 year survival, considering only PE related deaths was 95.3 +/- 2.7%. Follow-up was complete for all patients and averaged 3.0 years, for a 3 years PE-free rate of 90.8 +/- 3.6%. Persistent symptoms included increased limb tenseness in 12.5% and mild ankle edema in 25%. Bilateral strain-gauge plethysmography (SGP) was obtained in 65 limbs. The time necessary to obtain a 50, 75 and 100% decrease in calf volume (respectively T1/2, T3/4 and TT) was calculated for the operated limb and compared with the untreated limbs used as controls. A prolongation of T1/2 from 2.5 +/- 0.3 sec in controls to 4.3 +/- 0.4 sec in the operated limb (p less than 0.01) was found. Thus, our experience with ligation of the superficial femoral vein is favourable since long-term ill effects have been minimal and strain gauge plethysmography (SGP) showed only mildly altered venous drainage. 
4	Coronary pathology predicts conduction disturbances after coronary artery bypass grafting. Conduction disturbances after coronary artery bypass grafting may result from compromised septal blood flow. To examine this hypothesis we reviewed the preoperative coronary angiography of 55 consecutive patients undergoing coronary artery bypass grafting. Thirty-five patients had either no lesion or a discrete lesion in the left anterior descending coronary artery that did not include the septal perforator (type I anatomy). Twenty patients had a lesion of the left anterior descending coronary artery at the origin of the first septal branch, a lesion of the first septal artery, or a pair of lesions in the left anterior descending coronary artery that straddled the origin of the first septal artery; all lesions were proximal to the graft site (type II anatomy). None of the patients with type I anatomy had a major conduction disturbance after coronary artery bypass grafting. Eleven of the patients with type II anatomy had major conduction disturbances after coronary artery bypass grafting; right bundle-branch block in 1, right bundle-branch block and left anterior hemiblock in 2, left bundle-branch block in 5, and complete atrioventricular block that required pacemaker implantation in 3 (p less than 0.001). In the 20 patients with type II anatomy, the appearance of conduction disturbances correlated well with the absence of retrograde flow to the septal branches from the right coronary artery (p less than 0.01). Pathological lesions in the left anterior descending coronary artery that compromise flow in the first perforator and that do not provide an adequate circulation produce localized damage and conduction disturbances after coronary artery bypass grafting. This can be predicted from the preoperative angiographic anatomy. 
5	Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction. In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid ([99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of [99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl). 
3	An objective method for the assessment of psychosocial problems in adolescents with epilepsy. Psychosocial problems in adolescents with epilepsy have been of concern for many years, but have been difficult to assess. This article presents the multicenter development of the Adolescent Psychosocial Seizure Inventory (APSI), an empirically based self-report test patterned after the Washington Psychosocial Seizure Inventory, which is used to evaluate psychosocial problems in adults. After pilot work, 120 adolescents with epilepsy from five centers in North America took the APSI and were interviewed by professionals with respect to adequacy of adjustment in eight psychosocial areas. At least one parent or guardian was also interviewed. Interrater reliability of professional ratings in each area was established. Using an item-by-item, empirically based technique, eight psychosocial scales were developed as well as three validity scales. Reliability of the scales was established by both internal consistency and test-retest procedures. Results for each adolescent are presented in profile form. These results give a visual display of the types and extent of problems that likely would be identified in a detailed professional assessment. It is anticipated that the APSI will be of value in a variety of treatment and research contexts. 
1	Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified. The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas. 
1	Prospective study of the frequency and size distribution of polyps missed by colonoscopy. An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination. We prospectively examined 90 patients by tandem colonoscopy performed by two alternating examiners. In 69 (76.7%) patients, 221 neoplastic lesions were documented histologically. Of a total of 58 lesions detected in 31 patients, no neoplastic lesion greater than or equal to 10 mm in size was missed; 16% of diminutive (less than or equal to 5 mm) neoplastic polyps and 12.3% of medium-sized (6-9 mm) neoplastic polyps were missed by the first examiner. We conclude that an experienced colonoscopist will miss about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation. Large (greater than or equal to 10 mm) polyps were rarely missed, however, with the "miss" rate in our study equal to 0, with a 95% confidence limit of 4.64%. 
2	The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden. Previous population-based incidence studies of inflammatory bowel disease are limited by small numbers, short duration, or inadequate case-finding. To address these problems, we identified all persons with confirmed ulcerative colitis (n = 2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965 to 1983. Age-specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with Crohn's disease. Incidence rates for ulcerative colitis and Crohn's disease were higher in urban than rural areas. The annual incidence rate of ulcerative colitis increased from less than 7 per 100,000 to more than 12 per 100,000 during the study period, while the rate for Crohn's disease remained between 5 and 7 per 100,000. The increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis. Analyses by 5-year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and Crohn's disease, and that this effect was accounted for by those born in the first half of the year. The seasonality in the cohort effect, combined with the urban preponderance of disease, suggests that environmental causes may be involved in ulcerative colitis and Crohn's disease. 
2	Long-term follow-up of the ileoanal anastomosis in children and young adults. The purpose of this study was to carry out a long-term study of the ileoanal anastomosis (IAA) in children and young adults, comparing the straight IAA to the J pouch. One hundred twenty-one young people who had undergone IAA were studied, with 114 available for long-term follow-up. One hundred one were 18 years and under. Forty-nine patients had a straight IAA and 72 had a J-pouch reservoir. There were no deaths. After surgery, three children had intraabdominal sepsis and one had pelvic sepsis, but it did not lead to excision of the IAA. The mean stool frequency in all 114 patients was 5.0 +/- 2.5 per day and 1.2 +/- 1.1 at night. The mean number of stools for the straight IAA was 6 per day and 2.1 at night. The mean number of stools for the straight IAA with balloon dilations was 5.8 per day and 1.2 at night, and for the J pouch it was 4 per day and 1 at night. Patients with both the J pouch and straight IAA had good to excellent sensation, with patients with the J pouch always able to distinguish flatus from stool in 87% of patients and almost always in 13%. Daytime continence was very good in both groups. Moderate nighttime loss of stool occurred in 10 patients, 6 with a straight IAA and 4 with a J pouch. Ninety-five percent of the 114 patients were satisfied or very satisfied, with most children with a J pouch very satisfied. The J pouch remains the procedure of choice in young people. 
5	Thermal balance and tremor patterns during epidural anesthesia. Five healthy, nonpregnant volunteers were studied before and after induction of lumbar epidural anesthesia to determine the cause of central hypothermia during epidural anesthesia. Cutaneous heat loss was measured from 10 area-weighted sites using thermal flux transducers. Oxygen consumption was measured and converted to heat production in watts (W). After a 2-h control period at approximately 20 degrees C, epidural anesthesia was induced by injection of 30-50 ml 3% chloroprocaine. Additional boluses were given to extend the sensory blockade to at least the T5 dermatome. Tremor during epidural anesthesia was compared with normal shivering induced by rapid central venous infusion of approximately 4 l iced saline in six unanesthetized volunteers. Average skin temperature and cutaneous heat loss decreased during the control period, while tympanic membrane temperature remained stable. During the 1st h of epidural blockade, tympanic membrane temperature decreased 1.1 +/- 0.3 degrees C, and average skin temperature increased 0.9 +/- 0.5 degrees C. Cutaneous heat loss increased 16 +/- 6% (15 +/- 5 W), but metabolic heat production increased even more (and was associated with a shivering-like tremor). Tremor during epidural anesthesia and shivering induced by iced saline infusion had similar synchronous waxing-and-waning patterns. No abnormal EMG patterns were detected during epidural anesthesia. We conclude that central hypothermia during the 1st h of epidural anesthesia does not result from heat loss to the environment in excess of metabolic heat production, but results primarily from redistribution of body heat from central to peripheral tissues. Analysis of the tremor patterns suggests that oscillations recorded during epidural anesthesia in nonpregnant individuals is normal thermoregulatory shivering. Shivering occurred sooner and was more intense during iced saline infusion than during epidural anesthesia, despite comparable central hypothermia. The low intensity of shivering during epidural anesthesia, and in some individuals the delay in onset, may result from blockade of afferent cutaneous cold signals. 
4	Stress and sodium intake in neural control of renal function in hypertension. The interaction between genetic and environmental factors is important in the pathophysiology of hypertension. By examining the effects of two environmental factors--acute psychoemotional stress and dietary sodium intake--in rats with genetic hypertension, an important influence on central neural mechanisms governing the renal sympathetic neural control of renal function has been demonstrated. Additional studies of the central opioid systems have demonstrated an important role of opioid peptides in modulating the renal functional responses to acute psychoemotional stress. The observed renal functional alterations--antidiuresis, antinatriuresis, and renal vasoconstriction--are known to be capable of contributing to the initiation, development, and maintenance of the hypertensive process. 
5	Long-term 6-mercaptopurine treatment in adolescents with Crohn's disease Although 6-mercaptopurine is often used to treat adolescents with intractable Crohn's disease, its long-term efficacy has not yet been studied in this population. This study shows data derived from 36 adolescents (mean age +/- SD, 16.5 +/- 3.3 years; 27 males, 9 females) treated at least 6 months with 6-mercaptopurine (1.5 mg.kg-1.day-1, maximum of 75 mg/day). Sites of Crohn's disease at the start of 6-mercaptopurine therapy included 17 ileocolic, 9 pancolic, 7 small bowel, and 3 partial colon. All had received corticosteroids, sulfasalazine, antibiotics, and nutritional support for 5.0 +/- 3.0 years before administering 6-mercaptopurine, but intractable symptoms persisted. Disease activity lessened during the first year of 6-mercaptopurine, reflected by a higher Lloyd-Still disease activity score (pre, 64 +/- 9 vs. 6-mercaptopurine, 72 +/- 11; P less than 0.0001). General activity, physical examination, nutrition, and laboratory subscores all improved (P less than 0.004). Lessened disease activity occurred despite concomitant decrease in duration of prednisone use (pre, 9.5 +/- 4.2 vs. 6-mercaptopurine, 6.6 +/- 4.9 months/year; P less than 0.001) and cumulative annual prednisone exposure (pre, 3672 +/- 2106 vs. 6-mercaptopurine, 1964 +/- 1460 mg; P less than 0.0007). The frequency of perianal fistulae and abscesses also decreased (P less than 0.01) during treatment. Annual rates of hospitalization decreased in 44% of subjects during 6-mercaptopurine treatment, while increasing in only 22%. Follow-up beyond 1 year of 6-mercaptopurine treatment showed continued remission in 23 of 30 subjects. No serious complications were seen. 6-mercaptopurine is an effective long-term therapy for adolescents with intractable Crohn's disease. While inducing remission, it also has a significant steroid-sparing effect which may be of particular benefit to this population. 
5	Ph-negative chronic myeloid leukemia: molecular analysis of ABL insertion into M-BCR on chromosome 22. Leukemic cells from a patient with Ph-negative chronic myeloid leukemia (CML) had a normal karyotype. M-BCR was rearranged and chromosome in situ hybridization showed an ABL insertion between 5' and 3' M-BCR on an apparently normal chromosome 22. The association of 5' BCR and 3' ABL at the 5' junction of the chromosome 9 insert was typical of that found for the BCR-ABL fusion gene in other patients with the standard t(9;22) and CML. With an M-bcr-3' probe, we cloned and characterized a 3' junction fragment. Field inversion gel electrophoresis and chromosome in situ hybridization studies using a probe isolated from genomic DNA 5' of the junction showed that 3' M-BCR was joined to a region of chromosome 9q34 rich in repetitive sequences and lying some distance 3' of ABL. The chromosome 9 insert was at least 329 kilobases long and included 3' ABL and a larger portion of chromosome 9q34. Our results allowed us to exclude transposon- or retroviral-mediated insertion of ABL into chromosome 22. Instead, we favored a two-translocation model in which a second translocation reconstituted a standard t(9;22)(q34;q11) but left the chromosome 9 insert, including 3' ABL, in chromosome 22. 
1	Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil. Twenty eight tonsillar carcinomas of various histological types were investigated for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) types 6, 11, and 16 by in situ hybridisation using highly stringent procedures. In six cases an autoradiographic signal was obtained in the tumour cell nuclei with the HPV type 16 specific probe. No signal was obtained with any of the other probes. Immunohistochemical investigations with mouse monoclonal antibodies directed against the L1 protein of HPV type and a rabbit antiserum that detects common protein determinants of HPV gave negative results, thus indicating latent infection. Furthermore, a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology. These results indicate a possible role for HPV 16 in the aetiology of a proportion of tonsillar carcinomas. 
3	Bowel dysfunction in fibromyalgia syndrome. Fibromyalgia and irritable bowel syndrome frequently coexist. In this study, we utilized a previously validated self-administered questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123 patients with fibromyalgia as compared to 54 patients with degenerative joint disease (DJD) and 46 normal controls. Ninety (73%) of the fibromyalgia patients reported altered bowel function as compared to 20 (37%) DJD patients and none of the normal controls (P less than 0.001). Ninety-nine patients (81%) reported normal alternating with irregular bowel pattern, and 77 (63%) had alternating diarrhea and constipation. In contrast, only 24 (44%) of DJD patients and six (13%) of controls had regular alternating with irregular bowel pattern and only 12 (22%) of the DJD patients and none of the healthy controls had alternating constipation and diarrhea (P less than 0.01). Other bowel dysfunction complaints noted in the fibromyalgia group were abdominal gas (59%), nausea (21%), diarrhea (9%), and constipation (12%). Seventy-nine (64%) fibromyalgia patients reported frequent abdominal pain that was stress-related 47% of the time. Laxative use was frequent in the fibromyalgia group (19%) and absent in the other two groups. Fifty percent of fibromyalgia patients, compared to 28% of DJD patients, felt that their bowel complaints were worse during exacerbations of their joint disease (P less than 0.05). In conclusion, patients with fibromyalgia have a high prevalence of gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study. 
5	High incidence of hepatitis B infection and evolution of chronic hepatitis B infection in patients with advanced HIV infection. Two hundred eleven HIV-seropositive patients with AIDS, AIDS-related complex, or a CD4+ cell count less than 200 x 10(6) were examined for the presence of hepatitis B virus markers during the course of their HIV infection (median follow-up of 18 months; range of 1 to 107 months). Anti-HBs was detected initially in 138 patients (65%). Sixteen patients (8%) were HBsAg positive at entry. Fourteen had chronic HBV infection of whom 12 initially were positive for HBeAg and HBV DNA; 11 remained positive during follow-up, whereas one seroconverted to anti-HBe and lost HBV DNA. Two patients with chronic HBV infection were initially negative for HBeAg and HBV DNA: one later had reactivated HBV replication and one cleared HBeAg following onset of hepatitis D infection. The last two HBsAg-positive patients had resolving acute HBV infection. Six of the 57 patients who initially were negative for HBV markers acquired HBV infection during follow-up. Four of these six patients developed chronic infection whereas two patients had acute subclinical resolving hepatitis. In addition, four patients became HBsAg positive with their last serum samples, possibly indicating reactivation of HBV infection following progressive immunological and clinical deterioration. None of the patients developed clinical symptoms that could be ascribed to HBV infection, and transaminase elevations were only sporadically recorded. It is concluded that acquisition of HBV infections is not infrequent in HIV-seropositive patients with immune deficiency. Furthermore, the course of both previously established chronic HBV infection and newly acquired HBV infection is modified in such patients, whereas reactivation of past HBV infection seems to be a rare event. 
5	A study of the comparative efficacy of four common analgesics in the control of postsurgical dental pain. Four common oral analgesics were tested in a single-blind trial to determine their relative efficacy in the management of postsurgical pain in 103 patients who had their impacted third molars surgically removed under general anesthesia. The analgesics tested were acetylsalicylic acid (26 patients), ibuprofen (26 patients), a paracetamol/codeine/caffeine combination (Solpadeine) (25 patients), and dihydrocodeine (26 patients). The paracetamol/codeine/caffeine combination, ibuprofen, and acetylsalicylic acid preparations produced equally effective analgesia. Dihydrocodeine was found to be a poor analgesic in this pain model. There were no adverse reactions to any of the preparations. 
4	Deep venous thrombosis: longitudinal study with duplex US. Forty-nine patients with deep venous thrombosis (DVT) of the lower limb were studied with repeated duplex ultrasound (US) for at least 1 year or until the vein became normal at US. Standard anticoagulant therapy was given for 3 months. In 36 patients, the veins became normal within 1 year. The likelihood of normalization increased if the lesion was located in only one site, if the pelvic veins were unaffected, if the affected leg was the left one, if the initial clot was nonocclusive, if there was no history of DVT, and if the symptoms had lasted less than than 24 hours. The average time before normalization was shorter if the symptoms had lasted less than 24 hours, that is, 11 weeks versus 25 weeks (P less than .02). The rate of sequelae at 1 year was lower if the US scan was normal or showed regression at 3 months, 6% versus 83% (P less than .00005). 
4	Significance of fill-in after thallium-201 reinjection following delayed imaging: comparison with regional wall motion and angiographic findings To identify reversible defects, reinjection of a small amount of thallium-201 (201Tl) following 3-hr delayed imaging was performed in 60 patients with coronary artery disease who had perfusion abnormalities on their post-exercise 201Tl images. Thallium-201 uptake was visually scored and judged as normal (Group 1), reversible defect (Group II), new fill-in after reinjection (Group IIIa) and no fill-in even after reinjection (Group IIIb). New fill-in after reinjection was observed in 27 segments of the 85 segments (32%), showing persistent defect on the stress and delayed images. The wall motion in Group IIIa was worse than Group II but better than Group IIIb. Group IIIa showed Q-wave on ECG more often (69%) than Group II (27%) (p less than 0.01), but less often than Group IIIb (85%) (p less than 0.05). These data indicate that the reinjection 201Tl imaging often identifies new fill-in in the areas of no redistribution on the delayed images and it may hold promise for assessing tissue viability which the conventional imaging may underestimate. 
4	Are people more health conscious? A longitudinal study of one community. Secular changes in cardiovascular health awareness, knowledge and behavior were observed in four biennial cross-sectional surveys and a cohort survey in a New England community. These changes are not related to more health promotion activities in the social milieu of respondents, but are more likely due to national mass media health campaigns, the effects of which may influence outcomes of community-based cardiovascular disease prevention studies. 
5	Nocturnal faecal soiling and anal masturbation. Two cases of late onset faecal soiling as a result of anal masturbation in children who were neither mentally handicapped nor psychotic were studied. The role of soiling in aiding the young person and his family to avoid separating and maturing is highlighted. We suggest that the association of anal masturbation and resistant nocturnal soiling may be unrecognised. 
4	Relationship between blood groups and behavior patterns in men who have had myocardial infarction. Consistent correlations have been found between physical dysfunctional states and blood factors. Some of these disorders have possible psychosomatic components (eg, duodenal ulcer, myocardial infarction). This study focused on the relationship between blood types and various indices of behavior patterns (eg, type A behavior scores, anger ratings) in young patients who had had an initial myocardial infarction. Patients with blood type O scored significantly higher on type A behavior scales and related indices than those having blood type A. Those with blood group B responded on several scales between those with types A and O. We discuss the utility of blood groupings in future research in the prediction of myocardial infarction, methodologic limitations, the relationship of these results to temperament studies, Jenkins Activity Survey subtest patterns, anti-H reactivity pattern, and hypotheses relating blood factors and behavioral traits in patients with psychosomatic disorders. 
4	Prolonged and fractionated right atrial electrograms during sinus rhythm in patients with paroxysmal atrial fibrillation and sick sinus node syndrome. Intraatrial catheter mapping of the right atrium was performed during sinus rhythm in 92 patients: Group I = 43 control patients without paroxysmal atrial fibrillation or sick sinus node syndrome; Group II = 31 patients with paroxysmal atrial fibrillation but without sick sinus node syndrome; and Group III = 18 patients with both paroxysmal atrial fibrillation and sick sinus node syndrome. Atrial electrograms were recorded at 12 sites in the right atrium. The duration and number of fragmented deflections of the atrial electrograms were quantitatively measured. The mean duration and number of fragmented deflections of the 516 atrial electrograms in Group I were 74 +/- 11 ms and 3.9 +/- 1.3, respectively. The criteria for an abnormal atrial electrogram were defined as a duration of greater than or equal to 100 ms or eight or more fragmented deflections, or both. Abnormal atrial electrograms were observed in 10 patients (23.3%) in Group I, 21 patients (67.7%) in Group II and 15 patients (83.3%) in Group III (Group II versus Group I, p less than 0.001; Group III versus Group I, p less than 0.001). The mean number of abnormal electrograms per patient with an abnormal electrogram was 1.3 +/- 0.7 in Group I, 2.5 +/- 1.9 in Group II and 3.5 +/- 2.5 in Group III (Group I versus Group II, p less than 0.01; Group II versus Group III, p less than 0.05). A prolonged and fractionated atrial electrogram characteristic of paroxysmal atrial fibrillation can be closely related to the vulnerability of the atrial muscle. 
5	Myosin heavy chain turnover during cardiac mass changes by glucocorticoids. One aim of this investigation was to determine whether the cardiac enlargement observed with glucocorticoid treatment is temporary or remains a permanent adaptation if steroid treatment is prolonged. A second aim was to study whether myosin heavy chain (MHC) synthesis rates are coordinated with the cardiac mass responses. Female rats received either a vehicle (1% aqueous carboxymethyl cellulose in saline) or hydrocortisone 21-acetate for 1, 3, 7, 11, and 15 days. Peak cardiac enlargement (10-15%) was observed after 7 days of hormone treatment in two separate series of experiments. The enlargement was maintained through 11 days of steroid injections but by 15 days had declined toward control levels. MHC synthesis measurements were performed by constant infusion of [3H]leucine. Leucine specific activities were similar among precursor pools (intracellular, extracellular, and leucyl-tRNA) and did not vary with steroid treatments. Fractional synthesis rates of ventricular MHC (%/day) did not change during the period of increase in ventricular mass but were reduced to 56-59% of controls (-11/19.5) at 7 and 11 days of treatment, when ventricular mass increases were highest. MHC breakdown (%/day) was reduced to approximately 60% (-11.5/18.7) of controls at 7 and 11 days. Changes in total protein synthesis, which was measured in isolated perfused hearts, were similar to the MHC responses and indicated that the alterations in MHC synthesis are synchronized with the hormonal effects on total protein metabolism. These results demonstrate that peak cardiac enlargement is not maintained with long-term glucocorticoid treatment. 
5	Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study. To investigate blood-barrier leakage of plasma proteins in acute plaques of multiple sclerosis (MS) the authors used immunocytological methods to examine frozen tissue removed at autopsy from recently active cases. Annular patterns of protein-rich leakage were seen which may help to elucidate the patterns observed using gadolinium-enhanced nuclear magnetic resonance imaging. Vessel wall damage was found in all acute plaques examined and this was associated with the intramural deposition of complement on smooth muscle components and with an infiltration of HLA-DR +ve macrophages. In addition, all acute cases examined had small plaques which contained particulate material within macrophages and astrocytes, on which complement and immunoglobulins colocated. Attempts to find similar material in cases of chronic MS, subacute sclerosing panencephalitis and in perivenous encephalomyelitis were unsuccessful. These results suggest that the inflammatory changes in early MS plaques may have some specificity which could be related to the antigens whose presence is inferred by the colocation of complement and immunoglobulin on material within activated macrophages and astrocytes. 
3	Cat-scratch disease: an unusual cause of combative behavior. Acute encephalitis is an unusual manifestation of cat-scratch disease. The authors present the case of a 27-year-old man who exhibited the acute onset of encephalitis manifested by violent behavior and confusion. The diagnosis of drug abuse was presumed initially, but a careful examination revealed the true cause to be cat-scratch disease. Emergency physicians are frequently faced with the challenging task of evaluating confused and combative patients. This case demonstrates the importance of a complete physical examination and a thorough laboratory evaluation. 
3	Adult phosphorylase b kinase deficiency. Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both. 
4	Coarctation of the aorta. Coarctation of the aorta is a common cardiovascular disorder with an unknown etiology. In the preductal type, blood flows from a patent ductus into the distal aorta. When the coarctation is juxtaductal or postductal, blood flows to the lower extremities by way of the subclavian arteries and collaterals. Plain films may show the reverse sign in postductal coarctation. Arteriography is the gold standard for making the diagnosis. However, magnetic resonance imaging will probably become an increasingly important diagnostic tool. The treatment of choice is surgery, with complete resection of the stenosed segment. 
1	Osteosarcoma in young children. The clinicopathologic features of osteosarcoma in 12 children younger than 16 years of age treated at The Children's Hospital and Dana-Farber Cancer Institute, Boston, during a 70-year time period are presented. Only one of six children treated before 1972 is a long-term survivor. Four of six children (67%) treated after 1972 are disease-free with an average follow-up of 8.8 years. The year 1972 marked the onset of use of effective chemotherapy in osteosarcoma, namely, high-dose methotrexate and leucovorin rescue. It would appear that the pathologic features and behavior of osteosarcoma in young children is similar to that of osteosarcoma in older children and adolescents. A combination of complete (wide) surgical resection or amputation and aggressive chemotherapy offers the best chance of long-term survival. 
4	Effects of diltiazem on complications and restenosis after coronary angioplasty. A randomized, placebo-controlled, double-blinded trial was performed to evaluate the usefulness of empiric therapy with a calcium antagonist in patients who undergo coronary angioplasty. A total of 201 patients were randomized to placebo or to high-dose diltiazem (mean dose, 329 mg/day). Treatment began 24 hours before angioplasty. Restenosis was assessed by percent area stenosis as determined by quantitative angiographic techniques before, immediately and 1 year after angioplasty. All patients also received aspirin and dipyridamole before angioplasty. Heparin and verapamil were administered intravenously during the procedure. The 2 groups were similar with respect to age, extent of coronary artery disease, smoking history, and baseline lipid levels. Procedural complications, including death (1 vs 1), Q-wave infarction (0 vs 3), acute occlusion (5 vs 5) and focal spasm (0 vs 0), were not significantly different in the diltiazem and placebo patients, respectively. Freedom from all acute complications was noted in 85% of patients in both groups. One-year angiographic follow-up was obtained in 60% of patients. Restenosis rates were similar: 36% in the diltiazem group and 32% in the placebo group (p = 0.30). The incidence of late cardiac events (death, Q-wave myocardial infarction, recurrent angina or coronary bypass graft surgery) was similar in the 2 groups. Thus, diltiazem did not influence the overall restenosis rate or prevent late events after coronary angioplasty. 
5	Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep-vein thrombosis BACKGROUND. Isolated deficiencies of antithrombin III, protein C, protein S, and plasminogen have been implicated as a cause of deep-vein thrombosis. It is assumed that patients with recurrent, familial, or juvenile thrombosis are very likely to have such a deficiency. METHODS. We studied the prevalence of isolated deficiencies of these proteins in 277 consecutive outpatients with venographically proved acute deep-vein thrombosis, as compared with 138 age-matched and sex-matched controls without deep-vein thrombosis, and calculated the positive predictive value of a history of recurrent, familial, or juvenile venous thromboembolism for the presence of such a deficiency. RESULTS. The overall prevalence of deficiencies of any of these proteins in the patients with venous thrombosis was 8.3 percent (23 of 277 patients) (95 percent confidence interval, 5.4 to 12.4), as compared with 2.2 percent in the controls (3 of 138 subjects) (95 percent confidence interval, 0.5 to 6.1; P less than 0.05 for the comparison between groups). The positive predictive values for the presence of an isolated protein deficiency in patients with recurrent, familial, or juvenile deep-vein thrombosis, defined as the proportion of patients with the clinical finding who had a deficiency of one or more of the proteins, were 9, 16, and 12 percent, respectively. CONCLUSIONS. The cause of acute venous thrombosis in most outpatients (91.7 percent) cannot be explained by abnormalities of coagulation-inhibiting and fibrinolytic proteins. The information obtained from the medical history concerning recurrent or familial venous thrombosis or the onset of the disease at a young age is not useful for the identification of patients with protein deficiencies. 
1	Colorectal carcinoma: preoperative TNM classification with endosonography. Transcolorectal endosonography (TES) with use of both a nonoptic instrument and an echocolonoscope was performed in 91 patients with colorectal carcinomas (61 rectal and 30 colonic). Correlation of results at TES with results of histologic analysis of resected specimens according to the 1987 TNM classification demonstrated that TES allowed accurate staging of all tumors except T2 carcinomas, which were often accompanied by peritumoral inflammation or abscesses. Overall, the accuracy of staging rectal and colonic carcinomas with TES was 81% and 93%, respectively; overstaging occurred in 13% and understaging in 2%. For regional lymph nodes, the accuracy of staging with TES was 70%, the sensitivity was 94%, and the specificity was 55%. Correlations between findings at TES and the Dukes classification were as follows: for rectal carcinoma, 48% for class A, 50% for class B, and 96% for class C; for colonic carcinoma, 67% for class A, 46% for class B, and 91% for class C. Overall accuracy was 67%. With the addition of abdominal computed tomographic or ultrasonographic examinations to evaluate distant metastases, TES should become an important imaging technique for clinical TNM staging of colorectal carcinomas. 
1	Mohs micrographic surgery. Mohs micrographic surgery is a versatile technique for the treatment of nonmelanoma skin cancers, especially recurrent, invasive, or infiltrating basal cell carcinomas. It provides unsurpassed cure rates by using 100% surgical margin control, and it achieves maximal preservation of normal tissue. At the conclusion of tumor extirpation, the defect is ready for immediate reconstruction. With better understanding of the Mohs micrographic surgery technique, it can be more effectively used as part of a coordinated multidisciplinary approach to the treatment of patients with difficult cutaneous and paracutaneous neoplasms. 
4	Coronary angioplasty in symptomatic patients after bypass surgery. With the availability of percutaneous transluminal coronary angioplasty (PTCA), the management of patients who present with recurrent angina following coronary artery bypass surgery (CABG) has changed. From January 1987 to December 1988, 149 symptomatic post CABG patients underwent coronary angiography at our institution. Ninety were treated with medical antianginal therapy, 14 had repeat surgery, and 45 underwent PTCA. Complications of repeat CABG included one death, two perioperative myocardial infarctions, and four patients with postoperative supraventricular arrhythmia. PTCA was performed on 42 lesions in 37 native vessels (88% success rate), and on 24 lesions in 23 vein grafts (91.7% success rate). Complications included acute reocclusion (one patient), peripheral artery occlusion (one patient), hematoma formation (one patient), and periprocedure myocardial infarction (one patient). No deaths occurred. At a mean follow-up of 5.9 +/- 3.8 months, 10 patients had recurrent symptoms, six of whom were found to have restenosis. Repeat PTCA was successfully accomplished in four patients; the other two were treated medically. It is concluded that PTCA is a feasible alternative to repeat CABG in selected patients and can be achieved with a high success rate and minimal complications. 
5	Cardiac risk in vascular surgery. The oral dipyridamole-thallium stress test. The value of the oral dipyridamole-thallium stress test in identifying patients at high risk of myocardial infarction after vascular procedures has not been documented. We studied prospectively 46 patients who underwent an oral dipyridamole-thallium stress test before undergoing vascular operations. Twenty patients (43%) had a positive test result, defined by a thallium defect with reperfusion, while 26 patients had a negative test result. Myocardial infarctions were documented postoperatively in 5 (25%) of 20 of the group with positive results and 1 (4%) of 26 of the group with negative results. Three of the six myocardial infarctions were clinical; all three were in the group with positive results. No correlation was identified between dipyridamole-thallium stress test results and clinical cardiac history. A positive dipyridamole-thallium stress test result is a more sensitive predictor of postoperative myocardial infarction than ejection fraction or history of coronary artery disease. The oral dipyridamole-thallium stress test is as useful as the intravenous test in this setting. 
1	Colorectal adenocarcinoma in patients less than 40 years of age. From 1973 to 1985, 105 patients under 40 years of age were treated for colorectal adenocarcinoma at Roswell Park Cancer Institute. There were 51 males and 54 females. The mean age was 32 years. The majority of patients were treated for left colon or rectal carcinomas. Ninety-seven of 105 patients underwent surgical resection of their primary cancer, 70 (67 percent) of which were potentially curative. Twenty-seven patients underwent palliative resections. Dukes' A or B lesions were not seen in patients less than 20 years old, whereas these early lesions were seen in 11 percent of patients 20 to 29 years old and in 26 percent of patients greater than 30 years of age. The mean survival for patients between 20 and 29 years was 39 months and 46 months for patients 30 years and older. 
1	Limb reconstruction with vascularized fibular grafts after bone tumor resection. Limb-salvage operations are being used with increasing frequency for patients with malignant bone tumors. For children, when a biologic reconstruction is desired, the choice is often between conventional and vascularized fibular grafts. An experimental study was performed in dogs to compare the two types of fibular grafts for bridging segmental defects in the radius and ulna. Twenty-six adult dogs were divided into two groups and studied at intervals of two, three, four, six, and 12 months after transplantation. The conventional grafts healed by creeping substitution i.e., they were first partially resorbed before new bone was laid down. In contrast, the vascularized fibulae maintained their normal structure and hypertrophied by subperiosteal new bone formation. The conventional fibulae eventually hypertrophied but much later than the vascularized grafts. The vascularized grafts were stronger at four and six months. Between six and 12 months, both grafts remodeled to resemble the size and shape of the forearm bones they were replacing. These experimental results have influenced the treatment of patients. Vascularized fibular grafts are ideal for diaphyseal defects greater than 10 cm long, especially in very young children, a poorly vascularized bed, or when bone healing is delayed by chemotherapeutic agents. To maximize hypertrophy, an external fixator is used to immobilize the graft rather than a plate, which acts as a stress shield. 
1	Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin. Seven patients with advanced locoregional or metastatic squamous cell carcinoma of the skin were treated with cis-daimminedichloroplatin (cisplatin) and 5-fluorouracil (5-FU). Responses were seen in six of seven patients (three partial responses [PR] and three complete responses [CR]). One patient is alive and disease-free at 2 years. These results indicate that cisplatin and 5-FU is an effective combination regimen that should be used in future clinical trials in squamous cell carcinoma of the skin. 
2	Percutaneous transhepatic cholecystostomy for acute complicated cholecystitis in elderly patients. We report our experience with percutaneous transhepatic cholecystostomy in 10 elderly patients with acute cholecystitis, complicated by empyema formation. Most of these patients has severe underlying disease, rendering them at high risk for surgical intervention. In all patients, the percutaneous procedure was followed by a rapid regression of clinical symptoms and of radiologic abnormalities. Six were considered inoperable. Three of these remain free of biliary symptoms, respectively 22, 10, and 7 months after percutaneous cholecystostomy. Three others died of nonbiliary disease 1-4 months after cholecystostomy. Three patients underwent successful elective cholecystostomy 1-5 wk after percutaneous cholecystostomy. In one patient, cholecystectomy had to be performed because of recurrence of hydrops, 1 wk after catheter removal. In our opinion, percutaneous transhepatic cholecystostomy is a safe and effective procedure in the treatment of elderly patients with acute complicated cholecystitis. It can be followed by elective cholecystectomy in good surgical candidates, or by an expectant conservative management in high surgical risk patients. 
5	Spontaneous dural carotid-cavernous fistula with central retinal vein occlusion and iris neovascularization. Spontaneous dural carotid-cavernous fistulas are dural vascular malformations that usually run a benign course. We present a case of a spontaneously occurring dural carotid-cavernous fistula complicated by central retinal vein occlusion and iris neovascularization that led to progressive visual failure. 
4	Renal vein thrombosis. Initial manifestation of Goodpasture's syndrome. We report a patient who presented with renal vein thrombosis and nephrosis that progressed to alveolar hemorrhage and renal failure. Renal biopsy immunofluorescence and serum antiglomerular basement membrane antibody titer studies confirmed the diagnosis of Goodpasture's syndrome. To our knowledge, this is the first report of renal vein thrombosis as the initial presentation of Goodpasture's syndrome. 
3	Intraoperative dexamethasone irrigation in lumbar microdiskectomy. In 45 lumbar hemilaminectomy/microdiskectomy patients, a control group of 23 patients had the standard operative procedure. The remaining 22 patients were treated with intraoperative irrigation of long-acting dexamethasone before incision closure. Age, weight, gender ratio, mean postoperative hospital stay, mean in-hospital narcotics usage, and incidence of perioperative complications among the two groups were compared. Age and gender ratios were comparable, although the control group was significantly heavier in body weight than the steroid-irrigated group. The steroid-irrigated group had a significant reduction in hospitalization and a marked reduction in narcotics usage compared with the control group. Postoperative fever occurred in one patient in the steroid group. The control group had three postoperative complications. These preliminary observations suggest that dexamethasone irrigation during lumbar diskectomy is a safe and effective adjunct to surgical management. 
3	Mesenteric blood flow in patients with diabetic neuropathy. We examined flow velocities in the superior mesenteric artery and celiac artery in normal controls (group C, n = 11), diabetic patients (group D, n = 8), and diabetic patients with clinically evident autonomic neuropathy (group DN, n = 6) to further define the usefulness of duplex examination in the evaluation of the mesenteric circulation in normal and disease states. By use of a 3 MHz duplex scanner, peak systolic velocity, peak diastolic forward velocity, end-diastolic forward velocity, and peak diastolic reverse velocity were measured in centimeters per second before and after a standardized meal. The vessels' diameters in centimeters were also measured. After the meal peak diastolic reverse velocity disappeared in all patients. The average vessel diameter in the superior mesenteric artery (0.7 cm) and celiac artery (0.8 cm) did not change. Flow velocities in the celiac artery were not significantly altered by the meal. In the control group, peak systolic velocity in the superior mesenteric artery increased 38%, peak diastolic forward velocity rose 66%, and end-diastolic forward velocity increased by 70%. In the diabetic nonneuropathic group the changes were 15%, 98%, and 100%, respectively. These changes were statistically significant (p less than 0.01). On the other hand, the patients with diabetic autonomic neuropathy presenting a picture of gastroparesis did not exhibit the expected increases in postprandial velocities. Moreover, this alteration in blood flow velocity, although similar to that encountered in patients with intestinal angina, did not appear to be due to occlusive arterial disease on the basis of clinical examination and B-mode scanning. 
4	Perioperative myocardial injury in patients undergoing aortic valve replacement. In cases of myocardial hypertrophy myocardial protection may be insufficient. In order to determine the factors responsible for myocardial injury we assessed myocardial injury in 54 patients undergoing isolated aortic valve replacement. In all cases hypothermic cardioplegic arrest was induced. At 13 different times we measured the serum level of creatine-kinase (CK), myocardial bound creatine-kinase (CKmb), lactic dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), glutamic oxaloacetic transferase (GOT) and myoglobin. The mean duration of ischemia was 52.6 +/- 16.2 minutes and the mean time of extracorporeal circulation was 85.85 +/- 20.25 minutes. By performance of a multiple regression analysis a significant correlation between ischemia and LDH and alpha-HBDH was found; CK, GOT, LDH and alpha-HBDH correlated with duration of extracorporeal circulation. In none of the patients was a low cardiac output syndrome observed. From our results we conclude that in our study myocardial protection was sufficient and therefore the detrimental effects of extracorporeal circulation were the determining factors of enzyme release. 
2	Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study. A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease. 
4	Delayed death from aortic root trauma. A 40-year-old man suffered blunt chest trauma, had a myocardial infarct 58 days later, and died unexpectedly 19 days after that. Autopsy showed partial avulsion of a small branch of the right coronary artery with thrombus extending into the right coronary sinus of Valsalva occluding the right coronary artery and causing a myocardial infarct. Death was caused by a thromboembolus arising from the aortic root thrombus and occluding the left main coronary artery. The case is unusual in that the major consequences of the aortic root trauma were delayed, and death resulted from occlusion of both coronary arteries. 
2	Alcohol consumption in patients with colorectal adenomatous polyps. The risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors. We found an association with current alcohol and cigarette consumption. The risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink, with those who both drank and smoked having 12 times the risk of total abstainers. Since colonic adenomatous polyps are generally regarded as premalignant lesions, these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal carcinogenesis. The role of smoking, however, is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies. 
5	Operation Everest II: ventilatory adaptation during gradual decompression to extreme altitude. To assess the ventilatory adaptation during gradual ascent to extreme altitude, we studied seven healthy males as part of the 40 d simulated ascent of Mt. Everest in a hypobaric chamber. We measured resting ventilation (VE, l.min-1), arterial oxygen saturation (SaO2%), the ventilatory response to oxygen breathing, isocapnic hypoxic ventilatory response (HVR), and hypercapnic ventilatory response (HCVR) at sea level prior to the ascent (760 torr), 14,000 feet (428 torr), 24,000 feet (305 torr), and within 24 h of descent (765 torr). VE increased from 9.3 +/- 1.1 l.min-1 at 760 torr to 23.4 +/- 1.3 l.min-1 at 305 torr and remained elevated at 14.7 +/- 0.7 l.min-1 after descent. Oxygen breathing decreased VE by 9.6 +/- 1.3 l.min-1 at 305 torr. Isocapnic HVR (expressed as a positive slope of VE/SaO2, l.min-1.%SaO2(-1) increased from 0.18 +/- 0.07 at 760 torr to 0.34 +/- 0.11 and 0.38 +/- 0.5 at 428 torr and 305 torr (P less than 0.05) respectively. HVR was elevated further upon return to sea level (0.8 +/- 0.09, P less than 0.05). HCVR (S = VE/PETCO2, l.min-1.torr-1) increased from sea level (S = 4.4 +/- 0.09) to 305 torr (S = 18.7 +/- 3.5, P less than 0.01) and remained elevated upon return to sea level (S = 10.7 +/- 4.6, P less than 0.001). This study is the first to investigate the ventilatory response to such extreme altitude and so soon after descent and shows that hypoxic and hypercapnic responses increase during prolonged progressive hypoxic exposure and remain significantly elevated from pre-ascent levels immediately upon descent. 
5	Neuropsychological assessment of monozygotic twins discordant for schizophrenia. A comparison of monozygotic twins discordant for schizophrenia controls for genetic variance and reduces variance due to environmental circumstances, thus serving to highlight differences due to phenotypic-related variables. In this study, we assessed 16 such twin pairs on a wide range of neuropsychological tests. The affected twins tended to perform worse than their unaffected counterparts on most of the tests. Deficits were especially severe on tests of vigilance, memory, and concept formation, suggesting that dysfunction is greatest in the frontotemporal cortex. While manifest symptoms were not highly associated with neuropsychological scores, global level of functioning was. To address the issue of genetic liability, we also compared the sample of discordant unaffected twins with a sample of seven pairs of normal monozygotic twins. No significant differences between the groups were found for any neuropsychological test. In fact, the results suggest that neuropsychological dysfunction is a consistent feature of schizophrenia and that it is related primarily to the clinical disease process and not to genetic or nonspecific environmental factors. 
5	Recurrent Bell's palsy in pregnancy. A case of recurrent Bell's palsy occurring in two successive pregnancies in a 37-year-old woman is presented. The causes of facial nerve paralysis of the lower motor neurone type are discussed. The rate of recurrence of Bell's palsy during pregnancy is unknown. Treatment with corticosteroids of Bell's palsy during pregnancy poses the threat of possible side effects on the fetus. 
1	Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Translocations involving chromosome 11, band q23, are frequent recurring abnormalities in human acute lymphoblastic and acute myeloid leukemia. We used 19 biotin-labeled probes derived from genes and anonymous cosmids for hybridization to metaphase chromosomes from leukemia cells that contained four translocations involving band 11q23: t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13). The location of the cosmid probes relative to the breakpoint in 11q23 was the same in all translocations. Of the cosmid clones containing known genes, CD3D was proximal and PBGD, THY1, SRPR, and ETS1 were distal to the breakpoint on 11q23. Hybridization of genomic DNA from a yeast clone containing yeast artificial chromosomes (YACs), that carry 320 kilobases (kb) of human DNA including CD3D and CD3G genes, showed that the YACs were split in all four translocations. These results indicate that the breakpoint at 11q23 in each of these translocations occurs within the 320 kb encompassed by these YACs; whether the breakpoint within the YACs is precisely the same in the different translocations is presently unknown. 
5	A new ophthalmic electronic videoendoscope system for intraocular surgery. A new ophthalmic electronic videoendoscope system has a 20-guage probe for intraocular observation, a standard size for vitreous microsurgical instruments, and both endoscopic and operating microscopic images are displayed on a split-screen monitor system to provide surgeos a simultaneous view of both images. Using this endoscope system at any time during surgery, surgeons can examine the intraocular structure such as the ciliary sulcus, pars plana, or vitreous base and obtain valuable but otherwise unobtainable information for completing the surgery. 
1	Numb chin syndrome secondary to Burkitt's cell acute leukemia. We describe a case of Burkitt's cell acute lymphoblastic leukemia presenting with the bilateral numb chin syndrome as the initial symptom of the disease. Postmortem study of the trigeminal nerve showed heavy infiltrations of leukemic cells and destruction of axon and myelin by leukemic cells in the mandibular nerve. 
1	Flow cytometric DNA analysis of hepatocellular carcinoma. The prognostic value of nuclear DNA content was studied retrospectively using flow cytometry in 203 cases of resected hepatocellular carcinoma. The occurrence of DNA aneuploidy, which was detected in 50% of patients, correlated significantly with tumor size and the presence of vascular invasion or intrahepatic metastasis. Overall, patients with DNA aneuploid tumors had a significantly worse prognosis than those with DNA diploid tumors (P less than 0.001) and, also in subdivided groups by tumor size (P less than 0.01). Among DNA aneuploid patients, the survival times were significantly shorter for patients with a low DNA index (less than 1.5) than for those with a high DNA index (greater than or equal to 1.5) (P less than 0.05). In a Cox multivariate analysis, nuclear DNA content provided significant prognostic value (P = 0.008), as did vascular invasion (P = 0.001) and intrahepatic metastasis (P = 0.005). These results indicated that nuclear DNA content has an important prognostic value in hepatocellular carcinoma. 
5	Variants of intestinal metaplasia in the evolution of chronic atrophic gastritis and gastric ulcer. A follow up study. A follow up study with biopsy was initiated in 1982 to define the relations between variants of intestinal metaplasia and the evolution of chronic atrophic gastritis and gastric ulcer. All patients (58 with chronic atrophic gastritis and 66 with gastric ulcer) had intestinal metaplasia at the start of the study. In the six year period to 1988 a total of 241 biopsies were performed on the patients with chronic atrophic gastritis and 243 on the patients with gastric ulcer. Initially, 81% of the patients with chronic atrophic gastritis presented with type I intestinal metaplasia and 14% with type III intestinal metaplasia. During follow up type I was predominant, often associated with grades 2 and 3 active disease (81%) and 45% of these patients reverted to a non-intestinal metaplasia status by the third year of follow up. In contrast, type III metaplasia was more common in the absence of appreciable inflammation (78% of biopsy specimens), being persistent in five of seven patients in the third year of follow up, and was found to be associated with dysplasia in three of these patients. Similarly, the initial biopsy specimen showed type I metaplasia in most patients with gastric ulcer (82%) and type III in only 4%. Type I metaplasia was also predominant in these patients (80%), particularly in active disease (68%), gradually regressing with healing. In contrast, type III was associated with delayed ulcer healing and reactivation (75%; six of eight patients). 
3	Pain relief achieved by transcutaneous electrical nerve stimulation and/or vibratory stimulation in a case of painful legs and moving toes. A patient is described with painful legs and moving toes. The pain had been occurring for more than 15 years, and a variety of therapies had been attempted with only partial, if any, success. Only morphine had succeeded in relieving the pain, but it had to be discontinued to avoid tolerance and dependence. We devised a treatment consisting of transcutaneous electrical nerve stimulation (TENS), vibratory stimulation (VS), and a combination of the two methods (TENS + VS). TENS brought about partial pain relief, but was less effective than VS; dual stimulation (TENS + VS) led to complete alleviation of the pain. Four months later, the patient was applying dual stimulation himself at home and was thus able to maintain complete relief with 3 or 4 weekly sessions. We suggest that dual stimulation results in a large-scale recruitment of large-diameter afferent fibres and may thus set up a powerful inhibitory control of nociception in our patient. 
2	Natural history of congestive gastropathy in cirrhosis. The Liver Study Group of V. Cervello Hospital. In a prospective study of the natural history of congestive gastropathy, 212 consecutive cirrhotic patients (75 treated with sclerotherapy) were included. Mean follow-up was 46 months. Mild gastropathy (mosaiclike pattern) was found in 110 patients and severe gastropathy (granular mucosa with cherry spots) was found in 20. Prevalence of Helicobacter pylori, formerly Campylobacter pylori, was 50% in patients without, 43% in those with mild, and 28% in those with severe gastropathy. Congestive gastropathy was significantly more frequent in patients treated with sclerotherapy (83% vs. 50%, P less than 10(-5)). Sixty-month actuarial proportions of patients free of anemia (in the absence of hematemesis or melena), were 17% with severe, 62% with mild, and 93% without gastropathy (P less than 10(-8]. Corresponding figures for overt bleeding were 25%, 73%, and 87% (P less than 10(-7], whereas those for survival were 46%, 72%, and 85% (P = 0.0005), respectively. A multivariate regression analysis supported the following conclusions: (a) sclerotherapy and the presence of large esophageal varices significantly increase the risk of congestive gastropathy, which (b) is a significant risk indicator of both chronic and overt bleeding but does not independently affect survival. 
4	Resympathectomy of the upper extremity. Resympathectomy was performed in 27 patients (eight bilaterally) with ischaemic hand phenomena. An extended operative technique, resecting parts of the second and third intercostal nerves and their surrounding tissue, was used. In all 35 procedures the posterior extrapleural approach was used. Follow-up was from 3 to 12 years. Only the sympathetic ganglia had been removed during the previous surgery by the axillary approach (67 per cent of these patients had had a transient response for between 6 months and 2 years; 33 per cent had had no response at all). A direct subjective improvement was seen after 27 of the 35 reoperations (77 per cent). In 14 patients continuous wave Doppler ultrasound studies were available and showed a significant increase in peak forward frequency after operation (P less than 0.001). From these data it may be concluded that it is possible to obtain a resympathectomy effect, but reoperation should be reserved for special cases for whom survival of digits is essential. 
4	Is phase 2 cardiac rehabilitation necessary for early recovery of patients with cardiac disease? A randomized, controlled study. In this study the effects of rehabilitation teaching plus exercise testing on perceived self-efficacy for and performance of daily activities were compared with and without exercise training. Subjects were patients who had had myocardial infarction or cardiac surgery (mean age 57.7 +/- 11.3 years) and who had already received inpatient rehabilitation services. Subjects were randomly assigned to one of three groups. Treatment group 1 (n = 11) received teaching, treadmill exercise testing, and exercise training (three times weekly for 5 weeks). Treatment group 2 (n = 15) received only teaching and exercise testing. The control group (n = 14) received only routine care without supervised exercise or teaching. Measurements of self-efficacy and activity performance were made at hospital discharge and at 4 and 9 weeks after the cardiac event. Repeated-measures analysis of variance showed an increase in self-efficacy scores (p less than 0.001) and performance of physical activity (p less than 0.001) for all groups. Both treatment groups, especially the training group, obtained the highest scores, but differences between groups were nonsignificant (p greater than 0.05). These results indicate that in a sample of uncomplicated, motivated patients who had participated in a phase 1 inpatient rehabilitation program, substantial improvements in self-efficacy and performance of daily activities were made early in recovery, before the onset of phase 2, formalized outpatient therapy. 
5	Selective dopamine DA1 stimulation with fenoldopam in cirrhotic patients with ascites: a systemic, splanchnic and renal hemodynamic study. We studied the effects of fenoldopam, a selective dopamine DA1 agonist on systemic and splanchnic hemodynamics, renal blood flow and sodium excretion in 12 patients with alcoholic cirrhosis and ascites. Hepatic, azygos and renal veins were catheterized before and after intravenous administration of fenoldopam, 0.05 micrograms/kg/min for 1 hr and increased to 0.1 micrograms/kg/min for another hour. Mean arterial pressure progressively decreased (from 83 +/- 7 to a minimum of 77 +/- 8 mm Hg 100 min after starting the infusion) but returned to baseline level at 120 min. Plasma norepinephrine and renin activity increased (respectively from 567 +/- 297 to 919 +/- 375 pg/ml, p less than 0.05, and from 17 +/- 14 to 23 +/- 15 ng/ml/hr, p less than 0.05). Renal blood flow, urine output or sodium excretion did not change. Sodium output decreased at 1 hr from 6.9 mumol/min to 4.0 mumol/min, p less than 0.05. Both hepatic venous pressure gradient and azygos blood flow significantly increased by 21%. We conclude that the acute administration of fenoldopam did not improve renal hemodynamics or function in patients with cirrhosis and ascites. In addition, dopamine DA1 agonism caused further increases in norepinephrine concentration and plasma renin activity. Portal pressure also increased, probably because of an increase in mesenteric blood flow. These results question the renal benefit and raise concern about the use of dopamine agonists in patients with cirrhosis and ascites. 
4	Cardiovascular risk factors and the effects of intervention. Cardiovascular risk factors can be substantially modified by changes in life-style such as diet, exercise, smoking cessation, and moderation of alcohol consumption. In turn, these can reduce blood pressure, heart rate at rest, and blood lipid concentrations. Epidemiologic evidence shows that for every 1% change in serum cholesterol levels, there is a 3% change in the likelihood of developing coronary heart disease. In addition, a long-term (5-year) change of 5 to 6 mm Hg in diastolic blood pressure can reduce the chances of stroke by 35 to 40% and of coronary heart disease by 20 to 25%. The full impact of this broad range of interventions on population health has still to be fully realized in many countries, including the United Kingdom, however it is likely to be considerable. Some of the recent evidence in support of such cardiovascular risk factor modification is selectively reviewed. 
4	Sudden death in young competitive athletes: clinicopathologic correlations in 22 cases. PURPOSE: To investigate the pathologic substrates of sudden death in young competitive athletes. PATIENTS AND METHODS: Twenty-two cases of sudden death in young competitive athletes occurring in the Veneto region (northern Italy) in the period January 1979 to December 1989 were studied by postmortem examination. The athletes included 19 males and three females, ranging in age from 11 to 35 years (mean, 23 years). RESULTS: In 18 cases, sudden death occurred during (16 cases) or immediately after (two cases) a competitive sport activity. In 10 subjects, sudden death was apparently the first sign of disease. Postmortem examination disclosed that this fatality was due to arrhythmic cardiac arrest in 17 cases; among these, right ventricular cardiomyopathy, also known as "right ventricular dysplasia," was the most frequently encountered cardiovascular disease (six cases), followed by atherosclerotic coronary artery disease (four cases), conduction system pathology (three cases), anomalous origin of right coronary artery from the wrong aortic sinus (two cases), and mitral valve prolapse (two cases). In two athletes, the abrupt lethal complication was "mechanical" and consisted of pulmonary embolism and rupture of the aorta; in three athletes, death was due to a cerebral cause. All athletes with right ventricular cardiomyopathy died during effort, and most had a history of palpitations and/or syncope. Whenever available, electrocardiographic (ECG) tracings showed inverted T waves in precordial leads and/or left bundle branch block ventricular arrhythmias. CONCLUSIONS: Clinicopathologic correlations indicate that in the Veneto region of Italy, right ventricular cardiomyopathy is not so rare among the cardiovascular diseases associated with the risk of arrhythmic cardiac arrest, and seems to account for the majority of cases of sudden death in young athletes; this disorder can be suspected during life on the basis of prodromal symptoms and ECG signs. 
4	Planar imaging techniques used with technetium-99m sestamibi to evaluate chronic myocardial ischemia. The results of published and some unpublished studies comparing planar imaging performed with 2 radionuclides, thallium-201 (T1-201) and technetium-99m (Tc-99m) sestamibi, are reviewed. The average sensitivity for the detection of coronary artery disease (CAD) in studies involving 594 patients was 85% (range 73 to 96%). The average sensitivity for individual vessels was 65% (range 60 to 70%). The average segmental concordance between T1-201 and Tc-99m sestamibi was 89%. End-diastolic gated perfusion images improved the concordance between Tc-99m sestamibi and angiography in 22 patients from 83.4 to 87%. Semiquantitative analysis increased the concordance between T1-201 and Tc-99m sestamibi from 89 to 91%. Ventricular function derived from gated Tc-99m sestamibi perfusion images showed a significant correlation with echocardiography (n = 62, r = 0.85); with angiography (n = 70, r = 0.91); and with equilibrium radionuclide ventriculography (n = 18, r = 0.86). The ratio of lung to left ventricle uptake and the ratio of right ventricle to left ventricle uptake was assessed. Eight of 52 patients had an abnormally elevated lung index (greater than 42%) and these patients had the most severe CAD. Six of the 52 patients had an abnormally elevated right ventricular index (greater than 56%) and these patients had more severe CAD. 
1	Factors affecting recurrence in lumpectomy without irradiation for breast cancer. Between 1980 and 1988, 122 women with operable invasive breast cancers underwent wide excision and axillary dissection without subsequent irradiation. During the follow-up period of 1 to 8 years (median, 4 years), recurrences were observed in 23 patients (19%), 22 occurring in the breast and one in the axilla. This is a significant rate of recurrence and supports the need for breast irradiation after conservative surgery. The incidence of recurrence in the breast did not appear to be related to the presence or absence of axillary nodal metastasis. No recurrences were noted in 20 patients whose primary tumors were smaller than 1 cm. The incidence of recurrence was directly correlated to the increasing size of the tumor, but it also appeared to decrease with advancing age. In 31 patients over 70 years of age, only one (3%) recurrence was observed. If these early findings are confirmed, it is likely that patients with tumors smaller than 1 cm or patients over 70 years of age may be spared breast irradiation after wide excision. 
1	Oncocytic renal tubular adenoma (so-called oncocytoma) in seventeen-year-old girl. Renal tubular neoplasms (adenomas or adenocarcinomas) are rare in children or young adults. Herein, we report an oncocytic renal tubular adenoma (so-called oncocytoma) that was found in a seventeen-year-old girl. Preoperative evaluation included aspiration of this tumor, and we suggest that preoperative aspiration is an important procedure in the diagnosis and management of suspected renal tumors in children and young adults. 
5	Myoglobin depletes renal adenine nucleotide pools in the presence and absence of shock. To assess whether myoglobin adversely affects renal adenylate pools, rats were infused with purified myoglobin (50 mg/100 g body wt) for two hours and renal ATP, ADP, and AMP levels were measured in the absence of shock, after 25 minutes of hemorrhagic shock (55 to 60 mm Hg) or 30 minutes post-recovery. In the absence of shock, myoglobin lowered ATP by 24% (assessed 65 min post-infusion) without affecting renal blood flow (RBF). This effect was completely blocked by deferoxamine (DFO) treatment and it could not be reproduced by ribonuclease infusion (a non-Fe containing, but filtered, protein). Myoglobin + shock caused a three- to fourfold greater decline in ATP than did shock alone despite comparable RBFs. Shock plus myoglobin, but neither one alone, induced substantial S1/S2 proximal tubular morphologic damage and a severe reduction in creatinine clearance, confirming synergistic injury. Ribonuclease completely reproduced myoglobin's effect on shock-induced adenylate profiles. DFO +/- hydroxyl radical scavenger therapy (Na benzoate) did not block the myoglobin shock effect on adenylate pools. Post-shock adenylate recovery was not compromised by myoglobin pre-treatment. If renal artery occlusion (RAO), rather than shock, was used as the ischemic challenge, myoglobin had no discernible impact on adenine nucleotide content. This study concludes that: 1) myoglobin modestly lowers baseline adenylate pools due to an Fe dependent mechanism; 2) myoglobin drastically accentuates shock-induced adenylate depletion by a non-hemodynamic/non-Fe dependent mechanism; 3) myoglobin nephrotoxicity cannot be attributed solely to tissue iron loading; and 4) the RAO model can completely mask important influences on ischemic cellular energetics. 
3	Rehabilitation in spinal cord disorders. 2. Anatomy, pathogenesis, and research for neurologic recovery. This self-directed learning module highlights advances in this topic area. It is part of the chapter on rehabilitation in spinal cord disorders in the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. This article contains learning objectives on the anatomy of the spine and spinal cord, pathogenesis of spinal cord trauma, mechanisms of spinal fractures and dislocations, causes of nontraumatic spinal cord disorders, and research on neurologic recovery. Advances that are covered in this section include various experimental animal models for producing spinal cord injury and new approaches to limit damage in acute injury and to promote recovery in chronic injury. 
4	Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit. BACKGROUND. The site of the reentrant circuit in atrioventricular (AV) junctional reentrant tachycardia has not been defined; in particular, the existence of a common pathway of AV nodal tissue above the reentrant circuit is controversial. METHODS AND RESULTS. Two types of AV junctional reentrant tachycardia were induced in each of three patients at electrophysiological study. In one type of tachycardia (anterior), the onset of atrial activity occurred from 0 to 12 msec before the onset of ventricular activation, and earliest atrial activity was recorded near the His bundle. In the second type of tachycardia (posterior), the ventriculoatrial intervals were longer (76-168 msec), and earliest atrial activity was recorded near the mouth of the coronary sinus. In individual patients, the two types of tachycardia had different cycle lengths. Posterior AV junctional reentrant tachycardia was not a fast-slow form of AV junctional reentry in at least two of the three patients. Surgical cure was attempted in two patients. In one patient, anterior AV junctional reentrant tachycardia was abolished by dissection of the anterior perinodal atrium, but posterior AV junctional reentrant tachycardia could still be induced. At reoperation 4 months later, dissection of the posterior perinodal atrium abolished posterior AV junctional reentrant tachycardia while preserving AV conduction. CONCLUSION. Differences in ventriculoatrial intervals and cycle lengths and the results of selective surgery suggest that the two types of AV junctional reentrant tachycardia used different reentrant circuits. These observations imply that a common pathway of AV nodal tissue is not present above the reentrant circuit and suggest that perinodal atrium is part of these circuits. 
5	A controlled trial of nebulized isoetharine in the prehospital treatment of acute asthma. Acute asthma is a potentially life-threatening disorder, recognizable to the prehospital care provider. While therapies are available to the prehospital care provider for treating acute asthma, no previous controlled studies have been performed demonstrating the treatment in the field is efficacious and safe. The authors conducted a controlled trial of the prehospital use of nebulized isoetharine in an urban emergency medical services system. Fifty-two patients with acute asthma were studied. Patients were initially evaluated with a peak flow meter. Half of the patients received isoetharine, while the control group received basic life support only. There was no difference in baseline values. Peak expiratory flow increased from 138 L/min to 148 L/min in the control group, while it increased from 149 L/min to 218 L/min in the treatment group (P less than .001). The authors conclude that paramedic treatment of acute asthma with nebulized isoetharine is effective in improving pulmonary function and clinical status during transport. 
3	Utility of upright tilt-table testing in the evaluation and management of syncope of unknown origin PURPOSE: Vasovagally mediated hypotension and bradycardia are believed to be common, but difficult to diagnose, causes of syncope. Upright tilt-table testing has been proposed as a possible way to test for vasovagal episodes. This study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin. PATIENTS AND METHODS: Twenty-five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/minute given intravenously), in an attempt to provoke bradycardia, hypotension, or both. Of the 25 patients, there were 14 males and 11 females, with a mean age of 50 +/- 16 years. Six control patients with no history of syncope were also studied. All tilt-positive patients received therapy with either beta-blockers, disopyramide, transdermal scopolamine, or hydroflurocortisone, the efficacy of which was evaluated by another tilt-table test. RESULTS: Syncope occurred in six patients (24%) during the baseline tilt and in nine patients (36%) during isoproterenol infusion (total positives, 60%). None of the controls had syncope during the test. All patients who had positive test results eventually became tilt-table-negative by therapy, and over a mean follow-up period of 16 +/- 2 months no further episodes have occurred. CONCLUSION: From this study we conclude that upright tilt-table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy. 
5	Immunopathology of diabetes in the RT6-depleted diabetes-resistant BB/Wor rat. Insulin-dependent diabetes mellitus appears to be an autoimmune disease that is characterized morphologically by insulitis, an inflammation of the pancreatic islets of Langerhans that results in the destruction of the insulin-producing beta cells. The RT6-depleted DR rat provides a good model for the in situ study of insulitis. The authors used the anti-RT6.1 monoclonal antibody to selectively deplete RT6 T cells in DR rats and produce a synchronous and rapid development of insulitis that commences 10 days after treatment. The phenotype of cells that infiltrated the islets at different stages of insulitis in the RT6-depleted DR rat was determined by immunocytochemical techniques. A prodromal period of 10 days was present in which the authors could not detect morphologic alterations within the pancreas. This is followed by a second phase of early insulitis in which a few islets are infiltrated by macrophages and T cells. This rapidly progresses by 18 days to the final phase of generalized insulitis in which the islets are massively infiltrated by macrophages and T cells. 
4	Bioenergetic recovery processes of injured myocardium. We employed cervically transplanted nonworking myocardium to simulate the condition of a heart supported by a ventricular assist device, and to investigate the bioenergetic recovery processes of injured myocardium with 31P nuclear magnetic resonance (NMR) techniques. A heterotopic graft was placed in the cervical portion of a recipient rat. One week later, a control 31P NMR spectrum was obtained from the graft. On the same day, the aorta of the graft was clamped for 30 minutes at room temperature. After this procedure, 31P NMR measurements of the graft were performed for 1 week. The phosphocreatine (PCr)/Inorganic phosphate (Pi) ratio, and beta-phosphate from adenosine triphosphate (beta-ATP)/Pi ratio on the first and second day after injury were significantly lower than control (p less than 0.05). However, these ratios recovered to a significant extent on the third and fourth day. These results suggest that 3 or 4 days are required for bioenergetic recovery of reversibly injured myocardium, even under nonworking conditions. 
2	Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma. 
1	Ocular adnexal Kaposi's sarcoma in acquired immunodeficiency syndrome. We examined histopathologically 18 ocular adnexal Kaposi's sarcoma lesions related to acquired immunodeficiency syndrome. These lesions were classified into three types. Type I consisted of thin, dilated vascular channels lined by flat endothelial cells with lumen-containing erythrocytes. Type II featured plump, fusiform, endothelial cells, often with a hyperchromatic nucleus and foci of immature spindle cells and occasional slit vessels. Type III was characterized by large aggregates of densely packed spindle cells with hyperchromatic nuclei, occasional mitotic figures, and abundant slit spaces often containing erythrocytes in between. Clinically, type I and type II tumors were patchy and flat (less than 3 mm in height) and of less than four months' duration. Type III tumors were nodular and elevated (greater than 3 mm in height). We describe the clinical and histopathologic types of Kaposi's sarcoma that may help in diagnosis. 
3	Aggravation of human and experimental myasthenia gravis by contrast media. After observing a 72-year-old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic IV contrast material, an observation rarely described in the literature, we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation. There was significant worsening of the decremental response to 3 Hz repetitive nerve stimulation from 40 +/- 29% to 55 +/- 27% following the IV administration of contrast agent at doses similar to those used in humans. IV calcium partially reversed this aggravation. Caution is merited when myasthenic patients are administered contrast media. 
4	The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. On the basis of the known electrophysiologic mechanisms of atrial fibrillation, multiple surgical procedures were designed and tested in dogs to determine the feasibility of developing a surgical cure for human atrial fibrillation. These experimental studies culminated in a surgical approach that effectively creates an electrical maze in the atrium. The atrial incisions prevent atrial reentry and allow sinus impulses to activate the entire atrial myocardium, thereby preserving atrial transport function postoperatively. Since September 1987, this surgical procedure has been applied in seven patients, five with paroxysmal atrial fibrillation of 2 to 9 years' duration and two with chronic atrial fibrillation of 3 and 10 years' duration. All seven patients have been cured of atrial fibrillation and none is receiving any postoperative antiarrhythmic medications. 
3	Morbidity, mortality, and quality of life for patients treated with levothyroxine In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy. 
3	The "numb cheek-limp lower lid" syndrome. A patient developed isolated numbness, 1st confined to the lateral nose and upper lip, but later involving the cheek, lower lip, upper gingiva, and the palate. This numbness was later associated with paresis of the muscles of the upper lip and angle of the mouth and with ipsilateral lower lid droop (the "numb cheek-limp lower lid" syndrome). Squamous cell carcinoma was discovered infiltrating the infraorbital nerve and distal branches of the facial nerve. Cheek numbness associated with lower eyelid or upper lip weakness may herald a neoplasm affecting the infraorbital nerve and distal facial nerve branches. 
1	Fine needle aspiration biopsy in the diagnosis and management of fibroadenoma of the breast. Cytological and histological biopsies were obtained on 75 breast lumps clinically diagnosed as fibroadenomas. Of these, 95 per cent of lesions were benign. In 51 (68 per cent) confirmed as fibroadenomas histologically, cytology was benign in 78 per cent, but inadequate for diagnosis in 16 per cent. The remaining 24 lesions included three breast cancers and one lymph node with Hodgkin's disease. In this group cytology was inadequate for diagnosis in 54 per cent, including one breast cancer. No lesion with benign cytology was subsequently shown to be malignant. The study supports the view that clinical diagnosis and cytology are accurate in the diagnosis of benign breast disease of this type. Breast cancer may rarely present with the clinical features of a fibroadenoma and too few lesions have been studied to assess fully the performance of cytological biopsy in detecting these small mobile lesions. A non-excisional policy should therefore include prolonged follow-up and repeat biopsy. 
1	Pancreatic mucinous cystadenocarcinoma with pseudosarcomatous mural nodules. A report of a case with immunohistochemical study. A case of pancreatic mucinous cystadenocarcinoma (PMC) with two pseudosarcomatous mural nodules (PMN) is described. These nodules have not been previously described in this type of tumor. In ovarian mucinous tumors (OMT), similar nodules have been reported, the nature of which has been discussed in detail. Here the similarity between the tumor described here and ovarian tumors is stressed. The immunohistochemical study carried out disclosed in the nodules strong positive staining for vimentin and moderate positivity for keratin and epithelial membrane antigen. These findings, along with histologic details, favor the epithelial nature of the nodules. It was concluded that the nodules are foci of anaplastic carcinoma with high proliferative cell rate, which could explain the coexpression of vimentin and keratin. 
5	Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute bronchoconstriction. The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine (MCh). We studied six male asymptomatic asthmatics 18 to 35 yr of age. In a preliminary study we determined the concentration of MCh causing a 60% fall in FEV1 (PC60 FEV1). On two subsequent days, we measured breathing pattern, dyspnea sensation (Borg scale), mouth occlusion pressure (P0.1), and FEV1 before and 10 min after an intravenous injection of either naloxone (0.1 mg/kg) or saline according to a randomized double-blind crossover design. A MCh concentration equal to the PC60 FEV1 was then inhaled, and measurements were repeated 5 min later. Neither placebo nor naloxone affected baseline breathing pattern, P0.1, and FEV1. Naloxone pretreatment did not influence airway response to MCh; the mean percent fall in FEV1 was 65.9 +/- 1.3 and 64.7 +/- 1.2% (mean +/- 1 SE) on the placebo day and the naloxone day, respectively. After MCh inhalation no significant changes in VE, VT, and breathing frequency occurred when patients received placebo. However, P0.1 increased from 1.48 +/- 0.17 to 3.43 +/- 0.70 cm H2O (p less than 0.05), and VT/TI fell from 0.66 +/- 0.08 to 0.52 +/- 0.04 L/s (p less than 0.05). Naloxone pretreatment resulted in an increase in breathing frequency (from 18.2 +/- 1.7 to 22.8 +/- 2.6 breaths/min; p less than 0.05) and VT/TI (from 0.58 +/- 0.06 to 0.74 +/- 0.05 L/s; p less than 0.05) after MCh. 
5	Lateral medullary infarction: prognosis in an unselected series. We describe the acute and long-term prognosis in 43 patients with lateral medullary infarction (LMI) collected from a population-based stroke registry from 1982 to July 1988. Mean age was 63.9 years and median time of follow-up was 33 months. In the acute phase, 5 patients (11.6%) died from respiratory and cardiovascular complications and 2 new strokes occurred, both in the posterior circulation. During follow-up, recurrent vertebrobasilar territory strokes occurred in only 2 patients (a rate of 1.9% per year). The mechanisms of stroke were vertebral artery (VA) branch occlusion, causing a medial medullary syndrome, and basilar artery thrombosis propagating from a contralateral, distal VA stenosis. In the acute phase of LMI, respiratory and cardiovascular events, presumably caused by autonomic dysfunction related to the lateral medullary lesion, are the major hazards. Recurrent posterior circulation strokes were uncommon during follow-up. 
5	The use of gadolinium-enhanced magnetic resonance imaging to determine lesion site in traumatic facial paralysis. Gadolinium-enhanced magnetic resonance imaging has been used to evaluate 20 patients with surgically confirmed facial nerve lesions. When the nerve could be seen, gadolinium-enhanced magnetic resonance imaging accurately revealed the lesion site as well as the known extent, which in some cases was not predicted by topognostic testing. This technique appears to provide accurate lesion-site testing and may have importance in surgical planning. Currently used topognostic tests of facial nerve function are frequently inaccurate and can only determine the most proximal lesion site when there are multiple or extensive lesions. The focal nerve enhancement seen in nerve injury, globally increased signal intensity within the temporal bone after trauma, and increased signal intensity within the dura after surgery can occasionally mask nerve lesions and may be confused with tumors. 
4	Effects of chronic administration of a vasopressin antagonist with combined antivasopressor and antiantidiuretic activities in rats with left ventricular dysfunction. The present experiments were designed to study the long-term aquaretic effect of [d(CH2)5-D-Tyr(Et)VAVP], an antagonist to arginine vasopressin (AVP) with combined vascular (V1) and renal (V2) receptor inhibiting properties, in rats with left ventricular dysfunction resulting from myocardial infarction (MI). The continuous intravenous infusion of the AVP antagonist (36 micrograms/12 microliters/day) via osmotic minipumps over 11 days resulted in an increase in urine volume and a decrease in urinary osmolality by approximately 10-fold on the first day, but in subsequent days this response decreased in both the post-MI (n = 7) and normal (n = 6) rats. Nevertheless, the daily urine volume remained significantly higher and the urinary osmolality lower in the post-MI rats than in the normal ones throughout the study (p less than 0.05). In two other groups of post-MI (n = 5) and normal (n = 6) rats, intermittent intraperitoneal injections of the AVP antagonist (100 micrograms/kg) every third day resulted in a profound diuresis that was reproducible by each injection and was again significantly greater in the post-MI rats than in the normal rats (p less than 0.05). The cumulative urinary output over the first 10-day period of each treatment was greater with intermittent injections than with continuous infusion in both the post-MI and normal rats, but the difference was significant only in the post-MI rats (398.82 +/- 12.87 ml vs 309.07 +/- 32.44 ml, intermittent vs continuous, respectively, p less than 0.05), even though the cumulative dose of AVP antagonist given intermittently was only about one third of that given continuously. 
4	Pulmonary hypertension five years after left pneumonectomy for adenoid cystic carcinoma. We report the findings in a patient with shortness of breath due to pulmonary hypertension five years after left pneumonectomy. Mediastinal recurrence of an incompletely resected and slowly growing adenoid cystic carcinoma of the left main bronchus had encased the right main pulmonary artery. 
1	Genetic construction and characterization of a fusion protein consisting of a chimeric F(ab') with specificity for carcinomas and human IL-2. A genetic construct was created incorporating gene fragments encoding the H chain V region of the human carcinoma specific antibody L6, the CH1 domain of human IgG1, a linker region, and human IL-2. This construct was cotransfected with a chimeric L6 L chain construct into the murine myeloma cell line Ag8.653 for expression. First round clones produced the fusion protein at an estimated 5 to 10 micrograms/ml based on idiotypic reactivity. Dual binding activity was demonstrated through specific interaction with the L6 Ag on human tumor cells and the IL-2R on activated human T cells. The IL-2 portion of the molecule was shown to support the growth of the IL-2-dependent T cell line CTLL2, and the qualitative nature of the IL-2 signal was found to be the same as rIL-2 with respect to induction of tyrosine-phosphorylation of intracellular protein substrates. Tumor cells coated with the fusion protein were shown to cause T cell proliferation and the presence of the fusion protein was found to enhance cell-mediated destruction of human tumor cells. 
1	Epidermoid cysts of the brain stem. Report of three cases. The authors report the cases of three patients with epidermoid cysts which insinuated themselves into the brain stem. In all three patients, the tumor occupied the pons, although in one it was predominantly located in the medulla. The cyst contents and nonadherent tumor capsule were removed in all three patients, but no attempt was made to remove tumor densely adherent to the brain stem. One patient's cyst was removed in one operation, but maximal resection in the other two required two operations. After surgery, sixth nerve function completely returned in one patient; another patient had a stable pontine gaze palsy but developed new facial weakness; and the third patient had stable cranial nerve deficits with a diminished hemiparesis. The last patient developed a pseudomeningocele and communicating hydrocephalus, and required a lumboperitoneal shunt. In all three patients, computerized tomography scans demonstrated hypodense tumors not enhanced by contrast material. Magnetic resonance imaging was performed on two patients; in both, the tumors showed increased signal intensity relative to brain on T1-weighted images and decreased signal intensity relative to brain on T2-weighted studies. Magnetic resonance imaging, the most accurate modality for localizing these lesions and determining their extent, was also invaluable for postoperative monitoring and follow-up evaluation. Safe and adequate resection includes decompression of cyst contents and removal of nonadherent portions of the cyst capsule. Cyst wall adherent to the brain stem, however, should not be removed. 
4	Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. The endothelium plays a critical role in the control of vasomotor tone by the release of vasoactive substances. Because endothelial injury or dysfunction is considered important very early in atherogenesis, we hypothesized that abnormal endothelial function precedes the angiographic detection of coronary atherosclerosis in the human coronary circulation. The coronary vasomotor responses to three different endothelium-mediated stimuli (intracoronary infusion of acetylcholine 10(-8) to 10(-6) M, increase in blood flow to induce flow-dependent dilation, and sympathetic stimulation by cold pressor testing) were assessed by quantitative angiography and subselective intracoronary Doppler flow velocity measurements within the left anterior descending coronary artery in 38 patients. All three stimuli elicited epicardial artery dilation in all 11 patients with smooth coronary arteries and absence of risk factors for coronary artery disease (group 1). All nine patients with smooth coronary arteries but with hypercholesterolemia (group 2) demonstrated a selective impairment in endothelial function with vasoconstriction (35 +/- 12.7% decrease in mean luminal area) in response to acetylcholine but showed a preserved flow-dependent dilation (15.5 +/- 4.4% increase in mean luminal area) and vasodilation in response to cold pressor testing (14.2 +/- 4.6% increase in mean luminal area). In all nine patients with an angiographically defined smooth coronary artery segment but with evidence of atherosclerosis elsewhere in the coronary system (group 3), both acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/- 8.7% and 18.7 +/- 7.9% decrease in mean luminal area, respectively), whereas flow-dependent dilation was preserved (20.4 +/- 8.7% increase in mean luminal area). In the nine patients with angiographic evidence of wall irregularities (group 4), flow-dependent dilation was also abolished and vasoconstriction occurred in response to acetylcholine and cold pressor testing (34.5 +/- 10.7% and 19.9 +/- 6.3% decrease in mean luminal area, respectively). All coronary artery segments dilated in response to nitroglycerin, suggesting preserved function of vascular smooth muscle. Despite similar reductions in coronary vascular resistance in response to the smooth muscle relaxant papaverin, patients with hypercholesterolemia demonstrated a selective impairment of vasodilation of the resistance vasculature in response to acetylcholine (p less than 0.05 versus groups 1, 3, and 4). Thus, there is a progressive impairment of endothelial vasoactive functioning in coronary arteries of patients with different early stages of atherosclerosis, beginning with a selective endothelial dysfunction in angiographically defined normal arteries in patients with hypercholesterolemia and progressively worsening to a complete loss of endothelium-mediated vasodilation in angiographically defined atherosclerotic coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS). 
3	Ischemic optic neuropathy. ION typically affects the older population with a sudden decrease in vision, altitudinal visual field loss, and a swollen optic nervehead. Systemic hypertension and diabetes mellitus are the most commonly associated medical problems. Occlusion of the posterior ciliary arterial blood supply to the retrolaminar optic nerve leads to axoplasmic stasis and further compromise of vessels in the nerve substance, which causes the typical funduscopic appearance. Although there is no recognized medical treatment that can reverse the visual loss, a recent report suggests optic nerve sheath decompression for a select group of patients with a gradual decline in vision due to ION may be beneficial. When ION occurs in persons less than 50 years of age, such etiologies as juvenile diabetes mellitus, antiphospholipid antibody-associated clotting disorders, collagen-vascular disease, and migraines should be considered. Rarely, complications of intraocular surgery or acute blood loss may cause an ischemic event in the optic nerve. 
5	Elevated expression of the genes for transforming growth factor-beta 1 and type VI collagen in diffuse fasciitis associated with the eosinophilia-myalgia syndrome. Full-thickness skin biopsies obtained from four patients with rapidly progressive diffuse fasciitis associated with the Eosinophilia-Myalgia syndrome (EMS) were examined for the expression of transforming growth factor-beta 1 (TGF-beta 1), type VI collagen, and fibronectin genes employing immunohistochemistry and in situ hybridizations. The immunohistochemical studies demonstrated increased deposition of TGF-beta, type VI collagen, and fibronectin epitopes in the extracellular matrix of the fascia in comparison to the adjacent dermis in the same specimens. Increased levels of type VI collagen mRNA, as evidenced by positive in situ hybridization signals with an alpha 2(VI) collagen cDNA, were also found in the fascia in comparison with the dermis. In situ hybridizations of affected fascia with a human sequence-specific TGF-beta 1 cDNA demonstrated numerous fibroblasts displaying positive hybridization signals indicative of high levels of transcripts for this cytokine. In contrast, no hybridization signal for TGF-beta 1 was detected in fibroblasts in the adjacent dermis. These findings suggest that TGF-beta 1 may play an important role in the development of the connective tissue alterations present in EMS-associated diffuse fasciitis. 
5	Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity. 
5	Spermatic cord for onlay coverage of urethral defect. Segmental urethral necrosis may accompany scrotoperineal gangrene, and primary closure of the urethral defect may unacceptably reduce urethral dimensions. This dilemma has been managed successfully in 5 patients by application of the intact spermatic cord to the urethral defect and approximation to its margins. A representative case is described. 
1	Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation. We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose-dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo-CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors. 
5	Parkinsonian tremor loses its alternating aspect during non-REM sleep and is inhibited by REM sleep. Non-REM sleep transforms the waking alternating Parkinsonian tremor into subclinical repetitive muscle contractions whose amplitude and duration decrease as non-REM sleep progresses from stages I to IV. During REM sleep Parkinsonian tremor disappears while the isolated muscle events increase significantly. 
2	Cimetidine 800 mg twice daily for healing erosions and ulcers in gastroesophageal reflux disease. Although H2-receptor antagonists have been the mainstay of therapy for gastroesophageal reflux disease (GERD), none of these agents has been approved by the FDA as effective in healing lesions. Since proton pump inhibitors may be associated with long-term disadvantages, a healing regimen with cimetidine would be useful clinically. This multicenter, randomized, double-blind study was conducted to evaluate the efficacy of cimetidine 800 mg b.i.d. in healing lesions and in providing symptomatic relief in patients with ulcerative or erosive esophagitis. Patients with greater than or equal to 8 heartburn episodes during a 1-week screening period, reflux confirmed by esophageal pH monitoring, and esophageal ulcers or erosions confirmed by endoscopy were randomized to treatment with placebo or cimetidine for 12 weeks. Cimetidine provided significantly greater (p less than 0.01) improvement (74% vs. 51%) and complete healing (67% vs. 36%) of esophageal lesions than did placebo. In these patients with erosive or ulcerative esophagitis, the median time to achieve 24 h without heartburn was 13 days with cimetidine and 30 days with placebo (p = 0.01). The mean heartburn severity score in the cimetidine group decreased rapidly during the first week and was consistently lower than in the placebo group. Cimetidine, 800 mg twice daily, is effective in promoting healing of esophageal ulcers and erosions and in providing heartburn relief in patients with symptomatic erosive/ulcerative GERD. 
1	Circulating C1q-binding macromolecules and their relationship to radiographic characteristics of laryngeal cancer. Circulating macromolecules capable of binding the first component of complement (C1qBM) may represent subcellular components of tissue/tumor debris generated from rapidly proliferating invasive disease. Thirty-eight patients were randomly selected from 74 untreated patients with laryngeal cancer on the basis of disease stage and C1qBM levels. C1qBM levels were correlated with computed tomographic evidence of tumor necrosis and/or thyroid cartilage destruction. Results show that patients with stage III/IV disease with tissue necrosis and/or cartilage invasion had demonstrably higher C1qBM levels than did individuals with similarly staged disease with no evidence of these radiographically defined characteristics (120 +/- 81 micrograms/mL vs 18 +/- 15 micrograms/mL); the strongest association was reflected by the area of necrosis within regional lymph metastases. Elevated C1qBM level in patients with stage III/IV laryngeal cancer thus reflects highly aggressive disease, which is less responsive to therapeutic intervention. 
2	Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy, successful treatment of the malignancy, and response to a gluten free diet. A patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis. He was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet. The tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal, thus making this one of the earliest coeliac malignancies diagnosed. 
5	Lack of late skin necrosis in man after high-dose irradiation using small field sizes: experiences of grid therapy. Out of a total of 437 patients with superior vena caval syndrome or advanced malignancy, given single-dose grid radiotherapy, four survived to 7 years. The dose to the skin under each of the 77 holes in the grid was approximately 58 Gy. The lack of skin necrosis in the total of 308 skin circles of 1 cm diameter among these survivors, compared with known necrosis rates in larger irradiated areas, implies that there is a marked field-size effect for late necrosis in small areas of irradiated skin. 
3	Intrathecal anaesthesia for day-care surgery. A retrospective study of 160 cases using 25- and 26-gauge spinal needles. The records of 160 day-care surgical patients who received intrathecal anaesthesia were reviewed. No major complications were recorded. The incidence of postspinal headache after puncture with a 25-gauge spinal needle was nearly four times more frequent compared to a 26-gauge needle. The occurrence of postspinal headache in patients over the age of 45 years was significantly less frequent (p less than 0.05) than in younger patients. Intrathecal anaesthesia was acceptable to 91% of outpatients in this group. 
5	Managing geriatric arrhythmias, I: General considerations. Cardiac arrhythmias become increasingly common as people age, but they are not always clinically significant. Sinus node dysfunction, AV conduction disturbances, and ventricular and supraventricular arrhythmias will be found but are not always symptomatic. Treatment of asymptomatic arrhythmias is controversial and probably not indicated, but in symptomatic elderly, therapy is indicated, since even the very elderly have been found to benefit from it as much as younger patients. There are specific guidelines, however, that apply to this age group based on its susceptibility to side effects. 
3	Health status in patients with tension headache treated with acupuncture or physiotherapy. Sixty-two female patients with chronic tension headache were randomly divided into two treatment groups--acupuncture and physiotherapy. Their overall function (Sickness Impact Profile), and mental well-being (Mood Adjective Check List) and the intensity and frequency of headache were assessed before and after treatment. Before treatment the patients showed significantly more dysfunction and less positive mental well-being than a general population sample. Both treatment groups improved in overall function, the physiotherapy group somewhat more. The mental well-being increased only in the physiotherapy group. The intensity and frequency of headache was significantly reduced in both the physiotherapy group and the acupuncture group. The intensity of headache was significantly more improved in the physiotherapy group. The improvement of headache intensity persisted unchanged 7-12 months after treatment. 
3	Racial differences in cerebrovascular disease hospitalizations. We studied the relationship of race to incidence of hospitalization for cerebrovascular disease among 74,096 white and 33,041 black persons who took health examinations in a prepaid health care program. Analyses were controlled for age, sex, body mass index, coffee use, smoking, alcohol use, systolic blood pressure, and baseline disease. Blacks were at higher hospitalization risk than whites for hemorrhagic cerebrovascular disease (relative risk = 2.4, 95% confidence interval = 1.3-5.8), cerebral thrombosis (relative risk = 1.9, 95% confidence interval = 1.2-2.9), and nonspecific cerebrovascular disease (relative risk = 1.6, 95% confidence interval = 1.2-2.2) but at lower hospitalization risk for extracranial occlusive disease (relative risk = 0.4, 95% confidence interval = 0.2-0.7). Blood pressure had a similar relation to all types of cerebrovascular disease in both races, but there were disparities in the relations of other atherosclerosis risk factors to different types of cerebrovascular disease. Educational attainment had little relation to hospitalization for extracranial occlusive disease, a finding that reduces the likelihood that selection bias explains the racial disparity. These data show unexplained racial differences in the type and location of cerebrovascular disease. The differences are important in understanding the pathogenesis of cerebrovascular disease and have practical clinical implications. 
5	Aortic replacement with composite grafts created with a sutureless intraluminal ringed prosthesis. From 1980 to 1988, 30 patients from a total population of 123 recipients of sutureless grafts (24%) have required aortic reconstruction with a composite ringed graft. Replacement of the ascending aorta was required in 12 patients, of the aortic arch in six patients, of the descending aorta in two patients, of the thoracoabdominal aorta in two patients, and of the abdominal aorta in eight patients. Eight patients (27%) needed an emergency operation at the time of admission. No patients had permanent neurologic or renal deficits. There was no evidence of pseudoaneurysm formation, graft erosion, graft migration, or aortic bleeding in the postoperative period. Two operative deaths (7%) occurred, both in patients undergoing arch reconstruction. Composite grafts can be created that vary in length and shape, incorporate different graft materials, and accommodate the aorta and its branches. The ability to modify the sutureless prosthesis to suit the disease encountered at operation allows the quickest repair with the least chance of anastomotic complication. 
1	Prostatic duct adenocarcinoma. Findings at radical prostatectomy. Previous studies of prostatic duct adenocarcinoma have reported a poor prognosis, but they included few patients treated by radical prostatectomy. The authors studied 15 cases treated with radical prostatectomy to define more completely their pathologic features and determine the clinical outcome in these surgically treated patients. The study included morphometry and DNA image analysis using the CAS-200 system. The most common presentation was urinary outlet obstruction (n = 9), and most patients were clinical Stage B with palpable prostatic lesions (n = 12). Compared with acinar cancers of similar clinical stage, duct cancers were large (tumor volume, 8.4 +/- 10.0 cc) and occupied a large portion of the gland (23 +/- 21%). Duct cancers were in an advanced final pathologic stage with 93% having capsular penetration, 47% positive margins, 40% seminal vesicle invasion, and 27% positive pelvic lymph nodes. The DNA analysis on cells disaggregated from paraffin revealed that 54% of cases were diploid, 15% tetraploid, 8% aneuploid, and 23% tetraploid/aneuploid. On clinical follow-up, eight patients had no evidence of tumor at intervals ranging from 1 to 28 months, and seven patients (47%) had persistent tumor at intervals of 3 to 18 months. This study demonstrates that duct cancers are in an advanced pathologic stage by the time of presentation and have a much higher short-term failure rate after radical prostatectomy compared with acinar cancers. 
5	Mechanical deficit persists during long-term muscle hypertrophy. Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production. 
1	Needs and recommendations for behavior research in the prevention and early detection of cancer. Because life-style patterns affect many cancer risks, research on health-risk behavior and behavior change is critical to cancer prevention. This report recommends priorities for the next decade of psychosocial research on cancer prevention and detection. The leading priority for future research is to fill gaps in basic knowledge left by the rush to intervention and outcome studies. Such research must be theoretically driven and should aim to develop broad principles applicable to diverse health behaviors. Studies that include relevant process data on various stages of behavior change are considered more desirable than simple outcome studies. Epidemiologic investigations should be expanded to include measures of relevant behaviors, so that their impact on clinical outcomes might be established. More research is needed on lay perception of health risks and on individual and health-system barriers to effective cancer prevention and detection. Studies that address the needs of minority and underprivileged populations are crucial. Funding agencies' narrow categorical mandates impede interdisciplinary research on multiple risk factors and their interactions; these boundaries must be relaxed to promote such approaches. Funding agencies should also consider basic research as a long-term investment towards the development of effective interventions. 
2	Stools containing altered blood-plasma urea: creatinine ratio as a simple test for the source of bleeding. The plasma urea:creatinine ratio (U:C ratio) is known to be elevated in cases of upper gastrointestinal bleeding. Almost all patients with haematemesis have upper gastrointestinal (or generalized) bleeding so that in this study we characterized the diagnostic power of the U:C ratio in patients with stools containing altered blood without haematemesis in the hope that this simple laboratory test (used in conjunction, perhaps, with clinical data) might reduce the number of patients subjected to an unrewarding gastroscopy or colonoscopy. Of 76 cases seen in a provincial and a metropolitan hospital, 42 and 34 patients had upper and lower gastrointestinal bleeding, respectively. Fifty-four per cent of those with upper gastrointestinal bleeding and none of those with lower gastrointestinal bleeding had U:C ratios above 110 on admission. However, a discriminating level of 90 is considered to be more suitable, judged by the quadratic uncertainty score. At this level the odds for upper gastrointestinal bleeding were 15:1. 
4	Hindbrain ischemia produced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats. Hindbrain ischemia was induced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats (SHRs). Mean arterial blood pressure was lowered to 80 mmHg in SHRs and to 50 mmHg in Wistar-Kyoto rats (WKYs) by a controlled hemorrhage, and then the vertebral artery was bilaterally occluded through alar foramina of the first cervical vertebra. Following vertebral occlusion, blood flow of the cerebellum was significantly decreased to 9.4 +/- 2.0 mL/100g/min (+/- SEM) while flow of the cerebrum remained at 32.1 +/- 5.4 in SHRs. In contrast, cerebellar blood flow in WKYs was preserved at 24.2 +/- 2.9 mL/100g/min. Brain lactate, pyruvate, and adenosine triphosphate (ATP) were determined in SHRs after sixty minutes of hypotension with or without vertebral occlusion. Although infratentorial metabolites were actually unaltered in rats with hypotension alone, infratentorial lactate and lactate/pyruvate ratio significantly increased to 14.38 +/- 3.61 mmol/kg and 67.7 +/- 12.1, respectively, with a concomitant decrease in ATP in SHRs with hypotension and vertebral occlusion. Bilateral vertebral artery occlusion, together with moderate hypotension, was shown to produce a marked reduction of cerebellar blood flow and to induce ischemic metabolic changes in the infratentorial brain in SHRs. 
5	Randomised single blind trial to compare the toxicity of subconjunctival gentamicin and cefuroxime in cataract surgery. Comparatively little attention has been paid to the conjunctival toxicity of antibiotics administered at the time of cataract surgery. We have observed the effect of subconjunctival gentamicin and cefuroxime injection, using colour photography in a randomised single blind trial of 121 patients undergoing routine cataract surgery. Our results suggest that a hyperaemic eye is likely to occur about twice as often in patients injected with gentamicin (p less than 0.001). Gentamicin is associated with more pain postoperatively (p less than 0.05). Significant manifestations of gentamicin toxicity are conjunctival oedema and capillary closure. Cefuroxime has some theoretical advantages over gentamicin in its antibacterial spectrum. 
4	Safety and efficacy of thrombolytic therapy for superior vena cava syndrome The experience at the Cleveland Clinic from 1982 to 1990 using thrombolytic therapy for superior vena cava (SVC) syndrome was retrospectively reviewed. Sixteen patients, 11 of whom had indwelling central venous catheters, were treated with either urokinase (n = 11) or streptokinase (n = 5). Either urokinase (4,400 U/kg bolus followed by 4,400 U/kg/h) or streptokinase (250,000 U bolus followed by 100,000 U/h) was used, and venograms were performed before and after. Overall, 56 percent of patients had complete clot lysis and relief of symptoms. Thrombolytic therapy was effective in eight (73 percent) of 11 patients receiving urokinase and one (20 percent) of five patients receiving streptokinase. Of those with a central venous catheter, eight (73 percent) of 11 patients were successfully lysed, whereas only one (20 percent) of five patients was successfully lysed if no catheter was present. If thrombolytic therapy was performed less than or equal to five days of symptom onset, seven (88 percent) of eight patients were successful, if thrombolytic therapy was performed greater than five days after symptom onset, two (25 percent) of eight patients were successful. Symptoms were relieved and the catheter was preserved in patients in whom thrombolytic therapy was effective. Factors predicting success were as follows: (1) the use of urokinase compared with streptokinase; (2) the presence of a central venous catheter; and (3) a duration of symptoms less than or equal to five days. 
2	Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion. 
4	Transbronchial biopsies in children after heart-lung transplantation. Sixty transbronchial biopsies have been performed in eight children after heart-lung transplantation. The selection of fiber-optic bronchoscope or a small (4 mm; 30 cm) rigid bronchoscope was made according to the size of endotracheal tube required at surgery. If the endotracheal tube was size 7.5 or greater, a fiber-optic bronchoscope was used, whereas if the endotracheal tube size was below 7, a rigid bronchoscope was used. For the diagnosis of lung rejection, the histology of biopsies revealed a sensitivity of 91% and specificity of 69% (similar to the result in adults). The histology also distinguished lung infection from rejection. Complications included three pneumothoraces and two clinically significant episodes of hemorrhage, one of which led to a cardiorespiratory arrest, which may have been caused by hypoxia. As a result, arterial oxygen saturation is now monitored during the procedure using a pulse oximeter. 
5	A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial II Study Group BACKGROUND. Abnormalities of cellular calcium homeostasis have been implicated in the pathophysiology of postischemic encephalopathy. Calcium-entry-blocking drugs inhibit the influx of calcium into cells and have been shown to mitigate postischemic encephalopathy in animal models. METHODS. Five hundred twenty patients with cardiac arrest who remained comatose after the restoration of spontaneous circulation were randomly assigned to receive three doses of lidoflazine, an experimental calcium-entry blocker, or a placebo and were followed for six months. Four patients were lost to follow-up. Treated patients received an intravenous loading dose (1 mg per kilogram of body weight) of lidoflazine and two subsequent doses (0.25 mg per kilogram) 8 and 16 hours after resuscitation. The investigators were blinded to treatment assignment. RESULTS. There was no statistically significant difference between the lidoflazine group (n = 259) and the placebo group (n = 257) in the proportion of patients who died during the six-month follow-up (82 vs. 83 percent), who survived with good cerebral recovery (15 vs. 13 percent), or who survived with severe neurologic deficit (1.2 vs. 1.9 percent). Analysis of the best level of recovery achieved at any time during follow-up also did not show a difference between the treatment groups: 24 percent of those given lidoflazine and 23 percent of those given placebo recovered good cerebral function (normal or only moderately disabled cerebral performance) at some time. CONCLUSIONS. The administration of lidoflazine after cardiac arrest was not found to be beneficial. Our data do not support the routine use of this calcium-entry-blocking drug in comatose survivors of cardiac arrest. 
4	Prolonged cardiac preservation. Evaluation of the University of Wisconsin preservation solution by comparison with the St. Thomas' Hospital cardioplegic solutions in the rat. The University of Wisconsin solution differs from other types of solutions used for organ preservation because it contains high-energy phosphate precursors (adenosine and phosphate), impermeants (lactobionate and raffinose), an oncotic agent (pentafraction), and antioxidants (allopurinol and glutathione). These components have the potential to enhance the preservation of ATP, reduce intracellular and extracellular edema, and attenuate free-radical-mediated injury. The University of Wisconsin solution has been demonstrated to enhance and extend the preservation of the liver, pancreas, and kidney, but its potential role in the heart remains unproven. We have evaluated the University of Wisconsin solution (Du Pont) by comparing it with the St. Thomas' Hospital cardioplegic solutions No. 1 and No. 2 (Plegisol), which are used in Europe and the United States for routine cardiac surgery and transplantation. For each solution, 10 isolated working rat hearts were arrested by 10 ml of the solution (at 4 degrees C) and then maintained immersed in the same solution for 4 hours at 4 degrees C. Mean recovery of functional indexes (expressed as a percentage of their preischemic control values) after use of the University of Wisconsin solution were as follows: peak aortic pressure, 90.6 +/- 1.0; dP/dt, 71.5 +/- 5.5; aortic flow, 81.6 +/- 4.7; coronary flow, 87.5 +/- 3.5; and cardiac output, 82.6 +/- 3.5. In contrast, the mean recoveries after St. Thomas' Hospital solution No. 1 were as follows: peak aortic pressure, 82.8 +/- 1.3; dP/dt, 49.7 +/- 3.0; aortic flow, 58.4 +/- 5.3; coronary flow, 79.6 +/- 5.9; and cardiac output, 63.0 +/- 4.9. In contrast still, mean recoveries after St. Thomas' Hospital solution No. 2 were as follows: peak aortic pressure, 83.1 +/- 1.2; dP/dt, 40.7 +/- 6.1; aortic flow, 37.0 +/- 5.1; coronary flow, 65.8 +/- 3.6; and cardiac output, 43.1 +/- 5.6. The recovery of all indexes were significantly superior (p less than 0.005) after preservation with University of Wisconsin solution compared with either of the St. Thomas' Hospital solutions. 
5	Adaptive hyperphagia in patients with postsurgical malabsorption. The specific nutritional consequences of malabsorption after small-bowel surgery were studied in a consecutive series of 48 ambulatory patients who had had small-bowel resection (n = 43) or bypass (n = 5) and in 10 patients who had an ileal pouch (n = 10). The patients received a 3-day standardized oral regimen providing daily 30 kcal/kg of ideal body weight (IBW). Throughout the study, 41 patients had malabsorption (fecal fat greater than 5%); 17 had fecal fat less than 5% and served as controls. The malabsorption patients absorbed 70% of protein and 71% of fat. Twenty-one were normonourished and 20 had features of mild energy malnutrition, vs. 15 and 2 controls, respectively. Compared with controls, malabsorption patients had decreased body weight and triceps skin-fold but no features of protein malnutrition. their mean daily food intake at home was significantly enhanced (39.6 +/- 13.1 kcal/IBW kg) vs. controls (28.8 +/- 5.8 kcal/IBW kg, P less than 0.001). In the malabsorption group, caloric intake was higher in the normonourished patients than in those with mild malnutrition. This study shows that a chronic malabsorption has limited nutritional consequences. The patients compensate for their absorptive handicap by increasing their oral intake. 
4	Self-report of physical activity and patterns of mortality in Seventh-Day Adventist men. The Adventist Mortality Study provides 26-year follow-up through 1985 for 9484 males who completed a lifestyle questionnaire in 1960. The relationship of self-reported physical activity and all cause and disease-specific mortality was examined by survival analysis and with the Cox proportional hazards model, controlling for demographic and lifestyle characteristics. Moderate activity was associated with a protective effect on cardiovascular and all cause mortality in both analyses. In the Cox model, age-specific estimates of relative risk (RR) were obtained for several endpoints due to a significant interaction between level of physical activity and attained age (age at death or end of follow-up). This model permits calculation of the age at which the RR = 1.0, or the age at crossover of risk. For moderate activity, this age was 95.6 years (95% confidence intervals, 81.7-109.4 years) for all cause mortality and 91.5 years (95% confidence intervals, 79.0-104.0 years) for cardiovascular mortality. While the protective effect on mortality associated with moderate activity decreased with increasing age, it remained significant to the verge of the present life span. 
5	Code 9: a systematic approach for responding to medical emergencies occurring in and around a hospital. Members of the public expect to receive efficient and appropriate medical care if they become acutely ill or injured while in or around a hospital. Our institution became aware of the need for an organized system to respond to such emergencies involving patients, visitors, local community residents, and hospital employees, both inside the hospital and on the grounds surrounding the building. A search of the literature did not provide information regarding such a response; a survey of surrounding hospitals revealed no such plan in effect in other institutions. We therefore designed a plan to be superimposed onto our existing system for responding to in-house cardiac and respiratory arrests ("codes"). The results after one and one-half years appear encouraging. We recommend the establishment of such an emergency response system in all health care institutions. 
1	Reliability of colposcopy and directed punch biopsy A group of 118 women underwent laser cone biopsy. Data were collected routinely on proforma case notes and entered into a computerized database. The histology of the cone biopsies was compared with that of previous, colposcopically directed punch biopsies, with the cytology of smears taken in the clinic and with the colposcopic diagnosis. The punch biopsy had a 54% false negative rate and neither of the two microinvasive carcinomas biopsied in this way were detected by the biopsy. Ten of 24 women with negative punch biopsies had CIN III in the cone. When the punch biopsy showed CIN II or worse, the cone biopsy confirmed the presence of CIN in 86%. There was some evidence of false negative cone biopsies. The data suggest that management should not be based solely upon the punch biopsy result but should include consideration of the cytology and colposcopy findings. Excisional methods of treatment are more likely to reveal early invasion and adenocarcinoma-in-situ. 
4	Very high blood pressure in acute stroke. In a study sample consisting of 388 unselected, consecutive acute stroke patients, 27 with systolic blood pressure greater than or equal to 200 mmHg and diastolic blood pressure greater than or equal to 115 mmHg were compared with the other 361 patients. The patients with high blood pressure were younger (65 vs. 73 years) and much more often had a history of hypertension (78 vs. 42%). Cardiac and vascular hypertensive manifestations were more frequent, particularly when only those patients with a history of hypertension were compared in the two groups. Alcohol abuse was mentioned in a higher proportion of hypertensives in the summaries of their medical records. No definite conclusions could be drawn with regard to the size and location of the brain lesions. Clinical symptoms did not differ between the groups, neither did the proportion of patients who could be discharged from hospital immediately. Mortality was higher in the high blood pressure group (30 vs. 14%, P less than 0.05). Thus the characteristics of patients with very high blood pressure were: younger age, much more frequent and severe previous hypertension. Alcohol abuse might be an important factor. The type, size and location of the brain lesion itself could not be statistically related to the high blood pressure, but very large lesions, particularly haemorrhages, might be associated with a reactive blood pressure response. 
2	Imaging the gallbladder: a historical perspective. After Wilhelm Conrad Roentgen's discovery of the X-ray in 1895, it was initially thought that gallstones could not be visualized. Surgeons relied solely on the clinical examination to detect biliary disease. Today, no evaluation of the gallbladder would be complete without the performance of an imaging study. Radiology has gone through several eras in the imaging of gallstones. The plain film era, 1895-1924, was characterized by techniques that improved soft-tissue detail, allowing better detection of radiopaque stones. The contrast media era, 1924-1960, was initiated by the invention of IV cholecystography. In 1925, oral cholecystography was developed. During the era of expanding technology, 1960-1979, percutaneous transhepatic cholangiography, scintigraphy, and sonography came into use. The therapeutic era began in the 1980s. 
2	Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas. Polyamine content (putrescine, spermidine, and spermine) or ornithine decarboxylase (ODC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonoscopy. Comparisons were made between those with and those without adenomatous polyps. Colonic mucosal polyamine content was measured in 44 persons. Mean putrescine content was 1.25 +/- 0.26 (SE) nmol/mg protein in 22 patients with adenomatous polyps compared with 0.53 +/- 0.12 nmol/mg protein in patients without polyps (P less than 0.02). Tissue content of spermidine and spermine did not differ between these two groups. Ornithine decarboxylase activity was measured in tissue from 45 patients. Mean ODC activity was 2.84 +/- 0.73 pmol/hr/mg protein in 23 persons with adenomatous polyps compared with 1.15 +/- 0.18 pmol/hr/mg protein in persons without polyps (P less than 0.05). Mucosal putrescine and ODC activity are elevated in patients with adenomatous polyps compared with patients without polyps. These biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps. 
1	Lack of neural control and reactivity to vasoactive agents in malignant glioma arteries. Vessels in malignant brain tumors have a defective blood-brain barrier. It is important to know if tumor vessels respond to vasoactive agents, since systemic administration of vasodilatory agents together with chemotherapy could increase the access of these drugs to the tumor. It was found that arteries in human malignant gliomas have no neural control and are totally nonreactive to various vasoactive agents. The vessels lose their reactivity within 1 to 2 mm outside the visible tumor front. 
1	Serum ferritin and stomach cancer risk among a Japanese population. Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset. 
5	Granulomatous hepatitis and fever of unknown origin. An 11-year experience of 23 cases with three years' follow-up. Granulomatous hepatitis is a common cause of fever of unknown origin in up to 13% of patients with prolonged fever. Attempts to define an exact etiology of the granulomatous hepatitis frequently does not yield a precise diagnosis, so that the physician must consider empiric treatment. In this paper we retrospectively review 23 patients in whom granulomatous hepatitis was found as part of the initial assessment of fever of unknown origin, and we report on their outcomes after an overall prospective follow-up of 37 months. In 26% a precise diagnosis was established at the time of assessment: Q-fever in three, mycobacterial disease in two, and histoplasmosis in one. In the remaining 74% no etiology was established after 44 months follow-up. Forty-one percent of the idiopathic group resolved spontaneously without therapy, and 18% received short-term prednisone or indomethacin with a favourable outcome. The remaining 41% required long-term prednisone therapy for a mean of 33.1 months, but all have remained afebrile and otherwise healthy after 59.6 months follow-up. We conclude that patients with fever of unknown origin who are diagnosed as having idiopathic granulomatous hepatitis have an excellent prognosis, even the minority who require long-term corticosteroids. 
3	Eosinophilia-myalgia syndrome in association with L-tryptophan ingestion. The association between the recently described eosinophilia-myalgia syndrome and L-tryptophan is now well established. We describe a patient with eosinophilia-myalgia syndrome who developed incapacitating myalgias and peripheral eosinophilia responsive only to high dose corticosteroids. When massive upper gastrointestinal hemorrhage developed while receiving corticosteroid therapy, surgery was complicated by striking abdominal wall rigidness. A discussion of this case and of eosinophilia-myalgia syndrome is presented. 
1	P-31 spectroscopy study of response of superficial human tumors to therapy. Studies were performed to characterize phosphorus-31 magnetic resonance (MR) spectra obtained from 10 superficial human tumors outside the brain and to determine whether P-31 MR spectroscopy could allow detection of a response to therapy before a change in tumor size was measured. The ratio of phosphomonoester to adenosine triphosphate peak intensities (PME/ATP) was unusually large in all tumors studied. The average PME/ATP in lymphomas (1.8 +/- 0.5) was greater than in nonlymphoma cancers (1.1 +/- 0.15). The average PME/ATP for all tumors studied (1.4 +/- 0.5) was much greater than that of underlying skeletal muscle (0.23 +/- .09). Eight of the tumors were studied before and after therapy. Responders were distinguished from nonresponders on the basis of changes in tumor size. PME/ATP decreased during therapy in three lymphomas that responded to therapy. In an adenocarcinoma and Ewing sarcoma that did not respond to therapy, PME/ATP increased. PME/ATP remained constant in two squamous cell carcinomas that responded to therapy and decreased in one squamous cell carcinoma that decreased in size by 40% but was classified as a nonresponder. Changes in PME/ATP did not always parallel changes in tumor size during therapy. In two patients, a decrease in PME/ATP preceded a decrease in tumor size. In four patients, PME/ATP increased transiently during periods when tumor size remained constant. 
5	Fertility after contraception or abortion. There is a very small correlation, if any, between the prior use of OCs and congenital malformations, including Down's syndrome. There are few, if any, recent reports on masculinization of a female fetus born to a mother who took an OC containing 1 mg of a progestogen during early pregnancy. However, patients suspected of being pregnant and who are desirous of continuing that pregnancy should not continue to take OCs, nor should progestogen withdrawal pregnancy tests be used. Concern still exists regarding the occurrence of congenital abnormalities in babies born to such women. The incidence of postoperative infection after first trimester therapeutic abortion in this country is low. However, increasing numbers of women are undergoing repeated pregnancy terminations, and their risk for subsequent pelvic infections may be multiplied with each succeeding abortion. The incidence of prematurity due to cervical incompetence or surgical infertility after first trimester pregnancy terminations is not increased significantly. Asherman's syndrome may occur after septic therapeutic abortion. The pregnancy rate after treatment of this syndrome is low. The return of menses and the achievement of a pregnancy may be slightly delayed after OCs are discontinued, but the fertility rate is within the normal range by 1 year. The incidence of postpill amenorrhea of greater than 6 months' duration is probably less than 1%. The occurrence of the syndrome does not seem to be related to length of use or type of pill. Patients with prior normal menses as well as those with menstrual abnormalities before use of OCs may develop this syndrome. Patients with normal estrogen and gonadotropin levels usually respond with return of menses and ovulation when treated with clomiphene. The rate for achievement of pregnancy is much lower than that for patients with spontaneous return of menses. The criteria for defining PID or for categorizing its severity are diverse. The incidence of PID is higher among IUD users than among patients taking OCs or using a barrier method. The excess risk of PID among IUD users, with the exception of the first few months after insertion, is related to sexually transmitted diseases and not the IUD. Women with no risk factors for sexually transmitted diseases have little increased risk of PID or infertility associated with IUD use. There appears to be no increased risk of congenital anomalies, altered sex ratio, or early pregnancy loss among spermicide users. All present methods of contraception entail some risk to the patient. The risk of imparied future fertility with the use of any method appears to be low.(ABSTRACT TRUNCATED AT 400 WORDS). 
3	Unusually late onset of cerebrospinal fluid rhinorrhea after head trauma. Two cases of acute meningitis and cerebrospinal fluid rhinorrhea, in which the head trauma responsible occurred 10 and 30 years before, are presented. Intraoperatively, the brain parenchyma was found to be plugged into the fractured anterior fossa. By debridement and duraplasty from an intradural approach, both patients were cured. Several precipitating factors could be responsible for this unusually late reopening of the fistula. The possible accidental causes could be coughing or undetected microtraumas, but in the long run, atrophy of tissues and consequent changes in brain compliance with aging may play a role. 
3	Experimental models of temporal lobe epilepsy: new insights from the study of kindling and synaptic reorganization. Temporal lobe epilepsy is a common localization-related epileptic syndrome characterized by complex partial seizures, ictal and interictal epileptic discharges arising from limbic structures of the temporal lobe, and association with hippocampal sclerosis. Temporal lobe epilepsy may follow perinatal injury and febrile convulsions, may be progressive, and frequently becomes refractory to standard antiepileptic therapy. The neurobiology that underlies these features of temporal lobe epilepsy is not known. Recent studies in experimental models have provided new insights that may help clarify the relationship of seizures, hippocampal sclerosis, and temporal lobe epilepsy. Observations from the study of the hippocampus with kainic acid-induced lesions, the kindling model, and other experimental models of epilepsy have demonstrated that seizures induce structural and electrophysiologic alterations in hippocampal pathways that may lead to increased excitability and could play a role in the development and progression of temporal lobe epilepsy. These alterations include mossy fiber synaptic reorganization, induction of NMDA-mediated synaptic transmission, and progressive hippocampal neuronal loss induced by brief kindled seizures. Some of the structural alterations induced by kindling have also been observed in the human epileptic temporal lobe, raising the possibility that mechanisms operative in kindling may play a role in the pathogenesis of hippocampal sclerosis and in the syndrome of human temporal lobe epilepsy. 
1	Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts. We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells. 
5	Operative and conservative treatment of moderate spondylolisthesis in young patients. We made a retrospective study of 149 children and adolescents with moderate spondylolisthesis (slip less than or equal to 30%), 77 treated by fusion and 72 conservatively at an average follow-up of 13.3 years. Both groups were fully comparable with regard to age at diagnosis, sex distribution (46% girls), and mean slip. The patients who were treated operatively had more pain before treatment and showed more initial progression of the slip. They had better clinical results and less pain at latest review, but the total progression of the slip over the whole follow-up showed no statistical differences between the two groups. Patients with a pseudarthrosis after attempted fusion had had a longer period of postoperative pain, but at the latest review had no more pain than those with sound fusion. None of those treated conservatively came to fusion later and the long-term results in 18 patients who had refused the advised operation were no worse than those for other conservatively treated patients. Our results suggest that a moderate grade of spondylolisthesis in adolescents usually has a benign course. It seems that spontaneous segmental stabilisation occurs as a result of degeneration of the disc at the level of the slip. 
1	Clinical and prognostic assessment of patients with resected small peripheral lung cancer lesions. One hundred fifteen patients with small (less than or equal to 2 cm in diameter) peripheral lung cancer lesions underwent surgical treatment in the Department of Surgery, The Research Institute for Chest Diseases and Cancer, Tohoku University, Miyagi Prefecture, Japan. The authors investigated several prognostic factors of these cases. The 5-year survival rate of these 115 patients was 70%. Various factors such as histologic type, nodal involvement, pleural involvement, pathologic stage, and curativity of the operation were revealed to affect survival significantly. In patients with and without nodal involvement, there was no significant difference between the survival rate of patients with lung cancer lesions smaller than 2 cm and those with lesions 2.1 to 3 cm. However, the rate of lymph node metastasis was significantly different in the group with lesions smaller than 2 cm compared with those with lesions 2.1 to 3 cm (21% versus 43%, respectively). 
3	Surgical experience with cerebral amyloid angiopathy. Cerebral amyloid angiopathy can present as lobar intracerebral hemorrhage in an elderly person, presumably due to increased fragility of the vessels affected by amyloid deposition. For this reason, patients presenting with intracerebral hemorrhage and suspected of having cerebral amyloid angiopathy have often been treated nonsurgically. Since 1983 we have evaluated 11 patients with cerebral amyloid angiopathy (nine women and two men, mean age 73 years) who have undergone either intracerebral hematoma evacuation or brain biopsy. Nine of the 11 patients presented with intracerebral hemorrhage, which was unilobar in three patients and multilobar in six and involved the parietal lobes seven times, the frontal lobes four times, the temporal lobes four times, and the occipital lobes twice. These nine patients underwent hematoma removal, with no cases of abnormal intraoperative bleeding or recurrent hemorrhage. Six patients improved neurologically, and two were unchanged after hematoma evacuation; the remaining patient had a fatal cardiopulmonary arrest during the immediate postoperative period. During follow-up in seven patients (median 11 months, range 1 week to 74 months) none experienced a recurrent intracerebral hemorrhage and four continued to improve. Two of the 11 patients had cerebral amyloid angiopathy diagnosed by brain biopsy as part of an evaluation for dementia, also without surgical complications. This series suggests that patients with cerebral amyloid angiopathy may safely undergo operative procedures, and patients presenting with intracerebral hemorrhage may show neurologic improvement following evacuation of the hematoma. 
4	Therapeutic considerations in the elderly hypertensive. The role of calcium channel blockers. Hypertension is an extremely common problem in the elderly. The optimum antihypertensive agent to use in this population is not certain. In this paper, the factors influencing the choice of antihypertensive therapy are reviewed. They include efficacy, safety, comorbidity, utility in special populations, drug interaction, dosage schedule, cost, the mechanisms of action of the drug, and the pathophysiology of the patient's hypertension. Calcium channel blockers are effective and safe in the elderly. They improve other conditions frequently seen in that population and, with the exception of cardiac conduction abnormalities associated with some calcium channel blockers, do not adversely affect other comorbid diseases. They work well together with other antihypertensives and as vasodilators, they may be specifically appropriate in elderly hypertensives, whose hypertension is associated with reduced cardiac output and increased peripheral vascular resistance. Once- and twice-a-day preparations are available to foster compliance, but calcium channel blockers are expensive. 
2	Effect of indomethacin on gastric mucosal blood flow around acetic acid-induced gastric ulcers in rats. Repeated administration of indomethacin markedly delays spontaneous healing of experimental gastric ulcers induced in rats. To elucidate the underlying mechanism, the effect of indomethacin on the gastric mucosal blood flow around ulcers was examined. Gastric ulcers were induced 5 days after submucosal injection of an acetic acid solution into the stomachs of rats. Blood flow was determined by the hydrogen gas clearance method. The blood flow around ulcers was significantly higher than that in rats without ulcers up to 2 weeks after ulceration but had returned to within the normal range 3 or 4 weeks later. Indomethacin, administered SC at 1 mg/kg once or repeatedly for 1-4 weeks, had little or no effect on the blood flow in normal rats. However, such treatment significantly reduced the blood flow by 20%-30% of the corresponding control levels in rats with ulcers. Prostaglandin E2, administered SC at 3 mg/kg once, markedly prevented the reduction in the blood flow due to indomethacin. The administration of prostaglandin E2, with indomethacin for 4 weeks resulted in a significantly higher blood-flow level than the control and prevented the delay in ulcer healing. Omeprazole, administered SC at 30 mg/kg once or repeatedly with indomethacin for 4 weeks, had an insignificant effect on the blood flow around ulcers but prevented the delay in ulcer healing. In conclusion, the delayed ulcer healing caused by indomethacin might be partly related to the reduced blood flow around the ulcers. 
3	Verbal memory impairment correlates with hippocampal pyramidal cell density. Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures. 
3	Surgical management of oculomotor nerve palsy We treated seven patients with unilateral oculomotor nerve palsy by transposition of the insertion of the superior oblique tendon to a point anterior and medial to the insertion of the superior rectus muscle without trochleotomy (Scott procedure). Additionally, large recessions of the lateral rectus muscle of involved eyes and, occasionally, recess/resect procedures of horizontal recti muscles of non-involved eyes were performed. All patients were followed up between one and eight years. Orthophoria in the primary position was achieved and maintained with one operation in four patients. A fifth patient had only a small residual exotropia. In two patients who had aberrant regeneration of the oculomotor nerve, surgery on horizontal recti muscles of the noninvolved eye improved the eyelid position of the involved eye after three operations. 
4	Hydroxyethyl starch pretreatment in bacteremic sheep. Live bacteria were infused in a chronic ovine lung lymph model to determine if a preceding infusion of the colloid, hydroxyethyl starch (HES), exaggerated the cardiopulmonary dysfunction or impaired removal of bacteria by macrophages in the pulmonary circulation. HES was infused (3 mL/kg/hr; n = 6) from 24 to 12 hr before the bacteria and decreased plasma protein content and increased pulmonary lymph to plasma protein concentration because of its oncotic properties. Ringer's lactate (2 mL/kg/hr) was given after stopping HES and also to the control group (n = 6). Infusion of live Ps. aeruginosa (2.5 x 10(8) Ps./min for approximately 30 min) induced equivalent pulmonary hypertension, increased pulmonary microvascular permeability, and cardiovascular depression in the two groups. The removal of bacteria in the lungs was not affected, indicating that this measurement of the function of the mononuclear phagocytic system was not impaired by the preceding HES. 
4	Femoropopliteal angioplasty. Factors influencing long-term success. Prospective data was recorded on 217 percutaneous transluminal angioplasty (PTA) procedures performed in the superficial femoral and popliteal arteries over an 8-year period. After the initial procedure, patients were followed with serial noninvasive studies and, in 71 patients, repeat angiography. The mean follow-up period was 7 years (range, 2-11 years). Standard life-table survival analysis was used to assess the factors potentially affecting long-term outcome. Excluding an initial technical failure rate of 10%, overall patencies at 1, 3, and 5 years were 81%, 61%, and 58%, respectively. After the first year, the prognosis (i.e., failure rate) appears to be linear over the long term (i.e., up to 10 years). Factors negatively influencing long-term patency include the presence of diabetes mellitus, diffuse atherosclerotic cardiovascular disease, or threatened limb loss. Technical factors correlated with failure include lesion length, moderate eccentricity, and a poor post-PTA appearance. 
4	Both d-cis- and l-cis-diltiazem have anti-ischemic action in the isolated, perfused working rat heart. The effect of diltiazem (d-cis-diltiazem) on the ischemic myocardium was compared with that of l-cis-diltiazem, an optical isomer having less potent calcium channel-blocking action, in the isolated, perfused working rat heart. Ischemia decreased mechanical function and tissue levels of ATP and creatine phosphate, and increased tissue levels of nonesterified fatty acids (NEFA), AMP and lactate. Reperfusion did not restore mechanical function, but restored incompletely the levels of metabolites (except NEFA) that had been altered by ischemia. The ischemia-induced changes in NEFA were prevented by d-cis-diltiazem completely and by l-cis-diltiazem incompletely. Other metabolic changes induced by ischemia were attenuated by d-cis-diltiazem but not by l-cis-diltiazem. In heart pretreated with d-cis- or l-cis-diltiazem, both the mechanical function and the levels of metabolites recovered during reperfusion, the degree of recovery with both drugs being similar. These results indicate that not only d-cis-diltiazem but also l-cis-diltiazem has an anti-ischemic action probably due to inhibition of the tissue NEFA accumulation. These results also suggest that the mechanism of the protective effect of d-cis-diltiazem on the ischemic myocardium is not entirely due to the calcium channel-blocking action. Treatment with low Ca2+ (1.0 mM CaCl2) also attenuated the ischemia-induced changes. The interval between reoxygenation and start of function in the reperfused heart that had been treated with low Ca2+ was significantly longer than that with d-cis- or l-cis-diltiazem. The effect of these isomers to shorten this interval may contribute to their common anti-ischemic action. 
4	Bolus, front-loaded, and accelerated thrombolytic infusions for myocardial infarction and pulmonary embolism. Thrombolytic therapy decreases mortality in patients with acute myocardial infarction and is now widely used in such patients. The choice of which thrombolytic agent to use in such patients, either streptokinase or recombinant tissue plasminogen activator (rt-PA), is based on regional preferences. The standard dose of streptokinase is 1.5 million units over 60 min, and the dose of rt-PA that is commonly used is 100 mg over 3 h. Experiments in animals have demonstrated that rt-PA produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated and bleeding is reduced when rt-PA is administered over a short time period. Based on these studies, there have been a number of recent trials examining alternative dosage regimens for rt-PA (bolus, front-loaded, and accelerated) in patients with myocardial infarction. To date, there is no convincing evidence that such regimens are superior to the more traditional rt-PA regimen. Future randomized trials will determine whether attempts to optimize rt-PA regimens will result in more efficacious treatment regimens. Interest in the use of thrombolytic therapy for patients with acute pulmonary embolism has been rekindled. The traditional 12- to 24-h regimens of streptokinase and urokinase are not optimal because of their logistic complexity and associated hemorrhagic complications. Clinical studies have demonstrated that rt-PA, 100 mg over 2 h, is an effective thrombolytic agent in patients with acute pulmonary embolism. In a recent double-blind trial in patients with acute pulmonary embolism, rt-PA, 0.6 mg/kg infused over 2 min, improved pulmonary perfusion. This bolus regimen is attractive because it is simple to administer. Future studies will compare the relative efficacy and safety of these two rt-PA regimens in patients with acute pulmonary embolism. 
3	Pretreatment neuropsychological status and associated factors in children with primary brain tumors. We report on the neuropsychological status of 31 children with primary brain tumors who underwent assessment before receiving therapy. Overall, the children performed within normal limits in all test areas. The exception was the group with anterior hemispheric tumors who demonstrated deficits in executive cognitive functions. Also, when compared according to tumor type, children with midline tumors and hydrocephalus performed more poorly than others on measures of intelligence, executive abilities, visual-motor skills, and fine-motor functions. Although one-half to two-thirds of the children with supratentorial midline and infratentorial tumors had cranial nerve, oculomotor, or cerebellar deficits, only the latter were associated with specific neuropsychological deficits (poorer performance on fine-motor and visual-motor tests). Age did not appear to be a factor in these children's neuropsychological test performances. 
5	Tuberothalamic infarct after division of a hypoplastic posterior communicating artery for clipping of a basilar tip aneurysm: case report. The authors present a case of a tuberothalamic infarct subsequent to division of the posterior communicating artery for clipping of a high-lying aneurysm of the basilar bifurcation using the pterional approach. In view of this clinical observation and some particular aspects of the microsurgical anatomy of the perforating vessels of the posterior communicating artery, we conclude that interrupting this parent vessel carries a significant risk of infarction. 
5	Serum aldolase isozyme levels in patients with cerebrovascular diseases. A subunit specific radioimmunoassay was developed for the quantification of human aldolase A, B, and C. The method used was a double antibody radioimmunoassay using radioiodinated purified aldolase A, B, or C subunits as the ligand, specific chicken antibodies to aldolase isozymes and rabbit antibodies to chicken IgG. The Iodogen method was used for iodination of the purified isozyme subunits in this study. Human brain tissue contained similar concentrations of aldolase A and aldolase C, and a smaller amount of aldolase B, which was the main isozyme of liver tissue. Levels of serum aldolase A were greater than 203 ng/ml, the upper limit of normal, in six of 24 patients with cerebral infarction and in 11 of 31 patients with cerebral hemorrhage. Nine of 24 patients with cerebral infarction and 16 of 31 patients with cerebral hemorrhage had serum aldolase C levels greater than 4.1 ng/ml, the upper limit in normal sera. These data suggest that serum aldolase C may be a more specific and sensitive marker of cerebrovascular diseases than aldolase A. We also demonstrated that serial measurement of serum aldolase C in patients with cerebrovascular diseases might be useful in estimating prognosis, since serially increasing serum aldolase C levels during the course of these diseases were correlated with a high mortality rate. 
5	Human hepatic regenerative stimulator substance: partial purification and biological characterization of hepatic stimulator substance from human fetal liver cells. Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substance--a liver-specific growth factor--was partially purified from human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heat-stable, protease-sensitive, organ-specific and species-nonspecific. Human hepatic stimulator substance produced a two- to threefold increase of 3H-thymidine incorporation into hepatic DNA when injected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosamine (1.6 gm/kg body weight)-induced hepatic necrosis in rats were further evaluated. A survival rate of 4% (n = 24), 41% (n = 12, p less than 0.05), 33% (n = 12, p less than 0.05), 31% (n = 13, p less than 0.05) and 18% (n = 11, p greater than 0.05) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 x 10(8] intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning. 
1	The distribution of residual cancer in radical prostatectomy specimens in stage A prostate cancer. To assess the volume and distribution of residual cancer after transurethral resection of the prostate in stage A cancer patients 42 step-sectioned radical prostatectomy specimens were examined, and the volume, location, grade and extracapsular extension of the residual tumor were recorded. A total of 13 patients had stage A1 tumors (5% or less tumor in the transurethral resection specimen and a Gleason sum of 7 or less) and 29 had stage A2 disease. Residual cancer was present in the radical prostatectomy specimen in 41 patients (98%) with a mean volume of 1.28 cc. The location of residual cancer, that is multifocal (76%), peripheral (81%) and distal to the verumontanum (66%), makes complete removal or even identification of residual tumor (restaging) by repeat transurethral resection improbable. Of the stage A1 cancer patients 4 (30%) had more than 1 cc residual tumor volume, extracapsular extension or seminal vesicle invasion. On the other hand, 14 of the stage A2 cancer patients (48%) had less than 1 cc residual tumor completely confined to the gland. Foci of residual cancer were found in the transition zone in 67% and in the peripheral zone in 90% of the patients. The grade of the residual peripheral zone cancer was significantly higher than that of the transition zone cancer in the same gland (p = 0.0004). Eight of 13 instances of extracapsular extension and all 5 of seminal vesicle invasion were directly attributable to peripheral zone cancer. These observations imply that the greatest threat to patients with stage A prostate cancer may be a separate, associated cancer in the peripheral zone rather than the primary transition zone cancer incidentally removed at transurethral resection. 
3	Effect of parenterally administered gold therapy on the course of adult rheumatoid arthritis OBJECTIVE: To describe the course of rheumatoid arthritis over 5 years in adults and to evaluate the effect of parenterally administered gold salts on that course. DESIGN: A prospective observational study of adults with rheumatoid arthritis. Data derived from annual interviews with patients from 1983 to 1988 and from physician surveys in 1983 and 1987. SETTING: Rheumatology practices in the community. PATIENTS: The study began in 1982 with 822 adults who had rheumatoid arthritis and were under the care of rheumatologists. INTERVENTIONS: Those selected by rheumatologists in the management of their patients. MEASUREMENTS: Information describing sociodemographic and clinical characteristics, course, and therapy was collected from patients and verified by physician reports. Functional status, measured by the Health Assessment Questionnaire, and the number of painful joints were used as outcome variables. Outcome variables were adjusted for age, sex, disease duration, baseline values of the outcome variable, and the use of four disease-remittive agents other than gold. MAIN RESULTS: Multivariate repeated-measures analysis of variance showed no change in the course of rheumatoid arthritis over 5 years. The use of parenteral gold for at least 2 consecutive years at the start of the observation period produced, on average, no change in the course over 5 years in the two outcome variables. CONCLUSION: In our study of a community-based population of adults with rheumatoid arthritis who were under the care of community rheumatologists, we found that there was, on average, no statistically significant change in function or number of painful joints between 1983 and 1988. Patients receiving parenteral gold therapy for at least 2 consecutive years did not show a statistically significant difference in outcome when compared with those not receiving such therapy. 
5	Serum enzyme alterations in chronic muscle disease. A biopsy-based diagnostic assessment. The results of interpretation of muscle biopsies were compared retrospectively to activities of serum enzymes and isoenzymes. A total of 137 patients seen at the Cleveland Clinic Foundation in 1986 and 1987 were included in this study. Serum enzymes evaluated were CK, AST, LD, and aldolase (ALS), as well as the percentage CK-MB isoenzyme. The units of CK-MB and the ratios of CK to AST, LD, and ALS were calculated. Descriptive statistics, Kruskal-Wallis one-way analysis of variance, and stepwise logistic regression were performed. A diagnostic algorithm was constructed using a computer-assisted rule generation program. Myopathic diseases yielded a greater mean increase in serum enzyme activity than atrophic diseases. By multivariate stepwise logistic regression, increases in serum AST and CK activity were independently associated with the presence of inflammation in a muscle biopsy specimen. The diagnostic algorithm allowed for the separation of myopathies from atrophies and could identify cases of Duchenne's muscular dystrophy and polymyositis. 
1	Extramammary Paget's disease of the bronchial epithelium. We report the first case, to our knowledge, of extramammary Paget's disease of the bronchial epithelium. The tumor displayed Paget's cells scattered within the bronchial epithelium in most of the lesion, but infiltrating into the bronchial submucosa and pulmonary parenchyma with microglandular and papillary patterns in some area. In addition to the histologic findings of coexistence with adenocarcinomatous components, in situ involvement into bronchial glands and ducts by Paget's cells was observed, suggesting that extramammary Paget's disease of the bronchial epithelium may be a variant of pulmonary adenocarcinoma, which is associated with bronchial glands. 
5	Child care practices with respect to acute respiratory tract infection in a poor, urban community in Nigeria. A longitudinal study conducted over a 3-year period in a poor, urban community in Nigeria, a developing country, found that acute respiratory tract infection (ARI) was common, in particular among infants and boys. Between 81% and 95% of the children treated for ARI over the 3-year period were brought to the clinic by their mothers. About 32% of these children had been treated with cough medicines, 42% with antipyretics, 5% with antibiotics, and 10% with hematinics before they were brought to the clinic. The source of such medications included medicines left over from previous prescriptions and those bought from chemists' shops and street vendors. Up to 64% of the children treated for ARI had been force-fed local herbal teas by their mothers; herbal teas were used for both preventive and curative purposes. 
1	Endoscopic laser surgery for early glottic carcinoma: a clinical and experimental study. The purpose of this study is to define the indications for using the CO2 laser for the treatment of early glottic cancer. For this purpose, 52 consecutive laser resections of Tis to T2 vocal cord carcinomas were studied prospectively. In addition, laser resection was performed in eight human cadaver larynges, which were then examined histologically using whole organ sections. Both tumor size and tumor location had important influences on tumor resectability by laser. All of the Tis, 78% of T1, and one of four T2 carcinomas were successfully treated by laser surgery alone. Of the 10 carcinomas involving the anterior commissure, only four could completely be resected with the laser; of these four, two recurred in the anterior commissure. This finding is corroborated by the histologic study, which clearly shows that anterior commissure resection poses problems. The only laser resection complication of early glottic cancer was persistent hoarseness in one third of the patients. It is concluded that CO2 laser resection is a safe and effective alternative treatment for patients with Tis and T1 glottic carcinoma, provided the anterior commissure is free of tumor. 
1	Human interleukin-3 mRNA accumulation is controlled at both the transcriptional and posttranscriptional level. Interleukin-3 (IL-3) is a hematopoietic growth factor that regulates the differentiation of multilineage and committed progenitor cells and the functions of some mature blood cells. The expression of human IL-3 appears to be restricted to stimulated T lymphocytes. We have investigated the kinetics and mechanisms involved in the induction of IL-3 expression in the human T lymphocytic tumor cell line Jurkat. We show that accumulation of IL-3 mRNA is controlled at both the transcriptional and posttranscriptional level. Transcription of the IL-3 gene in these cells appears to be constitutive but no IL-3 mRNA was detected in unstimulated cells, indicating that in resting cells IL-3 mRNA is highly unstable. Treatment with phytohemagglutinin (PHA) induced a small and transient increase in the IL-3 gene transcription rate and led to the production of detectable levels of IL-3 mRNA and protein. Optimal induction of IL-3 expression required a second stimulus. Costimulation of Jurkat cells with both phorbol myristate acetate and PHA caused both a transient increase in IL-3 gene transcription, which is dependent on new protein synthesis, and also a transient increase in mRNA stability. 
3	Paratope- and framework-related cross-reactive idiotopes on anti-acetylcholine receptor antibodies. Cross-reactive idiotopes are a possible target for therapeutical interventions in autoimmune diseases. To investigate their role in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG) we analyzed the Id of rat anti-AChR mAb 6, 35, 61, 65 and a control myeloma protein IR27. Anti-Id 6, 35, 61, 65 bound in a direct binding assay with various affinity to all rat anti-AChR mAb that were tested. Anti-Id IR27 recognized none of the anti-AChR mAb. The specificity of these crossreactions was confirmed by inhibition studies with anti-AChR mAb and two control rat myeloma proteins (IR27 and IR241). In addition, the Id expression on mAb D6, a mouse anti-human AChR mAb was recognized by anti-Id 6, 35, and 65. Anti-Id, except anti-Id IR27, bound to affinity purified IgG from the sera of rats with EAMG, but not to preimmune Lewis IgG. These results suggest extensive sharing of idiotopes among anti-AChR mAb, which are also present in EAMG serum. Anti-AChR mAb against the main immunogenic region (6, 35, 65) from different rat strains, shared at least one paratope-related cross-reactive idiotopes. In the view of the fact that anti-main immunogenic region antibodies might form a predominant fraction of the polyclonal response against AChR, it is conceivable that an anti-Id recognizing these antibodies could have therapeutical applications as for example a selective immune absorbent or in immunotoxin therapy. 
1	Recurrence of resected esophagogastric adenocarcinoma: results of re-resection. Isolated local recurrence following potentially curative resection for carcinoma of the esophagus or esophagogastric junction does not necessarily imply pending systemic disease and early demise. While radiation alone or in combination with chemotherapy is standard treatment for such patients, resection is another available option. Resection may also be a consideration should localized disease persist after non-operative therapy in the absence of metastases. A 5 year retrospective review was performed examining 204 resections performed prior to 1989. Only 5 patients underwent resection of locally recurrent esophagogastric (EG) adenocarcinoma during this period. No squamous carcinoma recurrences were resected. One patient is well 15 months later while another died at 18 months of other causes without recurrence. Recurrence after re-resection occurred at 8, 11, and 24 months in the 3 other patients. Although there were no postoperative deaths, major complications occurred in 4 patients. All 5 patients swallowed normally after operation. 
1	Prognostic implication of ecto-5'-nucleotidase activity in acute lymphoblastic leukemia. Ecto-5'-nucleotidase (5'-N) activity was determined in 191 patients (71 children and 120 adults) with acute leukemia. Elevated values for 5'-N were registered in common acute lymphoblastic leukemia (ALL), but blast cells of T-cell ALL (T-ALL) and common ALL antigen-negative non-T-ALL had low enzyme activity comparable with the values of acute non-lymphocytic leukemia. Dependence of remission duration on 5'-N activity was analyzed in 74 adults with ALL, treated similarly in a prospective multicenter trial. The remission curves for ALL patients with 5'-N activity lower than 10 nmol/h x 10(6) cells were substantially and significantly better than those of patients with high activity (greater than 10 nmol/h x 10(6) cells). This difference was also evident in the immunologic subclass common ALL. Statistical evaluation showed that an interaction between immunologic subtype of the blast cells and their 5'-N activity had prognostic significance for remission duration. In addition to the independent factor, initial age, this interaction was also prognostic for survival. 
3	When epilepsy masquerades as heart disease. Awareness is key to avoiding misdiagnosis. Autonomic neural impulses that accompany discharges during a seizure can cause a variety of cardiac manifestations, including cardiac arrhythmias, sudden death, anginal chest pain, neurogenic pulmonary edema, and symptoms of pheochromocytoma. Either generalized or focal seizures may generate such signs and symptoms. A better appreciation of cardiac problems caused by epilepsy is helpful in preventing misdiagnosis, because the clinical picture in such a patient may be confusing. 
1	Proliferative mass found in the gingiva. The clinical course of peripheral ossifying fibroma is slow and the growth of most lesions is limited in size, usually up to 1.5 cm. Complaints are rare unless the surface becomes ulcerated, or the lesion compromises oral function or esthetic appearance. Treatment is surgical excision with close postoperative follow-up. Tooth extraction is seldom necessary. Proper surgical intervention, which includes excision of reactive tissue down to periosteum, affords a low recurrence rate of 14% to 16%. 
1	Lymphocele: the spectrum of scintigraphic findings in lymphoceles associated with renal transplant. Lymphocele is a well recognized complication of renal transplant surgery. We performed a retrospective review of 305 renal transplant patients with over 2,500 scintigraphic exams to describe the pattern of activity on technetium-99m-DTPA blood flow and dynamic imaging, and iodine-131-OIH studies. Diagnostic criteria for a lymphocele were ultrasonic evidence of a perirenal fluid collection and analysis of that fluid that demonstrated BUN, creatinine, and electrolytes similar to the patient's plasma. Scintigraphic findings were attributed to a lymphocele if abnormalities were in the same area as the ultrasound fluid collection. Scintigraphic findings attributable to lymphocele resolved in all patients following surgical drainage or peritoneal window placement. Six of the 11 documented lymphoceles demonstrated a cold defect on initial dynamic images that "filled in" to equal background activity and another exceeded background. Three cases showed a rim of increased activity surrounding the lymphocele ("rim sign"). 
3	Mild head injury classification. Inconsistencies across studies concerning outcome after mild head injury may reflect differences in the diagnostic criteria used for selection of patients. Consequently, we compared the neurobehavioral outcome in three groups of consecutively hospitalized patients (aged 16 to 50 years) who sustained a closed head injury (CHI) and had a Glasgow Coma Scale (GCS) score in the 9 to 15 range. These groups included patients with uncomplicated CHI with mild impairment of consciousness as reflected by a GCS score in the 13 to 15 range (n = 78), patients with initially mild impairment of consciousness complicated by brain lesion or depressed skull fracture (n = 77), and patients with moderate CHI (n = 60). Tests of memory, information processing, and verbal fluency were administered within 1 to 3 months after injury, and the Glasgow Outcome Scale was completed at 6 months. Neurobehavioral functioning was impaired in the groups with complicated mild CHI and moderate CHI as compared to the group with uncomplicated mild CHI. Although moderate CHI produced longer durations of impaired consciousness and posttraumatic amnesia than complicated mild head injury, patients in these groups did not differ in neurobehavioral performance. Global outcome at 6 months was better in the patients with mild CHI than in patients with complicated mild and moderate injuries. Analysis of the various complications of mild CHI revealed that the presence of an intracranial lesion was related to more severe neurobehavioral sequelae than injuries complicated by a depressed fracture. 
4	Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation. A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia. 
1	Salivary flow rates in patients with head and neck cancer 0.5 to 25 years after radiotherapy. In this clinical study at the University of Texas M. D. Anderson Cancer Center, unstimulated and stimulated salivary flow rates were obtained from 47 patients with head and neck cancer who had received mantle, unilateral facial, or bilateral facial field radiotherapy from 0.5 to 25 years earlier. The magnitude of salivary flow rate reduction compared with a healthy control group was primarily related to the radiation dosage and the amount of salivary gland tissue included in the irradiated fields. Flow rates were lower for women in all groups, but these differences were not statistically significant. 
3	Basilar artery occlusion in rats. The basilar artery is one of the three major sources of blood supply to the circle of Willis. To investigate the effects of basilar artery occlusion, we surgically exposed and coagulated the basilar artery in 25 rats. Basilar artery occlusion at any single point between the foramen magnum and the circle of Willis in 11 rats did not produce histologically detectable infarcts in the brain at 12-24 hours. Two-point occlusions of the basilar artery in 12 rats produced variable infarcts between the occlusion sites but no ischemic lesions elsewhere. After either single- or double-point occlusions, the proximal basilar artery refilled within 2-3 minutes. When the basilar artery was occluded above and below the origins of the anterior inferior cerebellar arteries, the artery segments between the occlusion points initially collapsed but refilled within 2-3 minutes in two rats. Basilar artery occlusions invariably suppressed cortical somatosensory evoked potentials by greater than 50%. Regardless of whether a brain stem infarct developed, somatosensory evoked potential amplitudes recovered to greater than baseline levels by 4 hours in seven of 17 rats and returned to baseline levels by 24 hours in every rat tested. We conclude that the occluded basilar artery receives extensive retrograde collateral blood flow and that somatosensory evoked potentials are exquisitely sensitive to basilar artery occlusion but are insensitive to whether brain stem infarcts develop. 
5	Microvascular right-to-left pulmonary shunt demonstrated by a radionuclide method. A 37-yr-old man with angiolymphoid hyperplasia (Kimura's syndrome), who had been treated unsuccessfully for suspected asthma, was investigated due to a decrease in arterial oxygen saturation (86%). Right heart catheterization and angiography of the pulmonary artery failed to demonstrate any right-to-left shunts. However, simultaneous scintigraphy over the lungs, kidneys, and head after injection of 150 MBq technetium-99m-labeled macroaggregated albumin i.v. and inhalation of 150 MBq krypton-81m demonstrated a right-to-left shunt in the lungs probably caused by precapillary pulmonary arteriovenous shunts. 
4	Recombinant human erythropoietin does not increase clotting in vascular accesses. The incidence of vascular access clotting was evaluated over 5.25 years. The first 32 months served as a control period. During the second period of 31 months, recombinant human erythropoietin (epoetin) was used for an average duration of 13 months (range, 2-32 months) in 79 patients. The overall incidence of vascular access clotting decreased from a monthly rate of 0.06 to 0.03 events per patient-month over the 5 year period. Distribution of the number of events per patient did not differ between the two periods, with 55% to 60% of patients having no clotting episode. Patients with recurrent clotting (two or more events) accounted for 68% of episodes. During the second period, there were no differences in the incidence of vascular access clotting in epoetin treated patients vs untreated patients (0.38 events per patient-year vs. 0.46 events per patient-year, both slightly lower than in period 1 [0.52 events per patient-year]). It is concluded that epoetin does not increase vascular access clotting. 
4	Role of endothelium in the response to endothelin in hypertension. The relation between endothelin and acetylcholine (ACh) was examined and compared in aortas from Wistar-Kyoto (WKY) rats and from stroke-prone spontaneously hypertensive rats (SHRSP). The relaxation produced by ACh in an endothelin-induced contraction was less in aortas from WKY rats than in those from SHRSP. In aortas from WKY rats but not in those from SHRSP, the contraction produced by endothelin was augmented when the intact aortic rings were treated with methylene blue (10(-5) M). This augmentation was also found in preparations of the WKY rat aortic rings in which the endothelium had been removed. The augmentation was not present in SHRSP aortic rings that had been similarly denuded. Treatment with indomethacin (5 x 10(-6) M) had no effect on endothelin-induced contraction in either WKY rat or SHRSP aortic rings. Our findings indicate that endothelin and ACh have in common the ability to release endothelium-derived relaxing factor (EDRF) in WKY rat aortic rings. The reduced endothelium-dependent relaxation in response to ACh in the WKY rat probably reflects the fact that endothelin had already released the EDRF in rings from this strain of rats. The release of EDRF by endothelin is less in SHRSP than it is in WKY rats. Because of this failure of endothelin to release EDRF in SHRSP, endothelin may contribute to the increase in total peripheral resistance in this form of hypertension. 
1	The role of cellular maturation in neutrophil heterogeneity. Previous studies have shown that many neutrophil (PMN) characteristics are heterogeneous but the origin of PMN heterogeneity is unknown. It is unclear if PMN functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities. The PMN 31D8 antigen is a useful probe for evaluation of PMN subpopulations. The majority of PMNs (approximately 85%) exhibit a high intensity fluorescence after 31D8 monoclonal antibody (MoAb) labeling (31D8 enriched or "bright" PMNs) as determined by flow cytometric analysis. These cells are more functional than cells with low intensity fluorescence (31D8 diminished or "dull" PMNs). Various immunologic, clonogenic and functional techniques were used to study the expression of the 31D8 antigen in HL-60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation. The results of this study indicate that the percentage of 31D8 antigen positive (31D8 antigen enriched and diminished) bone marrow cells increases from 20 +/- 11% in myeloblast cells to 68 +/- 10% in promyelocytes, 93 +/- 2% in myelocytes and 99 +/- 1% in bands and PMNs. 31D8 antigen enriched cells first appear at the myelocyte stage (32 +/- 10%) and increase in bands (52 +/- 13%), marrow PMNs (62 +/- 13%) and peripheral blood PMNs (88 +/- 4%). These data indicate that the heterogeneous expression of 31D8 antigen in PMNs is due, at least in part, to maturational differences within the PMN population and raise the possibility that other heterogeneously expressed PMN characteristics are also maturationally derived. They also suggest that 31D8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology. 
1	Systemic toxic effects associated with high-dose verapamil infusion and chemotherapy administration. Aside from its more conventional uses as a cardiovascular drug, the calcium channel blocker verapamil has recently been added to chemotherapeutic regimens to reduce drug resistance in B-cell and other neoplasms that express the P-glycoprotein. We recently treated patients with continuous-infusion verapamil (0.15 mg/kg per hour to 0.60 mg/kg per hour) over a 5-day period in combination with continuous-infusion vincristine and doxorubicin plus oral dexamethasone. Seventy-one courses involving 35 hospitalized patients were prospectively studied for cardiovascular and other side effects. Cardiovascular side effects were observed most frequently and consisted of first-degree heart block, hypotension, sinus bradycardia, and junctional rhythms. We observed higher degree heart block, but the QRS interval remained narrow and the ventricular escape rate remained relatively normal. Effects on mean arterial pressure, heart rate, and PR interval were both time and dose related. Severe, symptomatic congestive heart failure was rarely observed. The most common noncardiovascular side effects were constipation, peripheral edema, and weight gain. All systemic toxic effects observed were easily treated or disappeared with either temporary or permanent discontinuation of the verapamil infusion or by a decrease in the dose of verapamil. We conclude that the cardiovascular side effects associated with continuous, high-dose intravenous verapamil therapy are significant and dose limiting but are rapidly reversible. Less cardiotoxic chemosensitizers are needed to reverse multidrug resistance in cancer. 
5	Risks and benefits of paracetamol antipyresis in young children with fever of presumed viral origin To examine whether antipyretic therapy in young children is associated with potential risks (interference with enhanced host defences at febrile temperatures) or benefits (improved comfort and behaviour), a randomised, double-blind, placebo-controlled trial of paracetamol was conducted among 225 children 6 months to 6 years of age who presented with acute (less than or equal to 4 days) fever (greater than or equal to 38 degrees C per rectum) without evident bacterial focus of infection. Parents were asked to give paracetamol liquid 10-15 mg/kg or placebo every 4 h as needed for fever and to avoid bathing, sponging, or other pharmacological agents. Parents kept temperature and symptom diaries and recorded changes in child comfort and behaviour according to a pretested, 5-category Likert-type questionnaire 1-2 h after every dose. There were no significant differences between treated and placebo groups in mean duration of subsequent fever (34.7 vs 36.1 h) or other symptoms (72.9 vs 71.7 h). Paracetamol-treated children were more likely to be rated by their parents as having at least a 1-category improvement in activity (38 vs 11%; p = 0.005) and alertness (33 vs 12%; p = 0.036) but no significant differences were noted in mood, comfort, appetite, or fluid intake. That overall improvement in behaviour and comfort with paracetamol was not impressive is underscored by the inaccuracy of parents' "guess" at the end of the trial as to which agent their child had received-45% correct guesses for paracetamol and 52% for placebo. The data suggest that the clinically relevant hazards and benefits of paracetamol antipyresis have been exaggerated. 
5	Continuous infusion of interpleural bupivacaine maintains effective analgesia after cholecystectomy. Twenty-five patients who had undergone elective cholecystectomy were prospectively randomized to receive via an interpleural catheter either a continuous infusion of 0.25% bupivacaine at 0.125 mL.kg-1.h-1 (n = 13) or repeated bolus injections (n = 12) of 0.5% bupivacaine with epinephrine 1:200,000 at 0.4 mL/kg every sixth hour. Adequacy of pain relief was measured by the amount of patient-controlled analgesia morphine required postoperatively and by patient scores on a visual analog scale obtained every sixth hour. Two venous blood samples for measurements of serum bupivacaine levels were obtained from patients in the continuous group at hours 6 and 24; four blood samples were obtained from patients in the bolus group, both immediately before and 30 min after injections at hours 6 and 24. Among the patients receiving the bolus injections, morphine was required 62 +/- 15 (SEM) times over the 24-h study period with total morphine dosage averaging 30 +/- 15 mg. Corresponding values for patients in the continuous groups were 35 +/- 10 times and 23 +/- 5 mg of morphine. The difference was not, however, statistically significant, but when activity during the 2-h time periods immediately before reinjection were examined, patients in the bolus group required and received significantly more morphine than did those in the continuous group (P less than 0.05). Patients in the continuous group had visual analog scale scores that averaged 2.9 +/- 0.6 over the 24-h study period. Patients within the bolus group had visual analog scale scores before and again 30 min after injection that averaged 5.8 +/- 0.8 and 1.8 +/- 0.5, respectively (P less than 0.05). 
4	Right ventricular infarction: a clinical case study. In this article we review the specific case of Mrs. F., a 63-year-old white woman who recently had classical right ventricular infarction associated with left ventricular inferior wall myocardial infarction. The presentation covers her medical history, clinical course pathophysiology of the right ventricular infarction, and goals of the medical modalities used in treatment. Nursing problems are identified specifically related to right ventricular infarcts, and treatment considerations are discussed. A brief conclusion recaps Mrs. F.'s discharge course and reviews some specific problems associated with right ventricular infarcts, of which critical care nurses need to be aware. 
1	Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study. Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered. 
1	Surgical management of pulmonary metastatic leiomyosarcoma with gross endobronchial extension. Metastatic leiomyosarcoma occasionally is seen with gross endobronchial extension without invasion of the bronchial wall. These patients have major airway obstruction and partial or total atelectasis of the lung. Precise bronchoscopic assessment coupled with intraoperative bronchotomy allows the surgeon to determine the origin of the tumor and to save uninvolved pulmonary parenchyma. Our experience with 4 such patients illustrates the possibility of saving lung tissue despite total bronchial obstruction. 
5	The pitted duodenal bulb. The radiologic, endoscopic, and histologic findings in two patients with flaskshaped or collar-button collections of barium in the duodenum are presented. These abnormal mucosal depressions, which may be related to inflammation, were seen endoscopically and identified radiographically and have not been reported previously. 
4	Effect of weight reduction in moderately overweight patients on recorded ambulatory blood pressure and free cytosolic platelet calcium. Although platelet cytosolic calcium has been shown to decrease during pharmacological treatment of hypertension, there is no evidence that cytosolic calcium also falls during a nonpharmacological reduction in blood pressure. To provide such evidence, we examined prospectively the relation between platelet cytosolic calcium and ambulatory blood pressure during weight reduction in moderately overweight (body mass index [BMI] greater than 25), mildly hypertensive individuals. The experimental group (responders: BMI reduction greater than 5%) consisted of 19 patients who lost 8.5 +/- 2.9 kg (mean +/- SD, p less than 0.05) during a 10-week hypocaloric diet, whereas the control group (nonresponders: BMI reduction less than 5%) consisted of 12 patients who showed no relevant change in body weight (-2.0 +/- 1.3 kg) during the same period of time. The moderate weight loss of the responders decreased blood pressure by 14/5 mm Hg (p less than 0.05), as measured by ambulatory monitoring, which renders a placebo effect unlikely. This nonpharmacological reduction in blood pressure was accompanied by a proportional 11% decrease (p less than 0.05) in platelet cytosolic calcium and also by significant (p less than 0.05) decreases in plasma catecholamines and serum cholesterol. These findings establish the concept of a nonpharmacological reduction in free cytosolic platelet calcium in humans and add further evidence suggesting a link between intracellular calcium homeostasis and blood pressure regulation. 
3	Deteriorating ischemic stroke: risk factors and prognosis. To determine a risk profile of deterioration in cerebral infarction of less than 8 hours' duration, we studied prospectively a series of clinical and radiologic data in 98 patients. We evaluated the Canadian Neurological Scale Score and Barthel index during a follow-up period of 3 months. There was deterioration in the 1st 48 hours in 40.8% of the patients. High systolic blood pressure, elevated blood sugar concentration at admission, and carotid territory involvement were independently related with deterioration in the logistic regression analysis. Death occurred in 35% of the patients with deteriorating infarcts and in 8.6% of those with stable infarcts. At the end of the study, functional capacity was lower in those with deteriorating infarcts, but the 2 groups improved in parallel from the 4th day onward. 
3	HMPAO-SPECT imaging resembling Alzheimer-type dementia in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Single-photon emission computed tomography (SPECT) of the brain using hexamethyl propylene amine oxime (HMPAO) was performed in a 37-year-old patient suffering from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Reduced blood flow was observed bilaterally in the parieto-occipital regions (resembling Alzheimer type dementia) and in the right parietal lobe. 
1	Genital human papillomavirus infection Human papillomavirus is one of the most common causes of sexually transmitted diseases. In the past ten years, 60 different types of papillomavirus have been identified. Although the virus often causes asymptomatic genital infection, it has been strongly associated with lower genital tract carcinoma; therefore, its detection and eradication are important. All patients with evidence of human papillomavirus infection should undergo colposcopy and, depending on the extent of infection and the type of histology, should receive definitive treatment. 
4	Long-term follow-up of patients operated on for recurrent carotid stenosis. We reviewed our experience with 29 operations for recurrent carotid stenosis in 27 patients who underwent both their primary carotid endarterectomy and their reoperations at our institution. These 27 patients represent 4% of the 667 patients who underwent primary carotid endarterectomies at our institution and who are included in our carotid follow-up registry. Reoperation was prompted by recurrent symptoms in 19/29 (65.5%) cases. Comparison of long-term stroke prevention in those patients who did (84% at 5 years, 78.6% at 10 years) and did not (90.3% at 5 years, 83.6% at 10 years) develop recurrent stenosis requiring reoperation revealed no statistically significant difference (p = 0.48) when measured from the time of primary operation. The perioperative stroke and death rates for reoperation (3.4% and 0%) were acceptable. We conclude that with our acceptably low perioperative stroke morbidity (3.4%), surgery for recurrent carotid stenosis in symptomatic patients or in asymptomatic patients with high-grade (greater than or equal to 75%) stenosis maintains the durable stroke prevention offered by primary carotid endarterectomy. 
5	Adhesion formation after ovarian wound repair in New Zealand white rabbits: a comparison of ovarian microsurgical closure with ovarian nonclosure. Thirty female New Zealand white rabbits underwent standard laparotomy. Each ovary was bivalved and hemostasis was achieved with bipolar electrocautery. One ovary was then randomized to the closure group, whereas the other ovary was placed in the nonclosure group. In the closure group, the ovarian capsule was closed with a continuous suture of 8-0 Vicryl absorbable surgical suture material with microsurgical technique. In the nonclosure group, the ovaries were left open. Three weeks later the animals were killed and the ovarian adhesions were graded with a standardized scale by an observer (A. A. T.) blinded to the closure status of the animals. Five control animals underwent sham operations with minimal adhesion formation. Statistical analysis of the study animals by the paired Student t test showed a significantly higher adhesion score on the ovaries that were microsurgically closed compared with the ovaries not closed (p = 0.02). 
3	Failure to detect human T-cell leukemia virus-related sequences in multiple sclerosis blood. We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis. 
1	Comparative in situ hybridisation study of juvenile laryngeal papillomatosis in Papua New Guinea and Australia. A comparative study of cases of juvenile laryngeal papillomatosis from Papua New Guinea (n = 3) and Brisbane, Australia (n = 9) was carried out. In situ hybridisation reactions for human papillomavirus (HPV) types 6 and 11 occurred in 11 cases. All three cases from Papua New Guinea and eight from Australia gave positive signals. A negative reaction was observed in one Australian case. The intensity of the reaction was strong in seven cases, moderate in one, and weak in three. An equivocal reaction was also noted with probes for types 16 and 18, and types 31, 33, and 35 in two cases from Australia and one from Papua New Guinea. It is concluded that as similar staining patterns and intensities occurred in cases from both areas, the aetiology is the same. The equivocal reactions noted in three cases were probably due to cross hybridisation rather than multiple infection. 
2	Is primary repair of gastroschisis and omphalocele always the best operation? Optimal surgical management of neonates with gastroschisis and omphalocele remains controversial. Suggested benefits of primary fascial closure include earlier return of gastrointestinal function, decreased hospital stay, less sepsis, less risk of postoperative intestinal obstruction and fistulae, and lower mortality. Between 1978 and 1989, 40 neonates with gastroschisis or omphalocele underwent repair. Primary fascial repair was performed in 30 children, 18 of whom had a gastroschisis and 12 of whom had an omphalocele. Ten children had staged repair with the use of a silastic silo; seven of these had a gastroschisis and three an omphalocele. Comparison between the groups was made regarding birth weight, days on the ventilator before and after surgery, days to first feeding, days in the hospital after surgery, postoperative complications, and survival. There was no significant difference in birth weight, days on the ventilator, days to first feeding, and postoperative days in the hospital. There were nine complications in nine patients (30%) with primary repair and four complications in two patients (20%) with staged repair. Two infants died after primary repair (6.7%), and one (10%) died after staged closure. It was concluded that silastic silo repair and primary fascial closure are both acceptable alternatives. Primary closure is attractive whenever possible to avoid additional operations. 
1	Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene. We investigated the effect of an activated c-erbB-2 gene (also known as ERBB2) on metastatic potential. The c-erbB-2 gene was activated by mutation of the valine at position 659 within the transmembrane domain to glutamic acid. The activated c-erbB-2 expression vector was transfected into low-metastatic-potential NL-4 cells, which were established from a metastatic variant of murine colon adenocarcinoma 26. All 10 clones produced lung metastases in BALB/c mice injected via the tail vein. Eight of the 10 clones expressed messenger RNA (mRNA) of activated c-erbB-2 and showed morphological alteration; seven of the eight produced significantly enhanced experimental metastatic activity compared with that of untransfected NL-4 or NL-4neo cells, and one had metastatic ability similar to that of NL-4 cells. Two clones did not express c-erbB-2 mRNA and did not show morphological alteration or highly metastatic phenotype. Five of the 10 clones subcutaneously implanted in the flank failed to produce metastasis in the lungs or other organs of the mice. The metastatic ability of the other five clones was not determined. These results indicate that the activated c-erbB-2 gene can enhance experimental but not spontaneous metastatic potential in NL-4 cells, suggesting participation of the gene in the metastatic process after initial arrest and lodgement in the capillary bed. 
5	Congenital monomelic hypertrophy with progressive myopathy. We describe a patient with congenital monomelic hypertrophy who later developed progressive footdrop due to a degenerative myopathy. The clinical, electrophysiologic, and pathologic features of the case are described and compared with those of a previously reported case. 
5	Duodenal ulcer hemorrhage with and without dyspepsia. To clarify the clinical significance of dyspepsia in patients with bleeding duodenal ulcer, we studied 298 patients prospectively. Ages of patients ranged from 16 to 81 yr (mean 45.9). There were 244 (82%) dyspeptic and 54 (18%) nondyspeptic patients. In the dyspeptic group, significantly more patients were taking nonsteroidal anti-inflammatory drugs. In the nondyspeptic group, there was a higher percentage of patients with duodenal bulb deformity (p less than 0.005), which deformity was related to previous peptic ulcer disease. The age, sex, past history of dyspepsia or bleeding, consumption of alcohol and cigarettes, and the hospital course of the two groups of patients did not differ significantly. Our results show that the clinical course of duodenal ulcer hemorrhage is not significantly different in patients with or without dyspepsia, and indicate that bleeding and dyspepsia probably are two independent presentations in the natural course of the disease. The significance of the correlation between dyspepsia and duodenal bulb deformity is discussed. 
5	Clonal deletion of V beta 14-bearing T cells in mice transgenic for mammary tumour virus. Autoreactive T lymphocytes are clonally deleted during maturation in the thymus. Deletion of T cells expressing particular receptor V beta elements is controlled by poorly defined autosomal dominant genes. A gene has now been identified by expression of transgenes in mice which causes deletion of V beta 14+ T cells. The gene lies in the open reading frame of the long terminal repeat of the mouse mammary tumour virus. 
5	Postoperative cerebrospinal fluid leakage after lumbar spine operations. Conservative treatment. Cerebrospinal fluid (CSF) leakage from a postoperative wound after lumbar spine operation is an uncommon complication. It may result from excessive traction of the nerve roots, direct trauma, or laceration at the time of operation, causing the dura to be inadvertently opened. Other reasons for this complication are postlaminectomy residual bone spikes, traumatic myelography puncture, and improper suture of dura defects. Eight patients who had postoperative CSF leakage as the only complication after lumbosacral spine operations were examined. They were all treated conservatively with bed rest in the Trendelenburg position, antibiotic coverage, watertight skin suturing, and daily subcutaneous punctures. No patient was operated on for the same type of complication. 
5	Indications for use of ketoconazole in management of metastatic prostate cancer. Newer methods of androgen ablation for the treatment of metastatic prostatic carcinoma have been developed as alternatives to the standard forms of therapy, oral estrogens and surgical castration. The purpose of this review is to elucidate the indications and to determine the role of ketoconazole in the management of metastatic prostatic cancer. Eighteen patients have been treated with ketoconazole. The indications for usage have included: prompt therapeutic response, when orchiectomy is contraindicated, when estrogens are contraindicated, initial empirical therapy, and hormonally refractory disease. It can also be used in conjunction with luteinizing hormone-releasing hormone analogues. Ketoconazole is excellent for short-term usage prior to bilateral orchiectomy and when prompt therapeutic response is needed but orchiectomy cannot be performed. However, it is not particularly useful for long-term hormonal therapy. 
5	Systemic idiopathic fibrosis with T-cell receptor gene rearrangement. A case of systemic idiopathic fibrosis was analyzed by Southern blotting with probes to the immunoglobulin heavy chain and T-cell receptor genes. A 45-year-old man presented with bilateral neck swelling. He later developed lower back pain, and findings on a computed tomographic scan were consistent with idiopathic retroperitoneal fibrosis. A biopsy specimen of a neck lesion showed morphologic characteristics typical of idiopathic fibrosing cervicitis. Immunophenotyping of the lesion revealed a polymorphic lymphoid population. Molecular analysis with the use of probes to the immunoglobulin and T-cell receptor genes disclosed a germline DNA pattern for the immunoglobulin gene and a rearranged pattern for the T-cell receptor gene. 
4	Laser angioplasty in peripheral vascular disease: symptomatic versus hemodynamic results. Most early reports on the efficacy of laser angioplasty have used subjective symptoms rather than objective hemodynamic parameters to evaluate clinical results. We reviewed our experience with hot tip laser-assisted balloon angioplasty in 99 occluded or stenotic arterial segments during 80 procedures in 71 patients, ranging from the aortic bifurcation to the tibial-peroneal trunk. Initial failure to successfully recanalize occluded or stenotic segments occurred in 13 instances (16%). Forty-one procedure-related complications occurred in 31 patients (39%). Functional results were evaluated by use of life-table methods on the basis of symptomatic versus hemodynamic improvement. Cumulative patency rates for symptomatic and hemodynamic improvement were 91% and 64% at 1 month, 71% and 48% at 6 months, and 57% and 34% at 1 year, respectively. These data suggest that symptomatic improvement alone gives a misleadingly high estimate of the efficacy of laser angioplasty when compared with more objective hemodynamic criteria (p less than 0.005). Hemodynamic success was more likely in aortoiliac lesions than femoropopliteal lesions (58% vs 18% at 1 year, p less than 0.01). Hemodynamic parameters should be used to evaluate the success of laser angioplasty, which in its present form, is associated with frequent complications and poor long-term success. 
5	Intrahepatic arterioportal fistula after blunt hepatic trauma: case reports. Intrahepatic arterioportal fistula (APF) was found in five out of 65 consecutive patients following blunt hepatic trauma. In four patients the fistula was located peripherally and the blood flow was small. These fistulas closed spontaneously within 3 months. However, a centrally located fistula with early visualization of the trunk of the portal vein persisted in one patient and necessitated transcatheter embolization. The APF in this patient caused portal dilatation which was detectable by CT scan. We conclude that spontaneous closure can be expected when an APF is located peripherally and the shunt flow is small, while centrally located APF with large flow require active treatment, preferably by transcatheter embolization. An APF detectable by CT scan suggests the need of intervention. 
4	Captopril renography in the diagnosis of renal artery stenosis: accuracy and limitations. PURPOSE: The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration ("captopril renography") in diagnosing renal artery stenosis. PATIENTS AND METHODS: Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were then established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes. RESULTS: Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity. Among patients with bilateral stenoses, asymmetry identified the more severely affected kidney, but the presence or absence of stenosis in the contralateral kidney could not be reliably determined. When pre- and post-captopril studies were compared, the presence of captopril-induced scintigraphic changes was a highly specific finding for renal artery stenosis, but occurred in only 51% of the cases. OIH scintigraphy provided similar results, with slightly lower sensitivity and specificity. CONCLUSION: Asymmetry of DTPA uptake, time to peak uptake, or retention seen on a single post-captopril renogram is a highly sensitive and specific finding in detecting renal artery stenosis but does not distinguish unilateral from bilateral disease. If renograms are obtained both before and after captopril administration, the presence of captopril-induced change is a highly specific finding for the detection of renal artery stenosis, but the sensitivity of this finding is low. 
5	Periurethral colonic-type polyp simulating urethral caruncle. A case report. A 50-year-old, black woman presented with a 1-cm, polypoid lesion on the posterior edge of the urethral meatus that had the gross appearance of a urethral caruncle. The histologic features, however, revealed a superficially ulcerated lesion composed of colonic-type mucosal glands with focal regenerative atypia in response to inflammation. A similar histologic pattern is also found in so-called solitary rectal ulcer syndrome and inflammatory cloacogenic polyps arising in the anorectal area. Based upon an English-language literature review, this case appears to be the second reported one of an intestinal-type polyp in this location. The patient had no further problems after excisional biopsy. 
1	Oculo-bulbar myasthenic symptoms as the sole sign of tumour involving or compressing the brain stem. Four patients with tumours involving or compressing the brain stem are described whose initial clinical symptoms of fluctuating paresis of the external ocular muscles and/or the pharyngeal muscles without other neurological deficits led to the primary diagnosis of focal myasthenia. The combination of an unusual clinical pattern, involvement of muscles of only one ocular nerve or severe dysphagia/dysarthria without extension of the myasthenic symptoms, should lead to further investigation to exclude other reasons of a focal myasthenic syndrome such as a brain-stem tumour. 
5	Midterm surgical results of arterial switch operation for transposition of the great arteries with intact septum. Between April 4, 1984, and December 31, 1987, 156 consecutive neonates with simple transposition of the great arteries underwent an arterial switch operation (ASO) at our institution. Surgery was performed before the age of 15 days in 96%, and patient weight was less than 3 kg in 28%. Seventeen patients (10.9%) died after surgery. One patient was lost to follow-up. Of the 138 survivors, two died of myocardial infarction 35 and 40 days, respectively, after surgery. They were the only late deaths, and actuarial survival rates were 87% (70% confidence level [CL], 83-89%) at 45 days and 87% (70% CL, 68-95%) at 52 months. Another patient had a myocardial infarction 50 days after surgery and is well 50 months later. Pulmonary stenosis was observed in 14 patients (10.3%) during the first year after surgery; two patients were reoperated on 10 and 12 months, respectively, after ASO. Aortic regurgitation was observed in 17 patients: two had grades II and III, respectively, aortic regurgitation on aortography; in 15 patients, it was detected only by Doppler examination. At the last follow-up (2-52 months after ASO; mean, 27.3 +/- 11.3 months), all patients were asymptomatic and taking no medication. On bidimensional echocardiography, left ventricular fractional shortening was normal at rest in all survivors but one. One patient had junctional rhythm, and one had Wenckebach periods; the remainder were in sinus rhythm. For as long as 5 years after ASO, late death and reintervention were rare; 99% of the survivors were asymptomatic and had sinus rhythm and good systemic ventricular function. 
1	Chronic oral etoposide. Etoposide is an important drug that has been recently incorporated with other agents in the curative treatment of patients with advanced neoplasms, including germ cell tumors, non-Hodgkin's lymphomas (NHL), and small cell lung cancer (SCLC). Etoposide demonstrates remarkable schedule dependency. A randomized comparison has shown an impressive survival difference for patients with extensive SCLC receiving a 5-day course versus those receiving a 1-day course. Because of these and previous clinical and laboratory data, etoposide is now given intravenously or orally in a 3-day to 5-day schedule. It is generally accepted that approximately 50% of the orally administered drug is absorbed. The authors have initiated several etoposide studies using an extended administration schedule, believing that a prolonged schedule may be superior to the standard 3-day to 5-day schedule. This was initially tested in a Phase I study. Results showed that etoposide (50 mg/m2/d) given over 21 days was feasible and was associated with only moderate toxicity. Several Phase II studies have been completed or are nearing completion, including studies in patients with SCLC, NHL, germ cell tumors, soft tissue sarcoma, renal carcinoma, and ovarian carcinoma. Responses have been seen in all of these groups, particularly in patients with SCLC, lymphoma, and germ cell tumors. In these groups we saw responses in patients who were clearly resistant to etoposide plus cisplatin given in a standard schedule or in some patients who were resistant to high-dose etoposide with bone marrow transplantation. Investigators at Indiana University Medical Center who studied oral etoposide in a similar fashion in patients with advanced germ cell tumors and SCLC achieved results similar to those reported here. The authors have initiated a number of combination chemotherapy programs using the chronic oral form of etoposide. These include patients with SCLC, non-small cell lung cancer, and elderly patients with high-grade and intermediate forms of NHL. In addition, chronic intravenous oral etoposide is being used in salvage approaches for patients with acute myelocytic leukemia and recurrent resistant intermediate-grade and high-grade NHL. Preliminary pharmacokinetic data suggest that a 50-mg/m2 oral dose is highly bioavailable (91% to 96%). Therefore, during a prolonged oral course at 50 mg/m2, many patients maintain a minimum plasma concentration of 1 microgram/ml. Further studies of multiple dose or continuous infusion etoposide to maintain a potentially critical plasma level are in progress. Etoposide administered in this way could represent a "new" drug because many of its features are different, and its activity spectrum may be broader. 
3	Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals. Stagnara wake-up tests, blood flow measures, somatosensory evoked potentials (SEPs), and neurogenic-motor evoked potentials (NMEPs) were elicited from 20 hogs before and after spinal cord overdistraction at L3-L4. Overdistraction was maintained from 5 to 30 minutes after loss of NMEPs. Results suggest that the longer the duration of overdistraction the greater the likelihood of paraplegia. Blood flow measures indicated that reduced perfusion was greatest at the distraction site but extended proximally and distally. Finally, NMEPs were more sensitive to onset of overdistraction and a more valid indicator of paraplegia than SEPs. NMEPs should provide the surgeon with more time for initiation of intervention techniques than SEPs. Because NMEPs and SEPs provide information regarding different spinal cord tracts, the authors continue to use both methods for monitoring the functional integrity of the human spinal cord during corrective spine surgery. 
4	Reflections on the U.S. Preventive Services Task Force recommendations for screening for hypertension and hypercholesterolemia. The U.S. Preventive Services Task Force recommendations for screening for hypertension and high blood cholesterol are generally consistent with preexisting national guidelines promulgated by the Joint National Committee for Detection, Evaluation, and Treatment of High Blood Pressure and the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults. While a welcome addition to the armamentarium of the clinician, the Task Force recommendations represent only a partial solution to our current epidemic of blood-pressure- and cholesterol-related cardiovascular disease. A meaningful reduction in society's burden of cardiovascular disease can be achieved only by complementing the Task Force recommendations with community-based mass treatment strategies aimed at shifting the distribution of blood pressure and cholesterol toward a biologically more normal pattern. 
4	A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years, a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed, the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization, thus helping to reduce procedure related morbidity in these oftimes critically ill patients. 
3	Uniparental paternal disomy in Angelman's syndrome. Angelman's syndrome and Prader-Willi syndrome are both causes of mental retardation with recognisable, but quite different, clinical phenotypes. Both are associated with deletions of chromosome 15q11-13, of maternal origin in Angelman's and paternal in Prader-Willi. Prader-Willi can arise by inheritance of two chromosomes 15 from the mother and none from the father (uniparental maternal disomy). In 2 patients with Angelman's syndrome we found evidence of uniparental paternal disomy. The phenotypic effects of maternal and paternal disomy of chromosome 15 are very different and inheritance of two normal 15s from one parent does not lead to normal development--strong evidence in man for genomic imprinting, in which the same gene has different effects dependent upon its parental origin. 
4	Deficiency of calcitonin gene-related peptide in Raynaud's phenomenon. Skin biopsy samples from the fingers of nine patients with primary Raynaud's phenomenon, nine with the disorder associated with systemic sclerosis, and eleven healthy controls were examined by immunocytochemistry. There were no differences between the groups in the distribution of PGP 9.5 (a pan-neuronal marker) immunoreactivity, but there was a significant reduction in the number of calcitonin gene-related peptide (CGRP) immunoreactive neurons in the skin of patients with primary Raynaud's phenomenon and those with systemic sclerosis. These findings implicate dysfunction of the CGRP neurovascular axis in the pathophysiology of Raynaud's phenomenon. 
5	Rate-related left bundle branch block as a cause of non-ischemic chest pain. A case is presented of rate-dependent left bundle branch block associated with chest pain in a patient with angiographically normal coronary arteries. Lactate extraction showed no evidence of myocardial ischemia. It appears that in this case, chest pain was associated with sudden ventricular asynergy rather than myocardial ischemia. 
3	Evidence of a local immune activation in cystic brain tumors. The fluid of cystic brain tumors was characterized with regard to the protein content. In most malignant tumors, the concentrations of immunoglobulins G and M (IgG and IgM) were higher relative to other proteins in the cyst fluid than in the serum of the same patient. A markedly elevated ratio of monomeric to pentameric IgM was detected in the cyst fluid of two patients with glioblastomas. The results indicate a local immunoglobulin synthesis in malignant cystic brain tumors. It is hypothesized that higher-than-expected concentrations of IgG and IgM in cyst fluid as compared to plasma are a sign of an ongoing immune response triggered by the tumor. 
5	Influence of clinical and hemodynamic variables on risk of supraventricular tachycardia after coronary artery bypass. The influence of 45 variables on risk of postoperative supraventricular tachycardia was evaluated by univariate and multivariate analysis of data from 800 consecutive patients who underwent isolated coronary artery bypass during a 6-year interval. Postoperative supraventricular arrhythmias occurred in 186 patients (23%) but did not contribute to any of the six early deaths (30-day mortality rate, 0.8%). Mean (+/- standard deviation) length of hospital stay was longer (9.8 +/- 5.7 versus 8.3 +/- 3.5 days; p less than 0.0001) and mean age was older (65 versus 60 years; p less than 0.002) in patients with postoperative supraventricular tachycardia than in those with regular rhythm. Risk of supraventricular tachycardia was increased in patients with a history of atrial arrhythmias (45% versus 22%; p less than 0.002) or premature atrial contractions on the preoperative electrocardiogram (48% versus 22%; p less than 0.002). Multiple logistic regression analysis identified age 65 years or more, history of atrial arrhythmia or preoperative premature atrial contractions, and preoperative left ventricular end-diastolic pressure 20 mm Hg or more as independent predictors of postoperative supraventricular tachycardia. Six percent of patients converted to sinus rhythm spontaneously; 82% of patients converted within 1.1 +/- 1.9 days after onset of supraventricular tachycardia on treatment with digoxin or beta-adrenergic blocking drugs or both. Only 10% of patients with supraventricular tachycardia required electrical cardioversion. We conclude that the risk of supraventricular tachycardia after coronary artery bypass is influenced by patient-related variables and is effectively managed by conventional therapy. Prophylactic treatment should be reserved for elderly patients, especially those who have atrial arrhythmias or have preoperative left ventricular end-diastolic pressure 20 mm Hg or more. 
4	Effect of age on coronary circulation after imposition of pressure-overload in rats. We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy. 
3	Indwelling epidural catheters for pain control in gynecologic cancer patients. Seven patients with severe pain caused by an advanced, incurable gynecologic malignancy were treated with an indwelling epidural catheter connected to an implantable subcutaneous port through which morphine was infused. There were few major complications associated with insertion or maintenance of the system. The average usage was 60 days, although the system functioned continuously for 6 months in one patient. Pain distribution in these women ranged from the upper abdomen to the lower extremities. All patients, including one with liver metastases, reported good to excellent pain control with the epidural narcotics. Two subjects with upper abdominal pain occasionally required supplemental oral oxycodone, but the other five patients had adequate pain relief with the epidural system alone. The indwelling epidural system provides excellent analgesia for patients with advanced, incurable gynecologic cancer. 
3	Babbling in the manual mode: evidence for the ontogeny of language. Infant vocal babbling has been assumed to be a speech-based phenomenon that reflects the maturation of the articulatory apparatus responsible for spoken language production. Manual babbling has now been reported to occur in deaf children exposed to signed languages from birth. The similarities between manual and vocal babbling suggest that babbling is a product of an amodal, brain-based language capacity under maturational control, in which phonetic and syllabic units are produced by the infant as a first step toward building a mature linguistic system. Contrary to prevailing accounts of the neurological basis of babbling in language ontogeny, the speech modality is not critical in babbling. Rather, babbling is tied to the abstract linguistic structure of language and to an expressive capacity capable of processing different types of signals (signed or spoken). 
4	Female gout. Clinical spectrum and uric acid metabolism. We reviewed the clinical features and uric acid metabolism in 37 female patients with gout. In 32 female patients (86%), gout was diagnosed after menopause. Among the five premenopausal patients, four had renal insufficiency and one had superactivity of phosphoribosylpyrophosphate synthetase. More than 50% of the female patients had osteoarthritis, hypertension, or renal insufficiency or were treated with diuretics. Comparison with 220 male patients with gout showed that female patients developed gout significantly later, more frequently had associated diseases, and more often were receiving diuretics, whereas significantly more male than female patients had alcoholism. The articular features of gout were similar in both groups. However, the prevalence of tophi was higher and its localization different in female than in male patients. Female patients with gout had a higher mean serum urate concentration and a lower mean urinary uric acid excretion than did male patients with gout. These differences were significant and independent of the effects of age, renal insufficiency, alcoholism, or previous diuretic intake. Renal underexcretion of uric acid appears to be more severe in female than in male patients with gout. 
5	Acute osteomyelitis in children. Although relatively uncommon, osteomyelitis is an important disease because of the potential for chronicity or permanent sequelae. Diagnostic methods, the spectrum of the disease, and clinical situations that merit special consideration are reviewed in this article. 
5	The location of the maxillary os and its importance to the endoscopic sinus surgeon. As functional endoscopic sinus surgery continues to gain popularity and support, the necessity for a clear and accurate understanding of the anatomy of the ostiomeatal complex becomes essential. To clarify this anatomy, serial cadaver dissections were performed and the anatomy of the ostiomeatal complex was detailed in three dimensions, with an emphasis on precise localization of the internal os of the maxillary sinus as it relates to the orbit, natural antronasal canal, and ethmoid infundibulum. Measurements of the position of the internal os relative to the position of the anterior and posterior walls of the maxillary sinus and the position of the orbit were taken. The dimensions and configuration of the antronasal canal and its relationship to the infundibulum were also detailed. These measurements and relationships must be understood for an endoscopic sinus surgeon to locate the natural ostia without injuring the orbit. 
2	Long-term treatment of Crohn's disease with cyclosporine: the effect of a very low dose on maintenance of remission. Low-dose oral cyclosporine was used to maintain remission in patients with Crohn's disease. In seven patients, cyclosporine was used as a steroid-sparing agent; in 14 it was given for refractory active disease as an adjunct to conventional treatment, and then continued as maintenance treatment. Cyclosporine was given at an initial dose of 5 mg/kg reduced by 1 mg/kg at 2-month intervals until a maintenance dose of 2 mg/kg was reached. Of the seven patients in whom cyclosporine was used as a steroid-sparing agent, six had a relapse. Remission was achieved in seven of the refractory active group, but cyclosporine was withdrawn because of side effects in six of the patients in this group. Of the seven patients who had achieved remission, six subsequently had a relapse. Therefore, 12 of 14 patients (86%) in remission had a relapse despite cyclosporine maintenance. Ten of these (83%) had a relapse at a cyclosporine dose of 2 or 3 mg/kg. Cyclosporine levels at relapse (median, 74 ng/ml) were lower than the mean levels over the first 6 weeks of treatment (median, 130 ng/ml; p = 0.02). Our data do not support the use of cyclosporine to maintain remission in Crohn's disease. 
2	Effects of short-term pancreatic duct obstruction in rats. The short-term effects of rat pancreatic duct obstruction were evaluated and compared with those recently reported to follow obstruction of the rabbit pancreatic duct. In both species pancreatic edema and hyperamylasemia are noted, and the lysosomal hydrolase cathepsin B is redistributed from the lysosome-enriched to the zymogen granule-enriched subcellular fraction. Theoretically, this redistribution phenomenon might lead to digestive enzyme activation because cathepsin B is known to be capable of activating trypsinogen. The hyperamylasemia and pancreatic edema (but not the cathepsin B redistribution) that follow rat pancreatic duct obstruction were increased by infusion of a submaximally stimulating dose of the cholecystokinin analogue cerulein. Administration of the cholecystokinin-receptor antagonist L-364,718 reduced the hyperamylasemia but did not alter the pancreatic edema or cathepsin B redistribution. These observations indicate that cholecystokinin may modulate some but not all of the effects of duct obstruction. Secretin administration increased the degree of pancreatic edema and had no demonstrable protective effect. The rat duct-obstruction model described in this report may prove particularly useful in future studies designed to clarify the early events underlying the development of acute pancreatitis. 
4	Microheterogeneity of acute phase proteins in the differentiation of polymyalgia rheumatica from polymyositis. We studied an alpha-1-acid glycoprotein (AGP) and an alpha-1-antichymotrypsin (ACHT) microheterogeneity in sera of patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA/PMR), polymyositis/dermatomyositis (PM/DM) and healthy individuals by affinity electrophoresis with concanavalin A (Con-A) as the ligand. Our results are expressed as reactivity coefficients. The mean of AGP reactivity coefficients (AG-RC +/- SD) in PMR (0.92 +/- 0.17) and GCA/PMR (0.91 +/- 0.12) were significantly lower compared with the mean AG-RC in patients with PM/DM (1.48 +/- 0.52) as well as in healthy individuals (1.34 +/- 0.9). Moreover, an additional microheterogeneous form of AGP was noted in patients with PM/DM. In parallel, we also found that the mean of ACHT reactivity coefficients (AC-RC +/- SD) were lower in patients with PMR (2.94 +/- 1.24) and GCA/PMR (1.66 +/- 0.16) compared with healthy individuals (3.92 +/- 1.17). The mean of AC-RC in patients with PM/DM (6.74 +/- 4.35) was significantly higher than in patients with PMR and GCA/PMR as well as in healthy individuals. Our results show that the changes in reactivity of AGP and ACHT with Con-A are useful diagnostic markers for the differentiation of PMR and GCA/PMR from PM/DM. 
5	Elapsed time from symptom onset and acute myocardial infarction in a community hospital. STUDY OBJECTIVE: Previous reports have emphasized that thrombolytic therapy for acute myocardial infarction should be initiated within three or four hours of symptom onset to obtain the best clinical outcomes. However, our clinical impression was that late arrivers, who often do not receive thrombolytic therapy, have a good short-term prognosis. Therefore, we investigated the relationships among the elapsed time from symptom onset, thrombolytic therapy, and short-term prognosis in acute myocardial infarction patients. The research hypothesis was that late arrivers have a better in-hospital prognosis because they have less severe disease that may involve spontaneous thrombolysis. DESIGN: Observational cohort study based on reviewing medical records and emergency department service logs. SETTING: 500-bed teaching hospital with medical school affiliation in northeastern Ohio. TYPE OF PARTICIPANTS: Four hundred consecutive patients with acute infarction confirmed by chest pain and positive ECGs or elevated cardiac enzymes. MEASUREMENTS AND MAIN RESULTS: Patients arriving early (elapsed time less than or equal to 1.5 hours) were more likely to be in Killip class III or IV (P = .04) or to have hypotension (P = .0004); and they experienced twofold increased odds of ventricular tachycardia (P = .007), cardiac arrest (P = .03), or death (P = .01). Patients arriving late (elapsed time greater than 3.5 hours) were more likely to have a history of angina (P = .002) and had a better short-term prognosis. CONCLUSIONS: Time of ED arrival after onset of acute myocardial infarction symptoms distinguishes two patient groups that differ in their risk of in-hospital complications. Late arrivers have better short-term prognoses and less (acutely) severe disease, and may have less need for thrombolytic therapy because of possible spontaneous thrombolysis. Patients with prior angina may need education on seeking care if their symptoms change. 
2	Comparison of a new immunoassay for determining serum pancreatic isoamylase with two standard techniques. A method has recently been developed for measuring serum pancreatic (P) isoamylase, using two monoclonal antibodies specific for salivary isoamylase. We performed this test on 67 healthy controls and 133 patients: 15 with acute pancreatitis, 53 with chronic pancreatitis (20 during painful relapse and 33 in clinical remission), 18 with pancreatic cancer, 41 with nonpancreatic disease with abdominal pain, five with macroamylasemia, and one with total pancreatectomy. Results were compared with those of a wheat germ inhibition method and with electrophoresis on cellulose acetate. A close correlation was found between the results of immunoinhibition assay and those of the other two tests. All patients with acute pancreatitis had abnormally high values in all three tests. In the group with chronic pancreatitis studied during painful relapse, 16 had an increase in P-isoamylase, as determined with the immunoinhibition assay, 13 with the wheat germ inhibition test, and 15 with electrophoresis. In the group with chronic pancreatitis in clinical remission, we found low values in one patient, by immunoinhibition assay, but found low values in 17 and 19 patients by wheat germ inhibition and electrophoresis, respectively. Low P-isoamylase values corresponded to a severe exocrine pancreatic insufficiency. In the group with pancreatic cancer, the three tests showed similar results, and the majority of the patients had normal values. In the patients with nonpancreatic diseases, abnormally high levels were found in five, by immunoassay, in four by electrophoresis, and in three by the wheat germ inhibition method. In the five cases with macroamylasemia, both inhibition assays erroneously demonstrated an abnormal P-isoamylase elevation. The results show that the three tests are equally useful for the diagnosis of acute pancreatitis, or chronic pancreatitis during an acute relapse. In these diseases, the immunoinhibition test would be the preferred assay because it is simple and rapidly performed. 
3	Clinical features and associations of 560 cases of motor neuron disease. In 560 cases of motor neuron disease, studied retrospectively from their case notes in three teaching centres, the age at onset ranged from 13 to 87 years (mean 56 years), and the mean duration of illness until death was 2.6 years. In the subgroup of the disease presenting with progressive bulbar palsy presenting after age 59 years, there was a previously unrecognised excess of females sufficient to equalize the sex ratio of incidence of the disease in this age group. No potentially causative clinical associations emerged; no relation was noted between occupational exposure to leather products, trauma or surgical procedures and the disease. There was a trend for patients with motor neuron disease to give a history of abstention from alcohol. 
1	Progress and challenges in psychosocial and behavioral research in cancer in the twentieth century. Research in the psychosocial and behavioral aspects of cancer has shown steady growth since the 1950s, and its course of development has paralleled the history of medical techniques in treating cancer. Table 1 outlines this parallel evolution from the 1850s to the 1960s. The roles of the American Cancer Society and the National Cancer Institute (NCI) in spearheading and nurturing research in this area are documented. Interest in psychooncologic questions can be traced back for centuries to the search for etiologic factors and psychologic variables that would explain individual vulnerability to cancer. The first psychologic studies of cancer patients were reported in 1951 and 1952 from the Massachusetts General Hospital and Memorial Sloan-Kettering Cancer Center, respectively. The 1970s saw new interest in psychosocial and behavioral research with many issues being addressed for the first time: better care of the terminally ill through more humanistic approaches including better means of pain control; ethical concerns related to patient rights and their status as subjects in experimental protocols; trying to measure quality of life for cancer patients on protocols; seeing the need for multidisciplinary collaborative groups to make up for the absence of formal training in this area; and the need to design valid, accurate measuring scales specific to the symptomology of patients with cancer. Table 4 outlines how the 1980s gave increasing recognition and support to the psychosocial dimensions of cancer. This period produced a series of key conferences that examined a broad research and education perspective and produced recommendations that remain a benchmark in regard to instrumentation, conceptual models, pitfalls of psychosocial research, training, and education, and the organization of research efforts. New precision has been added to the field in the past 6 years: studies measuring concurrent psychologic, endocrine, and immune function; use of statistical modeling to incorporate quality of life data as a correction factor in survival data (TWiST and QALY); and broadened definitions of medical outcome to include functional status, thus allowing advances in psychiatric measurements to help answer questions in cancer. The challenges for the 1990s are identified in a summary in Table 9. Especially noteworthy is the observation that the comprehensive research needed today cannot be carried out by any one discipline alone. New approaches call for areas of the social sciences formerly inactive in cancer research (e.g., anthropology) to contribute the tools and expertise required to address the problems. 
3	Osteonecrosis of the knee after arthroscopic surgery: diagnosis with MR imaging. Spontaneous osteonecrosis about the knee typically is a disease of the elderly characterized by an acute onset of pain. The exact cause of this condition has long been debated, although a causative relationship between meniscal tears and spontaneous osteonecrosis about the knee has been postulated. Seven patients with knee pain, meniscal tears, and chondromalacia without initial evidence of osteonecrosis at magnetic resonance (MR) imaging underwent arthroscopic surgery with meniscal recontouring or repair and cartilage shaving. These patients returned within 2-14 months with recurrent pain in the treated knee. MR imaging then demonstrated abnormalities consistent with osteonecrosis. Osteonecrosis of the femoral condyle or tibial plateau may be a late sequela of meniscal injury in association with chondromalacia and arthroscopic surgery. This diagnosis should be suspected in patients with recurrent knee pain after arthroscopic repair of meniscal tears. The precise relationship of this pattern of osteonecrosis to that previously described as spontaneous requires further investigation. 
1	High-dose etoposide and marrow transplantation. Etoposide underwent conventional Phase I testing in the 1970s. The dose-limiting toxicity in these studies was mild myelosuppression; other toxicities were infrequent. If a greater degree of myelosuppression is accepted, higher than standard doses could be given. This approach takes advantage of the steep dose-response relationship for most chemotherapeutic agents, including etoposide, as shown in early in vitro and clinical studies. Thus, etoposide was considered an ideal agent for further dose-escalation studies, given its wide range of clinical antitumor activity at standard doses, steep dose-response curve, mild bone marrow suppression, and few nonmyeloid side effects. The high-dose etoposide studies that followed used improved and more intensive hematologic supportive care, including, in some trials, autologous marrow transplantation. When etoposide was used as a single agent in these high-dose trials, mucositis, and, to a lesser degree, hepatic dysfunction were dose-limiting. The maximum tolerated dose (MTD) in this setting was 2.4 to 3.0 g/m2. Multi-agent Phase I trials with etoposide and cyclophosphamide, total body irradiation, carmustine, or carboplatin also resulted in dose-limiting mucosal toxicity, with liver and lung problems appearing more often than with high-dose etoposide alone. The toxicity and MTD can be influenced markedly by the schedule of administration. Etoposide as a continuous intravenous infusion can be given at doses of 4.2 g/m2 (with 200 mg/kg cyclophosphamide) with similar toxicity, but without marrow support. The antitumor results in the lymphomas set the stage for treatment of solid tumors, where treatment of patients with "sensitive" relapses had the best outcome. Lymphoma patients had an 80% response rate; overall, long-term (greater than 2 years) disease-free survival was approximately 40%. Germ cell tumors were also responsive, and the same pattern of sensitive relapses and improvement in responding patients was seen (50% to 75% of patients greater than 1 year). In breast cancer and small cell lung cancer (SCLC), high-dose etoposide-containing regimens were used to intensify standard therapy. The results in these settings were not quite as good (breast cancer, 30% disease-free survival at 2 years; SCLC, 10% at 2 years). 
5	Popliteal artery aneurysms. Long-term follow-up of aneurysmal disease and results of surgical treatment. The natural history of aneurysmal disease was analyzed in 50 patients who were treated for 71 popliteal aneurysms. No patients were lost to follow-up (mean, 5.0 years). Initially, 25 popliteal aneurysms (25/71; 35%) were treated nonsurgically, and 46 (46/71; 65%) were treated surgically. Complications developed in 12 of the 21 asymptomatic popliteal aneurysms (57%) and in 2 of the 4 symptomatic popliteal aneurysms (50%), which were treated nonsurgically. The probability of developing complications increased with time to 74% within 5 years. When reconstruction of a popliteal aneurysm was performed, graft patency and foot salvage were 64% and 95% at 10 years, respectively. Particularly acute arterial thromboembolism was a severe presenting complication. Another important finding was the development of 23 arteriosclerotic aneurysms at other locations during follow-up in 16 patients (32%). The probability of developing these new aneurysms increased to 49% 10 years after repair of the initial popliteal aneurysm. The presence of multiple isolated aneurysms at the initial examination was the most significant risk factor limiting the survival of these patients. Consequently patients at risk could be identified early. This study confirms the limb-threatening potential of popliteal aneurysms when left untreated. Therefore prophylactic reconstructive surgery should be undertaken. Moreover, this study demonstrates that patients with a popliteal artery aneurysm have an increased risk of new aneurysm formation, both in the popliteal artery and at other locations. Therefore these patients should be followed and, in the event that new aneurysms develop, should be considered for elective reconstructive surgery to prevent limb-threatening or life-endangering complications. 
5	Indications for distal arterial reconstruction in the presence of palpable pedal pulses. Eight patients with severe pedal ischemia in the presence of palpable foot pulses are described. All had atherosclerosis, and seven patients also had diabetes. There were two anatomic patterns of disease, including supramalleolar obstruction with reconstitution of pulsatile flow in three patients and segmental occlusion of the pedal vessels in five. All patients underwent arterial reconstructive surgery. Patency was sustained in six patients, with limb salvage in five and below-knee amputation in one patient for persistent necrosis and infection of an open amputation. Of the two eventual bypass failures, a transmetatarsal amputation continued to heal in one patient, and the other required amputation below the knee. Palpable pedal pulses and satisfactory ankle/brachial indexes did not rule out the presence of surgically correctable distal arterial occlusive disease. Therefore arteriography is indicated in any patient with persistent forefoot ischemia that fails to respond to conservative measures. The safety and patency of the distal reconstructive procedures performed in this series suggest that salvage of weight-bearing tissue and rapid healing, as well as limb salvage, are legitimate indications for revascularization. 
1	Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck. Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months. 
2	The role of ERCP in children and adolescents. The diagnostic and therapeutic role of ERCP in 42 patients ranging from 1 to 19 years of age is discussed. ERCP provided useful additional information in 15 patients with biliary tract disease, 15 patients with pancreatic disease, and 9 patients with abdominal pain. The appropriate duct was cannulated in 95% of cases. Mild pancreatitis occurred in two patients after ERCP. Endoscopic papillotomy was successful in five patients. ERCP plays an important part in the investigation of unexplained biliary tract and pancreatic disease. It rarely demonstrates abnormal pathology in patients with otherwise unexplained abdominal pain. 
3	Cytoreductive hepatic surgery for neuroendocrine tumors. We retrospectively reviewed 37 patients who underwent hepatic resection between 1970 and 1989 to evaluate the role of cytoreductive hepatic surgery in patients with metastatic neuroendocrine tumors (carcinoid, 24; islet cell, 13). Seventeen resections were curative (no gross residual tumor); nine patients had symptomatic endocrinopathies and seven patients had symptoms caused by the primary tumor. Eight of nine patients with symptomatic endorcrinopathies obtained complete relief of symptoms; five are alive with no evidence of disease at 2 to 82 months (mean, 26 months). Six of seven patients with symptoms caused by the primary tumor obtained complete relief; five are alive with no evidence of disease at 5 to 28 months (mean, 14 months). One symptom-free patient underwent curative hepatic resection 5 years after abdominoperineal resection for a rectal carcinoid. Twenty resections were palliative (gross residual tumor); 16 patients had symptomatic endocrinopathies and 4 patients had symptoms caused by the primary tumor. Eight of 16 patients with symptomatic endocrinopathies obtained complete relief; five are alive at 2 to 30 months (mean, 11 months), with a mean duration of complete relief of 6 months (3 to 12 months). All four patients who underwent resection for symptoms caused by the primary tumor obtained complete relief; two are alive and symptom free at 10 and 101 months. Our experience suggests that curative surgery should be considered in all patients with completely resectable metastatic disease and that palliative surgery, despite the short duration of complete relief, should be considered in selected patients because it delays and may reduce the subsequent need for medical therapy. 
3	Cheilitis granulomatosa: report of six cases and review of the literature. Six cases of cheilitis granulomatosa, a rare inflammatory disorder of unknown origin, are reported. The condition produces nontender, persistent swelling of one or both lips and affects primarily young adults. Histologically, nonnecrotizing granulomatous inflammation is seen. The clinical findings and results of therapy in these six cases are presented. One patient was treated with hydroxychloroquine sulfate (Plaquenil) that stabilized the process. One of our patients had vesicular-appearing lesions. Microscopic examination showed the lesions to be dilated superficial lymphatic channels, a finding that to our knowledge has not been previously described. 
2	Microbiological studies of the enterocolitis of Hirschsprung's disease. The results of a prospective study of 20 cases of newly diagnosed Hirschsprung's disease (nine of whom developed enterocolitis) and 10 normal controls showed no variations in the bacterial flora (including Clostridium difficile) in the stools of the groups studied. Viral studies showed that rotavirus was present in the stools of seven of the nine cases of enterocolitis during the episode. We suggest that Hirschsprung's enterocolitis may have a complex infective aetiology and that rotavirus plays a part. 
3	Routine and quantitative EEG analysis in Gilles de la Tourette's syndrome. Gilles de la Tourette's syndrome (GdlT) is a neurobehavioral disorder, with a reportedly high frequency of EEG abnormalities. We performed EEGs on 48 consecutive patients with GdlT, and frequency analysis in 26 patients (17 males), and compared the results with those from age- and sex-matched normal controls. Routine 18-channel EEG revealed minimal diffuse nonspecific slowing in only 3 of 48 patients (6%) and in 2 of 26 controls (7.7%). The frequency analysis of the EEG of the 26 GdlT patients and their normal controls showed similar brain activity. We conclude that no significant differences exist between the EEG activity in GdlT patients as compared with that in sex- and age-matched controls in routine as well as in quantitative EEG. 
1	Tissue-specific transformation by epidermal growth factor receptor: a single point mutation within the ATP-binding pocket of the erbB product increases its intrinsic kinase activity and activates its sarcomagenic potential. Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal, ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products that have constitutive tyrosine kinase activity and that can induce erythro-leukemia but not sarcomas. We have found that a single point mutation within the ATP-binding pocket of the tyrosine kinase domain in this truncated molecule can increase the ability of this oncogene to induce anchorage-independent growth of fibroblasts in vitro and fibrosarcoma formation in vivo. Associated with this increased transforming potential is a corresponding increase in the kinase activity of the mutant erbB protein product. The mutation, which converts a valine to isoleucine at position 157 of the insertionally activated c-erbB product, is at a residue that is highly conserved within the protein kinase family. To our knowledge, this is the first demonstration of a point mutation in the ATP-binding pocket that activates a tyrosine kinase. 
1	Experience with photocoagulation in Behcet's disease. Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behcet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others. 
5	Hemodynamic consequences of carotid-carotid bypass for innominate artery stenosis. The carotid-carotid cervical bypass is one surgical option for symptomatic atherosclerotic lesions of the innominate artery. Controversy exists regarding the necessity of surgically excluding the innominate plaque from the cerebral circuit. A canine study was instituted to characterize the hemodynamic alterations that occur in the right common carotid artery proximal to the bypass graft, termed the critical segment. The direction of flow in the critical segment determines whether emboli originating in the innominate may be propelled cranially despite a patent bypass graft. Six mongrel dogs underwent placement of an autogenous arterial crossover graft as a carotid-carotid bypass. A stenosis of the innominate artery was quantitatively altered, and an electromagnetic flowmeter measured the magnitude and direction of flow in the critical segment at three levels of diameter reduction in the innominate artery. For low-grade stenoses, flow in the critical segment was always prograde. For high-grade stenoses, the flow was always reversed. Stenoses between 57% and 67% yielded flow values of 10 +/- 24 ml/min, and it was in this range that mean flow reversal was found to occur. Even when the mean flow was near zero in the critical segment, flow was not stagnant but oscillated in antegrade and retrograde directions throughout the cardiac cycle. These data indicate that a carotid-carotid bypass causes complete flow reversal in the critical segment when there is high-grade stenosis in the innominate artery. Theoretical analysis of the hemodynamic circuit indicated that arm exercise would augment retrograde flow in the critical segment. 
5	The many faces and phases of borreliosis II. Borrelia burgdorferi, the etiologic agent of Lyme disease, has also been associated with other cutaneous conditions. Acrodermatitis chronica atrophicans and lymphadenosis benigna cutis are also caused by B. burgdorferi. Recent evidence links some cases of progressive facial hemiatrophy of Parry-Romberg, benign lymphocytic infiltrate of the skin (Jessner-Kanof), lichen sclerosus et atrophicus, morphea, and Shulman syndrome with borreliae. This article reviews the manifestations of the diseases definitely linked to borreliosis and the evidence linking borreliae to progressive facial hemiatrophy, benign lymphocytic infiltrate, lichen sclerosus et atrophicus, morphea, and Shulman syndrome. 
2	Disturbed gastroduodenal motility in patients with active and healed duodenal ulceration. Disordered gastroduodenal motility may promote duodenal ulceration by allowing prolonged acid contact with the duodenal mucosa. Using a multilumen perfused catheter incorporating 3 pH microelectrodes, antral and duodenal pH and antropyloroduodenal pressure activity were recorded in 36 subjects (10 with healed duodenal ulceration, 11 with active duodenal ulceration, and 15 healthy volunteers) during fasting and after a radiolabeled solid test meal. Correct pH probe/catheter position was continuously verified by recording transmucosal potential difference across the pylorus. Patients with active and healed duodenal ulcer had similarly disordered gastroduodenal motility. The chief abnormalities consisted of an increase in postprandial duodenal retroperistalsis (healed duodenal ulceration, 12 +/- 1 events per hour; active duodenal ulceration, 12 +/- 1; control, 6 +/- 1; mean +/- SEM: healed and active duodenal ulceration vs. control, P = 0.004 and P = 0.03, respectively), a reduction in pressure waves sweeping aborally through the duodenum after the meal (healed duodenal ulceration, 22 +/- 4 events per hour; active duodenal ulceration, 23 +/- 3; control, 34 +/- 4: healed and active duodenal ulceration vs. control, P = 0.04 and P less than 0.05, respectively), and an increased incidence of atypical, complex forms of coordinated duodenal motor activity throughout the study (postprandial data; healed duodenal ulceration, 8 +/- 1 events per hour; active duodenal ulceration, 10 +/- 1; control, 4 +/- 1: healed and active duodenal ulceration vs. control, P = 0.02 and P less than 0.02, respectively). In addition, gastric emptying of the solid test meal was significantly delayed in healed, but not active, duodenal ulceration [half-emptying time, healed duodenal ulceration 185 minutes (117-235); active duodenal ulceration 102 minutes (80-200); control 107 minutes (78-130): healed duodenal ulceration vs. control, P less than 0.009]. Duodenal bulb pH was similar in controls and patients with active duodenal ulceration; however, bulb pH was less than 4 for a significantly greater period of time in healed duodenal ulceration compared with active ulcer patients, particularly after the meal. In conclusion, duodenal ulcer disease is associated with disturbed gastroduodenal motility, even when the ulcer is quiescent and when intraduodenal acidity is low. In healed duodenal ulceration, disturbed motility may promote ulcer relapse by impairing acid clearance from the bulb. However, in active ulceration other factors such as mucosal bicarbonate secretion may have a more influential role in determining intraduodenal pH. 
1	Vulvar Paget's disease. Is immunocytochemistry helpful in assessing the surgical margins? From January 1977 to December 1988, 19 patients with biopsy-proven Paget's disease of the vulva underwent simple or radical vulvectomy at the University of Miami/Jackson Memorial Medical Center. All vulvectomy specimens were evaluated immunocytochemically for the expression of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and low-molecular-weight keratins 8 and 18 (LMK), both in areas containing neoplastic cells and in histologically negative surgical margins. Neoplastic Paget's cells stained positively for CEA in all cases; they were positive for EMA and LMK in 18 and 17 cases, respectively. In all eight cases with underlying in situ or invasive carcinomas, CEA, EMA and LMK were localized in the underlying tumors as well. None of the histologically proven negative margins reacted for CEA, EMA or LMK on immunocytochemistry. CEA appears to be a valuable immunocytochemical marker for extramammary Paget's disease; EMA and LMK are also expressed by the majority of such cases. None of these markers, however, is of added value in identifying Paget's cells in surgical margins if those margins appear negative on routine hematoxylin-and-eosin staining. 
5	Skeletal muscle following tonic overload: functional and structural analysis. Functional overloading of skeletal muscle induces a compensatory hypertrophy as an adaptive response to increased functional demand. Overload of the extensor digitorum longus (EDL) muscle (129 ReJ strain male mouse) was induced by unilateral surgical removal of a synergistic muscle, tibialis anterior (TA). Response of the EDL to overload for 7, 21, and 42 d was analyzed for changes in 1) muscle weight, 2) myofiber type distribution, 3) myofiber cross-sectional area by fiber type, 4) speed of contraction and relaxation of the muscle, 5) force of contraction, and 6) myofiber morphologic integrity. The weight of the EDL significantly increased. The overload caused no impairment of muscle contractility and did not have a significant effect on isometric twitch contraction time to peak tension or the time to one-half relaxation of the twitch. Overloaded muscles demonstrated a transient shift in fiber type profile with preferential hypertrophy of Type IIA fibers that occurred in the early phase of overload while type IIB fibers were recruited by 42 d. No significant increase in myofiber number in overloaded muscles occurred. Some morphologic changes in over-loaded muscles parallel those found in patients with neurogenic muscular disorders. However, overloaded muscle did not exhibit a significant occurrence of fiber branching from controls in the midbelly region of the muscle. 
5	Is banding of the pulmonary trunk obsolete for infants with tricuspid atresia and double inlet ventricle with a discordant ventriculoarterial connection? Role of aortic arch obstruction and subaortic stenosis Banding the pulmonary trunk may exacerbate or promote the development of subaortic stenosis in patients with double inlet ventricle or tricuspid atresia with a dominant left ventricle and discordant ventriculoarterial connection and, therefore, may be an inappropriate palliative procedure for such patients. To examine this possibility, 102 consecutive infants were studied who presented with this anatomy between 1972 and 1987. Obstruction of the aortic arch was present in 52 patients. In 28 patients (17 with aortic arch obstruction), subaortic stenosis was already apparent at presentation. Of the remaining 74 patients, 19 received no palliative surgery and 55 underwent banding of the pulmonary trunk either with (n = 22) or without (n = 33) aortic arch repair. Outcome was significantly worse in patients with associated aortic arch obstruction. All such patients either died or developed subaortic stenosis by 3 years of age (survival free of subaortic stenosis 0 of 22 versus 22 of 33 for patients with isolated banding of the pulmonary trunk, p less than 0.001). After isolated banding, there was a lower ratio of the ventricular septal defect to ascending aorta diameters at presentation in the patients who developed subaortic stenosis than in the patients who did not (0.60 +/- 0.08 versus 1.03 +/- 0.15, p less than 0.001). Of the latter, 18 (95%) of 19 patients fulfilled criteria for a Fontan procedure at recatheterization. Thus, the presence of aortic arch obstruction is associated with rapid development of subaortic stenosis after banding of the pulmonary trunk. Alternative initial surgery, even though high risk, may be indicated. In the absence of such obstruction, banding the pulmonary trunk can be performed at reasonable risk and, provided that the ventricular septal defect is of adequate size, satisfactorily prepares most patients for a later Fontan procedure. 
5	The management of flail chest injury: factors affecting outcome. The records of 57 patients presenting with flail chest injury from 1981 through 1987 were reviewed to determine factors affecting morbidity and mortality. Fifteen patients (26%) had 8+ rib fractures with a unilateral flail and seven (12%) had multiple rib fractures with a bilateral flail. Thirty-two (56%) had moderate-severe pulmonary contusions and 44 (77%) required chest tubes for hemo-pneumothorax. Ventilatory assistance was used in 36 (63%). The major factors determining the need for ventilatory assistance were: an ISS greater than or equal to 23, blood transfusions in the first 24 hours, moderate-severe associated injuries (fractures, head injuries or truncal organs requiring operation), and shock on admission (p less than 0.001). An adverse outcome occurred in 15 (28%); nine required ventilatory assistance greater than or equal to 14 days and six died of sepsis with pneumonia. The main factors associated with an adverse outcome were: an ISS greater than or equal to 31 (p less than 0.001), moderate-severe associated injuries (p less than 0.001), and blood transfusions (p less than 0.005). Although the primary determinants of an adverse outcome were the associated injuries and blood loss, a bilateral flail (p less than 0.01) and age greater than or equal to 50 years (p less than 0.02) were contributing factors. 
1	Rhabdomyosarcoma of the ciliary body. Rhabdomyosarcoma is the most common malignant orbital tumor of childhood. It has twice been reported to arise within the globe from the iris. In addition, teratoid medulloepithelioma, a tumor arising from the ciliary epithelium, can contain a rhabdomyoblastic component, often in combination with other heteroplastic elements. The authors report what may be the first recorded case of an embryonal rhabdomyosarcoma of the ciliary body, possibly representing a one-sided differentiation of a malignant teratoid medulloepithelioma. 
4	Correlation of common carotid flow volume measured by ultrasonic quantitative flowmeter with pathological findings. To evaluate the possibility of quantitatively diagnosing carotid and cerebral atherosclerosis noninvasively, we measured common carotid flow volume in 60 sides (30 patients), using an ultrasonic quantitative flowmeter, and then compared these findings to the severity score of carotid and cerebral atherosclerosis as determined at autopsy. Stenosis decreased common carotid flow volume in the carotid and cerebral arteries. Increases in the severity score varied inversely with reduced flow volume, which was high in inverse correlation (r = -0.696). Patients with flow volumes of 8.5 ml/sec or greater did not have stenosis greater than or equal to 75%, whereas all patients with flow volumes of 6.4 ml/sec or less had stenosis greater than or equal to 50%, with 45% of these having stenosis greater than or equal to 75%. These pathological findings confirm that the common carotid flow volume reflects the degree of carotid and cerebral atherosclerosis present and that the lower limit of common carotid flow volume in healthy subjects is 6.5 ml/sec. 
1	Access to cancer prevention, detection, and treatment. The American Cancer Society Hearings on Cancer and the Poor made visible to the nation the harsh realities and consequences of lack of access to health care among the poor and uninsured in America. Access to care is more than mere availability; it is also financial accessibility, effectiveness, acceptability, appropriateness, and comprehensiveness of care. The problems and consequences of lack of health care access and its impact on the cancer problem among poor Americans are explored, and ways practitioners and public advocates can improve access are suggested. Local communities have risen to action to make health care more accessible. Successful programs have done their research to document access problems; then they have taken their findings to county governments to request additional funding and to health care institutions to request institutional policy and service changes to make health care more available and accessible. 
1	Changes in plasma high density lipoprotein cholesterol and phospholipid in acute viral hepatitis and cholestatic jaundice. Forty-four male and female subjects aged 22-57 years were studied. Thirteen patients had acute viral hepatitis, and eleven patients had cholestatic jaundice due to carcinoma of the head of the pancreas. Twenty healthy volunteers who served as controls were also included. In hepatitis patients, the mean plasma levels of total cholesterol (TC) and the high density lipoprotein (HDL)-phospholipid/phospholipid (HDLPL/PL) ratio were reduced, and HDL-cholesterol (HDLC), HDL-phospholipid (HDLPL) and the phospholipid/total cholesterol (PL/TC) ratio were normal, while total phospholipid (PL) levels and the HDLC/TC ratio were significantly increased compared to the control values. In patients with cholestatic jaundice the mean plasma total cholesterol, phospholipid and HDLC levels were elevated, and HDLPL/PL, HDLPL, HDLC/TC and PL/TC remained normal compared to the control values. A comparison within the patient groups showed that plasma TC, PL and HDLC levels were significantly increased in cholestatic jaundice when compared with the corresponding levels in hepatitis patients. The mean plasma levels of HDLPL, HDLC/TC and PL/TC did not show any significant variation within the patient groups. Alkaline phosphatase (ALP) correlated positively with TC, and total protein correlated negatively with TC and HDLPL, while albumin correlated negatively with TC, HDLC and HDLPL in cholestatic jaundice. Alanine amino-transferase (ALAT) also correlated positively with PL in cholestatic jaundice, while albumin correlated positively with TC in hepatitis. The results suggest that lipoproteins might be metabolized differently in these two forms of cholestasis. 
2	Plasma neurotransmitters and cortisol in duodenal ulcer patients. Role of stress. Levels of noradrenaline, adrenaline, dopamine, free serotonin, platelet serotonin, and cortisol were measured in the plasma of duodenal ulcer patients and controls. All subjects received antacids, and these substances were also measured. During relapse, all patients showed raised noradrenaline, adrenaline, dopamine, free serotonin, and cortisol values. In contrast, platelet serotonin showed very low values, which correlated negatively with all the former, except free serotonin. No correlations were found in parameters of the controls. After healing, significant reductions of noradrenaline, adrenaline, dopamine, free serotonin, and cortisol and significant increases of platelet serotonin values were observed. However, only dopamine, free serotonin, and cortisol reached normal values. Noradrenaline and adrenaline remained higher and platelet serotonin lower, both significantly more so than normals. These still-altered parameters showed similar correlations to those found during relapses. The present results demonstrate that some baseline autonomic system imbalance exists in patients, amplified and accentuated during relapse. We discuss the possibility that stress plays some role in triggering duodenal ulcer relapse. 
5	The role of vascular endothelial cells in transplantation. The interface between an allograft and the recipient's immune system is the endothelium of the allograft vasculature. In this boundary position, endothelial cells may play important roles in the afferent and efferent phases of allograft rejection, in the response of the allograft to pretransplant perfusion and to drug therapy, and in the response to viral infection of the host. The expression by endothelial cells of granule membrane protein-140 (GMP-140) and endothelial leukocyte adhesion molecule-1 (ELAM-1), increased tissue factor activity, increased secretion of plasminogen activator inhibitor, and decreased thrombomodulin may all contribute to hyperacute rejection. Similarly, endothelial cells may actively participate in acute cellular rejection and in the development of transplant-associated arteriopathy as a result of induction of antigen-presenting function (ie, HLA class II expression), upregulation of adhesion molecules for lymphocytes and monocytes, and release of platelet-derived growth factors. Endothelial cell functions, which are important for normal inflammatory responses and vessel behavior, may be pathogenic in the allograft. 
5	Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation. To assess the relation between genotype and severity of disease in cystic fibrosis (CF) the frequencies and extent of several features of its phenotypic expression were investigated in the 235 patients who attend the Danish CF Centre. 14 patients who attend irregularly and 3 who do not carry the delta F508 mutation at all were excluded. The case-reports of the remaining 218 patients (aged 4 months to 41 years) were carefully evaluated, and they were all analysed for the delta F508 mutation. 172 (79%) were homozygous for delta F508 and 46 (20%) were heterozygous. The mutation therefore occurs on 89% of the chromosomes analysed. There were no significant differences between the homozygous and heterozygous groups in the proportions with meconium ileus at birth, liver involvement, or chronic Pseudomonas aeruginosa infection. However, significantly more of the homozygous patients had onset of symptoms before the age of 6 months (p less than 0.025); they were significantly younger at diagnosis (p = 0.013) and centre referral (p = 0.006); they required greater pancreatic enzyme substitution (p = 0.0002) and had poorer lung function; and the calculated yearly incidence of chronic Ps aeruginosa infection and yearly mortality rates were greater than in heterozygous patients (p = 0.0001). 
2	Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations. Twenty cases of inflammatory myofibroblastic tumor (IMT) were studied; 19 involved the lung and 1 the esophagus only. The patients' ages ranged from 3 to 72 years. There were 9 males and 11 females. Involvement of a bronchus was seen in one case and of mediastinal structures in four. Chest pain and dyspnea were common symptoms; eight patients were asymptomatic. Seven patients underwent lobectomy, 12 local excision, and 1 biopsy alone. The lesions were nonencapsulated and ranged from 1.2 to 15 cm. Various proportions of plasma cells, histiocytes, and spindle cells were observed; the latter corresponded ultrastructurally to fibroblasts and myofibroblasts, were immunoreactive for vimentin and actin and focally for desmin, and were negative for epithelial markers. Plasma cells were polyclonal for light chains. One patient had two recurrences, and in one case a large pleural IMT was found eight years after the excision of a similar lesion in the lung. All patients with follow-up (ten) were well as long as ten years after the diagnosis (average, 3.7 years). 
5	Spontaneous reactivation in chronic hepatitis B: patterns and natural history. We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B. 
5	Anti-Kell in pregnancy. A review of data on haemolytic disease of the newborn (HDN) collected in Newcastle upon Tyne over 25 years revealed 194 pregnancies in which anti-Kell was the only antibody detected. Sixteen affected babies were born. None was hydropic, three had very severe disease but all survived. There were also three stillbirths, none of which had post-mortem appearances of HDN. The highest recorded anti-Kell titres in individual patients ranged from 1/1 to 1/2048 and bore no relation to the severity of the disease. Of the eight pregnancies in which amniotic fluid examination predicted a high risk of stillbirth, half resulted in unaffected babies. We suggest that haemolytic disease caused by anti-Kell is less severe than suggested by some workers. The use of guidelines developed from the study of Rhesus disease to determine the need for intervention in women with anti-Kell may be inappropriate. 
3	Radiographic manifestations of anomalies of the brain. Congenital brain anomalies are classified as developmental anomalies, effects of teratogens, errors of histogenesis, or sequelae of infections. The imaging options for delineation of these anomalies are many; a basic understanding of the disorder is central to the effective choice of imaging modality. This review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants. 
2	Pancreaticopleural fistula. Report of 7 patients and review of the literature. Pancreaticopleural fistula is an uncommon clinical condition. Its presentation is often confusing because of the paucity of clues suggestive of pancreatic disease and the preponderance of pulmonary symptoms and signs. Most patients are alcoholics but only one-half will have a clinical history of previous pancreatitis. Pleural effusions are large, recurrent, and highly exudative in nature. Many patients go through extensive pulmonary evaluation before the pancreas is identified as the site of primary pathology. An elevated serum amylase may be the first clue to the diagnosis. However, the key to the diagnosis is a dramatically elevated pleural fluid amylase. Effusions in association with acute pancreatitis, esophageal perforation, and thoracic malignancy are important to consider in the differential diagnosis of an elevated pleural fluid amylase but are usually easy to exclude. Computed tomography is excellent in defining pancreatic abnormalities and should be the first abdominal imaging study in suspected cases. Endoscopic retrograde cholangiopancreatography (ERCP) is used as a diagnostic tool only in confusing cases. Although no systematic study evaluates medical versus surgical therapy, we recommend an initial 2 to 4-week trial of medical therapy, including allowance of no oral intake, total parenteral nutrition, chest tube thoracostomy, and possibly a regimen of somatostatin or its analogs. The major complication in these patients is superinfection, which results in significant morbidity and mortality. Failure of medical therapy should be considered failure of pleural effusion(s) to clear, recurrence after reinstatement of oral intake, or superinfection. For those patients who fail to benefit from medical therapy, surgery is indicated. 
4	Regional diastolic mechanics of ischemic and nonischemic myocardium in the pig heart. To assess the role of segmental dyssynchrony as a determinant of ischemic diastolic dysfunction, systolic and diastolic mechanics of ischemic and nonischemic myocardium were compared in the open chest pig heart (n = 7). Pacing tachycardia (1.8 x heart rate at rest) was imposed for 3 to 5 min in the presence of a single critical stenosis of the left anterior descending artery (demand ischemia, n = 7). After 30 min of recovery, the left anterior descending artery was totally occluded for 1.5 min in the same pigs (primary ischemia, n = 6). Both demand and primary ischemia increased left ventricular end-diastolic pressure and prolonged the time constant of left ventricular pressure decline. Percent systolic shortening of ischemic segments (perfused by the left anterior descending artery) decreased by 32% during demand ischemia and by 120% during primary ischemia, but that of nonischemic segments (perfused by the left circumflex artery) did not change significantly during either type of ischemia. During demand ischemia (but not during primary ischemia), left ventricular diastolic pressure increased relative to segment length so that a higher diastolic pressure was needed to stretch the ischemic segment to the same length (decreased distensibility). In nonischemic areas, diastolic pressure and segment length increased commensurately during both types of ischemia, indicating no change in diastolic distensibility. During demand ischemia, peak early diastolic lengthening rates increased in nonischemic segments but remained unchanged in ischemic segments. Diastolic segmental dyssynchrony developed during both types of ischemia, but was more pronounced during primary ischemia. Therefore, segmental dyssynchrony is unlikely to account for the rise in diastolic pressure relative to segment length seen during demand ischemia. 
1	Peritoneal mesothelioma: an unusual cause of esophageal achalasia. Secondary esophageal achalasia due to malignancy is a rare condition; only 53 such cases have been reported to date. Sixty-two percent of the cases were due to gastric adenocarcinoma. Mesothelioma of the peritoneum is an uncommon neoplasm. The usual presenting symptoms are abdominal pain, abdominal mass, or abdominal distention. The patient we are reporting had peritoneal mesothelioma which presented with dysphagia and weight loss, in addition to the radiological and manometric picture of achalasia. Secondary achalasia was suspected clinically, and was confirmed by computed tomography and laparotomy. The diagnosis of peritoneal mesothelioma was made only by histopathological examination. We are not aware of any other report documenting the association of peritoneal mesothelioma and achalasia. 
4	Catheter-based intravascular ultrasound imaging of chronic thromboembolic pulmonary disease. Pulmonary thromboendarterectomy is now the treatment of choice for pulmonary hypertension due to chronic pulmonary thromboemboli. A precise assessment of location and extension of these thrombi is important because only proximal chronic pulmonary thromboemboli are accessible to surgery. Because intravascular ultrasound imaging can assess not only arterial luminal size, but also wall thickness, its value as a complement to angiography was assessed in 11 patients aged 35 to 64 years with severe pulmonary hypertension (systolic pulmonary artery pressure, mean +/- standard deviation 70 +/- 19 mm Hg; pulmonary artery resistance, 609 +/- 297 dynes.s.cm-5). Intravascular ultrasound was obtained in 10 of 11 patients and no complication occurred. Intravascular ultrasound identified 10 segments with suspected chronic pulmonary thromboemboli in 7 patients, all confirmed at operation. Nine segments were considered normal, all of which (except 1) were free of chronic pulmonary thromboemboli at operation. Image quality was highly dependent on pulmonary artery size and position of the catheter. Therefore, intravascular ultrasound of pulmonary arteries is feasible and safe in patients with pulmonary hypertension. It may help to assess the location and extension of the pathologic process involving pulmonary arteries. 
4	Carotid endarterectomy for chronic retinal ischemia. Carotid arterial disease may result in a variety of ischemic ocular problems that can eventually lead to permanent blindness. From 1984 to 1988, 18 patients underwent reconstruction of the carotid artery in an attempt to restore normal retinal arterial flow and, thereby, reverse or prevent progression of ischemic oculopathy. During a mean period of 21 months after carotid arterial reconstruction, subjective improvement in vision as well as a resolution in eye and periorbital pain was reported in 87.5 per cent of the patients. Measured visual acuity improved or stabilized in 94.4 per cent; macular photostress recovery times improved in 87.5 per cent, funduscopic examinations noted improvement or resolution in ischemic signs in 93.3 per cent and intraocular pressures improved in two of three patients. One patient experienced recurrent episodes of amaurosis fugax, which resolved after two weeks and did not recur. A second patient experienced an increase in intraocular pressures with visual deterioration, required laser photocoagulation after which the condition of the patient stabilized but only after significant visual impairment. Carotid arterial reconstruction is effective for the treatment of ischemic oculopathy and is most beneficial if performed early, before the onset of irreversible neovascular glaucoma. 
5	Hyperthecosis of the ovaries in a woman with a placental site trophoblastic tumor. Rapidly increasing testosterone levels were observed in a patient presenting with sudden onset of virilization. Exploratory laparotomy revealed a placental site trophoblastic tumor in the uterus. Wedge biopsies of the ovaries showed extensive luteinization of the ovarian stroma in both ovaries. Concentrations of testosterone, dihydrotestosterone, and androstenedione were markedly increased in the ovarian vein serum, indicating ovaries as the source of these steroids. The serum concentration of hCG was 69 mIU/mL. Pulsatile secretion of LH persisted in spite of elevated hCG levels. Follicle-stimulating hormone levels were low or undetectable. Elevated hCG levels and low FSH levels resulted in a hormonal environment similar to that seen in polycystic ovary disease (high LH to FSH ratio), resulting in extensive stromal luteinization. Decline in hCG levels after removal of the tumor resulted in the return of androgen levels to normal. 
1	Early inappropriate secretion of antidiuretic hormone after trans-sphenoidal pituitary adenomectomy. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a rare but life-threatening complication of trans-sphenoidal pituitary adenomectomy. It has previously only been described as a late phenomenon. We report an early presentation within the first week. The pathophysiology, clinical features and treatment are discussed. 
2	The Los Angeles experience with laparoscopic cholecystectomy. Surgeons should be competent in diagnostic laparoscopy before performing laparoscopic cholecystectomy (LC). Well-structured and endorsed courses with experienced faculty are important. Within 12 months, 418 LCs were performed in our hospital. The number of open cholecystectomies decreased to one third of all cholecystectomies performed. Cholangiography was attempted routinely and the duct was successfully cannulated in 90%. Inquiries were made at 6 other hospitals within a 5-mile radius where a total of 220 LCs were performed. The following gray areas need to be addressed: patients with slightly increased liver function tests but no jaundice, and unsuspected stones discovered by cholangiography. New projects are in progress to explore the common bile duct via the cystic duct or directly through the common bile duct with insertion of a T tube. The authors recommend proper training as well as caution and sound judgment before commencing with LC. 
5	Toxicities in rats with free versus liposomal encapsulated cisplatin. Wistar rats (five in each group) were given either 1 mg/kg of free cisplatin, 1 or 2 mg/kg of liposomal encapsulated cisplatin, or saline solution intraperitoneally biweekly for 15 injections. Rats in the free drug group showed significantly less weight gain; two rats died during the study. At necropsy, the free cisplatin--treated rats showed gross and microscopic evidence of peritoneal fibrosis that was not detected in any of the remaining groups. The free cisplatin--treated rats showed serum and histologic evidence of renal damage; all five rats had moderate or severe acute tubular necrosis. No renal abnormalities were detected in rats that received 1 mg/kg, and only focal or mild changes were found in rats that received 2 mg/kg of the liposomal preparation. Neurotoxicity, as determined by nerve conduction and inclined plane studies, developed in rats treated with free and liposomal cisplatin. These results are encouraging and warrant further investigation. 
2	Kawasaki-like syndrome after treatment with mesalazine. We report a patient who developed a severe hypersensitivity reaction, including rash, lymph node enlargement, fever, hepatitis, and eosinophilia, after sulphasalazine therapy. Five years later, he developed a similar reaction after exposure to mesalazine, the salicylic compound of sulphasalazine. We conclude that patients with known severe systemic reaction to sulphasalazine therapy are also at risk for such a reaction when treated with a 5-ASA preparation. 
2	Scintigraphic assessment of leukocyte infiltration in acute pancreatitis using technetium-99m-hexamethyl propylene amine oxine as leukocyte label. The infiltration of leukocytes has been linked to the pathophysiology of complicated or severe pancreatitis. We have tested the ability of leukocyte scintigraphy using technetium-99m-hexamethyl propylene amine oxine (HM-PAO) as label to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis. Twenty-eight patients with acute pancreatitis (eight with biliary, 13 with alcoholic, and seven with unknown origin) were studied with leukocyte scintigraphy using planar imaging and single photon emission computed tomography (SPECT). Fourteen patients had a mild (group I), II a severe (group II), and three a lethal outcome (group III) of pancreatitis. All patients of group III, six of group II, and two of group I had a positive leukocyte scan. Thus, the sensitivity of leukocyte scintigraphy for the detection of a lethal course of acute pancreatitis was 100%, of a severe course 54%, and of a severe or lethal course 64%. The specificity of a negative scan for a mild pancreatitis was 86%. Comparison of the results of leukocyte scintigraphy with those of contrast enhanced CT showed that six of eight patients with pancreatic necrosis in CT had a positive leukocyte scan, but only five of 20 patients without detectable pancreatic necrosis in CT. In summary, leukocyte infiltration into the pancreas during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy using technetium-99m-HM-PAO as label. A correlation between the severity of the disease and leukocyte infiltration exists. 
5	Bone marrow necrosis in leukemic-phase follicular lymphoma. Bone marrow necrosis has been regarded as a rare entity in specimens obtained from living patients and has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders, severe infections, and sickle cell anemia. We present an unusual case of a small-cleaved type follicular lymphoma associated with bone marrow necrosis and a leukemic phase occurring in a 55-year-old woman. Specimens were studied by morphologic, immunohistochemical, cytogenetic, and DNA hybridization techniques. 
5	Aortocaval and iliac arteriovenous fistulas: recognition and treatment. Despite the well characterized physiologic effects of aortocaval or iliac arteriovenous fistulas, patients with such uncommon lesions may manifest a diverse array of symptoms, and diagnosis is often delayed or overlooked. To examine clinical features that facilitate recognition and allow successful repair, a 30-year experience with 20 such fistulas was reviewed. Fourteen fistulas were caused by aneurysm erosion, four followed iatrogenic injury during lumbar disk surgery, and two developed from abdominal gunshot wounds. The interval from presumed occurrence to diagnosis ranged from 3 hours to 8 years. The diagnosis was not recognized before surgery in five (25%) patients. Back pain (70%) was the most common symptom. The presence of a typical abdominal bruit (80%) was the most reliable physical finding, but its significance was occasionally overlooked or misinterpreted. Congestive heart failure was prominent in only seven (35%) patients. Severe lower extremity edema and mottling was the primary manifestation in eight cases, often causing initial confusion with venous thrombosis. Hematuria (5 patients) and oliguric renal failure (4 patients), both fully reversible after fistula repair, also caused diagnostic uncertainty. The mean preoperative cardiac output was 12.2 L/min, falling to 5.4 L/min with fistula repair. Mean blood loss was 5960 ml, supporting use of intraoperative autotransfusion. Two operative deaths (10%) occurred, both in patients not correctly diagnosed before surgery. Despite varied modes of presentation, prompt recognition and use of appropriate operative techniques should achieve successful repair. 
5	Retrograde transurethral balloon dilation of prostate: innovative management of abacterial chronic prostatitis and prostatodynia. Retrograde transurethral balloon dilatation (RTBD) of the prostate recently has been suggested as alternative therapy for patients with benign prostatic hyperplasia (BPH). Seven patients with documented functional urinary outlet obstruction at the level of the bladder neck or prostatic urethra underwent RTBD of prostate. Each patient had a classic diagnosis of abacterial chronic prostatitis or prostatodynia based on history, physical examination, and localization cultures. Prior to RTBD of prostate, patients underwent cystoscopy, voiding cystourethrogram, urodynamic and uroflow studies. RTBD of prostate was done as an outpatient procedure requiring intravenous sedation or general anesthesia. Dilation was performed with a 25-mm urethroplasty balloon catheter inflated at 3.5 atm of pressure for twenty minutes. Improvement in voiding symptomatology was noted in all patients and graded numerically (0-10 scale), with ten indicating normal voiding. Follow-up to date ranges from one to five months. This technique may have promise as a treatment option in patients with abacterial chronic prostatitis and prostatodynia. 
4	Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy. The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had greater than 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders. 
2	Differential regulation of liver P-450III cytochromes in choline-deficient rats: implications for the erythromycin breath test as a parameter of liver function. Progressive liver fibrosis in rats develops when they are fed a diet deficient in choline. This diet also results in a pronounced and selective decrease in the liver microsomal content of a phase I drug-metabolizing enzyme belonging to the cytochrome P-450III gene family. Because P-450III cytochromes characteristically catalyze the N-demethylation of erythromycin, we believed that the production of breath CO2 from erythromycin would be dramatically reduced in choline-deficient rats. However, when 12 choline-deficient rats were compared with 9 control rats, the reduction in CO2 production from erythromycin (mean decrease 71%) was essentially identical to that from aminopyrine (mean decrease 69%), a substrate believed to be metabolized normally by the hepatocyte in fibrotic liver disease. Furthermore, we found that the relative erythromycin and aminopyrine demethylase activities were comparable when measured in vitro in liver microsomes prepared from the choline-deficient rats. To determine the molecular basis for the erythromycin demethylase activity in the choline-deficient rats, the liver microsomes were subjected to immunoblot analysis using a variety of polyclonal and monoclonal antibodies capable of distinguishing individual P-450III-related proteins. Our studies confirm that a major erythromycin demethylase belonging to the P-450III family, termed P-450p, was greatly reduced in the choline-deficient rat liver. However, the specific concentration of a second P-450p-related protein was essentially normal and that of a third P-450p-related protein was actually increased in the choline-deficient rat liver. 
2	Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. Hybrid HBV nucleocapsid-pre-S(2) fusion proteins were stably expressed in several aromatic-dependent attenuated Salmonella typhimurium and Salmonella dublin strains. When these live recombinant bacteria were administered i.p. to BALB/c mice they induced high titer anti-hepatitis B virus core Ag (HBc) and detectable anti-pre-S2 serum antibodies. Upon oral feeding of the recombinant salmonellae to mice, the rate of seroconversion to anti-HBc was dependent on the salmonella strain used. With the best carrier strain high titer anti-HBc antibodies and lower titer anti-pre-S2 serum IgG antibodies were observed two weeks after a single oral immunization. The Ig class and IgG subclass distribution of anti-HBc antibodies after i.p. and oral immunization is consistent with the induction of functional T cell help. 
5	Lower respiratory tract infections. Although lower respiratory tract infections are frequently diagnosed in a primary care setting, they are still associated with a significant morbidity and mortality, which warrants a careful approach to treatment. Knowledge of the most common cause based on the age of the patient, location where the infection was acquired, and clinical presentation helps to direct empiric treatment. A few basic laboratory studies, especially a sputum Gram stain, can allow for more specific treatment. Identification of patients at increased risk for virulent organisms should make the primary care physician consider inpatient treatment along with an aggressive diagnostic workup and broad-spectrum antimicrobial treatment. Prevention should always be considered. 
5	Parotid gland and facial nerve trauma: a retrospective review. Included in this study are all patients with trauma to the parotid region seen at our center from 1979 to 1989. There was a total of five patients with injury to the parotid area: two patients with isolated facial nerve injury; one with isolated parotid duct injury; two with combined duct and nerve injury. There were four males and one female, with a mean age of 34 years (range, 16 to 62 years). The three patients with parotid duct injury required other procedures for associated trauma. A total of eight nerve branches were severed in four patients. Seven of the eight nerve branches (82.5%) were primarily repaired, with excellent functional results. Two of the three ductal injuries were repaired primarily over a stent, and one was ligated. No complications resulted from either treatment. Based on our clinical experience and review of the literature, we suggest that the treatment of parotid region injuries should include: 1) a complete initial assessment; 2) primary repair of parotid duct transection within 24 hours when possible; 3) primary repair of all facial nerve injuries, although delayed nerve repair remains a viable alternative; and 4) nonsurgical treatment of sialoceles and fistulae. 
3	NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine-depleted rats. Systemically administered N-methyl-D-aspartate (NMDA) antagonists, MK-801 ((+)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) and CPP (3-[(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate), potentiate the ability of L-dopa (L-3,4-dihydroxyphenylalanine) to reverse akinesia and to alleviate muscular rigidity in monoamine-depleted rats. On the basis of these findings, it is proposed that NMDA antagonists may be beneficial as adjunctive treatment in the therapy of Parkinson's disease. CPP locally injected into the subthalamic nucleus, entopeduncular nucleus--the rat homologue of the internal pallidal segment--or substantia nigra pars reticulata of monoamine-depleted rats stimulates locomotor activity and alleviates rigidity, whereas local microinjection of CPP into the neostriatum is ineffective. These results make it unlikely that the neostriatum is the site of the antiparkinsonian action of NMDA antagonists in monoamine-depleted rats, whereas the subthalamic nucleus, internal pallidal segment, and substantia nigra pars reticulata appear to be important for the effects of NMDA antagonists. 
5	Prevalence and prognostic significance of exercise-induced ventricular arrhythmias after coronary artery bypass grafting. Exercise-induced ventricular arrhythmias occur often after coronary artery bypass grafting (CABG), but their prognostic significance is unknown. Two hundred patients examined by exercise electrocardiography and cardiac catheterization (including left ventriculography, bypass graft and native coronary artery angiography) before and 3 months after CABG were prospectively followed up. Exercise-induced ventricular arrhythmias occurred more often after (49 of 200 patients, 24.5%) than before (32 of 200 patients, 16.0%) CABG (p less than 0.05). There were no differences between the patients with and without ventricular arrhythmias in the prevalence of graft patency (79 vs 80%) or the postoperative ejection fraction (57 +/- 9 vs 57 +/- 12%). Ten cardiac deaths occurred during the mean follow-up time of 61 +/- 19 months, 8 of which were witnessed sudden cardiac deaths. All cardiac deaths occurred in patients who did not have exercise-induced ventricular arrhythmias after CABG. The postoperative ejection fraction was lower in the cardiac death patients (42 +/- 16%) than in the survivors (58 +/- 10%) (p less than 0.01). No other clinical or angiographic variable predicted the occurrence of cardiac death. Thus, the prevalence of exercise-induced ventricular arrhythmias increases after CABG, but the occurrence of ventricular arrhythmias does not indicate an increased risk of cardiac death. 
5	Synchronous positive and negative myoclonus due to pontine hemorrhage. We report a case of synchronous positive and negative myoclonus following pontine hemorrhage. Constant synchronous jerking of the eyes, tongue, face, mandible, larynx, pharynx, and diaphragms persisted during sleep. Jerking of limb muscles occurred during volitional activities, but not at rest. Inability to sustain glottic adduction during phonation contributed to severe dysarthria. Electromyography (EMG) revealed positive myoclonus of the branchial musculature with synchronous negative myoclonus in a generalized distribution. Treatment with trazodone reduced the ocular myoclonus but worsened the dysphagia. We suggest that a single neural rhythm generator may produce both positive and negative myoclonus. 
2	Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis. Human leukocyte antigen typing was performed in 81 patients with primary sclerosing cholangitis to investigate reported associations between human leukocyte antigen type and this disease. The results showed a significant increase in the frequency of the antigens B8 and DR3 compared with controls (53% vs. 23%, p less than 0.0005, and 56% vs. 21%, p less than 0.0005). This was caused by a significant rise in the frequency of the human leukocyte antigen A1 B8 DR3 haplotype (32 of 81 patients, 40% vs. 12 of 100 patients, 12%, p less than 0.0005). By contrast, a significant reduction was seen in the frequency of the antigens B44 and DR4 (12% vs. 31%, p less than 0.005, and 12% vs. 34%, p less than 0.001, pc less than 0.011) because of the complete absence of the B44 DR4 haplotype in the patient group (p = 0.027, Fisher's exact test). When all the DR3-positive individuals (including the DR2/DR3 heterozygotes) were eliminated, a significant secondary association with DR2 was noted, 25 (69%) of 36 remaining patients being DR2-positive compared with 27 (34%) of 79 DR3 negative controls (p less than 0.0005, pc less than 0.006). Only 9% of the patients were DR2-positive and DR3-positive. Kaplan-Meier analysis demonstrated that survival was not influenced by the presence of either haplotype nor by the individual antigens. Patients who were DR3-positive were first seen at a significantly younger age than those who were DR2-positive (mean ages = 33 yr and 44 yr, respectively, p less than 0.002, Student's t test). 
3	The concept of migraine as a state of central neuronal hyperexcitability. This article explores the hypothesis that migraine with aura is associated with a state of central neuronal hyperexcitability. The authors propose that this central neuronal hyperexcitability involves overactivity of the excitatory amino acids, glutamate, and possibly aspartate. Stimuli that activate the migraine attack evoke neuronal depolarization, slow depolarization shifts, and spreading suppression of spontaneous neuronal activity possible by glutamate and K+ dependent mechanisms. A low brain Mg2+ and consequent reduced gating of glutamatergic receptors may provide the link between the physiologic threshold for a migraine attack and the mechanisms of the attack itself by promoting glutamate hyperactivity, neuronal hyperexcitability, and susceptibility to glutamate-dependent spreading depression. 
5	Role of granulocyte elastase in tissue injury in patients with septic shock complicated by multiple-organ failure. To better understand the role of granulocyte elastase (GE) in mediating tissue injury during sepsis, GE levels were measured in plasma and bronchoalveolar lavage fluid (BALF) in patients with septic shock (n = 16) and hemorrhagic shock (n = 30). Granulocyte elastase levels were compared to levels of alpha 1-protease inhibitor (alpha 1-PI). Results show that although plasma GE-alpha 1-PI complex was initially elevated in patients with hemorrhagic and septic shock, elevations in plasma GE-alpha 1-PI complex (831 +/- 241 micrograms/L) persisted in septic shock patients. alpha 1-Protease inhibitor levels in serum were increased, resulting in an inhibition of serum GE activity. Granulocyte elastase activity in BALF, however, was significantly higher in those patients with septic, as compared to hemorrhagic shock (31.4 +/- 25.8 versus 3.7 +/- 4.0 U/L, respectively). In addition GE levels were compared to other parameters, including respiratory index, blood neutrophil count, and plasma levels of endotoxin, fibronectin, and coagulation factor XIII. Significant correlations were observed between GE-alpha 1-PI and increased endotoxin concentration and decreased fibronectin and coagulation factor XIII levels. Significant correlation was found also between GE activity in BALF and respiratory index. These findings suggest that severe tissue damage occurred in patients with septic shock complicated by multiple-organ failure. Although GE activity appeared to be adequately inhibited by alpha 1-PI in blood, increased GE activity in local tissues, such as lung alveoli, may be responsible for significant local tissue injury during septic shock. 
5	Effect of left ventricular aneurysm on risk of sudden and nonsudden cardiac death. Although left ventricular (LV) aneurysm is associated with increased mortality, its independent prognostic significance is controversial. To determine the effect of LV aneurysm on risk, 121 patients with healed myocardial infarction (MI), 55 manifesting akinesia on ventriculography (MI group) and 66 with LV aneurysm characterized by diastolic deformity (eccentricity) and systolic dyskinesia (LV aneurysm group) were studied. At a mean follow-up of 5.7 years, there were 32 cardiac deaths (12 MI vs 20 LV aneurysm), including 9 sudden deaths (1 MI vs 8 LV aneurysm). Multivariate analysis revealed decreasing ejection fraction to be the best predictor of total cardiac death, and revascularization to be protective. Nonsudden cardiac death was predicted by ejection fraction, absence of revascularization and right coronary artery disease, whereas sudden cardiac death was predicted by LV aneurysm and the frequency of ventricular ectopic complexes on Holter monitoring. In the MI group, ejection fraction was the only significant predictor of total cardiac death and nonsudden cardiac death. In the LV aneurysm group, total cardiac death, as well as nonsudden cardiac death, were predicted by ejection fraction, ventricular tachycardia and right coronary artery disease, whereas ventricular tachycardia predicted sudden cardiac death. It is concluded that the risk profile for total cardiac death differs between LV aneurysm and MI patients, and that LV aneurysm constitutes an independent predictor of late sudden cardiac death after MI. Moreover, on a substrate of LV aneurysm, the risk factors for sudden cardiac death and nonsudden cardiac death differ, with ventricular tachycardia being the sole predictor of sudden cardiac death. Furthermore, Holter monitoring is valuable in identifying patients at persistent risk of sudden cardiac death. 
4	Events following implantation of an intraluminal ringed prosthesis in the ascending, transverse, and descending thoracic aorta. From March 1978 through July 1985, 23 patients underwent implantation of 24 intraluminal ringed prostheses (IRP). There were 18 men and 5 women, with a mean age of 54.7 years, range 15-74 years. Eleven IRP were placed in the ascending aorta, two in the transverse arch, and 11 in the descending aorta. Pathology included acute aortic dissection in four patients, chronic dissection in four, and aortic aneurysm in 16. There were eight hospital deaths (35%). Causes of death included acute cardiac failure in seven patients, and ruptured abdominal aortic aneurysm in one. IRP complications requiring revision included right coronary artery occlusion in three of 11 patients (27%) with an IRP in the ascending aorta. Graft revision was also required in three of 11 IRP implanted in the descending aorta (27%), due to graft occlusion in one and graft stenosis in two. Of the six patients with IRP complications, there were three hospital deaths (50%). All 15 hospital survivors were followed for a mean of 68.5 months, range 5-112 months. There were four late deaths (26.7%). Causes of late death included hemoptysis in one, cardiomyopathy in one, and aortic redissection and rupture in two. We conclude that patients undergoing repair of aortic pathology with IRP have an important risk of early phase events, as technical problems can occur due to malposition and slippage of the securing rings. 
3	Portacaval shunt versus endoscopic sclerotherapy in the elective treatment of variceal hemorrhage. Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were included in a prospective controlled trial to assess the efficacy and safety of portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of variceal hemorrhage. Forty-one patients were randomized to portacaval anastomosis and 41 to sclerotherapy. After excluding dropouts, 34 patients were treated with portacaval anastomosis and 35 with sclerotherapy. The incidence of variceal rebleeding during follow-up (mean +/- SD, 20.6 +/- 14.2 months) was significantly higher in the sclerotherapy than in the portacaval groups, either considering the overall treated group or only patients completing sclerotherapy (40% and 25% vs. 2.9%; P = 0.0002 and P = 0.01, respectively). The 2-year probability of suffering from at least one episode of hepatic encephalopathy was significantly higher in patients submitted to portacaval anastomosis than in those treated with endoscopic sclerotherapy (40% vs. 12%; P = 0.04). However, disabling encephalopathy only appeared in 3 of 34 patients who underwent surgery (8.8%). Early and long-term mortality did not differ between the therapeutic groups; 2-year survival rates were 83% for portacaval anastomosis and 79% for sclerotherapy. It is concluded that portacaval anastomosis is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in spite of the greater incidence of hepatic encephalopathy. The role of portacaval anastomosis in the elective treatment of variceal rebleeding should be reassessed. 
5	Low-dose heparin. A cause of hematoma of rectus abdominis. Although hematomas of the rectus abdominis muscle are commonly reported complications of systemic anticoagulation treatment, they are a rare complication of prophylactic administration of low-dose heparin. The occurrence of a massive hematoma of the rectus sheath is reported in a woman with chronic obstructive pulmonary disease and acute respiratory failure who was receiving low doses of heparin for the prevention of deep venous thrombosis. Three other cases of hematoma of the rectus sheath resulting from prophylactic use of heparin are reviewed. The development of hematoma in these patients may have resulted from intramuscular abdominal injection of heparin and from strain of the rectus abdominis muscle caused by coughing. When prophylactic administration of heparin is necessary in patients with a tendency to paroxysmal cough, subcutaneous injections of heparin in the thigh may be preferable to subcutaneous injections in the abdomen. 
5	Diversity of outer membrane protein profiles of nontypable Haemophilus influenzae from children from Papua New Guinea and the Philippines. We determined capsular serotypes and, with use of SDS-PAGE, patterns of outer membrane proteins (OMP) of Haemophilus influenzae isolates from specimens of blood, lung, or CSF from children with acute respiratory tract infections or meningitis who were hospitalized in Papua New Guinea or the Philippines. Among 72 isolates from Papua New Guinea, 72% were type b, 14% were other encapsulated serotypes, and 14% were nontypable. The respective frequencies among 43 isolates from the Philippines were 56%, 7%, and 37%. The type b isolates could be subdivided into at least eight outer membrane subtypes, most of which have been described previously. In contrast, OMP profiles of the nontypable H. influenzae isolates from children in both countries were highly heterogeneous. These results differ markedly from those previously found for isolates from children with acute respiratory tract infections in Pakistan, for which encapsulated H. influenzae strains other than serotype b were not observed; 95% of type b isolates were of a single OMP subtype; and nontypable isolates showed evidence of clonal restriction. Candidate vaccines for use in developing countries as protection against disease caused by H. influenzae will need to include both capsular and noncapsular antigens and investigators must take into consideration regional differences among strains. 
1	Orofacial metastasis of pulmonary giant cell carcinoma. A patient was admitted to the hospital with multiple skin nodules of recent origin and signs and symptoms suggestive of acute pulmonary infection. Because one of the skin masses was located overlying the left mandibular body region, the patient was referred to the hospital dentistry clinic for evaluation. Historical, clinical, and radiographic assessments were consistent with reactive lymphadenopathy, and an intraoral excisional biopsy was performed. The biopsy results were indicative of giant cell carcinoma, which was confirmed by biopsy results from a similar skin lesion on the shoulder and by malignant cells recovered in the sputum and pleural fluids. Although this carcinoma has been shown to rarely metastasize to the skin and lymphatics of the neck, this is the first case report of metastasis to facial lymphatics. 
5	Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. Inadequate tissue oxygenation may occur in critically ill patients with sepsis despite an apparently adequate O2 transport (QO2), and this may contribute to the development of an O2 debt and also to multiple organ failure. It has been shown that increasing QO2 by infusing a vasodilator may reveal this O2 debt in septic patients. To investigate whether the site of action of vasodilators may be of importance in unmasking such an O2 debt, we administered prostacyclin, a prostaglandin with a preferential effect on the microcirculation, and phentolamine, an arteriolar vasodilator, in 11 patients studied during the first 48 hours after the onset of sepsis, and compared their effect on whole body oxygen consumption (VO2) and skin microvascular blood flow. The results demonstrated that increasing QO2 by prostacyclin but not by phentolamine significantly increases VO2 in critically ill patients with sepsis. The site of action of vasodilators may therefore play an important role in their ability to unmask an O2 debt. 
2	Development of multiple necrotizing enteritis induced by a tumor necrosis factor-like cytokine from lipopolysaccharide-stimulated peritoneal macrophages in rats. We report the development of an animal model of multiple necrotizing enteritis (MNE) in rats. When rats were injected directly with a culture supernatant of lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages into the abdominal aorta, the overt pathologic lesions of MNE developed within 30 minutes after injection. The rats showed an elevated level of blood fibrinogen degradation product content even 30 minutes after injection. Furthermore the rats that were pretreated intravenously with heparin sulfate did not develop MNE, indicating the acute disturbances of blood microcirculation in the intestine. Multiple necrotizing enteritis was developed also by the injection with recombinant tumor necrosis factor (rTNF) but rarely was observed with even a high dose of recombinant interleukin-1 (rIL-1) or platelet-activating factor (PAF). The supernatant was cytotoxic in vitro to TNF-susceptible LM and many other cells but was less cytotoxic to the TNF-resistant LR line. Partial purification of the supernatant suggested that the supernatant contained a cytokine that has biochemical features of TNF. Furthermore polyclonal anti-TNF antibody could inhibit not only the cytotoxicity in vitro but also MNE development in vivo by this factor. These data strongly indicate that MNE possibly could be caused by a TNF-like cytokine produced by macrophages that are stimulated by the endotoxin. 
5	Mycobacterium chelonei keratopathy with visual rehabilitation by a triple procedure. We report a chronic keratouveitis following an eye injury, the etiology of which remained obscure despite repeated corneal scrapings and cultures. Eventually, the diagnosis was established by culturing Mycobacterium chelonei from a corneal biopsy specimen. Topical amikacin resolved active inflammation, but dense corneal scarring and a cataract remained. Visual rehabilitation was achieved through a combined penetrating keratoplasty, extracapsular cataract extraction, and intraocular lens implantation. This case illustrates that there should be a high index of suspicion of atypical mycobacteria when faced with any unusual keratitis, particularly following penetrating injuries and corneal grafts. 
4	Fetal and maternal response to intravenous infusion of a thromboxane synthetase inhibitor. Pharmacologic inhibition of thromboxane synthetase activity has reversed the clinical manifestations of toxemia in the ovine model. To investigate placental transfer and fetal effects of a selective thromboxane synthetase inhibitor, CGS13080 (Ciba-Geigy, Summit, N.J.) was intravenously infused into eight singleton- or twin-bearing ewes near term. During CGS 13080 infusion (0.1 mg/kg/hr), maternal steady-state CGS 13080 levels of 102 +/- 18 ng/ml were achieved within 30 minutes and maternal serum thromboxane generation decreased significantly (13 +/- 3 to 4 +/- 1 ng/ml). However, fetal serum levels of CGS 13080 were only 4% of peak maternal concentrations and fetal serum thromboxane generation did not change. There was no evidence of change in uterine blood flow, maternal or fetal blood pressure, heart rate, blood gas values, or fetal or maternal metabolites of prostacyclin or prostaglandin E2 during the study. We speculate that CGS 13080 may be efficacious in the treatment of human pregnancy-induced hypertension. 
4	Emergency cardiopulmonary bypass support in patients with cardiac arrest. Emergency percutaneous cardiopulmonary bypass support was instituted in 11 patients in cardiac arrest refractory to conventional resuscitation measures. Emergency percutaneous cardiopulmonary bypass support was used in five patients in whom cardiac arrest occurred as a result of a complication in the cardiac catheterization laboratory (group 1) and in six other patients in cardiac arrest (group II). A 21F cannula and a 17F cannula were percutaneously inserted into the femoral vein and artery. Flow rates of 3 to 5 L/min were achieved with restoration of mean arterial pressure to 70 mm Hg (range 50 to 75). The status of all 11 patients was improved initially both clinically and hemodynamically with percutaneous cardiopulmonary bypass. Of the group II patients, three had anatomy unsuitable for percutaneous transluminal coronary angioplasty or coronary bypass grafting, could not be weaned from cardiopulmonary support, and died; three of these patients had coronary artery bypass grafting and two survived. All five group I patients underwent successful coronary bypass grafting and survived. Of the seven patients with anatomically correctable disease, all seven were discharged from the hospital. With conventional management nearly all seven of these patients would have died. Nine of 11 patients underwent a cardiac operation and seven of the nine survived. The operative mortality rate was 22% and the overall survival rate was 64%. At follow-up (mean 7 months), all seven patients are alive and six have resumed a normal and active life-style. In conclusion, emergency percutaneous cardiopulmonary bypass support is a powerful resuscitative tool that may stabilize the condition of patients in cardiogenic shock and cardiac arrest to allow for definitive intervention. 
1	Neuroendocrine carcinoma of the ampulla of vater. A case of absence of somatostatin in a vasoactive intestinal polypeptide-, bombesin-, and cholecystokinin-producing tumor. A 31-year-old patient with a clinical picture of obstructive jaundice had surgical treatment, and a primary carcinoid of the ampulla of Vater (VA) was found. The tumor was studied with light microscopy, immunohistochemistry, and electron microscopy. The neoplasm had histopathologic and cytopathologic features similar to those encountered in typical neuroendocrine neoplasms. It is interesting that immunohistochemical techniques disclosed the presence of vasointestinal polypeptide, cholecystokinin, and bombesin; however, unlike most neuroendocrine neoplasms arising in VA, no somatostatin-immunoreactive cells were found. 
5	Acute sensorineural deafness in Lassa fever A prospective audiometric evaluation of 69 hospitalized febrile patients in Sierra Leone, West Africa, revealed a sensorineural hearing deficit (SNHD) in 14 (29%) of 49 confirmed cases of Lassa fever and in 0 of 20 febrile controls. An SNHD was present in nine (17.6%) of 51 people who had evidence of previous Lassa virus infection. Twenty-six of 32 local residents who had previously sustained a sudden deafness had antibody titers to Lassa virus of 16 or greater, compared with six of 32 matched controls. Lassa fever is associated with an incidence of SNHD, which considerably exceeds that previously reported with any other postnatally acquired infection, and accounts for a prevalence of virus-related hearing impairment in the eastern province of Sierra Leone that is greater than that reported from anywhere else in the world. 
1	The incidence and prognostic significance of humoral hypercalcemia in renal cell carcinoma. This retrospective study was conducted to evaluate the incidence and prognostic significance of humoral hypercalcemia in 218 renal cell carcinoma patients during the last 20 years. Of 218 patients 20 (9.2%) were hypercalcemic, with serum calcium levels ranging from 10.7 to 16.0 mg./dl. The respective incidence of humoral hypercalcemia was 3% in patients with stage I, 5.9% with stage II, 14.1% with stage III and 18.9% with stage IV disease without bone metastasis. The survival curves between the hypercalcemic and eucalcemic groups among stages I to III cancer patients showed no statistical significance (p greater than 0.05). The survival curve deteriorated significantly in stage IV cancer patients with humoral hypercalcemia (p less than 0.005), with a median survival of 45.0 +/- 39.7 days versus 286.4 +/- 27.6 days in eucalcemic patients. No specific correlation was found between pathological cell type and humoral hypercalcemia. 
2	Alanine-based oral rehydration therapy for infants with acute diarrhea. Twenty male infants less than 1 year of age with acute diarrhea and dehydration were randomly assigned to a study group and studied in blind fashion in a metabolic unit to assess the efficacy of the addition of 30 mmol/L alanine to the standard World Health Organization (WHO) oral rehydration solution (ORS). Patients were exclusively rehydrated with one of two types of ORS during the first 24 hours of treatment. On the second day, oral feedings were started with a lactose-free formula, and ORS was given to replace stool losses. Body weight, ORS, food intake, vomitus, stool, and urine output were recorded at 6-hour intervals. Blood was drawn at the time of admission, after rehydration, and at 24 and 48 hours of hospitalization to monitor blood gases and electrolytes. Rehydration was satisfactory in both groups of patients. ORS that contained alanine did not reduce the purging rates of the infants compared with those who received standard ORS. Clinically no adverse effect of the alanine-based ORS was observed during hospitalization. None of the patients had significant hypernatremia or hyponatremia, and serum amino acid levels were not altered. These data show that the addition of 30 mmol/L alanine to the standard WHO-ORS produces no further improvement in the outcome of the infants with acute diarrhea compared with those fed the standard WHO-ORS. 
4	Oral contraceptives, lipoproteins, and atherosclerosis. A nonhuman primate model was developed to study the effects of oral contraceptives on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The first study compared a vaginal ring containing levonorgestrel and estradiol with an oral contraceptive containing norgestrel and ethinyl estradiol. A second study compared two oral combinations: norgestrel-ethinyl estradiol and ethynodiol diacetate-ethinyl estradiol. As predicted, use of all the contraceptives led to lowering of high-density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing oral contraceptives did not lead to an increase in the prevalence or extent of atherosclerosis. We concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of oral contraceptives. 
3	Psychological stress and the fibrositis/fibromyalgia syndrome. The relationship of stress and social support to the fibrositis/fibromyalgia syndrome (FS) was investigated by administration of 4 questionnaire instruments to 28 patients with FS, 20 patients with rheumatoid arthritis (RA) and 28 pain-free normal controls. FS showed higher levels of stress as measured by daily "hassles" than did RA or controls. However, on a measure of major life stress, they reported lower levels. No differences were found between groups with regard to daily "uplifts" or social support. Correlations between those measures of stress and social support with their scores on the Arthritis Impact Measurement Scale showed that the Hassles Scale was significantly related to the AIMS Psychological component. 
5	Sumatriptan in acute migraine: pharmacology and review of world experience. The introduction of sumatriptan, a novel abortive antimigraine agent, has generated a significant amount of preclinical and clinical interest during the past few years. At the scientific level, sumatriptan is unique in terms of its selective pharmacological properties. The effects of sumatriptan in various experimental paradigms have led to new insights into the pathophysiology of migraine. At the clinical level, sumatriptan appears to be an effective abortive anti-migraine agent with minimal side effects. Its ability to decrease, rather than exacerbate, the nausea and vomiting of migraine appears to be an important advance in the treatment of migraine. 
3	Neurological and ophthalmological phenomena after aortic conduit surgery. Transient neurological and visual signs have been observed in some patients after valved conduit replacement of the aortic valve and ascending aorta. Twenty-seven patients having valved conduit replacement between February 1982 and October 1988 were compared with 21 patients having combined aortic valve replacement (AVR) and ascending aorta (AA) graft replacement. Follow-up in 100% of both groups was obtained for 0.3-6.6 years (mean, 2.6 +/- 0.3 years). Among 20 surviving valved conduit patients, 10 (50.0%) experienced repetitive neurological and visual signs, including scotomata (seven), transient motor ischemic attacks (two), amaurosis fugax (four), and recurring attention lapses suggesting petit mal seizures (one). No patient with AVR + AA graft experienced any events (p = 0.004). All valved conduit and seven (53.8%) of AVR + AA graft patients were on warfarin (p = 0.0016). These events retained the same pattern although they diminished in frequency after 12 months in seven patients (70.0%) and after initiation of dipyridamole in two patients. Rehabilitation was similar in both groups: 18 of 20 (90.0%) valved conduit and 12 of 16 (75.0%) AVR + AA graft patients (p = NS). Transient, repetitive, nonprogressive neurological and ophthalmological phenomena are frequent after valved conduit replacement. The pathophysiological mechanism is unclear, but antiplatelet therapy may provide symptomatic control. 
1	Needle-localized mammographic lesions. Results and evolving treatment strategy. From January 1981 to December 1987, 932 needle-localization breast biopsies were performed at our institution for mammographically detected abnormalities. We reviewed 531 needle-localization breast biopsy procedures performed during two periods (January 1981 to June 1984, n = 311; and January to August 1987, n = 220) to compare results and treatment patterns, and to determine the prevalence of the missed lesions. Mammographic abnormalities detected on routine screening accounted for a larger proportion of needle-localization breast biopsies in the later series (94 [30%] of 311 vs 94 [43%] of 220). However, the rate at which carcinoma was identified remained constant at 29% as did the percentage of cancers that were invasive (46% vs 51%). Overall, the rate of malignant diagnoses after needle-localization breast biopsy was lowest in asymptomatic women undergoing routine screening mammography (44 [24%] of 188) and significantly higher in women undergoing mammographic follow-up of the contralateral breast after treatment for breast cancer (28 [43%] of 65). There were seven missed lesions in 531 needle-localization breast biopsies, necessitating a second procedure in six and interval mammograms in one. 
4	Prevention of cardiovascular disease: risks and benefits of aspirin. Aspirin has been tested for its benefit in preventing cardiovascular disease in randomized trials in three categories of patients. In secondary prevention among those with a history of myocardial infarction (MI), stroke or transient cerebral ischemia, or unstable angina pectoris, 25 randomized trials demonstrated significant reductions from aspirin of 25% for the occurrence of an "important vascular event" (nonfatal MI, nonfatal stroke, or vascular death), 32% for nonfatal MI, 27% for nonfatal stroke, and 15% for vascular mortality. Among those evolving an MI, the Second International Study of Infarct Survival (ISIS-2) showed a significant reduction of 23% in five-week vascular mortality among those started on a one-month regimen of daily aspirin within 24 hours of the onset of symptoms of suspected MI. Aspirin also significantly reduced reinfarction, nonfatal stroke, and important vascular events. Finally, in primary prevention, the US Physicians' Health Study (PHS) showed a significant 44% reduction in the occurrence of a first MI among apparently healthy male physicians; numbers of strokes and vascular deaths were insufficient to permit conclusions for these endpoints. Thus, aspirin is of clear benefit in reducing MI, stroke, and vascular death in secondary prevention and among those evolving an MI. It is also beneficial in the primary prevention of MI among men over 40, but data concerning its effects on stroke and vascular death remain inconclusive. 
5	Susceptibility to effects of UVB radiation on induction of contact hypersensitivity as a risk factor for skin cancer in humans. Normal, healthy human volunteers and patients with proved history of non-melanoma skin cancer have been tested for their capacity to develop contact hypersensitivity to dinitrochlorobenzene (DNCB) following exposure of buttock skin to acute, low-dose ultraviolet B (UVB) radiation. Using a radiation protocol that achieves virtually complete depletion of normal-appearing Langerhans cells from irradiated skin, it was learned that approximately 60% of healthy volunteers developed vigorous contact hypersensitivity (CH) when 2000 micrograms DNCB was painted on the irradiated site. These individuals were designated UVB-resistant, and were distinguished from other individuals, designated UVB-susceptible, who failed to develop contact hypersensitivity following an identical treatment protocol. It was then discovered that virtually all (92%) skin cancer patients exposed to UVB and DNCB failed to develop CH, i.e., were UVB-susceptible. In subsequent experiments, epicutaneous application of 2000 micrograms DNCB to unirradiated skin of UVB-susceptible individuals revealed a further distinction between normal persons and skin cancer patients. Approximately 45% of the latter (and none of the former) remained unresponsive (failed to develop contact hypersensitivity following this second attempt at sensitization), implying that they had been rendered immunologically tolerant. These tolerant individuals responded normally to the unrelated hapten, diphencyprone. We conclude that human beings resemble inbred strains of laboratory mice in that some individuals are UVB-susceptible, whereas others are UVB-resistant. Because the incidence of UVB-susceptibility was significantly higher in skin cancer patients, and as specific unresponsiveness could be demonstrated only in these patients, we propose that UVB-susceptibility, as we define it in this hapten system, may be a risk factor for the development of skin cancer. 
3	Rehabilitation of the pediatric patient with a neuromuscular disease. A rehabilitation program for a patient with a neuromuscular disease can be developed only after an accurate diagnosis has been established. The diagnosis and its ramifications should suggest a natural course of disease which, it is hoped, can be improved upon with a rational and realistic program. The program is best developed by an interdisciplinary team, including a pediatric neurologist, who should have the greatest understanding of the patient's problem and should ultimately be responsible for the implementation and monitoring of the program. A child with cerebral palsy commonly requires the services of physical and occupational therapists as well as knowledgeable orthopedists. Is the program appropriate? Does it consider the child's potential as well as his limitations? A child with a traumatic brain injury requires, in addition to the above, psychological intervention and an intensive educational program. Will the child and family need help from mental health professionals? A child with a motor unit disease such as Duchenne's muscular dystrophy requires, in addition to the above services, a "philosophy" of care. Will the child ever ambulate independently? If so, at what cost? What will be necessary for the child to reach this potential, including items such as orthoses and adaptive equipment? Will respirator care become necessary? What issues must be addressed for this form of care to be established? There is no one program for all children. The programs must be individualized to meet the needs of the patient and the family. This point cannot be overemphasized. 
4	Acute respiratory failure caused by pulmonary vasculitis after L-tryptophan ingestion. This report describes two women who presented with severe respiratory failure and diffuse pulmonary infiltrates in the fall of 1989. Both required prolonged assisted ventilation because of severe shunt physiology. Open lung biopsies on admission revealed a small vessel vasculitis as the sole morphologic abnormality in both patients. Both responded to high dose corticosteroids. Neither patient exhibited evidence of systemic vasculitis, and neither had serologic evidence of an immune disorder. Common to both patients was ingestion of L-tryptophan. One patient exhibited several features of the eosinophilia-myalgia syndrome. The other patient did not appear to have the syndrome, but the temporal relationship between the onset of symptoms and initiation of L-tryptophan treatment was striking. The presentation of these patients alters our notions concerning the spectrum of clinical manifestations caused by this agent, and the response to methylprednisolone supports its efficacy in the treatment of this disorder. 
5	Elective resection of 332 abdominal aortic aneurysms in a southern West Virginia community during a recent five-year period. This study analyzed 33 variables that might potentially affect outcome in a series of 332 consecutive elective abdominal aortic aneurysm repairs in a southern West Virginia community. One of the interesting features of this series was that the repairs were done by 22 surgeons with varying degrees of experience. The mortality and complication rates were compared for various potential risk factors by both univariant methods (chi 2, Fisher's exact, and Student t tests) and multivariant methods of analysis. Our early mortality (2.1%) and postoperative complication rates were consistent with those of other series. With multiple linear regression models, five factors were selected as significant independent risk factors associated with an increasing number of postoperative complications: the number of blood transfusions (p less than 0.0001), left renal vein ligation (p less than 0.0001), the presence of greater than 50% renal artery stenosis (p = 0.0012), the lesser experience of the surgeon (p = 0.0203), and the history of prior cardiac catheterization (p = 0.0245). The only factor statistically correlated with mortality rate was an increased number of postoperative complications (p less than 0.0001). Neither postoperative complications nor mortality rate was found to be significant and independently influenced by other demographic, clinical, or operative factors. It is tempting to speculate that surgeons with less experience might be well served to refer patients with significant renal artery stenosis and coronary artery disease. Our mortality and complication rates were not increased by performing preoperative angiography and therefore prudent surgeons may find this helpful in selecting patients for safer repair. 
5	Sincalide-aided ultrasonography of the common bile duct as a predictor of biliary obstruction determined by ERCP and biliary manometry. Sonographically observed changes in common bile duct caliber following intravenous sincalide injection were correlated with distal common duct pathology as defined by endoscopic retrograde cholangiopancreatography and biliary manometry. Thirty-two patients, 17 with prior cholecystectomies, were studied. In post-cholecystectomy patients, a 1-mm or greater diminution of duct caliber within 5 min represented a normal response. When gallbladder contraction occurred in normal patients with an intact gallbladder, no change or a diminution in duct caliber was observed. When gallbladder contraction was not observed, a normal response was considered to be the same as that in post-cholecystectomy patients with a diminution in duct caliber occurring. By using these criteria two false negatives, both with hypertensive sphincters of Oddi that responded normally to sincalide injection, were encountered. This technique was valuable in defining non-obstructed post-cholecystectomy dilated bile ducts which demonstrated a prompt diminution in caliber following sincalide injection. 
5	Management of acute uncomplicated urinary tract infection in adults. Acute uncomplicated UTI is one of the most common problems for which young women seek medical attention, and it accounts for considerable morbidity and health care costs. Acute cystitis is a superficial infection of the bladder mucosa, whereas pyelonephritis involves tissue invasion of the upper urinary tract. Localization tests suggest that as many as one third of episodes of acute cystitis are associated with silent upper tract involvement. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials. Because of the superficial nature of cystitis, single-dose and 3-day regimens have gained wide acceptance as the preferred methods of treatment. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole appear to be more effective than those with beta-lactams, regardless of the duration. Acute pyelonephritis does not necessarily imply a complicated infection. Upper tract infection with highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, and 14-day regimens are often used. We prefer to use antimicrobials that attain high renal tissue levels, such as trimethoprim-sulfamethoxazole or quinolones, for pyelonephritis. Women with frequently recurring infections can be successfully managed by continuous prophylaxis, either daily or thrice-weekly, by postcoital prophylaxis, or, in compliant patients, by early self-administration of single-dose or 3-day therapy as soon as typical symptoms are noted. Our drug of choice for all these regimens is trimethoprim-sulfamethoxazole. Acute uncomplicated cystitis in adult men is very uncommon, but it is occasionally noted in homosexual men who practice insertive and intercourse or in heterosexual men whose partners have vaginal colonization with E. coli. 
1	Differentiation in embryonal neuroepithelial tumors of the central nervous system. Ninety-six embryonal neuroectodermal tumors were studied histologically and immunohistologically with a panel of antibodies including glial, neuronal, epithelial, mesodermal, and myelin markers. In 71 tumors there was glial and neuronal differentiation and expression both of an S (photoreceptor) antigen and vimentin. In five tumors there was only glial differentiation and in 20 tumors only neuronal differentiation. No reactivity for myelin and epithelial markers was found. Histologic and immunohistologic findings identified various degrees of differentiation in different tumors, which was bipolar (glial and neuronal) in most tumors and unipolar in the remainder. The authors suggest that their findings may be the result of normal or aberrant oncogenic differentiation, agreeing with the nomenclature of the World Health Organization classification for these tumors with and the inclusion of a category for ependymoblastoma. 
5	Selective myectomy for postparetic facial synkinesis. Synkinetic movements are secondary to facial palsy because they appear like a late sequela to spontaneously healing facial nerve injury. They are produced by an involuntary contraction of a muscle group simultaneous with contraction of other homologous muscle groups. The disorderly regeneration of severed axons is responsible for these movements. According to the Lippschitz theory, the regenerating nerve fibers sprout into the wrong peripheral branches. Between 1975 and 1986, 71 patients with facial paralysis were evaluated. Spontaneous recovery from the facial paralysis occurred in 28 of these patients; 14 (50 percent) developed synkinetic movements, and surgical treatment was sought by only 6 patients. In all patients, the lesion of the facial nerve was in the trunk, proximal to the principal ramification. The most frequent clinical finding was simultaneous activation between the orbicularis oculi and the elevators of the corner of the mouth (12 patients) or the elevators of the upper lip (2 patients). In 8 patients, in whom the slight synkinesis was not noticed by the patients, surgical correction was not necessary, but in the other 6 patients with severe aesthetic disturbances, surgical treatment for "disconnection" of the wrong impulses was realized. I obtained this "disconnection" through resection of the involved perioral muscle groups instead of paralysis of the orbicularis oculi. Follow-up of the 6 patients operated with the surgical treatment proposed herein for between 4 and 8 years has shown good aesthetic results without functional or aesthetic sequelae. 
1	The use of interferon alpha-C in patients with metastatic renal cell carcinoma arising in a congenital solitary kidney. Three cases of renal cell carcinoma in a congenital solitary kidney are presented. Treatment with recombinant interferon alpha-C was administered in two cases. A subjective response occurred in one case. The literature is reviewed with respect to treatment options and prognostic factors. 
4	Major depression, panic disorder, and mitral valve prolapse in patients who complain of chest pain. PURPOSE: Patients with chest pain but without angiographic evidence of significant atherosclerotic coronary artery disease (CAD) are often found to have other medical or psychiatric disorders, including mitral valve prolapse, panic disorder (PD), and major depressive disorder (MDD). The purpose of this study was to determine the degree of comorbidity between MDD/PD and mitral valve prolapse in a group of patients with non-CAD chest pain. PATIENTS AND METHODS: Patients referred for cardiac catheterization and coronary angiography for suspected CAD who were 70 years of age or younger and without other significant medical illnesses or cardiac complications were eligible for study. The first 100 patients who agreed to a psychiatric diagnostic interview were recruited. RESULTS: Forty-eight of the 100 patients were found to be without significant CAD. Forty-two percent of these patients, compared to 19% of the patients with significant CAD, were found to have either MDD, PD, or both. Eighty percent of the patients without CAD who had mitral valve prolapse also had either MDD or PD (p less than 0.006). CONCLUSIONS: The finding that mitral valve prolapse was significantly associated with MDD/PD has implications for the diagnosis and treatment of patients with non-CAD chest pain, and may explain why these patients complain of symptoms. 
3	Heart rate changes as an autonomic component of the pain response. Autonomic variables have been recommended as measures of the affective-motivational component of the pain response in objective algesimetry. In the present study components of heart rate responses to painful heat stimuli and their relation to stimulus and sensation variables were analyzed. Twelve healthy subjects served. Sixty phasic stimuli of varying temperatures above and below pain threshold were delivered through a Marstock thermode in 1 session. Heart rate, respiration, and subjective stimulus ratings were recorded simultaneously. Phasic heat stimulation above and below pain threshold induced a tonic increase of the heart rate lasting up to more than 20 sec. High intensity stimulation generated steeper rises and greater mean increase than low intensity stimulation. In general, heart rate responses were more closely related to subjective sensation than to stimulus intensity. However, differential temporal analysis demonstrates that, until about 3 sec after stimulation, the autonomic response is determined solely by stimulus temperature, whereas, after approximately 6 sec, it is related only to subjective judgement. Accordingly, the heart rate responses reflect both a brief nocifensive reflex induced by the sensory component and, subsequently, a longer-lasting response which seems to be related to affective and/or cognitive evaluation. This separation of different stages of pain-processing by an autonomic indicator may be useful in clinical algesimetry. 
1	Selenium. Nutritional, toxicologic, and clinical aspects Despite the recent findings of environmental contamination, selenium toxicosis in humans is exceedingly rare in the United States, with the few known cases resulting from industrial accidents and an episode involving the ingestion of superpotent selenium supplements. Chronic selenosis is essentially unheard of in this country because of the typical diversity of the American diet. Nonetheless, because of the growing public interest in selenium as a dietary supplement and the occurrence of environmental selenium contamination, medical practitioners should be familiar with the nutritional, toxicologic, and clinical aspects of this trace element. 
2	The peritoneal environment during infection. The effect of monomicrobial and polymicrobial bacteria on pO2 and pH. Intraperitoneal (IP) abscesses frequently are composed of aerobes and anaerobes, and, in experimental models, a particulate adjuvant. The environmental changes effected by these components, either singularly or in combination, have not been well defined. The IP pO2, pH, and recoverable bacteria from the peritoneum of rats were quantified over 6 hours during simple aerobic and anaerobic infections and during mixed peritonitis with and without a sterile feces-barium sulfate adjuvant (SFA). Fourteen groups were studied, receiving intraperitoneally, at time of oxygen probe placement, 1 mL normal saline (control), Escherichia coli (EC), Bacteroides fragilis (BF), SFA alone, or a mixture of EC and BF, EC and SFA, BF and SFA, or EC, BF, and SFA. Control animals exhibited a stable IP pO2 and pH during 6 hours. In monomicrobial EC peritonitis, inocula well below the LD50 produced an increased IP pO2 and reduced arterial-peritoneal gradient (APG), with a stable IP pH. By 6 hours lethal doses of EC produced a dramatic decline in IP pO2, with no change in arterial pO2 as well as acidic IP and arterial pHs. Simple BF peritonitis caused no or minor elevations in IP and arterial pO2 with no change in pH. During mixed infections a significant decline in the IP pO2 and pH at 6 hours in those groups infected with both SFA and EC of a moderate, normally sublethal inoculation was observed, while arterial pO2 was unchanged and arterial pH was decreased only slightly. Concomitantly there was a significant increased number of aerobic bacteria in those groups with SFA as adjuvant compared to similar inocula without SFA. This study demonstrates the complex interactions of bacteria, sterile particulate adjuvant (SFA), and the host peritoneum. It suggests that the combination of SFA and aerobic bacteria alter the peritoneal environment to one permitting anaerobic growth and promoting abscess formation. 
1	Adjuvant, specific, active immunotherapy for resectable squamous cell lung carcinoma: a 5-year survival analysis. In 1976 Stewart et al. (Annals of the New York Academy of Sciences 277:436-466) reported the effectiveness of adjuvant specific active immunotherapy of lung carcinoma in improving the postoperative survival of stage I lung carcinoma patients in a phase II study using lung carcinoma-associated antigen (TAA) and complete Freund's adjuvant (CFA). A phase III study was then designed by the authors to see the effects of specific active immunotherapy compared to the conventional management (no treatment) and to nonspecific immunotherapy. From 1976 to 1981, 85 patients with resectable (stages I and II) squamous cell lung carcinoma were entered into a randomized study: 1) control group; 2) specific immunotherapy group--three monthly doses of 500 micrograms of TAA emulsified with CFA; 3) nonspecific immunotherapy group--three monthly doses of CFA emulsified in saline. All the patients in the study received skin tests with 100 micrograms of the same TAA used for the immunotherapy. Recently, a 5-year follow-up of all the patients became available: The life table 5-year survival of group 1 was 34%, of group 2 was 75%, and of group 3 was 53%. The median survivals for the three groups were group 1, 38 months; group 2, 106 months; and group 3, 71 months. The difference was significant at P = .007 (Cox-Mantel test). 
1	Tumor-antigen 4. Its immunohistochemical distribution and tissue and serum concentrations in squamous cell carcinoma of the lung and esophagus. The immunohistochemical distribution and concentrations of tumor-antigen 4 (TA-4) in tissues and serum were determined in patients with benign and malignant diseases, including 27 patients with squamous cell carcinoma (SCC; 15 in the lung and 12 in the esophagus). Tumor-antigen 4 immunoreactivity was present in the cytoplasm of many SCC tissues, especially in the hyperparakeratotic region, and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs, but not in those of other types of lung cancers or benign pulmonary diseases. Consistent with the results of immunostaining, the TA-4 concentrations in SCC tissues of the lung, esophagus, and normal squamous epithelia were much higher than in those of lung cancer other than SCC, benign pulmonary diseases, normal lung, and submandibular gland tissues. The TA-4 concentration in SCC tissue tended to increase with increasing grades of differentiation. Serum TA-4 was elevated in 15 of 27 patients with SCC but in no patients with other types of lung cancer or benign diseases. These results indicate that TA-4 is an antigen related to the differentiation of squamous cells and that tumor cells of SCC can release a large amount of TA-4 into circulation whereas normal squamous epithelia cannot. 
2	Incontinence and rectal prolapse: a prospective manometric study. A prospective, manometric study has been performed on 23 female patients with rectal prolapse and varying degrees of incontinence. Seven of the 14 incontinent patients regained continence after surgery, and a further two patients improved. Improvement in internal and external sphincter function follows correction of rectal prolapse. Preoperative resting anal pressure was significantly higher in continent patients than in incontinent patients (P less than 0.05), as was the maximum voluntary contraction pressure (P less than 0.027). Postoperatively there was a significant increase in the resting anal pressure (P less than 0.0001) and maximum voluntary contraction pressure (P less than 0.003) in the whole group. The preoperative resting anorectal angle was significantly more acute (P less than 0.028) in continent patients than in incontinent patients. There was no significant change in the resting anorectal angle following prolapse repair. Patients who remained incontinent had a significantly lower preoperative resting anal pressure (P less than 0.01) than patients who improved or regained continence. Similarly, maximum voluntary contraction pressure was lower preoperatively in these patients (P less than 0.02). Preoperative resting anal pressure below 10 mm Hg and maximum voluntary contraction pressure below 50 mm Hg are associated with persisting incontinence after surgery. 
4	Naloxone and spinal fluid drainage as adjuncts in the surgical treatment of thoracoabdominal and thoracic aneurysms. Forty-seven patients who were treated for thoracoabdominal or thoracic aneurysms over a 5 1/2-year period were analyzed for neurologic deficit risk. Patients were divided into two groups for analysis. Twenty-four patients, who were treated from January 1984 to December 1986, did not undergo spinal fluid drainage or naloxone administration (group A). Twenty-three patients, who were treated from January 1987 to August 1989, had spinal fluid drainage (group B); 12 patients in this group also received naloxone as an intravenous drip at 1 microgram/kg/hr for 48 hours after surgery. Permanent neurologic deficits occurred in seven (29%) group A patients but in only one (4%) group B patient, who did not receive naloxone (p less than 0.03). The first two group B patients to receive naloxone showed complete reversal of neurologic deficits on waking from anesthesia. This significant reduction in neurologic deficit was associated with an increased 1-year survival rate (72% in group A, 91% in group B). We conclude that the use of naloxone and spinal fluid drainage reduces the incidence of neurologic deficit that is associated with repair of thoracoabdominal and thoracic aortic aneurysms. This reduction in neurologic deficit is associated with improved survival in the long term. The observed reversal of postoperative neurologic deficits with naloxone implicates opiates as a major factor in the pathophysiology of spinal cord ischemia. 
3	Experimental nerve root compression. A model of acute, graded compression of the porcine cauda equina and an analysis of neural and vascular anatomy. Nerve root compression has been suggested as one important pathogenetic factor in low-back pain syndromes and sciatica. The underlying pathophysiologic mechanisms are, however, incompletely known, partly because of the lack of experimental data on this topic. In the present study, a model for experimental compression of the porcine sacrococcygeal cauda equina is presented. The model consists of surgical exposure of the cauda equina and compression of the cauda equina toward the ventral aspect of the spinal canal by an inflatable balloon fixed to the spine. This compression system was shown to have a high accuracy in pressure transmission from the balloon to the cauda equina. The gross and microscopic neural anatomy and the vascular anatomy of the porcine cauda equina were analyzed with light microscopic and ink-perfusion techniques. The porcine cauda equina showed a close anatomic resemblance to the human lumbosacral cauda equina. The presented model offers unique possibilities for experimental studies on nerve root compression injury because of the easy surgical exposure and the sufficient length of the nerve roots. In separate studies, this model, along with investigations of solute transport to the nerve tissue and of impulse propagation, has been used to analyze the effects of acute, graded compression on blood flow and edema formation in the cauda equina. The porcine cauda equina would also be particularly suitable for chronic compression studies because any neurologic deficit acquired would be restricted to the tail. 
4	Stridor: intracranial pathology causing postextubation vocal cord paralysis. During an 18-month period in a pediatric intensive care unit, nine patients with vocal cord paralysis were identified using flexible bronchoscopy. When tracheally extubated, each child was found to have stridor. The children ranged in age from 17 days to 5 1/2 years. Two patients had unilateral paralysis, but neither required tracheostomy. Seven patients displayed bilateral abductor vocal cord paralysis. Of these, six patients required tracheostomy. Surgical injury to the recurrent laryngeal nerve was the probable cause in two patients. The other seven patients had neurologic disorders with documented or suspected increases of intracranial pressure. Four of the seven patients with bilateral abductor vocal cord paralysis regained cord mobility within 4 months. Both children with unilateral cord paralysis have no stridor and vocalize well 1 year later. Cord paralysis in the setting of intracranial hypertension probably results from compression or ischemia of the vagus nerve before it exits the skull. Early visualization of the larynx should be done in patients who become stridulous when extubated, especially those with prior thoracic procedures or with neurologic disorders associated with intracranial hypertension. 
2	Hypertrophic smooth muscle in the partially obstructed opossum esophagus. The model: histological and ultrastructural observations. Obstruction is a complication of many esophageal diseases, but the morphological changes occurring in the obstructed esophagus are poorly understood. We developed a model of esophageal obstruction in the American opossum, Didelphis virginiana. A nonconstricting band around the gastroesophageal junction led to esophageal distention and tortuosity in the weeks following its placement. Despite a marked increase of the esophageal circumference, the esophageal wall was not thinned, and the circular muscle layer had actually increased its thickness. This was due to an increase in the size of individual smooth muscle cells with proportional increases in the cell surface area and volume. The electron density of hypertrophic smooth muscle cells varied much more than that of normal esophageal smooth muscle cells. As cell size increased, the tissue became more compact and the size of the extracellular space decreased. Also, the extracellular space was filled by an amorphous electron-dense material. Additional changes in the structure of hypertrophic smooth muscle cells included prominent intermediate filaments in the vicinity of thick filaments. There was no difference in the structure of the hypertrophic smooth muscle at 4 weeks and at 8 weeks after placement of the band. The morphological features described here resemble those seen in human esophageal spasm and achalasia of humans and could affect esophageal smooth muscle function. 
5	Perinatal grief and mourning. The grief and mourning that parents experience following a perinatal loss is as devastating as the loss of an older loved one. The pattern of mourning can be anticipated and interventions can be implemented. With proper help, the parents can pass through this catastrophic time in their lives with a minimum of scars. If the physician stops, reaches out, listens, and supports the parents, he or she can have a dramatic effect on the lives of these parents. In the same manner in which we started this paper, we close with a quotation from another parent who suffered a loss: Daughters may die, But why? For even daughters can't live with half a heart. Three days isn't much a life. But long enough to remember thin blue lips, uneven gasps in incubators, Racking breaths that cause a pain to those who watched. Long enough to remember I never held her Or felt her softness Or counted her toes. I didn't even know the color of her eyes. Dead paled hands not quite covered by the gown she Was to go home in. Moist earth smell. One small casket. And the tears. You see, I hold in my hand but souvenirs of an occasion. A sheet of paper filled with statistics, A certificate with smudged footprints, A tiny bracelet engraved "Girl, Smith." You say that you are sorry That you know how I feel. But you can't know because I don't feel. Not yet. 
2	Nonsteroidal antiinflammatory drug-induced colonic strictures: a case report. Adverse effects of nonsteroidal antiinflammatory drugs can occur throughout the whole gastrointestinal tract. Recently, several cases of "diaphragmlike" thin ileal strictures have been reported. These strictures seem to result from nonsteroidal antiinflammatory drug-induced inflammatory changes and apparently represent a newly recognized nosological entity. The case of a 61-year-old man who gradually developed similar inflammatory changes in the ascending colon during prolonged intake of a slow-release form of diclofenac is presented, and the literature on nonsteroidal antiinflammatory drug-induced intestinal strictures is briefly reviewed. 
5	Fatal pulmonary venoocclusive disease secondary to a generalized venulopathy: a new syndrome presenting with facial swelling and pericardial tamponade. We describe a patient who developed fatal pulmonary artery hypertension secondary to diffuse venulitis. This otherwise healthy young woman first presented with generalized venulopathy, with chemosis, facial swelling, pleural effusions, and pericardial tamponade. The symptoms partially responded to steroid therapy, but over a 2-year course, a rapidly progressive and fatal venoocclusive disease developed. No other primary condition was diagnosed, and at autopsy, the patient had striking venulitis throughout, including the pulmonary bed. We believe that this is a unique case of pulmonary hypertension resulting from a generalized venulopathy. 
1	Expression of VHIII-associated cross-reactive idiotype on human B lymphocytes. Association with staphylococcal protein A binding and Staphylococcus aureus Cowan I stimulation. It has been demonstrated that staphylococcal protein A (SPA) has an "alternative" binding site with specificity for human Ig H chain V region of the VHIII subgroup. Because the major mitogenic component of Staphylococcus aureus Cowan I (SAC) is SPA, it is possible that SAC stimulates a subpopulation of B cells expressing Ig of the VHIII H chain subgroup. In the present study, we have investigated further the relationship between SPA binding and the expression of VHI- or VHIII-associated cross-reactive idiotype (CRI) on the surface of tonsillar B lymphocytes enriched for the expression or nonexpression of the CRI, and we examined the Ig secreted by cell lines established from these populations of B cells by EBV transformation. The VHIII CRI (D12)-enriched population yielded 21 cell lines, with 67% of them secreting SPA-reactive Ig; in contrast, only 6% (1 of 16) of VHI CRI-expressing lines secreted SPA-reactive Ig. The CRI-negative B cell population yielded 54 cell lines, of which 20% secreted SPA-reactive Ig, as might be anticipated because a majority of VHIII Ig+ B cells will be CRI-. SAC stimulation of CRI+ and CRI- populations showed preferential stimulation of the D12 population. These data support the proposal that SAC stimulation of human B cells is mediated through binding of SPA by its alternative binding site to IgV regions of the VHIII subgroup. 
4	Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS) Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic. 
3	The role of antihistamine therapy in vascular headaches. Migraine (vascular) headache is a complex syndrome that involves vascular hyperreactivity. The functions of systemic mediators in migraine are not fully understood. It is unclear which mediators provoke this probably atopic disorder and which represent an attempt to correct an imbalance. However, it has been demonstrated fairly conclusively that increased histamine levels correlate with migraine attacks in susceptible persons. Recent studies showing that histamine seems to have many different receptors and to adopt different conformations for different receptors may serve as a useful guide to future scientific investigation. Further impetus may come from ongoing studies of H3 histamine receptors, which indicate that H3 agonists offer promise as prophylactic agents for people who suffer from vascular headaches. 
2	Localization of calcitonin gene-related peptide in human esophageal Langerhans cells. Previously undescribed calcitonin gene-related peptide-immunoreactive intraepithelial cells were seen in specimens of esophageal mucosa obtained by biopsy or surgical resection from 14 individuals. These calcitonin gene-related peptide-immunoreactive cells were sparsely seen in normal mucosa but increased markedly in esophagitis. They were inaccessible to routine histological stains, but osmication showed them as dendritic forms resembling Langerhans cells of the skin. Their cytological identity was determined with immunocytochemical tests for human antigenic markers such as Ia, HLA-DR, and OKT6 for Langerhans cells, Leu-M5 and Leu-M3 for intraepithelial macrophages, CD3 and TCR-1 for T-lymphocytes, Leu-14 for B-lymphocytes, S-100 for Merkel cells, and chromogranin for amine precursor uptake and decarboxylation cells. Double localization showed that calcitonin gene-related peptide immunoreactivity colocalized with Ia, HLA-DR, and OKT6 but not with the other markers. These studies show that intraepithelial Langerhans cells in the esophageal mucosa contain calcitonin gene-related peptide, which may serve as an immunomodulator. 
1	Dacron fabric-enveloped hydroxyapatite prosthesis for sternal tumor defect: an autopsy report. A 38-year-old housewife with solitary plasmacytoma of the manubrium who underwent a subtotal sternectomy treated by resection of the lesion is reported. This was followed by replacement with a Dacron fabric-enveloped hydroxyapatite prosthesis. The Dacron fabric was sutured to the surrounding tissues, and then the clavicle was passed through the cylindrical-shaped Dacron fabric to form a sternoclavicular joint capsule. The patient returned to her daily life 3 months after the operation. She had no trouble in her daily living, without any dislocation of the sternoclavicular joints or any displacement of the artificial sternum. The autopsy examination about 1 year after the operation showed that the Dacron fabric enveloping the artificial sternum became stronger with time. The sternoclavicular joint also was stably fixed, and the Dacron fabric fulfilled its function as an artificial articular capsule and biologic fixation of the surrounding supporting tissues. 
2	Primary peritoneal sarcoidosis. A 14-year-old male was admitted for the evaluation of tense exudative ascites. Despite thorough evaluation, the diagnosis remained cryptic until peritoneoscopy revealed diffuse studding of the entire visualized peritoneum with multiple miliary nodules, and peritoneal biopsy demonstrated multiple noncaseating epithelioid granulomas. After other causes were excluded, a diagnosis of sarcoidosis was considered and confirmed with classic endobronchial findings at bronchoscopy. Involvement of the peritoneum with sarcoidosis is rare and, to our knowledge, only one other case describes this as the initial manifestation of this disease. 
5	Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs BACKGROUND AND METHODS: This study was designed to explore the effect of mild cerebral and systemic hypothermia (34 degrees C) on outcome after prolonged cardiac arrest in dogs. After ventricular fibrillation with no flow of 10 min, and standard external CPR with epinephrine (low flow) from ventricular fibrillation time of 10 to 15 min, defibrillation and restoration of spontaneous normotension were between ventricular fibrillation time of 16 and 20 min. This procedure was followed by controlled ventilation to 20 hr postarrest and intensive care to 72 hr postarrest. In control group 1 (n = 10), core temperature was 37.5 degrees C; in control group 2 (n = 10), cooling was started immediately after restoration of spontaneous normotension; and in group 3 (n = 10), cooling was initiated with start of CPR. Cooling was by clinically feasible methods. RESULTS: Best overall performance categories achieved (1 = normal; 5 = brain death) were better in group 2 (p = .012) and group 3 (p = .005) than in group 1. Best neurologic deficit scores were 36 +/- 14% in group 1, 22 +/- 15% in group 2 (p = .02), and 19 +/- 18% in group 3 (p = .01). Brain histopathologic damage scores were also lower (better) in groups 2 (p = .05) and 3 (p = .03). Myocardial damage was the same in all three groups. CONCLUSION: Mild cerebral hypothermia started during or immediately after external CPR improves neurologic recovery. 
1	A critical analysis of the largest reported mass fecal occult blood screening program in the United States. Fecal occult blood testing for the detection of colon cancer remains controversial. We performed a mass screening program from January 24, 1988, to February 19, 1988, with intensive media promotion, including 121 minutes of televised air time. A total of 5,000 primary practitioners were notified by mail. Hemoccult-II tests were distributed to 156,000 individuals; 55,051 (35%) were returned. Ninety-five percent of the respondents were informed of the program by television. A total of 3,375 persons (6%) tested positive for fecal occult blood; of these, 2,469 (73%) informed the center that they saw their physician to initiate a work-up. Information from physicians regarding work-ups was returned on only 1,356 (55%) patients. Diagnostic tests numbered 2,227 (1.6 tests per patient). However, 5% had no testing, 16% had a repeat Hemoccult only, and 35% had neither a barium enema nor colonoscopy performed. Thirty-six colorectal cancers and 212 polyps were identified. The predictive value (i.e., number of cancers per number of patients who tested positive) increased directly by decade. Thirty-three of 36 patients (92%) with cancer underwent either a barium enema or colonoscopy versus only 185 of 438 (42%) patients with a "negative" work-up. Cancers found were carcinoma in situ in 10 patients (29%), Dukes A in 12 (35%), Dukes B in 4 (12%), and Dukes C in 8 (24%); distant metastases were not found in any participant. Thirty-six percent of the tumors were located in either the right or transverse colon. We conclude that: (1) Screening identified early cancers. All were potentially curable and 64% were limited to the bowel wall. (2) Massive Hemoccult distribution was possible over a short interval, but patient and physician compliance was disturbingly low. (3) Total colonic evaluation is mandatory, since at least 36% of tumors were beyond the reach of the flexible sigmoidoscope. (4) Many work-ups were unnecessary (repeat Hemoccults) or inadequate, indicating a need for physician education. 
4	Long-term follow-up comparing subclavian flap angioplasty to resection with modified oblique end-to-end anastomosis The definitive surgical procedure for correction of aortic coarctation remains controversial. Therefore, we retrospectively reviewed a total of 56 children under 4 years of age with coarctation repair between 1977 and 1986. Thirty-four had the subclavian flap angioplasty technique and 22 had resection with oblique end-to-end anastomosis. The group was further subdivided to include only the 23 infants less than 3 months of age--eight infants with resection with oblique end-to-end anastomosis (less than or equal to 3ETE) and 15 infants with subclavian flap angioplasty (greater than or equal to 3SFA). The remaining 33 patients older than 3 months of age were divided into 14 patients with resection and oblique end-to-end anastomosis (greater than 3ETE) and 19 patients with the subclavian flap angioplasty technique (greater than 3SFA). The overall mortality was not significantly different between techniques. Postoperative hypertension was significantly more prevalent with end-to-end anastomosis than with the subclavian flap angioplasty technique (p less than 0.01). Seven patients had recurrent coarctation. The 6-year actuarial freedom from recoarctation was 93% +/- 6% in the less than or equal to 3SFA group compared with 53% +/- 20% in the less than or equal to 3ETE group (p less than 0.02), but there was no significant difference in those children operated on at a later age regarding the type of coarctation repair. Therefore, we recommend subclavian flap angioplasty in patients less than 3 months of age. In those older than 3 months either procedure is safe and the risk of recoarctation is similar. 
2	Repeat operation for failure of antireflux procedures. The majority of patients who receive modern antireflux operations obtain substantial long-term relief of their symptoms. About 10% to 15% will have persistent or recurrent problems, some severe enough to warrant reoperation for correction. With careful symptom review, barium study, endoscopy, and manometry, the mechanism of failure becomes evident, and remedial surgical treatment may proceed. The results at reoperation are not as good as those of the primary procedure, which emphasizes the need for proper diagnosis and choice of procedure and for reliable execution of technique at the initial treatment. 
4	Comparison of ambulatory left ventricular ejection fraction and blood pressure in systemic hypertension in patients with and without increased left ventricular mass. To evaluate the effects of long-standing systemic hypertension on left ventricular (LV) function during daily activities, ambulatory radionuclide monitoring of LV ejection fraction (EF) and blood pressure was performed during exercise and other structured activities in 31 hypertensive patients. Patients were divided into 3 groups based on the absence of LV hypertrophy (group 1 [n = 16], LV mass 107 +/- 12 g/m2), presence of LV hypertrophy without electrocardiographic changes (group 2 [n = 10], LV mass 141 +/- 8 g/m2) and LV hypertrophy with associated electrocardiographic changes (group 3 [n = 5], LV mass 158 +/- 9 g/m2). The groups were similar with respect to age, baseline medication, treated and untreated blood pressure, resting EF and treadmill exercise time. Patients in group 3 had the longest history of hypertension. Peak filling rate was normal in group 1 (2.9 +/- 0.4 end-diastolic volume/s), but reduced at rest in groups 2 (2.4 +/- 0.4) and 3 (2.1 +/- 0.3). Patients in group 1 had normal EF responses to exercise and mental stress testing, as well as during routine ambulatory activities. Patients in group 2 had a blunted EF response to exercise, and those in group 3 had a significantly abnormal response. Both group 2 and 3 patients demonstrated abnormal EF responses to mental stress, as well as cold pressor testing in association with significant increases in mean arterial pressure and marked reduction in diastolic filling rate. Decreases in EF were also observed during routine patient monitoring in 3 group 3 patients and 4 group 2 patients. These events were associated with significantly increased blood pressure. 
4	Left ventricular dilatation and pulmonary thallium uptake after single-photon emission computer tomography using thallium-201 during adenosine-induced coronary hyperemia. This study examined the implications of left ventricular (LV) dilatation and increased pulmonary thallium uptake during adenosine-induced coronary hyperemia. The lung-to-heart thallium ratio in the initial images was significantly higher in patients with coronary artery disease (CAD) than normal subjects; 0.48 +/- 0.16 in 3-vessel disease (n = 16), 0.43 +/- 0.10 in 2-vessel disease (n = 20), 0.43 +/- 0.08 in 1-vessel disease (n = 16) and 0.36 +/- 0.05 in normal subjects (n = 7) (p less than 0.001, 0.09 and 0.06, respectively). There was a significant correlation between the severity and the extent of the perfusion abnormality (determined from the polar maps) and the lung-to-heart thallium ratio (r = 0.51 and 0.52, respectively, p less than 0.0002). There was also a significant correlation between lung thallium washout and lung-to-heart thallium ratio (r = 0.42, p = 0.0009) and peak heart rate (r = -0.49, p less than 0.0001). The LV dilatation was mostly due to an increase in cavity dimension (30% increase) and to a lesser extent (6% increase) due to increase in LV size. (The cavity dimensions were measured from the short-axis slices at the midventricular level in the initial and delayed images). The dilation was seen in patients with CAD but not in the normal subjects. These changes correlated with the extent and severity of the thallium perfusion abnormality. Thus, adenosine-induced coronary hyperemia may cause LV dilation and increased lung thallium uptake on the basis of subendocardial ischemia. 
4	Experimental contrast-associated nephropathy and its clinical implications. Acute renal failure after contrast media injection has been recognized for at least 35 years but the exact mechanism responsible for the renal injury remains an enigma. The clinical characteristics of contrast-induced nephropathy (CAN) are well-known although more recently the nonoliguric presentation has occurred at an increased frequency--in 70 to 90% of cases. For nonoliguric presentation of CAN, one can expect an asymptomatic increase in serum creatinine, the mean peak occurring at 4.2 days. If oliguric, the fractional excretion of sodium will be less than 1% and resistant to either fluid challenge or loop diuretics. Preexisting renal insufficiency, with or without diabetes mellitus, increases the risk of CAN 6- to 10-fold but recovery is expected, with less than 10% of all patients requiring dialytic support. Despite the growing body of published reports, the lack of a suitable animal model to evaluate various proposed mechanisms of renal injury has compromised our ability to devise a technique for preventing CAN. A popular scheme has been proposed to describe the possible sequence by which ischemia or nephrotoxins, or both, induce acute renal failure. In particular, a vascular mechanism (i.e., ischemia), is an appealing explanation for CAN since acute changes in renal hemodynamics after contrast media injection have been confirmed by several animal experiments. Unlike other vascular beds in which contrast media induce acute vasoconstriction followed by vasodilatation, the initial effect on the renal circulation is acute vasodilatation, followed by progressive vasoconstriction, increasing renal vascular resistance and a concomitant decrease in both renal blood flow and glomerular filtration rate. 
5	Use of somatostatin for complications occurring after liver transplantation. Somatostatin can be helpful after liver transplantation in some well-defined indications. In uncontrolled digestive haemorrhage, a short course of somatostatin therapy can be of great help in controlling the acute bleeding and to avoid emergency laparotomy. Somatostatin could also be helpful in bilio-pancreato-intestinal fistula, but in this case its advantage over elective surgical treatment remains to be confirmed. 
4	Gastric infarction. We have described a patient with an acute condition of the abdomen who had infarction of the stomach and the small intestine due to atheromatous thrombus of celiac and superior mesenteric arteries. We believe this unusual simultaneous occurrence of gastric and small intestinal infarction is coincidental. The outcome of gastric infarction is frequently fatal. 
5	Is there a place for conservative surgery in the treatment of renal carcinoma? Since 1981, 31 patients have undergone conservative surgery for malignant renal tumours and have been followed up for at least 2 years. The techniques included enucleation or resection (wedge resection or partial nephrectomy). In 10 patients the indications for kidney-sparing surgery were absolute, while in the remainder the conservative surgical approach was a deliberate choice. The tumours varied in diameter from 1.3 to 12 cm and no metastases were detected on pre-operative screening. One patient died post-operatively from myocardial infarction. In the remaining 30 there were no local recurrences. Two patients died from skeletal metastases (1 with bilateral malignancy) and 2 underwent surgery in the post-operative period for haemorrhagic complications. The efficacy of conservative surgery in the local control of renal cancer is an argument in favour of its wider use. 
5	The importance of routine surveillance of distal bypass grafts with duplex scanning: a study of 379 reversed vein grafts. To assess the utility of routine duplex surveillance, 379 infrainguinal reversed vein grafts performed at two independent teaching hospitals were prospectively entered into a surveillance protocol from March 1986 through August 1989. An average of 3.2 postoperative duplex graft flow velocity (GFV) measurements per graft was obtained during a mean follow-up interval of 21 1/2 months. Only 2.1% of 280 grafts with GFV measurements greater than 45 cm/sec failed within 6 months of a normal surveillance examination. GFV measurements less than 45 cm/sec in 99 grafts led to arteriography in 75 grafts, identifying 50 stenotic lesions in 48 bypasses (12.6% of series). Inflow lesions were present in 5%, outflow stenoses in 2%, and intrinsic graft stenoses in only 6% of bypasses. Only 29% of grafts identified as failing by duplex scan were associated with a reduction in ankle-brachial index of greater than 0.15. Secondary reconstructions were performed in 48 grafts based on detection of a reduced GFV measurement; all such reconstructions are patent after a mean follow-up of 5 months. Duplex surveillance is more reliable in identification of failing vein grafts than is determination of ankle-brachial index. 
5	CD11c (LEU-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia. Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are two common chronic lymphoproliferative disorders, each having characteristic clinical, morphologic, and immunologic features. Phenotypically, CD5 reactivity in CLL and CD11c (Leu-M5) reactivity in HCL have characterized these two leukemias among B-cell disorders. In this study, we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and CD11c expression, but morphologically similar to CLL. The patients' ages ranged from 46 to 81 years (median 62). Eleven had palpable splenomegaly, five with markedly enlarged spleens; only one patient had generalized lymphadenopathy. The white blood cell count ranged from 5.2 to 131.0 x 10(9)/L (median 20.8). The morphologic diagnosis in all cases was CLL, with the cells usually having abundant cytoplasm. No morphologic features, of hairy cells were evident; tartrate-resistant acid phosphatase cytochemistry was negative in all cases. Bone marrow biopsies were available in 8 of 14. Four showed focal nodular infiltrates and two had diffuse infiltrates similar to CLL; two showed only minimal interstitial involvement. All cases expressed multiple B-cell markers, and 12 of 14 had monoclonal surface immunoglobulin. The leukemic cells of all cases strongly expressed CD11c, while CD5 was expressed in 7 of 14; only 1 of the 14 cases expressed the lymph node homing receptor, Leu-8. This unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of CLL and that of HCL. CD11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients. 
5	Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets. The presence of disseminated intravascular coagulation (DIC) in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP) is debated. We assessed the occurrence of decompensated and compensated DIC (using predefined criteria) in 15 consecutive nulliparous pregnant patients with gestational hypertension combined with the HELLP syndrome and in 12 consecutive nulliparous controls with pregnancy induced hypertension (PIH) but without the HELLP syndrome. A combination of routine coagulation assays revealed the absence of decompensated DIC in all studied patients. However, using more specific and sensitive coagulation assays, compensated DIC was observed in all HELLP patients and in three patients in the control group. The mean values of antithrombin III, thrombin-antithrombin III complexes and protein C in the HELLP and the control group were 66 vs 87% (P = 0.0004), 21 vs 8 ng/ml (P = 0.0008) and 57 vs 90% (P = 0.0018) respectively. We conclude that HELLP patients show evidence of compensated DIC which may have pathophysiological significance for the observed organ damage. 
5	Serum and CSF levels of IL-2, sIL-2R, TNF-alpha, and IL-1 beta in chronic progressive multiple sclerosis: expected lack of clinical utility. We measured interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) by ELISA in paired sera and CSF from 50 chronic progressive multiple sclerosis (CPMS) patients during worsening disability, 19 patients with other neurologic diseases (OND), and in sera from 40 healthy volunteers. In the CPMS patients, 28% (14/50), 10% (5/50), 16% (8/50), and 6% (3/50) had elevated serum levels of IL-2, sIL-2R, TNF-alpha and IL-1 beta, respectively, compared with healthy controls. The only analyte we detected in the CSF was IL-2 in 1 CPMS patient (1/50, 2%). We also saw elevated serum sIL-2R in 16% (3/19) of OND patients. We found no significant difference in mean levels of serum sIL-2R between the 3 groups. Our study, the largest to date of CPMS patients, shows that serum and CSF levels of IL-2, sIL-2R, TNF-alpha, or IL-1 beta are not sensitive for, and the serum sIL-2R level is not specific for, CPMS. Therefore, measurement of these analytes will not be clinically useful for therapeutic or prognostic purposes in the majority of CPMS patients. 
5	GTPase-activating protein interactions with the viral and cellular Src kinases. GTPase-activating protein (GAP), which regulates the activities of Ras proteins, is implicated in mitogenic signal transduction by growth-factor receptors and oncoproteins with tyrosine kinase activity. Oncogenic viral Src (p60v-src) encoded in Rous sarcoma virus possesses elevated tyrosine kinase activity compared with its nononcogenic normal homolog, cellular Src (p60c-src). To examine molecular interactions between GAP and the two Src kinases, immunoprecipitates of Src or GAP prepared from cell lystates were resolved by gel electrophoresis and analyzed by an immunoblot procedure with antibodies to GAP or Src used as probes. Results suggest that p60c-src is associated with a complex containing GAP in immunoprecipitates from lysates of normal rat and chicken cells. However, GAP is not phosphorylated in p60c-src immunoprecipitates subjected to in vitro kinase reactions. By contrast, GAP undergoes tyrosyl phosphorylation in vitro when immunoprecipitates of p60v-src prepared from transformed cell lysates are incubated with ATP. Our findings suggest that p60v-src and p60c-src associate with complexes containing GAP and provide a biochemical link between both kinases and GAP/Ras signal transduction pathways. These results are consistent with the hypothesis that GAP has a role in mediating normal functions of p60c-src as well as oncogenic activities of p60v-src. 
2	Endoscopic variceal ligation in patients who have failed endoscopic sclerotherapy. Endoscopic variceal ligation has been developed as an alternative to endoscopic sclerotherapy. We report a series of 12 men with a history of bleeding esophageal varices who were treated with endoscopic variceal ligation after they had failed sclerotherapy. Hemostasis was achieved in all 10 patients who were bleeding at the time of initial endoscopy and again in those who subsequently re-bled. Over a follow-up period of up to 22 months, varices have been and remain eradicated in five patients; in four others, a reduction in grade was noted before death (two patients), liver transplant, or loss to follow-up (one patient each); two patients died before they could be re-evaluated, while in the remaining patient, no reduction in variceal grade was noted before loss to follow-up. No complication was recorded after 35 endoscopic treatment sessions involving a total of 245 rubber band ligations. Our results indicate that endoscopic variceal ligation may be used with success in patients who fail sclerotherapy. 
5	The value of the rectus abdominis myocutaneous flap in the treatment of complex perineal fistula. Complex perineal fistula and persistent perineal sinus are difficult to treat. We describe our experience with wide excision of the diseased perineum using a combined abdominoperineal approach. Ten patients were reconstructed by a rectus abdominis myocutaneous flap (n = 7), rectus abdominis muscle flap (n = 2), and omental graft (n = 1). Primary healing was achieved in all cases. A median follow-up of 18 months (range 6-54 months) has shown no recurrence of perineal disease or associated abdominal incisional hernia. There were no perioperative deaths. We propose that the rectus abdominis myocutaneous flap is indicated if large amounts of perineal skin has to be sacrificed. When less skin is removed a repair with greater omentum or rectus muscle alone is adequate. The abdominoperineal approach together with filling the residual pelvic cavity with well-vascularized tissue allows definitive treatment to be carried out in one stage. 
4	Detecting hypertension: screening versus case finding in Norway. OBJECTIVE--Evaluation of detection of hypertension in adults in the county of Nord-Trondelag, Norway. DESIGN--Cross sectional survey with clinical follow up examinations. SETTING--Health survey by screening teams from the national health screening service, and examinations by all 106 general practitioners in the county. SUBJECTS--During 1984-6, 74,977 persons (88.1% of those aged 20 years and over) participated in the health survey. MAIN OUTCOME MEASURES--Hypertension (when assessed by standardised recording and by questionnaires on drug treatment for hypertension) according to the blood pressure thresholds used in the Norwegian treatment programme. Subjects positive on screening were grouped after clinical examination into treatment groups. RESULTS--In all, 2399 subjects were positive for hypertension. Before screening 6210 (8.3%) patients reported taking antihypertensive drugs and another 3849 (5.1%) had their blood pressure monitored regularly. All who screened positive were referred to their general practitioner and evaluated according to a standard programme. As a result, drug treatment was started in 406 (0.5%) participants screened and blood pressure monitoring in another 1007 (1.3%). Of all patients taking antihypertensive drugs after the screening, 6399 (94.0%) had been diagnosed before screening, and of those whose blood pressure was monitored after the screening, 79.3% had been diagnosed before screening. CONCLUSIONS--At the blood pressure screening thresholds used, and when hypertension is defined by an overall clinical diagnosis, the results indicate that general practitioners can find and diagnose hypertensive patients with the case finding strategy. 
5	Combined laminoplasty and posterolateral fusion for spinal canal surgery in children and adolescents. Spinal deformities, especially kyphosis and instability, after laminectomy for tumors and other diseases, are major clinical problems. Since 1981, combined laminoplasty and posterolateral fusion for the prevention of postlaminectomy spinal deformities was performed on eight male and two female patients aged two to 26 years (average, 13.9 years). The follow-up period was from six months to seven years and three months (average, three years and five months). Two patients died six and ten months postoperatively because of brain metastases (astrocytoma) and lung metastases (neuroblastoma), respectively. Good alignment with no instability of the cervical or thoracic spine was obtained for all patients, including the two who died. Laminoplasty combined with posterolateral fusion was found to be very effective in preventing the development of spinal deformities after spinal canal surgery for spinal cord tumors or other diseases in children and adolescents. 
5	Acetazolamide-responsive vestibulocerebellar syndrome: clinical and oculographic features. Five patients who presented with long-standing episodic vertigo had ocular motor signs localizing to the vestibulocerebellum. In each patient, the episodic vertigo was either abolished or markedly decreased in frequency and severity with acetazolamide therapy. In 4, other family members had identical symptoms and signs. This syndrome is 1 of the few treatable causes of chronic episodic vertigo. 
1	Two-drug therapy in patients with metastatic germ cell tumors. Eighty-two patients with metastatic germ cell tumors (GCT) treated with two-drug therapy consisting of etoposide and cisplatin were evaluated for late relapse. Good-risk GCT was defined using Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. Etoposide was given at 100 mg/m2 on days 1 to 5 and cisplatin was given at 20 mg/m2 on days 1 to 5; therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000/microliters or a platelet count of less than 100,000/microliters. Drug doses were not attenuated for myelosuppression. Seventy-six of 82 evaluable patients achieved a complete response (CR). Seventy-two patients had a CR to chemotherapy alone. Forty-six (56%) patients had excision of residual abnormalities: 11 had teratoma in the resected specimen, 31 had necrotic debris or fibrosis, and 4 had a CR after chemotherapy plus complete excision of residual viable GCT. Six patients had an incomplete response to chemotherapy; one of these patients had unresectable mature teratoma and remains progression-free. The median etoposide dose (+/- standard deviation [SD]) was 500 mg/m2/course (+/- 35 mg/m2) and the median cisplatin dose (+/- SD) was 100 mg/m2/course (+/- 6 mg/m2). Nine patients experienced a relapse at 6 to 17.5 months; two patients with nonseminomatous GCT were salvaged by chemotherapy and one patient with seminoma was salvaged by chemotherapy and radiation therapy. The three patients who were salvaged by additional therapy are disease-free at 59 to 63 months. Seventy-one patients (87%) remain disease-free with a median follow-up time of 63 months (range, 33 to 92 months). No relapses have occurred beyond 17.5 months. Etoposide and cisplatin therapy at these doses and schedule results in durable CR without late relapse. 
4	Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second [edv/s]) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling. 
5	Minitracheotomy: complications and follow-up with fibreoptic tracheoscopy. Complications and changes in tracheal mucosa after minitracheotomy were evaluated in 28 patients. Tracheal mucosa was inspected fibreoptically after the insertion of a minitracheotomy cannula, and then at 3-day intervals until the cannula was removed. Thereafter, assessments were made every third day until the mucosa was considered normal. Three significant complications occurred: mediastinal puncture, paratracheal entrance of the cannula and subcutaneous emphysema. Difficulties at insertion of the minitracheotomy cannula were encountered in 15 of 28 patients (54%). Air flow detected through the cannula in one patient, and lack of air flow in another patient, were misleading signs of the position of the cannula. Passing a suction catheter in three patients and a normal end-tidal carbon dioxide tracing in one patient, were also found to be misleading. The correct position and possible complications could be verified only by fibreoptic tracheoscopy. Changes in the tracheal mucosa were independent of the duration of minitracheotomy therapy. 
3	Choroid plexus cysts and chromosomal defects During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts. 
3	Reference values for the Mini-Mental State Examination (MMSE) in octo- and nonagenarians The Mini-Mental State Examination (MMSE) was used in a population survey of all inhabitants of Leiden, the Netherlands, over 85 years (n = 1258). In this paper we report on 532 subjects without neurological or psychiatric disease. Results show that the median score and lowest quartile cut-off score remain high until the tenth decade (median score = 28, lowest quartile cut-off score = 26). Thus age, in itself, is not a major limitation in using the MMSE. In this study a comparatively low level of education (the majority had 6 to 7 years of education) did not affect the results on the MMSE in a negative way, nor did we find an association with the use of psychoactive drugs. 
5	Eclampsia. Early detection and hospitalization in women with mild preeclampsia may prevent eclampsia. In the event of severe preeclampsia or eclampsia, delivery is indicated for the benefit of both mother and fetus. Thereafter, pathologic changes of preeclampsia and eclampsia, including major multiple organ system dysfunction, undergo complete reversal. 
5	Cortical asymmetry of REM sleep EEG following unilateral pontine hemorrhage. A 24-year-old woman with a left pontine hematoma showed marked asymmetry in the EEG of REM sleep, suggesting that a unilateral pontine lesion is sufficient to disrupt normal REM sleep EEG in the ipsilateral hemisphere. Other REM sleep characteristics (rapid eye movements, muscle atonia) were unaffected by this lesion. 
4	Plasma histamine in patients with chronic renal failure and nephrotic syndrome. Plasma histamine concentrations were measured using a commercially available monoclonal antibody radioimmunoassay in 38 patients with nephrotic syndrome, end stage renal failure, those receiving haemodialysis, and those receiving continuous ambulatory peritoneal dialysis to determine whether histamine may mediate damage to glomerular capillaries and arterial endothelium. Plasma histamine concentrations were significantly increased in all four patient groups when compared with those of controls and were the highest in two patients with pruritus. Raised plasma histamine concentrations in such patients are consistent with the hypothesis that histamine may contribute to the damage to glomerular capillaries and to arterial endothelium. These effects may be relevant to the pathogenesis of glomerular disease and atherosclerosis. Histamine may also contribute to the pathogenesis of pruritus in patients with chronic renal failure. 
5	Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences. In a retrospective study of 198 patients with transitional cell carcinoma of the upper urinary tract, post-operative recurrences developed as contralateral tumours in 2.5%, in the ureteric stump after conservative resection in 19% and in the bladder in 36.4%. Upper tract recurrences resembled the primary tumours in terms of grade and stage; of the bladder tumours, 89% were similar in grade and 72% similar in stage to the primary tumours. Age, sex, grade and stage had no effect on the number of bladder recurrences, but ureteric tumours had significantly more recurrences than renal pelvicaliceal tumours. Sex, bladder recurrences and site of primary tumours did not influence survival. Thus grade and stage of the primary tumour were the only predictive variables of the final outcome. 
5	Prevalence of Helicobacter pylori in specific forms of gastritis. Further evidence supporting a pathogenic role for H. pylori in chronic nonspecific gastritis. Helicobacter pylori colonization of the gastric mucosa is strongly associated with chronic nonspecific gastritis; moreover, there is evidence to suggest that H. pylori may cause this form of gastritis. However, there is little or no information on the prevalence of H. pylori in specific forms of gastritis. Our hypothesis was that if H. pylori was pathogenic in chronic nonspecific gastritis, organisms would be found frequently in this type of gastritis but infrequently in specific forms of gastritis. Prevalence rates of H. pylori were determined independently in patients with eosinophilic and Crohn's gastritis, Menetrier's disease, and chronic nonspecific gastritis. The prevalence of H. pylori in patients with chronic nonspecific gastritis was 71%, whereas the organism was not identified in patients with any form of specific gastritis. This finding further supports the accumulating evidence that H. pylori is a primary pathogenic factor in chronic nonspecific gastritis. 
3	Changes in intracochlear and intracanalicular nerves after acoustic neurinoma excision confirmed by magnetic resonance imaging. Postoperative magnetic resonance imaging findings related to the vestibulocochlear and facial nerves within the internal auditory canal were analyzed in acoustic neurinomas. T1- and proton-weighted magnetic resonance images showed that the vestibulocochlear nerves distal to the internal auditory meatus increased in signal intensity after surgical intervention. These nerves were conspicuously enhanced after intravenous administration of gadolinium diethylene-triamine-pentaacetic acid. The preserved facial nerves were also markedly enhanced postoperatively. As a possible cause of these findings, we suggest operative disruption of the blood-nerve barrier with ensuing nerve edema, although the operative procedures were carefully carried out using a surgical microscope. The clinical significance of traumatic disruption of the blood-nerve barrier and subsequent nerve edema are discussed from the standpoint of preservation of cochlear nerve function. 
5	Epidemiology of heart failure. Analysis of 34 years of follow-up of Framingham Study data provides clinically relevant insights into the prevalence, incidence, secular trends, prognosis, and modifiable risk factors for the occurrence of heart failure in a general population sample. Heart failure was found to be highly prevalent, affecting about 1% of persons in their 50s and rising progressively with age to afflict 10% of persons in their 80s. The annual incidence also increased with age, from about 0.2% in persons 45 to 54 years, to 4.0% in men 85 to 94 years, with the incidence approximately doubling with each decade of age. Women lagged slightly behind men in incidence at all ages. Male predominance was because of a higher rate of coronary heart disease, which confers a fourfold increased risk of heart failure. Heart failure, once manifest, was highly lethal, with 37% of men and 33% of women dying within 2 years of diagnosis. The 6-year mortality rate was 82% for men and 67% for women, which corresponded to a death rate fourfold to eightfold greater than that of the general population of the same age. Sudden death was a common mode of exitus and accounted for 28% of the cardiovascular deaths in men and 14% in women with heart failure. Hypertension and coronary disease were the predominant causes for heart failure and accounted for more than 80% of all clinical events. Factors reflecting deteriorating cardiac function were associated with a substantial increase in risk of overt heart failure. These include low vital capacity, sinus tachycardia, and ECG evidence of left ventricular hypertrophy. 
5	Flow cytometric analysis of the mechanism of methylmercury cytotoxicity. Flow cytometric analysis of murine erythroleukemic cells (MELC) exposed in vitro to 2.5 to 7.5 mumol/l (micromolar) methylmercury (MeHg) reveals a dose-dependent decrease in the rate of DNA synthesis (rate of passage through the S phase of the cell cycle), manifested as the accumulation of most of the cells in the S phase, and a modest accumulation of cells in the G2/M phase of the cycle. Light microscopy reveals a progressive increase in chromosomal damage (condensation, pulverization). At or above 10 mumol/l MeHg, progression through all the phases of the cell cycle is blocked and mitotic cells are arrested irreversibly in anaphase, with most exhibiting arrangement of chromosomes in a wreathlike ring formation. Also the cells exhibit both nuclear propidium iodide (PI) fluorescence (indicative of loss of viability) and concurrent cytoplasmic carboxyfluorescein (CF) fluorescence (viable cells exhibit CF fluorescence and exclude PI). In addition, there is a dose-dependent increase in cellular refractive index (90 degrees light scatter), an apparent decrease in cell volume (axial light loss), and progressive resistance to detergent (NP-40)-mediated cytolysis. Resistance to detergent-mediated cytolysis is indicative of fixation (protein denaturation, cross-linking, and so on) of the plasma membrane/cytoplasm complex. Our findings indicate that DNA synthesis is the primary target of MeHg cytotoxicity and that apparent targets and degree of cytotoxicity are a complex function of dose. 
5	Comparison of Delphin and BioMedicus pumps. There is an increasing use of centrifugal pump systems for cardiopulmonary bypass (CPB) and circulatory assistance. The BioMedicus and Delphin centrifugal pump systems were tested in two side-by-side, identical in vitro flow loops for blood trauma and flow probe accuracy. Blood parameters tested were hemoglobin, hematocrit, lactate dehydrogenase, free plasma hemoglobin, and platelet counts. The Delphin pump demonstrated significant increases in plasma hemoglobin levels at the three flow rates tested: 2 L/min (p less than 0.05), 4 L/min (p less than 0.005), and 6 L/min (p less than 0.05). After 4 hr of pumping, the drop in platelet counts was significantly greater in the BioMedicus loop as compared with the Delphin loop (p less than 0.05) at the 2 L/min and 4 L/min flow rates; however, platelet levels remained within normal ranges in both systems. At 6 L/min, no statistical difference in platelet counts was noted. The flow probe readings were found to deviate by as much as 58% of stopwatch timed flow rate comparisons at low flow rates, but improved to within 10% or better at 6 L/min. 
5	Unilateral asterixis. We describe three patients with unilateral asterixis. One diabetic patient with a moderately-sized haematoma in the left putamen initially developed bilateral and symmetrical asterixis, which became confined to the right side as his diabetes mellitus was controlled. Two patients showed unilateral asterixis due to haematomas in the contralateral basal ganglia and thalamus, respectively. The present findings indicate that not only lesions of the thalamus but also those of the basal ganglia can cause unilateral asterixis, and bilateral and symmetrical asterixis does not necessarily exclude the presence of a focal mass lesion in the cerebrum. 
5	Fatigue. Fatigue is a pervasive, protective phenomenon affecting the totality of the individual. Assessment and management involve a wide range of activities to address the total human being's physical, psychological, cognitive, and spiritual dimensions. When elimination or neutralization of the effect of an antecedent condition is not an option, redesigning one's life-style may be the primary avenue of fatigue management. This protective mechanism, fatigue, may in fact herald the return of quality and purpose to one's life. 
3	Quinine-induced disseminated intravascular coagulation. Recurrent disseminated intravascular coagulation occurred in 3 women after ingestion of quinine tablets for cramp. All had circulating quinine-dependent antibodies to platelets and in 2 there was initial evidence of antibody consumption, with low titres that rose steeply over the next few days and remained high for many months. 
4	Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion. Thrombolysis and Angioplasty Study Group. Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 +/- 10 vs 65 +/- 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 +/- 11 vs 46 +/- 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population. 
5	Hemorrhoidectomy during pregnancy: risk or relief? Acute hemorrhoidal crisis can occur in the pregnant female. When medical therapy fails to relieve pain, operative intervention may be necessary. The surgeon, however, may be reluctant to operate due to potential complications to the mother and fetus. From July 1983 to July 1989, hemorrhoidectomy was performed in 25 of 12,455 pregnant women (0.2 percent) who delivered in our institution. Twenty-two women were in their third trimester, 80 percent were multiparous, and each had a remote history of hemorrhoidal symptoms, including intermittent pain, bleeding, and protrusion. Closed hemorrhoidectomy was performed under local anesthesia. The surgery was directed at removing only symptomatic disease, which included three quadrants in 14 patients, two quadrants in seven patients, and one quadrant in four patients. All patients experienced relief of intractable pain the day after surgery, except one patient who required a hemostatic packing during the immediate post-operative period. There were no other maternal or fetal complications. Subsequent follow-up for anorectal disease ranged from 6 months to 6 years. Six (24 percent) patients required additional hemorrhoid treatment. Hemorrhoidectomy in selected pregnant patients is safe in our experience. 
1	Small cell carcinomas of the large intestine. The authors studied the clinical and pathologic features of 38 small cell carcinomas of the large intestine. Most were located in the right colon. Overlying adenomas were present in 45% and squamous differentiation in 21% of tumors. Endocrine differentiation was present in all tumors by at least one method; neuron-specific enolase, dense-core granules, and synaptophysin were present in most cases. Seventy-one percent of tumors metastasized to the liver; 64% of patients were dead at five months follow-up. Twenty-one poorly differentiated adenocarcinomas and undifferentiated carcinomas of the large intestine accessioned during the same period showed less endocrine (7 of 21) and squamous differentiation (1 of 15) and fewer liver metastases (4 of 15) than did small cell carcinomas. Among all 59 tumors studied, small cell histologic characteristics correlated better with liver involvement than did endocrine markers or other histologic features. Small cell carcinomas of the large intestine are aggressive tumors with a propensity for early liver involvement. Although there is a spectrum of squamous, endocrine, and glandular features in large bowel tumors of low degrees of differentiation, the identification of a small cell component appears to be most clinically relevant. 
5	Biliary endoprostheses. Plastic versus metal stents. Plastic biliary endoprostheses relieved malignant obstructive jaundice in 80% to 90% of the patients. The comfort of a completely indwelling endoprosthesis should be offered to all palliatively treated tumor patients, and external-internal catheters should be reserved for the minority of patients who return with reoccluded endoprostheses. These patients have bacterial flora that rapidly contaminates the endoprosthesis and causes encrustations and reocclusions. Thus, a second endoprosthesis also would reocclude quickly. The mechanism of reocclusion of plastic and metal endoprostheses is completely different. In plastic endoprostheses, bacterial contamination causes decomposition of the bile and subsequent encrustation. In metal endoprostheses tumor ingrowths between the struts of the stent cause reocclusion. Tumor ingrowths were observed in only 6.5% of metal prostheses with a narrow woven mesh (Wallstent), whereas prostheses with large distances between the struts (Gianturco stent) had ingrowth rates of 19% to 50%. This fact shows that tumor ingrowths can be reduced by narrowing the spaces between the metallic network, and, therefore, improvements in the design of the metal stents should reduce the occlusion rate to or below that of plastic endoprostheses, which currently have a lower encrustation rate. The major advantages of expandable metal prostheses are the relative ease and the minimal trauma of the implantation procedure. The Wallstent endoprosthesis, in particular, can be inserted through a 7-F introducer sheath and offers the chance of single-step placement. The 30-day mortality rate, therefore, was only 5%. This is significantly lower than the 30-day mortality rate after insertion of plastic prostheses (15% to 24%). Even simple external catheter drainage procedures have a higher reported 30-day mortality rate (27%). Expandable metal endoprostheses would be the most useful device if the occlusion rate could be kept under 10% in large series. Increasing the length of the endoprostheses to 10 cm in the expanded state could also improve the long-term patency rates. 
4	Reoperation for myocardial revascularization using the internal mammary artery. From October 1984 up to February 1989, 40 patients had "redo" myocardial revascularizations using one or both internal mammary arteries (IMA) in over 1000 cases operated upon in our Department for coronary bypass grafts. Thirty-one patients had a further operation for unstable angina difficult to control with drugs. Mean interval of recurrence of angina after previous surgery was 48.5 months for all the cases, but the mean interval before the second bypass operation was 68 months. Severe disease of previous vein grafts was the reason for surgery in 25 patients and progressive atherosclerosis in native coronary arteries in 15 patients. Twenty-one patients had a single mammary artery; both mammary arteries were used in 19. Two cases had endarterectomy on left anterior descending (LAD). Four patients had peroperative acute myocardial infarction (AMI), 3 a low cardiac output syndrome, postoperative bleeding occurred in 3 cases and wound infection in one case. An intraaortic balloon pump was used preoperatively in one case and coming off bypass in two others. One patient died on the second day postoperatively from cardiac arrest following bilateral pneumothorax. There were no late deaths. At a mean follow-up of 20.5 months, 28 patients are free of symptoms but 11 are complaining of angina, 5 during exercise and 6 at rest. An exercise test was positive in 8 patients. 
1	Review of hepatic imaging and a problem-oriented approach to liver masses. We believe that imaging of the liver is complicated. The sporadic appearance of incidental benign lesions and variability in scanning techniques, equipment and artifacts add difficulties to the evaluation of liver masses. Therefore we emphasize the need to define the problem for which the patient is being imaged. This information helps in choosing the procedure of choice and the technique needed to give the most expedient, accurate answer. This will also help apply the lowest risk and most cost-efficient care. Imaging algorithms vary depending on the suspected pathological conditions. Dynamic bolus-enhanced CT is the modality of choice in most situations. Tc99m sulfur-colloid liver-spleen scans are helpful in patients with suspected FNH, and Tc99m-tagged-RBC-SPECT scans are recommended to confirm cavernous hemangiomas. Cysts are easily confirmed by US. Although MRI is competitive with CT, it has not become a primary modality because of cost, availability, patient selection and variability of scanner capabilities among the many manufacturers and models. It is hard to predict what future development of imaging techniques will bring. Many feel that significant advances have plateaued. Time and money will more likely be concentrated on improving image resolution, speed of scanning and ability to transfer this information to sites outside of the radiology department. In addition to faster scanning, we expect to soon have available safe intravenous and enteric contrast agents for MRI. Certainly this will lead to a new round of investigations to compare MRI with CT scanning. 
3	Diclofenac-associated hepatotoxicity Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death. Signs and symptoms developed within several weeks of initiation of drug use and generally resolved 4 to 6 weeks following discontinuation of use of the drug. The only patient rechallenged with the drug developed a recurrence of her hepatic abnormalities. In one patient, fatal, fulminant hepatitis developed despite early withdrawal of the drug. Review of the European literature disclosed three additional fatalities associated with diclofenac therapy. It is unclear whether the incidence of hepatotoxicity is higher with this drug compared with other nonsteroidal anti-inflammatory drugs. Careful patient monitoring is advised, and prompt discontinuation of the drug is suggested when signs or symptoms of liver disease develop. 
5	Escherichia coli in patients with renal scarring: genotype and phenotype of Gal alpha 1-4Gal beta-, Forssman- and mannose-specific adhesins. The frequency of Escherichia coli with Gal alpha 1-4Gal beta-specific adhesins is reduced among children who develop renal scars. The adhesion-negative phenotype may be due to the absence of the pap DNA sequences which encode these adhesins or to a phase variation event induced by in vitro culture. In the present study the frequency of pap and pil homologous DNA was determined by dot blot analysis with probes specific for the respective sequence using E. coli strains from children with recurrent pyelonephritis with and without renal scarring. The frequency of pap was 79% in the strains isolated from the nonscarring group compared with 39% in the strains from the scarring group (P less than 0.001). The Gal alpha 1-4Gal beta phenotype was expressed by 89% of the pap-positive strains from the nonscarring group compared with 71% in the scarring group (P less than 0.05). In addition 13 of 77 of the pap-positive E. coli strains agglutinated sheep erythrocytes but not the Gal alpha 1-4Gal beta latex beads; a reaction attributed to reactivity with the Forssman glycolipid. DNA sequences homologous with pil were found in 95% of all strains and there was no significant difference between the nonscarring and the scarring groups. The low frequency of Gal alpha 1-4Gal beta specific strains in the scarring group was therefore due to the absence of pap-homologous DNA sequences and to a reduced rate of phenotypic expression among pap-positive scarring strains. There was no support for a relationship between type 1 fimbriae and renal scarring. 
4	Hemodynamic effects of synchronous high-frequency jet ventilation in mitral regurgitation. We tested the hypothesis that increases in intrathoracic pressure (ITP), by decreasing the pressure gradient for anterograde left ventricular (LV) ejection, should augment cardiac output in acute mitral regurgitation (MR). In a pentobarbital-anesthetized closed-chest canine model, LV stroke volume (SLLV) was measured by integration from an aortic flow probe signal. MR was induced by a regurgitant ring. ITP was elevated over apnea by means of intermittent positive-pressure ventilation (IPPV), asynchronous (asynch) high-frequency jet ventilation (HFJV), and cardiac cycle-specific (synch) HFJV. IPPV resulted in the greatest increase in ITP. MR caused a fall in SVLV and a rise in LV filling pressure that were not altered by IPPV. Compared with IPPV or apnea, both asynch and synch HFJV increased SVLV and reduced LV filling pressures (P less than 0.05). Systolic synch HFJV induced a greater increase in SVLV (32%) than diastolic synch HFJV (26%) despite similar ventilatory settings. Our data suggest that when LV contractility is normal but MR impairs forward flow, cardiac cycle-specific increases in ITP will augment forward flow. 
5	Granulomatous prostatitis and poorly differentiated prostate carcinoma. Their distinction with the use of immunohistochemical methods. Granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic each other both clinically and histologically. To develop criteria useful in resolving problem cases, the authors compared the reactivities of these conditions (nine cases of granulomatous prostatitis and six cases of poorly differentiated carcinoma) with a panel of antibodies to cytokeratin (AE1/3), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), lysozyme, antimacrophage M, and leukocyte common antigen (LCA). In granulomatous prostatitis, histiocytes were not immunoreactive for PAP, PSA, or cytokeratin; however, histiocytes reacted to lysozyme in nine of nine cases, antimacrophage M in seven of nine cases, and LCA in one of nine cases. Tumor cells from all six carcinoma cases reacted with PAP, PSA, and cytokeratin; all failed to react with lysozyme, LCA, and antimacrophage M. The authors conclude that granulomatous prostatitis and poorly differentiated carcinoma can be reliably distinguished with immunohistochemical methods. 
2	Endoscopic nasobiliary catheter drainage in biliary and pancreatic disease. Nasobiliary catheter drainage was first introduced a decade ago. It provides drainage of the biliary system and facilitates interventional procedures of the biliary and pancreatic system, both for therapy and research purposes. The present review addresses the designs of nasobiliary catheters, the technique of insertion, and indications for drainage, with special emphasis on the management of bile duct stones and associated complications. Its potential application in biliary research is discussed further. Certain caveats in the performance of nasobiliary drainage are also included. All of these emphasize the need for this technique to be included in therapeutic endoscopy training. 
5	Infantile form of carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to carnitine palmitoyltransferase II deficiencies. Reported cases of carnitine palmitoyltransferase II (CPT II) deficiency are characterized only by a muscular symptomatology in young adults although the defect is expressed in extra-muscular tissues as well as in skeletal muscle. We describe here a CPT II deficiency associating hypoketotic hypoglycemia, high plasma creatine kinase level, heart beat disorders, and sudden death in a 3-mo-old boy. CPT II defect (-90%) diagnosed in fibroblasts is qualitatively similar to that (-75%) of two "classical" CPT II-deficient patients previously studied: It resulted from a decreased amount of CPT II probably arising from its reduced biosynthesis. Consequences of CPT II deficiency studied in fibroblasts differed in both sets of patients. An impaired oxidation of long-chain fatty acids was found in the proband but not in patients with the "classical" form of the deficiency. The metabolic and clinical consequences of CPT II deficiency might depend, in part, on the magnitude of residual CPT II activity. With 25% residual activity CPT II would become rate limiting in skeletal muscle but not in liver, heart, and fibroblasts. As observed in the patient described herein, CPT II activity ought to be more reduced to induce an impaired oxidation of long-chain fatty acids in these tissues. 
4	Atrial fibrillation in the elderly: management update. Non-valvular atrial fibrillation is associated with a markedly increased risk of embolic stroke in elderly persons. Evidence is accumulating that anticoagulation with warfarin or aspirin may be effective in reducing this risk. 
5	Coinheritance of two mild defects in low density lipoprotein receptor function produces severe hypercholesterolemia. A family is described in which the probands, twin girls, had severe hypercholesterolemia suggestive of familial hypercholesterolemia (FH). The mother of the twins had normal plasma cholesterol levels, and the father had only moderate hypercholesterolemia. Moreover, low density lipoprotein (LDL) binding studies in cultured fibroblasts and isolated lymphocytes in the parents failed to reveal significantly reduced LDL receptor activity that is typical of FH heterozygotes. Turnover studies of LDL in the parents, however, revealed low fractional clearance rates (FCRs) for LDL. In cultured fibroblasts and isolated lymphocytes from the twin probands, binding of normal LDL was half normal or less. LDL turnover studies in the twins revealed a marked reduction in FCRs for LDL. When the twins were treated with lovastatin, however, FCRs for LDL increased significantly, suggesting enhancement of LDL receptor activity. This finding along with LDL binding studies in the cultured cells infer that the twins did not have homozygous FH. In addition, all family members tested negative for familial defective apolipoprotein-B-100, and LDL isolated from the mother and twins showed normal binding to normal fibroblasts. The overall data suggest that the severe hypercholesterolemia in the offspring was due to inheritance of mild to moderate defects of LDL receptor function from both parents. Although the latter defects could not be detected with certainty by in vitro tests in each parent, they were evident from LDL turnover tests. Coinheritance of these defects apparently produced severe hypercholesterolemia in the offspring. 
5	Recurrent meningitis in a patient with congenital deficiency of the C9 component of complement. First case of C9 deficiency in Europe. We describe the first cases, to our knowledge, of C9 deficiency in Europe that were detected in a Swiss family, of which two members--one with a complete deficiency and the other with approximately half-normal C9 levels--experienced bacterial meningitis. The index patient, a 56-year-old white man with a history of purulent meningitis at the age of 23 years, presented with an acute meningococcal meningitis. No impairment of cellular immunity or immunoglobulin deficiency could be found. Complement assays showed a complete deficiency of the C9 component, while the other individual component levels were normal and the hemolytic activity (measured using the CH50 assay) was only slightly reduced. A family study revealed complete C9 deficiency in the patient's healthy brother and half-normal C9 concentrations in his sister, his son (who also had experienced an episode of bacterial meningitis), and his niece, consistent with an inherited C9 deficiency. This first case of recurrent meningitis in a white patient with complete C9 deficiency suggests that this complement defect may also be a risk factor for bacterial, especially neisserial, infections. 
5	A randomized, double-blind trial of nystatin therapy for the candidiasis hypersensitivity syndrome BACKGROUND. Candida albicans infection has been proposed to cause a chronic hypersensitivity syndrome characterized by fatigue, premenstrual tension, gastrointestinal symptoms, and depression. Long-term antifungal therapy has been advocated as treatment for the syndrome, which is most often diagnosed in women with persistent or recurrent candida vaginitis. METHODS. To determine the efficacy of nystatin therapy for presumed candidiasis hypersensitivity syndrome, we conducted a 32-week randomized, double-blind, cross-over study using four different combinations of nystatin or placebo given orally or vaginally in 42 premenopausal women who met present criteria for the syndrome and had a history of candida vaginitis. The outcomes studied were the changes from base line in scores for vaginal, systemic, and overall symptoms and in the results of standardized psychological tests. RESULTS. The three active-treatment regimens (oral and vaginal nystatin, oral nystatin and vaginal placebo, and oral placebo and vaginal nystatin) and the all-placebo regimen significantly reduced both vaginal and systemic symptoms (P less than 0.001), but nystatin did not reduce the systemic symptoms significantly more than placebo. On average, the scores for systemic symptoms improved 25 percent with the three active-treatment regimens and 23 percent with the all-placebo regimen, a difference of only 2 percent (95 percent confidence interval, -3 to 7 percent). As expected, the three active-treatment regimens were more effective than placebo in relieving vaginal symptoms (P less than 0.001). All four regimens reduced psychological symptoms and global indexes of distress; there were no significant differences among the treatment regimens. CONCLUSIONS. In women with presumed candidiasis hypersensitivity syndrome, nystatin does not reduce systemic or psychological symptoms significantly more than placebo. Consequently, the empirical recommendation of long-term nystatin therapy for such women appears to be unwarranted. 
1	Characterization of epidermal growth factor receptor in normal and neoplastic human endometrium. Growth factors, including epidermal growth factor (EGF), have been implicated in the growth of several types of cancer. This study compares EGF receptors in normal and neoplastic endometrium. Membrane fractions were isolated from surgical specimens. Radioreceptor assays demonstrated the presence of receptors with a dissociation constant of 0.64 nmol/l in normal endometrium. Affinity cross-linking revealed receptor molecular weight of 150 to 170 kiloDaltons (KD). A survey of samples (n = 37) revealed progressive decrease of EGF receptors in cancers of increasing grade: Grade 1-2 adenocarcinoma decreased 34% from control (n = 6, P less than 0.01), whereas Grade 3 adenocarcinoma decreased 90% (n = 7, P less than 0.01) and sarcoma decreased by 72% (n = 3, P less than 0.01). The dissociation constant and molecular weight of the receptor in neoplastic endometrium did not differ significantly from normal. The inverse relationship with grade suggests receptor alteration or down regulation by hormones and/or growth factors. 
2	A rare cause of colitis--Brucella melitensis. Report of a case. Documentation of gastrointestinal lesions in Brucella infections is sparse. A case of Brucella melitensis type 3 infection accompanied by erosive lesions of the colon, observed by endoscopy and histopathologic examination, is reported. Such gastrointestinal lesions have not been described since 1934. Before 1934 only postmortem observations are recorded. 
3	Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension. A series of 15 consecutive children with head and neck nonorbital rhabdomyosarcoma (RMSA) with meningeal extension were prospectively treated with chemotherapy consisting of Adriamycin (doxorubicin; Adria Laboratory, Columbus, OH) (ADM), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) followed by radiotherapy (60 Gy) to the primary tumor volume, along with intrathecal methotrexate (IT MTX). Thirteen of 15 responded to preradiation chemotherapy. Four of 13 relapsed. Relapse occurred at the level of the primary tumor in three of four. The 3-year progression-free survival (PFS) was 59%, similar to that achieved in a previous series treated with a comparable therapeutic approach that also included whole-brain radiotherapy as a prophylaxis of possible occult meningeal seeding. It is concluded that CNS prophylaxis with radiotherapy is questionable in the management of childhood RMSA with meningeal extension. 
1	Longitudinal study of women with negative cervical smears according to endocervical status A longitudinal study of 20,222 women who received negative cervical smear reports in 1987 showed that the incidence of definite or equivocal cervical intraepithelial neoplasia (CIN) was not significantly different between those whose first smear lacked an endocervical component and those whose smear included an endocervical component. The incidence of definite cytological evidence of CIN was significantly lower in women whose first smear did not include an endocervical component. It is concluded that women whose smears are reported as negative but lack an endocervical component should not be rescreened any earlier than women with negative smears that include an endocervical component. 
5	Photic sneeze reflex in nephropathic cystinosis Photic induced sneeze is a reflex that occurs in certain individuals after exposure to bright light. Cystinosis is an autosomal recessive inborn error of metabolism in which nonprotein cystine accumulates within lysosomes. The pathognomonic ocular manifestation of cystinosis is corneal crystal deposition. We observed photic induced sneezes during ophthalmoscopic examination in five of 19 patients with nephropathic cystinosis (26%). We report on this observation and discuss possible pathophysiological mechanisms for photic induced sneezing in cystinosis. 
1	Hepatocellular carcinoma presenting with pyrexia and leukocytosis: report of five cases. In the past 26 years we have encountered five patients with primary liver malignancy clinically characterized by high remittent fever and leukocytosis mimicking liver abscess. Two patients underwent exploratory laparotomy, and drainage was carried out in another. The clinical courses went rapidly downhill. The liver was cirrhotic in two patients. The interior of the main mass was almost totally necrotic in four cases. Histologically, the malignant cells in the main portion resembled sarcoma, but in some areas cells appeared epithelial with eosinophilic cytoplasm and were in a trabecular arrangement, except for one case not subjected to autopsy in which histological study was inadequate because of extensive necrosis. It seems that these neoplasms were very poorly differentiated hepatocellular carcinomas rather than combinations of sarcoma and hepatocellular carcinoma. These patients, therefore, may represent a distinct clinicopathological type of hepatocellular carcinoma that is very rare in Japan but perhaps more common in South Africa, where similar cases have been clinically described in larger numbers. 
4	Deterioration following delay in performing femoral angioplasty. It is not uncommon for a delay to occur between assessment arteriography and angioplasty attempt. We reviewed retrospectively the arteriograms of 61 patients where such a delay occurred to assess progression of superficial femoral artery (SFA) disease in this interval. A mean delay of 14.6 days (range 2-60 days) occurred between arteriogram and angioplasty attempt. Arteriographic deterioration was found in six of 61 patients (9.8%) and in three this precluded angioplasty. Of the six patients four had initial arteriography via the same side as the SFA disease whilst two had arteriography via the contralateral femoral approach. We discuss the aetiology of this phenomenon and suggestions are made to reduce its incidence. 
3	Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumors. The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (greater than 5 years old) had slowly progressive loss of vision. All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth. Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4 1/2 years following surgery. Six of these patients, with a follow-up period of 10 months to 4 1/2 years (mean 27 months), have had no adjuvant therapy following radical surgical resection. The authors conclude that: 1) radical surgical resection of chiasmatic-hypothalamic tumors can be performed with minimal morbidity; 2) radical resection may delay the time to disease progression in older children and postpone the need for irradiation; 3) resection of postirradiation recurrent tumors may provide neurological improvement and long-lasting clinical remission; and 4) chiasmatic-hypothalamic tumors of infancy are aggressive neoplasms that require multimodality therapy. 
3	Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. IV. Identification of an immunodominant T cell determinant on the N-terminal end of the VP2 capsid protein in susceptible SJL/J mice. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease serves as a relevant animal model of human multiple sclerosis. Myelin damage induced by TMEV infection appears to be immune mediated. Disease susceptibility correlates best with the temporal development of chronic, high levels of TMEV-specific, MHC class II-restricted delayed-type hypersensitivity (DTH) responses. We have proposed a model wherein these responses result in CNS demyelination via a macrophage-mediated terminal nonspecific bystander response. As virus-specific DTH responses appear to be intimately involved in the pathogenicity of CNS demyelination, it is critical to determine the specificity of these responses so that effector T cells specific for potential pathogenic epitopes can be targeted to serve as the focus of specific immunoregulatory processes. In the current study, the capsid protein specificity of the TMEV-susceptible SJL/J and TMEV-resistant C57BL/6 mouse strains was examined. DTH and Tprlf responses in both infected and immunized SJL/J mice were found to be predominantly directed toward the VP2 capsid protein, specifically to an epitope(s) contained within the N-terminal 150 amino acids of VP2. This same epitope was also found to be dominant in priming SJL/J mice for responses to challenge with intact virions. In contrast, the T cell-mediated responses of TMEV-resistant C57BL/6 mice did not show preferential reactivity towards VP2, because all three major capsid proteins (VP1, VP2, and VP3) elicited responses with essentially equal potency. The relationship of the restricted VP2 T cell epitope to predicted neutralizing antibody sites on the VP2 protein is discussed as is the potential use of this epitope for prevention and/or treatment of TMEV-induced demyelinating disease via the induction of epitope-specific tolerance. 
1	Predictive value of tumor estrogen and progesterone receptor levels in postmenopausal women with advanced breast cancer treated with toremifene. The predictive value of estrogen receptor (ER) concentrations was evaluated in a group of 113 postmenopausal patients with estrogen-receptor-positive (ER greater than 7 fmol/mg protein) advanced breast cancer. In 103 patients, tumors were also sampled for progesterone receptor (PgR) determination. All patients were treated with toremifene, a novel antiestrogen, 60 mg daily. The median ER in 51 responders was 78 fmol/mg protein, and in 62 nonresponders, 51 fmol/mg protein; the median PgR levels were 40 and 37 fmol/mg protein, respectively. The response rate in patients with ER less than 50 fmol/mg protein was 38%, and 51% in the group with ER greater than 50 fmol/mg protein (not significant [NS]). The response rate in patients with PgR less than 10 fmol/mg protein was 42%, and in patients with greater than 10 fmol/mg protein, 44%. The duration of response in patients with ER greater than 50 fmol/mg protein was significantly longer than with lower ER levels (P = 0.002). PgR was not associated with the duration of response. In Cox's multiple regression analysis, ER was an independent prognostic factor (P = 0.005) for response duration. Thus, the ER concentration of tumor tissue predicts the duration of response but not the response rate to toremifene in patients with advanced breast cancer. The PgR status does not predict the response rate or the duration of response. 
5	Co-trimoxazole for childhood febrile illness in malaria-endemic regions. The efficacy of co-trimoxazole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mg/kg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone. 
3	The relationship of pemphigus to neoplasia. A statistically increased incidence of malignancy has been observed in patients with pemphigus. A review of the literature reveals 42 cases of nonthymic malignancies and 18 cases of thymic malignancies. A significant predominance of men, with mean age at onset of 50 years, was observed. Pemphigus vulgaris is more common in patients with nonthymic neoplasms, whereas pemphigus foliaceus or pemphigus erythematosus and pemphigus vulgaris are equally common in patients with thymic neoplasms. Lymphoreticular malignancies, especially Kaposi's sarcoma, are most frequently observed. The majority of patients with nonthymic neoplasms have pemphigus before the detection of the malignancy and have a favorable 5-year survival rate after tumor resection. The majority of the patients with thymic neoplasms have a thymoma before the development of pemphigus. In some patients pemphigus develops after thymectomy and myasthenia gravis is often associated. Overall, 37 of the 60 patients, or 61%, had a neoplasm of the immune system. 
3	The patellofemoral joint after total knee arthroplasty without patellar resurfacing. One hundred total knee replacements with a total condylar prosthesis and without patellar resurfacing were followed for a minimum of two years. Eighty-four per cent of the knees were affected by osteoarthrosis. Graded according to the knee-rating system of the Hospital for Special Surgery, there were eighteen excellent, fifty-three good, eighteen fair, and eleven poor results. At the most recent follow-up, twenty-nine knees (29 per cent), nine of which were affected by rheumatoid arthritis, were still painful in the patellofemoral area. The height and weight of the patient definitely influenced the amount of patellofemoral pain postoperatively. Small patients who had osteoarthrosis were exceptionally free of pain, regardless of sex, age, or level of activity. It seems that the best approach to patellofemoral replacement includes resurfacing of the patella in all patients who have rheumatoid arthritis and in patients who have osteoarthrosis if they have preoperative patellofemoral pain, are more than 160 centimeters tall, weigh more than sixty kilograms, and have advanced changes in the patella at the time of the operation. 
3	Sleepwalking precipitated by treatment of sleep apnea with nasal CPAP. A 33-year-old man with a long history of snoring, observed apneic episodes, and excessive daytime sleepiness, underwent all-night polysomnography, which demonstrated severe obstructive sleep apnea. During the nasal CPAP trial, two episodes of sleepwalking were observed during a period of delta sleep rebound. 
1	Adenocarcinoma in Barrett's esophagus. A clinicopathologic study of 65 cases. The natural history of Barrett's esophagus, particularly the prevalence and incidence of malignant changes in it, remains controversial. Furthermore the prognosis of surgically treated patients with carcinoma in Barrett's esophagus has not been elucidated fully. To examine these and other issues, the records of 65 patients with carcinoma in Barrett's esophagus presenting at the Lahey Clinic Medical Center from January 1973 to January 1989 were reviewed. During this period, 241 patients with documented Barrett's esophagus were seen, for a prevalence of carcinoma of 27%. Adenocarcinoma in Barrett's esophagus accounted for 30% of the surgically treated carcinomas of the thoracic esophagus during this period. All but four of these patients were men. Symptoms of chronic reflux were present in less than one half of the patients and dysphagia was often the presenting symptom. In eight patients the carcinoma was discovered on routine surveillance endoscopy, and in four patients progression of disease from benign columnar epithelium to dysplasia to carcinoma was documented. Tumors developed in six patients who had undergone previous antireflux surgery, and in four other patients a second carcinoma developed in residual Barrett's epithelium after a previous resection. Of the 65 patients, 61 (94%) were considered to have operable disease, all of whom underwent resection. Two patients (3.3%) died within 30 days of operation. The resected specimens were staged as follows: stage 0, 4; stage I, 10; stage II, 17; stage III, 25; stage IV, 4. Of the resected specimens, 73% showed areas of dysplasia adjacent to the tumor. The overall adjusted actuarial 5-year survival rate was 23.7%. The 3-year survival rate was 100% for patients with stage 0 carcinoma, 85.7% for patients with stage I carcinoma, 53.6% for patients with stage IIA carcinoma, 45% for patients with stage IIB carcinoma, 25.2% for patients with stage III carcinoma, and 0% for patients with stage IV carcinoma. The premalignant nature of Barrett's esophagus requires endoscopic surveillance to detect early carcinoma because symptoms often occur late or are absent. Antireflux surgery does not protect against the development of carcinoma. All of the Barrett's epithelium must be resected because a second carcinoma may develop in residual columnar epithelium. Severe dysplasia should be considered an indication for resection. Although operability and resectability rates are high, long-term survival is not. Early detection is mandatory if long-term survival is to be achieved. 
5	Complications in the use of sodium hypochlorite during endodontic treatment. Report of three cases. In endodontic treatment, solutions of sodium hypochlorite are widely used as an irrigating agent. It is an effective solvent of both necrotic and vital tissues, which makes it toxic to the surrounding tissues. Complications are rarely reported. Nevertheless, the acute symptoms caused by the toxic reaction must not be underestimated. Causes, treatment, and prevention of complications of sodium hypochlorite use are discussed, and three case reports are presented. 
3	Impairment of vertical motion detection and downgaze palsy due to rostral midbrain infarction. We present two cases with acute onset of vertical gaze palsy, mainly consisting of impaired downgaze and apraxia of downward head movements, together with neuropsychological deficits (hypersomnia, impaired attention and disorders of memory and affective control). CT and MRI revealed bilateral post-ischaemic lesions in the dorsomedial thalamus and the mesodiencephalic junction, dorsomedial to the red nucleus, thus being restricted to the territory of the posterior thalamosubthalamic paramedian artery, which includes the region of the rostral interstitial nucleus of the medial longitudinal fascicle as the main premotor nucleus for the generation of vertical saccades. In our patients, oculographic examination with electro-oculography and magnetic search coil recording showed severe impairment of downward more than upward saccades and only minor deficits of vertical pursuit and the vestibulo-ocular reflex. Visual functions were normal, with one exception: a psychophysical test of motion perception revealed a significant deficit in the detection of vertical movements. This could be due to a central adaptive mechanism which, in order to minimize oscillopsia, might elevate thresholds for vertical motion perception in cases of vertical gaze palsy. As an alternative explanation, lesions within the midbrain tegmentum could have damaged subcortical visual pathways involved in motion perception. 
1	Suddenly symptomatic brain tumors at altitude. High-altitude cerebral edema can present with a wide variety of neurologic manifestations; these symptoms resolve with descent. The persistence of neurologic symptoms after descent suggests an intracranial lesion. Brain tumors suddenly becoming symptomatic at altitude have not been reported previously. We report three cases of previously unsuspected brain tumors that suddenly became symptomatic at high altitudes. 
1	Infarct of the conus medullaris simulating a spinal cord tumor: case report. A 71-year-old woman had the sudden onset of a neurogenic bladder and a stepwise increase in paraparesis that left her unable to stand or walk. Magnetic resonance imaging showed what appeared to be a tumor in the conus medullaris. After laminectomy, the lesion was localized by ultrasound examination, and a biopsy was performed. The deficits remained unchanged postoperatively. Microscopic examination of the biopsy specimen showed necrosis and pathologic changes consistent with infarction of the conus medullaris. An anomalous arterial supply of the conus medullaris is the most likely cause of this unusual problem. The patient gradually regained her ability to walk, but the neurogenic bladder persists. 
3	Effects of discontinuation of phenytoin, carbamazepine, and valproate on concomitant antiepileptic medication. We report a prospective, controlled study of the effects of the reduction and discontinuation of phenytoin (PHT) (22 patients), carbamazepine (CBZ) (23 patients), and valproate (VPA) (25 patients) with concomitant antiepileptic drugs (AEDs). The principal changes in the serum concentrations of concomitant AEDs were (a) phenobarbital (PB) concentrations decreased by a mean of 30% on discontinuation of PHT; (b) total CBZ concentrations increased by a mean of 48% and free CBZ concentrations increased by a mean of 30% on discontinuation of PHT, with no change in CBZ-10, 11-epoxide (CBZ-E) concentrations; (c) VPA concentrations increased by a mean of 19% on discontinuation of PHT; (d) VPA concentrations increased by a mean of 42% on discontinuation of CBZ; (e) ethosuximide (ESM) concentrations increased by a mean of 48% on discontinuation of CBZ; (f) PHT concentrations decreased by a mean of 26% on discontinuation of CBZ; (g) PHT free fraction decreased from a mean of 0.11 to 0.07 on discontinuation of VPA; and (h) the mean concentrations of total and free CBZ increased by a mean of 10 and 16%, respectively, on VPA discontinuation, with a concomitant mean 24% decrease in total CBZ-E and a 22% decrease in free CBZ-E. Apart from the decrease in PB concentrations on PHT discontinuation, all significant changes had occurred by 1 week after the end of AED discontinuation. The implication for clinical practice is that a serum AED concentration at this time reflects the new steady state. Free concentrations did not add any clinically useful information to that gained from analysis of total serum concentrations. 
1	Radioimmunoscintigraphy using iodine-131-anti-CEA monoclonal antibodies and thallium-201 scintigraphy in medullary thyroid carcinoma: a case report. This case report demonstrates the use of thallium-201 (201Tl) scans versus iodine-131- (131l) anti-CEA F(ab')2 scans in a patient with high serum CEA levels due to metastases of medullary thyroid carcinoma in the suprarenal region and sacroiliacal region. Scintigraphy using monoclonal antibodies directed against CEA showed a higher tumor uptake (0.26% dose and 0.64% dose, respectively) than a thallium scan and is believed to be promising for future radiotherapeutic applications. 
5	Evaluation of argon laser surgery in children under 13 years of age. Argon laser surgery is an effective treatment for ectasias and congenital port-wine stains; however, its use in children under the age of 13 is controversial. This paper reviews 202 children under the age of 13 who underwent argon laser treatments for congenital port-wine stains, spider angiomas, epidermal nevi, and lentigines. The clinical characteristics of port-wine stains in 170 children are discussed. Good to excellent results (moderate to complete clearing) in port-wine stains were obtained in 60 percent of patients and seemed to correlate best with lack of blanchability on pressure. Hypertrophic scarring was seen in only 7 children, all of whom had undressed wounds; no significant scarring has been seen in any subsequent child who had maintained a dressed wound postoperatively. 
5	Gastro-oesophageal reflux during elective laparoscopy. An oesophageal pH electrode was used to record gastro-oesophageal reflux in 73 women who had elective laparoscopy for various gynaecological procedures. No refluxes were recorded during the 63 procedures from which results could be analysed; the upper 95% confidence limit from this observation is 3 in 63 (4.8%). Two of the excluded women refluxed during episodes of hiccough that occurred shortly after induction of anaesthesia. Tracheal intubation may be required during laparoscopy, although the need to protect against the possibility of aspiration of gastric contents may not be a valid reason unless, with the same logic, it is suggested that all patients who hiccough should be intubated. 
1	Early gastric cancer. Endoscopic diagnosis of depth of invasion. In order to decide on a treatment strategy against gastric cancers, an accurate preoperative evaluation of the depth of cancer invasion is essential. Preoperative endoscopic diagnosis of the depth of invasion was compared with pathological results of the resected specimen in 206 early gastric cancers and 32 early-like advanced gastric cancers. The endoscopic distinction between early and early-like advanced cancers was correctly made in 83.6% of the cases. Among the early gastric cancers, mucosal and submucosal invasion was correctly presumed in 71.9% of the cases. When the tumor was an elevated type, or located in the antrum, the endoscopic diagnosis tended to be deeper than the true depth. The size of tumor contributed little to the depth diagnosis. Pathomorphological changes on the tips of converging folds were the important clue for diagnosing depth. 
4	Application of coronary angioplasty to the septal perforator arteries. Significant coronary artery disease affecting the septal perforator arteries can cause anginal pain, rhythm disturbances, or septal infarction. However, since these vessels are usually inaccessible to coronary bypass surgery, there is a tendency among angiographers and angioplasters to overlook lesions of the septal perforator arteries. Our experience suggests that if medical treatment is not sufficient to treat clinical manifestations resulting from septal perforator disease, then coronary angioplasty can be considered a therapeutic alternative for revascularization. We herein present 11 patients who underwent coronary angioplasty of a major septal artery and discuss angiographic and technical aspects of the procedure. 
5	Pathological changes in levator palpebrae superioris muscle treated with botulinum toxin in a case of carotico-cavernous fistula. We describe the case of a patient with carotico-cavernous fistula who had botulinum toxin A to induce a protective ptosis 4.5 days before death. The levator palpebrae superioris muscle from both sides and the superior rectus muscle from the injected side were obtained for examination. The preserved samples were stained with haematoxylin and eosin, Martius scarlet blue, Glees, S100, dehydrogenase, ATPase, and toluidine blue as well as being examined by electron microscopy. Inflammation and oedema were found that were probably due to the carotico-cavernous fistula. Axonal and some myelin sheath damage were also seen. 
3	The use of ultrasound in evaluating neurologic diseases of childhood. Real-time cranial sonography, intracranial Doppler, and neuromuscular sonography are the sonographic techniques that are applicable to the neurologic evaluation of infants and children. Although limited by age, specificity, and operator skill and experience, the advantages of real-time cranial and intracranial Doppler sonography make them useful techniques in the evaluation of the young infant, particularly in the serial assessment of ventricular size and in the study of the critically ill infant. The use of neuromuscular sonography in the assessment of the floppy infant and in the guidance of biopsy makes this an increasingly valuable tool. 
4	Treatment of severe acne with isotretinoin in patients with inflammatory bowel disease. Four patients with inflammatory bowel disease and severe cystic acne were treated with isotretinoin. Two patients had a successful course of treatment without any gastrointestinal side-effects. One patient had two episodes of profuse rectal bleeding that were probably related to pre-existing haemorrhoids. The fourth patient had a flare-up of his Crohn's disease after starting isotretinoin. 
4	Optimizing the exercise test for pharmacological investigations Exercise trials in cardiology are often hindered by inconsistent approaches to exercise testing. These inconsistencies include the choice of exercise protocol, exercise end points, points of analysis, and absence or misuse of gas exchange data. Gas exchange techniques greatly enhance the accuracy with which cardiopulmonary function is assessed by exercise. Commonly used protocols are not always appropriate for all patients or all studies. Both cardiovascular disease and the exercise protocol can have an important impact on the relation between changes in work rate and oxygen uptake. Ramp protocols appear to offer the greatest promise for assessing cardiopulmonary function. Analyzing hemodynamic and gas exchange responses at several points submaximally, in addition to those at peak exercise, can add important information concerning the efficacy of a drug. A great deal of confusion continues to hinder the application of the gas exchange anaerobic threshold, and many of the commonly used testing end points are not reliable. 
1	Rapid inactivation and phosphorylation of pyroglutamyl peptidase II in Y-79 human retinoblastoma cells after exposure to phorbol ester. Pyroglutamyl peptidase II (EC 3.4.19.-), a membrane-bound metalloproteinase, is a highly specific TRH-degrading enzyme. Exposure of Y-79 human retinoblastoma cells to 12-0-tetradecanoyl phorbol 13-acetate (TPA) decreased the activity of this enzyme in a time- and concentration-dependent manner (IC50 5 x 10(-9) M). After 15 min of TPA treatment, only 10% of pyroglutamyl peptidase II activity remained. TPA treatment did not affect the activity of the cytosolic enzyme pyroglutamyl peptidase I (EC 3.4.19.3) or the membrane-bound enzyme dipeptidyl peptidase IV (EC 3.4.19.3). Pretreatment of the cells with the protein kinase C inhibitors H-7 or sphingosine prevented the inactivation of pyroglutamyl peptidase II by TPA. The time course of the TPA-mediated effect paralleled the time course of translocation and activation of protein kinase C in this cell line. Immunoblot analysis demonstrated that inactivation of pyroglutamyl peptidase II was not due to dissociation or internalization of this enzyme molecule. Incubation of TPA-activated Y-79 cell membranes with gamma-[32P]-ATP followed by immunoprecipitation revealed a time-dependent phosphorylation of a 48 kilodalton subunit of pyroglutamyl peptidase II. These studies indicate that the phorbol ester effect is mediated by protein kinase C, and reveal a mechanism of potentiation of the action of TRH at its target sites. 
3	A study of the seasonal variation of migraine. Available evidence supports the contention that migraine involves a disturbance in serotonin function. Several parameters of serotonin function in humans have been found to vary seasonally and may underlie the seasonal fluctuations observed in many clinical neuropsychiatric phenomena that are thought to involve serotonin dysfunction. We therefore postulated that migraine headaches might also vary seasonally and examined the admissions to our hospital over a 20-year period with a primary diagnosis of migraine. Peak admissions were found to occur most frequently in the spring for females in comparison to males (p less than or equal to 0.04, chi-square). The implications of these findings are discussed. 
4	Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion. BACKGROUND AND METHODS: The purpose of this study was to determine the effects of nitric oxide (NO), believed to be endothelium-derived relaxing factor on reperfusion injury after myocardial ischemia (MI). The effects of NO were investigated in a 6-hr model of MI with reperfusion in open-chest, anesthetized cats. A solution containing NO was infused iv starting 30 min after occlusion of the left anterior descending coronary artery, continuing through reperfusion 1 hr later, and lasting for 5.5 hr. Estimated NO concentration in the circulation was 1 to 2 x 10(-9) M. RESULTS: The areas-at-risk expressed as a percentage of the total left ventricular weights were not significantly different among either of the MI groups. However, the necrotic area (expressed as a percentage of the myocardial area-at-risk) was significantly (p less than .01) lower in the NO-treated MI cats compared with the MI + vehicle group. Cardiac myeloperoxidase activities indicated that significantly (p less than .05) fewer neutrophils were attracted to the necrotic zone of the NO-treated MI cats when compared with MI cats receiving only the vehicle. Sodium nitrate (NaNO2) (pH 7.4), a major breakdown product of NO, failed to exert any protective effect in this same model of MI and reperfusion. CONCLUSIONS: NO appears to provide significant myocardial protection after ischemia and reperfusion. NO may afford cardioprotection by incorporation into circulating blood cells (i.e., neutrophils, platelets), thereby inhibiting their accumulation and adherence in the ischemic region, or by a direct cardiac cytoprotective effect. Further studies using NO donors rather than NO would be an appropriate clinically relevant mode of treatment in MI. 
5	Spontaneous rupture of a normal bladder. We have reported a case of spontaneous rupture of a normal urinary bladder. Patients with this rare condition characteristically have a recent history of heavy alcohol intake, sudden onset of abdominal pain coincidental with bloody urine, generalized peritonitis, and abnormal renal chemistry. A high index of suspicion will lead to early diagnosis and treatment, minimizing the mortality attributed to this condition. 
4	Combined orthopedic and vascular injury in the lower extremities: indications for amputation. A retrospective review was undertaken to determine risk factors associated with amputation after open fractures of the lower extremity that were complicated by vascular injury. During an 11-year period ending in December 1987, we observed open fractures in 31 patients and injuries to the popliteal artery in 16 patients, to the tibial arteries in eight patients, to the femoral artery in five patients, and to the dorsal artery of the foot in two patients. Vascular repair was accomplished in 25 patients; 12 patients had primary end-to-end anastomosis, 12 patients had reverse saphenous vein grafts, and one patient had a bovine graft. Of these 25 patients, five patients required amputation because of infection and three patients required amputation because of continued ischemia. Three patients with irreparable damage had immediate amputation, and three patients without distal ischemia had vessel ligation only. The risk factors associated with amputation were shock on admission (10 of 19 patients [p less than 0.02]) and a crushed extremity (10 of 18 patients [p less than 0.01]). The overall amputation rate, which included three immediate amputations and eight late amputations, was 35.2%. The data suggest that limb salvage is possible in two thirds of patients with combined orthopedic and vascular injuries of the lower extremity, but a history of shock or crush injury with vascular compromise is an unfavorable prognostic sign. 
3	Clinical and positron emission tomographic studies in the 'extrapyramidal syndrome' of dementia of the Alzheimer type. Extrapyramidal signs, particularly rigidity and tremor, have been reported in a proportion of patients with dementia of the Alzheimer type. To test the hypothesis that these extrapyramidal signs are similar clinically and neurochemically to the extrapyramidal signs of Parkinson's disease, a group of 20 patients satisfying clinical criteria for probable Alzheimer's disease were studied and assessed clinically for the presence of rigidity, tremor, and bradykinesia. In those patients with extrapyramidal signs, qualitative differences were observed between the signs in these patients and in subjects with Parkinson's disease. Fifteen of 20 patients underwent fluoro-18-dopa scans, which showed no significant difference in fluoro-18-dopa uptake into the caudate and putamen between normal subjects and the rigid and nonrigid patients with Alzheimer's disease, in contrast to the marked reduction in fluoro-18-dopa uptake into the putamen that is observed in Parkinson's disease. This provides clinical and in vivo neurochemical support for the hypothesis that extranigral factors may be involved in the pathogenesis of rigidity in Alzheimer's disease. 
5	Bronchodilator responses to anticholinergic and beta-adrenergic agents in acute and stable COPD Patients with COPD may respond differently to anticholinergic and beta-agonist bronchodilators. Previously, in acutely ill COPD patients, we showed similar improvements in pulmonary function after each drug (study 1). The responses of the same patients when stable are now reported (study 2). Patients received ipratropium bromide (54 micrograms) (n = 16) or metaproterenol sulfate (1.95 mg) (n = 14) via an MDI attached to a delivery device as in study 1. Ninety minutes after the first medication, patients received the second. Spirometry was measured at entry and at 30-min intervals following the first drug and at the same times after the second drug. Results were as follow: The groups did not differ in clinical characteristics. However, for both groups, there was significantly less airway obstruction at entry into study 2. In study 1, ipratropium resulted in significant improvement in FEV1 (0.62 +/- .08 to 0.88 +/- .11 L; mean increase 24 percent; p less than 0.05) with no further change after crossover. In study 2, ipratropium produced similar improvements in FEV1 by 90 minutes (0.94 +/- .09 to 1.3 +/- .09 L; mean increase 25 percent; p less than 0.05), with no further improvement after crossover. For metaproterenol, in study 1, the improvement in FEV1 was not significantly different than that for ipratropium (FEV1; 0.71 +/- .07 to 0.92 +/- 0.06 L; mean increase 18 percent; p less than 0.05), with no further improvement after crossover. In study 2, improvement with metaproterenol was significant and similar to study 1 (FEV1: 0.96 +/- .06 to 1.21 +/- .09 L; mean increase 18 percent; p less than 0.05). Thus, ipratropium and metaproterenol similarly improved pulmonary function in COPD patients when stable and during acute exacerbations. 
1	Immunohistochemical investigations of estrogen receptors in normal and neoplastic squamous epithelium of the vulva. Atrophic disease of the vulvar epithelium can be treated with steroids, but carcinoma of the vulva cannot be influenced with any hormone therapy. Seventy-one vulvar specimens were tested for estrogen receptor (ER) content by means of immunohistochemistry. Slight ER staining was found in nonkeratinizing squamous epithelium in 17 of 22 cases. A weak ER reaction in the basal and parabasal layers was found in only 2 of 17 specimens of keratinizing squamous epithelium. However, no ER was found in any neoplastic tissue of the vulva or the adjacent stroma. The loss of ER in neoplastic cells could explain the clinical experience that antihormonal treatment of vulvar carcinomas produces no appreciable improvement. 
4	Normal angiograms and carotid pathology. Nonstenotic ulcerated atherosclerotic plaques of the carotid arteries may be associated with symptoms of transient ischemic attacks, amaurosis fugax, and stroke. Preoperative evaluation of patients with these symptoms has traditionally included ultrasound and arch aortography angiograms of the area of the carotid bifurcation. Recent evidence has shown that ultrasound is more accurate in detection and morphologic delineation of these nonstenotic lesions. We analyzed the hospital records of 21 patients with ultrasonographic evidence of disease in whom arteriograms were negative. The patient group comprised 15 men and six women, with an average of 66 years. All patients had symptoms of hemispheric transient ischemic attacks and were evaluated with B-mode ultrasound and arteriography. Ultrasound was positive and arteriogram "negative" in all of the patients (i.e., described by the radiologist as without hemodynamic significant disease or ulceration, or as normal). The ultrasound diagnosis was confirmed at operation with findings of 20 to 50 per cent stenosis and ulcerative plaques. At retrospective review of the arteriograms, three ulcerations were found in the 21 patients. We conclude that B-mode ultrasound better defines nonstenotic ulcerative lesions and decisions to perform carotid endarterectomy may be based on either positive test. An ulcerative plaque by B-mode ultrasound and appropriate symptoms, therefore, may not require angiography before operation. 
5	NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Acute promyelocytic leukemia (APL) is a well-defined entity among acute leukemia, cytogenetically characterized by a t(15;17) (q22;q11-12) translocation. In vitro and in vivo studies suggest that all-trans retinoic acid (RA) treatment restores cell maturation. We have isolated the first permanent cell line with t(15;17), derived from the marrow of a patient with APL in relapse. The establishment of the cell line, its morphologic, karyotypic, and immunohistochemical features are reported. RA induced cell line maturation. Cells strongly expressed myeloid markers, but also some T-cell markers. Additional karyotypic abnormalities, a 12p rearrangement and the possible presence of a homogeneous staining region (HSR) on 19q+ are discussed both in relation to T-cell (CD2, CD4) and monocyte (CD9) markers, and to the acquired cell growth autonomy. The cell line represents a remarkable tool for biomolecular studies. 
5	A new syndrome: hearing loss and familial salivary gland insensitivity to aldosterone in two brothers. Two male siblings presented in infancy with hyponatremia. The levels of plasma renin activity and aldosterone were elevated. Sodium supplement was necessary to maintain normal sodium balance. The salivary sodium concentrations were markedly elevated, with sweat sodium levels being in the upper normal range. Urinary sodium concentration and renal epithelial exchange between sodium and potassium were normal. This was felt to be due to an autosomal recessive disorder. Both siblings were later diagnosed as having a bilateral moderate to severe sensorineural hearing loss with intermittent conductive overlay due to middle ear fluid. The sensorineural loss was also felt to be autosomal recessive in origin, but the possibility of a disturbance of sodium balance in the inner ear has been questioned. 
1	A phase I study of a new cisplatin derivative for hematologic malignancies. DWA2114R (DWA) is a new derivative of platin compounds that is currently being used in Phase II studies of solid tumors in Japan. The dose-limiting factor is myelotoxicity with mild extramedullary toxicity. This Phase I study consisted of adult patients with relapsed hematologic malignancies. Eight patients received a total of 15 treatment courses of DWA. The starting dose was 800 mg/m2 over 24 hours by continuous infusion. The dose was first increased to 1200 mg/m2 and then to 1600 mg/m2. Clinical toxicity and urinary excretion studies of DWA suggested that 1200 mg/m2/d for successive days would be the best type of administration. When 1200 mg/m2/d was given for 5 days, Grade 2 to 3 diarrhea and nausea and vomiting were encountered requiring parenteral fluids and nutritional support. This suggested that the dose-limiting factor with this schedule was gastrointestinal toxicity. Myelotoxicity was severe, as expected, but tolerable. One of the five patients with acute nonlymphocytic leukemia (ANLL) entered into complete remission and one patient with chronic myelogenous leukemia (CML) in crisis returned to the chronic phase. A Phase II trial of DWA is warranted for hematologic malignancies, especially in myeloid diseases. 
1	Broad spectrum penicillin as an adequate therapy for acute cholangitis. In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction. 
3	Unconsciousness associated with midazolam and erythromycin. An 8-yr-old boy suffering from an asymptomatic ventricular septal defect was given erythromycin for antibiotic prophylaxis before adenoidectomy. Sixty minutes after premedication with oral midazolam 0.5 mg kg-1 and oral atropine 0.03 mg kg-1, an infusion of erythromycin 400 mg was started. When 200 mg of erythromycin had been infused, the patient lost consciousness, but other vital functions remained normal. After 45 min, he awakened spontaneously. At the time the plasma concentration of midazolam was 134 ng ml-1. In order to investigate possible interactions between midazolam and erythromycin, we studied the pharmacokinetics of midazolam in six children of the same age undergoing minor otolaryngological surgery. The plasma concentration of midazolam in the patient who lost consciousness was significantly greater than in six other children without concomitant administration of erythromycin. The altered pharmacokinetics of midazolam may result from reduced hepatic clearance of midazolam caused by an enzyme inhibiting drug, erythromycin. 
3	Costs of operating a supported work program for traumatically brain-injured individuals. This paper presents a preliminary analysis of costs associated with a return-to-work program emphasizing a supported employment approach for persons who had sustained severe traumatic brain injuries. This analysis spans almost three years. Results indicated that a mean of 237.8 hours of staff intervention time was required to achieve job stabilization, at a cost of +6896. Ongoing follow-along and support services averaged 1.64 hours per week at a cost of +47.56. Over 68% of total staff time and costs were expended in job-site training and advocacy efforts. Application of these findings to state-level and agency-level policies should be weighed against individual characteristics and needs of clients, program design, and outcomes which clients achieve as a result of services. 
2	Truncal vagotomy and pyloroplasty combined with valvular replacement in patients with ulcer disease. In 1988, 5 patients (3 men and 2 women) with ulcer disease (mean age 56 +/- 8 years) underwent valvular replacement for aortic (No. = 4) or mitral disease (No. = 1). All patients had had gastroduodenal ulcers. Preoperative gastroscopy demonstrated active ulcers (No. = 4) and a healed pyloric ulcer with pyloric stenosis (No. = 1). Despite the presence of ulcers, a non-biologic prosthesis was preferred in each patient because of their young age (No. = 3), chronic atrial fibrillation requiring anticoagulant therapy (No. = 1), and refusal of the eventuality of subsequent reoperation (No. = 1). In each patient, a truncal vagotomy with pyloroplasty was performed simultaneously with the valvular procedures by the same incision. The postoperative courses were uneventful. With a mean follow-up of 15 +/- 3 months, no gastrointestinal bleeding was observed during anticoagulant therapy. With anticoagulant drugs, bleeding may occur with a frequency of 4% per patient treatment-year, half of which are gastrointestinal in origin. Nevertheless, in selected patients with gastroduodenal ulcers, performing a vagotomy-pyloroplasty simultaneously with valvular replacement allows implantation of a non-biologic prosthesis, with greater durability than bioprosthesis. 
5	HIV associated systemic necrotizing vasculitis. The spectrum of HIV associated rheumatic syndromes continues to expand as does our experience with the disease. The following is a case of HIV associated systemic necrotizing vasculitis documented by rectal biopsy. The patient was treated successfully with corticosteroids alone, and after 9 months of followup has no evidence of progression to frank AIDS. 
5	Comparison of four pulse oximeters: effects of venous occlusion and cold-induced peripheral vasoconstriction. The ability of four pulse oximeters (the Ohmeda 3700, Nellcor N100 and N200 and the Datex Oscar) to detect hypoxaemia was determined in the presence of venous obstruction and cold-induced peripheral vasoconstriction. Significant increases in detection time for hypoxaemia were found in both cases. There were no significant differences in detection time between the instruments, although the Ohmeda 3700 displayed smaller values of SaO2 under certain conditions. Peripheral vasoconstriction was induced using three differing methods which gave differing results, thus emphasizing the importance of methodology in assessments of pulse oximetry. 
5	Performance of cesarean section using absorbable staples. Although stapling techniques have gained wide acceptance in general surgery, they are still not commonly used in obstetrics. U.S. Surgical Corporation has introduced a stapling device suitable for use in cesarean sections. The copolymer staples (a blend of polylactic and polyglycolic acids) maintain their tensile strength until healing occurs and absorb without producing granulation tissue. The benefits include minimal trauma to tissue and reduced operating time, blood loss and postoperative morbidity. From July 1988 to February 1989, all patients undergoing low transverse cervical cesarean sections were randomized to either group 1 with the uterine incision performed in a routine manner or group 2 with the uterine incision cut and stapled using the Stapler. The preoperative management, intraoperative technique and postoperative surveillance were similar for both groups. The uterine incision was assessed by pelvic sonography during the postpartum period. Statistical analysis was performed using Fisher's exact test and chi-square analysis. Both groups were comparable for age, race, parity, gestational age and primary diagnosis. The length of the operative procedure was significantly shorter (p less than 0.05) in the stapled group. These patients also had a statistically significantly decreased incidence of uterine incisions and lacerations. All other parameters were not significantly different in the two groups. The stapled uterine incisions were visible by ultrasonography in more patients in the stapled group throughout the postpartum period than in the sutured group. Thus, stapling of the uterine incision was an acceptable alternative to traditional suturing techniques and it was possible to visualize clearly these incisions during the postpartum period. 
1	Giant cell tumor of bone. A clinicopathologic and DNA flow cytometric analysis. Flow cytometric DNA analysis was performed on 60 cases of giant cell tumor of bone and the results were correlated with the clinicopathologic features. Tumors studied were from 31 men and 29 women whose ages ranged from 18 to 62 years (median, 29 years). The most common sites were the distal end of the femur and proximal end of the tibia, accounting for 75% of the lesions. Treatment consisted of resection in 29 patients (48%), curettage with bone chip packing in 15 patients (25%), or curettage with cement packing in 16 patients (27%). Ten patients (17%) had local relapse within 1 to 3 years, and two had lung metastases. Forty-two patients (70%) exhibited tumors with a diploid DNA content, 16 aneuploid (27%), and two tetraploid (3%). Six (37.5%) of the aneuploid patients had relapses: one of those had been treated by resection of the tumor and five by curettage. Of the remaining ten (62.5%) unrelapsed aneuploid patients, nine had been treated by resection of the tumor and one by curettage. Four of the 42 diploid patients (9.5%) had relapses; all had been treated by curettage of the tumor. The two tetraploid tumors were treated by resection and none relapsed. Histologic parameters did not correlate with relapse rate or DNA pattern. Although relapse was more common among aneuploid tumors, our study shows that this appears to be influenced by the treatment modality rather than the ploidy status. Based on this study the DNA analysis of giant cell tumor of bone has a limited utility for predicting the tumor's biologic behavior. 
5	Plasma immunoreactive leukotriene C4 levels in patients with Kawasaki disease. The incidence of wheezing in Kawasaki disease (KD) has been investigated retrospectively. We measured plasma immunoreactive-leukotriene C4 (i-LTC4) levels of patients with KD. Wheezing was observed in 32 (12.5%) of the 256 patients with KD. Patients who had a prior history of bronchial asthma wheezed more frequently than other patients. During the acute stage of KD, plasma i-LTC4 levels both of wheezing and nonwheezing were significantly higher than those of healthy children. During the convalescent stage, plasma i-LTC4 levels of wheezing cases were higher than those of nonwheezing cases. We speculate that LTC4 contributes to the appearance of inflammatory symptoms during the acute stage of KD. During the convalescent stage when patients were taking aspirin, the presence of wheezing was associated with increased plasma levels of i-LTC4. More attention should be paid to the appearance of wheezing during the course of KD, especially in those cases in which the patient has a prior history of bronchial asthma. 
3	Treatment of chronic relapsing inflammatory demyelinating polyneuropathy by cyclosporin A and plasma exchange. A case report. A patient with chronic relapsing inflammatory demyelinating polyneuropathy was successfully treated with plasma exchanges and cyclosporin A (CsA). Dynamometric measurements of hand force during the time of CsA treatment showed a highly significant correlation between hand force and CsA blood levels. The largest influence of CsA on hand force occurred 11-13 days after CsA uptake. 
4	Abnormal hemodynamic response to Valsalva maneuver in patients with atrial septal defect evaluated by Doppler echocardiography. Hemodynamic responses to the Valsalva maneuver were studied in eight healthy subjects (group 1) and eight patients with ASD (group 2) using Doppler echocardiography. The acute changes of aortic blood flow profiles during the Valsalva maneuver were investigated on a basis of beat-to-beat estimation. During the active strain phase (phase 2), group 1 showed a significant decrease in systolic blood pressure, SV and CO with reflex tachycardia; in group 2, there was a significant decrease in SV and CO with reflex tachycardia, but not systolic blood pressure. The percentage decreases in SV and CO in group 2 were significantly less than those in group 1 (23 +/- 16 percent vs 48 +/- 10 percent for SV, p less than 0.01; 17 +/- 12 percent vs 40 +/- 13 percent for CO, p less than 0.05). After release of strain phase (phase 4), group 1 showed significant reversed changes in systolic blood pressure, SV and heart rate, indicating an overshoot effect which was, however, not observed in group 2. Thus, patients with ASD presented abnormal Valsalva response which was characterized by the absence of phase 4 overshoot and a less marked phase 2 change. The findings suggest that the decremental effect of impaired venous return on stroke output during active strain may be attenuated by the increased pulmonary blood volume due to left-to-right shunt. In patients with ASD, the lesser decrement of CO during phase 2 may not provoke sufficient sympathetic activity to induce overshoot response in phase 4. 
4	Degenerative aortic stenosis. One effect of the graying of America. Degenerative calcific aortic stenosis is evolving as a common geriatric problem. Once symptoms develop, it is a highly lethal disease that does not respond well to medical therapy. Aortic balloon valvuloplasty may offer palliation but is unlikely to alter the overall course of the disease. Aortic valve replacement is the therapy of choice, but high perioperative morbidity and mortality rates can be expected in the very elderly. The presence of other appreciable cardiac disorders may contribute to the occurrence of postoperative complications. Patients with asymptomatic aortic stenosis and normal left ventricular function can be treated medically and followed with serial aortic valve area determinations using Doppler echocardiography. 
5	Cadherin cell adhesion receptors as a morphogenetic regulator. Cadherins are a family of cell adhesion receptors that are crucial for the mutual association of vertebrate cells. Through their homophilic binding interactions, cadherins play a role in cell-sorting mechanisms, conferring adhesion specificities on cells. The regulated expression of cadherins also controls cell polarity and tissue morphology. Cadherins are thus considered to be important regulators of morphogenesis. Moreover, pathological examinations suggest that the down-regulation of cadherin expression is associated with the invasiveness of tumor cells. 
3	Failure of nine-month phenobarbital administration to reverse amygdaloid-kindled seizure susceptibility in cats. Upon completion of left amygdaloid kindling, 4 cats underwent long-term phenobarbital administration during the subsequent 5- to 9-month rest period. Plasma phenobarbital levels were maintained above 15 to 20 micrograms/ml and were restimulated following plasma phenobarbital washout. Three cats served as nonmedicated controls. All 7 cats were subjected to repeated 6-hour sleep monitoring for observation of interictal discharges, which were observed most often in the immediate postictal period. Their frequency decreased gradually throughout the experiment in both the medicated and control animals, but they never completely disappeared except from the contralateral amygdala in 1 medicated animal. Upon primary site restimulation, all of the medicated animals responded with a generalized convulsion once the afterdischarge was induced. When these animals underwent secondary-site amygdaloid kindling, 3 showed a positive transfer effect. The findings suggest that although phenobarbital is a potent anticonvulsant, it has little effect on the acquired seizure susceptibility of previously amygdaloid kindled cats. 
1	Complete remission in refractory anaplastic adult Wilms' tumor treated with cisplatin and etoposide. A 61-year-old woman underwent a left radical nephrectomy for Stage II anaplastic Wilm's tumor. She received no adjuvant therapy. One year later computerized tomography (CT) of the abdomen revealed a mass in the left renal fossa and retroperitoneal adenopathy. A CT-guided needle biopsy was nondiagnostic. The patient had progressive disease after treatment with dactinomycin, doxorubicin, and vincristine, but achieved a complete response after treatment with cisplatin and etoposide. The therapy of Wilms' tumor in adults is discussed. 
1	Staging of ureteral transitional cell carcinoma by CT and MRI. Intravenous urography and retrograde pyelography are the primary radiologic studies for detecting ureteral carcinoma but give limited information regarding stage of disease. Computed tomography (CT) and magnetic resonance imaging (MRI) delineate the extent of ureteral carcinomas with a high degree of accuracy by depicting the periureteral fat and presence or absence of lymphadenopathy. In selected cases, CT and MRI are valuable for assessing the presence or absence of tumor in a ureteral stump and for the differential diagnosis of ureteral obstruction. Five cases of ureteral carcinoma and 2 cases of stump carcinoma are presented with preoperative CT and/or MRI evaluation and staging. 
1	Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer. Previous studies in breast and bladder cancer have suggested that epidermal growth factor receptor is expressed by only a proportion of cancers and is associated with poor clinical outcome. We used a monoclonal antibody specifically reactive with the extracellular domain of the epidermal growth factor receptor to localize this receptor immunohistochemically in frozen sections of normal ovary and epithelial ovarian cancer. Normal ovarian epithelium was found to express epidermal growth factor receptor in all cases. Among 87 ovarian cancers, however, 23% did not express immunohistochemically detectable receptor. Epidermal growth factor receptor expression was not related to histologic grade or stage, but was associated with poor survival (p less than 0.05). The median length of survival of patients with tumors that did not express epidermal growth factor receptor was 40 months compared with 26 months in patients with tumors that did express epidermal growth factor receptor. As in breast and bladder cancer, expression of epidermal growth factor receptor in ovarian cancer appears to be a poor prognostic factor. 
1	Prognostic factors for outcome of and survival after second-look laparotomy in patients with advanced ovarian carcinoma. In ovarian cancer stages IIB-IV, pre-treatment variables and variables obtained intraoperatively at second-look laparotomy were investigated for their prognostic influence on the outcome of 109 patients and survival after second-look laparotomy in 131 patients. The subjects came from a randomized trial of sequential versus alternating combination chemotherapy. The overall median survival after second-look laparotomy was 62 months. Logistic regression analysis identified stage and hysterectomy plus bilateral salpingo-oophorectomy and omentectomy as significant prognostic covariates for second-look laparotomy outcome. Based on a Cox multivariate stepwise analysis, independent prognostic factors for survival after second-look laparotomy were secondary residual tumor size, pre-treatment histologic differentiation grade, and performance status. A high differentiation grade and a good performance status at the start of therapy thus still had a prolonging effect on survival after second-look laparotomy. The prognostic power of these pre-treatment variables was increased substantially by the addition of the secondary residual tumor size variable. The 3-year survival rate after second-look laparotomy for high- and low-risk patients was 15 and 87%, respectively. Second-look laparotomy thus provides prognostic information in patients with advanced ovarian carcinoma, but the benefit in terms of survival is still unclear. 
2	Gall-bladder perforation after long-term dapsone therapy. A 65-year-old man on maintenance dapsone therapy for dermatitis herpetiformis for 30 years was admitted to hospital with acute abdominal pain and vomiting. Investigations revealed a Heinz body haemolytic anaemia. Worsening symptoms prompted an emergency laparotomy that revealed a perforated gall bladder with pigmented biliary calculi. In previous reviews of the haematological abnormalities associated with dapsone therapy, life-threatening cholecystitis has not been described. 
5	Association of Escherichia coli HEp-2 adherence patterns with type and duration of diarrhoea. 373 (59%) out of 636 faecal specimens obtained during the first 2 years of life of 72 Mexican children yielded adherent Escherichia coli (HEp-2 cells). Strains with localised adherence were significantly associated with acute non-bloody diarrhoea, whereas strains with aggregative adherence were significantly associated with persistent diarrhoea. Half the strains with localised adherence were not enteropathogenic E coli serotypes nor did they hybridise with an enteropathogenic E coli adherence factor DNA probe. All strains with localised adherence gave a positive fluorescent actin staining (FAS) assay, irrespective of serotype. One-third of children colonised by aggregative strains had bloody diarrhoea. Isolation of strains with diffuse adherence was not related to type or duration of diarrhoea but was generally associated with isolation of another pathogenic organism. 
4	Effects of epidural anesthesia on the incidence of deep-vein thrombosis after total knee arthroplasty [published erratum appears in J Bone Joint Surg [Am] 1991 Jul;73(6):952] Epidural anesthesia has been reported to reduce the prevalence of deep-vein thrombosis after total hip arthroplasty compared with the prevalence after general anesthesia. However, the effect of epidural anesthesia on the rate of thrombosis after total knee arthroplasty has not been reported previously, to our knowledge. A review was conducted of 705 total knee arthroplasties (541 patients) that had been performed by a single surgeon between September 1984 and December 1988. During this period, the operative technique, the protocol for rehabilitation, and the regimen for prophylaxis against thromboembolism did not change meaningfully. The patients received either epidural or general anesthesia. Preoperative and postoperative perfusion scans of the lungs and a venogram of the lower limb or limbs that had been operated on were done for all patients. For the 227 patients who had received epidural anesthesia, the over-all rate of deep-vein thrombosis was 48 per cent, which was significantly lower than the 64 per cent incidence in the 264 patients who had received general anesthesia (p less than 0.0001). The greatest reduction was in the occurrence of proximal thrombosis, which was identified in 9 per cent of the patients who had had general anesthesia but in only 4 per cent of those who had had epidural anesthesia (p less than 0.05). The use of epidural anesthesia reduced the incidence of proximal thrombosis after both unilateral and one-stage bilateral arthroplasty. 
1	Flexible Nd:YAG laser palliation of obstructive tracheal metastatic malignancies. Flexible Nd:YAG endoscopic laser surgery may become an effective new modality for palliation in patients with obstructive endotracheal metastatic malignancies. We report the results of the treatment of two patients with severely obstructing intraluminal tracheal metastatic melanoma and medullary thyroid carcinoma, using the neodymium-YAG laser via the flexible fiberoptic bronchoscope. Both patients complained of significant dyspnea, orthopnea, cough, and hemoptysis and were not candidates for rigid bronchoscopy because of underlying medical contraindications and anatomical problems. Multiple treatment sessions were used with treatment intervals of 1 to 2 weeks. All treatments were performed in the operating room under sedation, without intubation, with topical lidocaine and standard superior laryngeal nerve block. Successful relief of airway obstruction with complete regression of the endotracheal masses was achieved and no recurrences were seen after 9 months' follow-up. Flexible Nd:YAG laser bronchoscopy offered an alternative for the relief of obstructing endotracheal or bronchial malignancies in patients in whom the rigid bronchoscope could not be passed. it seemed to prolong survival in selected cases, and provided definite improvement in quality of life. 
2	Prevalence of inflammatory bowel disease in family members of Jewish Crohn's disease patients in Israel. A familial study of 189 Jewish Crohn's disease patients was conducted in order to evaluate the risk for inflammatory bowel disease (IBD) in relatives of the patients and to try to understand better the genetic component in the etiology of the disease among Jews. One hundred fifty-seven patients filled out questionnaires that were verified by personal interviews. In 10 families (6.6%), a first-degree relative of the propositus was found to have IBD, seven Crohn's disease and three ulcerative colitis. Among first-degree relatives, siblings were more frequently affected: of 400, five had Crohn's disease and one ulcerative colitis. Among 304 parents, two had Crohn's disease and two ulcerative colitis, while none of the propositi's children had IBD. The prevalence of first-degree relatives with Crohn's disease was similar in the 98 and 45 families of Ashkenazi and non-Ashkenazi origin: 5.1% and 4.4%, respectively. The risk for siblings of the probands to be affected were also similar in the two groups: 1.5% and 1.8%; while parents of the probands were affected only in the group of Ashkenazi Jews. 
1	Functional character and augmentation of lymphocytes in regional lymph nodes of patients with lung cancer. It appears that lymph node metastases are more frequent in lung cancer than in other cancers because of impaired defensive mechanisms in the regional lymph nodes. However, little is known about the immunologic function of regional lymph node lymphocytes (RLNL) in patients with lung cancer. We have studied the immunologic properties of RLNL in comparison with peripheral blood lymphocytes (PBL). We measured the natural killer (NK) cell activity of RLNL and PBL in patients with lung cancer and found that the NK activity was significantly more depressed in the RLNL than in the PBL. In contrast, interleukin-2 (IL-2) production was markedly higher in the RLNL than in the PBL. The cytotoxic effect of RLNL in nonmetastatic lymph nodes on target cells (such as K562 cells) or PC-3 and PC-10 cells (NK-resistant, human lung cancer of adenocarcinoma and epidermoid carcinoma, respectively) was significantly enhanced by in vitro incubation with recombinant IL-2 (rIL-2). Furthermore, we clarified that both rIL-2 and OK-432, which is a biologic response modifier and IL-2 inducer as well, augmented the cytotoxicity of RLNL and that these effector cells were lymphokine-activated killer (LAK) cells. The depletion of lymphocyte subsets by pretreatment with specific monoclonal antibody showed that the LAK activity in RLNL was mediated by CD3+ and CD8+ cells, whereas the lymphocyte subsets contributing the LAK activity in PBL were CD3+ and CD16+ cells. It was concluded that a majority of the effector cells in RLNL were LAK cells of the cytotoxic T cell population. 
1	Solitary fibromatosis of bone. A rare variant of congenital generalized fibromatosis. Congenital generalized fibromatosis is part of the spectrum of the fibromatoses of infancy and childhood. The lesions are usually multiple and fibrous in nature. They may appear in virtually every organ outside the central nervous system. Congenital generalized fibromatosis can be limited to the skeleton and rarely manifests itself as a solitary bone lesion. Solitary osseous lesions often behave differently than multiple osseous lesions. Solitary lesions often do not regress without treatment and can have a high incidence of recurrence with less than marginal excision. Multiple osseous lesions often regress without treatment. 
5	A randomised double-blind study of interpleural analgesia after cholecystectomy. Continuous interpleural analgesia provided by 4 hourly injections of 20 ml bupivacaine 0.5% with adrenaline 5 micrograms/ml was compared with placebo in a randomised, double-blind study after cholecystectomy. All patients self-administered intravenous morphine using a patient-controlled analgesia device. There was a highly significant difference in mean morphine consumption between the groups (72 mg as compared with 22 mg). Visual analogue pain scores tended to be lower in the bupivacaine group throughout and this was significant at 2 hours. Respiratory function measurements were not significantly different between the groups. The mean peak venous plasma bupivacaine concentration after the sixth dose was 3.03 micrograms/ml and no symptoms suggestive of local anaesthetic toxicity occurred. It is concluded that this regimen can provide effective and continuous analgesia after cholecystectomy and that combined administration of interpleural bupivacaine and systemic morphine is more effective than morphine alone in the immediate postoperative period. The doses of bupivacaine required for optimal use of the technique lead to significant total plasma bupivacaine concentrations within 24 hours. 
1	Glucagonoma syndrome is an underdiagnosed clinical entity. Glucagonomas, considered among the rarest of the islet cell neoplasms, produce a well-defined clinical syndrome characterized by necrolytic migratory erythema, diabetes mellitus, glossitis, anemia, and weight loss. This report describes seven patients with glucagonoma treated at our institution. All seven had the characteristic dermatologic manifestations, present from 1 to 6 years prior to diagnosis. Five patients had extensive disease at the time of initial operation, three of whom underwent aggressive cytoreductive surgery, whereas the other two had biopsy only. The remaining two patients presented with a single nodule each, underwent distal pancreatectomy and splenectomy, and remain free of disease 2 and 6 years postoperatively. Earlier recognition of the distinctive physical findings peculiar to this syndrome should increase survival. Aggressive cytoreductive surgery results in prolonged remission. 
2	Esophageal motor disorder in alcoholics: result of alcoholism or withdrawal? Both acute and chronic ethanol consumption may cause esophageal dysmotility. In order to systematically evaluate the effect of ethanol on esophageal motility, we studied esophageal motility in 13 healthy subjects before and following acute intravenous administration of 0.8 g/kg ethanol and in chronic alcoholics within 6 hr of their last drink (n = 6) and following 24 to 48 hr of abstinence when signs of withdrawal were present (n = 13). Withdrawing alcoholics were also restudied after intravenous administration of 0.8 g/kg ethanol. Ethanol transiently decreased lower esophageal sphincter pressure (LESP) and inhibited LES relaxation in all control subjects; this inhibitory effect of ethanol on LESP in alcoholics was significantly less, indicating the development of tolerance. Ethanol moderately decreased esophageal contraction amplitude (ECA) in 10 of 13 controls and prolonged duration of contractions in all but had no effect on velocity of esophageal contractions. In contrast, ECA was significantly elevated in both groups of alcoholics, but this was significantly more marked in withdrawing alcoholics. Ethanol infusion returned ECA toward normal values in withdrawing alcoholics. Abnormal motility was noted in three intoxicated alcoholics and 10 (77%) withdrawing alcoholics. This included nutcracker esophagus in five and hypertensive LES in two. These data indicated that (1) esophageal motor dysfunction is common in alcoholics; (2) acute ethanol administration decreases LESP and esophageal contraction amplitude, whereas chronic ethanol consumption and withdrawal from ethanol increases ECA. This suggests development of a compensatory mechanism in chronic alcoholics leading to high pressure esophageal contractions during withdrawal. 
5	Stiff-man syndrome: a GABAergic autoimmune disorder with autoantigenic heterogeneity. Autoantibodies that reacted with cell bodies and axon terminals of gamma-aminobutyric acid (GABA)ergic neurons were present in the serum and cerebrospinal fluid in a patient with stiff-man syndrome with type I diabetes. Immunoblot experiments using this patient's serum and cerebrospinal fluid did not corroborate an earlier observation that these autoantibodies are directed against the GABAergic cytosolic enzyme, L-glutamic acid decarboxylase. While L-glutamic acid decarboxylase autoantibodies may be associated with this syndrome, they do not appear to be easily demonstrated. 
3	Controlling stability of a complex movement system. Human movement systems have frequently been treated as one-dimensional, single-axis, rigid bodies in order to simplify the gathering, analysis, and interpretation of data. The problem with this approach is that the results of such assumptions often lead to conclusions about the production and control of movement that do not relate to the control demands placed on the central nervous system. In order to truly understand how the central nervous system plans and produces movements to match environmental demands, we must take into account the many variations available within the body. The purpose of this article is to examine two movement systems that have the potential to act in multiple spatial dimensions with variable muscle action patterns when performing a stabilizing task. Methods of analyzing how the systems operate under differing task constraints and results of the experiments will be presented. Hypothetical models that have been proposed to explain how complex movement systems operate will also be discussed. 
3	Scales for rating motor impairment in Parkinson's disease: studies of reliability and convergent validity. Study 1 examined the reliability of the ratings assigned to the performance of five sign-and-symptom items drawn from tests of motor impairment in Parkinson's disease. Patients with Parkinson's disease of varying severity performed gait, rising from chair, and hand function items. Video recordings of these performances were rated by a large sample of experienced and inexperienced neurologists and by psychology undergraduates, using a four point scale. Inter-rater reliability was moderately high, being higher for gait than hand function items. Clinical experience proved to have no systematic effect on ratings or their reliability. The idiosyncrasy of particular performances was a major source of unreliable ratings. Study 2 examined the intercorrelation of several standard rating scales, comprised of sign-and-symptom items as well as activities of daily living. The correlation between scales was high, ranging from 0.70 to 0.83, despite considerable differences in item composition. Inter-item correlations showed that the internal cohesion of the tests was high, especially for the self-care scale. Regression analysis showed that the relationship between the scales could be efficiently captured by a small selection of test items, allowing the construction of a much briefer test. 
1	Crystal-storing histiocytosis and crystalline tissue deposition in multiple myeloma [published erratum appears in Arch Pathol Lab Med 1991 Aug;115(8):806] Systemic distribution of crystal-storing histiocytes, increasing in number, and widespread crystalline tissue deposition were found in a 75-year-old man with a 5-year history of IgG-kappa-type multiple myeloma associated with corneal opacity and chronic renal failure. Characteristic crystalline inclusions were present not only in myeloma cells but also in cornea, epithelial cells of glomeruli, tubuli, Bowman's capsules, and choroid plexus. Histiocytes had particularly infiltrated the renal interstitium. These inclusions were positive by immunofluorescence for kappa light and gamma heavy chains. By electron microscopy, the inclusions were filled with fine crystalline hexagonal columns, each possessing a core structure. Of various factors generally considered responsible for renal failure in multiple myeloma, marked infiltration of histiocytes and the nephrotoxic effects of light chain appeared most relevant in the present case. 
1	Clinoidal meningiomas. Anterior clinoidal meningiomas are frequently grouped with suprasellar or sphenoid ridge meningiomas, masking their notorious association with a high mortality and morbidity rate, failure of total removal, and recurrence. To avoid injury to encased cerebral vessels, most surgeons are content with subtotal removal. Without total removal, however, recurrence is expected. Recent advances in cranial-base exposure and cavernous sinus surgery have facilitated radical total removal. The author reports 24 cases operated on with vigorous attempts at total removal of the tumor with involved dura and bone. This experience has distinguished three groups (I, II, and III) which influence surgical difficulties, the success of total removal, and outcome. These subgroups relate to the presence of interfacing arachnoid membranes between the tumor and cerebral vessels. The presence or absence of arachnoid membranes depends on the origin of the tumor and its relation to the naked segment of carotid artery lying outside the carotid cistern. Total removal was impossible in the three patients in Group I, with postoperative death occurring in one patient and hemiplegia in another. Total removal was achieved in 18 of the 19 patients in Group II, with one death from pulmonary embolism. In the two patients in Group III, total removal without complications was easily achieved. 
4	Intraoperative detection of patent foramen ovale by transesophageal echocardiography. This study reports the intraoperative use of contrast and Doppler echocardiography techniques to diagnose patent foramen ovale (PFO). Fifty patients without known atrial septal defects undergoing elective cardiovascular surgery were studied. A 5-MHz esophageal echocardiographic probe was used to image the fossa ovalis (FO) and 10 ml agitated saline was injected into the right atrium during apnea. Echocardiographic contrast was then injected during end-inspiration at 20-cmH2O airway pressure. When opacification of the right atrium was complete, the airway pressure was released. During these maneuvers, color and pulsed-wave Doppler interrogation of the atrial septum were also performed. Right-to-left passage of saline contrast across the interatrial septum was seen in 11 of 50 patients (22%). Doppler echocardiography demonstrated a PFO in 2 patients without contrast evidence of shunting. Thus, the combination of contrast and Doppler echocardiography identified a 26% (13 of 50) prevalence of PFO, approximating the previously reported autopsy rate of 25%. These contrast and Doppler techniques may be useful in detecting patients at risk for paradoxical emboli and in identifying candidates for closure of the PFO. 
5	Miscellaneous adverse effects of low-versus high-osmolality contrast media: a study revised The authors analyzed data from two recent articles in Radiology in which the quality and results of randomized control trials (RCTs) comparing the efficacy or safety of the low-osmolality contrast media (LOM) iopamidol, iohexol, and ioxaglate with that of the high-osmolarity contrast media (HOM) diatrizoate, iodamide, iopamide, iothalamate, and metrizoate were assessed. One conclusion in the source articles was that no differences were seen between the two groups of contrast media in frequency of nausea, vomiting, and urticaria. However, the LOM group included both nonionic LOM (NIM) and the ionic contrast medium ioxaglate. The authors found that various complications associated with the use of contrast media were much less common with NIM than with HOM; statistically this lower frequency is highly significant. This difference was obscured in the previous studies by the pooling of RCTs in which the less toxic NIM were used and RCTs in which the more toxic ionic contrast medium ioxaglate was used. 
1	T-cell translocation gene 1 (Ttg-1) encodes a nuclear protein normally expressed in neural lineage cells. We previously identified and cloned T-cell translocation gene 1 (Ttg-1), a putative zinc finger protein, as a result of its deregulated expression in a T-cell acute lymphoblastic leukemia cell line (RPMI 8402) with a t(11;14)(p15;q11). We have now characterized its genomic organization and identified the major transcriptional start site to lie within an initiator-like motif. Ttg-1 is normally expressed in mouse brain and not in thymus. The mouse neuroblastoma cell line, N2a, also expresses Ttg-1. Antibodies raised against a TrpE-Ttg-1 fusion protein precipitate an 18-Kd nuclear protein from metabolically labeled 8402 cells. Immunofluorescence of N2a cells shows a nuclear pattern. The two potential zinc finger domains in Ttg-1 are highly homologous to similar regions in lin-11, mec-3, and lsl-1. This data suggests that Ttg-1 may be involved in gene regulation. 
1	Gemistocytic astrocytomas: a reappraisal. Although gemistocytic astrocytomas are considered slow-growing astrocytomas, they often behave aggressively. To clarify the biological and clinical behavior of these rare tumors, the authors retrospectively identified 59 patients with gemistocytic astrocytoma whose tumors were diagnosed and treated between June, 1976, and July, 1989. Three patients who were lost to follow-up review were excluded, as were two whose original slides could not be obtained and three whose tumors were diagnosed at recurrence or at autopsy. The pathological material of the remaining 51 patients was reviewed using two sets of histological criteria. Thirteen patients (Group A) had "pure" gemistocytic astrocytoma, defined as a glial tumor with more than 60% gemistocytes/high-power field and a background of fibrillary astrocytes. Fifteen patients (Group B) had "mixed" gemistocytic astrocytoma, defined as a glial tumor with 20% to 60% gemistocytes/high-power field and a background of anaplastic astrocytes. Twenty-three tumors did not meet these criteria and were excluded from analysis. The median age of the patients was 48.5 years in Group A and 38.3 years in Group B (p less than 0.05). In both groups, the median Karnofsky Performance Scale score was greater than 90%. All patients underwent surgical procedures (four total and 19 partial resections, and five biopsies) and postoperative radiation therapy. The majority also had interstitial brachytherapy, chemotherapy, or both. Ten patients had one reoperation for tumor recurrence and one had two reoperations; other treatments for recurrence included brachytherapy, chemotherapy, and repeat irradiation. All four patients who originally underwent gross total resection are still alive; all five who had a biopsy have died. There was no significant difference in median survival times between groups: 136.5 weeks in Group A (range 10 to 310+ weeks) and 135.6 weeks in Group B (range 31 to 460+ weeks). Analysis of all 28 patients showed a better prognosis for patients less than 50 years of age (185 vs. 36 weeks survival time; p less than 0.001), patients with preoperative symptoms lasting for more than 6 months (228.1 vs. 110.2 weeks survival time; p less than 0.05), and patients with seizures as the first symptom (185.7 vs. 80 weeks survival time; p less than 0.01). Survival time did not correlate with the presence of perivascular lymphocytic infiltration. The authors conclude that the presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic sign, irrespective of the pathological background. It is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly. 
3	Cerebral falciparum malaria mimicking thrombotic thrombocytopenic purpura. We have described a patient with cerebral falciparum malaria who had rapidly progressive CNS deterioration, renal failure, hemolytic anemia associated with striking and varied erythrocyte morphologic changes, and thrombocytopenia. The initial diagnosis was thrombotic thrombocytopenic purpura (TTP) of unknown origin. Reexamination of the peripheral smear of this comatose patient led to correct diagnosis and effective treatment in this case of cerebral falciparum malaria--another of medicine's great mimickers. 
1	Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. Report of three cases. Three examples of an unusual morphologic variant of papillary thyroid carcinoma (PTC) are reported. The presence of a prominent stromal component resulted in low-power microscopic appearances resembling fibroadenoma, phyllodes tumor, or fibrocystic disease of the breast in two cases. The carcinomatous component grew in the form of anastomosing narrow tubules, clustered glands, solid sheets with or without squamous differentiation, and/or papillae, and exhibited the typical nuclear features of PTC. The abundant stroma had a nodular fasciitis-like quality and was composed of short fascicles of spindle cells separated by varying amounts of mucoid matrix, collagen, and extravasated red blood cells; this was interpreted as an exuberant mesenchymal reaction to the carcinoma. The importance of recognizing this variant of PTC is that, when one encounters a fibroproliferative lesion of the thyroid, a diligent search should be made for papillary carcinoma. This variant also must be distinguished from the vastly more aggressive papillary carcinomas with anaplastic transformation and the so-called carcinosarcomas. 
1	Attributes and survival patterns of multiple primary cutaneous malignant melanoma. From a series of 1495 patients with primary cutaneous malignant melanoma (PCMM), 26 patients (1.73%) had multiple primary cutaneous malignant melanoma (MPCMM). This report describes the attributes and survival patterns in this small, but important, subgroup of patients with PCMM. Of 26 patients, 23 had two primaries, two had three primaries, and one had six primaries. Five patients had synchronous and 21 patients had metachronous MPCMM. The median interval between the occurrence of the first and subsequent PCMM in these patients was 1.93 years. The estimated 5-year survival rate from the first melanoma was 83.5%; that from the last melanoma was 53.1%. In summary, MPCMM is a distinct biologic phenomenon. A second or subsequent malignant melanoma should be treated like a primary melanoma. 
5	Clip repair of peripheral side-to-side arteriovenous fistulas. Evaluation of a method in dogs and preliminary results in humans. A simple technique for repair of peripheral arteriovenous fistula by clip application is presented. This procedure is rapid and effective, it minimizes the extent of dissection, and it eliminates the need for application of vascular clamps on the vessels and for anticoagulation. The safety of the procedure was confirmed in dog experiments and clinically applied successfully in four patients. It is suitable for simple, uncomplicated side-to-side fistulas amenable to this procedure. 
5	Quadriceps myopathy: forme fruste of Becker muscular dystrophy. We examined dystrophin, the protein product of the Duchenne muscular dystrophy gene, in muscle biopsy specimens from 4 male patients with quadriceps myopathy, all of whom showed a mild and slowly progressive myopathy confined to the quadriceps muscles. All 4 patients had clear abnormalities of dystrophin, and were diagnosed as having Becker muscular dystrophy by both immunofluorescence and immunoblot examinations; that is, dystrophin of an abnormal molecular mass was visualized in muscle cryosections as "patchy" or discontinuous immunostaining at the surface membrane of the muscle fibers. One patient had a brother who showed widespread myopathic changes consistent with typical Becker muscular dystrophy. We conclude that the syndrome called quadriceps myopathy includes a group of forme fruste Becker muscular dystrophy. 
2	Aerobic work capacity in patients with chronic fatigue syndrome OBJECTIVE--To determine the aerobic work capacity of patients with the chronic fatigue syndrome and compare it with that of two control groups, and to assess the patients' perception of their level of activity before and during illness. DESIGN--A symptom limited exercise treadmill test with on line gas analysis and blood sampling was used. Subjects were assessed by one investigator, who was blind to the group which they were in. SETTING--Department of medicine, Royal Victoria Hospital, Belfast. SUBJECTS--13 Patients (10 women, three men) who fulfilled the diagnostic criteria for chronic fatigue syndrome. Two control groups of similar age, sex, and body weight: 13 normal subjects (10 women, three men) and seven patients (five women, two men) with the irritable bowel syndrome. MAIN OUTCOME MEASURES--Aerobic work capacity as assessed by several variables such as length of time on treadmill, heart rate, and biochemical measurements; Borg score; and visual analogue scores of perceived level of physical activity. RESULTS--The patients with the chronic fatigue syndrome had a reduced exercise capacity compared with that of the other subjects, spending a significantly shorter time on the treadmill. They had a significantly higher heart rate at submaximal levels of exertion and at stage III exertion had significantly higher blood lactate concentrations. Using a Borg score, they showed a significantly altered perception of their degree of physical exertion with a mean score of 8.2 compared with 6.6 and 5.3 for the normal subjects and patients with the irritable bowel syndrome respectively. Using a visual analogue scale they indicated that they had a greater capacity for activity before illness than had the patients with the irritable bowel syndrome, but the scores were not significantly different between the two groups. Both groups of patients indicated reduced activity at the time of testing. Normal controls and patients with the irritable bowel syndrome aspired to a greater level of activity than their current level, but the patients with the chronic fatigue syndrome aspired to a level similar to that which they had had before their illness. CONCLUSIONS--Patients with the chronic fatigue syndrome have reduced aerobic work capacity compared with normal subjects and patients with the irritable bowel syndrome. They also have an altered perception of their degree of exertion and their premorbid level of physical activity. 
5	Cat-scratch disease. Acute encephalopathy and other neurologic manifestations. Seventy-six patients with neurologic complications of cat-scratch disease are discussed. Encephalopathy occurred in 61, while 15 had either cranial or peripheral nerve involvement. The average age of the patients with encephalopathy was 10.6 years (range, 1 to 66 years), and almost twice as many males as females were affected in contrast to patients with uncomplicated cat-scratch disease, in which the ratio was almost equal. Fever was not documented in 50% of patients with encephalopathy and only 26% had temperatures higher than 39 degrees C. Convulsions occurred in 46% and combative behavior in 40%. Lethargy with or without coma was accompanied by variable neurologic signs. Results of laboratory studies, including imaging of the central nervous system, were inconsistent and nondiagnostic. Biopsy tissue from 14 patients showed histopathologic findings compatible with cat-scratch disease. The "English-Wear bacillus" was demonstrated by the Warthin-Starry stain in 10 of 14 skin or lymph node specimens. Of the 15 patients without encephalopathy, two children with facial nerve paresis displayed cranial nerve symptoms and/or signs, 10 patients had cat-scratch disease neuroretinitis, and three women had peripheral neuritis. All 76 patients recovered within 12 months; 78% recovered within 1 to 12 weeks. There were no neurologic sequelae. Treatment consisted of control of convulsions and supportive measures. Commonly used antibiotics administered to more than half of the patients were apparently ineffective. 
1	A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the Log IgG-Index. A comparison and diagnostic applications. Cerebrospinal fluid and serum immunoglobulin G from 1007 patients with suspected neurological disease were analysed by 2 methods: isoelectric focusing for the detection of oligoclonal banding, and quantitative measurement of IgG and albumin for the formulation of a Log IgG-Index. A comparison of the 2 methods in the detection of local synthesis of IgG showed that isoelectric focusing not only gave a much higher yield overall, with 282 patients showing local synthesis versus 225 for the Log IgG-Index, but also a higher specificity, with a false positive rate of 0% versus 3.5%. In addition, of the 282 patients positive by isoelectric focusing only 163 (58%) were positive by the Log IgG-Index. Of the 1007 patients studied, 206 had multiple sclerosis (MS), and isoelectric focusing showed local synthesis in 95% of clinically definite cases, with a 90% detection rate overall. The Log IgG-Index was positive in only 67% of clinically definite cases, with an overall 59% detection rate. Thus with the exceptions noted above, local synthesis of IgG as defined by isoelectric focusing is confined to demyelinating, inflammatory, infectious and postinfectious disorders. Our results compare very favourably with the published sensitivities of magnetic resonance imaging in the detection of abnormalities in multiple sclerosis, and better than those for evoked potentials. Where both these investigations are readily available isoelectric focusing provides a useful adjunct. For the majority of physicians and neurologists who do not have ready access to magnetic resonance imaging, isoelectric focusing is an excellent alternative. We would also recommend that it become the standard for the measurement of IgG abnormalities in the cerebrospinal fluid and that the use of quantitative data be abandoned for routine purposes. 
1	Cerebellopontine angle lipoma in a teenager. Lipomas of the cerebellopontine angle are very rare lesions. To date, 18 patients have been reported, 17 of whom were adults. A second child is described with cerebellopontine angle lipoma. 
5	Postoperative bile duct strictures. Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to the bile duct during cholecystectomy. In addition, strictures can occur at the site of previous biliary anastomoses for reconstruction of the biliary tree. Most patients with benign bile duct strictures present soon after their initial operation; however, in some cases, presentation is delayed for years. Cholangiography is essential for defining the anatomy of the biliary tree prior to management. In many cases, nonoperative biliary drainage is useful to treat sepsis and biliary fistulas. A number of alternatives exist for elective repair of bile duct strictures. Experience would suggest, however, that a choledochojejunostomy or hepaticojejunostomy performed through a Roux-en-Y limb of jejunum is the preferable management in most cases. Postoperative biliary stenting may be valuable in optimizing the results. Nonoperative management by percutaneous transhepatic or endoscopic balloon dilatation has been reported to be successful in a number of small series. Long-term results are limited, however. Comparative data suggest that surgical repair for benign postoperative strictures is associated with fewer long-term problems and with similar overall morbidity and costs. 
1	Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence. The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease. 
4	Left ventricular mechanics of ejecting, postischemic hearts during left ventricular circulatory assistance. We measured the effects of left ventricular circulatory assistance on ventricular mechanics of ejecting sheep hearts before and after global ischemia. Flows from left atrium to femoral artery ranged between 20 and 100 ml/kg/min during circulatory assistance. In preischemic, ejecting hearts increasing flow through the left ventricular assist device progressively decreased stroke volume, end-diastolic volume, and circumferential systolic wall stress, but only slightly decreased end-systolic volume. In postischemic, ejecting hearts left ventricular assistance progressively and substantially decreased both end-diastolic volume and end-systolic volume; at high flows, end-systolic volume returned to the normal range of preischemic hearts. High flows through the assist device also shifted end-systolic points of pressure-volume loops leftward and increased the stroke work/end-diastolic volume ratio in ejecting postischemic hearts; these observations raise the possibility that left ventricular circulatory assistance acutely improves myocardial contractility of postischemic hearts. 
3	The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain, e.g., neuropathic pains, may be unresponsive to these drugs. This concept has important implications for both clinical practice and basic understanding of opioid mechanisms. We critically evaluate opioid responsiveness, particularly as it relates to neuropathic pain, and propose a clinically relevant definition and a paradigm for its investigation. The paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients, whose central pain responded promptly to an infusion of hydromorphone. From this analysis, we hypothesize that (1) opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of 'complete' or 'adequate' analgesia; (2) opioid responsiveness is a continuum, rather than a quantal phenomenon; (3) opioid responsiveness is determined by a diverse group of patient characteristics and pain-related factors, as well as drug-selective effects; and (4) a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs. Given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted, opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response. Both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects. 
5	Psychogenic purpura (autoerythrocyte sensitization): an unsolved dilemma. Experience at University Hospitals of Cleveland with 71 cases of Gardner and Diamond's syndrome of autoerythrocyte sensitization is reviewed. Gardner and Diamond attributed the pathogenesis of the inflammatory bruises typical of this syndrome to sensitization to the stroma of the patients' own erythrocytes, as demonstrated by reproduction of the lesion on intracutaneous injection of erythrocytic stroma. Nearly all the cases my colleagues and I have seen were in adult women, in whom the onset of inflammatory bruising could often be precisely dated, frequently some weeks after an injury or surgical procedure or, more often, severe emotional stress. Bouts of bruising were often preceded by sensations localized to the affected site. Cutaneous responses to the injection of erythrocytes were erratic. The patients described a wide range of both hemorrhagic and nonhemorrhagic complaints, including, among others, severe headaches, paresthesias, repeated syncope, diplopia (sometimes monocular), and "nervousness." Psychiatric studies indicated that patients had overt depression, sexual problems, feelings of hostility, and obsessive-compulsive behavior. The patients had traits that can be described as typical of a hysterical character disorder. Therapy of autoerythrocyte sensitization--that is, psychogenic purpura--has been difficult; in younger individuals, psychiatric therapy has appeared to be beneficial. 
5	Incisional hernioplasty with Mersilene. Thirty large incisional abdominal hernias (myoaponeurotic defects greater than 10 centimeters) were successfully repaired by a technique of incisional hernioplasty which implants a large Mersilene (polyester fiber) prosthesis in the space between the abdominal muscles and the peritoneum. The prosthesis extends far beyond the borders of the myoaponeurotic defect, and is solidly held in place by intra-abdominal pressure and later by fibrous ingrowth. The prosthesis protects against recurrence in two ways. First, it prevents peritoneal eventration by adhering to the visceral sac and rendering it indistensible. Second, the prosthesis unites and consolidates the abdominal wall. Consequently, the procedure uniquely exploits the very force which caused the hernia to prevent a recurrence. A prosthesis of Mersilene is essential for success because it is supple and elastic enough to conform freely to the curvatures of the visceral sac, has the necessary grainy texture to grip the peritoneum and prevent slippage and is reactive enough to induce a rapid fibroblastic response to ensure fixation. 
2	Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. The relation between sensory perception of rapid balloon distension of the rectum and the motor responses of the rectum and external and internal anal sphincters in 27 normal subjects and 16 patients with faecal incontinence who had impaired rectal sensation but normal sphincter pressures was studied. In both patients and normal subjects, the onset and duration of rectal sensation correlated closely with the external anal sphincter electrical activity (r = 0.8, p less than 0.0001) and with rectal contraction (r = 0.51, p less than 0.001), but not with internal sphincter relaxation. All normal subjects perceived a rectal sensation within one second of rapid inflation of a rectal balloon with volumes of 20 ml or less air. Six patients did not perceive any rectal sensation until 60 ml had been introduced, while in the remaining nine patients the sensation was delayed by at least two seconds. Internal sphincter relaxation occurred before the sensation was perceived in three of 27 normal subjects and 11 of 16 patients (p less than 0.001), and could be associated with anal leakage, which stopped as soon as sensation was perceived. The lowest rectal volumes required to induce anal relaxation, to cause sustained relaxation, or to elicit sensations of a desire to defecate or pain were similar in patients and normal subjects. In conclusion, these results show the close association between rectal sensation and external anal sphincter contraction, and show that faecal incontinence may occur as a result of delayed or absent external anal sphincter contraction when the internal anal sphincter is relaxed. 
5	Pityriasis lichenoides in children: a long-term follow-up of eighty-nine cases. Pityriasis lichenoides is usually classified into an acute and a chronic form. From a review of 89 cases of the disease seen since 1974 it seems that a more realistic classification into three main groups, according to the distribution of pityriasis lichenoides lesions, could be made, namely, a diffuse, a central, and a peripheral form, each characterized by a different clinical course. Conversely, no correlations were detected in our series between the severity of skin lesions and their distribution or the overall course of the disease. None of our cases suggests the possible evolution of pityriasis lichenoides into lymphomatoid papulosis. Although no infectious causative agent has been identified, a viral origin seems likely in some cases. Most patients responded favorably to UVB irradiation. Our conclusions are (1) that pityriasis lichenoides is probably a clinical disorder with a diverse etiology and (2) that its classification by distribution seems more useful than its subdivision into an acute and a chronic form. 
2	The pharmacist as a health consultant--ten years later. Pharmacists remain a readily accessible and trusted source of information about health. In order to assess the quality of counseling on health matters and the progress of the profession in this activity over the last decade, a study similar to one reported in 1978 was conducted. We visited 46 community pharmacies and requested advice from the pharmacists concerning the proper treatment of an infant with diarrhea. Interviewers volunteered no additional information, but questions asked by the pharmacist were answered according to a predetermined hypothetical case involving an 18-month-old infant with diarrhea and vomiting. Findings include the following: approximately one-third of the pharmacists recommended a product without caution and less than 20 percent inquired about fever, nausea, vomiting, diet, or the infant's condition. We believe pharmacists should approach health counseling with an increased awareness of the harmful potential in providing inappropriate medical information. 
5	Hypertrophic smooth muscle in the partially obstructed opossum esophagus. The model: histological and ultrastructural observations. Obstruction is a complication of many esophageal diseases, but the morphological changes occurring in the obstructed esophagus are poorly understood. We developed a model of esophageal obstruction in the American opossum, Didelphis virginiana. A nonconstricting band around the gastroesophageal junction led to esophageal distention and tortuosity in the weeks following its placement. Despite a marked increase of the esophageal circumference, the esophageal wall was not thinned, and the circular muscle layer had actually increased its thickness. This was due to an increase in the size of individual smooth muscle cells with proportional increases in the cell surface area and volume. The electron density of hypertrophic smooth muscle cells varied much more than that of normal esophageal smooth muscle cells. As cell size increased, the tissue became more compact and the size of the extracellular space decreased. Also, the extracellular space was filled by an amorphous electron-dense material. Additional changes in the structure of hypertrophic smooth muscle cells included prominent intermediate filaments in the vicinity of thick filaments. There was no difference in the structure of the hypertrophic smooth muscle at 4 weeks and at 8 weeks after placement of the band. The morphological features described here resemble those seen in human esophageal spasm and achalasia of humans and could affect esophageal smooth muscle function. 
5	Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes. Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other. 
5	Dorsal root ganglionectomy for failed back surgery syndrome: a 5-year follow-up study. Dorsal root ganglionectomy has been suggested as a method for the treatment of chronic intractable radicular pain, with theoretical advantages over dorsal rhizotomy, which does not interrupt ventral root afferents. The indications for these procedures in patients with persistent pain following lumbosacral spine surgery are not well established. Long-term results have been reported infrequently, and no published series has a mean follow-up period of more than 30 months. The authors have reviewed their experience with a series of 13 patients with failed back surgery syndrome, in whom dorsal root ganglionectomy was performed. Patients were selected on the basis of clinical presentation and diagnostic root blocks suggesting a monoradicular pain syndrome. Follow-up data were obtained at a mean of 5.5 years following dorsal root ganglionectomy. Follow-up interviews to assess outcome were conducted by a disinterested third party. Treatment "success" (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in two patients at 2 years after surgery and in none at 5.5 years. Equivocal success (at least 50% relief, without clearcut patient satisfaction) was recorded in one patient at 2 and at 5.5 years postoperatively. Improvements in activities of daily living were recorded in a minority of patients. Loss of sensory and motor function was reported frequently by patients. A minority of patients had reduced or eliminated analgesic intake. These results suggest that dorsal root ganglionectomy has a limited role in the management of failed back surgery syndrome, and that methods to select patients to receive this procedure should be refined or alternative approaches should be considered. 
5	Maintenance and relapse after weight loss in women: behavioral aspects. Obese women who regained weight after successful weight reduction (relapsers, n = 44); formerly obese, average-weight women who maintained weight loss (maintainers, n = 30); and women who had always remained at the same average, nonobese weight (control subjects, n = 34) were interviewed. Most maintainers (90%) and control subjects (82%) exercised regularly, were conscious of their behaviors, used available social support (70% and 80%, respectively), confronted problems directly (95% and 60%, respectively), and used personally developed strategies to help themselves. Few relapsers exercised (34%), most ate unconsciously in response to emotions (70%), few used available social support (38%), and few confronted problems directly (10%). These findings suggest the advisability of development and prospective evaluation of individualized treatment programs designed to enhance exercise, coping skills, and social support. 
5	Hepatopathy-thrombocytopenia syndrome--a complication of dactinomycin therapy for Wilms' tumor: a report from the United Kingdom Childrens Cancer Study Group. We have observed hepatopathy, associated with thrombocytopenia, in children receiving chemotherapy for Wilms' tumor. We have studied this hepatopathy-thrombocytopenia syndrome (HTS) in patients enrolled in the United Kingdom Childrens' Cancer Study Group (UKCCSG) Wilms' tumor trials (UKW1 and UKW2). At the time of this study, 501 patients had completed therapy. Treatment flow sheets were examined for evidence of hepatopathy (hepatomegaly with abnormal liver function tests) and severe thrombocytopenia (platelet count less than 25 x 10(9)/L). No child who developed the syndrome had received irradiation. HTS was seen in five of 355 (1.4%) of patients treated with combination chemotherapy but in none of the 146 patients treated with vincristine alone. In each instance, the onset was less than 10 weeks after diagnosis. In two children, hepatopathy was severe with jaundice, ascites, transaminases greater than 1,000 IU/L, and prolongation of prothrombin time. On average, HTS lasted 12 days, and resolved with supportive treatment. After recovery, the children tolerated chemotherapy, mostly at reduced dosage, without recurrence. There was no evident long-term morbidity. Dactinomycin is the probable cause of this syndrome. We conclude that the HTS is a rare but important complication of dactinomycin-containing combination chemotherapy for Wilms' tumor. Children developing "isolated" thrombocytopenia following dactinomycin are "at risk" of developing the full-blown syndrome and should have their treatment modified accordingly. 
1	Partial duplication of the face: case report and review. Complete or partial facial duplication is a rare congenital malformation. A spectrum of structural abnormalities varying in degrees of severity has been described in affected individuals. We present discordance for facial duplication between monozygotic twins in which maxillary and mandibular duplication was present in one. The involved twin showed the following findings: ocular hypertelorism, bifidity of the nose, duplication of the maxilla, macrostomia, cleft of the lower lip, hamartoma of the vomer, supernumerary teeth, duplication of the mandibular teeth, bifidity of the tongue, and hamartoma of the floor of the mouth. Surgical management of the facial anomalies is discussed. A review of the literature and discussion of this rare malformation are presented. 
4	Effect of lovastatin on intimal hyperplasia after balloon angioplasty: a study in an atherosclerotic hypercholesterolemic rabbit. Restenosis, the major limitation of balloon angioplasty, is the result of intimal hyperplasia after the procedure. Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitor, may influence intimal hyperplasia by lowering serum cholesterol and by blocking deoxyribonucleic acid (DNA) synthesis. To determine whether lovastatin reduces intimal hyperplasia, a prospective, randomized blinded study was performed in 60 atherosclerotic New Zealand White male rabbits. Atherosclerosis was produced by air desiccation injury followed by a 28 day diet of 2% cholesterol and 6% peanut oil that was terminated before balloon angioplasty was performed. Angioplasty could not be performed in 14 rabbits with bilateral femoral artery occlusion, and in one rabbit the procedure was a technical failure. Forty-five rabbits underwent balloon angioplasty performed with use of a 2.5-mm balloon inflated to 10 atm for three 1 min dilations at 1 min intervals. Seven rabbits died during the procedure. Thirty-eight rabbits were randomized to either a lovastatin group (6 mg/kg body weight per day) or a control group. Angioplasty was performed on all patent vessels (n = 54); the procedure was bilateral in 16 rabbits and unilateral in 22. Fifteen lovastatin-treated and 15 control rabbits survived 39 days after angioplasty and were then killed. Angiograms, obtained before and 10 min and 39 days after balloon angioplasty, were read with use of electronic calipers by two observers who had no knowledge of treatment data. After the rabbits were killed, vessels were pressure perfused using a standardized protocol to maintain in vivo dimensions for blinded quantitative histologic analysis. 
5	Morbidity of modified pelvic lymphadenectomy and radiotherapy for prostatic cancer. The records of 63 patients treated by pelvic lymphadenectomy and radiotherapy at the University of Tennessee, Memphis, Baptist Memorial Hospital of Memphis, and the Memphis Veterans Affairs Hospital were reviewed. Of those patients, 45 received external beam radiation therapy to the prostate while 16 were treated by Iodine-125 implantation. Two patients had only staging lymphadenectomy. The incidence of postoperative and late complications were analyzed. 
5	Dependence among host response parameters used to diagnose urinary tract infection. The host-response parameters fever, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are activated in concert by cytokines such as interleukin-6 (IL-6). Il-6 is secreted in response to Escherichia coli infection of the urinary tract. This study tested the hypothesis that the level of fever, CRP, and ESR is coregulated in individual patients. Body temperature, CRP, ESR, pyuria, and renal concentrating capacity were analyzed in 692 children with first-time urinary tract infections. The association of the parameters was evaluated by correlation and multiple regression analysis. The body temperature, CRP, and ESR were significantly correlated (r = .54, .58, and .58; P less than .001), and variation in CRP and ESR explained approximately 40% of the variation in fever. In contrast, the renal concentrating capacity and pyruia were weakly or not at all correlated with the febrile response (r = -.22; P less than .001), and less than 10% of the variation in renal concentrating capacity was explained by the other parameters. The results suggest that fever, CRP, and ESR describe the same aspect of the host response to UTI. 
1	Capillary hemangiomas and treatment with the flash lamp-pumped pulsed dye laser Strawberry, or capillary, hemangiomas are common vascular neoplasms, with an incidence of approximately 2.6% in neonates. They usually develop in the first few weeks of life, so that between 1 month and 1 year the incidence rises to between 8.7% and 10.1%. These lesions may grow quite large in the first year of life, and they may ulcerate or obstruct a vital organ or function. The great majority will spontaneously regress after the first year of life. Parents are often alarmed at the sight of these hemangiomas and need reassurance that the great majority will regress spontaneously. Treatments such as cryosurgery, irradiation, radium instillation, corticosteroid therapy, or surgical excision are often ineffective or cause significant morbidity. We describe 10 children with capillary hemangiomas treated with the flash lamp-pumped pulsed dye laser. The patients ranged in age from 7 weeks to 5.5 years at the beginning of laser therapy. The patients underwent 3.1 +/- 1 (mean +/- SD) laser treatments, with a mean regression of the lesions of 69.9% +/- 4.5%. All patients demonstrated some diminution in the size and color of their hemangiomas after the treatments, and there were no ill effects, such as ulceration, hemorrhage, infection, or scarring. There was no evidence of hyperpigmentation or hypopigmentation. Pulsed dye laser therapy should be considered as an option in the treatment of capillary hemangiomas, preferably prior to their full evolution. It is also a useful therapeutic approach in those hemangiomas that are slow to regress in older children. 
3	Advances in cluster headache. The physician may have to combine the art and science of medicine in the management of this most fascinating of human ailments. The choice of drugs and the length of treatment prescribed are greatly influenced by the individual physician's experience, convictions, and reasoning. Needless to say, chronic use of narcotics should be avoided. The author's own regimen is to use combinations of ergotamine prophylaxis with either verapamil or prednisone in episodic cluster headache and with lithium for chronic cluster headache. Management of the treatment-resistant patient remains problematic, but a carefully performed trigeminal radiofrequency thermocoagulation procedure may be worthwhile. 
4	Rebleeding from intracranial dissecting aneurysm in the vertebral artery. We describe two patients with rebleeding from intracranial vertebral artery dissecting aneurysms during the acute stage. One patient had excellent results after emergency surgery. A review of recent reports including 60 patients with this disorder revealed a rebleeding rate of 30%, mostly during the acute stage. This suggests that a ruptured dissecting aneurysm in the vertebral artery is at risk for rebleeding during the acute stage, similar to a saccular aneurysm in the same location. 
4	Ventilatory and diffusion abnormalities in potential heart transplant recipients. Few data are available concerning pulmonary function in patients with severe chronic congestive heart failure. Of 315 patients evaluated for potential cardiac transplantation at UCLA, 132 underwent pulmonary function tests. The latter patients had severe heart failure with a mean left ventricular ejection fraction of 19 percent and mean cardiac index of 2.1 L/min/m2. Diffusion impairment either alone or combined with restrictive and/or obstructive ventilatory defects occurred in 67 percent of the patients evaluated. Diffusion impairment occurred as the sole abnormality in 31 percent of the patients and in combination with a restrictive ventilatory defect in 21 percent. A reduction in diffusing capacity has not been previously described as a frequent finding in patients with chronic congestive heart failure. In contrast to other studies involving patients with acute heart failure, obstructive ventilatory defects were uncommon. None of the lung function abnormalities was associated with smoking status, prior drug use, chest roentgenographic changes, hemodynamic findings, or clinical features, including duration of congestive heart failure. The mechanism for the diffusion impairment is unclear but could be due to chronic passive congestion with pulmonary fibrosis and/or recurrent pulmonary emboli. Recognition of diffusion impairment as a common finding in patients with severe chronic congestive heart failure who are candidates for heart transplantation is important for proper interpretation of possible post-transplant changes in diffusing capacity due to other causes. 
5	Hereditary ovarian cancer. Heterogeneity in age at diagnosis. An unknown fraction of the ovarian cancer burden occurs in women with a family history indicative of a putative autosomal dominantly inherited cancer susceptibility syndrome. The results from a five-generation, extended, hereditary breast-ovarian cancer kindred are described 10 years after it was initially ascertained. Significantly more cancers were observed in high-risk family members during this decade than were expected (P less than 0.001). The age of ovarian cancer diagnosis was studied in additional ovarian cancer-prone families of three types: site-specific ovarian cancer syndrome, the breast-ovarian cancer syndrome, and Lynch syndrome II. The age of onset in each of the three sets was significantly (P less than 0.001) earlier than the general population mean of 59, and there were significant differences in the age of onset (P = 0.050) among these three cohorts. Ovarian cancer histology was similar to that of patients with negative family histories. There may be clinically significant heterogeneity in the age at diagnosis of ovarian cancer among these ovarian cancer-prone syndromes. This has important implications for understanding its natural history and targeting surveillance-management strategies. 
2	Role of surgery in antibiotic-induced pseudomembranous enterocolitis. With the increased use of prophylactic and broad-spectrum antibiotics, pseudomembranous colitis has emerged as a significant clinical problem. Management with specific anti-Clostridium difficile therapy (vancomycin or metronidazole) has reduced mortality to less than 2%. Nevertheless, the disease may progress to a fulminant toxic colitis or colonic perforation. Additionally, another subset of patients will present with a dramatic clinical picture, suggesting acute peritonitis, eventuating in unnecessary laparotomy. This report reviews both the medical and surgical literature during the past 15 years of patients treated for pseudomembranous colitis. Analysis of this clinical data has provided us with the opportunity to both define the role of surgery in this disorder and illustrate the necessity for a combined medical and surgical cooperative approach in the early management of this iatrogenic disease. 
5	Crystalluria, medullary matrix crystal deposits and bladder calculi associated with an acutely induced renal papillary necrosis. A single (100 mg/kg) intraperitoneal dose of 2-bromoethanamine hydrobromide induced renal papillary necrosis (RPN) acutely in rodents and caused a transient crystalluria between 4 and 8 h after dosing. These crystals comprised struvite or magnesium ammonium phosphate (MAP) as assessed by shape, solubility, infra-red spectrum and X-ray microprobe analysis. Acid-soluble, bi-refringent crystals were also present within the renal medullary matrix during the same time period as the crystalluria. The presence of the MAP was associated with loss of the anionic renal medullary mucopolysaccharides staining. A total of 5/64 rats with a 2-bromoethanamine-induced renal papillary necrosis and monitored for up to 160 days had bladder calculi that were predominantly MAP. These data suggest that medullary mucopolysaccharide matrix disruption associated with RPN leads to a release of previously bound cations, super-saturation and the nucleation of crystalline MAP. These processes could also be implicated in the formation of MAP bladder calculi. 
1	Urinary tissue factor activity in colorectal disease. Procoagulant activity (PCA) in normal urine has been recognized for over 50 years. Although tissue factor (TF) is produced by certain tumours, and is increased in both tumour-associated macrophages and blood monocytes, the possibility that it might also be increased in urine has not been studied in patients with cancer. We have measured urinary PCA in hospital controls without inflammatory or neoplastic disease (n = 79), in patients with rheumatoid arthritis (n = 8), inflammatory bowel disease (n = 19), colorectal cancer (n = 70) and in patients undergoing colonoscopy (n = 50). Urinary PCA was higher (P less than 0.001) in patients with colorectal cancer and inflammatory bowel disease than controls or patients with rheumatoid arthritis. Fourteen (88 per cent) out of 16 colonoscopy patients subsequently found to have carcinoma or inflammatory bowel disease had levels above the control upper quartile, compared with 8 (24 per cent) out of 34 with normal colonoscopy (P less than 0.001). TF inhibitors confirmed the nature of the PCA and Western blotting studies indicated a urinary TF molecular weight of approximately 38,000. These studies provide further evidence of abnormal haemostasis in malignancy and suggest that determination of urinary TF may provide a useful screening test in patients undergoing colonoscopy. 
1	Cells immunoreactive for neuropeptide in human thymomas. The presence of opioid peptides, bombesin, and substance P was investigated by immunohistochemistry in tissue sections from six human thymomas. The number of immunoreactive cells seemed to vary from one case to another. Ultrastructural investigation, showing the presence of desmosomes in labelled cells, allowed these cells to be classified as epithelial lineage cells. The occurrence of cells containing neuropeptide in thymomas suggest that peptide molecules could have modulated the behaviour of this tumour, given the reported influence of these molecules on immune functions and their growth promoting activity on several cell types, including mesenchymal and epithelial cells. 
1	Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone. 
5	Preseason strength and flexibility imbalances associated with athletic injuries in female collegiate athletes. One hundred thirty-eight female collegiate athletes, participating in eight weightbearing varsity sports, were administered preseason strength and flexibility tests and followed for injuries during their sports seasons. Strength was measured as the maximal isokinetic torque of the right and left knee flexors and knee extensors at 30 and 180 deg/sec. Flexibility was measured as the active range of motion of several lower body joints. An athletic trainer evaluated and recorded injuries occurring to the athletes in practice or competition. Forty percent of the women suffered one or more injuries. Athletes experienced more lower extremity injuries if they had: 1) a right knee flexor 15% stronger than the left knee flexor at 180 deg/sec; 2) a right hip extensor 15% more flexible than the left hip extensor; 3) a knee flexor/knee extensor ratio of less than 0.75 at 180 deg/sec. There was a trend for higher injury rates to be associated with knee flexor or hip extensor imbalances of 15% or more on either side of the body. These data demonstrate that specific strength and flexibility imbalances are associated with lower extremity injuries in female collegiate athletes. 
1	Reasons why mastectomy patients do not have breast reconstruction. Breast reconstruction after mastectomy is valuable, yet only a small percentage of eligible patients ever have reconstruction. Little has been done to determine why so few patients proceed with reconstructive surgery. A homogeneous population of mastectomy patients, some of whom underwent breast reconstruction while others did not, were surveyed regarding their attitudes about breast reconstruction. A total of 245 women were surveyed. One-hundred and fifty-eight (64 percent) responded, 71 of whom had been reconstructed while 87 had not. Comparison of the responses of the two groups suggests factors that play a role in determining whether the mastectomy patient will accept or decline the option of breast reconstruction. Considerations that made it less likely that a woman would pursue reconstruction included advanced age at the time of mastectomy, concern about complications from further surgery, uncertainty about outcome, and fear about the effect of reconstruction on future problems with breast cancer. Marital status, receiving chemotherapy, or knowing a patient who had a bad result from reconstruction did not affect the decision. An awareness and understanding of these factors may be helpful to physicians in counseling patients and in increasing the number of women who enjoy the benefits of breast reconstruction. 
5	Maternal genomic neutrophil FcRIII deficiency leading to neonatal isoimmune neutropenia. The healthy mother of a child with transient immune neutropenia was found to be "NA-null." The mother's neutrophils did not react with anti-NA1 and anti-NA2 antibodies (polyclonal human alloantibodies and mouse monoclonal antibodies). A healthy donor was discovered during routine neutrophil antigen typing whose neutrophils were also "NA-null." This NA-phenotype was due to the absence of FcRIII (CD16 antigen) on neutrophils as demonstrated with anti-FcRIII monoclonal antibodies. The neutrophils of these two individuals were not able to bind dimeric immunoglobulin G. However, their cells had a normal expression of other phosphatidylinositol (PI)-linked membrane glycoprotein (CD24, CD67, and CLB gran/5 antigens), ruling out the existence of a PI-linkage defect, such as paroxysmal nocturnal hemoglobinuria. The mother (propsitus) had isoantibodies in her blood against neutrophil-FcRIII without allospecificity, apparently produced during pregnancy and responsible for the neutropenia of her child. The expression of FcRIII on natural killer lymphocytes of both individuals was normal. FcRIII is encoded by two separate genes, one (FcRIII-1) for the neutrophil-PI-linked receptor, another (FcRIII-2) for the natural killer cell and macrophage-transmembrane receptor. By messenger RNA and DNA analysis (with an FcRIII-cDNA probe and restriction endonucleases) the neutrophil-FcRIII deficiency appeared to be due to deletion of the FcRIII-1 gene in both individuals, while the FcRIII-2 gene was normally present. The parents of the propositus were found to be heterozygous for this defect. Thus, FcRIII-1 gene deficiency of the mother may be a cause of (iso)immune neutropenia of the newborn. Whether this deficiency may have other clinical consequences has to be studied. 
2	Congenital duodenal diaphragm: conversion of stable chronic symptoms to subacute gastric outlet obstruction by penetrating foreign body. Congenital duodenal diaphragms (CDD) are rare lesions that usually become symptomatic and require surgery in childhood. We report a patient, who, although symptomatic since early childhood, had accommodated to the condition and finally required surgical correction in late life after an ingested foreign body traumatized the diaphragm, producing subacute gastric outlet obstruction. The condition, including the reconstruction of the precipitating event, was diagnosed endoscopically prior to surgery. 
5	Somatosensory-evoked potential monitored during total hip arthroplasty. One hundred consecutive patients were monitored using somatosensory-evoked potential (SEP) monitoring to detect intraoperative sciatic nerve compromise during total hip arthroplasty. The peroneal nerve was stimulated using the contralateral extremity to rule out systemic influences on the SEP tracings. Loss of amplitude or an increase in latency of greater than 10% was considered significant. Of the 18 patients who exhibited changes that met these criteria, 16 were female. Two patients had loss of amplitude of the tracings at the time of closure, and both of these patients exhibited postoperative sciatic nerve palsies. There were no false negatives. Femoral reaming and reduction are the surgical events most commonly associated with nerve reactions. Patients who have had prior hip procedures appear to be at higher risk. There was no correlation with intraoperative SEP changes and age, weight, surgical approach, or leg lengthening. Compared with unmonitored patients, there was no reduction in the incidence of sciatic palsy. 
1	Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. Forty-seven patients with metastatic malignant melanoma were treated with two 5-day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2. 
3	Optimum results of the surgical treatment of carotid territory ischemia. Continuing controversy over the role of carotid endarterectomy in stroke prevention is based largely on reports in which high perioperative morbidity and mortality rates obviate possible long-term benefit from the procedure. The purpose of this review is to examine optimal results of carotid surgery in order to describe the potential for the procedure in stroke prevention. Optimal surgical results are compared with optimal medical results in the therapy of symptomatic patients and with optimal nonsurgical results in the therapy of asymptomatic patients. Factors common to series with excellent results, such as patient selection and operative technique, are examined, and problems such as recurrent carotid stenosis and coexisting coronary disease, which continue to plague even the best surgical series, are discussed. 
3	Botulinum toxin treatment in spasmodic torticollis. Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial. Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments. Following the controlled trial, treatment with botulinum toxin was continued in an open fashion. A total of 60 patients with torticollis received toxin in a total of 117 treatment periods. The mean follow up period was 8.4 months. In 39 patients with pain there was benefit in 77% of treatment periods. Some improvement in neck posture occurred in 83% of the treatment periods with a mean duration of 12 weeks. Side effects were frequent with dysphagia being the most common (28% of treatment periods). Botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study (400-600 mouse units). 
1	Growth of cultured human cerebral meningiomas is inhibited by dopaminergic agents. Presence of high affinity dopamine-D1 receptors. We have found that microM concentrations of the dopamine agonist bromocriptine significantly decrease the proliferation rate of human meningioma cells in culture (25-56% inhibition). This effect was also seen with direct application of dopamine, as well as the dopamine-D1 agonist (+)-SKF-38393 (both applied in microM concentrations) to meningioma cell cultures. Receptor studies with the dopamine-D1 ligand (125I)SCH-23982 (dopamine-D1 antagonist) indicated that dopamine-D1 binding sites were present in the membranes of meningioma tissue. The mean dissociation constant (Kd) was 325 ( +/- 74.5 SEM) pM and the receptor density (Bmax) was 25.4 ( +/- 1.5 SEM) fmol/mg pellet protein in 5 human meningiomas. The pharmacological specificity was proven by (+)-SKF-38393, ( +/-SKF-83566 or (+)-butaclamol and their inactive isomers (-)-SKF-38393 and (-)-butaclamol in a 1000 fold excess. These results provide evidence that human meningiomas possess high affinity dopamine-D1 receptors and that dopamine agonists have an antiproliferative effect on these tumors in culture. We conclude that the proliferation of cerebral meningiomas may be under dopaminergic control and that dopamine agonists may have a role in the medical treatment of patients with meningiomas. 
3	Neurotologic findings in basilar migraine. Treatment of a patient with otologic symptoms and associated migraine-like headache presents the otolaryngologist with formidable problems. Although clinical practice and scientific publications recognize their frequent association, relationships have yet to be well defined. This study seeks to add order to disarray by delineating symptoms and signs of a clearly identified group of migraine patients. Fifty patients with well-defined basilar migraine underwent a thorough neurotologic examination, as well as comprehensive auditory and vestibular testing. Patients were selected from 5880 patients seen over a 2-year period and were prospectively entered into the study after detailed questionnaires and testing were completed for each patient. The most common symptoms found were dysequilibrium, phonophobia, and head pressure. The most common signs were positional nystagmus, low-frequency hearing loss, abnormal loudness discomfort level, and an abnormality on caloric examination. Advanced vestibular testing showed abnormal amplitude scaling, abnormal toes-down pertubation, and an abnormal sway (condition 6) on dynamic posturography. There was frequently an asymmetry on computerized rotation. The author concludes that the majority of patients have subtle findings on testing, but a few have severe peripheral injury due to the basilar migraine. Findings are consistent with the theory that basilar migraine is a central nervous system maladaptation syndrome which creates otoneurologic symptoms and, in a small percentage of cases, may injure the peripheral end-organ. 
4	Hemodynamic effects of a new right ventricular assist device. A right ventricular assist device (VAD) based on the principle of counterpulsation has been developed at our institution. The device is a valveless, pneumatically actuated, 40 cc, sac-type pump, with a single inlet-outlet port. For right ventricular support, the "Uniport" pump is anastamosed end-to-side to the pulmonary artery. In previous experimental trials, the device has been shown to impart minimal trauma to blood components. In this study, biventricular failure was induced in eight Holstein calves by normothermic ischemia during cardiopulmonary bypass. A Pierce-Donachy left VAD (LVAD) was used for left ventricular support following the ischemic insult. Hemodynamic measurements were obtained throughout the study, and each animal served as its own control. A significant increase in post injury cardiac output (33.5 +/- 11.4%) was obtained with use of the Uniport and LVAD, as compared to use of the LVAD alone (p less than or equal to 0.005). Other hemodynamic parameters of right heart failure, including right atrial pressure (RAP), pulmonary artery pressure (PAP), and left atrial pressure (LAP) were not significantly affected. These data suggest that the Uniport right ventricular assist device significantly improves cardiac output in this model of moderate right ventricular failure. Additional studies are required, however, to optimize pump stroke volume, and to further define the performance envelope of the device. 
5	Evaluation of metastatic cardiac calcification in a model of chronic primary hyperparathyroidism. Recent reports have fueled an interest in the prevalence and significance of metastatic calcium deposition in patients with chronic hyperparathyroidism. Experimental data are limited by the lack of suitable in vivo animal models. We have developed a model of marked hypercalcemia and overproduction of parathyroid hormone using somatic gene transfer. Briefly, the process involves infection of cultured rodent fibroblasts (RAT-1 cells) with a retroviral expression vector that contains the gene encoding human parathyroid hormone. Fibroblasts are grown to confluence on collagen-coated dextran microcarrier beads and are injected into the peritoneal cavities of syngeneic Fisher rats. Human parathyroid hormone production in rat serum is quantified by an immunoradiometric assay for human parathyroid hormone (1-84), which does not recognize rat parathyroid hormone. These rats consistently show production of human hormone within a week. Levels increase progressively, often to 1 ng/ml within 60 days of injection. Serum calcium showed a concomitant rise to an average of 15.5 mg/dl. In this study, 13 rats that had been transplanted with parathyroid hormone-producing fibroblasts were killed 80 days after injection. Examination of the skeleton revealed demineralization and histopathologic sequelae of parathyroid hormone excess with extensive osteoclastic bone resorption. Examination of the hearts revealed calcification in five of 13 hearts. There was no involvement of major coronary arteries or conducting systems, but there was calcification of cardiac myocytes, primarily in subepicardial region. This model may permit an understanding of the mechanisms for sudden cardiac death in severe hypercalcemia. 
4	The association of carotid artery stenosis with carotid sinus hypersensitivity. Transitory cerebral ischaemic attack provoked by carotid sinus reflex The association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity. Transitory cerebral ischaemic attack (TIA) will usually be manifested by activation of carotid sinus reflex. Eighteen patients were observed suffering from both carotid sinus hypersensitivity and TIA. The patients had had TIA's for many years. Unilateral internal carotid stenosis was detected in 15 cases, while 3 patients had bilateral carotid stenosis. On carotid sinus stimulation, syncope appeared and a TIA could be provoked. The mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree AV block in 4 cases. In all patients carotid artery disobliteration was performed; in 14 patients pacemaker implantation was necessary, while 4 patients could be treated by atropine medication. The development of a TIA could be abolished in every patient and 14 patients remained totally symptom free. 
2	Would you recognize celiac axis syndrome? Since its original description, celiac axis syndrome has been a topic of debate. Clinical findings include postprandial abdominal pain, weight loss, and an epigastric bruit. Diagnosis is often made by exclusion and is confirmed by lateral aortography. The role of surgery in treating celiac axis syndrome is controversial. 
5	Visceral perception in health and functional dyspepsia. Crossover study of gastric distension with placebo and domperidone. The symptoms of functional dyspepsia are still unexplained. To evaluate the possible role of abnormal visceral perception, we studied the symptomatic responses and the pressure variations during progressive gastric distension in 10 female healthy control subjects (mean age 33.6 years) and in 10 female patients with functional dyspepsia (mean age 35.2 years). A rubber balloon was positioned 4 cm below the lower esophageal sphincter (LES) and inflated with progressively larger volumes of air by steps of 50 ml; pressures at the gastric fundus and at the LES were continuously recorded by perfused manometric catheters. Each subject was studied on two separate occasions after randomized double-blind administration of either placebo or 20 mg of domperidone. Symptomatic responses and the manometric data were analyzed at the time of the initial recognition of distension (bloating step) and at the time of reporting pain or up to a maximum of 700 ml of balloon inflation (pain or 700-ml step). On placebo, the volumes of gastric distension were more than two times lower in patients than in control subjects at the bloating step (185 +/- 32 ml vs 470 +/- 40 ml, P = 0.001) and at the pain or 700-ml step (265 +/- 54 ml vs 600 +/- 34 ml, P less than 0.005), while the pressure gradients (pressure at inflation steps minus baseline pressure before beginning inflation) were not statistically different between the two groups. 
4	Differential therapy with calcium antagonists in pulmonary hypertension secondary to COPD. Hemodynamic effects of nifedipine, diltiazem, and verapamil. In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long-term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension. 
3	Thrombosis in a congenitally bifurcated superior sagittal sinus. A 26-year-old woman had a peripartum venous thrombotic stroke involving the right parietal lobe. The initial thrombus was present only in the right channel of a congenitally bifurcated superior sagittal sinus. This diagnosis and subsequent thrombus extension were readily shown by magnetic resonance imaging in contrast to equivocal angiography. A subsequent, prospective review of 100 patients undergoing cranial magnetic resonance imaging showed the presence of similarly bifurcated superior sagittal sinuses in two. The patient stabilized after therapy with intravenous heparin, but switching her medication to oral warfarin sodium was followed by clinical deterioration and propagation of the thrombus, necessitating resumption of intravenous heparin. No coagulopathy was identified. 
4	Advances in noninvasive detection of CAD. Advances in the noninvasive detection of myocardial ischemia are increasing our ability to diagnose coronary artery disease (CAD). Tomographic (SPECT) thallium imaging provides better identification of coronary arteries with atherosclerotic narrowing. Increased lung thallium uptake and transient ischemic dilatation of the heart are additional markers of severe CAD. Late thallium imaging, as well as reinjection imaging, provides more accurate identification of myocardial ischemia. Finally, new myocardial ischemia. Finally, new myocardial imaging agents, such as technetium Tc 99m sestamibi (Cardiolite), should improve detection of CAD by noninvasive methods. 
1	Analysis of interferon-inducible genes in cells of chronic myeloid leukemia patients responsive or resistant to an interferon-alpha treatment. Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic remission in patients with chronic myeloid leukemia. However, some patients are resistant and others develop late resistance to the IFN-alpha treatment. To understand the molecular mechanism of this resistance, we have analyzed the expression of 10 IFN-inducible genes in the cells of three resistant patients, two responsive patients, and six healthy controls. Northern blot hybridizations showed that all the genes were induced in in vitro IFN-alpha treated peripheral blood cells of the patients and healthy controls. These genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of IFN-alpha. We conclude that the resistance to the IFN-alpha treatment of the chronic myeloid leukemia patients we studied is not due to (1) the absence of induction of any of the 10 IFN-inducible genes we studied, including the low-molecular-weight 2'-5'oligoadenylate synthetase; (2) the presence of an antagonist of IFN-alpha in the peripheral blood or bone marrow cells; and (3) the presence of neutralizing anti-IFN-alpha antibodies. 
5	Thyroidectomy under local anesthesia. Thyroidectomy for benign and malignant disease is most commonly performed with the patient under general anesthesia, although the literature is sprinkled with reports of series of operations performed using local anesthetic techniques. A retrospective review of 43 sequential thyroidectomies compares 21 performed using local anesthesia with 22 performed using general anesthesia. No significant difference was demonstrated in the incidence of major complications. All patients who required a second operation to remove the remaining hemithyroid after the final pathology reports were reviewed elected local anesthesia for their second procedure, attesting to patient satisfaction. Some hemithyroidectomies performed using local anesthesia were outpatient procedures. The indications, guidelines for patient selection, and operative technique of this effective alternative approach to thyroid surgery are presented. 
5	Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization. Chronic myelogeneous leukemia (CML) is genetically characterized by fusion of the bcr and abl genes on chromosomes 22 and 9, respectively. In most cases, the fusion involves a reciprocal translocation t(9;22)(q34;q11), which produces the cytogenetically distinctive Philadelphia chromosome (Ph1). Fusion can be detected by Southern (DNA) analysis or by in vitro amplification of the messenger RNA from the fusion gene with polymerase chain reaction (PCR). These techniques are sensitive but cannot be applied to single cells. Two-color fluorescence in situ hybridization (FISH) was used with probes from portions of the bcr and abl genes to detect the bcr-abl fusion in individual blood and bone marrow cells from six patients. The fusion event was detected in all samples analyzed, of which three were cytogenetically Ph1-negative. One of the Ph1-negative samples was also PCR-negative. This approach is fast and sensitive, and provides potential for determining the frequency of the abnormality in different cell lineages. 
5	Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. To assess the magnitude of Creutzfeldt-Jakob disease (CJD) occurrence among recipients of pituitary-derived human growth hormone (HGH), we conducted an epidemiologic follow-up of 6284 recipients of HGH distributed through the National Hormone and Pituitary Program. Seven neuropathologically confirmed cases of CJD have occurred in this population to date: six patients with clinical CJD presented with ataxia and imbalance, rather than with altered mentation, which is the most common initial manifestation in sporadic CJD, and one patient died in the preclinical incubation state of the disease. All seven cases occurred among the nearly 700 HGH recipients who started therapy before 1970. Since only 10% of the cohort has been followed up for the 15-year average incubation interval from midpoint of HGH treatment to onset of symptoms, the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of CJD. The median duration of HGH therapy of 100 months in the CJD cases was significantly longer than 41 months for all patients starting treatment before 1970; thus, the duration of pituitary HGH therapy is a major risk factor for CJD. 
3	L-tryptophan associated eosinophilia-myalgia syndrome. Environmental chemicals are increasingly incriminated in the pathogenesis of several disease states. The eosinophilia-myalgia syndrome is a recently described entity attributed to the ingestion of the normal dietary amino acid L-tryptophan. We describe a patient who fulfills criteria for the eosinophilia-myalgia syndrome and who was ingesting supplemental L-tryptophan. Exhaustive investigations failed to reveal other causes for her eosinophilia or her myalgic/neuropathic complaints, and she improved dramatically when she discontinued the L-tryptophan supplements. The mechanisms whereby this chemical may induce this syndrome are discussed. 
5	Assessing the clinical effectiveness of preventive maneuvers: analytic principles and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination. This paper examines a process for evaluating clinical effectiveness and developing recommendations in which systematic methods are used to review evidence from published clinical research and to reach sound conclusions about appropriate medical policy. The methodology addresses four important components of the analytic process: (1) the criteria that must be satisfied for a clinical practice to be considered effective; (2) proper methods for reviewing evidence from published clinical research to determine whether a clinical practice meets these criteria (including methods for performing comprehensive literature reviews, for judging the quality of individual studies, and for synthesizing or pooling the results of multiple studies); (3) theoretical and practical concerns in translating the results of the scientific review into sound clinical practice recommendations; and (4) the importance of documentation, guidelines, and other safeguards to minimize the effect the reviewers themselves have on the objectivity and consistency of the analytic methods. 
5	Clinical results of axillobifemoral bypass using externally supported polytetrafluoroethylene Seventy-six axillobifemoral grafts with externally supported polytetrafluoroethylene prostheses were performed since 1983. The indications for operation were absolute (aortic sepsis) in 20 (26%) patients and relative (excessive operative risk or technical difficulty) in 56 (74%) patients. The life-table primary patency for these operations at 4 years follow-up (mean follow-up, 2 years, 4 months) was 85%. We conclude that the patency results achieved in this patient series are sufficiently satisfactory to warrant use of axillobifemoral grafts in an expanded number of patients with high operative risk and need for bypass of aortoiliac occlusive disease. 
1	Hepatic dynamic sequential CT: section enhancement profiles with a bolus of ionic and nonionic contrast agents. The enhancement characteristics in different portions of the liver during dynamic sequential bolus computed tomography (CT) with iodinated contrast material (DSBCT) were prospectively evaluated in 75 patients by using iothalamate meglumine, iopamidol, and iohexol (25 patients received each agent). After baseline noncontrast CT was performed, DSBCT was performed with a 180-mL intravenous bolus administered at 2 mL/sec. Scanning was started 25 seconds after the bolus was initiated, by using a 3-second scan time and rapid cephalocaudal table incrementation, yielding contiguous 8-mm-thick sections at a rate of nine sections per minute. On postcontrast images, peak enhancement was 115% for iopamidol and 117% for iohexol, both of which were superior to iothalamate meglumine at 95% (P less than .05). After peaking, enhancement then decreased for all three contrast agents, although the decline was more precipitous for iothalamate meglumine. Enhancement on the more caudal sections with both iopamidol and iohexol was superior to that with iothalamate meglumine (P less than .05). The data suggest that the enhancement characteristics for the two nonionic agents may be more optimal for detection of focal hepatic lesions than the ionic agent. 
1	Anxiety levels and cancer fear in patients admitted for elective operations. Patients who are to have elective operations project varying degrees of anxiety, and many spontaneously express fear (without basis) that their operation involves a diagnosis of malignancy. To measure total, covert, and overt anxiety objectively, we gave the Institute for Personality and Ability Testing anxiety test to 125 consecutive patients admitted for elective general surgical procedures. A simple survey of cancer fear was also completed. Chi-square and Fisher's exact test were used to compare categoric data, and linear regression and analysis of variance were used where appropriate. Total anxiety scores were in the upper quartile compared to the general population. Scores indicating fear of cancer were elevated in 75% of patients who had no history of or reason to suspect malignancy. Covert anxiety scores correlated with cancer fear scores, and both significantly decreased as age increased (P less than .05). Also, as age increased, the cancer fear scores decreased (P less than .002). Obese patients had higher scores of cancer fear than all other patients (P less than .0001). 
1	Mucocele of the cystic duct remnant in eight liver transplant recipients: findings at cholangiography, CT, and US. The case histories and radiologic studies of eight liver transplant recipients who developed a mucocele of the allograft cystic duct remnant were retrospectively evaluated. All patients had clinical and/or laboratory evidence of biliary obstruction or cholangitis from 2 weeks to 3.3 years following transplantation. Cholangiographic, ultrasound (US), and computed tomography (CT) images were available for review in eight, five, and four patients, respectively. Cholangiograms demonstrated an extrinsic mass compressing the common hepatic duct in seven of eight patients. US and CT showed fairly well- to well-defined round fluid collections adjacent to the common hepatic duct in three and two patients, respectively. The findings of this study suggest that the detection at cholangiography of an extrinsic mass compressing the common hepatic duct appears to be specific for a mucocele of the allograft cystic duct remnant. CT and US images may offer confirmatory evidence. 
5	Prognosis of patients with ventricular tachycardia or fibrillation and a normal electrophysiologic study. The outcome of 26 patients with sustained ventricular tachycardia (n = 16) or ventricular fibrillation (n = 10) and no inducible ventricular tachycardia (less than or equal to 10 beats) by baseline programmed stimulation was studied. Coronary artery disease was present in 14 patients, dilated cardiomyopathy was seen in seven, valvular heart disease was present in two, and no apparent cardiac abnormalities were found in three. The mean left ventricular ejection fraction was 53 +/- 14%. During the follow-up period of 24 +/- 16 months, actuarial survival rates at 1 and 2 years were 95% and 89% for sudden death and 95% and 83% for total cardiac death, respectively. No patients with a known ejection fraction greater than 30% died suddenly during the follow-up. Noninducibility by programmed stimulation in patients with sustained ventricular tachycardia or fibrillation is associated with a relatively preserved ventricular function. It may predict a low risk of sudden death in patients with preserved ventricular function. 
5	Grafting of venous leg ulcers. An intraindividual comparison between cultured skin equivalents and full-thickness skin punch grafts. Skin equivalents that consisted of a noncontracted collagen gel populated with allogeneic fibroblasts and covered with autologous cultured keratinocytes were used for grafting venous leg ulcers. The results were compared in the same patient with those obtained with a routinely used standard method of grafting with autologous full-thickness punch grafts. The skin equivalents and the punch grafts were grafted successfully in four of five patients. The median healing time of ulcers grafted with skin equivalents was 18 days whereas that of ulcers covered with punch grafts was 15 days. The cosmetic appearance of the skin equivalent-grafted ulcers was better than that of the punch-grafted ulcers. 
1	A risk-benefit analysis of elective bilateral oophorectomy: effect of changes in compliance with estrogen therapy on outcome. A bilateral oophorectomy at the time of elective hysterectomy is often performed to prevent ovarian cancer. The assumption that endogenous estrogen can be easily replaced with supplemental medication fosters the decision for routine oophorectomy. Published reports on the use of postmenopausal estrogen indicate that compliance is less than perfect. This fact could affect the overall outcome. Decision analysis techniques with Markov cohort modeling were used to evaluate the policy of elective bilateral oophorectomy. Results from studies judged methodologically sound were combined to determine values representing the influence of estrogen on coronary heart disease, breast cancer, and osteoporotic fracture. The decision tree also explicitly incorporated patient compliance. When compliance with estrogen therapy is assumed to be perfect, oophorectomy yields longer life expectancy than retaining the ovaries. When actual drug-taking behavior is considered, retaining the ovaries results in longer survival. This analysis highlights the importance of including the effects of patient compliance with treatment recommendations when the impact of a health policy decision such as prophylactic surgery is assessed. 
4	Low-dose heparinization can be used with DEAE-cellulose hemodialysis membranes. The ability of DEAE-cellulose (Hemophan) membranes to bind heparin may reduce bioavailable heparin and predispose to dialyzer clotting, thus preventing use of Hemophan with low-dose heparin. To examine this possibility, residual blood volumes were determined following 95 treatments with dialyzers containing Hemophan membranes in 11 patients. No heparin was added to the saline used to prime the dialyzers. The anticoagulant effect of heparin was measured using recalcified activated clotting times (RACT). Two heparin doses, calculated by a pharmacokinetic model to increase baseline RACT by 12.5% and 25%, were used for each patient. The mean heparin loading doses were 10.2 +/- 2.8 and 15.3 +/- 2.2 IU/kg, respectively, and the mean infusion rates were 11.1 +/- 3.2 and 14.7 +/- 3.2 IU/kg/h, respectively. Residual blood volumes were determined by red cell lysis and hemoglobinometry. In 88 treatments, residual blood volume averaged 1.6 +/- 1.5 ml. In the other seven treatments, residual blood volume greater than 10 ml was seen. In five of these cases, clotting appeared to propagate from the arterial drip chamber. Residual blood volume did not correlate with the level of heparin. The data show that low-dose heparin can be used with Hemophan membranes, and suggest that blood tubing design may be an important factor in blood circuit clotting during hemodialysis. 
5	Decompensation after Cotrel-Dubousset instrumentation of idiopathic scoliosis. Spinal decompensation after corrective surgery for scoliosis appears to be a significant problem after Cotrel-Dubousset instrumentation (CDI). CDI produces torsional changes in the instrumented and uninstrumented spine that could result in spinal imbalance. Preoperative and postoperative three-dimensional analysis including computed tomography (CT) scans to measure vertebral rotation and segmental rotation were performed to evaluate the importance of torsional changes. Moe/King Type II deformities had a substantially greater risk of imbalance. Deformities instrumented over fewer spinal segments were less likely to decompensate. Specifically, instrumentation excluding the mobile transition segment, determined by maximum segmental rotation and segmental Cobb angle, was likely to decompensate. Derotation and deformity correction excessive in relation to preoperative side bending flexibility and segmental rotation frequently resulted in imbalance. Spinal imbalance after CDI can be reduced by avoiding overcorrection and inclusion of mobile transition segments. 
4	Does blood rheology revert to normal after myocardial infarction? After myocardial infarction there is an acute deterioration of the flow properties of blood. The present study was designed to test whether the abnormality persists. Blood and plasma viscosity, red cell aggregation and deformability, haematocrit, erythrocyte sedimentation rate, white cell count, cholesterol, and triglycerides were measured in 51 patients who had had a myocardial infarction 5.4 (mean) years before. Results in patients and controls were compared and matched pairs with identical cardiovascular risk factors were also selected. Blood viscosity and red cell aggregation were increased and red cell deformability was decreased in the 51 patients. The abnormalities were independent of the interval since infarction and persisted for years. The rheological abnormalities present after myocardial infarction are at least partly independent of the acute event and acute phase reactions. They contribute to the reduced perfusion of the microcirculation of the heart. 
2	Possible transmission of serum hepatitis in liver surgery with the ultrasonic dissector. When the ultrasonic dissector is used during liver surgery, the possibility exists of the transmission of virus to the attending hospital personnel because of unavoidable splashing of the irrigating solution. It becomes apparent from this study that the titer of hepatitis B surface antigen in the aspirated irrigating solution is almost the same level as that in the serum. We therefore strongly recommend that eye shields should be used in hepatic surgery when the ultrasonic dissector is in use. 
2	Microprocessor-assisted solvent-transfer system for gallstone dissolution. In vitro and in vivo validation. To improve the efficacy, safety, and convenience of contact dissolution of gallbladder stones, a microprocessor-assisted solvent transfer system was developed. The system's two pumps simultaneously infuse and aspirate solvent into and from the gallbladder at a high flow rate through a multilumen catheter. The microprocessor controls the pumps using a closed feedback loop control algorithm to regulate intragallbladder pressure to prevent solvent escape into the duodenum. Turbulent solvent flow at the catheter end in the gallbladder is designed to induce rapid stone dissolution and to suspend insoluble residue, thus promoting its aspiration. The system's response and gallbladder emptying capacity was 160-fold faster than the natural gallbladder emptying rate. The rate at which gallstones were dissolved by methyl tert-butyl ether using the system was compared with that achieved with a syringe pump. For 6 of 11 pairs of stones that totally dissolved, the mean dissolution time with the system was 10 +/- 6 minutes compared with 112 +/- 81 minutes for the syringe pump. In the 5 of 11 stone pairs which dissolved incompletely, insoluble residue was completely eliminated by the system in 21 +/- 9 minutes but not by the syringe pump even at 360 minutes. When the system was used in gallstone patients, solvent recovery was 99% +/- 1%, and the concentration of a nonabsorbable marker did not change, confirming the lack of appreciable absorption of methyl tert-butyl ether. These studies suggest that the microprocessor-assisted solvent transfer system is a device capable of safe, complete, and fully automatic contact dissolution of cholesterol gallbladder stones using methyl tert-butyl ether or similar solvents. 
3	P300 brain activity in seizure patients preceding temporal lobectomy. Event-related potentials were recorded over occipital and parietal scalp from 20 patients suffering from intractable partial complex seizures prior to undergoing a temporal lobectomy. Subjects were presented with language and nonlanguage visual stimuli using a divided-field, "odd-ball" paradigm. Although behavioral performance (button-press accuracy, reaction time, and running counts) was comparable across all groups (although accuracy was worse for those in the left temporal group), patients showed tremendous variability in both the amplitude and latency of the P300 response. Particularly notable was the observation that more slow wave activity was present among the patients than among the control subjects, and those scheduled for a left temporal resection evinced more amplitude reduction than those scheduled for a right temporal resection. In addition, a number of patients appeared not to show a P300 response at all. These results are discussed in the context of the utility of using noninvasive event-related potential measures to examine both memory impairment and the integrity of the neural structures that mediate memory functioning in certain patient populations. 
5	Extradural abscess following local anaesthetic and steroid injection for chronic low back pain. A case is described of extradural abscess following extradural injection of local anaesthetic and steroid for the management of chronic low back pain. The common signs and symptoms are reviewed, possible causes discussed and the association with diabetes stressed. 
5	Platelet-activating factor: evidence against a role in hypoxic pulmonary vasoconstriction. The mechanism of hypoxic pulmonary vasoconstriction (HPV) remains unknown. The platelet-activating factor (PAF) antagonist WEB 2086 attenuated HPV in the isolated lung model of the rat. We evaluated the effect of WEB 2086 on HPV in an intact animal. Pigs were anesthetized, mechanically ventilated, and had their hemodynamic variables monitored with a pulmonary artery catheter and arterial line. Cardiac output was measured by thermodilution. Initial studies determined that PAF (0.03 to 1.0 micrograms) injected iv dose-dependently increased pulmonary vascular resistance (PVR) with a 262 +/- 58% increase in PVR 5 min after a dose of 1.0 microgram. WEB 2086 (25 mg/kg iv) completely blocked the increase in PVR caused by iv PAF. Additionally, indomethacin (2 mg/kg followed by 2 mg/kg.h iv) treatment of the animals attenuated the PAF-induced increase in PVR. To evaluate the effect of WEB 2086 on HPV, animals were alternately ventilated with 21% oxygen and 10-min periods of 10% oxygen to induce HPV. After three initial control episodes of hypoxic ventilation, WEB 2086 (25 mg/kg) was injected iv and two more episodes of ventilation with 10% oxygen were given. During the three control HPV episodes the increases in PVR were 80 +/- 10%, 108 +/- 10%, and 107 +/- 22% (n = 5). After WEB 2086, the increase in PVR during two episodes of hypoxia were 96 +/- 28% and 99 +/- 19%, respectively, which was not significantly different from the control response to hypoxia. We conclude that iv PAF dose dependently increases PVR in pigs, and can be blocked by WEB 2086, that its effect is partially mediated through cyclooxygenase products, and that PAF does not appear to mediate HPV in this species. 
2	Intraperitoneal femoral venous catheter insertion with free blood return in presence of tense hemoperitoneum. The authors report a case of intraperitoneal insertion of a femoral venous catheter, with blood return, in a patient with hemoperitoneum. In such patients, skin puncture at or below the inguinal ligament is important. Aspiration of unusually dark blood and medial catheter location should raise the possibility of intraperitoneal catheter placement. 
5	Pott's puffy tumor: a complication of frontal sinusitis. In children sinusitis is a frequent complication of upper respiratory infections but an infrequently considered diagnosis. Although most sinus infections are resolved without complications, when complications do occur they can be serious or life threatening. The most common ones occur in the orbit, but CNS extension is not infrequent. Osteomyelitis and resulting subperiosteal abscess of the frontal bone--the so-called Pott's puffy tumor--is a less common, and perhaps less frequently recognized, serious complication of frontal sinusitis. This paper describes two patients with subperiosteal abscess resulting from frontal sinusitis, one with CNS and orbital extension. A brief literature review is presented, and presentation, diagnosis, and treatment are discussed. 
5	Occlusion of umbilical artery in acardiac, acephalic twin. In the acardiac, acephalic twin malformation the normal co-twin is put at risk because of the extra cardiac work-load. Surgical procedures may be hazardous to the mother. We describe a novel approach--the insertion of a helical metal coil to induce thrombosis in the umbilical artery of the acardiac twin--which immediately interrupted flow. The co-twin was delivered at 39 weeks and his neonatal course has been normal. 
3	Familial autosomal recessive rigid spine syndrome with neurogenic facio-scapulo-peroneal muscle atrophy. Two sisters and a first cousin presented with rigid spine and facio-scapulo-peroneal muscle atrophy. The patients belonged to a family with two first-cousin marriages. Electromyography, muscle and nerve biopsy showed neurogenic muscle atrophy without peripheral nerve involvement. Follow up did not show progression of the disease. This is the first observation of an association of neurogenic facio-scapulo-peroneal and rigid spine syndrome. The double first-cousin marriage suggests autosomal recessive inheritance. 
1	In vitro evaluation of bleomycin-induced cell lethality from plastic and glass containers. To optimize cancer chemotherapy, a considerable amount of research has been expended to study pharmacologic, pharmacokinetic, biochemical, and pharmaceutic properties of antineoplastic agents. However, published data on the stability and compatibility of these agents in various administration fluids and containers are few in number. Evidence of a significant decrease in stability as shown by high-performance liquid chromatography has been reported when bleomycin was infused in plastic containers for prolonged periods (over 24 hours) as compared with the same procedure with glass containers. Because administration of bleomycin is usually given as a continuous infusion, we undertook this study to determine whether the drug loss of stability that occurs in plastic containers results in a therapeutic loss of efficacy (cytotoxicity). By using a tumor stem-cell assay we compared the quantitative effects of bleomycin in plastic and glass containers on cell lethality. The results from our assay showed no significant difference in cell lethality by bleomycin from its aqueous solution stored in glass and plastic containers over the time periods observed. If these results had been statistically significant, the tumor stem-cell assay may have been shown to be a more sensitive means of determining the clinical significance of these stability studies. 
5	Postoperative pancreatic abscess due to Plesiomonas shigelloides. Plesiomonas shigelloides is being recognized with increasing frequency as a human pathogen. The organism is ubiquitous in fresh and brackish water, and clinical illness has been associated with foreign travel and ingestion of inadequately cooked seafood. We describe a 64-year-old Filipino woman who presented 2 weeks after elective cholecystectomy and pancreatic biopsy with left upper quadrant pain, abdominal distention, and fever. Computerized tomography of the abdomen revealed an abscess in the tail of the pancreas with fluid accumulation in the lesser omental sac. Percutaneous aspiration yielded purulent material, and P. shigelloides was recovered in pure culture. To our knowledge, this is the first reported case of pancreatic abscess due to P. shigelloides. 
3	Intracranial arachnoid cysts in children. A comparison of the effects of fenestration and shunting. The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. The cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported. Five children with mild symptoms and small cysts that remained stable on follow-up studies have not required surgical intervention. Of 15 patients with cysts initially treated by fenestration, 10 (67%) showed no clinical or radiographic improvement postoperatively and have undergone cyst-peritoneal (eight patients) or ventriculoperitoneal (VP) shunting (one patient), or revision of a VP shunt placed for hydrocephalus before cyst fenestration (one patient). Two other patients with existing VP shunts required no further procedures. Thus, only three (20%) of 15 patients initially treated by fenestration remain shunt-independent after a median follow-up period of 8 years. The 20 other patients were initially treated by cysts shunting and all improved postoperatively; shunt revision has been necessary in six (30%) of these 20 patients because of cysts recurrence. Cyst location influenced the success of shunt treatment; none of the seven middle cranial fossa cysts treated by shunting have required revision, but results with cysts in other locations were less favorable. In all locations, though, shunting was more successful than fenestration. It is concluded that cyst-peritoneal or cyst-VP shunting is the procedure of choice for arachnoid cysts in most locations, including those in the middle cranial fossa. 
1	Giant eccrine acrospiroma. Four cases of large eccrine acrospiroma (three benign, one malignant) are reported. The benign tumors involved the lower extremities of two women and one man (73 to 89 years of age). The duration of the lesions ranged from 10 to 20 years. The malignant tumor involved the left side of the chest of a 60-year-old man. Its occurrence in a lesion that had been present for 40 years suggested malignant transformation of a pre-existing benign eccrine acrospiroma. Each tumor showed little to no cellular atypia. Mitotic rates (mitotic figures per 10 high-power fields) varied both between and within lesions. Average mitotic rates did not differentiate the benign from the malignant tumors. The most important distinguishing features of large benign eccrine acrospiromas are the relative circumscription, the lack of cellular atypia, and the absence of stromal, perineurial, and angiolymphatic invasion. 
5	Cerebellar voice tremor: an acoustic analysis. Patients with cerebellar disease may exhibit tremulous phonation as part of their dysarthria. The results of an acoustic analysis of cerebellar voice tremor in a patient with hereditary ataxia and presenting with a purely cerebellar syndrome are reported. Analysis included computation of speech intensity contours, fundamental frequency contours, and spectral parameters from sustained productions of vowels and voiceless fricatives. Fundamental frequency contours during sustained phonation of vowels showed rhythmic oscillations at a rate of about 3 Hz. No concomitant periodicity could be detected for the parameters characterising voiceless fricative production. The results indicate an impairment of phonatory control in relation to the maintenance of a constant isometric activity of the internal laryngeal muscles. Cerebellar voice tremor may therefore be classified as a form of postural tremor. 
5	Comparison of lymphatic and venous interpositional autografts in experimental microsurgery of the canine lymphatics. In mongrel dogs, 56 autologous lymphatic and vein grafts were interpositioned to bridge a defect in the femoral collecting lymphatics. In one group, 26 lymphatic autografts were interpositioned with good results. No obstruction was observed over 6 months. In another group, 20 venous autografts were interpositioned after irrigation with heparinized saline and another 10 autografts were interpositioned without irrigation. After 1 week, four irrigated grafts were partially occluded with a red thrombus; after 6 months, all grafts were totally occluded. In a third group, 15 lymphaticolymphatic anastomoses were enveloped by a silicone sheet to provoke prolonged devascularization. None of the vessels was patent. Anastomotic patency was inspected in vivo postoperatively. The specimens were studied with light microscopy and scanning and transmission electron microscopy. Prolonged devascularization damaged the endothelial cells. The results show that the lymphatic vessel autograft is the best choice for an interpositional autografting to bridge a defect in lymphatic vessels. 
5	Surgery for thoracoabdominal aortic aneurysms. From July 1985 to July 1989, Loma Linda University Medical Center evaluated 46 thoracoabdominal aortic aneurysms (TAAAs). Forty patients were taken to surgery--18 (45%) were operated on an emergency basis for reasons including rupture (12 patients, 30%), dissection (5 patients, 12.5%), and severe pain (1 patient). The overall mortality for all operated patients was five (12.5%-17% for emergency surgery versus 9% for elective surgery). Nonfatal complications occurred in 40 per cent of patients (16). The overall incidence of paraplegia was 10 per cent (4/40), emergency patients 17 per cent (3/18) versus elective patients 4.5 per cent (1/22). Careful preoperative evaluation, standardization of operative technique, and good postoperative management have improved the outlook for these patients who otherwise would progress to eventual rupture and death. Because mortality and morbidity are substantially reduced in elective patients, we recommend that all patients with TAAAs be evaluated for surgery as soon as diagnosis is made. 
5	The prevalence of Helicobacter pylori in nonulcer dyspepsia. Importance of stratification according to age Helicobacter pylori (formerly Campylobacter pylori) is causally related to active antral gastritis and is highly associated with duodenal and gastric ulcers. However, the relationship of H pylori to nonulcer dyspepsia is less clear. We determined the presence of H pylori in unselected patients who were undergoing upper gastrointestinal tract endoscopy, and we found a prevalence of 37% in 110 patients with nonulcer dyspepsia that was similar to previous data. Patients with nonulcer dyspepsia who had H pylori were found to be significantly older than patients with nonulcer dyspepsia who did not have H pylori. In addition, when stratified according to age, we detected an increased prevalence of H pylori in patients with nonulcer dyspepsia with increasing age, similar to that reported for asymptomatic control populations. This finding casts doubt as to the causal role of H pylori for most patients with nonulcer dyspepsia and stresses the importance of considering epidemiologic factors, such as age, when evaluating the role of H pylori in specific disease states. 
4	Reduced frequency of hypertensive disorders in placenta previa The isthmic segment of the uterine artery's ascending branch has a freer course and wider diameter than distal parts of the vessel. Therefore, we assumed that this arterial segment would provide better blood flow and prevent hypoxia of the trophoblast. As a result, placenta previa pregnancies would be complicated by hypertensive disorders less often than are pregnancies with normally implanted placentas. To test this hypothesis, 491 placenta previa pregnancies, among a population of 106,866 pregnant women, were compared with pregnancies with normally implanted placentas. Clinically meaningful and statistically significant reductions in the rates and risks of hypertensive disorders were found in placenta previa pregnancies (P = .002, relative risk = 0.44, 95% confidence interval 0.25-0.78). The differences persisted when primiparous and multiparous women were examined separately and when preterm and term deliveries were separated. In a multivariate logistic regression analysis, patients with placenta previa had a third of the risk for hypertensive disorders compared with pregnant women with normally implanted placentas (relative risk = 0.36, 95% confidence interval 0.20-0.64), even after controlling for parity and preterm or term delivery. In the same model, primiparity and preterm delivery were each associated with a doubling of risk for hypertensive disorders, regardless of the placental implantation site. Thus, regardless of parity and preterm or term delivery, placenta previa and hypertensive disorders are inversely related. 
3	The long-distance effects of brain lesions: visualization of myelinated pathways in the human brain using polarizing and fluorescence microscopy. We describe several new possibilities for the study of degenerated myelinated tracts in the human central nervous system (CNS). The methods are based on the visualization of myelin breakdown products that show birefringence in polarized light and, when stained with Nile blue and benzpyrene-3,4, exhibit fluorescence. Even after lengthy formalin fixation, the methods permit the localization of anterogradely degenerated tracts in a variety of fiber systems in the brains of patients who died between five and 20 months after the onset of neurological symptoms. Particularly the polarizing technique, because of its simplicity, can be added to the usual neuropathological methods for demonstrating the long-distance effects of a brain lesion. As research tools, these methods would also aid in the study of the anatomical substrate of human neurological symptomatology. 
4	Effects of adenosine on human coronary arterial circulation Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10-240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS). 
4	Anterior segment ischemia: a complication of retinal detachment repair in a patient with sickle cell trait. Anterior segment ischemia (ASI) is a dreaded complication of retinal detachment surgery particularly in patients with predisposing factors such as sickle cell disease. We report a case of ASI after scleral buckling in an otherwise healthy black patient with sickle cell trait. Conditions of relative hypoxia intraoperatively from either anesthesia or surgical manipulation may precipitate vasoocclusive phenomena in these normally asymptomatic patients. Since the incidence of sickle cell trait in the black population in the United States is 8.5%, we recommend these patients have a preoperative sickle test followed by hemoglobin electrophoresis with quantification if positive. The presence of sickle cell trait should alert the surgeon to the risk of ASI, and factors predisposing to hypoxia should be minimized when possible. 
3	Bone metastases: pathophysiology and management policy. The pathophysiology and options for management of bone metastases as well as criteria for determining response to therapy are reviewed. Bone metastases are frequently one of the first signs of disseminated disease in cancer patients. In the majority of patients, the primary tumor is in the breast, prostate, or lungs. Although almost all patients will die of their disease, a proportion of the patients will survive for several years. Treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and mobility, and, if possible, to prolong survival. Therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes, agents such as diphosphonates, which inhibit resorption of bone, as well as analgesic and antiinflammatory drugs. The mechanisms by which pain is relieved by several of these therapies remain unclear but actions beyond a simple tumoricidal effect appear to be important. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations that assess the efficacy of the various therapeutic possibilities by using well-defined and validated criteria of response. 
1	Increased serum beta 2-microglobulin concentrations in hyperthyroid states. Serum beta 2-microglobulin concentrations were determined in 21 untreated hyperthyroid patients (12 with Graves' disease, and nine with toxic nodular adenoma) and in 20 healthy controls. All subjects had normal serum creatinine concentrations and urine analysis. Both total and free thyroid hormones were significantly higher in the hyperthyroid groups than in controls. Beta 2-microglobulin concentrations were significantly increased in both groups of hyperthyroid patients compared with controls. No difference was found in the thyroid hormone and beta 2-microglobulin concentrations between both sets of patients. The beta 2-microglobulin and thyroid hormone concentrations were not correlated. These data show that hyperthyroidism is another cause of increased beta 2-microglobulin production along with viral infections, immunologically mediated diseases, and malignant neoplasms. The increased serum beta 2-microglobulin concentration in thyroid hyperfunction is probably related to metabolic rate, even if autoimmunity might contribute to its overproduction. 
5	Urinary excretion of Tamm-Horsfall protein in women with recurrent urinary tract infections. Since MS-fimbriated bacteria adhere to Tamm-Horsfall protein, it has been suggested that Tamm-Horsfall protein may trap urinary pathogens and prevent them from colonizing the mucosal surfaces of the urinary tract. To test the hypothesis that low urinary Tamm-Horsfall protein excretion rates predispose to urinary tract infection we obtained serial urine samples from 17 women with and 18 without a history of recurrent urinary tract infection. None of the women had known structural abnormalities of the urinary tract. Concentrations of Tamm-Horsfall protein in urine were measured with a sensitive enzyme-linked immunosorbent assay method. On the average, 3 urine samples per person collected within 3 to 6 months were analyzed. The mean Tamm-Horsfall protein excretion of women with recurrent urinary tract infection was 57.0 mg./l. and that of controls was 66.3 mg./l.; this difference was not statistically significant. The mean coefficient of variation was 44.2 and 62.1%, respectively. We conclude that urinary Tamm-Horsfall protein concentration is not significantly decreased in women with recurrent urinary tract infection compared with controls, and that excretion varies widely in repeat samples obtained from the same individual. 
5	Pharmacological characterization of LY233053: a structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action. This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity. The relatively short duration of action of LY233053 may make this compound particularly advantageous as a neuroprotective agent in the treatment of acute conditions such as cerebral ischemia. 
4	Prognostic value of thallium-201 perfusion defects in idiopathic dilated cardiomyopathy. To assess the prognostic significance of thallium-201 perfusion defects in patients with idiopathic dilated cardiomyopathy (IDC), 43 patients underwent thallium scintigraphy in addition to clinical, echocardiographic, angiographic and hemodynamic evaluation. Eleven patients had no significant thallium perfusion abnormality, 19 had multiple small defects and 13 had a large defect. During 3.2 +/- 2.2 years, 14 patients had disease-related mortality. The patients who died had a higher incidence of ventricular tachycardia (71 vs 31%; p less than 0.02), increased cardiothoracic ratio (60 +/- 6 vs 54 +/- 6; p = 0.005), decreased fractional shortening (11 +/- 6 vs 15 +/- 5; p less than 0.05), increased pulmonary wedge pressure (15 +/- 7 vs 10 +/- 6 mm Hg; p = 0.05), increased left ventricular end-diastolic pressure (21 +/- 8 vs 14 +/- 6 mm Hg; p = 0.02) and abnormal thallium perfusion defects (13 of 14 vs 16 of 26; p less than 0.05) compared with survivors. Age, gender, left ventricular end-systolic and end-diastolic dimensions, cardiac index and ejection fraction were not statistically different in the survivors versus the patients who died. Kaplan-Meier survival estimates at 1, 3 and 5 years were 100% in patients without significant perfusion abnormality; 89, 77 and 64%, respectively, in patients with multiple small defects; and 84, 76 and 30%, respectively, in patients with a large defect (p less than 0.025 by log rank test). 
5	Pancreas transplantation. A new program. Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen patients received a combined cadaveric pancreas/renal transplant with bladder drainage. One patient received a second pancreas transplant 24 hours after the first pancreas graft failed due to portal vein thrombosis. One patient received a pancreas graft 3 years after kidney transplantation. Complications included five cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux pancreatitis requiring conversion to pancreatico-enterostomy, and two late deaths. Average time to discharge was 17 days following transplant, with 2.9 re-hospitalizations per patient and an average of 38 in-hospital days during the first 6-12 months. Seventeen rejection episodes occurred in 12 patients, diagnosed by declining urine amylase and pH and/or finding of rejection on kidney biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival is 81 per cent (1-20 months follow-up). All patients are insulin-independent and normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post-transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7 mg/dl. A new program of pancreas transplantation can be successful in carefully selected diabetic patients, with special attention to avoidance of preservation injury to the pancreas during multiorgan donor procurement. Combined pancreatic/renal transplantation is believed to be the therapeutic treatment of choice in Type I diabetic patients who have impaired renal function and have no significant cardiovascular disease. 
3	Reversible myeloneuropathy of nitrous oxide abuse: serial electrophysiological studies. Detailed electrophysiological studies were performed in 4 patients with myeloneuropathy induced by abuse of nitrous oxide for 1 to 4 years. All presented with paresthesias, weakness, and Lhermitte's phenomena, and exhibited signs of sensorimotor polyneuropathy, ataxia, and arreflexia. Two had subnormal serum vitamin B12 levels. Baseline electrophysiologic testing revealed reduced motor unit potentials, prolonged F wave latencies, absent H reflexes, denervation potentials, and delays in motor and sensory conduction. Three had peripheral and nuchal delay after median nerve stimulation. All were reevaluated after 3 to 12 months' abstinence and treatment with vitamin B12, and all showed substantial clinical improvement. Parallel improvement in electrophysiologic findings occurred, but residual minor conduction delays, loss of H reflexes, electromyographic evidence of denervation, or abnormalities of posterior tibial SEP were noted. These findings confirm the reversibility of myeloneuropathy of nitrous oxide abuse and describe the profile of electrophysiologic recovery in subjects who abstain from further neurotoxic exposure. 
4	Hemodynamic effects of partial correction of chronic anemia by recombinant human erythropoietin in patients on dialysis. Eighteen patients on chronic hemodialysis with renal anemia were treated with recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting state were determined before and after successful treatment. Posttreatment cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860 dyne.cm.s-5) were increased significantly when compared with the pretreatment period. We conclude from our study that the increase of blood pressure as seen in patients on dialysis, who are effectively treated with r-HuEPO, is due to an increase in peripheral resistance. This increase overrules the decrease of cardiac index and might well be a result of peripheral vasoconstriction due to improved oxygen availability. 
1	Association between extent of colonic mucosal sialomucin change and subsequent local recurrence after curative excision of primary colorectal cancer. Two interrelated studies were carried out to determine whether extent of sialomucin change adjacent to a primary colorectal carcinoma predicted local tumour invasiveness and risk of local recurrence. In the first, depth of tumour penetration was correlated with the length of the sialomucin band adjacent to 72 primary colorectal cancers. There was a significant (P less than 0.05) increase in sialomucin band length adjacent to tumours invading adjacent structures compared with those which had not (Mann-Whitney U test), although there was no overall correlation between depth of penetration, Duke's classification or degree of differentiation (Kruskal-Wallis test). A sialomucin band of greater than 3 cm was associated with a 70 per cent probability of adjacent structure (T4) invasion. These observations were then tested prospectively in a second study involving 256 patients to determine whether the presence of a greater than 3 cm sialomucin band could predict local recurrence. Presence of a greater than 3 cm sialomucin band was a significant (x2 = 7.12, d.f. = 1, P less than 0.001) and independent predictor of local but not distant recurrence. In addition both the interval to local recurrence and survival were significantly shorter if a greater than 3 cm sialomucin band was present. However the accuracy of greater than 3 cm sialomucin band as a predictive test for local recurrence was only 70 per cent. The extent of sialomucin adjacent to a primary colorectal cancer does provide a crude assessment of tumour invasiveness and risk of local recurrence. 
4	Reperfusion and readmission of oxygen. Pathophysiological relevance of oxygen-derived free radicals to arrhythmogenesis. We have examined the pathophysiological role of readmission of oxygen (and hence production of oxygen-derived free radicals) in the initiation of reperfusion-induced arrhythmias by separating, on a temporal basis, readmission flow from readmission of oxygen. Isolated rat hearts (n = 12/group) were subjected to 10 minutes of regional ischemia and 10 minutes of reperfusion. In controls reperfused with oxygenated solution (Po2 greater than 600 mm Hg), 92% of hearts developed ventricular fibrillation (VF) during the first 20 seconds of reperfusion, whereas in hearts reperfused with hypoxic solution (Po2 9.3-12.2 mm Hg), the incidence of VF was only 17% (p less than 0.05). Subsequent readmission of control solution (Po2 greater than 600 mm Hg) to the latter group led, within 20 seconds, to the appearance of VF in seven of the 10 hearts (70%) that had not previously fibrillated. To examine whether hypoxic reperfusion had prevented VF or merely delayed its onset, the studies were repeated in separate groups of hearts with the duration of hypoxic reperfusion extended to 5 minutes. In addition, to examine the partial pressure dependence of the relation, the Po2 in the reperfusion solution was set at one of five different levels: greater than 600, 150-192.7, 69-85.6, 9.2-14.8, or 0.0 mm Hg. It was found that hypoxia merely delayed VF onset by 20-40 seconds and did not significantly reduce the incidence of VF, which was 83%, 92%, 67%, 58%, and 58%, respectively. This indicated that readmission of oxygen is unnecessary for the initiation of VF during reperfusion. The hearts that reverted to sinus rhythm during the ensuing 5 minutes (n = 8, 4, 5, 9, and 8, respectively) were used to assess the arrhythmogenic consequences of readmission of oxygen. When control solution (Po2 greater than 600 mm Hg) was readmitted, new episodes of VF were elicited within 20 seconds in a manner that was inversely proportional to the preceding Po2 (p less than 0.05), the incidence of new episodes of VF being 0%, 0%, 40%, 67%, and 86%, respectively. The arrhythmogenic effect of readmission of oxygen was not the result of a sudden increase in heart rate, because a similar arrhythmogenic effect of readmission of oxygen was seen in separate groups of hearts that were paced (350 beats/min) throughout hypoxia and readmission of oxygen. In conclusion, readmission of flow and readmission of oxygen are independent determinants of reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS). 
1	Efficacy of transesophageal echocardiography as a perioperative monitor in patients undergoing cardiovascular surgery. Analysis of 149 consecutive studies. To evaluate the usefulness of transesophageal echocardiography as a perioperative monitor in patients undergoing cardiovascular surgery, 149 consecutive patients were studied since 1985. Left ventricular function was assessed by measurement of left ventricular dimension and ejection fraction in patients with valvular disease. This monitoring was useful in detecting the changes in left ventricular performance in patients with volume overload and in managing patients in the early postoperative period. Cardiac tamponade was clearly demonstrated before changes in electrocardiogram and hemodynamic data. In 27 patients, transesophageal color Doppler echocardiography was used to confirm that there was no residual regurgitation immediately after valvular reconstructive surgery. Transesophageal color Doppler echocardiography was also useful in detecting the entry of false lumen before surgery in 7 patients with dissecting aortic aneurysm. There were no unsuccessful introductions, no traumatic or thermal injuries, 18 patients (12.1%) with hoarseness and 5 patients (3.4%) with transient arrhythmia. In conclusion, transesophageal echocardiography provides a good imaging window to the heart and great vessels perioperatively. This expedient, safe informative imaging method can be used more routinely in patients during surgery. 
1	HIV infection: clinical features and treatment of thirty-three homosexual men with Kaposi's sarcoma. The clinical findings of patients with oral Kaposi's sarcoma are reviewed. These oral findings commonly included candidiasis, hairy leukoplakia, gingivitis associated with human immunodeficiency virus (HIV), periodontitis, and other symptoms, including xerostomia. The other common symptoms of HIV disease that may be of importance in leading to a diagnosis are reviewed in this patient group. Treatment by local radiotherapy or by intralesional vinblastine of these oral Kaposi's sarcomas resulted in successful palliation, with more than 50% regression of the lesions in 80% of the patients treated. 
5	Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery. O2 consumption (VO2) of anesthetized whole mammals is independent of O2 delivery (DO2) until DO2 declines to a critical value (DO2c). Below this value, VO2 becomes O2 supply dependent. We assessed the influence of whole body DO2 redistribution among organs with respect to the commencement of O2 supply dependency. We measured DO2, VO2, and DO2c of whole body, liver, intestine, kidney, and remaining carcass in eight mongrel dogs during graded progressive hemorrhage. Whole body DO2 was redistributed such that the organ-to-whole body DO2 ratio declined for liver and kidney and increased for carcass. We then created a mathematical model wherein each organ-to-whole body DO2 ratio remained approximately constant at all values of whole body DO2 and assigned organ VO2 to predicted organ DO2 by interpolation and extrapolation of observed VO2-DO2 plots. The model predicted that O2 supply dependency without redistribution would have commenced at a higher value of whole body DO2 for whole body (8.11 +/- 0.89 vs. 6.98 +/- 1.16 ml.kg-1.min-1, P less than 0.05) and carcass (6.83 +/- 1.16 vs. 5.06 +/- 1.15 ml.kg-1.min-1, P less than 0.01) and at a lower value of whole body DO2 for liver (6.33 +/- 1.86 vs. 7.59 +/- 1.95, ml.kg-1.min-1, P less than 0.02) and kidney (1.25 +/- 0.64 vs. 4.54 +/- 1.29 ml.kg-1.min-1, P less than 0.01). We conclude that redistribution of whole body DO2 among organs facilitates whole body O2 regulation. 
5	Shortcut method to calculate the sample size in trials of screening for chronic disease. One of the first questions arising in the planning of a randomized trial to evaluate mortality reduction by screening concerns the sample size of the trial required to detect an expected mortality reduction in the study group for given significance level alpha, and power 1 - beta. If estimates exist of the underlying average annual incidence rate of the disease ra and the annual mortality rate delta a or survival data for patients in the population under consideration before screening started, then a simple formula for the probability of dying from the disease within T years after entry into the trial can be given for the control group. Standard formulas may then be used for sample size calculations in randomized trials, which compare the risk of death from the disease in the control and the study group accrued at T years after entry. A simple correction for loss of follow-up, due to mortality from other causes or, for instance, migration is possible. 
5	Bilateral Norrie's disease in identical twins. A case of Norrie's disease in an identical twins is reported. No positive family history was obtained. The couple had no other children. The older of the twins died at the age of 9 months of uncertain cause. To the best of my knowledge this is the first case of Norrie's disease reported in Malaysia. And its occurrence in an identical twins is very rare. 
3	Clinical characteristics of migraine and episodic tension-type headache in relation to old and new diagnostic criteria. Eighty-one patients were diagnosed as having migraine, tension headache or both according to previously used criteria. Then we performed a standardized interview to determine the frequency and severity of headache characteristics used in the new operational diagnostic criteria of the International Headache Society (IHS). In every patient the original diagnosis fulfilled also the IHS criteria, but in 9 patients the criteria were only fulfilled in half or less of the attacks, and applying the IHS criteria they also achieved an additional diagnosis. In one patient these attacks did not fulfill the pain criteria and in 8 (4 migraine, 4 tension headache) they did not fulfill the criteria for accompanying symptoms. Overall the IHS criteria are sensitive and specific, but they may possibly be improved with regard to accompanying symptoms. The present study suggests that recording of frequency and graded severity of characteristics using a headache diary may further improve the distinction between the different types of headache. 
2	Selective intestinal decontamination increases serum and ascitic fluid C3 levels in cirrhosis. Selective intestinal decontamination for 7 days with norfloxacin was performed in 14 cirrhotic patients with ascites and low ascitic fluid total protein. Variations in serum and ascitic fluid of C3 and C4 and ascitic fluid total protein after therapy were compared with those of a control group of 14 untreated patients with similar characteristics. After oral norfloxacin administration, we saw a significant increase of C3 in serum (p less than 0.05) and ascitic fluid (p = 0.01). A significant increase was also observed in ascitic fluid total protein (p less than 0.05) but not in serum and ascitic fluid C4. There were no changes in serum C3, ascitic fluid C3, ascitic fluid C4 or in ascitic fluid total protein in group 2. These data demonstrate that selective intestinal decontamination increases serum and ascitic fluid C3 levels and, therefore, might be useful in preventing spontaneous infections in cirrhotic patients at high risk of infection. 
5	Combined anterior and posterior fusion for spinal deformity in myelomeningocele. Since 1973, 50 of 54 children have been treated by the author with a combined anterior and posterior fusion. Twenty males and 34 females, ranging in age from 1 to 16 years, have been followed for a mean period of 5.5 years. Sixteen patients with a kyphosis averaging 113 degrees (range, 77 to 170 degrees) had correction of deformity to a mean of 35 degrees. Thirty-seven patients with a scoliosis averaging 73 degrees (range, 20 to 135 degrees) had correction to an average of 34 degrees (range, 0 to 75 degrees). There were 4 cases of deep wound infection successfully treated with drainage and antibiotics and only one case required implant removal after fusion/maturation. A pseudarthrosis was noted by radiograph in 6 patients, 3 of whom had isolated asymptomatic lumbosacral pseudarthroses. Three patients had pseudarthrosis at the thoracolumbar junction. These required repair and were successfully treated by supplemental posterior fusion resulting in an overall pseudarthrosis rate of 5.7%. Anterior fusion of the dysraphic spine allows greater correction of both spinal deformity and pelvic obliquity in addition to contributing significant strength to the fusion mass. Segmental spinal instrumentation with sublaminar and pedicular wiring to custom-contoured Luque rods provides excellent correction and immediate postoperative stability. 
3	Central nervous system involvement in Von Hippel-Lindau disease. Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions. The associated clinical features were also reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study. Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms. Multiple lesions were common. The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life. Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene. 
3	Vagal schwannoma. A patient with a benign encapsulated intrathoracic vagal schwannoma is presented and the literature is reviewed. The right paratracheal tumor was identified incidentally on a chest film and excised using a right thoracotomy. Although rare, vagal schwannomas should be considered for any mediastinal mass along the vagus nerves especially when the paratracheal tumor produces minimal or no respiratory symptoms suggesting a slow-growing, encapsulated process. 
1	Limb-salvage surgery in the treatment of osteosarcoma in skeletally immature individuals. Sacrifice of major growth plates during resection and fixed-length reconstruction of a limb in a skeletally immature child with osteosarcoma may result in a significant limb-length inequality as growth progresses. A limb-length discrepancy in the humerus may cause minor cosmetic problems but does not generally result in a significant functional deficit. In the lower extremity, tumors about the knee, including the distal femur and proximal tibia, usually present the dilemma of whether limb salvage by arthrodesis, osteoarticular allograft, or endoprosthetic replacement would result in a significant limb-length inequality and whether amputation of the extremity is a preferable procedure. The techniques of rotationplasty and an expandable endoprosthesis have been successfully used for treating skeletally immature patients with osteosarcoma of the distal femur. With regard to survival and function, the results obtained with these innovative methods are favorable compared with those of a high above-knee amputation. 
5	Dilated renal collecting systems: differentiating obstructive from nonobstructive dilation using duplex Doppler ultrasound. Two patients with ileal loop urinary diversions, studied with real-time and Doppler sonography ("duplex sonography") of the kidneys, were shown to have dilated intrarenal collecting systems. Resistive index measurements calculated from the Doppler signal correctly identified obstructive dilatation in 1 case and nonobstructive dilatation in the other. 
3	Intradural epithelial cyst at the craniovertebral junction. Case report. A case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37-year-old man. The classification of these rare lesions is discussed. 
4	Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease. A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men. No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation. The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth. No significant relations were detected with collagen-induced aggregation. Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease. Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets. 
5	Hypocalciuria of preeclampsia is independent of parathyroid hormone level. Hypocalciuria is a feature of preeclampsia. The roles of parathyroid hormone (PTH) and vitamin D 1,25(OH)2D3 (calcitriol) in its pathogenesis have not yet been determined. Fourteen preeclamptic women were compared with 12 women with chronic hypertension and 11 normotensives, all in the third trimester. Preeclamptics had the lowest urinary calcium excretion rate (62.1 +/- 32.8 mg/24 hours) compared with chronic hypertensive women (162.6 +/- 97.8 mg/24 hours) and normotensive controls (225.6 = 146.9 mg/24 hours) (P less than .05). Serum PTH was lowest in preeclamptics (9.8 +/- 5.5 pg/mL), in contrast to the chronic hypertensives (18.5 +/- 2.7 pg/mL) and normotensives (16.4 +/- 3.2 pg/mL) (P less than .005). Similarly, urinary cyclic adenosine monophosphate (cAMP) excretion was 2.9 +/- 1.4 mumol/24 hours in the preeclamptics, 5.1 +/- 1.7 mumol/24 hours in the chronic hypertensives, and 4.6 +/- 1.3 mumol/24 hours in the normotensive group (P less than .05). These data suggest that the mechanism of hypocalciuria in preeclampsia is independent of the PTH-calcitriol axis. Therefore, it is suggested that the hypocalciuria of preeclampsia is due to intrinsic renal tubular dysfunction. 
5	Bleeding from duodenal lymphangiectasia. An 8 year old girl with recurrent upper gastrointestinal bleeding was found to have localised duodenal lymphangiectasia by fibreoptic endoscopy. She did not show physical signs or laboratory evidence of significant enteric protein loss. A low fat diet seemed to prevent further bleeding. Duodenal lymphangiectasia may be associated with gastrointestinal bleeding in children. 
3	Unusual blink reflex with four components in a patient with periodic ataxia. Characteristic findings in blink reflex are reported in a 55-year-old female with periodic ataxia. The blink reflexes on the side ipsilateral to the stimulation consisted of four components with latencies of 11, 21, 35 and 47 ms, instead of the usual two components seen in normal subjects. On the contralateral side, the last three components were also present. The second component was different from the normal R2 response in that its latency was shorter than normal and it did not habituate by stimulation at a rate of 10 Hz. In addition, it was more affected by diazepam than the third or fourth components. It is considered that R2 may have consisted of three components and that a shorter latency of the second component could be explained by facilitation. 
2	Feasibility of digital teleradiology for imaging evaluation of patients with acute right upper quadrant abdominal pain. To assess the utility of a commercially available digital teleradiology system in evaluating patients with acute pain in the right upper quadrant, hard-copy images from 100 examinations (50 hepatobiliary scintigrams and 50 sonograms of the right upper quadrant) were digitized, transmitted via standard telephone lines, and viewed remotely on a video monitor. Video and hard-copy interpretations were then compared for degree of concordance. For the scintigraphic studies, hard-copy and video images were equal in demonstrating gallbladder and bile duct activity. Video images failed to depict the presence of bowel activity in one case. Gallstones were depicted equally well on hard-copy and video sonographic images. The video interpreters overestimated the presence of abnormal hepatic parenchyma and overlooked one case of right hydronephrosis. The video interpretations of the scintigrams and sonograms showed an overall error rate of 4%, comparable to the rate obtained when radiographs are interpreted remotely with digital teleradiology systems. 
4	Clinical use of the Berlin Biventricular Assist Device as a bridge to transplantation. The Berlin Artificial Heart System/Biventricular Assist Device (BVAD) was used in 38 patients. 1) Twenty-eight patients were awaiting cardiac transplantation (Tx) (age 23-56 yrs). All patients had contraindications not allowing immediate Tx. 2) Five patients were emergency cases not on our Tx list (postcardiotomy cardiac failure, acute myocarditis) (age 28-59). 3) Five patients were post Tx patients with graft failure (age 22-52). Extracorporal circulation was used for implantation of the BVAD. In group 1, 21 of 28 patients (pts) recovered, and all were subsequently transplanted after 6 hours to 39 days, when all organ function was restored. In 7 pts, mechanical circulation was terminated after 1-40 days because of further deterioration. Five of the transplanted pts died, 14 pts survived (greater than 30 days), and 2 pts were just transplanted with satisfactory postoperative courses. Of group 2 and 3 pts, two were successfully weaned. In one patient the allograft recovered after 11 days of support. 
5	The acute aseptic meningitis syndrome. The acute aseptic meningitis syndrome is an entity that presents a diagnostic challenge to the clinician. Although many infectious and noninfectious etiologies exist for this syndrome, viruses, especially nonpolio enteroviruses, are the classic and most important agents encountered. The incidence of polio and mumps meningitis has declined dramatically in the vaccine era, but recently described pathogens, such as human immunodeficiency virus and Borrelia burgdorferi (Lyme disease agent) are now important considerations in the differential diagnosis. Specifically treatable entities (eg, mycobacterial or fungal meningitis, herpes simplex encephalitis, parameningeal infection) that may mimic aseptic meningitis in their initial presentations must not be overlooked. A careful approach to the patient and a rational use of laboratory studies are the basis for establishing a specific diagnosis and assuring a favorable outcome. 
5	Familial autosomal recessive rigid spine syndrome with neurogenic facio-scapulo-peroneal muscle atrophy. Two sisters and a first cousin presented with rigid spine and facio-scapulo-peroneal muscle atrophy. The patients belonged to a family with two first-cousin marriages. Electromyography, muscle and nerve biopsy showed neurogenic muscle atrophy without peripheral nerve involvement. Follow up did not show progression of the disease. This is the first observation of an association of neurogenic facio-scapulo-peroneal and rigid spine syndrome. The double first-cousin marriage suggests autosomal recessive inheritance. 
5	End-stage renal disease--is infrainguinal limb revascularization justified? Reports of reconstructive surgery for peripheral vascular disease have been relatively uncommon in patients with end-stage renal disease. Between 1980 and 1989, 39 patients with end-stage renal disease underwent revascularization of 56 limbs. Fifty-two primary infrainguinal and four secondary infrainguinal bypass grafts were performed. In addition, nine thrombectomies were performed. At the time of surgery 37 patients were on dialysis; three had functioning kidney transplants. The indications for revascularization were gangrene, rest pain, or ulceration in all except three limbs with disabling claudication. Reversed, nonreversed, or in situ vein was used in 25 of the 52 primary infrainguinal revascularizations performed. Polytetrafluoroethylene was used in 25. Two procedures used a combination of polytetrafluoroethylene and vein. The primary patencies for all infrainguinal procedures at 1 and 2 years were 77% and 68%, respectively. Four perioperative deaths occurred in the infrainguinal group (7.7%). An additional death occurred after thrombectomy for late graft closure. Three deaths were a result of myocardial infarction. One patient on peritoneal dialysis developed uncontrolled sepsis. At 3 years 39% of patients were alive, and 84% of the limbs were salvaged. Among the cases studied no group was identified that represented unacceptable operative risk. Results compared well with reported patencies for patients subjected to infrainguinal revascularization procedures. Limb revascularization in patients with end-stage renal disease may be performed by use of similar criteria to those used for other patients with peripheral vascular disease. 
4	Comparison of silent and symptomatic ischemia during exercise testing in men OBJECTIVE: To compare angina and ST-segment depression during exercise testing, as markers for coronary artery disease. DESIGN: Retrospective analysis of exercise test responses and cardiac catheterization results. SETTING: A U.S. Veterans Affairs medical center. PATIENTS: Four hundred and sixteen men who were referred for the evaluation of symptoms, postmyocardial infarction testing, or both. Two hundred patients had no clinical or electrocardiographic evidence of previous myocardial infarction, whereas 216 were survivors of a previous myocardial infarction. INTERVENTIONS: All patients did a standard exercise test and had diagnostic coronary angiography with ventriculography within an average of 32 days (range, 0 to 90 days) of their exercise test. RESULTS: Two hundred patients without a previous myocardial infarction were divided into four groups: the no ischemia group had 80 patients; the angina pectoris only group had 23 patients; the silent ischemia group had 40 patients; and the ST-segment depression and angina pectoris group had 57 patients. In patients without a previous myocardial infarction, exercise-induced ST-segment depression was a better marker than exercise-induced angina for the presence of any coronary artery disease (P less than 0.005). Patients with symptomatic exercise-induced ischemia had a higher prevalence of severe coronary artery disease than did those with only silent ischemia (30% compared with 20%; 95% CI, - 7.3% to 27.0%; P = 0.005). For the 216 survivors of a myocardial infarction, divided into the same four groups, ST-segment depression again was a better marker for the presence of severe coronary artery disease compared with angina alone (P = 0.08). The prevalence rates of severe coronary artery disease in the no ischemia plus myocardial infarction group, the angina pectoris only plus myocardial infarction group, the silent ischemia plus myocardial infarction group, and the ST-segment depression and angina pectoris plus myocardial infarction group were 10%, 9%, 23%, and 32%, respectively (P less than 0.01). CONCLUSIONS: Exercise-induced ST-segment depression is a better marker for coronary artery disease than is exercise-induced angina. Symptomatic ischemia during the exercise test is a better marker for severe coronary artery disease than is silent ischemia. 
3	Congenital myasthenia associated with facial malformations in Iraqi and Iranian Jews. A new genetic syndrome. Fourteen Jewish patients from 10 families of either Iraqi or Iranian origin with congenital myasthenia had associated facial malformations which included an elongated face, mandibular prognathism with class III malocclusion and a high-arched palate. Other common features were muscle weakness restricted predominantly to ptosis, weakness of facial and masticatory muscles, and fatigable speech; mild and nonprogressive course; response to cholinesterase inhibitors; absence of antibodies to acetylcholine receptor; decremental response on repetitive stimulation at 3 Hz but no repetitive compound muscle action potential in response to a single nerve stimulus. This newly recognized form of congenital myasthenia with distinctive ethnic clustering and associated facial malformations is transmitted as an autosomal recessive disorder. The facial abnormalities may be secondary to the neuromuscular defect or may be primary and unrelated. Further studies are needed to elucidate the defect in neuromuscular transmission responsible for the pathogenesis of this syndrome. 
1	Phase I trial of piritrexim capsules using prolonged, low-dose oral administration for the treatment of advanced malignancies. A phase I trial of piritrexim was conducted by use of a prolonged, low-dose oral schedule. A number of different regimens were tested, including daily dosing for 21 days followed by 7 days of no drug therapy; continuous dosing; and daily dosing for 5 of 7 days for 3 consecutive weeks followed by a week of rest. Dose escalation was accomplished by increasing the dosing frequency from once a day to twice a day and then to three times a day and by increasing the number of days of administration. Fifty-one patients with advanced cancer were entered in the study. One hundred twenty-four (96%) of 129 courses were considered assessable. Myelosuppression proved to be the dose-limiting toxic effect. Other toxic effects included stomatitis, nausea and vomiting, anorexia, diarrhea, skin rash, fatigue, and elevation of liver transaminase levels. Antitumor activity was observed in patients with melanoma and bladder cancer, and disease stabilization occurred in those with sarcoma and pheochromocytoma. The recommended dosing schedule for phase II clinical trials is 25 mg three times a day for 5 days for 3 consecutive weeks followed by 1 week of no drug therapy. 
3	Central adenosinergic system involvement in ethanol-induced motor incoordination in mice. To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as enprofylline on ethanol-(i.p.)-induced motor incoordination was evaluated by rotorod. Adenosine agonists and antagonists dose dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i.p. Enprofylline, a weak adenosine antagonist but potent inhibitor of cyclic AMP phosphodiesterase, did not alter ethanol's motor incoordination, further supporting involvement of brain adenosine receptor mechanism(s) in ethanol-adenosine interactions. Results from R-PIA and N6-(S-phenylisopropyl)adenosine experiments showed nearly a 40-fold greater potency of R-vs. S-diastereoisomer, suggesting predominance of adenosine A1 subtype. However, 5'-(N-cyclopropyl)-carboxamidoadenosine data indicate complexity of the mechanism(s) and point toward an additional involvement of a yet unknown subtype of adenosine A2. No effect of ethanol on blood or brain levels of [3H]R-PIA was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol. There was no escape of i.c.v.-administered [3H]R-PIA from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol-adenosine interaction. 
4	Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease BACKGROUND. The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. METHODS. To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. RESULTS. The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (greater than or equal to 70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45 +/- 0.31 at rest to 0.91 +/- 0.24 during exercise (P less than 0.001) and recovered to 1.27 +/- 0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60 +/- 0.20 at rest and 1.62 +/- 0.18 during exercise (P not significant), as compared with 1.51 +/- 0.19 at rest and 1.02 +/- 0.26 during exercise before revascularization (P less than 0.02). CONCLUSIONS. The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with 31P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment. 
4	Immediate and short-term results of a 1988-1989 coronary angioplasty registry. To determine the relevance of recent refinements in angioplasty technology to our particular practice, the records of 507 consecutive patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) at our center between October 1988 and May 1989 were reviewed. At the time of PTCA, 41% of these patients had class IV angina and 44% were identified as having multivessel disease. Dilatation was attempted in 734 lesions (mean 1.5 per patient), of which 95 (13%) were chronic total occlusions. Overall, 69% of the 734 lesions were judged anatomically complex, and, in dilating these lesions, a rail-type device was used almost exclusively. Successful dilatation was achieved in 659 of the 734 (90%) attempted lesions. There were low incidences of the major complications of death (0.4%), myocardial infarction (1.8%) and emergency bypass surgery (1.8%). Acute rethrombosis occurred in 54 patients (11%). In these patients, initial strategy of repeat dilatation was successful in 38 of 47 patients (81%). Overall, primary clinical success at PTCA was achieved in 480 patients (95%). At a mean follow-up of 7.5 +/- 1.5 months in 497 of the study patients, the event-free rate (freedom from cardiac death, myocardial infarction, repeat PTCA or coronary bypass surgery or recurrence of severe [class III to IV] angina) was 71%. In conclusion, despite the often complex coronary disease in patients currently presenting to our center, a high initial success rate and acceptable short-term outcome of PTCA was achieved. 
5	Mycoplasma pulmonis infections cause long-lasting potentiation of neurogenic inflammation in the respiratory tract of the rat. These experiments were done to learn whether Mycoplasma pulmonis infections of the respiratory tract of rats can potentiate "neurogenic inflammation" and whether this potentiation is amplified by factors that exacerbate the infections. Pathogen-free F344 rats were inoculated intranasally with M. pulmonis or with sterile culture medium and then lived for 4 wk in an ammonia-free atmosphere or in air containing ammonia (100 parts per million). Neurogenic inflammation was evoked by an intravenous injection of capsaicin, and 5 min later the magnitude of the response was quantified by measuring the amount of extravasation of two tracers, Monastral blue pigment and Evans blue dye. We found that vascular permeability in the tracheas of all rats was normal in the absence of capsaicin. However, a 75-micrograms/kg dose of capsaicin, which caused almost no extravasation of Evans blue in the tracheas of pathogen-free controls (17 +/- 3 ng/mg; mean +/- SE), produced extensive extravasation in the infected rats (135 +/- 18 ng/mg; P less than 0.001). Similarly, this dose of capsaicin produced 30 times as much Monastral blue extravasation in the infected rats (area density = 47 +/- 8% of surface area) as it did in the pathogen-free rats (1.6 +/- 0.5%; P less than 0.001), a difference that resulted from increases in the number of Monastral blue-labeled postcapillary venules and in the amount of labeling per venule. Exposure of the infected rats to ammonia exacerbated the infections, further increased the number of Monastral blue-labeled vessels and the amount of labeling per vessel, and made the rats so sensitive to capsaicin that a normally tolerable dose of 150 micrograms/kg i.v. caused fatal apnea. Ammonia did not have these effects in pathogen-free rats. We conclude that M. pulmonis infections of the airway mucosa cause a potent, long-lasting potentiation of neurogenic inflammation, which results in part from an increase in the number and responsiveness of mediator-sensitive postcapillary venules. These changes can be amplified by environmental factors such as ammonia which exacerbate the infections. 
5	Dental patient reaction to electrocardiogram screening. Ninety-one patients receiving routine dental treatment at the University of Minnesota School of Dentistry participated in an electrocardiogram screening study. The purpose of the study was to evaluate patient reaction to electrocardiogram screening in a dental school clinic. The vast majority of patients indicated the test was easy and did not intrude on the dental appointment. Most of the patients reported that the test was a valuable service and should be available in the dental office. None of the patients indicated that the tests should not be performed in the dental office. Few patients expressed any significant concern or anxiety about the test either before or after it was completed. Twenty-six percent (24/91) of the patients were found to have a cardiac arrhythmia; however, most of these were nonserious arrhythmias (18/24) and would not have had an impact on planned dental procedures. Six patients were identified with arrhythmias that required medical referral before dental treatment was started. 
2	Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones. Percutaneous transhepatic catheterization of the gallbladder for dissolution of cholesterol stones by instillation of methyl tert-butyl ether (MTBE) is an invasive therapeutic procedure. The only non-invasive alternative available to now, endoscopic retrograde cannulation of the cystic duct, was difficult because of the cystic duct's tortuosity and spiral valves. We therefore developed a catheter system which, using conventional duodenoscopes during a routine endoscopic retrograde cholangiography (ERC) procedure, permits reliable and safe catheterization of the gallbladder without the need for endoscopic sphincterotomy. In 18 of 22 patients (82%) we were able to place a cysto-nasal catheter, and in 14 patients MTBE dissolution therapy was then performed. Eight patients (57%) were completely free of stones after treatment; the other six (43%) had residual debris. In 4 of 22 patients (18%) cannulation attempts failed, in 3 patients due to cystic duct blockage by a calculus. Endoscopic retrograde cannulation of the gallbladder (ERCG) represents a promising alternative to the invasive percutaneous transhepatic catheterization procedure. 
1	High-grade dysplasia in the columnar-lined esophagus. Abnormal columnar lining of the esophagus is a well-recognized premalignant condition. The management of patients with high-grade dysplasia without evidence of carcinoma remains controversial. Esophagectomy is proposed by some investigators, whereas others favor follow-up endoscopy and biopsy until microinvasive malignancy is documented. We reviewed our experience with nine patients referred with high-grade dysplasia on endoscopic biopsies without evidence of carcinoma. Eight patients had the columnar lining extending orad from the cardia, and one patient had heterotopic columnar epithelium in the cervical esophagus. All were white men ranging in age from 19 to 76 years (median: 47 years). Eight patients underwent esophagectomy with colon interposition. A sleeve resection of the cervical esophagus was done in one patient. Multifocal carcinoma was found in three patients, all of whom had severe dysplastic changes throughout the columnar lining. The patient with heterotopic columnar epithelium had microinvasive carcinoma. All four patients with carcinoma had negative nodes and are long-term survivors. No carcinoma was found in the resected specimens of the remaining five patients. High-grade dysplasia is an important marker of malignancy in patients with a columnar-lined esophagus. Esophagectomy is indicated in suitable candidates since carcinoma was found in 45% of our patients. 
3	Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea. An imbalance in the amplitude of electrical activity of the upper airway and chest wall inspiratory muscles is associated with both collapse and reopening of the upper airway in obstructive sleep apnea (OSA). The purpose of this study was to examine whether timing of the phasic activity of these inspiratory muscles also was associated with changes in upper airway caliber in OSA. We hypothesized that activation of upper airway muscle phasic electrical activity before activation of the chest wall pump muscles would help preserve upper airway patency. In contrast, we anticipated that the reversal of this pattern with delayed activation of upper airway inspiratory muscles would be associated with upper airway narrowing or collapse. Therefore the timing and amplitude of midline transmandibular and costal margin moving time average (MTA) electromyogram (EMG) signals were analyzed from 58 apnea cycles in stage 2 sleep in six OSA patients. In 86% of the postapnea breaths analyzed the upper airway MTA peak activity preceded the chest wall peak activity. In 86% of the obstructed respiratory efforts the upper airway MTA peak activity followed the chest wall peak activity. The onset of phasic electrical activity followed this same pattern. During inspiratory efforts when phasic inspiratory EMG amplitude did not change from preapnea to apnea, the timing changes noted above occurred. Even within breaths the relative timing of the upper airway and chest wall electrical activities was closely associated with changes in the pressure-flow relationship. We conclude that the relative timing of inspiratory activity of the upper airway and chest wall inspiratory muscles fluctuates during sleep in OSA. 
2	Treatment of severe acne with isotretinoin in patients with inflammatory bowel disease. Four patients with inflammatory bowel disease and severe cystic acne were treated with isotretinoin. Two patients had a successful course of treatment without any gastrointestinal side-effects. One patient had two episodes of profuse rectal bleeding that were probably related to pre-existing haemorrhoids. The fourth patient had a flare-up of his Crohn's disease after starting isotretinoin. 
5	Macrophage antigen presentation and interleukin 1 production after cecal ligation and puncture in C3H/HeN and C3H/HeJ mice. Following cecal ligation and puncture with a 25-gauge needle, endotoxin-sensitive C3H/HeN mice have a 45% mortality compared with no mortality in endotoxin-resistant C2H/HeJ mice. Macrophage production of interleukin 1 and antigen presentation were studied in these two strains of mice following cecal ligation and puncture at 2, 4, 8, 16, and 24 hours and at 2, 4, 6, and 8 days. Splenic macrophages were cultured with a T-helper cell clone (D10.G4.1), and antigen presentation and interleukin 1 production were measured by D10.G4.1 proliferation. Macrophage antigen presentation by C2H/HeJ mice was markedly increased compared with that in C3H/HeN mice at all times after cecal ligation and puncture, most strikingly at 2 days (185m740 cpm for C3H/HeJ mice vs 30,300 for C2H/HeN mice). Macrophage interleukin 1 production was significantly increased in C3H/HeJ mice vs C3H/HeN mice at all times after cecal ligation and puncture (except at 2 days) and was maximal at 8 days (25,000 cpm for C3H/HeJ mice vs 5190 for C3H/HeN mice). These data suggest that the differences in mortality after cecal ligation and puncture between these two strains of mice may relate to a supranormal response of macrophages of C3H/HeJ mice or to an inadequate response of macrophages of C3H/HeN mice. 
2	Hemodynamic changes in splenic blood flow during and after distal splenorenal shunt. The purpose of this study was to examine the hemodynamic changes of the spleen and the subsequent influence on the numbers of blood cells both during and 1 month after distal splenorenal shunt (DSRS) with splenopancreatic disconnection in 20 patients with portal hypertension. The intraoperative splenic blood flow, measured with an electromagnetic flowmeter, significantly increased after shunt insertion: the mean percentage increases within the splenic vein and artery were 60% (p less than 0.01) and 37% (p less than 0.05), respectively. The splenic venous blood flow, measured with a pulsed Doppler flowmeter, had not changed significantly 1 month postoperatively (676 +/- 501 to 540 +/- 306 ml/min). The WBC and platelet counts significantly (p less than 0.05 and p less than 0.01, respectively) increased 1 month postoperatively, whereas there was a small, but significant (p less than 0.05), decrease in RBC count. We concluded that splenic blood flow increases immediately after DSRS with splenopancreatic disconnection, but this increase may be only short term. The influence of the postoperative hemodynamic changes on blood cell count is uncertain. 
4	Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension BACKGROUND. To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS. Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS. Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS. In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction. 
5	Management of posterior urethral strictures secondary to pelvic fractures in children. Bulboprostatic anastomotic urethroplasty was performed in 20 children with posterior urethral strictures secondary to bony pelvic fractures. The approach was perineal in 4 children and transpubic abdominoperineal in 16, with good postoperative results in 100 and 62.5%, respectively. In some children the urethral disruption occurred within the prostate itself and not at the prostatomembranous junction. In such cases the proximal sphincteric mechanism may be at risk and immediate repair of the injury is advisable. In the case of common prostatomembranous disruption displacement of the urethra may be significant. In such cases a transpubic approach is preferable. If the proximal sphincteric mechanism is deranged, it can be managed at the same time. 
1	Management of stage A prostate cancer. Transrectal ultrasonography has defined a new category of stage A disease, namely nonpalpable lesions diagnosed by needle biopsy. How this type relates to classic stage A disease is unclear. Stage A1 carcinoma becomes clinically significant only in a distinct minority of patients, and even in this group, progression does not necessarily mean significant morbidity or death from prostate cancer. An aggressive approach is not justified. In contrast, stage A2 cancer is usually virulent, and aggressive therapy with curative intent is justified in patients of appropriate age and health. Both radical prostatectomy and external irradiation appear to provide long-term survival rates superior to those obtained with observation alone, but nearly 20% of these patients will die of cancer despite therapy. Unfortunately, forecasting the outcome in an individual case is still not possible, and efforts to identify prognostic features must continue. In the meantime, emotional arguments in favor of the treatment of all discovered cancers must be suppressed by an informed and objective understanding of the natural history of nonpalpable prostate cancer and the potential impact of treatment. 
1	Low incidence of asymptomatic brain metastases in patients with renal cell carcinoma. Brain metastases from renal cell carcinoma are uncommon. The present study was undertaken to determine the value of routine computerized tomographic (CT) scanning of the brain in patients with renal cell carcinoma. A review of 106 patients with renal cell carcinoma who had undergone CT scan of the brain revealed brain metastases in only 13.2 percent. Brain metastases were accompanied by central nervous system (CNS) symptoms in 78.6 percent of patients, with headaches constituting the most common presenting symptom (64.3%). Brain metastases were detected in only 3.3 percent of patients who had no CNS symptoms at the time of evaluation. It is concluded that CT scanning of the brain should be performed routinely only for those patients who report CNS symptoms at the time of evaluation. 
4	Traumatic and spontaneous extracranial internal carotid artery dissections. Seventy patients with spontaneous and 21 with traumatic extracranial internal carotid artery dissections were studied clinically and angiographically with mean follow-ups of 64 (spontaneous group) and 40 months (traumatic group). Sixty percent of the patients in the spontaneous group and 71% in the traumatic group also had follow-up angiograms. In traumatic dissections aneurysms were common, significantly fewer aneurysms resolved or became smaller and fewer stenoses resolved or improved, whereas more stenoses progressed to occlusion. Traumatic dissections were more likely to leave the patients with neurological deficits. A significantly higher percentage of the patients with spontaneous dissections were asymptomatic at follow-up compared with the traumatic group. Although both spontaneous and traumatic dissections of extracranial internal carotid arteries mostly carry a good prognosis, the outcome may be somewhat less favorable for the traumatic group. 
3	Physician practices in the diagnosis of dementing disorders. Because there are both treatable and untreatable causes of dementia, the physician's ability to conduct (or refer a patient for) a differential diagnosis could have a profound effect on health outcomes for patients and on health care costs. This study was undertaken to assess physician practices with regard to the diagnosis of dementing disorders. Data from 53 physicians (a response rate of 48%) in several specialties were obtained from a self-administered mail questionnaire. Results indicate that the majority of physicians provided history taking, physical examination, and neurological examination. Physicians were more likely to refer patients for psychiatric and neuropsychological examinations than to provide these services themselves. The results also point to deficiencies in two key areas: the use of formal, published diagnostic criteria, and the use of mental status and cognitive function tests. Over 75% of physicians surveyed did not use either DSM-III or NINCDS-ADRDA diagnostic criteria, and 42% of physicians did not provide any mental status tests themselves. The need for continuing education to close knowledge gaps is emphasized. 
4	Clinical interaction of salt and weight change on blood pressure level. Studies that examine the effect of altered body weight or dietary sodium on blood pressure level are reviewed. Emphasis is placed on studies that compare the effects of weight reduction or sodium restriction in separate comparison groups or analyze the independent effect of the two intervention modalities in multiple regression analysis. Additional analyses of the Hypertension Prevention Trial data are presented. Most studies, where comparison can be made, suggest a greater effect for weight reduction than for the achieved, moderate, or short-term reduction in sodium intake on subsequent lowering of blood pressure; the lowering effect on blood pressure of weight reduction is independent of the effect of dietary sodium restriction. However, long-term (over a year) substantial reductions (up to 70 meq/day) of dietary sodium have not been achieved in comparative trials, nor are the effects of combined weight and sodium reduction in the prevention and treatment of hypertension quantified. Future studies and potential problems are discussed. 
5	Alpha 1-acid glycoprotein and the binding of lidocaine in children with congenital heart disease. The purpose of this study was to evaluate the effect of congenital heart disease (CHD) on the serum concentrations of alpha 1-acid glycoprotein (alpha 1-AGP) and the serum binding of lidocaine. Thirteen children with acyanotic CHD and 12 children with cyanotic CHD were studied and compared with 28 children without heart disease (control). The mean (+/- SD) serum concentration of alpha 1-AGP, as determined by radial immunodiffusion, did not differ significantly among the three groups. Five minutes after administration of 1.5 mg.kg-1 intravenous lidocaine, the free fraction of lidocaine correlated inversely and linearly with the serum concentration of alpha 1-AGP in children with acyanotic CHD (r2 = 0.74; P less than 0.001) cyanotic CHD (r2 = 0.57; P less than 0.005), and control (r2 = 0.63; P less than 0.001). The slopes and intercepts of the linear regressions did not differ significantly among the three groups. We conclude that the serum concentration of alpha 1-AGP in children with CHD does not differ quantitatively or qualitatively from that in children without CHD. 
3	Alcohol-dependent unilateral vestibular impairment persisting after a closed head injury. A 20-year-old man suffered a closed head injury followed by symptoms of right-sided labyrinthine concussion with complete clinical recovery within 3 weeks. Episodic vertigo and ataxic gait occurred after the ingestion of small amounts of alcohol over the next 2 years. Electro-oculography revealed a right-sided peripheral type vestibular lesion, only after taking alcohol. This was interpreted as an alcohol-induced impairment of central compensation following an incomplete recovery from right-sided labyrinthine trauma. 
1	Lymphomatoid granulomatosis presenting as ulcerodestructive gastrointestinal tract lesions in patients with human immunodeficiency virus infection. A new association. We describe cases of severe odynophagia, extensive oral ulcerations, and bowel perforation in patients with human immunodeficiency virus infection that were caused by lymphomatoid granulomatosis. Such presentations in human immunodeficiency virus-infected individuals are usually ascribed to other causes and may be incorrectly treated on an empiric basis. In addition, deep tissue specimens obtained at the margin of ulcerative lesions are often necessary for definitive diagnosis. We review our limited treatment experience with zidovudine, interferon alfa, and H2 blockers in our patients. Based on the markedly increased frequency in which lymphomatoid granulomatosis is being diagnosed at our institution in the post-human immunodeficiency virus era, we postulated an association between these two entities. 
2	Noninvasive measurement of portal venous blood flow in patients with cirrhosis: effects of physiological and pharmacological stimuli. The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038 +/- 539 to 1572 +/- 759 ml/min, P less than 0.02); this effect was due to a significant rise in mean blood velocity (from 18.5 +/- 3.7 to 23.9 +/- 3.9 cm/sec, P less than 0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985 +/- 491 to 625 +/- 355 ml/min, P less than 0.05); a significant decline of mean blood velocity (from 18.8 +/- 4.5 to 14.5 +/- 2.5 cm/sec, P less than 0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension. 
1	Window operation: an alternative treatment method for Bartholin gland cysts and abscesses Recently, we developed the "window operation" as a more effective way to treat Bartholin gland cysts and abscesses. The window operation was used to treat 25 Bartholin cysts and 22 Bartholin abscesses during a 3-year period from October 1, 1986 to September 30, 1989. Under local anesthesia, a small piece of skin including the cyst wall was excised in an oval shape, and suturing was performed along the excised margin. Postoperative antibiotics were given in cases of acute inflammation. A new mucocutaneous junction was observed at the 4-week postoperative checkup. No complications or recurrences have been observed during the study period. The window operation can be an alternative method of treatment for Bartholin gland cysts or abscesses. 
5	Intracerebral hematoma complicating split calvarial bone-graft harvesting. A case is reported of an intracerebral hematoma following the harvest of split calvarial bone. Full recovery by the patient occurred. Complications following calvarial bone graft harvest are reviewed. Potential devastating complications warrant serious consideration of alternative sources of bone, especially in the purely elective surgical candidate. 
5	Chronic fetal hypoxia and sudden infant death syndrome: interaction between maternal smoking and low hematocrit during pregnancy. To investigate the hypothesis that chronic fetal hypoxia contributes to the etiology of sudden infant death syndrome (SIDS), a possible interaction between the effect of maternal cigarette smoking and low hematocrit during pregnancy on the risk of SIDS was studied using the US Collaborative Perinatal Project cohort. The 193 SIDS cases identified in the cohort were analyzed with 1930 controls randomly selected from infants who survived the first year of life. After adjustment for maternal age, infants born to mothers who smoked 10 or more cigarettes per day and who were anemic (hematocrit less than 30%) during pregnancy were at a much higher risk of SIDS than infants born to mothers who did not smoke and were not anemic (odds ratio = 4.0; 95% confidence limits, 2.1 and 7.4). Smoking 10 or more cigarettes per day vs none increased the risk of SIDS by 70% among women with hematocrit at or above 30% but increased risk threefold among women with hematocrit below 30%. After adjustment for more potential confounders in a logistic regression model, the effect of smoking on SIDS continued to increase with lower levels of hematocrit during pregnancy. Birth weight accounted for very little of these associations. Low hematocrit was not a risk factor for SIDS among nonsmokers but became an important predictor among heavy smokers. These findings are in agreement with the hypothesis that chronic fetal hypoxia may predispose to SIDS, possibly by impairing the normal development of the fetal central nervous system. 
2	Free radical inhibition and serial chemiluminescence in evolving experimental pancreatitis. Oxygen free radical activity and inhibition were examined in experimental pancreatitis. Twenty-five rats were randomized to five groups: controls received intravenous saline, to simulate pancreatitis one group received intravenous caerulein (5 micrograms kg-1 h-1), and three groups received sodium taurocholate via the pancreatic duct (0.2 ml, 5 per cent), either alone, following allopurinol or immediately before superoxide dismutase. Chemiluminescence (a phenomenon based on the emission of light during chemical reactions and which is dependent on oxygen free radical activity) was used as an index of oxygen free radical activity and was measured in tissue samples at 5-min intervals following induction of pancreatitis. The control mean(s.e.m.) serum amylase level 1 h after induction of pancreatitis was 635(13) units. It was significantly elevated in caerulein-induced pancreatitis, 1833(118) units (P less than 0.05) and exceeded 3000 units in all taurocholate-infused animals. Mean(s.e.m.) chemiluminescence ranged from 44 (8) mV 100 mg-1 at time zero to 404(113) mV 100 mg-1 at 1 h in controls. In caerulein-induced pancreatitis mean(s.e.m.) chemiluminescence peaked at 20 min (1399(239) mV 100 mg-1, P less than 0.02) and in taurocholate-induced pancreatitis at 15 min (2316(95) mV 100 mg-1, P less than 0.004). Superoxide dismutase significantly reduced chemiluminescence and hyperamylasaemia in taurocholate groups. Increasing oxygen free radical activity paralleled evolving pancreatitis. Superoxide dismutase may have a therapeutic role in pancreatitis. 
5	Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot. Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important. 
1	Diffuse hemangiomatosis of the spleen: splenic hemangiomatosis presenting with giant splenomegaly, anemia, and thrombocytopenia. In an elderly patient with oligosymptomatic giant splenomegaly, clinical and laboratory data were nondiagnostic, while nonhomogeneous splenic enlargement was the only finding detected by imaging procedures. Splenectomy was performed and diffuse hemangiomatosis of predominantly capillary-type found. The failure of imaging techniques to even hint at the nature of the underlying disorder is comprehensible in view of the organ being essentially replaced in toto by the abnormal vascular channels. Diffuse splenic hemangiomatosis, a rare condition, may cause hypersplenism, and its diagnosis may be elusive because of misleading patterns on imaging. 
4	Extracorporeal renal artery reconstruction for renovascular hypertension. Extracorporeal reconstruction can be applied to the successful repair of stenoses in the distal renal artery and its hilar branches. This study evaluates the short- and long-term results of extracorporeal renal artery reconstruction in 65 patients, including 5 children, with renovascular hypertension who were treated from 1974 through 1989. The mean age of the patients was 37 years (range, 7 to 67 years). The cause of the stenoses was arteriosclerosis in 8 patients, fibrodysplasia in 54 patients, and miscellaneous in 3. Hypertension was severe before treatment with a mean blood pressure of 187/147 mm Hg that was reduced to a mean of 159/102 mm Hg after medical therapy. Ten patients had renal dysfunction. Results were evaluated both at short-term intervals (mean, 7.9 months; 64 patients) and long-term intervals (mean, 5.9 years; 60 patients), after surgery. Blood pressure responses were classified as beneficial (cured/improved) or failures. Anatomic results were evaluated by angiography in 98% of the patients at the short-term interval and in 77% of the patients at the long-term interval. Extracorporeal renal artery surgery was performed on 78 kidneys among 65 patients (unilateral, 45 patients; bilateral, 13 patients; unilateral extracorporeal and contralateral in situ, 7 patients). In most of the cases autologous arterial graft was used for reconstruction. Early in the series one patient died as a result of the operative procedure (1/65, 1.5%). A beneficial blood pressure response occurred in 53 patients (53/65; 82%) at the short-term interval and in 49 patients (49/61; 80%) at the long-term interval, with the average blood pressure at the short-term interval being 138/85 mm Hg and at the long-term interval being 139/85 mm Hg. Renal function improved in all patients with preoperative renal dysfunction. Graft stenosis or occlusion of the main renal artery was neither observed at the short-term interval nor at the long-term interval. However, residual stenoses were observed in 9 of the 163 reconstructed distal branches (5.5%). Extracorporeal renal artery reconstruction with autologous arterial grafts can be effectively applied to lesions of the distal main renal artery and its hilar branches with durable functional results. 
5	Glucagonoma syndrome is an underdiagnosed clinical entity. Glucagonomas, considered among the rarest of the islet cell neoplasms, produce a well-defined clinical syndrome characterized by necrolytic migratory erythema, diabetes mellitus, glossitis, anemia, and weight loss. This report describes seven patients with glucagonoma treated at our institution. All seven had the characteristic dermatologic manifestations, present from 1 to 6 years prior to diagnosis. Five patients had extensive disease at the time of initial operation, three of whom underwent aggressive cytoreductive surgery, whereas the other two had biopsy only. The remaining two patients presented with a single nodule each, underwent distal pancreatectomy and splenectomy, and remain free of disease 2 and 6 years postoperatively. Earlier recognition of the distinctive physical findings peculiar to this syndrome should increase survival. Aggressive cytoreductive surgery results in prolonged remission. 
5	Serial left ventricular performance evaluated by cardiac catheterization before, immediately after and at 6 months after balloon aortic valvuloplasty. Although impaired ventricular function has been shown to improve after aortic valve replacement, there are few data on hemodynamic changes after balloon aortic valvuloplasty based on follow-up catheterization. Of 71 patients surviving 6 months after balloon aortic valvuloplasty, 41 agreed to late recatheterization. All patients had pre- and postvalvuloplasty and 6 month catheterization data measured with high fidelity micromanometer pressure recordings and simultaneous digital subtraction left ventriculography. The hemodynamic result immediately after valvuloplasty included a reduction in the aortic valve gradient and a moderate increase in aortic valve area (0.51 +/- 0.14 to 0.81 +/- 0.19 cm2, p less than 0.0001). Ejection fraction increased slightly (52 +/- 18 to 55 +/- 17%, p less than 0.0001) despite a decrease in peak positive rate of rise of left ventricular pressure (dP/dt 1,650 +/- 460 to 1,500 +/- 490 mm Hg/s, p less than 0.05). There was also a decrease in left ventricular afterload and a small decrease in preload. At 6 month recatheterization, the mean aortic valve gradient and area were similar to baseline values, with 31 (76%) of 41 patients demonstrating valvular restenosis. At 6 months many left ventricular hemodynamic variables, including peak positive dP/dt and stroke work, also resembled prevalvuloplasty values. However, left ventricular end-diastolic volume was reduced (111 +/- 40 ml at 6 months versus 136 +/- 52 ml before valvuloplasty, p less than 0.01). The mean left ventricular ejection fraction was unchanged from prevalvuloplasty values in the study group of 41 patients, but was significantly improved in 9 of 15 patients with a baseline ejection fraction less than 50%. 
5	Intravenous nicardipine: an effective new agent for the treatment of severe hypertension. Fifty-six patients with severe hypertension were treated with intravenous nicardipine for infusion periods of eight to twenty-four hours. Each patient achieved satisfactory blood pressure control during the infusion period with a mean controlling dose of 7.85 mg/hr. The dose of nicardipine needed for sustained blood pressure control correlated with untreated diastolic blood pressure but not with untreated systolic blood pressure. These results demonstrate the potential usefulness of intravenous nicardipine for the treatment of severe hypertension requiring rapid lowering, and they suggest also that the severity of pretreatment diastolic hypertension might be a useful indicator of the dose required for blood pressure control. 
5	Clinical and biologic effects of granulocyte colony stimulating factor in the treatment of myelokathexis. Successful treatment of a patient with myelokathexis, a rare form of chronic neutropenia associated with recurrent infections, is described. Rapid mobilization of bone marrow neutrophils and improved myeloid morphologic features were observed after treatment with human granulocyte colony stimulating factor. Transient thrombocytopenia and bone pain were observed during treatment. Although neutrophil chemotaxis, superoxide production, and FcRIII surface expression were reduced, the patient improved clinically after restoration of a normal neutrophil count. 
1	Interaction of chloramphenicol and metabolites with colony stimulating factors: possible role in chloramphenicol-induced bone marrow injury. We have recently demonstrated that two chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria, dehydro-CAP (DH-CAP) and nitrophenylaminopropane (NPAP), are much more cytotoxic to bone marrow in vitro than CAP itself. Since colony stimulating factors (CSFs) play an essential role in hematopoietic cell growth, toxicity from CAP metabolites could also involve interaction with CSF or CSF-producing cells. In the present study, we found that increasing concentrations of rhGM-CSF or rhG-CSF completely reversed the inhibitory effect of CAP (2 x 10(-4) M) on human CFU-GM growth and on the growth of KG-1 cells. GM-CSF also reversed the inhibitory effect of CAP on HL-60 cells. Inhibition by DH-CAP (50% at 5 x 10(-7) M), nitroso-CAP (NO-CAP) (60% at 5 x 10(-6) M) and NPAP (35% at 10(-5) M) was not affected by either CSF. In addition to their inhibitory effect on cell growth, DH-CAP (5 x 10(-6) M) and NO-CAP (5 x 10(-6) M) inhibited CSF production by buffy coat cells 50-70% without affecting cell viability. Neither CAP nor NPAP inhibited CSF production. It is suggested that the dual toxic-inhibitory effect of some intestinal metabolites of CAP such as DH-CAP on hematopoietic cell growth on the one hand, and on CSF production on the other, renders them very potent as potential mediators of CAP induced aplastic anemia. 
5	Tympanosclerosis of the middle ear: late results of surgical treatment. The late results of one stage operation for middle ear tymanosclerosis in 73 patients during the period January 1965 to December 1980 are presented. Mean observation time was 11.2 years (range 3-20.2 years), with a follow-up rate 86 per cent. Among 64 patients with stapes fixation, 59 had removal of tympanosclerotic masses and stapes mobilization, and five cases underwent stapedectomy. The series was divided into six groups and the results analyzed. The best and most stable results occurred in the group with stapes mobilization and an intact ossicular chain followed by the group with stapes mobilization and Type II tympanoplasty with incus interposition. The poorest late results were obtained in ears with lacking stapes crura and stapes mobilization, and in ears subjected to stapedectomy. No case of post-operative sensorineural hearing loss occurred. We recommend that care is taken to preserve an intact ossicular chain at stapes mobilization performed at the same stage as myringoplasty. Also in ears with a defective ossicular chain but intact stapes with tympanosclerotic fixation we recommend stapes mobilization in one stage. In ears with fixation of the stapes footplate and defective crura, we recommend stapedectomy or stapedotomy in two stages. 
4	Physicians' perspectives on cholesterol and heart disease. In early spring of 1988, questionnaires were mailed to 4,000 Midwestern physicians to survey their attitudes and practices regarding elevated serum cholesterol and their use of referrals for nutrition counseling; 633 physicians responded. Sixty-eight percent of the physicians thought that reducing high serum cholesterol levels would substantially affect heart disease; however, physicians attributed considerably less preventive value to reducing the cholesterol level than to reducing blood pressure (80.3%) or ceasing smoking (90.0%). The range of serum cholesterol for which diet therapy was most frequently initiated was 5.70 to 6.20 mmol/L. The most frequent range for initiation of drug therapy was 7.80 to 8.25 mmol/L. The physicians reported that although their medical school training did not prepare them adequately for providing diet counseling, they did feel prepared to provide, and were successful in, counseling on diet modifications for reducing serum cholesterol. Few (10%) of the total sample reported having registered dietitians available for dietary counseling, and most (88.8%) believed that it is the physician's responsibility to provide such counseling. Although the low response rate limits the conclusions of the survey, it is likely that those physicians most interested in the topic responded. We conclude that registered dietitians should explore the need for their special services further. More aggressive marketing of dietetic services could benefit both physicians and patients in the campaign to reduce serum cholesterol. 
5	Another way of pumping blood with a rotary but noncentrifugal pump for an artificial heart. This article describes an alternative mode of pumping blood inside the body. The device is a non centrifugal, valveless, low speed rotary pump, electrically powered, based on Wankel engine principle. The authors developed an implantable electrical actuator resulting in a compact, sealed motor-pump unit with electrical and magnetic components insulated from fluids. The results in the flow curve and in the pumping action show some common points but also some basic differences compared to classical pulsatile pumps or centrifugal pumps. The blood coming from the atrium follows a continuous movement without any stop flow but with variations creating pulsatility. Ejection and filling of the pump are simultaneous. It is always an active filling. Hydraulic efficiency depends on clearance in the pumping chamber and outlet port pressure. A 60 cc device allows flows up to 8-9 liters. The implantable motor is cyclindrical in shape, has a moderate weight (490 grams) and presents a good efficiency (32% for a rotary speed of 90 rpm against a mean aortic pressure of 150 mm of Hg). The authors conclude that their device could be proposed after further experimental studies, as an LVAD for shortterm assistance with a good promise for permanent application. 
2	A comparative study of gastrointestinal infections in United States soldiers receiving doxycycline or mefloquine for malaria prophylaxis. A double blind study of daily doxycycline (100 mg) vs. weekly mefloquine (250 mg) was performed on United States soldiers training in Thailand to assess the effect of doxycycline malaria prophylaxis on the incidence of gastrointestinal infections. During a 5 week period, 49% (58/119) of soldiers receiving doxycycline and 48% (64/134) of soldiers receiving mefloquine reported an episode of diarrhea. Infection with bacterial enteric pathogens was identified in 39% (47/119) of soldiers taking doxycycline and 46% (62/134) of soldiers taking mefloquine. Forty-four percent (59/134) of soldiers receiving mefloquine and 36% (43/119) of soldiers receiving doxycycline were infected with enterotoxigenic Escherichia coli (ETEC), while 9% (12/134) of soldiers receiving mefloquine and 4% of soldiers receiving doxycycline were infected with Campylobacter. Side effects from either medication were minimal. After 5 weeks in Thailand, the percent of non-ETEC strains resistant to greater than or equal to 2 antibiotics increased from 65% (77/119) to 86% (95/111) in soldiers on mefloquine and from 79% (84/106) to 93% (88/95) in soldiers on doxycycline. Doxycycline prophylaxis did not prevent or increase diarrheal disease in soldiers deployed to Thailand where ETEC and other bacterial pathogens are often resistant to tetracyclines. 
5	Immunophenotyping in the management of gastric lymphoma. Primary gastric lymphoma is a rare tumor in which surgical resection plays a major role in improving the response rate and reducing the incidence of bleeding and perforation after chemotherapy. In 17 consecutive patients, the diagnosis of gastric lymphoma was made by immunophenotyping snap-frozen endoscopic biopsy specimens. All neoplasms were B-cell lymphomas. Pan B surface marker antigens were present in all patients. Levels of Ki-67, a nuclear marker of tumor proliferation, were greater than 45% in two of the four patients who died after progression of their lymphoma. All patients alive had Ki-67 levels of less than 30%. A lower proliferation index, as measured by Ki-67, appears to be associated with better prognosis. Ten of 11 patients treated by resection prior to chemotherapy had no complications. Immunophenotyping is the key in the differential diagnosis when considering malignant lymphoma with gastric carcinoma and benign conditions such as pseudolymphoma. 
1	Outpatient percutaneous central venous access in cancer patients. A 1-year experience of percutaneous subclavian catheterization in outpatients with cancer was reviewed to document reliability, safety, and cost. There were 763 catheter insertions attempted with prospective documentation of complications in 664 consecutive patients. Catheter insertion was successful in 722 attempts (95%). There were only 13 pneumothoraces (2%). Thirty catheters required repositioning (4%). The average catheter duration was 191 days (range: 0 to 892 days). Fifty-six catheters (8%) were removed because of suspected infection. Documented catheter sepsis occurred in 21 patients (3%); catheter site infection occurred in 8 patients (1%). Thus, only 0.22 infections per catheter year occurred during this 382 catheter-year experience. The estimated cost of catheter insertion was $562, which is one-third the estimated cost for tunneled catheters ($1,403) and for reservoir devices ($1,738). In our experience, percutaneous subclavian catheterization is a reliable, cost-effective method compared with tunneled or reservoir devices, with an equivalent incidence of catheter-related infections. The cornerstone of our success with this program is a staff dedicated to catheter care and intensive patient education. In centers where a large number of patients require central venous access, percutaneous catheterization should be the technique of choice. 
2	Biliary pain in postcholecystectomy patients without biliary obstruction. A prospective radionuclide study. Biliary pain without obvious biliary obstruction is common in postcholecystectomy patients. We studied 20 symptomatic patients with episodes of biliary-type pain after cholecystectomy (all having undergone endoscopic retrograde cholangiography), and in 18 asymptomatic postcholecystectomy controls. We performed quantitative hepatobiliary radionuclide analysis with dimethyl-imidodiacetic acid. From a series of 90 dynamic images at 1-min intervals using a gamma camera coupled to a computer, time-activity curves were produced in regions of interest in the liver, intrahepatic biliary tree, common duct, and heart, from which quantitative biliary excretion indexes were obtained. The results demonstrate a biliary kinetic dysfunction in patients with postcholecystectomy pain without morphological abnormalities. 
5	Isolated congenital stapes ankylosis: surgical results in 32 ears and a review of the literature. Isolated congenital stapes ankylosis is described in 32 operated ears from 28 patients. In 27 ears, a regular stapedectomy was performed. In the remaining 5 ears, 2 had stapes gushers, 2 had bony stapedial tendons, and 1 had an aberrant facial nerve crossing the oval window. The average individual hearing gain was 20 dB. The mean hearing gain for the 24 successful stapedectomies was 29 dB. In 24 of 32 ears (75%), an essential hearing gain of at least 15 dB Fletcher's index hearing threshold could be achieved. A Fletcher's index not exceeding 30 dB could be achieved in 19 of 32 ears (60%), in spite of several cases with a sensorineural component in the hearing loss. A review of the literature and overview of longer series with isolated congenital stapes ankylosis is presented. 
1	Sunlight and dysplastic nevus risk. Results of a clinic-based case-control study. The dysplastic nevus (DN) is the most important risk factor and precursor for malignant melanoma. The authors compared the responses of 132 consecutive cases of DN, 186 consecutive cases of cutaneous melanoma, and 239 controls attending the same subspecialty clinic to questions regarding sun sensitivity, sun exposure, and other possible risk factors. Dysplastic nevus cases were younger than controls and were of a higher social class, as indicated by more years of formal education. Sun sensitivity (assessed by reported depth of tan after multiple exposures) was associated with both DN risk and melanoma risk after controlling for age and education in logistic regression analysis (P = 0.009 and 0.03, respectively), but for DN risk this association was nonlinear: the relative risks (versus deep tan) were 2.3 for average tanners, 2.8 for light tanners, and 1.6 for those who reported practically no tan. Sun exposure measures were not associated with DN risk after controlling for age and education, whether or not depth of tan was controlled in the analysis. These observations suggest a role for either sunlight or a trait linked with sun sensitivity in the development of dysplastic nevi. 
2	Bowel dysfunction in fibromyalgia syndrome. Fibromyalgia and irritable bowel syndrome frequently coexist. In this study, we utilized a previously validated self-administered questionnaire to assess the prevalence of symptoms of bowel dysfunction and irritable bowel syndrome in 123 patients with fibromyalgia as compared to 54 patients with degenerative joint disease (DJD) and 46 normal controls. Ninety (73%) of the fibromyalgia patients reported altered bowel function as compared to 20 (37%) DJD patients and none of the normal controls (P less than 0.001). Ninety-nine patients (81%) reported normal alternating with irregular bowel pattern, and 77 (63%) had alternating diarrhea and constipation. In contrast, only 24 (44%) of DJD patients and six (13%) of controls had regular alternating with irregular bowel pattern and only 12 (22%) of the DJD patients and none of the healthy controls had alternating constipation and diarrhea (P less than 0.01). Other bowel dysfunction complaints noted in the fibromyalgia group were abdominal gas (59%), nausea (21%), diarrhea (9%), and constipation (12%). Seventy-nine (64%) fibromyalgia patients reported frequent abdominal pain that was stress-related 47% of the time. Laxative use was frequent in the fibromyalgia group (19%) and absent in the other two groups. Fifty percent of fibromyalgia patients, compared to 28% of DJD patients, felt that their bowel complaints were worse during exacerbations of their joint disease (P less than 0.05). In conclusion, patients with fibromyalgia have a high prevalence of gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study. 
3	Gunshot wounds to the cervical spine. A retrospective review was performed on 28 patients with low-velocity gunshot wounds to the cervical spine. These composed 31% of all spinal gunshot wounds seen during the study period between 1979 and 1988. Surgical decompression did not seem to improve neurologic recovery in either the incomplete or complete patients. Neurologic recovery also appeared to be unaffected by the presence of retained intracanal bullet fragments. The authors found no advantage to routine neck exploration of this penetrating injury. Complications were seen in 93% of the patients. Most complications were thromboembolic, pulmonary, and urinary tract infections. No cases of instability occurred as a direct result of the gunshot wound. No deaths occurred in this series. Two cases of posttraumatic syrinxes were diagnosed. The authors' current treatment recommendations for these patients include selective wound management and observation of retained intracanal bullet fragments in patients with complete lesions. Surgical decompression after this injury is not recommended. 
1	Rapid, nonradioactive detection of clonal T-cell receptor gene rearrangements in lymphoid neoplasms. Southern blot hybridization analysis of clonal antigen receptor gene rearrangements has proved to be a valuable adjunct to conventional methods for diagnosing lymphoid neoplasia. However, Southern blot analysis suffers from a number of technical disadvantages, including the time necessary to obtain results, the use of radioactivity, and the susceptibility of the method to various artifacts. We have investigated an alternative approach for assessing the clonality of antigen receptor gene rearrangements in lymphoid tissue biopsy specimens. This approach involves the amplification of rearranged gamma T-cell receptor genes by the polymerase chain reaction and analysis of the polymerase chain reaction products by denaturing gradient gel electrophoresis. By use of this approach, clonal rearrangements from neoplastic lymphocytes constituting as little as 0.1-1% of the total cells in the tissue are detected as discrete bands in the denaturing gel after the gel is stained with ethidium bromide and viewed under ultraviolet light. In contrast, polyclonal rearrangements from reactive lymphocytes appear as a diffuse smear along the length of the gel. Our findings suggest that polymerase chain reaction combined with denaturing gradient gel electrophoresis may offer a rapid, nonradioactive, and sensitive alternative to Southern blot analysis for the diagnostic evaluation of lymphoid tissue biopsy specimens. 
1	Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans. PC2 and furin are two recently identified members of a class of mammalian proteins homologous to the yeast precursor processing protease kex2 and the bacterial subtillisins. We have used the polymerase chain reaction to identify and clone a cDNA (PC3) from the mouse AtT20 anterior pituitary cell line that represents an additional member of this growing family of mammalian proteases. PC3 encodes a 753-residue protein that begins with a signal peptide and contains a 292-residue domain closely related to the catalytic modules of PC2, furin, and kex2. Within this region 58%, 65%, and 50% of the amino acids of PC3 are identical to those of the aligned PC2, furin, and kex2 sequences, respectively, and the catalytically important Asp, His, and Ser residues are all conserved. On Northern blots, PC3 hybridizes to two transcripts of 3 and 5 kilobases. Tissue distribution studies indicate that both PC2 and PC3 are expressed in a variety of neuroendocrine tissues, including pancreatic islets and brain, but are not expressed in liver, kidney, skeletal muscle, and spleen. The high degree of similarity of PC3, PC2, and furin suggests that they are all members of a superfamily of mammalian proteases that are involved in the processing of prohormones and/or other protein precursors. In contrast to furin, PC3, like PC2, lacks a hydrophobic transmembrane anchor, but it has a potential C-terminal amphipathic helical segment similar to the putative membrane anchor of carboxypeptidase H. These and other differences suggest that these proteins carry out compartmentalized proteolysis within cells, such as processing within regulated versus constitutive secretory pathways. 
4	Contracturing granulomatous myositis: a separate entity. Granulomatous muscle disease is most commonly seen in sarcoidosis, but may be seen in association with a wide variety of other disorders or in isolation. Patients with granulomatous myositis usually present with slowly progressive muscle pain and weakness affecting mainly proximal muscles. There are, however, a few reports of granulomatous muscle disease presenting with flexion contractures of the limbs. Two further patients with granulomatous muscle disease and flexion contractures of the limbs, but with no evidence of systemic granulomatous disease, is presented. It is suggested that such patients represent a separate clinical entity that is distinct from idiopathic granulomatous myositis presenting with muscle pain and weakness. The association of contracturing granulomatous myositis with a long-standing vasculitis in one patient suggests that the two conditions may be related. 
5	Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. Endothelium-derived relaxing factor, now identified as nitric oxide (NO), is a labile humoral agent formed by vascular endothelial cells from L-arginine. NO mediates the action of substances that induce endothelium-dependent relaxation and plays a role in regulating blood pressure. In this study we investigated whether NO is involved in the pathogenesis of the bleeding tendency associated with renal failure. Rats with extensive surgical ablation of renal mass develop renal insufficiency due to progressive glomerulosclerosis. Like uremic humans, rats with renal mass reduction and uremia have a bleeding tendency that manifests itself by a prolonged bleeding time. We found that N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation from L-arginine, completely normalized bleeding time when given to uremic rats. L-NMMA injection also increased ex vivo platelet adhesion but did not affect ex vivo platelet aggregation induced by adenosine diphosphate, arachidonic acid, and calcium ionophore A23187. The shortening effect of L-NMMA on bleeding time was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. It thus appears that NO is a mediator of the bleeding tendency of uremia. 
2	Modulation of fluid absorption and the secretory response of rat jejunum to cholera toxin by dietary fat. To study the effects of dietary fat on jejunal water and ion absorption and on cholera toxin-induced secretion, 3 week old Sprague Dawley rats were fed isocaloric diets. Forty per cent of the total calories were given as fat, as butter (high saturated fat), olive oil (high monounsaturated fat), or corn oil (high polyunsaturated fat), with one group on low fat (10% of calories) standard laboratory diet as controls. During in vivo jejunal perfusion studies we found that (i) a polyunsaturated fat (corn oil) supplemented diet improves jejunal absorption of water and electrolytes and these changes are independent of the observed concentrations of luminal prostaglandins; (ii) high dietary fat appreciably reduced the secretory response to cholera toxin, probably without fundamentally changing the mechanism by which cholera toxin induces secretion. We conclude that dietary fat composition altered the permeability and transport characteristics of the small intestine. This observation might have relevance to some human diarrhoeal disorders. 
5	Growth abnormalities in children with juvenile rheumatoid arthritis. Growth abnormalities in juvenile rheumatoid arthritis can be divided into two groups: local and systemic. Local disorders of growth often result in increased bone length and bone age or in marked decreases in longitudinal growth due to immobilization, premature epiphyseal closure, or fusion. Common growth defects seen in the knee, hand, wrist, hip, spine, and jaw are discussed. Systemic growth delay is most commonly secondary to active disease or treatment with corticosteroids. Nutritional aspects such as decreased appetite, reduced caloric intake, metabolic caloric requirements greater than available intake, or lack of essential vitamins could be the cause for decreased weight and stature. 
1	Regulation of the truncation of luteinizing hormone receptors at the plasma membrane is different in rat and mouse Leydig cells. Regulation of the truncation of LH receptors was investigated in two types of mouse tumor Leydig cells (MA10 and MLTC-1), rat testis Leydig cells (RTL), and a rat tumor Leydig cell (R2C). Receptor numbers were measured by binding [125I]hCG to the cells cultured in monolayers. Addition of 3.3 nM LH for 2 h at 34 C had no detectable effect on binding sites in RTL or R2C cells, but in MA10 and MLTC-1 cells it caused a loss in binding sites. The effect on MA10 and MLTC-1 cells could be mimicked by inhibiting receptor internalization with 5 mM NaN3 and prevented by the addition of protease inhibitors. Incubating RTL and R2C cells with protease inhibitors caused a 2- to 3-fold increase in binding sites and a 2- to 3-fold increase in LH (0.033 and 0.33 nM)-stimulated cAMP production. When RTL and MA10 cells were incubated in the presence of [125I]hCG, a radioactive protein complex with an approximate mol wt of 80,000-90,000 was released into the incubation medium. We conclude that LH receptors are regulated by proteolysis at the plasma membrane in both mouse and rat Leydig cells. Furthermore, truncation of the LH receptor in the mouse Leydig cells is involved in down-regulation, whereas in the rat it is a continuous process. 
3	Neurobehavioral effects of phenytoin, carbamazepine, and valproic acid: implications for use in traumatic brain injury. Due to the risk of posttraumatic epilepsy, phenytoin, carbamazepine, and valproic acid are often prescribed for patients with traumatic brain injury (TBI). In this review the literature is examined for evidence of neurobehavioral impairment due to carbamazepine, phenytoin, and valproic acid. No comparative studies have been performed in the TBI population, making if difficult to determine if one of these medications is preferable. Direct inference from studies on epilepsy patients to TBI patients is hazardous due to underlying differences in the two populations. Reported findings for epilepsy patients are subtle and not consistent across studies. All three drugs appear to exert some effect on cognitive and motor functions in epileptic patients, and these impairments worsen at increasing serum levels. The varied length of experience with each drug makes it difficult to assign relative weight to the evidence for or against each. A comparative assessment of cognitive and behavioral effects of anticonvulsants should be done in the TBI population. 
1	Achievement of life goals by adult survivors of modern treatment for childhood cancer. To assess the impact of the diagnosis and modern treatment of childhood cancer on achievement of adult goals, the authors evaluated employment, health and life insurance coverage, marriage, divorce, and reproduction in 227 former pediatric cancer patients. Each area was evaluated in relation to a common set of disease and demographic factors that included age at follow-up, age at diagnosis, gender, marital status, history of disease recurrence, and diagnosis. Patients were younger than 20 years of age at diagnosis, and their diagnoses were made between January 1, 1960, and December 31, 1984. The median age at diagnosis was 11.4 years, and the median age at follow-up was 26.6 years. The percentage of unemployed male respondents did not differ from population norms. The percentage of unemployed female respondents, however, was slightly higher than that of the United States population. Approximately 11% of the survivors reported some form of employment-related discrimination, a level significantly lower than that of prior reports. Company-offered health insurance was provided to 92.4% of full-time and 90.0% of part-time employed respondents. Life insurance was purchased by 60% of full-time employed men and 55% of women. These percentages were lower than those reported for the United States population. Twenty-four percent of those with life insurance had difficulty obtaining it. Fifty-eight percent of the subjects were married or lived as married. The percentages of married men and women were significantly lower than United States norms. Twenty percent of those who were married or lived as married have divorced or separated or no longer live as married. Women aged 20 to 24 years were less likely to marry, and women aged 35 to 44 years had a significantly higher frequency of divorce than similarly aged United States women. In general, the history of childhood cancer did not influence the decision to marry or live as married but was occasionally (20%) important in the decision to dissolve a marital relationship. Many former patients indicated that their diagnosis and treatment for childhood cancer influenced their decision to have children. The current study suggests that most former pediatric cancer patients achieve adult life goals. Additional research is necessary to define those populations at greatest risk of failure to achieve these goals. 
5	Leishmania (Viannia) braziliensis: comparative pathology of golden hamsters infected with isolates from cutaneous and mucosal lesions of patients residing in Tres Bracos, Bahia, Brazil. The histopathology of primary forepaw and metastatic lymph node, spleen, and liver lesions produced in golden hamsters infected with cutaneous leishmaniasis (CL) strains (LTB 111 and LTB558) and mucocutaneous leishmaniasis (MCL) strains (LTB12 and LTB201) of Leishmania (Viannia) braziliensis isolated from patients residing in Tres Bracos, Bahia, Brazil is described. No pathological features providing clear differentiation of the CL and MCL strains were found. Although amastigotes were plentiful early in the development of primary forepaw lesions, they were either absent or could not be identified with certainty in sections of late stage lesions. Similarly, amastigotes were not found in histologic lesions at metastatic sites; however, leishmanial DNA was detected in both early and late stage forepaw lesions and metastatic lesions using Leishmania kinetoplast DNA and the gene coding for gp63 as hybridization probes. The DNA recovered from metastatic lesions was extracted from formalin-fixed paraffin-embedded tissues that had been stored at room temperature for prolonged periods. 
5	Dissection of the aorta and dissecting aortic aneurysms. Improving early and long-term surgical results. We report the improving surgical results in a consecutive series of 690 patients referred to one of us (E.S.C.) for aortic dissection between December 1956 and September 1989, a substantial portion of whom had dissection as a complication of either previous aortic (n = 113, 16) or previous cardiac (n = 54, 8%) operation. Our initial operation of choice in patients requiring multiple operations in this group of 690 patients was based on the most life-threatening or symptomatic aortic segment involved, which was ascending aorta and/or aortic arch (Asc/Arch) in 301 (44%) patients, descending thoracic aorta (Desc) in 195 (28%) patients, and thoracoabdominal aorta (TaA) in 194 (28%) patients. As detailed below, considerable improvement occurred in the 30-day survival rates over time, particularly for acute dissection: [table; see text] The independent determinants of both early and long-term mortality were identified. Independent determinants of late fatal rupture, reoperation, and neuromuscular dysfunction for distal dissectors were also identified. In our experience, continued aggressive surgical intervention for aortic dissection with modern operative techniques has resulted in markedly improved 30-day operative survival (approaching 95% including those patients with acute dissection) and significant improvement in late results. 
5	Repair of pelvic fracture posterior urethral defects using an elaborated perineal approach: experience with 74 cases. A total of 74 patients with posterior urethral distraction defects (1.5 to 7 cm. long) that followed pelvic fracture was managed by a 1-stage perineal repair. End-to-end anastomosis was performed in all cases but in 66 a variety of surgical maneuvers were necessary to accomplish a tension-free anastomosis. These techniques, which included distal urethral mobilization, corporeal body separation, inferior pubectomy and supracrural urethral rerouting, were resorted to in a sequential manner as needed. Excellent results were achieved in 96% of the cases. These surgical techniques are described and discussed. 
5	Coagulation-fibrinolysis abnormalities in acute and chronic phases of cerebral thrombosis and embolism. We assayed plasma concentrations of fibrinogen, fibrinopeptide A, plasmin-alpha 2 plasmin inhibitor complex, D dimer, and antithrombin III activity in 40 patients with cerebral thrombosis and nine patients with cerebral embolism during the acute (less than 7 days), subacute (7-27 days), and chronic (greater than or equal to 28 days) periods and compared these with 69 controls. In cerebral thrombosis, fibrinogen and fibrinopeptide A levels were elevated significantly in all stages (p less than 0.001), whereas plasmin-alpha 2 plasmin inhibitor complex and D dimer levels were elevated significantly in the subacute and chronic periods. The antithrombin III activity was significantly decreased in the acute stage. The elevation of fibrinogen and plasmin-alpha 2 plasmin inhibitor complex levels in the acute stage was significantly greater in patients with an infarct size greater than 10 mm2 compared to patients with an infarct size less than 10 mm2. We observed similar changes in patients with cerebral embolism. These results suggest that enhanced coagulation exists at all stages and endogenous fibrinolysis is activated in the subacute and chronic periods in a large proportion of patients with cerebral thrombosis and embolism. 
1	Concentration of tumor-associated trypsin inhibitor (TATI) in pleural effusions. We measured the concentration of tumor-associated trypsin inhibitor (TATI) in plasma and pleural fluid of 84 patients with pleural effusions of various causes. We observed elevated (greater than 30 micrograms/L) TATI levels in pleural fluid in 45 percent of patients with pleural effusion associated with malignant disease and in 15 percent of patients with benign disease. Similar results were obtained for TATI in plasma. The concentration of TATI in pleural fluid closely parallelled that in plasma. In patients with renal insufficiency and in patients with biliary obstruction, the TATI levels were elevated both in plasma and pleural fluid. A positive correlation was seen between the concentration of TATI and the activity of alkaline phosphatase in plasma. The results show that simultaneous determination of TATI in plasma and pleural fluid improves the diagnosis of cancer only marginally. Our results also support the hypothesis that elevated TATI levels may reflect an acute phase reaction caused by inflammatory disease or tissue destruction associated with cancer not only in inflammatory conditions, but also in malignant disease where the tumor itself is not producing TATI. 
5	DNA analysis of neoplasia: an introduction for the family physician. Pathologic evaluation of a neoplastic process has traditionally consisted of microscopic examination of a stained section of tissue. Although this method is generally reliable when performed by an experienced pathologist, the morphologic features of a lesion may not consistently predict biologic behavior. The DNA content of tumors can be studied with a flow cytometer to help determine the prognosis and risk of tumor recurrence. DNA analysis of a neoplasm may provide the clinician with important prognostic information and, at some future date, may help direct chemotherapy or other treatment protocols. 
5	Operative choledochoscopy: common bile duct exploration is incomplete without it. This paper reviews the reported experience of operative choledochoscopy. Development of choledochoscopes to the currently available rigid and flexible instruments is described. The collected results of both rigid and flexible choledochoscopy are reported. Retained stones occurred in 97 of 2712 stone-positive explorations with the rigid choledochoscope (3.6 per cent) and in 35 of 1726 stone-positive explorations with the flexible choledochoscope (2.0 per cent). Choledochoscopy should now be a mandatory part of common bile duct exploration. 
5	Recent trends in cesarean section use in California. Cesarean section use in the United States has increased to 24.7% of deliveries in 1988 and is the most common hospital surgical procedure. California cesarean section rates were examined to measure recent trends in obstetric practices and to project future patterns of cesarean section use. Using discharge abstracts from 1983 to 1987 California hospital deliveries, total cesarean section rates were found to increase from nearly 22% in 1983 to 25% in 1987, an increase of 15%. Using a series of least-squares regression models, time trends in the distribution of indications associated with cesarean section among all deliveries and indication-specific cesarean section rates were evaluated. Increases in the number of women with previous cesarean section and fetal distress contributed to rising cesarean section rates. In addition, indication-specific cesarean section rates increased for breech presentation and dystocia. These trends were counterbalanced, in part, by declining rates of repeat cesarean sections. Trends noted for July 1985 through 1987 did not differ substantially from those observed for January 1983 to June 1985, suggesting that recent policy attempts to alter cesarean section use have not had a measurable effect on existing trends. Projections suggest that California cesarean section rates will rise to a level of 34% by the year 2000. 
5	Eosinophilic ascites due to hyperinfection with Strongyloides stercoralis. We report the case of a patient with cryptogenic cirrhosis, new onset ascites, and hyperinfection with Strongyloides stercoralis who had significant eosinophilia of the peritoneal fluid. The eosinophilia resolved with treatment of the S. stercoralis infection, and did not recur during two subsequent episodes of ascites and spontaneous bacterial peritonitis. Eosinophilic ascites is rare in parasitic infection, but it has been described in a variety of disorders which are discussed. 
5	Increased survival of ARDS patients with severe hypoxemia (ECMO criteria). The adult respiratory distress syndrome (ARDS) is a form of diffuse lung injury associated with multiple risk factors. Patients with severe hypoxemia who meet blood gas criteria defined by the extracorporeal membrane oxygenation trial (ECMO) of 1974 to 1977 have a reported survival of 11 percent. The reported survival has remained unchanged for 15 years despite numerous technologic advances. We prospectively studied ARDS patients who met ECMO blood gas criteria. One hundred seventy-eight ARDS patients were prospectively screened over a 30-month period. Fifty-one of these patients met ECMO blood gas criteria and 23 (45 percent) survived (p less than 0.001 vs ECMO trial). No obvious differences in etiology, APACHE II score, organ system failure, or the incidence of sepsis was found between survivors and nonsurvivors. We conclude that survival of ARDS patients who met ECMO blood gas criteria in our institution is higher than that previously reported from both other centers and our own hospital. 
3	Organ procurement in patients with fatal head injuries. The fate of the potential donor. A 46-month, retrospective review of all victims of fatal head injury at a level 1 trauma center was undertaken to estimate donor organ availability, determine causes of procurement failure, and analyze the functional results of organs transplanted from this group of donors. Causes of procurement failure in 126 patients who died principally from their head injuries included failure of initial resuscitation (14%), ineligibility (28%), failure of physiologic support (14%), and denial of consent (20%). Of 73 eligible donors, 29 (41%) were able to donate one or more vascular organs (heart, liver, kidney). In only one instance was an eligible donor not appropriately identified as such. Failure of physiologic support to prevent early death (25%), and denial of consent (34%) were found to be the two major, potentially remediable causes of procurement failure in this series. Based on this data, an estimated 29 patients/million population/year will survive initially and meet all eligibility requirements for organ donation. Data on 47 kidneys transplanted from the donor group demonstrated a 77% overall graft survival rate at a follow-up period averaging 23 months. Prolonged donor hypotension, but not the use of high-dose vasopressors, adversely affected allograft survival. The current limitations of organ procurement in victims of fatal head injury stem from a limited ability to maintain cardiopulmonary function long enough for the procurement process to be completed and a high overall rate (46%) of denial of consent for organ harvest by next of kin. 
5	Study of the influence of left bundle branch block on the signal-averaged electrocardiogram: a qualitative and quantitative analysis. To study the influence of left bundle branch block (LBBB) on the signal-averaged electrocardiogram (SAECG), quantitative and qualitative analyses of SAECG parameters were undertaken in 48 patients with electrocardiographic evidence of intrinsic LBBB and in 39 patients with a "normal" surface QRS duration (less than 120 msec) who underwent right ventricular pacing-induced LBBB. We assumed pacing of the right ventricular apex to be a suitable model of this conduction defect. Sustained monomorphic ventricular tachycardia (SMVT) was inducible in 16 of 48 patients with intrinsic LBBB and in 23 of 39 patients with pacing-induced LBBB. Utilizing a filter setting of 25 to 250 Hz, late potentials were defined as a total filtered QRS duration greater than or equal to 120 msec, a root mean square voltage in the terminal 40 msec (RMS 40) of less than or equal to 25 microV, and the duration of signals less than 40 microV (LAS 40) of greater than or equal to 38 msec. Only RMS 40 and LAS 40 criteria were used in patients with LBBB. Prolongation of LAS 40 and fragmentation of signals in the terminal portion of the filtered QRS were characteristic of all patients with LBBB aberration. Of those patients with intrinsic LBBB, the mean total filtered QRS duration, RMS 40, and LAS 40 for inducible and noninducible patients were significantly different (170 +/- 28, 16 +/- 10, 55 +/- 24, and 153 +/- 18 msec, 25 +/- 10 microV, 33 +/- 16.9 msec; p = 0.04, 0.009, and 0.007, respectively). Noninducible patients with a normal QRS duration demonstrated a 60% decrement in the mean RMS 40 value during pacing-induced LBBB. These changes resulted in a 59% false positive incidence of late potentials during pacing-induced LBBB. This correlated with a similarly low mean RMS 40 value in patients with intrinsic LBBB and no inducible SMVT, hence giving rise to a false positive incidence of late potentials of 63%. Since "standard" RMS 40 and LAS 40 criteria resulted in low specificity and positive predictive value, new parameters were selected and analyzed. The combination of RMS 40 less than or equal to 17 microV plus LAS 40 greater than or equal to 55 msec yielded the best overall statistical result, with a sensitivity, specificity, and total predictive accuracy of 69%, 81%, and 77%, respectively. In conclusion: (1) A reduction of RMS 40, prolongation of LAS 40, and fragmentation of signals in the terminal portion of the filtered QRS are characteristics of LBBB.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Increased Ca2+ signaling after alpha-adrenoceptor activation in vascular hypertrophy. In an effort to explain the increased sensitivity to agonists of hypertrophic vascular muscle, intracellular Ca2+ concentration ([Ca2+]i)-signaling mechanisms were studied in normal and hypertrophic rat aortas from normotensive and coarctation-hypertensive rats. Based on both fura 2 fluorescence and aequorin luminescence measurements, qualitatively different patterns of Ca2+ mobilization occur in normal and hypertrophic rat aortic muscle. Normal rat aortic muscle contracts to phenylephrine with little or no increase in [Ca2+]i, whereas the angiotensin II-induced contraction is accompanied by a marked [Ca2+]i transient. In contrast, hypertrophic rat aortic muscle shows a dramatic increase in Ca2+ signaling after phenylephrine stimulation. Moreover, both the amplitude of the angiotensin-induced [Ca2+]i transient and the contractile sensitivity to this agonist are decreased in the hypertrophic muscle. Our results strongly suggest that the amplitude of the [Ca2+]i transient after agonist stimulation determines the contractile sensitivity and that there is an altered coupling of the alpha-adrenoceptor in the hypertrophic vascular muscle. 
3	Evidence against leukotrienes as mediators of brain edema. Leukotrienes are powerful metabolites of arachidonic acid which are known to increase the permeability of peripheral blood vessels. These substances are found in brain tissue in association with cerebral ischemia, and in brain tumors. Therefore, it has been proposed that leukotrienes have a mediator function in brain edema. This hypothesis was subjected to further experimental analysis in this study, in which the authors investigated whether: 1) superfusion of the exposed brain surface with leukotrienes increases the permeability of extraparenchymal blood vessels in vivo; 2) intraparenchymal infusion of leukotrienes induces brain edema; and 3) pharmacological inhibition of leukotriene formation by BW755C, an inhibitor of leukotriene synthesis, reduces formation of brain edema from a standardized traumatic insult. The pial vessels of the parietal cortex of cats were examined by fluorescence microscopy during cerebral superfusion with the leukotrienes C4 (LTC4), D4 (LTD4), or E4 (LTE4) by using an open cranial window preparation. Intravenous Na(+)-fluorescein served as an in vivo blood-brain barrier (BBB) indicator. Superfusion of the pia with leukotrienes (up to 2 microM) did not open the barrier to fluorescein, but was associated with a significant constriction (up to 25%) of arterial and venous vessels. In experiments with slow infusion of leukotriene B4 (LTB4) or LTC4 into the white matter of feline brain, the tissue water content was subsequently determined in serial brain slices using the specific gravity method. Tissue water profiles obtained after a 15-microM infusion of either LTB4 or LTC4 were virtually identical with those of control animals infused with mock cerebrospinal fluid. Thus, neither LTB4 nor LTC4 led to an augmentation of infusion-induced brain edema. In a final series, a cold lesion of the left parietal cortex was induced in rabbits. Twenty-four hours later, swelling of the exposed hemisphere was quantified by gravimetrical comparison of its weight with that of the contralateral nontraumatized hemisphere. Eight animals received BW755C intravenously prior to and after trauma to inhibit formation of leukotrienes. Seven rabbits were infused with an equivalent volume of saline as a control study. The resulting hemispheric swelling was 7.7% +/- 0.6% (mean +/- standard error of the mean) 24 hours later in animals receiving BW755C and 7.8% +/- 1.2% in the control group, indicating that inhibition of leukotrienes was ineffective in preventing formation of vasogenic brain edema. The findings demonstrate that leukotrienes administered to the brain in concentrations occurring under pathological conditions do not open the BBB nor do they induce brain edema.(ABSTRACT TRUNCATED AT 400 WORDS). 
4	Myocardial magnesium: relation to laboratory and clinical variables in patients undergoing cardiac surgery. Magnesium concentration was measured in the right atrial appendage of 100 patients undergoing cardiac surgery and associations with serum and mononuclear blood cell magnesium, other laboratory values and patient clinical variables were studied. In addition, magnesium was measured in the right atrial appendage and left ventricular free wall in 23 autopsy subjects to determine whether there was a proportional relation between right atrial appendage and left ventricular free wall magnesium. The mean left ventricular free wall/right atrial appendage magnesium ratio was 2.13 +/- 0.39 (r = 0.67, p = 0.0009). In the group with cardiac surgery, the right atrial appendage magnesium concentration correlated inversely with age (r = -0.54, p = 0.001). The mean right atrial appendage magnesium concentration (micrograms/g wet weight tissue) was lower in patients with postoperative cardiac arrhythmia than in those without arrhythmia (103 +/- 13 versus 111 +/- 10, p = 0.009) and in diabetic than in nondiabetic patients (103 +/- 13 versus 109 +/- 12, p = 0.02). The right atrial appendage magnesium concentration also tended to be lower in patients receiving potassium/magnesium-losing diuretics, although this difference did not achieve statistical significance (105 +/- 14 versus 109 +/- 11, p = 0.16). Right atrial appendage magnesium concentration correlated positively with serum creatinine concentration (r = 0.31, p = 0.002) and negatively with serum calcium concentration (r = -0.29, p = 0.013). Serum magnesium did not correlate with right atrial appendage or mononuclear blood cell magnesium concentration or clinical variables. There was a statistically significant correlation between mononuclear blood cell and right atrial appendage magnesium concentrations in some subgroups of patients. 
5	Xeroderma pigmentosum: review and report of a case. Xeroderma pigmentosum is a rare inherited dermatosis that provides insight into the basic mechanism of carcinogenesis. It is a model disorder linking defective DNA repair with clinical abnormalities and neoplasia. UV light-induced damage to the skin begins early and results in multiple benign and malignant skin tumors, especially in sun-exposed areas of the head and neck. Oral cancers, primarily squamous cell carcinomas of the anterior third of the tongue, occur with greatly increased frequency. A patient with multiple facial neoplasia and oral manifestations of xeroderma pigmentosum is presented. The role of the dentist in surveillance of oral and perioral structures is emphasized. The dentist is advised against the use of UV light-curing units in these patients because UV-induced epithelial damage may cause dysplasia when DNA repair mechanisms are dysfunctional. 
1	A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome. Sixteen patients with metastatic neuroendocrine tumors and the malignant carcinoid syndrome were treated with cyproheptadine (Periactin, Merck, Sharp & Dohme, West Point, PA) at maximum tolerable doses that ranged from 12 to 48 mg daily. Usual side effects were mild sedation and dry mouth, but three patients found it impossible to sustain treatment due to nausea and vomiting. Most patients had significant relief of diarrhea, frequently associated with weight gain. Relief of flushing was uncommon. The therapeutic benefit produced by cyproheptadine would appear to be a peripheral effect because 5-hydroxyindoleacetic acid (5-HIAA) excretion in these patients was not reduced. Although there have been case reports of objective tumor regression with cyproheptadine therapy, this was not observed in any of these 16 patients. Cyproheptadine would appear to be a useful therapeutic tool for the management of diarrhea associated with the malignant carcinoid syndrome. An appropriate initial total daily dose is 0.4 mg/kg divided in three fractions with prompt modification to produce minimal and tolerable side effects. 
4	Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients. The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial. 
5	Acute hypervolaemic haemodilution to avoid blood transfusion during major surgery 16 patients underwent acute hypervolaemic haemodilution with dextran 40 and Ringers lactate, to see whether this procedure could avoid preoperative blood transfusion. Packed cell volume (PCV) and oxygen extraction decreased, and cardiac index and pulmonary wedge pressure increased, although end-systolic area was unchanged. PCV was not significantly different between patients who lost less than or greater than 20% of their initial blood volume. This preoperative manoeuvre, which reduces loss of red blood cells, allowed major surgery to be completed safely without blood transfusion. 
5	Long-term results of Ionescu-Shiley valve in the tricuspid position. A retrospective analysis of the long-term results of using the Ionescu-Shiley pericardial bioprosthesis in the tricuspid position was carried out on 73 patients (8 men, 65 women). Of these procedures, ten were tricuspid valve replacement alone and the remainder were in combination with other valve procedures. The mean follow-up was 9.6 years (range, 4 to 18 years). The mean age of the patients was 53 years (range, 27 to 78 years). Seventy-one of the patients suffered tricuspid valve dysfunction from rheumatic heart disease. There were 13 postoperative deaths (within 30 days), giving a mortality rate of 17.8%. The actuarial survival at 10 years was 71% +/- 4.2%. Of the survivors, 49 (79.6%) were in functional class I or II. Primary tissue valve failure in the tricuspid position occurred in 1 patient 12 years after implantation and required reoperation. In another patient bioprosthetic tricuspid valve endocarditis developed. There was no incidence of thromboembolic complications. We conclude that the Ionescu-Shiley pericardial bioprosthesis was a satisfactory prosthesis in the tricuspid position in patients with acquired valvar dysfunction. 
5	Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes. To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range, 91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2; range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group (379 mL/1.73 m2; range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range, 347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged. 
1	Human papillomavirus type 16 associated with oral squamous carcinoma in a cardiac transplant recipient. Human papillomavirus type 16 (HPV 16) has been associated with a variety of squamous carcinomas, particularly those involving the anogenital tract. The authors report the development of an oropharyngeal carcinoma in a 43-year-old man approximately 20 months after cardiac transplantation while he was on a maintenance regimen of cyclosporine A and prednisone. The carcinoma was resistant to treatment, and he died of complications related to metastatic disease 3 years posttransplantation. Molecular biologic studies using nonisotopic-labeled viral DNA probes were done. In situ hybridization demonstrated the presence of HPV 16 DNA in the tumor cells. DNA dot blot analysis confirmed the presence of multiple copies of HPV 16 DNA within the tumor cells and their absence from adjacent normal-appearing tissue. Southern blot analysis suggested that the HPV 16 DNA was integrated into the tumor cell genome. With increasing recognition of the carcinogenicity of HPV type 16 infection, a role for this virus in the development of squamous cell malignancies in immunosuppressed organ transplant recipients is likely to be noted with increasing frequency. 
2	Lipid peroxidation and hepatic antioxidants in alcoholic liver disease. The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation. 
3	Florid refractory schizophrenias that turn out to be treatable variants of HLA-associated narcolepsy. Narcolepsy in which the hallucinatory component is unusually prominent may lead to the development of an illness indistinguishable from the schizophrenic syndrome. Psychotic symptoms dominate the symptomatology, so that the primary illness is obscured. Five patients are described for whom conventional antipsychotic drugs were ineffectual, but for whom treatment with stimulants produced substantial improvement. The diagnosis of narcolepsy was confirmed by Human Leukocyte Antigen typing and sleep laboratory testing. These results support the "REM intrusion" hypothesis of the causation of schizophrenia in as many as 7% of a series of schizophrenic patients. Implications for diagnosis and treatment are discussed. 
4	The leukocyte count: a predictor of hypertension. In an exploratory study of 1031 persons observed to progress from normotension to essential hypertension and 1031 matched subjects who remained normotensive, the initial leukocyte count (WBC) was found to be related to the development of hypertension, with risk increased 40% (95% confidence interval 12-82%) in persons in the highest as compared to the lowest quartile of WBC. This relationship proved to be largely independent of body mass index, body fat distribution, alcohol and tobacco consumption, and parental history of hypertension. An increased WBC may reflect greater sympathetic tone or may directly increase peripheral vascular resistance by impeding circulation through small blood vessels. If confirmed, this study adds another condition to the growing list for which the WBC is predictive. This simple, cheap test should be considered for inclusion in prospective epidemiological studies of many different diseases. 
5	A prospective assessment of the Garren-Edwards Gastric Bubble and bariatric surgery in the treatment of morbid obesity. Morbid obesity is a serious medical hazard, and effective alternatives to surgery have been unsuccessful. In 1985, the Garren-Edwards Gastric Bubble (GEGB) was offered as an adjunct to dietary and behavioral therapy for weight loss treatment. The safety and efficacy of the GEGB were compared with bariatric surgery, the current standard for the treatment of morbid obesity. Fifty-seven patients received GEGB and 77 underwent bariatric surgery. GEGB patients were divided into two groups: those who attended group therapy and those who did not. This study showed that bariatric surgery was far more effective in reducing excess body weight during a 12-month period compared with the GEGB plus group therapy and the GEGB alone. The morbidity from bariatric surgery was greater than in the GEGB-treated groups, while the cost for uncomplicated cases for a year's treatment was comparable. It is concluded that the GEGB does not offer an effective alternative to bariatric surgery in the treatment of morbid obesity. 
2	Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts. Uric acid stone formation ordinarily is prevented by increases in the urinary pH after meals. This postprandial alkaline tide is lost in patients who make such calculi. Single dose, alternate day administration of an alkaline potassium salt will increase urinary pH and simulate this normal physiological mechanism. An important part of the regimen is patient self-monitoring to verify that the urinary pH increases to greater than 6.8, 1 1/2 to 2 hours after the medication is taken. In contrast to multiple dose daily regimens, this mode of base administration is tolerated better and easier to follow. In 17 patients, 7 with the recurrent gravel/colic syndrome and 10 with prior stones, this regimen abolished calculus formation during an average followup of 2 1/2 years. However, further studies are needed before this regimen can be recommended as standard therapy for uric acid stone prophylaxis. 
4	Peripheral arterial occlusive disease of the extremities in the United States: hospitalization and mortality. PAODE is an important cause of morbidity and health care expenditures among the elderly. Data from the NHDS and National Vital Statistics System were used to assess its impact in the U.S. In 1985 to 1987, an estimated 229 thousand men and 184 thousand women per year were discharged with any diagnosis of chronic PAODE. Discharge rates were much higher in men and increased sharply with age. Lower extremity arteriography was performed during 88 thousand hospitalizations and aorta-iliac-femoral bypass procedures were done during 31 thousand hospitalizations per year. Numbers of procedures increased markedly since 1979. An estimated 60 thousand men and 50 thousand women per year were discharged with any diagnosis of acute PAODE. Embolectomy or thrombectomy of lower limb arteries was listed for 28 thousand discharges per year. Few deaths were attributed to PAODE. Although these data are limited by likely incomplete reporting and by the nonspecificity of diagnostic codes, they provide an indication of the magnitude of the problem. An aging population and advances in surgical techniques suggest continued monitoring using multiple data sources. Vigorous primary prevention programs are needed to lessen the impact of all atherosclerotic diseases. 
5	Surgical treatment of laryngeal web with mucosa graft. Surgical treatment of laryngeal webbing varies with the extent and site of the web. An extensive one seems to be best treated by laryngofissure and skin or mucosa transplantation. Recent experiences with four cases of thick glottal webbing indicated that a mucosa graft was better for the voice result than a skin graft. For success in the airway and voice results, the salient points in surgery include 1) precise midline thyrotomy, 2) shaping of the vocal cord under fiberoptic control, and 3) mucosa grafting with the combined use of a pliable stent or fibrin glue for fixation. 
5	Esophageal verrucous carcinoma: histologically a low-grade malignancy but clinically a fatal disease. A 76-year-old woman had a verrucous carcinoma of the esophagus with a fistula of the left main bronchus. We discuss this case together with those of eleven other patients with verrucous carcinoma of the esophagus reported previously. Differentiation between this tumor and squamous cell papilloma is often difficult. The central cores of fibrous tissue in verrucous carcinoma are heavily infiltrated with inflammatory cells, which accounts for the stenosis often found. The mortality in verrucous carcinoma of the esophagus is 67% even though histologically it is a low-grade malignancy. 
1	The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages. The human immunodeficiency virus (HIV) genetic determinant(s) responsible for tropism in human T cells or macrophages are not well defined. We studied the role of the HIV type 2 (HIV-2) nef and vpr genes in viral tropism. HIV-2 mutants, lacking either vpr or nef genes, or both vpr and nef, were obtained by site-specific mutagenesis of a biologically active HIV-2 proviral clone (HIV-2sbl/isy), which is infectious in both human T cells and macrophages. Viral progeny carrying mutations of nef, vpr, or of both nef and vpr genes replicated more efficiently than the parental virus in primary human peripheral blood cells and in the human Hut 78 T-cell line. In contrast, the HIV-2 nef- mutant infected human macrophages as efficiently as the parental virus, whereas viruses lacking the vpr gene either alone or in conjunction with the lack of the nef gene did not replicate in macrophages. Thus, some lack of nef in HIV-2 enhances viral replication in T cells and does not interfere with viral replication in primary macrophages, whereas vpr is essential for replication of HIV-2 in human macrophages. Because the parental HIV-2sbl/isy cloned virus also infects rhesus macaques, the use in animal studies of these HIV-2 mutants with differences in cell tropism and rates of replication will be highly useful in understanding the mechanism of viral infectivity and possibly pathogenicity in vivo. 
5	Thromboembolytic complications during circulatory assistance with a centrifugal pump in patients with valvular prostheses. This article describes two patients with artificial heart valves who suffered thromboembolytic complications during circulatory assistance using a Biomedicus centrifugal pump. The first case involved a 25-year-old man who presented acute blockage of a mechanical aortic valve. Emergency surgery was performed to replace this valve with a bioprosthesis. Postoperatively the patient developed severe left heart insufficiency and a Biomedicus centrifugal pump was placed between the left atrium and the ascending aorta. After 3 days of total left ventricular assistance, weaning was started and successfully completed with explanation on the 5th day. Two days later the patient died of multiple coronary embolism with thrombosis of the valve. The second case involved a 30-year-old man. Six months before, he underwent surgical procedure with placement of Bio-prosthesis for dissecting aortic aneurysm due to annuloectasia. Upon admission for terminal dilated myocardiopathy, the patient was in kidney failure almost requiring dialysis. Because of this patient's size (Marfan syndrome), no donor heart was immediately available and left circulatory assistance with a Biomedicus pump had to be initiated. The patient lived without mechanical ventilation, in good clinical condition until day 23 when he presented acute right heart failure due to extensive valvular and coronary thrombosis. From these two cases, several important comments can be made about anticoagulation therapy, partial unloading of left ventricle, or need for biventricular assistance, and efficiency of centrifugal devices in these clinical applications. 
4	Genetic traits related to hypertension and electrolyte metabolism. The genetic and cultural heritability and intercorrelation of traits related to hypertension have been carried out in 98 Utah pedigrees (2,500 person) and 58 sibships with two or more hypertensive persons (131 hypertensive persons). Although none of these traits has been established as a marker for "sodium-sensitive hypertension," many of them are related at least indirectly to both electrolyte metabolism and risk of hypertension. Significant recessive monogenic effects and high total heritability (52-84%) were found for urinary kallikrein, high fat pattern index, intraerythrocytic sodium, Na-Li countertransport, and ouabain binding sites. Familial correlations more strongly attributable to shared environment than to genetic effects were found for Na,K-ATPase pump activity, intraerythrocytic magnesium, plasma digoxin-like factor, plasma renin activity, and plasma sodium concentration. All anthropometric variables tested showed highly significant genetic heritability with low and insignificant shared family environmental effects. Several of the genetically determined cellular cation tests also correlated with other genetic traits including plasma lipids, anthropometric measurements, and other cellular cation tests. Among hypertensive individuals with familial dyslipidemic hypertension, plasma insulin levels correlated with obesity and lipid abnormalities and with several cellular cation flux tests associated with hypertension. 
5	Pruritic papular eruption of the acquired immunodeficiency syndrome: a clinicopathologic study. The pruritic papular eruption of the acquired immunodeficiency syndrome is characterized by generalized, pruritic, skin-colored papules and nodules. Chronic lesions are excoriated and hyperpigmented. The eruption and pruritus typically wax and wane and are resistant to oral antihistamine and topical steroid therapy. The characteristic histologic features are (1) superficial and mid dermal perivascular and perifollicular mononuclear cell infiltrate with numerous eosinophils and (2) follicular damage of varying degrees. When compared with control subjects, these patients did not demonstrate any significant difference in laboratory or demographic data. 
2	Microvillus inclusion disease. In vitro jejunal electrolyte transport. Microvillus inclusion disease is an inherited intestinal brush border membrane defect that causes severe fluid and electrolyte malabsorption. In an infant with microvillus inclusion disease (confirmed by electron microscopic evaluation of rectal, jejunal, and gallbladder mucosae), basal stool output was massive (greater than 125 mL . kg-1 . day-1) and was not altered by treatment with clonidine or octreotide. A proximal jejunostomy with mucous fistula was placed, allowing separation of proximal from distal tract outputs (60 mL . kg-1 . day-1 and 100 mL . kg-1 . day-1, respectively). A 10-cm jejunal segment was excised during surgery and mounted in Ussing chambers for determination of transepithelial Na+ and Cl fluxes. Compared with intestine of normal infants, this infant's epithelium showed transmural conductance and unidirectional ion fluxes that were only 30% of normal. With respect to both Na+ and Cl, the excised jejunum was in a net secretory state. Theophylline (5 mmol/L) increased net Cl secretion slightly. In response to mucosal D-glucose (30 mmol/L), jejunal mucosal-to-serosal Na+ flux doubled. In the infant, glucose-electrolyte solution administered intrajejunally did not significantly change stool output, suggesting that all of the solution (40 mL/kg) was absorbed. Subtotal enterocolectomy, in theory, could have decreased purging by 66% in this infant with microvillus inclusion disease, but diarrhea would still have been significant. 
4	Complete left main coronary artery occlusion: angiographic evaluation of collateral vessel patterns and assessment of hemodynamic correlates. An angiographic study of eight patients with total occlusion of the left main coronary artery identified six patients with chronic occlusion and two with acute complete occlusion. In each of six patients, there were two to six different intercoronary collateral pathways. Altogether, a total of 13 specific collateral channels were recognized. One patient had evidence of unique homocollaterals represented by enlarged vasa vasorum, which created a vascular cuff that surrounded a totally obstructed left main artery. The ventricular function and hemodynamic parameters in these patients not only depend on the collateral vessels but may also be affected by the severity of coronary artery disease in the artery that supplies collaterals. 
2	Defects in the precore region of the HBV genome in patients with chronic hepatitis B after sustained seroconversion from HBeAg to anti-HBe induced spontaneously or with interferon therapy. Hepatitis B virus DNA clones were propagated from sera of six patients with chronic hepatitis B who seroconverted from HBeAg to antibody to HBeAg either spontaneously or after administration of alpha-interferon. Defects in the precore region blocking synthesis and secretion of HBeAg were detected in all 46 hepatitis B virus DNA clones from three patients who remained positive for antibody to HBeAg and in whom hepatitis resolved. Defective clones had point mutations from guanine to adenine at nucleotide 83 in the precore region, converting codon 28 from tryptophan (TGG) to a stop codon (TAG). In contrast, this defect was not found in any of 39 hepatitis B virus DNA clones from three patients who seroconverted to antibody to HBeAg but then redeveloped HBeAg with reactivation of hepatitis. Using these results, the G-to-A point mutation at nucleotide 83 in the precore region would predict sustained positivity for antibody to HBeAg and remission of hepatitis in patients who have seroconverted either spontaneously or with interferon therapy. 
3	Age at onset of Alzheimer's disease. Relation to language dysfunction. A later age at onset of Alzheimer's disease (AD) was found to be related to diminished language performance in 86 patients with probable AD. A hierarchical linear model was constructed to assess effects of age at onset and disease duration on the performance of patients with AD on four language tasks (naming, reading, auditory comprehension, and writing to dictation) after controlling for disease severity. Results of univariate analysis, in which the dependent variable was the averaged language task performances, revealed a significant effect for age at onset of AD, but not for disease duration. To assess the possibility that the relationship between the age at onset of AD and language performance reflects effects of normal aging, the language tasks were given to 33 normal subjects of similar ages who scored perfectly on dementia severity measures. A convincing relationship was not found between test score and age. 
3	Geographic patterns of parkinsonism-dementia complex on Guam. 1956 through 1985. Average annual age-adjusted incidence rates of parkinsonism-dementia complex were obtained for the 19 election districts of Guam from 1956 through 1985. The highest rates were found in the southern and central districts, and the lowest rates were found in the northern and western districts. Geographic and temporal patterns of incidence were associated with socioeconomic status but not with geochemical factors. The risk of parkinsonism-dementia complex in susceptible sibships was much higher than that in the general population--even in districts with the highest incidence rates, but especially in districts with the lowest incidence rates. Our evidence tends to support the hypothesis that multiple factors linked to cycad use play an important role in the cause of PDC. Hypotheses related to metal exposure and simple genetic factors were unsatisfactory explanations for the epidemiologic patterns observed. 
4	Long-term outcome after surgical repair of isolated atrial septal defect. Follow-up at 27 to 32 years BACKGROUND. Atrial septal defects have been surgically correctable for more than 30 years. The long-term survival rates among patients treated in the early era of cardiac surgery are poorly documented, but such data are of critical importance to the future medical care, employability, and insurability of these patients. METHODS. To determine the natural history of surgically corrected atrial septal defects, we studied all 123 patients who underwent repair of an isolated defect (ostium secundum or sinus venosus) at the Mayo Clinic between 1956 and 1960, 27 to 32 years after the procedure. The follow-up status of all patients was determined by written questionnaires and telephone interviews. Hospital records and death certificates were obtained if interim hospitalization or death had occurred. RESULTS. The overall 30-year actuarial survival rate among survivors of the perioperative period was 74 percent, as compared with 85 percent among controls matched for age and sex. The perioperative mortality was 3.3 percent (four deaths). Actuarial 27-year survival rates among patients in the younger two quartiles according to age at operation (less than or equal to 11 years and 12 to 24 years) were no different from rates among controls--97 percent and 93 percent, respectively. In the two older quartiles (25 to 41 years and greater than 41 years), 27-year survival rates were significantly less (P less than 0.001)--84 percent and 40 percent, respectively--than in controls (91 and 59 percent). Independent predictors of long-term survival according to multivariate analysis were age at operation (P less than 0.0001) and systolic pressure in the main pulmonary artery before operation (P less than 0.0027). When repair was performed in older patients, late cardiac failure, stroke, and atrial fibrillation were significantly more frequent. CONCLUSIONS. Among patients with surgically repaired atrial septal defects, those operated on before the age of 25 have an excellent prognosis, but older patients require careful, regular supervision. 
5	Facial nerve injury and hemifacial spasm. We studied evidence of facial nerve damage in patients with hemifacial spasm. Three types of evidence of nerve damage were analyzed: objectively measured weakness in eyelid protractor strength, clinically evident weakness of muscles innervated by the seventh nerve, and clinically evident aberrant seventh nerve regeneration. Of the 60 patients in the study, 54 (90%) had at least one of these features of seventh nerve damage. Objectively measured eyelid protractor weakness was noted in 27 of 58 patients (47%) who were tested. Clinically apparent weakness of at least one of four facial muscle groups was noted in 42 of 60 patients (70%). Aberrant seventh nerve regeneration was documented in 25 of 60 patients (42%). These findings indicate that facial nerve damage is common in patients with hemifacial spasm. 
5	Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy. To identify patients with left ventricular ejection fractions less than 20% who are likely to survive on tailored medical therapy after referral to transplantation, this study of 152 patients addressed the hypotheses that (1) severely elevated filling pressures initially measured at referral would not necessarily predict poor outcome, (2) survival would be best when low pulmonary wedge pressures could be achieved with therapy tailored for hemodynamic goals, and (3) coronary artery disease would be an independent risk factor for early mortality. Despite an average initial ejection fraction of 0.15, cardiac index of 2.0 liters/min/m2 and pulmonary artery wedge pressure of 28 mm Hg, the actuarial survival with tailored therapy was 63% at 1 year, with 34 of 41 (83%) deaths occurring suddenly. Survival was not related to initial filling pressure elevation, but was best predicted by the pulmonary artery wedge pressures during therapy; patients achieving pressure of less than or equal to 16 mm Hg had 1-year survival of 83 vs 38% (p = 0.0001). The other independent predictors were serum sodium and coronary artery disease. Patients with high filling pressures during therapy and coronary artery disease had 21% survival at 1 year. Survival after referral to transplantation with an ejection fraction less than or equal to 20% is better than previously described. Patients in whom left ventricular filling pressures cannot be adequately reduced by tailored therapy, particularly if coronary artery disease is present, should be considered for early transplantation. 
2	Crohn's disease and retinal vascular disease. Patients with Crohn's disease may manifest extraintestinal findings including ocular involvement. We treated two patients with Crohn's disease who manifested retinal vascular disease that may have been related to the immune nature of the underlying disease or possibly to changes in the vasculature or coagulation system. One patient had a central retinal vein occlusion and the other had retinal vasculitis involving retinal arteries and veins with an apparent branch retinal artery occlusion. Both patients were in excellent health except for Crohn's disease, which was confirmed by a biopsy specimen. In one patient, the diagnosis of retinal vasculitis preceded the clinical diagnosis of Crohn's disease, whereas for the second patient the symptomatology of the intestinal disease preceded the ocular manifestations. We suggest that inflammatory bowel disease should be considered in the differential diagnosis of retinal vascular occlusive disease, especially in a young patient. 
1	Cytomegalovirus in the brain: in vitro infection of human brain-derived cells. Models for human cytomegalovirus (HCMV) brain infection have been developed in a variety of brain-derived cells in which the factors governing virus infectivity might be studied in vitro. Studies were initiated with brain endothelial cells, the likely portal of entry for virus into the central nervous system. Primary explant cultures of brain endothelial cells, derived from homogenates of healthy human brain, supported complete viral gene expression and cytopathic effect (CPE). Endothelial cells do not appear to be a barrier for HCMV passage into the central nervous system. Astroglial lines (primary explant or tumor-derived) varied in their ability to support HCMV replication. Some (T98G) supported incomplete (immediate-early) gene expression while others (A-172) did not support any detectable gene expression. Some astroglial lines (HS-683) supported extensive virus replication with minimal viral CPE. Neuronal cell lines (SK-N-MC) were fully permissive. The more differentiated glial lines (astrocytoma) were fully permissive to HCMV infection; however, the less differentiated glial lines (glioblastoma) were partly or nonpermissive. 
1	Combined modality therapy for locally advanced non-small cell lung carcinoma. Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting. 
1	Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women. Women with ovarian hyperandrogenism frequently have insulin resistance, whose underlying mechanism remains to be determined. In the present study we have investigated the relationship between insulin sensitivity and the acute effect of endogenous insulin secretion on circulating androgen levels. Insulin sensitivity, glucose-mediated insulin release, and glucose/insulin-stimulated androgen responses were determined during a frequently sampled iv glucose tolerance test in a group of 19 women with clinical evidence of polycystic ovary syndrome (PCOS) and 9 age- and weight-matched controls. Insulin (I), glucose, androstenedione, testosterone (T), free T, and dehydroepiandrosterone (DHEA) levels were measured before and during the 3 h following iv administration of glucose (300 mg/kg). Intravenous tolbutamide (300-500 mg) was injected 20 min after the glucose injection. Insulin sensitivity (SI) was calculated by application of the minimal model of glucose kinetics. Fasting androstenedione, T, free T, and I concentrations were significantly higher in the women with PCOS than in controls (P less than 0.02). In PCOS subjects, fasting I was correlated with both T (r = 0.51; P less than 0.05) and DHEA (r = 0.706; P less than 0.01). SI was significantly lower in PCOS subjects [SI, 68.35 +/- 8.34 min-1/(nmol/mL] than in control subjects (SI, 133.36 +/- 21.7 min-1/(nmol/mL)]. A significant decline in DHEA levels was observed in control subjects 3 h after glucose administration (from 28.4 +/- 3.0; final, 16.2 +/- 2.4; P less than 0.02). PCOS women with normal insulin sensitivity [SI, greater than 75.0 min-1/(nmol/mL)] showed a similar fall in DHEA (from 20.3 +/- 2.5 to 12.8 +/- 1.8 nmol/L; P less than 0.02). No significant change occurred in insulin-resistant PCOS subjects [SI, less than 75.0 min-1/(nmol/mL)]. Other androgen levels showed a modest nonsignificant decline during the study in PCOS and control groups. These findings confirm the weight-independent insulin resistance of some hyperandrogenic women. The failure of glucose-stimulated endogenous insulin secretion to significantly depress DHEA levels in insulin-resistant women with PCOS may account in part for their androgen excess. 
5	Multiagent chemotherapy in relapsed acute lymphoblastic leukemia in children. Twenty-seven evaluable children with early first bone marrow relapse of acute lymphoblastic leukemia were treated with an intensive induction/consolidation and ongoing maintenance therapy. Induction therapy consisted of a 35-day course of daunomycin, vincristine, and prednisone, immediately followed by teniposide, cytosine arabinoside (Ara-C), and L-asparaginase. Intrathecal methotrexate, hydrocortisone, and Ara-C were given through the induction/consolidation phase. Twenty-three of 27 patients achieved remission by the end of induction/consolidation. Maintenance with the same drugs in a modified dosage schedule continued for approximately 2 years. A small subgroup of patients who were M3 at day 35 but M1 at day 56 (end of induction/consolidation) and had a cumulative event-free survival (EFS) of only 0.40 at 6 months, all had relapsed by 15 months. However, the EFS for M1 patients by day 35 and maintained on chemotherapy was 0.64 at 12 months and 0.32 at 30, 36, and 48 months, respectively. Although good reinduction and remission duration rates at 12 to 24 months were achieved and an apparent plateau in survival occurs at 30 months, fall-off in survival would not be unexpected with probably less than 20% alive after 5 years. 
1	5-year results of cisplatin and fluorouracil infusion in head and neck cancer. As part of the developmental process for the Head and Neck Intergroup trial of adjuvant chemotherapy for advanced resectable head and neck carcinoma, in 1981 the Radiation Therapy Oncology Group, Philadelphia, Pa, conducted two nonrandomized pilot studies using chemotherapy consisting of three courses of cisplatin and fluorouracil infusion. Chemotherapy was administered prior to surgery in 42 patients (induction) and after surgery in an additional 29 patients (sequential). The populations were roughly comparable with respect to tumor site and stage. Twelve of the 42 patients in the induction group and seven of the 29 in the sequential group are alive and with no evidence of disease at the last reported follow-up. The median survival was 31 months in the sequential group vs 20 months in the induction group. Only two of the 26 patients with less than a complete clinical response following induction chemotherapy are still alive. Twenty-seven of the 42 patients who received induction chemotherapy did not undergo surgery as initially planned. Despite the lack of surgery, at 5 years the survival between the two groups was not significantly different (27% for the induction group vs 23% for the sequential group). 
5	Multiple-pulse stimulation and dantrolene in malignant hyperthermia. A potentially fatal condition, yet preventable, malignant hyperthermia (MH) lacks a satisfactory noninvasive diagnostic test. Studying the effects of intravenous dantrolene (3 mg/kg) on electrically stimulated skeletal muscle, we found that this approach does not conclusively distinguish between normal humans and those susceptible to malignant hyperthermia but nonetheless yielded important information about the action of dantrolene in man and in MH. Supramaximal single- and multiple-pulse stimulation of the common peroneal nerve produced stable torque responses of the dorsiflexor muscles (monitored in vivo), which dantrolene suppressed. With the multiple-pulse stimulation (5-6 pulses) this torque suppression was significantly less in MH-susceptible subjects than in control subjects. This distinction, also observed in MH swine, confirms this animal as a good model for human MH. That dantrolene's effect in MH can be more completely reversed with high frequency stimulation is intriguing; presumably, excitation-contraction coupling differs in MH and normal muscle. 
5	Detection and direct sequencing of hepatitis B virus genome by DNA amplification method. Hepatitis B virus (HBV) DNA was detected with amplification by the polymerase chain reaction method. Cloned HBV DNA equivalent to one virus genome (3 x 10(-6) pg) was detectable by ethidium bromide staining after 50 cycles of polymerase chain reaction. By applying this method, presence of HBV DNA was studied in 23 hepatitis B surface antigen (HBsAg)-positive and 11 HBsAg-negative sera from patients with chronic liver disease. Hepatitis B virus DNA was positive in 8 of 8 hepatitis B e antigen (HBeAg)-positive, in 2 of 2 HBeAg- and anti-HBe-negative, and in 12 of 13 anti-HBe-positive sera. Hepatitis B virus DNA was undetectable in all HBsAg-negative sera even with amplification. To confirm specificity, the amplified product was directly sequenced. Sequences around 122nd and 160th codon of HBs gene, which determines subtypes d/y and w/r, respectively, were analyzed. The results were compatible with recent reports regarding the relation between HBV subtypes and HBV DNA sequence at those codons. Hepatitis B virus DNA could be detected at the level of one virion by gene amplification method, and its sequence could be determined by direct sequencing in a few days. 
5	Growth hormone deficiency in children has psychological and educational co-morbidity. Growth delay caused by growth hormone deficiency (GHD) is a condition presented with increased frequency to pediatricians. Recent evidence suggests these patients should be evaluated developmentally for behavioral and educational problems. Such assessment would assure a comprehensive approach to treatment and increase the likelihood of a satisfactory outcome in young adulthood. This article briefly reviews what is known about the behavioral and educational difficulties experienced by growth hormone deficient patients. Specific recommendations for educational assessment and anticipatory guidance are presented. 
1	Ultrasound-guided fine-needle aspiration biopsy of neck nodes. The assessment of nodal involvement in patients with squamous cell carcinoma of the head and neck is still a major diagnostic problem. Although the sensitivity of imaging techniques for detection of neck nodes is gradually improving, the specificity for metastases remains low. Cytologic examination could, theoretically, supply additive information. Computed tomographic-and magnetic resonance-guided aspiration techniques have been described, but these were not efficacious and laborious. In 1984, we developed a technique for ultrasound-guided (UG) fine-needle aspiration biopsy (FNAB). This technique is described herein, and the value of UGFNAB is compared with conventional FNAB. All statistical characteristics of UGFNAB appeared to be superior to conventional FNAB (sensitivity, 98% vs 88%; specificity, 95% vs 82%; positive predictive value, 98% vs 93%; negative predictive value, 95% vs 74%; and accuracy, 97% vs 87%). Furthermore, UGFNAB was characterized by less nondiagnostic aspirations. It is concluded that UGFNAB is a reliable technique for differentiation between benign nodes and cervical lymph node metastases and it may, therefore, contribute to a more accurate assessment of the neck in squamous cell carcinoma of the head and neck. 
5	Delayed rupture of a pseudoaneurysm of the costocervical trunk: treatment with therapeutic embolization. Fourteen days after removal of an internal jugular catheter inserted prior to renal transplantation, a patient presented with brisk arterial hemorrhage from the insertion site. The hemorrhage, caused by a ruptured pseudoaneurysm of the costocervical trunk, was controlled by transcatheter embolization with gelatin particles. One year later the patient reported no problems related to the pseudoaneurysm or its management. 
1	Choroidal osteoma (osseous choristoma): an atypical case. A case of choroidal osteoma presenting in a 22-year-old girl is reported. The tumour, unilateral and in a juxtapapillary site, appeared markedly elevated on the retinal plane, not flat or slightly elevated as in previous reports. Visual acuity was not affected, and there was a complete absence of subjective symptoms. Echography, fluorangiography, computerised tomography, and visual field tests were performed. Echography is the best method for identifying and differentiating this lesion from a malignant tumour. 
5	Primary adenocarcinoma of the bladder: favorable prognostic significance of deoxyribonucleic acid diploidy measured by flow cytometry. Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy. 
2	Cholecystokinin enhanced hepatobiliary scanning with ejection fraction calculation as an indicator of disease of the gallbladder. Chronic acalculous cholecystitis represents 5 to 20 per cent of electively treated diseases of the gallbladder. A 70 per cent success rate in relieving these patients of chronic pain was reported when surgical treatment was recommended based on symptoms alone. The cholecystokinin ejection fraction, which is a quantitative measure of emptying of the gallbladder, was 95 per cent accurate in predicting which patients would be relieved of symptoms by surgical treatment. In this study, we report our consecutive experience during a 20 month period with 83 patients. 
5	Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis. The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach. 
5	Pulmonary arterial and venous constriction during hypoxia in 3- to 5-wk-old and adult ferrets. We have determined the sites of hypoxic vasoconstriction in ferret lungs. Lungs of five 3- to 5-wk-old and five adult ferrets were isolated and perfused with blood. Blood flow was adjusted initially to keep pulmonary arterial pressure at 20 cmH2O and left atrial and airway pressures at 6 and 8 cmH2O, respectively (zone 3). Once adjusted, flow was kept constant throughout the experiment. In each lung, pressures were measured in subpleural 20- to 50-microns-diam arterioles and venules with the micropipette servo-nulling method during normoxia (PO2 approximately 100 Torr) and hypoxia (PO2 less than 50 Torr). In normoxic adult ferret lungs, approximately 40% of total vascular resistance was in arteries, approximately 40% was in microvessels, and approximately 20% was in veins. With hypoxia, the total arteriovenous pressure drop increased by 68%. Arterial and venous pressure drops increased by 92 and 132%, respectively, with no change in microvascular pressure drop. In 3- to 5-wk-old ferret lungs, the vascular pressure profile during normoxia and the response to hypoxia were similar to those in adult lungs. We conclude that, in ferret lungs, arterial and venous resistances increase equally during hypoxia, resulting in increased microvascular pressures for fluid filtration. 
3	Hyperhomocysteinemia: an independent risk factor for vascular disease. BACKGROUND. Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency. METHODS. We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0 mumol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age. RESULTS. Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia. CONCLUSIONS. Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency. 
5	Synthesis of platelet activating factor by ocular tissue from inflamed eyes. Platelet activating factors (PAFs) are a family of ether lipids with properties that suggest a major role in inflammation. We have previously implicated PAFs in ocular inflammation based on the inhibition of several rabbit models of iritis with a specific PAF receptor antagonist. We have tested ocular tissues for the ability to synthesize PAF. Iris, ciliary body, cornea, and/or retina were carefully dissected from New Zealand white rabbits, and tissue from four eyes was pooled. Tissues were stimulated with calcium ionophore (10 mumol/L), and supernatants were extracted with chloroform-methanol. Platelet-aggregating activity was found in the chloroform phase in 2 of 9, 1 of 8, 0 of 9, and 3 of 9 studies involving iris, retina, ciliary body, or cornea, respectively. Twenty-four hours after the intravitreal injection of 125 ng of endotoxin, aggregating activity was consistently detectable from supernatants of stimulated iris and ciliary body, occasionally present from stimulated retina but not detectable from cornea. The shape of the aggregation curve resembled that produced by 0.5 to 2.0 ng of authentic PAF. Moreover, the aggregation could be completely inhibited by a PAF receptor antagonist and the aggregating activity chromatographed identically on high-performance liquid chromatography to a PAF standard. These studies indicate that PAF-like activity could be detected from several ocular tissues subsequent to inflammation. Iris, ciliary body, retina, vascular endothelium, and/or leukocytes could each contribute to the presence of this inflammatory mediator. 
3	Successful treatment of neonatal Citrobacter freundii meningitis with ceftriaxone. Citrobacter meningitis is an uncommon enteric gram-negative infection that afflicts neonates and young children. Approximately 30 percent of children treated or untreated die from the infection. We report a case of C. freundii meningitis that was resistant to ampicillin and was successfully treated with ceftriaxone, a third-generation cephalosporin. A 13-day-old, full-term baby was admitted to the hospital with a one-day history of fever up to 38.8 degrees C. On admission the infant had a temperature of 39.2 degrees C, pulse of 140 beats/min, and a respiratory rate of 32 breaths/min. Except for a slightly bulging fontanelle, the rest of the physical examination was within normal limits. Complete blood count revealed a white blood cell (WBC) count of 12.5 x 10(9)/L, with 0.66 polymorphonuclear cells, 0.10 bands, 0.18 lymphocytes, and 0.06 monocytes. A stat lumbar puncture showed 10 WBCs per high-power field with gram-negative rods. Empiric therapy with ampicillin 225 mg q12h and gentamicin 11 mg q8h was started. Both antibiotics were discontinued after culture and sensitivity results were positive for C. freundii in the blood and spinal fluid. The patient was successfully treated with nine days of ceftriaxone 250 mg q12h. 
4	Quantification of vascular stenosis with color Doppler flow imaging: in vitro investigations. The accuracy of quantifying the degree of vascular stenosis with color Doppler flow imaging (7.5-MHz, linear array system) was determined in an experimental study carried out on six concentric and five eccentric model stenoses (cross-sectional area reduction, 13.4%-93.8%). The measurements were made with use of pulsatile flow at four different flow rates (70.8-339.0 mL/min). The degree of stenosis was calculated from the ratio of prestenotic to intrastenotic flow velocity. The most exact measurement of the degree of stenosis could be achieved with Doppler spectral analysis by determining the maximum peak systolic velocity (r = .994, y = 0.98x - 3.2). With the velocity values derived only from the color-coded image, it was also possible to find the most exact degree of stenosis (r = .995, y = 0.99x - 2.9). For quantification of stenosis, pre- and intrastenotic Doppler spectral analysis is no longer necessary if the stenosis can be imaged sufficiently with color Doppler. 
5	Percutaneous biliary drainage for high obstruction. PBD is the preferred route of palliative drainage for patients with high biliary obstruction. The frequency of bifurcational obstruction in this setting requires familiarity with drainages from both the right and the left transhepatic approach. The preferred right transhepatic approach is fluoroscopically guided; on the left, ultrasonography is the guidance of choice. Large caliber drainage catheters are required, and dilatation of the necessary transhepatic tracts is extremely painful unless adequate inhalation anesthesia or, preferably, epidural anesthesia, is provided. Long-term biliary drainage requires a choice between internal-external external drainage catheters and endoprostheses that is made by considering the patient's life expectancy and his or her adjustment to a stent extending to the outside. The feasibility of corrective procedures if an internal-external drainage catheter or an endoprosthesis becomes blocked needs to be considered before definitive placement. The interventional radiologist becomes intimately involved in the follow-up care of patients and frequently has to direct appropriate patient evaluation. Familiarity with antibiotic regimens is important. 
5	Smoking cessation in chronic Reinke's oedema. In evaluating the long term results of surgical treatment of Reinke's oedema, there has been found to be a high incidence of recurrence. The recurrence rate is significantly lower amongst those patients who gave up smoking after treatment. A group of patients with chronic Reinke's oedema were followed for six months. Maximum efforts were made to help the patients to stop smoking. Twenty-nine patients entered the study, but only eight of them (28 per cent) refrained from smoking; all were women (39-70 years) and all experienced reduced discomfort, although none of the voices were restored to normal. Diffuse laryngitis disappeared completely, but the oedema did not disappear entirely in any patient. Before treatment of chronic Reinke's oedema patients must be well advised and informed, and if surgery is decided upon, they must be urged most strongly to stop smoking, if they wish to enhance the possibility of satisfactory long-term results. 
3	Discordant nephron function. A pathogenic factor in hypertension and its vascular complications of stroke and heart attack. Morphologic evidence from patients with essential hypertension and Goldblatt-type hypertension reveals a subpopulation of narrowed afferent arterioles to ischemic nephrons. These ischemic nephrons, responding individually to their perception of underperfusion, secrete renin. In response, the normal nephrons are in adaptive natriuresis and have appropriately shut off their renin production. Nevertheless, they are affected adversely by the discordant renin-angiotensin II arising from the ischemic nephrons' presence, which exerts an unwanted sodium-retaining effect on the proximal tubules of the adapting nephrons. The end result is elevated blood pressure from too much sodium retention for the level of renin activity, that is, an abnormal renin-sodium product. Thus, "normal" renin levels in a hypertensive individual are abnormal because healthy kidneys shut off renin production entirely when blood pressure rises. This construction explains why angiotensin converting enzyme inhibition often corrects "normal" renin hypertension. Although such hypertension may be partly sodium-mediated as a consequence of inappropriate sodium retention by the normal and ischemic nephrons, the source of the problem lies in the renin production from ischemic nephrons. The correct treatment, then, is an antirenin therapy designed to block renin synthesis or secretion or angiotensin II formation or action. In view of modern studies suggesting that renin excesses also correlate with an increased risk of heart attack and stroke, the role of antirenin and antiangiotensin agents in treatment assumes additional relevance. 
1	Childhood blindness in Peru. A survey of childhood blindness in Peruvian children was done. Although most causes of blindness were due to congenital and hereditary conditions, measles accounted for almost 10% of blindness. With widespread measles immunization, this preventable cause of blindness in children can be eliminated or dramatically reduced. 
4	Dialysis-induced alterations in left ventricular filling: mechanisms and clinical significance. Quantitative two-dimensional (2-D) and Doppler echocardiography were used to determine whether hemodialysis results in alterations in left ventricular (LV) diastolic filling that might contribute to dialysis-induced hypotension, as well as to assess whether any hemodynamic variables or indices of diastolic filling might be used to identify which patients were at the greatest risk of becoming hemodynamically unstable during dialysis. Sixteen male patients undergoing routine maintenance hemodialysis for end-stage renal disease were prospectively studied before and after hemodialysis. Following hemodialysis there was a significant prolongation (P less than 0.05) in LV isovolumetric relaxation time (IVRT), as well as a significant reduction in the rate and extent of early rapid ventricular filling (P less than 0.005); in contrast, late atrial-assisted filling did not change significantly. A multiple stepwise linear regression analysis of predialysis hemodynamic parameters and noninvasive indices of LV filling showed that there was a significant independent inverse relationship between the frequency of dialysis-related hypotensive episodes and the duration of early LV filling (r = -0.81; P less than 0.001). These results suggest that hemodialysis results in discrete alterations in early LV filling, with no significant compensatory increase in late atrial-assisted ventricular filling. Further, patients with the shortest early LV filling times appeared to have the greatest predilection for becoming hemodynamically unstable during dialysis. 
3	Visual evoked potentials and visual prognosis following perinatal asphyxia. Twenty-five children born at term with perinatal asphyxia were studied at age 2.5 to 4.5 years to evaluate visual function and to determine the prognostic value of postnatal assessments of visual outcome. Postnatal assessments included several visual evoked potentials and electroretinograms in the first week of life. Follow-up assessments included flash and pattern visual evoked potentials, visual evoked potential threshold measurements, and clinical eye examinations. Nineteen children had normal visual function, three were visually impaired, and three remained blind. A strong association was found between normal, abnormal, or absent visual evoked potentials in the early postnatal period and long-term visual outcome (P less than .0001). Other perinatal indicators of asphyxia, including neurologic status, Apgar scores, and arterial pH values, were poor predictors of visual outcome. The risk of visual impairment was limited to those survivors with neurodevelopmental deficits. 
1	Neuroendocrine carcinoid tumours of the breast: a variant of carcinoma with neuroendocrine differentiation. Carcinoid tumours most frequently develop in the gastrointestinal tract but have been described in many organs of the body. In 1977 the first cases were reported in the mamma, followed by descriptions of argyrophilic carcinoid-like, neuroendocrine mammary tumours by many investigators who performed immunohistochemical and ultrastructural examinations. The existence of true carcinoids in the mamma is still a controversial issue. Eight mammary neoplasms with monomorphous cytonuclear features, five of the small cell carcinoid-like variety and three composed of larger cells, were examined by immunohistochemical and ultrastructural examination. We believe this kind of tumours are ductal or lobular carcinomas with focal or more extensive neuroendocrine features and are the result of a dual differentiation of neoplastic precursor stem cells along epithelial and endocrine lines. Consequently, we consider that treatment of such cases should not be different from that of the ordinary type of mammary carcinomas. 
3	A review of techniques employed to estimate the number of motor units in a muscle. Being the smallest functional units under neural control, motor units play an integral role in muscle physiology. However, at the present time, there does not exist any widely accepted technique for quantifying or estimating the number of motor units in a muscle. Specifically, the existing techniques are the increment-counting technique, a technique based on spike-triggered averaging, and a macro-EMG based technique which vary in invasiveness from noninvasive to highly invasive, respectively. We discuss each of these techniques, along with their associated shortcomings, in detail. 
4	Limitations of magnetic resonance imaging and ultrasound-directed (duplex) scanning in the diagnosis of subclavian vein thrombosis. To investigate the potential role of magnetic resonance imaging and duplex scanning in the diagnosis of catheter-induced subclavian vein thrombosis, we correlated the results of 43 arm phlebograms with duplex scans; 28 of these phlebograms were also correlated with magnetic resonance imaging scans of the thoracic veins. Eighteen of the 43 phlebograms were normal, and all had normal magnetic resonance imaging and duplex studies. Eleven subclavian veins were totally occluded on phlebography; all had duplex scans, and five were also scanned with magnetic resonance imaging. Duplex scans detected 6 of 11 occlusions, whereas magnetic resonance imaging detected 4 of the 5 occlusions scanned. The five occlusions that were not detected by either magnetic resonance imaging or duplex scans were short segmental occlusions of the medial one third of the left subclavian vein. Of 14 nonocclusive thrombi seen on phlebography, duplex scans correctly identified 8. Magnetic resonance imaging was done on eight nonocclusive thrombi but identified only two. All abnormal findings on duplex scanning and magnetic resonance imaging were confirmed by phlebography. Short occlusions of the proximal portion of the left subclavian vein were often undetected by duplex scanning but occasionally seen with magnetic resonance imaging. Neither modality was sensitive to the presence of nonocclusive mural thrombi. Magnetic resonance imaging is highly reliable in ruling out the presence of a thrombotic process in the subclavian vein, but it may on occasion fail to detect the presence of subclavian thrombi. For this reason, in cases with suspected subclavian vein thrombosis magnetic resonance imaging cannot be used as the only diagnostic modality. 
5	A hospital-based study of acute viral infections of the respiratory tract in Thai children, with emphasis on laboratory diagnosis. The hospital-based study described here examined the viruses found in 738 children less than 5 years old who presented at Ramathibodi Hospital, Bangkok, Thailand, from January 1986 to December 1987 with acute respiratory tract infections. Three methods for detection of viral infection are compared: direct examination of epithelial cells of the respiratory tract with the use of fluorescent antibody staining, isolation of virus, and measurement of antibody in acute- and convalescent-phase sera. Viral infections were found in 44.7% of the study population. Diagnosis by the examination of epithelial cells with the fluorescent antibody staining procedure was found to have several deficiencies; however, this technique was the most sensitive for diagnosis of infection due to respiratory syncytial virus. Isolation of virus was the best method for identification of adenoviruses, parainfluenza 1 and 3 viruses, and influenza B virus. Problems associated with serodiagnosis included failure to obtain specimens of convalescent-phase blood in 24.5% of cases and insensitivity of serodiagnosis for young children except for the identification of antibody to influenza A virus. The combination of all three tests yielded the best rate of detection of virus. 
4	Muscle oxidative capacity and work performance after training under local leg ischemia. Healthy young men executed supine one-legged cycle training four times per week for 4 wk with legs and the cycle ergometer inside a pressure chamber, the opening of which was sealed by a rubber membrane at the level of the crotch. Each training session started by training one leg under ischemic conditions induced by increased chamber pressure (50 mmHg) at the highest intensity tolerable for 45 min. Then the other leg was trained with the same power profile but normal atmospheric chamber pressure. Before and after the training period, both legs executed one-legged exercise tests under both normal and increased chamber pressure and muscle biopsies were taken from the vastus lateralis. Ischemic training increased performance more than normal training, the difference being greater for exercise executed under ischemic conditions. The difference in performance increase between the legs was paralleled by a greater muscle citrate synthase activity in the ischemically than in the normally trained leg. 
4	Association between post-dexamethasone cortisol level and blood pressure in depressed inpatients. We examined the clinical data for 230 depressed inpatients who had completed a dexamethasone suppression test (DST) to determine whether those with an elevated post-DST serum cortisol level exhibited any of the classic physiological stigmata of Cushing's syndrome. Hypertension was significantly more frequent among DST nonsuppressors (21.2%) than among normal suppressors (11.3%). Percent blood lymphocyte count was significantly lower among nonsuppressors. Confounders such as gender, age, body weight, and use of antihypertensives did not account for the findings. Implications for morbidity and mortality rates among patients with affective disorder are discussed. 
5	Permanent venous access via subcutaneous infusion port in severe asthma. A subcutaneous infusion port was implanted in a 34-year-old patient with frequent and severe asthma attacks to ensure prompt and reliable venous access. Difficulties with peripheral venous access were possible cofactors necessitating mechanical ventilation on two occasions before this implantation. The method described is simple and seems useful for asthmatics in need of frequent parenteral medication. 
4	Analysis and predictors of pulmonary vascular resistance after cardiac transplantation. Elevated pulmonary vascular resistance is a known risk factor for early death from acute right ventricular failure after orthotopic cardiac transplantation. Patients in whom the elevated pulmonary vascular resistance is due primarily to increased left atrial pressure ("reactive") frequently have normalization of resistance after transplantation, but few studies have detailed the time course and magnitude of these changes. To analyze the response of pulmonary vascular resistance to cardiac transplantation, we analyzed data from 4353 right heart catheterizations on all 182 patients undergoing cardiac transplantation between 1981 and Jan. 1, 1990. Before transplantation 18% of patients had a pulmonary vascular resistance greater than 4 WU, 16% had a pulmonary artery systolic pressure greater than 60 mm Hg, and 16% had a transpulmonary gradient greater than 14 mm Hg. In the overall group of patients, pulmonary vascular resistance (mean value 2.63 WU), transpulmonary gradient (mean value 9.9 mm Hg), and pulmonary artery systolic pressure (mean value 48.0 mm Hg) were normalized within 1 week of cardiac transplantation. In patients with a high preoperative pulmonary vascular resistance (greater than or equal to 4 WU), the resistance fell promptly within 1 week of transplantation but continued to be slightly elevated throughout the period of follow-up. By multiple regression analysis, pulmonary vascular resistance at 1 week and 1 year after transplantation was significantly correlated with the pretransplantation resistance. Pulmonary vascular resistance anytime after transplantation was related to preoperative resistance, body surface area, and pulmonary artery diastolic pressure. Inferences: (1) As a group, cardiac transplant recipients have a normal pulmonary vascular resistance, transpulmonary gradient, and pulmonary artery systolic pressure within 1 week after transplantation with little change thereafter for at least several years. (2) Patients with reversible elevation of pulmonary vascular resistance before cardiac transplantation typically have a reactive and a fixed component. Cardiac transplantation relieves the reactive but not the fixed component. As a result, pulmonary vascular resistance early (within 1 week) and late after transplantation will have fallen but not completely normalized. 
1	Fibromatous epulis in dogs and peripheral odontogenic fibroma in human beings: two equivalent lesions. This article compares the clinical and histopathologic features of the peripheral odontogenic fibroma in human beings and the fibromatous epulis in dogs. They are apparently equivalent lesions. Both are odontogenic tumors of limited growth potential that do not recur if adequately excised; both occur in middle and late adulthood of the species concerned. The one difference is that the peripheral odontogenic fibroma is a rare condition, whereas the canine fibromatous epulis is common. 
5	Visual impairment in a rural Appalachian community. Prevalence and causes. A population-based survey of 1136 subjects aged 40 years and older was conducted in a rural valley of Kentucky to determine the nature and extent of visual disability in an underserved area of rural America. Data on corrected visual acuity and ocular history, along with demographic, socioeconomic, and health care utilization parameters, were gathered. Those subjects with an acuity below 20/60 in either eye underwent a comprehensive ophthalmologic examination. The prevalence of binocular blindness (acuity worse than 20/400 in the better eye) was 0.44% and of monocular blindness (acuity worse than 20/400 in one eye) was 3.3%, approximately twice the national rates. The chief cause of bilateral visual impairment was macular degeneration among men and cataract among women. Cataract, trauma, and amblyopia were the major causes of monocular visual impairment in both sexes. Risk factor analysis revealed younger age, higher education, active employment, access to a health care facility, and comprehensive health insurance coverage to be inversely associated with visual impairment. 
5	Rapid admixture blood warming: technical advances. The technique of rapid admixture blood warming of cold erythrocyte units is designed to warm erythrocyte units rapidly (less than 30 sec) while simultaneously providing saline for dilution. However, questions have been raised about the recommended use of a standard 250-ml bolus of 70 degrees C admixture saline, the uniformity and speed of blood unit warming, the difficulties inherent in keeping saline bags at 70 degrees C, and the safety of the methodology. To answer these questions, a series of tests were performed and modifications of the technique were introduced. The mean weight of 1000 successive units of erythrocytes for adult infusion was 305 g (range 220 to 410). The maximum temperature was 44 degrees C, using an internal temperature probe (1-cm temperature gradations; 2-sec recording intervals) when the smallest unit was admixed with a 250 ml 70 degrees C saline bolus; the largest unit had a minimum temperature of 30 degrees C. Plasma Hgb, osmotic fragility, and K of the minimum size erythrocyte unit showed no significant deviation from its control. Both thermographic photographs and the internal temperature recordings of the erythrocyte units demonstrated that solely due to fluid turbulence, uniform mixing occurs within approximately 30 sec of beginning the admixture process. Inverting the blood units caused a thermal layering of fluids and an unacceptable maximum blood temperature of 50 degrees C. There was no difference between the mixing time or efficacy in the presence of standard or large-bore iv tubing or additional in-line filters. Volumes of the 250-ml saline bags for admixture decreased markedly with deviations in electrolyte composition after greater than 2 wk at 70 degrees C. 
5	Proximal gastric vagotomy: follow-up at 10-20 years. From August 1969 to December 1989, 600 patients had elective proximal gastric vagotomy for duodenal ulceration with an operative mortality of 0.2 per cent. Of these, 372 patients had surgery over 10 years ago. Three hundred and forty-two patients survived for more than 10 years and, in a prospective study, 305 were reviewed, forming the basis of this 10-20-year follow-up report. Forty-six (15 per cent) have had recurrent ulceration; 80 per cent of these developed symptoms within 5 years and no patient has had recurrence after 13 years. Although 29 patients required reoperation for recurrent ulceration, the current patient satisfaction rate for Visick grades I and II is 92 per cent. Only two patients required reoperation because of gastric stasis. It is concluded that proximal gastric vagotomy is a safe and satisfactory first choice operation for duodenal ulceration. 
5	Third-trimester fetal death in triplet pregnancies. During the last decade, 89 sets of triplets were born in Denmark with a gestational age of more than 25 completed weeks. Fifteen pregnancies (16.9%) were complicated by fetal death in the third trimester, with a total of 17 intrauterine deaths. Six neonatal deaths occurred, leaving 22 survivors among these 15 patients. Four triplet gestations were diagnosed as twins until delivery. Eight women conceived spontaneously, two gestations followed assisted fertilization and embryo transfer, and five women had had various forms of ovulation stimulation. The mean maternal age was 27.8 years (range 17-38). Seven women were parous and eight wer nulliparous. Maternal complications included hydramnios (three), preeclampsia/hypertension (three), and anemia (nine). All women delivered preterm. Of the 11 gestations diagnosed as triplets, fetal death was diagnosed at 32.2 +/- 2.9 weeks (mean +/- SD) and delivery occurred at 32.6 +/- 3.0 weeks. Nine of 11 women had cesarean deliveries. Continuation of pregnancy after fetal death could be considered in only three subjects. In eight women, obstetric reasons required immediate delivery. Fetal death was associated with monochorionic or dichorionic placentation, and growth retardation was a frequent complication before fetal death. Anencephaly of one fetus, umbilical cord problems in two, and severe hydrops in two were the only obvious causes of fetal death. Fetal death should not be the sole indication for delivery. In cases with severe prematurity and a stable intrauterine situation, frequent assessments of fetal well-being are recommended, with prompt delivery when indicated. 
5	Role of alcohol in recurrences of atrial fibrillation in persons less than 65 years of age. The role of alcohol in recurrences of atrial fibrillation (AF) was assessed in a consecutive series of 98 patients (75 men) aged less than 65 years. In addition to etiologic assessment using clinical and laboratory methods and echocardiography, the patients' drinking habits were evaluated by recording the amount of alcohol used during the week preceding AF, by responses to the CAGE (Cut, Annoying, Guilt, Eye; see below) questionnaire (a screening test for alcohol abuse) and by selected laboratory tests. Two groups of control subjects were studied: 98 sex- and age-matched patients admitted to the emergency ward for acute illnesses, and 50 subjects selected randomly from the local out-of-hospital population. The mean alcohol consumption among men during the study week was 186 g (median 45 g; range 0 to 2,100 g) among patients, whereas among male hospital and population control subjects it was 86 g (30 g; 0 to 1,050 g) and 94 g (35 g; 0 to 630 g), respectively. When the weekly alcohol consumption was analyzed in 3 categories (0; 1 to 210 g; greater than 210 g), there was a significant difference between AF cases and hospital control patients (p = 0.03), but not between AF cases and population control subjects. Multivariate analysis of data of AF cases and population control subjects showed that alcohol intake and a positive response to 1 or more of the CAGE questions were independently related to AF in men. Other independent risk factors were the presence of heart disease, low serum potassium and lack of sleep or experience of excess psychologic stress, or both. 
5	Carbamazepine overdose: a prospective study of serum levels and toxicity. A cooperative prospective study of consecutive cases of carbamazepine overdose was conducted to determine if serum levels were predictive of toxicity and if risk factors such as age, chronic exposure, or previous disorder or cardiovascular disease could be used as prognostic indicators. Seventy-three consecutive cases were collected from two regional certified poison control centers from January 1989 to August 1989. There were 25 exposures in children less than 6 yrs., 11 exposures in adolescents, and 37 exposures in adults. Ten adult cases and one adolescent case were excluded from the study due to the presence of coingestants or inadequate information. Peak measured serum levels ranged from 0.3 to 56 mcg/ml. Using the presence of coma, seizure activity or respiratory depression requiring mechanical ventilation as measures of toxicity, we found poor correlation between rising serum levels of carbamazepine and toxicity. Increased serum levels of carbamazepine did appear to correlate with increased hospital stay, but not with ICU stay. History of a seizure disorder appears to pose increased risk of a seizure in carbamazepine overdose. In this series chronic exposure to carbamazepine did not appear to increase the risk of coma or respiratory depression for a given toxic serum level and may add some protective effect. Serum levels below 40 mcg/ml do not appear to accurately predict the severity of toxicity. Cardiac conduction defects were rare (one child). Anticholinergic findings, as evidence by decreased bowel motility and sinus tachycardia were common. Previous cardiovascular disease and age did not appear to be important prognostic indicators. 
5	Long-term efficacy of primary laser trabeculoplasty. Sixty glaucomatous eyes of 60 patients treated with laser trabeculoplasty as primary therapy were reviewed retrospectively. There were 42 eyes with capsular glaucoma and 18 with simple glaucoma. The mean prelaser intraocular pressure (IOP) was 35.2 (SD = 6.5) mmHg. Success was defined as IOP less than or equal to 22 mmHg without medication. The probability of success was 0.73 at 1 year, 0.66 at 2 years, 0.57 at 3 years, and 0.50 at 4 years. Three eyes experienced progressive visual field loss or disc damage in spite of an intraocular pressure below 22 mmHg without medication. High prelaser pressure and the severity of the visual field defects were significant predictors of treatment failure. 
4	Retinal vasculitis as a complication of rheumatoid arthritis. Two middle-aged women developed retinal vasculitis in the moderately active phase of classical rheumatoid arthritis. Fluorescein angiography disclosed diffuse leakage from the retinal capillaries and cystoid macular edema, which subsided in response to oral steroid. They did not show any clinical signs of vasculitis in other parts of the body. Retinal vasculitis should be included in the list of complications observed in rheumatoid arthritis. 
5	Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Platelet-derived growth factor receptors are composed of two subunits (alpha and beta) that associate with one another to form three functionally active dimeric receptor species. The two subunits are encoded by separate loci in humans and other species. In this study, we used conventional interspecific backcross mapping and an analysis of a deletional mutation to establish close linkage between the alpha-subunit gene (Pdgfra) and the dominant spotting (W) locus on mouse chromosome 5. Further, by analyzing the restriction fragment length polymorphisms in interspecific F1 hybrids, we were able to demonstrate that the closely associated patch (Ph) locus carries a deletion in Pdgfra. This observation was confirmed by both DNA and RNA analysis of 10.5-day fetuses produced from crosses between Ph heterozygotes. Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes). We also determined that the deletion associated with the Ph mutation does not extend into the coding sequences of the adjacent Kit gene, by analysis of the genomic DNA from both the interspecific F1 hybrids and the presumptive Ph homozygotes. The absence of Pdgfra genomic sequences and the lack of detectable message associated with the Ph mutation should make this mutant a valuable asset for understanding the role of the receptor alpha subunit during mammalian development. 
2	Modified technique of Pringle's maneuver in resection of the liver. Crushing of the hepatic parenchyma with hepatic clamps to minimize blood loss during resection of the liver leads to mechanical damage of hepatocytes. Pringle's maneuver may precipitate liver failure by hepatic warm ischemia as well. Therefore, we controlled bleeding from the surface of the resection by using light compression on the hepatic parenchyma with a band while applying a hepatic arterial clamp at the hepatic hilus. This vascular control method can be done because the portal pressure is about one-tenth of the hepatic artery pressure and provides an efficient and harmless transection of the liver. 
1	Nuclear shape as a prognostic discriminant in colorectal carcinoma. In search for a more reliable prognostic discriminant, a retrospective analysis of 100 cases of colorectal carcinoma having undergone curative resection and followed for at least 5 years were assessed by nuclear morphometry. Each case was staged according to the Dukes' classification as well as graded histologically. For all patients in this series, the perimeter, area, and nuclear shape factor of 50 interphase nuclei were determined for each carcinoma. The information was obtained through the use of an image analysis system by tracing the nuclear profiles (magnification 1000x) as digitized on a video screen. The nuclear shape factor was defined as the degree of circularity of the nucleus, a perfect circle recorded as 1.0. A nuclear shape factor greater than 0.84 was associated with poor outcome. Multiple regression models showed that the single nuclear parameter of the shape factor was the most highly significant predictor of survival (P less than 0.0001). This variable remained highly significant even when corrected for sex, age, histologic grade, and Dukes' classification. These findings indicate that a nuclear shape factor greater than or equal to 0.84 as determined by nuclear morphometry is an independent morphometric nuclear variable of great importance in the prognosis of large bowel carcinoma. 
5	Duplex Doppler examination of a perinephric abscess in a renal transplant. Perinephric abscess has no characteristic ultrasonic appearance or location. Differentiation from urinoma, lymphocele, or hematoma depends on clinical and laboratory findings. Therapy consists of percutaneous catheter drainage, surgical drainage, and antibiotic therapy. Acute rejection is the most common cause of decreased diastolic flow during the immediate postoperative period. Acute tubular necrosis does not usually alter blood flow unless it is severe. Duplex doppler ultrasonic assessment of the renal transplant during the immediate postoperative period may provide a valuable baseline for comparison if complications develop. Baseline and follow-up ultrasonography to evaluate diastolic flow can help determine whether a posttransplant patient should receive emergency or conservative therapy for complications. 
1	Hoarseness as the sole presenting symptom of foramen magnum meningioma. Foramen magnum tumours are rare. They may present with bizarre symptoms and mimic many conditions. We report a presentation with the sole complaint of hoarseness, never previously described in the literature. Voice returned to normal after surgical removal of the foramen magnum meningioma. 
2	Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity. Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease. 
5	Reactivity of eccentric and concentric coronary stenoses in patients with chronic stable angina. Dynamic coronary stenoses may be the cause of a variable angina threshold and rest angina in patients with chronic stable angina. It has been suggested that eccentric but not concentric coronary artery stenoses have the potential for dynamic changes of caliber in response to vasoactive stimuli. The vasomotor response of eccentric (asymmetric narrowing) and concentric (symmetric narrowing) coronary stenoses to ergonovine (20 micrograms intracoronary or 300 micrograms intravenous) and isosorbide dinitrate (1 mg intracoronary) was studied in 51 patients with chronic stable angina. Diameter of reference segments (angiographically normal segments proximal to the stenoses) and that of eccentric (n = 30) and concentric (n = 35) coronary stenoses that ranged from 50% to 90% luminal diameter reduction were measured by computerized quantitative angiography before and after ergonovine and isosorbide dinitrate. Ergonovine reduced stenosis diameter (by greater than or equal to 10%) in 80% of eccentric stenoses and 42% of concentric stenoses (p less than 0.05). Mean (+/- SEM) diameter reduction with ergonovine was 19 +/- 3% and 9.5 +/- 2% for eccentric and concentric stenoses, respectively (p less than 0.05). Isosorbide dinitrate increased coronary diameter (by greater than or equal to 10%) in 70% of eccentric and 43% of concentric stenoses (p less than 0.05). Mean diameter of eccentric stenoses increased from 1.15 +/- 0.05 to 1.35 +/- 0.06 mm after nitrate (18.6 +/- 2.5%), whereas diameter of concentric stenoses increased from 1.05 +/- 0.05 to 1.14 +/- 0.05 mm (10 +/- 2.5%) (p less than 0.05). Average dilation of reference segments with administration of isosorbide dinitrate and constriction with ergonovine were not significantly different in patients with concentric and eccentric stenoses. 
1	Extragonadal and poor risk nonseminomatous germ cell tumors. Survival and prognostic features. One hundred forty-nine patients with poor risk nonseminomatous germ cell tumors (NSGCT) treated between 1975 and 1988 were studied. Patients were considered poor risk if they had an extragonadal primary site or testicular NSGCT with low predicted probability of achieving a complete response (CR). Primary sites were the testis (99 patients), retroperitoneum (18 patients), and mediastinum (32 patients). Patients with mediastinal NSGCT had lower human chorionic gonadotropin (HCG) (P less than 0.0001) and lactate dehydrogenase (LDH) levels (P less than 0.0001), and more frequent yolk sac elements (P = 0.002). CR rates were 38% for mediastinal, 61% for retroperitoneal, and 38% for testicular primary sites. Mediastinal NSGCT patients more frequently required resection of residual malignancy to attain a CR (6 of 12). Mediastinal NSGCT had the worst event-free survival (P = 0.02). Cox regression analysis identified brain or liver metastases as the most important predictor of event-free survival in poor risk patients. Retroperitoneal NSGCT often have a poor outcome due to advanced presentation, but the likelihood of a CR to therapy can be predicted using criteria applicable to testicular primary tumors. Therefore, not all retroperitoneal NSGCT are poor risk, and retroperitoneal tumors are probably of occult testicular origin. Mediastinal NSGCT have distinct clinical and pathologic features, do not respond as well to chemotherapy, relapse more frequently, and have the worst survival. The likelihood of a CR cannot be predicted using criteria developed for primary testicular tumors, suggesting that mediastinal primary NSGCT is a distinct clinical entity. 
5	Mitochondrial encephalomyopathies. The mitochondrial diseases present with great heterogeneity. They are often multisystemic and vary considerably in age at onset, distribution of weakness, severity, and course. Only nonthyroidal hypermetabolism has a distinctive clinical presentation. Therefore, attempts at classification have generated some controversy. This article discusses the general classification that takes into account genetic and biochemical features, which has resulted from the fast pace of biochemical and molecular genetic investigations. 
1	A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. The purpose of this study was to determine the efficacy of autogenous vein grafts as nerve grafts (AVNC) for bridging of small peripheral sensory nerve gaps as compared with direct repair and with conventional nerve grafting techniques (ANG). Patients with painful neuroma or segmental nerve injury of 3 cm were chosen as the test group. Those amenable to direct repair were classified as controls. Between 1982 to 1988, a total of 22 patients were enrolled in this study. A total of 34 nerves were repaired, 15 with a venous nerve conduit, 4 with a sural nerve graft, and 15 with direct repair. Significant symptom relief and satisfactory sensory function return were uniformly observed. The two-point discrimination measurements indicated superiority of direct repair and probably of conventional nerve grafting. However, the universally favorable patient acceptance and the return of measurable two-point discrimination indicates the effectiveness of autogenous vein grafts as nerve conduits when selectively applied to bridge a small nerve gap (less than or equal to 3 cm) on nonessential peripheral sensory nerves. 
5	Obstruction of mechanical heart valve prostheses: clinical aspects and surgical management. One hundred patients (32 male) aged 5 months to 82 years (median 32 years) underwent 106 surgical procedures for 112 mechanical prosthetic valves obstructed by a thrombus (n = 61) or pannus (n = 7), or both (n = 44), between January 1, 1980 and December 31, 1989. The position of the obstructed prosthesis was aortic in 51 patients (48%), mitral in 49 (46%) and both aortic and mitral in 6 (6%). The types of obstructed prosthetic valves were Bjork-Shiley (n = 51), St. Jude (n = 41) and Medtronic-Hall (n = 20). The time interval between valve replacement and obstruction ranged from 6 weeks to 13 years (median 4 years). Of 63% of patients in whom coagulation variables were available at the time of obstruction, 70% were receiving inadequate anticoagulant therapy. In 63% of the procedures the patient was in New York Heart Association functional class IV. Two patients underwent preoperative thrombolysis with incomplete results. Operative procedures included valve replacement (n = 81), valve declotting and excision of pannus (n = 23) and aortic valve replacement and mitral valve declotting (n = 2). The early mortality rate was 12.3% (13 patients), and there was no difference between surgery for mitral prostheses (12.2%) versus aortic prostheses (13.7%). The perioperative mortality rate was 17.5% (11 of 63 patients) in patients in functional class IV and 4.7% (2 of 43 patients) in those in functional classes I to III (p less than 0.05). For valve replacement, the mortality rate was 12% (10 of 81 patients) and for declotting of the prosthesis 13% (3 of 23 patients). 
5	Three-year outcomes for maintenance therapies in recurrent depression. We conducted a randomized 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy. A five-cell design was used to determine whether a maintenance form of interpersonal psychotherapy alone or in combination with medication could play a significant role in the prevention of recurrence. A second question was whether maintaining antidepressant medication at the dosage used to treat the acute episode rather than decreasing to a "maintenance" dosage would provide prophylaxis superior to that observed in earlier trials in which a maintenance dosage strategy was employed. Survival analysis demonstrated a highly significant prophylactic effect for active imipramine hydrochloride maintained at an average dose of 200 mg and a modest prophylactic effect for monthly interpersonal psychotherapy. We conclude that active imipramine hydrochloride maintained at an average dose of 200 mg is an effective means of preventing recurrence and that monthly interpersonal psychotherapy serves to lengthen the time between episodes in patients not receiving active medication. 
5	Simplified technique for control of femoral arterial bleeding after coronary angioplasty. A method of achieving arterial control by inserting an embolectomy catheter through the femoral introducer sheath in the patient with femoral arterial bleeding after PTCA is described herein. This approach allows quick control with less dissection and negligible blood loss. 
5	Beneficial effect of upper thoracic epidural anesthesia in experimental hemorrhagic shock in dogs: influence of circulating catecholamines. The question as to whether reduction of plasma catecholamine concentration contributes to the beneficial effects of upper thoracic epidural anesthesia on survival during hemorrhagic shock was examined. Twenty-six dogs were anesthetized with halothane and nitrous oxide, and blood was withdrawn to reduce the mean arterial blood pressure (MAP) to 40 mmHg. The 12 dogs in group A received both upper thoracic epidural anesthesia before the hemorrhage and intravenous infusion of epinephrine (450 ng.kg-1.min-1) and norepinephrine (150 ng.kg-1.min-1) during hemorrhage. The 14 dogs in group B received none of these. At 20 min after the start of the bleeding, plasma catecholamine concentrations were increased in both groups more than ten-fold. There were no significant intergroup differences with respect to these concentrations at any point during the experimental period. During the 100-min period of hemorrhage, 1 of the 12 animals in group A and 10 of the 14 in group B died. A significant difference in survival was seen between the two groups over the 100-min hypotensive period (P less than 0.01 by the generalized Wilcoxon test). These results suggest that the survival benefit of upper thoracic epidural anesthesia cannot be explained simply by differences in the level of catecholamines in the plasma, and that perhaps differences in the level of catecholamines at the nerve endings or other factors may be more important. 
4	Excimer laser angioplasty during aortocoronary bypass grafting. Laser coronary angioplasty using the 308-nm Excimer laser was successfully performed intraoperatively during coronary artery bypass grafting. It achieved a reduction of the left anterior descending artery stenosis from 99% to 25% as seen on angioscopy, without evidence of vascular perforation or intimal disruption. The Excimer laser offers the opportunity for intraoperative endovascular remodeling and recanalization and has a potential role as an adjunct to existing standard coronary artery bypass grafting protocol. 
1	Relationship between blood plasma prostaglandin E2 and liver and lung metastases in colorectal cancer. The relationship of prostaglandin E2, of which a large amount is produced in various neoplasms, and hematogenous distant metastases was investigated in a total of 44 colorectal cancer patients because of its varied pathophysiologic potentials. The authors found significantly high levels of PGE2 in local venous blood draining the carcinoma and in peripheral blood in cases with liver or lung metastasis, as well as a significantly large amount of PGE2 production in the carcinoma tissue. The results suggest that increased local blood PGE2 could enhance the metastasis formation, and increased peripheral blood PGE2 may be useful in the detection of such metastasis in colorectal cancer. 
3	Magnetic resonance imaging of radiation optic neuropathy. Three patients with delayed radiation optic neuropathy after radiation therapy for parasellar neoplasms underwent magnetic resonance imaging. The affected optic nerves and chiasms showed enlargement and focal gadopentetate dimeglumine enhancement. The magnetic resonance imaging technique effectively detected and defined anterior visual pathway changes of radionecrosis and excluded the clinical possibility of visual loss because of tumor recurrence. 
5	Spontaneous renal rupture during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis during pregnancy has been previously reported in 16 cases. In the case we describe in this report, the patient initially had right flank pain and nausea for 48 hours, which progressed to severe abdominal symptoms that necessitated exploratory laparotomy. Cystoscopic placement of a ureteral stent relieved the obstruction and allowed spontaneous healing of the renal pelvis. Dilatation of the urinary collecting system commonly occurs during pregnancy. Spontaneous rupture of the renal parenchyma or renal pelvis, however, is unusual and often associated with diseased kidneys. Our case is the 8th one of spontaneous rupture of the renal collecting system with no identifiable underlying pathologic condition and the 17th case of spontaneous renal rupture overall. 
4	In vitro and in vivo effects within the coronary sinus of nonarcing and arcing shocks using a new system of low-energy DC ablation. DC shocks within the coronary sinus have been abandoned because of the risk of cardiac rupture and tamponade. Catheter ablation using DC energy to electrodes straddling the ostium of the coronary sinus, when used clinically, has been reported to result in cardiac tamponade in as many as 16% of patients. A new system of energy delivery maximizes voltage while decreasing the undesirable effects caused by barotrauma. This system includes 1) a low-energy ablation power supply with a brief time-constant capacitive discharge that delivers up to 40 J and 3,000 V and 2) a low-energy ablation catheter with a contoured distal electrode. We performed in vitro and in vivo studies of this new system and compared arcing shocks with nonarcing shocks. Ablations were performed using unipolar distal shocks (D) and unipolar shocks to both electrodes made electrically common (P-D). In vitro studies were done in a large tank filled with physiological saline while recording voltage, current, and pressure. High-speed cinematography (32,000 frames/sec) of shocks of 10-40 J permitted detailed analysis of the vapor globe. Anodal shocks of less than 20 J showed no arcing or only minimal vapor globe formation. For D and P-D anodal shocks of 40 J, the diameters of the vapor globe were 31 and 22 mm, respectively, corresponding to pressure recordings of 11 and 4.9 atm. The pressure rise lasted less than 50 mu sec. In vivo studies involved 18 dogs that received nonarcing shocks (one to six shocks of 15 J) and 18 dogs that received arcing shocks (one to three shocks of 40 J). Each group was divided between D and P-D shocks; catheter ablation was performed at a mean +/- SEM distance of 2.94 +/- 0.92 cm within the coronary sinus. All dogs tolerated the procedure without cardiac rupture or tamponade. When killed 2-4 days later, the dogs had edema and hyperemia or hemorrhage in the area of the coronary sinus. We compared the effects of multiple (three to six) nonarcing shocks with the effects of one to three arcing shocks. Disruption or rupture of the coronary sinus within the epicardial fat space occurred in two of 12 dogs (17%) with multiple nonarcing shocks but in 13 of 18 dogs (72%) with arcing shocks (p less than 0.003). Occlusion of the coronary sinus occurred in two of 12 dogs (17%) with multiple nonarcing shocks and in nine of 18 dogs (50%) with arcing shocks (p less than 0.06).(ABSTRACT TRUNCATED AT 400 WORDS). 
2	Anorectal sensory and motor function in neurogenic fecal incontinence. Comparison between multiple sclerosis and diabetes mellitus. We measured anorectal sensory and motor function in 11 patients with multiple sclerosis and fecal incontinence, 11 continent patients with multiple sclerosis, 10 diabetics with fecal incontinence, and 12 healthy control subjects. The threshold volume at which patients with multiple sclerosis and fecal incontinence experienced rectal sensation was higher than that in healthy controls (42.7 +/- 6.2 mL vs. 13.3 +/- 2.8 mL; P less than 0.01) and was similar to that in incontinent diabetics (36.5 +/- 5.7 mL). Patients with multiple sclerosis and incontinent diabetics also showed increased thresholds of phasic external sphincter contraction compared with controls (P less than 0.05). Diabetics with incontinence had reduced resting and maximal voluntary anal sphincter pressures compared with controls (P less than 0.05), whereas patients with multiple sclerosis and incontinence showed only decreased maximal voluntary anal sphincter pressures (P less than 0.01 vs. controls and diabetics). Incontinent patients with multiple sclerosis also required smaller volumes of rectal distention to inhibit internal sphincter tone compared with diabetics and controls (P less than 0.01). Decreased maximal voluntary squeeze pressures were less severe in continent patients with multiple sclerosis than in incontinent patients with multiple sclerosis. We conclude that impaired function of the external anal sphincter and decreased volumes of rectal distention to inhibit the internal anal sphincter or both may contribute to fecal incontinence in multiple sclerosis. In addition, increased thresholds of conscious rectal sensation in some incontinent patients with multiple sclerosis and diabetes mellitus may contribute to fecal incontinence by impairing the recognition of impending defecation. 
5	Characterization of glial involvement in proliferative diabetic retinopathy. We studied the relationship of glial cells and other supporting tissues associated with newly formed blood vessels in proliferative diabetic retinopathy. Seventeen postmortem, freshly enucleated eyes from diabetic patients and 34 epiretinal and preretinal membranes removed during vitreous surgery for proliferative diabetic retinopathy were analyzed using the peroxidase-antiperoxidase method for light microscopy and protein A/gold labeling of ultrathin cryosections for transmission electron microscopy in addition to routine transmission and scanning electron microscopy. We found that glial cells are commonly and characteristically found in elevated diabetic proliferations and present at the vitreous surface. The newly formed blood vessels, however, were not seen at the edge of elevated epiretinal and preretinal membranes in early and intermediate stages. These results suggest that glial cells may extend beyond the vascularized areas of the proliferative tissue. It is possible that glial cells and their extracellular matrix contribute to the framework leading to the development of new blood vessels. 
1	Clinical trials. A family physician's perspective. Primary care specialists diagnose and manage a wide variety of problems. Cancer is one relatively small part of the practice of these clinicians. Patients with newly diagnosed cancer usually are referred to surgical specialists. Primary care physicians often determine future events after surgical care. Oncologists may or may not be consulted depending on tumor type and past experiences of the physician, patient, and patient's family. Many primary care physicians think that chemotherapy regimens given empirically have little if any scientific evidence to support their use. Side effects of cancer treatment regimens often cause suffering and profoundly effect quality of life. There is a lack of communication between oncologists and primary care physicians. Dialogue between oncologists and primary care doctors may help solve communication problems. Clinical trials help determine which treatments are effective. Many clinical trials are conducted at the community hospital level. Most primary care physicians support clinical trials once they know about them. Education activities should be directed at promoting patient referral for participation in clinical trials. 
5	The effect of screws and pegs on the initial fixation stability of an uncemented unicondylar knee replacement. Two uncemented unicompartmental tibial components were examined for initial fixation stability. A conventional design that employed a single posteriorly angled peg was compared with a new design that was held in place by cancellous bone screws. The components were implanted into the medial condyles of 12 preserved human tibiae, and a cyclic load was first applied anteromedially and then posteromedially. The screwed implants failed at significantly higher loads (1634.8 +/- 121.6 N, mean +/- standard error of the mean) than the pegged implants (1103.3 +/- 152.0 N). On application of a 19.6-N preload, the screwed implants moved significantly less than the pegged implants. Although the differences in micromotion and subsidence were not always significant, there were definite trends. The screwed implants had much lower levels of temporary and permanent displacement compared with the pegged implants for all load levels from the initial load of 245.2 N up to and including the failure load. When the motion that resulted from moving the load from the anterior position to the posterior position was examined, the screwed implant's average total motion was less than 10 microns compared with almost 135 microns for the pegged implant after the 245.2-N load cycle. For the cycle before failure, the screwed implant's average motion increased to less than 29 microns, whereas the pegged implant's average total motion was almost 354 microns. From this information it appears clear that screws provide better initial fixation stability than angled pegs for uncemented unicondylar tibial components. 
5	Improved postoperative course after spinous process segmental instrumentation of thoracolumbar fractures. This article compares the postoperative course of 40 patients who had Harrington instrumentation with 40 patients who had Harrington instrumentation and interspinous process segmental instrumentation of unstable thoracolumbar fractures and reviews the findings. The two groups of patients were otherwise homogeneous, and average operative time, total blood loss, and days to oral intake were similar for both groups of patients. On average, however, patients undergoing interspinous process segmental instrumentation were out of bed sooner (4.5 versus 7.7 days, P less than 0.0001), discharged sooner (32 versus 38 days, P less than 0.079), and brace-free earlier (2.1 versus 5.9 months, P less than 0.001) and had fewer fixation-related complications than did patients undergoing Harrington instrumentation alone. Comparison of average hospital costs documented a savings of $5,160 for the typical patient undergoing interspinous process segmental instrumentation. 
5	Low-dose sufentanil in major surgery. The purpose of this study was to assess the efficacy of sufentanil 1 micrograms.kg-1 during N2O-O2 and intermittent isoflurane anaesthesia in major non-cardiac surgery. Thirty-one patients (18 females, 13 males; mean age 47 yr), undergoing cholecystectomy received a 1 microgram.kg-1 bolus of sufentanil before the induction of anaesthesia with thiopentone. On average, three sufentanil increments were administered, to a total (bolus + maintenance) dose of 1.5 micrograms.kg-1. Cardiovascular stability was not achieved in eleven patients who then were given isoflurane. The arterial pressure decreased after sufentanil (P less than 0.05), reaching a nadir (mean 108/65 mmHg, heart rate 63 bpm) at one minute post-incision. Clinically important hypertension or hypotension did not occur in any patient. One patient, receiving beta-blocker therapy, required atropine to control bradycardia. Postoperative respiratory depression did not occur in patients who received less than one micrograms.kg-1.hr-1 with the last increment being given more than 20 minutes before the end of anaesthesia. Slight respiratory depression in the recovery room was reported in one patient, who had received a total of 1.3 micrograms.kg-1.hr-1 of sufentanil, and the last sufentanil increment 24 min before the end of surgery. The most frequently reported side-effects were nausea (35 per cent) and vomiting (23 per cent). Induction, maintenance and recovery from anaesthesia were rated as "good" in 87, 87, and 74 per cent of the cases, respectively, and "satisfactory" in the remainder. We conclude that this technique is valuable to assure good protection of the cardiovascular system without undue respiratory depression during recovery. 
1	Ampullary tumor caused by metastatic renal cell carcinoma. In this paper we report the case of a renal cell carcinoma (RCC) metastatic to the ampullary region. The patient presented with severe anemia due to blood loss from the ampullary tumor 11 years after nephrectomy for the primary renal cancer. The diagnosis was established by means of endoscopy and biopsy. 
1	Epidemiologic perspectives on life-style modification and health promotion in cancer research. The clinical, patient-oriented focus of medicine and psychology is contrasted with the epidemiologic (public health) approach in assessing the role of life-style factors and health promotion in cancer research. The unifying host-agent-environment epidemiologic paradigm is applied to contemporary cancer prevention issues, principally smoking cessation and dietary modification, to demonstrate differences in inferences, prevention strategies, and research opportunities. An integration of population-based approaches with the dynamics of patient behavior and risks for cancer is especially salient when considering the role of psychosocial stress and personal and social resources. The social epidemiologic perspective, the study of the psychosocial determinants of physical health status, offers one approach for resolving the outlined differences in perspectives and is particularly relevant for understanding the etiology of life-style behaviors and how they might be altered. 
1	Tumor-associated neurological dysfunction prevented by lazaroids in rats. The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier permeability and tumor-associated neurological dysfunction was evaluated in a brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2-methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on Days 6 through 10 following implantation. Neurological function and vascular permeability were assessed on Day 10. Methylprednisolone and U-74006F were equally effective at preventing neurological dysfunction compared to the control group (p less than 0.01); U-78517F was slightly less effective than U-74006F and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction. Delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability (p less than 0.006) while U-74006F and U-78517F had no effect on permeability. This suggests that U-74006F and U-78517F prevented tumor-associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries, and that U-74006F or U-78517F could prove useful in the treatment of brain tumors. 
5	Population aging patterns: the expansion of mortality. We used the hypothesis of mortality compression as a framework to examine patterns of mortality from 1962 to 1984. Data from national vital statistics records were used for analysis of the changing age at death for percentiles of the population. Data from the Social Security Administration and the U.S. Census Bureau were used to calculate the force of mortality. The mean age at death for all percentiles, including the oldest groups, has risen during the interval. Examination of the coefficient of variation for the mean age at death suggests that there is a relative increase in the variability of age at death among the oldest old. The available data do not fit a hypothetical sequence of normal density distributions with an increasing mean and declining standard deviation. The force of mortality in those over 85 years appears to be decreasing in a pattern similar to that for those under 85 years. Current mortality patterns suggest an "expansion," rather than compression, of mortality at the oldest ages. Further refinement of these observations, with improved data on mortality among the oldest old, will be helpful in delineating mortality patterns. 
5	Arsenic poisoning: acute or chronic? Suicide or murder? The case of the death by arsenic poisoning of a 62-year-old white man is presented. One year prior to death, he developed intermittent bouts of severe gastroenteritis with vomiting and diarrhea, hyperpigmentation and keratosis of the skin, neutropenia, and Guillain-Barre-like neuropathy for which he was hospitalized several times. Urine test results 6 months prior to death indicating 36 mg/L arsenic were believed to be in error. At the patient's last admission, he appeared in the emergency room with severe gastroenteritis, hypotension, and dehydration. He died 3 days later. Antemortem as well as autopsy specimens revealed elevated arsenic concentrations. Arsenic micrograms/g analysis by neutron activation of hair pulled from the man's head revealed by centimeter segmental analysis proximal to distal: 226, 104, 28, 56, 41, 40, and 74. The wife of the decedent was charged with murder by arsenic poisoning of this, her fifth, husband. The defense alleged that the decedent had committed suicide. The judge awarded a directed verdict of "not guilty." Particulars of the medical, toxicological, and investigative findings are presented. 
2	Oral manifestations of Crohn's disease. An analysis of 79 cases. We report four new cases of oral manifestation in Crohn's disease (CD) and evaluate 75 reported cases for morphology and site of oral and intestinal manifestations of CD, clinical manifestation, and treatment. Oral CD was the presenting symptom in 43 of 72 (60%) patients and relapsed in 34 of 60 (57%). Median age at presentation was 22 (range 6-57) years, and males were affected more often (1.85:1, male:female ratio). From a total of 228 oral lesions in 79 patients, lips (57 lesions), gingiva (40 lesions), vestibular sulci (31 lesions), and buccal mucosa (25 lesions) were the sites most frequently affected. Edema (62 lesions), ulcers (57 lesions), and polypoid papulous hyperplastic mucosa (45 lesions) were the most common type of lesions. The rate of granuloma detection was high in oral (67-77%) and intestinal lesions (45-71%). A total of 66 courses of drug therapy in 51 patients were analyzed. Complete remission of oral symptoms was achieved by systemic steroids and/or azathioprine in 13 of 26 (50%) patients, whereas strictly topical treatment with steroids resulted in complete remission of oral symptoms in 7 of 12 (58%). We conclude that oral CD exhibits a characteristic morphologic appearance, as often as not preceding intestinal symptoms in adolescents and young adults. Thus, patients with orofacial granulomatosis CD should be vigorously searched for by complete gastrointestinal endoscopic investigation. Oral CD may cause disabling pain and facial distortion, and results of treatment remain unrewarding. In the absence of data from controlled therapeutic trials, systemic steroids and/or azathioprine are recommended if topical treatment has failed to control symptoms. 
5	Trans-scleral application of a semiconductor diode laser. We used a diode laser with an output power of 1 W through a fiberoptic light pipe (200 microns diameter) to deliver laser energy through the sclera of pigmented rabbits. Ciliary body destruction occurred with energy levels of 300-400 mW and exposure time of 0.5 sec. Retinal photocoagulation was achieved with energy levels of 200-500 mW in 0.5 sec. Histologic examination of acute lesions demonstrated thermal destruction of ciliary body processes and retina. Chorioretinal scar formation was observed clinically and histologically within 2-3 weeks. Our data indicate that the transscleral diode laser may be used for destruction of the ciliary body processes or peripheral retinal coagulation in pigmented eyes. 
5	Cerebrospinal fluid fistula and endoscopic sinus surgery. Seven cases of cerebrospinal fluid fistulae occurring as a result of endoscopic sinus surgery in a total of 800 ethmoidectomies are discussed, along with 1 case referred for consultation. One cerebrospinal fluid fistula was intrasphenoid, 4 were posterior ethmoid/base of skull, 2 were anterior ethmoid, and 1 was ethmoid cribriform. Six of 8 fistulae were closed endoscopically. The sphenoid sinus cerebrospinal fluid fistula was closed successfully with fibrin glue and Gelfoam. Five cerebrospinal fluid fistulae were closed successfully using fascia, muscle, and Gel-foam. Two cerebrospinal fluid fistulae were treated conservatively, and only 1 stopped. Anatomic and technical aspects related to the occurrence of cerebrospinal fluid fistulae are discussed. Management and treatment of cerebrospinal fluid fistulae occurring during and after endoscopic sinus surgery is emphasized. When identified intraoperatively or delayed, cerebrospinal fluid fistulae can be managed successfully by endoscopic technique. 
4	Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction. This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo. We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD. Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD. CHF was particularly frequent in the patients with LVD who were randomized to diltiazem. Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF. This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD. 
1	Lack of effect of chronic administration of oral beta-carotene on serum cholesterol and triglyceride concentrations. Previous studies suggest that chronic oral administration of retinol and other retinoids causes elevation of plasma triglyceride concentrations. The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, we studied 61 subjects over 12 mo while they were enrolled in a skin-cancer-prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/d orally (n = 31). At study entry and 1 y later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, HDL cholesterol, retinol, and beta-carotene. Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 +/- 47 nmol/L in the placebo group and 4279 +/- 657 nmol/L in the active-treatment group. Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in HDL cholesterol. Daily oral administration of 50 mg beta-carotene/d did not affect plasma lipid concentrations. 
3	Spinal man after declaration of brain death Complex spinal automatism in a patient who was declared brain dead is described. These movements tend to appear once cerebrospinal shock has abated. We postulate that these manifestations are a reflection of the physiological potential of the isolated spinal cord. These spinal movements should be included in the revised guidelines for the determination of cerebral death. 
5	Application of INSTAT hemostat in the control of gingival hemorrhage in the patient with thrombocytopenia. A case report. Gingival bleeding in the patient with thrombocytopenia can be a difficult management problem. Primary therapy with platelet transfusions may not be sufficient to control the hemorrhage and adjunctive local therapy may be required. Currently, few local management techniques can effectively control this problem. INSTAT collagen absorbable hemostat can be used as a local adjunct with platelet transfusions and has certain application advantages over topical thrombin and microfibrillar collagen. Two successful techniques of INSTAT application to control gingival hemorrhage in a patient with severe thrombocytopenia in leukemic relapse are described. 
5	Prevalence of chronic bronchitis among US Hispanics from the Hispanic Health and Nutrition Examination Survey, 1982-84. In the Hispanic Health and Nutrition Examination Survey (HHANES), Puerto Ricans had a higher age-adjusted prevalence of self-reported chronic bronchitis (2.9 percent, 95% CI = 2.2, 3.6) than Mexican Americans (1.7 percent, 95% CI = 1.3, 2.1) or Cubans (1.7 percent, 95% CI = 0.9, 2.5). The prevalence of chronic bronchitis was at least 2 times higher in smokers as compared to nonsmokers among Puerto Ricans and Cubans, but not for Mexican Americans. 
5	Patterns of neuropsychological impairment after severe blunt head injury. A consecutive series of 100 subjects with severe blunt head injuries was followed up 6 years after trauma. Neuropsychological test performances of 82 subjects and of a noninjured control group were analyzed by two principal components analyses (PCAs). Each PCA extracted 15 factors relating to a range of cognitive impairments, as well as neuropsychological features consistent with posttraumatic personality changes. Measures identified by the PCAs were applied to 85 head-injured subjects in the series to examine the incidence of impairment in four neuropsychological areas: disorders of learning and memory, neuropsychological features consistent with posttraumatic personality change, slowness in rate of information processing, and a range of basic neuropsychological skills. Overall, impairments occurred in 70% of the series. Disorders of learning and memory were the most common type of deficit (56.5%), with disturbances in basic neuropsychological skills the least frequent (16.5%). Variability among subjects with respect to the types and combinations of neuropsychological impairments was a characteristic feature of this clinical group, but the largest proportion (one-third) demonstrated isolated impairments. The implications of the incidence and selectivity of neuropsychological impairments are discussed. 
5	Reduced platelet aggregability and thromboxane release after rebleeding in patients with subarachnoid hemorrhage. Serial blood samples were obtained from 80 patients with subarachnoid hemorrhage (SAH) to study adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release. The goal of the investigation was to detect whether reduced platelet function is involved in rebleeds. Seventeen patients (21%) suffered a rebleed, six of those experiencing their first rebleed within 24 hours after SAH. Therefore, most platelet function studies were performed after rebleeds. Thromboxane release was lower in patients with rebleeds than in the others, both before and after rebleeding, although statistical significance was reached only in samples collected after rebleeds. Patients rebleeding within 24 hours after SAH had lower platelet aggregability (p = 0.037) than patients without a rebleed in the samples taken within 3 days after SAH. The results suggest that reduced platelet aggregability and thromboxane release are involved in rebleeds following primary SAH. 
4	Outcome of renal replacement treatment in patients with diabetes mellitus. OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients. 
1	Diagnosis of malignant cardiac disease by endomyocardial biopsy Among oncology patients, endomyocardial biopsy has been used primarily for the evaluation of anthracycline cardiotoxicity. In addition, however, endomyocardial biopsy may be useful for the detection of malignant cardiac neoplasms. Between 1982 and 1989, metastatic involvement of the heart was diagnosed by endomyocardial biopsy in seven patients at our institution. All except one of these patients were older than 50 years of age and had dyspnea as an initial symptom, and all had a known malignant lesion. Results of endomyocardial biopsy confirmed cardiac involvement by a hematologic malignant lesion in four patients and metastatic melanoma in two patients. In one patient, who had a history of breast cancer and lymphoma, a metastatic neoplasm of uncertain differentiation was observed. Myocyte damage was evident in endomyocardial biopsy specimens from two of the four patients with hematologic malignant disease. Endomyocardial biopsy was performed to confirm the possibility of metastatic involvement in five patients; in the other two, endomyocardial biopsy was performed to determine whether anthracycline cardiotoxicity was present, and metastatic involvement was unanticipated. 
2	Laparoscopic cholecystectomy Laparoscopic cholecystectomy is a new endoscopic technique that has diffused throughout the surgical community with great rapidity. Although the DATTA panelists considered the procedure appropriate with respect to both its safety and effectiveness, recognition was made that there are no comparative trials of this technique vs open cholecystectomy and virtually no literature on complication rates. The Society of American Gastrointestinal Endoscopic Surgeons has developed minimal credentialing criteria for determining competence in laparoscopic surgery. This includes completion of an approved residency training in general surgery, training in laparoscopic technique either by a surgeon experienced in this procedure or by completion of an approved course in the technique requiring hands-on laboratory practice, and observation or proctoring of an actual surgical procedure. Many of the DATTA panelists (35 of 40 [87.5%]) reiterated the importance of requiring that the procedure be performed first with animals and that subsequent laparoscopic procedures on patients be done under the supervision of an expert in laparoscopic cholecystectomy. 
5	Corticosteroids for acute, severe asthma. Corticosteroids have been used in the therapy of acute, severe asthma since the early 1950s. Numerous randomized, double-blind, placebo-controlled trials in adults and children have proven corticosteroids to be efficacious. Only the results from less rigorously designed trials have failed to show a beneficial effect. The onset of response, dose, and mode of administration have been relatively well defined; however, other aspects (i.e., duration of therapy, need to taper the dose, and risks of multiple short bursts) require further study. Early institution of corticosteroids in well-defined patient populations will decrease the need for hospitalizations. However, administration of corticosteroids to every patient presenting to the clinician's office or emergency room prior to aggressive bronchodilator therapy is unwarranted. All patients demonstrating an incomplete response or the inability to maintain a complete response following one to two hours of aggressive bronchodilator therapy should receive a course of corticosteroids. Courses as short as three to five days have proven efficacy in outpatients, whereas hospitalized patients usually are treated for seven to ten days. The duration of therapy depends on the individual rate of response. 
3	HTLV-I viral-associated myelopathy after blood transfusion in a multiple trauma patient. This may be the first documented case in the United States and in the orthopedic literature of transfusion-transmitted human T-cell leukemia virus Type I (HTLV-I)-associated myelopathy (HAM). Progressive myelopathy occurred in a 58-year-old white man with serologic and molecular evidence of HTLV-I infection after multiple trauma and subsequent transfusion with multiple units of banked blood products. Symptoms of myelopathy occurred 15 months after the transfusions. Myelopathy from HTLV-I infection simulates a disorder of orthopedic interest. Physicians should be aware of the symptoms of HAM and unexplained myelopathy. 
2	Dental enamel defects in first-degree relatives of coeliac disease patients. To find out whether dental changes can be used to screen for coeliac disease among apparently healthy relatives of patients with the disorder, 56 healthy first-degree relatives of such patients were subjected to dental examination and small bowel biopsy. 25 had coeliac-type general permanent-tooth enamel lesions. All 7 who had histological evidence of coeliac disease also had enamel lesions. The finding that enamel defects may occur without small bowel changes must be borne in mind in screening. The coeliac-type enamel changes were strongly associated with HLA-DR3, and most of the DR3 alleles belonged to the extended haplotype A1; B8; DR3 group. 
1	In vitro rosetting, cytoadherence, and microagglutination properties of Plasmodium falciparum-infected erythrocytes from Gambian and Tanzanian patients. To understand the molecular mechanisms that lead to sequestration of red blood cells infected with mature stages of Plasmodium falciparum and to examine the relevance of earlier studies on adherence properties of laboratory-derived P falciparum parasites to the natural parasite population, we analyzed Gambian and Tanzanian isolates for in vitro cytoadherence and antibody-mediated microagglutination. Eighteen cryopreserved isolates of ring-stage parasites were cultured for 20 to 30 hours in vitro, in the patients original erythrocytes, to the trophozoite and schizont stage. All parasites were positive in the microagglutination assay with at least one of four African hyperimmune sera. In a rosetting assay, only 2 of the 18 isolates were strongly positive (35% and 41% of parasitized erythrocytes with more than two uninfected cells bound). Thirteen isolates showed either intermediate (5% to 18%) or low (less than 5%) rosetting while three isolates did not form rosettes. Infected cell-binding of the different isolates to immobilized CD36 or thrombospondin, or C32 melanoma cells correlated with the percentage of mature parasites in the blood samples (r = .932 for CD36, r = .946 for thrombospondin, and r = .881 for C32 melanoma cells). There was a high correlation between binding to CD36 and thrombospondin (r = .982). The extent of infected cell rosetting with uninfected cells in these blood samples was not correlated with these other receptor properties. We also observed coexpression of rosetting and cytoadherence receptors on the same parasitized erythrocytes. 
5	Prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal end of the tibia. A report of sixteen cases. The results of a specific type of prosthetic reconstruction of the knee (total replacement arthroplasty) after resection of a sarcoma of the proximal part of the tibia in sixteen patients were retrospectively reviewed. The diagnosis was stage-IIB osteogenic sarcoma in nine patients, stage-IIB malignant fibrous histiocytoma in three patients, and stage-IB sarcoma of various types in four patients. The length of tibial resection ranged from 100 to 257 millimeters. Of the eleven patients who were available for functional examination (mean duration of follow-up, sixty-three months), three patients had an excellent result, seven had a good result, and one had a fair result. Of the five patients who were not available for functional testing, one who was doing well was lost to follow-up at eighty months, one had died of metastases at sixteen months, and three had had a secondary amputation for infection or for loosening of the prosthesis. 
3	Operative and conservative treatment of moderate spondylolisthesis in young patients. We made a retrospective study of 149 children and adolescents with moderate spondylolisthesis (slip less than or equal to 30%), 77 treated by fusion and 72 conservatively at an average follow-up of 13.3 years. Both groups were fully comparable with regard to age at diagnosis, sex distribution (46% girls), and mean slip. The patients who were treated operatively had more pain before treatment and showed more initial progression of the slip. They had better clinical results and less pain at latest review, but the total progression of the slip over the whole follow-up showed no statistical differences between the two groups. Patients with a pseudarthrosis after attempted fusion had had a longer period of postoperative pain, but at the latest review had no more pain than those with sound fusion. None of those treated conservatively came to fusion later and the long-term results in 18 patients who had refused the advised operation were no worse than those for other conservatively treated patients. Our results suggest that a moderate grade of spondylolisthesis in adolescents usually has a benign course. It seems that spontaneous segmental stabilisation occurs as a result of degeneration of the disc at the level of the slip. 
5	Endothelium-derived relaxing factors. A perspective from in vivo data. We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions. 
5	Anatomic, metabolic, neuropsychological, and molecular genetic studies of three pairs of identical twins discordant for dementia of the Alzheimer's type. Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation. 
3	Alcoholic blackouts: legal implications. Alcoholic blackouts are defined as the temporary, complete inability to form long-term memory as the result of a high blood alcohol level. This means that a neuron-to-neuron system has been blocked. Since that is the case, such central nervous dysfunction should have legal implications, both from the blackout itself and also from the fact that this degree of neural interference in one system is at least suggestive that other dysfunction may be present. The subject of blackouts is updated with recent developments in neuroscience. The legal significance of the blackout is examined in enough depth to allow for further discussion and exploration. 
2	"Healed" experimental gastric ulcers remain histologically and ultrastructurally abnormal. The present study was designed to assess histologic and ultrastructural features of gastric mucosa in the areas of grossly healed ulcers (acetic acid-induced gastric ulcers) in rats. The specific question we studied was whether the structure and cellular composition of the gastric mucosa in an area of grossly healed ulcer were fully restored. Eighty Sprague-Dawley rats underwent laparotomy; 100% acetic acid was applied to the lower gastric corpus serosa for 30 s and the abdomen was closed. The stomachs were reopened after 2 weeks or after 2, 3, or 4 months. Standardized gastric wall specimens from the area of grossly healed ulcers were obtained, processed, and evaluated by light microscopy and by transmission electron microscopy. The gastric mucosa of grossly healed ulcers demonstrated re-epithelialization at each study time but the mucosa beneath the surface epithelium displayed prominent histologic and ultrastructural abnormalities. Two different patterns of scar could be distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% reduction vs. normal), with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; or (b) the mucosa displayed ballooning dilatation of gastric glands, reduction in the microvascular network, and poor differentiation of glandular cells. We conclude that (i) the subepithelial mucosa of grossly healed gastric ulcer displays disorganized restoration of glandular and vascular structures and remains histologically and ultrastructurally abnormal; (ii) these abnormalities may interfere with oxygenation, nutrient supply, and with mucosal resistance and defense, and therefore could be the basis for ulcer recurrence. 
5	Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients Histopathologic examination was performed in 20 patients undergoing antemortem coronary angioplasty. Thirty-four lesions were dilated and the interval between coronary angioplasty and death ranged from several hours to 4 years. Intimal proliferation of smooth muscle cells, as a major cause of restenosis, was observed in 83% to 100% of 28 lesions examined 11 days to 2 years after coronary angioplasty. In 20 lesions examined within 6 months, proliferating smooth muscle cells were predominantly of the synthetic type and there was abundant extracellular matrix substance chiefly composed of proteoglycans. In eight lesions examined between 6 months and 2 years, contractile type smooth muscle cells were dominant and extracellular matrix was composed chiefly of collagen. In three lesions examined after 2 years, evidence of antemortem coronary angioplasty was hardly identifiable and these lesions were almost indistinguishable from conventional atherosclerotic plaque. These temporal changes in histologic pattern provide a pathologic background for clinical reports that restenosis is predominantly found within 6 months after coronary angioplasty. Morphometric analysis revealed that the extent of intimal proliferation was significantly greater in lesions with evidence of medial or adventitial tears than in lesions with no or only intimal tears. 
5	Electrophysiologic effects of exogenous phosphocreatine in cardiac tissue: potential antiarrhythmic actions. The cellular electrophysiologic effects of exogenous phosphocreatine (PCr) were analyzed to ascertain its purported antiarrhythmic properties during myocardial ischemia and reperfusion. Transmembrane potentials were recorded from isolated guinea pig papillary muscles and Purkinje fibers studied in vitro. Under control, normoxic conditions, 10 mmol/L PCr significantly increased the action potential duration (measured at 90% of repolarization) in ventricular muscle by 14.6 +/- 3.3 msec and the effective refractory period by 11.5 +/- 3.8 msec (both p less than 0.01). Under ischemic-like conditions (hypoxia, lactic acidosis, elevated [K+]o, zero substrate) PCr had no effect. Phosphocreatinine, a related compound that is not a direct substrate in the creatine kinase reaction, acted similarly to PCr suggesting that alterations induced by PCr did not involve a change in the energy state of cells. However, PCr reduced free [Ca2+]o by nearly 20%, and its electrical effects under normoxic conditions could be largely reversed by a concomitant 20% increase in [Ca2+]o. In Purkinje fibers superfused with low [K+]o-Tyrode's solution to elicit conditions of Ca2+ overload, delayed afterdepolarizations and triggered responses were reversibly inhibited by PCr. These data suggest that the antiarrhythmic effects of PCr in situ may involve prolongation of the effective refractory period in nonischemic tissue or attenuation of membrane changes elicited by Ca2+ overload in ischemic cells. The mechanism by which PCr produces these effects may be related in part to changes in extracellular Ca2+ composition. 
4	Does carotid restenosis predict an increased risk of late symptoms, stroke, or death? The identification of carotid restenosis as an unexpected late complication of carotid endarterectomy has prompted concerns regarding its importance as a source of new cerebral symptoms, stroke, and death. To investigate these concerns, we analyzed a consecutive series of 507 patients undergoing 566 carotid endarterectomies, each documented as technically satisfactory. Post-operative duplex Doppler examination data at 3 days, 1, 3, 6, 12 months, and annually thereafter in 484 arteries (85.5%) permitted classification of these arteries according to the most severe degree of postoperative stenosis: normal (n = 306); 1% to 19% (n = 89); 20% to 50% (n = 40); more than 50% (n = 49, including 8 occluded). The incidence of more than 50% restenosis was 14.5% in female and 7.7% in male patients (p = 0.003). Life table analyses to 10 years revealed a significantly greater life expectancy among those with restenosis (p = 0.05). Stroke was also less likely in patients with restenosis, although this difference did not reach statistical significance. When survival and stroke were both endpoints, the likelihood of patients with more than 50% restenosis remaining alive and stroke free was also greater than the less than 20% stenotic group (p = 0.03). Thus patients with carotid restenosis were less likely than patients with normal postoperative scans to have late symptoms, stroke, or early death. 
2	Peptic ulcer surgery during the H2-receptor antagonist era: a population-based epidemiological study of ulcer surgery in Helsinki from 1972 to 1987. To evaluate the effects of improvements in medical therapy on the incidence of, indications for and operative methods used in peptic ulcer surgery, all cases of primary peptic ulcer surgery among adults in the city of Helsinki in the years 1972, 1977, 1982 and 1987 were analysed. There was a total of 565 such cases in a population which consisted of 5.2 X 10(5) individuals in 1972 and 4.8 X 10(5) individuals in 1987. The introduction of H2-receptor antagonists in 1979 was associated with a fall in the annual incidence of elective duodenal ulcer operations, from 15.5 to 6.7 per 10(5) individuals, and a fall in the annual incidence of elective gastric ulcer operations, from 9.4 to 3.1 per 10(5) individuals (P less than 0.05). The decrease was greatest among males with duodenal ulcer. In contrast, the annual incidence of emergency surgery for ulcer haemorrhage and perforation (all types of ulcers) remained relatively stable, varying from 7.2 to 10.2 per 10(5) inhabitants over the observation period (n.s.). The mean age of patients undergoing elective surgery remained essentially unchanged. The mean age of patients undergoing emergency surgery increased. The decrease in the annual incidence of elective duodenal ulcer surgery occurred mainly in relation to proximal gastric vagotomy. There was a concomitant relative increase in the incidence of gastric resection. The types of operative procedures used in cases of pyloric, prepyloric and gastric ulcer remained unchanged over the years 1972 to 1987. 
4	Mitral valve repair by replacement of chordae tendineae with polytetrafluoroethylene sutures. Expanded polytetrafluoroethylene sutures have been used for replacement of diseased chordae tendineae during reconstructive procedures on the mitral valve in 43 patients. There were 28 men and 15 women whose mean age was 55 years, range 21 to 76. Three fourths of the patients were in New York Heart Association class III or IV. Replacement of primary chordae tendineae of the anterior leaflet was performed with 4-0 or 5-0 polytetrafluoroethylene sutures. A double-armed suture was passed twice through the fibrous portion of the papillary muscle head and tied down. Each arm of the suture was brought up to the free margin of the leaflet and passed through the area where the native chorda was attached. After the lengths of the two arms were adjusted, the ends were tied together on the ventricular side of the leaflet. Thirty patients had degenerative disease of the mitral valve; the incompetence was due to prolapse of the anterior leaflet in 14 patients and prolapse of the anterior and posterior leaflets in 16. Eleven patients had rheumatic mitral valve disease: four had stenosis, three had regurgitation, and four had mixed lesions. Two patients had ischemic mitral regurgitation caused by rupture of a papillary muscle head. There were no operative deaths. Patients have been followed up from 5 to 61 months, mean 13. Doppler echocardiographic studies were performed at regular intervals after the operation and revealed normal mitral valve function in most patients There were two failures that necessitated mitral valve replacement: one because of acute mitral regurgitation and the other because of hemolysis. There have been two late deaths, neither one valve related. Replacement of chordae tendineae with polytetrafluoroethylene sutures is simple and allows for reconstruction of the mitral valve in many patients who would otherwise require mitral valve replacement. Because our patients have been followed up for a limited time, the long-term results of this procedure remain unknown. 
5	Mediastinitis following coronary artery bypass surgery: a 3-year review. Twenty cases of mediastinitis after coronary artery bypass graft operations in 1985-1987 were reviewed to determine risk factors. Two distinct clusters with a methicillin-resistant Staphylococcus aureus (MRSA) strain occurred in 1986. One resident was exposed to six cases but to only 5 of 24 controls (P less than .008). Cultures of his nares in January and November 1986 revealed the same MRSA strain as that of the cases. An attempt to eradicate the resident's nasal carriage of MRSA in January 1986 failed; eradication of his carrier state was achieved only after treatment with mupirocin. In a case-control study examining patients exposed to the resident, a prolonged duration of surgery (P less than .05) and a preoperative albumin level of less than 3.0 g/dl (P less than .009) were associated with mediastinitis with this MRSA. For the other 14 mediastinitis patients, who were not exposed to the resident, a preoperative albumin level of less than 3.0 g/dl was also a risk factor (8/14 cases vs. 8/43 controls, P less than .009). Thus, this study suggests that it is important to follow MRSA disseminators and to recognize that preoperative serum albumin levels are a risk factor for mediastinitis. 
1	Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer. An updated analysis. A randomized trial was performed to determine if therapy with tamoxifen (TAM) plus fluoxymesterone (FLU) was more efficacious than TAM alone for postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 (42%) TAM patients and 64 of 119 (54%) TAM plus FLU patients (two-sided P = 0.07). Time to disease progression was better for TAM plus FLU (medians: 11.6 versus 6.5 months; Cox model, P = 0.03). Duration of response and survival were similar in the two treatment arms. Among 97 patients with estrogen receptor (ER) of 10 or greater and 65 years of age or older, there were highly significant advantages for treatment with TAM plus FLU in both response rate and time to progression. Of particular note is that in this patient group TAM plus FLU showed a survival advantage (Cox model, P = 0.05). Although these data require confirmation in a prospective randomized trial, they suggest that there is a substantive therapeutic advantage for TAM plus FLU over TAM alone in elderly women with ER of 10 fmol or greater. 
5	Gender differences in age effect on brain atrophy measured by magnetic resonance imaging. A prospective sample of 69 healthy adults, age range 18-80 years, was studied with magnetic resonance imaging scans (T2 weighted, 5 mm thick) of the entire cranium. Volumes were obtained by a segmentation algorithm that uses proton density and T2 pixel values to correct field inhomogeneities ("shading"). Average (+/- SD) brain volume, excluding cerebellum, was 1090.91 ml (+/- 114.30; range, 822.19-1363.66), and cerebrospinal fluid (CSF) volume was 127.91 ml (+/- 57.62; range, 34.00-297.02). Brain volume was higher (by 5 ml) in the right hemisphere (P less than 0.0001). Men (n = 34) had 91 ml higher brain and 20 ml higher CSF volume than women (n = 35). Age was negatively correlated with brain volume [r(67) = -0.32, P less than 0.01] and positively correlated with CSF volume (r = 0.74, P less than 0.0001). The slope of the regression line with age for CSF was steeper for men than women (P = 0.03). This difference in slopes was significant for sulcal (P less than 0.0001), but not ventricular, CSF. The greatest amount of atrophy in elderly men was in the left hemisphere, whereas in women age effects were symmetric. The findings may point to neuroanatomic substrates of hemispheric specialization and gender differences in age-related changes in brain function. They suggest that women are less vulnerable to age-related changes in mental abilities, whereas men are particularly susceptible to aging effects on left hemispheric functions. 
1	Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences. In a retrospective study of 198 patients with transitional cell carcinoma of the upper urinary tract, post-operative recurrences developed as contralateral tumours in 2.5%, in the ureteric stump after conservative resection in 19% and in the bladder in 36.4%. Upper tract recurrences resembled the primary tumours in terms of grade and stage; of the bladder tumours, 89% were similar in grade and 72% similar in stage to the primary tumours. Age, sex, grade and stage had no effect on the number of bladder recurrences, but ureteric tumours had significantly more recurrences than renal pelvicaliceal tumours. Sex, bladder recurrences and site of primary tumours did not influence survival. Thus grade and stage of the primary tumour were the only predictive variables of the final outcome. 
3	Effects of uvulopalatopharyngoplasty on sleep architecture and patterns of obstructed breathing. In this retrospective study, 72 obstructive sleep apnea patients with polysomnograms taken before and after uvulopalatopharyngoplasty were evaluated. Postoperatively, there was a significant improvement of sleep architecture and respiratory indices. In addition, a second group of 17 patients also had position recordings with their polysomnograms. Time spent in supine and lateral sleep positions changed postoperatively. There was significant decrease of the apnea plus hypopnea index in the lateral position. This study indicates that there is significant improvement of sleep architecture and respiratory indices in the majority of patients after uvulopalatopharyngoplasty, particularly in the lateral sleep position. 
2	Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemical analysis of surgical liver samples. A group of 100 human liver samples obtained from three different network sources was divided into groups of normal, cirrhotic, metastatic cancer and other disease groups. These samples were analyzed for amounts of cytochrome P-450 IA2, IIC, IIE1 and IIIA and epoxide hydrolase per unit of microsomal protein using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical staining. For each enzyme the amount of protein detected varied by two orders of magnitude, even within the set of normal liver samples. With respect to the liver samples judged to be normal, the cirrhotic samples showed decreased levels of P-450 IA2 and IIE1 and epoxide hydrolase (P less than .05). The level of P-450 IIIA proteins also appeared lower but the high variance did not allow such a statistically valid conclusion. The liver samples obtained from metastatic cancer patients did not show decreased levels of any of the proteins examined, and levels of P-450 IIC proteins were enhanced in this group compared to the controls. In the samples obtained from patients with other liver diseases, the only major change was a decrease in the level of P-450 IA2. These findings are of use in explaining some of the known effects of hepatic disease on the in vitro and in vivo metabolism of certain drugs. 
3	Vascularized full-thickness parietal bone grafts in maxillofacial reconstruction: the role of the galea and superficial temporal vessels. Reconstruction of bony structures of the face is always a problem as big as the defect and the function that must be replaced. Everything from simple grafts to sophisticated distant bone flaps has been used. Based on the studies of Cutting et al., Psillakis et al., and Casanova et al., we have developed the full-thickness galeoparietal bone flap, initially for mandibular reconstruction, but of great use for all maxillofacial reconstructions. From July of 1987 to December of 1988, 14 patients have been operated on. The experience with this flap is shown in four patients as follows: primary reconstruction of a mandible as a result of ameloblastoma, secondary reconstruction of a mandible with associated old fractures and malalignment of segments, bilateral malar reconstruction in a patient with Treacher Collins syndrome, and severe sequelae of an already treated Romberg case. Small variations could be made to best accommodate the technique used to the defect we were treating. Some technical details, the experience, the results, and possible sequelae or complications are also discussed. 
1	Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients. Colon cancers typically produce mucin. However, it is not known whether tumor mucin plays a biological role in cancer cell behavior. To address this issue, the expression of a mucin-associated antigen, sialosyl-Tn, was examined by immunohistochemical study in 128 primary colorectal carcinoma specimens from 137 patients who underwent curative surgical resection. Antigen expression was correlated with disease-free and overall 5-year survival. Sialosyl-Tn antigen expression occurred in 112 (87.5%) tumors, and was independent of age, gender, tumor location, Dukes' stage, depth of invasion, degree of differentiation, and ploidy status. Survival at 5 years for patients with sialosyl-Tn-negative versus sialosyl-Tn-positive tumors was 100% versus 73% (P less than 0.05) and disease-free survival was 94% versus 73%, respectively (P = 0.12). Although more advanced Dukes' stage, deeper invasion, and aneuploidy were all associated with poorer overall 5-year survival, antigen-negative tumors within each of these groups had much better prognoses than antigen-positive tumors. Multivariate regression analysis revealed that tumor ploidy (P less than 0.001) and sialosyl-Tn expression (P less than 0.05) were the two variables of most importance for predicting both disease-free and overall survival. The authors conclude that sialosyl-Tn expression is an independent predictor of poor prognosis in colon cancer, and therefore suggest that qualitative mucin alterations may reflect important differences in the biological behavior of these neoplasms. 
1	Comparison of DNA content in gastric cancer cells between primary lesions and lymph node metastases. Cytophotomtric DNA contents of tumor cells in primary lesions and the corresponding metastatic lymph nodes were compared in 61 cases of gastric cancer to determine whether the DNA content remains stable during lymph node metastasis. The DNA distribution patterns were grouped into three types, according to the proportion of aneuploid cell population. Changes in DNA patterns between primary and metastatic lesions were evident in 36 of 61 patients (59.0%); in the remaining 25 (41.0%), the same DNA distribution patterns were noted for both lesions. In 33 of these 36, DNA pattern in the primary carcinoma was transformed into a more narrowly scattered one in the metastatic lesion of the lymph node. Mean and modal values and the frequency of cells over tetraploid (4c) or hexaploid (6c) were significantly higher in the primary lesion compared with findings in the metastatic lesions. This reduction in DNA content in the metastatic lesions was a more frequent occurrence in differentiated (18 of 23) than in undifferentiated adenocarcinoma (15 of 35) (P less than 0.01). Therefore, in primary lesions with a widely scattered DNA ploidy, the tumor cells with a smaller DNA ploidy frequently metastasized to lymph nodes, particularly in cases of a differentiated carcinoma. Such observations may be pertinent in future designing of treatment protocols. 
3	Driving in Parkinson's disease. Altered motor or mental skills in Parkinson's disease (PD) could adversely affect driving ability. We interviewed 150 patients regarding their driving habits and compared them with 100 controls. Thirty patients had stopped driving because of PD. PD patients had no more lifetime accidents than controls. With increased disability, however, there was a smaller percentage of patients still driving with fewer miles traveled and with proportionately more accidents occurring. Though disability scores did not correlate well with driving ability, there were significantly more accidents in subjects with more severe PD. The presence of cognitive impairment was associated with an increased accident rate. We conclude that driving in PD may be a public health problem and that some PD patients should not drive. 
4	Limitations of electroencephalographic monitoring in the detection of cerebral ischemia accompanying carotid endarterectomy. An analysis was undertaken of 458 consecutive carotid endarterectomies performed over 6 years with the patient under general anesthesia and with electroencephalographic monitoring. Seventy patients (15%) had electroencephalographic changes suggestive of ischemia with carotid clamping and had shunts placed. Ischemic encephalographic changes occurred in 26% of patients with an occluded contralateral carotid artery, 21% of patients with a prior stroke history, and 12% of patients with no stroke history and a patent contralateral carotid artery. Nineteen strokes (4.1%), nine transient deficits (2.0%), and one death (0.2%) occurred in the 458 endarterectomies in this experience. Ten of the 19 strokes and five of nine transient deficits were immediately apparent when patients awoke from anesthesia. Five of 10 patients with immediate strokes and all five patients with immediate transient deficits had no ischemic electroencephalographic changes during the procedure. Two other patients with immediate strokes initially had ischemic electroencephalographic changes after carotid clamping that reversed with increased blood pressure or shunting. Therefore 7 of 10 patients with immediate strokes and all 5 patients with immediate transient deficits had electroencephalographs unchanged from baseline at completion of the procedure, and thus deficits not manifest by operative electroencephalographic changes developed. Our data do not support the tenet that electroencephalographic monitoring will always predict neurologic deficits accompanying carotid endarterectomy. 
2	Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. OBJECTIVE: To estimate the relative risk for peptic ulcer disease that is associated with the use of oral corticosteroids. DESIGN: A nested case-control study. SETTING: Tennessee Medicaid program. PARTICIPANTS: The case patients (n = 1415) were hospitalized between 1984 and 1986 for gastric or duodenal ulcer or for upper gastrointestinal hemorrhage of unknown cause. The controls (n = 7063) were randomly selected from Medicaid enrollees not meeting the study criteria for inclusion as case patients. MEASUREMENTS AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer disease among current users of oral corticosteroids was 2.0 (95% CI, 1.3 to 3.0). However, the risk was increased only in those who concurrently received nonsteroidal anti-inflammatory drugs (NSAIDs); these persons had an estimated relative risk associated with current corticosteroid use of 4.4 (CI, 2.0 to 9.7). In contrast, the estimated relative risk for those corticosteroid users not receiving NSAIDs was 1.1 (CI, 0.5 to 2.1). Persons concurrently receiving corticosteroids and NSAIDs had a risk for peptic ulcer disease that was 15 times greater than that of nonusers of either drug. CONCLUSION: Discrepant findings among earlier studies regarding steroids and the risk for peptic ulcer disease could in part be due to differences in the use of NSAIDs among study participants. The high risk for peptic ulcer disease associated with combined use of NSAIDs and corticosteroids indicates the need to prescribe this drug combination cautiously. 
4	Endocarditis in the emergency department. Clinical presentations and pathogeneses of endocarditis and aspects of its diagnosis and management relevant to emergency department practice are reviewed. Guidelines for admission, laboratory evaluation, and decisions regarding the initiation of therapy in the ED are offered. Also discussed are the role of the emergency physician in the prevention of iatrogenic infection and current recommendations regarding administration of prophylactic antibiotics for ED procedures. 
5	Glucose-induced exertional fatigue in muscle phosphofructokinase deficiency BACKGROUND. The exercise capacity of patients with muscle phosphofructokinase deficiency is low and fluctuates from day to day. The basis of this variable exercise tolerance is unknown, but our patients with this disorder report that fatigue of active muscles is more rapid after a high-carbohydrate meal. METHODS AND RESULTS. To determine the effect of carbohydrate on exercise performance, we asked four patients with muscle phosphofructokinase deficiency to perform cycle exercise under conditions of differing availability of substrate--i.e., after an overnight fast, and during an infusion of glucose or triglyceride (with 10 U of heparin per kilogram of body weight) after an overnight fast. As compared with fasting and the infusion of triglyceride with heparin, the glucose infusion lowered plasma levels of free fatty acids and ketones, reduced maximal work capacity by 60 to 70 percent, and lowered maximal oxygen consumption by 30 to 40 percent. Glucose also increased the relative intensity of submaximal exercise, as indicated by a higher heart rate at a given workload during exercise. The maximal cardiac output (i.e., oxygen delivery) was not affected by varying substrate availability, but the maximal systemic arteriovenous oxygen difference was significantly lower during glucose infusion (mean +/- SE, 5.5 +/- 0.3 ml per deciliter) than after fasting (7.6 +/- 0.4 ml per deciliter, P less than 0.05) or during the infusion of triglyceride with heparin (8.9 +/- 1.3 ml per deciliter, P less than 0.05). CONCLUSIONS. In muscle phosphofructokinase deficiency, the oxidative capacity of muscle and the capacity for aerobic exercise vary according to the availability of blood-borne fuels. We believe that glucose infusion lowers exercise tolerance by inhibiting lipolysis and thus depriving muscle of oxidative substrate (plasma free fatty acids and ketones); this impairs the capacity of working muscle to extract oxygen and lowers maximal oxygen consumption. 
1	Current urinary mass screening for catecholamine metabolites at 6 months of age may be detecting only a small portion of high-risk neuroblastomas: a chromosome and N-myc amplification study. We studied 96 infants and children with untreated neuroblastomas. Chromosomes of tumor cells were analyzed in 68, and N-myc copy numbers were determined in 67 patients. Patients found by a mass screening program for 6-month-old infants (group A1, 39 patients) or those less than 12 months of age found clinically (group A2, 13 patients) were rarely in the disseminated stage (A1, three of 39; A2 one of 13); their tumors usually had near-triploid (3n) or hypertetraploid (greater than 4n) karyotypes (A1, 28 of 37; A2, nine of 11), and never had N-myc amplification (A1, zero of 34; A2, zero of 11). In contrast, children 12 months or over (group B, 27 patients) were usually in the disseminated stage (19 of 27) (P less than .0001); their tumors usually had near-diploid (2n) or near-tetraploid (4n) karyotypes (16 of 20) (P = .0027), and often had N-myc amplification (nine of 22) (P less than .0001). Of the 40 clinically found patients (A2 and B), six had undergone the screening with a negative result at the age of 6 months. Two of the six patients had N-myc amplification in the tumors. Most tumors found by the screening showed known characteristics predicting a good prognosis, and the majority of tumors showing characteristics predicting a poor prognosis were found in patients aged between 12 and 36 months. Our chromosome and N-myc amplification studies suggest that a low-risk tumor does not usually evolve to a high-risk tumor. Thus, the current mass screening program may be detecting only a small portion of highly malignant neuroblastomas at the earliest stage. Infants should be screened twice, at 6 months as well as at 12 months of age, for the early detection of high-risk neuroblastomas. 
3	Receptor changes in the spinal cord of sheep associated with exposure to chronic pain. There is evidence that post-injury hypersensitivity is partly due to changes in the central nervous system. Sheep with foot rot were used to investigate the effect of chronic pain on some receptors thought to be involved in spinal nociceptive processing systems (alpha 2 adrenoceptor and mu and delta opioid receptors). Saturation binding studies showed a variable distribution of [3H] clonidine (alpha 2 adrenoceptor agonist) in the spinal cord of normal sheep. The number of receptors (Bmax) present in areas thought to be involved in nociceptive processing, laminae I and II and lamina X, increased to 131% and 169% of control sheep values respectively in animals exposed to chronic pain. The affinity of the receptors (KD), however, remained unchanged at approximately 2 nM. There was less [3H]DAGO (mu opioid agonist) and [3H]DPDPE (delta opioid agonist) binding in the sheep spinal cord. Both opioid receptor types being mainly located in the superficial dorsal horn. The [3H]DPDPE binding was unchanged in the sheep with foot rot, whilst the number (Bmax), but not the affinity, of the [3H]DAGO binding sites increased in laminae I and II in lame animals to 130% of the control sheep values. Hence, in animals in chronic pain, the number of alpha 2 adrenoceptors and mu opioid receptors increased mainly in areas of the sheep spinal cord associated with nociception. 
1	Upper tract tumours following cystectomy for bladder cancer. Is routine intravenous urography worthwhile? The incidence and presentation of upper tract tumours were studied in 180 patients who had previously undergone cystectomy for transitional cell carcinoma of the bladder. Intravenous urography was performed routinely 3 months after cystectomy, 1 year later and at 3-yearly intervals thereafter. Ten patients developed upper tract tumours; 1 presented with loin pain and the remainder with haematuria. Six patients underwent nephroureterectomy and 5 of them lived for at least 4 years; 4 were inoperable and only 1 survived longer than 6 months. In this series, all patients with upper tract tumours presented with symptoms and routine intravenous urography failed to detect any asymptomatic lesions. Routine radiological assessment of the upper tracts to detect tumours is not justified following cystectomy. 
4	Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography. A statement by a Task Force Committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology. Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase. 
4	Potential usefulness of combined thromboxane A2 and serotonin receptor blockade for preventing the conversion from chronic to acute coronary artery disease syndromes. Evidence suggests that unstable angina, non-Q-wave myocardial infarction and Q-wave myocardial infarcts represent a continuum, such that transient reduction in coronary blood flow associated with platelet aggregation and dynamic vasoconstriction at sites of coronary artery stenosis and endothelial injury lead to abrupt development of unstable angina. Factors potentially responsible for the conversion from chronic to acute coronary artery disease include endothelial injury at sites of stenosis. The endothelial injury may be the result of plaque fissuring or ulceration, hemodynamic factors (including systemic arterial hypertension or flow shear stress), infection, smoking, coronary arteriography or balloon angioplasty. Clinical and experimental animal studies suggest that interference with thromboxane and serotonin contributions to platelet aggregation and dynamic coronary artery constriction may prevent chronic coronary artery disease syndromes from converting to acute disease. To protect against this process may require both thromboxane and serotonin receptor antagonists or a combination of thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist. Further studies are needed to test this hypothesis. 
5	Allelic variants at insulin-receptor and insulin gene loci and susceptibility to NIDDM in Welsh population. A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM. 
5	Leucine kinetics in patients with benign disease, non-weight-losing cancer, and cancer cachexia: studies at the whole-body and tissue level and the response to nutritional support. We have performed intraoperative isotopic infusions of carbon 14-labeled leucine in 65 patients to define the abnormalities in protein metabolism at both the whole-body and tissue level in patients with weight-losing and non-weight-losing cancer. Eighteen patients had benign disease, 26 had non-weight-losing cancer, and 21 had cancer cachexia. Samples of plasma and expired breath were taken to determine rates of whole-body protein synthesis (WBPS), whole-body protein catabolism (WBPC), net protein catabolism, and albumin fractional synthetic rates. Tissue samples were taken to determine the fractional synthetic rates (FSR) of protein in muscle, liver, cancer, and the tissue in which the cancer arose. In addition, in 14 patients the effect of nutritional support on protein metabolism was assessed. In all parameters examined we were unable to detect any significant differences between patients with no cancer and the patients with non-weight-losing cancer. In contrast, patients with cancer cachexia had a significant elevation (p less than 0.005) in WBPC compared with the other two groups. WBPS was also elevated (to a lesser extent) in the patients with cancer cachexia, and the rate of net protein catabolism was increased significantly (p less than 0.05). Patients with cancer cachexia also had significantly higher values of FSR of protein in muscle (p less than 0.05), liver (p less than 0.05), and albumin (p less than 0.01) compared with the other two groups. In addition, the protein FSR in the cancer rose progressively when the values for the primary cancer were compared with those for nodal and systemic metastases. Further, although nutritional support resulted in an increase in host muscle protein synthesis (p less than 0.04), there was no promotion of FSR of protein in cancer. We conclude that patients with cancer cachexia are actively losing protein as a result of an increase in WBPC that is only partially compensated for by an increase in WBPS. There are compensatory increases in protein synthesis in muscle and liver, but these increases in host protein synthesis are insufficient to keep pace with the combined effect of the accelerated rate of protein synthesis in the cancer per se and the accelerated rate of net protein catabolism at the whole-body level. In response to nutritional support, there is a significant increase in the muscle protein synthesis, but we could not demonstrate any increase in cancer protein synthesis. 
2	Epstein-Barr virus associated oesophageal ulcers in AIDS. Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration. 
5	Simultaneous 'dual system' rehabilitation in the treatment of facial paralysis. Simultaneous dual system rehabilitation of facial paralysis involves using two independent reanimation techniques to optimize facial movement in both a quantitative and qualitative manner. These techniques involve the use of nerve grafting or crossover procedures combined with a dynamic muscle transfer. A group of 37 patients who underwent five different combinations of reanimation was analyzed. The techniques were evaluated using a standard rating scheme for judging success of reanimation procedures. The combination of a masseter muscle transfer to the lower region of the face and a cable graft of the upper facial nerve division appeared to offer excellent results in terms of independent motion of the upper and lower regions of the face and good eye closure, while allowing spontaneous mimetic function in 50% of cases. The advantages and disadvantages of the other techniques are described. The clinical situations in which these techniques have advantage over single reanimation techniques are outlined. 
5	Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene. We investigated the effect of an activated c-erbB-2 gene (also known as ERBB2) on metastatic potential. The c-erbB-2 gene was activated by mutation of the valine at position 659 within the transmembrane domain to glutamic acid. The activated c-erbB-2 expression vector was transfected into low-metastatic-potential NL-4 cells, which were established from a metastatic variant of murine colon adenocarcinoma 26. All 10 clones produced lung metastases in BALB/c mice injected via the tail vein. Eight of the 10 clones expressed messenger RNA (mRNA) of activated c-erbB-2 and showed morphological alteration; seven of the eight produced significantly enhanced experimental metastatic activity compared with that of untransfected NL-4 or NL-4neo cells, and one had metastatic ability similar to that of NL-4 cells. Two clones did not express c-erbB-2 mRNA and did not show morphological alteration or highly metastatic phenotype. Five of the 10 clones subcutaneously implanted in the flank failed to produce metastasis in the lungs or other organs of the mice. The metastatic ability of the other five clones was not determined. These results indicate that the activated c-erbB-2 gene can enhance experimental but not spontaneous metastatic potential in NL-4 cells, suggesting participation of the gene in the metastatic process after initial arrest and lodgement in the capillary bed. 
5	Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes BACKGROUND. Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist. METHODS AND RESULTS. The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%). CONCLUSION. Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis. 
4	Renal protective effects of angiotensin converting enzyme inhibitors. Renal dysfunction and hypertension are closely associated. Hypertension causes approximately 25% of end-stage renal disease (ESRD) and develops in virtually every patient with advanced renal insufficiency from any cause. Although normalization of blood pressure can reduce mortality from uremia and ameliorate the progression of renal impairment in patients with established renal insufficiency from hypertension and diabetes, antihypertensive therapy alone is not totally effective in preventing progressive compromise of renal function--especially in blacks and diabetics, who are at high risk for developing ESRD. Of particular promise is the rapidly increasing understanding of the intrarenal autocrine and paracrine functions of angiotensin II produced locally by a tissue renin-angiotensin system. Consistent and convincing experimental data have demonstrated that angiotensin II plays many roles in the control of renal function and the kidney's response to injury. The intrarenal effects of angiotensin II include: 1) increase in the efferent arteriolar tone, resulting in increased glomerular capillary pressure, 2) promotion of mesangial cell contraction, 3) stimulation of proximal tubular Na+ reabsorption, and 4) possible growth hormone effects leading to hypertrophy or hyperplasia of vascular smooth muscle. Because of their favorable intrarenal hemodynamic effects (particularly reduction of glomerular capillary pressure), ACE inhibitors may provide a renal protective effect in addition to their systemic antihypertensive effects. Clinical trials evaluating the effect of ACE inhibition on the progression of renal insufficiency in hypertensives and diabetics are currently under way. Favorable results could lead to a significant decrease in the morbidity and mortality associated with hypertension. 
4	Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects. A prospective study was conducted to compare the frequency of renin gene polymorphisms in normotensive and hypertensive subjects. Hypertensive (n = 102, blood pressure 168 +/- 17/103 +/- 9 mm Hg) and normotensive (n = 120, blood pressure 122 +/- 10/75 +/- 9 mm Hg) subjects were white, had similar age and sex distributions (hypertensive group, 45 +/- 10 years old and 52% female; normotensive group, 44 +/- 9 years old and 55% female) and similar body mass index (hypertensive group, 23.2 +/- 2.6; normotensive group, 22.5 +/- 2.4 kg/m2, p = 0.048). The familial susceptibility to hypertension was defined as at least one parent and one sibling who were hypertensive before age 65; subjects in the normotensive group had no familial history of hypertension. Renin gene polymorphisms located throughout the renin gene were identified by using three restriction enzymes (Taq I, HinfI, HindIII). For each polymorphic restriction site, allele frequencies were similar in the hypertensive and the normotensive groups. In the absence of parental genotypes, the haplotype frequencies combining the three restriction fragment length polymorphisms were estimated by using maximum likelihood techniques and were similar in both groups (hypertensive group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for the three most common haplotypes). A rare haplotype detected by Taq I/Hind III was apparently more frequent in the hypertensive than in the normotensive group (hypertensive group, tH 0.086, th 0.022; normotensive group, tH 0.038, th 0.050), but the difference was not statistically significant. In conclusion, no association between renin gene polymorphisms and essential hypertension was demonstrated in the present study. 
5	Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guerin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value. 
4	Warning: fatal reaction to the use of fibrin glue in deep hepatic wounds. Case reports. Two cases of severe hypotension following the use of fibrin glue for hemostasis in hepatic injuries are reported. A systemic reaction to bovine thrombin via large venous lacerations is suspected. A preliminary animal study supports this hypothesis. Caution is advised in the use of fibrin glue for hemostasis in deep hepatic wounds. 
5	A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa. Autosomal dominant retinitis pigmentosa (ADRP) has recently been linked to locus D3S47 (probe C17), with no recombination, in a single large Irish family. Other ADRP pedigrees have shown linkage at zero recombination, linkage with recombination, and no linkage, demonstrating genetic heterogeneity. The gene encoding rhodopsin, the rod photoreceptor pigment, is closely linked to locus D3S47 on chromosome 3q. A point mutation changing a conserved proline to histidine in the 23d codon of the gene has been demonstrated in affected members of one ADRP family and in 17 of 148 unrelated ADRP patients. We have sequenced the rhodopsin gene in a C17-linked ADRP family and have identified in the 4th exon and in-frame 3-bp deletion which deletes one of the two isoleucine monomers at codons 255 and 256. This mutation was not found in 30 other unrelated ADRP families. The deletion has arisen in the sequence TCATCATCAT, deleting one of a run of three x 3-bp repeats. The mechanism by which this occurred may be similar to that which creates length variation in so-called mini- and microsatellites. Thus ADRP is an extremely heterogeneous disorder which can result from a range of defects in rhodopsin and which can have a locus or loci elsewhere in the genome. 
4	Easy dissection of hard and thickened pericardium on constrictive pericarditis. The keys to successful pericardiectomy for constrictive pericarditis are early operation and as complete a pericardiectomy as possible. With the high-speed burr it is easy and safe to dissect the calcified pericardium and define the epicardium even in a small operative field such as the inferior or posterior portion of the heart. This method has the important ability to perform very complete pericardiectomy. 
3	Comparison of functional and structural brain disturbances in Wilson's disease. We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD. 
1	A phase II study of combined methotrexate and teniposide infusions prior to reinduction therapy in relapsed childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study. Teniposide (VM-26) can increase intracellular methotrexate (MTX) and its polyglutamate derivatives in vitro and thus has the potential to improve the therapeutic index of regimens containing MTX. In this phase II study, children and adolescents with acute lymphoblastic leukemia (ALL) in first or second marrow relapse were randomly assigned to receive either simultaneous (n = 11) or sequential (n = 12) continuous infusions of MTX and VM-26 prior to reinduction. Infusions of VM-26 were begun 12 hours after completion of MTX infusion in the sequential group. Dosages were individually adjusted to maintain plasma concentration levels of 10 microns for MTX and 15 microns for VM-26; total infusion times were 24 and 72 hours, respectively. Significant toxicity in the first six patients who received the scheduled 72-hour VM-26 infusion (including one drug-related death) prompted a 50% reduction in infusion duration. The reduced dose was associated with similar but more manageable toxicity. Examination of bone marrow aspirates 10 days after therapy was begun showed one complete and two partial marrow remissions; a fourth patient who had an aplastic marrow on day 10 received no further chemotherapy and had a complete remission (CR) documented on day 31. There was no obvious clinical advantage associated with either infusion schedule, although small sample sizes preclude definitive conclusions. The 17% response rate to the MTX/VM-26 therapeutic window in patients with refractory disease suggests the need for further investigation to evaluate alternative schedules and concomitant therapy for this drug combination. 
3	Neurologic abnormalities in a patient with human ehrlichiosis. Human ehrlichiosis is a tick-borne rickettsial disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In our patient, changes in mental status, upper motor neuron signs, cerebrospinal fluid pleocytosis, and increased serum protein levels were found in association with serologically confirmed ehrlichiosis and were most likely due to vasculitis involving the central nervous system. Intraleukocytic inclusions, although observed in our case, have been infrequently found in other reported cases of ehrlichiosis. 
5	Sweet's syndrome: a clinicopathologic review of twenty-nine cases. Twenty-nine patients with Sweet's syndrome were studied. Not all of Sweet's original criteria were necessarily present and diagnosis was dependent on the recognition of the typical, acute, tender, erythematous plaques and the characteristic histologic features of a neutrophilic infiltrate with leukocytoclasis. Women are affected much more frequently than men. The origin of Sweet's syndrome is still unclear, but an underlying disease was found in more than 50% of our cases. A streptococcal infection was evident in six cases, inflammatory bowel disease in three cases, malignancy in four cases, and pregnancy in two others. Treatment with oral prednisolone for an average of 6 weeks was the usual treatment, although in four patients the disease cleared spontaneously. Resolution of the eruption is occasionally followed by milia and scarring. Recurrences are common and affect up to one third of patients. 
2	Magnetic resonance angiography of abdominal vessels: early experience using the three-dimensional phase-contrast technique. Based on three-dimensional acquisition of three sequences sensitive to one flow-direction, abdominal magnetic resonance phase-contrast angiography (MRA) was performed in 13 volunteers and 20 patients. The subjects received no antiperistaltic medication and were allowed to breath normally during the three acquisition periods of 11 minutes. The frequency of demonstration of the normal aorta, superior mesenteric and right and left renal arteries was 100%/100%/91%/100%, and of the inferior vena cava, splenic, superior mesenteric and portal veins was 92%/67%/92%/100%, respectively, whereas other abdominal vessels were seen less constantly. In renal artery stenosis or occlusion, MRA detected eight out of nine pathological arteries, missed only a minimal stenosis and was never false positive. In all 10 cases of portal hypertension, MRA demonstrated the venous collaterals detected by conventional angiography and in six cases showed more collaterals, particularly paravertebral vessels. A Budd-Chiari syndrome was investigated as well. If the accuracy of MRA can be proved in larger studies, it may become an important diagnostic tool in evaluating abdominal vascular pathology, such as renal artery stenosis or portal hypertension. 
1	Results of multiple pulmonary resections for metastatic osteogenic sarcoma after two decades. A 20-year follow-up of children who had complete resection of pulmonary metastases from osteogenic sarcoma of the extremities was undertaken. Four of six 10-year survivors survived more than 19 years even with multiple metastases and as many as nine thoracotomies. Fifty percent of the 10-year survivors developed second primary cancers during the second decade of follow-up. 
5	Pharmacokinetics and clinical experience of 20-h infusions of methohexitone in intensive care patients with postoperative pyrexia. We have studied the pharmacokinetics of 20-h infusions of methohexitone in young patients with postoperative fever undergoing artificial ventilation of the lungs. The infusion rate was adjusted so that patients were unresponsive to vocal stimulation but reacted to tracheal suction. The mean steady state concentration of methohexitone required was 2.6 mg litre-1 (unbound 0.53 mg litre-1). The mean (SD) total clearance of methohexitone was 16.3 (4.2) ml min-1 kg-1, which is greater than that for volunteers or normal surgical patients. The unbound clearance correlated positively with body temperature during the infusion (r = 0.796, P = 0.017). The terminal half-life of methohexitone was 6.3 (3.8) h and that of the 4'-hydroxy metabolite 5.8 (2.1) h. There were no marked haemodynamic effects of the infusion, and no excessive sedation after the infusion. However, the clearance of methohexitone was high and variable, possibly as a direct effect of postoperative fever. Consequently, the need for individual titration of the rate of infusion is emphasized. 
4	Maximal oxygen uptake in severe aortic regurgitation: a different view of left ventricular function. Respiratory gas exchange was used to assess left ventricular (LV) function in 22 patients with severe aortic regurgitation (19 men and three women, aged 18 and 70 years, mean 49 years). Anaerobic threshold and symptom-limited maximal oxygen consumption (VO2 max) were measured during treadmill exercise, and the results were compared with conventional echocardiographic and radionuclide indices of LV systolic function. The results were considered with respect to the patients' New York Heart Association functional class. Both rest and exercise LV ejection fractions were variable, but the mean results were similar in all classes. The echocardiographic indices of LV cavity dimensions, fractional shortening, radius/thickness ratio, and systolic wall stress also showed a wide range but with similar mean results in each class. In contrast, VO2 max and anaerobic threshold showed a relationship to functional class. VO2 max was 32.4 +/- 3.4 ml/kg/min in age-matched control subjects; in the patients it was 27.9 +/- 4.7 in class I, 24.7 +/- 5.7 in class II, and 14.2 +/- 2 in the combined class III/IV. Results in patients in classes I and II were similar, but both groups were significantly different from control subjects (p less than 0.05) and from patients in class III/IV (p less than 0.01). About half of the patients with moderate LV dysfunction (judged by reduced VO2 max) were asymptomatic, and LV function was impaired in 4 of 10 patients in class I. Thus, unlike conventional indices of LV function, VO2 max appeared capable of distinguishing patients with moderate-to-severe LV dysfunction from those with little or no LV dysfunction. Measurement of respiratory gas exchange appears to be a valid and useful supplementary means of assessing LV function in severe aortic regurgitation. Further long-term evaluation is required. 
4	Analysis of baroreflex control of heart rate in conscious dogs with pacing-induced heart failure. The autonomic components of the baroreflex control of heart rate were evaluated in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250 beats/min). Arterial baroreflex sensitivity (BRS) was determined by the slopes of linear regression of pulse interval versus the preceding systolic arterial pressure in response to bolus injections of either phenylephrine or nitroglycerin. BRS was significantly depressed in the heart failure state [nitroglycerin slope, 5.0 +/- 2.7 (mean +/- SD) versus 16.6 +/- 5.1 msec/mm Hg, p less than 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 msec/mm Hg, p less than 0.005]. There was no depression in BRS in dogs that were used as time controls or were acutely paced for 30 minutes. After beta 1-adrenergic blockade with metoprolol, the resting heart rate in the heart failure state was depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p less than 0.001). Atropine significantly increased resting heart rate more in the normal state than in the heart failure state (115.8 +/- 36.7% versus 25.4 +/- 14.5%, p less than 0.005). Thus, dogs in the heart failure state appear to have high resting cardiac sympathetic tone and low resting vagal tone. For nitroglycerin administration, metoprolol depressed BRS by 47.6 +/- 26.3% in the normal state and by 63.6 +/- 58.5% in the heart failure state. Atropine decreased the BRS by 86.7 +/- 7.8% in the normal state and by 39.5 +/- 30.2% in the heart failure state. 
3	Alcohol consumption--a risk factor for hemorrhagic and non-hemorrhagic stroke. PURPOSE: The risks of alcohol consumption and its association with stroke were studied in 621 patients with stroke and 573 control subjects using case-control methods. PATIENTS AND METHODS: Patients with stroke were subdivided into 193 with subarachnoid hemorrhage, 91 with intracerebral hemorrhage, and 337 with cerebral infarction. Data on recent alcohol consumption were obtained by questionnaire in patients with stroke and compared with data from an occupational screening survey in control subjects. RESULTS: Relative risks, adjusted for confounding variables, exhibited J-shaped associations with increasing levels of alcohol consumption classified into four categories--abstainer, 1 to 90 g, 100 to 390 g, and greater than or equal to 400 g weekly). The individual risks were 1, 0.7, 0.5, and 1.3 for subarachnoid hemorrhage; 1.0, 0.6, 0.5., and 2.5 for intracerebral hemorrhage, and 1.0, 0.6, 0.7, and 2.4 for cerebral infarction for men and women combined. CONCLUSIONS: The results suggest that low levels of alcohol consumption may have some protective effect upon the cerebral vasculature, whereas heavy consumption predisposes to both hemorrhagic and non-hemorrhagic stroke. 
1	Resection of the superior vena cava for primary lung cancer: 5 years' survival. We describe a patient with squamous cell carcinoma of the right lung that required a resection of the superior vena cava combined with a tracheal sleeve pneumonectomy. The superior vena cava was totally replaced with a polytetrafluoroethylene graft with 115 minutes cross-clamping of the superior vena cava. The patient remains healthy and the polytetrafluoroethylene graft remains patent 5 years 4 months after operation. 
2	Human liver regeneration after major hepatectomy. A study of liver volume by computed tomography. Regeneration of the remnant liver after major hepatectomy in humans was studied by computed axial tomography (CT) in 12 noncirrhotic and five cirrhotic patients. Liver volumes were measured by abdominal CT 3 days, 10 days, 3 months, 6 months, 1 year, and 1.5 years after resection. Of the 17 patients, liver remnant volume was increased in 21.2% +/- 6.7% and 30.6% +/- 12.7% at 3 months and 6 months after resection, respectively. Noncirrhotic livers were 28.4% +/- 9.5% and 48.4% +/- 17.8% larger at 3 and 6 months. For cirrhotic livers, the increase was 8.5% +/- 3.6% and 12.9% +/- 4.5%. In five patients with right hepatectomy (65% resection), the liver remnant volumes were increased 38.4% +/- 11.7%, 48.0% +/- 16.2% and 95.1% +/- 4.5% at 3 months, 6 months, and 1 year after resection, respectively. In seven patients with right partial hepatectomy (30% to 35% resection), the percentages were 7.4% +/- 3.2%, 21.8% +/- 8.4%, and 63.9% +/- 18.3% and in five patients with left lateral segmentectomy (15% resection), they were 15.6% +/- 8.2%, 27.8% +/- 12.2%, and 33.0% +/- 14.5% 3 months, 6 months, and 1 year after resections, respectively. Noncirrhotic livers showed better regeneration than cirrhotic livers. Complete regeneration took about 1 year. The noncirrhotic liver that underwent right lobectomy also needed 1 year to double its postresection volume. 
4	Use of autologous blood in total hip replacement. A comprehensive program. We evaluated the effectiveness of a comprehensive program for the use of autologous blood in reduction of the need for transfusion of homologous blood in total hip replacement in a prospective study of a consecutive series of patients. Transfusion of homologous blood was minimized through transfusion of preoperatively deposited autologous blood, intraoperative and postoperative salvage of washed red blood cells, and use of the clinical condition of the patient as the sole criterion for transfusion of non-autologous blood, regardless of the hematocrit. The cases of 143 patients who had had 154 primary total hip replacements were studied. One hundred and forty-three procedures were done on patients who had not been prevented from donating blood for medical reasons, and 93 per cent of these 143 procedures were performed with the availability of one to five units of preoperatively deposited autologous blood. The patients predeposited an average of 2.6 units of blood for each procedure. Ninety-two per cent of the procedures for which autologous blood had been predeposited were performed without transfusion of homologous blood. In the entire group of patients, almost 90 per cent of the transfused blood was autologous blood. Intraoperative salvage of red blood cells was successful in 148 procedures, and salvage was continued in the recovery room for all of these patients. An average of 408 milliliters of red blood cells was saved and reinfused, and this was 28 per cent of the average total loss of blood (1435 milliliters) for this series of procedures. 
5	Intraventricular diamorphine via an Ommaya shunt for intractable cancer pain. We describe two patients in whom diamorphine was administered into the intraventricular space via an Ommaya reservoir, producing excellent pain relief. The use of this technique for long term administration of analgesia is reviewed. 
4	Emergent signs of cancer. Recognizing them early in the office or ER. Primary care physicians have a crucial role in recognition of potentially emergent conditions in patients with known or suspected cancer. This task presents a significant challenge because the initial manifestations of these conditions are usually nonspecific. In most cases, therapy is far more effective when diagnosis is made at the earliest possible point. Thus, physicians should become familiar with conditions commonly seen in cancer patients, such as superior vena cava syndrome, malignant pericardial effusion, spinal-epidural metastasis, and altered mentation from brain metastases, metabolic encephalopathy, or hypoglycemia. 
5	Methionine dependency of malignant tumors: a possible approach for therapy When methionine (Met), an essential amino acid, was substituted for by its precursor homocysteine (Hcy) in the culture medium, normal cells such as fibroblasts proliferated normally. In contrast, many tumor cells failed to grow or grew at a lower rate. Met dependency is acquired simultaneously with cell transformation, as observed with HBL 100, a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number, and NIH/3T3 (J10), a mouse fibroblast line transformed by transfection with the human HRAS oncogene. A relationship was observed between Met dependency and metastatic potential of the RMS-21, RMS-S4T, and RMS-J1 sublines derived from RMS-0, a rat rhabdomyosarcoma cell line: the higher the metastatic potential of the cell line, the higher the concentration of Met required to maintain its proliferation. Met-independent cells derived from the RMS-0 line, obtained by a progressive decrease of Met in the culture medium lost their tumorigenicity when injected into rats fed with Met-deprived diets. In addition, the in vitro motility of RMS-S4T tumor cells, a marker of metastatic capability, decreased in Met-free Hcy-complemented (Met- Hcy+) medium. Similarly, RMS-0 tumor cells, preincubated in a Met- Hcy+ culture medium for 24 hours, evidenced a decreased capacity to form lung colonies when injected into syngeneic rats: the median number of lung colonies was 27 and 3 (P less than .05) for cells cultivated in Met+ Hcy- and Met- Hcy+ media, respectively. An amino acid-defined mixture reproducing casein composition was used as a protein source in the diets fed to RMS-J1 tumor-bearing rats. Dietary substitution of Hcy for Met (i.e., met deprivation) resulted in decreased tumor growth (from 44.4 +/- 1.0 to 40.6 +/- 1.4; P less than .05) and prevention of metastatic spread (from 37 to 0; P less than .05). In conclusion, exogenous Met can be substituted for Hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro. Therefore, this defect of cancerous versus normal cells could be used for a therapeutic purpose. 
1	Association of expression between N-myc gene and major histocompatibility complex class I gene in surgically resected human neuroblastoma. Amplification of the N-myc gene in neuroblastoma correlates with advanced stage and poor prognosis. Association of the expression between N-myc and major histocompatibility complex (MHC) class I genes in 33 neuroblastomas obtained from Japanese children was investigated. Amplification of the N-myc gene was observed in two of five cases in Stage III, six of 11 cases in Stage IV, and one of five cases in Stage IV-S. In each case, the expression of N-myc gene was significantly increased. The expression was also increased in cases without amplification of the N-myc gene, the origin being from the suprarenal region. Expression of the MHC class I gene was significantly decreased in five of these nine with a high level of N-myc expression with amplification. These results suggest that the down-modulation of the MHC class I expression may be associated with the high level of expression and amplification of N-myc gene in the advanced stage of neuroblastoma. 
3	Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease. We evaluated whether patients with young-onset Parkinson's disease (PD) (onset between 21 and 40 years) develop levodopa-induced dyskinesias and motor response fluctuations more frequently and earlier than patients with older-onset PD (onset after 40 years) by determining the period from levodopa introduction to development of dyskinesias or fluctuations in 25 young-onset (mean age at onset, 33.54 years) and in 25 matched older-onset PD patients (mean age at onset, 55.76 years). Young-onset PD patients had significantly higher frequency for both dyskinesias and fluctuations after both 3 and 5 years of levodopa. Young-onset PD patients also developed both levodopa-induced dyskinesias and fluctuations earlier than older-onset PD patients. We suggest that the introduction of levodopa therapy in patients with young onset PD should be postponed as long as possible. 
4	Sensitivity of exercise electrocardiography for acute cardiac events during moderate and strenuous physical activity. The Lipid Research Clinics Coronary Primary Prevention Trial. We determined whether the exercise electrocardiogram predicted acute cardiac events during moderate or strenuous physical activity among 3617 asymptomatic, hypercholesterolemic men (age range, 35 to 59 years) who were followed up in the Coronary Primary Prevention Trial. Submaximal exercise test results were obtained at entry and at annual follow-up visits in years 2 through 7. ST-segment depression or elevation (greater than or equal to 1 mm or 10 microV-sec) was considered to be a positive test result. The circumstances that surrounded each nonfatal myocardial infarction and coronary heart disease death were determined through a record review. The cumulative incidence of activity-related acute cardiac events was 2% during a mean follow-up period of 7.4 years. The risk was increased 2.6-fold in the presence of clinically silent, exercise-induced, ST-segment changes at entry (95% confidence interval [Cl], 1.3 to 5.2) after adjustment for 11 other potential risk factors. Of 62 men who experienced an activity-related event, 11 had a positive test result at entry (sensitivity, 18%; 95% Cl, 8 to 27). The specificity of the entry exercise test was 92% (95% Cl, 91 to 93). The sensitivity and specificity were similar when the length of follow-up was restricted to 1 year after testing. For a newly positive test result on a follow-up visit, the sensitivity was 24% (95% Cl, 12 to 36), and the specificity was 85% (95% Cl, 84 to 86); for any positive test result during the study (mean number of tests per subject, 6.2), the sensitivity was 37% (95% Cl, 25 to 49), and the specificity was 79% (95% Cl, 77 to 80). Our findings suggested that the presence of clinically silent, exercise-induced, ischemic ST-segment changes on a submaximal test was associated with an increased risk of activity-related acute cardiac events. However, this test was not sensitive when used to predict the occurrence of activity-related events among asymptomatic, hypercholesterolemic men. For this reason, the utility of the submaximal exercise test to assess the safety of physical activity among asymptomatic men at risk of coronary heart disease is likely to be limited. 
5	Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. A 65 year old patient who was exposed to topical bovine thrombin during cardiac surgery developed markedly prolonged clotting times and a severe bleeding diathesis. Mixing studies with normal plasma failed to correct the clotting times. Platelet transfusions, immunosuppressive and immunomodulatory therapies were ineffective, but plasmapheresis was effective in decreasing clotting times and in the resolution of clinical bleeding events. The patient's purified IgG reacted with bovine thrombin by immunoblotting and enzyme-linked immunosorbent assay (ELISA). However, the IgG reacted minimally with human thrombin. In view of the severe bleeding, a coexisting inhibitor was sought. The patient's factor V activity was 1% of normal and was not corrected by mixing with normal plasma, demonstrating the presence of an inhibitor against factor V. The patient's IgG reacted with both bovine and human factor V. Immunoblotting localized the site of antibody binding to the light chain of activated bovine factor V. Detectable amounts of bovine factor V were found in commercial bovine thrombin preparations by ELISA. The data suggest that patients exposed to topical bovine thrombin may develop antibodies to thrombin and factor V. Anti-thrombin antibodies may mask coexisting factor V inhibitors responsible for clinical bleeding. 
5	Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells. A human cDNA library obtained from cultured normal mammary epithelial cells (HMECs) was searched by subtractive hybridization for genes whose decrease in expression might be relevant to epithelial transformation. One clone identified by this procedure corresponded to a 1.4-kilobase mRNA, designated NB-1, whose expression was decreased greater than 50-fold in HMECs tumorigenically transformed in vitro after exposure to benzo[a]pyrene and Kirsten sarcoma virus. Sequence analysis of NB-1 cDNA revealed an open reading frame with a high degree of homology to calmodulin. NB-1 expression could be demonstrated by polymerase chain reaction amplification in normal breast, prostate, cervix, and epidermal tissues. The presence of NB-1 transcripts was variable in primary breast carcinoma tissues and undetectable in tumor-derived cell lines of breast, prostate, or other origins. NB-1 mRNA expression could be down-regulated in cultured HMECs by exposure to reconstituted extracellular matrix material, while exposure to transforming growth factor type beta increased its relative abundance. The protein encoded by NB-1 may have Ca2+ binding properties and perform functions similar to those of authentic calmodulin. Its possible roles in differentiation and/or suppression of tumorigenicity in epithelial tissues remain to be examined. 
1	The importance of anatomic site in prognosis in patients with cutaneous melanoma. To determine the prognostic relevance of the anatomic site of origin of cutaneous melanoma to survival, we retrospectively analyzed a computerized database of 3428 patients with stage I and II cutaneous melanoma. Patients were stratified by the recognized prognostic variables of stage of disease, Clark's level of invasion of the primary lesion, and the nodal involvement at the time of lymphadenectomy. Melanoma arising in skin of the upper part of the back, back of the arms, neck, and scalp (BANS) region occurred more frequently in male than female patients. There were no statistically significant differences in the distribution of Clark's level of invasion of BANS and non-BANS region primary melanomas or in the extent of nodal involvement in patients with stage II disease. The 5-year actuarial survival of patients with stage I BANS region melanomas was 87%; stage I non-BANS, 89%; stage II BANS, 38%; and stage II non-BANS, 69%. The BANS region appears to have prognostic significance in cutaneous melanoma and, particularly, in patients with stage II melanoma. 
5	Intracranial arachnoid cysts in children. A comparison of the effects of fenestration and shunting. The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. The cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported. Five children with mild symptoms and small cysts that remained stable on follow-up studies have not required surgical intervention. Of 15 patients with cysts initially treated by fenestration, 10 (67%) showed no clinical or radiographic improvement postoperatively and have undergone cyst-peritoneal (eight patients) or ventriculoperitoneal (VP) shunting (one patient), or revision of a VP shunt placed for hydrocephalus before cyst fenestration (one patient). Two other patients with existing VP shunts required no further procedures. Thus, only three (20%) of 15 patients initially treated by fenestration remain shunt-independent after a median follow-up period of 8 years. The 20 other patients were initially treated by cysts shunting and all improved postoperatively; shunt revision has been necessary in six (30%) of these 20 patients because of cysts recurrence. Cyst location influenced the success of shunt treatment; none of the seven middle cranial fossa cysts treated by shunting have required revision, but results with cysts in other locations were less favorable. In all locations, though, shunting was more successful than fenestration. It is concluded that cyst-peritoneal or cyst-VP shunting is the procedure of choice for arachnoid cysts in most locations, including those in the middle cranial fossa. 
1	Ubiquitin hybrid protein gene expression during human colon cancer progression. Ubiquitin is involved in cell-cycle control and DNA replication through a specific proteolytic pathway. Our previous studies demonstrated selected higher expression of a gene encoding ubiquitin-ribosomal protein S27a in poorly differentiated colon carcinoma cell lines. In this study, we evaluated this ubiquitin hybrid protein gene expression in surgical specimens of colon cancers. Northern blot analysis showed that ubiquitin hybrid protein messenger RNA was overexpressed in primary colon cancers compared with adjacent normal colon mucosae in 17 of 20 patients. Dot blot analysis of RNA of 27 tumor samples revealed significantly greater expression in higher Dukes' stage primary colon tumors and liver metastases. These data imply that protein translation machinery is highly activated during progression and metastasis of colon tumors, and that ubiquitin hybrid protein may be useful as a marker of biological aggressiveness. 
2	Fine structure of active and healed duodenal ulcer. In order to characterize the fine structure of active and healed duodenal ulcers, we examined tissue specimens of patients with active duodenal ulcer disease (n = 30) before and after treatment with either antacids (n = 16) or H2-receptor antagonists (n = 14), by light microscopy and various electron microscopic techniques, e.g., scanning and transmission electron microscopy. The characteristic histological feature of both the active and healed duodenal ulcer was the appearance of periodic acid-Schiff (PAS)-positive epithelial cells at the edge of the ulcers. Electron microscopy revealed that these cells were similar to a special type of mucus-secreting cell in the antrum (surface mucous cell). Their mucus granules contained mainly neutral glycoproteins. Helicobacter pylori were found attached to these cells in tissue specimens from 12 of 30 patients (40%). The mucous structure destroyed during the ulcerative phase regained its normal net-like structure after treatment. The ultrastructural healing process of duodenal ulcer was characterized by the presence of gastric metaplasia, by stunted microvilli of the duodenal epithelium (p less than 0.001 vs. control group), and an increased number of lysosome-like bodies (p less than 0.001 vs. control group) of the epithelial cells. These results were independent of the type of treatment, and showed that the repair mechanisms were incomplete after a 4-wk period of treatment. 
2	The role of the mast cell in clinical gastrointestinal disease with special reference to systemic mastocytosis. The gastrointestinal tract is a rich source of mast cells with an enormous surface area that permits a high degree of interaction between the mast cell and intestinal luminal contents. The active metabolic products of the mast cell influence gastrointestinal secretion, absorption, and motility through paracrine effects of local mast cell degranulation and also cause systemic effects through the release of cellular products into the blood stream. Systemic mastocytosis influences physiologic function through the systemic effects of mast cell products released from focal (e.g., bone marrow) or wide spread increases in mast cell number. Local gastrointestinal proliferation of mast cells in response to recognized (e.g., gluten in celiac sprue) or obscure stimuli can alter gastrointestinal function and induce systemic symptoms. Celiac sprue, inflammatory bowel disease, and non-ulcer dyspepsia are three examples of gastrointestinal diseases in which mast cells can be implicated in the pathophysiology of the symptoms. 
4	Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene The relation between risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene was examined in a population case-control study of 110 cases of angina, identified by the Chest Pain Questionnaire, and 394 controls selected from a sample of 6000 men aged 35-54. Plasma concentrations of vitamins C and E and carotene were significantly inversely related to the risk of angina. There was no significant relation with vitamin A. Smoking was a confounding factor. The inverse relation between angina and low plasma carotene disappeared and that with plasma vitamin C was substantially reduced after adjustment for smoking. Vitamin E remained independently and inversely related to the risk of angina after adjustment for age, smoking habit, blood pressure, lipids, and relative weight. The adjusted odds ratio for angina between the lowest and highest quintiles of vitamin E concentrations was 2.68 (95% confidence interval 1.07-6.70; p = 0.02). These findings suggest that some populations with a high incidence of coronary heart disease may benefit from eating diets rich in natural antioxidants, particularly vitamin E. 
3	Atelectasis affects the rate of arterial desaturation during obstructive apnea. Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed. 
5	Ultrasonographic assessment of placental abnormalities. Current ultrasonographic techniques offer a novel approach for the identification of a wide variety of placental abnormalities usually described postnatally by the pathologist. Placental vascular lesions, placental tumors, and abnormal placentation are potentially associated with perinatal complications and their diagnosis in utero may influence the pregnancy management. An ultrasonographic classification of placental lesions that is based on their location, size, echogenicity, and number is proposed. Repeated ultrasonographic examination, together with biologic investigations, is important for the prenatal differential diagnosis of most these lesions and for full understanding of their pathophysiologic characteristics and significance. 
5	Modulation of neurogenic inflammation by neutral endopeptidase. The enzyme neutral endopeptidase (NEP) is bound to the membranes of selected cells in the airways that have receptors for tachykinins. The location of the enzyme, along with its selectivity of substrates (tachykinins are a preferred substrate), allows the enzyme to cleave tachykinins that come close to the cell-surface receptors. By cleaving and thus inactivating tachykinins released during stimulation of the sensory nerves, NEP limits the degree of neurogenic inflammation. Neutral endopeptidase exists in the basal cells of the airway epithelium, nerves, smooth muscle, glands, blood vessels, and perhaps other cells. Thus, the enzyme modulates smooth muscle contraction, gland secretion, cough, vascular permeability, and neutrophil adhesion. Decreased NEP activity occurs with epithelial removal, during respiratory viral infections, and during exposure to irritants (e.g., cigarette smoke and toluene diisocyanate). Delivery of recombinant NEP (rNEP) by aerosol suppressed cough responses during neurogenic inflammation. We suggest that decreased NEP activity will result in exaggerated neurogenic inflammation and may play an important role in inflammatory diseases in airways. Furthermore, drugs that cause up-regulation of NEP may play a therapeutic role by suppressing neurogenic responses. Replacement therapy with rNEP may be useful in diseases where inflammatory peptides (e.g., tachykinins, bradykinin) play a role in pathogenesis. 
5	Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells. The function of the c-myc gene and its role in tumorigenesis are poorly understood. In order to elucidate the role of c-myc oncogene activation in B cell malignancy, the phenotypic changes caused by the expression of c-myc oncogenes in human B lymphoblastoid cells immortalized by Epstein-Barr virus were analyzed. C-myc oncogenes caused the down-regulation of lymphocyte function-associated antigen-1 (LFA-1) adhesion molecules (alpha L/beta 2 integrin) and loss of homotypic B cell adhesion in vitro. Down-regulation of LFA-1 occurred by (i) posttranscriptional modulation of LFA-1 alpha L-chain RNA soon after acute c-myc induction, and (ii) transcriptional modulation in cells that chronically express c-myc oncogenes. Analogous reductions in LFA-1 expression were detectable in Burkitt lymphoma cells carrying activated c-myc oncogenes. Since LFA-1 is involved in B cell adhesion to cytotoxic T cells, natural killer cells, and vascular endothelium, these results imply functions for c-myc in normal B cell development and lymphomagenesis. 
1	Central odontogenic fibroma: clinicopathologic features of 19 cases and review of the literature. The odontogenic fibroma is a benign neoplasm infrequently reported in the literature (20 cases). Nineteen additional examples are reported. This lesion occurs most frequently in the maxilla anterior to the molars and displays a striking female predilection. On occasion, it may be associated with an unerupted mandibular third molar. Histomorphologically, it is not encapsulated. A spectrum of fibrous connective tissue stroma is present: from myxoid to densely hyalinized and from relatively acellular to cellular. Calcification may or may not be present. It is distinguished by the presence of sparse cords and islands of inactive odontogenic epithelium. Enucleation or surgical curettage is appropriate therapy and recurrence is low. As there appears to be no correlation of histologic pattern with clinical behavior, it seems unnecessary to try to separate the tumor into two variants. 
5	Total unilateral lung gangrene in Hodgkin's disease: treatment by thoracostomy. Total gangrene of the left lung developed in a 30-year-old male patient with a pulmonary recurrence of Hodgkin's disease after mediastinal irradiation and chemotherapy. Clinically, tension pyopneumothorax and severe septic shock were present. Surgical repair was done by thoracostomy, resecting three ribs. A 2 x 0.5-cm hole in the necrotic wall of the left main bronchus was covered with an intercostal muscle bundle. The necrotic pleural surfaces were treated openly by daily change of dressings. The patient recovered satisfactorily and underwent four further courses of chemotherapy without any complications. 
5	The prophylactic use of octreotide in a patient with ovarian carcinoid and valvular heart disease. This case report describes the use of octreotide, a long-acting somatostatin analogue, in the management of a patient with an ovarian carcinoid tumour and severe cardiac valvular disease. This patient underwent laparotomy and tumour resection without complication. Anaesthesia was induced with midazolam, fentanyl, and vecuronium, and maintained with isoflurane as well as additional fentanyl and vecuronium. However, we feel that it was the use of octreotide that prevented a life-threatening crisis intraoperatively, and recommend its use in patients with carcinoid syndrome undergoing anaesthesia and surgery. 
5	Anaesthetic management of a 2-month-old infant for laser resection of vocal cord granuloma. A 2-month-old infant underwent excision of granulomata of vocal cords with a carbon dioxide laser. High frequency jet ventilation was given through a surgical metal suction tube during the operation. The anaesthetic technique for the infant and the problems of the use of carbon dioxide laser in laryngeal surgery are discussed. 
4	Noninvasive detection of patients with ischemic and nonischemic heart disease prone to ventricular fibrillation. Abnormalities in the fast Fourier transforms of signal-averaged electrocardiograms (ECGs) obtained during sinus rhythm appear to distinguish patients with ischemic heart disease and sustained monomorphic ventricular tachycardia from those without ventricular tachycardia. This study was performed to determine the power of frequency analysis to detect patients with a history of ventricular fibrillation, to determine the extent to which spectra of signal-averaged ECGs from patients with ischemic and nonischemic heart disease are comparable and to compare results of signal-averaged ECG analysis in patients with ventricular fibrillation with results of programmed ventricular stimulation. Signal-averaged ECGs were obtained during sinus rhythm from 60 patients with sustained ventricular tachycardia (Group I) and 34 patients with ventricular fibrillation (Group II). Results of signal-averaged ECG analysis were abnormal in 92% of patients with ventricular tachycardia and 85% of patients with ventricular fibrillation (p = NS). Abnormal spectra were detected in the signal-averaged ECGs from 90% of patients with ischemic and from 86% of patients with nonischemic heart disease (p = NS). In contrast, the results of programmed stimulation differed markedly between the two patient groups. Sustained ventricular arrhythmias were induced in 91% of the patients with ventricular tachycardia compared with only 46% of those with ventricular fibrillation (p less than 0.0001). Moreover, ventricular tachycardia was inducible in 81% of patients with ischemic heart disease compared with only 50% of those with nonischemic heart disease (p less than 0.02). Thus, abnormalities in the spectra of signal-averaged ECGs were found in the majority of patients with ventricular fibrillation and were detectable even in those whose arrhythmia was not inducible by programmed stimulation. These results broaden the potential clinical application of noninvasive interrogation of signal-averaged ECGs to include the prospective identification of patients with ischemic or nonischemic heart disease prone to ventricular tachycardia or ventricular fibrillation. 
1	Bone marrow stromal cell changes in haematological malignancies. Stromal cell numbers from subjects with no haematological disease and those with acute myeloid leukaemia (AML), chronic granulocytic leukaemia (CGL), acute lymphatic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) were compared to determine their role in malignancy. Frozen sections of trephine biopsy specimens from iliac crests were stained for endogenous alkaline phosphatase activity, endogenous acid phosphatase activity, and, using immunocytochemical methods, for endothelial cells (anti-factor-VIII related antigen) and macrophages and related cells (EBM/11). In granulocytic malignancies, whether acute or chronic, alkaline phosphatase positive reticulum cells (AL-RC) and vascular endothelial cells were generally increased. In lymphoid malignancies, the numbers of AL-RC were generally reduced. Numbers of vascular endothelial cells seemed to be normal in ALL but reduced in foci of NHL. Macrophages are numerous in normal marrow, and their numbers seemed to be normal in granulocytic lesions but were more variable and sometimes reduced in ALL and NHL. Lymphoid malignancies, therefore, have a destructive effect on some stromal elements; granulocytic malignancies are associated with normal or increased numbers of stromal cells. A possible consequence of depleted stromal cells might be slower reconstitution of normal haemopoiesis after treatment. The large numbers in granulocytic malignancies raises the possibility of synergistic stimulation between stromal and neoplastic cells. 
5	Experience with the Sarns centrifugal pump as a ventricular assist device. The authors used the Sarns centrifugal pump (Sarns 3M, Ann Arbor, MI) as a ventricular assist device (VAD) in 30 patients between May 1985 and February 1990. Sixteen patients were unweanable from cardiopulmonary bypass at the time of surgery; nine were patients who developed cardiogenic shock postoperatively in the intensive care unit. One was a donor organ failure; one had a failed PTCA; and one an acute myocardial infarction with cardiogenic shock preoperatively. Two patients were bridged to cardiac transplantation. Of the 28 nontransplant candidates, 20 (71.4%) were weaned successfully, 14 (50%) were discharged from the hospital, and 13 (46%) are alive from 1 to 46 months postoperatively (mean, 21.1 months). Three patients received right ventricular support alone; all three were weaned, and two (66.7%) were discharged. Ten patients received left ventricular assistance alone. Six (60%) were weaned, and four (40%) were discharged. Two patients received left ventricular support initially but were taken back for right VAD insertion because of right-sided heart failure; one (50%) is alive. Fifteen patients received biventricular support. Eleven (77.3%) were weaned, and eight (53.3%) were discharged. Patient ages ranged from 19 to 73 years, with a mean age for men of 59 years and 50.5 years for women. There were no thromboembolic events. Various clinical parameters were evaluated to determine effect on weanability and survival. These results show survival equivalent to any other VAD at this time. The centrifugal pump is a convenient and effective means of maintaining ventricular support in individuals who are believed to have salvageable myocardium. 
3	Retrovirus-induced spongiform myeloencephalopathy in mice: regional distribution of infected target cells and neuronal loss occurring in the absence of viral expression in neurons. The Cas-Br-E murine leukemia virus (MuLV) induces a spongiform myeloencephalopathy resulting in a progressive hindlimb paralysis. We have used in situ hybridization with a Cas-Br-E MuLV-specific probe to study viral expression in the central nervous system. Infected cells were concentrated in regions where spongiform lesions and gliosis are detected (lumbosacral spinal cord, brainstem, deep cerebellar regions), suggesting a causative link between the level of virus expression and the degree of pathological changes in this disease. However, viral expression was not in itself sufficient to cause disease, since significant viral expression was observed in regions that did not exhibit pathological changes (cerebellar cortex, hippocampus, corpus callosum, peripheral nervous system). In both diseased and nondiseased regions, endothelial and glial cells were identified as the main target cells. Neurons in diseased regions did not show viral expression. The regional distribution of the spongiform changes appears to be laid down very early following infection, since expression could be detected at 10 days postinfection in regions that become diseased. These results indicate that nonneuronal cells have distinct properties in various regions of the central nervous system and suggest an indirect mechanism of neuronal loss consequent to viral expression in nonneuronal cells. 
4	Use of quinapril in the elderly patient. Quinapril hydrochloride is a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor that has been extensively tested and found effective when administered once-a-day to hypertensive patients of both sexes and all degrees of hypertension and cardiac compromise, including those with left ventricular hypertrophy, with and without congestive heart failure. Observations with earlier ACE inhibitors led to reports that this class of drugs was relatively ineffective in older hypertensive patients. To ascertain the role of quinapril (greater than or equal to 10 mg/day) in older patients, its blood pressure-lowering effects in 1,175 hypertensive patients less than or equal to 65 years of age were compared with those in 304 patients greater than 65 years of age. An excellent response was observed in patients greater than 65 years of age with mild to moderate hypertension (diastolic BP, 95 to 105 mm Hg) and moderate to severe hypertension (diastolic BP, 106 to 115 mm Hg). The reductions in blood pressure achieved with quinapril were at least comparable to those obtained in the younger hypertensives, and were numerically (but not statistically) greater in the mild to moderate group (-14 mm Hg v-12 mm Hg). In addition, the percentage of patients who experienced adverse experiences was lower in the greater than 65 group than in the less than or equal to 65 group (15% v 19%). The main adverse experiences reported included dizziness, headache, cough, fatigue, and hypotension. These findings indicate that quinapril is at least as safe and effective in older hypertensives as in younger patients. 
1	Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival. Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved 3-year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3-year, disease-free survival of 89%, 73%, and 43% for Stage IB-IIA, IIB, and III, respectively, was found. Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB-IIA, IIB, and III, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress. 
1	Increase in incidence of disease due to diagnostic drift: primary liver cancer in Denmark, 1943-85. OBJECTIVE--To examine the extent to which changes in diagnostic methods and classification are responsible for the striking increase in incidence of primary liver cancer in Denmark since 1943. DESIGN--Analysis of the time trends in sex specific, age standardised incidence of primary liver cancer and unspecified liver cancer (either secondary without known primary cancer or not specified as primary cancer) in the entire population from 1943 to 1985. By review of the 727 notifications from three periods of 5 years (1948-52, 1963-7, and 1978-82) the changes in histological diagnosis and classification were assessed. SETTING--Denmark. SUBJECTS--Notifications of liver cancer to the Danish cancer registry. RESULTS--Concomitant with the increase in primary liver cancer, the incidence of the unspecified liver cancer declined. The proportion of histologically diagnosed primary liver cancer rose from 85% to 98%, whereas the proportion for unspecified liver cancer rose from 12% to 51%. When the proportion of primary versus unspecified liver cancer obtained by histological diagnosis was extrapolated to all cases, the annual incidence of primary liver cancer was 4.4 rather than 1.6 per 100,000 population in 1948-52 and 6.0 rather than 5.5 per 100,000 in 1978-82. CONCLUSION--The increase in the incidence of primary liver cancer may be much smaller than the numbers of registered cases indicate. This example emphasises the need to consider diagnostic drift in time trend studies of disease incidence. 
2	Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations. It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin. 
5	Audiometric and subjective assessment of hearing handicap. This study compares self-perceived assessment of hearing handicap with audiometrically derived measures of hearing handicap in a sample of elderly persons. Subjects were evaluated by traditional audiometric tests, the Speech Perception in Noise test, and the Hearing Handicap Inventory for the Elderly, a self-assessment questionnaire. Hearing handicap was also calculated by the audiometrically derived American Academy of Otolaryngology (1979) method. Our results are consistent with other studies that indicate a low correspondence between audiometric measures of hearing handicap and self-assessment of hearing handicap. Furthermore, if the Hearing Handicap Inventory for the Elderly is considered the true measure of hearing handicap, our data indicate that the American Academy of Otolaryngology method tends to overestimate handicap among persons with no self-perceived hearing handicap and underestimates handicap among persons with significant self-perceived hearing handicap. 
4	Normalization of Doppler indices of diastolic dysfunction during pacing is a sign of ischemic mitral regurgitation. Twenty-three patients with angina who were undergoing diagnostic cardiac catheterization underwent cardiac pacing with simultaneous hemodynamic and Doppler echocardiographic evaluation to assess the effects of pacing-induced ischemic on mitral valve velocity. Seventeen patients had significant coronary artery disease, and six patients had normal coronary arteries. Doppler and hemodynamic measurements were performed at rest and immediately after pacing was discontinued to 91% +/- 7% of maximal predicted heart rate. Seven patients experienced new or significant increases in severity of mitral regurgitation after pacing as revealed by Doppler examination. This group had a significant increase (p = 0.007) in early but not in late peak filling velocities immediately after pacing was discontinued, with a resultant decrease in late to early ratios, which decreased from 1.01% +/- 0.12 to 0.70% +/- 0.19 (p = 0.006). Left ventricular end-diastolic pressure increased significantly from 16.7% +/- 6.8 mm Hg to 29.4% +/- 5.3 mm Hg after cardiac pacing (p less than 0.001). Patients with coronary disease who did not develop mitral regurgitation also had significant increases in left ventricular end-diastolic pressure from 18.7% +/- 5.8 mm Hg to 24.3% +/- 8.6 mm Hg (p less than 0.05). There were no changes in late or early wave amplitude, late to early ratio, or other Doppler measurements in any of the other groups. We conclude that mitral regurgitation caused by pacing-induced myocardial ischemia normalizes Doppler indices of mitral inflow, which in turn, may mask persistent or worsened left ventricular diastolic dysfunction. 
1	Induction of cytotoxicity of the renal hilar lymph nodes by pedal subcutaneous administration of interleukin-2 in patients with renal cancer. The authors attempted to increase the cytotoxicity of the renal hilar lymph nodes in ten patients with renal cell carcinoma by administration of recombinant interleukin-2 (IL-2) into the subcutaneous tissue of the instep. A total of 5000 to 21,000 units was given over 3 to 12 preoperative days. Mononuclear cells separated from the lymph nodes excised from the renal hilum at surgery served as the effector cells. Fresh autologous tumor cells and three cultured cell lines, K562, Raji, and ACHN, served as the target cells. Cytotoxicity was measured by a chromium-releasing assay. The results showed that the mononuclear cells from the lymph nodes of the patients given IL-2 became cytotoxic to all target cells. Surface markers of lymphocytes in the lymph nodes were unchanged. Peripheral blood lymphocytes showed increased cytotoxicity only against Raji cells. Adverse effects were mild or moderate and included local redness, high fever, liver dysfunction, and toxic erythema. 
1	Nipple discharge in women. Is it cause for concern? Nipple discharge is one of the most common breast complaints in women. Galactorrhea (milky discharge) may occur during pregnancy or breast-feeding or as a result of drug therapy, hypothyroidism, or hyperthyroidism. Nonbloody discharge is most common and is usually benign. Bloody discharge should be considered a sign of cancer until proved otherwise. Persistent galactorrhea and nonbloody discharge can be treated by transecting the mammary ducts. Simple mastectomy may be appropriate in patients with persistent bloody discharge who have a strong family history of breast cancer. 
3	Antibodies to synthetic peptide (125-148) of the alpha-subunit of human nicotinic acetylcholine receptor in sera from patients with myasthenia gravis. We measured the amount of antibodies to a synthetic peptide that corresponds to the alpha-subunit residues Lys125-Thr148 of human acetylcholine receptor (AChR) in myasthenic sera. We detected anti-peptide antibodies in 52% (89/171) of the patients with myasthenia gravis (MG), but none in any of the healthy controls. Anti-peptide antibodies should provide a valuable immunologic parameter for the clinical evaluation of MG, but no apparent correlation was observed between the titers of anti-peptide and anti-AChR antibodies. 
4	Increased arterial adrenaline is related to pain in uncomplicated myocardial infarction. Plasma levels of catecholamines, beta-thromboglobulin (BTG) and arginine vasopressin (AVP), and degree of pain were examined in 22 patients with suspected uncomplicated myocardial infarction within 24 h following onset of chest pain. Sixteen patients developed infarction with peak creatine phosphokinase at 1280 Ul-1 (range 293-3770 Ul-1). Fifteen healthy men served as controls (C). Arterial adrenaline levels were significantly higher in patients with pain (1.15 +/- 0.23 nmol l-1, n = 8, mean value +/- SEM) than in those without pain (0.60 +/- 0.10 nmol l-1, n = 14, P less than 0.05). Plasma catecholamines were moderately but significantly elevated in myocardial infarction; the concentration of arterial adrenaline was 0.83 +/- 0.14 nmol l-1 and that of arterial noradrenaline was 2.70 +/- 0.28 nmol l-1 compared with 0.44 +/- 0.04 nmol l-1 (P less than 0.025) and 1.47 +/- 0.05 nmol l-1 (P less than 0.0005), respectively, in C. One week later, plasma catecholamines had returned to baseline levels. Plasma BTG showed borderline elevation (1.0 +/- 0.1 pmol l-1) compared with C (0.6 +/- 0.1 pmol l-1, P = 0.04), and remained unchanged 1 week later. Plasma AVP was at baseline level. Uncomplicated myocardial infarction, regardless of size, was associated with only moderately increased sympathetic tone. Plasma adrenaline was related more to the degree of pain than to the presence of acute myocardial infarction. Arterial adrenaline may be a sensitive marker of sympatho-adrenal activity related to pain. 
2	Gastroduodenal mucosal prostaglandin generation in patients with Helicobacter pylori before and after treatment with bismuth subsalicylate. To determine whether Helicobacter pylori has an effect on gastroduodenal mucosal prostaglandin generation, mucosal biopsies were obtained from the gastric body, antrum, and duodenal bulb of 30 patients who were undergoing upper gastrointestinal endoscopy for clinical indications. One biopsy from the gastric body and one from the antrum were tested for urease activity (urea broth) and one biopsy from each area including the duodenum was processed for histology. Two other biopsies form each area were incubated and the accumulation of prostaglandin E2 and 6-keto prostaglandin F1 alpha in the incubation medium was measured by radioimmunoassay. Twelve of the 17 H. pylori-positive patients and seven of the 13 H. pylori-negative patients agreed to take bismuth subsalicylate (Pepto-Bismol) two tablets four times a day for four weeks. One week after treatment, these patients again underwent endoscopy and the above studies. This study indicates that: (1) mucosal PGE2 generation may be increased in the duodenum, gastric body, and antrum in H. pylori-positive patients compared to H. pylori-negative patients, and (2) treatment with bismuth subsalicylate for four weeks results in reduction of mucosal PGE2 in the duodenum, gastric body, and antrum of H. pylori-positive patients and fails to eradicate H. pylori or reduce gastric inflammation. 
1	Malignant melanoma of the biliary tract: a case report. A 58-year-old man was seen with obstructive jaundice and discomfort in the upper abdomen. Computed tomographic and ultrasound examinations revealed a soft-tissue mass in the gallbladder. Cholecystectomy and choledochotomy revealed a soft black mass in the gallbladder and a second one in the intrapancreatic portion of the common bile duct. Each was diagnosed as malignant melanoma. Subsequently, a Whipple resection of the pancreas, duodenum, and distal bile duct revealed a melanoma circumferentially invading and obstructing the distal common duct. No lymph node or distant metastasis was identified. Repetitive searches for another primary site have been negative. The tumor apparently originated in the biliary tract. The patient remains almost well 2 years after diagnosis. 
5	Use of the polymerase chain reaction to monitor the effectiveness of ex vivo tumor cell purging. The polymerase chain reaction (PCR) was used to detect residual malignant disease before and after ex vivo purging with monoclonal antibodies and complement or immunomagnetic treatment of BM samples contaminated with known numbers of t(14;18)-carrying tumor cells. Sensitivity of the PCR was demonstrated by detecting a specific t(14;18) amplification product in DNA extracted from a preparation consisting of one tumor cell among 10(5) normal cells. When BM contaminated with 1% to 5% t(14;18)-carrying cells from the B-cell lymphoma line SU-DHL-4 was subjected to two rounds of anti-B-cell pool of antibodies and complement (Ab-C) treatment a 3- to 4-log reduction of the pretreatment PCR signal was observed. A similar log-cell kill was detected using an independent clonogenic assay confirming the utility of the PCR approach. BM contaminated with a second B-cell lymphoma cell line, OCI-Ly8, was more resistant because a third cycle of Ab-C treatment was required to obtain a similar reduction in the PCR signal. A similar 4 logs of tumor cell removal was obtained using anti-B-cell antibodies conjugated to magnetic beads. These studies demonstrate that the t(14;18) PCR can be used to detect levels of tumor cells as low as 0.001%. This approach can be used to determine the effectiveness of BM purging in patients undergoing autologous BM transplantation as well as to assess the biologic role of minimal marrow disease. 
5	Improved molecular diagnostics for ornithine transcarbamylase deficiency. Since the cloning of the cDNA for X-linked ornithine transcarbamylase (OTC) in 1984, diagnostic accuracy of OTC deficiency for prenatal and carrier detection has been greatly improved by the use of linkage analysis. However, the use of RFLP-based diagnosis is limited in this and in other new mutation diseases. Here we report both the use of direct mutation detection by new PCR-based techniques and our experience with linkage-based diagnosis in 18 families. We have previously reported the use of chemical mismatch cleavage to detect mutations first in amplified mRNA and then in genomic DNA of patients. This technique has now been utilized for prenatal diagnosis. Primers for specific amplification of OTC exons 1, 3, 5, 9, and 10 have been developed and been employed to map deletions of the OTC gene in two families. These primers also have been used to detect alterations in the TaqI sites found in exons 1, 3, 5, and 9. Four novel mutations of the OTC gene leading to abolition of a TaqI site in the OTC cDNA were discovered. One of these mutations is in exon 1; two lie in exon 3; and one is in exon 9. In addition, we have used the PCR products as probes to identify the exon-specific bands seen on Southern blots and to map the polymorphic BamHI and MspI sites, which are commonly used for linkage analysis. This information will facilitate the interpretation of altered band patterns seen in deletion cases and in cases of point mutations affecting restriction sites. Utilization of the appropriate combination of these molecular techniques permitted accurate diagnostic evaluations in 17 of 18 families. 
4	Coronary artery disease in African-Americans. Contrary to opinions generally accepted in the past, CHD is very common in both African-American men and women, with incidence rates approaching those of US Caucasians. Higher prevalence of hypertension, diabetes, cigarette smoking, and obesity all contribute to the high level of CHD in African-Americans. Additional research is needed about the interrelations and management of various risk factors for CHD in African-Americans outside of the sudden death of African-Americans outside of the hospital is urgent, and special attention should be given to accessibility and use of health services by minority populations. 
1	Tricuspid valve papillary fibroelastoma: echocardiographic characterization. We report a tricuspid valve papillary fibroelastoma initially detected by transthoracic two-dimensional echocardiography and subsequently characterized by transesophageal two-dimensional echocardiography. The mass was excised during open heart operation, and the diagnosis was verified grossly and histopathologically. Transesophageal echocardiography usually provides images far superior to those from transthoracic echocardiography and may be a useful adjunct for intraoperative localization of intracardiac tumors for excision. 
5	Reduced psychological morbidity after breast conservation. Psychological morbidity was compared in 52 patients treated by mastectomy and 67 patients treated by lumpectomy for early breast cancer. An informal counselling service was provided for all patients. Morbidity was measured at 6, 9 and 12 months after surgery with two self-rating scales: the general health questionnaire and the Leeds depression and anxiety scales. There was a significant excess of severe depression in the mastectomy group. In contrast to the findings of previous research, this result suggests that breast conservation reduces psychological morbidity. 
1	Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration. A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway. 
1	Radiation therapy of laryngeal cancer: a twenty year experience. This paper reviews a 20 year experience of radiation treatment of 286 laryngeal cancers and presents results with a minimum five year follow-up. All cases presented had glottic or supraglottic squamous cell carcinomas with no clinical evidence of nodal metastasis. A policy of primary radiotherapy with surgery for salvage of treatment failures, produced control of primary disease and prevention of metastases superior to most other regimes documented in the literature. 
5	Stenosis of the sphincter of Oddi. "Stenosing papillitis" is a descriptive term for an anatomic deformity of the papilla of Vater that is characterized by narrowing of the lower end of the bile duct and the proximal end of the duct of Wirsung. The defect is secondary to inflammation and fibrosis from the chronic passage of gallstones, episodes of acute pancreatitis, chronic pancreatitis, sclerosing cholangitis, peptic ulcer disease, and cholesterolosis. Patients with papillary stenosis from gallstones may present with episodes of severe upper-abdominal pain several years after cholecystectomy. The pain is often incapacitating, and patients are often addicted to narcotic analgesics. The work-up includes abdominal ultrasonography and CT scanning and endoscopic retrograde cholangiopancreatography even though the findings usually are normal. Liver and pancreatic enzymes are not frequently elevated with the painful episodes. Transendoscopic manometry may reveal elevated pressures within the papillary portion of the distal bile duct. Some patients are relieved of their pain by transduodenal sphincteroplasty and transampullary septectomy, thereby ablating the sphincter of Oddi around the bile and pancreatic ducts and enlarging their openings. 
3	Diabetic amyotrophy without pain. A puzzling clinical picture. A patient with weight loss and weakness presents a diagnostic challenge. Drs Moeser and Kent describe an unusual case of diabetic amyotrophy that required extensive workup to arrive at the diagnosis and rule out more serious disease. Symptoms were dramatic, and recovery was spontaneous following conservative treatment. 
1	Characterization of the morphonuclear features and DNA ploidy of typical and atypical carcinoids and small cell carcinomas of the lung. The authors analyzed several cytomorphonuclear parameters related to chromatin distribution and DNA ploidy in typical and atypical carcinoids and in small cell lung cancers. Nuclear measurements and analysis were performed with a SAMBA 200 (TITN, Grenoble, France) cell image processor with software allowing the discrimination of parameters computed on cytospin preparations of Feulgen-stained nuclei extracted from deparaffinized tumor tissues. The authors' results indicate a significant increase in DNA content--assessed by integrated optical density (IOD)--from typical carcinoids to small cell lung carcinomas, with atypical carcinoids showing an intermediate value. Parameters related to hyperchromatism (short and long run length and variance of optical density) also characterize the atypical carcinoids as being intermediate between typical carcinoids and small cell lung cancers. The systematic measurement of these cytomorphonuclear parameters seems to define an objective, reproducible "scale" of differentiation that helps to define the atypical carcinoid and may be of value in establishing cytologic criteria for differential diagnosis. 
5	Tissue-specific transformation by epidermal growth factor receptor: a single point mutation within the ATP-binding pocket of the erbB product increases its intrinsic kinase activity and activates its sarcomagenic potential. Avian c-erbB is activated to a leukemia oncogene following truncation of its amino-terminal, ligand-binding domain by retroviral insertion. The insertionally activated transcripts encode protein products that have constitutive tyrosine kinase activity and that can induce erythro-leukemia but not sarcomas. We have found that a single point mutation within the ATP-binding pocket of the tyrosine kinase domain in this truncated molecule can increase the ability of this oncogene to induce anchorage-independent growth of fibroblasts in vitro and fibrosarcoma formation in vivo. Associated with this increased transforming potential is a corresponding increase in the kinase activity of the mutant erbB protein product. The mutation, which converts a valine to isoleucine at position 157 of the insertionally activated c-erbB product, is at a residue that is highly conserved within the protein kinase family. To our knowledge, this is the first demonstration of a point mutation in the ATP-binding pocket that activates a tyrosine kinase. 
5	Pathologic involvement of the left ventricle in chronic cor pulmonale. To determine whether or not the left ventricle is pathologically involved in patients with chronic cor pulmonale, right and left ventricular weights, wall thickness, myocyte diameters, and percentage of fibrosis in 18 autopsied hearts were examined in patients with chronic pulmonary disease (CPD); ten had right ventricular hypertrophy on their electrocardiograms, and eight were without right ventricular hypertrophy. Five with extracardiopulmonary disease were used as controls. The weight of the right ventricle was significantly increased in CPD when compared to control subjects. Walls of both ventricles were significantly thicker in CPD. Myocyte diameters of both ventricles were significantly greater in CPD. The percentage of fibrosis in the right ventricle was significantly greater in CPD. The percentage of fibrosis in the left ventricle was significantly greater only in patients with right ventricular hypertrophy. We concluded that the left ventricle was also involved pathologically in patients with chronic cor pulmonale in the end stage of the disease. 
5	Transient cyst-like cortical defects following fractures in children. Medullary fat within the subperiosteal haematoma. Asymptomatic cyst-like cortical defects appearing after fractures in children have been occasionally reported. Typically, these defects appear during fracture consolidation, within the newly formed subperiosteal bone, proximal to the fracture line, do not enlarge, and progressively disappear. We have previously shown a fatty density on CT scan within the early cortical defect. We now present two additional cases in which early CT scans appeared to confirm that these transient cortical defects may consist of fat, and probably result from the inclusion of medullary fat within the subperiosteal haematoma. 
5	Effect of thiopental on neurologic outcome following coronary artery bypass grafting To determine if thiopental reduces the incidence of neurologic sequelae after coronary artery surgery, we prospectively studied 300 patients undergoing coronary artery bypass grafting. Patients who had no history of neurologic or psychiatric illness were randomly assigned to receive either a thiopental infusion or a saline placebo infusion beginning with the administration of heparin and ending just after aortic decannulation. The patients received an opioid-relaxant anesthetic administered by an anesthesiologist who was not involved in this investigation and who was blinded to the test infusion. One of the investigators infused either saline or thiopental to produce an isoelectric electroencephalogram with 30-45 s between bursts. Standardized neurologic examinations were performed preoperatively and on the 2nd and 5th postoperative days by one of the blinded investigators. The group of patients receiving thiopental required a longer time for awakening (6.4 +/- 3.9 vs. 4.0 +/- 2.4 h, mean +/- SD, P less than 0.05) and for tracheal extubation (22.4 +/- 18.4 vs. 17.4 +/- 9.6 h, P less than 0.05), and a greater number of these patients were lethargic on the 2nd postoperative day. More patients receiving thiopental required vasoconstrictors during the thiopental loading and cardiopulmonary bypass (CPB) periods, while a greater number of patients receiving placebo required vasodilators. A greater number of patients receiving thiopental required inotropic drugs during separation from CPB. Despite the above differences, only 2 of the 151 patients in the placebo group (1.3%) and 5 of the 149 patients in the thiopental group (3.3%) experienced strokes (P = 0.2535). 
3	Reappraisal of surgical treatment of traumatic transection of the thoracic aorta. Since Crawford's report in 1973, repair of traumatic transection of the thoracic aorta without shunt or bypass has emerged as a popular technique which simplifies the operation and avoids use of heparin. Growing evidence, however, indicates that the incidence of paraplegia is higher with this method and may outweigh its advantages. With this in mind, we have examined our experience with 40 patients who underwent repair of aortic transection from 1975-1988. The operated patients in our series all survived. Fourteen were repaired using some type of bypass or shunt, none of whom developed paraplegia. The remaining 26 patients were repaired without a shunt and 9 (34.6%) developed paraplegia or paraparesis (p less than 0.02). Paraplegia was related to aortic occlusion time (p less than 0.002). It did not occur in 11 patients with times less than 27 minutes, but happened in 2 of 8 patients with times between 28 and 35 minutes and in all 7 patients with clamp times over 35 minutes. These data suggest that shunt or bypass should be used in most cases of aortic transection. 
1	Lipomatous hypertrophy of the interatrial septum: an unusual intraoperative finding. Lipomatous hypertrophy of the interatrial septum was an incidental finding in a man of 45 undergoing coronary artery bypass grafting for unstable angina. He was not overweight and did not have any rhythm disturbances. The diagnosis was made on frozen section. 
5	Contraceptive effects of extended lactational amenorrhoea: beyond the Bellagio Consensus. We have recorded the duration of lactational anovulation and amenorrhoea in a well-nourished group of Australian women who breastfed their babies throughout the study. The data enabled us to compare the theoretical cumulative probability of conception among breastfeeding women who had unprotected intercourse irrespective of their menstrual status with that of those who had unprotected intercourse only during lactational amenorrhoea. Breastfeeding alone is not an effective form of contraception, since all the women in our study resumed normal ovulation while still breastfeeding. However, among women who have unprotected intercourse only during lactational amenorrhoea but adopt other contraceptive measures when they resume menstruation, only 1.7% would have become pregnant during the first 6 months of amenorrhoea, only 7% after 12 months, and only 13% after 24 months. Thus for our women it would be possible to extend the Bellagio Consensus Conference guidelines which stated that lactational amenorrhoea can only be relied on as a contraceptive for the first 6 months post-partum in women who are fully or almost fully breastfeeding. The lactational amenorrhoea method can be relied on for excellent contraceptive protection in the first 6 months of breastfeeding, irrespective of when supplements are introduced into the baby's diet; for women who continue to breastfeed the method can also give good protection for up to 12 months post partum. Once menstruation has returned, other forms of contraception are essential to prevent pregnancy. 
5	One-year outcome after cerebral infarction in whites, blacks, and Hispanics. Little is known about outcome after cerebral infarction for different ethnic groups. Of 590 stroke patients hospitalized from 1983 to 1986 at the Neurological Institute, cerebral infarction over age 39 years occurred in 135 whites, 177 blacks, and 82 Hispanics. Outcome after cerebral infarction differed by ethnicity. The 1-month mortality rate was similar in whites and blacks and least in Hispanics. Whites had a slightly greater risk of recurrent stroke or death than blacks or Hispanics until 6 months after infarction, when their risk stabilized, while the risk in blacks and Hispanics continued to rise for the entire year of follow-up. By 1 year, the rate of recurrent stroke or death was 34.8 +/- 4.2% in whites, 31.1 +/- 3.6% in blacks, and 21.4 +/- 4.8% in Hispanics (p = 0.04). Differences were found in the distribution of various stroke risk factors in the three ethnic groups. A Cox proportional hazards model demonstrated that the ethnic differences in stroke risk factors and infarct subtype were responsible for the ethnic differences in outcome. An abnormal first electrocardiogram was a risk factor for stroke recurrence or death in all three ethnic groups, while a nonlacunar infarct subtype and a history of diabetes were significant only in Hispanics. Understanding the associations of stroke determinants with ethnicity may lead to more focused secondary prevention of recurrent stroke. 
5	The effect of age on treatment choice and survival in elderly breast cancer patients. To investigate the effect of age on treatment choice and survival in patients with breast cancer, data from the cancer registry of the Netherlands Cancer Institute (NKI, Amsterdam, The Netherlands) on 611 women have been analyzed. All patients 55 years and older admitted to the NKI for primary treatment of breast cancer between 1981 and 1986 were selected. For women 75 years and older, physicians were less likely to use treatment of adjuvant radiation therapy after a mastectomy and more often employed primary hormonal therapy only for local stage disease than for younger patients. Life-table analysis showed that disease-specific survival at 7 years for patients 65 through 74 years of age was significantly better (65%) than that of the youngest (55%) and the oldest age group (50%). In multivariate regression analysis (Cox), age older than 74 years was significantly and independently associated with a shorter disease-specific survival as compared with patients younger than 75 years. This difference in survival, however, does not seem to be the result of the difference in treatment between the age groups, but suggests an influence of age-related factors such as comorbid diseases and weak physical condition, which manifest themselves most strongly in the oldest age category and make the older woman more vulnerable to the course of malignant disease. 
1	Chemoprotective effects of recombinant human IL-1 alpha in cyclophosphamide-treated normal and tumor-bearing mice. Protection from acute toxicity, hematologic effects, development of late mortality, and enhanced therapeutic efficacy. In this study, recombinant human IL-1 alpha (rhIL-1 alpha) was used to protect normal and tumor-bearing BALB/c mice from the acute toxicity caused by lethal doses of cyclophosphamide (Cy) and 5-fluorouracil. Pretreatment of mice for 7 days with 10,000 U/day of rhIL-1 alpha protected 70 to 100% of mice from the acute death induced by lethal doses of both Cy (380 mg/kg) and 5-fluorouracil (250 mg/kg). In contrast, post-treatment of mice with single or multiple doses of rhIL-1 alpha was not chemoprotective. Pretreatment of mice with rhIL-1 alpha increased the acute LD90 of Cy from 380 mg/kg to greater than 500 mg/kg in normal mice, an LD90 dose-modifying effect of at least 1.25, was accompanied by a more rapid recovery from neutropenia and a less severe reduction in the number of bone marrow single lineage monocyte, myeloid, or myelomonocytic colonies. Some of the mice (10 to 50%) that were successfully protected by pretreatment with rhIL-1 alpha died after day 50. These mice consistently presented with extensive pulmonary inflammation and fibrosis at death. Mice bearing murine renal cancer (Renca) were also protected from the acute toxic effects of Cy (450 mg/kg) by pretreatment with rhIL-1 alpha. Renca-bearing mice pretreated with rhIL-1 alpha and either sublethal (300 mg/kg) or lethal (450 mg/kg) doses of Cy exhibited enhanced survival times over those of untreated Renca-bearing mice. Interestingly, the cause of death in Renca-bearing mice that ultimately failed treatment with rhIL-1 alpha plus 300 mg/kg Cy was recurrent tumor, whereas most mice treated with rhIL-1 alpha plus 450 mg/kg Cy had no detectable tumor, although several died from late pulmonary inflammation and fibrosis. Thus, the dose escalation of Cy in rhIL-1 alpha-pretreated mice results in greater antitumor effects of Cy. However, the dose escalation of some cytotoxic agents allowed by the use of myelostimulatory agents can result in late fatal complications not detected in acute toxicity testing. 
4	Antecedent medical diseases in patients with amyotrophic lateral sclerosis. A population-based case-controlled study in Rochester, Minn, 1925 through 1987. Odds ratios (ORs) were estimated for the prevalence of antecedent endocrine, metabolic, or vascular diseases among 45 patients with amyotrophic lateral sclerosis from the Rochester, Minn, population compared with 90 control subjects matched for sex, year of birth, period of observation, and residence. Hypertension occurred less frequently in male patients with amyotrophic lateral sclerosis (4%) than in control subjects (30%; OR = .10). Because of small population size, no conclusions can be drawn with respect to the following antecedent conditions: thyroid disease (OR = 1.61), coronary artery disease (OR = .58), obesity (OR = .52), diabetes (OR = 1.00), cerebrovascular disease (OR = .21), and peripheral vascular disease (OR = 1.23). The heterogeneity of antecedent thyroid disease makes it highly unlikely that any specific thyroid lesion is causally associated with most cases of amyotrophic lateral sclerosis. Hypertension may be a marker for protective factors against the development of amyotrophic lateral sclerosis in men. 
1	Genetic counselling in retinoblastoma: importance of ocular fundus examination of first degree relatives and linkage analysis. We report an unusual family pedigree segregating the retinoblastoma predisposition gene. Expression of the phenotype in different individuals in this family ranges from asymptomatic gene carriers, regressed tumours, through unifocal to bilateral multifocal lesions. Because of the unusual pattern of inheritance in this family, initial genetic counselling at a local hospital did not take into account the possibility of incomplete penetrance of the gene, and complete ophthalmological examination of unaffected family members was not undertaken. We have used DNA probes from within the retinoblastoma predisposition gene for unequivocal identification of gene carriers. The subsequent demonstration of regressed tumours in founder members of the family confirmed the diagnosis of a dominantly inherited disease. The circumstances of the management of this family emphasises the need for specialist ophthalmic examination of first degree relatives and detailed genetic analysis of all such families with DNA probes. 
5	Gastric duplication cyst communicating with the pancreatic duct: a rare cause of recurrent abdominal pain. A 41-year-old woman with recurrent attacks of postprandial abdominal pain was found on endoscopic retrograde cholangiopancreatography and subsequent computed tomographic scan to have an enteric duplication within the substance of the pancreas with communication to the pancreatic duct. Celiotomy demonstrated a noncontiguous gastric duplication cyst. Internal drainage was curative. 
4	Relationship of left ventricular mass to impairment of coronary vasodilator reserve in hypertensive heart disease. An impaired coronary vasodilator reserve has been demonstrated in all stages of hypertensive heart disease but is most likely in the setting of hypertrophy. The decrease in coronary flow reserve has, however, not been predictable previously. We postulated that flow reserve depression might be related to a left ventricular mass threshold. Seventy-two patients (82% with hypertension) with suspected ischemic heart disease who were found to be free of significant coronary artery disease at cardiac catheterization were evaluated utilizing the intracoronary Doppler catheter and two-dimensional directed M-mode echocardiography for determination of coronary flow reserve and left ventricular mass. For left ventricular mass indexed (LVMI) by body surface area (BSA) greater than or equal to 50% above normal using established gender-specific norms, American Society of Echocardiography (ASE) and PENN methods (correction of LV mass by regression equation agreeing with necropsy estimates of mass) predicted impairment of flow reserve (p = 0.005 and 0.009, respectively). Unindexed left ventricular mass and LVMI by height were not helpful in this regard. Using the ASE method for LV mass determination, coronary flow reserve was moderately depressed (2.4 +/- 1.0) for those with LVMI greater than or equal to 50% above normal; in comparison, flow reserve was normal (3.5 +/- 1.3) for those with LVMI less than 50% above normal. A rare patient was able to maintain a normal flow reserve when ASE- and Penn-indexed mass estimates were greater than or equal to 50% above normal, but only in the setting of a markedly elevated mean arterial pressure. 
1	The operative management of coexisting thyroid and parathyroid disease. Three hundred eight patients who underwent operation for hyperparathyroidism were studied. Fifty-two (17%) were identified who had a concomitant thyroid nodule. All 52 underwent parathyroidectomy and thyroid resection in a single operation. Eleven of these patients (21% of those with a thyroid nodule) had differentiated thyroid cancer. One patient with parathyroid hyperplasia developed permanent hypocalcemia. None had permanent vocal cord paralysis and none required tracheostomy. Thorough visual inspection and palpation of the entire thyroid gland should be performed during operations for hyperparathyroidism. Incidentally discovered thyroid nodules should prompt formal lobectomy with frozen section diagnosis; unanticipated thyroid malignancies should then be treated as independent entities. Treating simultaneous hyperparathyroidism and nodular thyroid disease with a single operation can be done safely; it avoids the expense and risk associated with neck reexploration and can detect unsuspected cancers. 
1	DNA ploidy in the primary tumor from patients with nonseminomatous testicular germ cell tumors clinical stage I. The DNA stemline ploidy was assessed in paraffin-embedded, formalin-fixed primary tumor tissue from 68 patients with nonseminomatous germ cell cancer (NSCGT) clinical Stage I (CS I). Forty-three patients had a single aneuploid (greater than 1C) DNA stemline, whereas 24 patients had multiple aneuploid stemlines. In one tumor there was no evidence of an abnormal DNA stemline. Most DNA stemlines had DNA indices around the 3c value. In 13 patients there was a good correlation between the DNA stemline values observed in the primary tumor and in the retroperitoneal lymph node metastases. No correlation was found between the DNA index and the histologic subclassification or the metastatic behavior. The size of the S-phase fraction did not appear to be predictive of subclinical metastases. In CS I patients with NSCGT determination of DNA stemline values does not yield information of predictive or prognostic significance but may contribute to the understanding of the pathogenesis of NSCGT. 
1	Cellular immune response toward human articular chondrocytes. T cell reactivities against chondrocyte and fibroblast membranes in destructive joint diseases. Articular cartilage is one of the major targets in destructive joint diseases in humans. We studied cellular immune reactions against cartilage cell-surface membranes, because it has recently been suggested that these represent possible antigenic structures, based upon the observation of autoantibodies with this specificity in certain joint diseases. A striking T cell reactivity toward chondrocyte membranes was found both in blood and synovial tissue from patients with rheumatoid arthritis. This reactivity was strongly dependent on the presence of monocytes and had all the characteristics of an antigen-driven process. Clonal analysis demonstrated high precursor frequencies in peripheral blood T cells that were reactive against chondrocyte membranes. This response to chondrocyte membranes greatly exceeded the T cell stimulation induced by membranes from other sources such as fibroblasts or epithelial cells. In contrast to patients with rheumatoid arthritis, individuals with osteoarthritis showed a strong peripheral blood and synovial fluid T cell response not only to chondrocyte membranes, but also to fibroblast membrane material. However, there was no reactivity to epithelial cell membranes. Normal donors generally did not show significant responses to any membrane preparation. These data indicate that there is a strong T cell reactivity toward chondrocyte membranes in destructive joint disorders, and this may significantly contribute to the pathogenetic processes that occur in these diseases. 
1	Management of stage D1 adenocarcinoma of the prostate: the Johns Hopkins experience 1974 to 1987. There is no consensus on the proper management of men with stage D1 adenocarcinoma of the prostate. Although cure is unlikely, many men survive for long intervals apparently free of metastatic disease. Thus, effective palliation of the local lesion with low morbidity is desirable. From 1974 to 1987, 120 consecutive men with stage D1 prostate cancer were treated with 3 primary modes of therapy (mean followup 48 months): 1) expectant therapy (35), 2) external beam radiotherapy (21) and 3) radical prostatectomy (64). These patients were statistically homogeneous as determined by Gleason grade but not by extent of metastatic disease. The over-all 5 and 10-year projected actuarial survival rates for the radical prostatectomy patients were 97 and 62%, respectively, and the apparent clinical survival free of disease at 5 years and 80 months, respectively, was 83 and 68%. The direct disease-specific 10-year survival free of disease was 46%. However, only 3 of 27 patients followed for 3 years or longer had undetectable levels of prostate specific antigen. Using a Cox univariate proportional hazards model several factors appeared to have significant prognostic value including volume of lymph node metastases (macroscopic greater than 2 mm.), percentage of positive lymph nodes sampled and frozen section diagnosis. Gleason grade, clinical stage and the number of positive nodes did not have significant prognostic value. Local recurrence requiring an operation was noted in 8 of 35 patients (23%) treated expectantly, 5 of 21 (24%) treated with radiotherapy and 2 of 64 (3%) treated with radical prostatectomy. Significant gastrointestinal or genitourinary complications occurred in 33% of the men treated with radiotherapy and 1.5% of those undergoing radical prostatectomy. Since the introduction of nerve-sparing radical prostatectomy in 1982, potency resumed in 55% of the 33 patients who were potent preoperatively and have been followed 1 year or longer. These data suggest that in properly selected patients radical prostatectomy, although not curative, can provide excellent palliation of the local lesion with acceptable morbidity and that symptomatic local recurrence of prostatic cancer achieved with radiation therapy is identical to the results in men who were managed expectantly. 
1	Terminal duct adenocarcinomas of salivary tissues. Terminal duct adenocarcinoma is recommended as an encompassing diagnostic designation for a preponderantly intraoral salivary gland carcinoma that has also gone under the names of polymorphous low-grade adenocarcinoma, lobular carcinoma, and low-grade papillary adenocarcinoma. The carcinoma is biologically low grade, with its papillary phenotype manifesting a more aggressive behavior than nonpapillary forms. 
1	Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity. 
5	Dominant negative regulation of the mouse alpha-fetoprotein gene in adult liver. Transcription of the mouse alpha-fetoprotein gene is activated in the developing fetal liver and gut and repressed in both tissues shortly after birth. With germline transformation in mice, a cis-acting element was identified upstream of the transcription initiation site of the alpha-fetoprotein gene that was responsible for repression of the gene in adult liver. This negative element acts as a repressor in a position-dependent manner. 
5	Relatively enhanced S cone function in the Goldmann-Favre syndrome. Using electrophysiologic and psychophysical tests that measure rod, midspectral, and S (blue) cone function, we studied four patients with the Goldmann-Favre syndrome, an autosomal recessive vitreoretinal degeneration. With spectral electroretinography, the predominant signal was from the S cones. With dark-adapted perimetry, all patients had severely reduced rod sensitivities and subnormal midspectral cone sensitivities. With S cone perimetry, the patients had normal or subnormal S cone function. Sensitivity differences between S and midspectral cones were significantly different from normal; there was relatively higher sensitivity to S cones compared to midspectral cones throughout the visual field. This relationship of dysfunctional cone mechanisms in the Goldmann-Favre syndrome is similar to that in the enhanced S cone syndrome, a recently identified retinal degeneration with S cone hypersensitivity. The results suggest that the Goldmann-Favre and the enhanced S cone syndromes are linked by a common pattern of retinal dysfunction. 
3	Neuropsychological profile linked to low dopamine: in Alzheimer's disease, major depression, and Parkinson's disease. A distinct pattern of neuropsychological deficits was associated with low homovanillic acid (HVA) in the cerebrospinal fluid of 21 patients with: Alzheimer's disease (9), Parkinson's disease (8) and major depressive disorders (4). Regardless of clinical diagnosis, patients with low HVA were slower on a test of efficiency of processing timed information, and showed greater benefit from semantic structure on a verbal fluency task than patients with high HVA. However, low HVA subjects were not significantly impaired on confrontation naming (Boston Naming Test). Across three diagnostic groups, patients with lower HVA also tended to have more extrapyramidal motor signs and were significantly more depressed. These results demonstrate a significant relationship between specific neuro-behavioural deficits and dopaminergic activity which cuts across traditional diagnostic categories. 
4	Stressful experience and cardiorespiratory disorders. Ever since Selye's time, the belief has persisted that the outcome of stressful experience is disease. The likelihood of this eventuality is increased when the experience is damaging, unavoidable, or uncontrollable. However, in most stressful instances, these conditions do not occur. The experience either is overcome or produces disturbances in physiological functions without structural change. The prevalence of "functional" disorders are far more common in medical practice than is disease. Among the most interesting of these is the hyperventilation syndrome, which may mimic or be confused with ischemic heart disease. Its symptomatology and physiology are complex. The syndrome may produce coronary vasospasm, but it may also complicate ischemic heart disease. It is even believed that chronic hyperventilation may be a risk factor for ischemic heart disease. Stressful experience consisting of various tasks and challenges may also produce myocardial perfusion deficits in ischemic heart disease, presumably secondary to vasospasm. These deficits are in turn considerably more frequent in any one patient than ST segment changes in the electrocardiogram or the incidence of angina pectoris. Vasospasm is in turn related to cardiac arrhythmias, which may occur with ischemic heart disease during a variety of stressful experiences and during outbursts of anger. Finally, the role of stressful experience in inciting ischemic heart disease and its complications remains moot. 
3	Multiple sclerosis and narcolepsy: possible similar genetic susceptibility. We have studied 2 patients with multiple sclerosis and narcolepsy. In both patients, the DR 2 histocompatibility antigen was positive. In each of the patients, the diagnosis of narcolepsy was confirmed by polygraphic testing. 
2	Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis. Substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein. In the colonic mucosa of animals, phenols are inactivated predominantly by conjugation with sulphate. The purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol, paracetamol, in rectal dialysis bags. The incubation of paracetamol with colonocytes isolated from resected colon specimens (n = 7) yielded a mean (SE) value of 7.0 (0.9) mumols/g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide. Paracetamol sulphate was detected in rectal dialysates from all control subjects, with a mean (SE) value of 4.2 (0.8) nmol/hour. Sulphation was significantly impaired (p less than 0.01) in 19 patients with active ulcerative colitis (0.6 (0.2) nmol/hour) and in 17 patients with ulcerative colitis in remission (1.1 (0.4) nmol/hour). Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was similar to that in control subjects. Impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells, which are continuously exposed to endogenous phenols from the colonic lumen. 
3	Quantitative evaluation of sway as an indicator of functional balance in post-traumatic brain injury. The test of sway, using different conditions of stance with measurements of the average radial deviation of the center of pressure and its path length of sway per unit of time, has been shown to be a useful clinical tool in determining balance problems in traumatic brain injury (TBI) patients. Normative values were established to determine if an individual patient's sway values fell within the normal range (mean +/- 2SD). The tests have shown good test-retest reliability for TBI patients. In addition, it has been shown that the sensitivity of the test is sufficient to identify changes in patients' performances as their clinical conditions change. It has been demonstrated that the different stance conditions of the battery of tests become progressively more difficult to perform (from comfortable stance, eyes open and eyes closed, through narrow stance, eyes open and eyes closed, to tandem stance with right or left foot forward, eyes open and eyes closed). By using these subtests, it is easy to distinguish between the performances of able-bodied patients and TBI patients with very mild balance problems. The validity of the measure has been documented by correlating the sway performance with clinical functional performance tests. The test performance also correlates with the patient's own assessment of his or her gait difficulties. The limited data available suggest that the test of sway relates difficulties in static balance to the frequency of falls. Finally, subtests permit identification of specific problems in maintaining balance as a basis for therapeutic intervention. 
3	Neglected factors in chronic pain treatment outcome studies--referral patterns, failure to enter treatment, and attrition. An increasing number of chronic pain treatment outcome studies have appeared in the literature. In general, these studies support the efficacy of multidisciplinary pain programs, as well as specific treatment modalities such as biofeedback and relaxation. Reviews of this literature have tended to be cautiously optimistic. Some concerns, however, have been raised about the methodological adequacy of these studies, particularly in terms of the lack of control groups, the brief duration of follow-up periods, and the vague criteria used for establishing the success of the therapeutic interventions. Other factors that mitigate conclusions regarding the generalizability of the favorable results reported need to be considered. In this paper 3 rarely discussed topics that are implicit within most treatment outcome studies and that need to be given greater attention are examined. These topics include: (1) referral patterns to pain clinics (who are referred to pain clinics, when, and how representative is the referred sample?); (2) failure to enter treatment (e.g., exclusion criteria, lack of available financial support to cover the cost of treatment, patient's refusal to accept recommendations), and consequently, the representativeness of the treated sample; and (3) patient's attrition. In this paper we discuss each of these factors as they underscore important qualifications that have to be made in evaluating treatment outcome studies. 
1	A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer [published erratum appears in JAMA 1991 Sep 11;266(10):1362] To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7). 
5	Myelopathy presenting decades after surgery for congenital cervical cutaneous lesions. We report on two patients in whom cervical myelopathy developed decades after they had undergone surgery for congenital cervical cutaneous lesions. Preoperative magnetic resonance imaging demonstrated dorsal tethering and cavitation of the cervical cord in the area of the previous surgery and was helpful in decision making regarding surgical exploration and in planning for it. We stress the importance of long-term follow-up by both clinical examination and magnetic resonance imaging in children who have been operated on for cervical cutaneous masses that may have central connections. 
2	Alkaline reflux gastritis. Alkaline reflux gastritis and the symptoms associated with alkaline reflux gastritis have been reported in the medical literature since shortly after Billroth successfully performed his first gastrectomy in the 1880s. The disease process is produced by, or at least is associated with, the reflux of alkaline secretions into the gastric remnant. Although it occurs after any procedure that ablates the pylorus including pyloroplasty, it would appear to be most common after a Billroth II gastrojejunostomy. How the alkaline secretions cause the gastritis is still controversial. Clearly, the most effective therapy is to reroute the secretions from the biliary tract, pancreas, and duodenum so that they will not reflux into the gastric remnant. This is most effectively accomplished by a Roux-en-Y gastrojejunostomy with the afferent limb measuring at least 18 inches (40 cm). The surgeon and the patient should be aware that the construction of such a gastric outlet channel is associated with delayed gastric emptying. The etiology of this impaired emptying is also controversial. If the patient has symptoms of dumping (either early or late), these symptoms may also be abated using the Roux limb. At least 40% of patients will have gastric outlet obstruction. Supportive therapy is appropriate in the majority of these patients. 
3	Neurologic and psychiatric manifestations of HIV disease. Neuropsychiatric problems have assumed an increasingly prominent role in HIV-infected individuals. Disease occurs at all levels of the central and peripheral nervous systems by a variety of mechanisms. The AIDS dementia complex is the prototypical example of "direct" effects of HIV on the neuraxis, while infections such as toxoplasmosis and cryptococcal meningitis are complications of HIV-induced immunosuppression. Neurologic manifestations vary in frequency depending upon the overall stage of HIV disease; diagnostic difficulties may be encountered because of HIV's effect on cerebrospinal fluid parameters. The uncertainties of management of neurosyphilis in this setting provide and example of these problems. As is the case with other organ systems, the main goal of neurodiagnostic efforts is to find the increasing number of treatable components of neuropsychiatric dysfunction. 
2	Rapid intravenous rehydration in the pediatric emergency department Children suffering from mild to moderate (3 to 6%) dehydration likely caused by viral gastroenteritis are often hospitalized because they are unable to tolerate oral fluids. We studied 17 such children, aged one to six years, who were otherwise healthy. All had isonatremic dehydration and were treated with 30 ml/kg of 3.3% dextrose and 0.3% saline over a period of three hours in the emergency department before being discharged. No patient required admission to the hospital. Only one patient required another course of rapid intravenous rehydration and subsequently improved without hospitalization. Although all our patients experienced vomiting before treatment, 65% had no vomiting after treatment. Rapid intravenous rehydration is an effective treatment, for children with mild to moderate dehydration secondary to presumed viral gastroenteritis, that obviates the need for hospitalization. 
3	Neurotoxic action of veratridine in rat brain neuronal cultures: mechanism of neuroprotection by Ca++ antagonists nonselective for slow Ca++ channels. The effect of various Ca++ antagonists and local anesthetics on neuronal cell degeneration induced by veratridine was studied in primary rat brain neuronal cultures. Cell death was quantified by measuring lactate dehydrogenase (LDH) released in the culture medium. The neuronal cell degeneration was Ca+(+)-dependent because, in the absence of extracellular Ca++, 16 hr of exposure to 30 microM veratridine failed to produce release of LDH. Ca++ antagonists, nonselective for slow Ca++ channels (flunarizine, cinnarizine, lidoflazine, prenylamine and bepridil) inhibited veratridine-induced release of LDH with IC50 values between 0.11 and 0.47 microM. Ca++ antagonists selective for slow Ca++ channels were less potent and inhibited veratridine-induced release of LDH at concentrations in the following order of potency: nicardipine greater than gallopamil and verapamil greater than niludipine greater than nitrendipine greater than nifedipine greater than nimodipine greater than diltiazem. Tested local anesthetics were incomplete inhibitors of veratridine-induced release of LDH. A good correlation was found between the potency of the drugs to inhibit released LDH induced by 30 microM veratridine in neuronal cultures and their binding affinity for the batrachotoxin binding site of Na+ channels in rat cortex synaptosomal preparation. It is concluded that protection against veratridine-induced neurotoxicity can be mediated by blocking a veratridine-sensitive Na+ channel. It is a property of certain nonselective Ca++ antagonists. There is apparently no direct relationship with Ca++ antagonistic activity. The effect is unrelated to local anesthetic activity. 
2	The influence of sclerotherapy on gastric mucosal blood flow distribution. Hemodynamic events and structural vascular changes of the gastric mucosa in cirrhotics have caught the attention of investigators in the recent past, but as yet it is not known whether therapeutic interruption of variceal blood flow at gastroesophageal level alters such portal hypertensive mucosal features. The newly developed endoscopic laser-Doppler technique was used to assess whether variceal eradication by means of endoscopic sclerotherapy influences the gastric mucosal congestion in portal hypertension patients. Gastric mucosal blood flow was determined at ten defined sites of the stomach, before the first session of sclerotherapy and after complete variceal eradication had been achieved in 15 patients. A statistically significant decrease (P less than 0.01 to 0.05) in microcirculation was found at the gastric antrum and corpus, an increase at the pylorus (P less than 0.05), but no change in the fundic area. An important question following these findings is: What are the consequences of such aggravation of gastric congestion on the integrity of the gastric mucosa?. 
1	Systemic chemotherapy for urothelial cancer in patients with ureteric obstruction. The aims of this study were to document the toxicity of systemic chemotherapy and response rates in patients with ureteric obstruction caused by urothelial cancer. The study group included 91 patients who received cisplatin and methotrexate; 36 (40%) had upper tract dilatation, 9 of whom had drainage by stenting or nephrostomy and 55 (60%) had normal upper tracts. The response rate was documented in 65 patients (71%) who had measurable primary or metastatic disease. No significant differences were found between the dilated/drained group, the dilated/undrained group and the normal group in biochemical measurements of renal function during or after the courses of chemotherapy. Serious haematological toxicity occurred in 10% (10/104 cycles) of the dilated/undrained group and in 6% (12/200 cycles) of the normal group. The complete response rate in the dilated group was 15% compared with 41% in the normal group. No increased chemotherapy toxicity was observed in patients with upper tract dilatation and a significant complete response rate was found in patients with upper tract dilatation without renal impairment. 
1	Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas. Histopathologic grading of salivary gland neoplasms has been done with various degrees of success and hence various degrees of acceptance among pathologists and otolaryngologists-head and neck surgeons. Given their histopathologic diversity, three carcinomas--mucoepidermoid, adenoid cystic, and acinic cell--would seem to be suitable candidates for grading. In this, the first of a three-part series, the authors present a three-level grading scheme for mucoepidermoid carcinomas. It combines histocytologic and growth features of the carcinomas that independently or together, in other grading proposals, have shown prognostic value. 
5	Cardiopulmonary perfusion and cerebral blood flow in bilateral carotid artery disease The fear of cerebral complications after cardiopulmonary bypass in patients with heart disease and severe carotid artery disease has led many authors to suggest combined approaches in these patients. The pathogenetic mechanism for stroke is based partly on the stenotic narrowing of the carotid artery. A diameter reduction of 75% is frequently considered hemodynamically significant and indicative of an increased risk for neurological morbidity. We studied the cerebral blood flow in 7 patients undergoing coronary artery bypass grafting who also had severe bilateral carotid disease. The results were compared with the results in 17 patients without carotid disease who had bypass grafting. The cerebral blood flow was measured by xenon 133 washout technique before, during, and after cardiopulmonary bypass with moderate hypothermia. Acid-base regulation was according to the alpha-stat theory, and blood pressure was kept greater than 50 mm Hg. The cerebral blood flow levels (mL.100g-1.min-1) before, during, and after cardiopulmonary bypass in the study group (30 +/- 11, 31 +/- 8, 47 +/- 20) (mean +/- standard deviation) were almost identical to those in the control group (30 +/- 11, 28 +/- 8, 47 +/- 12). The cerebral blood flow levels for the left and right hemispheres in the group with carotid disease were comparable and within normal ranges. In 2 patients, slight differences were noted between hemispheres, and this finding may indicate an increased risk for ischemia. These patients, however, did not show any signs of postoperative deficit. The flow limitations of critical carotid stenoses do not seem to imply a risk for cerebral hypoperfusion if cardiopulmonary perfusion is performed in a controlled manner. 
2	Pelvic pain and infections. Infectious etiologies of both acute and chronic pelvic pain are common and may involve multiple organ systems. In the evaluation of the acute pain, it is important to remember that rapidity of diagnosis is important because of the possibility of significant morbidity and even death if a condition is not attended to rapidly. In recent years, laparoscopic evaluation of the pelvis has provided a better understanding of the pathophysiology of some of these infections, as well as possible therapeutic maneuvers. The evaluation of chronic pelvic pain requires a thorough attempt at careful diagnosis with minds open to the possibility that other organ systems besides the genital tract may be involved. Laparoscopy also may be an important diagnostic and therapeutic tool in the evaluation of the sequelae of pelvic inflammation leading to chronic pelvic pain. All therapeutic modalities that are instituted on the basis of the diagnostic evaluation must take into consideration that a strong emotional component is generally associated with chronic pelvic pain. Such components must be addressed in order to achieve the best possible results for the patient. 
5	Epidural morphine with butorphanol for postoperative analgesia after cesarean delivery. Epidural morphine has been used more and more to provide long-lasting postoperative analgesia after cesarean delivery. However, the incidence of pruritus (20%-93%) and nausea (17%-60%) detract from the usefulness of epidural morphine. The purpose of this study was to evaluate, in 30 patients having epidural anesthesia for cesarean delivery, the analgesic efficacy and side effects when a combination of epidural morphine, a mu-receptor agonist, and butorphanol, a mu-receptor antagonist and kappa-receptor agonist, was administered. After clamping of the umbilical cord, patients received 4 mg epidural morphine with 3 mL of normal saline (group 1), 4 mg epidural morphine with 1 mg butorphanol and 2 mL of normal saline (group 2), or 4 mg epidural morphine with 3 mg butorphanol (group 3). Patients were monitored for 24 h after administration of the study medications. There were no significant differences between the groups in visual analogue pain scores, time to first analgesic request, respiratory rate, or Trieger dot test performance in the 24 h immediately after these epidural injections. There were three patients in group 1 and one patient in group 2 who experienced oxygen saturations less than 90%. (No patients in group 3 developed an oxygen saturation less than 92%.) The patients in group 3 did not require treatment for pruritus or nausea, a response significantly different (P less than 0.001 and P less than 0.05, respectively) from group 1 or group 2. 
2	Perforated duodenal ulcer: an unusual complication of gastroenteritis. A 7 year old boy was admitted to hospital with gastroenteritis, which was complicated by an acute perforated duodenal ulcer. After oversewing of the perforation he made an uncomplicated recovery. Peptic ulceration is under-diagnosed in childhood and this leads to delay in diagnosis and appropriate management. Ulceration is associated with severe illness and viral infections, but perforation is rare. 
2	Yersinia enterocolitica abscess of the transverse colon. Report of a case. Yersinia enterocolitica abscess of the bowel is a rare entity. Only five cases have previously been reported--none in the surgical literature. A unique presentation for Yersinia infection, abscess of the transverse colon, is described, and the literature of Y. enterocolitica intestinal perforation and abscess is reviewed. 
4	Prognostic significance of valvular regurgitation in patients with infective endocarditis. PURPOSE: Doppler ultrasound is a sensitive modality for detecting and quantitating valvular regurgitation in patients with infective endocarditis. Because valvular regurgitation leads to heart failure, we evaluated the prognostic significance of Doppler-detected valvular regurgitation in patients with endocarditis who had not yet developed clinical heart failure. PATIENTS AND METHODS: We reviewed the medical records of 65 patients with a clinical diagnosis of infective endocarditis from May 1985 to March 1990. A total of 49 patients were included in the study: 33 patients with native valve endocarditis and 16 patients with prosthetic valve endocarditis. The initial Doppler echocardiogram was examined in these patients to determine the presence and degree of valvular regurgitation. RESULTS: Significant (moderate to severe) valvular regurgitation was detected in 23 (47%) patients. The presence or absence of significant valvular regurgitation did not predict the development of congestive heart failure, the need for surgery, or death (p = NS). The development of congestive heart failure was significantly associated with the need for surgery (p less than 0.0001) and death (p less than 0.05). CONCLUSION: We conclude that the detection of significant valvular regurgitation in patients with infective endocarditis who have not yet developed heart failure is not predictive of future complications nor does the absence of significant valvular regurgitation identify a group of patients with a more favorable prognosis. In our series, patients who developed congestive heart failure had a significantly higher incidence of surgery and death. Therefore, decisions regarding clinical management in patients with infective endocarditis should not be made solely on the presence or absence of echocardiographically detected valvular regurgitation. 
5	Is emotional disturbance a precipitator or a consequence of chronic pain? The present study examined the relationship between psychological factors and pain in order to assess the contribution of emotional disturbance to the perpetuation of pain. A group of 163 chronic pain suffers in multiple settings was compared with 81 control subjects on measures of personal history antecedent to pain onset, as well as on measures of current emotional disturbance. In addition, these psychological variables were examined for their associations with subjectively rated pain intensity. Overall, pain was found to be related to more current depression and less current life satisfaction, but was not associated with most of the personal history variables examined. These results suggests that emotional disturbance in pain patients is more likely to be a consequence than a cause of chronic pain. The dangers of routinely ascribing intractable pain to psychological causation are discussed in the light of these findings. 
1	Significance of positive margins in oral cavity squamous carcinoma. Three hundred ninety-eight consecutive, previously untreated patients undergoing surgery for epidermoid carcinoma of the oral cavity from 1979 to 1983 were reviewed. One hundred twenty-nine patients were classified as having positive surgical margins. Of these, 83 patients had tumor within 0.5 mm of the surgical margin, 9 had premalignant changes at the margin, 9 had in situ carcinoma at the margin, and 28 had invasive cancer at the margin. The remaining 269 patients had uninvolved margins. The significance of positive margins relating to survival, subsequent clinical course, local recurrence, and patterns of treatment failure was examined, along with the impact of adjuvant postoperative radiotherapy on positive margins. The percentage of patients having positive margins progressively increased with increasing T stage: 21% in T1 versus 55% in T4 primary cancer. The overall 5-year survival for patients with negative margins was 60%. For patients with positive margins, 5-year survival was 52%. This difference was statistically significant. The incidence of local recurrence in patients having positive surgical margins was twice as much as in those with negative margins (36% versus 18%). Metastasis rates in the neck and at distant sites were not significantly influenced by the status of the surgical margin. Of the 129 patients with positive margins, 49 received postoperative radiotherapy. In those patients so treated, a trend toward lower recurrence rates was noted. Differences were not statistically significant. This retrospective review confirms the importance of adequate resection of the primary tumor as well as the relative ineffectiveness of adjuvant postoperative radiotherapy in the improvement of local control in patients with positive surgical margins. 
5	Transpalpebral decompression of endocrine ophthalmopathy (Graves' disease) by removal of intraorbital fat: experience with 147 operations over 5 years. From 1984 to October 1989 at the Plastic Surgery Unit in Wesseling, we carried out 147 operations on 75 patients with Graves' disease. Intraorbital fat was removed through a transpalpebral incision to achieve decompression. The average amount of fat was 6.0 cm3. We have made a long-term follow-up (more than 6 months postoperatively) study of 57 patients who experienced 108 operations. The first results were published in September 1988. When we compared the results to a traditional decompression operation (with resection of one or two orbital walls), we found that the postoperative complication rate was significantly lower and that the success rate was much higher. Thus the range of indications for surgery may be much wider than previously considered. Patients who are about to lose their vision as well as those experiencing lesser symptoms can be much improved with this operation. At the beginning, before the technique was fully developed, complications such as supraorbital nerve palsy occurred. 
3	Dopamine beta-hydroxylase activity in cerebrospinal fluid of idiopathic torsion dystonia. Since a postmortem biochemical study and a genetic linkage study of idiopathic torsion dystonia suggested possible involvement of dopamine beta-hydroxylase (DBH), we determined CSF DBH activities of Jewish and non-Jewish patients with childhood-onset idiopathic torsion dystonia and found no differences from a control population. 
4	Autonomic nervous system and coronary blood flow changes related to emotional activation and sleep. Experimental models have been developed to investigate the influences of anger, fear, and sleep on coronary blood flow. Studies of anger in dogs with coronary stenosis indicate that the postarousal phase is particularly conducive to myocardial ischemia. Specifically, a delayed coronary vasoconstrictor response has been observed within 1-3 minutes after cessation of behavioral arousal. The response is prevented by bilateral stellectomy and can be elicited in anesthetized animals by electrical stimulation of the right or left stellate ganglion. The latter effect is averted by alpha-adrenergic blockade with prazosin. Although the basis for the protracted nature of the delayed vasoconstriction remains to be clarified, the current hypothesis is that the phenomenon results from a time-dependent imbalance between the vasoconstrictor effects of adrenergic input and the vasodilator influences of coronary pressure and/or cardiac metabolic activity. A behavioral model emulating the fear state has also been developed. When dogs that fail to exhibit anger are placed in a food-access confrontation protocol, the animals demonstrate a fearlike state evidenced by a cowering posture and somatic tremor. There is a distinct plasma catecholamine profile that is characterized by a predominant increase in epinephrine compared with norepinephrine. This is in contrast to the pattern observed during anger, in which a prevalent increase in norepinephrine is observed. Fear results in significant increases in heart rate, arterial blood pressure, and coronary arterial flow. Sleep is also associated with substantial alterations in coronary hemodynamic function. 
5	Fungal pulmonary infections after bone marrow transplantation: evaluation with radiography and CT. The authors reviewed 55 pairs of chest radiographs and computed tomographic (CT) studies obtained in 33 febrile bone marrow transplant (BMT) recipients. The images were read separately, without knowledge of the clinical diagnosis. Twenty-one episodes of fungal infection were documented. One chest radiograph showed a pneumonia-like opacity, and 17 showed nodular opacities, five with cavitation. In 20 of 21 episodes, CT showed nodules with cavitation (n = 7), halo (n = 4), hazy margin (n = 5), air bronchogram (n = 2), cluster of fluffy nodules (n = 1), or sharp margin (n = 1). In none of the nine bacteremic episodes, however, were there opacities on chest radiographs or CT studies. CT studies demonstrating complicated nodules in febrile BMT patients strongly suggest a fungal infection, whereas negative CT studies suggest bacteremia or non-filamentous fungal infection of nonpulmonary origin. CT appears to add useful information to radiographic analysis during the assessment of febrile episodes in BMT patients, especially when invasive diagnostic procedures pose a high risk. 
5	Percutaneous support devices for high risk or complicated coronary angioplasty. Indications for coronary angioplasty have expanded to include patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease and impaired left ventricular function. Several mechanical approaches have been developed as adjuncts to high risk coronary angioplasty to improve patient tolerance of coronary balloon occlusion and maintain hemodynamic stability in the event of complications. These percutaneous techniques include intraaortic balloon counterpulsation, anterograde transcatheter coronary perfusion, coronary sinus retroperfusion, cardiopulmonary bypass, Hemopump left ventricular assistance and partial left heart bypass. The intraaortic balloon pump provides hemodynamic support and ameliorates ischemia by decreasing myocardial work; it may be inserted for periprocedural complications or before angioplasty in patients with ischemia or hypotension. Anterograde distal coronary artery perfusion may be accomplished passively through an autoperfusion catheter or by active pumping of oxygenated blood or fluorocarbons through the central lumen of an angioplasty catheter. Synchronized coronary sinus retroperfusion produces pulsatile blood flow via the cardiac veins to the coronary bed distal to a stenosis. Both perfusion techniques limit development of ischemic chest pain and myocardial dysfunction in patients undergoing prolonged balloon inflations. Percutaneous cardiopulmonary bypass provides complete systemic hemodynamic support which is independent of intrinsic cardiac function or rhythm and has been employed prophylactically in very high risk patients before coronary angioplasty or emergently for abrupt closure. These and newer support devices, while associated with significant complications, may ultimately improve the safety of coronary angioplasty and allow its application to those who would otherwise not be candidates for revascularization. 
5	Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation defect in the offspring. A case of a 29-year-old woman who has had two episodes both clinically and biochemically consistent with acute fatty liver of pregnancy is described. These episodes occurred in two successive pregnancies, and liver biopsy confirmed the diagnosis in the second pregnancy. Both pregnancies were managed by prompt fetal delivery; on both occasions this led to a complete biochemical resolution of the liver function abnormalities. Two healthy babies were delivered by ceasarian sections. This case is of particular importance because a rapidly progressive and devastating illness developed in both infants, leading to death at 6 1/2 and 6 months, respectively. The illness in both babies was characterized by wide-spread fatty infiltration of several vital organs and a failure of any treatment to influence the outcome of that illness. Studies suggested that the illness in the children was caused by a still ill-defined disorder of fatty acid oxidation. The biochemical disorder evidenced in this family is discussed, in an attempt to shed light on the etiology of acute fatty liver of pregnancy. 
5	Chronic diarrhea in essential mixed cryoglobulinemia: a manifestation of visceral vasculitis? Gastrointestinal involvement occurs frequently in essential mixed cryoglobulinemia, and most often involves the liver and spleen. Intestinal involvement is much less common and is generally felt to be a late and often catastrophic manifestation of the disease due to severe vasculitis. Occasionally, the disorder mimics inflammatory bowel disease, both clinically and radiographically. We recently cared for a patient with essential mixed cryoglobulinemia who developed persistent diarrhea. Endoscopic evaluation revealed scattered petechial lesions in the duodenum and colon as well as prominent lymphoid hyperplasia in the terminal ileum. Mucosal biopsies disclosed the presence of diffuse inflammation. We suggest that this patient's diarrhea was due to intestinal vasculitis and that prominent ileal lymphoid hyperplasia may be a manifestation of essential mixed cryoglobulinemia. 
5	CR leads in cardiac emergencies. A preliminary study. The purpose of this study was to find a set of simplified electrocardiographic (ECG) leads that would be useful in cardiac emergencies. In 27 ambulatory cardiac patients and in 15 patients admitted to the hospital, we found that ECG records obtained with six bipolar CR leads were, in most respects, similar to records obtained previously in the same patients with six V leads. Records obtained with two abdominal-upper extremity leads, tested as possible alternatives to limb leads 2 and 3, were quite similar to records obtained with leads 2 and 3 in patients with an inferior wall infarction. Records obtained with leads CR7, CR8, and CR9 in a patient with a posterior wall infarction revealed a QS pattern that was not seen in the conventional 12-lead hospital record. In patients with anterolateral and inferior myocardial infarctions and in patients with unstable angina, the diagnostic patterns recorded with 11 bipolar leads described in this report were identical to patterns recorded with 12-lead ECGs. Although a larger number of observations, including patients with arrhythmias, would be required to reach a definitive conclusion, our results provide preliminary evidence that cardiac potentials may be adequately analyzed by using only two electrodes, using CR and abdominal leads, in succession. The technique described in this report, in which the reference electrode is attached to the right arm, and the exploring electrode is moved successively over nine preselected chest sites and over the umbilicus, can be completed in less than 3 minutes in a given patient, and provides records that are comparable to those obtained with the conventional 12-lead system. 
4	Sudden death in hypertrophic cardiomyopathy with normal left ventricular mass An active, healthy, and symptom free 16 year old boy with a family history of hypertrophic cardiomyopathy died suddenly while walking home from school. Necropsy showed absence of left ventricular hypertrophy (that is, normal heart weight), though the characteristic histological abnormalities of hypertrophic cardiomyopathy, such as cardiac muscle cell disorganisation and abnormal intramural coronary arteries, were present. It is likely that this patient had hypertrophic cardiomyopathy and died before left ventricular hypertrophy developed. 
2	Development of acute myelocytic leukemia in patients with Crohn's disease. In our hospital within one year two patients with Crohn's disease were seen who developed an acute myelocytic leukemia. A review of the literature reveals eight previously reported patients with both Crohn's disease and leukemia. Six of the reported 10 patients have had acute myelocytic leukemia and, interestingly, three of them, including our two patients, have shown monocytic differentiation (FAB type M4). It has been suggested that the relative risk of leukemia, especially acute myelocytic leukemia, is increased in patients suffering from ulcerative colitis. More data of patients with Crohn's disease and acute leukemia are needed to evaluate the possible association between these diseases. 
5	Sudden death during empiric amiodarone therapy in symptomatic hypertrophic cardiomyopathy. Amiodarone is reported to improve symptoms and to prevent sudden death in patients with hypertrophic cardiomyopathy (HC). Amiodarone treatment (loading dose 30 g given over 6 weeks; maintenance dose 400 mg/day) was prospectively evaluated in 50 patients with HC in whom the drug was initiated because of symptoms refractory to conventional drug therapy (calcium antagonists and beta blockers). Twenty-one (42%) patients had ventricular tachycardia (VT) during Holter monitoring. Amiodarone significantly and often markedly improved the patients' New York Heart Association functional class status (from 3.3 to 2.7 at 2 months, p less than 0.001) and treadmill exercise duration (p less than 0.001). Eight patients, however, died (7 suddenly) during a mean follow-up period of 2.2 +/- 1.8 years. Of the 7 sudden deaths, 6 occurred within 5 months of initiation of treatment. The 6-month and 1- and 2-year survival rates were 87, 85 and 80%, respectively. The survival rate of patients with VT was significantly worse than that of patients without VT (61 vs 97% at 2 years; p less than 0.01). Sudden death occurred despite abolition of VT on Holter monitoring. Amiodarone increased left ventricular peak filling rate by radionuclide angiography in 20 of 33 patients (61%) (p less than 0.01). Decrease in peak left ventricular filling rate within 10 days of amiodarone therapy (8 of 33 patients) was associated with subsequent sudden death (p less than 0.04). 
5	Clinical significance of white cell antibodies in febrile nonhemolytic transfusion reactions. Febrile nonhemolytic transfusion reactions (FNHTRs) are associated with white cell (WBC) antibodies. The purposes of this study were to determine the frequency of WBC antibodies, to associate the severity of reactions with antibody specificity, and to distinguish FNHTRs from infection and postoperative fever. By using the granulocyte indirect immunofluorescence test in conjunction with lymphocytotoxicity testing, it was found that 70 percent of FNHTRs in 24 patients involved WBC antibodies. The remaining 30 percent of apparent FNHTRs were associated with infections and postoperative fever. Granulocyte-specific antibodies were as prevalent as HLA antibodies and were associated with the severest reactions. Because FNHTRs occur with granulocyte-specific antibodies, HLA antibodies, and possible monocyte-specific antibodies (untested in this and other studies), these reactions could be grouped together as WBC-associated reactions. 
2	Pancreatic cancer versus chronic pancreatitis: diagnosis with CA 19-9 assessment, US, CT, and CT-guided fine-needle biopsy. The authors prospectively performed serum CA 19-9 assessment, ultrasound (US), computed tomography (CT), and CT-guided fine-needle aspiration biopsy (FNAB) of the pancreas in 81 consecutive patients with suspected chronic pancreatitis or pancreatic neoplasm. The final diagnosis was pancreatic cancer in 54 patients and chronic pancreatitis in 27 patients. CA 19-9 assessment, US, CT, and FNAB were considered nondiagnostic, respectively, in 0%, 25%, 19%, and 6% of cases. When a definite diagnosis was rendered, the positive predictive value was 90% for CA 19-9 assessment, 95% for US, 98% for CT, and 100% for FNAB; the negative predictive value was, respectively, 69%, 95%, 86%, and 100%. The accuracy of all diagnostic and nondiagnostic studies was 81% for CA 19-9 assessment, 72% for US, 77% for CT, and 94% for FNAB. It is concluded that CT-guided pancreatic FNAB is the most reliable examination for enabling differential diagnosis of pancreatic cancer and chronic pancreatitis. When the pancreas is well visualized at US, the negative predictive value for pancreatic cancer is more accurate than that of CA 19-9 assessment and CT. 
1	Incidence of hairy cell leukemia, mycosis fungoides, and chronic lymphocytic leukemia in first known HTLV-II-endemic population. Unlike human T cell leukemia-lymphoma virus type I (HTLV-I), HTLV-II has not been convincingly linked to a malignancy. In the first 10 months of serologic screening for HTLV-I/II among blood donors in New Mexico in 1988-1989, HTLV-I/II infection was found in 27 donors. HTLV-I/II infection was present in 1.0%-1.6% of American Indian and 0.16%-0.27% of Hispanic donors compared with 0.009%-0.06% of non-Hispanic white donors. HTLV-II was identified by DNA amplification in 12 of 13 samples from Indian and Hispanic seropositive donors. Despite apparent endemic HTLV-II infection in these populations, New Mexico Tumor Registry data showed that the incidences of hairy cell leukemia, mycosis fungoides, and chronic lymphocytic leukemia were comparable among the three ethnic groups. A population with endemic HTLV-II infection has been identified, and there is no evidence of increased risk for these three malignancies in the endemic groups. 
4	Jets over Labrador and Quebec: noise effects on human health. OBJECTIVE: To determine whether the noise from low-level flights over Labrador and Quebec is harmful to human health. DATA SOURCE AND SELECTION: Search of MEDLINE for articles on the effect of noise, particularly impulse noise associated with low-level flights, and a search of the references from identified articles. DATA SYNTHESIS: The noise levels from low-level flights could affect hearing acuity. However, the more important consequences appear to be stress-mediated physiologic effects, especially cardiovascular ones, and psychologic distress, particularly in children. Subjective perception of control over the noise has been found to mitigate some physiologic effects. CONCLUSION: There is sufficient evidence to show that the noise from low-level flights is harmful to human health. 
3	Neuro-ophthalmic manifestations of human immunodeficiency virus infection. Both the afferent visual pathways and ocular motor system may be affected by human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Coexisting infections and neoplastic processes in the eye and brain create a diagnostic challenge for the clinician. This article discusses neuroophthalmic manifestations associated with HIV and AIDS, with emphasis on clinical presentation, diagnosis, and treatment. 
4	The evaluation of the abdominal aorta: a "how-to" for cardiac sonographers. A thorough evaluation of the abdominal aorta can be readily achieved by use of the standard views of the echocardiographic examination. The ultrasound evaluation of the abdominal aorta represents a logical extension of the standard echocardiographic examination of the adult patient. This article provides the information needed to carry out a complete ultrasound examination of the abdominal aorta including the anatomy, the vascular disease, and the steps involved in accomplishing the ultrasound examination of the abdominal aorta. 
2	Clinical features of adenovirus enteritis: a review of 127 cases. We retrospectively analyzed the clinical features of 127 hospitalized pediatric patients whose fecal samples were positive for adenovirus (Ad) by electron microscopy during an 18-month period. Serotyping results obtained by microneutralization tests and restriction endonuclease analysis were available for 105 of 127 cases. There were 69 males and 58 females and 94% of patients were less than 4 years of age. The average body temperature was 38 degrees C rectal (range, 36.2-40.8 degrees C) with an average duration of fever of 1.6 days. The average duration of clinical illness was 8.8 days (range, 1 to 32 days). Although Ad 40 and Ad 41 were isolated in the majority of cases (59 of 105 (56%], Ad 31 was associated with 18 of 105 cases (17%). Of the 18 cases associated with Ad 31, 14 were nosocomial and associated with diarrhea. Our survey confirms the importance of fastidious enteric Ad in infantile diarrhea (Ad 40, Ad 41) and suggests that Ad 31 produces a clinical syndrome indistinguishable from that caused by Ad 40 and Ad 41. The occurrence of Ad enteritis in patients admitted for unrelated illnesses well after initial hospitalization suggests that Ad is also an important cause of nosocomial enteritis in our hospital. 
3	The induction dose of propofol in infants 1-6 months of age and in children 10-16 years of age. The propofol dose needed for satisfactory induction of anesthesia was determined in 22 infants 1-6 months of age and 22 children 10-16 yr of age. A single bolus of propofol was given over 10 s. Thirty seconds after injection the lid reflex was tested and the anesthesia mask was applied. The patient was considered to be asleep if there were no gross movements during the next 30 s while the patient breathed O2. The dose required for satisfactory induction in 50% of patients (ED50) (+/- SE) was 3.0 +/- 0.2 mg/kg in infants and 2.4 +/- 0.1 mg/kg in older children (P less than 0.02). Pain on injection occurred in 50% of the infants and 18% of the children. 
5	Metabolic bone disease in lumbar pseudarthrosis. Pseudarthrosis occurs in many patients who undergo lumbar spine fusion and it has been suggested that abnormalities of bone metabolism contribute to it. The authors evaluated 47 patients with pseudarthrosis for metabolic bone disease. Symptomatic patients with pseudarthrosis underwent metabolic bone evaluation. Abnormal results of laboratory tests were found in 7 patients (14.9%): 3 low or borderline 1,25 dihydroxy vitamin D3, 2 elevated 24-hour urine calcium, and 2 low serum testosterone. None of these abnormalities correlated with other clinical findings. Bone density was low in 14 of 24 patients in whom it was measured. Low values did not correlate with smoking or abnormal laboratory values. Metabolic bone abnormalities do not appear to play a frequent or significant role in pseudarthrosis after attempted lumbar spine fusion. 
2	Severe gastrointestinal hemorrhage in Crohn's disease. Twenty-one of fifteen hundred twenty-six patients with Crohn's disease (CD) treated at The Mount Sinai Hospital between 1960 and 1986 developed severe gastrointestinal hemorrhage. There were 26 separate episodes of severe hemorrhage: 17 patients bled only once, three bled twice and one bled three times. The frequency of bleeding was significantly higher among patients with colonic involvement (17 of 929; 1.9%) than among those with small bowel disease alone (4 of 597; 0.7%) (p less than 0.001). Twelve patients required surgery on 13 occasions, which involved colon resection in all but one case. Eleven of these patients underwent surgery during their first hemorrhagic episodes, and 1 of 11 had a second operation for recurrent bleeding; the 12th patient, whose first hemorrhage had been treated medically, had surgery during a repeated episode of hemorrhage. The precise bleeding points could be located in only 2 of the 26 bleeding episodes, both at the ileocecal area. Three patients died, of whom two had not undergone surgery when they had bled a few weeks earlier. Primary bleeding episodes subsided without surgery in 10 of 21 cases, but 3 of these 10 patients (30%) rebled massively. By contrast primary excisional surgery was followed by recurrent hemorrhage in only 1 of 11 cases (9%). These differences in mortality and in recurrent bleeding rates, although not statistically significant, seem to favor removal of diseased bowel at the time of the first episode of massive hemorrhage. 
4	Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now. 
3	Post-traumatic intracerebral pneumatocele: case report. Pneumocephalus occurs in 0.5 to 1.0% of head trauma, but may also occur after neurologic surgery, or as a result of eroding infection or neoplasm. The pathophysiology involves the presence of craniodural fistula allowing ingress of air. A ball-valve mechanism may allow air to enter but not exit the cranium, or CSF leak permits air entrance as fluid leaves the intracranial space. While a "succession splash" is considered diagnostic of pneumocephalus, most patients have nonspecific signs and symptoms such as headache. Therefore, a high index of suspicion in a patient with recent head trauma is necessary. The diagnosis is made radiographically by CT scan. This is generally performed to rule out intracranial hematoma or cerebral contusion in head trauma, but will reveal even very small quantities of air to the unsuspecting physician. Therapy is often noninvasive, allowing the craniodural defect to heal spontaneously. Selected situations require immediate operative repair of the fistula. 
1	Fluorescent cytochemical detection of estrogen and progesterone receptors in breast fine-needle aspirates. Estrogen and progesterone receptors were studied in fine-needle aspiration biopsy specimens of 56 patients with primary, recurrent, or metastatic breast carcinoma. The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesterone hemisuccinate bovine serum albumin tetramethyl rhodamine isothiocyanate (TMRITC-BSA progesterone), were used in the fluorescent cytochemical method. The findings obtained from the aspirated cells with the use of the fluorescent cytochemical technique were compared with results obtained from the cell population of the same tumor after removal with the use of both the fluorescent cytochemical technique and the biochemical dextran-coated charcoal (DCC) assay. For the needle aspirates, there was 89% concordance for estrogen receptor and 86% concordance for progesterone receptor between biochemical and cytochemical results. A high degree of correlation was also demonstrated between fine-needle aspirates and imprint preparations with the use of the cytochemical technique. This study suggests that the fluorescent cytochemical technique is an effective tool in assessment of estrogen and progesterone receptor content in fine-needle aspirates of primary and metastatic breast cancer. The fluorescent cytochemical technique can be performed easily at community hospitals and is well suited for specimens of insufficient size for biochemical assay. 
2	Gastroesophageal reflux and sclerotherapy strictures. The development of esophageal stricture is common following endoscopic variceal sclerotherapy (EVS). Gastroesophageal reflux may be at least partly responsible. Twelve randomly selected male patients underwent chronic EVS for the management of bleeding esophageal varices. Six patients developed strictures during or after EVS, six did not. There were no significant differences between stricture and nonstricture patients during 24 hour esophageal pH monitoring. Three of the six stricture patients and four of the six nonstricture patients had an abnormal amount of reflux. Gastroesophageal reflux occurs frequently in patients undergoing EVS, and it is not likely to play a major role in EVS stricture formation. 
4	Coronary artery fistula formation secondary to permanent pacemaker placement. We present the findings in two patients who apparently developed a coronary artery fistula as a complication of an endocardial pacing electrode. This complication may actually be occurring more frequently than recognized because the patient may be asymptomatic or minimally symptomatic and therefore not undergo a coronary angiogram. Awareness of this potentially serious complication is important and stresses the need for proper electrode placement without excess pressure on the tip. 
3	Eosinophilic meningitis: cause of a chronic pain syndrome. Three tourists developed eosinophilic meningitis after visiting the Fijian Islands. Two had a severe and long lasting illness with chronic intractable pain. In one patient electrophysiological studies and MRI scan of the brain were abnormal and provided evidence of both radicular and cerebral parenchymal involvement by the most likely causative agent, Angiostrongylus cantonensis. 
5	Intraoperative protection of cranial nerves and perforating arteries by silicone rubber sheets. Technical note. The authors describe a technique whereby, during microneurosurgery, vital structures are covered or wrapped with small pieces of silicone rubber sheeting to protect them from intraoperative injury. In this way, perforating arteries located behind a large aneurysm can be covered to avoid their inclusion within the blades of the clip, and the cranial nerves coursing around or through a tumor can be wrapped to protect them from injury by a suction or forceps. By insulating nerves and arteries, this silicone rubber sheet has the added advantage of protecting them from injury due to electrical current of bipolar forceps. The silicone rubber sheet described here is smoother, thinner, and lighter than a cotton pattie. 
5	Aggravation of human and experimental myasthenia gravis by contrast media. After observing a 72-year-old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic IV contrast material, an observation rarely described in the literature, we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation. There was significant worsening of the decremental response to 3 Hz repetitive nerve stimulation from 40 +/- 29% to 55 +/- 27% following the IV administration of contrast agent at doses similar to those used in humans. IV calcium partially reversed this aggravation. Caution is merited when myasthenic patients are administered contrast media. 
5	Sciatic nerve monitoring during revision total hip arthroplasty. This study presents a simple method of intraoperative sciatic nerve monitoring during revision total hip arthroplasty (THA), utilizing intraoperative, somatosensory evoked potentials. Using this method, the sciatic nerve was protected when surgical correction of shortened limb length was necessary during revision THA. Twenty-three revision THAs were performed using intraoperative sciatic nerve monitoring. No postoperative peripheral nerve complications occurred, with an average increase of 18 mm in leg length, ranging from 6 mm to 43 mm. 
1	Current strategies in the management of locoregional and metastatic gastric carcinoma. Gastric carcinoma remains a significant cause of death worldwide. A patient's prognosis depends on the degree of gastric wall penetration, presence of lymph node metastases, and location of the primary site. Metastatic gastric carcinoma is currently incurable. However, chemotherapy continues to evolve at a rapid pace. Active agents include 5-fluorouracil (5-FU), doxorubicin, cisplatin, methotrexate, mitomycin, and etoposide. Combination etoposide, doxorubicin, and cisplatin (EAP) has been reported to result in encouragingly high response rates, including a 10% complete response rate in patients with metastatic gastric carcinoma. Trials are now under way to confirm these results. Similarly, another etoposide-based combination, etoposide, leucovorin, and 5-FU (ELF), has resulted in an equally good response rate but less toxicity than EAP. The 5-FU, doxorubicin, and methotrexate (FAMTX) regimen, previously reported to have an excellent response rate, is also being investigated further. For patients with locoregional carcinoma, curative resection rate is often unsatisfactorily low; however, curative resection is consistently associated with improved survival (between 23 and 26 months). In patients with potentially resectable carcinoma, two significant problems must be recognized: (1) a low rate of curative resection and (2) the development of widespread carcinoma despite curative resection. Despite many attempts, the postoperative strategies of adjuvant chemotherapy have been ineffective. New strategies must be investigated aggressively. Combination etoposide, 5-FU, and cisplatin (EFP) has been administered preoperatively and postoperatively to patients with resectable gastric carcinoma, resulting in an encouraging curative resection rate (greater than 70%) and manageable toxicity. Based on promising results reported with EAP in patients with unresectable locoregional carcinoma of the stomach, a trial of preoperative and postoperative EAP in potentially resectable carcinoma of the stomach is now under way. 
5	Usefulness of labetalol in chronic atrial fibrillation. Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation (AF) but often reduce exercise capacity. To investigate the advantage of labetalol--a unique beta blocker with alpha-blocking property--in chronic AF, 10 patients without underlying structural heart disease were studied with treadmill test, 12-minute walk and 24-hour ambulatory electrocardiographic monitoring. Patients were randomized and crossed over to receive 4 phases of treatment (placebo, digoxin, digoxin with half-dose labetalol, and full-dose labetalol). Exercise durations were 14.1 +/- 1.5, 14.2 +/- 1.5, 16.1 +/- 1.1 and 15.6 +/- 1.1 minutes, respectively, indicating that labetalol did not reduce exercise tolerance. Although digoxin had no advantage over placebo in controlling maximal heart rate (177 +/- 2 vs 175 +/- 3 beats/min), labetalol, both as monotherapy or as an adjunct to digoxin, was advantageous (156 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, and 154 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, respectively). The rate-pressure product was consistently lowered by labetalol at rest and during exercise. At peak exercise, the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 +/- 1300 to 24,100 +/- 2,000 mm Hg/min (p less than 0.01) and the maximal rate-pressure product was lowest with full-dose labetalol (22,300 +/- 1,600 mm Hg/min). During submaximal exercise on treadmill or during the 12-minute walk, the combination of labetalol and digoxin produced the best heart rate control, whereas labetalol monotherapy was comparable to digoxin therapy. 
5	Retrograde nephrostolithotomy in management of complex renal calculi. From October 1986 to July 1990 we evaluated 22 patients with complex renal calculi in 25 kidneys for initial therapy using retrograde percutaneous nephrostolithotomy. In 3 patients we could not attain renal access in a retrograde fashion. In the remaining patients residual fragments after percutaneous nephrostolithotomy were treated with a combination of extracorporeal shock wave lithotripsy (ESWL), chemolysis and retrieval of small calculi with a flexible nephroscope. Successful treatments were achieved in 6 of the 22 kidneys (27%) using percutaneous nephrostolithotomy alone and in 17 (77%) using all modalities. Retrograde and antegrade percutaneous nephrostolithotomy in conjunction with ESWL, chemolysis and flexible nephroscopy in the treatment of patients with complex calculi yield comparable success rates. However, retrograde percutaneous nephrostolithotomy can be performed without the aid of an interventional radiologist and it provides easy access to the nondilated collecting system. 
4	Human atherosclerotic coronary artery xenografts: a model for investigation of transluminal recanalization. A model for testing transluminal recanalization techniques was developed. Fragments of human atherosclerotic coronary arteries were transplanted into carotid arteries of dogs and evaluated by angiographic, angioscopic, and histologic study within a three-month period. An inflammatory response was most intense within the first week. By two weeks no inflammation was noted. Total occlusion (n = 13) and stenosis (n = 11) of the carotid arteries were achieved without complications. The model is easy to produce within a short period and the arterial occlusion resembles human vascular disease. This model has been used to evaluate laser recanalization of vascular obstructions. 
5	Lovastatin. Warfarin interaction. Two patients who developed hypoprothrombinemia and bleeding due to lovastatin-warfarin drug interaction are described. Because of the wider use of lovastatin and warfarin, heightened clinical awareness of this potentially serious interaction must be publicized. Therefore, prothrombin time should be monitored diligently when warfarin is prescribed to patients receiving lovastatin. 
5	Carbamazepine maintenance treatment in outpatient schizophrenics. A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena. 
1	The role of interleukin-2 in cancer immunotherapy. The arena of cellular immunotherapy is an emerging field of study. The field has strong foundations in numerous animal tumor models, which provide avenues of research for refinements in human immunotherapy. Experience from a number of research centers can be generalized: LAK cell trials in humans have demonstrated that PBMCs activated with IL-2 possess reproducible antitumor activity in vitro. Exogenous IL-2 administration to patients is required to maintain the biologic activity of the activated cells, although the requirement for LAK cells in tumors like melanoma is not clear-cut. Overall, the response rate to immunotherapy in humans is approximately 30%. The toxicity of immunotherapy, which is related to the dose of systemic IL-2, can be significantly reduced. The next generation of trials of cellular immunotherapy in humans will use TILs. Murine experiments indicate that this population of cells is more powerful and potentially more specific for tumor than LAK cells. Like LAK cells, TILs also require exogenous IL-2 for optimum performance in vivo. The difficulty in reproducible TIL growth can be overcome by the use of monoclonal antibody activation and IL-2. Improvements in TIL therapy are anticipated from the use of TILs combined with hybrid antibodies, the addition of other biologic response modifiers, and the implementation of genetically engineered cells and cell products. 
2	Investigation of mode of action of biofeedback in treatment of fecal incontinence. A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence. Subjects were initially allocated to one of two groups; one group was trained to perceive small rectal volumes (active retraining), the other group carried out the same maneuvers but were not given any information or instruction. Active sensory retraining reduced the sensory threshold from 32 +/- 8 to 7 +/- 2 ml (P less than 0.001), corrected any sensory delay that was present (P less than 0.004), and reduced the frequency of incontinence from 5 +/- 1 to 1 +/- 1 episodes per week (P less than 0.01). Sham retraining caused a modest reduction in the sensory threshold (from 29 +/- 9 to 20 +/- 8; P less than 0.05) but did not significantly reduce the frequency of incontinence. Subsequent strength and coordination training did not significantly improve continence, although at the end of the study, 50% of patients had no incontinent episodes at all and 76% of patients had reduced the frequency of incontinence episodes by more than 75%. This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation. The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up. In conclusion, the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence. 
2	Demonstration of two distinct subsets of gastric varices. Observations during a seven-year study of endoscopic sclerotherapy. Over a seven-year period, assessment of gastric varices was made on 225 patients receiving endoscopic sclerotherapy for variceal hemorrhage. Of 170 patients with complete data, gastric varices were observed in 26 (15.3%). Importantly, two distinct subsets of gastric varices were identified: varices distal to the gastroesophageal junction without extension into the fundus, termed "junctional varices," occurred in 11.2%, and varices that were confined only to the fundus, termed "fundal varices," occurred less frequently in 4.1%. Although rebleeding was increased in both subsets of gastric varices, junctional varices were more amenable to sclerotherapy. Patients with fundal varices (N = 7) had a significantly higher rebleeding rate, increased complications with sclerotherapy, and significantly decreased survival (P less than 0.005) when compared to patients with esophageal varices alone (N = 87) who were followed for more than three months. Cumulative survival was not significantly different (P less than 0.08) in patients with junctional varices (N = 19) when compared with patients with esophageal varices alone. We conclude that not all patients with gastric varices have a poor result with sclerotherapy. Recognition of these subsets may improve treatment strategies in patients with gastric varices. 
5	Total-hip arthroplasty: periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection Indium-111-labeled leukocyte images of 92 cemented total-hip arthroplasties were correlated with final diagnoses. Prostheses were divided into four zones: head (including acetabulum), trochanter, shaft, and tip. The presence (or absence) and intensity of activity in each zone was noted, and compared to the corresponding contralateral zone. Though present in all 23 infected arthroplasties, periprosthetic activity was also present in 77% of uninfected arthroplasties, and was greater than the contralateral zone 51% of the time. When analyzed by zone, head zone activity was the best criterion for infection (87% sensitivity, 94% specificity, 92% accuracy). Fifty of the arthroplasties were studied with combined labeled leukocyte/sulfur colloid imaging. Using incongruence of images as the criterion for infection, the sensitivity, specificity, and accuracy of the study were 100%, 97%, and 98%, respectively. While variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection, the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure. 
5	Caffeine as an analgesic adjuvant. A double-blind study comparing aspirin with caffeine to aspirin and placebo in patients with sore throat. Despite its frequent clinical use in analgesic agents, caffeine has not been accepted unequivocally as an analgesic adjuvant. To evaluate this activity of caffeine, we used new study methods in a randomized controlled trial on patients with acute sore throat due to tonsillopharyngitis. Patients were randomly assigned to receive a single dose of one of three treatments: 800 mg of aspirin with 64 mg of caffeine (n = 70), 800 mg of aspirin (n = 68), or placebo (n = 69). Under double-blind conditions, during a 2-hour evaluation period, patients used different rating scales to assess pain intensity, change in pain, relief, and two qualities of throat pain, how swollen the throat felt, and difficulty swallowing. Aspirin with caffeine and aspirin alone were significantly more effective than placebo for all efficacy measurements from 30 minutes through 2 hours and overall. The aspirin-caffeine combination also showed evidence of activity at 15 minutes on the relief scale. Aspirin with caffeine was more effective than aspirin alone after 30 minutes and over the entire study period. For patients with fever, both active treatments were equally effective antipyretic agents. We conclude, therefore, that 800 mg of aspirin, given alone or with 64 mg of caffeine, is an effective analgesic and antipyretic agent. Because the aspirin-caffeine combination is significantly more effective than aspirin alone as an analgesic, we also conclude that 64 mg of caffeine is an analgesic adjuvant. 
5	Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. The t(4;11)(q21;q23) chromosomal abnormality was identified in 40 (2%) of 1,986 children with newly diagnosed acute lymphoblastic leukemia (ALL). This translocation was associated with female sex (63%), age less than 1 year (60%), hyperleukocytosis (median leukocyte count, 156.5 x 10(9)/L), CD10-/CD19+ B-precursor cell immunophenotype, and myeloid-associated antigen (CD15) expression (63%). Nearly all cases had at least some CD24- blast cells. The CD10-/CD15%/CD19+/CD24/+ phenotype was found in 20 of the 32 t(4;11) cases tested. None of the 40 cases had the cytogenetic finding of hyperdiploidy greater than 50, which is a favorable prognostic feature. For clinical comparison, the t(4;11) cases were divided into three groups according to age at diagnosis: less than 1 year (n = 24), 1 to 9 years (n = 8), and greater than or equal to 10 years (n = 8). Compared with older patients, infants were more likely to have initial central nervous system leukemia (P = .05) and less likely to have pre-B-cell ALL (P = .05). Complete continuous remission has been maintained in only 7 of 24 infants and 2 of 8 patients aged greater than or equal to 10 years, in contrast to 7 of 8 children in the intermediate age group (P = .048). These findings suggest that the t(4;11) is an adverse prognostic feature in these two age groups. 
5	Venous stasis and vein lumen changes during surgery The mechanisms underlying the development of postoperative deep vein thrombosis remain to be fully elucidated. Previous studies have suggested that peroperative venous distension may be a factor associated with venous thromboembolism. In this study we have obtained high resolution ultrasound images of gastrocnemius and posterior tibial veins in 62 patients undergoing a range of general surgical procedures. From these we determined the changes in vein diameter occurring during the operative procedures, in response to induction of anaesthesia, and after completion of surgery. Veins showed no evidence of dilatation in response to the induction of anaesthesia, but by the end of the operative procedure showed distension of 22-28 per cent. Distension was most prominent in the gastrocnemius veins, and lesser distension was observed in the posterior tibial veins. In a series of patients who received an infusion of 1 litre of saline in addition to basal requirements, distension was 57 per cent compared with 22 per cent in the corresponding control group. Intraoperative venous distension is associated with factors that lead to deep vein thrombosis and may be involved in the mechanisms which result in the commencement of deep vein thrombosis. 
4	Percutaneous excimer laser coronary angioplasty. To determine the efficacy of percutaneous excimer laser coronary angioplasty as an adjunct or alternative to conventional balloon angioplasty, 55 patients were studied in a multicenter trial. These patients underwent the procedure using a modification of conventional balloon angioplasty technique. A first-generation, 1.6-mm diameter catheter constructed of 12 individual silica fibers concentrically arranged around a guidewire lumen was used. Catheter tip energy density varied from 35 to 50 mJ/mm2. The mean number of pulses delivered at 20 Hz was 1,272 +/- 1,345. Acute success was defined as a greater than or equal to 20% increase in stenotic diameter and a lumen of greater than or equal to 1 mm in diameter after laser treatment. Acute success was achieved in 46 of 55 (84%) patients. Adjunctive balloon angioplasty was performed on 41 patients (75%). The percent diameter stenosis as determined by quantitative angiography decreased from a baseline of 83 +/- 14 to 49 +/- 11% after laser treatment and to 38 +/- 12% in patients undergoing adjunctive balloon angioplasty. The mean minimal stenotic diameter increased from a baseline of 0.5 +/- 0.4 to 1.6 +/- 0.5 mm after laser treatment and to 2.1 +/- 0.5 mm after balloon angioplasty. There were no deaths and no vascular perforations. One patient (1.8%) required emergency coronary bypass surgery. These data suggest that excimer laser energy delivered percutaneously by specially constructed catheters can safely ablate atheroma and reduce coronary stenoses. 
5	The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance. Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty-four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti-IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common. 
4	Coronary stent implantation in acute vessel closure 48 hours after an unsatisfactory coronary angioplasty. We report the implantation of a balloon-expandable stent in a patient with acute vessel closure in the state of evolving myocardial infarction following 48 hr after unsatisfactory coronary angioplasty. The stent was implanted after successful recanalization of an occluded left anterior descending artery, with repeated unsatisfactory results of balloon angioplasty. Adjunct thrombolytic therapy was contraindicated. No residual stenosis was documented in immediate control angiograms, or after 24 hr, 3 weeks, and 4 months. 
3	Lymphocytic adenohypophysitis presenting as infertility. Case report. The authors report a nulliparous patient presenting with infertility and hyperprolactinemia. She underwent transsphenoidal surgery after radiological investigation disclosed an enlarged pituitary gland which did not respond to bromocriptine therapy. The removed tissue had histological features consistent with adenohypophysitis including a diffuse lymphocytic infiltrate. The lymphocyte subsets present in the infiltrate were characterized by immunohistochemical methods to establish the contribution of different elements of the cellular immune response. Lymphocytes bearing CD4 antigen (helper-inducer cells) were most prominent and appeared to bear the majority of the interleukin-2 receptor (expressed during lymphocytic activation) present in the pituitary gland. A few B lymphocytes were also observed. The location of the major histocompatibility antigen (classes I and II) and interleukin-2 receptor correlated with the lymphocytes and macrophages rather than with the stromal or parenchymal elements of the pituitary. Lymphocytic adenohypophysitis is an unusual cause of pituitary enlargement which can mimic a pituitary tumor, and is sometimes associated with hyperprolactinemia. In women of child-bearing age, it almost always occurs during pregnancy or the postpartum stage. The autoimmune disorder reported here has not previously been associated with infertility nor has the lymphocytic infiltrate of the pituitary previously been analyzed in detail by modern immunological methods. 
1	Clinical management of port-wine stain in infants and young children using the flashlamp-pulsed dye laser. The flashlamp-pulsed dye laser (FLPDL) at 585 nm, a wavelength well absorbed by oxyhemoglobin, causes highly selective vascular injury. In addition, the 450 microsecond pulse duration produced by this laser approximates the thermal relaxation time for dermal blood vessels thereby confining the energy to the target. This new laser effects excellent lightening of port-wine stain (PWS) in infants and young children without the adverse complications of hypertrophic scarring, permanent pigmentation abnormality, or textural changes, complications often seen with conventional laser systems. The FLPDL now permits treatment of this patient population expected to gain the most benefit from early laser therapy in a much safer manner, before the psychological complications of being a "marked" person develop. The purpose of this report is to: (1) describe the theoretical considerations behind achieving selective removal of PWS that can be understood and used by a nonsurgically-oriented practitioner; and (2) describe the practical application of the device used in the clinical management of infants and young children. 
1	Piroxicam decreases postirradiation colonic neoplasia in the rat. This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 
5	Airway luminal liquid. Sources and role as an amplifier of bronchoconstriction. The release of mediators from inflammatory cells into the airway lumen can initiate a series of events leading to airway obstruction, particularly smooth muscle contraction and alteration of endothelial and epithelial permeability leading to mucosal edema and subsequent influx of liquid into the airway lumen. In this report we briefly review the effects of several inflammatory mediators, including eicosanoids, platelet-activating factor, and histamine, as well as the effects of plasma proteins and tachykinins that may be secondarily released because of the presence of inflammatory mediators on endothelial and epithelial permeability. We then consider physical mechanisms whereby the resulting airway luminal liquid could amplify the response of an airway previously constricted because of smooth muscle contraction. Specifically, liquid in the interstices between epithelial projections that are formed during muscular contraction could amplify the degree of luminal compromise by (1) further decreasing luminal cross-sectional area by occupying space, and (2) providing an additional source of inward recoil because of the surface tension of the air-liquid interface. 
2	Accumulation and pepsin solubility of collagens in the bowel of patients with Crohn's disease. The collagen content of resected strictured intestine, with and without fistulas, from patients with Crohn's disease has been compared with that in macroscopically normal intestine removed from the same patients and from others without inflammatory bowel disease. Collagen content per unit wet or dry weight of tissue was significantly increased in all grossly diseased tissue whether fistulated or not. Although there was a significant increase in collagen types I, III, and V in diseased tissue, the relative proportions of major collagen types extracted by limited pepsin digestion were similar for both Crohn's and non-Crohn's intestine (type I, 65 to 70 percent; type III, 25 to 30 percent; type IV, 2 to 3 percent; and type V, 2.5 to 3 percent). CNBr digestion of pepsin insoluble material showed a similar relative abundance of types I and III, indicating no major change in collagen type distribution between older (insoluble) and more newly synthesized collagen. There was no evidence of the presence of type I trimer collagen. Type VI collagen, although not quantitated, was observed in 70 percent of intestinal specimens. The proportion of total collagen solubilized by pepsin treatment was significantly greater in both grossly diseased and macroscopically normal Crohn's bowel compared with non-inflammatory bowel disease bowel. These findings suggest that there are disturbances of collagen metabolism in Crohn's intestine, which account for the stricturing process and which may predate gross pathologic changes. 
5	Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus infection in twins. Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed. 
1	Prostate specific antigen in hormonally treated stage D2 prostate cancer: is it always an accurate indicator of disease status? The clinical significance of serum prostate specific antigen (PSA) values in hormonally treated prostate cancer patients and the effect of hormonal therapy on the serum PSA concentration, independent of the response observed from its antitumor activity, are not well defined. To elucidate further the influence of antiandrogen therapy on serum PSA expression, 81 randomly selected patients with stage D2 prostate cancer were evaluated with respect to serum PSA concentration. These patients were divided into 2 groups on the basis of previous hormonal therapy. Group 1 consisted of 43 patients 55 to 89 years old (mean age 71 years) who had received no prior therapy for prostate cancer. Group 2 included 38 men 58 to 84 years old (mean age 72 years) who had received only androgen deprivation therapy with either bilateral orchiectomy or diethylstilbestrol. The mean interval between initiation of antiandrogen therapy and evaluation of these patients was 14 months (range 8 to 31 months). At the time of PSA determination both groups were similar in all respects, including tumor grade, disease symptoms and bone scan findings. The median serum PSA concentration was 96.0 ng./ml. in group 1 and 16.5 ng./ml. in group 2 (p less than 0.001), despite both groups having similar symptoms and widespread metastatic disease on radionuclide bone scan. In group 1 only 1 patient (2%) had a serum PSA level less than 4.0 ng./ml., whereas 13 men (34%) in group 2 had a serum PSA concentration below 4.0 ng./ml. (p less than 0.001). Of the patients in group 1, 2% and of the men in group 2, 45% had a serum PSA concentration less than 10 ng./ml. (p less than 0.001). These findings demonstrate that the serum PSA level in prostate cancer patients treated hormonally may have a significantly different meaning than the same serum PSA value in patients without hormonal therapy. In addition, these observations suggest that PSA expression may be under hormonal regulation and that androgen deprivation therapy may have a direct effect on the serum PSA concentration, independent of the response obtained from any antitumor activity. However, the exact mechanism of this androgenic influence on PSA expression awaits further investigation at the cellular level. 
4	The use of angiotensin converting enzyme inhibitors in combination with other antihypertensive agents. Angiotensin converting enzyme (ACE) inhibitors have additive effects with most other antihypertensive agents, but the mechanisms of these interactions vary. With diuretics the interaction with ACE inhibitors can be explained by their contrasting effects on the renin-angiotensin system, while with calcium antagonists it may be attributed to independent mechanisms of action. With beta-blockers there is a variable additive effect, which has been proposed to be due to more complete blockade of the renin-angiotensin system than can be obtained with either type of agent alone. 
5	Characteristics of accessory pathways exhibiting decremental conduction. The prevalence, electrophysiologic characteristics and functional significance of decremental conduction over an accessory pathway were examined in this retrospective study of 653 patients who had an accessory pathway demonstrated at electrophysiologic study. Decremental conduction was identified in 50 patients (7.6%). In 15 patients with anterograde decremental conduction, the accessory pathway was right parietal or septal in 14 patients and left parietal in 1 patient. In the 40 patients with retrograde decrement, the accessory pathway was left parietal in 19, posteroseptal in 13, right parietal in 2 and right anteroseptal in 6 patients. Anterograde conduction over the accessory pathway was absent in 11 of the 40 patients with retrograde decrement. Retrograde conduction over the accessory pathway was absent in 9 patients with anterograde decrement. There was no significant difference in the accessory pathway effective refractory period, or shortest cycle length with 1:1 conduction over the accessory pathway in anterograde and retrograde directions. The shortest RR interval in atrial fibrillation between 2 preexcited QRS complexes was longer in patients with anterograde decremental conduction than in a control group of patients with anterograde-conducting accessory pathways without decremental properties. These data demonstrate that decremental conduction over accessory pathways is uncommon. Anterograde decremental conduction usually occurs in right-sided or septal pathways that often do not conduct in the retrograde direction. 
1	Chemical shift imaging of human brain: axial, sagittal, and coronal P-31 metabolite images. Multivoxel magnetic resonance (MR) spectroscopy and novel data analysis techniques were developed to obtain high-quality phosphorus-31 metabolite images from the human brain and to overlay each metabolite distribution directly onto corresponding hydrogen-1 MR images. The P-31 MR spectroscopic data were acquired by means of three-dimensional chemical shift imaging (phase encoding in three spatial dimensions) on a 1.5-T clinical instrument equipped with a specially designed quadrature P-31 birdcage coil constructed in the authors' laboratory. Axial, sagittal, and coronal metabolite images based on the area for any one of five peak regions (phosphodiester; phosphocreatine; gamma, alpha, and beta adenosine triphosphate) were generated from 8 X 8 X 8 or 12 X 12 X 8 CSI arrays with voxel sizes of 27 cm3 and 12 cm3, respectively. The positions of these images were aligned with anatomic features by means of the voxel-shifting capability of the Fourier transform. Direct overlays of these metabolite images on corresponding proton images demonstrated excellent correlation with anatomy, factors indicating the utility of this technique for viewing P-31 metabolite levels in all areas of the brain simultaneously. 
1	Technetium-99m(v) dimercaptosuccinic acid planar scintigraphy in head and neck cancer: clinical, scintigraphic and radiological study. Technetium-99m (Tc99m)(v) Dimercaptosuccinic Acid (DMSA) is an imaging agent which has been proposed as a scintigraphic marker for head and neck squamous cell carcinoma. Fifty-four patients were studied of whom 51 had a head and neck tumour. All patients were examined and then imaged using Tc99m(v) DMSA scintigraphy and computerized tomography. Scintigraphy was less sensitive than clinical examination in the detection of patients with cancer, patients with primary tumours and patients with metastatic neck disease. CT was as sensitive and as accurate as clinical examination but more sensitive than Tc99m(v) DMSA in detecting patients with cancer and with primary tumours. CT was more sensitive and more accurate than both clinical examination and Tc99m(v) DMSA scintigraphy in predicting which patients had metastatic neck disease. Although Tc99m(v) DMSA is accumulated by squamous cell carcinoma, its inability to detect low volume disease and apparent low specificity means it has no role to play in the management of patients with head and neck squamous cell carcinoma. 
5	Umbilical cord hematoma following diagnostic funipuncture. Major complications associated with funipuncture have been reported but are rare. This is a report of a diagnostic funipuncture performed on a 29-week fetus with a single umbilical artery and multiple malformations. Immediately after the procedure, a voluminous hematoma developed at the site of needle insertion in association with a severe fetal bradycardia. Fetal death was confirmed within 5 minutes of needle insertion. It is hypothesized that the risk of complications of funipuncture may vary according to the clinical indication for the procedure and may be increased in the presence of certain fetal malformations. The rapid evolution of complications, as occurred in the present case, underlines the importance of having a clear plan of management in the event of mishap and discussing this plan with the parents before undertaking diagnostic funipuncture. 
3	The neurologic workup in patients with cervical spine disorders. Care must be exercised in interpreting the clinical and radiologic findings when assessing patients with cervical spondylosis and involvement of neural structures for surgery. If the clinical picture cannot logically be explained by the radiologic findings, further investigation is indicated to exclude a coexistent disorder. Investigations may include electrophysiologic tests, transcranial magnetic stimulation, cerebrospinal fluid (CSF) analysis, and magnetic resonance imaging (MRI). Only then can the indication for surgical intervention be properly determined. 
5	Ultrasonographic findings of testicular microlithiasis associated with intratubular germ cell neoplasia. Testicular microlithiasis is an uncommon condition in which calcified concretions fill the lumina of seminiferous tubules. We report the case of a twenty-three-year-old white man with a metastatic germ cell tumor and normal findings on testicular physical examination, but abnormal ultrasonography of the right testis. Orchiectomy revealed intratubular germ cell neoplasia with testicular microlithiasis. Multiple circular echogenic foci on ultrasound correlated with the histologic finding of testicular microlithiasis. Further studies are indicated for assessing ultrasonography as an adjunct for screening the population at risk for intratubular germ cell neoplasia. 
2	Death, after swallowing and aspiration of a high number of foreign bodies, in a schizophrenic woman. A 46-year-old woman who had had a long-term schizoid psychosis collapsed on the street. Upon admission to the hospital, she was determined to have an acute abdomen. The chest radiograph showed metallic foreign bodies in both main bronchi; foreign bodies in the stomach were not observed clinically. The woman died from repeated cardiac arrest shortly after hospital admission. At the autopsy a screw and a nail were found in both main bronchi. The abdominal cavity contained 2 L of greenish purulent fluid and a massive fibrinoid peritonitis was observed. Two perforations of the stomach, each 1 cm in diameter, were detected. The stomach was completely filled with a mass of metallic foreign bodies, greenish fluid, and a bezoar of a total weight of 1,400 g; 422 distinguishable and mostly metallic foreign bodies were counted. Death was attributed to cardiac arrest in delayed shock after massive purulent peritonitis caused by two gastric perforations combined with obstruction of the airways by aspirated foreign bodies. Cases of massive swallowing of foreign bodies are mainly restricted to mentally handicapped persons, especially schizophrenics, whereas acute impaction of the larynx by large food particles occurs nearly exclusively in heavily intoxicated adults. 
3	Remote effect of deep-seated vascular brain lesions on cerebral blood flow. We measured regional cerebral blood flow using the xenon-133 inhalation method, at approximately 1 month after onset, in 60 stroke patients who had no evidence of major carotid artery stenosis or occlusion. Their single lesions (43 infarcts and 17 hematomas) were located in the capsulothalamolenticular region, sparing the cortex. Hemispheric mean cerebral blood flow was reduced on the side of the lesion in 25 patients and on both sides in 20. Regional hypoperfusion was observed in 46 patients (ipsilaterally in 34, bilaterally in 10, and contralaterally in two). Regional hypoperfusion was observed most frequently in the frontal lobe, particularly in the motor and premotor cortices of the prerolandic area. The 46 patients with regional hypoperfusion were compared with the 14 patients without regional hypoperfusion, considering the size and location of the lesion as well as the functional and analytic motor performances. As a rule, the lesion was slightly smaller and more posterior and the functional (p less than 0.001) and analytic (p less than 0.05) motor performances were significantly better in the 14 patients without regional hypoperfusion. Since the xenon-133 inhalation method examines cortical blood flow, we can attribute blood flow reductions resulting from deep-seated lesions to a functional depression akin to diaschisis. Interpretation of the clinical consequences and pathogenesis of this phenomenon requires further sequential and pathologic studies. 
2	Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation. The objective of this study was to determine the changes in systemic hemodynamics (systemic vascular resistance [SVR], cardiac output [CO], systemic blood pressure [SBP]) and cardiac function (pulmonary artery pressure [PAP] and pulmonary wedge pressure [PWP]) during the 96 hours following orthotopic liver transplantation (OLT) and correlate these with changes in hepatic and renal function and patient outcome. The study took place in a 12-bed medical respiratory intensive care unit in a large teaching hospital. Twenty-one patients had OLT performed over a 21.5-month period (January 1988 to October 15, 1989) for end stage liver disease (ESLD) from a variety of causes. A flow-directed right heart catheter and an indwelling arterial cannula were inserted for hemodynamic monitoring over a 96-hour postoperative period. Liver and renal function studies, total serum calcium, serum albumin, and fluid balance were determined daily. The SVR increased significantly to 12.8 +/- 0.6 U at 48 hours compared with immediate (less than 8 hours) postoperative levels (p less than 0.05) and remained elevated for 96 hours. The CO fell progressively and was significantly lower than baseline values from 64 to 96 hours. There was significant inverse correlation between the increase in SVR and the fall in CO (r = .85, p less than 0.01). The SBP was stable except for a small, but significant fall at 16 and 24 hours postoperatively. The PWP increased significantly from a baseline value of 12.5 +/- 0.9 mm Hg to 15 +/- 0.9 mm Hg at 32 hours and remained elevated through 96 hours (p less than 0.05). The serum bilirubin level fell progressively postoperatively and the prothrombin time and partial thromboplastin time (PTT) shortened significantly. Bile flow increased progressively from 107 +/- 120 ml/24 hours at the end of the first 24 hours to 188 +/- 125 ml/24 hours by 96 hours postoperatively. Five patients died from nine to 43 days postoperatively. These patients' hemodynamic parameters were not significantly different from the patients who survived. Successful OLT is associated with a rapid increase in SVR and a fall in CO without changes in SBP. These findings tend to parallel the improvement found in results of liver function tests. However, there is no correlation between the improvement in the hemodynamic state and long-term survival. 
2	Chest pain in teenagers. When is it significant? Chest pain in teenagers often has no obvious organic cause. Onset of symptoms with an emotionally stressful situation may indicate psychogenic chest pain. The differential diagnosis also includes cardiac, musculoskeletal, gastrointestinal, and respiratory disorders. Routine testing generally does not help to establish a diagnosis and may even do harm by reinforcing a patient's unspoken fear of serious illness. Most teenagers with chest pain have no such illness, and symptoms usually resolve without therapy. An important role for primary care physicians is to provide support during evaluation and follow-up. 
3	Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials. In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment. 
2	Gastrointestinal function and structure in HIV-positive patients. We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy. 
5	v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid. Experimental carcinogenesis has led to a concept that defines two discrete stages in the development of skin tumors: (i) initiation, which is accomplished by using a mutagen that presumably activates a protooncogene, and (ii) promotion, which is a reversible process brought about most commonly by repeated application of phorbol esters. We have created a transgenic mouse strain that carries the activated v-Ha-ras oncogene fused to the promoter of the mouse embryonic alpha-like, zeta-globin gene. Unexpectedly, these animals developed papillomas at areas of epidermal abrasion and, because abrasion can also serve as a tumor-promoting event in mutagen-treated mouse skin, we tested these mice for their ability to respond to phorbol ester application. Within 6 weeks virtually all treated carrier mice had developed multiple papillomas, some of which went on to develop squamous cell carcinomas and, more frequently, underlying sarcomas. We conclude that the oncogene "preinitiates" carrier mice, replacing the initiation/mutagenesis step and immediately sensitizing them to the action of tumor promoters. In addition, treatment of the mice with retinoic acid dramatically delays, reduces, and often completely inhibits the appearance of promoter-induced papillomas. This strain has use in screening tumor promoters and for assessing antitumor and antiproliferative agents. 
5	Total parathyroidectomy and autotransplantation in hyperplasia of the parathyroid gland. Hyperparathyroidism caused by multiple-gland hyperplasia has traditionally been treated by subtotal parathyroidectomy. Excellent results have been reported by some, particularly in primary hyperparathyroidism, but other have reported a significant incidence of recurrent hyperparathyroidism. Since 1979, we have chosen to avoid the possibility of remedial exploration of the neck and its attendant risks by treating all patients with primary and secondary hyperplasia with total parathyroidectomy and heterotopic autotransplantation. A total of 20 patients were studied. There were no failures of grafts and no operative complications. We conclude that this procedure is a reliable and safe alternative in the treatment of primary or secondary hyperplasia of the parathyroid gland. 
4	Prediction of the frequency and duration of ambulatory myocardial ischemia in patients with stable coronary artery disease by determination of the ischemic threshold from exercise testing: importance of the exercise protocol The relation between ambulatory myocardial ischemia and the results of exercise testing in patients with ischemic heart disease remains undefined, because of the dissimilar results of previous reports. To further investigate this issue and, in particular, to ascertain the importance of the exercise protocol in determining that relation, 70 patients with stable coronary artery disease underwent 48 h ambulatory electrocardiographic (ECG) monitoring and treadmill exercise tests after withdrawal of medications. Patients exercised using two different protocols with slow (National Institutes of Health [NIH] combined protocol) and brisk (Bruce protocol) work load increments. Exercise duration was longer with the NIH combined protocol (14.1 +/- 5 versus 6.8 +/- 2 min; p less than 0.0001), but the maximal work load and peak heart rate achieved were greater with the Bruce protocol (9.8 +/- 2 versus 6.5 +/- 2 METs, and 142 +/- 19 versus 133 +/- 22 beats/min, respectively; p less than 0.0001). A close inverse correlation between exercise testing and the results of ambulatory ECG monitoring was observed using the NIH combined protocol; the strongest correlation was observed between time of exercise at 1 mm of ST segment depression and number of ischemic episodes (r = -0.86; p less than 0.0001). With the Bruce protocol a significantly weaker inverse correlation was found (r = -0.35). The mean heart rate at the onset of ST segment depression was similar during monitoring and during exercise testing with the NIH combined protocol (97.2 +/- 13 versus 101.0 +/- 17 beats/min, respectively) but it was significantly higher (110.4 +/- 13) when using the Bruce protocol (p less than 0.001). 
1	Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors. Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally. 
1	Influence of age and endocrine factors on the volume of benign prostatic hyperplasia. To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH. 
5	Amenorrhea, osteopenia, and the female athlete. Athletic amenorrhea is a problem because it is associated with an increased risk of injuries and potentially an increased risk of osteoporosis in later life. This article gives suggestions for the evaluation of the athlete with amenorrhea and for treatment protocols. Primary care physicians should routinely screen female adolescent athletes for amenorrhea and, if athletic amenorrhea is present, initiate treatment or referral for treatment for this important problem with short- and long-term complications. 
3	Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme-linked immunosorbent assay. We have found a hepatotrophic factor in plasma or sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of these patients. In this study we developed an enzyme-linked immunosorbent assay with high specificity and sensitivity for human hepatocyte growth factor in human serum. This assay for serum human hepatocyte growth factor is a sandwich method consisting of three steps. The standard curve for human hepatocyte growth factor appeared to be linear in the range of 0.20 to 12.50 ng purified human hepatocyte growth factor/ml (2.35 to 147 pmol/L). The assay took about 4 hr. Serum human hepatocyte growth factor values in patients with fulminant hepatic failure measured by enzyme-linked immunosorbent assay showed a strong positive correlation with that by bioassay using rat hepatocytes in primary culture. The mean value of serum human hepatocyte growth factor for 30 normal subjects was 0.24 +/- 0.12 (S.D.) ng/ml; that for 23 patients with fulminant hepatic failure was 8.06 +/- 1.76 (S.E.M.) ng/ml- greater than 30 times greater than the mean value for normal subjects. Serum human hepatocyte growth factor levels in patients with acute hepatitis, chronic hepatitis and cirrhosis were found to be slightly higher than those in normal subjects, but only the increase in serum human hepatocyte growth factor of acute hepatitis patients was statistically significant. The enzyme-linked immunosorbent assay for serum human hepatocyte growth factor should prove useful for serum human hepatocyte growth factor level measurement in patients with various liver diseases. 
5	Window operation: an alternative treatment method for Bartholin gland cysts and abscesses Recently, we developed the "window operation" as a more effective way to treat Bartholin gland cysts and abscesses. The window operation was used to treat 25 Bartholin cysts and 22 Bartholin abscesses during a 3-year period from October 1, 1986 to September 30, 1989. Under local anesthesia, a small piece of skin including the cyst wall was excised in an oval shape, and suturing was performed along the excised margin. Postoperative antibiotics were given in cases of acute inflammation. A new mucocutaneous junction was observed at the 4-week postoperative checkup. No complications or recurrences have been observed during the study period. The window operation can be an alternative method of treatment for Bartholin gland cysts or abscesses. 
5	CO2 laser for suppurative hidradenitis of the vulva. Chronic suppurative hidradenitis is a disease of the apocrine glands occurring predominantly in the axillae of the anogenital region. Treatment, to date, has been frustrating. Prolonged antibiotic therapy and multiple incisions and drainage have been the usual form of therapy, but those surgical procedures leave patients with ugly scars; retracted, hypertrophic skin edges; and pitted, indurated and disfiguring abscesses. The only successful treatment to date has been wide excision of the entire apocrine gland-bearing tissues, such as radical vulvectomy, which often necessitates grafts to cover the surgically exposed areas. That has left patients with unsatisfactorily functioning vaginas and a mutilated appearance. Recently we instituted the use of the CO2 laser to treat these patients with the goal of eradicating the suppurative sinus tracts and the infected apocrine glands without removing large volumes of adjacent, unaffected tissue. Over the past eight years we treated 11 patients who had extensive, chronic hidradenitis of the anogenital area with the CO2 laser. The use of laser therapy for these patients has produced effective and less-mutilating results. Such treatment has been a successful option for treating this debilitating disease. 
3	Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Recent neuropathologic investigations in schizophrenia report smaller volume of medial temporal lobe structures. These findings are confirmed by preliminary magnetic resonance imaging (MRI) studies. Direct stimulation of lateral temporal lobe structures in the region of the superior temporal gyrus provokes hallucinations. The authors' MRI study of young schizophrenic patients demonstrates smaller volume of the superior temporal gyrus (an auditory association area) and of the left amygdala. Smaller size of the left superior temporal gyrus and left amygdala is not accounted for by smaller size of the overall brain or temporal lobe. Shrinkage of the left superior temporal gyrus is strongly and selectively correlated with severity of auditory hallucinations. 
3	Urologic function after experimental cauda equina compression. Cystometrograms versus cortical-evoked potentials. Twenty female beagle dogs underwent an L6-7 laminectomy and six dogs each had 25, 50 or 75% constriction of the cauda equina and 2 control dogs had laminectomy only. Cystometrograms were performed pre- and post-operatively and three months after constriction. Cortical evoked potentials were monitored pre- and post-operatively and monthly for three months. After three months of constriction, the cauda equina of these dogs in each group was examined histologically and vascular circulation was examined by latex and India ink injection (Spalteholz technique). The control dogs had normal CMGs and CEPs. Twenty-five percent constriction caused no CMG changes and mild CEP changes. Fifty percent constriction caused no statistically significant CMG changes, major CEP changes and venous congestion of the nerve roots and dorsal root ganglia. Seventy-five percent constriction produced severe CMG changes with detrusor areflexia, increased bladder capacity and clinical incontinence. CEPs also had marked deterioration. Vascular analysis revealed severe arterial narrowing at the level of constriction and venous congestion of the nerve roots and dorsal root ganglia. Blockage of axoplasmic flow and nerve root atrophy was seen in all dogs with 75% constriction. Cortical evoked potentials were the most sensitive predictor of neural compression. CMGs were not sensitive until severe compression was achieved. Bladder dysfunction, i.e., detrusor areflexia, appears to occur with blockage of axoplasmic flow and early sensory changes occur with neurovenous congestion. 
4	Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin. Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay. 
5	Glutamic acid and gamma-aminobutyric acid neurotransmitters in central control of breathing. We review recent cross-disciplinary experimental and theoretical investigations on metabolism of the amino acid neurotransmitters glutamic acid and gamma-aminobutyric acid (GABA) in the brain during hypoxia and hypercapnia and their possible role in central control of breathing. The roles of classical modifiers of central chemical drive to breathing (H+ and cholinergic mechanisms) are summarized. A brief perspective on the current widespread interest in GABA and glutamate in central control is given. The basic biochemistry of these amino acids and their roles in ammonia and bicarbonate metabolism are discussed. This review further addresses recent work on central respiratory effects of inhibitory GABA and excitatory glutamate. Current understanding of the sites and mechanisms of action of these amino acids on or near the ventral surface of the medulla is reviewed. We focus particularly on tracer kinetic investigations of glutamatergic and GABAergic mechanisms in hypoxia and hypercapnia and their possible role in the ventilatory response to hypoxia. We conclude with some speculative remarks on the critical importance of these investigations and suggest specific directions of research in central mechanisms of respiratory control. 
5	Cumulative load as a risk factor for back pain. The association between cumulative load (biomechanic load and exposure time integral over the entire work experience) and back pain was investigated in a group of institutional aides with physically stressful jobs. A questionnaire/interview was conducted with 161 of these institutional aides. The point prevalence of back pain in this sample was 62%. Men had worked a mean duration of 14.3 years and women 11.6 years at the time of the onset of the first pain episode. Every job performed was analyzed by the use of a two-dimensional static mathematical model. The compression and shear at the thoracolumbar and lumbosacral discs were computed by the use of a biomechanic model. Cumulative compression and shear were significantly higher in institutional aides with pain compared with those without pain (P less than 0.05-0.01). The pain group was similar to the no-pain group in age, weight, and height. 
5	Mediastinitis following nasal intubation in the emergency department. A patient who developed a retropharyngeal abscess and fatal mediastinitis following emergent nasal intubation is described. Despite aggressive surgical therapy the patient died of mediastinitis. Although mediastinitis as a complication of oral intubation has been described, mediastinitis following nasal intubation has not previously been reported. 
1	Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes. Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other. 
4	How to select a drug for the long-term treatment of chronic heart failure. First-line drugs for the treatment of chronic congestive heart failure should produce immediate symptomatic benefit, improve exercise tolerance, and thereby improve the quality of life. They should preferentially be active as monotherapy or at least reduce the need for comedication. The drugs must be safe and well tolerated by patients and change, in the end, the natural history of the disease, so that sudden death will be prevented and life expectancy improves. None of the currently available drugs satisfies all these criteria. Diuretics, digitalis, converting-enzyme inhibitors, and ibopamine come close to the described ideal. 
1	The diagnosis of ovarian cancer by pathologists: how often do diagnoses by contributing pathologists agree with a panel of gynecologic pathologists? The Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study of ovarian, breast, and endometrial cancer in women 20 to 54 years of age, permitted the diagnoses of contributing pathologists to be compared with those of a panel of three gynecologic pathologists. A diagnosis of ovarian cancer was made by contributing pathologists on 477 subjects. Agreement between the two groups of pathologists was 97% for primary epithelial ovarian cancer and 89% for primary nonepithelial ovarian malignancies. Agreement on diagnosis of major cellular subtypes of ovarian malignancy ranged between 73% for endometrioid cancer and 100% for clear cell carcinomas. We conclude that the diagnosis of pathologic features of primary ovarian cancer is highly predictable. Nonetheless, diagnosis by histologic type varies sufficiently that a review process should be considered for clinical or investigative decisions involving specific histologic diagnoses of ovarian cancer. 
4	Endoscopic laser surgery. A single-center comprehensive experience. A retrospective review of endoscopic procedures using the Nd:YAG laser was carried out for patients treated between October 1985 and March 1989. During this 42-month period 165 procedures were performed on 100 patients. The study encompasses a unique period of time in this center, as it includes the initial application, and finally, the time when its use became routine. Indications for laser surgery included the treatment of tumors, bleeding, benign strictures, arterial occlusions, and hemorrhoids. Nd:YAG laser was found to be effective in the treatment of these lesions. The overall success rate was 81 per cent. Patients who are poor surgical candidates would especially benefit from this therapeutic alternative. 
2	The surgical management of children with ulcerative colitis. The old vs. the new. The authors' experience with children who have chronic ulcerative colitis was reviewed to compare their current surgical approach (ileoanal anastomosis) with earlier methods of management. Between 1960 and 1984, 137 children with chronic ulcerative colitis underwent surgery (mean duration of follow-up, 7.1 years). In 91 patients, the procedures were a total proctocolectomy with ileostomy or Kock pouch (66) or a lesser colectomy with either an ileostomy (16) or an ileorectal anastomosis (9) (group I). Forty-six patients underwent an ileoanal anastomosis procedure (group II). Children in group I were more likely to have significant preoperative loss of weight, a debilitated condition, and malnutrition. Urgent or emergency surgical intervention was required in 25 percent of patients in group I but in only 4 percent of patients in group II. Trends included 1) a younger age at operation in group II, 2) a higher mortality in group I (7.7 percent) than group II (0 percent), and 3) a higher perioperative mortality with emergency operations (23 percent) than elective procedures (1.6 percent). In group I, 98 percent of patients had an abdominal ostomy, but no patients in group II had an abdominal ostomy. The children with an ileoanal anastomosis had an average of 4.8 stools during waking hours and 1.3 stools each night. On the basis of this experience, the authors recommend use of the ileoanal anastomosis procedure in the surgical treatment of chronic ulcerative colitis in children. 
3	Magnetic motor-evoked potentials in epilepsy: effects of the disease and of anticonvulsant medication. Magnetic motor-evoked potentials were recorded in 53 patients with medically intractable, mainly temporal lobe epilepsy and compared with potentials of 110 healthy volunteers. The motor-evoked potentials were reevaluated in 16 of the 53 patients after substantial reduction of antiepileptic drug doses. The objective was to assess the effect of epilepsy and of anticonvulsant medication on the central motor system. In subjects receiving antiepileptic treatment, cortical threshold intensities were markedly elevated and peripheral latencies were prolonged. Cortical threshold intensities and peripheral latencies decreased to approach control values after anticonvulsant medication was reduced but were increased in patients treated with 2 or 3 anticonvulsant agents instead of 1. Additionally, high levels of interictal epileptiform activity and a high frequency of seizures significantly decreased the central motor conduction time and, in part, threshold intensities. The central motor conduction time was further diminished after reduction of anticonvulsant treatment and increased when several drugs were administered. The duration of epilepsy, the location of the epileptic focus, and the type of the epileptic seizure did not affect motor-evoked potentials. Conclusively, central motor pathways are endogenously facilitated by epileptiform activity even if clinical signs of their involvement are absent. Anticonvulsant medication exerts major reversible effects on magnetic motor-evoked potentials. 
5	Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis. Anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis, although its exact mechanism has not been defined clearly. In this study of 18 women with antepartum pyelonephritis, although only a third had anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all 18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from admission to discharge. With scanning electron microscopy, we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women, and the former had significantly increased proportions of echinocytes in particular, but schistocytes and spherocytes were increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes, especially echinocytosis, have been induced in vitro by lipopolysaccharide, and they are known to lead to premature red blood cell destruction in vivo. We conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane damage. 
4	A multifactorial analysis of mortality and morbidity in perforated peptic ulcer disease. Perforated peptic ulcer disease remains a source of considerable morbidity and mortality, and the suggested methods of surgical therapy are diverse. We reviewed the course of 113 patients who were treated surgically and identified 14 factors that influenced the morbidity or mortality rates, or both. Multiple regression analysis showed that the number of coexisting medical conditions, a lower mean blood pressure level and the duration of acute perforation were independent risk factors for death, while age, use of a bronchodilator, a lower mean blood pressure level and the number of coexisting medical conditions correlated positively with all complications. A duodenal site was independently favorable with respect to all complications. The type of operation performed either simple closure, vagotomy and drainage or resection, did not influence morbidity or mortality. The most severely ill patients also did not benefit from any particular type of operation in the short term. Long term results were improved with definitive operation, as measured by the Visick classification and the need for reoperations. Definitive operations are recommended for virtually all patients with perforated peptic ulcer. 
4	Sympathetic neural contribution to salt-induced hypertension in Dahl rats. The Dahl strain provides a model for examining mechanisms involved in the genetic sensitivity or resistance to salt-induced hypertension. Dahl salt-sensitive rats develop hypertension when fed a high salt diet; Dahl salt-resistant rats remain normotensive. Based on early experiments, it was thought that hypertension in Dahl salt-sensitive rats epitomized the overriding importance of renal and humoral mechanisms in salt-induced hypertension, but studies in the past 15 years have demonstrated that alterations in sympathetic neural mechanisms also participate critically in the genetic predisposition to salt-induced hypertension in Dahl salt-sensitive rats. This article briefly reviews sympathetic neural mechanisms in Dahl rats, including evidence for a role of afferent baroreceptor as well as central neural and peripheral adrenergic mechanisms in salt-induced hypertension in Dahl salt-sensitive rats. 
3	OKT3 encephalopathy. OKT3 therapy for induction immunosuppression in a patient who underwent renal transplantation produced obtundation and quadriparesis associated with computed tomographic scan evidence of brain edema. These findings resolved over 3 days with supportive therapy and OKT3 withdrawal. 
4	Incidental blood pressure elevations: a MIRNET project. BACKGROUND. A prospective study was undertaken to determine the prevalence of hypertension in office patients with an incidental diastolic blood pressure greater than or equal to 90 mm Hg. METHODS. During routine screening of 14,890 patients, 174 patients with elevated diastolic blood pressures but no previous diagnosis of hypertension were identified over a 3-month period. Only 115 (64%) returned as requested for two subsequent blood pressure readings. RESULTS. Sixty percent of those returning fit the definition for hypertension using the criteria of the Joint National Committee on Detection, Evaluation, and Treatment of Hypertension. Sixty-nine percent (43/62) of the men and 49% (26/53) of the women were hypertensive. Women under 40 years old were less likely to be hypertensive, but age did not predict hypertension in men. Among those patients with a diastolic pressure reading below 105 mm Hg, progressively higher diastolic readings on the first visit did not predict a higher probability of hypertension. Among those patients with a diastolic pressure reading above 105 mm Hg, however, 90% (9/10) were hypertensive. CONCLUSIONS. Physicians should take incidental elevation of diastolic pressure seriously because of the high prevalence of confirmed hypertension in this group of patients. 
4	Changes in quality of care for five diseases measured by implicit review, 1981 to 1986 We measured quality of care before and after implementation of the prospective payment system. We developed a structured implicit review form and applied it to a sample of 1366 Medicare patients with congestive heart failure, acute myocardial infarction, pneumonia, cerebrovascular accident, or hip fracture who were hospitalized in 1981-1982 or 1985-1986. Very poor quality of care was associated with increased death rates 30 days after admission (17% with very good care died vs 30% with very poor care). The quality of medical care improved between 1981-1982 and 1985-1986 (from 25% receiving poor or very poor care to 12%), although more patients were judged to have been discharged too soon and in unstable condition (7% vs 4%). Except for discharge planning processes, the quality of hospital care has continued to improve for Medicare patients despite, or because of, the introduction of the prospective payment system with its accompanying professional review organization review. 
5	Reclosure of disrupted abdominal incisions. We evaluated prospectively a technique of delayed reclosure of disrupted abdominal incisions. Forty-one consecutive postoperative obstetric and gynecologic patients with abdominal incisions that had opened because of infection, hematoma, or seroma and had intact fascia participated in the study. All wounds were first managed identically, with surgical drainage and debridement, for a minimum of 4 days. The patients then were randomized to either wound reclosure by a standardized en bloc technique (35) or healing by second intention (six). Reclosure was successful in 30 of 35 cases (85.7%). The mean time to complete healing was 15.8 days in successful cases, 67.2 days in failed cases, and 23.2 days for all patients who were reclosed. Failure to heal after reclosure was due to subcutaneous infection in two patients and seroma in three; these women were significantly heavier than those in whom reclosure was successful. There were no other major complications of wound reclosure. Patients randomized to healing by second intention required a mean of 71.8 days of wound care. The time to complete healing in the wound-reclosure group was significantly shorter compared with the group that healed by second intention (P = .002, log rank test). We conclude that en bloc reclosure of disrupted surgical incisions, compared with nonsurgical treatment, significantly decreases the time required for wound healing and has minimal morbidity. 
3	Cervicocephalic kinesthetic sensibility in patients with cervical pain. Head orientation in space makes use of multiple sensory afferents, among which the cervical proprioceptive cues could play a predominant role. To quantify the alteration of neck proprioception in patients with cervical pathology, we proposed a test for the clinical evaluation of the ability to relocate the head on the trunk after an active head movement, for 30 healthy subjects and 30 patients with cervical pain. The data demonstrated that this ability was significantly poorer in the patient group, indicating an alteration in neck proprioception. This test permits a discriminant classification of healthy and sick subjects, justifies proprioceptive rehabilitation programs, and allows a quantitative evaluation of their results. 
2	Colobronchial fistula: a rare complication of Crohn's colitis. A 29-yr-old white woman presented with chronic pneumonia in the left lower lobe and with left pleural effusion. She was known to have inflammatory bowel disease, but she was asymptomatic under maintenance treatment with 5-ASA. She received numerous antibiotic regimens according to susceptibility testing of microorganisms cultured from sputum and bronchial lavage and on an empiric basis was also given antituberculosis treatment, but there was no clinical improvement or change in the chest radiographic findings. Sputum was repeatedly examined and yielded, among other organisms, Clostridium inocuum, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. On one microscopic examination of sputum, the presence of feculent material was suspected. A subsequent gastrografin enema revealed a cologastric and colobronchial fistula between the splenic flexture of the colon and the greater curve of the stomach and the bronchial system. Segmental resection of the colon and resection of the lower lobe of the left lung were performed. Histologic findings of the resected colon were consistent with Crohn's disease. After a long period of postoperative recovery, the patient returned to good general health and well-being. To our knowledge, a colobronchial fistula caused by Crohn's colitis has not been previously reported. 
2	A new method for mapping hepatic subsegment: counterstaining identification technique. Hepatic subsegmentectomy requires identification of the borders of tumor-bearing subsegment, usually achieved by injecting dye into the portal veins feeding the domain. We describe an alternative technique for performing systematic subsegmentectomy in patients with cirrhosis and hepatocellular carcinoma, in whom hepatic arterial and portal venous embolizations were already performed as a preoperative adjuvant. Under ultrasonic guidance, each of the neighboring portal units is sequentially stained, thus defining the avascular subsegment to be resected as the nonstaining area. This allows the subsegment to be totally resected. This counterstaining identification technique can be used for all subsegments undergoing complete embolization and for other situations in which the usual staining method is impossible because of the presence of arterioportal shunting or portal tumor thrombus. 
1	Prevalence of common and dysplastic naevi in a Swedish population. The naevus profile was examined in a Swedish population that was randomly selected from a census file. The participation rate was considered high at 82%. The number of common naevi (CN) and the prevalence of dysplastic naevi (DN) were investigated in 379 subjects (aged 30-50 years). The mean total body count of CN greater than or equal to 2 mm was 67 (range 1-300). As many as 22% of the population had 100 naevi or more and only 18% had less than 25. The counts were not influenced by age or sex. DN were diagnosed clinically in 18% (CI 14-22%) of the subjects and histologically in 8% (CI 5-11%). Subjects with dysplastic naevi had a significantly larger number of common naevi and a more sun-sensitive skin type than subjects without DN, P less than 0.001. 
1	Matched group study of surgical resection versus cobalt-60 plaque radiotherapy for primary choroidal or ciliary body melanoma. We report the results of a nonrandomized, matched-group, survival and visual preservation study of patients with a choroidal or ciliary body melanoma managed by microsurgical resection of the tumor versus cobalt-60 episcleral plaque radiotherapy. Each treatment group consisted of 30 patients. All patients were matched on a case-by-case basis in terms of tumor size (largest linear tumor dimension), location of the anterior tumor margin relative to the ora serrata, location of the posterior tumor margin relative to the equator, and age at the time of treatment. Although the estimated actuarial 5-year survival probability was slightly greater in the resection group (85.2%) than in the cobalt plaque group (81.8%), this difference was neither clinically impressive nor statistically significant. In contrast, there was a substantially higher rate of early posttreatment severe visual loss in the resection group (P = .0008, Mantel-Haenszel test). 
4	An in vitro evaluation of an artificial heart. Interactions between human blood and the Penn State Artificial Heart were examined in vitro to study the effects of various operating conditions on the hematologic response. A dual-loop recirculating flow system that accommodated human blood was developed and blood was subjected for 3 hr to various operating conditions known to alter fluid mechanics in the artificial ventricle. The operating conditions investigated were: 60 beats/min at 50% systolic duration, 60 beats/min at 30% systolic duration, and 90 beats/min at 50% systolic duration. Quantification of plasma free hemoglobin provided a direct indicator of hemolysis in the flow system. Platelet number and beta-thromboglobulin levels were monitored to investigate thrombotic activity, and levels of complement 3a were measured to examine complement system activation. The system was effective in demonstrating the relative hemolytic properties of the operating conditions. Ninety beats/min induced 37% more hemolysis than 60 beats/min at 50% systolic duration, and 50% systolic duration induced 32% more hemolysis than 30% systolic duration at 60 beats/min. There were no statistically significant changes in either platelet number or beta-thromboglobulin levels during the 3 hr recirculation period. Increases were seen in complement 3a levels, but these appeared to be surface-induced and not sensitive to the different operating conditions. These studies demonstrate the usefulness of the flow system in examining the relative hemolytic properties of the artificial ventricle, and suggest that bulk turbulent stresses may play a more important role than laminar wall shear stresses in mediating blood damage in this artificial ventricle. 
4	Calcium regulating hormones in essential hypertension. Importance of gender. Alterations of calcium metabolism have been described in human essential hypertension and experimental hypertension. We investigated the interrelationship of parathyroid hormone (PTH) and 1,25(OH)2-vitamin D (1,25(OH)2D) in patients with untreated essential hypertension as compared to normotensive controls. The hypertensive subjects (n = 75; 43 men, 32 women) had a mean blood pressure of 138 +/- 8/95 +/- 5 mm Hg as compared with 120 +/- 11/80 +/- 8 in the normotensive group (n = 40; 22 men, 18 women). Serum PTH was measured with an intact molecule immunochemiluminometric assay and 1,25(OH)2D was measured with radioimmunoassay after HPLC separation. Hypertensive men had PTH levels that were 36% higher than normotensive men (5.3 +/- 2.9 v 3.9 +/- 0.8 pmol/L, P = .005). When blood pressure was analyzed as a continuous variable, there was a direct correlation between it and serum PTH in men (r = .31, P = .004). In women, by contrast, there was no difference in serum PTH between hypertensive and normotensive subjects and no relationship between blood pressure and the serum PTH concentration. Blood pressure was inversely correlated with serum phosphorus levels in both sexes (r = -0.20, P = .04). In men, the elevated serum PTH levels and depressed serum phosphorus levels would have predicted that serum 1,25(OH)2D would be higher in the hypertensive subjects. However, that was not observed, as serum 1,25(OH)2D was slightly lower in hypertensive (38.3 +/- 15.2 pg/mL) than normotensive men (42.7 +/- 11.3, P = .21). 
4	Extracorporeal LDL cholesterol removal: role of LDL-pheresis in combination with other hypolipidemic therapy to regress vascular disease. The direct relationship between hypercholesterolemia and atherosclerosis has resulted in formal cholesterol-lowering recommendations for patients at increased risk. The incomplete response to therapy of some forms of hypercholesterolemia as well as not uncommon drug intolerance prompted the development of extracorporeal techniques to reduce serum cholesterol levels. Nonhuman primate data and an analysis of human cholesterol epidemiology and reduction trials were used to establish guidelines that would maximize the likelihood of stabilizing or regressing established coronary artery atherosclerosis. These goals are a total cholesterol (TC) level of less than or equal to 150 mg/dL (3.9 mmol/L) and a ratio of TC to high-density lipoprotein cholesterol (HDL) of less than 2.8. Selective, extracorporeal removal of LDL cholesterol (LDL-pheresis) was combined with diet and hypolipidemic drugs in a pilot study at The Rogosin Institute to achieve these lipid end-points. Technical aspects of LDL-pheresis, the background rationale for its use as part of a combined hypolipidemic therapy, the initial experience at The Rogosin Institute, and plans for future studies and applications are presented. 
3	Interactions between substance P, calcitonin gene-related peptide, taurine and excitatory amino acids in the spinal cord. Using in vivo microdialysis in the dorsal spinal cord of the rat, we have previously observed increases in glutamate and aspartate during exposure to a noxious stimulus. The present investigation was designed to determine whether these increases may be mediated by substance P. Infusion of 1 mM of substance P in the dialysis fluid increased the concentrations of glutamate and aspartate, similar to the response seen during noxious stimulation. In addition, substance P also increased the concentrations of the inhibitory amino acids glycine and taurine. Calcitonin gene-related peptide, previously shown to enhance substance P-induced biting and scratching behavior, produced no effect on amino acid release by itself but potentiated the apparent release of taurine by substance P. To assess the importance of substance P-induced amino acid release in sensory processing, we examined the influence of taurine and of excitatory amino acid antagonists on the biting and scratching behavior produced by excitatory amino acids and substance P. Taurine selectively inhibited only substance P-induced biting and scratching while excitatory amino acid antagonists inhibited only excitatory amino acid-induced behavior. To further explore the ability of taurine to inhibit the substance P-induced behavior, 3 tests of nociception were then used. Pretreatment with taurine inhibited the nociceptive-related writhing behavior produced by an intraperitoneal injection of acetic acid in mice but failed to alter the latency of response in the hot plate or tail flick assay. 
5	Childhood blindness in Peru. A survey of childhood blindness in Peruvian children was done. Although most causes of blindness were due to congenital and hereditary conditions, measles accounted for almost 10% of blindness. With widespread measles immunization, this preventable cause of blindness in children can be eliminated or dramatically reduced. 
1	Depression of serum melatonin in patients with primary breast cancer is not due to an increased peripheral metabolism. Serum melatonin and its main metabolic product 6-sulfatoxymelatonin were determined in 17 patients with breast cancer (BC) with either a fresh primary tumor (nine) or a secondary tumor (eight) as well as in four patients with untreated benign breast disease (controls). Circadian rhythms were detected in all groups with acrophases around 2 AM for melatonin and around 3 AM for 6-sulfatoxymelatonin. The nocturnal melatonin and 6-sulfatoxymelatonin concentrations were significantly depressed in the group of patients with primary breast cancer compared with controls (P less than 0.01, P less than 0.025). The circadian amplitudes of melatonin and 6-sulfatoxymelatonin were also depressed by 81% (P less than 0.01) and 63% (P less than 0.01). In contrast, patients with secondary BC had nocturnal melatonin and 6-sulfatoxymelatonin concentrations and amplitudes similar to controls. These results demonstrate that the depression of circulating melatonin in patients with primary BC is not due to an enhanced degradation to 6-sulfatoxymelatonin in the liver but must be due to a reduced activity of the pineal gland. 
5	Two types of abnormal somatosensory evoked potentials in chronic cerebellar ataxias. To investigate subclinical sensory impairment in spinocerebellar degenerations, median nerve somatosensory evoked potentials (SEPs) were examined in 16 patients with chronic cerebellar ataxia who were originally diagnosed by clinical neurologists as having olivopontocerebellar atrophy (OPCA). Two types of abnormal SEP patterns were found in six patients. Two patients had the SEP pattern of peripheral neuropathy, which was also detected by peripheral sensory nerve conduction studies. Four patients had abnormal SEPs seen in patients with the lesions in the central nervous system (dorsal column, medial lemniscus). Magnetic resonance imaging (MRI) showed multiple sclerosis (MS). It is possible that clinically diagnosed OPCA sometimes includes a similar form of Friedreich's ataxia with subclinical sensory fiber neuropathy detected by SEPs and peripheral sensory conduction studies. In cases of lesions in the central nervous system demonstrated by both SEPs and MRI, there must be a follow-up in order to make a final diagnosis. In those cases, an alternative diagnosis of MS must be considered when the temporal profile of symptoms and signs characteristic of MS is observed. 
4	Acute rheumatic fever in West Virginia. Not just a disease of children. Rheumatic fever is a poststreptococcal disease that is receiving renewed attention by the medical community. We describe a recent increase in the number of observed cases of acute rheumatic fever (ARF) in West Virginia. This is the fifth report of a recent increase in the incidence of ARF in the Ohio Valley area in the last 4 years. In contrast to the other reports, nearly two thirds of our cases of ARF were in adults, more than half of whom had suffered previous bouts of ARF. In these adults with recurrences, none was taking prophylactic penicillin at the time of presentation. Carditis was present in seven adults, two without a history of carditis. Arthritis was present in all adult patients. These data indicate a possible geographic phenomenon related to the increased number of observed cases of ARF and document that ARF is not simply a disease of childhood. Furthermore, our findings highlight the need for extended penicillin prophylaxis for secondary prevention of ARF, especially for those with an increased risk of acquiring a streptococcal upper respiratory tract infection. 
4	Outcome and predictors of outcome in pediatric submersion victims receiving prehospital care in King County, Washington Predictors of outcome in pediatric submersion victims treated by Seattle and King County's prehospital emergency services were studied. Victims less than 20 years old were identified from hospital admissions and paramedic and medical examiners' reports. The proportion of fatal or severe outcomes in patients were compared with various risk factors. Of 135 patients, 45 died and 5 had severe neurologic impairment. A subset of 38 victims found in cardiopulmonary arrest had a 32% survival rate, with 67% of survivors unimpaired or only mildly impaired. The two risk factors that occurred most commonly in victims who died or were severely impaired were submersion duration greater than 9 minutes (28 patients) and cardiopulmonary resuscitation duration longer than 25 minutes (20 patients). Both factors were ascertained in the prehospital phase of care. Submersion duration was associated with a steadily increasing risk of severe or fatal outcomes: 10% risk (7/67) for 0 to 5 minutes, 56% risk (5/9) for 6 to 9 minutes, 88% risk (21/25) for 10 to 25 minutes, 100% risk (4/4) for greater than 25 minutes. None of 20 children receiving greater than 25 minutes of cardiopulmonary resuscitation escaped death or severe neurologic impairment. Our rates for saving all victims, particularly victims in cardiopulmonary arrest, are considerably higher than has been reported before the children. Prompt prehospital advanced cardiac life support is the most effective means of medical intervention for the pediatric submersion victim. Prehospital information provided the most valuable predictors of outcome. 
1	Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989). Twenty-eight of 124 (23%) advanced germ cell tumor (GCT) patients who were treated on four successive platin-based induction regimens and who failed to achieve a durable complete response (CR) remain alive (median follow-up, 50 months). An analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy. Survival and/or response to salvage therapy were significantly enhanced for patients with a prior CR to induction chemotherapy, treatment with a cisplatin-based salvage regimen, a testis primary site, a normal serum human chorionic gonadotropin level, a normal serum lactate dehydrogenase level, one site of metastasis, and an Indiana Class of 6 or less. Patients with a prior incomplete response (IR) had a particularly poor prognosis (P = 0.00007) with only 4 of 52 (9%) patients alive (median follow-up, 37 months) compared with 15 of 42 (36%) patients with a prior best response of a CR (median follow-up, 35 months). The poor survival of patients who fail to achieve a durable CR to induction chemotherapy warrants the continued investigation of new salvage therapy. The identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens. 
2	Hepatic lesions in the rabbit induced by acoustic cavitation. Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma. 
4	High-normal blood pressure progression to hypertension in the Framingham Heart Study. This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category. Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure. The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for women (95% CI, 1.5-2.3; p less than 0.0001). The age-adjusted relative risks estimated by the proportional hazards model were 3.36 for men and 3.37 for women (p less than 0.001). Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal. For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension. These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure. 
1	Monoclonal antibody-purged autologous bone marrow transplantation therapy for multiple myeloma. Eleven patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT). The majority of patients had advanced Durie-Salmon stage myeloma at diagnosis, all were pretreated with chemotherapy, and six had received prior radiotherapy. At the time of ABMT, all patients demonstrated good performance status with Karnofsky score of 80% or greater and had less than 10% marrow tumor cells. Eight patients had residual monoclonal marrow plasma cells and 10 patients had paraprotein. Following high-dose melphalan and total body irradiation (TBI) there were seven complete responses, three partial responses, and one toxic death. Granulocytes greater than 500/mm3 were noted at a median of 21 (range 12 to 46) days posttransplant (PT) and untransfused platelets greater than 20,000/mm3 were noted at a median of 23 (12 to 53) days PT in 10 of the 11 patients. Natural killer cells and cytotoxic/suppressor T cells predominated early PT, with return of B cells at 3 months PT and normalization of T4:T8 ratio at 1 year PT. Less than 5% polyclonal marrow plasma cells were noted in all patients after transplant. Three of the seven complete responders have had return of paraprotein, two with myeloma, and have subsequently responded to alpha 2 interferon therapy. Eight patients are alive at 18.9 (8.9 to 43.1) months PT and four remain disease-free at 12.3, 17.5, 18.9, and 29 months PT. This preliminary study confirms that high-dose melphalan and TBI can achieve high response rates without unexpected toxicity in patients who have sensitive disease, and that MoAb-based purging techniques do not inhibit engraftment. Although the follow-up is short- and long-term outcome to be determined, relapses post-ABMT in these heavily pretreated patients suggest that ABMT or alternative treatment strategies should be evaluated earlier in the disease course. 
2	Milk protein enteropathy after acute infectious gastroenteritis: experimental and clinical observations. Animal models of allergic gastroenteropathy have defined both morphologic and physiologic changes that accompany the immune-mediated reaction to a dietary protein. In such models a broadening of the allergic response to other dietary proteins present in the gastrointestinal tract may occur during the localized anaphylactic reaction. The characteristic histologic intestinal findings of food protein-induced enteropathy may develop in selected infants with protracted diarrhea after infectious enteritis. Mechanisms underlying the induction of this response remain to be explained, but they may in part be similar to the broadening of the hypersensitivity response seen in experimental models of allergic enteropathy. 
3	Effect of epilepsy and sleep deprivation on the rate of benign epileptiform transients of sleep. Seventy-eight individuals with EEG records containing benign epileptiform transients of sleep (BETS) were identified among 7,400 records reviewed in our laboratory in a 6-year period. The records contained no other abnormality in 51 patients (65%). Genuine epileptiform discharges were found in the records of 19 patients; 14 had a history of epilepsy. Thirty-five patients (45%) had a proven history of epilepsy with antiepileptic drug (AED) therapy. In the records of these patients, the mean number of BETS per unit of time was significantly higher (11.88 +/- 2) than in the record of the rest of the laboratory population with BETS (6.89 +/- 0.9) (p less than 0.02). Among five conventional surface montages, ipsilateral ear referential montage (IERM) showed a significantly higher number of BETS per unit of time than did any other surface montage used in the study. Thirty-nine records (50%) were performed after sleep deprivation (SD). When only IERM was considered, SD records showed a significantly higher number of BETS per unit of time (7.36 +/- 1.1) than did non-SD records (3.89 +/- 0.69) (p less than 0.01). Our findings support the general consensus that individual BETS may be normal variants, but a high occurrence of BETS in the record should raise suspicion of underlying epilepsy. 
1	Examination of HTLV-I integration in the skin lesions of various types of adult T-cell leukemia (ATL): independence of cutaneous-type ATL confirmed by Southern blot analysis. The various clinical features of adult T-cell leukemia/lymphoma (ATL) are frequently accompanied by skin eruptions. Recently, a cutaneous type of ATL has been proposed by clinical studies. We analyzed the viral integration of human T-cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL patients with various clinical features and skin eruptions. We classified them by the results of Southern blot analysis and propose a cutaneous-type ATL accordingly. In two of them, we could detect the monoclonal integration of HTLV-I and T-cell monoclonality only in the skin but not in the peripheral lymphocytes. We also demonstrated the time course study in one patient. Clinicians should be aware of the HTLV-I positive cutaneous T cell lymphoma that can be named cutaneous-type ATL. Examination of viral integration and T-cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous ATL. 
3	Progression of diabetic autonomic neuropathy over a decade in insulin-dependent diabetics. The prognosis for diabetics with autonomic neuropathy is little known. We therefore studied the progress of young insulin-dependent diabetics, first identified as having abnormal autonomic function 10-15 years ago. We have shown that the mortality of diabetics with symptomatic autonomic neuropathy is increased, but is less than previously reported. Mortality in asymptomatic diabetics with an isolated abnormality in autonomic function tests is not increased. The heart rate variability declines at 1.02 +/- 0.47 (SD) per annum in diabetics with an initially normal heart rate variability. While symptoms of autonomic neuropathy do not usually remit even over a decade, they do not commonly progress. Three groups of young insulin-dependent diabetics had heart rate variability tested between 1972 and 1977 and have been reviewed 10-15 years later. Group A (n = 49) had symptomatic autonomic neuropathy and an abnormal heart rate variability (less than 12), Group B (n = 24) were asymptomatic yet had an abnormal heart rate variability and Group C (n = 38) were asymptomatic and had a normal heart rate variability (16-26). The 10-year survival in Group A (73.4 per cent) was less (P less than 0.05) than in Groups B (91.7 per cent) or C (89.5 per cent) which did not differ from each other. The 18 Group A deaths were due predominantly to renal failure (n = 4), myocardial infarction in patients with nephropathy (n = 3) and sudden unexpected death (n = 3). The chief symptoms of autonomic neuropathy--diarrhoea, postural hypotension and gustatory sweating, were very persistent but did not necessarily deteriorate or become disabling in the majority of patients. The development of autonomic symptoms in asymptomatic patients with abnormal heart rate variability was uncommon over a decade. 
4	Anginal symptoms without ischemic electrocardiographic changes during ambulatory monitoring in men with coronary artery disease. Episodes of angina pectoris without electrocardiographic (ECG) signs of myocardial ischemia during 24-hour ambulatory monitoring were studied in 128 patients with a history of stable angina, angiographically proven coronary artery disease and positive exercise test results. In all, 341 episodes of ischemic ECG changes (ST-segment depression greater than 1 mm for greater than 1 minute) and 190 episodes of angina pectoris were observed: 86 episodes consisted of both ECG changes and angina pectoris, 255 episodes consisted only of ECG changes, and 104 episodes only of angina pectoris. Duration and magnitude of ST-segment deviation and heart rate at the onset of ischemia were similar in the 86 symptomatic and the 255 asymptomatic episodes with ECG changes. The 104 episodes of angina pectoris without ECG changes were detected in 44 patients (34%) (group A); 29 of them had only episodes with angina pectoris and 15 patients had both--episodes of angina pectoris with and without ECG changes. In 84 patients (66%) (group B) angina pectoris without ECG changes was not observed; all episodes were accompanied by ischemic ECG changes in these patients. No differences in the angiographic extent of coronary artery disease and in exercise test data were seen in both groups A and B; however, maximal ST-segment depression during exercise testing was significantly greater in group B than in group A patients (2.4 +/- 0.8 mm vs 1.9 +/- 0.9 mm; p less than 0.05). 
4	Ventricular free-wall rupture after myocardial infarction. Treatment and outcome. Ventricular free-wall rupture remains one of the leading causes of death after myocardial infarction (MI). With increased abilities for diagnosis and resuscitation techniques, surgical correction of free-wall myocardial defects resulting from ischemia and necrosis may become a simple modality of treatment, resulting in improvement of the survival rate. We are reporting our experience with four patients with ventricular free-wall rupture after MI, with emphasis on clinical presentation, diagnosis, and surgical management. 
4	The long-term prognosis of patients with out-of-hospital cardiac arrest but no inducible ventricular tachycardia. The long-term prognosis of patients successfully resuscitated from cardiac arrest who do not have acute precipitating factors and in whom ventricular arrhythmias cannot be induced during baseline electrophysiologic testing is controversial. The purpose of this investigation was to evaluate the long-term risk of recurrent sudden death and determine the clinical, angiographic, hemodynamic, and electrophysiologic predictors of recurrent cardiac arrest in such patients. Twenty-six (37%) of 71 consecutive patients with a single episode of aborted sudden death did not have inducible ventricular arrhythmias (less than 7 intraventricular responses) during baseline drug-free electrophysiologic study and they form the basis of this report. Their mean age was 54 +/- 13 (mean +/- SD) years and the left ventricular ejection fraction (LVEF) was 0.47 +/- 0.17. After a mean follow-up period of 16 months, 11 patients (42%) had a recurrent cardiac arrest (fatal in 10 patients). The actuarial incidence of recurrent cardiac arrest was 30 +/- 10% at 1 year and 55 +/- 13% at 3 years. Patients with LVEF less than or equal to 0.40 had a significantly higher occurrence of recurrent cardiac arrest than those with LVEF greater than 0.40 (p = 0.02; 1-year actuarial incidence of 57 +/- 17% versus 13 +/- 19%). Patients with recurrent sudden death had a significantly greater incidence of dilated cardiomyopathy (55% versus 7%; p = 0.02) and baseline frequent premature ventricular contractions (PVCs greater than 10/hr; 64% versus 17%, p = 0.036) or nonsustained ventricular tachycardia (36% versus 0%; p = 0.37) than patients without these characteristics. 
5	Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. The role of oxygen-derived free radicals and lipid peroxidation in the pathogenesis of acute gastric mucosal erosion was investigated in rat models produced by burn shock stress, by treatment with regional hyperthermia, platelet activating factor, and compound 48/80, and by ischemia-reperfusion. In all experimental models, the increase in the gastric erosions and in TBA reactants in the gastric mucosa were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase, prevented considerably the gastric injury (a) induced by burn shock, (b) produced by treatment with compound 48/80, and (c) caused by ischemia-reperfusion. By the treatment with anti-rat neutrophil antibody, the gastric mucosal injuries induced by regional hyperthermia, platelet activating factor, and compound 48/80 were significantly inhibited; however, burn shock and ischemia-reperfusion injuries were not inhibited. These results suggest that oxygen-free radical and lipid peroxidation contribute to the formation of gastric mucosal lesions, and that the sources of oxygen radicals seem to be different among these experimental models. 
4	Neuropsychological outcome of survivors of out-of-hospital cardiac arrest. Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest. 
5	Pancreatic duct abnormalities in gall stone disease: an endoscopic retrograde cholangiopancreatographic study. This study was carried out to assess pancreatic duct abnormalities in gall stone disease. Endoscopic retrograde cholangiopancreatograms of 50 patients with gall stone disease were analysed and the results compared with those obtained in 33 patients investigated for cholestatic jaundice who were found to have a normal biliary tree (control group). Abnormal pancreatograms were obtained in 24 (48%) patients with gall stone disease and in only two (6%) in the control group; the differences were statistically significant (chi 2 = 14.3; p less than 0.001). The patients in the control group showed mild abnormalities as did those in the gall stone group. The frequency of various abnormalities were: mild 16 (32%), moderate five (10%), and severe three (6%). Pancreatic duct abnormalities were more severe and occurred more frequently in patients with gall stones who had stones in the biliary tree than in patients with a normal biliary tree (postcholecystectomy patients, 55% v 25%) but the difference between the two groups just failed to be significant (chi 2 = 3.34). In conclusion, nearly half of all patients with gall stone disease have pancreatic duct abnormalities and in 16% these were severe enough to be labelled as chronic pancreatitis. 
2	Prospective study of a prosthetic H-graft portacaval shunt. This study was undertaken to prospectively evaluate the 8-mm Gore-Tex interposition H-graft portacaval shunt. Thirty-six high-risk patients at the University of South Florida-affiliated hospitals received small-diameter shunts because of bleeding esophagogastric varices over a recent 2-year period. Portal vein and portal vein-inferior vena cava gradients were significantly reduced after shunting. These pressure changes were manifested clinically by the absence of variceal rebleeding and improvement of ascites; in addition, the incidence of encephalopathy was low. The 8-mm graft maintained hepatopedal flow in 67% of the patients, but reversal of flow did not result in complications commonly associated with poor portal perfusion. Graft thrombosis occurred in four (11%) patients. All grafts were successfully revised, three by operative revision and one by an interventional radiologist. Operative mortality was low (11%), and morbidity was unusual. The small-diameter H-graft portacaval shunt is a safe and effective method of treatment for bleeding esophagogastric varices. 
5	Helicobacter pylori and associated duodenal ulcer. Twenty three children with coexistent duodenal ulcer and Helicobacter pylori infection were treated with either two weeks of amoxycillin (25 mg/kg/day) in addition to six weeks of cimetidine, or cimetidine alone. Endoscopy with antral and duodenal biopsies for urease test, microaerophilic culture, and histological studies were performed at entry, six weeks, 12 weeks, and at six months. Children with persistent H pylori infection at six weeks were given a further two weeks' course of amoxycillin. H pylori persisted in all children not receiving amoxycillin treatment but cleared in six of the 13 children (46%) treated with amoxycillin. With failure of H pylori clearance at six months, only two out of six (33%) ulcers had healed and 50% of patients had experienced ulcer recurrence. In contrast, when H pylori remained cleared all ulcers healed and no ulcer recurred. Persistent H pylori infection was associated with persistent gastritis and duodenitis despite endoscopic evidence of ulcer healing. Detection and eradication of H pylori deserves particular attention in the routine management of duodenal ulceration in children. 
1	Acute renal failure in obstructive jaundice in cholangiocarcinoma. This study was aimed at defining the natural history of renal failure in obstructive jaundice due to cholangiocarcinoma, which is an important health problem in northeastern Thailand. Sixty-four patients among a total of 130 patients with obstructive jaundice secondary to cholangiocarcinoma who developed acute renal failure were studied retrospectively. Analysis was made with respect to clinical features, laboratory findings, and outcome. The development of renal failure before surgery was observed in all patients. It was nonoliguric in 80% and was associated with severe jaundice, gram-negative infection (42%), hypotension (31%), hypoproteinemia (30%), hyponatremia (56%), and hypokalemia (63%). The mean duration of renal failure was 2 weeks. All patients underwent surgery for the relief of jaundice. Seventy-seven percent of the patients survived and had recovery of renal function after the relief of jaundice. Twenty-three percent of the patients died of infection. Clinical data highlight the higher serum bilirubin levels and the frequent occurrence of hyponatremia, hypokalemia, and hypotension in renal failure. Their possible roles in contributing to the development of renal failure are discussed. 
4	Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits. Previous studies have demonstrated that bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of bupivacaine cardiovascular toxicity. To investigate the mechanisms by which bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv) bupivacaine or intravenous (iv) phenylephrine resulted in dysrhythmias and hypertension. In group 1 (n = 5), icv bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or hypertension. In group 2 (n = 9), icv bupivacaine-induced hypertension and dysrhythmias were abolished by icv midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and hypertension recurred (22 +/- 0.9 min), hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and hypertension (14 +/- 1 s). In group 3 (n = 10), icv bupivacaine-induced dysrhythmias and hypertension were not affected by increasing the inspired halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv phenylephrine-induced dysrhythmias and hypertension were not affected by icv midazolam. These results suggest that icv bupivacaine produces dysrhythmias and hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by hexamethonium rapidly terminated dysrhythmias and hypertension supports this mechanism. We speculate that icv bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS. 
1	Molecular methods to detect the Philadelphia chromosome. The Ph1 chromosome has two molecular subtypes: a bcr-positive seen in CML and some cases of ALL, and the bcr-negative subtype mainly seen in ALL. In CML, because of the restriction of chromosome 22 breakpoints to the bcr, Southern analysis to detect bcr rearrangements also can be used to detect the Ph1 chromosome. In contrast, the translocation breakpoints on the Ph1 chromosome are scattered in ALL, so that other methods such as PFGE and PCR are necessary to detect the Ph1 chromosome. In both CML and ALL, use of these methods to detect molecular abnormalities may be superior to cytogenetics in detecting chromosomal abnormalities. Southern analysis also can be used in CML to map breakpoint locations within the bcr. This may offer prognostic information as to the length of chronic phase, but there is conflicting information as to the validity of this approach. The modified PCR (using cDNA from mRNA) can be used to detect the Ph1 chromosome and to define which of the molecular subtypes are present. The exquisite sensitivity of this method, which is capable of detecting as little as a single abnormal molecule of RNA or DNA, makes it suited for the detection of minimal residual disease in both CML and ALL. This is particularly useful after intensive therapies, such as bone marrow transplantation. Whether these low levels of fusion gene expression are of prognostic significance is still unclear. 
5	Dialysis arthropathy: a clinical, biochemical, radiological and histological study of 36 patients. Out of a population of 97 haemodialysis patients, 36 patients with dialysis arthropathy were identified. Dialysis arthropathy is a chronic symmetrical polyarthritis which affected 97 per cent of the patients who had been undergoing cuprophane haemodialysis for more than 10 years. It commonly affected the shoulders, hips, hands, knees and wrists, worsening with time and extending to other joints. Fifty-eight per cent of the patients complained of morning stiffness and 47 per cent complained of exacerbation of shoulder pain during or after haemodialysis. Half of the patients also suffered from carpal tunnel syndrome, which recurred and was associated with a long-lasting disability. The most common radiological abnormality was periarticular bone cysts, followed by articular erosions and a destructive spondyloarthropathy, but clinical symptoms were more common than radiological signs. Patients with dialysis arthropathy had a higher C-reactive protein level than patients without arthropathy (18.6 mg/l versus 11.4 mg/l), indicative of an inflammatory process. Some of the clinical manifestations of the disease correlated with levels of C-reactive protein and ferritin. Serum ferritin levels correlated strongly with the units of blood transfused in the past five years (RS = 0.83), and the logarithm of ferritin level correlated weakly with C-reactive protein (r = 0.32). Haemarthroses were documented in 19 per cent of patients. Mean serum beta 2-microglobulin was elevated in the patients with (57.3 mg/l) and without arthropathy (50.7 mg/l), and there was no difference in the parathormone or aluminium levels between these groups. Articular tissue was obtained in 25 patients; beta 2-microglobulin amyloid was present in 24. Larger deposits were present in the capsular tissue, and these appeared to replace collagen bundles in eight cases. Amyloid deposits replaced the lining layer in six cases. It is likely therefore that amyloid disrupts normal joint function by replacing normal joint tissue. Mild chronic synovitis with haemosiderin deposition were found in approximately 60 per cent of cases. These findings suggest that amyloid derived from beta 2-microglobulin has a primary role in the pathogenesis of dialysis arthropathy, but there was also evidence of inflammatory processes. It is suggested that iron overload or haemarthroses might contribute to the inflammation, but other factors, such as dialysis-related bioincompatibility reactions, may also have a role. 
5	The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators BACKGROUND. Nonrheumatic atrial fibrillation increases the risk of stroke, presumably from atrial thromboemboli. There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke. METHODS. We conducted an unblinded, randomized, controlled trial of long-term, low-dose warfarin therapy (target prothrombin-time ratio, 1.2 to 1.5) in patients with nonrheumatic atrial fibrillation. The control group was not given warfarin but could choose to take aspirin. RESULTS. A total of 420 patients entered the trial (212 in the warfarin group and 208 in the control group) and were followed for an average of 2.2 years. Prothrombin times in the warfarin group were in the target range 83 percent of the time. Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently. There were 2 strokes in the warfarin group (incidence, 0.41 percent per year) as compared with 13 strokes in the control group (incidence, 2.98 percent per year), for a reduction of 86 percent in the risk of stroke (warfarin:control incidence ratio = 0.14; 95 percent confidence interval, 0.04 to 0.49; P = 0.0022). There were 37 deaths altogether. The death rate was markedly lower in the warfarin group than in the control group: 2.25 percent as compared with 5.97 percent per year, for an incidence ratio of 0.38 (95 percent confidence interval, 0.17 to 0.82; P = 0.005). There was one fatal hemorrhage in each group. The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups. The warfarin group had a higher rate of minor hemorrhage than the control group (38 vs. 21 patients). CONCLUSIONS. Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring. 
1	Clinical recognition and evaluation of peptic ulcer disease. When a patient has epigastric pain that worsens 1 to 3 hours after meals, the possibility of peptic ulcer disease should be considered. Completely typical clinical presentations in patients younger than age 50 justify empirical therapy when no physical or laboratory findings suggest a mimicking disorder. Esophagogastroduodenoscopy should be undertaken when response to therapy is incomplete, symptoms recur quickly, or dyspeptic symptoms present for the first time in a patient older than age 50. When gastric ulcers are diagnosed radiographically, endoscopy and biopsy at multiple sites should be done to exclude malignant disease. Intractable duodenal ulcers may necessitate endoscopic biopsy of antral and duodenal mucosa to rule out an associated Helicobacter pylori infection, which may modify therapeutic approaches. Zollinger-Ellison syndrome is rare but should be suspected when ulcer disease presents atypically or aggressively or in families. Diagnosis is not difficult to confirm. 
3	Gadolinium-MRI in acute transverse myelopathy. A patient with acute transverse myelopathy (ATM) had serial magnetic resonance imaging (MRI) studies before and after administration of gadolinium (Gd-DTPA). Gd-DTPA-MRI was useful in estimating the pathologic extent and residual deficit expected in ATM. 
4	Loss of nocturnal decline of blood pressure in hypertension due to chronic renal failure. The aim of this study was to assess the blood pressure profile of chronic renal failure in comparison with essential hypertension. Thirty hypertensive patients with chronic renal failure due to non-vascular nephropathies were matched by age, sex, and mean 24 h blood pressure, with 30 patients affected by uncomplicated mild-to-moderate essential hypertension. They were studied in an open hospital ward. Diet, meal times, sleep times, and activity schedules were standardized. Noninvasive, automatic, blood pressure recordings were performed for 48 h at sampling intervals of 15 min. The mean 24 h blood pressure almost coincided in the two groups. However, in essential hypertension a mean (+/- SD) nocturnal fall of systolic and diastolic blood pressure was found (12.7 +/- 3.8 and 12.9 +/- 4.8 mm Hg, respectively), while renal patients displayed an average nocturnal increase of 2.7 +/- 8.9 mm Hg and 3.7 +/- 7.8 (P less than .001). The renal patients had also higher heart rates, with a significantly blunted nocturnal fall (4.4 +/- 4.5 beats/min as compared to 9.3 +/- 3.1 beats/min of essential hypertension; P less than .001). Among the renal patients, the day-night blood pressure changes showed no significant correlation with age, creatinine clearance, hematocrit, nocturnal change in heart rate, or day or night mean blood pressure levels. These data suggest that an abnormal day-night pattern of blood pressure is present in chronic renal failure patients independently from external interfering factors. Hence, casual measurements of blood pressure confined to daytime may underestimate a hypertensive condition associated with chronic renal failure. 
4	Congenital diaphragmatic hernia: impact of prostanoids in the perioperative period. A prospective study of 10 neonates with congenital diaphragmatic hernia and five controls to determine the importance of prostanoid concentrations perioperatively and the relation with persistent pulmonary hypertension (PPH) is reported. In neonates with congenital diaphragmatic hernia postoperative concentrations of the vasoconstrictor thromboxane B2 rose significantly and were higher during episodes of PPH; this rise may provoke PPH and subsequent right to left shunting. 
4	Abnormal baroreflex control of heart rate in decompensated congestive heart failure and reversal after compensation. Congestive heart failure (CHF) causes impairment of baroreflex control of heart rate (HR). To determine if this derangement is reversible, the cardiac chronotropic control was assessed in 10 patients with class IV chronic CHF of various etiologies before and after compensation achieved by bed rest, salt restriction, diuretics and vasodilators. Mean time between the 2 studies was 15 +/- 3 days. The management was modified 3 days before the second autonomic evaluation, so as to reestablish the same diet and pharmacologic conditions of the previous study. Compensation led to significant reduction in symptom-based class, body weight, and pulmonary and systemic congestion. Mean +/- standard error of the mean HR responses (beats/min) before and after compensation were, respectively: (1) to atropine (0.04 mg/kg): 10 +/- 2 and 27 +/- 2 (p less than 0.01); (2) to handgrip (30% maximum capacity, 1 minute): 9 +/- 2 and 19 +/- 3 (p less than 0.005); (3) to headup tilt (5 minutes): 4 +/- 3 and 20 +/- 4 (p less than 0.005). Mean +/- standard error of the mean baroreflex sensitivity (ms/mm Hg) of RR responses to phenylephrine and amyl nitrate-induced changes in systolic pressure was, respectively, in each condition: phenylephrine, 0.9 +/- 0.2 and 8 +/- 2.3 (p less than 0.05); amyl nitrate, 0.3 +/- 0.2 and 4.1 +/- 1.1 (p less than 0.05). A significant correlation between improvement in HR responses to atropine and tilt and changes in body weight was obtained. These findings show a reversible component of impaired baroreflex control of HR in severe CHF, possibly due to its congestive effects. 
3	Neonatal subependymal giant cell astrocytoma associated with tuberous sclerosis: MRI, CT, and ultrasound correlation. We describe a term newborn with tuberous sclerosis who presented with a neonatal brain tumor, diagnosed as a subependymal giant cell astrocytoma. We compare the various imaging modalities used in the diagnosis of this tumor. 
5	Treatment of acute hydrocephalus after subarachnoid hemorrhage with serial lumbar puncture. Computed tomography demonstrated acute hydrocephalus less than or equal to 72 hours after subarachnoid hemorrhage in 24 (23%) of 104 patients. Of these 24 patients, six (25%) had no impairment of consciousness. In nine (11%) of the remaining 80 patients, acute hydrocephalus developed within 1 week after subarachnoid hemorrhage. With the exception of three patients, all 104 patients received antifibrinolytic treatment. Delayed clinical deterioration from acute hydrocephalus occurred in seven (29%) of the 24 patients with acute hydrocephalus on admission and in six (8%) of the remaining 80 patients. Serial lumbar puncture was performed in 17 patients. Twelve (71%) of the 17 patients treated with serial lumbar puncture, including 10 (77%) of the 13 patients with delayed deterioration from acute hydrocephalus after admission, achieved improvement in the level of consciousness. Four of these 17 patients (4% of all 104 patients) required an internal shunt. No patient deteriorated from coning following serial lumbar puncture. The rebleeding rate within 12 days after subarachnoid hemorrhage in hydrocephalic patients with serial lumbar puncture was not higher than the rate in those without hydrocephalus (two [12%] of 17 versus nine [13%] of 71). Neither meningitis nor ventriculitis was observed. We conclude that if neither a hematoma with a mass effect nor an obstructive element exists, cerebrospinal fluid drainage with serial lumbar puncture is a good alternative to ventricular drainage in patients with acute hydrocephalus after subarachnoid hemorrhage. 
2	Successful control of bleeding from gastric antral vascular ectasia (watermelon stomach) by laser photocoagulation. We report a case of gastric antral vascular ectasia in a patient with primary biliary cirrhosis in whom chronic blood loss was a major problem. She required repeated blood transfusions that were complicated by reactions and still had persistent anaemia. She was treated with laser phototherapy in the form of quadrantic photocoagulation with a neodynium yttrium-aluminium-garnet laser. This greatly improved the endoscopic appearance of the gastric lesions and effectively controlled blood loss. She required no further transfusions. Bleeding recurred after 11 months which was controlled by further laser photocoagulation. 
3	Single unit analysis of the human ventral thalamic nuclear group. Activity correlated with movement. During neurosurgical operations for the relief of movement disorders, single thalamic neurons (n = 107) were identified with activity which was related to verbally cued active movements (movement-related cells). The activity of each neuron was examined during different contralateral movements in order to determine the movement which was associated with the most consistent and pronounced change in firing rate (the optimal response). The optimal response was determined by analysis of histograms of neuronal activity which were constructed by using the onset of EMG activity to synchronize successive repetitions of the active movement. Movement-related cells exhibited optimal responses associated with such movements as making a fist, extension or flexion of the wrist, flexing or extending the elbow, pointing with the entire upper extremity, extending the tongue and lifting the leg. Most movement-related cells recorded in a single parasagittal plane in an individual patient had optimal responses related to movements involving the same part of the body. Movement-related cells were classified into those that were activated in response to somatosensory stimulation (combined cells, n = 20) and those which were not (voluntary cells, n = 87). Combined cells were activated in advance of EMG activity during active movement and so could be distinguished from cells responding only to sensory stimulation (sensory cells). Movement-related cells (combined and voluntary cell types) were located anterior to sensory cells and tended to show a mediolateral somatotopic organization parallel to that of sensory cells with cutaneous receptive fields. Combined cells responded to somatosensory stimulation of the same part of the body as that involved in the active movement related to the optimal response of the cell. Combined cells responding to passive movements of a joint always had their optimal response during active movement about the same joint. The activity of combined cells during parkinsonian tremor may clarify the role of sensory feedback in tremor. 
5	Postpartum hemorrhage: placenta accreta, uterine inversion, and puerperal hematomas. Puerperal hematomas, although rare, can be potentially morbid or life-threatening events. Early surgical management, including clot evacuation, layered closure, drainage, antibiotics, and fluid replacement (including blood), usually result in satisfactory outcome. Prevention is clearly preferable and often achievable with careful initial repair of episiotomies and lacerations. 
2	Should alcoholics compete equally for liver transplantation? The circumstances of liver transplantation are unique among organ transplantation because of the dire, absolute scarcity of donor livers and the predominance of one disease--alcohol-related end-stage liver disease--as the principal cause of liver failure. We propose that patients who develop end-stage liver disease through no fault of their own should have higher priority for receiving a liver transplant than those whose end-stage liver disease results from failure to obtain treatment for alcoholism. We base our proposal on considerations of fairness and on whether public support for liver transplantation can be maintained if, as a result of a first-come, first-served approach, patients with alcohol-related end-stage liver disease receive more than half the available donor livers. We conclude that since not all can live, priorities must be established for the use of scarce health care resources. 
3	Aids for visual impairment. This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue. 
3	Pharmacologic treatment of noncognitive behavioral disturbances in elderly demented patients. Fifty-nine elderly residents of long-term care facilities who had DSM-III diagnoses of dementia were studied in an 8-week randomized, double-blind comparison trial of haloperidol, oxazepam, and diphenhydramine to test the efficacy of these agents in the treatment of clinically significant behavioral disturbances in patients with dementia. All three agents demonstrated modest but significant efficacy as measured by clinician ratings of agitated behavior and activities of daily living. The absolute magnitude of improvement was greater for haloperidol and diphenhydramine than for oxazepam, but differences among groups did not approach statistical significance. Frequencies of acute adverse events during the trial were similar across the drug treatment groups. Although these drugs may differ in terms of long-term safety and efficacy, they appear to be equivalent for short-term management of agitated behavior in severely demented patients. 
4	A case of unilateral posterior ischemic optic neuropathy after radical neck dissection. We present a case of unilateral posterior ischemic optic neuropathy after bilateral radical neck dissection. Etiologic factors are discussed. 
5	Stair climbing as an exercise test to predict the postoperative complications of lung resection. Two years' experience. The results of a clinically performed preoperative stair climb was compared to the presence of postthoracotomy complications in the retrospective hospital record review of 54 adult men. The stair climb was a maximum of five flights (125 steps) performed at the patient's rate and terminated at his request. Pulmonary function measurements and facets of the stair climb physiology were also examined in reference to the presence, type, and severity of complications experienced. Most minor complications such as transient arrhythmias, atelectasis, and pneumonia were clearly not predicted by the stair climb performance. The ability to climb three flights preoperatively most clearly separated those patients having the longer postoperative intubation and hospital stay, greater frequency of complications, and cumulative complication score (p less than 0.005). This retrospective study did not have sufficient numbers of fatal cardiopulmonary complications to exclude the possibility that these may be predicted by the results of this simple test. 
3	Sensory visual testing in idiopathic intracranial hypertension: measures sensitive to change. Management decisions in idiopathic intracranial hypertension (IIH; pseudotumor cerebri) are based on the presence and change of visual loss. To study this change, we evaluated tests of sensory visual function over time. We used the results of the right eye of 19 patients whose clinical status improved (decrease in papilledema grade), and compared the outcome measures of the initial and final examinations. Contrast sensitivity testing showed significant improvement in the middle and high spatial frequency targets. Snellen acuity and color tests did not change significantly over the same period. Both Goldmann and automated visual field grade significantly improved from the initial to the final visit, while the presence of a defect on confrontation visual fields did not. Numerical analyses of automated perimetry thresholds also showed significant improvement. Generalized loss, most pronounced on the nasal side of the visual field, was present on the initial examination. Generalized improvement followed, least in the central and inferior paracentral areas. Patients with IIH should be followed with contrast sensitivity testing and perimetry using a disease-specific strategy. 
5	Effect of activity on supraventricular tachyarrhythmias after coronary artery bypass surgery. The purpose of this study was to evaluate patient activities, professional staff activities, backrest position, and diurnal variations as factors that may contribute to the onset of supraventricular tachyarrhythmias (SVT) after coronary artery bypass surgery (CABG). The activities surrounding the recognition of first-onset SVT, as well as preoperative and postoperative data and patient characteristics were examined in 249 patients having CABG. One hundred seventy-three patients qualified for the study; 28% of these patients (n = 49) had SVT. No statistical difference was found between the subjects with SVT and those without SVT when sex, cross-clamp time, creatine kinase peak, hemoglobin and hematocrit levels, and number of bypasses were examined. Patients who had SVT were older than those who did not: 64.8 years for the SVT group versus 60.7 years for the non-SVT group (p less than 0.01). SVT was rare in the first 24 hours after surgery, whereas 60% of the cases occurred during the next 48 hours, without significant diurnal variation: mean time of onset was 11:50 AM. No particular activity of the patient or nurse influenced the onset of SVT during the postoperative period in this group. 
5	Primary balloon dilatation of coarctation of the aorta in neonates. Primary balloon dilatation of coarctation of the aorta was attempted in 10 consecutive neonates (age range 2-23 days). The coarctation site was crossed and the balloon inflated in all but one patient. In two patients with associated severe isthmal hypoplasia there was no change in the gradient after dilatation. In the remainder, the residual gradients were trivial and angiography showed complete relief of coarctation. Severe recoarctation developed 5-12 weeks after dilatation in five patients, each considered to have had an excellent initial result. The coarctation was rapidly progressive in three patients in whom Doppler studies within two weeks of the development of recoarctation had shown no significant gradient. In the other two patients progressive restenosis was charted by Doppler examinations over the course of 6-8 weeks. Three patients had a second, initially successful, dilatation procedure. One patient remained well with no residual gradient 18 weeks later. Stenosis recurred within eight weeks in the other two, and both have undergone successful surgical repair. Balloon dilatation of a native coarctation of the aorta gave excellent immediate results in most neonates. Severe isthmal hypoplasia is, however, a contraindication to balloon dilatation and early restenosis is an important problem. These results do not support the continued use of primary balloon dilatation of coarctation of the aorta in neonates. 
3	Neonatal monosodium glutamate abolishes corticotropin-releasing factor-induced epileptogenic activity in rats. Intracerebroventricular (i.c.v.) injection of rat corticotropin-releasing factor (rCRF) at doses of 5-20 micrograms in rats induces epileptogenic activity characterized by pacemaker-like spikes localized in the hippocampal leads. Such an effect was still present in rats neonatally treated with saline but was absent in those neonatally treated with monosodium glutamate (MSG), a treatment that caused marked changes in the concentration of several brain neurotransmitters and neuropeptides in hypothalamic nuclei where CRF is highly concentrated and is believed to induce endocrinologic and behavioral effects. The present results suggest the rCRF-induced spiking activity is mediated by activation of neuronal pathways sensitive to MSG neurotoxic effect. 
5	Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. The APACHE II severity of disease classification system has been examined prospectively in 160 patients with acute pancreatitis. Using clinical and simple laboratory data APACHE II was able to provide useful discrimination between uncomplicated, complicated and fatal attacks within a few hours of admission. Peak APACHE II scores (recorded during the first 3 days) had a prognostic accuracy similar to the multiple factor scoring systems, but then incurred a similar delay. Patients could be graded according to their risk of death or of developing a major complication; no deaths occurred in patients with a peak APACHE II score less than 10. APACHE II can be repeated daily, uncomplicated attacks demonstrating falling scores in association with clinical improvement, in contrast to the rising scores associated with clinical deterioration in those dying early. APACHE II appears to reflect any continuing disease activity and may prove a useful means of monitoring the course of the illness and response to therapy. 
1	Surgical treatment of cardiac myxomas: long-term results. Between 1965 and 1988, 22 patients underwent 24 operations for cardiac myxomas. Two patients had the complex myxoma syndrome. Mitral valve replacement was required at initial operation in 2 patients. One patient died perioperatively, and 5 others died subsequently. The 16 surviving patients recently underwent evaluation at a mean duration of 9 years after operation. Ten are asymptomatic and 6 have New York Heart Association class II symptoms. Nine patients continue to be employed. Eleven are in sinus rhythm, 3 have permanent pacemakers, and 2 have chronic atrial arrhythmias. Echocardiography showed atrioventricular valve insufficiency in 3 patients and reduced contractility in 4, but no new tumor recurrences. The long-term prognosis of this relatively large group of patients with cardiac myxomas has been good. Patients without the complex myxoma syndrome had no recurrence, whereas 2 patients did require reoperation for mitral valve replacement. Long-term disability and chronic arrhythmias have been infrequent, and functional status and employability of these patients have been very good. 
3	Febrile status epilepticus As part of a study of status epilepticus in children (Maytal J, Shinnar S, Moshe SL, Alvarez LA. Pediatrics. 1989; 83:323-331); 44 children with febrile convulsions lasting more than 30 minutes were followed for a mean of 28 months (range 4 to 72). Thirty children were followed prospectively. Children with prior afebrile seizures or evidence of acute central nervous system infection were excluded. Nine (20%) children had prior neurological deficits. The duration of the febrile seizure was 0.5 to 1 hour in 41 cases (85%), 1 to 2 hours in 5 (10%), and greater than 2 hours in 2 children (5%). No child died or developed new neurological deficits following the seizures. The risk of recurrent seizures was increased, but only in the group with prior neurological abnormality. Six (66%) of these children had subsequent febrile seizures compared with 12 (34%) of the normal children (P = .08). Three (33%) had recurrent febrile status epilepticus compared with only 1 (3%) normal child (P = .023). The 2 children in the prospective arm of the study with recurrent febrile status epilepticus were both neurologically abnormal (P = .035). All 3 of the children who subsequently had afebrile seizures (2 prospective) were neurologically abnormal (P = .006 overall, P = .035 for prospective only). It is concluded that the occurrence of febrile status epilepticus in a neurologically impaired child is a risk factor for subsequent febrile as well as afebrile seizures. The occurrence of febrile status epilepticus in an otherwise normal child does not significantly increase the risk for subsequent febrile (brief or prolonged) or afebrile seizures in the first few years following the episode. 
2	Pharmacology of pravadoline: a new analgesic agent. Pravadoline is a new chemical entity with analgesic activity in humans. This report describes the pharmacology of pravadoline and compares the activity of pravadoline with that of two major classes of analgesics, the opioids and the nonsteroidal anti-inflammatory drugs (NSAIDs). Like the NSAIDs, pravadoline inhibited the synthesis of prostaglandins (PGs) in mouse brain both in vitro (IC50, 4.9 microM) and ex vivo (ED50, 20 mg/kg p.o.) and displayed antinociceptive activity in rodents subjected to a variety of chemical, thermal and mechanical nociceptive stimuli. Administration of pravadoline prevented the writhing response induced by i.p. administration of acetylcholine (ED50, 41 mg/kg p.o.) or PGE2 (ED50, 24 mg/kg p.o.) and prolonged the response latency induced by tail immersion in hot water at a temperature of 55 degrees C (minimum effective dose, 100 mg/kg s.c.). In the rat, treatment with pravadoline prevented acetic acid-induced writhing (ED50, 15 mg/kg p.o.), brewer's yeast-induced hyperalgesia (Randall-Selitto test) (minimum effective dose, 1 mg/kg p.o.), the nociceptive response induced by paw flexion in the adjuvant-arthritic rat (ED50, 41 mg/kg p.o.) and bradykinin-induced head and forepaw flexion (ED50, 78 mg/kg, p.o.). The antinociceptive activity of pravadoline cannot be explained by an opioid mechanism, because pravadoline-induced antinociception was not antagonized by naloxone (1 mg/kg s.c.) and pravadoline did not bind to opioid receptors at concentrations up to 10 microM. However, like the opioid analgesics, pravadoline diminished the electrically induced twitch response of mouse vas deferens preparations, but, in contrast to opioids, this action of pravadoline was not attenuated by naloxone. The possibility is discussed that this effect of pravadoline upon isolated tissues may contribute to its antinociceptive activity. In contrast to NSAIDs, pravadoline was more potent ex vivo as an inhibitor of the formation of PGs in brain vs. stomach. In addition, pravadoline failed to produce gastrointestinal lesions when administered p.o. to rats or mice, and did not possess significant anti-inflammatory activity at antinociceptive doses. Also unlike NSAIDs, pravadoline inhibited rat gastrointestinal transit when administered at doses similar to those which were antinociceptive. The overall pharmacologic profile of pravadoline suggests that the compound may be capable of managing more diverse or more severe pain than is achieved by anti-inflammatory analgesics, without producing side effects commonly associated with either the opioid or the nonopioid analgesics. 
1	Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma. Twenty-eight patients with alpha-fetoprotein-positive (AFP+) nonresectable hepatoma have been enrolled in a new multimodality Phase I, II program. Induction therapy consisted of 50 mg/m2 intravenous cisplatin followed by 2100 cGy irradiation to the tumor volume in seven fractions over 10 days. Hepatic arterial infusion of 50 mg/m2 cisplatin (IA-CDDP) was then administered at monthly intervals. Twenty-one patients have completed induction and at least two cycles of IA-CDDP. Twelve-month cumulative survival was 52% for all 28 patients and 69% for the 21 patients completing induction and IA-CDDP. Median survival has not yet been reached. Response rate (complete and partial) was 36% overall and 48% among the 21 patients who completed treatment. The improved survival of the present series of patients as well as the minimal hematologic toxicity suggests possible further integration of new modalities for therapy. 
5	Diagnosis, classification, and course of myelodysplastic syndromes. The myelodysplastic syndromes are bone marrow stem cell disorders that result in disorderly and ineffective hematopoiesis. They are prognostically heterogenous. Approximately one third of cases evolve to acute myeloid leukemia. Many additional cases terminate in severe bone marrow failure. The French-American-British Working Group classification of the myelodysplastic syndromes defines morphologic and prognostic groups. Cytogenetic and in vitro cell culture characteristics are important prognostic indicators. 
1	Single polypoid cystitis cystica and glandularis presenting as benign bladder tumor. A case report of a ten-year-old boy with a benign polypoid bladder tumor is presented. The rarity of benign or malignant bladder tumors in children is reviewed, as well as the possible etiology of this unique lesion. 
1	Induction of DNA fragmentation in chronic B-lymphocytic leukemia cells. Chronic lymphocytic leukemia of B cell type (B-CLL) is a neoplastic disorder characterized by the accumulation of small resting lymphocytes in the periphery. The phenotype of these cells suggests that they are "frozen" at an early stage of maturation. Glucocorticoid hormones are commonly used to treat patients with B-CLL, resulting in a reduction in the peripheral lymphocyte count by an undefined mechanism. Here we report that glucocorticoids stimulate DNA fragmentation characteristic of a suicide process known as apoptosis or programmed cell death (PCD) in suspensions of cells from patients with B-CLL. The effects can be mimicked by Ca2+ ionophore and involve a sustained increase in the cytosolic Ca2+ concentration. Specific antibodies binding to membrane-associated IgM on the leukemic cells can also induce PCD by a similar mechanism. Phorbol esters block DNA fragmentation and cell killing in response to all of the agents, suggesting that activation of protein kinase C desensitizes the cells to PCD. Targeting the B-CLL cells with antibodies that induce an unbalanced, sustained Ca2+ increase may therefore represent a rational strategy for the destruction of leukemic cells. 
5	Eosinophilia-myalgia syndrome associated with L-tryptophan use. The eosinophilia-myalgia syndrome associated with the use of oral preparations of the amino acid L-tryptophan was recognized in late 1989. We describe the clinical and laboratory manifestations, pathological findings and early clinical course of 20 patients with the eosinophilia-myalgia syndrome. Prominent clinical findings included severe myalgias limiting function, fatigue, rashes, edema and weight gain, weight loss, muscle weakness and shortness of breath. Laboratory findings included eosinophilia (often marked), normal erythrocyte sedimentation rate, and elevated aldolase with normal or low creatine kinase values. On biopsy fascial inflammation was always seen consisting of lymphocytes, histiocytes and eosinophils in a perivascular distribution. Invasion of the vascular wall by lymphocytes was seen in 20%. Capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25% of cases. Two patients improved with no therapy. Ten patients responded to therapy with prednisone alone. Three patients have had progressive disease and one of these died. The relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed. 
2	Decreased toxicity of polymorphonuclear neutrophils toward hepatocytes isolated from rats with acute inflammatory reaction. We have recently demonstrated that polymorphonuclear neutrophils were toxic to hepatocytes through a protease-mediated mechanism. Since synthesis of antiproteases is markedly increased during acute inflammatory reaction, the aim of this work was to investigate the toxicity of neutrophils against normal vs. inflammatory rat hepatocytes. Acute inflammatory reaction was induced by subcutaneous injection of turpentine 24 hr before the experiments. Hepatocytes from normal and turpentine-treated rats were isolated by collagenase digestion. They were incubated with human neutrophils stimulated by 1 mg/ml opsonized zymosan. Cytotoxicity was quantified by the percentage of alanine aminotransferase activity released by hepatocytes in culture medium after an 18-hr incubation period. By comparison to normal hepatocytes, inflammatory hepatocytes were more resistant to the toxicity of neutrophils. At a neutrophil/hepatocyte ratio of 20:1, the alanine aminotransferase activity releases were 53.7% +/- 5.4% (mean +/- 1 S.E.) and 27.4% +/- 4.8% for normal and inflammatory hepatocytes, respectively. Similarly, inflammatory hepatocytes were found to be less sensitive than normal hepatocytes to the toxic effect of purified neutrophil cathepsin G. In contrast, both types of hepatocytes exhibited the same sensitivity to H2O2 generated by a system consisting of glucose and glucose oxidase. Two arguments suggested that the resistance of inflammatory hepatocytes to protease toxicity was explained by an increased production of antiproteases by these cells: (a) when tested against cathepsin G and porcine pancreatic elastase activities, the protease inhibitory capacity of conditioned medium from inflammatory hepatocytes was higher than that of conditioned medium from normal hepatocytes; (b) conditioned medium from inflammatory hepatocytes markedly reduced the toxicity of stimulated neutrophils as that of cathepsin G. 
5	Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin. The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio. 
3	Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and surgery. A prospective, consecutive series of 307 patients with aneurysmal subarachnoid hemorrhage ranging from Grades 1 to V according to the classification of Hunt and Hess on admission were evaluated to determine the incidence of epilepsy 1 to 3 years (mean, 1.4 years) after aneurysmal subarachnoid hemorrhage (SAH) and surgery. Sixty-three patients had died and one patient was lost to follow-up. Twenty-nine patients developed epileptic seizures after the SAH and surgery. The mean time from the SAH to epileptic seizure varied from 0 days (day of the SAH) to 2 years (mean, 6.7 months). The seizures were classified as focal in 9 patients (31%) and as generalized in 20 patients (69%). All patients received anticonvulsant medication after more than one seizure. The risk factors for development of posthemorrhagic/postoperative epilepsy were, in order of importance: a history of hypertension; an infarct on late computed tomographic scan; and the duration of coma after the ictus. Of the 85 patients with histories of hypertension, 17 (20.0%) developed epilepsy. Only 12 (5.4%) of the 222 nonhypertensive patients developed epileptic seizures. The difference between the groups was significant (P = 0.0001). Computed tomographic scans were undertaken in 237 patients 1 to 3 years (mean, 1.4 years) after the SAH and surgery. Postoperative epilepsy was significantly associated with infarcts visualized on computed tomographic scan (P = 0.0005). 
1	Increased DNA synthesis and repair-enzyme expression in lymphocytes from patients with chronic lymphocytic leukemia resistant to nitrogen mustards. Resistance to the nitrogen mustards in patients with chronic lymphocytic leukemia (CLL) correlates with an enhanced removal of melphalan-induced DNA interstrand cross-links. This finding suggests that DNA repair enzymes may be involved in this process. The activity of 3-methyladenine-DNA glycosylase, which can release altered bases, including adducts at the N-7 position of guanine, was increased significantly in lymphocytes from patients with resistant CLL compared with those from untreated CLL patients. Since glycosylase activity varies with cell proliferation, the amount of [3H]thymidine incorporated into DNA was determined and found to be elevated almost threefold in lymphocytes from patients with resistant CLL. The ratio of glycosylase activity to level of thymidine incorporation did not differ between these two groups of patients. Northern blot analysis of ERCC1 gene (a putative DNA repair enzyme involved in nucleotide excision repair) expression in lymphocytes from patients with CLL revealed multiple gene transcripts (1.1, 3.4, and 3.8 kilobases). In addition, analysis of two samples revealed the presence of a 2.6-kilobase transcript. The 2.6-kilobase transcript was recognized by specific RNA probes that hybridize to antisense ERCC1 transcripts. Levels of expression of the 1.1-kilobase protein encoding transcript in lymphocytes from patients with resistant CLL were increased twofold to threefold above those of untreated patients with CLL. These results indicate that increased expression of ERCC1 and increased activity of 3-methyladenine-DNA glycosylase occur with the development of resistance to the nitrogen mustards in patients with CLL, suggesting a role for enhanced DNA repair in this process. 
4	Catheter modification of the atrioventricular junction with radiofrequency energy for control of atrioventricular nodal reentry tachycardia. BACKGROUND. The utility of transcatheter application of radiofrequency energy to eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated. METHODS AND RESULTS. Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86 years) with medically refractory AVNRT underwent perinodal ablation with radiofrequency energy. A custom-designed 6F catheter with a large (3-mm-long) distal electrode and interelectrode pacing of 2 mm was used in the majority of cases. The catheter used for ablation was initially positioned across the tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to obtain the largest atrial:ventricular electrogram ratio, with a small His bundle electrogram (less than or equal to 100 microV). Each application of radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds or if PR prolongation or an impedance rise was noted. The endpoints of the procedure were persistent modification of atrioventricular nodal conduction (either first-degree atrioventricular block or impairment of ventriculoatrial conduction) and noninducibility of AVNRT before and during isoproterenol administration. Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per session. After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%) have been free of AVNRT, and did not have high grade AV block. Three patients (8%) developed complete atrioventricular block and had pacemakers implanted. Two patients had unsuccessful initial procedures, and two patients had initially successful ablations but had recurrences of tachycardia 4-6 weeks later. Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway in most patients. CONCLUSIONS. Radiofrequency ablation of the perinodal right atrium appears to be safe and effective for treatment of typical AVNRT. 
5	Detection of breakpoint cluster region- negative and nonclonal hematopoiesis in vitro and in vivo after transplantation of cells selected in cultures of chronic myeloid leukemia marrow. Philadelphia (Ph1) chromosome-positive clonogenic progenitors usually disappear within 4 to 6 weeks in long-term cultures established from the marrow of patients with chronic myeloid leukemia (CML). In contrast, coexisting chromosomally normal hematopoietic cells are relatively well maintained. Thus, even though normal cells are initially undetectable, they may become the predominant population. Recently, we have begun to explore the potential of such cultures as a strategy for preparing CML marrow for autografting, and based on cytogenetic studies of the differential kinetics of Ph1-positive and Ph1-negative clonogenic cells, have chosen a 10-day period in culture to obtain maximal numbers of selectively enriched normal stem cells. Here we present the results of molecular analyses of the cells regenerated in vivo for the initial three CML patients to be treated using this approach by comparison with the differentiated cells generated by continued maintenance of an aliquot of the autograft in vitro (using a slightly modified culture feeding procedure to enhance the production and release of cells into the nonadherent fraction after 4 weeks) for the one patient whose genotype made molecular analysis of clonality status also possible. These analyses showed that cells with a rearranged breakpoint cluster region (BCR) gene were not detectable by Southern blotting in either in vitro or in vivo populations of mature cells that might be assumed to represent the progeny of primitive cells present at the end of the initial 10 days in culture. Production of BCR-negative cells was also shown to be temporally correlated with the appearance of nonclonal hematopoietic cells both in culture and in vivo. These findings provide support for the view that prolonged maintenance of CML marrow cells in long-term culture may allow molecular characterization of both the BCR-genotype and clonality status of cells with in vivo regenerative potential. 
3	The community hospital-based stroke programs in North Carolina, Oregon and New York--V. Stroke diagnosis: factors influencing the diagnostic evaluation of patients following acute stroke. Among the 4129 patients of the Community Hospital-based Stroke Program, 30% had an unspecified stroke diagnosis. Since specific diagnosis and, perhaps, eventual treatment, derives in part from diagnostic testing, we examined the effect of clinical condition, geographic and demographic factors on the incidence of certain diagnostic tests after acute stroke. In this multivariable analysis, race, sex, history of hypertension and history of diabetes did not influence the chance of having any test, but older age strongly reduced the chances of receiving extensive evaluation. When CT scanning was available, the utilization of a CT as well as other diagnostic studies including cerebral angiography, radionuclide brain scan, EEG and EKG was increased. The odds of receiving a CT scan increased if the patient was married, and decreased with a history of previous stroke. A history of previous TIA increased the chance of having a cerebral angiogram while a history of cardiac disease decreased the chance. There were striking regional geographic differences in the use of CT, radionuclide brain scanning and cerebral angiography which may, in part, reflect differences between the availability of these technologies in urban and rural hospitals. These results indicate that evaluation of stroke patients remains heterogenous. 
5	An analysis of abnormalities of the retinoblastoma gene in human ovarian and endometrial carcinoma. The altered expression of the human retinoblastoma (RB) gene has been demonstrated to play an important role in the pathogenesis of RB and other tumors. To determine whether the RB gene might be involved in the pathogenesis of human ovarian and endometrial cancer, DNA from 24 human ovarian tumors, 3 normal ovaries, 3 endometrial carcinomas, and 1 endometrial hyperplasia was examined with an RB complementary DNA probe. Evidence for homozygous deletion of the RB gene was observed in only one specimen. Interestingly, the specimen was an endometrioid tumor of the ovary of low malignant potential (LMP). This patient experienced rapid progression of the tumor and died 8 months after diagnosis. Abnormalities of the RB gene may be involved in the aggressive biologic behavior of certain forms of ovarian carcinoma, particularly those of LMP. 
1	Relationship between lung asbestos fiber type and concentration and relative risk of mesothelioma. A case-control study. Lung tissue from 221 definite and probable cases of malignant mesothelioma reported to the Australian Mesothelioma Surveillance Program from January 1980 through December 1985 and from an age-sex frequency matched control series of 359 postmortem cases were examined by light microscopic (LM) and analytical transmission electron microscopic (TEM) analysis and energy dispersive x-ray analysis (EDAX). Concentrations of total fibers (coated and uncoated) (LM), crocidolite, amosite, chrysotile, and unidentified amphibole (TEM) (fibers/g dry lung tissue) were measured. Fiber concentrations less than 10 microns in length and greater than or equal to 10 microns in length were separately quantified. By comparing cases (221) and controls (359 LM, 103 TEM), odds ratios for increasing fiber concentrations compared with less than 15,000 fibers/g (LM) and less than 200,000 fibers/g (TEM) (the respective detection limits) were calculated. Univariate analyses showed statistically significant dose-response relationships between odds ratio and fiber concentration for all fiber concentration measures. The relationship between log(odds ratio) and log(fiber concentration) was linear. Multiple logistic regression analysis showed that a model containing crocidolite greater than or equal to 10 microns, amosite less than 10 microns, and chrysotile less than 10 microns as explanatory variables best described the data. The odds ratios for a X10 increase in fiber concentration (fibers/micrograms) were as follows: crocidolite greater than or equal to 10 microns, 29.4 (95% confidence interval [CI], 3.6 to 241); chrysotile less than 10 microns, 15.7 (95% CI, 6.1 to 40); amosite less than 10 microns, 2.3 (95% CI, 1.0 to 5.3). An additive risk model gave similar results. In a subgroup of cases and controls with only chrysotile in the lungs, a significant trend in odds ratio with increasing fiber content was found. 
3	Low-level lead exposure in the prenatal and early preschool periods: language development. Inconsistent results continue to be reported from studies linking low-level lead exposure and child development. This inconsistency is seen for both prenatal exposure and exposure in the preschool years. The primary outcome measures in most reports are indices of cognitive development, including IQ. Verbal skills may be particularly vulnerable to toxic insult. The fact that 2 y of age is both a time of peak exposure and also a time of rapid language development suggests that this may be a critical period for such an effect. The later prenatal and early infancy period, at which time the nervous system is developing rapidly, may also be critical exposure period. We examined the relationship of maternal and cord blood lead (PbB) at birth and venous PbB at 6 mo, 2 y, and 3 y with language measures at 1, 2, and 3 y of age. The sample consisted of disadvantaged urban children. Multivariate analyses revealed no statistically significant relationship of either prenatal PbB or early preschool PbB with language measures after control of cofactors. Supplementary partial correlations revealed a marginal relationship of cord PbB and mean length of utterance (MLU), which describes a child's ability to form meaningful word combinations. Because this analysis was one of a large number of analyses with both positive and negative regression coefficients, the possibility that this was a chance effect was considered. If there is an effect of low-level lead exposure on language development, that effect is not robust. 
5	The hyperimmunoglobulinaemia E and recurrent infections syndrome in an adult [published erratum appears in Thorax 1990 Dec;45(12):984] A 27 year old white woman with a history of chronic eczema and episodes of serious infection of the chest, skin, and bone presented with acute respiratory failure. She was found to have a spontaneous right pneumothorax and a pneumatocele in the left upper lobe. Despite a left upper lobectomy she was left with chronic respiratory failure, bullous lung disease, and bilateral bronchiectasis. The hyperimmunoglobulinaemia E and recurrent infections syndrome was diagnosed only in adult life. 
4	Magnetic resonance imaging--the evaluation of choice in residual shunt after congenital heart disease surgery? Accurate anatomic diagnosis presents a dilemma in patients with residual shunt after corrective surgery for congenital heart disease. We describe a patient who, after atrial septal defect repair, developed dyspnea and central cyanosis despite normal pulmonary arterial pressures and right heart chamber size. A role for early MRI is suggested. 
4	Ascites after rupture of dissecting aortic aneurysm into the right atrium. We report successful repair of an aneurysmal aorta-right atrial fistula causing intractable ascites. The clamped "ascending aorta" was drained for mixed return after perfusion through the femoral vessels and opened during hypothermic arrest. Return cannulation through the fistula permitted definitive repair. 
5	Large telangiectatic focal nodular hyperplasia presenting with normal radionuclide studies: case report. A 9 cm-lesion of telangiectatic focal nodular hyperplasia was incidentally identified in a 31-yr-old female. Despite a typical appearance by X-ray computed tomography and ultrasonography, scintigraphy with technetium-99m-(99mTc) colloid, 99mTc-diethyliminodiacetic acid, and 99mTc-labeled red cells failed to demonstrate any abnormalities. These findings are felt to reflect the relative lack of architectural disruption that histologically characterizes this particular lesion. The present report described the imaging characteristics of the telangiectatic form of focal nodular hyperplasia. 
3	Cat-scratch disease. Acute encephalopathy and other neurologic manifestations. Seventy-six patients with neurologic complications of cat-scratch disease are discussed. Encephalopathy occurred in 61, while 15 had either cranial or peripheral nerve involvement. The average age of the patients with encephalopathy was 10.6 years (range, 1 to 66 years), and almost twice as many males as females were affected in contrast to patients with uncomplicated cat-scratch disease, in which the ratio was almost equal. Fever was not documented in 50% of patients with encephalopathy and only 26% had temperatures higher than 39 degrees C. Convulsions occurred in 46% and combative behavior in 40%. Lethargy with or without coma was accompanied by variable neurologic signs. Results of laboratory studies, including imaging of the central nervous system, were inconsistent and nondiagnostic. Biopsy tissue from 14 patients showed histopathologic findings compatible with cat-scratch disease. The "English-Wear bacillus" was demonstrated by the Warthin-Starry stain in 10 of 14 skin or lymph node specimens. Of the 15 patients without encephalopathy, two children with facial nerve paresis displayed cranial nerve symptoms and/or signs, 10 patients had cat-scratch disease neuroretinitis, and three women had peripheral neuritis. All 76 patients recovered within 12 months; 78% recovered within 1 to 12 weeks. There were no neurologic sequelae. Treatment consisted of control of convulsions and supportive measures. Commonly used antibiotics administered to more than half of the patients were apparently ineffective. 
5	Empiric treatment of fungal infections in the neutropenic host. Review of the literature and guidelines for use. Persistent fever that is refractory to broad-spectrum antibacterials is common in neutropenic patients undergoing induction chemotherapy of acute leukemia. Clinical experience suggests that many of these patients are infected with fungi. Until recently, data supporting the role of empiric antifungal therapy in this setting were limited to small groups of patients or postmortem reports. Evolving evidence in larger patient populations supports data from smaller series: febrile neutropenic patients who have failed to respond to a 4- to 7-day course of broad-spectrum antibacterials may benefit from the early initiation of antifungal therapy. Patients with fungal colonization or pulmonary infiltrates and adult patients who have not received previous fungal prophylaxis may especially benefit from the early use of antifungal drugs. Amphotericin B has been the "gold standard" for empiric antifungal therapy, although the newer azoles may be useful in certain situations. 
1	Transcatheter oily chemoembolization in the management of advanced hepatocellular carcinoma in cirrhosis: results of a Western comparative study in 60 patients. Transcatheter oily chemoembolization is widely used as palliative therapy for inoperable hepatocellular carcinoma in high-incidence Asiatic areas. To assess its usefulness in the Western form of this cancer, 30 French patients were treated between 1987 and 1990 by intraarterial hepatic injection of a Lipiodol-doxorubicin emulsion followed by embolization with 0.5 to 1 mm gelatin sponge particles. The number of procedures ranged from one to five. All patients had advanced, symptomatic and inoperable hepatocellular carcinoma (Okuda's staging: I, n = 8; II, n = 14; III, n = 8); none was found under systematic screening. All had underlying cirrhosis (Child-Pugh's class: A, n = 15; B, n = 12; C, n = 3) that was alcoholic in origin in 27 cases and posthepatitic B in origin in 3 cases. The results of the treatment were assessed by comparison with a group of 30 untreated patients admitted to the same unit between 1984 and 1987. Patients of both groups were closely matched for clinical presentation, global disease staging and precise anatomical extension. The overall 1- and 2-yr survival rate was 59% and 30%, respectively, for the treated patients vs. 0% at 1 yr for the untreated patients. The latter all died from local disease with end-stage liver failure and/or uncontrollable variceal bleeding. In the former, the three patients with Child's class C cirrhosis died after the first procedure. During the follow-up (range = 3 to 26 mo), 11 additional patients died, 8 from metastatic generalization. 
1	Incidence, causes and mechanism of hypercalcaemia in a hospital population in Hong Kong. To determine the incidence and causes of hypercalcaemia in a hospital population in Hong Kong, all 29,107 samples received in the laboratory in one year were analysed for plasma calcium and albumin, and samples with a plasma calcium concentration adjusted for albumin greater than 2.55 mmol/l were investigated. Plasma calcium greater than 2.55 mmol/l was found in 462 patients. Repeat samples were received from 302 of these and hypercalcaemia was confirmed in 183. The main causes of hypercalcaemia were malignancy (72.1 per cent), tuberculosis (6.0 per cent), and primary hyperparathyroidism (5.5 per cent). In the malignant hypercalcaemia group, carcinoma of lung was the most common (31.8 per cent) and carcinoma of breast was uncommon (3.0 per cent). Secondary deposits in bone were detected in 35 of the 122 solid tumours. In order to identify the mechanism of hypercalcaemia the contributions of renal tubular reabsorption and increased bone resorption to the plasma calcium concentration were calculated. Increased tubular reabsorption was the main contributor to hypercalcaemia in primary hyperparathyroidism and carcinoma of liver (none of whom had bony metastases) and it contributed significantly to hypercalcaemia in carcinoma of lung without bony metastases and carcinoma of oesophagus. We conclude that in Hong Kong (a) primary hyperparathyroidism is uncommon, (b) tuberculosis is an important cause and (c) humoral factors may be responsible for a relatively high proportion of cases of malignant hypercalcaemia. 
5	Increased microvascular permeability in vivo in response to intradermal injection of neutrophil-activating protein (NAP-2) in rabbit skin. Neutrophil-activating protein-2 (NAP-2), an NH2-terminally processed form of the platelet-release product beta thromboglobulin (beta TG), was purified to homogeneity from stimulated human blood leukocytes. In the presence of a vasodilator substance (PGE2, CGRP) picomolar (pmol/l) amounts of NAP-2 induced neutrophil accumulation and plasma leakage on intradermal injection in rabbit skin, whereas the longer forms, beta TG itself and connective tissue-activating peptide III (CTAP-III), had no such effect. NAP-2-induced increased in microvascular permeability was neutrophil dependent and fast in onset, with a half-life of 65 to 75 minutes, comparable to that previously reported for the structural-related neutrophil-activating protein-1/interleukin-8 (NAP-1/IL-8). However NAP-2 showed a lower potency in that more protein was needed to provoke skin reactivity. Nevertheless the finding that a platelet release product can elicit neutrophil-mediated inflammation further narrows the gap between thrombotic events and inflammatory disorders. 
4	Thromboxane mediates diapedesis after ischemia by activation of neutrophil adhesion receptors interacting with basally expressed intercellular adhesion molecule-1. Ischemic injury is characterized by neutrophil (PMN)--endothelial cell adhesion and diapedesis associated with thromboxane (TX) generation. Neutrophil-endothelial cell interaction is regulated in part by the leukocyte adhesion receptor CD 18 glycoprotein complex and the endothelial intercellular adhesion molecule-1 (ICAM-1). This study tests the role of TX in ischemia-induced diapedesis and evaluates whether the diapedesis is regulated by neutrophil or endothelial adhesion receptors. Plasma derived from rabbit hind limbs made ischemic for 3 hours (n = 6) and reperfused for 10 minutes had increased levels of TXB2 3,450 pg/ml, which was higher than sham rabbit (n = 6) values of 653 pg/ml (p less than 0.05). When introduced into abraded skin chambers placed on the dorsum of other normal rabbits (n = 6), this ischemic plasma induced 1,000 pg/ml of new TX synthesis and diapedesis of 1,235 PMN/mm3. The total TX concentration and PMN accumulations in blister fluid were correlated (r = 0.88, p less than 0.05). In contrast, sham rabbit plasma induced no TX synthesis and diapedesis of only 77 PMN/mm3 (p less than 0.05). Administration of 50 ng/ml of authentic TXB2 into blisters induced an accumulation of 453 PMN/mm3, which was higher than that in saline controls (18 PMN/mm3) (p less than 0.05). Pretreatment of normal rabbits used for the diapedesis assay (n = 4) with the TX synthetase inhibitor OKY 046 (2 mg/kg/hr) limited ischemic plasma and authentic TXB2 induced diapedesis to 142 and 76 PMN/mm3, respectively (both p less than 0.05). 
4	Clinical and electrophysiologic characteristics of patients with antidromic circus movement tachycardia in the Wolff-Parkinson-White syndrome. Antidromic circus movement tachycardia was documented in 36 of 345 consecutive patients with Wolff-Parkinson-White syndrome undergoing detailed electrophysiologic evaluation. Twenty-six patients were men and 10 were women (mean age +/- standard deviation 26 +/- 12 years [range 12 to 45]). Multiple accessory pathways were identified in 12 of these 36 patients (33%). Ten of the patients (67%) with clinically documented antidromic tachycardia had multiple accessory pathways. Dizziness and syncope occurred in 61 and 50% of patients with antidromic circus movement tachycardia. Six patients had clinical documentation of atrial fibrillation, and 4 patients (11%) were resuscitated from ventricular fibrillation. In the 36 patients, 56 distinct antidromic tachycardias were recorded and several different pathways were observed. Orthodromic tachycardia was the most frequently associated arrhythmia (72%). Dual atrioventricular nodal pathways were present in 12 patients (33%); however, atrioventricular nodal tachycardia could be initiated in only 2 of them. Interruption of the accessory pathway was successfully performed in all 20 patients undergoing surgery. 
5	Neurological sequelae of cerebral malaria in children. Out of 604 Gambian children admitted with falciparum malaria to one hospital between September and December, 1988, 308 had cerebral malaria and 203 were severely anaemic (haemoglobin less than 60 g/l). 14% of those with cerebral malaria died, as did 7.8% of those with severe anaemia. 32 (12%) of children surviving cerebral malaria had residual neurological deficit. 69 other children were admitted with clinical features strongly suggestive of cerebral malaria but with negative blood films; 16 of these died and 3 had residual neurological deficits. The commonest sequelae of cerebral malaria were hemiplegia (23 cases), cortical blindness (11), aphasia (9), and ataxia (6). Factors predisposing to sequelae included prolonged coma, protracted convulsions, severe anaemia, and a biphasic clinical course characterised by recovery of consciousness followed by recurrent convulsions and coma. At follow up 1-6 months later over half these children had made a full recovery, but a quarter were left with a major residual neurological deficit. Cerebral malaria in childhood may be an important cause of neurological handicap in the tropics. 
5	Melanocytic hyperplasia of the oral mucosa. Lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa. They are even more rare than the various morphologic types of nevomelanocytic lesions. This article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex, junctional lentigo ("jentigo"), atypical melanocytic hyperplasia (melanoma in situ), and melanocanthoma. The proper terminology for these lesions is also discussed. 
3	Safety, stability, and effectiveness of immunoadsorption under membrane plasmapheresis treatment for myasthenia gravis. Nine patients (five women and four men, average age 50.4 years) with refractory myasthenia gravis (MG) underwent thymectomy and were then treated with immunoadsorption under membrane plasmaphersis (IAP). Thymic histology showed hyperplasia in nine patients. An immunoadsorption column (ASAHI, Med, Co) was made with tryptophan. A Plasouto 1,000 (ASAHI, Med, Co) was used as the machine. The plasma separator was a first filter (ASAHI, Med, Co), and immunoadsorption columns were used for plasma perfusion. IAP treatment was performed three times weekly for a total of six times, after which IAP was done every 3 weeks. The removal rate of anti-Ach-R titer was 54 +/- 12%; IgG, IgA, and IgM levels improved in nine of nine patients after IAP treatment, and improvement of gait disturbances were seen in two of two. Muscle strength improved in all nine patients, whereas speech disturbances improved in two of three. Eye ptosis improved in nine of nine patients. Subjective improvement was reported by nine of nine patients, and none had severe side effects with IAP. In conclusion, IAP is a safe, stable, effective, and clinically useful treatment. for MG. 
5	Perianal appearances associated with constipation. The perianal appearances were studied prospectively of 136 constipated children (mean age 3.9 years, 67 boys, 69 girls). Anal dilatation, fissures, tags, warts, perianal oedema, redness, blueness, and veins were recorded. It was noted whether dilatation occurred immediately or at 30 and 60 seconds with the buttocks minimally separated, and on subsequent firm lateral traction of the buttocks. The degree of faecal loading was assessed in all children. Anal dilatation was found in 24 (18%) and first appeared on lateral traction in eight (6%). In three quarters of the children with dilatation faecal loading or perianal signs were present. Fissures were found in 35 (26%) children and tags in seven (5%). Perianal redness was more likely to be associated with fissures, and blueness with dilatation. We conclude that there are no pathognomonic perianal signs in childhood constipation and that the technique of anal examination should be standardised. 
5	A preliminary study of dye-enhanced laser photosclerosis. Laser ablation of veins after injection of wavelength-specific dyes to enhance and localize energy absorption could provide a useful adjunct to current treatment options. To enhance the absorption of diode laser energy at 808 nm, ear veins of 41 rabbits were infused with 2 to 3 ml of indocyanine green dye (maximum absorption, 805 nm) and exposed for 2 to 20 seconds. Animals were killed between 0 and 28 days after operation. Discrete time intervals of laser exposure exist during which various-sized vessels can be ablated without significant thermal injury to the overlying tissue. Small vessels (0.2 mm in diameter) blanch after 2 to 3 seconds of exposure, whereas medium-sized vessels (2 mm in diameter) require 8 to 10 seconds. Vessels can be ablated with a power density as low as 11.1 W/cm2. Specimens taken immediately after laser exposure show vessel wall thinning and a reirradiation effect, created as laser energy initially absorbed by dye is reemitted. By the seventh day after operation, a brisk inflammatory response and acanthosis of the overlying epidermal layer develop. The lumen is partially filled by thrombus with cellular invasion. By postoperative day 28, the epidermal thickening and inflammatory reaction have resolved; the vessel walls are fibrotic. The use of low-power, air-cooled diode lasers, in conjunction with wavelength-specific dyes, may provide a simple, viable, and cosmetically appealing alternative to the treatment of superficial varicosities of the extremities. 
2	Gaucher's disease complicated by bleeding esophageal varices and colonic infiltration by Gaucher cells. We report a 10-yr-old child with Gaucher's disease who developed upper gastrointestinal bleeding from esophageal varices, as well as hemorrhage from a colonic polyp infiltrated with Gaucher cells. Both the varices and polyp were treated endoscopically, and the outcome was successful. Although gastrointestinal hemorrhage due to portal hypertension is considered a rare complication of Gaucher's disease, colonic infiltration with Gaucher cells has not been recognized previously. 
1	Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study. We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function. 
5	Late potentials in progressive muscular dystrophy of the Duchenne type. This study describes the late potentials (LPs) obtained by signal-averaged electrocardiography (SAECG) in 66 patients with Duchenne's progressive muscular dystrophy (DMD). It also assesses the possible relationships between LPs and the severity of DMD, and the findings of two-dimensional echocardiography, as well as ventricular arrhythmias examined with the Holter system. SAECGs were performed with a Marquette MAC-1 unit. Based on Swinyard-Deaver's system of stages, ranging from the mildest, S1, to the most severe, S8, one patient each could be assigned to S2 and S4, 6 to S5, 20 to S6, 21 to S7, and 17 to S8. LPs were observed in 21 of the 66 patients (32%), including 3 of the 20 assigned to S6 (15%), 10 of the 21 in S7 (48%), and 8 of the 17 in S8 (47%). The total wall motion index evaluated by the method of Hegar was significantly greater in the patients with LPs (8.4 +/- 4.4) than in those without LPs (5.8 +/- 3.1) (p less than 0.05). The incidence of LPs was found to be higher in the dilated cardiomyopathy (DCM) type (8 of 12;67%) than in the normal type (9 of 41;22%) (p less than 0.01). The incidence of ventricular premature complexes (VPCs) was significantly higher in patients with LPs (13 of 21;62%) than in those without LPs (13 of 45;29%) (p less than 0.05). No sustained ventricular tachycardia (VT) was observed, although nonsustained VT was noted in three patients with LPs. The LPs in patients with DMD were thus associated with left ventricular dysfunction, and the presence of LPs might be correlated with the extent of myocardial derangement in DMD. 
5	Epidemiology of pelvic inflammatory disease in parous women with special reference to intrauterine device use. Up to the end of 1989, 206 parous women in the Oxford Family Planning Association contraceptive study had been referred to hospital with a first episode of pelvic inflammatory disease. Of these, 65 suffered from definite disease described as acute, 81 from definite disease not described as acute and 60 from 'other disease'. Considering all forms of disease together, referral was less common in those aged 25-29 and in those aged 45 or more than in those aged 30-44. Referral was more common in those of low social class, in those who smoked and in those who married young. All these factors were taken into account in analyses considering the effects of contraceptive methods. In these analyses, women currently using the contraceptive pill, the diaphragm, the sheath, female sterilization or an intrauterine device (IUCD) were compared with those currently using other methods or no method of contraception. IUCD ex-users were, however, placed in a separate category, irrespective of their current method of contraception. The relative risks obtained in these analyses, with 95% CI, were as follows: contraceptive pill 0.5 (0.2-0.9), diaphragm 0.6 (0.3-1.2), sheath 1.2 (0.6-2.4), female sterilization 0.7 (0.3-1.5), non-medicated IUCD 3.3 (2.3-5.0), medicated IUCD 1.8 (0.8-4.0), IUCD ex-users 1.3 (0.7-2.3). These data suggest that oral contraceptives, the diaphragm and female sterilization protect against pelvic inflammatory disease and that IUCDs increase the risk. Medicated devices, however, appear to carry only about half the risk of non-medicated devices, and the elevation of risks in IUCD ex-users appears to be small. Special analyses examined the risk associated with use of a Dalkon Shield. Among women currently using an IUCD (of any kind), those who had used a Dalkon Shield (at any time) had nearly five times as great a risk of hospital referral for pelvic inflammatory disease as those who had never used a Dalkon Shield (relative risk 4.7, 95% CI 2.1-9.0). 
2	Intrathoracic Nissen fundoplication: long-term clinical and pH-monitoring evaluation. From 1976 until April 1989, 31 intrathoracic total fundoplications were performed for reflux esophagitis and irreducible hiatus hernia. In the first 16 patients (group 1) the operation was complicated with acute perforation of the wrap in 4 cases, bronchogastric fistula in 1, and herniation of the wrap higher in the chest in 1. Technical modifications were applied to 15 more recent patients (group 2). These are enlargement of the hiatus, looseness of the wrap and its appropriate anchorage, avoidance of forceps when handling the stomach, care with the vagi, and efficient gastric decompression in the postoperative period. The postoperative course was always uneventful in group 2. Twenty-six patients, who still have their initial wrap, were considered for clinical evaluation: 11 from group 1 (mean follow-up, 81.5 months) and 15 from group 2 (mean follow-up, 32.8 months). All are free from any symptom of reflux; gas-bloat syndrome is infrequent and dysphagia is relieved. Twenty-four-hour pH monitoring, performed in 14 patients (3 from group 1 and 11 from group 2) (mean follow-up, 42 months), was normal in 13; a pathological upright reflux (time pH less than 4, 8.4%) was demonstrated in one symptom-free woman in whom endoscopy was unremarkable. Mechanisms of complications experienced in group 1 are analyzed in the light of the technical evolution of the procedure, and the place of the intrathoracic total fundoplication in the management of short esophagus is defined, considering the other available surgical techniques. 
5	Bilateral intrapulmonary hematomas. A 67-yr-old man, known to have chronic obstructive lung disease, developed bilateral localized pulmonary densities on chest radiographs after cardiopulmonary resuscitation. An autopsy disclosed bilateral intrapulmonary hematomas without communication with bronchi, pulmonary arteries, or pleural cavities. We suggest blunt pulmonary injury is the most probable cause of the hematomas and discuss its pathogenic mechanism. Intrapulmonary hematomas should be considered in the differential diagnosis of pulmonary densities developing after a vigorous resuscitation. 
4	Admissions to the intensive care unit after complications of anaesthetic techniques over 10 years. 2. The second 5 years Compared with the first 5 years there was a 19% increase in general anaesthetics, a 171% increase in local and (or) sedation techniques and a 9% increase in obstetric epidurals with no increase in anaesthetic staffing. In this second 5-year period, 46 patients were admitted to the Intensive Care Unit as a result of a complication of an anaesthetic technique. These patients represented 1 in 2371 anaesthetic techniques carried out in the District compared with the previous 5 years where the incidence was 1 in 1543. Seven patients died (15.2%). The complication was considered to be wholly or partially avoidable in 14 instances (30.4%). Four of these subjects died. 
1	Carcinoma of the male breast: a review of 41 cases. We reviewed the cases of 41 consecutive men treated for breast carcinoma from 1950 through 1987 at Vanderbilt University Affiliated Hospitals to examine controversies in and methods of therapy for this disease. Twenty-two patients (52%) had stage I or II lesions potentially curable by operative therapy. The overall 5-year survival rates were 100% for stage I, 65% for stage II, 56% for stage III, and 0% for stage IV. Radical mastectomy offered no advantage over modified radical mastectomy in terms of survival or rate of recurrence. Diagnosis at an early clinical stage and no finding of disease in axillary lymph nodes were important factors in survival in this series of patients. All tumors evaluated for hormone receptors were positive. Although experience was limited, encouraging results were obtained with the use of tamoxifen citrate in adjuvant as well as palliative roles. With the exception of a predominance of centrally located lesions and a uniquely high frequency of positive hormone receptor status, carcinoma of the male breast appears biologically similar to the disease in women, and treatment should be guided by similar principles. 
2	Severe hypertension after liver transplantation in alpha 1 antitrypsin deficiency. Five children with alpha 1 antitrypsin deficiency and terminal liver disease received liver grafts; all five became hypertensive and four developed hypertensive encephalopathy. There was evidence of renal disease preoperatively and renal biopsy specimens showed variable glomerulonephritic histology with IgA nephropathy in one, mesangial-proliferative changes in two, and mesangio-capillary glomerulonephritis type I in two. Four hypertensive episodes were preceded by a fall in creatinine clearance. The association of glomerulonephritis with alpha 1 antitrypsin deficiency in children is more common than has been recognised. Affected patients are prone to severe hypertension of probable renal origin after liver transplantation and the renal lesion may affect long term prognosis. 
1	Power drills to fenestrate exposed bone to stimulate wound healing. Power drills can be used to stimulate the formation of granulation tissue over exposed cortical bone. These tools allow for the rapid fenestration and selective abrasion of large areas of exposed bone; fenestration and abrasion create the multiple bleeding points essential for the production of granulation tissue. The granulation tissue thus produced is allowed to grow out through the holes to cover bone. This procedure can be performed in an outpatient setting, usually without the need for either local or general anesthesia; it is particularly useful for patients considered to be poor risks for general anesthesia. Healing by granulation tissue is a somewhat slow process, but it has a high success rate, causes few complications, and produces very good cosmetic results. Two cases illustrate the method of fenestration of exposed cranial bone to stimulate granulation tissue. Specific instructions describe the needed care of exposed bone. 
3	Carbamazepine-induced antinuclear antibodies and systemic lupus erythematosus-like syndrome. A 20-year-old woman developed a systemic lupus erythematosus (SLE)-like syndrome and a positive antinuclear antibody (ANA) soon after initiation of carbamazepine (CBZ) therapy. Symptoms and serology became normal after CBZ was discontinued. CBZ-induced SLE is an important but underecognized phenomenon. 
3	Outpatient sedation: an essential addition to gynecologic care for persons with mental retardation. Routine gynecologic care for persons with mental retardation may be difficult to provide, especially to those women who do not allow a pelvic examination to be performed. Of 275 women referred to a multidisciplinary clinic addressing the reproductive health concerns of mentally retarded women, 61 patients (22%) did not allow a gynecologic examination to be performed. The administration of ketamine alone, midazolam alone, or a combination of midazolam and ketamine allowed for the successful performance of a gynecologic examination in 81% of previously uncooperative women. No adverse effects of the medications were noted. We conclude that sedation of difficult-to-examine, mentally handicapped women can be safely performed in the outpatient setting, thus avoiding the need for general anesthesia and its inherent risks. 
4	Clinical spectrum of symptomatic external iliac fibromuscular dysplasia. External iliac fibromuscular dysplasia is a rare and usually asymptomatic disorder. We report eight symptomatic patients seen over a 15-year period and review pathophysiologic mechanisms accounting for the three following distinct lower extremity ischemic sequelae: (1) Emboli--episodic focal digital ischemia (blue toe) was seen in three patients. Resection and primary anastomosis of focal iliac ulcerative fibromuscular dysplasia (one patient) or resection and replacement (two patients) removed the embolic source and relieved the symptoms. (2) Chronic ischemia--gradual onset of full leg claudication in four patients was treated by operative graduated intraluminal dilation in three patients and prosthetic bypass in one. Arteriography subsequently showed a remodeled lumen in the three patients who underwent dilation. (3) Dissection--acute onset leg ischemia resulted from presumed dissection of the external iliac segment. After 4 months of conservative management of antiplatelet agents and exercise, symptoms resolved completely, and arteriogram showed spontaneous restoration of a normal lumen in the dissected segment. The clinical presentation of fibromuscular dysplasia may mimic other arterial processes such as atherosclerosis. Diagnosis is made only by arteriography with specific magnification views of the external iliac arteries and careful surveillance of the renal arteries. Appropriate treatment should be tailored to the clinical presenting symptom. For microembolic disease, resection and replacement are required. For chronic ischemia, intraluminal dilation is generally sufficient and durable and has proved to be a simpler and acceptable alternative to replacement or bypass. In acute dissection, surgical intervention may be deferred if the limb is viable to allow spontaneous healing and remodeling. Persistent symptoms may be the only indication for intervention in this ischemic manifestation of external iliac fibromuscular dysplasia. 
5	Pregnancy outcome in hematologic malignancies. By means of a mail questionnaire, information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals. Seven patients conceived while receiving treatment for their neoplasms; in 22 patients, the hematologic disease was diagnosed during pregnancy, and the remaining 27 patients became pregnant after completion of the antineoplastic treatment. When a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population, no increase in the incidence of complications was observed: 64% of the pregnancies went to term, 9% resulted in spontaneous abortion, and 5% resulted in premature births. The observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals. There were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy. In spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed, the data here support the hypothesis that the cytostatic treatment of hematologic malignancies, if deemed necessary, should not be postponed because of pregnancy. Moreover, the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided, especially to those fields involving the pelvic area. 
5	Hilger facial nerve stimulator: a 25-year update. Percutaneous nerve excitability testing using the Hilger facial nerve stimulator was introduced about 25 years ago. The test is reliable, easy to use, and inexpensive; it continues to be the most frequently used method for predicting prognosis of facial nerve disorders. Between 1966 and 1974, we recorded 10,243 nerve excitability tests on 865 patients with a mean of 3.29 tests for each peripheral branch and 3.43 for the trunk. Using a multiple regression model, we determined the effect on nerve stimulation values of age, sex, race, diabetes, hypertension, partial or complete clinical paralysis, diagnosis of herpes zoster, year of testing, and eventual facial paralysis recovery profile. We discuss statistical reliability, provide a table of interpretive results, and offer "tips and traps" invaluable to the practitioner. A prospective study of 25 patients with residual facial paralysis was evaluated by two separate otolaryngologists to determine intertester reliability. 
5	Endoscopic treatment of biliary tract strictures in sclerosing cholangitis: a larger series and recommendations for treatment. We report a group of 35 patients with primary sclerosing cholangitis who had long-term follow-up after endoscopic treatment of major ductal strictures in the primary or secondary biliary ducts. Our patients were all symptomatic with ascending cholangitis or jaundice. There was significant improvement as measured by clinical parameters of hospitalization rates and laboratory data and comparable radiography. Long-term follow-up averaged 24 (+/- 2.8 months). We believe endoscopic treatment of sclerosing cholangitis should be attempted in selected symptomatic cases with major ductal strictures before liver transplantation. 
1	Inactivation of the retinoblastoma gene in human lymphoid neoplasms. The absence of wild type retinoblastoma (Rb) gene expression in a wide variety of human solid tumors suggests an etiologic role for this tumor suppressor gene in human cancer. We have evaluated the involvement of Rb gene inactivation in the pathogenesis and progression of human lymphoma and leukemia. We examined the genomic configuration and transcription of the Rb gene in cultured cell lines and primary cases of T- and B-cell lymphomas and leukemias. By Southern analysis, abnormalities of the Rb locus were identified in 1 of 5 T-cell acute lymphoblastic lymphoma (T-ALL) cell lines, 1 of 26 primary cases of T-ALL, 1 of 40 primary cases of chronic lymphocytic lymphoma/well-differentiated lymphoma (CLL/WDL), and 1 of 15 primary cases of intermediately differentiated lymphoma (IDL). By Northern analysis, markedly reduced or abnormal expression of the Rb gene was identified in 2 of 5 T-ALL cell lines, 1 of 7 primary cases of T-ALL, 1 of 5 primary cases of CLL/WDL, and 1 of 6 primary cases of IDL. These findings show that Rb gene inactivation can be associated with a broad range of lymphoid neoplasms and that loss of the tumor suppressor function of Rb may influence the pathogenesis and progression of lymphoma/leukemia. 
1	Metastatic small cell tumor of bone with 'true' rosettes and glial fibrillary acidic protein positivity. A 15-year-old black girl was admitted to St. Jude Children's Research Hospital with a lytic lesion involving the right fourth metacarpal bone with a solitary metastasis to the ipsilateral axillary lymph node. Histologic examination of both the primary lesion and metastasis revealed a primitive small round cell lesion. Abundant rosettes with central lumina were present in the metastasis. Immunohistochemical stains performed on sections of the metastasis were strongly positive for glial fibrillary acidic protein (GFAP) and negative for neuron-specific enolase (NSE), S-100 protein, and Leu-7. Electron microscopic examination of the metastasis revealed lumen formation with apical microvilli and juxtaluminal junctional complexes. This tumor exhibits features that are suggestive, but not definitive, of primitive ependymal differentiation and further expands the morphologic and immunophenotypic range of small round cell tumors of bone. 
1	A simple and sensitive microtiter plate estrogen bioassay based on stimulation of alkaline phosphatase in Ishikawa cells: estrogenic action of delta 5 adrenal steroids. We have developed an estrogen bioassay using the Ishikawa human endometrial adenocarcinoma cell line growing in 96-well microtiter plates. Alkaline phosphatase enzyme activity (AlkP) in these cells is markedly stimulated by estrogens, and this enzyme can be easily quantified in situ using a chromogenic substrate. These cells are very sensitive to estrogens; estradiol induces AlkP at levels as low as 10(-12) M. Antiestrogens completely block the action of estradiol. Various estrogens stimulate AlkP with potencies comparable to those achieved in vivo. The induction of AlkP is specific for estrogens; no other type of steroid, including androgens, progestins, mineralocorticoids, or glucocorticoids produce this effect. The stimulation of AlkP in Ishikawa cells is specific for estrogens, is highly reproducible and sensitive, and permits large numbers of samples to be assayed with ease. We have used this assay to investigate the estrogenic action of the adrenal delta 5-3 beta-hydroxysteroids. While pregnenolone is inactive, dehydroepiandrosterone and its sulfate ester induce AlkP slightly. However, the C19 steroid, 5-androstene-3 beta, 17 beta-diol is considerably more estrogenic in this assay, although it stimulates Ishikawa AlkP with a potency of 1/30,000 that of estradiol. The stimulation by 5-androstene-3 beta,17 beta-diol is inhibited by antiestrogens, but it is not blocked by the delta 5-3 beta-hydroxysteroid isomerase/dehydrogenase inhibitor, cyanoketone, or by the aromatase inhibitor, 4-hydroxy-androstenedione. Thus, neither conversion to a delta 4-3-ketone nor aromatization is required for the action of this unusual estrogen. 
5	Systolic wall stress and ventricular arrhythmia: the role of acute change in blood pressure in the isolated working rat heart. 1. The effect of a sudden acute change in blood pressure upon arrhythmia provocation has been studied in an isolated working heart model from the Wistar-Kyoto strain of rat. Twenty-four hearts were studied. 2. They were perfused with two different, modified, Krebs-Henseleit solutions at a fixed left atrial pressure. 3. Acute changes in pressure, both increases and decreases, were arrhythmogenic. Whilst ectopic activity was more predictably produced by pressure reductions, this consisted of simple ventricular ectopics only. Pressure increases, in contrast, were capable of provoking more complex and sustained arrhythmias. 4. The effect of pressure changes were highly dependent upon electrolyte concentrations in the perfusate. Low potassium and magnesium concentrations increased the amount of arrhythmia provoked by pressure increases but tended to reduce that provoked by pressure reductions. 5. We conclude that the direct effect of an acute change in pressure upon the myocardium is arrhythmogenic. However, the myocardial response to a pressure change is interdependent upon prevailing electrolyte concentrations. 
3	A comparative trial of three agents in the treatment of acute migraine headache. STUDY OBJECTIVES: A study was conducted to evaluate the relative efficacy of three non-narcotic agents, chloropromazine, lidocaine, and dihydroergotamine, in the treatment of migraine headache in an emergency department setting. DESIGN: The trial was randomized and single blinded. SETTING: The study was conducted in two university-affiliated EDs. TYPE OF PARTICIPANTS: All patients had an isolated diagnosis of common or classic migraine. INTERVENTIONS: Patients were pretreated with 500 mL (IV) normal saline before randomization. Study drugs as administered were dihydroergotamine 1 mg IV repeated after 30 minutes if the initial response was inadequate; lidocaine 50 mg IV at 20-minute intervals to a maximum total dose of 150 mg as required; or chloropromazine 12.5 mg IV repeated at 20-minute intervals to a total maximum dose of 37.5 mg as required. Patients were asked to grade headache severity on a ten-point scale before and one hour after the initiation of therapy. Follow-up by phone was sought the following day. MEASUREMENTS AND MAIN RESULTS: Of 76 patients completing the trial, 24 were randomized to receive chloropromazine, 26 to receive dihydroergotamine, and 26 to receive lidocaine. Reduction in mean headache intensity was significantly better among those treated with chloropromazine (P less than .005). Persistent headache relief was experienced by 16 of the chloropromazine-treated patients (88.9%) contacted at 12 to 24 hours follow-up compared with ten of the dihydroergotamine-treated patients (52.6%) and five of the lidocaine-treated group (29.4%). CONCLUSION: The relative effectiveness of these three antimigraine therapies appears to favor chloropromazine in measures of headache relief, incidence of headache rebound, and patient satisfaction with therapy. 
4	Influence of catheter technology and adjuvant medication on acute complications in percutaneous coronary angioplasty. We report on the complication rates in 660 consecutive coronary angioplasties (725 lesions) performed using four procedures that differed with respect to catheter technology and adjuvant medication. After the PTCA regimen in our laboratory had been changed from conventional steerable systems to the monorail technique, we observed a significant increase in the incidence of transient vessel occlusions from 2.6% to 7.7%, of permanent occlusions from 3.6% to 8.8%, and of intracoronary thrombus-formation from 2.6% to 5.5%. This was associated with the frequent observation of thrombotic material on the partially Teflon-coated guidewires. Coronary perfusion with urokinase (1,670-6,670 U/min) lead to a further increase in the complication rates (10.4%/10.3%/6.5%). Our present percutaneous transluminal coronary angioplasty (PTCA)-regimen (monorail technique with P.E.T. balloons, fully silicon-coated guidewires, no urokinase) shows an incidence of 3.8% for intermittent and recurrent coronary occlusions and 1.9% for permanent occlusions. Urokinase did not prevent intracoronary thrombus formation with the monorail technique. Furthermore, we suspect that in the case of PTCA-induced regional intimal dissection, fibrinolysis can prevent reestablishment of intima adherence to the vessel wall. Because five procedural deaths were observed in the 212 patients treated with i.c. urokinase as opposed to three deaths in the 448 procedures without urokinase, we feel that i.c. urokinase in PTCA is a potentially harmful regimen. We suggest that the monorail technique should be performed with fully silicon-coated guidewires and without urokinase. 
2	Natural history and prognostic factors for chronic hepatitis type B. One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n = 46) or chronic active hepatitis without cirrhosis (n = 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3.7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p less than 0.0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p less than 0.0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis. 
4	The management of atypical non-cardiac chest pain. Atypical, non-cardiac chest pain is common and disabling, and often persists despite negative medical investigations. Aetiology is disputed and management is difficult. A multi-causal model in which both psychological and physical factors play a part is helpful; a fundamental factor is continued misinterpretation of minor physical symptoms as evidence of heart disease. We report supportive evidence and describe a psychological treatment derived from the model. In a randomized trial, cognitive behavioural methods were effective in reducing chest pain, disability and use of medication, in patients both with and without psychiatric disorder. The clinical implications are discussed. 
1	Undifferentiated carcinomas of salivary glands. Undifferentiated carcinomas of salivary glands are those epithelial malignancies whose light-optic histopathologic features are not sufficient to place them in other defined classes of carcinoma. They are ultrastructurally heterogeneous and can manifest neuroendocrine differentiation. With or without the latter, the carcinomas are biologically high-grade and rank with salivary duct and high-grade mucoepidermoid carcinomas in terms of morbidity and mortality. 
4	Incidence of perioperative myocardial ischemia detected by different electrocardiographic systems To determine the extent to which different electrocardiographic systems account for differences in reported incidence of perioperative myocardial ischemia, the authors simultaneously recorded in 109 patients undergoing coronary artery bypass grafting (CABG) the V5 or modified CM5 lead on five ECG systems by means of a specially constructed common V5 lead. The systems included a Spacelabs Alpha 14 Model Series 3200 ECG Cardule at bandwidths of 0.05-125 Hz and 0.5-30 Hz (a typical operating room monitor), a Marquette Electronics MAC II ECG at 0.05-40 Hz and 0.05-100 Hz (a standard ECG), and a Del Mar Holter recorder at 0.1-100 Hz. Relative ST-segment position and incidence of new ischemia compared to the preoperative ECG were determined in 109 sets of preinduction traces and 877 sets of intraoperative traces. ST-segment position on the three recording systems conforming with the American Heart Association (AHA) low-frequency response recommendations (0.05 Hz) were similar. Compared to the standard ECG, ST-segment position on the Spacelabs at 0.5-30 Hz was consistently more negative. Displacement on the Holter was consistently less negative and less positive. By the 0.1-mV displacement criterion for diagnosis of myocardial ischemia on any one ECG system, 16.5% of patients on arrival and 32.1% of patients intraoperatively suffered new myocardial ischemia. Based on the operating room monitor, arrival and intraoperative ischemia were present in 15.6 and 27.5% of patients, respectively. Ischemia at the same periods was less frequent by the standard ECG system (5.5 and 12.8%, respectively) and least frequent by the Holter recorder (4.6 and 8.3%, respectively). 
5	Receptor changes in the spinal cord of sheep associated with exposure to chronic pain. There is evidence that post-injury hypersensitivity is partly due to changes in the central nervous system. Sheep with foot rot were used to investigate the effect of chronic pain on some receptors thought to be involved in spinal nociceptive processing systems (alpha 2 adrenoceptor and mu and delta opioid receptors). Saturation binding studies showed a variable distribution of [3H] clonidine (alpha 2 adrenoceptor agonist) in the spinal cord of normal sheep. The number of receptors (Bmax) present in areas thought to be involved in nociceptive processing, laminae I and II and lamina X, increased to 131% and 169% of control sheep values respectively in animals exposed to chronic pain. The affinity of the receptors (KD), however, remained unchanged at approximately 2 nM. There was less [3H]DAGO (mu opioid agonist) and [3H]DPDPE (delta opioid agonist) binding in the sheep spinal cord. Both opioid receptor types being mainly located in the superficial dorsal horn. The [3H]DPDPE binding was unchanged in the sheep with foot rot, whilst the number (Bmax), but not the affinity, of the [3H]DAGO binding sites increased in laminae I and II in lame animals to 130% of the control sheep values. Hence, in animals in chronic pain, the number of alpha 2 adrenoceptors and mu opioid receptors increased mainly in areas of the sheep spinal cord associated with nociception. 
5	Antenatal phenobarbital for the prevention of periventricular and intraventricular hemorrhage: a double-blind, randomized, placebo-controlled, multihospital trial. To determine whether the neuroprotective properties of phenobarbital would alter the incidence and severity of intracranial hemorrhage in premature infants, we randomly assigned 110 women at less than 31 weeks of gestation to receive 10 mg/kg phenobarbital or placebo in a blinded fashion before delivery. Infants were examined postnatally with real-time ultrasonography for evidence of intracranial hemorrhage. Maternal demographics, pregnancy complications, antenatal management, and route of delivery did not differ between the phenobarbital group (n = 50) and the placebo group (n = 60). The total incidence of periventricular-intraventricular hemorrhage did not differ between the phenobarbital-treated (n = 54) and the placebo-treated (n = 67) infants. However, the frequency of grade 3 and grade 4 hemorrhages was 15% (10 infants) in the placebo group and 3.7% (2 infants) in the phenobarbital group (p less than 0.05). There were no differences in the severity of associated conditions in the babies to explain the difference in the incidence of severe hemorrhage between the study groups. We conclude that antenatal administration of phenobarbital appears to be effective in decreasing the severity of periventricular-intraventricular hemorrhage in infants delivered at less than 31 weeks of gestation. 
5	Frequency of low-grade residual coronary stenosis after thrombolysis during acute myocardial infarction. The clinical, angiographic and demographic characteristics of 42 patients with low-grade (less than 50%) residual stenosis at the infarct lesion after thrombolysis for acute myocardial infarction (MI) were assessed. The study group (group I) represented 21% of 198 consecutive patients receiving thrombolytic therapy over a 59-month period. Data on the 156 remaining patients were pooled for comparison (group II). Group I patients were predominantly men (86%) who were cigarette smokers (81%). Group II patients were predominantly men (75%, p greater than 0.10) but were significantly older (52 +/- 12 vs 56 +/- 10 years, p = 0.02). Prior acute MI or angina was unusual in group I. Sixty percent had no significant (greater than 50%) residual coronary artery disease while 25% had residual single artery disease. Average significant (greater than 50% diameter stenosis) residual vessel disease was 0.6 +/- 1.0 for group I and 1.9 +/- 0.9 for group II (p less than 0.001). In group I, average residual infarct lesion diameter stenosis was 36 +/- 7% in the right anterior oblique and 34 +/- 8% in the left anterior oblique views. Thirty-nine group I patients were discharged with medical therapy and 100% follow-up was obtained over a mean interval of 18 +/- 17 months. Fifteen patients experienced chest pain after acute MI accounting for 17 discrete events. Fifty-nine percent of group I had a benign course on follow-up. Eight events were classified as unstable angina, 4 as acute MI and 5 as atypical angina. Documented coronary vasospasm occurred in 3. 
1	Kaposi's sarcoma of the rectum in patients with the acquired immunodeficiency syndrome. We retrospectively reviewed eight patients with biopsy-proven anorectal Kaposi's sarcoma (KS) treated between 1984 and 1989 at San Francisco General Hospital. All patients were homosexual men with the acquired immunodeficiency syndrome (AIDS). The average age was 34 years. Three patients had primary rectal KS without metastases. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients with advanced AIDS received no specific treatment for anorectal KS. Follow-up ranged from 1 month to 5 years. Three of the untreated patients and the three patients treated with chemotherapy or radiotherapy were alive 1 month to 5 years after diagnosis. Aggressive surgical treatment of anorectal KS is not indicated. 
2	Gastroesophageal reflux in infants. Clinically significant gastroesophageal reflux occurs in one in 500 infants. Symptoms resolve in 60 to 80 percent of infants by 18 months of age. Thickened formula and position changes are often recommended. Medication and surgical intervention may be needed in refractory cases. 
4	Lacunar transient ischaemic attacks: a clinically useful concept? Lacunar ischaemic stroke syndromes are clinically, pathophysiologically, and prognostically distinguishable from cortical ischaemic stroke syndromes. Could cerebrovascular transient ischaemic attacks (TIAs) share similar heterogeneity? 130 patients with TIAs were prospectively studied, 71 of whom underwent carotid angiography. Symptoms were associated with a 50% or greater stenosis of the ipsilateral internal carotid artery in 36 (67%) of 54 patients with presumed cortical TIAs, but in only 1 (6%) of 17 patients with presumed lacunar TIAs (p less than 0.0001). These findings support the view that cortical TIAs are associated with ipsilateral extracranial internal carotid artery atheromatous disease, whereas patients with lacunar TIAs may have absent or insignificant large-vessel disease, and probable intracranial small-vessel disease. Accurate distinction between lacunar and cortical events may have implications for investigation and treatment of patients with TIAs. 
5	Hypothalamic-pituitary-adrenal function in patients with the premenstrual syndrome. Patients with primary affective disorders, such as melancholic depression and anorexia nervosa, frequently have a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, characterized by hypersecretion of CRH and a blunted ACTH response to exogenous CRH. Premenstrual syndrome (PMS) is a luteal phase dysphoric disorder characterized by primarily affective and behavioral disturbances. HPA axis function was compared in PMS patients and control women, respectively, diagnosed by DSM3-R criteria or found to have no current psychiatric disorders, determined by the Schedule for Affective Disorders and Schizophrenia-Lifetime Interview. Urinary free cortisol excretion was the same in PMS and normal women, and no differences in urinary free cortisol excretion between the follicular and luteal phases occurred in either group. Two HPA axis abnormalities, however, were noted when PMS patients were compared to normal women. First, basal evening cortisol concentrations in plasma were significantly decreased, while the time-integrated response of plasma cortisol to ovine (o) CRH was significantly increased. Second, the negative correlation between time-integrated plasma ACTH and cortisol responses to oCRH and basal luteal progesterone concentrations present in normal control women was not seen in the PMS patients. These changes in basal and oCRH-stimulated plasma cortisol levels in association with normal urinary free cortisol excretion suggest that women with PMS might have transient or episodic disturbances of their HPA axis, which appear adequately corrected by this system's servomechanisms. This probably explains the maintenance of regular menstrual cycles in PMS patients, which contrasts with the irregular menses observed in patients with depression, anorexia nervosa, or women who participate in chronic strenuous exercise. 
3	Cyst of the choroid plexus in the lateral ventricle: case report and review of the literature. We report an intraventricular cyst in a 2-year-old boy who had myoclonic jerks of the extremities. The cyst had no communication with the ventricular system or subarachnoid space. Total removal of the cyst adhering to the choroid plexus was accomplished. The glial cyst wall was lined in part by flattened or cuboidal epithelium. The preoperative and postoperative computed tomographic scans and magnetic resonance images are presented, and congenital benign cysts in the lateral ventricle are reviewed and discussed. 
5	A prospective, randomized study of three surgical techniques for treatment of acute ruptures of the anterior cruciate ligament. Treatment of ACL tears is controversial. Recent reports on nonoperative treatment have shown poor results. Results after primary repair have deteriorated with time, leading to augmentation procedures that seem to have improved the results. However, there have been few prospective, randomized studies in this field. Our goal was to compare primary repair with a bone-patellar tendon-bone augmentation method and with a new method using the Kennedy Ligament Augmentation Device. One hundred fifty patients aged 16 to 50, all of whom had acute ACL tears, were randomized with the closed envelope method to one of three groups treated with open surgical methods. Fifty patients were treated with primary repair, 50 patients with patellar tendon augmentation, and 50 patients were augmented with the Kennedy Ligament Augmentation Device. All patients were operated on within 10 days of injury. The rehabilitation protocol was identical, consisting of a long leg cast for 2 weeks, followed by a brace with no weight-bearing and limited motion for 6 weeks. The patients were followed prospectively by one surgeon (LE) using the Lysholm functional score, Tegner activity level score, clinical evaluation and KT-1000 arthrometer at 6 months, 1, and 2 years. Three patients were lost to followup. There was no age or activity level difference between the groups. Sport activities led to 85% of the injuries, with skiing, soccer, and European handball representing 80% of injuries. All three groups reduced their activity level the 1st year. The repair group remained at the same level after 2 years. 
3	Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16). Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime. However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary. 
2	A case of cecocolic intussusception with complete invagination and intussusception of the appendix with villous adenoma. Villous adenoma of the appendix is a rare neoplasm and intussusception of the appendix is a rare pathologic condition. A very rare case seen in a 35-year-old male with pain in the right lateral abdomen is reported. In this patient, the appendix along with the villous adenoma intussuscepted and invaginated into the cecal lumen, and presented as cecocolic intussusception. A polypoid lesion was diagnosed in the cecum by fiberoptic colonoscopy. Unlike polypoid lesions at other sites in the large intestine, polypoid lesions of the cecum may accompany intussusception and invagination of the appendix. Consequently, caution is required in performing endoscopic polypectomy in cases of polypoid lesions of the cecum. 
2	Dysphagia as a manifestation of occult hypoxemia. The role of oximetry during meal times. A 25-year-old woman with severe kyphoscoliosis reported a six-month history of increasing dysphagia to both liquids and solids. A barium swallow and esophageal motility studies showed no significant gastrointestinal abnormalities. Trials of antispasmodic agents were unsuccessful in relieving her symptoms. Pulmonary function tests showed a severe restrictive ventilatory defect (vital capacity = 0.67 L) with adequate oxygenation and alveolar ventilation as reflected by arterial blood gas testing during quiet wakefulness. However, continuous noninvasive oximetry demonstrated desaturation to 85 percent while eating. These transient episodes of desaturation were abolished by the administration of supplemental oxygen delivered by nasal prongs. Following the prescription of supplemental oxygen, dysphagia resolved immediately, with weight gain following over several weeks. We conclude that dysphagia may be a presenting feature of hypoxemia. This case report draws attention to the usefulness of continuous noninvasive monitoring of oxygenation and the clinical importance of at least some transient hypoxemic events. 
5	Clinical and physiological study of anal sphincter and ileal J pouch before preileostomy closure and 6 and 12 months after closure of loop ileostomy. Spontaneous evolution of pouch and anal function, and absorption features has been assessed in 15 patients who underwent proctocolectomy with J ileal pouch anastomosis without conservation of a rectal muscular cuff. All the patients were studied before preileostomy closure and six and 12 months after the closure of the protection loop ileostomy. Stool frequency was identical at six and 12 months (mean +/- SEM: 5.0 +/- 0.4 and 5.3 +/- 0.5/day, respectively). Sixty-six percent of patients at six months and 40% of patients at 12 months need to defecate at least one time during night. Stool weight as well as steatorrhea decreased significantly six months after the closure of loop ileostomy (P less than 0.05). Mean resting anal pressure remained unchanged six and 12 months after closure of the loop ileostomy (41 +/- 6 and 45 +/- 5 cm H2O, respectively). Maximum squeeze anal pressures increased significantly at six (P less than 0.05) and 12 months (P less than 0.05). The rectoanal inhibitory reflex was always absent at the same period. The maximum pouch capacity increased significantly during the first six months (P less than 0.01) from 142 +/- 17 to 279 +/- 27 ml. The maximum infused volume during a saline continence test was not significantly different at six and 12 months; the percentage of evacuation of the reservoir and the volume at which the first ileal contraction appeared in the reservoir increased significantly (P less than 0.05) at six and 12 months. In conclusion, in patients with ileoanal anastomosis and pouch reservoir, the closure of the loop ileostomy is associated with spontaneous modifications of the anal and pouch parameters. 
1	Neoadjuvant chemotherapy in invasive bladder cancer: the evolving role of surgery. The role of an operation in patients receiving neoadjuvant chemotherapy for clinically localized but invasive transitional cell carcinoma of the bladder currently is evolving. An operation is essential for case selection and evaluation of local response but it also contributes to bladder preservation and survival. The procedure that is necessary to select for and assess response to chemotherapy may itself alter the actual or proceed to evolution of invasive bladder cancer. Neoadjuvant chemotherapy is a reasonable therapeutic strategy in selected patients but it remains to be seen whether the results will prove to be superior to those achieved with standard endoscopic and open operations. 
1	Malignant melanoma presenting as nasal obstruction. Mucosal melanomas arising in the nasal cavity are rare tumors comprising less than 1 percent of all melanomas. Often, the common clinical symptom is nasal obstruction. Grossly, they may or may not be pigmented and frequently attain large sizes. Histologic diagnosis of these tumors may be difficult, requiring immunohistochemical or electron microscopic confirmation. Aggressive surgical management is the treatment of choice in clinical stage I disease. Subsequent surveillance for recurrence is mandatory. Markers such as 5-S-cysteinyldopa may prove useful in staging, prognosticating, and postoperative surveillance for early recurrence, but their exact role has yet to be delineated. Ultimate prognosis is poor. 
1	Application of 1 nm gold probes on paraffin wax sections for in situ hybridisation histochemistry. An in situ hybridisation technique that uses 1 nm immunogold reagents and silver enhancement was devised to detect biotinylated DNA viral probes in formalin fixed, paraffin wax sections of human cervix. DNA probes labelled with biotin-11-deoxyuridine triphosphate were detected after hybridisation to nucleic acid sequences by an antibiotin antibody, followed by a gold labelled secondary antibody. Silver enhancement then permitted visualisation of the signal at the light microscopic level. The method was reliable and produced less background staining than previously described methods. The signal could be enhanced by epi polarisation microscopy. Furthermore, biotinylated DNA probes may be detected directly by a 1 nm gold labelled goat antibiotin antibody without loss of labelling intensity, and this may be preferable to the longer two layer technique, previously described. 
2	The Indian experience with hypertrophic pyloric stenosis. A study of 58 consecutive Indian infants operated for congenital hypertrophic pyloric stenosis revealed an accentuated male predominance in the incidence of the disease and far less preoperative hemetemesis as compared to that in their Western counterparts. 'Pyloric tumor' was palpable in 89% of cases. Only 34.5% of these infants were first born. Postoperative vomiting occurred in 13.8% of patients and wound sepsis was not encountered. Air contrast radiography confirmed the diagnosis in clinically doubtful cases. 
3	Cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage. The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia, as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. A technique for the measurement of intracellular free calcium is described, along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia. Additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels (nimodipine, which blocks voltage-sensitive calcium channels, and MK-801, which blocks receptor-operated channels) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium. 
5	Mutation of the p53 gene in human acute myelogenous leukemia. Heterogeneity of p53 protein expression is seen in blast cells of patients with acute myelogenous leukemia (AML). p53 protein is detected in the blasts of certain AML patients but not in others. We have identified p53 protein variants with abnormal mobility on gel electrophoresis and/or prolonged half-life (t 1/2). We have sequenced the p53 coding sequence from primary blast cells of five AML patients and from the AML cell line (OCIM2). In OCIM2, a point mutation in codon 274 was identified that changes a valine residue to aspartic acid. A wild type p53 allele was not detected in these cells. Two point mutations (codon 135, cysteine to serine; codon 246, methionine to valine) were identified in cDNA from blasts of one AML patient. Both mutations were present in blast colonies grown from single blast progenitor cells, indicating that individual leukemia cells had sustained mutation of both p53 alleles. The cDNAs sequenced from blast samples of four other patients, including one with prolonged p53 protein t 1/2 and one with no detectable p53 protein, were fully wild type. Thus, the heterogeneity of p53 expression cannot be explained in all cases by genetic change in the p53 coding sequence. The prolonged t 1/2 of p53 protein seen in some AML blasts may therefore reflect changes not inherent to p53. A model is proposed in which mutational inactivation of p53, although not required for the evolution of neoplasia, would confer a selective advantage, favoring clonal outgrowth during disease progression. 
4	Postangiographic femoral artery injuries: nonsurgical repair with US-guided compression Ultrasound-guided compression repair (UGCR) of catheterization-related femoral artery injuries was evaluated as a possible new imaging-guided interventional procedure. Thirty-nine femoral artery injuries (35 pseudoaneurysms, four arteriovenous fistulas) were detected with color Doppler flow imaging in patients with enlarging groin hematomas and/or groin bruits 6 hours to 14 days after catheterization procedures. UGCR was not performed in 10 patients due to spontaneous thrombosis (n = 4), infection (n = 1) or skin ischemia (n = 1), unsuitable anatomy (n = 3), or excessive discomfort (n = 1). The remaining 29 patients underwent a full trial of compression therapy, and the lesion was eliminated in 27. Follow-up color flow scans were obtained after 24-72 hours in all 27 successful cases and at 1-15 months in 19; no recurrences or complications occurred. UGCR for acute injuries is safe and technically simple and is promising as a cost-effective, first-line treatment for uncomplicated catheterization-related femoral artery injuries. UGCR is probably not appropriate for long-standing injuries. 
2	A videofluoroscopy chair for the evaluation of dysphagia in patients with severe neuromotor disease. Due to the difficulties encountered in positioning severely neurologically impaired individuals for videofluoroscopic studies, the Rehab Tech Video FluoroChair was developed. The purpose of the chair is to provide the severely disabled patient with safe, stable postural support in an upright position for videofluoroscopic studies, with anterior-posterior, lateral, and rotational views easily performed. The chair features a removable headrest, a full back support, armrests, lateral truncal supports, and a patented base which is clamped to the footboard of the radiology table and allows for 200 degrees rotation of the patient. Two case studies illustrate the practical use and versatility of the Rehab Tech Video FluoroChair. 
1	Plasma cell granuloma of the nasal cavity treated by radiation therapy. Plasma cell granuloma is a rare, benign tumor most commonly found in the lungs in patients younger than 30 years. Although presentation has been reported at a number of other anatomic sites, this report is the first of plasma cell granuloma of the nasal cavity. The tumor was initially resected, but progression was seen at 1-month follow-up. Because further surgery to completely eradicate the tumor would have been extensive and disfiguring, 40-Gy external beam radiation was given in 20 fractions using a three-field wedge technique. Most recent clinical follow-up at 27 months showed local control. Surgery remains the treatment of choice for plasma cell granuloma when the disease can be completely resected. However, irradiation can also be effective in patients with recurrent or inoperable local disease. 
3	Syringomyelia as a postoperative sequela of the resection of a chordoma of the clivus: case report. Syringomyelia has been described frequently in association with various abnormalities of the skull base but rarely with tumors of the skull base. Syringomyelia as a postoperative sequela of surgery of the skull base has not been reported. The authors describe a case of cervical syringomyelia developing after the partial resection of a chordoma and combined conventional and proton beam irradiation. The possible mechanisms causing this abnormality are discussed. 
5	Pharmacomechanical thrombolysis and angioplasty in the management of clotted hemodialysis grafts: early and late clinical results. The results of pharmacomechanical thrombolysis and angioplasty of 121 thrombosed hemodialysis grafts were reviewed. The initial pharmacomechanical method (used in 65 cases) employed clot maceration with hook-shaped catheters and clot lacing with highly concentrated urokinase. The current technique (used in 56 cases) consisted of pulsed-spray injection of urokinase into the clot. All fully treated grafts (117 cases) underwent complete or near-complete thrombolysis, and 93% remained patent after 1 day. Mean time for pulsed-spray lysis was 46 minutes +/- 21. One patient (less than 1%) had gastrointestinal bleeding and received a transfusion; minor complications occurred in 3% of patients. Primary and secondary graft patency rates for both methods at 1 year were 26% and 51%, respectively. While graft age and results of angioplasty did not influence future graft patency, shorter intervals between graft thromboses was predictive of earlier subsequent graft failure. Results suggest that pharmacomechanical thrombolysis and angioplasty provide rapid, consistent, and safe recanalization of clotted hemodialysis grafts and represent a promising additional therapeutic approach to long-term graft management. 
2	Integration of hepatitis B vaccination into rural African primary health care programmes. OBJECTIVE--To determine the efficacy of hepatitis B vaccine when added to the routine expanded programme on immunisation under field conditions in rural Africa. DESIGN--Infants were immunised according to two schedules--an early schedule at birth, 3 months, and 6 months and a later schedule to correspond with routine vaccination in the expanded programme on immunisation at 3 months, 4 1/2 months, and 6 months. SETTING--Venda, northern Transvaal, South Africa, a self governing region of 7460 square kilometers varying from rural villages to small towns. SUBJECTS--The 1989 birth cohort of Venda. MAIN OUTCOME MEASURES--Coverage for hepatitis B vaccine at first, second, and third doses; serological assessment of vaccine efficacy by prevalence of antibodies to hepatitis B surface antigen in infants who had completed the three dose course of immunisation; antibodies to hepatitis B core antigen to determine if natural infection occurred. RESULTS--Vaccine coverage for hepatitis B dropped sharply from 99% to 53% to 39% for the first, second, and third dose respectively. In contrast, vaccine coverage was maintained at 97-99% for the three doses of poliomyelitis vaccine. Serological evaluation of vaccine efficacy showed that only 3.5% of recipients of all three doses failed to develop antibodies to hepatitis B surface antigen. Only 6.6% of vaccine recipients were vaccinated according to either the early or later schedules whereas 93.4% received their doses of vaccine at intervals beyond the limits of either of the planned schedules. There was, however, no significant difference in seroconversion to the surface antigen between the "unscheduled" or scheduled groups of those who were vaccinated according to the early or late schedules. The pattern of prevalence of antibodies to hepatitis B core antigen, which showed a sharp fall in children aged over 7 months, suggested that the antibodies were acquired passively rather than by active infection. CONCLUSIONS--Supplementation of the present expanded programme on immunisation with hepatitis B vaccine in rural Africa is fraught with difficulties. However, the vaccine was effective within a fairly wide spacing of dosage. Adding hepatitis B vaccine to diphtheria, tetanus, and pertussis as a tetravalent vaccine is proposed as a means of effectively integrating it into the expanded programme on immunisation in Third World settings. 
5	Multifocal gastric carcinoma arising from hyperplastic and adenomatous polyps. This paper is a presentation of the unusual case of a 61-yr-old woman operated on for multiple gastric cancers. Two of the cancers were found in the hyperplastic polyps and one in the adenoma. Apart from cancers that arose from these polyps, there were four separate polypoid or flat gastric carcinomas and three other hyperplastic polyps with no signs of malignancy, in this case. The presentation is followed by a detailed discussion focusing on the possible development of carcinoma in gastric hyperplastic polyps in view of the data from the literature. 
5	Acute myocarditis simulating myocardial infarction in a child. Pediatric chest pain usually occurs in benign conditions. However, this case portrays the dramatic electrocardiographic appearance of acute myocardial ischemia in a boy with biopsy-proven myocarditis who had only mild chest pain. This underscores the need for eliciting a detailed history when evaluating a patient with chest pain. If the pain cannot be clearly attributed to chest wall phenomena, or if there are historical or physical findings suggestive of an arrhythmia or angina, then further investigation with a chest radiograph and a 12-lead electrocardiogram is recommended. Myocarditis must be considered in the differential diagnosis of any child whose electrocardiogram is indistinguishable from an acute myocardial infarction. Finally, endomyocardial biopsy allows early diagnosis and institution of therapy, which may have beneficial effect on decreasing morbidity and mortality. Further follow-up and research is still needed to evaluate the effect of early treatment of myocarditis on long-term myocardial function and the development of chronic cardiomyopathy. 
2	The clinical importance of drug interactions with antiulcer therapy. The overall safety of a given drug is determined by its toxicity, side effects, and drug-drug interactions. Thus, a clarification of the mechanisms, importance, and clinical implications of any drug-drug interaction with antiulcer therapy is critical to the use of antiulcer medications. Drug-drug interactions may occur as a result of changes in absorption, metabolism, distribution, or excretion. Fortunately, drug distribution or protein binding is unchanged by antiulcer therapy. Antiulcer drugs may affect absorption by several mechanisms. Ionized medications may bind to the divalent cations of antacids and sucralfate to result in poorly absorbed complexes. Reduced gastric acid may decrease the absorption of medications that are weak bases while enhancing the absorption of weak acids. Drug absorption may be impaired by delayed gastric emptying. Several H2-receptor antagonists, including cimetidine and to a lesser extent ranitidine, and the proton pump inhibitor, omeprazole, may reduce the hepatic degradation of drugs metabolized by the cytochrome P450 system. The degree to which such agents alter drug metabolism is determined by the patient's age, genetics, duration of therapy, degree of cytochrome P450 binding, and the regimen. Because the clinical importance of this interaction cannot always be predicted, caution is recommended whenever drugs metabolized by this system are used concurrently. Development of an understanding of the ways in which drug metabolism interactions occur may lead to more effective and safe use of these medications. 
3	A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study. In prospective epidemiologic studies of coronary heart disease, a single measurement of cholesterol is made to assess its relationship to the risk of coronary disease. Statistical theory states that if this measurement is subject to within-individual variability, the strength of the relationship will be underestimated. This is empirically shown for the example of plasma cholesterol. For the Lipid Research Clinics Follow-up Study population (comprising 2170 white men over 30 years of age), the age-adjusted coronary heart disease mortality regression coefficient increases from .453 to .496 if the average of two cholesterol measurements is used instead of a single measurement. Since the correlation between the two repeated cholesterol measurements is .815, an increase in the regression coefficient up to .556 would be expected if the true cholesterol values were available. Thus, epidemiologic studies have substantially underestimated the strength of the relationship between cholesterol levels and the risk of coronary disease by calculating the relationship on the basis of a single cholesterol determination. 
5	Infectious mononucleosis presenting as bilateral acute dacryocystitis. A case of infectious mononucleosis presenting as bilateral acute dacryocystitis in a 7-year-old girl is reported. Acute dacryocystitis is uncommon in this age group, and an underlying systemic illness should be suspected particularly when it is bilateral. 
4	Regional wall thickening of left ventricle evaluated by gated positron emission tomography in relation to myocardial perfusion and glucose metabolism. Regional wall thickening was assessed by electrocardiographically gated positron emission tomography (ECG-gated PET) in 26 patients with coronary artery disease. The standardized percent count increase from end-diastole to end-systole (S-percent Cl) was calculated as an index of wall thickening. The S-percent Cl was 77.8% +/- 28.9% in the segments with normal perfusion at rest, 51.9% +/- 29.5% in those with mild hypoperfusion, and 32.8% +/- 30.9% in those with severe hypoperfusion (p less than 0.001, each). Among the segments with resting hypoperfusion, the S-percent Cl was 38.9% +/- 31.5% in those without stress-induced ischemia and 48.7% +/- 30.9% in those with ischemia (p less than 0.05). Furthermore, among resting severe hypoperfusion, the S-percent Cl was 23.0% +/- 23.9% in the segments without fluorine-18-fluorodeoxyglucose (FDG) uptake and 37.8 +/- 32.9% in those with FDG uptake (p less than 0.05). These results suggest that stress-induced ischemia and FDG accumulation correlated with wall thickening. Thus, quantitative analysis of regional wall thickening seems to be useful for combined analysis of regional function, perfusion and metabolism in coronary patients. 
4	Susceptibility to Coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr alpha and Myhc alpha loci on chromosome 14. This study was undertaken to determine the genetic control of host susceptibility to coxsackievirus B3 (CVB3)-induced chronic myocarditis in a mouse model. An autosomal recessive autoimmune myocardial disease (amd) gene (possibly more than one gene), which determined susceptibility to CVB3-induced chronic myocarditis in the A/J and DBA/2J inbred mouse strains, was mapped to a segment of chromosome 14. Data from both the AXB/BXA recombinant inbred (RI) strains and the B10.D2(57N) H-8b congenic mice supported this linkage relationship. Analysis of the AXB/BXA RI strain distribution patterns suggested that amd maps distal to the Np-2, Tcr alpha, and Myhc alpha loci. 
5	Nortriptyline treatment of depressed cardiac transplant recipients. The safety of tricyclic antidepressants in cardiac transplant recipients has not been established. The author used nortriptyline to treat major depressive episodes in eight cardiac transplant recipients. Nortriptyline therapy was associated with increased QRS interval and heart rate but did not significantly affect other hemodynamic or ECG variables or cyclosporine dose requirements. It appears that nortriptyline may be used safely in depressed cardiac transplant patients. 
5	Titration streptomycin therapy for bilateral Meniere's disease. Follow-up report. Initial reports of the use of parenteral streptomycin for bilateral Meniere's disease (MD) have demonstrated success in reducing the vestibular symptoms and, in some patients, stabilizing hearing. The long-term follow-up (mean, 5.1 years) of 19 patients treated with intramuscular streptomycin for bilateral MD is presented. The amount of streptomycin administered (5 to 50 g) was determined by clinical symptoms and by serial testing of the reduction in the slow-phase velocity on electronystagmography. Episodic vertigo was totally relieved in 12 patients and improved in severity and frequency in an additional 4 patients. Permanent posttreatment dysequilibrium occurred in 47% of the patients treated. The changes in hearing (speech reception threshold) were independent of the therapeutic effect of streptomycin on the vestibular system. The overall results suggest that the intramuscular titration of streptomycin should continue to be considered as one of the therapeutic options in patients with disabling vertigo due to bilateral MD. 
5	Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome. 
5	Rett syndrome: cerebellar pathology. The cerebellar pathology at autopsy of 5 patients with Rett syndrome is described. The patients ranged in age from 7-30 years. All had markedly reduced brain weights with proportionately small cerebella. Microscopic examination revealed loss of Purkinje cells, atrophy, astrocytic gliosis of the molecular and granular cell layers, and gliosis and loss of myelin in the white matter. Cortical atrophy occurred focally along the folia and was often more marked in the tips of the folia. The 2 oldest patients had been treated with phenytoin which may have contributed to the morphologic changes. Atrophy and gliosis increased with age or in patients without phenytoin treatment; the youngest patient demonstrated only minor microscopic changes. In addition to the generalized alterations, 1 patient had several adjacent folia with severe atrophy. The results indicate that cerebellar changes in Rett syndrome consist of general hypoplasia with the addition of atrophy beginning in childhood and progressing over many years. 
3	Delayed anterior decompression in patients with spinal cord and cauda equina injuries of the thoracolumbar spine. Forty-nine patients with complete and incomplete injuries of the spinal cord or cauda equina who had undergone anterior decompression at a minimum of 3 months after injury were examined. Follow-up was from 12 months to 19 years. Postoperative neurologic improvement occurred in 46.5% of patients with incomplete injuries. If the surgery was performed less than 2 years after injury, neurologic improvement occurred in 68% with an improvement in Frankel grade of 32%. Bladder function improved in 27% of patients and if operated on less than 2 years after injury improvement occurred in 43%. Conus medullaris decompression resulted in a 50% improvement. There was an 83% improvement in the pattern of pain after decompression. Of 23 patients with preoperative spasticity, 10 improved but 6 were worse after surgery. 
4	Angioedema from angiotensin converting enzyme inhibitors: a cause of upper airway obstruction. Angiotensin-converting enzyme (ACE) inhibitors have several side effects of concern to the otolaryngologist. Angioedema is a rare, but potentially lethal adverse effect when associated with upper airway obstruction. Four cases of ACE-inhibitor-induced angioedema, three with significant upper airway obstruction, are reported. Angioedema secondary to ACE inhibition appears to be mechanism based. The probable link is the potentiation of bradykinin, which results in vasodilation, increased vascular permeability, and angioedema. Since angioedema can progress to upper airway obstruction, otolaryngologists must be aware of this association. The differential diagnosis and treatment of this adverse effect is discussed, as well as a review of ACE inhibitors and other causes of angioedema. 
5	Heat induced radial segmentation of leukocyte nuclei in patients with polymyalgia rheumatica and other inflammatory diseases. Heat induced radial segmentation of leukocyte nuclei is an in vitro phenomenon accompanying inflammatory diseases. We studied 62 patients with suspected polymyalgia rheumatica (PMR) to determine, whether heat induced radial segmentation can help in discriminating PMR from other conditions. At the initial presentation patients with PMR had more radial segmentation formation than patients with other inflammatory conditions. Prednisone induced a rapid and marked decrease in radial segmentation formation in patients with PMR. This latter finding was much less marked in patients with other inflammatory conditions. We conclude that heat induced radial segmentation at the initial presentation and during prednisone treatment can help in discriminating PMR from other inflammatory conditions. 
5	Nuclear DNA profiles in primary melanomas and their metastases. DNA-aneuploid primary melanomas are said to show a greater propensity to metastasize than those without an aneuploid profile. A higher aneuploid rate has also been reported in metastatic melanomas than in primary lesions. The ploidy profile was determined of 26 primary melanomas and their first subsequent secondaries on Feulgen-stained sections from routinely processed material using a computerized video image-analysis system. In 18 of 26 cases, both primary and secondary tumor showed similar corresponding DNA patterns. These were aneuploid in 13 of 18 of the cases. A hyperdiploid pattern was present in one case in both the primary and its metastasis, and a diploid pattern was seen in four cases. There were only eight cases in which a disparity between the nuclear ploidy profile in the primary and secondary tumor was evident. Although the results suggest that ploidy studies are not useful for predicting the metastatic potential of a primary melanoma, the maintenance of similar DNA profiles in the metastases in most of these cases was interesting in regard to tumor biology. 
4	New calcium antagonists: relevance of vasoselectivity. The calcium antagonists are a heterogeneous class of drugs used to treat a number of cardiovascular disorders. A new generation of calcium antagonists under development have a higher degree of selectivity for vascular smooth muscle and coronary vasculature compared with verapamil, nifedipine, and diltiazem. The clinical relevance of vasoselectivity and its impact on drug selection are discussed. The newer calcium antagonists are important alternatives to older agents and may be associated with improved tolerance and a reduced incidence of adverse effects. Their place in therapy has yet to be defined by comparative studies of efficacy and safety. 
2	Postoperative analgesic requirements in patients exposed to positive intraoperative suggestions. OBJECTIVE--To establish whether positive suggestions given to a patient under general anaesthesia reduce postoperative pain and analgesic requirements. DESIGN--Prospective double blind randomised study. SETTING--Operating theatre and gynaecology ward of a teaching hospital. PATIENTS--63 Woman undergoing elective abdominal hysterectomy were randomised to be played either a tape of positive suggestions or a blank tape during the operation through a personal stereo system. INTERVENTIONS--Three women were withdrawn from the study. Anaesthesia was standardised for all of the women. Postoperative analgesia was provided through a patient controlled analgesia system for the first 24 hours. Pain scores were recorded every six hours. MAIN OUTCOME MEASURES--Morphine consumption over the first 24 hours after the operation; pain scores. RESULTS--Mean morphine requirements were 51.0 mg (95% confidence interval 42.1 to 60.0 mg in the women played positive suggestions; and 65.7 mg (55.6 to 75.7 mg) in those played a blank tape. The point estimate (95% confidence interval) for the difference of means was 14.6 mg (22.4%) (1.9 (2.9%) to 27.3 mg (41.6%] (p = 0.028). Pain scores were similar in the two groups. CONCLUSION--Positive intraoperative suggestions seem to have a significant effect in reducing patients' morphine requirements in the early postoperative period. 
2	Differential alpha-fetoprotein lectin binding in hepatocellular carcinoma. Diagnostic utility at low serum levels. The reactivity of serum alpha-fetoprotein (AFP) from 20 patients with hepatocellular carcinoma (HCC) with immobilized lentil lectin was examined and found to be significantly greater (39% +/- 18%) than that of the same protein from seven patients with chronic liver disease (CLD, 11.2% +/- 3.3%), seven with fulminant hepatic failure (FHF, 10% +/- 8.4%), and eight normal pregnant women (4.1% +/- 2.7%). The reactivity with Concanavalin A (Con A) was also significantly greater for AFP from HCC patients (44.5% +/- 12.5%) than that from FHF patients (7.7% +/- 4%) and normal pregnant women (5.3% +/- 3.3%), but not from patients with CLD. The reactivity with lentil lectin permitted distinction between those with HCC (31.3% +/- 14.1%) and those with uncomplicated CLD (11.2% +/- 8.4%) even when the absolute levels of serum AFP were in the same range (80-400 ng/ml). Evaluation of the alterations by lectin binding methodology may be useful in overcoming problems associated with distinguishing between malignant and CLD, particularly at moderate serum AFP elevations. 
4	Intravital detection of skin capillary aneurysms by videomicroscopy with indocyanine green in patients with progressive systemic sclerosis and related disorders. Conventional capillaroscopy and infrared fluorescence videomicroscopy with indocyanine green were performed at the nailfold in 12 healthy controls and 38 patients with microangiopathy due to systemic sclerosis or related disorders. Saccular aneurysms featuring head and neck (type 1) and aneurysmatic enlargements (type 2) were defined. Microaneurysms were located at the apex or near the apex of capillary loops and were significantly more common in patients than in controls (p less than 0.02 for type 1 and p less than 0.001 for type 2). Combination of the two lesions was found only in patients and appears to be a valuable new diagnostic sign for the presence of microangiopathy. In comparison with conventional capillaroscopy, about twice as many microaneurysms were detected by videomicroscopy with indocyanine green coupling almost completely to plasma proteins. The new technique allows visualization of capillary aneurysms even when filled only by plasma. 
5	Catheterization laboratory events and hospital outcome with direct angioplasty for acute myocardial infarction To assess the safety of direct infarct angioplasty without antecedent thrombolytic therapy, catheterization laboratory and hospital events were assessed in consecutively treated patients with infarctions involving the left anterior descending (n = 100 patients), right (n = 100), and circumflex (n = 50) coronary arteries. The groups of patients were similar for age (left anterior descending coronary artery, 59 years; right coronary artery, 58 years; circumflex coronary artery, 62 years), patients with multivessel disease (left anterior descending coronary artery, 55%; right coronary artery, 55%; circumflex coronary artery, 64%), and patients with initial grade 0/1 antegrade flow (left anterior descending coronary artery, 79%; right coronary artery, 84%; circumflex coronary artery, 90%). Cardiogenic shock was present in eight patients with infarction of the left anterior descending coronary artery, four with infarction of the right coronary artery, and four with infarction of the circumflex coronary artery. Major catheterization laboratory events (cardioversion, cardiopulmonary resuscitation, dopamine or intra-aortic balloon pump support for hypotension, and urgent surgery) occurred in 10 patients with infarction of the left anterior descending coronary artery, eight with infarction of the right coronary artery, and four with infarction of the circumflex coronary artery (16 of 16 shock and six of 234 nonshock patients, p less than 0.001). There was one in-laboratory death (shock patient with infarction of the left anterior descending coronary artery). 
5	Early identification of hearing loss: listen to parents. Families of 49 hearing-impaired children responded to a questionnaire requesting information about the identification of their child's hearing loss. Parents were the first to suspect the hearing loss in 48 cases but more often than not were told that the child would outgrow it or was too young to test. When professionals agreed with the parents and attended to their concerns, confirmation of the hearing loss occurred significantly more rapidly than when they disagreed with parents and ignored their concerns. A child whose hearing loss is not clearly identified and whose communication is inadequate or nonexistent, causes frustration and stress within the family and prevents the child from receiving the maximum benefit from early language input and amplification. It would benefit both the child and family if professionals would listen to parental concerns regarding their child and assist in the early identification process. 
3	Embolic stroke after smoking "crack" cocaine. A 39-year-old woman had an embolic upper division middle cerebral artery branch occlusion 3 hours after smoking the free base of cocaine ("crack"). Radionuclide ventriculography demonstrated cardiomyopathy, and echocardiography documented a left atrial thrombus. This case demonstrates that embolism is one mechanism of ischemic stroke after cocaine use, and that cardiomyopathy, possibly cocaine induced, may be the source of embolus. A cardiac source of embolus should be sought in patients with cocaine-associated cerebral infarction. 
3	Acceleration of scrapie in trisomy 16----diploid aggregation chimeras. We studied the susceptibility to prion infection of the trisomy 16----diploid chimeric mouse, a putative model of Down syndrome. When weanling chimeras were inoculated intracerebrally with scrapie prions, the time until appearance of the first symptoms of scrapie was reduced by 17 days (from a mean control time of 153 days) and the time to death was reduced by 30 days (from control time of 170 days). Our results with trisomy 16 chimeras argue that the susceptibility to central nervous system degeneration caused by prions can be modulated by chromosome imbalance. 
5	The prevalence of Helicobacter pylori infection in the Peoples Republic of China. Meta-analysis on data from 16 (two volunteer and 14 endoscopic) studies ahs been performed to investigate the prevalence of Helicobacter pylori infection in the stomachs of individuals within the Peoples Republic of China. In this survey covering 2216 cases (89 volunteers and 2127 endoscopy patients), the incidence of H. pylori infection in 15- to 22-yr-old healthy volunteers, and in 13- to 88-yr-old symptomatic patients undergoing gastroscopy was 49.4% and 64.5%, respectively. The frequency of H. pylori infection in chronic gastritis (63.6%), gastric ulcer (71.9%), and duodenal ulcer disease (73.1%) differed significantly from that in histologically normal individuals (8.2%), confirming the relationship of H. pylori infection with those disease states. We found no significant association between H. pylori infection and symptoms. 
4	Skeletal muscle depressed calcium and phosphofructokinase in chronic heart failure are upregulated by captopril--a double-blind, placebo-controlled study. The effects of the angiotensin converting enzyme inhibitor captopril, after treatment for 5-6 weeks with 25 mg t.i.d., were studied in 12 patients with stable moderate heart failure. Five patients received placebo treatment, and the two groups were comparable at baseline. Angiotensin II levels decreased in response to captopril therapy. Skeletal muscle potassium, magnesium and chloride levels did not differ from reference values. Calcium was subnormal (P less than 0.0001), but increased to the reference range during captopril treatment. Phosphofructokinase, a rate-limiting glycolytic enzyme, was in the lower reference range and increased (P less than 0.04) in response to captopril therapy. In conclusion, stable moderate heart failure is associated with low levels of skeletal muscle calcium and phosphofructokinase activity, these metabolic changes tending to return to normal levels with captopril treatment. 
2	Normeperidine-induced seizures in hereditary coproporphyria. Seizures are common in acute exacerbations of hepatic porphyria, even though the etiology is not identified in most cases. We have reported a case of normeperidine-induced seizures in a patient with hereditary coproporphyria. Although meperidine is commonly used for pain control during acute attacks in these patients, this report suggests that meperidine is not a good analgesic choice in porphyria. Normeperidine-induced seizures in patients with porphyria may be treated by withdrawal of meperidine therapy and selective use of anticonvulsants. 
2	Impairment of esophageal emptying with hiatal hernia. Concurrent videofluoroscopy and manometry were used to analyze esophageal emptying during barium swallows in 22 patients with axial hiatal hernias and in 14 volunteers. Subjects were divided into three groups: (a) volunteers with maximal phrenic ampullary length less than 2 cm (controls); (b) patients or volunteers with maximal ampullary/hiatal hernia length greater than or equal to 2 cm that reduced between swallows (reducing-hernia group); and (c) patients with hernias that did not reduce between swallows. Complete esophageal emptying without retrograde flow was achieved in 86% of test swallows in the controls, 66% in the reducing-hernia group, and 32% in the nonreducing-hernia group (P less than 0.05). Impaired emptying in the reducing-hernia group was attributable to "late retrograde flow," whereby barium squirted retrograde from the hernia during emptying. Impaired emptying in the nonreducing-hernia group was attributable to "early retrograde flow" that occurred immediately after LES relaxation. The nonreducing-hernia group also had longer acid clearance times than the controls (P less than 0.05). We conclude that gastroesophageal junction competence is severely impaired in patients with nonreducing hiatal hernias, suggesting a mechanism whereby this subgroup of hiatal hernia is involved in the pathogenesis of reflux disease. 
4	Cardiovascular risk reduction: the role of antihypertensive treatment. The effects of antihypertensive drugs on mortality from stroke, coronary artery disease (CAD), and nonvascular causes have been studied in 14 trials involving more than 37,000 patients. In the treated patients, blood pressure was 5 to 6 mm Hg lower than that in placebo-treated patients, and whereas mortality from stroke was reduced by 42%, CAD mortality was reduced by only 14%. A major reason for this lack of effect on CAD mortality is apparently the adverse effects of the primary drugs used in these trials (diuretics and beta blockers) on glucose tolerance, lipid levels, and insulin resistance. The angiotensin-converting enzyme inhibitors favorably influence many CAD risk factors, and their use can be expected to reduce CAD mortality in patients treated for hypertension. 
4	Septal ventricular pacing in the immature canine heart: a new perspective. Cardiac pacing initiated from epicardial or transvenous apical right ventricular electrodes causes asynchronous ventricular contraction. This alters myocardial stress vectors and results in adverse cellular and subcellular changes in the experimental animal. Clinically, such changes may contribute to the adverse hemodynamics reported with long-term ventricular pacing. To determine the feasibility of direct stimulation of the ventricular specialized conduction systems and therefore the potential for maintenance of normalized depolarization patterns, 13 beagle puppies were studied. Baseline ventricular activation and contraction patterns were obtained using intracardiac electrograms and multigated nuclear acquisition (MUGA) imaging. Septal electrode insertion from the aortoatrial groove was accomplished by use of two-dimensional echocardiography and continuous electrocardiographic (ECG) monitoring of the surface ECG during pacemaker implantation in five puppies. Standard right ventricular epicardial electrodes were implanted in five additional animals, with three remaining as age-matched non-paced controls. After 4 months of observation, repeat MUGA imaging and intracardiac electrograms demonstrated nearly normal biventricular activation and contraction patterns among the septal-paced group. Histopathologic examination illustrated normal cellular morphology in the septal-paced animals. This study demonstrates that pacing electrode insertion into the proximal interventricular septum is feasible and results in utilization of the normal ventricular conduction pathway. Such an approach to initiation of ventricular stimulation may attenuate the adverse effects of long-term ventricular pacing. 
3	Fundoplication and gastrostomy in familial dysautonomia. Fundoplication with gastrostomy has become a frequent treatment for patients with familial dysautonomia, so we evaluated the use of both procedures in 65 patients. Although patients differed widely in presenting signs and age, from 5 weeks to 40 years, gastroesophageal reflux was documented in 95% of patients by cineradiography or pH monitoring. Panendoscopy was a useful adjunct. Preoperative symptoms of gastroesophageal reflux included vomiting, respiratory infections, and exaggerated autonomic dysfunction. Severe oropharyngeal incoordination frequently coexisted and resulted in misdirected swallows with aspiration, dependence on gavage feedings, or poor weight gain and dehydration. Follow-up after surgical correction ranged from 3 months to 11 years; 55 patients (85%) were available for a 1-year postoperative assessment. We had no instances of surgical death. The long-term mortality rate was 14%, primarily related to severe preexisting respiratory disease. Beyond the first postoperative year, 30 patients had pneumonia attributed to continued aspiration, exacerbation of preexisting lung disease, or recurrence of gastroesophageal reflux. Of 11 patients who vomited postoperatively, six had recurrence of reflux. Recurrence of gastroesophageal reflux was documented in eight patients (12%), and we revised the fundoplication in three patients. The number of patients with cyclic crises was reduced from 18 to 7; retching replaced overt vomiting in all but two of these seven patients, neither of whom had recurrence of reflux. Because oropharyngeal incoordination was prominent, concomitant use of gastrostomy and an antireflux procedure was especially effective in the treatment of younger patients with familial dysautonomia, before the development of severe respiratory disease. Despite the development of severe morning nausea in 15 patients, the combination procedure resulted in significantly improved nutritional status, decreased vomiting, and decreased respiratory problems. Appropriate use of gastrostomy feedings also contributed to success of the operation. The generally good outcome of fundoplication with gastrostomy confirms the benefit of this procedure in familial dysautonomia. 
5	Diffusing capacity of the lung and nifedipine in systemic sclerosis. Lung involvement in systemic sclerosis may be due in part to a functional abnormality of the pulmonary vasculature. To investigate the possible role of a pulmonary vasospastic process in this disorder, 21 non-smoking patients who had no evidence of cardiac disease or pulmonary hypertension were evaluated with pulmonary function tests prior to administration of nifedipine, 30 minutes after a single oral dose of nifedipine (20 mg), and after 4 weeks of treatment with nifedipine (10 mg 3 times daily). Treatment with nifedipine did not significantly change any of the pulmonary function values, except for the carbon monoxide diffusing capacity (DLCO). The linear trend between the individual DLCO values at baseline and their changes immediately following the initial 20-mg dose of nifedipine (r = -0.603, P = 0.02) and after 4 weeks of treatment (r = -0.636, P = 0.01) showed that the lower the DLCO value at baseline, the greater the improvement caused by nifedipine. These findings support the hypothesis of a potentially reversible pulmonary vasospasm in systemic sclerosis and suggest that nifedipine may be useful in the treatment of lung disease in these patients; however, further studies are needed. 
5	Emergency laparoscopy. Unnecessary abdominal explorations in severely injured patients can be reduced by employing emergent or urgent laparoscopy in blunt abdominal trauma and the obscured, acute abdominal cases. In 150 blunt abdominal trauma cases, a mini-laparoscopy was used in the emergency room or the intensive care unit without major complications. In 56%, the findings were negative. In 19%, the laparoscopic findings were corroborated by surgery. In 25%, a minimal to moderate hemoperitoneum was found and the laparoscopic impression dictated close observation. Unnecessary exploration was avoided except in one case. In the elderly high-risk patient with a poor history, abdominal examination can be noninformative. Laparoscopy can detect acute appendicitis or organ perforation. In the young female, appendicitis can be differentiated from pelvic inflammatory disease. Laparoscopy is more accurate and gives a larger latitude for decision-making than lavage. It can also be useful in the obscured problematic abdominal case. 
4	Subarachnoid hemorrhage caused by a fungal aneurysm of the vertebral artery as a complication of intracranial aneurysm clipping. Case report. Intracranial aneurysms are an uncommon manifestation of fungal infection. A case is described in which the formation of an aneurysm followed an intracranial intraoperative Aspergillus infection attributable to a long period of preoperative antibiotic medication and immunosuppressive therapy with steroids. 
3	Trends in systolic blood pressure, 24-hour sodium excretion, and stroke mortality in the elderly in Belgium. Data from six surveys of systolic blood pressure conducted in Belgium between 1967 and 1986 were analyzed. The mean ages of the six groups of 3,328 subjects ranged from 70 to 81 years. The prevalence of systolic blood pressure levels above 159 mm Hg decreased between 1967 and 1986 from 51% to 21% in men and 66% to 22% in women; severe hypertension (systolic blood pressure greater than 220 mm Hg) nearly disappeared. During the same period, body mass index increased 1.1 kg/m2 in men and was unchanged in women; mean systolic blood pressure decreased from 159 to 142 mm Hg in men and from 171 to 147 mm Hg in women; the proportion of subjects receiving treatment for hypertension increased from 10% to 36% in men and from 18% to 41% in women; and the mean standardized 24-hour sodium excretion decreased from 265 to 188 mmol in men and from 208 to 160 mmol in women. Systolic blood pressure levels were significantly and independently related to sodium excretion in the 1967 and 1972 studies. The decrease in systolic blood pressure in Belgium was influenced by the combined effects of more and better treatment for hypertension and a decrease in sodium intake. 
5	Comparison of the Goode T-tube with the Armstrong tube in children with chronic otitis media with effusion. Treatment of otitis media with effusion is focused on reaeration of the middle ear cavity. In achieving long-term aeration, the insertion of ventilation tubes that have a long duration of stay can be beneficial. The results are presented of a trial in which the Goode T-tube was compared with the Armstrong tube. Fifteen children were treated between 1981 and 1986 with a T-tube in one ear and a conventional tube in the other. The results are different with regard to duration of stay in the tympanic membrane. Re-insertions were necessary in 47 per cent in the Armstrong group and in 20 per cent in the T-tube group. Otorrhoea occurred in 20 per cent of the Armstrong and 13 per cent of the T-tube intubated ears. A persistent perforation was present in 6 per cent of the ears in both groups. It is concluded that the Goode T-tube is indicated primarily in cases when long-term ventilation is needed. 
2	Scleroderma esophagus. Scleroderma (systemic sclerosis) is a connective tissue disorder characterized by thickening and fibrosis of the skin and visceral involvement that may include the heart, lungs, kidneys, and gastrointestinal tract. At least 40-50% of patients with scleroderma experience esophageal symptoms such as heartburn and dysphagia, while up to 90% of patients have esophageal dysfunction on objective testing at some point in their disease. The disease results in smooth muscle dysfunction that causes esophageal aperistalsis and reduced lower esophageal sphincter pressures. Gastroesophageal reflux with poor acid clearance results with an increased incidence of complications such as peptic stricture and Barrett's esophagus. Aggressive medical therapy is necessary to prevent these and other complications of gastroesophageal reflux. 
4	Inflammatory abdominal aortic aneurysm masquerading as occlusion of the inferior vena cava. Inflammatory aneurysms are an uncommon disorder that represent between 5% and 10% of abdominal aortic aneurysms. Their presentation is often variable and may include pain and obstruction of adjacent anatomic structures. This report describes a 68-year-old man who sought treatment after insidious onset of progressive bilateral lower extremity edema over a 6-month period. Noninvasive studies were suggestive of bilateral iliac vein occlusion, and a venogram showed a nearly obstructed vena cava from external compression. A CT scan showed a thick-walled infrarenal abdominal aneurysm. At exploration an inflammatory abdominal aortic aneurysm was found. Because of the presence of dense inflammatory changes surrounding the aneurysm and extending into the pelvis, the surgical procedure of choice was an aortobifemoral bypass graft done with Dacron. The aneurysmal wall was debrided from the vena cava. His postoperative course was uneventful, his edema resolved, and follow-up noninvasive studies were normal. Postoperative venography showed resolution of the extrinsic compression of the vena cava. 
5	Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial patients Laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy. However its safety, efficacy, and morbidity have yet to be fully evaluated. During the first 6 months of 1990, we performed 100 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 8% (8 of 100 patients; 4 major, 4 minor). There were 81 women and 19 men, with a mean age of 46.1 years (range, 17 to 84 years). All patients had a preoperative history consistent with symptomatic biliary tract disease, and most had proved gallstones by sonography. This included four patients with acute cholecystitis. Mean operating time improved significantly from month 1 to month 6 (122 +/- 45.4 minutes versus 78.5 +/- 30 minutes, respectively), indicating a rapid learning curve. Mean hospital stay was 27.6 hours, reflecting a policy of overnight stay. Postoperative narcotic requirements were limited to oral or no medications in more than 70% of patients. A regular diet was tolerated by 83% of the patients by the morning following the procedure. Median time of return to full activity was 12.8 +/- 6.8 days after operation. In addition analysis of the hospital costs of these 100 cases demonstrates a modest cost advantage over standard open cholecystectomy (n = 58) (mean, $3620.25 +/- $1005.00 versus $4251.76 +/- $988.00). There was one minor bile duct injury requiring laparotomy and t-tube insertion, two postoperative bile collections, and one clinical diagnosis of a retained stone that passed spontaneously. Four patients required conversion to open cholecystectomy because of technical difficulties with the dissection. Although there is a significant learning curve, laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk. Laparoscopic cholecystectomy should be performed by surgeons who are trained in biliary surgery and knowledgeable in biliary anatomy, and, as with all operations, it should be performed with meticulous attention to technique. 
1	Nasal midline masses in infants and children. Dermoids, encephaloceles, and gliomas. Nasal dermoids, gliomas, and encephaloceles are uncommon congenital lesions that result from aberrant embryologic development. We have treated 46 children with these nasal lesions. In view of the potential intracranial connection, patients are at risk for intracranial infection, and early surgical correction is thus imperative. Neuroimaging studies may help to predict intracranial involvement. 
3	Physical and pharmacologic restraint of nursing home patients with dementia. Impact of specialized units This case-control study of 31 specialized dementia units and 32 traditional units in five states investigated use of physical and pharmacologic restraints among 625 patients with the diagnosis of dementia. Physical restraints were observed in use on 18.1% of dementia unit patients and on 51.6% of comparison unit patients who were out of bed during the day (adjusted odds ratio, 0.283;95% confidence interval, 0.129 to 0.619). Pharmacologic restraints were routinely given to 45.3% of dementia unit patients and 43.4% of comparison unit patients (adjusted odds ratio, 0.950; 95% confidence interval, 0.611 to 1.477). We used multivariate logistic regression to identify residence in a nonspecialized nursing home unit, nonambulatory status, transfer dependency, mental status impairment, hip fracture history, and a high nursing staff-to-patient ratio, which we found to be independent predictors of physical restraint use. Physically abusive behavior, severe mental status impairment, and frequent family visitation were found to be significant predictors of pharmacologic restraint use, while advanced patient age, large nursing home size, and patient nonambulatory status were protective against such use. These results support the conclusion that physical and pharmacologic restraint constitute separate treatment modalities with different risk factors for use, and indicate that specialized dementia units are successful in reducing the use of physical but not pharmacologic restraints. 
2	Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. Pearson's marrow-pancreas syndrome (McKusick No. 26056) is a fatal disorder of hitherto unknown etiology involving the hematopoietic system, exocrine pancreas, liver, and kidneys. The observation of high lactate/pyruvate molar ratios in plasma and abnormal oxidative phosphorylation in lymphocytes led us to postulate that Pearson's syndrome belongs to the group of mitochondrial cytopathies. Since rearrangements of the mitochondrial genome between direct DNA repeats were consistently found in all tissues tested, our results show that this disease is in fact a multisystem mitochondrial disorder, as suggested by the clinical course of the patients. Based on these observations, we would suggest giving consideration to the hypothesis of a defect of oxidative phosphorylation in elucidating the origin of other syndromes, especially those associated with an abnormal oxidoreduction status in plasma. 
5	Extramedullary hematopoiesis in the liver in sudden infant death syndrome. Liver extramedullary hematopoiesis was examined in 54 victims of sudden infant death syndrome and in 21 infants who died of other causes in an attempt to confirm Naeye's findings of increased extramedullary hematopoiesis in cases of sudden infant death syndrome. Our data showed greater extramedullary hematopoiesis in victims of sudden infant death syndrome (F = 23.52), supporting Naeye's hypothesis that victims of sudden infant death syndrome have suffered a subtle, chronic hypoxemic condition before death. 
2	Management of perineal wounds following abdominoperineal resection with inferior gluteal flaps. Our experience treating perineal wounds secondary to abdominoperineal resection, either for inflammatory bowel disease or cancer, is presented. A total of 16 patients were treated either on a delayed basis or at the same time as the abdominoperineal resection. All wounds were closed using the inferior gluteal myocutaneous flap. Fifteen of 16 patients have achieved healing, eight of whom had no complications. Only minor revisions or local wound care were required in the remaining patients, with only one patient failing to heal. Our results compare favorably with previous reports of treatment of this difficult problem. 
4	Deposits of crystalline material containing silicon in surgically excised human valves. Ninety-seven surgically excised natural cardiac valves were examined by scanning electron microscopy and x-ray energy spectroscopy to assess the occurrence of crystalline deposits that contain the element silicon. Valves examined included 33 mitral valves, 63 aortic valves, and 1 tricuspid valve. To reduce the possibility of surface contamination, the deep layers of some valves were examined after exposure by fracture of the valve. Crystalline material containing silicon was observed in the deep tissue. Such crystalline material was sometimes entwined within subendothelial fibers. Crystalline deposits that contained silicon were associated with 34 of 97 of these valves (35%). Among the 34 valves that showed silicon, 24 (71%) also showed microdeposits of calcific material. In view of evidence that silicon may participate in the calcification of bone, and is found in the intima of arteries, a role for this element in ectopic calcification of valves may exist. 
3	Lyme disease: neurologic and ophthalmic manifestations. Lyme disease is tick-borne infection which produces early and late manifestations in many organ systems. Prominent symptoms and signs occur in skin, heart, joints and nervous system. Many ocular and neuro-ophthalmic abnormalities recently have been attributed to Lyme disease, but some cases have not been well established as direct sequelae. This review of the contemporary state of knowledge about Lyme disease was undertaken so that more rigorous criteria can be applied in future diagnosis. 
4	Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome. We examined 61 patients an average of 9.6 years (range 5 to 18 years) after an episode of childhood hemolytic-uremic syndrome. Twenty-four (39%) had one or more abnormalities. Seven (11%) had proteinuria and six (10%) had low creatinine clearance as solitary abnormalities. Eight (13%) had both proteinuria and reduced creatinine clearance; three (5%) had a combination of hypertension, proteinuria, and low creatinine clearance. Abnormalities sometimes appeared after an interval of apparent recovery. Logistic regression analysis showed that duration of anuria was the best predictor of disease at follow-up. No patients who had anuria lasting longer than 8 days or oliguria exceeding 15 days escaped chronic disease. However, 45% of those with disease had no anuria, and a third had no oliguria. Physicians should therefore be cautious in assuming recovery from HUS on the basis of a single evaluation and should periodically evaluate patients for an extended period. 
1	Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma. 
5	Postoperative myocardial ischemia in patients undergoing coronary artery bypass graft surgery. S.P.I. Research Group. Cardiac morbidity and mortality after coronary artery bypass graft (CABG) surgery continue to be significant problems. To determine the prevalence, characteristics, and prognostic importance of postoperative myocardial ischemia after CABG surgery, the authors monitored 50 patients continuously for 10 perioperative days with the use of two-lead electrocardiography (ECG). ECG changes consistent with ischemia were defined as a reversible ST depression of 1 mm or greater or an elevation of 2 mm or greater from baseline, lasting at least 1 min. Baseline was adjusted for positional changes and temporal drift. All episodes were verified, with the use of the ECG monitor printout (ECG complexes), by two independent blinded investigators. Clinical care was not controlled by study protocol, and clinicians were unaware of the research data collected. Twenty-six of 50 patients (52%) had 207 episodes of perioperative ischemia (3,409 ischemic minutes). Postoperatively, ischemia developed in 48% of patients, compared with 12% preoperatively and 10% intraoperatively before bypass. Postoperative ischemia was most common in the early period (postoperative days [PODs] 0-2; 38% of patients), peaking during the first 2 h after revascularization, and less common during the late postoperative period (PODs 3-7; 24% of patients). Almost all (120 of 122; 98%) postoperative episodes (after tracheal extubation) were asymptomatic: only 9 of 70 (13%) early episodes were detected by clinical ECG monitoring. Postoperative ischemia did not appear to be related to acute changes in myocardial oxygen demand: only 39% of the postoperative episodes were preceded by a greater than 20% increase in heart rate. However, tachycardia persisted throughout the postoperative week (22-33% of all heart rates greater than 100 beats per min), and patients with postoperative ischemia (POD 0) more frequently had tachycardia (median 43% vs. 12% of the time; P less than 0.01). Five adverse cardiac outcomes occurred on the day of surgery; all five were preceded by postoperative ischemia, three by intraoperative ischemia before bypass, and none by preoperative ischemia. Patients with late postoperative ischemia did not have an adverse cardiac outcome. The authors conclude the following: 1) ischemia is more prevalent postoperatively than preoperatively or intraoperatively before bypass; 2) the incidence of postoperative ischemia peaks shortly after revascularization, during which time it is symptomatically silent, difficult to detect, and related to adverse cardiac outcome; 3) late postoperative ischemia also is silent, but it is less prevalent and not associated with in-hospital adverse cardiac outcome; and 4) a relationship between ischemia and persistently elevated postoperative heart rate may exist and warrants additional investigation. 
5	Effects of carotenoids in cellular and animal systems. It has been suggested that carotenoid pigments may function as chemopreventive agents for reducing the risk of cancer in humans. Part of this suggestion rests on epidemiological evidence, and part rests on work done in cellular and animal systems. In this article, the experimental evidence for carotenoid inhibition of mutagenicity, malignant transformation, tumor formation, and immunoenhancement is reviewed. Although a mechanism for these effects cannot yet be identified, it is clear that the overwhelming evidence in these systems would indicate that carotenoids exert an important influence in modulating the actions of carcinogens. 
3	Postauricular cerebellar encephalocoele secondary to chronic suppurative otitis media and mastoid surgery. Cerebellar herniation into the mastoid through the posterior aspect of the temporal bone as a result of chronic suppurative otitis media and mastoid surgery is a rare event. A case is reported in which such a hernia presented subcutaneously behind the pinna; its repair is discussed. 
3	Glossopharyngeal neuralgia associated with cardiac syncope: long term treatment with permanent pacing and carbamazepine. Glossopharyngeal neuralgia associated with cardiac syncope developed in a 53 year old man. Symptoms were controlled with temporary and permanent transvenous pacing and carbamazepine. 
1	Disseminated Kaposi's sarcoma not associated with HIV infection in a bisexual man. We report a 42-year-old white bisexual man with disseminated Kaposi's sarcoma limited to the skin and gastrointestinal tract. Results of several serum tests for human immunodeficiency virus (HIV) antibodies have been negative. The CD4/CD8 ratio has remained normal, and his Kaposi's sarcoma has had a benign clinical course during 30 months of follow-up. Similar reports of disseminated Kaposi's sarcoma with a benign clinical course in homosexual or bisexual men without demonstrable HIV infection are reviewed. Some cellular immune impairment that might be more prevalent in the homosexual population may be implicated in the pathogenesis of this type of Kaposi's sarcoma. 
5	Naloxone and spinal fluid drainage as adjuncts in the surgical treatment of thoracoabdominal and thoracic aneurysms. Forty-seven patients who were treated for thoracoabdominal or thoracic aneurysms over a 5 1/2-year period were analyzed for neurologic deficit risk. Patients were divided into two groups for analysis. Twenty-four patients, who were treated from January 1984 to December 1986, did not undergo spinal fluid drainage or naloxone administration (group A). Twenty-three patients, who were treated from January 1987 to August 1989, had spinal fluid drainage (group B); 12 patients in this group also received naloxone as an intravenous drip at 1 microgram/kg/hr for 48 hours after surgery. Permanent neurologic deficits occurred in seven (29%) group A patients but in only one (4%) group B patient, who did not receive naloxone (p less than 0.03). The first two group B patients to receive naloxone showed complete reversal of neurologic deficits on waking from anesthesia. This significant reduction in neurologic deficit was associated with an increased 1-year survival rate (72% in group A, 91% in group B). We conclude that the use of naloxone and spinal fluid drainage reduces the incidence of neurologic deficit that is associated with repair of thoracoabdominal and thoracic aortic aneurysms. This reduction in neurologic deficit is associated with improved survival in the long term. The observed reversal of postoperative neurologic deficits with naloxone implicates opiates as a major factor in the pathophysiology of spinal cord ischemia. 
5	The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival. 
5	Use of the diaphragm to reinforce anastomosis of the intestines. Use of a diaphragmatic flap to buttress and help secure persistent intestinal fistula is described. The potential for the use of muscle flaps in the management of recurrent intestinal fistula is presented. 
4	Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty. To assess the incidence and clinical significance of elevated total plasma creatine kinase (CK) and MB isoenzyme fraction after apparently successful coronary angioplasty, a prospective study of 272 consecutive elective procedures was undertaken. Total CK (normal less than 100 IU/liter) and CK MB isoenzyme (normal less than 4%) were measured immediately after successful completion of the procedure and every 6 h for 24 h. All nonelective procedures and results not fulfilling all American Heart Association/American College of Cardiology Task Force guideline criteria for a successful result were excluded from analysis. Of the 272 elective procedures, 249 (92%) were successfully; abnormally elevated CK or CK MB serum levels, or both, were found in 38 (15%) of the successful outcomes. Three patterns of abnormal enzymes were identified: 15 patients with CK greater than or equal to 200 IU/liter and CK MB greater than or equal to 5% (group 1), 4 patients with CK greater than or equal to 200 IU/litter and CK MB less than or equal to 4% (group 2) and 19 patients with CK less than 200 IU/liter and CK MB greater than or equal to 5% (group 3). The three groups were distinguishable by the nature of the complications causing the enzyme release (in particular, the etiology and clinical manifestations). There were significantly more clinically apparent events in group 1 than in the other groups (13 of 15 versus 11 of 23, p less than 0.01) and more events associated with persistent electrocardiographic changes (p = 0.05) and chest pain (p less than 0.05). However, no clinically important sequelae were recognizable in any group at hospital discharge. Thus, abnormal cardiac serum enzyme release after apparently successful coronary angioplasty is 1) relatively common; 2) has many possible causes, including both minor complications and early reversibility of impending major complications; and 3) results in no permanent clinical sequelae. 
1	Vestibular papillae of the vulva. Lack of evidence for human papillomavirus etiology. Vestibular papillae of the vulva are usually considered as anatomical variants of the vestibular mucosa. Clinically, however, they are quite often interpreted as condylomata acuminata and recent studies have suggested that they could be related to human papillomavirus infection. This prompted us to search for human papillomavirus DNA using the Southern blot hybridization technique, by analyzing biopsy specimens taken from 29 patients who presented with papillae of the vestibular mucosa. Human papillomavirus sequences were detected only in two (6.9%) cases. By the same technique, human papillomavirus sequences were detected in 24 (96%) of 25 vulvar warts used as the control specimens. Thus, it appears unlikely that vestibular papillae are related to human papillomavirus infection. They are usually distinguishable from condylomata acuminata by clinical examination alone. 
4	Bretylium tosylate versus lidocaine in experimental cardiac arrest Bretylium tosylate has been shown effective in the treatment of ventricular fibrillation and in the prevention of its recurrence. However, lidocaine is generally preferred because bretylium could have adverse hemodynamic effects related to its antiadrenergic action. To explore further the differences between these two antiarrhythmic agents, the authors compared the effects of bretylium, lidocaine, and saline on a standardized dog model of ventricular fibrillation followed by electromechanical dissociation (EMD). The protocol included three successive episodes of cardiac arrest in each animal. Three minutes before each episode of ventricular fibrillation, 5 mg/kg of bretylium tosylate (n = 11), 1 mg/kg of lidocaine (n = 9) or saline (n = 12) were administered blindly. There was no difference in the duration of cardiac arrest (bretylium, 8 min 18 sec; lidocaine, 7 min 54 sec; saline, 8 min 20 sec) or the total doses of epinephrine required to resuscitate the animals. Both bretylium and lidocaine appeared to preserve cardiac function 5 minutes after recovery, as stroke volume increased from 17.8 +/- 6.7 to 18.7 +/- 6.7 mL (NS) after bretylium and from 17.7 +/- 7.7 to 19.0 +/- 7.0 mL (NS) after lidocaine, but decreased from 19.0 +/- 5.3 to 14.6 +/- 6.0 mL (P less than .05) after saline. During the first 10 minutes of EMD, ventricular fibrillation or ventricular tachycardia recurred in 4 dogs treated with lidocaine, 3 dogs treated with saline, but no dog treated with bretylium (P less than .05 between bretylium and saline). 
1	Combined hepatic and vena caval resection with autogenous caval graft replacement. Right-sided and caudate hepatic lobectomy with resection of the retrohepatic vena cava were performed in a 34-year-old woman with recurrent adrenal carcinoma. The vena cava was replaced with a graft constructed from autogenous superficial femoral vein. Included herein is a review of the literature detailing the three previously reported cases of combined hepatic and caval resection; to our knowledge, there are no prior reports of the use of an autogenous vein graft in this setting. With surgical and anesthetic techniques, including total vascular exclusion of the liver and venovenous bypass, methods that were developed in large part through experience in liver transplantation, this type of surgery can be performed with a high rate of success. 
3	Participation of serotonergic mechanisms in the pathophysiology of experimental neoplastic spinal cord compression. We evaluated the role of serotonin (5-HT) in neoplastic cord compression in paraplegic rats harboring a thoracolumbar epidural tumor. We measured serotonin and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in the C-1 to C-7, T-1 to T-6, T-7 to T-12, and T-13 to L-3 spinal segments of tumor-free and tumor-bearing rats. In normal controls, a consistent rostral-to-caudal gradient for 5-HT and 5-HIAA was evident, but the 5-HIAA/5-HT ratio remained constant. In paralyzed rats, 5-HT levels were unchanged, but the 5-HIAA/5-HT ratio was elevated, especially in the compressed segments. Treatment with either dexamethasone or indomethacin delayed onset of paraplegia but had no effect on 5-HT metabolism. Blocking 5-HT receptors by cyproheptadine, evaluated 30 hours after onset of paralysis and treatment, resulted in a reduction in the high water content, vascular permeability, and prostaglandin E2 synthesis in the compressed cord. Early administration of cyproheptadine effectively delayed the onset of paraplegia. These data indicate that receptor-activated serotonergic mechanisms participate in the disruption of the blood-spinal cord barrier and that these effects can be manipulated pharmacologically. 
5	Treatment of chronic facial palsy by transplantation of the neurovascularized free rectus abdominis muscle. We performed neurovascularized free rectus abdominis muscle transplantations in two patients with chronic facial palsy. In one patient, the postoperative course was uneventful, but the patient died from rupture of esophageal varices. In the other patient, both morphologic and functional results were satisfactory. Therefore, the rectus abdominis muscle is considered to be a suitable donor for muscle transplantation for the treatment of chronic facial palsy. The rectus abdominis muscle is advantageous in that (1) simultaneous operations by two teams are possible with the patient in the supine position, (2) it is supplied by long nerves and long and large vessels, (3) it is flat and consists of segments with appropriate lengths, (4) the force and distance of contraction are appropriate, and (5) the tendinous intersections are suitable for anchoring sutures. 
4	Percutaneous coronary excimer laser-assisted balloon angioplasty: initial clinical and quantitative angiographic results in 50 patients. The initial clinical experience and quantitative angiographic results of percutaneous coronary excimer laser-assisted balloon angioplasty are described for 55 lesions in 50 patients. With use of a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% reduction in absolute percent diameter stenosis) was achieved in 41 (75%) of 55 lesions, with 100% subsequent balloon angioplasty success (less than 50% residual stenosis). By quantitative digital caliper technique, the percent diameter stenosis (mean +/- SE) was reduced from 81 +/- 1% to 50 +/- 3% after excimer laser angioplasty (p less than 0.001) and to 20 +/- 1% after balloon angioplasty (p less than 0.001); minimal luminal diameter increased from 0.56 +/- 0.04 to 1.46 +/- 0.08 mm (p less than 0.001) and 2.03 +/- 0.07 mm (p less than 0.001), respectively. By videodensitometric techniques, the percent area stenosis decreased from 86 +/- 2% to 54 +/- 3% after excimer angioplasty (p less than 0.001) and to 26 +/- 3% after balloon angioplasty (p less than 0.001). There were no perforations, need for emergency bypass surgery or deaths. The overall incidence of abrupt closure (3.6%), dissection (1.8%), embolization (1.8%), filling defect (6%), myocardial infarction (5.5%), side branch occlusion (3.6%) or spasm (3.6%) was infrequent and more related to subsequent balloon angioplasty than to the laser procedure. 
1	Surgical indication and significance of portal vein resection in biliary and pancreatic cancer. Tumor and vascular resection was carried out in 27 patients with biliary and pancreatic cancer. Vascular resection included resection and reconstruction of the both the portal vein and hepatic artery in two of the patients. Portal vein resection only was carried out in 23 patients, and resection of the side wall and plasty of the portal vein was carried out in the other two patients. The technical limit of portal vein resection without graft was 4 cm in the hepatic hilus and 7 cm after total pancreatectomy or pancreatoduodenectomy without grafts. On temporary occlusion of the portal vein between resection and reconstruction, simple occlusion was sufficient if it occurred within 30 minutes. In occlusion of more than 30 minutes, simultaneous occlusion of the superior mesenteric artery is better to prevent congestion of the intestine. If occlusion of more than 60 minutes is anticipated, a bypass between the superior mesenteric vein and the femoral vein with Anthron tube is recommended. The postoperative course was uneventful in 20 of the 27 patients. Two patients died within 1 month after surgery. The mortality rate for this aggressive surgery was 8.4%. Minor complications such as hydrothorax, small bile leakage, and localized abscess were observed but soon subsided in five patients. Fourteen of 27 patients survived or are alive after more than 1 year, and 9 of 14 patients survived or are alive after 2 years. Forty-seven percent of the patients who had no lymph node metastasis or peritumor lymph node metastasis without cancerous invasion of the portal vein intima survived more than 2 years. The longest length of survival of a patient with nonfunctioning islet cell carcinoma of the pancreatic head was 5 years 9 months. The longest surviving patient with ductal cell carcinoma of the pancreas is still living after 4 years. This approach is recommended in certain patients with vascular involvement but without lymph node metastasis or those patients with only peritumor lymph node involvement. Frozen section of mesenteric and paraaortic nodes should be standard practice before this aggressive resection. 
2	Gallstone clearance: a randomized study of extracorporeal shock wave lithotripsy and chemical dissolution Following extracorporeal shock wave lithotripsy it is not known whether gallstone fragments are cleared from the gallbladder without the use of oral dissolution therapy. To assess the efficacy of lithotripsy and dissolution therapy, alone or in combination, 35 patients were randomized to one of three treatment groups: lithotripsy alone, dissolution therapy alone or combined lithotripsy and dissolution therapy. All patients had symptomatic gallstones, functioning gallbladders and comparable stone profiles. Lithotripsy was administered using a piezoelectric lithotripter. Dissolution therapy consisted of combined bile acid and terpene. Clearance was assessed at 6 months using ultrasound and oral cholecystography. Patients with less than 50 per cent stone clearance at the end of 6 months were considered failures. The number of patients with total or partial clearance in the combined group (7/10) was significantly greater than those in the lithotripsy alone group (0/10, P less than 0.002). Gallstone clearance following lithotripsy appears to be dependent upon dissolution therapy. 
1	Treatment of squamous cell carcinoma of the anal canal. Progress in the prognosis of patients with squamous cell carcinoma of the anal canal has followed the use of multimodality therapy. From 1977 to 1985, 42 patients with squamous cell carcinoma of the anal canal were treated with mitomycin C (15 mg/m2) and 5-fluorouracil (750 mg/m2) on day 1, 5-FU (750 mg/m2/d) alone on days 2 to 5, and radiation therapy (3000 cGy) on days 7 to 28. They were evaluated 4 to 6 weeks after completion of the chemotherapy/radiation therapy protocol and received local excision, abdominoperineal resection, or both. Patient follow-up times ranged from 7 to 161 months, with a mean follow-up time of 71 months. Pathologic examination showed no residual carcinoma in 19 (45%) patients. The authors could not predict, based on clinical evaluation, which patients would have a complete response. Of the patients with a complete clinical response, 44% had tumor in the pathology specimen. Wide local excision was the most common initial operation (23 of 42 patients; 55%), with five of these patients subsequently requiring abdominoperineal resection. Anal continence was retained in 18 of 42 (43%) patients. Eleven patients experienced recurrent disease: six local recurrences, one distant, and four both local and distant. The 5-year overall survival rate was 82% and the 5-year disease-specific survival rate was 87%. There were no treatment related deaths. Preoperative tumor size was the only factor significantly related to survival. Contrary to other reports, tumor in the pathology specimen did not adversely affect long-term survival. Hence, patients should be treated after chemotherapy/radiation therapy with surgical therapy sufficient to control local disease. 
1	Chordoma: a 20-year clinicopathologic review of the experience at Groote Schuur Hospital, Cape Town. Eighteen chordomas (11 females and 7 males) were seen over a 20-year period; 61% of the tumors occurred in the sphenoid region. The youngest patient was 3 years old and had a family history of chordoma. Histologically, the tumors were divided into classical (epithelial) and chondroid variants, which in this series, had no effect on outcome. Follow-up on 12 patients ranged from 3 to 170 months, and they were treated with various combinations of surgery and radiotherapy. One patient was administered the neutron beam and died after 94 months. The mean survival of this series is 73.4 months, with a survival rate of 50% (6 out of 12 patients alive). Surgical resection offers the best chance of survival, but chordomas have a propensity to metastasize, hence have a poor prognosis. 
1	Characterization of astrocytomas, meningiomas, and pituitary adenomas by phosphorus magnetic resonance spectroscopy. Phosphorus magnetic resonance (MR) spectroscopy allows noninvasive measurement of phosphate-containing compounds and pH within brain cells. The authors obtained localized phosphorus MR spectra from 10 normal brains, four low-grade astrocytomas, six glioblastomas, four meningiomas, and three pituitary adenomas and found differences in the spectra of each tumor type. Compared to normal brain, the spectra from low-grade astrocytomas showed a significant reduction of the phosphodiester (PDE) peak. Glioblastomas were characterized by a significant reduction of the PDE peak, elevation of the phosphomonoester (PME) peak, and a relatively alkaline intracellular pH. The spectra from meningiomas and pituitary adenomas were markedly different from the glial tumors. Meningiomas showed significant reductions in phosphocreatine, PDE, and inorganic phosphate, as well as a relatively alkaline pH. Pituitary adenomas resembled meningiomas, but had a much higher PME peak. Although the number of tumors studied was small, there appears to be a characteristic spectrum associated with these different tumor types. The present findings can be useful in the preoperative identification of these tumors and in furthering understanding of their growth and metabolism in vivo. 
5	Effect of closing dead space on incidence of seroma after mastectomy. Seromas are a significant cause of morbidity after modified radical mastectomy. The effect of closing dead space by suturing skin flaps to underlying muscle combined with early removal (48 hours postoperatively) of closed suction drains on formation of the seroma was evaluated prospectively in 37 patients. Thirty-three underwent modified radical mastectomy for invasive carcinoma while four underwent total mastectomy with a level 1 axillary dissection for multifocal intraductal carcinoma. Seromas occurred in three, all were minor, two required one aspiration only and one required two aspirations. Two were seromas of the lower flap while one was an axillary seroma. Except for one patient who had a wound hematoma develop, no other instances of morbidity were noted. Closing dead space by suturing skin flaps to underlying muscle combined with early removal of closed suction drains is associated with a low incidence of seroma formation after mastectomy. Use of this technique has important economic and clinical implications for patients who had mastectomy. 
5	Reoperation for myocardial revascularization using the internal mammary artery. From October 1984 up to February 1989, 40 patients had "redo" myocardial revascularizations using one or both internal mammary arteries (IMA) in over 1000 cases operated upon in our Department for coronary bypass grafts. Thirty-one patients had a further operation for unstable angina difficult to control with drugs. Mean interval of recurrence of angina after previous surgery was 48.5 months for all the cases, but the mean interval before the second bypass operation was 68 months. Severe disease of previous vein grafts was the reason for surgery in 25 patients and progressive atherosclerosis in native coronary arteries in 15 patients. Twenty-one patients had a single mammary artery; both mammary arteries were used in 19. Two cases had endarterectomy on left anterior descending (LAD). Four patients had peroperative acute myocardial infarction (AMI), 3 a low cardiac output syndrome, postoperative bleeding occurred in 3 cases and wound infection in one case. An intraaortic balloon pump was used preoperatively in one case and coming off bypass in two others. One patient died on the second day postoperatively from cardiac arrest following bilateral pneumothorax. There were no late deaths. At a mean follow-up of 20.5 months, 28 patients are free of symptoms but 11 are complaining of angina, 5 during exercise and 6 at rest. An exercise test was positive in 8 patients. 
4	Frequency of myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass grafting. The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium-111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium-111 antimyosin uptake was present in 19 of 23 patients (82%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited ST-segment changes. No good relation was found among indium-111 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG. 
3	Cerebral infarction and release of platelet thromboxane after subarachnoid hemorrhage. Platelet aggregation induced by adenosine diphosphate and the release of thromboxane B2 were studied in 68 patients with subarachnoid hemorrhage during the second week after the hemorrhage, when delayed ischemic deterioration most often occurs. Follow-up computed tomographic scans were performed later than 1 month after subarachnoid hemorrhage to reveal permanent hypodense areas consistent with cerebral infarction. Occurrence of hypodense lesions on the follow-up computed tomographic scan was significantly associated with the presence of delayed ischemic deterioration (DID) (P less than 0.01). Patients with subcortical or cortical cerebral infarctions due to DID released more platelet thromboxane B2 than those with no evidence of a hypodense lesion on the computed tomographic scan (P less than 0.05). Hypodense areas caused by an intracerebral hematoma or small, deep-seated infarcts due to DID were not associated with significantly elevated release of thromboxane B2, but the lacunar type infarcts were associated with increased aggregation of platelets. The results suggest that augmented platelet function may be involved in the pathogenesis of cerebral infarction due to DID. 
5	Acute lead poisoning in nursing home and psychiatric patients from the ingestion of lead-based ceramic glazes. To our knowledge, acute inorganic lead poisoning from single ingestions of lead compounds has been only rarely reported. During a 14-month period, we were contacted regarding eight instances of acute ingestions of liquid lead-based ceramic glazes by mentally impaired residents of nursing homes or psychiatric facilities participating in ceramic arts programs. While some ingestions did not cause toxic effects, some patients developed acute lead poisoning characterized by abdominal pain, anemia, and basophilic stippling of red blood cells. In the blood of several patients, lead concentrations were far above normal (4 to 9.5 mumol/L). Urinary lead excretions were tremendously elevated during chelation therapy, with one patient excreting 535.9 mumol/L of lead during a 6-day period, the largest lead excretion ever reported in a patient suffering from acute lead poisoning, to our knowledge. All patients recovered following supportive care and appropriate use of chelating agents. Lead-based glazes are commonly found in nursing homes and psychiatric facilities. We suspect that acute or chronic lead poisoning from the ingestion(s) of lead-based ceramic glazes may be an unrecognized but not uncommon problem among such residents. We urge physicians to take ingestions of lead-based glazes seriously and to consider the diagnosis of lead poisoning in nursing home and psychiatric patients who have participated in ceramic crafts programs. 
5	Ventriculoperitoneal shunt malfunction during pregnancy. Many women with cerebrospinal fluid shunts are now reaching reproductive age. Shunt malfunction may occur during pregnancy, and management requires a well-planned, combined neurosurgical and obstetrical approach. We present a case of ventriculoperitoneal shunt obstruction manifesting during the third trimester managed successfully in a conservative fashion. The literature on ventriculoperitoneal shunt malfunction during pregnancy is reviewed. 
5	Myocardial preservation using lidocaine blood cardioplegia. Prevention of ventricular fibrillation after aortic unclamping using lidocaine hydrochloride as an additive to cold potassium blood cardioplegia was studied prospectively in 46 patients undergoing elective myocardial revascularization. Patients were similar with respect to age, ventricular function, severity of coronary artery disease, cross-clamp time, completeness of revascularization, frequency of internal thoracic artery grafting, systemic temperature at the time of cross-clamp removal, and mean infusate volume and temperature. Patients receiving lidocaine blood cardioplegia (group 1, 23 patients) had a significant reduction in the incidence of ventricular fibrillation (22% versus 74%; p less than 0.0005) and in the mean number of cardioversion attempts required to defibrillate the heart (0.5 +/- 1.3 versus 1.9 +/- 0.97; p less than 0.0005) after cross-clamp removal compared with controls (group 2, 23 patients). There were no differences between the two groups postoperatively with regard to cardiac enzyme release, hemodynamic measurements, or clinical outcome. Patients receiving lidocaine blood cardioplegia tended to have a lower incidence of new postoperative atrial fibrillation (9% versus 26%). Ventricular function was preserved equally in both groups. We conclude that lidocaine is a safe additive to potassium blood cardioplegia and significantly reduces the incidence of ventricular fibrillation after aortic unclamping. 
2	The freckle sign--an endoscopic feature of the cecum. Mucosal spots, or "freckles," surrounding the appendiceal orifice are an endoscopic feature of the cecum. These are clusters of 1 to 2 mm round or oval slightly raised spots, each with a pale center and an erythematous border. They correlate microscopically with subepithelial and submucosal lymphoid follicles. The freckling pattern, identified in about one third of colonoscopies, was seen best with the videoendoscope and was identified more commonly in patients with systemic illness. Recognition of mucosal freckling around the appendiceal orifice helps identify the cecum and may be useful in the evaluation of cecal and appendiceal pathology. 
3	Coronary bypass surgery: is the operation different today? Patients undergoing coronary bypass grafting have undergone an evolution in recent years. To document this change, we analyzed two groups of patients in 1981 (n = 1586) and 1987 (n = 1513) to document preoperative and postoperative variables important in determining immediate morbidity and mortality after isolated coronary bypass. Between 1981 and 1987, patients were found to be older (greater than or equal to 70 years, 8.7% versus 21.8%, p less than 0.0001), more often diabetic (15% versus 24%, p less than 0.0001), have a greater prevalence of triple vessel disease (14.5% versus 46.1%, p less than 0.0001), and have more left ventricular dysfunction (ejection fraction 0.60 +/- 14 versus 0.54 +/- 13, p less than 0.0001). To facilitate analysis and because of overlap between subgroups, we subdivided patients into three subgroups for statistical comparison of the years 1981 and 1987: subgroup I, no prior procedure (n = 1546 in 1981 and 1396 in 1987); subgroup II, optimal group (n = 503 in 1981 and 292 in 1987, and defined as no prior procedure, ejection fraction greater than or equal to 0.50 and age less than 65 years); subgroup III, patients having reoperations (n = 40 in 1981 and 117 in 1987). Internal mammary artery grafting was infrequently used in 1981 but was used in 72.1% in 1987. Major postoperative morbidity between the 2 years for the total population increased significantly: need for intraaortic balloon pumping, 1.4% versus 4.7%, p less than 0.0001; myocardial infarction 3.5% versus 5.5%, p less than 0.008; stroke, 1.4% versus 2.8%, p less than 0.008; and wound infection, 1.0% versus 3.0%, p less than 0.001. Wound infection (all types) in 1987 was increased sevenfold in patients having a perioperative myocardial infarction (0.7% versus 5%, p less than 0.0001). For young patients with good left ventricular function (subgroup II), there was no increase in these morbid events between 1981 and 1987. Hospital mortality in the total population increased significantly between 1981 and 1987 from 1.2% to 3.1% (p less than 0.0002), respectively. It was lowest for the patients in optimal condition (subgroup II) in both years, 0.8% versus 1.1%, and highest for reoperative patients, 5.3% versus 4.3%. In 1981, 58% of patients (503/870) were in the optimal group compared with 35% (292/828) in 1987 (p less than 0.0001). The last six years have seen a progressive trend in surgically treating older, sicker patients who have more complex disease, with a significant reduction in the best candidate group.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	The headache-specific locus of control scale: adaptation to recurrent headaches. This paper describes the development, psychometric properties, and construct and incremental validity of a Headache-Specific Locus of Control Scale (HSLC). The HSLC is a 33 item scale designed specifically for recurrent headache sufferers. It assesses the individual's perceptions that headache problems and headache relief are determined primarily by: the individual's behavior (Internal factors), Health Care Professionals, or Chance factors. The psychometric properties of the HSLC were satisfactory. Among our findings were that: (1) the belief that headache problems and relief are determined by chance factors was associated with higher levels of depression, physical complaints, reliance on maladaptive pain coping strategies (p less than .001), and greater headache-related disability (p less than .01); (2) the belief that headache problems and relief are influenced primarily by the ministrations of health care professionals was associated with higher levels of medication use (p less than .01) and preference for medical treatment (p less than .001); and (3) the belief that headache problems are determined by the individual's responses and behaviors was associated with a preference for self-regulation treatment (p less than .01). These findings suggest adaptation to headache problems is influenced not only by the frequency and severity of the headache episodes, but by locus of control beliefs. The assessment of locus of control beliefs may provide useful information not typically obtained from standard medical evaluations. 
2	Renal scintigraphy in the diagnosis and surgical management of a patient with caliceal colic: a case report. A patient with persistent renal colic and a caliceal stone is presented. Furosemide renography, commonly used to differentiate functional stasis from mechanical obstruction of an entire kidney or duplicated collecting system, can make this determination at the caliceal level. As in this case such determination can affect clinical management of the patient. 
4	Vagal schwannoma associated with syncopal attacks and postural hypotension: a case report. A case of vagal schwannoma in the cerebellomedullary angle is reported. Preoperatively, the patient had paroxysmal episodes of postural hypotension with syncope. After total removal of the vagal tumor, her systemic blood pressure returned to normal. 
4	Effect of beta-adrenergic blocking agents on the circadian occurrence of ischemic cardiovascular events. Clinical observations suggest that beta-adrenergic blocking agents can modify the circadian occurrence of a variety of ischemic events. Morning awakening is associated with a rapid increase in blood pressure and pulse, serum catecholamine content and platelet activation, at a time of decreased blood thrombolytic activity. Beta-adrenergic blocking agents have the potential to modify many of these events. Current data indicate that these agents modify blood pressure and pulse, but do not prevent their early morning increase. In addition, beta-adrenergic blocking agents decrease ventricular ectopy and its circadian variation. Recent studies in humans indicate, however, that metoprolol does not affect the circadian increase in platelet activity or serum catecholamines. The specific mechanism by which beta blockers affect the circadian occurrence of ischemic events remains uncertain. 
5	Time course and prognostic significance of serial signal-averaged electrocardiograms after a first acute myocardial infarction. The prognostic significance of serial signal-averaged electrocardiograms recorded during the first 3 days (period 1), in the second week (period 2) after a first acute myocardial infarction (AMI) and 6 months later (period 3) was prospectively assessed in 190 patients. No patients were treated with thrombolytic therapy. Patients with conduction disturbances were excluded. Mean age of the 190 patients was 57 years (range 34 to 74) and mean left ventricular ejection fraction was 40 + 6% (range 12 to 70). Eighty-four patients had an anterior wall AMI and the remaining 106 patients an inferior wall AMI. After a mean follow-up of 24 months, 16 patients developed sustained symptomatic monomorphic ventricular tachycardia, 7 patients were resuscitated from an episode of ventricular fibrillation, and 10 patients died suddenly. Multivariate regression analysis using continuous variables showed that the strongest predictor of sustained ventricular tachycardia and ventricular fibrillation was the left ventricular ejection fraction (p less than 0.0001) followed by the duration of QRS complex on the signal-averaged electrocardiogram recorded during the first 3 days of AMI (p less than 0.0005). Sudden death was only predicted by left ventricular ejection fraction (p less than 0.02). 
5	Doppler echocardiographic assessment of the St. Jude Medical prosthetic valve in the aortic position using the continuity equation. To test whether the continuity equation can be applied to the noninvasive assessment of prosthetic aortic valve function, Doppler echocardiography was performed in 67 patients (mean age, 58 +/- 14 years) within 10 +/- 6 days after valve replacement with St. Jude Medical valves. All patients were clinically stable and without evidence of valve dysfunction. Valve size ranged from 19 to 31 mm, and ejection fraction ranged from 30% to 75%. With the parasternal long-axis view, the left ventricular outflow diameter measured just proximal to the prosthetic valve correlated well with valve size (r = 0.92). Doppler-derived maximal gradients ranged from 9 to 71 mm Hg. Effective prosthetic aortic valve area by the continuity equation ranged between 0.73 cm2 for a 19-mm valve and 4.23 cm2 for a 31-mm valve. With analysis of variance, effective orifice area differentiated various valve sizes (p less than 10(-14)) better than did gradients alone (p = 0.003) and correlated better with actual valve orifice area (r = 0.83 versus - 0.40). A Doppler velocity index, the ratio of peak velocity in the left ventricular outflow to that of the aortic jet, averaged 0.41 +/- 0.09 and was less dependent on valve size (r = 0.43). Thus, the continuity equation can be applied to the assessment of prosthetic St. Jude valves in the aortic position. By accounting for flow through the valve, it provides an improved assessment over the sole use of gradients in the evaluation of prosthetic valve function. 
1	AIDS-associated polyclonal lymphoma: identification of a new HIV-associated disease process. High-grade non-Hodgkins B-cell lymphoma is one of the principle malignancies that occurs in individuals infected with the human immunodeficiency virus (HIV-1). Immunoblastic lymphomas that arise in immunosuppressed transplant patients have been described as both monoclonal and polyclonal, and occur in association with Epstein-Barr virus (EBV) infection. To test whether polyclonal lymphoma occurred in patients with AIDS we studied tumors from multiple sites in three patients who died with widespread AIDS-associated large cell or large cell immunoblastic lymphoma. All biopsy specimens contained invasive lymphoma. Tumor cells were mature IgM-positive immunoblasts by immunohistochemical analysis, with the same B-cell phenotype observed in all tumor sites. Only a minority of sites from all patients analyzed were monoclonal as measured by immunoglobulin gene rearrangements, with one case having several foci of monoclonal disease with other histologically identical metastases showing no evidence of monoclonal proliferation. Similar to the transplant-associated polyclonal B-cell proliferations. EBV gene sequences were present in multiple sites from one autopsy. In the other two autopsies, polyclonal B-cell proliferations occurred in the absence of EBV involvement except at one site, where a minor clone of EBV-infected cells was found. In contrast to HIV-associated Burkitt's lymphoma, no c-myc rearrangements were found at any site. These studies describe the occurrence of polyclonal lymphoma in AIDS and suggest that EBV-negative polyclonal lymphoma may be a distinct disease entity unique to HIV-infected individuals. 
4	Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: results of 24-hour ambulatory blood pressure monitoring. PURPOSE: This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients. PATIENTS AND METHODS: A randomized, open-label, parallel controlled trial was conducted. After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design. The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline. Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments. Labetalol demonstrated a significantly greater reduction (p less than 0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period. Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart rate (p less than 0.05) more than enalapril. The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p less than 0.01). The two treatments were equally well tolerated. CONCLUSIONS: The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day. 
5	Evaluating hematuria in children. Where to start and how to proceed. Bleeding from somewhere along the urinary tract is not unusual in children. Of the many causes, systemic infection and trauma are among the most common. History taking and physical examination should be careful and complete, because the results obtained help direct the laboratory evaluation. Diagnostic testing always begins with urinalysis but may progress to intravenous urography, voiding cystourethrography, endoscopic procedures in the upper and lower urinary tract, sonography, arteriography, or renal biopsy. Some cases remain unexplained and require follow-up to assess renal function. 
5	Experience with photocoagulation in Behcet's disease. Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behcet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others. 
2	Effects of aging on the swallowing mechanism. Normal swallow involves a number of closely coordinated neuromuscular events. Investigators have identified some small temporal changes in the swallow of older adults as compared with young adults. Further research is needed to define completely the primary effects of aging on deglutition. Many medical conditions that commonly affect the elderly can cause dysphagia. These are discussed in terms of their effects on swallow physiology. Diagnosis and treatment of dysphagia in the elderly should be pursued as aggressively as in the younger adult. 
5	Neurologic assessment. Neurologic nursing assessment requires the knowledge of anatomic and physiologic principles as well as the mastery of complex assessment skills. The nurse who is often the first and most consistent health team member interacting with clients may provide the key to the early recognition, prevention, and treatment of neurologic problems. The nurse, as the dynamic member of the health team, may then be the first line of defense in initiating cost-effective and perhaps life-saving measures in neurologically impaired clients. 
1	Bronchial anomaly of the right upper lobe. This case report presents a rare anomaly of right upper lobe bronchial anatomy. During routine right upper lobe resection for carcinoma, a common right upper and middle lobe bronchus was found. The resection was completed as a right upper and middle bilobectomy. Knowledge of this uncommon variant was beneficial in performing the pulmonary resection. A review of the literature is presented. 
4	Therapeutic cardiac catheterization in children Cardiac catheterization, once the mainstay of diagnosis in children with congenital heart disease, has become a therapeutic modality for many conditions. Balloon dilatation can now open stenotic valves and vessels, coils and umbrellas can now close unwanted communications, and emboli can be withdrawn without surgical intervention. 
5	Recovery from vegetative state of six months' duration associated with Sinemet (levodopa/carbidopa). Certain pharmacologic interventions may improve outcome for brain injury in animals and humans. Medications affecting the dopaminergic pathway appear to be important. We present the case of a 24-year-old man with traumatic brain injury who remained unresponsive to commands and unchanged for six months despite periodic aggressive therapy. Within days of beginning Sinemet (levodopa/carbidopa), the patient became conversant and responsive. The reported low likelihood of spontaneous recovery of cognition in patients who are vegetative for six months suggests that Sinemet was responsible for this patient's recovery. In this case, the relatively small risk of side effects from Sinemet was greatly outweighed by the change in functional outcome. 
1	The significance of low-grade prostate cancer on needle biopsy. A radical prostatectomy study of tumor grade, volume, and stage of the biopsied and multifocal tumor. Twenty-one cases showing only low Gleason grade prostate carcinoma on needle biopsy were identified. In 15 cases radical prostatectomy was performed with the entire prostate embedded for thorough evaluation of grade, volume, and stage of tumor at the needle biopsy site as well as of multifocal tumor. Eight specimens had solitary low grade and low volume tumor, with only one of these cases showing minimal capsular penetration and the others confined to the prostate. Four cases had low-grade tumor at the biopsy site, yet multifocal higher grade tumor. All of these tumor nodules were low volume and confined to the prostate. In three cases there was both low-grade and high-grade tumor in the nodule sampled by needle biopsy. In two of these cases the tumor was large and in the third it was small but mostly higher grade, with two of these cases showing capsular penetration. Although transrectal ultrasound and repeat needle biopsy would most likely have identified either the tumors' large size or high-grade component in these latter three cases, it is unlikely that these techniques would have identified the cases of multifocal higher grade tumor because of their relatively small size. Furthermore, preoperative serum prostate specific antigen levels and clinical stage failed to distinguish those cases with higher grade tumor. Because of the difficulty in identifying these areas of high-grade tumor preoperatively, it is uncertain whether expectant therapy could be recommended even for patients with very low-grade cancer on needle biopsy. 
1	Lymph nodes in incipient adult T-cell leukemia-lymphoma with Hodgkin's disease-like histologic features. Lymph nodes were examined from four patients with incipient adult T-cell leukemia-lymphoma (ATLL) who had mild lymphadenopathy, fatigue, no or a few atypical lymphocytes in their peripheral blood, and integrated proviral human T-cell lymphotrophic virus type I (HTLV-I) DNA in the nodes. The HTLV-I DNA was detected by southern blot analysis and/or polymerase chain reaction in the lymph nodes of all cases. The nodal architecture was preserved. Some scattered or aggregated highly lobular, cerebriform, or Reed-Sternberg-like giant cells were observed, with occasional mitoses and diffuse infiltration of small to medium-sized lymphocytes, with no or minimal nuclear abnormalities in the enlarged paracortex. The giant cells were usually positive for Ki-1 and also for UCHL-1 and other T-cell markers but negative for Ber-H2. Rearrangement and/or deletion of T-cell receptors were found in three of four patients. All patients died within 2 years, with transformation to overt leukemia-lymphoma occurring in three patients, and pulmonary carcinoma in one. The incipient or prelymphomatous phase of ATLL should be differentiated from Hodgkin's disease because of the distinctly different prognoses of these two diseases. 
1	Long-term (5 to 20 years) Evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias. In the presence of aplastic anemia (AA), therapeutic choices should be determined while taking into account not only changes for immediate improvement, but also both the risks for late-occurring complications and the following quality of life. We report here data concerning a long-term clinical survey (5 to 18 years with a median of 12 years) including 156 nongrafted patients receiving androgen therapy; all patients were alive more than 5 years after diagnosis (40% of patients included at time of diagnosis in our multicentric analysis). Between the 5th and the 13th year follow-up, 21 patients died of various causes either related to AA or to its treatment: 12 of infection or hemorrhage secondary to pancytopenia (6 relapses and 6 that had never been improved; 2 with paroxysmal nocturnal hemoglobinuria [PNH]); 5 of leukemia; 1 of a non-Hodgkin's lymphoma; 2 of late side effects following transfusion (1 acquired immunodeficiency syndrome and 1 chronic B hepatitis); and a single case of myocardial infarction (the latter could possibly result of androgen therapy). Thirteen patients in total developed PNH (among which 10 had clinical symptoms including 2 deaths, and 3 exhibited only biologic abnormalities). Few long-term side effects of androgens could be noticed. Adult height was normal in patients treated during childhood and so was young women's fertility. No malignant hepatoma occurred. This survey allows the recording of late spontaneous hematologic improvement (between 5 and 10 years of evolution). This occurred in 50% of patients that had remained cytopenic 5 years after diagnosis. Although bone marrow stem cell concentration remained abnormal after 10 years of evolution. 85% of patients had a normal red blood cell count, 80% a normal polymorphonuclear count, and 66% a normal platelet count. All patients who did not show late complications had an excellent quality of life. 
5	Causes, diagnosis, and treatment of pharyngitis. Pharyngitis is a common disease of the respiratory tract that can be caused by several different viruses and bacterial organisms. Clinically speaking, the most important causative agent is group A streptococcus (Streptococcus pyogenes). Although rare, postpharyngitis complications arise as a result of disease caused almost exclusively by group A streptococcus. Because group A streptococcal pharyngitis usually responds well to antimicrobial treatment, it is important to diagnose it. Penicillin, erythromycin, and peroral first-generation cephalosporins have been documented to be effective. In addition to group A streptococcus, C. pneumoniae and M. pneumoniae have also been detected in patients with pharyngitis. The possibility of diagnosing these organisms is limited at the present. Clinical surveys are still needed, moreover, to evaluate the effect of antimicrobial treatment on the disease caused by these organisms. Although routine viral diagnostic methods do not help primary care physicians in treating patients with pharyngitis, information on bacteria and viruses in the immediate environment could prove to be of great help in daily clinical work. 
1	The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer The importance of the interval between methotrexate (MTX) and fluorouracil (5-FU) was studied in 168 patients with previously untreated, measurable, advanced colorectal cancer. They were randomized to receive MTX 200 mg/m2, followed by 5-FU 600 mg/m2 either 24 hours (arm A) or 1 hour (arm B) after MTX. All patients received leucovorin (LV) 24 hours after MTX, 10 mg/m2 orally every 6 hours for six doses. The regimen was repeated every 2 weeks, with 5-FU escalation as tolerated. Arm A was significantly better than arm B with respect to overall response rate (29% v 14.5%, P = .026), time to progression (TTP; median, 9.9 months v 5.9 months, P = .009), and survival (median, 15.3 months v 11.4 months, P = .003). Significant differences between arms were not found in response rate, median TTP, or median survival for the subgroup of patients with rectal primaries who comprised 20% of the patients in each arm. Significant factors prognostic for survival were performance status and number of metastases, as well as treatment. Age did not influence survival. Toxicity was similar in both arms and was primarily gastrointestinal. More mucositis was seen in arm A. There were four toxic deaths secondary to neutropenia and infection (one from arm A and three from arm B) and three other deaths (two from arm A and one from arm B) that were possibly drug-related. The combination of MTX with LV rescue and 5-FU is an active regimen in advanced colorectal cancer; its efficacy is increased in colon, but not rectal cancer, when the interval between MTX and 5-FU is long (24 hours) rather than short (1 hour). 
2	Medical treatment of esophageal achalasia. Double-blind crossover study with oral nifedipine, verapamil, and placebo Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia. 
1	A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer. The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit. 
5	Reference values for the Mini-Mental State Examination (MMSE) in octo- and nonagenarians The Mini-Mental State Examination (MMSE) was used in a population survey of all inhabitants of Leiden, the Netherlands, over 85 years (n = 1258). In this paper we report on 532 subjects without neurological or psychiatric disease. Results show that the median score and lowest quartile cut-off score remain high until the tenth decade (median score = 28, lowest quartile cut-off score = 26). Thus age, in itself, is not a major limitation in using the MMSE. In this study a comparatively low level of education (the majority had 6 to 7 years of education) did not affect the results on the MMSE in a negative way, nor did we find an association with the use of psychoactive drugs. 
5	Active vs passive rhythms as an explanation of bigeminal rhythm with similar P waves. We describe the criteria for differential diagnosis between 3:2 sinoatrial block from atrial bigeminy due to an ectopic focus in the sinus or parasinus zone. In the 3:2 sinoatrial block the RR interval of the basic rhythm is similar to the short R-R interval of the paired rhythm. In atrial bigeminy, the R-R interval of the basic rhythm is similar to the long R-R interval of the paired rhythm. 
3	Coccidioidomycosis during human immunodeficiency virus infection. A review of 77 patients. Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions. 
4	Flosequinan: a vasodilator with positive inotropic activity. Flosequinan is an oral arterial and venous vasodilator that is currently under investigation for the treatment of congestive heart failure. The effects of flosequinan on ventricular performance and myocardial contractility were studied in 10 patients with severe congestive heart failure during right and left cardiac catheterization. Sixty minutes after a 100 mg oral dose of flosequinan, the peak rate of rise in left ventricular pressure (dP/dt) increased from 940 +/- 180 to 1050 +/- 240 mm Hg/sec (p less than 0.05), while left ventricular end-diastolic pressure decreased from 32 +/- 5 to 26 +/- 8 mm Hg (p less than 0.05), and cardiac index increased (2.1 +/- 0.4 to 2.3 +/- 0.5 L/min/m2, (p less than 0.05). The mean pulmonary artery pressure and vascular resistance decreased from 40 +/- 8 to 33 +/- 12 mm Hg (p less than 0.05) and from 330 +/- 240 to 290 +/- 170 dyne-sec/cm5 (p less than 0.05), respectively. Heart rate, mean aortic pressure, right atrial pressure, systemic vascular resistance, and serum norepinephrine levels did not change significantly. The increase in left ventricular peak dP/dt that was concomitant with a decrease in left ventricular end-diastolic pressure, and no change in systemic arterial pressure or sympathetic tone, argue for a direct positive inotropic effect of flosequinan. 
3	Onset phase of spinal bupivacaine analgesia assessed quantitatively by laser stimulation. Analgesia was assessed quantitatively at various dermatomes (C7, T8, T10, T12, L1, L3, S1) for the first 30 min after subarachnoid administration of 0.5% bupivacaine 3.5 ml. Stimulation with 10 needles and laser stimulation could evoke pain in dermatomes with adequate analgesia to single needle stimulation. Analgesia was assessed by thresholds (sensory and pain) and by pain-related brain potentials (amplitude and latency) to laser stimulation. Little analgesia was found at T10, but it increased gradually towards caudal segments. The dermatome related to the site of the injection (L3) was not blocked to a greater extent than the surrounding dermatomes. Conduction time (the latency of the evoked brain potential) was increased relatively more from the S1 dermatome compared with L1. 
5	Interpleural analgesia after thoracotomy. We examined the effects of the following variables on interpleural analgesia after thoracotomy: addition of epinephrine to local anesthetic, thoracostomy drainage, two-catheter placement, and location of catheter tips. Twenty patients were randomized to have one catheter (paravertebral tip location) or two catheters (paravertebral and lateral thoracic wall tip locations). Interpleural catheters were sutured to the parietal pleura by the surgeon at time of wound closure. Patients were then randomly assigned to receive 20 mL of 0.5% bupivacaine with 1:200,000 epinephrine through the single catheter or 10 mL of 0.5% bupivacaine with or without 1:200,000 epinephrine through each of the two catheters while supine. Bupivacaine concentrations in whole blood and in thoracostomy drainage fluid were assayed by gas chromatography. Actual content of bupivacaine in the drainage fluid was calculated. Degree of analgesia was assessed by verbal numerical pain scores over the first 4 h and opioid demand thereafter. Addition of epinephrine to bupivacaine did not influence the degree of analgesia. Approximately 30%-40% of any administered dose of bupivacaine was lost via the thoracostomy tube over a 4-h period. There was no correlation between the true initial dose (100 mg minus thoracostomy drainage) and Cmax. Use of two catheters resulted in significantly less opioid requirements after an initial 8-h period. Failure to achieve adequate interpleural analgesia in postthoracotomy patients may be related to loss of anesthetic via thoracostomy drainage, presence of extravasated blood and tissue fluid in the pleural space, and possibly sequestration and channeling of flow of local anesthetic by restricted motion of an operated lung. 
4	Endocarditis due to ampicillin-resistant nontyphoid Salmonella: cure with a third-generation cephalosporin. A case of ampicillin-resistant salmonella bacteremia complicated by endocarditis in a 78-year-old man is presented. Previous rheumatic valvular heart disease and the lack of response to initial treatment with chloramphenicol prompted us to consider this diagnosis. There was a good clinical response after treatment with ceftriaxone alone and corresponding improvement on the echocardiogram. This case demonstrates the possible endovascular complications of salmonella bacteremia in elderly people and that endocarditis should be included among the invasive infections due to ampicillin-resistant Salmonella that could potentially be treated with the newer cephalosporins. 
5	Hypertension after operative correction of club-foot deformity. Severe hypertension occurred as a postoperative complication after correction of a club-foot deformity in four children (seven feet) who were between the ages of two and three years and had no history of hypertension. The hypertension subsided slowly after administration of antihypertensive medications or more rapidly after release of the correction that had been obtained operatively. 
5	Acute leukemia and related entities. Impact of new technology. Twenty-seven cases of acute leukemia and related entities were evaluated by morphologic examination, cytochemical study, terminal deoxynucleotidyltransferase study, immunophenotyping, cytogenetic analysis, ultrastructural cytochemical study, and gene rearrangement analysis to determine the impact on the determination of the French-American-British (FAB) classification and the definitive diagnosis. The definitive diagnosis contained prognostic, diagnostic, and treatment information beyond the FAB classification that affected the disease course and patient management. All diagnostic variables were evaluated in each case and were labeled essential, ambivalent, supportive, or noncontributory. Except for gene rearrangement analysis, all variables we studied contributed essential data to establish the definitive diagnosis. Ambivalent findings were rare but could be explained with the knowledge of the total data. All variables, except cytochemical study, whose results were almost always essential, contributed supportive data. Noncontributory data only occurred with cytogenetic analysis in cases that demonstrated normal karyotypes. The FAB classification was established in 20 (74%) of the cases by use of morphologic examination, cytochemical study, and terminal deoxynucleotidyltransferase study. With use of the same variables, however, the definitive diagnosis, whose determination required all data, was established in only 15 (55.5%) of the cases. The addition of immunophenotyping increased the definitive diagnosis to 25 (92.5%) of the cases. The use of ultrastructural myeloperoxidase and platelet peroxidase analysis enabled us to definitively diagnose the remaining two cases (27 cases [100%]). Cytogenetic analysis revealed four cases in which essential information was added to the diagnosis. However, because the cytogenetic information usually was not immediately available, the result did not affect the immediate diagnosis or treatment. Surprisingly, the gene rearrangement studies did not yield essential data in any case and in a few cases contributed ambivalent data. This finding should not exclude gene rearrangement analysis in selected cases; however, the data should always be interpreted in light of all clinical and laboratory findings. This study clearly demonstrates the importance of a multifaceted approach to the understanding of the acute leukemias and related entities and shows the impact of newer technologies on reaching a definitive diagnosis. 
1	Sphincter preservation in rectal cancer by local excision and postoperative radiation therapy. The authors report the preliminary results of 14 patients with localized, mobile, resectable rectal cancer treated with local excision and postoperative radiation therapy (RT). All had negative surgical resection margins and two received 5-fluorouracil (5-FU). The median follow-up was 29 months (4-43 months). The 3-year actuarial survival was 88%. The incidence of local failure was 7% (only site of failure) and 21% (component of failure). The incidence of local failure increased with T stage (T1, 0/3 [0%]; T2, 1/7 [14%]; and T3, 2/4 [50%]) and tumor size (greater than 3 cm, 33%, versus less than or equal to 3 cm, 0%). Three patients developed local failure at 6, 15, and 21 months. Three underwent a salvage abdominoperineal resection and were locally controlled at 2 and 28 months following salvage surgery. One patient underwent an abdominoperineal resection for a clinically presumed local failure; however, no tumor was found in the specimen. Therefore, the 13 patients who either were initially locally controlled or underwent salvage or nonsalvage surgery had no evidence of disease in the pelvis at the time of last follow-up. Local excision and postoperative RT may be an alternative to standard surgery in selected cases. However, additional follow-up and more experience are needed in order to determine if this approach will ultimately have local control and survival rates similar to those of a low anterior resection or an abdominoperineal resection. 
1	Status of sex steroid hormone receptors in large bowel cancer. To determine the potential role of sex steroid hormones in the development of colorectal tumors in humans, specific androgen (AR), estrogen (ER), and progesterone (PGR) receptors were investigated in normal mucosa (NM) and in tumor (T) paired biopsy specimens from 94 patients. Androgen receptors were detected in 98% and 96% of NM and T samples, ER in 91% and 83% of NM and T biopsy samples, whereas PGR were detected only in 14% and 10% of NM and T specimens, respectively. These incidences are independent of the sex and age of the patients. They are not related to tumor localization, histologic grade, or stages of Dukes' classification. Scatchard analysis of labeled ligand binding indicated the existence of one single class of high affinity binding sites; the calculated dissociation constant (Kd) was 1.7 +/- 0.6 10(-9) molar concentration (M) for 5 alpha-dihydrotestosterone (DHT) and 0.6 +/- 0.3 10(-9) M for estradiol (E2). These values were identical in NM and T tissue for both AR and ER. The binding capacity for DHT was 148 +/- 67 and 93 +/- 43 fmol/mg of cytosol protein in NM and T tissues, respectively (P less than 0.05). The ER content was lower and similar in NM and T biopsy specimens: 19 +/- 9 and 18 +/- 10 fmol/mg protein, respectively. The PGR content was 10 +/- 4 in NM versus 17.5 +/- 6 fmol/mg protein in T specimens. It is observed that the elevated AR in normal mucosa is not related to any known function for androgens in the digestive tract. The receptor pattern observed in tumors does not support the hypothesis previously raised in the case of chemically induced colonic tumors in rodents. 
1	The efficacy of comprehensive neck dissection with or without postoperative radiotherapy in nodal metastases of squamous cell carcinoma of the upper respiratory and digestive tracts. Neck recurrence-free curves corrected for local recurrence were compared for 494 patients who underwent 565 comprehensive neck dissections. In 42 dissections, no radicality could be obtained. Of the 523 histologically radical dissections, examination revealed tumor in 352 cases. Patients in whom three or more positive nodes or extranodal spread in one or more nodes were found received postoperative radiotherapy. In the histologically N0 group, the incidence of neck recurrence after 5 years was 3%; in the N+ group as a whole, it was 10%. Analysis of the influence of extranodal spread and the number of positive nodes showed that the group with one or two positive nodes without extranodal spread (that did not receive postoperative radiotherapy) did not statistically differ from the other groups. This suggests that the results of the group with one or two positive nodes without extranodal spread can be improved by postoperative radiotherapy. 
5	A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group BACKGROUND. Cytomegalovirus (CMV)-associated interstitial pneumonia is a major cause of death after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir in recipients of bone marrow transplants who had asymptomatic pulmonary CMV infection. We also sought to identify risk factors for the development of CMV interstitial pneumonia. METHODS. After bone marrow transplantation, 104 patients who had no evidence of respiratory disease underwent routine bronchoalveolar lavage on day 35. The 40 patients who had positive cultures for CMV were randomly assigned to either prophylactic ganciclovir or observation alone. Ganciclovir (5 mg per kilogram of body weight intravenously) was given twice daily for two weeks and then five times per week until day 120. RESULTS. Of the 20 culture-positive patients who received prophylactic ganciclovir, 5 (25 percent) died or had CMV pneumonia before day 120, as compared with 14 of the 20 culture-positive control patients (70 percent) who were not treated prophylactically (relative risk, 0.36; P = 0.01). No patient who received the full course of ganciclovir prophylaxis went on to have CMV interstitial pneumonia. Four patients treated with ganciclovir had maximal serum creatinine levels greater than or equal to 221 mumol per liter (2.5 mg per deciliter), as compared with none of the controls (P = 0.029). Of the 55 CMV-negative patients who could be evaluated, 12 (22 percent) had CMV pneumonia--a significantly lower rate than in the untreated CMV-positive control patients (relative risk, 0.33; P = 0.003). The strongest predictors of CMV pneumonia were a lavage-fluid culture that was positive for CMV and a CMV-positive blood culture, both from specimens obtained on day 35. CONCLUSION. In recipients of allogeneic bone marrow, asymptomatic CMV infection of the lung is a major risk factor for subsequent CMV interstitial pneumonia. Prophylactic ganciclovir is effective in preventing the development of CMV interstitial pneumonia in patients with asymptomatic infection. 
1	The prognostic value of modal deoxyribonucleic acid in low grade, low stage untreated prostate cancer. We selected for a prospective surveillance study 167 patients with untreated grades 1 and 2 prostate cancer. The tumors were classified regarding modal deoxyribonucleic acid value (ploidy) by flow cytometry, cytological grade by transrectal fine needle aspiration biopsy and local tumor stage. Of the patients 146 could be evaluated. Mean followup was 50 months. The initial ploidy was statistically correlated to cytological grade but not to initial local tumor stage, prostatic acid phosphatase activity or patient age. Initial ploidy and cytological grade had a prognostic value regarding local tumor progression when considered as single predictors and in combination. Two patients with diploid and 8 with nondiploid tumors initially had metastases during the surveillance. Five patients (1 with diploid and 4 with nondiploid disease) died of prostatic cancer. Modal deoxyribonucleic acid value and cytological grade were of prognostic value in untreated prostate cancer. 
5	Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects. Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients. 
1	Two distinct loci on the short arm of chromosome 16 are involved in myeloid leukemia. We report a case of acute nonlymphocytic leukemia (ANLL) M5 with the characteristic t(8;16)(p11;p13). The breakpoint in the short arm was regionally localized using nonradioactive in situ hybridization with a series of cosmids of chromosome 16. The results show that a difference exists between the breakpoint in chromosome 16(p13) in this t(8;16) and the breakpoint involved in the short arm in the characteristic inversion 16 (p13;q22)) that occurs in ANLL M4eo. Two different loci appear to be involved in these chromosomal rearrangements. 
1	Oral squamous cell carcinoma arising in a patient with long-standing lichen planus. A case report. The risk of malignant transformation of oral lichen planus remains a controversial point. Many previous reports have been discounted on the basis of inadequate information or lack of histologic confirmation of lichen planus. We report a well-documented case of long-standing cutaneous and oral lichen planus in which squamous cell carcinoma of the dorsal portion of the tongue occurred. There is an apparent difference in the sites of oral carcinomas in patients with lichen planus compared with the general population. This suggests that lichen planus increases the risk of oral cancer in affected sites. 
1	The pattern of intrathoracic Hodgkin's disease assessed by computed tomography. Computed tomography (CT) was used to define the sites of intrathoracic abnormality in Hodgkin's disease, determine a pattern of progression of disease in the thorax, and establish the place of this pattern of spread in the differential diagnosis of thoracic abnormalities. One hundred eight patients with newly diagnosed Hodgkin's disease were studied by chest CT. Seventy-seven patients had intrathoracic abnormalities. The pattern seen was one of contiguous spread from the anterior mediastinal/paratracheal area to the other mediastinal lymph node groups (aortopulmonary, subcarinal, posterior mediastinal, and internal mammary), to the hila, and then into the lung by extension or as discrete nodules. Involvement of the pleura, pericardium, or chest wall occurred only after the anterior mediastinal/paratracheal mass had enlarged to greater than 30% of the thoracic diameter. The probability that this pattern of contiguous lymph node spread occurred by chance alone was very small. Hodgkin's disease spreads from the anterior mediastinal/paratracheal area in a contiguous manner. Exceptions are unusual enough that when they occur, diagnoses other than Hodgkin's disease are more likely. 
4	Time course of hemodynamic responses to sodium in elderly hypertensive patients. Thirty-one patients with essential hypertension (81.6 +/- 6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SST. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SST patients on day 7 of the high sodium diet remained in the SST group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SST group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SST and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SST patients. 
4	A simple method to improve the accuracy of non-invasive ultrasound in selecting TIA patients for cerebral angiography. A prospective study is reported of the ability of B mode ultrasound imaging and continuous wave Doppler flow studies to detect different degrees of stenosis of the extracranial internal carotid artery (ICA) in 186 arteries in 99 patients with transient ischaemic attacks (TIA) and minor ischaemic stroke. A simple mathematical equation has been developed which combines the image and flow data to provide a single predictor of the degree of angiographic stenosis which has advantages over either ultrasonic modality used alone. The sensitivity and specificity of the predictive model in the detection of stenosis greater than or equal to 25% was 73% and 98%, of stenosis greater than or equal to 50% was 90% and 93%, of stenosis greater than or equal to 75%, 65% and 99% and occlusion 100% and 94% respectively. The principal clinical value of ultrasound screening is to spare patients with "non-significant" stenosis the risk of unnecessary angiography. Thus a simple measure of the Duplex screening tests' performance is the proportion of all strokes occurring as a complication of angiography that are avoided by changing the investigation policy from "angiograms for all carotid TIA and minor ischaemic stroke patients" to "angiograms for all patients with abnormal ultrasound results". If Duplex scanning were used to select patients most likely to have a significant abnormality on angiography, depending on the degree of stenosis to be detected, 52-85% of angiographic strokes might be avoided. If the predictive equation were used 62-88% of angiographic strokes might be avoided. 
4	Splenorenal arterial shunt in the treatment of renovascular hypertension. Approach by a lumbar-retroperitoneal incision. In a period of 16 years, 29 consecutive patients were operated on for a splenorenal arterial shunt through a lumbotomy incision and a retroperitoneal approach. There were 18 males and 11 females with a medium age of 42 years. All cases had uncontrollable and severe hypertension for an average medium time of 48 months, 11 patients had variable degrees of renal insufficiency. The diagnosis was made utilizing standard methods including in all cases angiography of the abdominal aorta, celiac axis and renal arteries. One patient died after the operation due to intestinal infarction, the remaining have been followed for a medium time of 50 months. All patients improved or cured their renal insufficiency. The hypertension was cured in 23, improved in 4 and failed in 1, this latter patient was successfully autotransplanted. A precise exposition of the surgical technique is presented with comments about their advantages and indications. A review of the literature in surgical experience with the technique of splenorenal arterial anastomosis has been done. 
1	Perioperative blood transfusion adversely affects prognosis of patients with stage I non-small-cell lung cancer. It has been speculated that blood transfusion might adversely affect prognosis in cancer patients by immunosuppression. To avoid the confounding affect of advanced disease, we tested this hypothesis in 117 patients with stage I non-small-cell lung cancer. Mean and median follow-up were 49.7 months and 47 months, respectively. Patients who died during the postoperative period were not included. Perioperative transfusion was defined as administration of whole blood or packed cells within 30 days of operation. The overall cumulative 5-year disease-free survival rate was 67%. In patients with transfusion, it was 53% and in patients without transfusion it was 81% (p = 0.0055). A multivariate analysis was performed that included patient age, race, sex, cell type, extent of operation (pneumonectomy versus lobectomy/segmentectomy), operative blood loss, admission hematocrit, discharge hematocrit, and the presence or absence of perioperative transfusion. The only variable that significantly correlated with 5-year disease-free survival was the presence or absence of perioperative transfusion (p = 0.0278), and this effect was not related to the number of transfusions. Retrospective analysis of long-term results of patients surviving curative operation for stage I lung cancer shows that any perioperative transfusion significantly worsens the patient's prognosis and suggests very strongly that this association is due to an adverse effect of the transfusion rather than the transfusion serving as a marker for another risk factor. 
3	Clinical features and treatment of obstructive sleep apnea. OBJECTIVE: To review the clinical features and treatment of obstructive sleep apnea (OSA). DATA SOURCE AND SELECTION: All articles on OSA published in French and English between 1970 and 1990 and indexed in Index Medicus were reviewed. Studies addressing the epidemiologic features and clinical aspects of OSA were selected, and special emphasis was given to articles reporting the effects of treatment on morbidity and mortality rates. MAIN RESULTS: OSA is characterized by episodes of upper airway obstruction during sleep that result in repetitive hypoxemia and sleep disruption. OSA leads to various neuropsychologic and cardiovascular complications, including daytime hypersomnolence, cognitive impairment, systemic and pulmonary hypertension and cardiac arrhythmias. There is suggestive evidence that the death rate among affected people is increased. The true incidence of OSA is unknown, but estimates have varied from 1% upwards among men. The current treatment with the greatest overall effectiveness and acceptability is nasal continuous positive airway pressure. CONCLUSION: This common, readily treatable disorder is associated with serious complications and therefore must be widely recognized by health professionals. 
4	Impact of orifice geometry on the shape of jets: an in vitro Doppler color flow study. To investigate the influence of orifice geometry on the three-dimensional shape of jets, an in vitro Doppler color flow study was performed. Jets were formed by discharging blood through round orifices and through orifices with major/minor axis ratios of 2:1, 3:1 and 5:1. These were repeated with orifice areas of 0.1, 0.3 and 0.5 cm2. For turbulent and laminar jets formed by these orifices, Doppler color flow images were obtained from two orthogonal scanning planes aligned with the major and minor orifice axes. Jet width was measured at 1 cm intervals from 0 to 5 cm from the orifice and used to calculate jet eccentricity (ratio of major to minor axis widths) and the rate of divergence of the jet walls. Jets were observed to diverge more rapidly along walls aligned with the orifice minor axis rather than along the major axis. This differential spreading led to the development of circular symmetry at a short distance from the orifice. Jet divergence (theta) occurred more rapidly for turbulent jets and for jets formed by larger orifices: theta (zero) = 0.80 + 6.3.A + 7.0.T + 0.47.E-OR (r = 95, p less than 0.0001, n = 48), where A is orifice area (cm2); T is 0 for laminar jets, 1 for turbulent jets and E-OR combines orifice eccentricity and scanning orientation, ranging from -5 for 5:1 orifices imaged along the major axis, 0 for circular orifices to 5 for 5:1 orifices imaged along the minor axis. Within the jet, eccentricity decayed approximately exponentially with distance from the orifice, more rapidly for turbulent jets, more slowly for the larger and more eccentric orifices. 
4	Usefulness of labetalol in chronic atrial fibrillation. Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation (AF) but often reduce exercise capacity. To investigate the advantage of labetalol--a unique beta blocker with alpha-blocking property--in chronic AF, 10 patients without underlying structural heart disease were studied with treadmill test, 12-minute walk and 24-hour ambulatory electrocardiographic monitoring. Patients were randomized and crossed over to receive 4 phases of treatment (placebo, digoxin, digoxin with half-dose labetalol, and full-dose labetalol). Exercise durations were 14.1 +/- 1.5, 14.2 +/- 1.5, 16.1 +/- 1.1 and 15.6 +/- 1.1 minutes, respectively, indicating that labetalol did not reduce exercise tolerance. Although digoxin had no advantage over placebo in controlling maximal heart rate (177 +/- 2 vs 175 +/- 3 beats/min), labetalol, both as monotherapy or as an adjunct to digoxin, was advantageous (156 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, and 154 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, respectively). The rate-pressure product was consistently lowered by labetalol at rest and during exercise. At peak exercise, the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 +/- 1300 to 24,100 +/- 2,000 mm Hg/min (p less than 0.01) and the maximal rate-pressure product was lowest with full-dose labetalol (22,300 +/- 1,600 mm Hg/min). During submaximal exercise on treadmill or during the 12-minute walk, the combination of labetalol and digoxin produced the best heart rate control, whereas labetalol monotherapy was comparable to digoxin therapy. 
2	Abnormal liver enzyme levels. Evaluation in asymptomatic patients. Chronic elevation of serum aminotransferase levels, even in the absence of symptoms, often reflects chronic hepatitis or other significant underlying liver disease. Patients with persistently abnormal alkaline phosphatase levels may have extrahepatic biliary tract disease or a chronic cholestatic disorder. Physicians can discover unsuspected liver disease without undue risk, expense, or inconvenience to the patient by means of the following: a carefully taken history and thorough physical examination, appropriate timing of follow-up blood tests, and timely referral for percutaneous liver biopsy or endoscopic retrograde cholangiopancreatography. 
4	Effect of coronary hyperemia on Emax and oxygen consumption in blood-perfused rabbit hearts. Energetic consequences of Gregg's phenomenon. To assess the relation between increases in contractile function and oxygen consumption (VO2) during increased coronary flow (Gregg's phenomenon), we measured the end-systolic pressure-volume relation and the relation between VO2 and left ventricular systolic pressure-volume area (PVA, a measure of total mechanical energy output) in blood-perfused, isovolumically contracting rabbit hearts during control and intracoronary adenosine infusion. During adenosine infusion at a constant perfusion pressure (93 +/- 11 mm Hg), coronary flow increased by 99 +/- 76% (p less than 0.01), and the slope of the end-systolic pressure-volume relation, Emax (ventricular contractility index), increased by 18 +/- 15% (p less than 0.01). When compared at the same left ventricular volume, PVA increased by 20 +/- 14% (p less than 0.01) and VO2 by 19 +/- 15% (p less than 0.01) with adenosine. The VO2-PVA relation was linear under each condition (both median r = 0.98). With increased coronary flow, the VO2-intercept of the VO2-PVA relation (unloaded VO2) increased by 22 +/- 18% (p less than 0.01) without a change in the slope; that is, a parallel upward shift was observed, indicating that the contractile efficiency (energy conversion efficiency of the contractile machinery) remained constant. These increases in Emax and unloaded VO2 were not eliminated by beta-adrenergic blockade with propranolol. We conclude that increased coronary flow with adenosine at a constant perfusion pressure augments both Emax and the nonmechanical energetic cost for excitation-contraction coupling and basal metabolism via nonadrenergic mechanisms, without changing contractile efficiency. 
3	Causes and consequences of blood pressure alterations in obstructive sleep apnea. The obstructive sleep apnea (OSA) syndrome has been considered to be a cause of both transient blood pressure elevations during sleep and sustained hypertension during the awake state. The purpose of this review was to examine critically the existing literature regarding (1) the blood pressure alterations associated with OSA, (2) causal mechanisms relating specific blood pressure alterations to OSA, and (3) potential consequences of the systemic circulatory abnormalities associated with OSA. Particular attention was directed at studies that assessed the prevalence of OSA in patients with hypertension and that examined the effects on blood pressure of treatment of OSA. We conclude that patients with OSA have abnormal sleep blood pressure patterns, manifested most frequently by apnea-associated blood pressure elevations. Confounding factors such as obesity and antihypertensive drug therapy, and conflicting evidence regarding changes in daytime blood pressure after therapy for OSA, make it premature to conclude that OSA and daytime hypertension are directly associated. Circumstantial evidence suggests that the blood pressure alterations that occur during sleep could contribute to the high cardiovascular morbidity in patients with OSA. Further research into the relationship between OSA and hypertension should improve the future care of patients with these conditions and enhance our understanding of cardiopulmonary pathophysiology. 
4	Severe hypotension due to intramyometrial injection of prostaglandin E2 Treatment of postpartum haemorrhage because of uterine atony with intramyometrial prostaglandin E2 1 mg, in an anaesthetised patient resulted in life-threatening hypotension. Anaesthetists should be aware of the potential cardiovascular side effects of prostaglandins. 
1	Constitutional symptoms in patients with germ cell neoplasms. A patient with a mediastinal germ cell neoplasm evidenced fever, weight loss, pruritus, and painful adenopathy on ingestion of alcohol. Retrospective review revealed that 9 percent of 104 patients with advanced germ cell neoplasm evidence constitutional symptoms at presentation. 
3	Impaired awareness of behavioral limitations after traumatic brain injury. Sixty-four traumatically brain injured patients were divided into three groups. Patients in Group I overestimated their behavioral competencies. Patients in Group II showed behavioral ratings similar to relatives' reports concerning behavioral competencies. Patients in Group III underestimated their behavioral competencies. Group I patients had greater evidence of bilateral and multiple-site lesions than group II and III patients. Speed of left-hand finger tapping was also worse in Group I than groups II and III, but other standard neuropsychologic test findings failed to separate the groups. Specific brain lesion sites were not related to group membership. Impaired awareness of behavioral limitations after traumatic brain injury may be related to neuropsychologic changes not measured by standard tests. Bilateral impairment of heteromodal cortex may be important to this phenomenon when it exists several months or years postinjury. 
1	A case of dyschondroplasia associated with brain stem glioma: diagnosis by stereotactic biopsy. We present a 24-year-old patient with multiple chondromas of both hands, the pelvis, the left leg, and an associated brain stem glioma. There was no evidence of hemangioma or dyschromia, and the condition was diagnosed as Ollier's disease, a special type of dyschondroplasia like Maffucci's syndrome and Kast's disease. An increased overall risk for development of malignant skeletal and nonskeletal tumors is associated with Maffucci's syndrome. The risk of malignant degeneration is lower in Ollier's disease. A glioma in the pons and the right lobe of the cerebellum was found in this patient. The literature describes an association with gliomas in only 12 cases of dyschondroplasia and an infratentorial localization in just one case. Signs of malignancy were histologically confirmed in 7 cases without significant preponderance of any one type. Our patient had a low-grade brain stem astrocytoma with fibrillar and gemistocytic components. A stereotactic serial biopsy made it possible to rule out malignant degeneration. Stereotactic brain tumor biopsy as a routine neurosurgical procedure is particularly valuable for deep space-occupying processes and forms the basis for therapy. In the present case, irradiation was not recommended. 
2	Factors influencing the development of metabolic bone disease in primary biliary cirrhosis. The prevalence, type, and factors that may influence the development of bone disease in primary biliary cirrhosis, have been investigated in 20 consecutive patients, who, in addition to liver function tests and mineral and vitamin D metabolism studies, were submitted to a transiliac bone biopsy after tetracycline double-labeling for quantitative histomorphometric examination. Intestinal calcium absorption was also assessed in 16 patients. Seven patients (35%) had reduced bone volume and were considered osteoporotic. Three also had bone mineralization impairment, but did not have criteria for osteomalacia. Bone formation was depressed in 15 patients, and bone resorption was low or normal in 19 cases. Eroded surfaces were reduced in all osteoporotic patients. Duration of primary biliary cirrhosis was significantly longer in patients with osteoporosis (6.3 +/- 0.6 yr) than in those without osteoporosis (2.6 +/- 0.6, p = 0.004). Moreover, osteoporosis was more prevalent in postmenopausal women, and in those who had intestinal calcium malabsorption, which was present in 80% of osteoporotic patients but in only 18% of nonosteoporotic patients (p = 0.03). Osteoporosis and mineralization bone impairment were unrelated to the severity of cholestasis. 25-Hydroxyvitamin D was significantly lower in those patients with intestinal calcium malabsorption. The results of this study indicate that osteodystrophy in primary biliary cirrhosis is characterized mainly by "low-turnover" osteoporosis, which is related to the duration of the liver disease, postmenopausal condition, and calcium malabsorption. 
3	Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine. 
1	Invasive migration of epidemic Kaposi's sarcoma cells in vitro. Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS). It is also found in elderly men where it is usually limited to the skin (classic KS). The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts. Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages, whereas fibroblasts did not invade either barrier. Epidemic KS cells in late passages did not show any invasive migration. Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells, whereas classic KS cells showed an increased migration through the type I collagen barrier. 
3	Steroid anabolic drugs and arterial complications in an athlete--a case history. Serious side effects and complications have been attributed to anabolic and androgenic steroids when used for medical reasons or when taken in sports in hopes of increasing strength and, hence, performance. The author presents a case of an athlete who experienced two metachronous arterial complications after taking these drugs: a cerebrovascular accident caused by a carotid artery thrombus that partially embolized to the brain and, later, a severe ischemic episode in a lower limb caused by a diffused distal arterial thrombosis. This patient represents the first reported case of vascular events in an otherwise healthy athlete taking androgens to increase his skeletal muscle mass. 
5	Angioplasty of coronary bifurcation stenoses: immediate and long-term results of the protecting branch technique. Percutaneous transluminal angioplasty (PTCA) of coronary stenoses involving major bifurcations carries a small but significant risk of side branch occlusion which can be avoided by simultaneously using multiple dilatation systems. Among 1,275 PTCA procedures performed between 1984 and 1988 in 1,035 consecutive patients, 42 double wire procedures were applied (4%) to protect and/or dilate major coronary side branches. A total of 80 coronary stenoses were attempted of which 76 were located on a bifurcation and 4 on other segments. In the first 11 patients (group A), 2 guiding catheters were used and PTCA of each vessel was successfully performed by means of separate double lumen over-the-wire balloon catheters. In the next 31 patients (group B), 2 guidewires were advanced through a single guiding catheter and PTCA was attempted using "Monorail" balloon catheters sequentially advanced over the wires. In group B, a successful PTCA was obtained in 29 patients (93%) but twisting of the wires hampered balloon progression in 5 cases, such that dilatation could only be performed by stepping back to a single wire technique. The procedure time in group B was significantly shorter than in group A: 144 +/- 30 versus 230 +/- 52 minutes (p = .01). Repeat angiography was performed in 35 out of 40 patients (87%) after a mean of 180 +/- 46 days following successful PTCA. Angiographic restenosis was present in 37% (24/65) of bifurcation segments which, in our experience, is not significantly different from the angiographic restenosis rate in less complex lesions (248/740; 34%; NS). 
1	Pancreatic involvement in human immunodeficiency virus infection. Involvement of the pancreas by human immunodeficiency virus (HIV) infection has not been adequately addressed and is the object of this review. I analyzed the English language literature, including single case reports of pancreatic involvement and larger series reporting detailed pathological findings of patients with HIV infection. Nonspecific pathological changes in the pancreas are frequently seen at autopsy of HIV-infected patients, but are not more common than in controls. Several types of infections (mainly cytomegalovirus, Cryptococcus neoformans, and Mycobacteria) and neoplasms (lymphoma and Kaposi's sarcoma) can involve the pancreas because they are usually disseminated. Although the serum amylase may be elevated, the patient remains asymptomatic. Occasional instances of severe and even fatal pancreatitis have been reported with HIV infections and attendant drug toxicity. Pentamidine has a predictable incidence of hypoglycemic episodes and 2',3'-dideoxyinosine provokes pancreatitis in a minority of treated patients. Such drug toxicity seems to deserve greater clinical concern than opportunistic infections or neoplasms. 
1	Oral or intravesical bacillus Calmette-Guerin immunoprophylaxis in bladder carcinoma. A total of 71 patients with superficial transitional cell carcinoma underwent transurethral resection of bladder tumor. All patients had stage pTa or pT1 transitional cell carcinoma or carcinoma in situ without other concurrent malignancies. The patients were assigned to 3 treatment groups: control group--transurethral resection discontinued within the study, oral bacillus Calmette-Guerin (BCG) group--transurethral resection of bladder tumor plus BCG (Moreau) and intravesical BCG group--transurethral resection of bladder tumor plus BCG. Of 9 patients in the control group 8 (89%) experienced tumor recurrence during a mean followup of 20 months. Of the 28 patients in the oral BCG group 11 (39.3%) had recurrence during a mean followup of 36 months. Of the 34 patients in the intravesical group 6 (18%) had recurrence in a 24-month mean followup. The incidence of complications was higher in the intravesical (41.2%) than in the oral BCG group (28.5%). These results show that intravesical BCG is a more effective immunotherapy; however, oral BCG can be used in patients who do not accept intravesical BCG administration. 
5	The effect of established and gestational diabetes on pregnancy outcome. OBJECTIVE--To study the prevalence and type of glucose intolerance in pregnancy and the effect of different types on perinatal mortality and fetal size. DESIGN--A prospective case-control study with data collected by patient interview and examination of all available records during a 16-months period between 1984 and 1986. SETTING--A large maternity hospital in Kuwait where diabetes in pregnancy is common. SUBJECTS--The cases were a consecutive sample of 731 women, delivered during the study period, recorded in the labour ward register as being diabetic or having abnormal glucose tolerance, the control group was formed from the next woman in the register (provided she was not known to be diabetic). MAIN OUTCOME MEASURES--Type of diabetes followed the WHO classification, with subdivision depending on level of fasting plasma glucose. Type of perinatal death was examined in detail and birthweight centile calculated. RESULTS--Of the 731 cases, 22% were established diabetics, most were treated with oral hypoglycaemic drugs before pregnancy and insulin during pregnancy. Of those discovered during pregnancy, 43% were classified as gestational diabetes and the remainder as impaired glucose tolerance. Overall, 50% of cases were treated with insulin. Established diabetics had a perinatal mortality rate nearly four times greater than non diabetics (RR, 3.7, 95% CI 2.6 to 6.4) and for gestational diabetics RR was 2.0 95% CI 1.2 to 3.7). Unexplained deaths were particularly common, both in established diabetics (RR, 18.4, 95% CI 3.9 to 85.7) and in gestational diabetics (RR, 13.4, 95% (CI 2.9 to 61.6). Cases with impaired glucose tolerance had no stillbirths and had a lower perinatal loss than the controls, though this was not statistically significant. Heavier babies were seen in all case groups compared with controls, though the impaired glucose tolerance group had lower birthweights than the other two case groups. CONCLUSIONS--Type 2 diabetes was found to be common, most cases being diagnosed in pregnancy. Under the conditions found in Kuwait, diabetes, in the sense of a raised fasting glucose, is accompanied by a high rate of perinatal loss from unexplained stillbirth. This applies whether the condition was present before pregnancy or was discovered during pregnancy. Fetal macrosomia was also common in both situations. Impaired glucose tolerance, where fasting levels remain normal, does not appear to increase fetal loss, but may be associated with fetal macrosomia. As these women age they are likely to develop overt diabetes in the non-pregnant state, and subsequently to develop serious complications of this disease. Improving glycaemic control, both during preg. 
5	Therapy of diseased stroke-prone spontaneously hypertensive rats with nimodipine. We investigated the therapeutic effect of nimodipine or parathyroidectomy in old, diseased stroke-prone spontaneously hypertensive rats by observing 98 male 1-year-old rats over 5 months. After stroke had occurred, the rats were divided into three groups: 1) parathyroidectomy, 2) nimodipine, and 3) controls. In the nimodipine group, the rats survived longer than those in the other groups. Blood pressure of the controls did not differ from the nimodipine-treated and parathyroidectomy animals. The increase in calcium content of brain and kidney tissues and of plasma renin activity, urea, and creatinine was attenuated by nimodipine or parathyroidectomy. The histology of the kidneys revealed widespread fibrinoid necrosis of arteries in all rats. In the nimodipine-treated or parathyroidectomy groups, healing of the lesions was detectable. Cerebral lesions were mainly characterized by fibrinoid necrosis. Nimodipine-treated as well as parathyroidectomied animals showed significantly fewer hypertensive cerebral lesions. In old, diseased stroke-prone spontaneously hypertensive rats, therapy with nimodipine or parathyroidectomy increased their survival rate. The cerebrovascular and renovascular lesions of treated animals were attenuated, and morphologic signs of healing were observed. Reduction of calcium overload by nimodipine or parathyroidectomy, even in an advanced stage of disease, had a therapeutic effect. 
5	Esophageal malignancies: is preoperative radiotherapy the way to go? During the period 1969 to 1988, 68 patients with esophageal malignancy were subjected to preoperative radiotherapy consisting of 30 Gy over 3 weeks followed by esophagectomy after a wait of 2 weeks. Sixty-two of 68 patients (91%) were followed up retrospectively (5-year survival rate, 17.2%; 10-year survival rate, 4.8%). Radiosensitivity of the tumor was graded by a radiation effect scoring method devised by us, and this was found to correlate with long-term prognosis (p = 0.05). Radiotherapy "sterilized" malignant involvement of adventitia and draining lymph nodes in 8 patients and thereby converted "palliative" into potentially "curative" resections with a mean survival of 57.2 months in this group of patients. Preoperative radiotherapy was found to increase the survival, decrease the incidence of residual tumor at the resected stump, reduce the incidence of local recurrence, and increase the resectability rate. 
5	Changes in interferon receptors on peripheral blood mononuclear cells from patients with chronic hepatitis B being treated with interferon. We studied the binding of 125I-labeled human interferon-alpha to peripheral blood mononuclear cells and the activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells obtained from 21 patients with chronic hepatitis B who were treated with human interferon-alpha or interferon-beta. Fourteen patients were given interferon daily for 4 wk. Interferon receptors per cell decreased to about 50% of baseline but increased to baseline by 2 wk after therapy ended. The activity of 2',5'-oligoadenylate synthetase rose about fivefold during therapy, decreasing to baseline by 1 wk after the end of therapy. The seven other patients were given interferon daily for 2 wk, no interferon for 2 wk and then interferon daily for 2 wk more. During both periods of therapy on this schedule, interferon receptors decreased to about 50% but returned to baseline 1 wk after the interferon was stopped. The activity of 2',5'-oligoadenylate synthetase increased about fivefold during both the first and second periods of therapy and decreased to baseline 1 wk after interferon was stopped. Close negative correlation existed between the number of interferon receptors and the 2',5'-oligoadenylate synthetase activity. The results of interferon therapy could not be predicted by either the numbers of interferon receptors before therapy or by the decrease in this number during therapy. 
1	Risk factors for breast cancer. Despite the numerous risk factors for the development of breast cancer that have been investigated, only a few demonstrate a clear association with breast cancer development. Female gender and increasing age are the most important factors, followed by factors involving a woman's menstrual, reproductive, and family history. The risks related to menstruation and reproduction are probably related to the duration of estrogenic breast stimulation. The relationship of family history and breast cancer risk is unclear, but there may be a true genetic basis. The previous occurrence of breast cancer (invasive or in situ), the presence of proliferative pathological changes, especially with atypia, and the presence of other malignancies (e.g., primary ovarian and endometrial cancer) are histological risk factors for the development of new or recurrent breast cancer. Radiation exposure, the use of exogenous estrogens (both estrogen replacement therapy and oral contraceptives), diet (especially fat consumption), and alcohol intake may all play a role in cancer risk. Certain medications as well as patient demographics may also have a weak association. Cigarette smoking, caffeine consumption, and stress presently have little support for an association with breast cancer risk. It should be noted that in only one in four patients can breast cancer be accounted for by the known risk factors. This demonstrates that although presently known risk factors may help in screening for the early detection of breast carcinoma, in its possible prevention by modulation of influenceable factors, and in advising patients about their risks, these factors are merely strong associations with breast cancer incidence and not actual causations. The mechanisms of the development of breast cancer are as yet unknown. 
1	Increased expression of the laminin receptor in human colon cancer. It has been proposed that among the various cell-surface proteins capable of interacting with laminin, the 67-kd high-affinity laminin receptor plays a crucial role during tumor invasion and metastasis. In this study, the expression of laminin-receptor-precursor messenger RNA (mRNA) and 67-kd protein was analyzed in human colon adenocarcinoma. In 22 of 23 patients with colon cancer, we found a 2- to 23-fold increase in levels of laminin-receptor-precursor mRNA in the cancer tissues compared with those in matched normal adjacent colonic mucosa. In 10 of 11 cases studied, the level of 67-kd laminin receptor, detected by affinity-purified anti-laminin-receptor synthetic peptide antibodies on immunoblots of matched tumor and normal tissue extracts, was higher in the colon carcinoma tissue. Immunodetection of laminin receptor in tissue sections using anti-laminin-receptor-peptide antibodies confirmed that the increased expression of laminin receptor was specifically associated with the cancer cells. In a series of 72 paraffin sections of colon lesions, we observed a correlation between the expression of the laminin receptor and the Dukes' classification. Our observations indicate that increased expression of laminin-receptor-precursor mRNA is associated with enhanced levels of the 67-kd laminin receptor as well as with the invasive phenotype of colon carcinoma. Detection of this metastasis-associated gene product may be a valuable adjunct in the evaluation of human colon cancer. 
4	Synchronous reconstruction for combined aortoiliac and femoropopliteal occlusive lesions. The role of proximal bypass. Between January 1984 and December 1986, 31 patients underwent synchronous revascularization (SR) because of the serious clinical condition of a lower limb and presence of arteriographically visible lesions. Average follow-up was 30 months. Operative mortality was 10%. Two patient populations were identified: Group I (N = 13): patients who underwent ilio-femoral or aorto-femoral proximal revascularization (PR); Group II (N = 18): patients who had axillo-femoral PR. Group I patients were younger than those in Group II (64 yr versus 72 yr; p less than 0.01). An association of pre-operative risk factors (arterial hypertension; coronary, renal or respiratory insufficiency) was twice as frequent in Group II as in Group I (p less than 0.02). The rate of SR compared to PR alone was 15%. However, there was no statistically significant difference between Groups I and II. Comparison of the actuarial survival curves for patients ahd the patency rates of SR in Groups I and II failed to reveal any statistically significant differences. Axillo-femoral bypass can be used for PR when SR is necessary in high risk patients. 
5	Contracturing granulomatous myositis: a separate entity. Granulomatous muscle disease is most commonly seen in sarcoidosis, but may be seen in association with a wide variety of other disorders or in isolation. Patients with granulomatous myositis usually present with slowly progressive muscle pain and weakness affecting mainly proximal muscles. There are, however, a few reports of granulomatous muscle disease presenting with flexion contractures of the limbs. Two further patients with granulomatous muscle disease and flexion contractures of the limbs, but with no evidence of systemic granulomatous disease, is presented. It is suggested that such patients represent a separate clinical entity that is distinct from idiopathic granulomatous myositis presenting with muscle pain and weakness. The association of contracturing granulomatous myositis with a long-standing vasculitis in one patient suggests that the two conditions may be related. 
2	Group B streptococcus: an unusual cause of severe peritonitis in young children treated with continuous ambulatory peritoneal dialysis. Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients is only rarely caused by beta-hemolytical streptococci species. We describe two young children, aged 15 months and 5 years, respectively, who presented an unusually severe course of peritonitis due to group B beta-hemolytical streptococci. This course of the disease showed a strong similarity with neonatal streptococcal septicemia. In neonates, IgG2 deficiency is thought to be partly responsible for the severity of this condition. This may also be true for young children treated with CAPD, since IgG2 deficiency has been established for children. 
1	Monomorphic adenomas of the major salivary glands: clinicopathological study of 44 cases. We report 44 cases of monomorphic adenoma (MA) of the major salivary glands observed during the years 1979-1989. All of these tumours were reviewed and classified on the basis of the World Health Organisation (WHO) criteria. Histological type, site, sex and age were considered. 34 cases of adenolymphoma were observed, all of them located in the parotid glands; 10 MA without lymphoid stroma were located in both parotid and submandibular glands. Distinctive histological and clinico-pathological features of the latter group of tumours are discussed, as well as the diagnostic criteria in distinguishing these tumours from pleomorphic adenoma and adenoid-cystic carcinoma. 
2	Intracorporeal biliary lithotripsy. Most bile duct calculi can be removed with standard percutaneous or endoscopic techniques. Very large stones are the most common cause for failure. Intracorporeal lithotripsy, and EHL in particular, can be used safely in either the biliary tree or gallbladder to fragment these large stones and allow percutaneous removal or passage. Intracorporeal EHL requires direct vision to prevent damage to the bile duct mucosa. Intracorporeal laser lithotripsy may offer some safety advantages, but the laser requires much more expensive equipment than intracorporeal EHL. Additional studies are needed to determine the technique that is better in each circumstance. 
5	Delayed-onset dystonia due to perinatal or early childhood asphyxia. We report 10 patients with delayed-onset dystonia associated with perinatal asphyxia and 2 associated with asphyxia in childhood. In the perinatal group, the mean age of onset was 12.9 years. Among these patients, dystonia continued to progress for a mean of 7 years, and as long as 28 years. These patients had moderate motor disability; none was wheelchair-bound, and thus their prognosis was better than that of the childhood-onset idiopathic torsion dystonias. The most frequently beneficial drugs were anticholinergics. Since some of these patients closely resembled cases of idiopathic torsion dystonia, the prior occurrence of asphyxia should be used as a criterion of exclusion for that diagnosis. 
4	Intercostal arteriovenous fistula due to pleural biopsy A 32 year old woman had a pleural biopsy for a left pleural effusion, which showed caseating granuloma typical of tuberculosis. When the fourth biopsy specimen was removed considerable bleeding occurred from the puncture site. Four days later a bruit was audible over the punctured area, radiating to the back. Eight days after the procedure the patient had a massive bleed into the left pleural space. Selective aortic angiography showed an arteriovenous fistula between the 9th intercostal artery and vein and a pseudoaneurysm in the intercostal punctured area. Thoracotomy showed bleeding from the site of the pleural biopsy. The intercostal vessels were ligated and pleural decortication was performed, and the patient recovered uneventfully. 
1	Allograft reconstructions of the shoulder after bone tumor resections. Large skeletal defects resulting from tumor resections about the shoulder create reconstructive challenges for the orthopedic surgeon. Bone allografts offer several advantages compared with other reconstructive techniques, and functional outcomes are generally satisfactory. They may be used either as osteoarticular grafts, intercalated segments to create an arthrodesis, or in combination with standard proximal humerus metallic implants. Patient expectations and specific oncologic factors must be considered when selecting the optimal method of reconstruction. 
1	Surgical prophylaxis of malignant melanoma. A review of a 14-year experience with prophylactic pigmented skin lesion removal is presented. Data obtained during a 4-year interval of this 14-year experience is analyzed specifically. During this 4-year interval, 250 patients with melanoma were seen. Of these patients, 75 with a history of stage I (localized) melanoma and three patients with stage II (history of controlled regionally metastatic melanoma) underwent removal of multiple skin lesions on a prophylactic basis. Of the removed lesions, 28% showed hyperplasia, atypia, dysplasia, or melanoma. Nine unsuspected in situ, or level I melanomas, and three unsuspected invasive melanomas were removed from these 75 melanoma patients while excising lesions prophylactically during the 4-year interval. It is estimated that four to six additional melanomas were prevented by excision of precursor lesions. During the same 4-year interval, an additional 112 of approximately 1000 patients without a previous history of melanoma underwent prophylactic lesion removals. In 31% of the 112 patients, there was a history of melanoma in a first-degree relative. In 22% of the removed lesions there was hyperplasia, atypia, or dysplasia. Three cases of melanoma in situ were detected and it is estimated that an additional three to five cases of melanoma were prevented. Atypical findings occurred in 71, or 63%, of the patients biopsied, which represented 7% of the approximately 1000 patients screened. During the 4-year interval, an average of 17.7 lesions were removed from each of the 190 melanoma and nonmelanoma patients undergoing prophylactic skin lesion excision. This was accomplished in one to four sessions per patient. This average reflects only those patients who underwent one excision or more and does not include those patients treated without operation. When including the nonoperated patients screened during this interval, the average number of lesions removed was 2.7 per patient. Death from new melanomas was prevented during the 14-year period of this study as evidenced by the fact that no patient died or developed metastatic disease from a cutaneous melanoma that was not apparent or known about at the time of first examination. 
4	Angiography, angioscopy, and ultrasound imaging before and after percutaneous balloon angioplasty. We report two patients undergoing peripheral percutaneous transluminal angioplasty in whom angiography, angioscopy, and ultrasound imaging were performed before and after balloon angioplasty. The first case with smooth atheroma diagnosed by angiography was found to have unrecognized partially occlusive thrombus by angioscopy. After angioplasty, an intimal tear was identified by angioscopy and ultrasound but it was not seen by angiography. The intravascular ultrasound image showed the tear to extend to the adventitia. In the second case, an apparently smooth intimal surface as imaged by angiography was found by angioscopy and ultrasound to have extensive damage, including subintimal hemorrhage, intimal flaps, and arterial dissection at the angioplasty site. These data suggest that the type of information derived from the three imaging techniques is quite different, and that each may have a specific role in intravascular diagnosis. 
4	Pregnancy-induced hypertension and acute fatty liver of pregnancy: atypical presentations. Severe pregnancy-induced hypertension and markedly elevated levels of serum alkaline phosphatase developed in a 29-year-old-woman in whom one pregnancy resulted in intrauterine death. Acute fatty liver of pregnancy developed with good fetal outcome in the next pregnancy. This case suggests that pregnancy-induced hypertension and acute fatty liver of pregnancy are part of a clinical spectrum. Moreover, classic abnormalities of liver function tests need not be present in acute fatty liver of pregnancy. 
5	Small-volume resuscitation from hemorrhagic shock in dogs: effects on systemic hemodynamics and systemic blood flow. BACKGROUND AND METHODS: This study compared canine systemic hemodynamics and organ blood flow (radioactive microsphere technique) after resuscitation with 0.8% saline (Na+ 137 mEq/L), 7.2% hypertonic saline (Na+ 1233 mEq/L), 20% hydroxyethyl starch in 0.8% saline, or 20% hydroxyethyl starch in 7.2% saline, each in a volume approximating 15% of shed blood volume. Twenty-four endotracheally intubated mongrel dogs (18 to 24 kg) underwent a 30-min period of hemorrhagic shock, from time 0 to 30 min into the shock period, followed by fluid resuscitation. Data were collected at baseline, 15 min into the shock period, immediately after fluid infusion, 5 min after the beginning of resuscitation, and at 60-min intervals for 2 hr, (65 min after the beginning of resuscitation, and 125 min after the beginning of resuscitation). The animals received one of four randomly assigned iv resuscitation fluids: saline (54 mL/kg), hypertonic saline (6.0 mL/kg), hydroxyethel starch (6.0 mL/kg) or hypertonic saline/hydroxyethyl starch (6.0 mL/kg). RESULTS: Mean arterial pressure increased in all groups after resuscitation. Cardiac output increased with resuscitation in all groups, exceeding baseline in the saline and hypertonic saline/hydroxyethyl starch groups (p less than .05 compared with hypertonic saline or hydroxyethyl starch). Sixty-five minutes after the beginning of resuscitation, cardiac output was significantly (p less than .05) greater in either of the two colloid-containing groups than in the hypertonic saline group. After resuscitation, hypertonic saline and hydroxyethyl starch produced minimal improvements in hepatic arterial flow, hypertonic saline/hydroxyethyl starch increased hepatic arterial flow to near baseline levels, and saline markedly increased hepatic arterial flow to levels exceeding baseline (p less than .05, saline vs. hydroxyethyl starch). One hundred twenty-five minutes after the beginning of resuscitation, hepatic arterial flow had decreased in all groups; hepatic arterial flow in the hypertonic saline group had decreased to levels comparable with those during shock. Myocardial, renal, and brain blood flow were not significantly different between groups. CONCLUSIONS: Small-volume resuscitation with the combination of hypertonic saline/hydroxyethyl starch is comparable with much larger volumes of 0.8% saline, and is equal to hypertonic saline or hydroxyethyl starch in the ability to restore and sustain BP and improve organ blood flow after resuscitation from hemorrhagic shock. 
3	MRI, CT, SPECT, PET: their use in diagnosing dementia. The differential diagnosis of the dementia syndrome may pose a difficult clinical problem, since the most common dementia, Alzheimer's disease (AD), is marked by normal laboratory tests. Neuroimaging has played an important role in evaluating the demented patient, and its uses are growing. Computed tomography (CT) is useful for excluding reversible and treatable causes of dementia, such as subdural hematoma and tumor. More recently, magnetic resonance imaging (MRI) has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on CT. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), techniques that visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence supportive of the diagnosis of AD. 
5	Omeprazole in the management of intractable esophageal ulceration following injection sclerotherapy. Transient esophageal ulceration is a common finding after sclerotherapy of varices. A small proportion of these ulcers become chronic and resistant to conventional therapy. Such chronic ulcers have been associated with pain, stricture formation, and recurrent hemorrhage. The use of omeprazole, a proton pump inhibitor, was examined in the current study in the treatment of 10 patients (6 women, 4 men; age range, 27-86 years) with cirrhosis (PBC, 4; sclerosing cholangitis, 2; chronic active liver disease, 2; alcohol, 1; and cryptogenic, 1) who developed an esophageal ulcer after a mean of 13 (range, 8-21) sessions of sclerotherapy. The ulcers had been present for 3-54 months despite prolonged treatment with high-dose H2-receptor antagonists and sucralfate. In each case one or more complications had occurred: severe pain in 3, stricture formation in 4, and recurrent hemorrhage in 7 cases. After an 8-week course of omeprazole, 40 mg daily, endoscopy confirmed complete healing of the ulceration in all 10 cases with symptom resolution. In 2 cases the ulcer recurred, with associated bleeding within 6 weeks of discontinuing the treatment in 1 patient. Both cases responded to repeat therapy. These results confirm the efficacy of omeprazole for postsclerotherapy ulceration and imply that acid-pepsin has a role in perpetuating such ulcers. 
5	The stroke syndrome of striatocapsular infarction. Striatocapsular infarction has recently been described as a distinct stroke entity and forms an important subgroup of subcortical infarctions. In a prospective study of 50 consecutive patients over a 10 yr period with this syndrome, clinical and neuropsychological features, pathogenesis and outcome were studied to provide information concerning management and prognosis. The most common clinical presentation was that of a stroke affecting mainly the upper limb with cortical signs such as dysphasia, neglect or dyspraxia. Evidence from EEG, angiographic and neuropsychological data supported a vascular/haemodynamic basis for the presence of the acute neuropsychological changes, while the chronic changes were more likely to be due to diaschisis. A study of risk factors and cerebral angiography enabled 4 pathophysiological subgroups to be identified: (1) cardiac emboli to the origin of the middle cerebral artery; (2) severe extra-cranial cranial carotid artery occlusive disease with presumed embolism to the same site and/or involvement of haemodynamic factors; (3) proximal middle cerebral artery abnormalities causing occlusion of multiple lateral striate arteries at their origins; (4) normal angiography where pathogenesis was uncertain. The risk factors of cardiac disease and smoking were significantly increased as compared with age and sex-matched controls with other forms of ischaemic stroke. Stroke or vascular death rate was 2.7% per yr during a mean follow-up period of 2.25 yrs. Predictors of an excellent recovery with return to normal lifestyle were younger age, only brachial or brachiofacial weakness with absence of cortical signs at presentation and minimal change on angiography. This stroke entity deserves particular recognition in the spectrum of subcortical infarctions because of its specific pathogenesis, distinct neuropsychological features and reasonable prognosis. 
1	Detection of loss of heterozygosity in formalin-fixed paraffin-embedded tumor specimens by the polymerase chain reaction. A polymerase chain reaction-based procedure was used for the detection of DNA length polymorphisms generated by naturally occurring genetic deletions or insertions of known sequence. This method consists of a simple one-step assay that does not require any restriction enzyme analysis or Southern blot hybridization, allowing identification in ethidium bromide-stained gels. The procedure described here was used to detect loss of heterozygosity at various loci, including the Hbb beta-globin gene cluster, in chemically induced mouse skin tumors, using a variety of tissue preparations, including microdissection of formalin-fixed, paraffin-embedded specimens, short-term cultures, and fluorescence-activated cell sorting of epithelial populations. This approach may be useful in detecting tumor-specific reduction to homozygosity at polymorphic chromosomal loci, allowing the mapping of putative tumor-suppressor loci involved in carcinogenesis. 
4	Percutaneous right brachial artery approach with 5F catheters for studying coronary artery disease. We prospectively studied 60 ischemic patients with 5F catheters (Pigtail and Amplatz) using the percutaneous right brachial artery approach (group I), in order to compare this technique with two groups of 100 patients each randomly studied by the femoral route with either 5F (group II) or 8F (group III) catheters (Pigtail and Judkins). The following parameters were analyzed: need to change the initially elected catheter diameter or/and artery approach; technical difficulty for obtaining LV, LCA, and RCA angiograms; total time of X-ray exposure; quality image of LV, LCA, and RCA angiograms; incidence of arterial puncture related hematomas or total arterial occlusion; and duration of local compression after sheath removal. There were no differences between 5F brachial and femoral approaches except for the arterial compression time (p less than 0.01) and the X-ray exposure time (p = 0.03) which were longer with the brachial approach. Whatever the route used, 5F showed a mild increase difficulty (brachial p = 0.001; femoral p = 0.01) and a mild decreased quality image for LCA (branchial p = 0.006; femoral p less than 0.05). Mild hematomas were more frequent with 8F catheters (p less than 0.05). The procedure could be completed by the elected first artery and type of catheter (5F or 8F) in 57/60 patients in group I, in 95/100 in group II, and in 96/100 in group III (nonsignificant differences). Thus, the percutaneous right brachial artery approach using 5F catheters is similar to the femoral artery approach with the same catheters. Although both of them showed a mild increased technical difficulty and a mild decreased quality image compared to 8F, mainly for LCA angiograms, they allowed complete and reliable angiograms reading and analysis. 
5	Cholesterol cysts of the temporal bone: diagnosis and treatment. Cholesterol cyst (or granuloma) of the temporal bone, a recognized clinical entity distinct from cholesteatoma, is more common than previously thought. Apparently it is caused by obstruction of previously pneumatized temporal bone air cells. Surgical cure is achieved by drainage and reestablishment of normal pneumatization. This paper reviews 14 cholesterol cysts of the temporal bone, emphasizing the importance of preoperative imaging and surgical approach. Use of magnetic resonance imaging differentiates cholesterol cysts from cholesteatoma or other neoplasms. Computed tomography delineates the location of the lesion and defines temporal bone anatomy essential to surgical approach. The two studies together allow the surgeon to properly plan drainage, as in the case of a cholesterol cyst, versus excision or exteriorization, as in the case of cholesteatoma. The infralabyrinthine approach to a petrous apex cholesterol cyst is the procedure of choice when hearing preservation is desired. 
1	Brain tumors. Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. 
3	Rediscovering tactile agnosia. Eighty-four patients with damage to various levels of the nervous system, ranging from the peripheral nerves to the cerebral cortex, underwent somesthetic assessment in order to determine the degree to which basic and complex perceptual and motor disorders affect tactile object recognition (TOR) and to determine whether TOR can be impaired in the absence of more basic sensorimotor imperception. The results suggest that (1) basic and intermediate disorders of somesthetic function impair TOR but are commensurately more severe for any given degree of TOR impairment in patients with peripheral lesions than in patients with cortical lesions; (2) neither hemiparesis nor hemianopia alone precludes normal TOR; (3) hemineglect contributes substantially to TOR impairment; (4) impairment of TOR can occur in the absence of more basic somesthetic dysfunction and constitutes tactile agnosia; (5) tactile agnosia is a subtle, nondisabling disorder that should be distinguished from the nonagnosic, severe and disabling disorder, astereognosis; and (6) tactile agnosia results from unilateral damage to parietotemporal cortices, possibly including the second somatosensory cortex, in either hemisphere. 
1	Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin BACKGROUND. In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk of cancer. METHODS. We conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the United States that produced chemicals contaminated with TCDD. Occupational exposure was documented by reviewing job descriptions and by measuring TCDD in serum from a sample of 253 workers. Causes of death were taken from death certificates. RESULTS. Mortality from several cancers previously associated with TCDD (stomach, liver, and nasal cancers, Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in this cohort. Mortality from soft-tissue sarcoma was increased, but not significantly (4 deaths; standardized mortality ratio [SMR], 338; 95 percent confidence interval, 92 to 865). In the subcohort of 1520 workers with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency, however, mortality was significantly increased for soft-tissue sarcoma (3 deaths; SMR, 922; 95 percent confidence interval, 190 to 2695) and for cancers of the respiratory system (SMR, 142; 95 percent confidence interval, 103 to 192). Mortality from all cancers combined was slightly but significantly elevated in the overall cohort (SMR, 115; 95 percent confidence interval, 102 to 130) and was higher in the subcohort with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency (SMR, 146; 95 percent confidence interval, 121 to 176). CONCLUSIONS. This study of mortality among workers with occupational exposure to TCDD does not confirm the high relative risks reported for many cancers in previous studies. Conclusions about an increase in the risk of soft-tissue sarcoma are limited by small numbers and misclassification on death certificates. Excess mortality from all cancers combined, cancers of the respiratory tract, and soft-tissue sarcoma may result from exposure to TCDD, although we cannot exclude the possible contribution of factors such as smoking and occupational exposure to other chemicals. 
5	Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). We report the immunological characteristics of five patients with Omenn's syndrome, a rare inherited immunodeficiency also known as combined immunodeficiency with hypereosinophilia. The syndrome is characterized by T cell infiltration of skin, gut, liver, and spleen leading to diffuse erythroderma, protracted diarrhea, failure to thrive, and hepatosplenomegaly. Blood T cells as well as those infiltrating the skin and gut were found to express activation markers and were partially activated by mitogens but not by antigens. Although the lesions resembled those in graft-versus-host disease, the blood T cells were shown by DNA haplotype analysis using probes revealing variable number of tandem repeats to belong to the patients as well as the T cells infiltrating the gut and skin in one patient. A given T cell subset (TCR alpha beta+, CD4+/CD8+, or TCR gamma delta+) was predominant in each patient, with a specific distribution in the skin lesions. Moreover, the study of T cell receptor beta, gamma, and delta gene rearrangements in four patients revealed oligoclonality involving C beta 1, C beta 2, or different V gamma J gamma or V delta J delta genes. This indicates that restricted heterogeneity of the T cell repertoire, previously reported in one case, is a major feature of this syndrome. The occurrence of alymphocytosis-type severe combined immunodeficiency in the brother of one of the patients suggests that the restricted heterogeneity of T cell receptor gene usage in Omenn's syndrome may arise from leakiness, within the context of a genetically determined faulty T cell differentiation. 
5	Maternal feeding behavior and child acceptance of food during diarrhea, convalescence, and health in the central Sierra of Peru. Feeding patterns by mothers and child acceptance of food were measured in a Peruvian village to determine changes on days when children had diarrhea as compared to days of convalescence and health. Morbidity surveillance identified 40 children, aged 4-36 months, with diarrhea. Children were followed using twelve-hour in-home structured observations during two to four days each of diarrhea, convalescence, and health. Using scales of maternal encouragement to eat and child acceptance of food and cumulative logistic regression analyses, maternal encouragement to eat decreased significantly during convalescence compared to diarrheal days (OR: 0.54, 90% CI: 0.35, 0.82) and health compared to diarrhea (OR: 0.65, 90% CI: 0.46, 0.93). In contrast, child acceptance of food increased during health compared to diarrhea (OR: 1.55, 90% CI: 1.02, 2.35). Results illustrate the importance of carefully examining the behavioral aspects of nutritional intake. Decreases in intake during diarrhea are due to anorexia and not withdrawal of food by mothers. In response to reductions in child appetite during illness, mothers are more likely to encourage children to eat, while they tend to become more passive feeders after the diarrhea has stopped. Program efforts should focus on messages to feed children more actively especially after diarrhea episodes, when appetite levels increase. 
2	Crohn's disease in the city of Derby, 1951-85. An epidemiological survey of Crohn's disease in the city of Derby showed that the incidence of the condition increased from 0.7/10(5) per year between 1951 and 1955 to 6.67/10(5) per year between 1981 and 1985 but seemed to reach a plateau between 1976 and 1985. Large bowel Crohn's disease was more common in patients presenting aged 60-79 years than in those aged 20-39 years. The increase in incidence was not solely due to the detection of milder disease. There was no evidence that the Asian (Indian subcontinent) population of Derby was resistant to the development of Crohn's disease. 
4	Tongue ischemia from a soft-drink can: report of case. A young girl was brought to the emergency department because her tongue became entrapped while she was drinking from an aluminum soft-drink can. A dental drill was used to remove the can. The tongue was observed for 48 hours, during which an ischemic area recovered spontaneously. 
5	Cardiac arrest during hip arthroplasty with a cemented long-stem component. A report of seven cases. Seven patients had a cardiac arrest during hip arthroplasty with a cemented long-stem femoral component. Four patients died in the operating room, and three patients were successfully resuscitated. When the three survivors were eventually discharged from the hospital, they had no known permanent cardiac, pulmonary, or neurological sequelae. Factors that were common to all of the patients were advanced age, osteoporotic bone, a previously undisturbed intramedullary canal, and use of a long-stem femoral component and several batches of methylmethacrylate. Hip arthroplasty with a long-stem femoral component is associated with substantial risk in these patients. Excessive pressurization of cement should be avoided, and invasive hemodynamic monitoring should be used when the described conditions are present. 
1	Surgical management of islet cell dysmaturation syndrome in young children. Islet cell dysmaturation syndrome (ICDS) encompasses the causes of infantile hyperinsulinemic hypoglycemia histologically described as islet cell hyperplasia, pancreatic adenomatosis and nesidioblastosis. Eleven infants underwent 14 pancreatic resections for ICDS from 1965 to 1990 at the University of California at Los Angeles Medical Center for severe hypoglycemia unresponsive to medical therapy. Seizures were the presenting symptoms of hypoglycemia in eight infants. Six patients had nesidioblastosis, four had islet cell hyperplasia and one patient had an adenoma with histologically normal pancreatic islet cells. Four neonates underwent 80 per cent pancreatic resection; three with nesidioblastosis required reoperation (90 to 95 per cent resection). Four older infants underwent 80 per cent pancreatic resection but required diazoxide for less than six months postoperatively. Three infants underwent 90 to 95 per cent pancreatic resection. None have required reoperation or postoperative medications. All infants are normoglycemic without pancreatic exocrine insufficiency and none had postoperative complications. Five infants had preoperative neurologic impairment, with three having severe retardation; all showed some improvement postoperatively, but only one infant now has normal findings on neurologic examination. Early diagnosis and aggressive surgical resection should minimize neurologic complications of the ICDS. 
5	Acute lobar atelectasis. A comparison of two chest physiotherapy regimens. Fourteen cases of acute lobar atelectasis were alternately allocated to one of two chest physiotherapy regimens for treatment. Treatment in group 1 comprised positioning, vibrations, hyperinflation, and suction, and in group 2, treatment consisted of hyperinflation and suction alone. Treatment in either group was given hourly for six hours. Patients in group 1 had a significantly higher mean percentage resolution of their atelectasis (mean value, 60.1 percent), as seen on chest roentgenogram, after one treatment intervention than patients in group 2 (mean value, 7.6 percent; p less than .006). After the intensive six-hour treatment period, the difference between the groups was marginally statistically significant, still favoring group 1 over group 2 (p less than .055). Follow-up roentgenograms at 24 and 48 hours revealed no significant difference between the treatment groups (p greater than .10 and greater than .20, respectively). These results suggest that, at least initially in the course of acute lobar atelectasis, positioning and vibrations add to the efficacy of a treatment of hyperinflation and suction alone. 
5	Percent tumor necrosis as a predictor of treatment response in canine osteosarcoma. The percent tumor necrosis was determined in 200 dogs with spontaneously occurring osteosarcoma. One hundred dogs had no treatment before amputation or death. One hundred other dogs were treated with either radiation therapy alone (n = 23), intraarterial (IA) cisplatin alone (n = 16), intravenous (IV) cisplatin alone (n = 6), radiation therapy plus IA cisplatin (n = 47), or radiation therapy plus IV cisplatin (n = 8). Eighty-nine of these 100 dogs had their tumors resected 3 weeks after the end of therapy (6 weeks after the initiation of therapy) and replaced with a cortical bone allograft. Dogs with preoperative treatment were evaluated for local tumor control and time to metastasis. The mean percent tumor necrosis in untreated osteosarcoma was 26.8%. The mean percent tumor necrosis for dogs receiving radiation only, IA cisplatin only, and IV cisplatin only was 81.6%, 49.1% and 23.8%, respectively. The mean percent tumor necrosis for dogs receiving radiation therapy plus IA cisplatin or radiation therapy plus IV cisplatin was 83.7% and 78.2%, respectively. There was no significant difference between percent tumor necrosis in untreated osteosarcoma compared with those receiving IV cisplatin, but there was a significant increase in percent tumor necrosis with all other treatments. A mathematic model for the effect of cisplatin and radiation dose was developed using multiple regression analysis. The radiation dose calculated to cause at least 80% tumor necrosis was 42.2 Gy (95% confidence interval [CI], 38.0 to 47.6 Gy) when radiation was given alone and 28.1 Gy (95% CI, 21.3 to 36.6 Gy) when radiation was combined with IA cisplatin. Areas of viable tumor tended to be most frequent adjacent to the articular cartilage and in the joint capsule. Percent tumor necrosis was strongly predictive for local tumor control; 28 of 32 dogs with greater than 80% tumor necrosis had local control, and only eight of 29 dogs with less than 79% tumor necrosis had local control (P = 0.0047). There was no correlation between percent tumor necrosis and time to metastasis. 
5	Early postoperative mortality following hysterectomy. A Danish population based study, 1977-1981. The main objective of this cohort study was to analyse the early postoperative mortality after 'simple' hysterectomy for benign indications and to compare it with that of a randomly selected reference group of women matched for age. Registry data covering the entire Danish female population were used. Included in the study were all patients operated in the period 1977-1981. Patients were only included if no cancer was diagnosed and if no major co-surgery was performed (29,192 patients). Cancer patients were also excluded in the reference group (16,182 women). Mortality was studied according to characteristics of patients, their residential area, the surgical approach and operating hospital. Overall 47 patients died within 30 days of admission for hysterectomy (overall mortality 16.1 per 10,000). Only seven deaths were expected on the basis of the population sample, and adjusted for age, the relative risk (RR) for hysterectomy patients was 6.38 (95% CI 4.33-9.39). Early postoperative mortality increased with age, and the risk was elevated among emergency patients (RR = 3.22; 1.72-6.04). Patients with more than one diagnosis at discharge (RR = 4.53; 2.12-9.70) were at high risk, but early postoperative mortality was independent of surgical approach. Causes of death are discussed. Compared to the general population, patients who undergo 'simple' hysterectomy are faced with a sixfold risk of dying within 30 days, but a complete assessment of the risks and benefits of hysterectomy requires prospective studies of survival and morbidity, including quality of life for longer periods of time following operations. 
1	trans-Activation of genes encoding activation-associated human T lymphocyte surface proteins by murine retroviral sequences. The mechanisms whereby RNA leukemia viruses cause T lymphocyte leukemias or lymphomas after a long latent period are not understood. We report here that infection of human T lymphocyte lines with a murine leukemia virus results in up-regulation of a number of lymphocyte-specific cell surface Ag. These proteins include CD2, CD3, CD4, the TCR, and MHC class I Ag. The expression of other cell surface proteins, such as LFA-3, are unaffected by the presence of the retrovirus. This up-regulation occurs at the level of the mRNA transcripts encoding these proteins, and is the result of increased transcription of the respective genes. The increases in transcription are the result of a trans-activation process by the leukemia virus. The transient introduction of chimeric genes consisting of MHC class I gene promoter sequences attached to the reporter gene CAT into human T cells containing murine retrovirus produces stimulated transcription of the reporter gene. Subgenomic portions of the murine leukemia virus containing the long terminal repeats and the 5' untranslated region are sufficient to produce transactivation of the same set of T cell genes as the whole leukemia virus. The finding that murine leukemia viruses enhance transcription and expression of a group of T cell surface proteins, all of which have been reported to be capable of transducing an activating signal to the lymphocyte, may be relevant to the pathophysiologic mechanisms whereby these viruses induce leukemias and lymphomas. 
1	Pattern of urological malignancy in Zambia. A hospital-based histopathological study. The pattern of urological malignancy among the indigenous population of Zambia (determined on the basis of histopathological reports from a major national hospital during an 8-year period) is presented. A total of 6514 malignancies were observed, of which 784 (12%) were of urological origin. Bladder carcinoma, predominantly squamous type, was the commonest urological tumour (51%), followed by carcinoma of the prostate (26%), carcinoma of the penis (18%), renal tumours (4.3%) and testicular malignancy (0.7%). In nearly 32% of the bladder tumours, bilharzial ova were demonstrated histopathologically. Nephroblastoma accounted for 70% of the renal tumours and from a total of 7 cases of testicular tumours 5 were embryonal carcinoma and 2 seminoma. A brief reference is made to the pattern and aetiology of urological malignancies in some neighbouring countries. 
4	Progressive inflammatory lesions of the brain parenchyma in localized scleroderma of the head. A patient with localized scleroderma of the head, uveitis, and Raynaud's phenomenon presented with generalized seizures, spastic hemiparesis, and local IgG production in the cerebrospinal fluid. Magnetic resonance imaging revealed progressive cortical and subcortical brain parenchymal lesions mainly adjacent to the cutaneous and bony lesions and probably of inflammatory origin. 
5	Edrophonium provocative test in noncardiac chest pain. Evaluation of testing techniques. Edrophonium chloride is used frequently as a provocative agent in the assessment of noncardiac chest pain (NCCP). However, the optimum dose and most appropriate method of interpreting test results is controversial. We studied 150 consecutive NCCP patients and 50 age-matched controls who alternately received either 80 micrograms/kg or 10 mg intravenous bolus doses of edrophonium preceded by saline placebo injections. Distal esophageal pressures were measured before and after drug injection in response to ten 5-cc wet swallows. Following 10 mg of edrophonium, 33% of patients and 4% of controls reported chest pain, while 29% of patients and no controls receiving the 80 micrograms/kg dose complained of chest pain. Amplitude changes after either dose were not significantly different for all comparisons, but the duration of response did distinguish the two doses in patients with chest pain. A significantly greater (P = 0.01) increase in distal contraction duration occurred after 10 mg (74 +/- 12%; +/- SE) compared to 80 micrograms/kg dose (43 +/- 6%). However, individual responses to the two doses overlapped considerably. If a positive test is redefined to include both chest pain and manometric changes that are significantly different from controls, the positivity rate changes drastically; 33% to 9% in the 10-mg group and 30% to 3% in the 80-micrograms/kg group. Side effects were similar between doses, but there was a significant (P = 0.02) linear relationship between intensity of side effects and the edrophonium dose per kilogram of body weight. 
2	Dissociation between systemic and mucosal humoral immune responses in coeliac disease. We examined humoral immunity in coeliac disease as expressed in serum (systemic immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal immunity). The aims were to define features of the secretory immune response (IgA and IgM concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay (ELISA)) in active disease and remission, and to establish whether secretions obtained by relatively non-invasive techniques (saliva and gut lavage fluid) can be used for indirect measurements of events in the jejunum. Serum, saliva, and jejunal aspirate from 26 adults with untreated coeliac disease, 22 treated patients, and 28 immunologically normal control subjects were studied, together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects. Jejunal aspirate IgA and IgM and gut lavage fluid IgM concentrations were significantly raised in patients with untreated coeliac disease; the lavage fluid IgM concentration remained higher in patients with treated coeliac disease than in controls. Serum and salivary immunoglobulin concentrations were similar in the three groups. Patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested; these were predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in jejunal aspirate and gut lavage fluid. Values of salivary IgA antibodies to gliadin were significantly higher in untreated coeliacs, though antibody values were generally low, with a large overlap between coeliac disease patients and control subjects. 
5	Laryngeal framework reconstruction with miniplates. Defects of the laryngeal framework after trauma, cancer, and thyroplasty have been reconstructed with mini-reconstruction plates. Six patients had miniplates used to repair the thyroid cartilage defect after type I thyroplasty to prevent lateralization of the Silastic implant; three patients had miniplates used after hemilaryngectomy to bridge the thyroid cartilage remnants, resulting in better deglutition after hemilaryngectomy; and three patients had miniplates used to repair laryngeal fractures. The plates were tolerated well by the patients; there were no major complications. Rigid fixation using miniplates for laryngeal reconstruction has unique advantages over the use of wires. It offers the advantages of rigid and immediate stabilization with the ability to bridge large defects. It can be an alternative to existing techniques of laryngeal reconstruction. 
5	Growth hormone for short stature not due to classic growth hormone deficiency. The advent of recombinant DNA technology has resulted in potentially unlimited supplies of growth hormone. Sufficient quantities are now available not only for the long-term, uninterrupted treatment of GH-deficient children but potentially for the treatment of non-GH-deficient patients with other short stature or growth attenuating disorders. Short-term studies have demonstrated an improvement in the growth rates of subjects with isolated short stature, Turner syndrome, and chronic renal failure; and additional studies are under way to assess the efficacy of GH therapy of other short stature syndromes. However, the long-term efficacy and possible adverse effects of GH treatment in these situations is not known. Until there has been more experience, GH deficiency should remain the primary indication for GH treatment. Growth hormone should not be considered routine therapy for other conditions associated with or resulting in short stature. However, research should continue in these areas to define which children may benefit from GH treatment. 
5	Chronic upper lobe cavitary lung disease. Chronic upper lobe cavitary lung disease may be caused by infections, emphysema, cystic fibrosis, lung cancer, sarcoidosis and rheumatologic syndromes. The diagnostic evaluation includes a complete history, a physical examination, a chest radiograph, and sputum examination and culture. In some cases, computed tomographic scanning and biopsy are required. 
5	Pharmacologic stress imaging. Pharmacologic stress imaging has increasingly been employed as an alternative to exercise imaging for detection of coronary artery disease and risk stratification particularly in patients who are unable to perform adequate exercise. Sensitivity and specificity of thallium 201 scintigraphy using intravenous dipyridamole infusion as a stress for coronary artery disease detection average 85% and 91%, respectively. Dipyridamole imaging is also useful for differentiating between ischemia and scar and identifying patients who have an increased risk for subsequent cardiac events. Dipyridamole imaging is particularly useful for preoperative risk stratification in patients undergoing surgery for peripheral vascular or aortic disease. Dipyridamole imaging is also useful for identifying residual myocardial ischemia after myocardial infarction and detecting restenosis after coronary angioplasty. Adverse side effects of dipyridamole are promptly reversed by aminophylline. Dipyridamole stress can also be employed in association with echocardiography for detection of ischemia-induced regional wall motion abnormalities. 
4	Transoesophageal echocardiography in the longitudinal axis: correlation between anatomy and images and its clinical implications. Transoesophageal echocardiographic imaging in the longitudinal axis is a recent addition to the non-invasive evaluation of congenital and acquired heart disease. The technique provides unique images of intracardiac anatomy but their interpretation remains difficult. A heart specimen was therefore cut according to the echocardiographic imaging planes to elucidate the morphological details. The results suggested that longitudinal transoesophageal imaging complements the transverse axis approach. It gave new imaging information on the right ventricular outflow tract and the pulmonary trunk, the atrioventricular valves, the interventricular septum, the cardiac apex, and the thoracic aorta. In particular, it showed the entire length of the right ventricular outflow tract. When longitudinal imaging was used in combination with transverse imaging almost all the thoracic aorta could be examined. Imaging in the longitudinal axis may also allow better assessment of the mechanisms of atrioventricular valve regurgitation. 
1	A recurrent pelvic desmoid tumor successfully treated with tamoxifen. A case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen (Nolvadex tablets, ICI Pharma, Division of ICI Americas, Wilmington, DE) is reported. The patient presented late in her second pregnancy with a large retroperitoneal pelvic desmoid tumor that was treated with surgical excision and megestrol acetate. When the tumor recurred 12 months later, it was again treated with surgery, this time followed by radiation therapy. The desmoid tumor quickly recurred. The patient was then treated with tamoxifen, resulting in a complete tumor regression that has remained stable for 27 months. Tamoxifen should be considered as first-line therapy in recurrent desmoid tumors. 
5	Delayed facial nerve palsy after temporal lobectomy for epilepsy: report of four cases and discussion of possible mechanisms. Four cases of idiopathic peripheral facial nerve palsy were documented after 110 consecutive resections of the temporal lobe for intractable epilepsy. In 3 of the 4 cases, the palsy was ipsilateral to the side of the temporal lobectomy. The onset of facial weakness was delayed 7 to 13 days after surgery (mean, 9.7 days). One patient underwent facial electroneurography, which documented 17% of normal facial motor function at the height of his weakness and the absence of the acoustic stapedius reflex. All patients were treated with prednisone (60-80 mg per day by mouth for 10-14 days, tapering off throughout the subsequent week). Facial function recovered fully in all patients within 6 to 8 weeks. Possible mechanisms are discussed, including heat and/or mechanical trauma to the facial nerve near the geniculate ganglion during resection of mesial temporal lobe structures. 
5	Fascinating rhythm: a primer on chaos theory and its application to cardiology. Nonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible. 
4	Enhanced chemiluminescence as a measure of oxygen-derived free radical generation during ischemia and reperfusion. It has been suggested that oxygen-derived free radicals may contribute to the myocardial injury associated with ischemia and reperfusion. As the presence of enhanced free radical generation is a prerequisite for such damage, several techniques have been used to provide evidence of increased oxygen free radical production during reperfusion; however, all such techniques have substantial limitations. In this study, we used enhanced chemiluminescence to evaluate oxygen free radical generation during ischemia and reperfusion in the isolated Langendorff-perfused rat heart. The chemiluminescent technique, which has high sensitivity and can monitor radical generation continuously, avoids some of the limitations of earlier methods. Chemiluminescence (expressed as counts per second) decreased from 219 +/- 11 at baseline to 142 +/- 9 during ischemia and markedly increased to a peak of 476 +/- 36 during the first 3-5 minutes of reperfusion. This was followed by a slow decline over 11-16 minutes to a steady-state level of 253 +/- 14 (each sequential change in chemiluminescence was highly significant; p less than 0.001). Superoxide dismutase (2,000 units/min) significantly decreased peak reperfusion chemiluminescence to 316 +/- 17 (p less than 0.01). Hearts subjected to a second period of ischemia and reperfusion had a higher peak chemiluminescence (626 +/- 62), which also was significantly attenuated by 1,000 units/min superoxide dismutase (398 +/- 16; p less than 0.01). 
5	The severity of coronary atherosclerosis at sites of plaque rupture with occlusive thrombosis. Atherosclerotic plaque rupture with superimposed thrombosis is recognized as the lesion causing greater than 90% of acute myocardial infarctions. To determine the severity of atherosclerosis at the site of plaque rupture, 184 coronary arteries from autopsies of 162 patients who died of acute myocardial infarction were studied. There were 102 men, 72 +/- 10 years old (mean +/- SD), and 60 women, 75 +/- 8 years old. All arteries were dissected from the heart, fixed, decalcified, cut at 2 to 3 mm intervals and processed routinely for histologic examination. A planimeter was used to measure artery, plaque, thrombus and luminal cross-sectional area at the site of plaque rupture with thrombosis in sections projected at x13.8 magnification. At the site of atherosclerotic plaque rupture with superimposed thrombosis, the degree of stenosis due to plaque was: 90 +/- 7% for the right (n = 67), 91 +/- 6% for the left anterior descending (n = 79) and 91 +/- 6% for the left circumflex (n = 38) coronary arteries. Plaque rupture in fatal acute myocardial infarction occurs at sites of severe narrowing (mean 91%, range 67% to 99%). Thus, plaque rupture with thrombosis is unlikely to cause the fatal acute myocardial infarction in patients with mild to moderate coronary stenosis. 
1	Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear. 
1	Flow cytometric determination of breast tumor heterogeneity. Flow cytometric analysis was done on the DNA content of nuclei obtained from different sites of small breast tumors. Although specimens for analysis were obtained within a few millimeters of each other, dramatic differences were occasionally observed in the DNA histograms. In a limited study involving 141 consecutive breast specimens submitted for flow cytometry, 52% (74) were found to have at least one DNA aneuploid population. In 18% of DNA aneuploid tumors, one or more specimens from areas grossly identified as tumor had no DNA aneuploid population. Because of the proposed correlation of aneuploidy with a poorer prognosis and possible responsiveness to chemotherapy, multiple sites should be assayed when flow cytometric DNA analysis is done. 
5	Pneumomediastinum, pneumothorax and subcutaneous emphysema following the measurement of maximal expiratory pressure in a normal subject. Mediastinal and subcutaneous emphysema have been reported as a consequence of deliberate manipulations of the breathing pattern producing a Valsalva-like maneuver in healthy subjects. We present a case of pneumomediastinum, pneumothorax and subcutaneous emphysema occurring in a normal volunteer after repeated measurements of the PEmax. 
5	Predicting failure following shunting of pleural effusions. We placed 43 shunts in 34 patients in five years. Twenty-four had malignant effusions and ten had benign effusions. Thirty-one patients had unilateral shunts, three had bilateral shunts and six required revisions for shunt failure. Two patients died after shunt placement from disease progression. Of the nine patients who experienced poor results, one was noncompliant in operating the shunt and eight had occluded shunts. In the 30 patients, who were compliant and had adequate length of follow-up, five had excellent results, 12 had good results, and five had fair results. Two of the patients with occluded shunts had good results after shunt revision; 24 patients had some symptomatic relief with shunting. Evaluation of factors including a history of prior abdominal surgery, performance status, and pleural fluid cell counts, differential, chemistries, and cytology revealed no significant differences between the patients who experienced shunt failure and those who had patent shunts. Shunting of pleural effusions is well tolerated and has good success rates in properly selected patients. 
2	Role of epidermal growth factor, prostaglandin, and sulfhydryls in stress-induced gastric lesions. Epidermal growth factor promotes the growth of and protects gastric mucosa against various ulcerogens, including stress, but little is known about its role in the pathogenesis of stress ulcerations. In this study, Wistar rats with intact and resected salivary glands were exposed to water-immersion and restraint stress. During 2-14 hours of water-immersion restraint stress, the formation of gastric ulcerations increased progressively and the duration of stress was accompanied by a decrease in DNA synthesis in the gastric mucosa. Following sialoadenectomy, a significant increase in the number of stress ulcerations and further reduction in DNA synthesis were observed. Exogenous epidermal growth factor and dimethyl prostaglandin E2 significantly reduced the ulcerations in the stressed rats with intact salivary glands, but this reduction was significantly less pronounced after sialoadenectomy. Water-immersion restraint stress also resulted in about 50% reduction in mucosal prostaglandin E2 generation, and the pretreatment with indomethacin, which suppressed prostaglandin E2 by about 90%, almost doubled the number of stress ulcerations and abolished the gastro-protective effect of exogenous epidermal growth factor (but not dimethyl prostaglandin E2) against the stress lesions. An inhibition of ornithine decarboxylase activity by difluoromethyl ornithine also augmented stress-induced ulcerogenesis and abolished the protective action of epidermal growth factor while the administration of spermine almost completely prevented stress ulcerations in rats both without and with pretreatment with difluoromethylornithine. Water-immersion restraint stress also significantly reduced mucosal content of glutathione. Cysteamine increased tissue glutathione and reduced stress ulcerations but N-ethylmaleimide, an sulfhydryl blocker, decreased mucosal content of glutathione without affecting the stress ulcerations. This study indicates that the stress ulcers are accompanied by the reduction in mucosal synthesis of DNA, prostaglandin, and glutathione and that the presence of salivary glands attenuates the stress ulcerogenesis probably by releasing epidermal growth factor which acts, in part, by enhancing ornithine decarboxylase activity, mucosal growth, and prostaglandin and glutathione formation. 
5	11 beta-hydroxylase deficiency in hyperandrogenism. OBJECTIVE: to determine the 11-deoxycortisol (S) response and incidence of 11 beta-hydroxylase deficiency in hyperandrogenism. DESIGN: Hyperandrogenic women prospectively and consecutively underwent acute adrenal stimulation studies. SETTING: Tertiary institution. PATIENTS: Two hundred sixty women complaining of hirsutism and/or hyperandrogenic oligomenorrhea were studied, excluding five unrelated families (1.9% of total) suffering from 21-hydroxylase deficient late-onset adrenal hyperplasia. Forty-one healthy premenopausal eumenorrheic women served as controls. MAIN OUTCOME MEASURES: Only two unrelated women (0.8%) had a poststimulation or net increment S level value greater than or equal to threefold the upper 95th percentile of controls and were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. One hundred nine (42%) of hyperandrogenic women had at least one S value above the 95th percentile of controls. These women also demonstrated higher basal (F0) and stimulated cortisol levels, but a similar increment compared with controls. RESULTS: Patients with high S measures had higher testosterone, dehydroepiandrosterone sulfate, and androstenedione levels, but similar luteinizing hormone/follicle-stimulating hormone ratios, than hyperandrogenic cohorts with no abnormal S measures. Basal values of S (S0), F0, or S0/F0 were not useful to predict an abnormal S response to stimulation. CONCLUSIONS: Although adrenocortical hyperactivity was present in 42% of our hyperandrogenic patients, only 0.8% were presumed to suffer from 11 beta-hydroxylase deficient late-onset adrenal hyperplasia. A systemic search for this deficiency in hyperandrogenism is probably unwarranted. 
3	The association of hydrocephalus with intramedullary spinal cord tumors: a series of 25 patients. 171 patients with intramedullary spinal cord tumors were operated on, of which 25 patients (15%), mostly children, developed symptomatic hydrocephalus. Twenty patients (12%) had malignant tumors, with 13 of the 20 cases (63%) complicated by increased intracranial pressure and ventriculomegaly. Of the remaining 151 patients with benign tumors (89%), only 12 (8%) developed symptomatic hydrocephalus. In an effort to understand the relationship between hydrocephalus and intramedullary spinal cord tumor, the authors analyze the level and histology of the neoplasm, as well as its association with spinal cysts. A review of the neurosurgical literature reveals that 34 similar cases of hydrocephalus associated with intramedullary spinal cord tumors have been reported to date. The authors note that the presence of hydrocephalus in patients with malignant intramedullary astrocytomas is associated with a shorter rate of survival than in those patients with high-grade lesions but without hydrocephalus, apparently due to rapid tumor progression. The ventriculomegaly seen with benign spinal cord gliomas has no statistically significant effect upon long-term prognosis. 
5	Uterine rupture. Uterine rupture is a sudden, unforeseeable event that carries a high rate of maternal and perinatal mortality. When the diagnosis of uterine rupture is suspected, prompt surgical intervention with an experienced pelvic surgeon and blood product replacement should be considered. At the time of uterine rupture, the patient should be evaluated for possible repair or hysterectomy. It appears, based on the aforementioned information, that repair is a reasonable consideration. In those patients who have undergone a repair, early delivery by elective cesarean after assessment of fetal lung maturity at or around 36 weeks gestation would appear prudent. In those patients with a prior cesarean, continuous electronic fetal monitoring to detect intrapartum fetal distress would appear prudent. In these patients fetal distress is the most common sign or symptom of uterine rupture and frequently precedes any other clinical manifestations of this complication. 
1	A randomized trial of the effect of three non-steroid anti-inflammatory agents in ameliorating cancer-induced fever. Paraneoplastic fever is well known, and is not an uncommon problem in daily practice. In an effort to ameliorate tumour-induced fever we randomized 48 patients to receive three different non-steroid anti-inflammatory drugs: Naproxen (500 mg d-1), Indomethacin (75 mg d-1) or Diclophenac sodium (75 mg d-1). All patients had solid tumours, and microbial infection had been excluded. All three drugs were equally effective in bringing the temperature down to normal for a period of 30-33 d. Naproxen had the most rapid effect. In cases of fever relapse with the first drug, when the other two drugs were given instead, both proved equally effective. No side-effects were observed. We conclude that Naproxen, Indomethacin and Diclophenac sodium are equally effective in ameliorating paraneoplastic fever. In relapse, a second drug given subsequently can be effective as well. 
1	Hyperplastic polyps seen at sigmoidoscopy are markers for additional adenomas seen at colonoscopy. Asymptomatic individuals undergoing screening flexible sigmoidoscopy were prospectively studied. Polyps were found in 185 subjects. The endoscopist recorded an opinion on the polyps' histology based on endoscopic appearance. No polyps were removed at sigmoidoscopy. All subjects with rectosigmoid polyps then underwent colonoscopy and polypectomy. Of them, 99 subjects (54%) had at least one rectosigmoid adenoma, 69 (37%) had only hyperplastic polyps, and 17 (9%) had other findings. The endoscopists' opinion of the histopathology of polyps at sigmoidoscopy was correct for 61% of the lesions. Of subjects with adenomatous rectosigmoid polyps, 29% had additional adenomas at more proximal sites. Proximal adenomas were found in 28% of patients with hyperplastic rectosigmoid polyps. Patients with rectosigmoid hyperplastic polyps had the same risk for additional proximal adenomas as patients with rectosigmoid adenomatous polyps. 
5	Multiple cranial nerve deficits after ethylene glycol poisoning. We report the cases of two patients who developed cranial nerve palsies after drinking ethylene glycol. A 33-year-old man developed multiple cranial nerve deficits nine days after the ingestion of ethylene glycol in a suicide attempt. Clinical findings included profound bilateral cranial nerve VII palsies and severe dysfunction of cranial nerves IX and X. The neuropathy occurred despite treatment with hemodialysis. The dysphagia completely cleared within two weeks, but at six months a severe bilateral cranial nerve VII dysfunction persisted. A 22-year-old man undergoing hemodialysis for ethylene glycol-induced renal failure developed bilateral cranial nerve VII dysfunction 14 days after ingestion. At a three-month follow-up, the patient demonstrated only moderate functional recovery. The etiology of the cranial nerve deficits is unknown but may be related to oxalate crystal deposition of ethylene glycol-induced pyridoxine dysfunction. 
4	Wegener's granulomatosis presenting as temporal arteritis. A granulomatous giant cell vasculitis of the temporal artery was observed in a biopsy specimen from a patient with corresponding clinical symptoms. Within weeks, the new onset of pulmonary infiltrates and renal failure prompted biopsy of the patient's kidney. A necrotizing glomerulonephritis, compatible with a diagnosis of Wegener's granulomatosis, was present. Vasculitis of the temporal artery may be a feature of Wegener's granulomatosis. 
4	Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. The Cholesterol Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol-niacin therapy in 162 subjects. Two-year results (CLAS-I) showed decreased atherosclerosis progression and increased regression. We now describe a subgroup of 103 subjects treated for 4 years (CLAS-II). Changes in blood lipid, lipoprotein-cholesterol, and apolipoprotein levels were maintained, and at 4 years significantly more drug-treated subjects demonstrated nonprogression (52% drug- vs 15% placebo-treated) and regression (18% drug- vs 6% placebo-treated) in native coronary artery lesions. Significantly fewer drug-treated subjects developed new lesions in native coronary arteries (14% drug- vs 40% placebo-treated) and bypass grafts (16% drug- vs 38% placebo-treated). These results confirm CLAS-I findings and indicate that regression can continue for 4 years. They reaffirm the need for early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects. 
5	Expression of a soluble and functional form of the human beta 2 integrin CD11b/CD18. Polymorphonuclear cells and monocytes (phagocytes) are a critical component of host defense against infections. However, these cells also play a significant role in host tissue damage in many noninfectious diseases, such as ischemia-reperfusion injury syndromes and rejection of transplanted organs. The leukocyte adhesion molecule family CD11/CD18 (beta 2 integrins) is critical to the function of polymorphonuclear cells and monocytes in inflammation and injury. Inherited deficiency of CD11/CD18 impairs phagocyte chemotaxis, adhesion and transmigration across endothelium, and clearance of invading microorganisms through phagocytosis and cell-mediated killing. Furthermore, murine monoclonal antibodies directed against the CD11b/CD18 (CR3) heterodimer have been shown to reduce, by 50%-80%, phagocyte-mediated ischemia-reperfusion injury in several organ systems, such as the myocardium, liver, and gastrointestinal tract and to inhibit development of insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice. Expression of CD11b/CD18 in a soluble and functional form might therefore be potentially useful as an anti-inflammatory agent. We have now expressed a recombinant soluble heterodimeric form of this human beta 2 integrin, normally expressed as two noncovalently associated membrane-bound subunits. The secreted receptor exhibited direct and specific binding to its ligand, iC3b, the major complement C3 opsonin, and inhibited binding of polymorphonuclear cells to recombinant interleukin 1-activated endothelium. 
2	Azathioprine in the treatment of children with inflammatory bowel disease. During a 6-year period, we treated 21 patients with azathioprine, 2 mg/kg/day, as an adjunct to their customary regimen. Nine patients had ulcerative colitis and 12 patients had Crohn disease; the patients' ages ranged from 3 to 17 years. The median duration of disease before the start of azathioprine therapy was 2 years, and median follow-up was 2 years. Sixteen patients seemed to respond to azathioprine therapy: six patients in each disease group had complete responses and four patients (one with ulcerative colitis and three with Crohn disease) had partial responses. Two patients with ulcerative colitis and three patients with Crohn disease did not respond. The median time until patients responded was less than 3 months for patients with ulcerative colitis and 4 months for those with Crohn disease. Reduction of corticosteroid dose was possible for all patients who responded to azathioprine therapy. Only minimal side effects were attributable to the drug. We conclude that azathioprine is an effective adjunctive agent for the treatment of inflammatory bowel disease in childhood, but because questions remain regarding its long-term safety, its use should be reserved for children with refractory disease or severe and unacceptable side effects of corticosteroids. 
3	Diffuse axonal injury: analysis of 100 patients with radiological signs. One hundred patients with head injuries who showed diffuse axonal injury on computed tomographic scans are reported. Evaluation of the Glasgow Coma Score, pupillary signs, and computed tomographic findings on admission led to an improved ability to forecast outcomes. Our relatively good results as compared with other series, can be explained by the high proportion of children and by the liberal use of computed tomography to evaluate head injuries, thus revealing that concussion may sometimes be regarded as an early form of diffuse axonal injury. 
5	Factor XIII deficiency and intracranial hemorrhages in infancy. We report an infant with Factor XIII deficiency who had 2 seemingly spontaneous intracranial hemorrhages. It is important to consider Factor XIII deficiency as a possible cause of unexplained intracranial hemorrhages in infancy. Ongoing factor replacement therapy is recommended to prevent further bleeding episodes. 
5	Management of infants at risk for occult bacteremia: a decision analysis. Because febrile infants with no obvious source of bacterial infection may have bacteremia, and because bacteremia is difficult to diagnose on clinical grounds, we used decision analysis to evaluate whether such infants should be treated with antibiotics, tested further, or sent home. Using a simple decision tree, we found that the decision to give empiric antibiotic treatment is the decision of choice. The difference in quality-adjusted life expectancy between the "best" and "worst" decisions was only 11 days. However, this difference translated to prevention of death or permanent disability in 60 cases per 100,000 febrile children. Further, empiric treatment remained the best management alternative unless the probability of bacteremia was less than 1.4% (less than any published prevalence), or the efficacy of treatment was less than 21%. Our analysis demonstrated that a test with far greater sensitivity than leukocyte count or other tests currently in use is needed to justify testing rather than treating empirically. Further, an enormous patient population would be needed to find a difference of both clinical and statistical significance between treated and untreated patients in a controlled trial. In the absence of such trials, we recommend blood culture and empiric antibiotic treatment of all infants at risk for occult bacteremia. 
5	Anatomical relationship between the renal venous arrangement and the kidney collecting system. The anatomical relationships between the renal venous arrangement and the pelviocaliceal system were studied in 52, 3-dimensional polyester resin corrosion endocasts. In 53.8% of the cases, there were 3 large venous trunks and in 28.8% there were 2 venous trunks joining to form the main renal vein. Intrarenal veins demonstrated free anastomoses that were disposed in 3 systems of longitudinal arcades (stellate, arcuate and interlobar veins). There were large venous collars around caliceal necks and also horizontal arches crossing over calices to link anterior and posterior veins. In 84.6% of the cases the upper caliceal group was encircled anteriorly and posteriorly by venous plexuses, which coursed parallel to the infundibulum. In 50.0% of the cases the lower caliceal group also was enriched by 2 venous plexuses. A close relationship existed between a large inferior tributary of the renal vein and the anterior aspect of the ureteropelvic junction in 40.4% of the cases. In 69.2% of the cases there was a posterior (retropelvic) vein: in 48.1% this vein had a close relationship to the junction of the pelvis with the upper calix and in 21.1% it crossed the middle posterior surface of the renal pelvis. 
4	Transesophageal echocardiography in the diagnosis of ostial left coronary artery stenosis. The diagnosis of ostial stenosis of the left main coronary artery is usually made by use of coronary angiography. However, positioning of the catheter across the obstruction may obscure this diagnosis during contrast injection. Although a damping of arterial pressure when the catheter enters the left coronary artery may suggest ostial stenosis, it may not be possible to make this diagnosis with certainty during cardiac catheterization. We report a series of four patients in whom the left coronary ostium and proximal left coronary arteries were visualized by means of transesophageal echocardiography. Both ostial narrowing by plaque and abnormally fast flow velocities were seen. In each case the echocardiographic findings contributed to the subsequent management of the patients. 
1	Primary lymphoma of bone: a clinicopathologic study of 25 cases reported over 10 years. Twenty-five cases of primary lymphoma of bone (PLB) reported over a 10-year period were reviewed. The presenting symptom was related to involvement of a single bone with or without regional nodal disease. None showed dissemination of lymphoma in the subsequent six months. Patients affected were 7-65 years of age. An equal predilection for the axial and appendicular skeleton was noted. Histologically, the commonest subtype was diffuse histiocytic lymphoma (DHL, 17 cases), whereas four were poorly differentiated lymphocytic (PDL) type and another four were unclassifiable. Follow-up was available in 18 out of 25 patients for periods ranging from 7 months to 8 years. On clinicopathologic correlation we found that 75% of disease-free patients had a DHL whereas 60% of those alive with disease had a PDL. This study reiterates the view that PLB has a good prognosis and the DHL subtype is especially amenable to complete eradication. 
5	Emerging techniques in the diagnosis of sinusitis. In recent years, the high prevalence of chronic sinusitis has been noted in isolation and in association with bronchial asthma, aspirin sensitivity, and perennial rhinitis. Many sinus-associated symptoms arise from nasal rather than sinus pathology; thus, it is important to detect the presence, extent, and nature of any disease within the sinus cavities. Conventional plain radiographs have limited sensitivity and have been supplanted by more widespread use of computerized tomography. The role of other modalities such as ultrasound and magnetic resonance imaging has not yet been completely determined. Other tests such as cytology and endoscopy can detect the presence of infection without the need for invasive antral puncture. Practitioners should consider the impact of a negative imaging test on their therapeutic plan and order tests on that basis. 
1	Brake mechanics, asbestos, and disease risk. Health risks posed by inhalable asbestos fibers are known to exist in a variety of industrial and nonindustrial settings. Although early studies described an increased risk of asbestosis, lung cancer, and mesothelioma in asbestos-industry workers, subsequent research revealed the existence of a potential asbestos-related health hazard in nonasbestos industries such as the textile and railroad industries. Brake mechanics and garage workers constitute a large work force with potential exposures to levels of asbestos capable of producing disease. Unfortunately, the health risk faced by these workers has received little attention. This article briefly discusses currently available information on the asbestos health risks of workers in this setting, and highlights the need for further investigations of this occupational group. 
2	Microsurgical epididymovasostomy by tubule intussusception: a new technique in rat model. This experimental study on 15 adult male rats with bilateral epididymovasostomies evaluates a new technique of tubule intussusception as an improved form of end-to-end anastomosis. This paper describes in detail the steps in this technique and offers physiological, anatomical, and histological follow-up after 3 months. With this technique there is a 97% patency rate and a 23.3% incidence of macroscopic spermatic granuloma. Complications are discussed in detail. 
1	Preoperative cytology and mammography in patients with single-duct nipple discharge treated by surgery. Microdochectomy has been the routine management for single-duct nipple discharge. Our review of 176 consecutive patients surgically treated between 1975 and 1988 revealed eight patients with in situ carcinomas and seven with infiltrative carcinomas. Seventeen patients had multiple papillomas, two had atypical hyperplasia and two had atypical epitheliosis. Case selection for surgery has recently been advocated. In our study, nipple discharge cytology was helpful in 67 per cent of cases with underlying malignant pathology. Mammography was found to be unreliable, alerting suspicion in only two of 15 cases. 
4	Transient mitral regurgitation due to mitral valve prolapse accompanied by systolic anterior motion of the mitral valve. A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure. 
5	Frontal dysfunction and memory deficits in the alcoholic Korsakoff syndrome and Alzheimer-type dementia. This study investigated the intercorrelation of 8 'frontal' tests in 32 patients with Korsakoff's syndrome and Alzheimer's disease, and examined the relationship of frontal dysfunction to impaired release from proactive interference and impoverished retrieval from retrograde memory. Amongst the frontal tests, there were statistically significant intercorrelations between 3 'fluency' tests and 3 'card-sorting' tests, although the degree of shared variance was relatively low. The relationship of another test--picture arrangement errors--was more equivocal; performance for 'cognitive estimates' was unrelated to performance in the other frontal tests, possibly because it may reflect pathology at a different frontal site. There was no evidence in this study that variability in release from proactive interference was related to measures of frontal function in either patient group, and the conditions under which these patient groups fail to show 'normal' release appear to be tightly constrained. On the other hand, the defective retrieval of retrograde memories was correlated with frontal dysfunction in both patient groups. There was a suggestion of a double dissociation with a measure of nonverbal short-term forgetting, impairment at which was related to the degree of general cortical atrophy rather than frontal dysfunction. A stepwise regression equation based on 3 frontal tests could account for 64% of the variability in retrograde memory performance within the total patient group, 68.5% in the Korsakoff group and 57% in the Alzheimer group. By comparison, the severity of anterograde memory impairment predicted only 21% of the variance in retrograde memory performance. It is concluded that frontal dysfunction produces a disorganization of retrieval processes which contributes to the temporally-extensive retrograde amnesia of these two disorders. 
5	Glycolysis as primary energy source in tumor cell chemotaxis. The energy requirements via glycolytic pathways were directly measured in migrating tumor cells. Motility in the metastatic human melanoma cell line A2058, stimulated by insulinlike growth factor I (IGF-I), depends on glycolysis in the presence of glucose as its principal source of energy. Motility in glucose-free medium was 75% reduced and utilized mitochondrial respiration (inhibited by oligomycin). With increasing (physiologic) glucose concentrations, there was a dramatic shift to anaerobic glycolysis as the energy source and 93% elimination of the oligomycin inhibition of motility. Oxamate, an inhibitor of glycolysis, inhibited motility at all glucose concentrations. CO2 production from glycolysis and from the hexose monophosphate shunt was measured in migrating tumor cells. The time course and glucose-dose dependence of glycolytic CO2 production correlated directly with motility. In contrast, mitochondrial CO2 production was inversely related to glucose concentration. A monoclonal antibody for the IGF-I receptor inhibited both motility and glycolytic CO2 production, indicating that both processes are receptor mediated. 
4	Occult cancer in patients with deep venous thrombosis. A systematic approach. The authors prospectively studied 113 consecutive patients with deep venous thrombosis of the lower extremities to determine the most appropriate workup study for searching for a hidden cancer. After a careful physical examination, the following routine tests were performed: erythrocyte sedimentation rate (ESR), whole blood counts, biochemistry, carcinoembryonic antigen (CEA) levels, chest radiograph, upper gastrointestinal endoscopy, abdominal ultrasound and computed tomography (CT) scan. If a malignant lesion was suspected, further appropriate studies were performed. After discharge, periodic follow-up was performed on all patients in the outpatient clinic. A malignant neoplasm was detected in 12 patients. Of these 12 patients, six were asymptomatic with the exception of experiencing thrombophlebitis. Cancer was found more commonly in patients with idiopathic deep vein thrombosis (DVT) (7 of 31 versus 5 of 82 patients with secondary DVT; P = 0.012), and in those patients with abnormal lactic dehydrogenase (LDH) levels (6 of 23 versus 6 of 90; P = 0.007). Abnormal CEA levels allowed diagnosis of two cases of colonic cancer (on colonoscopy). Both ultrasound and CT scan of the abdomen showed two cases of urinary bladder carcinoma at a very early stage. Furthermore, two cases of adenomatous polyps in colon were found, a condition considered by most authors to be a colorectal cancer precursor. In addition, there were five patients with large benign pelvic tumors, and two patients with absent inferior vena cava. The most striking finding was that some cases of cancer were at a very early stage. It was concluded that blood cell counts, LDH, CEA, chest radiograph, and abdominal ultrasonography (or CT scan) should be routinely performed on all patients with deep venous thrombosis (particularly those with idiopathic DVT). Malignancy would not have been recognized in some patients if these tests had not been performed. 
2	Factors affecting the enterohepatic circulation of oral contraceptive steroids. Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol. 
4	Toxic carbamazepine concentrations following cardiothoracic surgery and myocardial infarction. Carbamazepine is being used more frequently in the U.S. as an initial agent of choice to treat generalized tonic-clonic, mixed, and partial seizures with complex symptomatology. Carbamazepine is extensively metabolized in the liver; however, there is little information available on its pharmacokinetics in patients following surgery or myocardial infarction, or in those with liver disease. We report a case of a patient who attained toxic carbamazepine serum concentrations (ranging from 18.2 to 21.5 micrograms/mL) two days after cardiothoracic surgery and an intraoperative myocardial infarction, and experienced lethargy, diplopia, dysarthria, diaphoresis, and horizontal and downgaze nystagmus. These alterations in serum carbamazepine concentration normalized ten days after surgery. They may have been due to a combination of changes in protein binding and decreased elimination due to altered intrinsic hepatic clearance. With carbamazepine achieving a more prominent place in anticonvulsant therapy, the influence of various procedures and disease processes on the pharmacokinetics and pharmacodynamics of carbamazepine, as well as the clinical consequences of such changes, need further investigation. 
4	Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery. Accumulation of complement factors has been found to occur in the myocardium after infarction. We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium. In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass. Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10). From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB. Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05). The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05). No significant difference was found after 30 min of reperfusion. Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury. 
5	Dermatology and the human gene map. Chromosomal localization has been established for many genetic traits. Gene mapping may lead to the identification of disease genes, an understanding of pathogenesis, and the development of rational therapy, as well as facilitating antenatal diagnosis and genetic counselling. 'The new genetics' is therefore of great interest to the clinician. Unfortunately the complex technology and unfamiliar vocabulary of molecular biology often deter non-specialists from keeping abreast of these developments. This account explains the principles of gene mapping, discusses its relevance to dermatologists, and lists the established loci of dermatologically important genes. 
2	Can the blood urea nitrogen/creatinine ratio distinguish upper from lower gastrointestinal bleeding? We wanted to know if the blood urea nitrogen to creatinine (BUN/Cr) ratio could help distinguish upper from lower gastrointestinal bleeding. We analyzed retrospectively patients admitted to our hospital for gastrointestinal bleeding over the past 5 years. A total of 126 patients represented 74 upper bleeds and 52 lower bleeds. The mean BUN/Cr ratio was significantly higher in upper than lower bleeders, 34.8 and 17.8 respectively (p less than 0.001). No lower bleeder had a ratio of greater than or equal to 36, whereas 38% of upper bleeders had a ratio of greater than or equal to 36. The BUN/Cr ratio may be an easy, cheap method of distinguishing upper from lower gastrointestinal bleeding in some cases. A BUN/Cr ratio of greater than or equal to 36 suggests upper gastrointestinal bleeding, whereas a ratio of less than 36 is not helpful in locating the source of bleeding. 
5	Genetics and psychiatry: an unheralded window on the environment. Two recent reviews in the American Journal of Psychiatry and the British Journal of Psychiatry reported on progress in understanding the genetics of psychiatric disorder. Both reviews focused on this progress as a prelude to psychiatric diagnostics and therapeutics based on molecular biology. Neither review recognized that the latest data in behavioral genetics support environmental causes for abnormal development and psychopathology as much as they support genetic causes. Moreover, these genetic data point clearly to a type of environmental cause with central importance: the environment that is specific or unique to each sibling in a family. 
3	Neuromuscular diseases: evaluation with high-frequency sonography. Forty-four patients with clinically suspected neuromuscular disease and 12 healthy volunteers underwent high-frequency ultrasound examination of the rectus femoris, vastus medialis, vastus lateralis, and biceps brachii muscles, and the number of perimysial septa was determined. These numbers and muscle/soft-tissue ratios of the lower extremity were compared. Findings were correlated with results of muscle biopsy in all patients with suspected disease. Using the number of perimysial septa in the lower extremity, the authors found significant differences between the muscles of healthy volunteers and those of patients with Duchenne muscular dystrophies, other muscular dystrophies, and spinal muscular atrophies: The receiver operating characteristic curve showed that an average of 12 perimysial septa within 1 cm of muscle is the ideal cutoff value to differentiate subjects without morphologic changes from those with pathologic findings. The authors conclude that this measurement is useful for differentiation of neuromuscular diseases and may be a noninvasive, reproducible means with which to evaluate disease progression. 
1	Free radical-derived quinone methide mediates skin tumor promotion by butylated hydroxytoluene hydroperoxide: expanded role for electrophiles in multistage carcinogenesis. Free radical derivatives of peroxides, hydroperoxides, and anthrones are thought to mediate tumor promotion by these compounds. Further, the promoting activity of phorbol esters is attributed, in part, to their ability to stimulate the cellular generation of oxygen radicals. A hydroperoxide metabolite of butylated hydroxytoluene, 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH), has previously been shown to be a tumor promoter in mouse skin. BHTOOH is extensively metabolized by murine keratinocytes to several radical species. The primary radical generated from BHTOOH is a phenoxyl radical that can disproportionate to form butylated hydroxytoluene quinone methide, a reactive electrophile. Since electrophilic species have not been previously postulated to mediate tumor promotion, the present study was undertaken to examine the role of this electrophile in the promoting activity of BHTOOH. The biological activities of two chemical analogs of BHTOOH, 4-trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH, were compared with that of the parent compound. 4-Trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH have a reduced ability or inability, respectively, to form a quinone methide; however, like the parent compound, they both generate a phenoxyl radical when incubated with keratinocyte cytosol. The potency of BHTOOH, 4-trideuteromethyl-BHTOOH, and 4-tert-butyl-BHTOOH as inducers of ornithine decarboxylase, a marker of tumor promotion, was commensurate with their capacity for generating butylated hydroxytoluene quinone methide. These initial results were confirmed in a two-stage tumor promotion protocol in female SENCAR mice. Together, these data indicate that a quinone methide is mediating tumor promotion by BHTOOH, providing direct evidence that an electrophilic intermediate can elicit this stage of carcinogenesis. 
1	Multiple spinal metastases from paraganglioma. Isolated vertebral body metastases from paraganglioma are exceedingly rare. They have been reported to occur in the presence of active primary tumor in the neck, local recurrence, or widespread metastases. A unique case of carotid body tumor (paraganglioma) is reported with the following features: (1) multiple vertebral body metastases (C6, T9, and L3) presenting with spinal cord compression, and no evidence of local recurrence or other metastatic disease; (2) absence of mitoses on the original specimen or the metastatic deposit; and (3) a prolonged interval (9 years) to the development of symptomatic metastases. 
5	Oxygen-exacerbated bleomycin pulmonary toxicity Bleomycin is an antineoplastic agent with potential for producing pulmonary toxicity, attributed in part to its free radical-promoting ability. Clinical and research experiences have suggested that the risk of bleomycin-induced pulmonary injury is increased with the administration of oxygen. We report a case in which the intraoperative administration of oxygen in the setting of previous bleomycin therapy contributed to postoperative ventilatory failure. Our patient recovered with corticosteroid therapy. Physician awareness of a potential interaction between oxygen and bleomycin may help reduce the morbidity and mortality related to bleomycin therapy. 
4	Mild ischemia predisposes the S3 segment to gentamicin toxicity. The purpose of these studies was to determine if a functionally insignificant ischemic insult, occurring prior to gentamicin administration, enhanced gentamicin nephrotoxicity. Bilateral renal pedicle clamp studies demonstrated that 15 minutes of ischemia did not increase the plasma creatinine yet markedly enhanced gentamicin nephrotoxicity. Further studies, in uninephrectomized rats, demonstrated that following fifteen minutes of renal ischemia and four hours of reperfusion inulin clearance, FENa+ and cellular morphology were normal. This model, therefore, was used in all subsequent studies. While the plasma creatinine concentrations were normal 24 hours following 15 minutes of ischemia and only slightly increased following gentamicin administration (100 mg/kg, i.p.) gentamicin administered four hours following 15 minutes of renal ischemia resulted in significantly increased 24-hour plasma creatinine values. Light microscopic quantitation of tissue injury, performed 24 hours following experimental manipulation, was notable for S3 segment damage in the ischemia plus gentamicin group. This was not observed in either the ischemia group or the sham operated gentamicin group. Cortical gentamicin levels were elevated in the ischemia plus gentamicin group, despite similar plasma gentamicin half-lives. However, the elevation in cortical gentamicin levels was dissociated from the enhanced nephrotoxicity seen following mild ischemic injury. Taken together these data indicate that mild renal ischemia, occurring prior to gentamicin administration, greatly enhanced gentamicin nephrotoxicity with the greatest damage occurring to S3 cells. 
1	Null cell adenoma of the pituitary with features of plurihormonality and plurimorphous differentiation. The case of a 35-year-old man with pituitary macroadenoma who was complaining of reduced sexual activity is presented. Histologic examination showed a chromophobic adenoma corresponding mainly to a null cell adenoma at the ultrastructural level. Focal plurihormonality and plurimorphous differentiation of adenoma cells were demonstrated by immunohistochemical and electron-microscopic studies. It is suggested that adenomatous null cells represent pluripotent progenitor cells capable of transforming to different hormone-producing cell types. The factors accounting for differentiating to various cell populations have yet to be elucidated. 
1	Lack of relationship between perioperative blood transfusion and survival time after curative resection for gastric cancer. To better comprehend the relationship between perioperative blood transfusion and survival time after curative gastrectomy for advanced gastric cancer, the authors reviewed retrospectively data on 568 patients treated in their clinics from 1965 to 1983. Of these 568, 195 (34.3%) required no blood transfusion and 373 (65.7%) required transfusions within the perioperative period. Univariate analysis indicated that the survival time of the transfusion recipients was significantly less than that of the patients who had no transfusions (P less than 0.01). In subgroups of the authors' patients stratified to adjust for stage of disease, there was, however, no significant difference between the survival rates. Subsequently, multivariate analysis, using the Cox regression analysis, which adjusted for sex, age, and other covariates, indicated that perioperative blood transfusion was not a useful factor for predicting survival time. Multivariate analysis suggested that tumor size (P less than 0.01), degree of invasion into the gastric wall (P less than 0.01) and status of lymph node metastasis (P less than 0.01) were the most important covariates after curative gastrectomy for advanced gastric cancer. The authors' findings revealed the lack of any relationship between perioperative blood transfusion and survival time of patients who underwent curative resection for advanced gastric cancer. 
5	Endoscopic palliative intubation of the esophagus invaded by lung cancer. Thirty-two patients with esophageal involvement by lung cancer were managed by endoscopic intubation. In 22 patients with extrinsic esophageal strictures, the success rate of intubation was 91%, and 82% were discharged with their dysphagia relieved and esophageal patency restored. The mean survival rate was 4.4 months. In 10 patients with esophago-bronchial fistulas, 3 had the fistulous tract obliterated and lived a mean of 5 months. This low success rate of closing fistulas is due to failure to seal off the space between the stent and the fistula because of absence of tumor-associated stenosis. The overall morbidity rate was 28.1% (18.8% perforation, 6.3% hemorrhage, and 3.1% tracheal obstruction). The overall mortality rate was 18.8%. Although complications were more frequent than in primary esophageal tumors, endoscopic intubation was the only way to palliate this desperate condition and provided 66.6% of patients with relief of symptoms, nutritional improvement, and a mean survival time of 4.5 months. 
1	Fourth ventricular schwannoma. Case report. A schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described. A ventricular schwannoma has not previously been reported in the literature. The presenting clinical and radiographic features and the pathology of this tumor are summarized, and an explanation is sought for its unusual location. 
5	Addition of clonidine enhances postoperative analgesia from epidural morphine: a double-blind study. This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05). 
1	Comparative epidemiology of cancer between the United States and Japan. A second look. Vital statistics were examined for the years 1955 through 1985 for Japanese natives and United States whites to elucidate changes in cancer mortality and related antecedent patterns of life-style in these two populations. Results show that lung cancer rates are rapidly accelerating among Japanese males as a consequence of their prior history of heavy cigarette smoking. Oropharyngeal cancer rates are also rising in Japan paralleling increases in alcohol and tobacco utilization. As the Japanese life-style and diet continue to become more "westernized," the rates of malignancies of the breast, ovary, corpus uteri, prostate, pancreas, and colon also continue to rise. Nevertheless, the mortality patterns of certain malignancies, viz., laryngeal, esophageal, and urinary bladder cancer, are discrepant with their established risk factor associations, suggesting the existence of other differences in risk factor exposure between the two countries. Epidemiologists and health educators need to develop innovative international programs of investigation and health promotion with preventive impact on common malignancies associated with risk factors of life-style. 
5	Procainamide-induced respiratory insufficiency after cardiopulmonary bypass. A 46-year-old man could not be weaned from ventilatory support while receiving procainamide. When the drug was discontinued, the patient was successfully weaned shortly thereafter. 
4	Stroke in systemic lupus erythematosus [published erratum appears in Stroke 1991 Mar;22(3):417] We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti-deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman-Sacks endocarditis are closely associated with occlusive cerebrovascular disease. 
5	Stapling or suturing for anastomoses of the left side of the large intestine. Two hundred and fifty patients undergoing elective surgical treatment involving anastomoses of the left side of the colon or colon and rectum have been studied in a randomized trial in which the EEA (U. S. Surgical Corp.) circular stapler has been compared with single layer sutured anastomoses. Only patients in whom either technique was feasible were included in the analysis. The operative techniques were largely standardized. Patients were studied by means of a limited barium enema on the ninth or tenth postoperative day. The data have been analyzed for leakage rate (clinical and roentgenologic), other complications and degree of experience of the surgeon. Eleven patients were excluded from the analysis because the selected technique could not be carried out; of these, eight were in the stapled group in which it was possible to perform a sutured anastomosis. There were no instances in which it was possible to staple but not possible to suture. The remaining three exclusions were patients in whom either a coloanal anastomosis or a Hartmann procedure was performed. There was no over-all difference in the leakage rate--roentgenologic, clinical or total--between the two groups. However, when analyzed by the surgeon, the clinical leakage rate for surgeons in training was greater for sutured anastomoses than for stapled anastomoses (p = 0.053). Thus, it appears that the benefits of experience are more pronounced for sutured anastomoses but that, in experienced hands, neither technique is superior. 
4	Intraoperative assessment of cerebral ischemia during carotid surgery. One of the problems in carotid surgery is the intraoperative detection of brain ischemia. None of the methods (EEG; stump pressure) applied so far have been successful. Branston et al. (1974) found a threshold relationship between cortical cerebral blood flow and cortical somatosensory evoked potential (SEP). As the local blood flow fell below about 16 ml/100 g/min a progressive reduction occurred in the amplitude of the cortical evoked potential (N20/P25), implying a fundamental failure of neuronal function in the somatosensory cortex. We have monitored cortical SEP (somatosensory evoked potential) during 734 CEA's (carotid endarterectomies) in order to find an index of risk of incipient cerebral ischemia during carotid cross-clamping, to determine the need for shunting and the causes of early irreversible neurologic deficits. In 59 cases evaluation of SEP was not possible because of technical difficulties. During 586 CEA's no alteration of SEP occurred. However, 4 patients had an immediate postoperative neurologic deficit, while the SEP remained normal. Abnormal SEP occurred in 89 cases and in 6 of these an irreversible loss of SEP was seen. These patients awoke with a new neurologic deficit. We found a reversible abnormal SEP in 83 cases. Reversible changes of SEP occurred mainly during carotid clamping. The diagnostic sensitivity of intraoperative SEP monitoring in predicting neurologic outcome was 60% with a specificity of 100%. 
5	Life-threatening hemorrhage after placement of an endosseous implant: report of case This article reports an unusual but dangerous complication of implant surgery. Minimal perforations of the lingual plate and inferior border of the mandible had been considered previously to be benign occurrences. This report demonstrates the importance of managing acute airway problems resulting from perforations. 
3	Semantic deterioration in Alzheimer's: the patterns to expect. Differentiating language changes between the normal aged and those in the early stages of dementia is never simple. Knowing the differences and what to expect can aid in making this diagnosis. 
1	Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Juvenile chronic myelogenous leukemia (JCML) is a good model for the study of myeloproliferation because JCML hematopoietic progenitor cells grow in vitro at very low cell densities without the addition of exogenous stimulus. Previous studies have demonstrated that this proliferation is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF), and that removal of monocytes from the cell population before culture eliminates this "spontaneous" myeloproliferation, suggesting a paracrine role of monocyte stimulation. However, subsequent studies have shown that increased GM-CSF production from the JCML monocytes is not a consistent finding and therefore not a plausible sole mechanism. In examining hematopoietic growth factor dose-response curves, both JCML GM and erythroid nonadherent progenitor cell populations displayed a marked and selective hypersensitivity to GM-CSF. Responses to interleukin-3 and G-CSF were identical to control dose-response curves. This is the first demonstration of a myeloid leukemia in which hypersensitivity to a specific growth factor appears to be involved in the pathogenesis of the disease. 
5	Pediatric HIV disease. The newest chronic illness of childhood. HIV disease has emerged as a major chronic illness of childhood. Children with HIV infection and children with other chronic health impairments have much in common, including the need for comprehensive, multidisciplinary, coordinated care that includes special attention to the psychosocial effects on the child and family. However, because the mother and often the father and siblings share this lethal viral infection, the impact of HIV disease upon the family surpasses that of virtually all other chronic conditions. This is compounded by the association of the disease with drug use, its preponderance among the most disenfranchised populations in the United States, and the persistent public fear and discrimination surrounding AIDS. We have made substantial progress already in the medical management of this infection, and while we await the development of more effective therapies, we already have the tools and knowledge in hand to help these families. 
4	Esophageal contribution to chest pain in patients with coronary artery disease. We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients. 
4	Multivessel coronary angioplasty from 1980 to 1989: procedural results and long-term outcome From June 1980 to January 1989, 3,186 patients had coronary angioplasty of two (2,399 patients) or three (787 patients) of the three major epicardial coronary systems. A mean of 3.6 lesions (range 2 to 14) were dilated per patient, with a 96% success rate. Acute complications were seen in 94 patients (2.9%) and included Q wave infarction in 47 (1.4%), urgent coronary artery bypass surgery in 33 (1%) and death in 31 (1%). Multivariate correlates of in-hospital death included impaired left ventricular function, age greater than or equal to 70 years and female gender. Complete long-term follow-up data were available for the first 700 patients and the follow-up period averaged 54 +/- 15 months in duration. Actuarial 1 and 5 year survival rates were 97% and 88%, respectively, and were not different in patients with two or three vessel disease. By Cox regression analysis, age greater than or equal to 70 years, left ventricular ejection fraction less than or equal to 40% and prior coronary artery bypass surgery were associated with an increased mortality rate during the follow-up period. Repeat revascularization procedures were required in 322 patients (46%). Restenosis resulted in either repeat angioplasty or bypass surgery in 227 patients (32%). Repeat coronary angioplasty was performed for isolated restenosis in 126 patients (18%), for restenosis and disease progression at new sites in 85 patients (12%) and for new disease progression alone in 54 patients (8%). Coronary bypass surgery was required in 110 patients (16%) during the follow-up period. 
4	Cardiovascular effects of the somatostatin analog octreotide in acromegaly. OBJECTIVE: To determine the cardiovascular effects of the somatostatin analog octreotide in patients with acromegaly. DESIGN: Prospective nonrandomized study. SETTING: Referral-based endocrinology clinic. PATIENTS: Seven patients with active acromegaly, three of whom had refractory congestive heart failure. The other four patients were free of symptoms associated with heart failure. INTERVENTIONS: All patients were treated with octreotide, 100 to 500 micrograms subcutaneously three times daily. The three patients with heart failure continued to receive cardiovascular therapy (angiotensin converting enzyme inhibitors, digitalis, diuretics). MEASUREMENTS AND MAIN RESULTS: During octreotide therapy, patients showed a rapid decrease in growth hormone and insulin-like growth factor 1 (IGF-1): Mean levels (+/- SD) fell from 28.1 +/- 32.7 micrograms/L to 5.2 +/- 8.3 micrograms/L and 740 +/- 126 micrograms/L to 372 +/- 64 micrograms/L, respectively (P less than 0.025). Plasma volume returned to normal and heart rate decreased significantly. In the four patients without heart failure, right-heart catheterization done before and after 3 months of octreotide therapy showed an 18.3% +/- 11% reduction in stroke volume and a return to normal of the cardiac index. The three patients with congestive heart failure, evaluated before and after 40 days and up to 2 years of therapy, showed a dramatic clinical improvement that was associated with an increase in stroke volume (by 24% to 51%). In these patients, the cardiac index remained in the normal range, filling pressures were markedly decreased, and pulmonary wedge pressure returned to normal. This improvement was sustained for up to 3 years in the two patients with heart failure who were receiving long-term treatment. CONCLUSION: The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure. 
4	Neurologic abnormalities in a patient with human ehrlichiosis. Human ehrlichiosis is a tick-borne rickettsial disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In our patient, changes in mental status, upper motor neuron signs, cerebrospinal fluid pleocytosis, and increased serum protein levels were found in association with serologically confirmed ehrlichiosis and were most likely due to vasculitis involving the central nervous system. Intraleukocytic inclusions, although observed in our case, have been infrequently found in other reported cases of ehrlichiosis. 
5	The effect of long-acting somatostatin analogue on enzyme changes after endoscopic pancreatography. The effect of the long-acting somatostatin analogue, octreotide acetate (Sandostatin) on enzyme elevation after endoscopic pancreatography was studied in a prospective, randomized, double-blind trial. Sixty-three consecutive patients undergoing ERCP were randomly allocated to two group. In the control group, 34 patients received isotonic sodium-chloride, and in the treated group 29 patients received 0.1 mg of octreotide acetate subcutaneously before the pancreatography. After the endoscopy, amylase levels increased to pathological range in 15 of the controls and in 3 of the treated patients, whereas lipase levels showed a pathological rise in 17 of the controls and in 5 of the treated patients. A significant difference (p less than 0.01) was observed in the amylase and lipase changes between the two groups at 90 and 180 min after pancreatography. The enzyme levels showed at 90 min, mean +/- SD amylase: controls 540 +/- 185 units/liter, treated patients 261 +/- 108 units/liter; lipase: controls 304 +/- 98 units/liter, treated patients 198 +/- 88 units/liter. These findings suggest that the use of long-acting somatostatin analogue ameliorates the enzyme increases in the serum after endoscopic pancreatography. 
4	Surgical treatment of renovascular hypertension and respective late results. A twenty years experience. This paper presents the long term results following operative reconstruction for renovascular hypertension in 115 patients operated upon over a period of 20 years. There were 71 (61.7%) males and 44 (38.3%) females with a median age of 46 years (range 16-67). Renal revascularization was unilateral in 96 (83.4%) cases and bilateral in 19 (16.6%). Dacron knitted bypass grafts, were used in 51 and PTFE in 33 instances. Saphenous vein grafts were used in 11 patients. In 15 cases treatment was by local endarterectomy with concomitant angioplasty (12 unilateral and 3 bilateral). Simultaneous aortorenal reconstruction was undertaken in 38 (33%) patients. There were no deaths in the group with isolated renal artery reconstruction. In the group of aortorenal reconstructions, two deaths were encountered (5.7%). Postoperatively, blood pressure was either normal or improved in 83 (72%) patients at a mean follow-up period of 48.3 months (range 1-195 months). The best results were obtained in younger individuals with segmental renal artery lesions. Linear progression analysis, showed age to be a major determinant in the postoperative response to hypertension. There was a greater degree of long term success in patients with fibromuscular dysplasia, as compared to individuals with atherosclerosis. Crude survival probabilities, were 78% and 61% at 5 and 10 years respectively. Late deaths encountered in the present series, were mostly attributable to myocardial infarction (7.8%). In this series, the best results were obtained in individuals younger than 50 years of age, with segmental renal artery lesions. 
3	Definition of the role of contemporary surgical management in cisternal and parenchymatous cysticercosis cerebri. With increasing immigration from endemic regions, the incidence of neurocysticercosis in North America is rising. This retrospective study was undertaken to examine the role of surgery in those cases presenting with large cystic parenchymal and cisternal lesions in the current era of anthelminthic agents administered orally. A total of 237 patients presented with newly diagnosed neurocysticercosis to our institution over a recent 5-year period (mean age, 31.2 years). Among those who presented with cystic mass lesions predominantly affecting the brain parenchyma and cisternal spaces, 20 (8.4%; mean age, 40.2 years) with large cystic lesions subsequently underwent surgical intervention, either because of an emergent presentation or because they were refractory to medical management. Clinical presentation included increased intracranial pressure, focal neurological deficit, and seizure. Radiographic imaging (computed tomography and/or magnetic resonance imaging) demonstrated 12 cases with cisternal lesions, 7 with parenchymal lesions, and 1 involving both compartments. Based on imaging guidelines, 30 operative procedures (excluding shunt revisions) were performed (14 craniotomies, 8 cerebrospinal fluid diversions, 7 stereotactic procedures, and 1 burr hole drainage). Fifteen (75%) showed neurological or symptomatic improvement over a median follow-up period of 36.4 months. There were three surgery-related complications and no deaths. 
5	Measurements of right ventricular volumes during fluid challenge. The effects of fluid loading on RV function were studied in 41 acutely ill patients monitored with a modified pulmonary artery catheter equipped for measuring RVef. Hemodynamic evaluation was performed before and after infusion of 300 ml of 4.5 percent albumin solution in 30 min. Changes in SI did not correlate with Pra or Ppao but did with RVEDVI. For the entire group, RVef was unchanged (27 +/- 9 vs 27 +/- 9 percent). In the eight patients with an initial RVEDVI greater than 140 ml/m2, the fluid challenge increased Pra and Ppao and reduced LVSWI without any other significant effect. There was no significant correlation between RVEDVI and Pra and only a weak correlation between RVESVI and Ppa. However, there was a highly linear correlation between both RVEDVI and RVESVI and changes in RVEDVI and in RVESVI, suggesting that in the absence of severe pulmonary hypertension RV output is primarily dependent on RV preload. 
1	Pigmented Bowen's disease arising from pigmented seborrheic keratoses. We report three cases of pigmented Bowen's disease that clinically and histologically had features of seborrheic keratoses. We speculate about the mechanism of pigmentation in these lesions and suggest that they arise from pigmented seborrheic keratoses. 
5	Evidence that a receptor-operated event on the neutrophil mediates neutrophil accumulation in vivo. Pretreatment of 111In-neutrophils with pertussis toxin in vitro inhibits their accumulation in vivo. The role of neutrophil chemoattractant receptors in neutrophil stimulation in vitro is well established, however, the precise mechanisms underlying local neutrophil accumulation at inflammatory sites in vivo have not been defined. A fundamental question that remains open is whether chemoattractants act on the endothelial cell or the neutrophil to initiate the process of neutrophil migration in vivo. To address this question we have investigated whether neutrophil accumulation in vivo can occur if chemoattractant receptor occupancy is uncoupled from neutrophil stimulation. For this purpose we have used pertussis toxin (PT) as the pharmacologic tool. We have investigated the effect of in vitro pretreatment of rabbit neutrophils with PT on their responses in vitro and on their accumulation in vivo. Pretreatment of rabbit neutrophils with PT inhibited FMLP- and C5a-, but not PMA- induced increases in CD18 expression, neutrophil adherence, and degranulation in vitro. This pretreatment procedure with PT inhibited the accumulation of radiolabeled neutrophils in vivo in response to intradermally injected FMLP, C5a, C5a des Arg, leukotriene B4, IL-8, and zymosan in rabbit skin. Further, in contrast to the in vitro results, PT inhibited the PMA-induced 111In-neutrophil accumulation in vivo. Interestingly, pretreatment of neutrophils with PT also inhibited accumulation in response to intradermally injected IL-1, despite the reports that IL-1 lacks neutrophil chemoattractant activity in vitro. Although the experimental techniques used cannot distinguish the different stages of neutrophil migration involved, these results suggest that the accumulation of neutrophils induced by local extravascular chemoattractants in vivo depends on a pertussis toxin-sensitive receptor operated event on the neutrophil itself. Further, PMA and IL-1 may release secondary chemoattractants in vivo. 
5	Effect of motilin on gastric emptying in patients with diabetic gastroparesis. OBJECTIVES: Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances. RESEARCH DESIGN AND METHODS: The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects. RESULTS: During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values. CONCLUSIONS: These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects. 
4	Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL.kg-1.min-1 and pressure at greater than 50 mm Hg. Flows and pressures less than target occurred in 21.6% and 97.1% of patients, respectively. Fifteen patients (3.0%) suffered new renal and 13 (2.6%) new central nervous system dysfunction. Low pressure or flow during cardiopulmonary bypass, expressed in absolute values or in intensity-duration units, were not predictors of either adverse outcome. Multivariate analysis identified use of postoperative intraaortic balloon counterpulsation (p less than 10(-6], excessive blood loss in the ICU (p less than 10(-4], need for vasopressors before cardiopulmonary bypass (p less than 10(-4], postoperative myocardial infarction (p less than 10(-3], emergency reoperation (p less than 0.002), excessive postoperative transfusion (p less than 0.02), and chronic renal disease (p less than 0.03) as independent predictors of postoperative renal dysfunction. Independent predictors of postoperative central nervous system dysfunction were cardiopulmonary resuscitation in the intensive care unit (p less than 10(-6], intracardiac thrombus or valve calcification (p less than 0.02), and chronic renal disease (p less than 0.03). Age greater than 65 years (40.7% of patients) did not predict either outcome. We conclude that failure of the native circulation during periods other than cardiopulmonary bypass rather than the flows and pressures considered here is the major cause of renal and clinically apparent central nervous system dysfunction after cardiac operations. 
5	Chronic care needs to be a higher priority. Although acute care remains the focus of the U.S. health care delivery system, a shift is taking place toward chronic-illness mortality. Developing effective chronic-disease management processes is tough in the context of today's acute care orientation, according to William F. Henry, president of ForeSight Strategy Associates, St. Paul, MN. 
3	Ehrlichiosis in children. Tick-borne rickettsiae of the genus Ehrlichia have recently been recognized as a cause of human illness in the United States. In the years 1986-1988, 10 cases of ehrlichiosis were diagnosed in children in Oklahoma. Fever and headache were universal: myalgias, nausea, vomiting, and anorexia were also common. Rash was observed in six patients but was a prominent finding in only one. Leukopenia, lymphopenia, and thrombocytopenia were common laboratory abnormalities. Six patients were treated with tetracycline, three with chloramphenicol, and one was not treated with antibiotics: all recovered. The onset of illness in spring and early summer for most cases paralleled the time when Amblyomma americanum and Dermacentor variabilis are most active, suggesting that one or both ticks may be vectors of human ehrlichiosis in Oklahoma. 
5	Treatment of vaginal candidiasis: orally or vaginally? Vaginal candidiasis continues to be the most common cause of vaginal discharge. A large variety of topical drugs and a selection of orally active antifungals are currently available. The choice between the use of oral drugs or intravaginal agents will depend on the therapeutic results obtained with the different agents, side effects, pregnancy status, and patient preference. The results obtained in the Maria Hospital, Tilburg, The Netherlands, and a review of foreign data suggest the following: (1) For acute infection oral and topical agents produce equivalent results. (2) For chronic infections oral medication is preferred. (3) Oral therapy should not be given to pregnant patients or to patients not using reliable contraceptive measures. (4) Half the patients prefer oral medication; only 5% prefer intravaginal therapy, and the others had no clear preference. 
5	The treatment of Gilles de la Tourette syndrome by limbic leucotomy. A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy. 
1	Serial immunocytologic analysis of blood for tumor cells in two patients with neuroblastoma. Tumor surveillance tests are used to determine whether malignant cells are responsive or resistant to therapeutic regimens. For patients with neuroblastoma, conventional methods of surveillance are not sensitive enough. Because tumor cells are shed into the circulation, immunocytologic analysis of blood may function as a sensitive monitoring system. In this study, five blood samples were obtained from two patients with disseminated neuroblastoma at diagnosis and during therapy. These samples were analyzed with monoclonal antibodies and immunoperoxidase staining to determine whether circulating neuroblasts were present. In both patients, the presence or absence of circulating neuroblasts yielded information that was more sensitive than that from conventional tests. The authors conclude that immunocytologic analysis of blood should be included with conventional monitoring methods for surveillance of patients with disseminated neuroblastoma. 
1	Large cystic optic glioma. A 5 1/2-year-old boy developed a huge cyst in his chiasmal glioma 4 years after radiation therapy. The cyst produced obtundation but was successfully treated. 
1	Leukocyte larceny: spurious hypoxemia confirmed with pulse oximetry Leukemic patients with extremely high white blood counts may exhibit the phenomenon of leukocyte larceny, in which white blood cells metabolize plasma oxygen in arterial blood gas samples (ABG) producing a spuriously low oxygen tension. We report the case of a leukemic patient with a white blood count in excess of 500,000 in whom multiple ABGs documented hypoxemia out of proportion to his clinical picture. Pulse oximetry was used to confirm higher hemoglobin oxygen saturation to establish the leukocyte larceny. 
1	Percent tumor necrosis as a predictor of treatment response in canine osteosarcoma. The percent tumor necrosis was determined in 200 dogs with spontaneously occurring osteosarcoma. One hundred dogs had no treatment before amputation or death. One hundred other dogs were treated with either radiation therapy alone (n = 23), intraarterial (IA) cisplatin alone (n = 16), intravenous (IV) cisplatin alone (n = 6), radiation therapy plus IA cisplatin (n = 47), or radiation therapy plus IV cisplatin (n = 8). Eighty-nine of these 100 dogs had their tumors resected 3 weeks after the end of therapy (6 weeks after the initiation of therapy) and replaced with a cortical bone allograft. Dogs with preoperative treatment were evaluated for local tumor control and time to metastasis. The mean percent tumor necrosis in untreated osteosarcoma was 26.8%. The mean percent tumor necrosis for dogs receiving radiation only, IA cisplatin only, and IV cisplatin only was 81.6%, 49.1% and 23.8%, respectively. The mean percent tumor necrosis for dogs receiving radiation therapy plus IA cisplatin or radiation therapy plus IV cisplatin was 83.7% and 78.2%, respectively. There was no significant difference between percent tumor necrosis in untreated osteosarcoma compared with those receiving IV cisplatin, but there was a significant increase in percent tumor necrosis with all other treatments. A mathematic model for the effect of cisplatin and radiation dose was developed using multiple regression analysis. The radiation dose calculated to cause at least 80% tumor necrosis was 42.2 Gy (95% confidence interval [CI], 38.0 to 47.6 Gy) when radiation was given alone and 28.1 Gy (95% CI, 21.3 to 36.6 Gy) when radiation was combined with IA cisplatin. Areas of viable tumor tended to be most frequent adjacent to the articular cartilage and in the joint capsule. Percent tumor necrosis was strongly predictive for local tumor control; 28 of 32 dogs with greater than 80% tumor necrosis had local control, and only eight of 29 dogs with less than 79% tumor necrosis had local control (P = 0.0047). There was no correlation between percent tumor necrosis and time to metastasis. 
2	Evidence for role of prostacyclin as a systemic hormone in portal hypertension. The possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein. In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1 alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in all vascular beds (systemic arterial, systemic venous, and portal venous) when compared with levels in control animals. In PHT rabbits, exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial, systemic venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics. These hemodynamic changes were of equal magnitude irrespective of site of infusion in PHT. In controls there was no significant change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion. We conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension. 
1	Coeliac disease and malignancy of the duodenum: diagnosis by endoscopy, successful treatment of the malignancy, and response to a gluten free diet. A patient presented with subtotal villous atrophy and a malignant duodenal tumour of uncertain histogenesis. He was successfully treated by resection and chemotherapy and the small bowel mucosa recovered on a gluten free diet. The tumour was diagnosed at upper gastrointestinal endoscopy when barium studies and abdominal computed tomography were normal, thus making this one of the earliest coeliac malignancies diagnosed. 
1	The in vivo biologic effect of interleukin 2 and interferon alfa on natural immunity in patients with head and neck cancer. Given the association of deficient natural immunity with the risk of metastatic disease, the ability to activate natural killer cell function may have a therapeutic significance. The effect of continuous infusion of interleukin 2 plus intramuscular interferon alfa on natural immune status was, therefore, analyzed in eight patients with head and neck cancer. Also evaluated was the effect of interleukin 2-interferon alfa therapy on lymphokine-activated killer cell activity as well as total lymphocyte count, percent of lymphocyte subsets, and levels of both circulating immune complexes and antibody classes. Both the percent and absolute number of natural killer cells (ie, CD56+ CD3- lymphocytes) within peripheral blood as well as natural killer cell activity against K562 targets increased significantly with treatment. The remaining immune parameters were not significantly altered. The demonstrated capacity to modulate natural immune function supports the potential use of interleukin 2-containing regimens as a preventive measure against metastatic disease in patients with head and neck cancer. 
3	Platelet volume, aggregation, and adenosine triphosphate release in cerebral thrombosis. We compared whole blood platelet aggregation, adenosine triphosphate release, platelet count, platelet crit (percentage volume of platelets), and mean platelet volume during the acute, subacute, and chronic periods of cerebral thrombosis in 22 patients with value in 29 controls. During the acute and subacute periods, platelet aggregation, platelet count, platelet crit, and mean platelet volume were significantly less in the patients than in the controls (p less than 0.05-0.01) while the adenosine triphosphate release rate per volume of platelets was significantly greater (p less than 0.05). During the acute period, infarct size showed a significant positive correlation with platelet aggregation (r = 0.59, p less than 0.01) and adenosine triphosphate release rate (r = 0.70, p less than 0.001) but a negative correlation with platelet count (r = -0.44, p less than 0.05). Our results suggest that platelet aggregation is reduced during the acute period due to the consumption of platelets during thrombogenesis but that the remaining individual platelets are hyperactive. Platelet consumption during the acute period increases with infarct size. During the chronic period, platelet crit and mean platelet volume were significantly less in the patients than in the controls (p less than 0.01) while the adenosine triphosphate release rate was significantly greater (p less than 0.01), suggesting sustained platelet consumption and chronically enhanced secretion of individual platelets. 
1	A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. Several hormones, including insulin, glucagon, and glucocorticoids, regulate the expression of the rate-limiting gluconeogenic enzyme, phosphoenolpyruvate carboxykinase [GTP: oxaloacetate carboxy-lyase (transphosphorylating); EC 4.1.1.32; PEPCK] in liver. In this report we demonstrate that retinoic acid (RA) also regulates PEPCK expression by inducing a 3-fold increase in the rate of transcription of the PEPCK gene. A RA response element located between -468 and -431 in the PEPCK promoter mediates a 7-fold increase in expression of a chimeric construct containing the basal PEPCK promoter ligated to the chloramphenicol acetyltransferase reporter gene. This element confers RA responsiveness through the heterologous thymidine kinase promoter and functions relatively independent of position and orientation. An 18-base-pair core sequence (-451 to -434) (i) mediates an effect of RA on PEPCK gene expression and contains motifs found in two other RA response elements; (ii) corresponds to AF1, an accessory factor element that is an integral component of the complex glucocorticoid response unit in the PEPCK gene promoter; (iii) is in a region involved in the developmental expression of the PEPCK gene; and (iv) shows homology to elements involved in the tissue-specific regulation of genes, including the hepatic apolipoprotein genes and the alpha 1-antitrypsin gene. 
3	Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography The study of blood flow by means of magnetic resonance techniques has led to a noninvasive magnetic resonance angiography (MRA) technique for imaging large cerebral vessels. Ten children with sickle cell hemoglobinopathy and a history of acute neurologic syndromes were studied with combined parenchymal magnetic resonance imaging (MRI) and MRA. Six had abnormal MRI findings and MRA-defined luminal lesions in the vascular distribution of these parenchymal infarctions. The three children with previous intraarterial angiography had MRA abnormalities that corresponded with vascular lesions on conventional angiograms. Four had normal MRI and MRA findings. We conclude that a combination of MRI and MRA provides a noninvasive screening test for large-vessel disease in this population. 
1	Chromogranin A: posttranslational modifications in secretory granules. The primary structure of chromogranin A indicates multiple domains which might be subject to posttranslational modification. We explored chromogranin A's proteolytic cleavage, glycosylation, and possible intermolecular disulfide links, using biochemical and cell biological approaches. Anti-chromogranin A region-specific immunoblots on chromaffin granules suggested bidirectional endoproteolytic cleavage of chromogranin A; control experiments ruled out artifactual cleavage during granule isolation or lysis. Isolation of chromogranin A-derived peptides by gel filtration chromatography or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by N-terminal amino acid sequencing, established several cleavage sites, including at least two at dibasic sites. Secretion of chromogranin A from bovine chromaffin cells did not initiate further cleavage, nor did prolonged exposure of secreted chromogranins to the secretory cells. The chromogranin A cleavage pattern was qualitatively similar in other neuroendocrine tissues, though cleavage was more complete in adrenal medullary than in anterior pituitary hormone storage vesicles, and N-terminal fragments of 45 and 55 kilodaltons were more prominent in the hypothalamus. A similar cleavage pattern was seen in human pheochromocytoma granules, as judged by chromogranin A region-specific immunoblots, fragment isolation by SDS-PAGE, and microsequencing. The presence of full-length chromogranin A as the core protein of a chromaffin granule soluble proteoglycan was suggested in bovine (but not human) chromaffin granules by glycoprotein staining, chondroitinase ABC digestion, chemical deglycosylation, and region-specific immunoblotting. Human (but not bovine) chromogranin A displayed intermolecular disulfide crosslinks on SDS-PAGE gels and immunoblotting. These results document diverse structural paths that the chromogranin A molecule may take in endocrine secretory cells after its translation. 
5	Patient-related variables and restenosis after percutaneous transluminal coronary angioplasty--a report from the M-HEART Group. As part of a randomized prospective study designed to investigate the restenosis process after percutaneous transluminal coronary angioplasty (PTCA), the relation between patient-related variables and restenosis rate was examined. A total of 722 patients had successful PTCA. Angiographic follow-up was scheduled for 6 +/- 2 months after the procedure and achieved in 510 patients (71%), yielding 598 lesions for analysis. The overall restenosis rate was 40%. The rate was higher in patients undergoing early restudy for a clinical event than in those undergoing routinely scheduled follow-up restudy (71 vs 22%, p less than 0.0001). Age, sex, cigarette smoking history, diabetes mellitus and history of previous myocardial infarction were not associated with restenosis rate. Angina duration and severity before PTCA were also unrelated to restenosis rate. In summary, these variables, many of which have been previously implicated in restenosis, were not found to be predictors of restenosis. The decision to perform PTCA in individual patients should not be negatively influenced by the presence of these factors. 
3	Diffuse idiopathic skeletal hyperostosis (DISH) of the shoulder: a cause of shoulder pain? Shoulder pain is a common complaint and shoulder hyperostosis a frequent radiological condition. However, little is known about the association between the clinical and radiological findings. To evaluate the clinical relevance of shoulder hyperostosis we performed a controlled, blind study of 99 hospitalized probands with and without thoracospinal hyperostosis on lateral chest X-rays. The study included grading of the shoulder hyperostosis on the basis of three bilateral standard radiographs, assessing shoulder pain in a standardized way by an interviewer and recording extraskeletal causes of shoulder pain. The prevalence of shoulder hyperostosis was doubled in probands with thoracospinal hyperostosis compared to controls (chi 2 = 5.90, P less than 0.025, n = 99). Shoulder hyperostosis, irrespective of thoracospinal hyperostosis, predisposed to shoulder pain (40% versus 18%, chi 2 = 4.06, P less than 0.05, n = 74). Shoulder hyperostosis in combination with thoracospinal hyperostosis (shoulder DISH) predisposed to shoulder pain to an even greater extent (46% versus 12%, chi 2 = 6.64, P less than 0.01, n = 47). We conclude that shoulder hyperostosis is a radiological finding of potential clinical relevance. 
3	Bladder function in the mentally retarded. A group of 21 mentally retarded patients with severe, long-standing urinary symptoms underwent urodynamical investigation. The most common abnormalities were detrusor areflexia and detrusor hyper-reflexia. Of 11 patients treated surgically, 10 derived marked benefit. Drugs were successful in reducing micturition problems in 3/6 patients. Severely retarded patients with spastic quadriplegia are difficult to investigate and if this is associated with detrusor hyper-reflexia it is impossible to treat them in any way. Severely retarded patients with detrusor areflexia and infrequent voiding can benefit from bladder outlet surgery. Patients with moderate (especially mild) retardation can be investigated and treated in the same way as non-retarded people. 
3	Hydromyelic hydrocephalus. Correlation of hydromyelia with various stages of hydrocephalus in postshunt isolated compartments. The clinical features and pathophysiology of specific forms of hydromyelia are analyzed in this report together with the chronological changes of associated hydrocephalus. Nine patients were studied; all had hydromyelia with varying degrees of associated hydrocephalus. Clinically applicable classification systems were used to evaluate the progression of hydrocephalus (Stages I to IV) and to define the compartment isolated after shunting in the previously communicating cerebral ventricles (Types I to IV). Four patients had Stage IV disease (holoneural canal dilatation); one had Stage II and four had Stage I disease (both Stages I and II with supratentorial hydrocephalus). All patients were initially treated by ventriculoperitoneal shunting at an average age of 9.9 years. Five patients had progressive spinal symptoms before or after treatment of their hydrocephalus. Two patients had Type III isolation (an isolated rhombencephalic ventricle) with a functioning ventricular shunt; ventriculography confirmed a communication between the fourth ventricle and the hydromyelia, and both patients improved after placement of a shunt in the fourth ventricle. The remaining patients had Type IV isolation (isolated central canal dilatation) with a functioning ventricular shunt. This study indicates that in some cases the pathophysiology of hydromyelia is closely related to associated hydrocephalus. A new concept of the development of an isolated compartment after shunting is proposed to explain the progression of hydromyelia in these cases. 
5	Sensitivity to titanium. A cause of implant failure? Tissues from five patients who underwent revision operations for failed total hip replacements were found to contain large quantities of particulate titanium. In four cases this metal must have come from titanium alloy screws used to fix the acetabular component; in the fifth case it may also have originated from a titanium alloy femoral head. Monoclonal antibody labelling showed abundant macrophages and T-lymphocytes, in the absence of B-lymphocytes, suggesting sensitisation to titanium. Skin patch testing with dilute solutions of titanium salts gave negative results in all five patients. However, two of them had a positive skin test to a titanium-containing ointment. 
4	The incidence of deep vein thrombosis after cementless and cemented knee replacement. The incidence of deep vein thrombosis in 244 patients who had total knee replacement has been studied. In 120 the prosthesis was cemented and in 124 it was cementless. In all cases the replacement was primary and a porous-coated prosthesis with a porous-coated central tibial stem was used. Deep vein thrombosis was diagnosed by venography, and pulmonary embolism by perfusion scanning. The incidence of deep vein thrombosis in the cementless knees (23.8%) and in the cemented (25%) was approximately the same. The only significant predisposing factors for deep vein thrombosis in both groups were obesity, prolonged postoperative immobilisation, previous venous disease and hyperlipidaemia. 
3	Epidural morphine for analgesia after caesarean section: a report of 4880 patients This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated. 
3	Aberrant regeneration in a case of syringobulbia: selective co-activation of abducens and facial nerves during saccades. A patient suffering from syringobulbia and syringomyelia exhibited a phasic contraction of the ipsilateral facial muscles, mainly the levator labii, whenever he looked to the left or right. Facial muscle twitches occurred exclusively with saccades. The selective co-activation of abducens and facial nerves is interpreted as the result of bilateral misrouting of regenerating neurons from the parapontine reticular formation to the facial nerve in the tegmentum pontis. 
5	The scimitar syndrome. The clinical spectrum of the scimitar syndrome ranges from severely ill infants to asymptomatic adults. The true incidence of the disorder is unknown because the syndrome may remain undetected in asymptomatic patients until a chest roentgenogram is obtained. We have presented the contrasting clinical experiences of two adult women, one with few symptoms and a benign course, and the other with exacerbation of her asthma from recurrent upper respiratory tract infections originating in the lower lobe of her right lung. Improvement resulted from surgical resection of this congenitally abnormal, bronchiectatic segment of lung. 
3	Flecked retina associated with ring 17 chromosome. We report the case of a mentally retarded male with a ring 17 chromosome who had subretinal drusen-like deposits in each eye. This is the second report of flecked retina in a patient with ring 17 chromosome, suggesting that there may be a causal relationship between abnormalities of chromosome 17 and retinal pigment epithelial or photoreceptor dysfunction. 
5	Low-dose bupivacaine does not improve postoperative epidural fentanyl analgesia in orthopedic patients [published erratum appears in Anesth Analg 1991 May;72(5):718] Epidural infusions of 10 micrograms/mL fentanyl combined with low-dose bupivacaine (0.1%) were compared with epidural infusions of fentanyl alone for postoperative analgesia after total knee joint replacement. There were no detectable differences between the two groups in analgesia (visual analogue scale ranging between 15 and 40 mm), infusion rates (which averaged 7-9 mL/h), or serum fentanyl levels (which reached 1-2 ng/mL). The incidence of side effects, including nausea, vomiting, and pruritus, was also similar. Of the patients receiving fentanyl and low-dose bupivacaine, one developed a transient unilateral motor and sensory loss, and one developed significant hypotension and respiratory depression. The addition of low-dose bupivacaine does not improve epidural fentanyl infusion analgesia after knee surgery and may increase morbidity. 
5	Clinical features and treatment of obstructive sleep apnea. OBJECTIVE: To review the clinical features and treatment of obstructive sleep apnea (OSA). DATA SOURCE AND SELECTION: All articles on OSA published in French and English between 1970 and 1990 and indexed in Index Medicus were reviewed. Studies addressing the epidemiologic features and clinical aspects of OSA were selected, and special emphasis was given to articles reporting the effects of treatment on morbidity and mortality rates. MAIN RESULTS: OSA is characterized by episodes of upper airway obstruction during sleep that result in repetitive hypoxemia and sleep disruption. OSA leads to various neuropsychologic and cardiovascular complications, including daytime hypersomnolence, cognitive impairment, systemic and pulmonary hypertension and cardiac arrhythmias. There is suggestive evidence that the death rate among affected people is increased. The true incidence of OSA is unknown, but estimates have varied from 1% upwards among men. The current treatment with the greatest overall effectiveness and acceptability is nasal continuous positive airway pressure. CONCLUSION: This common, readily treatable disorder is associated with serious complications and therefore must be widely recognized by health professionals. 
2	Acute upper gastrointestinal bleeding in elderly persons [clinical conference] We have seen that UGI bleeding is a serious and apparently growing problem for seniors. Of special concern in the older patient are the frequency with which serious peptic disease presents silently, the limitation frequently imposed on adequate pain relief from NSAIDs, and the higher complication rates from most of the causes of UGI bleeding. Care of the elderly would be enhanced by research focused on defining those older patients most at risk of experiencing NSAID-induced peptic complications, improved methods for preventing or treating NSAID-induced ulceration that are well tolerated and cost-effective, and better regimens for preventing the recurrence of ulcers and UGI bleeding in these patients. In regard to the last, future investigation of the role of H. pylori, methods for successfully eliminating the organism, and the effect of eradication on patients' subsequent course may be particularly helpful. 
1	Mediastinal hibernoma, a rare tumor. Hibernoma is an uncommon soft tissue tumor that is derived from the remnants of fetal brown fat. Review of the world medical literature revealed 90 cases, 6 of which were intrathoracic. We present the seventh case of intrathoracic hibernoma; in this case, the hibernoma was within the mediastinum without direct invasion of other structures. 
4	Atherosclerotic carotid disease and the eye. The evaluation and management of retinal ischemia from atherosclerotic carotid disease is in a state of flux reflected by the change from emphasizing surgical management in the '70s toward skepticism about the benefit of surgery in the '80s. In addition, reliable noninvasive diagnostic testing of the carotid artery has reduced the risk. The decision to consider surgical versus medical management must be made on an individual basis based on the patient's health, age, and the risk of angiography and surgery at each institution. In children and young adults, amaurosis fugax is a benign condition. In the older population amaurosis fugax is often the sentinel event of diffuse atherosclerotic disease and possible early death from myocardial infarction. A team including the neurologist, internist, ophthalmologist, and surgeon optimizes care of the whole disease and not just the symptom. It is hoped that information in the next decade will supply additional guidance in the care of this multifaceted malady. 
5	Spontaneous perinephric hemorrhage: imaging and management. We report on 10 patients with spontaneous perinephric hemorrhage associated with underlying disease, including renal cell carcinoma (5), angiomyolipoma (2), malignant melanoma (1), periarteritis nodosa (1) and severe portal hypertension (1). The etiology could not be identified with computerized tomography (CT) in 5 cases (50%), including 2 renal cell carcinomas, 1 angiomyolipoma, 1 periarteritis nodosa and 1 portal hypertension. Arteriography demonstrated underlying lesions in 4 of these 5 cases (80%) including the case of vasculitis. CT combined with magnetic resonance imaging is accurate for the diagnosis of spontaneous perinephric hemorrhage but the underlying pathological condition is often undetectable in the acute phase due to the perinephric blood. CT should be the first study performed if this diagnosis is suspected. Arteriography is recommended if a renal mass is not detected. If a mass is not identified with these 2 imaging studies and the patient is clinically stable, followup thin slice CT should be performed. 
3	Correlation of clinical and computed tomographic findings in stroke patients. We evaluated the correlation between clinical features and computed tomographic findings in a prospective study of 1,191 consecutive patients with acute cerebrovascular disease seen during 1 year. In the 386 patients in whom symptoms and signs initially suggested a cerebrovascular disorder, computed tomography revealed a relevant lesion in 154 (hemorrhagic in 52 [33.8%], ischemic in 102 [66.2%]) and a significant nonstroke abnormality in 14 (3.1%). Among the remaining 805 patients with symptoms and signs suggesting some central nervous system disorder other than stroke, computed tomography revealed a cerebrovascular lesion in 38 (4.7%); 35 of these lesions were ischemic. The computed tomographic findings was compatible with the final clinical diagnosis in 192 (84.2%) of the 228 patients with lesions. In the entire sample of 1,191 patients, a cerebrovascular disorder would have been missed in 38 (3.2%) without computed tomography. On the other hand, computed tomography failed to visualize a cerebrovascular lesion in 40 patients in whom such a lesion was clinically obvious. Our results emphasize that both careful neurologic assessment and a policy of early computed tomography are of crucial importance in the diagnosis of stroke and for therapeutic considerations. 
5	Clinical features of adenovirus enteritis: a review of 127 cases. We retrospectively analyzed the clinical features of 127 hospitalized pediatric patients whose fecal samples were positive for adenovirus (Ad) by electron microscopy during an 18-month period. Serotyping results obtained by microneutralization tests and restriction endonuclease analysis were available for 105 of 127 cases. There were 69 males and 58 females and 94% of patients were less than 4 years of age. The average body temperature was 38 degrees C rectal (range, 36.2-40.8 degrees C) with an average duration of fever of 1.6 days. The average duration of clinical illness was 8.8 days (range, 1 to 32 days). Although Ad 40 and Ad 41 were isolated in the majority of cases (59 of 105 (56%], Ad 31 was associated with 18 of 105 cases (17%). Of the 18 cases associated with Ad 31, 14 were nosocomial and associated with diarrhea. Our survey confirms the importance of fastidious enteric Ad in infantile diarrhea (Ad 40, Ad 41) and suggests that Ad 31 produces a clinical syndrome indistinguishable from that caused by Ad 40 and Ad 41. The occurrence of Ad enteritis in patients admitted for unrelated illnesses well after initial hospitalization suggests that Ad is also an important cause of nosocomial enteritis in our hospital. 
3	Relative validity of self-reported snoring as a symptom of sleep apnea in a sleep clinic population The purpose of this study was to evaluate the relative validity of responses to three different questions about snoring as indicators for sleep apnea in a population referred to a sleep clinic. Secondary goals were to evaluate the meaning of a "don't know" response to these questions and to examine how the associations between snoring and sleep apnea are influenced by demographics. Results from 1,409 patients in a sleep clinic indicated that nearly all levels of estimated snoring frequency were associated with a greater likelihood of sleep apnea. In addition, a "don't know" response indicated a likelihood of sleep apnea. In the sample from this clinic, sensitivities approximating 90 percent were obtained in men, and specificities approximating 90 percent were obtained in women, but high diagnostic accuracy (high specificity in men; high sensitivity in women) could not be achieved with the three snoring questions used here. Generally, associations between snoring and sleep apnea were independent of age and sex. Single persons, persons living alone, and persons customarily sleeping alone of both sexes all showed associations between self-reported snoring and the presence of sleep apnea. 
3	Recurrent lateral rectus palsy in childhood. Five patients with recurrent, lateral rectus palsy in childhood, examined at the University of Iowa Hospitals over a period of 22 years, are reported. During the same period, 131 abducens nerve palsy patients, younger than 18 years of age, were evaluated. Eighteen similar patients, most single case reports, are reviewed from the literature. All reported patients, including our own, shared the following features: spontaneous recovery within 6 months in the majority of patients, ipsilateral recurrence, and painless palsy. There is female and left-sided preponderance. Etiology is undetermined. Hypotheses include viral etiology, neurovascular compression by aberrant artery, and migraine. 
5	Prevalence of angioid streaks and other ocular complications of Paget's disease of bone. Seventy randomly selected patients with Paget's disease of bone were examined for ocular complications. The prevalence of macular degeneration and cataract was 24.3%. Only one patient was found to have angioid streaks. Eight patients had peripapillary chorioretinal atrophy. These findings suggest that the prevalence of serious ocular complications of Paget's disease is not as high as previously thought. The significance of peripapillary chorioretinal atrophy requires further evaluation. 
2	Sterol-dependence of gastric protective activity of unsaturated phospholipids. The major aim of this study was to investigate the gastric protective effect of unsaturated phospholipids and to determine the ability of neutral lipids to enhance this activity. We found that although a liposomal suspension of unsaturated phosphatidylcholine (PC) administered intragastrically failed to protect rats from acid-induced gastric ulcer formation, addition of cholesterol to unsaturated PC induced a dose-dependent protective response with the maximally effective dose, reducing lesion score greater than 70%. This effect also was seen with the plant sterol, beta-sitosterol (reducing lesion score by 81.6 +/- 36%) but was blocked if cholesterol was esterified to fatty acids of varying chain length. Addition of sterols to liposomes of saturated dipalmitoylphosphatidylcholine, in contrast, attenuated the gastric protective action of the saturated PC. It appears that the protective mechanism elicited by sterols and unsaturated PC is not mediated by alterations in gastric emptying rate or prostaglandin biosynthesis, although maintenance of surface hydrophobicity may be involved. These results suggest that the sterol may promote the packing of adjacent unsaturated phospholipid molecules of either the cell membrane or a putative extracellular hydrophobic lining of the gastric epithelium to provide the mucosa with protection against luminal acid. 
5	The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. With the euglycemic clamp technique, we evaluated the effects of graded doses of insulin on glucose turnover rates and forearm lactate balance in five weight-losing patients with cancer before surgery and five age- and weight-matched healthy volunteers (control subjects). Insulin was infused sequentially at increasing rates of 0.5 (low physiologic), 1.0 (high physiologic), and 4.0 (supraphysiologic) mU/kg.min for 120 minutes each. Concurrently, rates of glucose appearance and disappearance were derived from [3-3H] glucose infusion. The mean postabsorptive rate of glucose appearance in patients (2.9 +/- 0.1 mg/kg.min) was significantly higher (p less than 0.02) than that of control subjects (1.98 +/- 0.16 mg/kg.min). Complete suppression of endogenous glucose production occurred at high physiologic insulin concentrations. With progressive insulin infusion, the rate of glucose disappearance increased to 3.6 +/- 1.2, 8.7 +/- 0.8, and 13.7 +/- 1.1 mg/kg/min in control subjects and 2.9 +/- 0.4, 5.3 +/- 0.3, and 10.9 +/- 0.9 mg/kg.min in patients, significantly different from that of control subjects (p less than 0.05) during the intermediate (high physiologic) insulin infusion. A comparable slight increase in arterial plasma lactate concentration was observed in both groups with progressive hyperinsulinemia. Baseline peripheral lactate flux was identical in patients (-272 +/- 56 nmol/100 gm.min) and in controls (-271 +/- 57 nmol/100 gm.min). Progressive physiologic hyperinsulinemia resulted in significantly (p less than 0.05) augmented peripheral lactate efflux in patients (-824 +/- 181 nmol/100 gm.min) compared with control subjects (-287 +/- 64 nmol/100 gm.min). Supraphysiologic insulin abolished this increased lactate efflux in patients. Postabsorptive rates of endogenous glucose appearance in weight-losing patients with cancer were elevated, but complete suppression was achieved with insulin concentrations in the physiologic range. Total body glucose use was diminished in these patients, consistent with a state of insulin resistance. This impaired insulin action on peripheral glucose use was associated with an increase in peripheral lactate release in patients. 
2	Cecal diverticulitis presented as a cecal tumor. Seven patients diagnosed as having acute appendicitis were operated on and a cecal wall mass due to cecal diverticulitis was found. In two patients the mass could not be separated from the cecal wall and right colectomy was performed. In five patients, in whom the mass could be separated from the cecum, conservative operations (three diverticulectomies and two wedge resections) were performed, thus avoiding needless, more extensive surgery. 
4	Time course of cellular enzyme release in dog heart injury. The transport time of enzyme from heart to plasma was studied in two experimental models. First, the enzyme alanine aminotransferase was slowly infused into the left ventricular wall in open-chest dogs. The half-life for the washout of alanine aminotransferase activity into plasma was 20 +/- 4 minutes (mean +/- SEM, n = 8) and was not different in ischemic and normally perfused tissue. From measurements of arteriovenous differences in alanine aminotransferase activity and left ventricular blood flow, it was concluded that 77 +/- 14% of total enzyme washout from ischemic tissue occurred by direct entry into the bloodstream. The corresponding value for the vascular permeability-surface area product was 264 +/- 55 ml.kg-1.hr-1. For a second model, we studied myocardial enzyme release into plasma after abrupt heart injury induced by 10 minutes of calcium-free coronary perfusion followed by reintroduction of calcium (calcium-paradox mechanism). The half-life for the release into plasma was 1.9 +/- 0.2 hours (mean +/- SEM, n = 6) and was again not influenced by sustained ischemia. Slower washout, as observed for this second model, is consistent with increased interstitial protein space and corresponds to a permeability--surface area product between 135 and 285 ml.kg-1.hr-1. These results were used to calculate the time course of cellular enzyme leakage from the rate of enzyme release into plasma in various forms of heart injury. Significant shifts between the time curves of evolving cellular injury and enzyme release into plasma are observed after 2 hours of ischemia followed by coronary reperfusion, but not after permanent ischemia. 
1	Mutagen sensitivity in patients with head and neck cancers: a biologic marker for risk of multiple primary malignancies. Eighty-four patients with head and neck cancers were evaluated for in vitro sensitivity to mutagens and then followed longitudinally for development of multiple primary malignancies. We assessed mutagen sensitivity by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromosomal breaks per cell. The mutagen-hypersensitive patients, ie, those who expressed greater than 1.0 break per cell, were significantly more likely to develop multiple primary cancers than were patients who were less sensitive (less than or equal to 1.0 break per cell) (relative risk = 4.4; 95% confidence limits = 1.2, 15.8). This relationship was independent of age, sex, site, and treatment of first primary cancer and tobacco or alcohol exposures. Sensitivity to bleomycin-induced chromosomal damage serves as an indicator of genetic susceptibility to multiple primary malignancies in patients with head and neck cancers. 
4	Anorectal varices--their frequency in cirrhotic and non-cirrhotic portal hypertension. Anorectal varices in portal hypertension have been little studied: Seventy eight per cent of 72 patients with portal hypertension had anorectal varices shown at flexible sigmoidoscopy. Significantly more patients with noncirrhotic portal hypertension had these varices than patients with cirrhosis (89% v 56%, p less than 0.01). 
1	Common nonvenereal genital lesions. There are a wide variety of local and systemic skin diseases that produce lesions in the genitoanal region. These lesions may resemble those produced by sexually transmitted microorganisms. The purpose of this article is to make physicians aware of the common skin diseases that produce lesions on the genitalia to avoid the inappropriate diagnosis of a sexually transmitted disease. 
5	Advances in noninvasive detection of CAD. Advances in the noninvasive detection of myocardial ischemia are increasing our ability to diagnose coronary artery disease (CAD). Tomographic (SPECT) thallium imaging provides better identification of coronary arteries with atherosclerotic narrowing. Increased lung thallium uptake and transient ischemic dilatation of the heart are additional markers of severe CAD. Late thallium imaging, as well as reinjection imaging, provides more accurate identification of myocardial ischemia. Finally, new myocardial ischemia. Finally, new myocardial imaging agents, such as technetium Tc 99m sestamibi (Cardiolite), should improve detection of CAD by noninvasive methods. 
1	What to do when an x-ray film suggests lung cancer. The chest film is one of the most common methods of detecting lung cancer, which often appears as solitary nodules or hilar masses. Once the diagnosis is established, the most effective treatment can be determined and staging of the tumor can be done. Surgical resection is the only cure for non-small-cell carcinoma, although radiotherapy and chemotherapy may shrink some tumors. Because 90% of all cases are caused by smoking, a preventive approach to the disease is crucial. Screening of high-risk patients (ie, smokers with airflow obstruction) using chest films and sputum cytology may aid this approach. 
4	Elevated plasma noradrenaline concentrations in patients with low-output cardiac failure: dependence on increased noradrenaline secretion rates. 1. Plasma noradrenaline concentrations are elevated in patients with congestive heart failure; however, the pathogenesis of these elevated noradrenaline levels is controversial. 2. Possible mechanisms for elevated noradrenaline concentrations in patients with congestive heart failure include increased noradrenaline secretion, decreased clearance of noradrenaline, and a combination of increased secretion and decreased clearance. 3. In the present study, plasma noradrenaline clearance and apparent secretion rates were determined using a whole-body steady-state radionuclide tracer method in six otherwise healthy patients with moderate degrees of low-output cardiac failure and in six normal control subjects. 4. The venous plasma noradrenaline level was elevated in the patients with congestive heart failure as compared with the control subjects (4.18 +/- 1.34 versus 1.54 +/- 0.16 nmol/l, P less than 0.05). There was no stimulation of the adrenal medulla as evident by normal plasma adrenaline levels in both groups (0.19 +/- 0.04 versus 0.18 +/- 0.02 nmol/l, not significant). The apparent secretion rate of noradrenaline was elevated in the patients with congestive heart failure (4.75 +/- 1.95 versus 1.78 +/- 0.18 nmol min-1 m-2, P less than 0.05), whereas the clearance rate of noradrenaline was similar in the two groups (1.26 +/- 0.27 versus 1.16 +/- 0.02 l min-1 m-2, not significant). 5. We conclude that the high peripheral venous plasma noradrenaline concentrations in patients with mildly decompensated low-output cardiac failure are initially due to increased secretion, rather than to decreased metabolic clearance, perhaps in response to diminished effective arterial blood volume. 
3	Ethyl chloride and venepuncture pain: a comparison with intradermal lidocaine. One hundred and twenty unpremedicated patients undergoing gynaecological surgery were randomly allocated to one of three equal treatment groups to assess the effectiveness of ethyl chloride in producing instant skin anaesthesia to prevent the pain of venepuncture from a 20 G cannula. They received either no anaesthetic, 0.2 ml one per cent lidocaine plain intradermally or a ten-second spray of ethyl chloride at the cannulation site. Ethyl chloride produced skin anaesthesia that significantly reduced the pain of venepuncture. However, it was not as effective as intradermal lidocaine. It had no effect on vein visualisation or ease of cannulation. Ethyl chloride can be recommended as a method of producing instant skin anaesthesia. 
2	Radiology of esophagitis: a pattern approach. This article presents a pattern approach for diagnosing esophagitis at double-contrast esophagography. In patients with nodular elevations of the mucosa, discrete plaques should suggest Candida esophagitis, whereas poorly defined nodules should suggest reflux esophagitis and a distinctive reticular pattern of the mucosa should suggest Barrett esophagus, particularly if adjacent to the distal aspect of a high stricture. In patients with ulceration, one or more shallow ulcers at or near the gastroesophageal junction should suggest reflux esophagitis, whereas discrete, superficial ulcers in the midesophagus should suggest herpes or drug-induced esophagitis, depending on the clinical setting. In contrast, one or more giant, relatively flat ulcers should suggest cytomegalovirus esophagitis, particularly in patients with acquired immunodeficiency syndrome. Finally, thickened longitudinal folds may be caused by esophagitis, varices, or, rarely, "varicoid" carcinoma, but these conditions usually can be differentiated on radiologic grounds. By carefully analyzing the appearance and location of nodules, plaques, ulcers, or abnormal folds in the esophagus, one can usually suggest a cause of the disease. 
5	Febrile status epilepticus As part of a study of status epilepticus in children (Maytal J, Shinnar S, Moshe SL, Alvarez LA. Pediatrics. 1989; 83:323-331); 44 children with febrile convulsions lasting more than 30 minutes were followed for a mean of 28 months (range 4 to 72). Thirty children were followed prospectively. Children with prior afebrile seizures or evidence of acute central nervous system infection were excluded. Nine (20%) children had prior neurological deficits. The duration of the febrile seizure was 0.5 to 1 hour in 41 cases (85%), 1 to 2 hours in 5 (10%), and greater than 2 hours in 2 children (5%). No child died or developed new neurological deficits following the seizures. The risk of recurrent seizures was increased, but only in the group with prior neurological abnormality. Six (66%) of these children had subsequent febrile seizures compared with 12 (34%) of the normal children (P = .08). Three (33%) had recurrent febrile status epilepticus compared with only 1 (3%) normal child (P = .023). The 2 children in the prospective arm of the study with recurrent febrile status epilepticus were both neurologically abnormal (P = .035). All 3 of the children who subsequently had afebrile seizures (2 prospective) were neurologically abnormal (P = .006 overall, P = .035 for prospective only). It is concluded that the occurrence of febrile status epilepticus in a neurologically impaired child is a risk factor for subsequent febrile as well as afebrile seizures. The occurrence of febrile status epilepticus in an otherwise normal child does not significantly increase the risk for subsequent febrile (brief or prolonged) or afebrile seizures in the first few years following the episode. 
5	Prognosis of hospital survivors after salvage from cardiopulmonary bypass with centrifugal cardiac assist. Since October 1986, 6 hospital survivors who were salvaged from cardiopulmonary bypass (CPB) with the Sarns centrifugal pump were observed. Centrifugal assist was employed only after failure to wean with usual resuscitative measures, including multiple high dose inotropes and intraaortic balloon pumping. There were five men and one woman, 46-59 years of age (mean 61 years). All patients had undergone coronary artery bypass grafting, with two patients having had concomitant left ventricular aneurysmectomy and two aortic valve replacement. Five patients had left ventricular assist only and one had biventricular assist. Duration of assist ranged from 26 to 72 hr (mean 48 hr). Complications were ubiquitous, and the resultant prolonged hospitalization was resource intensive. All hospital survivors remain alive and are in New York Heart Association functional Class II, with an average follow-up of 24 months, (6-41 months). Compared with preoperative values, current left ventricular function is improved in 2 patients, has deteriorated in 3, and is unchanged in 1. Thus, the Sarns centrifugal pump will allow salvage of some patients who otherwise are not weanable from CPB. Survivors can expect a reasonable functional capacity as reflected by this experience. 
4	Complications of general anesthesia for Nd:YAG laser resection of endobronchial tumors. We studied the incidence and mechanisms of cardiovascular complications and postoperative respiratory insufficiency associated with GA and Nd:YAG laser endobronchial tumor resection. The records of 73 patients undergoing 87 procedures were reviewed. Preoperative status, anesthetic methods and perioperative complications were analyzed by multiple regression to determine predictors of outcome. Twenty-three percent of patients had greater than 90 percent mainstem bronchus obstruction. Longer serum elimination half-life of relaxant drug was significantly correlated with longer duration of mechanical ventilation after neuromuscular blockade reversal. Cardiovascular complications were noted in 24 procedures and often required therapeutic intervention. Variables predicting cardiovascular complications included longer duration of GA and increasing age. Perioperative respiratory and cardiovascular complications are common after GA for Nd: YAG laser resection. Short-acting neuromuscular relaxants, careful assessment prior to postoperative extubation, limiting duration of GA and cardiovascular monitoring are recommended when implementing GA for Nd: YAG laser resection of endobronchial tumors. 
4	The cutaneous manifestations in children with familial Mediterranean fever (recurrent hereditary polyserositis). A six-year study. In a six-year study of 46 children with familial Mediterranean fever (recurrent hereditary polyserositis), 20 children (43 per cent) developed cutaneous manifestations. Ten children had 18 episodes of erysipelas-like erythema which proved to be specific for the disease. Twelve children (26 per cent) had 31 episodes of non-specific purpuric rash and six children (13 per cent) had nine episodes of Henoch-Schonlein purpura. Other manifestations included diffuse erythema of the face, and/or trunk, angioneurotic oedema, diffuse erythema of the palms and soles followed by mild desquamation of the skin, Raynaud's phenomenon and a subcutaneous nodule. The mean frequency of the cutaneous lesions was 1.6/patient/year before colchicine therapy and 0.4/patient/year after colchicine therapy (p = 0.0005). The high incidence of cutaneous manifestations and their response to colchicine strongly suggest that skin involvement is an integral part familial Mediterranean fever. 
2	Intestinal cryptosporidiosis: pathophysiologic alterations and specific cellular and humoral immune responses in rnu/+ and rnu/rnu (athymic) rats. In order to develop an experimental model of symptomatic cryptosporidiosis in an immunosuppressed mammal, we investigated the pathophysiology of infection with Cryptosporidium and the humoral and cellular host responses in rnu/rnu (athymic) rats and their heterozygous (rnu/+) littermates by challenging suckling rats with greater than or equal to 2.5 x 10(6) Cryptosporidium oocytes oro-gastrically. Normal and immunodeficient animals were followed for onset and duration of infection (fecal oocysts), physiologic consequences (diarrhea, impaired weight gain, brush-border enzyme activities), and immunologic response (both B- and T-lymphocyte-mediated). Homozygosity for the rnu gene was associated with protracted cryptosporidial infections; shedding for up to 52 days occurred, and delay in weight gain was noted in rnu/rnu-infected compared with rnu/rnu-uninfected rats (p less than 0.05). In contrast, cryptosporidial challenge of rnu/+ rats resulted in self-resolving infections, occasionally with transient diarrhea lasting four days or less occurring 10-15 days after oro-gastric challenge. The latter animals mounted a cell-mediated immune response to Cryptosporidium: three months after challenge, five of five rnu/+ rats demonstrated positive skin test responses to a subcutaneous 3.5 micrograms dose of cryptosporidial antigen. Further, sera from 6 rnu/+ rats taken two to three months after oro-gastric oocyst challenge exhibited specific anticryptosporidial immunoglobulin binding (A405 = 0.96), compared to that of seven uninfected rnu/+ controls (A405 = 0.09, P less than 0.02). Macromolecules of 150, 105, and 88 kD in the Cryptosporidium antigen preparation were bound by serum immunoglobulin from previously infected, recovered rnu/+ rats. Two brush-border enzymes (lactase and alkaline phosphatase) were markedly reduced in the ileum 8-10 days after oro-gastric challenge in rats with diarrhea and oocyst shedding. We find the rnu/rnu (athymic, nude) rat provides a useful model for study of prolonged cryptosporidial infection with impaired weight loss, brush-border enzyme alteration and intermittent diarrhea. These studies further suggest that a T-lymphocyte population is involved in recovery from Cryptosporidium infection and that this recovery is associated with both cellular and humoral immune responses to specific cryptosporidial antigenic macromolecules. This model should open further avenues for the study of the pathogenesis and protective immunity in cryptosporidial infection. 
5	Echographic diagnosis of dural carotid-cavernous sinus fistulas. I used standardized ophthalmic echography to identify specific abnormalities in four patients with low-pressure, low-flow dural arteriovenous malformations. In all of the patients, B-scan ultrasonography showed engorgement of the ipsilateral vertical vein. A-scan ultrasonography dynamically imaged rapid blood flow through the superior ophthalmic vein and enlargement of the culpable ocular muscles in patients with restrictive ophthalmopathy. The 30-degree test distinguished between venous engorgement of the optic nerve sheath and apical compression of the optic nerve by enlarged ocular muscles. 
4	Stress management in the treatment of mild primary hypertension. The use of simple relaxation-based stress management procedures in the treatment of mild primary hypertension has been the subject of extensive study. Stress management appears to lead to reliably greater reductions in pressure than a variety of control procedures. The mechanisms underlying these effects are obscure, and research has not identified which patients will benefit most from treatment. Preliminary data suggest that stress management may reduce the risk of coronary heart disease, but much research must be done if this is to be confirmed. It is suggested that such research should take into account the possibility that stress management may have beneficial effects on more than just hypertension-related aspects of the cardiovascular disease process. 
3	Traumatic retinal detachment. Seventy-seven patients developed retinal breaks following an episode of ocular contusion, and 65 (84.4%) of these developed rhegmatogenous retinal detachment. Surgical treatment successfully restored or maintained retinal apposition in 74 (96.1%) of the eyes. Thirty-six (46.8%) eyes recovered visual acuity of 6/9 or better. Of the retinal breaks recognised dialysis at the ora serrata was observed in 49 eyes, of which 28 were situated at the lower temporal quadrant. Seventeen eyes had irregular breaks arising within necrotic retina at the site of scleral impact. Twenty-four (31.2%) patients had retinal break or retinal detachment diagnosed within 24 hours of injury and 49 (63.6%) within six weeks. Immediate retinal detachment was a feature of necrotic retinal breaks, while inferior oral dialyses led to a slow accumulation of subretinal fluid. Delayed diagnosis of retinal detachment was due either to opaque media or to failure to examine the retina after injury. Visual prognosis was good when retinal break or detachment were diagnosed within six weeks of injury. However, those patients who escaped initial retinal examination and were lost to follow-up had a less favourable visual outcome. 
3	HLA class II antigens and DNA restriction fragment length polymorphism in myasthenia gravis in Japan. Human leukocyte phenotypes and genes in the HLA class II regions were studied in 46 Japanese patients with myasthenia gravis. When the HLA phenotypes of the patients with myasthenia gravis were compared with the controls, an increased frequency of HLA-DRw53 was observed in females less than 30 years of age. The genomic DNAs of the HLA-DRw53-positive patients and DRw53-positive controls were analyzed by using four complementary DNA probes for HLA class II genes. With DQB complementary DNA as the probe, a higher incidence of the 6.5-kb or 8.2-kb BamHI fragment was observed in the patients (76.0%) compared with the controls (19.0%). In contrast, no significant difference was observed between patients and controls when complementary DNAs for DRB, DQA, and DPB were used as probes. These results indicate that the genetic background of Japanese females with early-onset myasthenia gravis is different from other patients with myasthenia gravis, and that DQB genes can greatly influence the onset of myasthenia gravis. 
5	Embolism during caesarean section. We investigated the occurrence of gas embolism during Caesarean section using a Doppler ultrasound probe and found that it occurs between uterine incision and delivery. Embolism is less common during general anaesthesia than has been reported during regional anaesthesia. Both ruptured membranes and a protracted uterine incision to delivery interval predispose to embolism. 
4	A study of the effects of delapril, a new angiotensin converting enzyme inhibitor, on the diurnal variation of arterial pressure in patients with essential hypertension using indirect and direct arterial pressure monitoring methods. In order to investigate the effect of delapril, a new angiotensin converting enzyme inhibitor, on the diurnal variation of arterial pressure in patients with essential hypertension, this study examined 24 h arterial pressure using an indirect or a direct monitoring system. When the effect of twice-a-day administration of delapril at daily doses of 30 to 90 mg was examined using the indirect monitoring system in 12 outpatients, delapril decreased systolic and diastolic arterial pressures significantly only at limited points during the day. However, each of the averaged 24 h daytime and nighttime arterial pressures showed significant reductions. The 24 h intraarterial pressure monitoring demonstrated that delapril decreased systolic and diastolic arterial pressure at most of the measurement points. The arterial pressure reductions during daytime and nighttime were not significantly different, that is, there was no excessive reduction in nighttime arterial pressure. Heart rate and its variability were virtually unaffected by the delapril treatment in either monitoring study. No adverse reactions were observed in the indirect or direct monitoring studies. Thus, it is concluded that twice-a-day administration of delapril at daily doses of 30 to 90 mg brings about a safe and stable antihypertensive effect, without affecting the diurnal variation of arterial pressure. 
5	Unusual cerebral manifestations in hereditary fructose intolerance. Five children with hereditary fructose intolerance developed symptoms of neurological impairment. In three of them, neurological involvement was related to the acute hepatic toxicity of fructose (hypoglycemia, abnormal coagulation, cardiovascular collapse); in the other two, such a relationship could not be demonstrated. Neurological impairment is not classic in hereditary fructose intolerance, but its occurrence in the acute phase of the disease is possible and does not constitute an argument against the diagnosis. 
5	Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma. Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. 
4	A predominantly adrenaline-secreting phaeochromocytoma. A 61-year-old woman who presented with diabetes, nausea, weight loss and sweating was found to have a phaeochromocytoma secreting adrenaline, with a small amount of N-methyladrenaline. There was no significant increase in noradrenaline secretion. She was normotensive, and developed profound hypotension in response to the alpha-adrenergic antagonist phenoxybenzamine. These features are unusual in phaeochromocytoma, but similar features occurred in the very few previous reported cases of pure adrenaline-secreting phaeochromocytoma. We conclude that it is important to identify such patients, so that they should not be given alpha-adrenergic antagonist drugs. 
1	Epidermoid cyst (monodermal teratoma) of the testis. We report 14 patients with epidermoid cyst of the testis (monodermal teratoma). In 7 patients (5 treated within the last 5 years) the mass was excised and adjacent testicular tissue was biopsied. Seven patients underwent radical inguinal orchiectomy. Carcinoma in situ was not detected in any testicular tissue examined. There was no evidence of tumour recurrence in any patient after a mean follow-up of 10 years. Ultrasonographic appearance was not specific for a diagnosis of epidermoid cyst and exploratory surgery was required in all cases. Excision of the tumour and biopsy of adjacent testicular tissue to determine the presence or absence of carcinoma in situ is adequate treatment for this rare testicular neoplasm. 
5	Percutaneous transluminal coronary angioplasty of gastroepiploic artery graft. The right gastroepiploic artery is being used as a third arterial conduit for coronary artery bypass surgery. Presented here is a case demonstrating successful percutaneous transluminal coronary angioplasty of the gastroepiploic artery graft. This successful accomplishment may avoid repeat surgical revascularization in case of failure of the gastroepiploic artery graft, hence may encourage people to use it more often. 
1	Reoperation for colorectal carcinoma. In the management of the patient with intra-abdominal recurrence of colorectal carcinoma, surgery remains the primary mode of therapy when cure or significant palliation is anticipated. Appreciation of the importance of close follow-up after primary resection coupled with improved diagnostic modalities has allowed the surgeon not only to detect earlier recurrence but also to select the patients most likely to benefit from resection of recurrent disease. Improved surgical techniques with resultant decreases in the rates of morbidity and mortality have allowed safe hepatic resection of metastatic disease. In selected patients, this procedure produces 5-year survival rates approaching 50%. Although a clear consensus has not been reached, most studies agree that positive prognostic indicators include absence of extrahepatic disease, a small number of intrahepatic lesions, a low CEA level, and a better Dukes stage of the primary. Likewise, in the patient with recurrent disease locally, surgery provides the only means of cure and also plays a significant role in palliation. Aggressive resection with generous surgical margins in patients with contained disease may yield 5-year survival rates approaching 35%. In patients with unresectable disease and even in those with carcinomatosis, palliation can be obtained by surgical therapy. Judgment is necessary in treating these patients both preoperatively and intraoperatively. Surgical intervention for obstruction, perforation, or other anatomic or physiological compromise is often indicated and can improve the quality of life of the patient with intra-abdominal recurrence. 
5	Sudden death and sleeping history among Finnish men. An autopsy was performed in 460 consecutive cases of sudden death among 35- to 76-year-old men. The closest cohabiting individual known to each decreased subject was interviewed. Snoring history was obtained in 321 of the 371 interviews. In 86 cases there was a history of 'habitual' (almost always or always) snoring, and 88 men snored 'often'. The mean age of subjects was 55.4 years. The mean body mass index (BMI) was 26.3 kg m-2. Among the obese snorers (n = 82), apnoeas had been observed 'occasionally', 'often', or 'habitually' in 49 cases. Death was classified as cardiovascular in 186 (40.4%) cases. Cardiovascular cause of death was more common among those who snored habitually or often than among those who snored occasionally or never (P less than 0.05). 'Habitual' snorers died more often while sleeping (P less than 0.05). Habitual snoring was found to be a risk factor for morning death (P less than 0.01). The possibility of obstructive sleep apnoea as a cause of sudden death should at least be considered if the decreased is known to have been a habitual snorer. 
3	Migraine and vertebrobasilar ischemia. I studied 9 patients with migraine and posterior circulation ischemia. Inclusion criteria were (1) brainstem or cerebellar infarcts or transient ischemic attacks, (2) satisfactory vertebrobasilar angiograms, and (3) migraine. Excluded were patients with only occipital lobe ischemia, known arteriosclerosis, or other nonmigrainous vascular disease. Two women and 7 men, ages 6 to 58 years (mean, 34.7), had transient attacks only (2), single strokes (4), single stroke followed by attacks (1), or multiple strokes (2). Five had antecedent classic, 2 common migraine, and classic migraine began only after the initial ischemic event in the other two. The 7 stroke patients all had CT- or MRI-documented brainstem (4) or cerebellar (6) infarcts. Angiography was normal (3) or demonstrated basilar artery (BA) narrowing (2) or occlusion (4), or branch occlusion (1). In 3 patients the initially occluded BA later reopened. At follow-up (average 4.3 years, range 1 to 9 years), 5 were normal and 4 had important clinical deficits. I conclude that (1) "basilar migraine" is not always benign; it affects both sexes and a wide age range; (2) the pattern of headaches, attacks, and strokes varies; (3) migraine may appear only after ischemia; (4) some patients have BA occlusion or diffuse narrowing; and (5) BA occlusion can be temporary. 
5	Sweet's syndrome with lung involvement. Severe dyspnea and pulmonary infiltrates were associated with recurrent episodes of Sweet's syndrome (acute febrile neutrophilic dermatosis) in a 54-yr-old woman with myelodysplasia. Lung and skin biopsies revealed a sterile infiltration of the interstitial tissues by mature neutrophils. Corticosteroid therapy resulted in rapid clinical improvement; however, recurrent episodes were increasingly resistant to therapy, and she ultimately died from respiratory failure. Sweet's syndrome involving the lung is rare, with only two previously reported cases documented by lung biopsy. Prompt recognition of Sweet's syndrome with lung involvement is important because of the potential for severe respiratory compromise. 
5	Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause. 
1	Endometrial ablation for the treatment of menorrhagia: a comparison of patients with normal, enlarged, and fibroid uteri. One hundred sixty-one patients underwent endometrial ablation with the Nd:YAG laser for the treatment of refractory menorrhagia. Patients were divided into one of three groups: those with a normal-sized uterus; those with an enlarged uterus (greater than 10 cm); and those with uterine fibroids, which had been documented clinically, ultrasonographically, or by a combination of hysteroscopy and laparoscopy or by one or the other. All patients were considered candidates for hysterectomy. Both preoperatively and postoperatively, patients monitored their menstrual cycles and evaluated their flow according to predetermined categories of amenorrhea, light flow, normal flow, heavy flow, and severe flow. After treatment, 68% of patients with normal-sized uterus and 91% of patients with an enlarged uterus (greater than 10 cm) and 88% of patients with uterine fibroids became amenorrheic or had light flow. None of the patients in this last group have had to undergo hysterectomy. This study indicates that the patient with an enlarged or fibroid uterus may not have contraindications for endometrial ablation. Endometrial ablation may be effective in at least temporarily controlling bleeding in those patients with enlarged or myomatous uterus. 
4	The value of pulmonary artery and central venous monitoring in patients undergoing abdominal aortic reconstructive surgery: a comparative study of two selected, randomized groups. One hundred two patients undergoing abdominal aortic reconstructive surgery were prospectively, randomly allocated to two groups, one of which was monitored with a central venous catheter and the other with a pulmonary artery catheter. Patients with uncompensated cardiopulmonary or renal disease were excluded from the study. General anesthesia was administered for the surgical procedure, and the patients were followed through hospital discharge. No statistically significant differences occurred between the two groups with regard to morbidity (perioperative cardiac, pulmonary or renal sequelae), mortality rate, duration of intensive care, postoperative hospital stay, or cost of hospitalization. The one statistically significant difference between groups was the professional fee charged for anesthetic care, which was higher for patients with pulmonary artery catheters than for those with central venous catheters. In conclusion, we prospectively gathered data from most patients presented for abdominal aortic reconstructive surgery. Our data seem to indicate that the choice of central venous catheter or pulmonary artery catheter monitoring makes little difference in outcome after abdominal aortic reconstructive surgery, and that for many patients pulmonary artery catheters are not necessary to give appropriate, adequate care. Because of the size of the sample, however, declarations of epidemiologic significance would be unfounded. Therefore large-scale, multicenter studies addressing such outcomes remain necessary. 
5	Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome. Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS. 
4	Salvage from cardiogenic shock by atherectomy after failed emergency coronary artery angioplasty. In this case report of a patient undergoing angioplasty for cardiogenic shock during acute myocardial infarction, recurrent occlusion resulted in recurrence of shock. Atherectomy reestablished lasting patency and reversed the patient's hemodynamic collapse. Atherectomy deserves further investigation as a means to salvage vessel patency during unsuccessful coronary angioplasty. 
3	Late effects of paralytic poliomyelitis in Olmsted County, Minnesota. We identified a cohort of 300 individuals who had paralytic polio between 1935 and 1955. All lived in Olmsted County, Minnesota. From the 247 survivors, we selected 50 subjects for detailed historical, functional, psychological, clinical, and electrophysiologic evaluation. Sixty-four percent of these 50 survivors complained of new symptoms of muscle pain, fatigue, and weakness after a period of prolonged stability. This led to changes in lifestyle or activity in only 18%. The likelihood of expressing new complaints was not related to present age or interval since polio, and electrophysiologic testing did not distinguish between those with or without new problems. The development of new difficulties in a limb was most strongly predicted by significant paralysis of that limb at the time of the acute illness. Patients with leg weakness were twice as likely to complain of new problems compared to those with arm weakness. Elevated creatine kinase levels were present only in those with new complaints. 
1	Bladder cancer. Human leukocyte antigen II, interleukin-6, and interleukin-6 receptor expression determined by the polymerase chain reaction. The prediction of tumour biology rarely rests upon a single characteristic of the malignancy. The analysis of a single gene can complement standard histologic evaluation. The investigation of new parameters as well as the routine clinical analysis of gene expression is often limited because of the small amount of tissue available. This is particularly true of de novo human bladder cancers because they are generally small or handled in such a way as to hinder the analysis of multiple different parameters. Analysis of expressed mRNA by the polymerase chain reaction (RNA/PCR) is a method that allows the development of a profile of bladder cancer gene expression. The authors report the use of the RNA/PCR method to examine in bladder cancer the expression of the human leukocyte antigen (HLA) class II gene family (HLA-DR, DQ, and DP) as well as interleukin-6 (IL-6) and the interleukin-6 receptor (IL-6R). All de novo transitional cell carcinomas, one squamous carcinoma, and two transitional cell carcinoma cell lines expressed the majority of HLA class II genes. All samples expressed IL-6R RNA whereas production of IL-6 message was limited to one of the cell lines and to the high-grade bladder cancers. These results were combined with stage, grade, and DNA content to develop a profile of the cancers examined. Although an improved predictive index based on gene expression analysis by RNA/PCR has not been realized, a broader survey of human tumors for expression of these genes and others is likely to refine the classification of bladder cancer. 
4	Cardiac disease in the alcoholic patient. Ethanol in acute low doses is believed to be relatively nontoxic to the normal myocardium, despite data indicating low-level contractility impairment. In patients with myocardial disease, or as the serum ethanol concentration is increased to high levels, angina, myocardial infarction, and arrhythmia may be potentiated. Chronic ethanol use, at moderate doses, may be protective against coronary artery disease, despite increased rates of hypertension. Alcohol consumption at high doses may result in dilated cardiomyopathy and a dismal prognosis. Alcohol abuse is associated with increased mortality. 
5	Primary peritoneal sarcoidosis. A 14-year-old male was admitted for the evaluation of tense exudative ascites. Despite thorough evaluation, the diagnosis remained cryptic until peritoneoscopy revealed diffuse studding of the entire visualized peritoneum with multiple miliary nodules, and peritoneal biopsy demonstrated multiple noncaseating epithelioid granulomas. After other causes were excluded, a diagnosis of sarcoidosis was considered and confirmed with classic endobronchial findings at bronchoscopy. Involvement of the peritoneum with sarcoidosis is rare and, to our knowledge, only one other case describes this as the initial manifestation of this disease. 
3	Reversible nerve conduction block in patients with polyneuropathy after ultrasound thermotherapy at therapeutic dosage. This study investigated the effect of ultrasound on nerve conduction in patients with polyneuropathy. Eight able-bodied controls (Group C) and 16 patients with clinical and physiologic evidence of polyneuropathy were tested. Eight patients (Group NP) had no aching pain symptoms; eight patients (Group P) had severe aching pain, burning sensation, unpleasant tingling, and/or hyperesthesia in the lower extremities. For two minutes, therapeutic ultrasound in doses of 0.5, 1.0, and 1.5W/cm2 were applied over the anterior surface of the leg along the pathway of the deep peroneal nerve. Peroneal nerve conduction studies were performed before, during, and after ultrasound treatment. The compound muscle action potential (CMAP) was recorded from the extensor digitorum brevis muscle. Nerve conduction studies on all eight patients in Group P revealed a significant decrease (41.4% and 44% reduced for doses of 1.0W/cm2 and 1.5W/cm2, respectively; p less than .05) in amplitude of CMAP (from baseline to the first negative peak), and an increase (6.4% and 6.7% increased for doses of 1.0W/cm2 and 1.5W/cm2, respectively; p less than .05) in proximal latency one minute after ultrasound application with a dose of 1.0 or 1.5W/cm2, but not with a dose of 0.5W/cm2 (p greater than 0.1). Changes returned to pretreatment values within five minutes of cessation of ultrasound therapy. In Groups C and NP, there were no significant changes in amplitudes of CMAP or proximal latency before, during, or after ultrasound therapy at a dose of 0.5, 1.0, or 1.5W/cm2. It was concluded that ultrasonic therapy with therapeutic dosage may cause a reversible conduction block on patients with painful polyneuropathy. 
5	Limitations of faecal chymotrypsin as a screening test for chronic pancreatitis. Faecal chymotrypsin was measured in patients with chronic pancreatitis and in healthy black urban and rural control subjects. In the patients, significantly lower values of faecal chymotrypsin were obtained (mean (SD) 2.4 1.79 U/g stool) whereas in urban control subjects, values were within the normal range (mean (SD) 13.2 (11.9)). In rural black control subjects, however, the faecal chymotrypsin value was significantly lower (mean (SD) 7.1 (5.1)) than in urban black control subjects. It is suggested that faecal pH may influence faecal chymotrypsin values. The mean faecal pH in rural black subjects (pH 6.14) was significantly lower than that in urban control subjects (pH 6.77) and in patients with chronic pancreatitis (pH 6.61). Moreover, mean faecal chymotrypsin is high (20.0 U/g stool) at a pH greater than 7. Between pH 6 and 7 the mean value drops to 8.6 U/g stool and below pH 6 mean faecal chymotrypsin is in the abnormal range (4.4 U/g stool). Hence, low values for faecal chymotrypsin may be due to lower faecal pH (less than 6) in healthy control subjects. For diagnostic purposes, the faecal pH value should be determined if a low faecal chymotrypsin value is obtained. 
5	Levels of serum granulocyte colony-stimulating factor in patients with infections. To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age-matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo. 
4	Collateral circulation in Kawasaki disease with coronary occlusion or severe stenosis. Forty patients with Kawasaki disease with severe coronary sequelae were investigated. All had at least a 90% reduction in the diameter of the major coronary artery. Collateral vessels were seen in 32 of 33 (97%) patients with total occlusion. All patients with severe stenosis but not total occlusion had no or poorly developed collateral vessels. Analysis according to the presence or absence of collateral vessels showed no significant differences in the results of treadmill stress testing and myocardial imaging between these two groups. In patients treated surgically, the abnormalities recognized by these tests were normalized or improved when the bypass was patent. These data indicate that collateral circulation in patients with Kawasaki disease cannot be seen angiographically unless there is total occlusion and the presence of collateral circulation cannot provide protection against stress-induced myocardial ischemia. 
3	Examination by logistic regression modelling of the variables which increase the relative risk of elderly women falling compared to elderly men. In a community based, prospective study to determine risk factors for falls, 465 women and 296 men 70 years and over were followed for 1 year and 507 falls were documented. A greater proportion of women (32.7%) than men (23.0%) experienced at least one fall in which there was no or minimal external contribution. Using unconditional logistic regression models we investigated the effect of physical and sociological variables on the sex difference in fall rate. Controlling for the variables age, use of psychotropic drugs, inability to rise from a chair without using arms, going outdoors less than daily and living alone decreased the relative risk of women falling compared to men from 2.02 (95% CI, 1.40-2.92) to 1.55 (95% CI 1.04-2.31). Some of the increased risk of falling associated with being a women was able to be explained and is potentially correctable. But even after controlling for the physical and social variables which we had assessed, women compared to men still had a significantly increased relative risk of falling. 
5	Mutations in the K-ras oncogene induced by 1,2-dimethylhydrazine in preneoplastic and neoplastic rat colonic mucosa. These experiments were conducted to determine whether point mutations activating K-ras or H-ras oncogenes, induced by the procarcinogen 1,2-dimethylhydrazine (DMH), were detectable in preneoplastic or neoplastic rat colonic mucosa. Rats were injected weekly with diluent or DMH at 20 mg/kg body wt for 5, 10, 15, or 25 wk, killed, and their colons dissected. DNA was extracted from diluent-injected control animals, histologically normal colonic mucosa from carcinogen-treated animals, and from carcinomas. Ras mutations were characterized by differential hybridization using allele-specific oligonucleotide probes to polymerase chain reaction--amplified DNA, and confirmed by DNA sequencing. While no H-ras mutations were detectable in any group, K-ras (G to A) mutations were found in 66% of DMH-induced colon carcinomas. These mutations were at the second nucleotide of codons 12 or 13 or the first nucleotide of codon 59 of the K-ras gene. The same type of K-ras mutations were observed in premalignant colonic mucosa from 2 out of 11 rats as early as 15 wk after beginning carcinogen injections when no dysplasia, adenomas, or carcinomas were histologically evident, suggesting that ras mutation may be an early event in colon carcinogenesis. 
2	Percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections. Operative drainage is the cornerstone of therapy for pancreatic abscess. Recently it has been suggested that successful percutaneous catheter drainage of infected pancreatic and peripancreatic fluid collections may serve as definitive therapy. We undertook therapeutic, computed tomography-directed percutaneous drainage in a selected group of 29 patients with infected pancreatic and peripancreatic fluid collections. Twenty-three patients (79%) were successfully treated with percutaneous drainage. Of six patients (21%) representing failures of percutaneous drainage, four died and two recovered after operative drainage. The four patients who died had a mean APACHE (acute physiology and chronic health evaluation) II score of 23 and five of Ranson's prognostic signs. Ranson's signs and APACHE II scores were predictive of success and mortality. We conclude that in selected patients, infected pancreatic and peripancreatic fluid collections can be treated definitively with therapeutic percutaneous catheter drainage. Based on this experience, recommendations regarding patient selection are included. 
1	The contribution of routine follow-up mammography to an early detection of asynchronous contralateral breast cancer. The role of routine mammography was assessed in the early detection of asynchronous contralateral breast cancer (ACBC). The breast cancer patient populations of two cities, Nijmegen and Eindhoven, The Netherlands, which were subjected to a well-defined follow-up program, were compared. The program consisted of regular physical examination and annual mammography in Nijmegen and physical examination only in Eindhoven. From 1975 until 1987, 24 ACBC patients were detected within a group of 880 breast cancer patients in Nijmegen (3%) and, from 1971 until 1984, 14 ACBC patients within a group of 411 patients in Eindhoven (3%). In Nijmegen, eight of the 23 evaluable patients (35%) had a contralateral tumor with a histologic size smaller than 10 mm or an in situ carcinoma, compared with one of the 14 of the Eindhoven patients (7%), whereas 18 of the 24 (75%) versus eight of the 14 patients (57%) were node-negative. Thus annual mammography is very likely a contribution in the early detection of contralateral breast cancer as compared with follow-up by regular physical examination only. 
3	Rehabilitation of quadriparesis secondary to spinal cord sarcoidosis. Sarcoidosis is a multisystem granulomatous disorder that rarely involves the spinal cord. This report describes the presentation and rehabilitative course of a 31-yr-old man with quadriparesis secondary to spinal cord sarcoidosis. The patient had insidious, progressive weakness in his arms and legs for six weeks before evaluation. Examination revealed a C4 incomplete spinal cord injury. Computed tomography demonstrated an intrinsic cord lesion from the brainstem to approximately T8. Magnetic resonance imaging (MRI) suggested the lesion was granulomatous and cervical laminectomy confirmed noncaseating granulomas. The patient was started on high dose steroids, subsequently gained strength in the distal upper extremities, and was sent for spinal cord rehabilitation. Examination revealed 3 to 4+/5 strength in the upper extremities, 2- to 3-/5 in the lower extremities. The right side was slightly stronger than the left, with proximal musculature stronger than distal. Sensory examination was intact except in the C-8 to T-2 dermatomes. The patient was dependent in self-care and mobility except for feeding. Initial progress was inhibited by severe spasticity requiring medication, but by discharge he was independent at the wheelchair level with 4/5 strength in all four extremities except for his hands, which had 3/5 strength. Sensory exam did not change. Follow-up MRI studies revealed reduction of the lesion. Review of previous cases revealed that myelopathy is the most common presenting complaint and cervical segments are most commonly involved. Survival averaged almost three years and significant gains were made in functional status. Rehabilitative course and special considerations, treatment and follow-up recommendations are discussed. 
5	A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy. PURPOSE: To construct and test prospectively a bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy. PATIENTS AND METHODS: In an inception cohort of 617 patients starting long-term anticoagulant therapy in one hospital, data were gathered retrospectively and bleeding was classified using reliable explicit criteria. We constructed a bleeding risk index by identifying and weighting independent predictors of major bleeding using a multivariate proportional-hazards model. The bleeding risk index was tested in 394 other patients prospectively identified in a second hospital. The index was compared to physicians' predictions. RESULTS: Major bleeding developed before discharge in 61 of all 1,011 patients (6%). The bleeding risk index included four independent risk factors for major in-hospital bleeding: the number of specific comorbid conditions; heparin use in patients aged 60 years or older; maximal prothrombin or partial thromboplastin time 2.0 or more times control; liver dysfunction worsening during therapy. In the testing group, the index predicted major bleeding, which occurred in 3% of 235 low-risk patients, 16% of 96 middle-risk patients, and 19% of 63 high-risk patients (p less than 0.001). The bleeding risk index performed as well as physicians' predictions, and integration of the bleeding risk index with physicians' predictions led to a classification system that was more sensitive (p = 0.03) than physicians' predictions alone. In 86% of patients with a high risk of major bleeding, we identified specific ways of improving therapy, e.g., avoiding overanticoagulation and nonsteroidal anti-inflammatory agents. CONCLUSION: The bleeding risk index provides valid estimates of the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy and complements physicians' predictions. The possibility that bleeding can be prevented in high-risk patients warrants prospective evaluation. 
5	Rare variant of isolated lower pole hydronephrosis: primary obstructive megaureter. Hydronephrosis in the lower pole moiety of a duplex system is relatively uncommon, usually associated with vesicoureteric reflux. We report on a patient with primary obstructive megaureter of a lower pole moiety that we believe is the first case report in the literature. 
4	Anticardiolipin antibodies in polymyalgia rheumatica-giant cell arteritis: association with severe vascular complications. PURPOSE: We studied a group of patients with polymyalgia rheumatica (PMR) with or without biopsy-proven giant cell arteritis (GCA) in order to determine the prevalence of anticardiolipin antibodies (aCL) in these disorders and their association with vascular complications. PATIENTS AND METHODS: The study consisted of 50 patients, 30 with PMR alone and 20 with associated GCA. Determinations of IgG and IgM aCL by enzyme-linked immunosorbent assay were done in the patients and in 50 age- and sex-matched healthy control subjects. We also measured von Willebrand factor (vWF) antigen, C-reactive protein, and erythrocyte sedimentation rate. RESULTS: Twenty-four (48%) of the 50 patients had aCL. Eleven were positive for IgG and five for IgM, whereas eight were positive for both. In the group of patients with PMR alone, only eight (26.6%) had aCL, while 16 of 20 patients (80%) with GCA had these antibodies (p less than 0.01). In the control group, 10 of 50 patients (20%) had positive aCL, a finding that was statistically significantly different only when compared with the finding in patients with GCA (p less than 0.01). Both isotypes of aCL were seen mainly in patients with GCA, and five of these patients had severe vascular complications. Levels of vWF antigen were significantly higher in patients with GCA as compared with patients with PMR alone; however, the highest titers did not correlate with vascular complications. Erythrocyte sedimentation rate and C-reactive protein were increased but comparable in both groups. CONCLUSION: This study demonstrates that aCL are prevalent in patients with GCA. These antibodies might imply severe vascular damage and could play an important role in the pathogenesis of the vasculopathy observed in this disease. 
5	Endoscopic comparison of cimetidine and sucralfate for prevention of naproxen-induced acute gastroduodenal injury. Effect of scoring method. Nonsteroidal antiinflammatory drug-induced gastroduodenal mucosal damage observed endoscopically is usually categorized as hemorrhages, erosions, or ulcerations. We undertook this study to determine whether the injury produced by a commonly prescribed NSAID, naproxen, could be reduced by cotherapy with sucralfate or cimetidine and to determine how dependent the differences in the degree of protection against mucosal injury measured were on the scoring system used. Four groups of 20 healthy volunteers with endoscopically normal gastric and duodenal mucosa received naproxen (500 mg twice a day) plus cimetidine (300 mg four times a day or 400 mg twice a day), sucralfate (1 g four times a day), or placebo for seven days. After seven days of therapy, a second endoscopy was performed. Separate scoring systems were used for the presence of hemorrhages, erosions, and a combination of both types of injury. There were significantly fewer mucosal hemorrhages present when naproxen and cimetidine were administered than when naproxen was administered with placebo or sucralfate (placebo vs 300 mg cimetidine, P = 0.04, and placebo vs 400 mg cimetidine, P = 0.006, placebo vs sucralfate, P = 0.26). Both cimetidine dosages resulted in significantly fewer hemorrhages than were present following cotherapy of naproxen and sucralfate (P less than 0.05). In contrast, there was no discernible difference in the mucosal injury between placebo and any drug or between any two active therapies when the injury was evaluated based on the presence of gastric erosions. 
5	Assessment of ventricular septal defect closure by intraoperative epicardial ultrasound. Intraoperative epicardial two-dimensional echocardiographic imaging, color flow mapping and contrast echocardiography were used in 31 patients after patch closure of a ventricular septal defect to determine their respective values in the assessment of residual shunting after cardiopulmonary bypass and for the prediction of long-term results. Epicardial imaging showed no incidence of patch dehiscence. Residual shunting detected by color flow mapping or contrast echocardiography was graded into one of four categories (0 to III). Real time analysis of color flow mapping studies suggested no shunting (grade 0) in 2 patients, grade I shunting in 20, grade II in 8 and grade III in 1; contrast studies suggested grade 0 in 15, grade I in 6, grade II in 8 and grade III in 2. Interobserver variation in real time encoding of grade I or II shunting was 25% by color flow mapping and 6% by contrast echocardiography. Subsequent frame by frame analysis revealed that both diastolic and early systolic right ventricular turbulence gave rise to false positive results during real time analysis of color flow mapping studies. Color flow mapping allowed exact localization of residual shunting, whereas contrast echocardiography allowed better semiquantification. Postbypass results were correlated in 30 patients with late postoperative precordial studies (mean interval 7.5 months). Persistent shunts were found in 6 (20%) of 30 patients. No patient required reoperation for residual shunting. The predictive value of immediate grade I or II shunting as a marker for persistent long-term shunting was poor, whereas both patients with immediate grade III shunting had shunt persistence, indicating that immediate revision should be considered in such patients. Intraoperative epicardial ultrasound is valuable for the immediate exclusion of important residual shunting after ventricular septal defect closure. Maximal information is obtained when color flow mapping and contrast echocardiography are used in combination. 
3	Ichthyosis, mental retardation, and asymptomatic spasticity. A new neurocutaneous syndrome with normal fatty alcohol:NAD+ oxidoreductase activity. A number of inherited disorders of cornification have been related to abnormal lipid metabolism. In the recessively inherited Sjogren-Larsson syndrome, defined by the triad of ichthyosis, mental retardation, and spasticity, fatty alcohol:NAD+ oxidoreductase deficiency has recently been reported. These patients accumulate fatty alcohol in the plasma and cultured fibroblasts. A 19-year-old woman with ichthyosis, mental retardation, and mild spasticity is described in whom fatty alcohol metabolism was normal, as determined by plasma octadecanol level and fibroblast fatty alcohol:NAD+ oxidoreductase activity. Ultrastructural studies on skin from the patient revealed morphologically abnormal epidermal lamellar bodies, not unlike those seen in neutral lipid storage disease with ichthyosis. We postulate that this patient has a novel neurocutaneous syndrome that may be secondary to abnormal lipid metabolism. 
3	Evaluation and treatment of mental disorders in patients with AIDS. Mental symptoms are common in patients with AIDS. Optimal management involves the identification and treatment of underlying mental disorders rather than symptomatic treatment alone. Organic mental disorders are very frequent in AIDS, particularly with seriously ill patients who are medical inpatients. There is a high priori probability that such common symptoms as agitation, irritability, and insomnia will be caused by an organic mental disorder. Psychopharmacology in the patient with AIDS requires considerable caution. Lower doses and careful surveillance for subtle neuropsychiatric side effects are necessary. Routine medical contact with a compassionate physician may be of inestimable value to the patient in coping with the fear and dread that surround the illness. 
5	Treatment of de Quervain tenosynovitis. A prospective study of the results of injection of steroids and immobilization in a splint. In a prospective study of non-operative treatment of de Quervain tenosynovitis, ninety-nine wrists of ninety-five consecutively seen patients who had this diagnosis had an injection of one milliliter of a 1 per cent lidocaine solution and one milliliter of a suspension containing forty milligrams of methylprednisolone acetate. Twelve patients (twelve wrists) were lost to follow-up. Of the remaining eighty-seven wrists, fifty-four (62 per cent) had a satisfactory outcome at a mean of eighteen months (minimum follow-up, twelve months). The duration of symptoms before treatment did not affect the outcome. The result in thirty-three wrists (38 per cent) was considered unsatisfactory. Thirty of these wrists were subsequently treated with operative release of the first dorsal compartment, and twenty-two (73 per cent) of the thirty were found to have a separate compartment for the extensor pollicis brevis. The prevalence of a separate compartment is significantly higher than that in the general population, as shown in anatomical studies of cadavera. 
4	Quality of life among hypertensive patients with a diuretic background who are taking atenolol and enalapril. The cardioselective beta-blocker atenolol and the angiotensin-converting enzyme inhibitor enalapril were compared for efficacy, safety, and quality-of-life factors in 30 patients with hypertension whose hypertension was inadequately controlled with diuretic alone. Atenolol (50 to 100 mg once a day) and enalapril (2.5 to 40 mg once a day), combined with hydrochlorothiazide (25 mg once a day), had similar levels of efficacy and safety. A comprehensive battery of psychologic assessments for quality of life was administered, including measures of anxiety, depression, psychiatric symptoms, memory, and psychomotor function. These five conceptually based clusters were first analyzed by multivariate analysis of variance procedures, followed by univariate analyses of the individual variables composing each domain. In general, neither atenolol nor enalapril was associated with major changes in psychologic functioning. The only data cluster with a statistically significant change was memory function, primarily as a result of lower scores of the digit span (backward) test, for atenolol relative to enalapril. These preliminary findings suggest that atenolol and enalapril have comparable degrees of efficacy and safety, with no major disparities in quality-of-life effects, for hypertensive patients with a history of taking diuretics and this sort of quality-of-life assessment can be performed during trials of antihypertensive drugs. 
4	Triiodothyronine treatment for Raynaud's phenomenon: a controlled trial. The effects of 80 micrograms triiodothyronine (T3) daily were compared with placebo in a double blind controlled crossover trial in 18 patients with Raynaud's phenomenon. Reductions in the frequency, duration and severity of attacks while taking T3 were gradual but highly significant. Four of 6 subjects had skin ulcer healing. Skin temperatures in the hands increased significantly. The skin temperature recovery times after cold exposure were significantly shorter during T3 therapy compared with placebo. Although large dosages of T3 were well tolerated, 6 patients experienced episodic palpitations, and slight but significant increases in heart rate and pulse pressure were observed. Evaluation of the use of physiological doses of T3 (60 micrograms daily or less) in the treatment of Raynaud's phenomenon is suggested. 
3	Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia. Vitamin B12 and folate concentrations were measured in serum and cerebrospinal fluid (CSF) in 293 neurological patients. Serum and CSF vitamin B12 concentrations showed a positive correlation. In individual patients CSF B12 concentrations varied considerably for a given serum concentration. The median serum vitamin B12 concentration of the Alzheimer's type dementia group was significantly lower compared with that of a control group. Lower median CSF vitamin B12 concentrations were found in groups of patients with multiple sclerosis and Alzheimer's type dementia. Five patients with heterogeneous clinical pictures had unexplained low serum and CSF B12 concentrations without macrocytosis. Two patients had very high serum B12 and low-normal CSF concentrations which could be explained by a blood-brain barrier transport defect. Serum and CSF folate concentrations did not show significant differences between the various groups. 
5	Oral estrogens decrease bleeding time and improve clinical bleeding in patients with renal failure. PURPOSE: A prolonged bleeding time is associated with platelet dysfunction and clinical bleeding in patients with renal failure. Parenteral estrogens have been shown to shorten the prolonged bleeding time in patients with chronic renal failure, although the mechanism of action is unknown. We conducted a study to evaluate the efficacy of oral conjugated estrogens in this setting. PATIENTS AND METHODS: Four patients with renal failure, prolonged bleeding time, and clinical bleeding were given 50 mg of conjugated estrogen (Premarin) daily. RESULTS: Bleeding time normalized in two cases and was reduced to less than 50% of the pretreatment value in one of the remaining two cases. Bleeding stopped in all patients within two days. Ten dialysis patients with prolonged bleeding time were randomized to a course of 50 mg of Premarin daily or placebo. The bleeding time in all five patients in the Premarin group normalized or decreased to below 50% of the pretreatment value after 7.0 +/- 4.2 days of therapy. The bleeding time did not normalize in the five patients treated with placebo. No side effects attributable to therapy were reported. CONCLUSION: We conclude that orally administered conjugated estrogens effectively improve the bleeding tendency in patients with chronic renal failure. 
1	1,25-Dihydroxyvitamin D3 receptor RNA: expression in hematopoietic cells. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] induces differentiation and inhibits proliferation of myeloid leukemic cells from various lines and patients; these effects are probably mediated through the 1,25(OH)2D3 receptor. Little is known of expression of 1,25(OH)2D3 receptor RNA in hematopoietic cells. We examined the expression and modulation of expression of 1,25(OH)2D3 receptor RNA in various proliferating and nonproliferating hematopoietic cells. Constitutive expression of 1,25(OH)2D3 receptor RNA was detected in various kinds of hematopoietic cells, including macrophages and activated T lymphocytes, as well as in cell lines KG-1 (myeloblasts), HL-60 (promyelocytes), ML-3 (myelomonoblasts), U937, THP-1 (monoblasts), K562 (erythroblasts), and S-LB1 (HTLV-1-transfected T lymphocytes). Receptor transcripts were 4.6 kilobases (kb), and no variant sizes were observed. All cell lines examined in this group also expressed 1,25(OH)2D3 receptors. Most B lymphocyte lines expressed negligible levels of 1,25(OH)2D3 receptor RNA and protein; however; analysis of a lymphoid/myeloid somatic hybrid suggested that suppression of expression of 1,25(OH)2D3 receptor RNA in B lymphocytes may be a dominant characteristic. HL-60 cells were cultured with 10(-7) mol/L 1,25(OH)2D3 for 24 to 72 hours, and levels of expression of 1,25(OH)2D3 receptor and its RNA were examined. Levels of RNA coding for the receptor were not modulated by exposure to high levels of ligand. Levels of occupied 1,25(OH)2D3 receptor protein increased in these HL-60 cells; but the total number of 1,25(OH)2D3 receptors decreased about 50% at 24 hours and returned toward normal at 72 hours. Steady-state levels of 1,25(OH)2D3 receptor RNA were not affected by terminal differentiation of HL-60 toward either granulocytes or macrophages. Nondividing macrophages from normal individuals also expressed 1,25(OH)2D3 receptor RNA. In contrast, nondividing peripheral blood lymphocytes from normal individuals did not express 1,25(OH)2D3 receptor RNA; with stimulation of proliferation of these cells, accumulation of 1,25(OH)2D3 receptor RNA increased markedly. Half-life (t1/2) of 1,25(OH)2D3 receptor RNA in T lymphocytes was short (1 hour) as determined by measuring decay of the message after addition of actinomycin D. Consistent with this short t1/2, accumulation of 1,25(OH)2D3 receptor RNA increased in cells as their protein synthesis was inhibited. Further studies are required to understand the physiologic role of 1,25(OH)2D3 receptors in myeloid cells and proliferating T lymphocytes. 
5	Sinus arrest induced by trivial nasal stimulation during alfentanil-nitrous oxide anaesthesia. A case is reported of bradycardia and sinus arrest induced by insertion of a nasal temperature probe. Other possible causes of bradycardia and sinus arrest under anaesthesia are reviewed briefly. Evidence for the neurological basis of a nasocardiac reflex, similar to the oculocardiac reflex, is presented. A minor, trivial stimulus may elicit this reflex. 
4	Intraoperative ultrasonic imaging of the ascending aorta in ischemic heart disease. In an attempt to locate any atherosclerotic lesion in the ascending aorta and to prevent embolization, intraoperative B-mode ultrasonography was performed in 100 patients with ischemic heart disease (31 women and 69 men). Ultrasonography was carried out with a 10-MHz probe placed directly on the ascending aorta. Ultrasonic imaging demonstrated an atherosclerotic lesion in the lower half of the aorta in 76 patients (76%), a lesion in the upper half of the aorta in 89 patients (89%), and a lesion at the orifice of the innominate artery in 99 patients (99%). Prospective palpation identified an atherosclerotic lesion in 12 (25%) of 48 patients. Thoracic computed tomography in 79 patients showed calcification in the lower half of the aorta in 6 patients (7.6%) and in the upper half of the aorta in 11 (13.9%). Palpation and thoracic computed tomography underestimated the frequency of atherosclerotic lesions. Intraoperative ultrasonography accurately identified atherosclerotic disease. This technique allows the surgeon to modify cannulation, aortic clamping, and operative technique to reduce the risk of perioperative stroke due to embolization of atherosclerotic debris from the ascending aorta. 
5	Bronchial asthma. Asthma is one of the most common respiratory problems in modern industrialized countries, affecting over 5% of the population. It affects all age groups from infants to senior citizens, and mortality rates from asthma appear to be increasing during the past few years in the United States as well as in other industrialized countries. Asthma tends to occur in families, associated with other allergic disease, and may be induced by a wide variety of environmental antigens, most commonly inhaled allergens such as pollen and dust. Bronchial challenge with a specific allergen results in an early bronchospastic response with a relatively brief duration, and in a significant number of patients there is a late response with onset after 3 to 4 hours, lasting hours to days. This late response is associated with a bronchial hypersensitivity reaction, which is demonstrable by nonspecific challenge testing in the laboratory. During the period of bronchial hyperresponsiveness patients are prone to develop attacks following exposure to a wide variety of "triggers," including cold air, fumes, or cigarette smoke. The current approach to management of patients with asthma emphasizes prevention, with avoidance of specific allergens when possible, and chronic use of anti-inflammatory agents including corticosteroids and cromolyn sodium. The goal is to decrease the bronchial hyperresponsiveness. Management of the acute asthma attack consists of bronchodilator therapy, primarily with inhaled beta-adrenergic agonists, and administration of oral or systemic corticosteroids if the attack is not rapidly relieved. Additional therapeutic agents including theophylline and anticholinergics may be useful in some situations. Response to therapy during the first couple of hours in the emergency room is the most important predictor of the course of the acute attack, and patients who have not responded significantly after 2 hours of maximum therapy are candidates for hospital admission or prolonged emergency room observation. The goal of acute therapy is to wean the patient from intravenous drugs and place him or her on rapidly tapering doses of oral prednisone while initiating a vigorous program of preventive therapy. Follow-up observation, both in the office and in the patient's home, is vital and involves extensive patient education and objective testing of peak airflow. In general, the course of asthma is relatively benign compared with other obstructive airway diseases; however, significant mortality exists, especially in older patients and those with late-onset asthma. 
4	Complete heart block and severe aortic incompetence in relapsing polychondritis: clinicopathologic findings. We describe a patient with relapsing polychondritis who developed fatal cardiac involvement comprising complete heart block, acute aortic incompetence, and cardiovascular collapse. Pathologic studies showed fibrosis of the cardiac conducting system and necrotizing inflammation of the aortic valve, features not previously described in relapsing polychondritis, as well as evidence of coronary artery vasculitis. 
3	Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study. The cosegregation of the O-demethylation of codeine to morphine with the sparteine oxidation polymorphism was confirmed. Hence morphine could not be detected in the plasma of any of the poor metabolizers, whereas detectable morphine plasma levels were found in 10 of 12 extensive metabolizers. Pain thresholds to laser stimuli were determined before drug intake and 90, 150, and 210 minutes after drug intake. Codeine significantly increased the pricking pain thresholds in the extensive metabolizers (p less than 0.05), whereas there were no significant changes in the poor metabolizers. No change in pain thresholds occurred with placebo in any of the two phenotypes. In the extensive metabolizers there was a significant positive correlation between the increase in pain threshold and plasma concentration of codeine. The study supports the hypothesis that morphine formation is essential for achievement of analgesia during codeine treatment. 
2	Metabolic and health complications of obesity. Overnutrition manifested by obesity has emerged as a major health problem in affluent countries. In spite of increased interest in fitness, obesity is on the increase in the United States. This is particularly so among children and adolescents. Although obesity is associated with many risk factors for diseases, the mechanisms whereby it enhances disease risk are not fully understood. Such an understanding is needed to develop strategies for management of these conditions. In this report we suggest that overnutrition produces clinical diseases only in individuals who already possess a metabolic weakness or "defect" in a given system. In the absence of such underlying defects, overnutrition, or obesity, is well tolerated. One of the most common consequences of obesity is dyslipidemia, that is, elevations of very low-density lipoprotein (VLDL) triglycerides and low-density lipoprotein (LDL) cholesterol and low concentrations of high-density lipoprotein (HDL) cholesterol. The major effect of overnutrition on lipoprotein metabolism is to stimulate the production of VLDL. For patients who have an underlying defect in lypolysis of VLDL triglycerides, hypertriglyceridemia will develop in the obese state. For those who have defective clearance of LDL, obesity will accentuate hypercholesterolemia. Both of these effects can be explained by overproduction of VLDL, due to obesity, combined with a genetic defect in clearance of VLDL or LDL. The mechanism whereby obesity causes a lowering of HDL cholesterol is uncertain, although it could enhance removal of HDL by an excess of adipose tissue. Another disease associated with obesity is cholesterol gallstones. The presence of obesity more than doubles the risk for gallstones. Two underlying factors increase the danger for gallstones: a deficiency of hepatic secretion of bile acids and a tendency for formation of cholesterol crystals in bile. Overnutrition promotes the synthesis of whole-body cholesterol, and the only route for excretion of this excess cholesterol is through the biliary tree.(ABSTRACT TRUNCATED AT 400 WORDS). 
4	Primary angioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99m isonitrile. Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion. Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy. Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction. Thirteen patients had anterior infarction. The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans. There was no correlation between the time to therapy and the reduction in defect size. Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size. Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence. The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS). Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials. 
5	Pontine supranuclear facial palsy. Two patients presented with a unilateral supranuclear facial palsy. Additional dysarthria was attributed to the pontine origin documented by magnetic resonance imaging on the contralateral side. The pontine disorder also was indicated by an isolated delay of the blink reflex R1 component or of the masseter reflex. We attribute the facial palsy to a lesion of a supranuclear fiber bundle supplying the facial nucleus. The location of the lesions favors these fibers taking a separate course from the main pyramidal tract at the mid- to upper pontine level. 
1	Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells. Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions. 
5	Pediatric blunt liver injury and coagulopathy managed with packs and a silo: case report. Packing the abdomen can be lifesaving when severe hepatic trauma is complicated by refractory hypothermia, coagulopathy, and continuing hemorrhage requiring large-volume transfusion. This report describes the successful use of abdominal packs and a modified silo in a child following blunt liver injury. 
5	Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. To clarify the course of adenomatous hyperplasia (AH) of the liver, 17 patients with 20 biopsy-proven AH nodules were followed clinically for 1-5 years. At the initial biopsy the mean nodular diameter was 10 (SD 4) mm and the relative cellularity [( mean cellularity of AH divided by mean parenchymal cellularity] x 100) 141 (27). The criteria for diagnosis of malignant transformation of AH were both a doubling of nodular volume and changes on imaging. Between 6 and 50 months after biopsy, 9 of the 18 nodules which could still be accurately identified met the criteria for transformation; histological proof of hepatocellular carcinoma (HCC) was obtained later for 7 of these 9 nodules. The product of diameter and cellularity (transformation index) was the strongest predictor of the time to transformation. 9 AH nodules did not undergo transformation--7 did not meet one or both criteria and 2 became undetectable by imaging. Because of the high risk of malignant transformation, it can be concluded that AH is an absolute precursor of HCC. It should therefore be treated as a potential malignant disorder. 
5	Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain. Fourty-four unselected patients with noncardiac chest pain were studied using conventional manometry with additional edrophonium provocation and 24-hour ambulatory esophageal pH and pressure recording with a system developed by our group. New, fully automated techniques of statistical analysis of the complete set of esophageal pressure and pH signals were used to examine the temporal relation between pain, esophageal motility disturbances, and gastroesophageal reflux. The analysis used the 97.5th percentile of amplitude and duration of all esophageal contractions in each patient as well as a chi 2 test of the distribution of contraction types to determine whether a pain episode was related to abnormal motility or not. The edrophonium test results were positive in 2 patients. Only 25 patients (56.8%) had at least one pain episode (total, 111 episodes) during 24-hour recording. Thirty-three percent of the pain episodes were related to reflux and 23.4% to abnormal motility, and 43.2% were not related to an esophageal function disturbance. In the patient-oriented analysis in this study, it was required for a positive correlation that the symptom index (percentage of related pain episodes) was higher than 75%. It was found that the pain was related to reflux in 2 patients (4.6%), to reflux and motor abnormalities in 4 (9.2%), and to motor abnormalities in 2 patients (4.6%). In 36 patients (81.8%), no relation with an esophageal abnormality could be established, either because the patients had no pain during the 24-hour study, or because the pain seemed unrelated to reflux or abnormal motility. 
5	Papular-purpuric "gloves and socks" syndrome. We report five cases of an acute, self-limiting dermatosis that has not been previously described. It consists of a pruritic edema and erythema of the hands and feet in a gloves-and-socks distribution and is associated with oral lesions and fever. The clinical course is characterized by the rapid development of petechial purpura and clearing of lesions within 1 to 2 weeks. The disease appears to affect only young and otherwise healthy persons and occurs mostly during the spring. The etiology is unknown but might be of infectious origin. 
1	Complications of general anesthesia for Nd:YAG laser resection of endobronchial tumors. We studied the incidence and mechanisms of cardiovascular complications and postoperative respiratory insufficiency associated with GA and Nd:YAG laser endobronchial tumor resection. The records of 73 patients undergoing 87 procedures were reviewed. Preoperative status, anesthetic methods and perioperative complications were analyzed by multiple regression to determine predictors of outcome. Twenty-three percent of patients had greater than 90 percent mainstem bronchus obstruction. Longer serum elimination half-life of relaxant drug was significantly correlated with longer duration of mechanical ventilation after neuromuscular blockade reversal. Cardiovascular complications were noted in 24 procedures and often required therapeutic intervention. Variables predicting cardiovascular complications included longer duration of GA and increasing age. Perioperative respiratory and cardiovascular complications are common after GA for Nd: YAG laser resection. Short-acting neuromuscular relaxants, careful assessment prior to postoperative extubation, limiting duration of GA and cardiovascular monitoring are recommended when implementing GA for Nd: YAG laser resection of endobronchial tumors. 
3	Brain retractor edema during induced hypotension: the effect of the rate of return of blood pressure. This study evaluated the hypothesis that the postoperative formation of cerebral edema may be influenced by the rate of blood pressure return after induced hypotension in a graded brain retractor injury. Nineteen cats underwent unilateral craniotomy, isoflurane-induced hypotension to a mean of 50 mm Hg, and application of a brain retractor at 20 mm Hg of pressure for 1 hour. Blood pressure was returned to normal either within 3 minutes or over 20 minutes. The degree of cerebral edema formation was determined by Evans blue dye and coronal magnetic resonance imaging. All animals showed extravasation of Evans blue dye in the retracted hemisphere that was most marked at the periphery of the retractor. T1 relaxation times were significantly prolonged in the retracted hemispheres of both the fast return and slow return groups (18.8% and 17.8%, respectively) and more so at the Evans blue sites (42.8% and 40.8%), although not so strikingly beneath the retractor itself (6.3% and 7.8%). T2 relaxation times were similarly prolonged but to approximately half the degree of the T1 times. In the nonretracted hemisphere, drug-induced hypotension alone did not result in significant acute cerebral edema or blood-brain barrier alteration. There was no significant difference between the fast and slow groups in Evans blue extravasation or magnetic resonance changes. Thus, in a retractor-induced brain injury, restoration of arterial pressure to normal either gradually or rapidly did not influence the degree or extent of edema formation. 
4	Roles of renal and vascular renin in spontaneous hypertension and switching of the mechanism upon nephrectomy. Lack of hypotensive effects of inhibition of renin, converting enzyme, and angiotensin II receptor blocker after bilateral nephrectomy. Inhibitors of angiotensin converting enzyme, renin, and the angiotensin II (Ang II) receptor lower the blood pressure of spontaneously hypertensive rats (SHR) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of renin in SHR, antirenin antibodies, the converting enzyme inhibitors delapril, enalapril, and the Ang II receptor antagonist DuP 753 were administered to intact and bilaterally nephrectomized SHR and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of renal origin is a dominant factor. Gradual but complete disappearance of antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin converting enzyme in the maintenance of the spontaneous hypertension. 
2	Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome. In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency. 
5	Widespread inflammatory response to osteoblastoma: the flare phenomenon. A case of vertebral osteoblastoma caused a diffuse, reactive inflammatory infiltrate in two vertebrae, adjacent ribs, and the paraspinous soft tissues. The authors call this the flare phenomenon. On magnetic resonance images the diffuse inflammatory response caused a misleading appearance that simulated a malignant process (lymphoma or Ewing sarcoma). A computed tomographic myelogram was diagnostic. 
5	The empiric use of naloxone in patients with altered mental status: a reappraisal. STUDY OBJECTIVE: To determine whether clinical criteria (respirations of 12 or less, mitotic pupils, and circumstantial evidence of opiate abuse) could predict response to naloxone in patients with acute alteration of mental status (AMS) and to evaluate whether such criteria predict a final diagnosis of presence or absence of opiate overdose as accurately as response to naloxone. CASES AND SETTING: Seven hundred thirty patients with AMS who received naloxone for diagnostic or therapeutic purposes at the discretion of two large, urban, paramedic base teaching hospitals. METHODS: We reviewed paramedic run sheets and audiotapes on all 730 patients as well as available hospital records of all patients who demonstrated any response to naloxone to determine whether overdose was responsible for their clinical presentations. We also reviewed hospital records for a selected sample of naloxone nonresponders. MAIN RESULTS AND CONCLUSION: Only 25 patients (3.4%) demonstrated a complete response to naloxone, whereas 32 (4.4%) manifested a partial or equivocal response. Nineteen of 25 complete responders (76%), two of 26 partial responders (8%) (with known final diagnosis), and four of 195 non-responders (2%) (with known final diagnosis) were ultimately diagnosed as having overdosed. Respirations of 12 or less or the presence of any one of the three clinical findings as a group were each highly sensitive in predicting response to naloxone, and at least as sensitive as response to naloxone in predicting a diagnosis of opiate overdose. Selective administration of naloxone for AMS would have decreased the use of this drug by 75% to 90% while still administering it to virtually all naloxone responders who had a final diagnosis of opiate overdose. 
2	Quantification of hepatobiliary function as an integral part of imaging with technetium-99m-mebrofenin in health and disease. A study was undertaken to check the feasibility of measuring the hepatic extraction fraction (HEF) and excretion T-1/2 values as an integral part of hepatobiliary imaging with technetium-99m-mebrofenin in health and disease. In 18 controls subjects, the HEF was 100% and the T-1/2 excretion mean +/- s.e. value was 15.23 +/- 1.4 min. The mean appearance times of the common bile duct (CBD), gallbladder (GB), and small intestine were 15.8 +/- 1.52, 20.2 +/- 2.7, and 23.8 +/- 3.08 min, respectively. Rising serum bilirubin in patients decreased HEF and increased T-1/2 excretion value resulting in delayed appearance of CBD, GB, and small intestine. In control subjects and patients with bilirubin less than 5 mg%, T-1/2 excretion values at 30, 40, and 50 min were similar to those values calculated using the entire 60 min of data, suggesting that the hepatic phase study time could be reduced to 30-40 min and still use the normal reference values established for 60 min. In patients with bilirubin greater than 5 mg%, the data collection duration should be continued for 60 min. 
4	Studies of myocardial protection in the immature heart. IV. Improved tolerance of immature myocardium to hypoxia and ischemia by intravenous metabolic support. Thirteen immature puppies (2 to 4 kg) underwent 1 hour of acute hypoxia (oxygen tension 25 to 30 mm Hg), followed by 45 minutes of normothermic global ischemia on total vented bypass with normal blood reperfusion. Ventricular function was assessed by inscribing Starling function curves and measuring stroke work indices before hypoxia and after reperfusion. Seven puppies (control) received normal saline infusion at 4 ml/kg/hr. Six other puppies received a 4 ml/kg/hr intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, mercaptopropionyl glycine, carnitine, and catalase during hypoxia and reperfusion. In control hearts, acute hypoxia depleted myocardial glutamate and aspartate by 52% (p less than 0.05 versus prehypoxia) and 48% (p less than 0.05 versus prehypoxia) and caused severe hemodynamic deterioration (55% decrease of stroke work index) (p less than 0.05 versus prehypoxia); three of seven (43%) required premature institution of bypass. Postischemic left ventricular function recovered to only 40% of control levels (p less than 0.05 versus prehypoxia). In contrast, intravenous metabolic infusions maintained tissue glutamate (p less than 0.05 versus control group) and aspartate (p less than 0.05 versus control group) in treated hearts during hypoxia and allowed cardiac index to rise 20% (p less than 0.05 versus prehypoxia); all treated hearts tolerated 1 hour of hypoxia, and stroke work recovered 70% (p less than 0.05 versus control group) of stroke work index after subsequent ischemia. Impaired tolerance of immature hearts to acute hypoxia and subsequent ischemia is due to substrate depletion. This impairment can be reduced by intravenous metabolic support during hypoxia and reperfusion and leads to improved recovery of postischemic function. 
5	An unusual complication of cardiac transplantation--infected aortic pseudoaneurysm. Infections after cardiac transplantation are a frequent cause of early morbidity and mortality. An unusual site for such a complication is at the aortic anastomotic suture line. We report a case of an infected aortic pseudoaneurysm, seen as recurrent septicemia, during the first 6 months after cardiac transplantation. 
5	Extramedullary hematopoiesis involving the esophagus in myelofibrosis. In this report, we describe a case of myelofibrosis with myeloid metaplasia; a 53-yr-old man was splenectomized for a massively enlarged spleen in which multiple foci of myeloid metaplasia were histologically demonstrated. The patient was referred to us for endoscopic examination, following the repeated occurrence of melena. Upper gastrointestinal endoscopy revealed two active ulcerative lesions in the bulb, and only a moderate erythema in the lower third of the esophagus, which showed no varices. There was no endoscopic evidence of active or recent bleeding. Subsequent histologic examination of biopsies taken from the esophageal lesion surprisingly revealed the presence of hematopoietic tissue. 
1	Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications. Of 310 patients with port-wine stains, 68% had more than one dermatome involved; 85% had unilateral and 15% had a bilateral distribution of their port-wine stain. At the time of examination, 8% of all patients with trigeminal port-wine stains had evidence of eye and/or central nervous system (CNS) involvement. Extensive involvement, with port-wine stain over the trunk and extremities as well as the head and neck, was observed in 12%. Patients who did not have port-wine stains on the areas served by branches V1 and V2 of the trigeminal nerve had no signs or symptoms of eye and/or CNS involvement. Port-wine stains of the eyelids, bilateral distribution of the birthmark, and unilateral port-wine stains involving all three branches of the trigeminal nerve were associated with a significantly higher likelihood of having eye and/or CNS complications. Twenty-four percent of those with bilateral trigeminal nerve port-wine stains had eye and/or CNS involvement compared with 6% of those with unilateral lesions. All those who had eye and/or CNS complications had port-wine stain involvement of the eyelids; in 91% both upper and lower eyelids were involved, whereas in 9% only the lower eyelid was involved. None of those with upper eyelid port-wine stains alone had eye and/or CNS complications. In addition, 3 (75%) of the 4 subjects with seizures alone had bilateral port-wine stain involvement. A third group, these with unilateral V1, V2, and V3 port-wine stains, had eye and/or CNS complications in 3 (19%) of 16 subjects. 
5	Effects of pill-giving on maintenance of placebo response in patients with chronic mild depression Fifty outpatients with mild, chronic, mood-reactive depression whose mood improved markedly after a 10-day single-blind placebo trial were randomly assigned in a double-blind design either to have their placebo medication discontinued or to have it maintained for an additional 6 weeks. Half of the patients in each condition relapsed within 6 weeks, indicating that pill-taking itself does not influence maintenance of placebo response. Placebo response was more likely to be maintained in patients who were currently married. At the end of 3 months, the overall relapse rate was 58%. The authors raise questions about the utility of the initial 10-day placebo washout in antidepressant clinical trials, and they discuss limits on the generalizability of their findings. 
4	Takayasu's disease with axillary, right coronary artery, and right internal mammary stenosis treated with angioplasty. A 47-year-old woman presented with progressive angina and failed medical therapy. After an unsuccessful attempt at angioplasty of a totally occluded right coronary artery, coronary artery bypass using the right internal mammary artery was performed. She presented 2 years later with stenosis in the mammary graft, right coronary artery, and axillary artery. These lesions were all treated with angioplasty. 
4	Opioids in cerebrospinal fluid in hypotensive newborn pigs. This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. Closed cranial windows were used to determine pial arteriolar diameter. Periarachnoid cortical and cisterna magna CSF was collected from piglets during normotension and hypotension (systemic arterial pressure decreased from 63 +/- 1 to 33 +/- 1 mm Hg). Opioid profiles were assessed qualitatively by radioreceptor assay, and individual opioids were measured quantitatively by radioimmunoassay. Periarachnoid cortical and cisterna magna CSF methionine enkephalin-, leucine enkephalin-, dynorphin-, and beta-endorphin-like receptor active values all were increased by hypotension. When quantified by radioimmunoassay, periarachnoid cortical CSF values for methionine enkephalin-like immunoreactivity were 1,167 +/- 58 and 2,975 +/- 139 pg/ml for normotension and hypotension, respectively. Periarachnoid cortical CSF radioimmunoassay values for dynorphin-like immunoreactivity were 15 +/- 2 and 28 +/- 2 pg/ml for normotension and hypotension, respectively. When applied topically to the cortical surface, synthetic methionine enkephalin increased pial arteriolar diameter (134 +/- 4, 158 +/- 4, and 163 +/- 4 microns for control, 574 pg/ml [10(-10) M], and 5,740 pg/ml [10(-9) M], respectively). Similarly, topical synthetic leucine enkephalin and dynorphin elicited pial arteriolar dilation. However, beta-endorphin produced arteriolar constriction. Hypotension attenuated methionine and leucine enkephalin-induced dilation and reversed dynorphin-induced dilation to concentration-dependent constriction. beta-Endorphin-induced constriction was not changed by hypotension. Therefore, opioids could contribute to the control of the cerebral circulation during hypotension. 
4	Responses of cytosolic free calcium to ADP in platelets of spontaneously hypertensive rats. Abnormalities of Ca2+ handling have been reported in patients with essential hypertension and in spontaneously hypertensive rats (SHR). In this study, responses of cytosolic Ca2+ to ADP in platelets of SHR were examined. Four- and seven-week-old male SHR and age- and sex-matched Wistar-Kyoto rats (WKY) were used. Basal levels of the intracellular Ca2+ concentration in platelets and responses to ADP were estimated using fluorescent indicator fura-2 in the medium containing 1 mmol/L CaCl2 and Ca2(+)-free buffer with 1 mmol/L EGTA. Basal levels of platelet cytosolic Ca2+ of SHR were significantly higher than those of WKY at 4 and 7 weeks of age in the presence of external Ca2+. However, no significant difference was observed in basal levels of platelet cytosolic Ca2+ in the Ca2(+)-free EGTA-containing buffer between SHR and WKY. The peak cytosolic Ca2+ concentration evoked by ADP was significantly diminished in SHR compared with WKY in the absence of external Ca2+, whereas the responses of platelet cytosolic Ca2+ to ADP were similar in SHR and WKY in the presence of external Ca2+. These results suggest that release from intracellular Ca2+ store is reduced in SHR and that the regulation of cytosolic Ca2+ in SHR is more dependent on extracellular Ca2+ compared with WKY. 
2	Pelvic floor descent in women: dynamic evaluation with fast MR imaging and cinematic display. The authors present a new method for assessing pelvic prolapse with dynamic fast magnetic resonance (MR) imaging. Twenty-six women with signs and symptoms suggesting pelvic prolapse and 16 control subjects were studied with a series of fast (6-12-second) MR images. Sagittal and coronal images were obtained with graded increase in voluntary pelvic strain, allowing for dynamic display and quantification of the pelvic prolapse process. The distance from the pubococcygeal line was used as an internal reference for measurement of descent in the maximal strain position. With use of control results for normal limit values, prolapse involving the anterior pelvic compartment (cystocele), the middle compartment (vaginal prolapse, uterine prolapse, and enterocele), and the posterior compartment (rectocele) was easily demonstrated. Significant differences between control subjects and patients with prolapse were seen at maximal strain but not in the relaxed state. Quantification of the pelvic descent process with use of fast MR imaging may be of value in surgical planning and postsurgical follow-up. 
4	End-stage renal disease--is infrainguinal limb revascularization justified? Reports of reconstructive surgery for peripheral vascular disease have been relatively uncommon in patients with end-stage renal disease. Between 1980 and 1989, 39 patients with end-stage renal disease underwent revascularization of 56 limbs. Fifty-two primary infrainguinal and four secondary infrainguinal bypass grafts were performed. In addition, nine thrombectomies were performed. At the time of surgery 37 patients were on dialysis; three had functioning kidney transplants. The indications for revascularization were gangrene, rest pain, or ulceration in all except three limbs with disabling claudication. Reversed, nonreversed, or in situ vein was used in 25 of the 52 primary infrainguinal revascularizations performed. Polytetrafluoroethylene was used in 25. Two procedures used a combination of polytetrafluoroethylene and vein. The primary patencies for all infrainguinal procedures at 1 and 2 years were 77% and 68%, respectively. Four perioperative deaths occurred in the infrainguinal group (7.7%). An additional death occurred after thrombectomy for late graft closure. Three deaths were a result of myocardial infarction. One patient on peritoneal dialysis developed uncontrolled sepsis. At 3 years 39% of patients were alive, and 84% of the limbs were salvaged. Among the cases studied no group was identified that represented unacceptable operative risk. Results compared well with reported patencies for patients subjected to infrainguinal revascularization procedures. Limb revascularization in patients with end-stage renal disease may be performed by use of similar criteria to those used for other patients with peripheral vascular disease. 
5	Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival. From 1976 to 1989, 21 adult patients with previously untreated acute promyelocytic leukemia were seen at the University of Virginia Hospital. We reviewed their cases retrospectively to determine the impact of hemorrhagic complications and other factors on treatment outcome. We observed a complete remission rate of 35%; the median survival in complete responders was 15 months. Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis. Fatal intracranial hemorrhage was the leading cause of death, occurring in eight (40%) of the 20 patients evaluated. Initial leukocyte count greater than 4.0 x 10(9)/L and platelet count less than 20 x 10(9)/L were significantly associated with an increased risk of intracranial hemorrhage. In patients with disseminated intravascular coagulation, the rate of intracranial hemorrhage was reduced by treatment with heparin. The high mortality of 40% (8/20) due to intracranial hemorrhage during induction was a major contributor to the low complete remission rate of 35% (7/20) in this series of consecutive unselected patients with newly diagnosed acute promyelocytic leukemia. 
1	Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation. 
3	Syphilitic meningomyelitis. A 28-year-old nonimmunocompromised man developed secondary syphilis confirmed by serum and CSF findings. His course was complicated by chorioretinitis, extensive skin lesions, and spastic paraparesis secondary to syphilitic meningomyelitis. MRI of the spinal cord was strikingly abnormal. 
3	Tonic contraversive ocular tilt reaction due to unilateral meso-diencephalic lesion. We studied 4 patients with tonic contraversive ocular tilt reactions due to unilateral, paramedian, mesodiencephalic lesions. This is in contrast to the only 2 previously reported patients with ocular tilt reactions due to unilateral mesodiencephalic lesions, each of whom had a paroxysmal ipsiversive ocular tilt reaction. This new finding is considered in the context of previous clinical and experimental data on the various types of ocular tilt reactions that follow stimulation or destruction of the peripheral and central vestibular system. Otolithic inputs to the interstitial nucleus of Cajal from the contralateral vestibular nucleus and motor outputs from the interstitial nucleus of Cajal to cervical and ocular motoneurons could be involved in the ocular tilt reaction. We propose that in patients with unilateral meso-diencephalic lesions, a tonic contraversive ocular tilt reaction could be due to persistently decreased resting activity of ipsilateral interstitial nucleus neurons, whereas a paroxysmal ipsiversive ocular tilt reaction could be due to transiently increased activity of the same interstitial nucleus neurons. Cases of ocular tilt reaction due to unilateral meso-diencephalic lesion point to the existence of a crossed graviceptive pathway between the vestibular nucleus and the contralateral interstitial nucleus of Cajal. 
4	Effects of calcium on vascular smooth muscle tone. It is generally acknowledged that calcium plays a major role in the generation of vascular tone. However, in recent years it has become increasingly evident that relatively calcium-insensitive pathways of excitation-contraction coupling also exist in the vascular smooth muscle cell. Possible mechanisms of vascular smooth muscle contraction and their possible role in the pathophysiology of hypertension are reviewed. The rationale for the use of calcium channel blockers in the treatment of hypertension is discussed. 
1	Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor-cell vaccines modified with live but avirulent Newcastle disease virus [published erratum appears in Cancer 1991 Apr 15;67(8):2124] Sixteen patients with colorectal carcinoma Dukes' Stage B2, C, or D were treated with an autologous virus-modified tumor-cell vaccine after potential curative tumor resection (R0-Resection). An inoculum of 1 X 10(7) cells incubated with 32 hemagglutination units of nonirradiated Newcastle disease virus (NDV) was given intracutaneously up to four times at 10-day intervals. The delayed-type hypersensitivity (DTH) skin reaction was measured. The vaccination was well tolerated. In 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. A challenge test using autologous tumor cells without NDV after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients. The DTH response was not due to bacterial contamination or sensibility to the virus. Histologic examination of the vaccination site showed a dense infiltration of predominantly helper T-lymphocytes. We conclude that in most of the patients treated active, specific immunization led to a specific antitumor sensitivity. 
5	Refeeding of infants with acute diarrheal disease. The purpose of this study was to determine which infant formula among five would be the most efficacious for the refeeding of infants during an acute episode of diarrhea. Fifty male infants less than 12 months of age with severe diarrhea and at least 5% dehydration were admitted to a metabolic unit and studied in a prospective, single-blind protocol. Ten infants randomly received one of five types of formula: two-thirds diluted cow milk, cow milk formula (Nanon, Nestle, Inc., Sao Paulo, Brazil), Portagen, Pregestimil, or Prosobee (Mead Johnson & Co. Division, Evansville, Ind.). They continued to receive the same formula for 72 hours unless dehydration occurred. There were no associated infections, and they received no prior antibiotic treatment. Oral hydration together with intravenous fluid therapy was given to all patients during the initial treatment. During the first 72 hours of refeeding, patients fed Portagen excreted the least amount of stool and required reduced quantities of intravenous fluids or oral hydration. In contrast, patients fed diluted cow milk or any other formula had more severe diarrhea. Nine of the 10 patients fed Portagen completed the 72-hour treatment, whereas only 2 of 10 fed diluted cow milk tolerated it. Similarly, the cumulative proportions for high purging rate, dehydration, carbohydrate intolerance, and vomiting were more favorable for Portagen and least acceptable for diluted cow milk. No differences were found among the remaining three formulas tested. These data show that diluted cow milk is poorly tolerated by infants with severe diarrhea, whereas Portagen is more effective. 
5	The use of the Cytobrush cervical sampler in patients with cervical stenosis. In 37 of 43 patients (86%) with cervical stenosis (inability to undergo passage of the cotton-tipped applicator), the Cytobrush cervical sampler was successfully passed into the endocervical canal. The use of the Cytobrush sampler for cervical cytologic screening appears to be valuable in patients with cervical stenosis. 
5	Combined computed tomography and dacryocystography for complex lacrimal problems. Two imaging modalities, computed tomography (CT) and dacryocystography (DCG), were combined to demonstrate the relationships between the lacrimal system and the surrounding soft-tissue structures. In selected cases, such as those involving severe facial trauma, midfacial tumours, significant sinus disease, or previous lacrimal, nasal or sinus surgery, this imaging technique may be useful in better evaluating the anatomy of the lacrimal system and planning a surgical approach. 
5	Postoperative complications after Molteno implant surgery. We performed Molteno implant surgery in one eye each of 41 patients with uncontrolled glaucoma. Intraocular pressure was controlled (intraocular pressure less than or equal to 18 mm Hg) in 32 eyes (78%). The mean preoperative intraocular pressure was 40 +/- 13.2 mm Hg, whereas the mean postoperative intraocular pressure was 16 +/- 6.6 mm Hg. Patients were followed up for an average of 16 months after the operation. Visual acuity was unchanged in 23 eyes (56%), improved in nine eyes (22%), and poorer in nine eyes (22%). The major complications included shallow anterior chamber and hypotony in six eyes (14.6%), vitreous hemorrhage in two eyes (4.9%), retinal detachment in one eye (2.4%), and malignant glaucoma in two eyes (4.9%). Less grave complications included hyphema in four eyes (9.8%), peripheral choroidal effusion in 15 eyes (36.6%), obstruction of the tube in six eyes (14.6%), recession of the tube into the angle in two eyes (4.9%), erosion of the tube in one eye (2.4%), and Tenon's cyst formation in three eyes (7.3%). 
5	Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a correlative clinical-histomorphometric study. We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface. Parametric and nonparametric statistical analyses performed on a pooled sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and correlated positively with osteoid parameters and the mineralization lag time. Serum alkaline phosphatase showed similar relationships. These results as well as the clinical, biochemical, and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D reflects the degree of the primary renal phosphate leak, but is not involved in the pathogenesis of the bone disease. 
4	Arteriovenous malformation of the tongue. Polyvinyl alcohol particles used to embolize an arteriovenous malformation of the tongue were only temporarily successful. Additional embolization therapy was necessary and was complicated by ischemic ulcers of the tongue. We conclude that embolization therapy can be used, but the efficacy of this therapy in the longer term remains to be determined. 
5	Different patterns of gene expression in ras-resistant and ras-sensitive cells. We have shown previously that nontumorigenic NIH 3T3 cells can be made tumorigenic and metastatic by transfection and expression of activated ras, whereas in LTA cells, which are tumorigenic but nonmetastatic, the degree of malignancy is not altered by ras. To investigate possible mechanisms of natural ras resistance, we compared the expression patterns of several genes thought to be involved in ras-induced metastatic progression in LTA (ras-resistant) and NIH 3T3 (ras-sensitive) cells, before and after constitutive expression of transfected T24-H-ras. We examined the expression of the nuclear "early-response" genes jun and fos and the "tumor-suppressor" retinoblastoma (Rb) gene, as well as genes involved in invasion (major excreted protein [MEP], tissue inhibitor of metalloproteinases [TIMP]), and cell adhesion (secreted phosphoprotein 1 [SPP1; also known as osteopontin]). We found distinct differences in both the basal and ras-induced levels of expression of most of these genes in LTA versus NIH 3T3 cells. High levels of MEP and low levels of TIMP were induced in ras-transfected NIH 3T3 cells, whereas LTA cells showed intermediate levels of MEP and high levels of TIMP that were only marginally affected by the expression of transfected ras. Similarly, SPP1 expression was strongly induced by ras in NIH 3T3 cells but was repressed by ras in LTA cells. Enzymogram assays for functional gelatinase activity showed an increase in 67-kd and 62-kd bands in NIH 3T3 cells in the presence of ras. LTA cells showed no gelatinolytic activity in the presence or absence of ras. Data from an in vitro assay for chemoinvasiveness showed a pattern as predicted from the expression of invasion-related genes; chemoinvasiveness in ras-transfected NIH 3T3 was greater than in LTA and ras-transfected LTA cells, which was greater than in NIH 3T3 cells. Differences in expression of the genes examined are believed to contribute to the ras responsiveness of NIH 3T3 cells and the ras resistance of LTA cells. 
3	Anisocoria in unilateral ophthalmic disease. Pupillary diameters in the affected and unaffected eyes of 327 patients with uniocular red eye were assessed during fixation of a distant target. The mean pupillary diameters were similar in the unaffected eyes in each of eight diagnostic groups, but were significantly different (F = 3.84, p less than 0.001) in the diseased eyes. With corneal abrasions (p less than 0.001), marginal keratitis (p less than 0.05), and acute anterior uveitis (p less than 0.001) the mean pupillary diameter for the affected eye was significantly smaller than that of the unaffected eye. The observed differences of pupillary diameter probably reflect the role of neuronal and autocoid mechanisms in the unilateral control of pupillary size. 
5	Rectal bleeding. Patient delay in presentation. Patient delay in presentation of rectal bleeding has been identified as a factor in delayed diagnosis among patients with colorectal cancer. The aim of this study was to identify demographic or psychological factors, or beliefs or behaviors related to delay in presentation of rectal bleeding. In 93 patients presenting with this symptom to their general practitioner, delay ranged from 0 to 249 days with a median of 7 days; 27 (29 percent) delayed more than 14 days. Delay was unrelated to age, sex, ethnic origin, competence in English, length of schooling, social status, availability of social support, measured psychologic traits, and to the belief that the cause might be cancer. The proportions delaying more than 14 days were statistically significantly elevated among those who were not worried by the bleeding (47 percent delayed); those who did not regularly look at their feces or the toilet paper after use (37 percent); and those who took some other action before presenting to their general practitioner (43 percent). 
5	Slowly progressive aphasia: three cases with language, memory, CT and PET data. Three cases of slowly progressive speech and language disturbance were studied at various points post onset (three, five and 15 years respectively). Language, neuropsychological and brain imaging (computer tomography and positron emission tomography) evaluations were completed on all three patients. The data suggest that the syndrome of "progressive aphasia": 1) does not involve a uniform symptom complex; 2) does not necessarily develop into a full blown dementia syndrome; 3) varies greatly in rate of progression from case to case; 4) is associated with normal brain structure (on computer tomography); and 5) is associated with abnormal left temporal lobe metabolism as measured by fluorodeoxyglucose (FDG) positron emission tomography (PET). One patient had histological findings consistent with Alzheimer's disease at necropsy. 
5	Genotypic analyses of Richter's syndrome. The authors report the immunogenotype of two cases of Richter's syndrome. The immunoglobulin gene rearrangement pattern obtained on Southern Blot analysis was found in both cases to be the same in leukemic blood cells and in the tissue involved by the lymphoma. The beta chain and gamma chain T-cell receptor gene rearrangement pattern exhibited a germ-line configuration in the peripheral blood cells and in the lymph node in Case 2, whereas in Case 1 the lymph node had a gene rearrangement in the beta chain, as well as in the gamma chain T-cell receptor, and the leukemic cells from bone marrow were found to be in a germ-line configuration for T-cell receptors (beta and gamma chains). 
1	Human liver regeneration after major hepatectomy. A study of liver volume by computed tomography. Regeneration of the remnant liver after major hepatectomy in humans was studied by computed axial tomography (CT) in 12 noncirrhotic and five cirrhotic patients. Liver volumes were measured by abdominal CT 3 days, 10 days, 3 months, 6 months, 1 year, and 1.5 years after resection. Of the 17 patients, liver remnant volume was increased in 21.2% +/- 6.7% and 30.6% +/- 12.7% at 3 months and 6 months after resection, respectively. Noncirrhotic livers were 28.4% +/- 9.5% and 48.4% +/- 17.8% larger at 3 and 6 months. For cirrhotic livers, the increase was 8.5% +/- 3.6% and 12.9% +/- 4.5%. In five patients with right hepatectomy (65% resection), the liver remnant volumes were increased 38.4% +/- 11.7%, 48.0% +/- 16.2% and 95.1% +/- 4.5% at 3 months, 6 months, and 1 year after resection, respectively. In seven patients with right partial hepatectomy (30% to 35% resection), the percentages were 7.4% +/- 3.2%, 21.8% +/- 8.4%, and 63.9% +/- 18.3% and in five patients with left lateral segmentectomy (15% resection), they were 15.6% +/- 8.2%, 27.8% +/- 12.2%, and 33.0% +/- 14.5% 3 months, 6 months, and 1 year after resections, respectively. Noncirrhotic livers showed better regeneration than cirrhotic livers. Complete regeneration took about 1 year. The noncirrhotic liver that underwent right lobectomy also needed 1 year to double its postresection volume. 
4	Apical hypertrophic cardiomyopathy in a non-Oriental man. Japanese investigators first described apical HCM in 2.9% of patients who had diagnostic left ventricular catheterization for suspected ischemic heart disease or cardiomyopathy. This entity was initially thought to be limited to individuals of Asian origin and has been uncommonly described in patients of Western origin. Patients of Western origin differ in several ways from those in the original description of Yamaguchi et al, but they both share the same classic criterion of hypertrophy of the left ventricular apex. The major differences probably relate to the anatomic variation in the distribution of the left ventricular hypertrophy as described by Maron et al. It is not known whether racial, genetic, or environmental factors account for the variation of disease expression in Asian and Western patients. Our case illustrates that this diagnosis should be considered in patients who have chest pain (anginal or atypical) and markedly abnormal findings on electrocardiograms in the absence of hypertension or significant coronary artery disease. 
2	Sudden death due to delayed rupture of hepatic subcapsular hematoma following blunt abdominal trauma. Blunt abdominal trauma can cause sudden, unexpected death due to injuries to internal organs. Rupture of a hepatic subcapsular hematoma is a relatively rare cause of sudden death following minor blunt abdominal trauma. Death may be delayed several days to weeks. The autopsy is an invaluable diagnostic tool that can be utilized to uncover sudden deaths due to abdominal trauma. The case of an alcoholic who died of a ruptured hepatic subcapsular hematoma is presented. The death investigation revealed that the victim had sustained blunt abdominal trauma during a fall a few days prior to death. 
4	The automatic implantable cardioverter-defibrillator in young patients. An international survey identified 40 patients less than 20 years old who underwent surgical implantation of an automatic implantable cardioverter-defibrillator (AICD). There was a history of aborted sudden cardiac death or sustained ventricular tachycardia in 92.5% of these patients. Twenty-two patients (55%) had structural heart disease; dilated and hypertrophic cardiomyopathy were the most common diagnoses. Eighteen patients (45%) had primary electrical abnormalities including seven with the congenital long QT syndrome. There were no perioperative deaths associated with device implantation. Concomitant drug therapy was administered to 75% of the patients. Defibrillator discharge occurred in 70% of the patients, with 17 patients (42.5%) receiving at least one appropriate shock. There were two sudden and two nonsudden deaths at 28.2 months' median follow-up. Sudden death-free survival rates by life table analysis at 12 and 33 months were 0.94 and 0.88, respectively. Total survival rates at 12 and 33 months were 0.94 and 0.82, respectively. The AICD represents an effective treatment approach for young patients with life-threatening ventricular tachyarrhythmias. 
4	Mental activity, adrenergic modulation, and cardiac arrhythmias in patients with heart disease. All of the electrophysiological mechanisms of arrhythmias are sensitive to the influences of the autonomic nervous system, particularly to its adrenergic limb. Arrhythmogenic areas may also be dependent on the inhomogeneity of these influences because of their pathophysiological structure and/or the neurogenic or humoral nature of the vector of modulation. The complexity of the various possible scenarios, combined with the role of the rate dependence, explains why standardized protocols exploring the autonomic nervous system in clinical arrhythmias are difficult to define. Invasive electrophysiology is not adapted to address the problem. Isoprenaline infusion only reproduces the humoral adrenergic stimulation to which only a few types of arrhythmias are sensitive. The exercise test is a very complex investigation if the multiple parameters involved are considered. Only a part of its limitations are obviated by the mental stress. Under natural conditions, the neurogenic origin, the intensity of the sympathetic stimulation, and its suddenness are all critical factors responsible for severe tachyarrhythmias. Arrhythmias of the long QT syndrome are particularly demonstrative of the importance of the autonomic nervous system, but this evidence can also be documented in more trivial circumstances of diseased or apparently undiseased hearts. Exploring the autonomic nervous system behavior through heart rate variability in ambulatory recordings is the most recent and fruitful method of investigation. This nonprovocative approach has technical obstacles and practical and theoretical limitations related to the fundamental nature of the autonomic nervous system, which is both a marker of the cardiac status and a determinant of arrhythmias. 
2	Undetected fatal acute pancreatitis: why is the disease so frequently overlooked? An analysis of postmortem investigations between 1980 and 1985 revealed 43 patients with acute pancreatitis. In 13 (30.2%) of them, the diagnosis was first established at autopsy. In eight of the latter patients, the diagnosis could have been present on admission. The etiology was alcoholism in three patients, hypothermia in one, biliary tract disease in one, and unknown in three patients. In five patients, acute pancreatitis developed after gastric, pancreatic, or biliary tract surgery. Abdominal pain was present in only one patient. Amylase levels had been estimated in 11 patients, but the level was in the diagnostic range (greater than or equal to 3 times of upper normal level) in only four. Consequently, ultrasound examination was performed in only two of the latter four patients, but failed to show the pancreas because of intestinal gas. To diagnose acute pancreatitis at an earlier stage and to improve therapy and prognosis, we recommend that serum amylase levels be measured and ultrasound examination be performed. If the results are inconclusive, this should be followed by computed tomography for all abdominal emergency cases and for patients who have undergone cardiopulmonary or upper abdominal surgery, especially when the patients deteriorate or fail to improve postoperatively. 
2	Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility. Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying. 
1	A cohort study of fat intake and risk of breast cancer. Between 1982 and 1987, 519 newly incident, histologically confirmed cases of breast cancer were identified in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a dietary questionnaire before the occurrence of their breast cancer, and this has been used to estimate their intake of dietary fat and several other nutrients. There is evidence of a positive association between breast cancer and total fat intake, with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per day, and some evidence of a dose-response relationship (P = .052). 
4	Left ventricular remodeling after acute myocardial infarction: clinical course and beneficial effects of angiotensin-converting enzyme inhibition. LV enlargement is an important determinant of survival after AMI. Pathophysiologic mechanisms leading to LV dilatation after an AMI include early thinning and stretching of the infarcted segment (e.g., infarct expansion) and hypertrophy of the noninfarcted myocardium. Such LV dilatation may adversely affect subsequent cardiac function, leading to heart failure and death. Experimental data in animals and preliminary studies in humans have demonstrated that early administration of captopril, an angiotensin-converting enzyme inhibitor, may limit infarct expansion and will attenuate progressive LV dilatation. This article discussed the clinical importance of the dilated left ventricle and reviewed advances and ongoing research in the use of angiotensin-converting enzyme inhibitors in the chronic phase after AMI. 
2	Advantages of a narrow-range, medium molecular weight hydroxyethyl starch for volume maintenance in a porcine model of fecal peritonitis OBJECTIVE: To compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis. DESIGN: Randomized prospective trial. SETTING: Laboratory investigation. SUBJECTS: Adolescent female pigs weighing approximately 30 kg. INTERVENTIONS: We compared diafiltered 6% pentastarch with 6% high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis. The number average molecular weight of pentastarch is higher than hetastarch, although the weight average molecular weight is lower, i.e., a narrow range of medium weight molecules. The infusion rate of each agent was adjusted to maintain baseline arterial Hct for less than or equal to 7 hr after instrumentation and induction of fecal peritonitis. MAIN OUTCOME MEASUREMENTS: The volume of fluid required to maintain arterial Hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents. RESULTS: Significantly less pentastarch was required to prevent hemoconcentration than hetastarch (109 +/- 22.8 vs. 150 +/- 10.3 mL/kg; p less than .05) while hemodynamics, colloid osmotic pressure, and oxygen transport responses were similar. Capillary patency was greater (21.99 +/- 3.68 vs. 10.09 +/- 1.17%; p less than .05) and mean alveolar capillary barrier thickness was less (2.36 +/- 0.13 vs. 3.06 +/- 0.17 microns; p less than .05) with pentastarch than with hetastarch, as judged by electron microscopy. CONCLUSIONS: These data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch. 
4	Effect of high-dose furosemide in refractory congestive heart failure. High-dose firosemide is considered effective in primary renal sodium retention but is not generally recommended in congestive heart failure. In order to evaluate efficacy and safety of high-dose furosemide (greater than 500 mg/day), the authors studied 20 patients (pts) resistant to therapy (including furosemide less than 500 mg/day) selected from 161 pts admitted for chronic heart failure. All refractory pts (15 men and 5 women, mean age sixty +/- 12 years) were in NYHA class IV and showed hyponatremia (130 +/- 5 mEq/L) and impaired renal function (BUN 31 +/- 14 mg/dL, serum creatinine 1.3 +/- 0.3 mg/dL and BUN/creatinine ratio 23 +/- 7). In addition to digitalis, dopamine, angiotensin-converting enzyme inhibitors, or vasodilators, IV high-dose furosemide (775 +/- 419 mg/day, 500-2000) was given for ten +/- five days under daily clinical and laboratory monitoring. Three pts died of low-output syndrome while 16 pts were upgraded to NYHA class III and 1 pt to class II; a mean weight reduction of 7.3 +/- 2.9 kg in ten + five days (0.80 +/- 0.4 kg/day) and a mean diuresis increase of 88 +/- 57% occurred. The maximal dose of furosemide did not correlate with serum creatinine but did correlate with BUN/creatinine ratio (r = 0.78, p less than .001). Pts were discharged on with chronic heart failure, and 43% in the subgroup in NYHA class IV with hyponatremia. High dose furosemide was effective for rapid removal of excess water and salt in "furosemide-resistant" congestive heart failure. The relationship between renal impairment and maximal furosemide doses seems to confirm the role of renal pharmacokinetics in the appearance of furosemide resistance. 
4	Is obesity-related hypertension less of a cardiovascular risk? The Framingham Study. The hypothesis that obesity-related hypertension is relatively innocuous was explored by an examination of cardiovascular events over 34 years of follow-up when related to biennially measured weights and blood pressures using time-dependent covariate proportional hazards analysis. The 5209 participants were also classified by age, cigarette smoking, and antihypertensive treatment at each of four baseline examinations with 8-year follow-up periods. Over the period of follow-up, there were 978 cardiovascular events in men and 836 in women. Risk of cardiovascular morbidity and mortality in general and of CHD in particular was as strongly related to hypertension at all levels of body mass index. This was also found to apply when adjustment was made for possible confounding by cigarette smoking. Age and smoking-adjusted absolute risks of cardiovascular events were found to be higher in hypertensive individuals with high than with low BMIs. Furthermore, the relative risk of cardiovascular disease did not vary significantly with BMI. Thus hypertension is at least as dangerous in obese as in lean persons at all ages in either sex, providing no support for the hypothesis that hypertension in the obese is more benign. This is important, since obesity predisposes to hypertension and most who have hypertension are obese. This report examines the hypothesis for CVD outcomes considered by previous reports and also the subcategories of CVD disease such as myocardial infarction and stroke, and includes data on both men and women and on young and old. 
1	Significance of blasts in low-cell-count cerebrospinal fluid specimens from children with acute lymphoblastic leukemia. The purpose of this study was to determine whether the presence of more than 5% blasts in a differential count of cytocentrifuged cerebrospinal fluid (CSF) with less than 6 leukocytes/microliter was predictive of central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL). A double concentrate method of cytocentrifuge preparation was used to analyze 4543 consecutive CSF specimens from 349 children with ALL between January 1, 1982, and September 30, 1988. One hundred nine CSF specimens from 58 evaluable children had less than 6 leukocytes/microliter and more than 5% blasts on cytocentrifuge differential count (low-cell-count specimen with blasts [LCB]). During the study period, 25 of 332 evaluable children (7.5%) had CNS leukemic recurrence. In 22 of 25 (88%), the CNS relapse was preceded by at least one abnormal low-cell-count CSF specimen. One of 34 patients with a single LCB at diagnosis (3%) had subsequent CNS relapse compared with five of eight patients (62.5%) with a single LCB during remission (P = 0.0002). Of 16 children with two or more LCB during remission, nine (56%) had CNS relapse defined by standard criteria, whereas six additional patients in this group were declared to be in CNS relapse on the basis of their repetitive LCB. Whether diagnosing CNS recurrence earlier in its course based on a modification of the definition of CNS leukemia will change the frequency of subsequent adverse events or make possible decreased intensity of CNS retreatment remains to be determined. 
5	The role of infection in the morbidity and mortality of patients with head and neck cancer undergoing multimodality therapy. Cancer of the head and neck is a common cancer worldwide. The majority of patients present with locally advanced disease. Recently a great deal of improvement has been made in multimodality therapy of this disease, warranting more careful consideration of factors affecting quality of life, disease course, and treatment. Infection is clearly a factor. Analysis of 662 hospital admissions of 169 head and neck cancer patients was performed. A definite infection was documented in 86 febrile episodes, pneumonia contributed to 40%, bacteremia to 13%, skin and soft tissue infection to 12%, and tracheobronchitis to 10%. Among the evaluated risk factors, foreign bodies, specifically intravenous (IV) cannulae and gastrostomy tubes, race, performance status, alcohol intake, and nutritional status were statistically significant variables that predicted for or were associated with infection. Infection contributed to 44% of the deaths. 
4	Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrates severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 +/- 4.0 versus 22.7 +/- 6.1 ml/kg per min; p less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p less than 0.0001) and cardiac index (r = 0.80; p less than 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 +/- 9.1 versus 7.1 +/- 4.4 mm Hg; p less than 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling. 
5	Obliterative bronchiolitis: virus induced? This report describes a 28-year-old patient with an acute onset of respiratory symptoms associated with clinical and roentgenographic features of an interstitial lung disease which proved fatal. The entity of bronchiolitis obliterans, which was diagnosed on transbronchial biopsy, is discussed, with particular emphasis on the postinfectious type. 
5	Sudden death associated with undiagnosed Graves' disease. Hyperthyroidism may result in multiple symptoms attributable to an excess of thyroid hormone. We report a case of Graves' disease in association with sudden death in a previously healthy, undiagnosed young female. This case illustrates an unusual initial presentation of Graves' disease. 
4	Diagnostic significance of flow separation within the carotid bifurcation demonstrated by digital subtraction angiography. The presence of an area of reversed blood flow due to flow separation in the interval carotid artery is a normal finding in Doppler ultrasound studies in vivo as well as in model carotid bifurcations. This flow separation phenomenon is caused by the geometry of the carotid bifurcation and the fluid dynamics of blood. We demonstrated the flow separation phenomenon on lateral-projection intra-arterial digital subtraction angiograms in 99 of 100 carotid bifurcations. The mean duration of flow separation was 5.8 seconds, with values up to 14 seconds in normal carotid bifurcations. The presence of this flow separation phenomenon is almost independent of atherosclerotic lesions and is not correlated with cerebral ischemia. Therefore, the angiographic finding of a flow separation has no diagnostic value. However, our results refer to a factor that may be important in the genesis of atherosclerosis at the carotid bifurcation, namely the duration of the stay of blood and its components within the area of flow separation. 
5	Inflammatory pseudotumor of intra-abdominal lymph nodes manifesting as recurrent fever of unknown origin: a case report. A 27-year-old man presented with a 7-month history of debilitating recurrent fever and weight loss. Extensive clinical evaluation led to the discovery of splenomegaly and retroperitoneal lymphadenopathy. The patient underwent splenectomy as well as liver and lymph node biopsy. Histologic examination of the lymph nodes, but not the liver and spleen, revealed inflammatory pseudotumor of lymph nodes. The patient has remained asymptomatic for more than 3 years following the surgical procedure despite the absence of further intervention. Inflammatory pseudotumor of lymph nodes should be considered in the differential evaluation of prolonged or relapsing fever of unknown etiology. 
1	A6--a new 45RO monoclonal antibody for immunostaining of paraffin-embedded tissues. The authors report on the extensive characterization, on normal and pathologic tissues, of the T-cell-specific monoclonal antibody (MoAb) A6, which the authors previously found to identify a fixation- and paraffin-embedding-resistant epitope. A6 reacted with most T lymphocytes, macrophages, and Langerhans' cells of normal tissues and with peripheral T-cell lymphomas (31 of 34), Ki-1+ lymphomas (12 of 18), and T-cell leukemias (1 of 5). All cases of X and non-X histiocytosis examined and monocytic leukemias with mature phenotype only were A6 positive. Three of 47 cases of B-cell lymphoma and leukemia were labeled. Hairy cell leukemias, multiple myelomas, and Hodgkin's and Reed-Sternberg cells were negative. The A6 reactivity was preserved with different fixatives (formalin, Bouin's fluid, Carnoy's fixative, and B5) and decalcification procedures and was slightly enhanced by trypsin digestion. The pattern of reactivity of A6 was similar to that obtained with MoAb UCHL-1, recognizing the CD45RO determinant of leukocyte common antigen; however, in pathologic tissues, A6 labeled a higher percentage of cells than UCHL-1. Cross-blocking and enzyme digestion studies (Pronase E [Sigma Chemical, St. Louis, MO] and neuraminidase [Sigma Chemical]) indicated that the two MoAbs may identify close epitopes on the same molecule. In conclusion, the authors' study indicates that A6 is an excellent reagent for detection of the CD45RO molecule on paraffin-embedded normal and pathologic tissues. 
3	Blepharospasm-oromandibular dystonia associated with a left cerebellopontine angle meningioma. Blepharospasm-oromandibular dystonia is characterized by the presence of spasms of the orbicularis oculi (blepharospasm) and of the lower facial or oromandibular muscles. A patient with this syndrome is presented in which a left cerebellopontine angle meningioma appeared to act as a triggering mechanism for the development of this disorder. On the basis of this report, we recommend that physicians search for this tumor in patients with this disorder. 
3	Drug induced refractory headache--clinical features and management. Two hundred patients who were taking daily symptomatic or immediate relief medications, often in excessive quantities, yet suffering from daily or near daily severe headaches were studied. One hundred and sixteen (58%) of them were also taking concomitant prophylactic medications and they were ineffective. Low tyramine, low caffeine dietary instructions and biofeedback training were given to all patients. The effect of continuing symptomatic medications, discontinuing symptomatic medications, and adding or changing prophylactic medications were studied in the various treatment groups. It is concluded that; 1.) Daily use of symptomatic or immediate relief medications result in chronic daily headache. 2.) Discontinuing daily symptomatic medications itself result in improvement of headache. 3.) Concomitant use of symptomatic medications nullifies the effect of prophylactic medications. 4.) Discontinuing daily symptomatic medications enhances the beneficial effect of prophylactic medications. 
2	Oral indomethacin for acute renal colic. A number of studies have suggested that nonsteroidal antiinflammatory agents can relieve renal colic by a mechanism of action different from that of narcotics, offering the potential advantage of avoiding narcotic side-effects such as alteration of mental status. The authors prospectively administered oral indomethacin, 50 mg, to 25 nonvomiting patients with acute renal colic due to a documented stone. Eleven patients group (I) received the drug in an unblinded, nonrandomized fashion after failure of oral or parenteral narcotics to provide satisfactory pain relief, either at home or in the emergency department. In 14 additional patients group (II) indomethacin was given as the only initial treatment. Pain intensity before and after treatment was reported using a 1-to-10 scale. In group I, pain decreased from 5.8 +/- 2.7 to 3.6 +/- 3.8 (P less than .02). Six of the 11 patients reported a decrease in pain intensity of 50% or more, which occurred within 25 +/- 11 minutes, and in 5 of these 6, pain decreased to a 0 or 1 level. In group II, pain decreased from 7.6 +/- 1.5 to 4.6 +/- 4.0 (P less than .008). Eight of the 14 patients reported a decrease in pain intensity of 50% or more, which occurred within 40 +/- 14 minutes, and in 5 of these 8 pain decreased to a 0 or 1 level. Among all 25 patients who received indomethacin, pain relief was not significantly associated with the duration of pain before treatment or with patient age or sex. There was a trend for pretreatment pain intensity to be higher among nonresponders (P = .07). 
3	Factors predicting satisfactory home care after stroke. This study prospectively investigated factors predicting optimal poststroke home care. One hundred and thirty-five first occurrence stroke patients and their primary support persons were evaluated during the initial hospitalization after stroke and again one year poststroke. Discriminant function analysis was used to identify two groups from the baseline data: home care situations which were rated optimal and those which were not. Group membership was predicted and validated with 72.6% accuracy. Patients at risk for less than optimal home care had caregivers who were (1) more likely to be depressed, (2) less likely to be married to the patient, (3) below average in knowledge about stroke care, and (4) reporting more family dysfunction. Our findings suggest that caregiver-related problems can have a collective effect on rehabilitation outcome and that treatment should reduce caregiver depression, minimize family dysfunction, and increase the family's knowledge about stroke care. 
4	Sodium sensitive and sodium retaining hypertension. The differences between sodium sensitive and sodium retaining hypertension were theoretically considered using a water tank model of body fluid volume-blood pressure regulation. If an outlet valve is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume and output from the outlet, which represent mean arterial pressure (MAP), cardiac output (CO) and urinary Na+ excretion. The height of the outlet from the tank bottom and the size cross-sectional area, of the outlet correspond to the x-intercept and slope of the renal function (pressure-natriuresis) curve, respectively. In both nonsodium sensitive hypertension, due to the shift of the curve toward a higher blood pressure level (elevated height of the outlet) without change in the slope (size of the outlet), and sodium sensitive hypertension, due to the depressed slope of the curve (reduced outlet size), not only MAP (water level) but also CO (water volume) are increased, resulting in sodium retaining hypertension, if TPR (reciprocal of base area) remained unchanged, while CO is relatively unchanged, resulting in nonsodium retaining hypertension, if TPR is elevated. Thus, the MAP and its sensitivity to sodium intake is determined by the renal function curve. Since body fluid volume is determined by both the renal function curve and TPR, however, changes in TPR during the development of hypertension is a major factor in determining whether or not the body fluid volume has to change only a small amount or a large amount. Therefore, the sodium sensitivity of blood pressure and sodium retention must be considered separately. 
2	Pancreatic pseudocyst in the left hepatic lobe: a report of two cases. The ultrasound and computed tomographic imaging features in a rare pancreatic pseudocyst of the liver are described in two patients. The pseudocysts occurred in the left lobe in both cases, one after a traumatic injury and the other after alcoholic pancreatitis. The possible topographical sequences with which pancreatic secretions entered the left hepatic lobe to form a cyst are discussed. 
1	Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer Indium-111-antimyosin (111In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01]. HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy. 
4	An outpatient anticoagulation protocol managed by a vascular nurse-clinician. Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events. 
1	Blood transfusion and recurrence of colorectal cancer: the role of platelet derived growth factors. Efforts to explain the possible effects of blood transfusion on the recurrence of colorectal cancer have been based entirely on the immunosuppressive effects of blood transfusion. However, the relationship between solid tumour development and the immune system is inconclusive. We have investigated an alternative mechanism involving the potential role of growth factors in this phenomenon. Using a human fibroblast: [125I]deoxyuridine uptake mitogenesis assay, the relative amounts of growth factor in the plasma of stored blood were measured. There was a progressive increase in mitogenesis from day 0 (n = 6) to day 28 (n = 6; P less than 0.001, Mann-Whitney U test). The effect of growth factors on the development of liver and intraperitoneal metastases was studied in Hooded Lister rats. Following an intraportal injection of 10(5) MC28 tumour cells, the experimental group (n = 25) received 2 ml of syngeneic serum intravenously for 4 days. Likewise, colonic anastomoses were performed on omentectomized rats and the peritoneal cavity seeded with 10(3) cells. The experimental groups (n = 20) received either 2 ml serum intravenously repeatedly or 3 ml serum intraperitoneally (n = 19). There was no significant increase in liver metastases or peritoneal disease following intravenous infusion of serum but serum delivered intraperitoneally resulted in a significant increase in tumour from 22 per cent in the controls to 89 per cent in the study group (P less than 0.01). Growth factors released from platelets following blood loss into the peritoneal cavity may be important in enhancing local recurrence of colorectal cancer. 
5	Hypoxia induces a specific set of stress proteins in cultured endothelial cells. Vascular endothelial cells (EC) are the initial cells within the vascular wall exposed to decreases in blood ambient oxygen concentration. The mechanisms by which they tolerate low levels of oxygen are unknown, but may parallel the response to other cellular stresses, such as heat shock. After 4-8 h of hypoxia, we found a decrease in total protein synthesis in both cultured bovine aortic and pulmonary arterial EC. SDS-PAGE and autoradiographic analysis of [35S]methionine-labeled proteins demonstrated the concomitant induction of a specific set of proteins (Mr 34, 36, 47, and 56 kD) in both cell types. These hypoxia-associated proteins (HAPs) were cell-associated and up-regulated in a time- and oxygen concentration-dependent manner. Comparison of these proteins with heat shock proteins (HSPs) demonstrated that HAPs were distinct from HSPs. EC maintained chronically in 3% O2 continued to synthesize elevated levels of HAPs, yet further up-regulated these proteins when exposed to 0% O2. The presence of five times the normal media glucose concentration did not alter the appearance of HAPs. Hypoxia sensitive renal tubular epithelial cells up-regulated no proteins corresponding to HAPs and were irreversibly damaged within 8 h of exposure to 0% O2. In vitro translation experiments demonstrated that the steady-state level of several mRNAs was higher in the anoxic EC than in normoxic EC and encoded for proteins of Mr 32, 35, 37, 40, and 48 kD that were different from proteins encoded by HSP mRNAs. The induction of HAPs during acute hypoxia and their continued synthesis in chronic hypoxia suggest that HAPs may be important in the maintenance of endothelial cell integrity under conditions of decreased ambient oxygen. 
5	Surgical epicardial ablation of left ventricular pathway using sling exposure We report our experience with 43 consecutive patients with left free wall pathways operated on since December 1988 using a modified direct epicardial approach through a medial sternotomy, without the adjunct of normothermic cardiopulmonary bypass. The left atrioventricular sulcus is exposed by dislocating the heart cephalad and to the right using a sling made of a large sponge passed around the ventricle through the transverse sinus. While the arterial pressure is monitored, the heart is positioned to obtain adequate exposure without compromising the ventricular function. The left atrioventricular junction is exposed using a direct approach. The epicardium is incised along the ventricular edge and a plane of dissection is identified and opened using blunt dissection over the ventricular wall. The entire left atrioventricular junction can be exposed. After dissection, electrophysiological testing is repeated to assess accessory pathway conduction. Epicardial cryoablation was used when accessory pathway conduction was not present (42 patients). Transmural cryoablation was used under normothermic cardiopulmonary bypass when accessory pathway conduction persisted after dissection (subendocardial pathway). In all, cardiopulmonary bypass was not used in 41 patients. There was one early relapse that required transmural cryoablation. There were no complications. 
2	Extrauterine findings of ectopic pregnancy of transvaginal US: importance of echogenic fluid. Transvaginal ultrasound (US) studies of 232 consecutive patients with positive serum pregnancy tests who were considered to be at risk for ectopic pregnancy were prospectively evaluated to determine the significance of various extrauterine findings, including echogenic fluid in the cul-de-sac. All patients were found to have a surgically proved ectopic gestation (group 1, 68 patients [29.3%]), reliable evidence of intrauterine pregnancy at initial transvaginal US (group 2, 83 patients [35.8%]), or no evidence of pregnancy at initial transvaginal US, but subsequent proof of an intrauterine pregnancy (group 3, 81 patients [34.9%]). Adnexal findings were demonstrated in 45 (66%) group 1 patients, including a living extrauterine embryo in 10 (15%), an extrauterine gestational sac in 21 (31%), and an adnexal mass in 14 (21%). Intraperitoneal fluid was detected in 43 (63%) group 1 patients and in 81 (31%) group 3 patients. Echogenic fluid was the only abnormal finding at US in 10 (15%) group 1 patients and added confidence to the diagnosis of ectopic pregnancy in many others. Echogenic fluid correlated with hemoperitoneum at the time of surgery. The presence of echogenic fluid indicates a high risk for ectopic pregnancy in women referred with this clinical indication. 
5	Microscopic Wegener's disease: a particular form of Wegener's granulomatosis. We describe a case of Wegener's granulomatosis in which the disease was manifested with crescentic glomerulonephritis, upper airway ulcerations, and microangiopathic hemolytic anemia with consumptive coagulopathy. No granuloma was identified but antibodies to cytoplasmic components of neutrophils were strongly positive with a diffuse pattern. Because microscopic vessels were predominantly involved (capillaritis), and granuloma were absent, were refer to this particular form of the disease as "microscopic Wegener's disease.". 
4	Effect of a leukocyte-platelet removal filter on ischemia induced reperfusion injury. The effect of leukocyte and platelet depletion on reperfusion injury using a leukocyte-platelet removal filter (LRF) in intracoronary thrombolysis is reported. To better define the usefulness of LRF in evaluating the effectiveness of intracoronary thrombolysis with this device, several cardiovascular variables were examined in rabbits during ischemia followed by reperfusion. The rabbits underwent cytoapheresis with LRF (n = 5) and were compared with controls without LRF (n = 5). LRF was composed of a nonwoven polyester fabric (1.8 microns, 4.6 gm). Removal of leukocytes and platelets by LRF was 98% for both. A period of 30 min equilibration was allowed before any experimental intervention, at which time the diagonal artery was occluded for 20 min and then reperfused. All arrhythmias were defined and quantified in accordance with the Lambeth Convention. Regional wall thickening was examined by a pulsed Doppler dimension system. No significant differences were observed in hemodynamic variables between the two groups; however, rabbits treated with a LRF demonstrated greater regional wall thickening (LRF group: 17 +/- 0.9%, control group: 11 +/- 0.3%, p less than 0.01), as well as significant improvement in the frequency of ventricular arrhythmias (LRF group: 12.5%, control group: 47.2%, p less than 0.01). The data suggest that LRF may help prevent arrhythmias, and preserve left ventricular contraction, during and after intracoronary thrombolysis. 
5	Serum amylase in patients with renal insufficiency and renal failure. Results vary with regard to the upper limits of serum amylase seen in patients with renal failure, and very little has been reported with patients with renal insufficiency not yet requiring dialysis. To determine the level of serum amylase elevation in renal insufficiency and renal failure, we determined serum amylase values in 128 subjects with creatinine clearances less than 90 ml/min. Serum amylase remained in the normal range when creatinine clearance was greater than 50 ml/min, and did not become elevated until creatinine clearance was less than 50 ml/min. The highest serum amylase recorded in the absence of acute pancreatitis was 503 IU/L (normal, less than 128 IU/L). Serum lipase and trypsin values paralleled those for serum amylase; values remained normal when creatinine clearance was greater than 50 ml/min, and were normal or elevated when creatinine clearance was less than 50 ml/min. These results indicate that elevations of serum amylase (i.e., amylase greater than 128 but less than 500 IU/L) in asymptomatic patients with impaired renal function are not evident until creatinine clearances fall below 50 ml/min, and probably do not represent acute pancreatitis. 
5	Reversible myopathy due to labetalol. A severe, generalized myopathy developed in 2 children treated with labetalol. An 11-year-old girl and a 14-year-old boy demonstrated proximal weakness and markedly elevated creatine kinase levels during labetalol therapy. Clinical improvement began immediately when labetalol administration was halted; muscle strength was normal within 2 months. Muscle biopsies were consistent with rhabdomyolysis. 
4	Vena caval flow: assessment with cine MR velocity mapping. The authors used cine magnetic resonance (MR) velocity mapping to study flow in the superior vena cava (SVC) and inferior vena cava (IVC) of 13 healthy control subjects and 13 patients with right-sided cardiac disease. In the control subjects, peaks of flow in systole and diastole were observed, and mean SVC flow was 35% of the cardiac output. Respiratory gating was used in six control subjects to acquire images at end inspiration and end expiration, and although the systolic peak was reduced at end expiration, total flow was unchanged. A reduced systolic peak and retrograde flow in the IVC were observed in patients with tricuspid regurgitation. A reduced diastolic peak was seen in patients with pulmonary hypertension, pericardial constriction, and right ventricular dysplasia, reflecting reduced diastolic compliance of the right ventricle. In the patient with obstruction of the SVC, absence of flow was confirmed, and retrograde flow was seen in the azygos vein. The authors believe that cine MR velocity mapping is a reliable method of studying vena caval flow noninvasively and that it has important potential applications for the investigation of disorders of the right side of the heart. 
1	Bone sarcomas as second malignant neoplasms following childhood cancer. This study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood. Sarcomas of bone were the most common second malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13-institution consortium consisting of pediatric oncology centers from western Europe, Canada, and the United States. The authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import. The literature concerning the subtypes of bone tumors, clinical and experimental, is also reviewed. The authors also investigated the effect of several factors on the time interval from the first diagnosis to the SMN (i.e., the bone sarcoma). Anthracyclines significantly shortened the interval by about 3 years. The primary diagnosis also significantly affected the interval, with leukemia/lymphomas having the shortest interval and retinoblastoma the longest. The authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions. However, lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the SMN developed. 
1	Variations on the temporoparietal fascial flap. An improved understanding of the vascular supply of the layers of the temporal fossa has increased the potential of this region for new and ingenious reconstructive techniques. Separate and independently vascularized layers of this region include hair-bearing scalp, glabrous skin, tempororoparietal fascia (and galea aponeurotica), temporalis muscle and fascia, and pericranium. Island flaps of glabrous skin and scalp provided esthetically appropriate tissue to cover a variety of defects. The malleable bulk of the subcutaneous fascial layers were combined with skin grafts to restore thin lining, and used as a vascularized bed for cartilage grafts in otherwise unsatisfactory recipient sites. Illustrative cases from our 5-year clinical experience are presented to demonstrate various combinations of the temporoparietal fascial pedicle with tissues from the temporal region to reconstruct the eyebrows, eyelids, orbits, cheeks, and lips. 
5	Timing of operation for aortic regurgitation: relation to postoperative contractile state. With angiography and pressure measurement, we determined left ventricular volume, wall stress, and systolic performance in 30 patients with aortic regurgitation before and after successful aortic valve replacement. End-systolic wall stress was greatly elevated preoperatively and decreased to normal postoperatively. Systolic pump performance assessed as ejection phase indexes was severely depressed preoperatively and improved to normal or near-normal postoperatively in most patients. The ratio of end-systolic wall stress to end-systolic volume index (ESS/ESVI), an index of myocardial contractility, was greatly decreased before operation. Postoperatively, the ratio increased in all patients, becoming normal in 12 of the 13 patients who had a preoperative ESS/ESVI of 2.9 or greater. However, 15 of 17 patients in whom the ESS/ESVI ratio was less than 2.9 still had subnormal ratios, which indicates the presence of irreversible contractile dysfunction. Stepwise multivariate analysis showed that preoperative ESS/ESVI was the only independent discriminator of postoperative normalization of the contractile function as assessed by ESS/ESVI. After aortic valve replacement, myocardial contractile state does not return to normal in a considerable number of patients. It is important to offer aortic valve replacement for aortic regurgitation before the chance for a good functional result is lost. The ESS/ESVI ratio may be a useful index in determining the timing of operation in patients with aortic regurgitation. 
3	Hemiparkinsonism as a complication of an Ommaya reservoir. Case report. The authors describe the case of a 28-year-old woman who developed the following symptoms in her right hand: a lasting resting tremor, transient focal rigidity, and paresthesia. These deficits occurred following treatment with intrathecal methotrexate via an Ommaya reservoir which was placed too deeply, resulting in trauma to the contralateral mesencephalon. 
4	Lack of prognostic value of syncope in patients with Wolff-Parkinson-White syndrome Syncope in patients with Wolff-Parkinson-White syndrome may be considered a premonitory event heralding the future development of sudden death. Therefore, the clinical and electrophysiologic data of 101 patients with Wolff-Parkinson-White syndrome referred for invasive evaluation of known arrhythmias were reviewed to assess the incidence and clinical relevance of syncope. Thirty-six patients reported the occurrence of one or more syncopal episodes (group 1) and 65 patients had no syncope (group 2). These two groups did not differ significantly with regard to age, gender, incidence and characteristics of arrhythmia, clinical history, frequency of arrhythmic events and presence of associated cardiac disease. There were 10 patients in group 1 and 12 in group 2 who had ventricular fibrillation. There were no statistical differences between the two groups with respect to the effective refractory period of the right atrium, atrioventricular node, accessory pathway and right ventricle. Furthermore, no differences between the two groups were noted with respect to cycle length of circus movement tachycardia, mean heart rate during atrial fibrillation, and minimum RR interval during atrial fibrillation. In addition, the accessory pathway location was not significantly different between group 1 and group 2. The occurrence of syncope could not be predicted from any electrophysiologic finding and this symptom had a low sensitivity and specificity for recognition of dangerous rapid heart rates. Furthermore, the prognostic value of syncope was less accurate and predictive than the shortest RR interval during atrial fibrillation and the anterograde effective refractory period of the accessory pathway for aborted sudden death occurrence. 
4	Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes BACKGROUND. Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist. METHODS AND RESULTS. The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%). CONCLUSION. Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis. 
5	Treatment of severe acne with isotretinoin in patients with inflammatory bowel disease. Four patients with inflammatory bowel disease and severe cystic acne were treated with isotretinoin. Two patients had a successful course of treatment without any gastrointestinal side-effects. One patient had two episodes of profuse rectal bleeding that were probably related to pre-existing haemorrhoids. The fourth patient had a flare-up of his Crohn's disease after starting isotretinoin. 
4	Doxazosin: a study in a cohort of patients with hypertension in general practice--an interim report. The objective of this study was to assess the safety and efficacy of doxazosin in a substantial cohort of hypertensive patients drawn from general practice. A total of 4027 patients entered the study, 1472 of whom (36.6%) were untreated hypertensive patients. Patients were not advised to change diet, smoking habit, or life-style during the study. Twenty-one percent were cigarette smokers, and concurrent diabetes was present in 2.3%. Baseline blood cholesterol exceeded 200 mg/dl (5.2 mmol/L) in 90% and 250 mg/dl (6.5 mmol/L) in 56% of patients. The mean decrease in blood pressure produced by doxazosin was 22/15 mm Hg after 10 weeks of therapy; there was a mean decrease in heart rate of 1 beat/min. The mean maintenance dose for all patients was 3.1 mg/day. Side effects considered related or possibly related to treatment were reported in 705 patients. Treatment was discontinued in 233 patients (5.8%) because of adverse events related or possibly related to treatment with doxazosin. Doxazosin produced a significant (p less than 0.001) decrease in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and a significant increase in high-density lipoprotein cholesterol and the ratio of high-density lipoprotein:total cholesterol. The potential reduction in 10-year coronary heart disease risk (according to the Framingham equation) was calculated to be 20.4%. 
1	Clinical significance of the "palpable mass" in patients with muscle-infiltrating bladder cancer undergoing cystectomy after pre-operative radiotherapy. Between 1976 and 1985, 132 patients with T2/T3/T4a bladder cancer underwent cystectomy after pre-operative radiotherapy (46 Gy: 67 patients; 20 Gy: 65 patients). After a median time of 41 months, 62 patients were alive; 51 had died from recurrent bladder cancer and 19 from intercurrent disease without recurrence of their malignancy. Distant metastases developed in 40 patients, accompanied in 5 cases by local recurrence. Local recurrence was the first sign of relapse in 11 patients. In 3 patients the localisation of the relapse remained unknown. The corrected 5-year survival rate was 60%. T category and a palpable bladder tumour were independent pre-treatment prognostic factors in a Cox regression analysis, together with the interval between initial diagnosis and cystectomy. The presence of a palpable tumour before the start of treatment was associated with a particularly poor prognosis in T3/T4a tumours, whereas the survival of patients with non-palpable T3/T4a tumours was similar to that of patients with T2 bladder cancer. Another important prognostic factor was post-irradiation stage reduction (no residual muscle infiltration in the cystectomy specimen). Significantly more patients with non-palpable bladder tumours experienced post-radiation stage reduction than did those with a palpable tumour. However, the prognostic value of stage reduction was statistically significant only in patients with palpable bladder tumours. 
1	Accessory arm--dysraphism or disparity? Case report. The case of a 3-month-old infant with an accessory third arm is reported. The extra appendage was attached at the midcervical region and was associated with posterior cervical dysraphism and a cervical cord lipoma. Possible theories of origin are examined. 
1	Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. The disposition of total and non-protein-bound etoposide was investigated in 21 cancer patients receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined using a specific high-performance liquid chromatography (HPLC) method, and etoposide plasma protein binding was determined by equilibrium dialysis. The patients had a wide range of renal function (creatinine clearance, 32 to 159 mL/min/m2) and hepatic function (total bilirubin range, 0.3 to 21.5 mg/dL; aspartate aminotransferase [AST] range, 14 to 415 IU/L; serum albumin range, 2.7 to 4.1 g/dL). The mean etoposide total systemic clearance was not different in 15 patients with total bilirubin less than 1.0 mg/dL versus six patients with total bilirubin 1.1 to 21.5 mg/dL (18.7 +/- 5.9 mL/min/m2 v 26.4 +/- 10.7 mL/min/m2; t-test P = .06), with a trend toward higher total clearance in the patients with abnormal bilirubin values. However, the mean clearance of unbound etoposide was significantly lower in patients with increased total bilirubin (220 +/- 90 mL/min/m2 v 135 +/- 61 mL/min/m2; t-test P = .027). The fraction of etoposide unbound (fu) in plasma was significantly higher in patients with increased bilirubin (9% +/- 3% v 27% +/- 15%; t-test P = .002), explaining the trend toward higher total clearance in these patients. Etoposide clearance (total or unbound) in the 14 patients with measurable hepatic metastases was not different from the clearance in the seven patients without hepatic metastases. This study provides an explanation for why patients with increased bilirubin do not have lower total systemic clearance of etoposide, and indicates that such patients have a higher exposure to unbound etoposide. The results of ongoing pharmacodynamic studies of total and unbound etoposide in patients with increased bilirubin will determine the clinical relevance of altered etoposide protein binding. 
5	Optimum results of the surgical treatment of carotid territory ischemia. Continuing controversy over the role of carotid endarterectomy in stroke prevention is based largely on reports in which high perioperative morbidity and mortality rates obviate possible long-term benefit from the procedure. The purpose of this review is to examine optimal results of carotid surgery in order to describe the potential for the procedure in stroke prevention. Optimal surgical results are compared with optimal medical results in the therapy of symptomatic patients and with optimal nonsurgical results in the therapy of asymptomatic patients. Factors common to series with excellent results, such as patient selection and operative technique, are examined, and problems such as recurrent carotid stenosis and coexisting coronary disease, which continue to plague even the best surgical series, are discussed. 
5	Pylorus preserving pancreatoduodenectomy: an overview. Pylorus preserving pancreatoduodenectomy (PPPD) was reintroduced 12 years ago. Since that time, over 400 patients have undergone PPPD with approximately 41 per cent having chronic pancreatitis and 54 per cent having pancreatic and other periampullary malignancies. Reported 5-year survivals in this latter group have been comparable to those achieved by the classic Whipple procedure. The postoperative mortality rate in 339 reported patients has been 3.8 per cent. Postoperative morbidity, including delayed gastric emptying, has been similar to that of the classic Whipple operation. However, PPPD has been associated with fewer late problems with dumping, diarrhoea, delayed gastric emptying (8.6 per cent), and marginal ulceration (3.6 per cent). Moreover, most patients undergoing PPPD have been able to return to their preoperative and preillness weight. The additional advantage of decreased operative time makes PPPD an attractive alternative to the classic pancreatoduodenectomy. 
3	Localization of stereotactic targets by microrecordings of thalamic somatosensory evoked potentials. To improve the localization of stereotactic targets, somatosensory evoked potentials (SEPs) were recorded from the thalamus and subthalamic area using a specially designed semimicroelectrode in 61 patients and a conventional "macroelectrode" in 17 patients. By means of the semimicroelectrode, median nerve stimulation evoked two distinct SEPs, consisting of a diphasic wave with a huge positivity restricted to the nucleus ventrocaudalis (Vc) and a triphasic wave of lower amplitude with a major negativity in the ventral part of the nucleus ventrointermedius (Vim) and nucleus ventrooralis posterior (Vop) as well as the subthalamic lemniscal pathway. The Vim-Vc junction could thus be clearly delineated by an abrupt transition of SEPs from one type to the other with a precision of 1 mm. The parvicellular part of the Vc (Vcpc), situated in its basal region, was distinguishable from the Vc proper by a significant reduction of the positivity elicited by stimulation of the median nerve and by a rapid growth of a diphasic SEPs to stimulation of the posterior tibial nerve. In the other thalamic nuclei, stimulation of the median nerve elicited triphasic SEPs of a very small amplitude, suggesting a volume conduction current from the lemniscal pathway. With the macroelectrode, the positivity in the Vc was sensitive to electrode manipulation and the thalamic nuclei could not be distinctly outlined. SEP monitoring using the semimicroelectrode significantly improved the precision of target localization, which allowed minimizing of the volume of the therapeutic lesion without losing surgical effectiveness, while avoiding complications associated with increased penetration of the coagulating electrode. It is suggested that recording serial thalamic SEPs with the semimicroelectrode is a practical method to refine stereotactic targets in the thalamus. 
5	Airways inflammation in nocturnal asthma. Nocturnal asthma is a frequent problem, but the mechanism is unclear. We investigated the possibility that airways inflammation occurred during the night. Bronchoalveolar lavage fluid was analyzed in asthmatic patients with (n = 7) and without nocturnal asthma (n = 7) at 1600 and 0400 h. The nocturnal asthma group had an increase in the total leukocyte count (24.0 +/- 7.0 to 41.1 +/- 9.9 x 10(4) cells/ml, p less than 0.05), neutrophils (1.1 +/- 0.6 to 3.7 +/- 1.5 x 10(4) cells/ml, p less than 0.05), and eosinophils (0.5 +/- 0.1 to 1.7 +/- 0.7 x 10(4) cells/ml, p less than 0.05) from 1600 to 0400 h. Cellular components for the non-nocturnal asthma group did not change. Between groups, the 1600-h cells were similar. At 0400 h the nocturnal asthma group had significantly higher total leukocyte, neutrophil, eosinophil, lymphocyte, and epithelial cell counts. For all subjects, the overnight fall in peak expiratory flow rates was correlated to the change in neutrophils (r = 0.54, p less than 0.05) and eosinophils (r = 0.77, p less than 0.05). We conclude that the nocturnal worsening of asthma has an associated cellular inflammatory response that is not seen in patients without overnight decrements in lung function. This inflammatory response together with epithelial damage may be important factors in the etiology of nocturnal asthma. 
2	Gallstone pancreatitis. Gallstone pancreatitis is caused by transient obstruction of the ampulla of Vater by a migrating gallstone. Intraglandular activation of pancreatic enzymes occurs (by an unclear mechanism), and their entry into the circulation causes most of the local and systemic events of pancreatitis. The diagnosis is based on history and physical examination, an elevation of serum amylase above 1000 IU/L, and ultrasound and CT scans. Endoscopic retrograde cholangiopancreatography can be used in less certain cases to confirm the presence of common bile duct stones. Because of the absence of an agent that can abort progression of the disease, therapy should consist of adequate resuscitation, nutritional support, and careful monitoring to detect early complications. In patients with mild pancreatitis, surgery usually can be performed within 48 or 72 hours of admission or as soon as symptoms and amylase levels return to normal. For patients with severe disease, endoscopic sphincterotomy is emerging as the therapeutic modality of choice. Elective treatment of the associated biliary disease should be performed during the same hospitalization after the acute phase of the disease has subsided. 
5	Aerobic and anaerobic bacteriology of wounds and cutaneous abscesses. The aerobic and anaerobic microbiologic characteristics of 584 wounds and 676 skin or soft-tissue abscesses were studied and correlated with the infection site. In wounds, aerobic or facultative bacteria only were present in 223 specimens (38%), anaerobes only in 177 specimens (30%), and mixed flora in 184 specimens (32%). In total there were 1470 isolates, 558 aerobic and 912 anaerobic, an average of 2.5 isolates per wound (1.6 anaerobic and 0.9 aerobic isolates). In abscesses, aerobic or facultative bacteria were recovered in 177 specimens (26%), anaerobes only in 243 specimens (36%), and mixed flora in 256 specimens (38%). In total there were 1702 isolates, 602 aerobic and 1100 anaerobic, an average of 2.5 isolates per abscess. The highest rates of anaerobes in wounds were in the inguinal, buttocks, and trunk areas and in abscesses in the perirectal, external genitalia, neck, and inguinal areas. The predominant aerobic organisms were Staphylococcus aureus (363 isolates), group A streptococci (98 isolates), and Escherichia coli (97 isolates). The predominant anaerobic organisms were Bacteroides species (986 isolates), Peptostreptococcus species (559 isolates), Clostridium species (153 isolates), and Fusobacterium species (109 isolates). The predominance of certain isolates in certain anatomical sites was correlated with their distribution in the normal flora adjacent to the infected site. These data highlight the polymicrobial nature of wounds and cutaneous abscesses. 
5	Autosomal dominant neovascular inflammatory vitreoretinopathy. Twenty-eight of 61 members of a six-generation family are affected by an autosomal dominant eye disease which has not been described previously. Affected patients are asymptomatic in early adulthood, but have vitreous cells and the selective loss of the b-wave on the electroretinogram. Later, peripheral retinal scarring and pigmentation, peripheral arteriolar closure, and neovascularization of the peripheral retina at the ora serrata or occasionally neovascularization of the optic disc develop. Cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma can cause profound visual loss. Vitrectomy reduces traction on the retina and allows for retinal reattachment. The role of argon laser photocoagulation or cryopexy in reducing the neovascular complications remains uncertain. 
1	Multifocal, synchronous inverted papillomas involving the ureter. Inverted papillomas involving the upper urinary tract remain a rarely diagnosed phenomenon. A case of bilateral ureteral inverted papillomas is presented. The treatment and diagnosis of this lesion remain a challenge. 
4	Management of aortobronchial fistula with graft replacement and omentopexy. Massive hemoptysis due to a recurrent aortobronchial fistula after repair of a thoracic aortic aneurysm developed in a 64-year-old woman. The infected aortic tissue was resected and replaced with an in situ Dacron graft covered by omentum. The patient is alive and well 15 months later. 
1	Herniation of the antral membrane through an extraction site. Report of a case. A case of herniation of the antral membrane through a recent extraction site is presented. The lesion was initially diagnosed as a tumor by the referring dentist. Oroantral fistulas are not an uncommon finding after dental extractions. It is rare, however, to see herniation of the antral membrane with large polyps extending through the fistula into the oral cavity. A search of the literature revealed only two other such cases. Surgical removal of the polyps and closure of the oroantral fistula by means of a buccal sliding flap technique is discussed. 
5	Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver. The authors describe the histopathologic evolution of Lyme disease in severe combined immunodeficiency (scid) and normal C.B-17 and C57BL/6 mice inoculated with Borrelia burgdorferi. Starting on day 7 after inoculation, all scid mice infected subcutaneously in the tail with a low-passage European tick isolate of B. burgdorferi had clinical evidence of arthritis characterized by reddening and swelling of tibiotarsal joints. Later on, other joints, ie, metatarsal and ulnacarpal joints were also affected. The infection of scid mice resulted in a persistent spirochetemia and the development of a multisystem disease with chronic progressive inflammation of joints, heart, and liver. Major histopathologic alterations included 1) severe joint lesions, characterized by the presence of hyperplastic inflamed synovial lining cells associated with the erosion and destruction of cartilage and/or bone; 2) pancarditis with infiltrations of mononuclear cells in the endocardium, myocardium, and pericardium; and 3) hepatitis with mononuclear cell infiltrations confined to the portal field and central vein, granulomatous reactions, and eventually the development of liver fibrosis. In addition, smaller more confined lesions were found in kidneys, lung, brain, and striated muscle. The inflammatory infiltrates in the various organs were associated mostly with Mac-1+ cells, largely monocytes and macrophages, as well as some polymorphonuclear leukocytes, but not B and T lymphocytes. Infective spirochetes could be readily isolated from blood and joints and were found at the site of inoculum and the myocardium. In contrast, subcutaneous inoculation of normal C.B-17 or C57BL/6 mice with spirochetes in general did not result in clinical signs of arthritis. Only 10% to 20% of the C57BL/6 mice, but none of the C.B-17 mice, showed clinical evidence of oligoarthritis, which appeared not before day 36 after inoculation. In general, the infection of normal mice resulted in minimal lesions in various organs, and no spirochetes could be visualized or reisolated from their tissues. The data demonstrate that Lyme borreliosis may develop in mice in the absence of detectable specific B and T cells and thus suggest an immunologic control of the disease in this species. The scid mouse model therefore can be used to define the components of the immune system responsible for the suppression and/or the progression of the disease. 
5	Pelvic floor descent in women: dynamic evaluation with fast MR imaging and cinematic display. The authors present a new method for assessing pelvic prolapse with dynamic fast magnetic resonance (MR) imaging. Twenty-six women with signs and symptoms suggesting pelvic prolapse and 16 control subjects were studied with a series of fast (6-12-second) MR images. Sagittal and coronal images were obtained with graded increase in voluntary pelvic strain, allowing for dynamic display and quantification of the pelvic prolapse process. The distance from the pubococcygeal line was used as an internal reference for measurement of descent in the maximal strain position. With use of control results for normal limit values, prolapse involving the anterior pelvic compartment (cystocele), the middle compartment (vaginal prolapse, uterine prolapse, and enterocele), and the posterior compartment (rectocele) was easily demonstrated. Significant differences between control subjects and patients with prolapse were seen at maximal strain but not in the relaxed state. Quantification of the pelvic descent process with use of fast MR imaging may be of value in surgical planning and postsurgical follow-up. 
5	Induction of inflammatory cell infiltration and necrosis in normal mouse skin by the combined treatment of tumor necrosis factor and lithium chloride. Previously we reported that lithium chloride (LiCl) potentiates tumor necrosis factor (TNF)-mediated cytotoxicity in vitro and in vivo. Here, using a murine normal skin model, it is shown that a subcutaneous injection of TNF plus LiCl induces acute dermal and subcutaneous inflammation and necrosis. Histology showed a marked initial dermal and subcutaneous neutrophil infiltrate by approximately 2 hours, followed by a predominantly mononuclear infiltrate by 24 hours, which remained present for several days. Tumor necrosis factor or LiCl alone induced negligible inflammation, disappearing after 6 hours; furthermore there was never necrosis or ulceration of the overlying skin in case of single-agent application. In vitro studies showed that the combination of TNF and LiCl, but not either agent alone, was directly cytotoxic to fibroblastic cells of murine skin. No inflammatory infiltration was visible in tumors treated intratumorally or perilesionally with TNF plus LiCl, although the latter treatment resulted in a perilesional leukocyte infiltration. Furthermore the combination of TNF and LiCl had no effect on macrophage cytotoxicity to L929 tumors. 
4	Expert testimony based on decision analysis: a malpractice case report. OBJECTIVE: Expert testimony in malpractice cases is often subjective and biased. Decision-analytic techniques might provide an objective basis for such testimony. DESIGN: Case report. This article reports the case of a patient with chest pain that resulted in a malpractice suit alleging a delay in diagnosis of coronary artery disease. SETTING: The case occurred in a private practice; the expert witnesses and the decision analysis originated from a university teaching hospital. METHODS: A decision tree and threshold analysis were used to define the thresholds of disease probability at which either testing or treatment should be implemented. The expert testimony of two witnesses that exercise stress testing was the standard of care was compared with the results of the decision analysis. MAIN RESULTS: Decision analysis supported the view that cardiac catheterization would have been the more appropriate test. CONCLUSIONS: Techniques of decision analysis provide a structured and quantitative basis for empirical judgment and may help to minimize current problems with expert testimony. 
3	Cardiac echinococcosis with fatal intracerebral embolism. A previously well 7 year old boy presented with sudden loss of consciousness and fitting. No evidence of trauma or space occupying lesion was identified. Death occurred the next day due to cerebral infarction caused by embolised fragments from a ruptured left ventricular hydatid cyst that was found at necropsy. 
4	Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. A randomized, placebo-controlled, crossover trial in patients tolerating oral therapy. OBJECTIVE: To test the hypothesis that propafenone, administered orally, prevents symptomatic paroxysmal supraventricular arrhythmias. DESIGN: a 6-month, open-label, dose-finding phase followed by a randomized, double-blind, placebo-controlled, crossover phase, with each treatment period lasting up to 60 days. SETTING: An outpatient clinic. PATIENTS: Thirty-three patients with either paroxysmal supraventricular tachycardia (n = 16) or paroxysmal atrial fibrillation (n = 17) were enrolled. Their arrhythmias were documented by electrocardiogram before enrollment. Twenty-three patients (14 with paroxysmal supraventricular tachycardia and 9 with paroxysmal atrial fibrillation) were randomized and the data obtained from these patients were used in the efficacy analysis. INTERVENTION: Propafenone (300 mg three times daily in 19 patients, 300 mg twice daily in 3 patients, and 150 mg twice daily in 1 patient) and matching placebo tablets were administered in a randomized sequence. MEASUREMENTS: Symptomatic arrhythmia was documented by telephone transmission of the electrocardiogram. MAIN RESULTS: The time to first recurrence was prolonged for the overall group of 23 patients while they received propafenone (P = 0.004). The recurrence rate of arrhythmia during treatment with propafenone was estimated to be approximately one fifth of the recurrence rate during treatment with placebo. CONCLUSIONS: Propafenone is effective in reducing symptomatic paroxysmal supraventricular arrhythmias. 
5	Human papillomavirus type 16 associated with oral squamous carcinoma in a cardiac transplant recipient. Human papillomavirus type 16 (HPV 16) has been associated with a variety of squamous carcinomas, particularly those involving the anogenital tract. The authors report the development of an oropharyngeal carcinoma in a 43-year-old man approximately 20 months after cardiac transplantation while he was on a maintenance regimen of cyclosporine A and prednisone. The carcinoma was resistant to treatment, and he died of complications related to metastatic disease 3 years posttransplantation. Molecular biologic studies using nonisotopic-labeled viral DNA probes were done. In situ hybridization demonstrated the presence of HPV 16 DNA in the tumor cells. DNA dot blot analysis confirmed the presence of multiple copies of HPV 16 DNA within the tumor cells and their absence from adjacent normal-appearing tissue. Southern blot analysis suggested that the HPV 16 DNA was integrated into the tumor cell genome. With increasing recognition of the carcinogenicity of HPV type 16 infection, a role for this virus in the development of squamous cell malignancies in immunosuppressed organ transplant recipients is likely to be noted with increasing frequency. 
1	Scintigraphic evaluation of aggressive fibromatosis. Despite its benign microscopic appearance, aggressive fibromatosis has potential to recur and infiltrate neighboring tissues. Therefore, it is necessary to determine the exact extent before therapy. In the present study, 11 cases of aggressive fibromatosis were examined scintigraphically using [99mTc(V)]dimercaptosuccinic acid (11 cases) and 67Ga-citrate (7 cases). Technetium-99m-(V)-dimercaptosuccinic acid demonstrated all lesions, while 67Ga-citrate detected 57% of the cases. 
4	Failure of Hancock pericardial xenografts: is prophylactic bioprosthetic replacement justified? The incidence of major valve-related complications was evaluated in a series of patients in whom the Hancock pericardial xenograft was used for aortic (AVR; n = 84), mitral (MVR; n = 17) and mitral-aortic (MAVR; n = 13) valve replacement. At 7 years actuarial survival is 66% +/- 8% after AVR, 64% +/- 13% after MVR, and 41% +/- 15% after MAVR, whereas actuarial freedom from valve-related death is 79% +/- 7% after AVR, 78% +/- 13% after MVR, and 81% +/- 12% after MAVR. Actuarial freedom from thromboemboli and anticoagulant-related hemorrhage at 7 years is 93% +/- 4% and 98% +/- 2% after AVR and 83% +/- 10% and 88% +/- 11% after MVR; no such complications occurred after MAVR. Structural valve deterioration determined at reoperation, at autopsy, or by clinical investigation was observed in 34 patients with AVR (10.0 +/- 0.2%/patient-year), in 10 with MVR (10.6 +/- 3.3%/patient-year), and in 9 with MAVR (16.6 +/- 5.5%/patient-year). After AVR, 19 patients underwent reoperation and 2 died before reoperation; 4 patients with MVR underwent reoperation, and 7 patients with MAVR underwent reoperation and 1 died before reoperation. Seventy-eight percent of the current survivors (13 patients with AVR, 7 with MVR, and 1 with MAVR) have clinical evidence of valve failure. At 7 years actuarial freedom from structural deterioration of the Hancock pericardial xenograft is 25% +/- 7% after AVR, 29% +/- 14% after MVR, and 0% after MAVR. 
1	The association of hydrocephalus with intramedullary spinal cord tumors: a series of 25 patients. 171 patients with intramedullary spinal cord tumors were operated on, of which 25 patients (15%), mostly children, developed symptomatic hydrocephalus. Twenty patients (12%) had malignant tumors, with 13 of the 20 cases (63%) complicated by increased intracranial pressure and ventriculomegaly. Of the remaining 151 patients with benign tumors (89%), only 12 (8%) developed symptomatic hydrocephalus. In an effort to understand the relationship between hydrocephalus and intramedullary spinal cord tumor, the authors analyze the level and histology of the neoplasm, as well as its association with spinal cysts. A review of the neurosurgical literature reveals that 34 similar cases of hydrocephalus associated with intramedullary spinal cord tumors have been reported to date. The authors note that the presence of hydrocephalus in patients with malignant intramedullary astrocytomas is associated with a shorter rate of survival than in those patients with high-grade lesions but without hydrocephalus, apparently due to rapid tumor progression. The ventriculomegaly seen with benign spinal cord gliomas has no statistically significant effect upon long-term prognosis. 
5	Botulinum-induced changes in monkey eyelid muscle. Comparison with changes seen in extraocular muscle. Botulin type A was injected into the eyelids of adult monkeys, and structural alterations in the orbicularis oculi muscle were evaluated after survival times of 7 to 84 days. The most profound change seen at both the light- and electron-microscopic levels was nonselective atrophy of virtually all muscle fibers. Moreover, the botulin-induced blockade of neuromuscular transmission was nonspecific in producing alterations in the three orbicularis fiber types. Muscle structural changes appeared to be reversible, with no apparent long-term consequences. While sprouting of preterminal axons was noted in botulin-treated muscle, formation of collateral sprouts did not appear to be widespread. These changes contrast with the fiber type-specific, long-term alterations induced in extraocular muscle by botulin treatment. However, this differential response may be attributed to the very clear differences in fiber type composition and motor control mechanisms between eyelid and extraocular muscle groups. The efficacy of botulin treatments for strabismus and focal dystonia may then be directly related to both the anatomic fiber type composition and the functional properties of motor control systems of the injected muscle. 
5	Computed tomography for evaluation of puerperal infections. Pelvic computed tomography was used to evaluate 74 women with persistent puerperal infection. There was at least one abnormal roentgenographic finding in 57, and these are correlated with clinical and surgical findings. In 16 women, a palpable pelvic mass was seen on tomography, however, masses not appreciated clinically were visualized in another 29 women, and in five, a clinically palpable mass was not visualized by tomography. In 12 women who had a normal pelvic examination, septic pelvic thrombophlebitis was diagnosed by tomography. Over-all, there was poor correlation with roentgenographic findings and uterine incisional necrosis and dehiscence. We conclude that pelvic tomography is useful to evaluate some women with persistent puerperal infection, but that these studies must be correlated with clinical findings. 
5	Impact of active immunisation against enteritis necroticans in Papua New Guinea. Enteritis necroticans, known locally as pigbel, has been a major cause of illness and death among children in the highlands of Papua New Guinea. After a successful trial of active immunisation against the beta toxin of the causative organism, Clostridium perfringens type C, immunisation of children was begun in 1980. The effects of the immunisation programme on pigbel admissions in 3 of the 5 major highland hospitals were assessed. In each of the centres studied the proportion of admissions due to enteritis necroticans dropped significantly after immunisation was introduced (p less than 0.001) and hospital admissions for pigbel in 1984-86, when immunisation was well established, were less than one fifth of previous figures. 
2	Pathophysiology, monitoring, and management of the ventilator-dependent patient: considerations for drug therapy, emphasis on stress ulcer prophylaxis. Adult respiratory distress syndrome (ARDS), or noncardiac pulmonary edema, is a form of acute hypoxemic respiratory failure. The goals of treatment for patients with ARDS are to provide supportive therapy, to reverse the underlying etiology or pathology, and to prevent subsequent complications. Supportive therapy consists of supplemental oxygen, positive end-expiratory pressure, and, often, mechanical ventilation. The reversal of the underlying pathology varies according to the etiologic origin of ARDS. Complications from ARDS include stress ulcers, which occur when gastric aggressive and defensive functions become unbalanced. Antacids and cytoprotective agents are used for stress ulcer prophylaxis, but histamine H2-receptor antagonists are now regarded as the standard of care. Because all the marketed H2-receptor antagonists are efficacious, choice of the agent is based on the adverse effect profile and drug interactions. No definitive data currently exist linking stress ulcer prophylaxis regimens that raise intragastric pH to a significant risk for nosocomial pneumonia. 
1	Interleukin-5 is a human basophilopoietin: induction of histamine content and basophilic differentiation of HL-60 cells and of peripheral blood basophil-eosinophil progenitors. Cytokine-induced differentiation of basophils may contribute to various inflammatory processes. We examined the effects of recombinant human interleukin-5 (IL-5) and other human cytokines in vitro on myeloid colony formation in methylcellulose and on alkaline passaged HL-60 basophilic cell differentiation. Myeloid colonies (CFU-C) at day 14, formed in the presence of either IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), or G-CSF included peripheral blood-derived progenitors of the eosinophil/basophil lineage. IL-5 stimulated a greater proportion of basophil-containing, histamine-positive, eosinophil-type colonies compared with GM-CSF, IL-3, or G-CSF. IL-5 also stimulated dose-dependent increases in histamine content of alkaline-passaged, butyrate cotreated HL-60 cells. The concentration of IL-5 required for half-maximal induction of HL-60 histamine content was similar within twofold to that needed for half-maximal stimulation of the multifactor dependent TF-1 erythroleukemic cell line. Neutralizing rat monoclonal antibodies to human IL-5 were developed and used to demonstrate that each of these IL-5 bioactivities could be specifically blocked. We conclude that in addition to its previously described eosinophil differentiation activity, IL-5 may be considered a basophilopoietin. 
5	Penetrating iliac vascular injuries: recent experience with 233 consecutive patients. During a recent 11-year period, 233 consecutive patients with 358 penetrating iliac vascular injuries were treated at our institution. Injuries of the common and external iliac arteries were most often repaired with lateral suture (31%) although several other techniques were also employed. Lateral suture and ligation were used with nearly equal frequency in the management of venous injuries. The hospital mortality rate for the series was 28%, and 56/66 deaths (85%) were due to exsanguination or shock. One patient, initially treated with an end-to-end anastomosis of the iliac artery, died a year after discharge from a ruptured false aneurysm. Two patients treated with lateral suture of venous injuries died of pulmonary embolism. Arterial complications occurred in 15% of patients with arterial injuries and three patients required amputation. No graft infections occurred in 16 patients treated with PTFE interpositions, including four with associated colorectal injuries. Venous complications occurred in 12% of patients with venous injuries, and most were noted in those treated with ligation. Four patients treated by venous ligation developed chronic venous insufficiency. The prevention of death from exsanguination is the greatest problem in the management of patients with iliac vascular injuries. Although some late deaths and many complications may be related to the technique of vascular repair, circumstances often prohibit alternative methods. Despite two deaths from pulmonary embolism, insufficient data exist to condemn lateral suture of venous injuries. 
1	Respiratory epithelium in a cystic choristoma of the limbus. A female newborn had a cystic, whitish gray mass at the inferotemporal limbus of the left eye. At age 3 weeks, the newborn underwent excision of the tumor, corneal patch grafting, and superior sector optical iridectomy. Histopathologic and electron microscopic examination of the excised tissue revealed a choristoma consisting of cysts lined with respiratory epithelium. To our knowledge, respiratory epithelium in a limbal choristoma has not been previously reported. 
1	Effects of carotenoids in cellular and animal systems. It has been suggested that carotenoid pigments may function as chemopreventive agents for reducing the risk of cancer in humans. Part of this suggestion rests on epidemiological evidence, and part rests on work done in cellular and animal systems. In this article, the experimental evidence for carotenoid inhibition of mutagenicity, malignant transformation, tumor formation, and immunoenhancement is reviewed. Although a mechanism for these effects cannot yet be identified, it is clear that the overwhelming evidence in these systems would indicate that carotenoids exert an important influence in modulating the actions of carcinogens. 
1	Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion. From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement. 
5	Acute pain relief. Pain is a multidimensional psychophysiologic phenomenon. Systematic multidimensional assessment is an essential first component of an effective plan to relieve the pain. Nurses are key to effective pain management because of the close, 24-hour-a-day relationship with the hospitalized patient. It is the nurse who is most critical to the adequate assessment of pain, to the implementation of the treatment plan, and to the evaluation of efficacy. Nurses should continue to develop a better knowledge base about pain and pain therapies and assessment skills, be assertive in obtaining effective treatment for their patients, and perceive themselves as responsible for pain relief. 
5	Surgical aspects of malaria. The spread of drug-resistant organisms and increased international travel makes malaria a disorder of ever-increasing importance. This report reviews those aspects of malaria of surgical relevance. The importance of the spleen in host defence against malaria and other infections makes splenic preservation desirable whenever possible after rupture of the spleen. Tropical splenomegaly is caused by an abnormal immune response to malaria and is best managed medically. Careful selection of blood donors is essential to prevent transfusion malaria, and routine antimalarial prophylaxis is indicated for blood recipients in many endemic areas. The risk of postoperative malaria may justify chemoprophylaxis in certain patients. 
1	Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas. Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., spread of the tumors. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features relating to the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors, and that loss of H-antigen expression is related to the stage of tumor and invasion of carcinoma cells. 
4	Complement activation is a secondary rather than a causative factor in rabbit pulmonary artery ischemia/reperfusion injury. We have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema, transient leukopenia, and intravascular leukocyte aggregation. We hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury. In the preliminary phase of the study, we found that ischemia followed by reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion (p less than 0.05). We then studied three groups of animals to determine if complement depletion with cobra venom factor (CVF) prior to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF but without occlusion and reperfusion did not develop significant lung edema, with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12, respectively. For rabbits that were not treated with CVF but underwent ischemia and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p less than 0.05 for right versus left). For CVF-treated rabbits that underwent ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48 versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3 deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in complement activation, but it is not a complement-dependent injury. 
1	An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987) BACKGROUND. Phenacetin abuse is known to produce kidney disease; salicylate use is supposed to prevent cardiovascular disease. We conducted a prospective, longitudinal epidemiologic study to examine the effects of these drugs on cause-specific mortality and on cardiovascular morbidity. METHODS. In 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin, as measured by urinary excretion of its metabolites, and a matched control group of 621 women. Salicylate excretion was also measured. All subjects were examined over a period of 20 years. RESULTS. Life-table analyses of mortality during the 20 years, with adjustment for the year of birth, cigarette smoking, and length of follow-up, revealed significant differences between the groups in overall mortality (study group vs. control group, 74 vs. 27 deaths; relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.3), deaths due to urologic or renal disease (relative risk, 16.1; 95 percent confidence interval, 3.9 to 66.1), deaths due to cancer (relative risk, 1.9; 95 percent confidence interval, 1.1 to 3.3), and deaths due to cardiovascular disease (relative risk, 2.9; 95 percent confidence interval, 1.5 to 5.5). The relative risk of cardiovascular disease (fatal or nonfatal myocardial infarction, heart failure, or stroke) was 1.8, and the 95 percent confidence interval 1.3 to 2.6. The odds ratio for the incidence of hypertension was 1.6, and the 95 percent confidence interval 1.2 to 2.1. The effects of phenacetin on morbidity and mortality, with adjustment for base-line salicylate excretion, were similar. In contrast, salicylate use had no effect on either mortality or morbidity. CONCLUSIONS. Regular use of analgesic drugs containing phenacetin is associated with an increased risk of hypertension and mortality and morbidity due to cardiovascular disease, as well as an increased risk of mortality due to cancer and urologic or renal disease. The use of salicylates carries no such risk. 
1	Inflammatory pseudotumor of the liver. Inflammatory pseudotumor of the liver is an extremely rare entity. Because of its unusual clinical presentation and confusing histologic picture, a diagnosis of malignancy is frequently made. Thus the surgeon is closely involved with the case and extensive procedures are not uncommon. However, this lesion is benign and will even regress spontaneously, making radical surgical procedures contraindicated. The difficulty lies in establishing an accurate diagnosis and the histologic pitfalls of this particular process. Conservative therapy can then be applied, avoiding surgical morbidity. 
5	Sudden death in hypertrophic cardiomyopathy with normal left ventricular mass An active, healthy, and symptom free 16 year old boy with a family history of hypertrophic cardiomyopathy died suddenly while walking home from school. Necropsy showed absence of left ventricular hypertrophy (that is, normal heart weight), though the characteristic histological abnormalities of hypertrophic cardiomyopathy, such as cardiac muscle cell disorganisation and abnormal intramural coronary arteries, were present. It is likely that this patient had hypertrophic cardiomyopathy and died before left ventricular hypertrophy developed. 
1	Behavioral and psychosocial cancer research. Building on the past, preparing for the future. This report identifies five general conclusions that emerged from the Second Workshop on Methodology in Behavioral and Psychosocial Cancer Research. These conclusions address diverse topics, including a focus on areas other than methodology; an emphasis on the transfer of technology and knowledge to applied settings; a recognition of the role of basic behavioral research in answering clinical questions; the need to recognize and strengthen ties between the field of behavioral and psychosocial oncology and the basic behavioral and social science fields from which it emerged; and the importance of additional research on minorities and other special populations. It is suggested that meeting the challenges posed in each of these five areas is critical to continued progress in the field. 
4	Transient myocardial ischaemia after acute myocardial infarction. The prevalence and characteristics of transient myocardial ischaemia were studied in 203 patients with recent acute myocardial infarction by both early (6.4 days) and late (38 days) ambulatory monitoring of the ST segment. Transient ST segment depression was much commoner during late (32% patients) than early (14%) monitoring. Most transient ischaemia (greater than 85% episodes) was silent and 80% of patients had only silent episodes. During late monitoring painful ST depression was accompanied by greater ST depression and tended to occur at a higher heart rate. Late transient ischaemia showed a diurnal distribution, occurred at a higher initial heart rate, and was more often accompanied by a further increase in heart rate than early ischaemia. Thus in the first 2 months after myocardial infarction transient ischaemia became increasingly common and more closely associated with increased myocardial oxygen demand. Because transient ischaemic episodes during early and late ambulatory monitoring have dissimilar characteristics they may also have different pathophysiologies and prognostic implications. 
1	Temporal bone: three-dimensional CT. Part II. Pathologic alterations. Three-dimensional (3D) surface renderings were obtained from routine axial computed tomographic (CT) images in 15 patients with a variety of complex temporal bone abnormalities. The 3D CT reformations served as an adjunct to conventional sectional CT examination. While no diagnosis was substantially changed because of the 3D CT images, they did provide a more global perspective in cases of large tumors and fractures and at the postmastoidectomy site. Three-dimensional CT surface reformations are now practical and may be potentially useful for visualizing temporal bone lesions characterized by complex destructive change. 
5	Clinical and manometric aspects of diffuse esophageal spasm in a cohort of subjects evaluated for dysphagia and/or chest pain. Manometric criteria for diffuse esophageal spasm have recently been restated. In this study, a cohort of 358 subjects was evaluated in a gastrointestinal motility laboratory for dysphagia and/or chest pain. Applying the recently proposed criteria of Richter and Castell, 18 subjects (5%) were diagnosed as having DES. Dysphagia was the major complaint (89%), while 44% of patients complained of chest pain and 33% of both symptoms. All patients shared more than 30% simultaneous contractions after wet swallows interspersed with normal peristaltic sequences. Associated manometric findings were repetitive (greater than 3 peaks) contractions (67%), high-amplitude contractions (33%), spontaneous activity (22%), prolonged duration (11%), and lower esophageal sphincter abnormalities (5%). Radiology disclosed significant abnormalities in only 27% of DES patients. 
1	Clinical evaluation of interferons in malignant melanoma. The evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents. Studies of the value of interferons as adjuvant therapy in high-risk primary melanoma patients are necessary, but no results have been published to date. Human interferon alpha produces low response rates as a sole agent, but in combination with cimetidine, a 30% response rate has been achieved. Recombinant alpha interferons give responses of 15%-20% in advanced melanomas, and combination with cimetidine does not enhance the response rate. Recombinant alpha interferons have been used in combination with other interferons, cimetidine, monoclonal antibodies, and cytotoxics, with either no or small improvement in response rates. DTIC with recombinant interferon alpha-2a has been shown to produce objective response rates of 26%, with low toxicity and maintenance of quality of life. A randomized trial with DTIC as the sole agent, compared with combination treatment, is being conducted to determine the significance of this finding. 
5	Neurogenic inflammation of the rat trachea: fate of neutrophils that adhere to venules. The goal of this study was to determine whether neutrophils that adhere to the vascular endothelium in association with neurogenic inflammation in the respiratory tract migrate out of the blood vessels or whether they detach and reenter the circulation. We also sought to determine whether the fate of the neutrophils is influenced by neutral endopeptidase (NEP), an enzyme that degrades the tachykinins that produce neurogenic inflammation. Neutrophils in the tracheal mucosa of anesthetized pathogen-free rats were examined 5 min or 4 h after neurogenic inflammation was produced by an injection of capsaicin (100 or 200 micrograms/kg iv). In whole mounts of these tracheae stained histochemically for myeloperoxidase, adherent intravascular neutrophils had a spherical or teardrop (regular) shape and migrating neutrophils had a polarized amoeboid (irregular) shape. The number of regular neutrophils in the tracheae was increased at both times, but the increase at 4 h was only half that present at 5 min. The reduction between 5 min and 4 h was not offset by an appreciable increase in the number of irregular neutrophils, unless NEP was inhibited by phosphoramidon. We interpret these results as indicating that the rapid adherence of neutrophils to the vascular endothelium after an injection of capsaicin is followed by a gradual reentry of the neutrophils into the circulation and comparatively little neutrophil migration. However, when the effect of the stimulus is increased and/or prolonged by inhibition of NEP, some of the adherent neutrophils migrate out of the vessels. Thus the activity of NEP can regulate both the magnitude of the neutrophil adherence and the fate of the adherent cells. 
5	Intestinal metaplasia is age related in Barrett's esophagus. The correlation among cellular characteristics of Barrett's esophagus, patient age, and malignant neoplasm is not well documented. This study, which describes a population of 66 patients with Barrett's esophagus spanning 1 to 80 years of age, analyzes the cellular constituents of their lesional tissues by endoscopic biopsy and histochemical and morphometric studies. Goblet cell metaplasia, identified in 50% (n = 14) of pediatric patients, increased significantly to involve 84% (n = 32) of biopsy specimens from adult patients with Barrett's esophagus. This increase was exponential by linear regression analysis (R2 = .64) between the ages of 5 and 29 years. Pediatric patients usually had 25 or less goblet cells per square millimeter of Barrett mucosa with no identifiable epithelial dysplasia or cancer; Nissen fundoplication lessened esophageal inflammation, but the Barrett mucosa persisted. Goblet cell metaplasia maintained a plateau (mean of 57 cells per square millimeter of Barrett mucosa) between the ages of 41 and 80 years. Dysplasia, in situ carcinoma, or invasive carcinoma was found in patients with Barrett's esophagus who were aged 41 years or older. This study demonstrates persistence of Barrett mucosa, increased incidence of goblet cell metaplasia, and predictable changes in goblet cell number with advancing patient age. The relationship between Barrett mucosa and malignant neoplasm remains uncertain, but the goblet cell may serve as a marker of disease chronicity in which setting neoplasia evolves. 
2	Gastric outlet obstruction caused by traumatic pseudoaneurysm of superior mesenteric artery. Traumatic pseudoaneurysms of the superior mesenteric artery (SMA) are extremely rare. We describe two cases of posttraumatic proximal SMA pseudoaneurysms with symptoms of gastric outlet obstruction. Repair was accomplished by aorta-SMA bypass with saphenous vein. Injuries to the proximal SMA are easily missed at laparotomy, especially if intestinal ischemia or hematomas are absent. Recognition and repair are stressed to avoid the complications associated with pseudoaneurysm formation. 
4	Changes in myocardial ischemic threshold during daily activities. This study assesses the variations in myocardial ischemic threshold (heart rate at the onset of ischemia) during daily activities in patients with ischemic episodes on Holter monitoring. Eighty patients with known coronary artery disease, positive treadmill stress test results and greater than or equal to 2 ischemic episodes during a 24-hour period of Holter monitoring were studied. The lowest and the highest ischemic thresholds were determined for each patient. The mean lowest ischemic threshold was 85 beats/min, and the mean highest ischemic threshold was 109 beats/min. The highest ischemic threshold was identical to ischemic threshold values noted during exercise. Of the 895 ischemic episodes, 654 (74%) were preceded by a moderate (greater than 10%) increase in heart rate. The variability of ischemic threshold (difference in percentage between the highest and lowest ischemic thresholds) increased with the number of ischemic episodes (range 2 to 60%). However, in different patients with a similar number of ischemic episodes, different variability was observed. These differences in ischemic thresholds are probably indirect indicators of the vasomotor activity of the coronary arteries in different patients. 
1	Metastatic ciliary body carcinoid tumor. A 50-year-old man with a history of systemic carcinoid had decreased right eye vision and a darkly pigmented cilio-choroidal mass. Results of ultrasonographic and fluorescein angiographic examinations were consistent with a malignant melanoma. Fine-needle aspiration biopsy of the lesion identified it as a carcinoid metastasis. The patient refused both radiation and enucleation; complete excision with a cyclochoroidectomy was performed. Histopathologic examination showed a carcinoid neoplasm covered by marked hyperplasia of the retinal pigment epithelium that produced the pigmented appearance of the lesion. 
4	Cholesterol and coronary heart disease. Future directions. The importance of high serum cholesterol levels as a risk factor for coronary heart disease and the benefit of lowering cholesterol levels for reducing risk are being increasingly accepted. A broad consensus to this effect has led to the establishment of the National Cholesterol Education Program. Although the available evidence fully justifies this program, its practical application to the American public has generated a series of new questions that must be explored. For example, it can be questioned whether reduction in coronary risk through lowering cholesterol levels extends to both sexes and all age groups. For people with high cholesterol levels, dietary modification is undoubtedly the first step of management, but the fraction of people responding adequately to dietary change remains to be determined. Finally, indications for drug therapy and choice of drugs need further exploration, particularly in the area of cost vs benefit. Thus, continuing research must be carried out in parallel with clinical and public health application of cholesterol education. 
3	Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder. Twelve children with IQ scores of 50 to 74 (educable mental retardation) who met rigorous diagnostic criteria for attention deficit hyperactivity disorder participated in a double-blind crossover study of the efficacy of two doses of methylphenidate compared with placebo. Dependent measures included behavioral ratings, classroom work output, laboratory measures of attention and learning, and direct observations of social behavior. Improvement with medication on the Conners Hyperactivity Index was observed in 75% of subjects. Significant increases in work output, on-task behavior, and attentional skills were associated with methylphenidate. However, gains in measures of attention were not associated with improvement in learning, as measured by a paired associate learning task. Additionally, no significant increases in appropriate social interactions during free play were associated with methylphenidate. The results suggest that mentally retarded children with attention deficit hyperactivity disorder respond to methylphenidate at similar rates and in similar domains to that of the nonretarded population. 
2	Drug-induced colonic pseudo-obstruction. Report of a case. Colonic pseudo-obstruction may have many possible causes. Some of these are well described and pose no diagnostic problems. Drug-related colonic pseudo-obstruction remains underreported, but is of importance in modern society where drugs are endemically abused. This case highlights the importance of drugs in altering colonic motility and emphasizes the nonsurgical management of this condition. 
1	Continuous 5-fluorouracil infusion and alpha interferon in advanced cancers: a report of initial treatment results. Twenty-four patients with advanced metastatic cancer were treated with continuous intravenous 5-fluorouracil infusion 200-300 mg/m2/day and alpha interferon 3 million units subcutaneously 3 times per week. The average duration of treatment was 87 days (range 22-204 days). 5-fluorouracil could be infused 66% of the planned time on treatment, and patients received an average of 60% of the planned interferon injections. Objective tumor responses were seen in 6 of 17 previously untreated patients (35%). Twenty-two of the 24 patients (92%) experienced toxicity (greater than or equal to ECOG grade II) that required treatment interruption and subsequent dose reduction predominantly for the following reasons: mucositis (67%), hand-foot syndrome (21%), and leukopenia (25%). The incidence of treatment limiting toxicity is higher than previously observed with 5-fluorouracil infusion alone. This suggests true augmentation of 5-fluorouracil effect by interferon. 5-Fluorouracil infusion and alpha interferon is a potentially useful combination that needs further evaluation in future phase II and phase III trials. 
1	Effects of hypovolemia and transfusion on tumor growth in MCA-tumor-bearing rats. Pretransplant blood transfusion has been shown to significantly affect the outcome of renal transplantation. Evidence regarding the association of blood transfusions with growth or recurrence of solid tumors is still conflicting both in clinical and in experimental studies, although diminished survival has been suggested in several studies. To determine the influence of blood transfusions and hypovolemia, as separate or combined factors, on tumor growth, we evaluated the weight of a subcutaneously implanted sarcoma (methylcholanthrene-induced) in 35 rats. After reaching 1% tumor burden (day 0), the animals were separated into two groups: hypovolemia (shed volume, 15 ml/kg) or normovolemia. These groups were further divided according to resuscitation: OO (no resuscitation), BL (receiving syngeneic blood stored in citrate phosphate dextrose for 4 days, 15 ml/kg), SL (receiving 0.9% sodium chloride, 45 ml/kg). Tumor dimensions were determined daily by external measurement, and tumor weight was calculated. Hypovolemia exerted a significant influence on tumor growth, independent of the resuscitation modality. The rats that received blood transfusions showed an increased rate of tumor growth, compared to the animals that received saline solution or no treatment. No interaction was noted between the effects produced by hypovolemia and blood transfusion. We conclude that the hypovolemic event enhanced tumor growth independently of the resuscitation, and transfusion of citrate phosphate dextrose-blood stored for 4 days did influence tumor growth in this model. We suggest that the effect of blood transfusion in patients with cancer has to be redefined to account for the influence of possible hypovolemic events. 
5	Susceptibility to invasive Haemophilus influenzae type b disease and the immunoglobulin G2m(n) allotype. There has been considerable controversy about the role of the immunoglobulin G2m(n) allotype and risk of invasive Haemophilus influenzae type b (Hib) disease. This allotype was studied in a large cohort of Finnish children (178) with invasive Hib disease. The G2m(n) allotype distribution was similar to that in the normal white Finnish population. No increased risk of Hib disease could be associated with the n-/n- genotype [i.e., lack of G2m(n) allotype]. Thus, the G2m(n) allotype does not seem to be a major determinant of susceptibility to Hib infection among white populations in industrialized countries. 
1	Interleukin-2 immunotherapy in children. Immunotherapy with interleukin (IL)-2 possesses great potential in the treatment of immune-mediated diseases and cancers. However, only a few reports on a small number of children have appeared in the literature. From March 1988 to March 1989, 11 children and adolescents were treated with IL-2. They included 1 patient with hepatocellular carcinoma, 1 with hepatoblastoma, 6 with childhood atopic dermatitis, and 3 with juvenile rheumatoid arthritis. The dosages ranged from 10,000 to 50,000 U/kg every 8 hours by intravenous drip. The following side effects were observed: anorexia, fever, and chillness (100%), general malaise (82%), irritability (64%), diarrhea (100%), nausea and vomiting (73%), weight gain (82%), edema (82%), abdominal distension (73%), oliguria (82%), cough (91%), dyspnea (27%), pleural effusion (40%), hypotension (82%), skin eruption (82%), oral ulcer (18%), enlarged liver (73%) liver function abnormalities (82%), renal function impairment (36%), electrolyte imbalance (73%), anemia (91%), thrombocytopenia (54%), leukopenia (18%), and eosinophilia (73%). Immunologically, numbers of natural killer cells were increased and natural killer and lymphokine-activated killer cell activities were augmented after IL-2 treatment. There was a tendency for serum levels of IL-2 and receptor IL-2 to decrease, especially in patients with atopic eczema. Ten patients (91%) completed one course (9 to 12 days) of therapy, and the remaining patient interrupted the treatment because of intolerable adverse effects. Clinically, complete remission for 3 months was obtained in 1 juvenile rheumatoid arthritis patient, transient improvement (2 to 6 weeks) in all atopic dermatitis patients, minor response in the hepatoblastoma patient, and no response in the patient with hepatocellular carcinoma. 
1	CD11c (LEU-M5) expression characterizes a B-cell chronic lymphoproliferative disorder with features of both chronic lymphocytic leukemia and hairy cell leukemia. Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are two common chronic lymphoproliferative disorders, each having characteristic clinical, morphologic, and immunologic features. Phenotypically, CD5 reactivity in CLL and CD11c (Leu-M5) reactivity in HCL have characterized these two leukemias among B-cell disorders. In this study, we report 14 cases of a novel chronic lymphoproliferative disorder characterized by lymphocytosis and CD11c expression, but morphologically similar to CLL. The patients' ages ranged from 46 to 81 years (median 62). Eleven had palpable splenomegaly, five with markedly enlarged spleens; only one patient had generalized lymphadenopathy. The white blood cell count ranged from 5.2 to 131.0 x 10(9)/L (median 20.8). The morphologic diagnosis in all cases was CLL, with the cells usually having abundant cytoplasm. No morphologic features, of hairy cells were evident; tartrate-resistant acid phosphatase cytochemistry was negative in all cases. Bone marrow biopsies were available in 8 of 14. Four showed focal nodular infiltrates and two had diffuse infiltrates similar to CLL; two showed only minimal interstitial involvement. All cases expressed multiple B-cell markers, and 12 of 14 had monoclonal surface immunoglobulin. The leukemic cells of all cases strongly expressed CD11c, while CD5 was expressed in 7 of 14; only 1 of the 14 cases expressed the lymph node homing receptor, Leu-8. This unique group of leukemias appears to represent the malignant transformation of lymphocytes arising from a stage of lymphocyte differentiation between that found in typical cases of CLL and that of HCL. CD11c is known to have an important function in cellular adhesion and may be important in determining the pattern of lymphocyte tissue distribution found in this group of patients. 
4	Comparison of left ventricular ejection fraction by magnetic resonance imaging and radionuclide ventriculography in idiopathic dilated cardiomyopathy. To assess the validity of gated magnetic resonance imaging (MRI) in determining left ventricular (LV) ejection fraction (EF), MRI (Spin Echo, multislice-multiphase technique on the short-axis plane) was compared with equilibrium radionuclide ventriculography in 32 patients with idiopathic dilated cardiomyopathy. All patients underwent MRI and radionuclide ventriculography, performed consecutively on the same day (mean time interval between the 2 examinations: 40 minutes). Comparison with LVEF showed a high correlation (y = 0.79 X +3.51, r = 0.91; p less than 0.001). Mean difference between radionuclide ventriculography and MRI data was 1.7, with the 95% confidence interval 0.71 to 2.68: MRI slightly underestimated LVEF. MRI interobserver and intrapatient variability (assessed in 15 of 32 patients) showed a high correlation (r = 0.91, r = 0.98). In conclusion, data suggest that MRI, using the short-axis approach and the multislice-multiphase technique, is an accurate, noninvasive, highly reproducible method of evaluating LVEF in patients with idiopathic dilated cardiomyopathy. 
3	Ocular defects in infants of extremely low birth weight and low gestational age. The eyes of 49 babies who weighed less than 1,000 g at birth or who were born at or before 28 weeks gestation were examined at the age of 4 years. Twenty-one children were normal. The remaining 29 children (59%) had ocular abnormalities which ranged from mild amblyopia to blindness from retinopathy of prematurity. The need to examine children at risk is stressed. 
5	Coronary vascular remodeling and myocardial fibrosis in the rat with renovascular hypertension. Response to captopril. Progressive myocardial fibrosis, including the accumulation of collagen within the adventitia of intramyocardial coronary arteries, is seen in the hypertrophied rat myocardium secondary to renovascular hypertension (RHT) and has been held responsible for alterations in myocardial diastolic stiffness. This study was undertaken to test the hypothesis that this presumptive angiotensin-aldosterone mediated fibrosis and its functional consequences could be favorably altered by an antihypertensive oral dose (50 mg/kg/day) of the angiotensin converting enzyme (ACE) inhibitor captopril. Three groups were studied: control; untreated RHT for 8 weeks; treated RHT, with captopril started 48 h before banding and continued for 8 weeks. Interstitial collagen volume fraction and perivascular collagen area (morphometry), the fibrillar nature of collagen (picrosirius polarization), and the end diastolic stress-strain relation of the intact left ventricle were examined in each group. In comparison to untreated animals with RHT, we found that captopril, begun prior to banding, attenuated interstitial and perivascular fibrosis and prevented hypertrophy and the rise in diastolic stiffness 8 weeks later. Thus, an adverse accumulation of collagen in the interstitium and around intramyocardial coronary arteries, and its functional consequences in the rat with RHT, can be prevented by captopril. Other ACE inhibitors may have similar salutary effects, but remain to be evaluated. The pathogenetic origin of myocardial fibrosis in RHT requires further investigation, but appears to be related to the angiotensin-aldosterone system. 
4	Tolerance to organic nitrates: evidence, mechanisms, clinical relevance, and strategies for prevention. OBJECTIVE: To review the available information about nitrate tolerance, its potential mechanisms, clinical implications, and strategies for prevention. DATA IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database and bibliographies of the reviewed articles. STUDY SELECTION AND DATA EXTRACTION: Studies were selected from the English language literature with an emphasis on recent studies and, when available, randomized placebo-controlled studies. Old studies were selected on the basis of their historical value and originality. A total of 134 retrieved articles were considered relevant and were reviewed in depth. RESULTS: The available information about the experimental as well as the clinical evidence for tolerance to organic nitrates has been summarized. In addition, information related to potential mechanisms, clinical implications, and possible methods for prevention have been reviewed. CONCLUSIONS: Evidence indicates that prolonged in-vitro exposure to organic nitrates, continuous intravenous or topical administration of nitrates, and frequent in-vivo oral dosing result in the rapid development of tolerance to the peripheral as well as to the coronary vasodilatory effects of the drugs. This phenomenon leads to the rapid attenuation of the hemodynamic and anti-ischemic effects of nitrates in patients with ischemic heart disease or congestive heart failure, or both. Tolerance development seems to be dose- and time-dependent, and its main mechanism seems to be a depletion of sulfhydryl groups at the vascular cell. Although the repletion of sulfhydryl groups with the use of sulfhydryl-containing drugs may help to prevent tolerance, the efficacy and safety of this approach requires further evaluation. Intermittent therapy allowing a sufficiently long, daily nitrate-washout interval seems to be the most effective and the most safe strategy currently available for the prevention of nitrate tolerance. 
5	Pilot study of nicardipine for acute ischemic stroke. The author performed a pilot study of nicardipine (NC), a Ca(+)+ channel blocker, to study its dosing, toxicity, and possible efficacy for hemispheric cerebral infarction within 12 hours (mean 6.9 hr) of onset to determine the advisability of proceeding with a multi-centered controlled trial. NC was administered IV (3 to 7 mg/hr) X 72 hours by titrating dose to mean arterial blood pressure (MABP not less than 10% of baseline), then orally X 30 days. Forty-three patients have been entered; mean age 63 (range 34-89), 25 male and 18 female. Only 3 had CT evidence of infarct on entry. Results have shown improvement in a 100-point (pt) graded exam (40 pts at entry, 68 pts at 3 months). Of 20 patients completing 3 months' evaluation, 17 improved and none worsened. Sixteen out of 20 were at home and 8 had minimal or no impairment. Mean Barthel's index was 72. Mean maximal serum NC level was 75 ng/mL. MABP decreased from 103 (entry) to 83 (72 hours). A larger controlled study is warranted to determine the efficacy of NC for acute cerebral infarct. 
4	Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation Transesophageal echocardiography allows the evaluation of proximal coronary artery anatomy and coronary blood flow velocity (CBFV). To assess the potential of transesophageal echocardiography in evaluating CBFV and its variations induced by coronary-active drugs, we studied 15 patients by high-quality pulsed wave Doppler recordings of CBFV. In these patients, transesophageal Doppler evaluation of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg injected 4 minutes after cessation of dipyridamole infusion). The following CBFV parameters were evaluated at each of the three steps of the study protocol: maximal and mean diastolic velocities and maximal and mean systolic velocities. Furthermore, the following indexes of coronary flow reserve were evaluated: the ratio between maximal diastolic velocity recorded after and before dipyridamole administration and the ratio between mean diastolic velocity recorded after and before dipyridamole administration. Nine of the 15 patients had a normal left anterior descending coronary artery (group A), whereas the remaining six had significant (less than or equal to 75%) stenosis (group B). In group A patients, all CBFV parameters increased significantly during dipyridamole infusion and returned to near baseline values after aminophylline infusion. In group B patients, on the other hand, none of the CBFV parameters increased after dipyridamole infusion. Dipyridamole/baseline maximal diastolic velocity and mean diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p less than 0.01 versus group A) in group B patients. 
5	Reversal of chronic hepatic encephalopathy by colonic exclusion: poor correlation with blood GABA levels. Previous studies have suggested that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is a key factor in the syndrome of portasystemic encephalopathy. We report the case of a patient with medically intractable portasytemic encephalopathy after portacaval shunt who had marked clinical improvement after creation of an end ileostomy. Plasma GABA and serum ammonia levels were measured before and after ileostomy. Although the clinical syndrome and the EEG improved markedly after the ileostomy, the plasma GABA levels remained markedly elevated. Preoperative and postoperative GABA levels were 865 and 633 pmol/ml, respectively (nl = 100-180 pmol/ml). Our findings confirm previous reports of the efficacy of colonic exclusion in patients with intractable portasystemic encephalopathy. However, our results conflict with the hypothesis that GABA itself is the key mediator of the syndrome. 
2	Importance of the omentum in the development of intra-abdominal metastases. Areas of trauma are preferred sites for metastatic tumour growth. In extensive intra-abdominal tumour recurrence the omentum is invariably involved. The importance of the omentum in the development of tumours at sites of intra-abdominal trauma has been investigated. Colonic anastomoses were performed in Hooded-Lister rats with and without omentectomy. Animals received intraluminal or intraperitoneal injections of a syngeneic tumour. With intraluminal injection, tumour occurred at the anastomosis and in the omentum in 38 and 43 per cent of animals respectively but following omentectomy the values were 14 and 9 per cent (omental remnant). With intraperitoneal administration tumour occurred in 53 per cent at the anastomosis and in 79 per cent in the omentum compared with 16 and 29 per cent (in omental remnant) following omentectomy. In this model a reduced ability of an anastomosis to support 'seeded' tumour following removal of the omentum is demonstrated and the development of local recurrence from spilled tumour cells during operation may be enhanced by, or be dependent on, the proximity of the omentum. 
1	Vagal schwannoma associated with syncopal attacks and postural hypotension: a case report. A case of vagal schwannoma in the cerebellomedullary angle is reported. Preoperatively, the patient had paroxysmal episodes of postural hypotension with syncope. After total removal of the vagal tumor, her systemic blood pressure returned to normal. 
5	A comparison of neurological, metabolic, structural, and genetic evaluations in persons at risk for Huntington's disease. We compared four diagnostic data sets for the assessment of individuals at risk for Huntington's disease. Fifty-four chorea-free persons were evaluated by neurological examination, positron emission tomography measurement of glucose metabolism, radiographic computerized tomographic measurement of caudate size, and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125. Twelve (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities of motor control, and 7 (13%) had computed tomographic evidence of caudate atrophy, compared with an expected gene frequency of 34% for this population. In 20 persons with unambiguous genetic test results or the subsequent phenotypic expression of Huntington's disease (chorea), there was a greater sensitivity of the positron emission tomographic measurement of caudate metabolism (75%) relative to computed tomography (33%) or the clinical examination (17%) for the determination of a subpopulation of probable Huntington's disease gene carriers. Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the precentral gyrus were also associated with a high probability of carrying the Huntington's disease gene. The findings support the hypothesis that abnormalities of cerebral metabolism precede clinical or structural (computed tomographic) abnormalities in gene-positive individuals at risk for Huntington's disease. 
5	The perineal artificial sphincter for acquired incontinence--a cut and dried solution? Sixteen males with stress incontinence due to sphincter damage were investigated with videourodynamic studies after implantation of a perineal artificial urinary sphincter. Twelve patients were rendered dry; 4 remained incontinent, all of whom were shown by cystometry to have incontinence from detrusor instability. Of these, 2 also had stress incontinence proven by videourography. Detrusor instability was present in 9 patients before implantation; the instability worsened considerably in 2 patients and new instability was shown in another 2 patients. The limitations of the artificial urinary sphincter and the implications of detrusor instability in patients with an artificial sphincter are discussed. The artificial urinary sphincter is an extremely successful device for the treatment of acquired stress incontinence. 
4	Response of angiographically normal and atherosclerotic left anterior descending coronary arteries to acetylcholine. Acetylcholine-induced constriction of human coronary arteries in vivo is commonly attributed to endothelial dysfunction. To examine the effects of 2 other important determinants of vascular responses--namely, agonist concentration and the segment of circulation under study--the diameters of proximal, middle and distal segments of the left anterior descending artery (LAD) and coronary sinus oxygen saturation were measured in 10 patients with angiographically normal coronary arteries (group 1) and in 7 patients with coronary atherosclerosis (group 2) after intracoronary acetylcholine was infused at concentrations from 10(-7)M to between 10(-4)M and 10(-2)M. In group 1, acetylcholine caused minor (less than or equal to 6%) but progressive dilatation of the LAD up to 10(-4)M, but constriction, particularly of the distal segments and tertiary branches, occurred at higher concentrations. Over the same concentration range, coronary sinus oxygen saturation rose progressively from a basal level of 36 +/- 3% to a maximum of 72 +/- 3% in the absence of changes in heart rate and blood pressure, suggesting marked progressive dilatation of resistance vessels. Concentrations greater than or equal to 10(-3)M caused intense constriction of distal epicardial vessels and, in some cases, anginal pain and objective signs of ischemia. Conversely, in group 2, acetylcholine (infused only up to 10(-4)M for ethical reasons) failed to cause significant changes in LAD diameter. These data suggest that the local acetylcholine concentration and coronary vascular segment under study may determine the observed response to at least an equivalent extent as does the presence or absence of coronary atherosclerosis, raising the question of whether a constrictor response to intracoronary acetylcholine reliably indicates the presence of coronary atherosclerosis. 
4	Hirudin interruption of heparin-resistant arterial thrombus formation in baboons. To determine the role of thrombin in high blood flow, platelet-dependent thrombotic and hemostatic processes we measured the relative antithrombotic and antihemostatic effects in baboons of hirudin, a highly potent and specific antithrombin, and compared the effects of heparin, an antithrombin III-dependent inhibitor of thrombin. Thrombus formation was determined in vivo using three relevant models (homologous endarterectomized aorta, collagen-coated tubing, and Dacron vascular graft) by measuring: (1) platelet deposition, using gamma camera imaging of 111In-platelets; (2) fibrin deposition, as assessed by the incorporation of circulating 125I-fibrinogen; and (3) occlusion. The continuous intravenous infusion of 1, 5, and 20 nmol/kg per minute of recombinant hirudin (desulfatohirudin) maintained constant plasma levels of 0.16 +/- 0.03, 0.79 +/- 0.44, and 3.3 +/- 0.77 mumol/mL, respectively. Hirudin interrupted platelet and fibrin deposition in a dose-dependent manner that was profound at the highest dose for all three thrombogenic surfaces and significant at the lowest dose for thrombus formation on endarterectomized aorta. Thrombotic occlusion was prevented by all doses studied. In contrast, heparin did not inhibit either platelet or fibrin deposition when administered at a dose that maximally prolonged clotting times (100 U/kg) (P greater than .1), and only intermediate effects were produced at 10-fold that dose (1,000 U/kg). Moreover, heparin did not prevent occlusion of the test segments. Hirudin inhibited platelet hemostatic function in concert with its antithrombotic effects (bleeding times were prolonged by the intermediate and higher doses). By comparison, intravenous heparin failed to affect the bleeding time at the 100 U/kg dose (P greater than .5), and only minimally prolonged the bleeding time at the 1,000 U/kg dose (P less than .05). We conclude that platelet-dependent thrombotic and hemostatic processes are thrombin-mediated and that the biologic antithrombin hirudin produces a potent, dose-dependent inhibition of arterial thrombus formation that greatly exceeds the minimal antithrombotic effects produced by heparin. 
2	Fluorescence assays to monitor membrane fusion: potential application in biliary lipid secretion and vesicle interactions. Membrane fusion constitutes an essential, intermediate step in numerous cell biological processes, occurring for example during endocytosis, membrane recycling and exocytosis. Also less desirable events such as the infection of cells by animal viruses are mediated by membrane fusion during which the viral envelope merges with a cellular membrane, causing the expulsion of the viral nucleocapsid into the cytoplasm of the cell as an initial step in virus replication. Much of our current knowledge concerning the mechanism of membrane fusion has been derived from studies using simple artificial membranes, such as liposomes or phospholipid vesicles, as model systems. A most essential feature of these studies has been the development of membrane fusion assays that register in a sensitive and continuous fashion the mixing of membranes or the aqueous volumes initially enclosed by these membranes. Not only do these assays allow one to readily detect and quantify fusion, but they also provide the possibility to relate the kinetics of fusion to the rate by which certain molecular changes in membranes take place. Obviously, this insight is of relevance for understanding the mechanism of membrane fusion. The principles and applications of some representative assays that rely on the use of fluorescence spectroscopy will be discussed. Assays that monitor membrane mixing are commonly based on the detection of changes in resonance energy transfer efficiency or the relief of fluorescence self-quenching of appropriate fluorescent lipid analogs. Contents mixing assays rely on either the formation of a (aqueous-soluble) fluorescent complex or quenching of a fluorophore, encapsulated in one vesicle population, by a suitable quencher, entrapped in a second population. 
3	Angiotropic intravascular large-cell lymphoma (malignant angioendotheliomatosis): report of a case and review of the literature. We present a case of angiotropic large-cell lymphoma and review the literature in order to define the neurologic features of this rare disorder. This is the first report of gadolinium-DTPA imaging in angiotropic large-cell lymphoma that demonstrates infarcts of multiple ages, as well as striking meningeal enhancement. Angiotropic large-cell lymphoma should be suspected in patients with clinical evidence of small and large cerebral vessel disease and diagnosis requires skin, liver, renal, meningeal, or brain biopsy. Single modality treatment, using either radiation therapy or steroids, has been ineffective, and new findings of a lymphomatous origin of this neoplasm suggest that combination chemotherapy may be indicated. 
5	Long-term follow-up of patients operated on for recurrent carotid stenosis. We reviewed our experience with 29 operations for recurrent carotid stenosis in 27 patients who underwent both their primary carotid endarterectomy and their reoperations at our institution. These 27 patients represent 4% of the 667 patients who underwent primary carotid endarterectomies at our institution and who are included in our carotid follow-up registry. Reoperation was prompted by recurrent symptoms in 19/29 (65.5%) cases. Comparison of long-term stroke prevention in those patients who did (84% at 5 years, 78.6% at 10 years) and did not (90.3% at 5 years, 83.6% at 10 years) develop recurrent stenosis requiring reoperation revealed no statistically significant difference (p = 0.48) when measured from the time of primary operation. The perioperative stroke and death rates for reoperation (3.4% and 0%) were acceptable. We conclude that with our acceptably low perioperative stroke morbidity (3.4%), surgery for recurrent carotid stenosis in symptomatic patients or in asymptomatic patients with high-grade (greater than or equal to 75%) stenosis maintains the durable stroke prevention offered by primary carotid endarterectomy. 
5	Brain magnetic resonance imaging and neuropsychologic evaluation of patients with idiopathic dilated cardiomyopathy. We compared brain magnetic resonance imaging and neuropsychologic performance in 20 neurologically asymptomatic patients suffering from idiopathic dilated cardiomyopathy (mean age 41 [range 18-49] years) and 20 age-matched controls (mean age 38 [range 28-49] years). Patients exhibited a significantly higher rate of cerebral infarcts (20% versus 0%, p less than 0.05) and cortical (50% versus 5%, p less than 0.01) and ventricular (55% versus 15%, p less than 0.02) atrophy than controls. Accordingly, semiquantitative volumetric measurements yielded a significantly increased ventricular-to-intracranial cavity ratio in the patients (6.2 +/- 2.9% versus 4.1 +/- 1.3%, p less than 0.01). This ratio and the cortical atrophy ratings correlated positively with disease duration (r = 0.63 and 0.54, p less than 0.05). Cognitive test performance was significantly worse in patients than in controls and was most impaired in those patients with morphologic cerebral abnormalities. 
3	Eosinophilia-myalgia syndrome associated with L-tryptophan use. The eosinophilia-myalgia syndrome associated with the use of oral preparations of the amino acid L-tryptophan was recognized in late 1989. We describe the clinical and laboratory manifestations, pathological findings and early clinical course of 20 patients with the eosinophilia-myalgia syndrome. Prominent clinical findings included severe myalgias limiting function, fatigue, rashes, edema and weight gain, weight loss, muscle weakness and shortness of breath. Laboratory findings included eosinophilia (often marked), normal erythrocyte sedimentation rate, and elevated aldolase with normal or low creatine kinase values. On biopsy fascial inflammation was always seen consisting of lymphocytes, histiocytes and eosinophils in a perivascular distribution. Invasion of the vascular wall by lymphocytes was seen in 20%. Capillary and arteriolar endothelial cell thickening was found in most cases on electron microscopy and endothelial cell necrosis or mural invasion by lymphocytes was seen in 25% of cases. Two patients improved with no therapy. Ten patients responded to therapy with prednisone alone. Three patients have had progressive disease and one of these died. The relationship of this syndrome to previously described disease entities associated with eosinophilia is discussed. 
2	Aspiration in bilateral stroke patients. Seventy patients with bilateral strokes underwent neurologic and videofluoroscopic barium swallowing examinations; 34 (48.6%) aspirated. Patients with aspiration were more likely to have posterior circulation strokes, abnormal cough, abnormal gag, and dysphonia. However, patients likely to aspirate can be identified best by the presence of an abnormal voluntary cough, an abnormal gag reflex, or both. The prediction of patients at risk for aspiration was not improved by additional clinical information (ie, presence of dysphonia or bilateral neurologic signs). 
5	The lateral approach for operative release of post-traumatic contracture of the elbow. A lateral approach was used to release a post-traumatic contracture of the elbow in seven patients, and the results were evaluated an average of thirty-eight months postoperatively. Extension improved from an average flexion contracture of 45 degrees preoperatively to one of 12 degrees postoperatively, and the average point of maximum flexion increased from 116 degrees preoperatively to 129 degrees postoperatively. The average arc of motion increased 46 degrees. All patients began using a continuous-passive-motion device immediately after the operation. There were no problems with wound-healing or formation of heterotopic bone. 
5	Identification of three related human GRO genes encoding cytokine functions. The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate. One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide. 
5	Histologic abnormalities of large and small coronary arteries, neural structures, and the conduction system of the heart found in postmortem studies of individuals dying from the toxic oil syndrome. Hundreds died and thousands were poisoned by rapeseed oil adulterated with aniline and sold illegally in Spain in 1981. The clinical manifestations, now known as the toxic oil syndrome, include pulmonary hypertension and right ventricular hypertrophy plus widespread vascular and neural lesions in other organs. Many of the late deaths ended with a scleroderma-like illness. Because scleroderma involves the heart, in this study we examined the small and large coronary arteries, neural structures, and conduction system from eight victims dying with the toxic oil syndrome. Dense fibrosis of the sinus node in two hearts resembled changes found in scleroderma. Atrionodal junctional hemorrhages and cystic degeneration of the sinus node present in the other six hearts resembled changes found in lupus erythematosus. Small and large coronary arteries exhibited focal fibromuscular dysplasia and a proliferative cystic myointimal degeneration. This latter abnormality was associated with sloughing of the inner wall and embolization of the detached fragment downstream in the same coronary artery. Every heart had many degenerative lesions within nerves, ganglia, and the coronary chemoreceptor. Both the arterial and neural abnormalities prominently involved the conduction system. Based upon observations by others with experimental feeding of rapeseed oil containing either high or low erucic acid, we suggest that this oil must remain a major suspected cause of the toxic oil syndrome, particularly in conjunction with some as yet unexplained facilitative influence by oleoanilids. If this is so, it is important to reconsider the widely recommended use of any rapeseed oil product as a suitable food for man or other animals. 
4	Plasma norepinephrine and dihydroxyphenylglycol in essential hypertension. The aim of the present study was to examine whether essential hypertension is associated with altered plasma concentrations of dihydroxyphenylglycol, the principal presynaptic metabolite of norepinephrine. Forearm venous plasma dihydroxyphenylglycol and norepinephrine were determined at rest and during graded orthostasis in 47 normotensive control subjects and 58 outpatients with essential hypertension. There was no group difference in age. At supine rest as well as during sitting and standing, hypertensive subjects had plasma norepinephrine concentrations similar to those in normotensive control subjects, but plasma dihydroxyphenylglycol concentrations were higher than those in normotensive control subjects. Both groups showed a linear relation between plasma dihydroxyphenylglycol (ordinate) and plasma norepinephrine (abscissa). The resulting regression line was steeper (p less than 0.02) and its ordinate intercept higher (p less than 0.01) in hypertensive than in control subjects. Eleven normotensive and 14 hypertensive subjects were also tested 3 hours after desipramine (1.5 mg/kg orally) was administered to inhibit neuronal norepinephrine reuptake. The drug did not alter plasma norepinephrine, but did reduce plasma dihydroxyphenylglycol and did abolish plasma dihydroxyphenylglycol responses to upright posture in both groups of subjects. The mean plasma dihydroxyphenylglycol concentration observed in the presence of desipramine again was higher in the hypertensive than in the control group (p less than 0.01) and closely agreed, in both groups, with the dihydroxyphenylglycol concentration given by the ordinate intercept of the dihydroxyphenylglycol versus norepinephrine regression line in the absence of desipramine. 
4	Duplex scanning of normal or minimally diseased carotid arteries: correlation with arteriography and clinical outcome. This study evaluated the role of duplex scanning in the management of patients with normal or minimally diseases carotid arteries. Carotid duplex scans were interpreted according to previously established criteria and considered normal when pulsed Doppler spectral waveforms showed laminar flow or only minor flow disturbances. Normal flow patterns were noted by duplex scanning in 100 carotid bifurcations of 72 patients who also underwent carotid arteriography. Neurologic symptoms (amaurosis fugax, transient ischemic attack, or stroke) were present in relation to 23 arteries and absent in relation to 77 arteries. On the 23 symptomatic sides arteriography was interpreted as normal in eight, 1% to 15% stenosis in 14, and 16% to 40% stenosis in one. For the 77 asymptomatic sides, arteriography showed normal vessels in 15, 1% to 15% stenosis in 43, and 16% to 40% stenosis in 19. One symptomatic patient was treated by carotid endarterectomy for an irregular 1% to 15% stenosis. None of the asymptomatic lesions were in the range of 80% to 99% stenosis, which would justify endarterectomy for asymptomatic disease. Clinical follow-up for a mean interval of 28 months on 20 of the 22 symptomatic patients not undergoing surgery revealed no strokes and transient recurrent symptoms in two patients. Assuming that the single operation in this study was indicated, duplex scanning correctly identified lesions not requiring carotid endarterectomy in 96% (22/23) of the symptomatic patients. A normal duplex scan also predicted a benign clinical outcome without operation. Duplex scanning can reliably exclude surgically treatable carotid bifurcation lesions in asymptomatic patients, and endarterectomy is rarely indicated in symptomatic patients with normal duplex scan results. This study supports a nonoperative therapeutic approach for most patients with neurologic symptoms and a normal carotid duplex scan on the appropriate side. 
5	Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. The lumbar and cervical spinal dorsal horns of adult rats with a chronic (8 days) constriction injury of the sciatic nerve on one side (and a sham operation on the other) were examined for signs of transsynaptic degeneration. The incidence of neurons with signs of degeneration (pyknosis and hyperchromatosis; 'dark neurons') was significantly increased in the lumbar dorsal horn on both sides. The ipsilateral lumbar increase was significantly greater than the contralateral increase. There was no increase in the incidence of dark neurons in the cervical dorsal horns of the same rats. The distribution of lumbar dark neurons was similar bilaterally. The majority of the dark neurons were found in the sciatic nerve's territory in laminae I-II. A second group of rats received the same surgery but in addition received a series of 7 daily subconvulsive doses of strychnine. Dark neurons were again found bilaterally (with ipsilateral predominance) in the sciatic nerve's territory in lumbar laminae I-II, but the incidence was significantly greater than that found in the group that did not receive strychnine. The same result was obtained in a third group of strychnine-treated rats when the sham operation was omitted. Thus the appearance of contralateral dark neurons is not dependent on unintentional nerve damage created by the sham procedure. An additional group of rats was sacrificed 8 days after receiving a unilateral sciatic nerve transection, a contralateral sham operation, and the 7 daily strychnine injections. There was no increase in the incidence of dark neurons in any of these rats. 
1	Correlations of acoustic tissue typing of malignant melanoma and histopathologic features as a predictor of death. Forty-six eyes with uveal melanoma were scanned with a computerized diagnostic ultrasound system before enucleation, and light microscope sections were obtained. Tumors were characterized by ultrasonically measured dimensions and power spectrum analysis, which provided information not available in conventional A- or B-scan ultrasonography. Histopathologic features, including cell clustering pattern, cell type, pigmentation, vascularity, and necrosis, were quantified. Statistically significant correlations were found between parameters derived from the power spectrum and histologic characteristics. Patients were followed up for up to ten years with 14 deaths occurring because of metastases. Using a Cox relative risk model with histopathologic data, a risk model comprising pigmentation and cell type (P less than .0001) was obtained. Using ultrasonic characteristics, a model comprising tumor volume and scatterer concentration (P = .0062) was obtained. The results suggest that ultrasonic tissue characterization and three-dimensional biometry may provide improved in vivo prognostic indicators for uveal melanoma. 
5	Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood. In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO. 
2	In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity. 
3	Centrifugal intensity and duration as countermeasures to soleus muscle atrophy. Mechanical acceleration is a countermeasure that may be employed to prevent atrophy of slow-twitch muscle during non-weight bearing. In the present study, daily centrifugation of rats for different durations (1 or 2 h) and at different gravitational intensities (1.5 or 2.6 G) was used to test whether mechanical acceleration could ameliorate the atrophy of the soleus muscle induced by non-weight bearing (tail-traction model). The soleus muscle atrophied 32% during 7 days of non-weight bearing without countermeasures. Centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Non-weight-bearing groups receiving 2-h daily treatments of 1, 1.5, or 2.6 G had 48, 56, and 65%, respectively, of the atrophy observed in the non-weight-bearing-only group compared with the precontrol group. No evidence was obtained that centrifugation at 2.6 G was more effective than exposure to 1 or 1.5 G as a countermeasure to non-weight-bearing-induced atrophy of the soleus muscle. 
5	Palliative treatment of bile duct tumoral compression by an endoprosthesis: clinical results. The palliative therapy of stenoses of the biliary tract is a difficult choice. Because percutaneous or endoscopic drainage methods are fraught with complications, an endoprosthesis for surgical intubation of the biliary tract has been developed. Thirty patients were treated by this method. After choledochotomy, the endoprosthesis is positioned surgically above the sphincter of Oddi, thereby avoiding ascending cholangitis. Twenty-nine patients (13 with gallbladder cancer, 11 with cholangiocarcinomas, 5 with metastases) presented with neoplastic compression, and one patient had an early postoperative stricture with loss of substance after right hepatectomy for hepatic metastases. The operative mortality was 3.3% (one pulmonary complication). Resolution of jaundice was obtained in all but two patients, and pruritus always resolved. The mean survival time for the patients with cholangiocarcinoma was 12.2 months and 6.33 months for those with gallbladder cancer. Indices of satisfaction (Bismuth's method) were 71% (gallbladder cancer), 93.5% (hilar cholangiocarcinoma), and 92% (metastatic compressions). This new type of surgical endoprosthesis is an alternative in the palliative treatment of neoplastic hilar compression because it is well tolerated, has a low rate of operative mortality or morbidity, and affords an acceptable quality of life for the patients. 
1	Myogenic regulatory protein (MyoD1) expression in childhood solid tumors: diagnostic utility in rhabdomyosarcoma. Transcripts for the muscle regulatory gene MyoD1 are expressed during normal skeletal muscle myogenesis and in rhabdomyosarcomas but not in other tissues or in soft-tissue sarcomas. Here we report the distribution of MyoD1 protein, determined by reactivity with anti-MyoD1 polyclonal sera in normal tissues, rhabdomyosarcoma cell lines, and in a variety of pediatric solid tumors. The distribution of MyoD1 protein was highly restricted in normal tissues and was detected only in fetal skeletal muscle and more faintly in adult skeletal muscle. All six human rhabdomyosarcoma cell lines analyzed expressed MyoD1 mRNA transcripts as well as immunoreactive protein. The immunohistochemical expression of MyoD1 protein was then examined in 49 surgical specimens from a variety of pediatric solid tumors. Each of 16 rhabdomyosarcoma specimens was positive for MyoD1, including four that did not express the intermediate filament protein desmin. Two of five specimens originally designated sarcoma type indeterminate (STI) and two of three specimens originally designated extraosseous Ewing's sarcoma (EOE) were positive for MyoD1, suggesting commitment to myogenic differentiation. Three of eight Wilms' tumors, which also expressed desmin and had clearly evident myogenic elements, also were positive for MyoD1. Tumors that failed to express MyoD1 protein included neuroblastoma, primitive neuroectodermal tumor, non-Hodgkins lymphoma, embryonal sarcoma of the liver, malignant fibrous histiocytoma, malignant rhabdoid tumor, and Ewing's sarcoma of the bone. These results indicate that expression of MyoD1 protein is highly restricted in normal human tissues and that expression of this gene product in malignant tissue may be diagnostic for rhabdomyosarcoma. Furthermore MyoD1 staining may be a valuable adjunct in the classification of pediatric soft-tissue sarcomas. 
3	The Children's Orientation and Amnesia Test: relationship to severity of acute head injury and to recovery of memory. The Children's Orientation and Amnesia Test (COAT) was developed to assess cognition serially during the early stage of recovery from traumatic brain injury in children and adolescents. The norms for the COAT, which is composed of 16 items evaluating general orientation, temporal orientation, and memory, were defined from data obtained from 146 children aged 3 to 15 years. In 37 patients with head injuries, the duration of posttraumatic amnesia, as indicated by the number of days COAT scores were in the impaired range, was significantly related to both verbal and nonverbal memory at the baseline and 6 and 12 months after injury. COAT scores were a better predictor of verbal and nonverbal memory performance than the Glasgow Coma Scale score at 6 and 12 months after the injury. This study shows that the COAT has adequate reliability and validity as a measure of the duration of posttraumatic amnesia in children and adolescents. 
2	Brain and liver dolichol in chronic alcoholism: a necropsy study. Cerebral gray and white matter and liver dolichol levels were measured in postmortem samples from chronic alcoholics and nonalcoholic controls following recent suggestions that dolichol levels may be used as a marker for alcoholism. No significant differences in brain dolichol were found between the control and alcoholic groups. A significant reduction in the liver dolichol was observed in the alcoholic group. This was most marked in those alcoholics with liver disease. 
1	Technetium-99m-HMPAO brain SPECT in medically intractable temporal lobe epilepsy: a postoperative evaluation. The aim of the present study was to evaluate the predictive value of interictal single-photon emission computed tomography (SPECT) using technetium-99m-labeled hexamethyl propyleneamine oxime (HMPAO) for the outcome after temporal lobectomy in patients with complex partial seizures. Out of 40 patients, 21 underwent right-sided and 19 left-sided temporal lobectomy. EEG and CT/MRI were primarily used to select the side of surgery. SPECT results correlated with temporal lobectomy in 68% of the patients. After surgical intervention, memory function was tested for both sides. Following left-sided temporal lobectomy, verbal memory was impaired in 8% of the patients, if SPECT agreed with the side selected for surgery, but in 83%, if it diverged from it. In the present study, there was no relationship between SPECT concordance with the side of temporal lobectomy and outcome as to seizure frequency and non-verbal memory. We conclude that preoperative interictal HMPAO/SPECT can contribute to the prediction of postoperative verbal memory function and that this method should be considered for use prior to temporal lobectomy. 
1	Efficacy of radical neck dissection for the control of cervical metastasis after radiotherapy for nasopharyngeal carcinoma. Fifty-one patients who had persistent or recurrent neck disease from nasopharyngeal carcinoma after radiotherapy underwent radical neck dissection. The follow-up period ranged from 0.5 to 9 years (median: 2 years). Multiple cervical lymph node involvement was present in 51% of the patients (26 of 51). Malignant cells were detected in 88% of the resected specimens (45 of 51). The clinical sign of fixation of lymph node is the only factor that affects the successful control of neck disease (p = 0.04). Extracapsular extension of the nodal disease was present, and 35% of the lymph nodes were adherent to surrounding structures at operation (18 of 51). There was one hospital mortality and the overall morbidity was minimal. The actuarial survival at 5 years was 38%, and the probability of control of neck disease was 66%. Radical neck dissection is effective in controlling post-irradiation cervical metastasis from nasopharyngeal carcinoma. 
5	Functional heart replacement with the spindle pump: first results. The spindle pump is a nonpulsatile blood pump with a double function, i.e., it works centrifugally and represses simultaneously. The first experiences with this type of pump used as a biventricular assist device in four short-term animal experiments (up to 13 hours) are described. It can be demonstrated that in cases of a normally beating heart, this BVAD decompresses both ventricles by 60-70%, while the aortic pressure is slightly increased; on the other hand, in case of ventricular fibrillation, the BVAD with two spindle pumps maintained the entire circulation, at an arterial pressure between 80 and 90 mmHg with a flow volume between 3.5 and 4 L/min. 
5	Leukocyte larceny: spurious hypoxemia confirmed with pulse oximetry Leukemic patients with extremely high white blood counts may exhibit the phenomenon of leukocyte larceny, in which white blood cells metabolize plasma oxygen in arterial blood gas samples (ABG) producing a spuriously low oxygen tension. We report the case of a leukemic patient with a white blood count in excess of 500,000 in whom multiple ABGs documented hypoxemia out of proportion to his clinical picture. Pulse oximetry was used to confirm higher hemoglobin oxygen saturation to establish the leukocyte larceny. 
1	Clinical management of gastric cancer and concomitant esophagogastric varices. We report the late results of treatment of 13 consecutive patients with gastric cancer and concomitant esophagogastric varices. Of seven good-risk patients classified as Child's class A or B, gastrectomy together with selective shunt operation was performed in two, total gastrectomy with splenectomy in three, and distal partial gastrectomy with paraesophageal devascularization without splenectomy in one. The remaining patient with early gastric cancer underwent distal partial gastrectomy following repeated endoscopic injection sclerotherapy (EIS) for treatment of the esophageal varices. Although the majority of patients who underwent surgical repair of varices (i.e., shunt, splenectomy, or devascularization) died, total gastrectomy with splenectomy was the only procedure that led to control of the esophageal varices. Since partial gastrectomy combined with EIS limits the morbidity and mortality of an extensive resection and at the same time controls esophageal variceal bleeding, it is probably the procedure of choice for patients with a carcinoma in the lower two-thirds of the stomach. Concerning non-surgical cases, two patients were effectively treated using laser endoscopy and EIS, without the occurrence of variceal bleeding. The remaining four patients, given chemotherapy or irradiation for treatment of gastric carcinoma, died within 4 months with variceal bleeding or liver failure. For the poor-risk patients with evidence of severe liver dysfunction, laser treatment and EIS would be the treatment of choice. 
3	Serious migraine: a study of some epidemiological aspects. Data are scant concerning some epidemiological aspects of those severe headaches which cause serious personal and economic morbidity. Our purpose was to study the incidence and other epidemiological features of patients suffering from severe migraine exacerbations, in an unselected population. The 64 patients who suffered from severe migraine bouts represented 10.5% of all the new walk-in neurological consultations in the area covered in this study. 70% of these patients were between 10 and 39 years old. Although females clearly predominated in all ages after fifteen, below this age there was a slight male predominance. The calculated incidence of serious migraine exacerbations was 90 per 100,000 people per year, the corrected incidence for females being 143/100,000 and for males 37/100,000. The highest incidence for females was in 15-19 year-olds (377/100,000) and for males in 10-14 year-olds (166/100,000). Our data seem to confirm the periodic nature of this condition since in 80% of patients the migraine bouts (ie: groups of attacks) lasted between two and nine months. Also they support the reported existence of genetic and hormonal factors in the susceptibility to migraine exacerbations. Our results may help in planning the public health aspect of migraine and add some light to the natural history of this common condition. 
2	Geriatric constipation: brief update on a common problem. Constipation occurs frequently in the elderly and is often multifactorial in origin. A search for an underlying cause is necessary, and can often be found by taking an adequate history and performing a thorough physical examination. A minority of patients require further investigation, guided by the clinical setting. Management should be directed at correcting the underlying cause and providing dietary advice and, less commonly, medication to allow restoration of a normal bowel habit. 
4	The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion. The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion. Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group). The mean arterial pressure fell to similar levels (p less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and 27 +/- 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals tested in the low-dose group, but did not increase (p greater than 0.05) in the four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05). Mean cerebral blood flow levels decreased in all groups during hypotension (p less than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/- 13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to 22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the high-dose group. In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue. In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered. It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model. 
1	Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome Tumour suppressor genes, whose usual function seems to be controlling normal cell proliferation, have been implicated in many inherited and sporadic forms of malignancies Much evidence supports the concept of tumour formation by loss-of-function mutations in suppressor genes, as predicted by the two-hit model of Knudson and DeMars. The suppressor gene, p53, is affected in such a manner by numerous mutations, which occur in a variety of human tumours. These mutations usually represent the loss of one allele and the substitution of a single base in the other. We have now analysed the p53 gene in a family affected by Li-Fraumeni syndrome, a rare autosomal dominant syndrome characterized by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites. In some instances the neoplasms seem to be related to exposure to carcinogens, including ionizing radiation. The Li-Fraumeni family that we studied had noncancerous skin fibroblasts (NSF) with an unusual radiation-resistant phenotype. DNA derived from the NSF cells of four family members, spanning two generations, had the same point mutation in codon 245 (GGC----GAC) of the p53 gene. This mutation leads to substitution of aspartic acid for glycine in one of the regions identified as a frequent target of point mutations in p53. The NSF cell lines with the mutation also retained the normal p53 allele. This inherited p53 mutation may predispose the members of this family to increased susceptibility to cancer. 
2	Duodenal ulcer hemorrhage with and without dyspepsia. To clarify the clinical significance of dyspepsia in patients with bleeding duodenal ulcer, we studied 298 patients prospectively. Ages of patients ranged from 16 to 81 yr (mean 45.9). There were 244 (82%) dyspeptic and 54 (18%) nondyspeptic patients. In the dyspeptic group, significantly more patients were taking nonsteroidal anti-inflammatory drugs. In the nondyspeptic group, there was a higher percentage of patients with duodenal bulb deformity (p less than 0.005), which deformity was related to previous peptic ulcer disease. The age, sex, past history of dyspepsia or bleeding, consumption of alcohol and cigarettes, and the hospital course of the two groups of patients did not differ significantly. Our results show that the clinical course of duodenal ulcer hemorrhage is not significantly different in patients with or without dyspepsia, and indicate that bleeding and dyspepsia probably are two independent presentations in the natural course of the disease. The significance of the correlation between dyspepsia and duodenal bulb deformity is discussed. 
3	Validation of a surveillance case definition of carpal tunnel syndrome The National Institute for Occupational Safety and Health (NIOSH) has proposed a surveillance case definition for work-related carpal tunnel syndrome (CTS). The case definition requires the presence of median nerve symptoms; one or more occupational risk factors; and objective evidence of CTS including one of three physical examination findings or nerve conduction tests diagnostic of CTS. We evaluated the performance of the NIOSH case definition, restricting our analysis to cases in which physical examination findings served as the objective criterion. Nerve conduction studies were used as the gold standard. Seventy-eight workers were studied; 38 percent had CTS. The NIOSH case definition had sensitivity of 0.67 (95% CI = 0.57, 0.77), specificity of 0.58 (95% CI = 0.47, 0.69), and positive and negative predictive values of 0.50 (95% CI = 0.39, 0.61) and 0.74 (95% CI = 0.64, 0.84), respectively. Overall 38 percent of subjects were classified incorrectly. In a sample with a prevalence of 15 percent, as might be encountered in high risk workplaces, the positive predictive value would be 0.22. In conclusion, when physical examination findings serve as the objective criterion the performance of the case definition is modest reflecting the limited diagnostic value of its component tests and indicating that effective screening for CTS awaits improved diagnostic techniques. 
3	Evaluating oxygen delivery and oxygen utilization with mixed venous oxygen saturation monitoring: a case study approach. Three cases studies are presented to demonstrate clinical application of mixed venous oxygen saturation (SvO2) monitoring in critical care nursing practice. Examples of critically ill patients are used to demonstrate how SvO2 monitoring can be used in clinical practice to reflect an imbalance between oxygen delivery and oxygen utilization. In the first case, the patient had a problem with oxygen delivery. Continuous SvO2 data aided nurses in guiding, adjusting, and assessing therapy. The second case demonstrates how SvO2 monitoring can provide an early sign of a life-threatening complication. The final case is one in which the patient had a problem with oxygen utilization. In all the cases, continuous SvO2 data provided important information about the balance between oxygen delivery and oxygen utilization. 
5	Ulcerative lesions and herpes simplex virus type 2 in a patient with Evan's syndrome. We have described a case of herpes genitalis in a patient with Evans's syndrome who had violaceous macules leading to deep ulcerations. This case serves as a reminder that HSV infection may be atypical and have an unusual course in immunocompromised patients. With the availability of specific therapy for this infection, it is important to consider HSV in the differential diagnosis of all ulcerative skin lesions. 
1	A comparison of Ho's, International Union Against Cancer, and American Joint Committee stage classifications for nasopharyngeal carcinoma. Five hundred sixty-four nasopharyngeal carcinomas (NPC), mostly of undifferentiated histologic type, were studied for survival, distant metastasis, and local recurrence. All had computerized tomography of the nasopharynx and skull base (CT-NP) and fiberoptic nasopharyngoscopy for evaluation of the primary tumor. Regional disease was assessed by palpation. A computer data base was formed on presentation, containing all information required for staging according to Ho's, the International Union Against Cancer (UICC), and the American Joint Committee (AJC) classifications. The three were compared for their efficacy in predicting prognosis. Ho's classification was superior to the other two because its overall stages differed from one another more significantly in the actuarial survival (ASR), disease-free survival (DFS), and freedom from distant metastasis (FDM) rates, and its N staging was more accurate in predicting FDM. Stages T1 and T2 of UICC/AJC were similar in the freedom from local recurrence rate (FLR) and should be grouped together, equivalent to Ho's T1. A more even patients number distribution among the stages also favored the use of Ho's classification. 
2	Reduction in hepatic venous pressure gradient as a consequence of volume contraction due to chronic administration of spironolactone in patients with cirrhosis and no ascites. The effect of plasma volume contraction induced by a 4-wk administration of spironolactone or furosemide on the hepatic venous pressure gradient was evaluated in consecutively allocated patients with cirrhosis and no ascites. In the spironolactone group (n = 15), the hepatic venous pressure gradient decreased significantly (p less than 0.005), by 21.8%, with a significant contraction of circulating plasma volume (p less than 0.01). Although there were no statistically significant correlations between the change in hepatic venous pressure gradient and changes in circulating plasma volume or in simultaneously determined systemic hemodynamics, a significant negative correlation (r = -0.74, p less than 0.01, n = 12) between the hepatic venous pressure gradient change and the post-treatment plasma aldosterone levels was found. However, in the furosemide group (n = 10), the hepatic venous pressure gradient and circulating plasma volume did not significantly decrease. Our data demonstrated a significant reduction in the hepatic venous pressure gradient on a chronic administration of spironolactone, which may have been due to volume contractions in patients with cirrhosis and no ascites. 
1	Generation of "soft x-rays" by using the free electron laser as a proposed means of diagnosing and treating breast cancer. The diagnosis and treatment of breast lesions may be markedly enhanced by the use of a unique new source of near-monochromatic x-rays. Concentric beams of near-monochromatic x-ray photons may be generated by collision of the free electron laser (FEL) electron beam with the optical beam in an interaction zone that delivers the x-rays to a shirtsleeve environment. The absence of Compton scatter and the photoelectric interaction within tissues improves conspicuity of lesions by two to six times. Increased attenuation of x-rays in malignant vs. normal tissues makes tumors more obvious. K-edge subtraction allows chemical analysis of tumors in vivo--all at radiation doses that are one-tenth to one-fiftieth that delivered by the lowest-dose mammographic x-ray technique available. This allows for an increased sensitivity and specificity and permits prediction of histology, negating necessity for biopsies. Selective bond-breaking at depth in tissues as well as x-ray-activated photodynamic therapy are also being explored. 
2	Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis. We report 2 patients with Guillain-Barre syndrome (GBS) following Campylobacter jejuni enteritis. Electrophysiologic studies indicated that the predominant process was axonal degeneration of motor nerves, and clinical recovery was poor. Serum testing by thin-layer chromatography and enzyme-linked immunosorbent assay revealed that the sera from both patients contained high titers of IgG antibody against GM1 ganglioside. These cases may represent a subgroup of GBS as acute axonal polyneuropathy following C jejuni enteritis associated with anti-GM1 antibodies. 
5	Hemodynamic effects of partial correction of chronic anemia by recombinant human erythropoietin in patients on dialysis. Eighteen patients on chronic hemodialysis with renal anemia were treated with recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting state were determined before and after successful treatment. Posttreatment cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860 dyne.cm.s-5) were increased significantly when compared with the pretreatment period. We conclude from our study that the increase of blood pressure as seen in patients on dialysis, who are effectively treated with r-HuEPO, is due to an increase in peripheral resistance. This increase overrules the decrease of cardiac index and might well be a result of peripheral vasoconstriction due to improved oxygen availability. 
1	Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature. Mesothelioma of the peritoneum is a rare malignant neoplasm easily mistaken by both surgeon and pathologist for one of the more common neoplasms of the abdomen. Review of our records from metropolitan-area hospitals for the past 15 years identified seven patients with primary peritoneal mesotheliomas. Their diagnosis, management, and survival is analyzed. We report a case of an extended survivor (7 years) and one of a long-term survivor (15 years), as well as what we believe to be the only case in the literature presenting with a coexistent malignant neoplasm. Prevention of this commonly fatal neoplasm is linked to avoiding occupational exposure to asbestos; long-term survival for a few patients may be achieved with correct identification of the neoplasm and aggressive management. This report includes a review of the literature. 
5	Urothelial hyperplasia and neoplasia. III. Detection of nitrosamine production with different bacterial genera in chronic urinary tract infections of rats. Various agents have been implicated in inducing urothelial cancer. Although drugs, occupational and environmental carcinogens are more widely accepted as playing a major role as urothelial carcinogens, several investigations suggest that bacteria may play a role. The mechanism of how bacteria may interact with the host to augment the development of urothelial carcinoma is not well understood. Clinically, investigators have linked the development of infection, urinary stones and indwelling catheters with urothelial cancer. Other investigators have suggested that the mechanism may be related to the production of carcinogenic compounds (nitrosamines) which can be detected during urinary tract infection. In our laboratory, we showed that rats with chronic urinary tract infections produced increasing urinary levels of N,N dimethylnitrosamine over a 24 week period and that the production correlated with hyperplasia and early neoplasia of the bladder epithelium. Three bacterial genera were used and two of these (Escherichia coli and a protein sp.) showed production of increasing levels of urinary nitrosamine and correlated with infection. The purpose of this current study is to determine if other bacterial genera and strains can also produce similar increasing nitrosamine levels in the rat model of chronic urinary tract infection and thus provide evidence that a number of bacterial genera and strains can produce nitrosamines in vivo. Also, the histology of the chronically infected bladder was examined for hyperplasia and neoplasia. 
5	Immunotherapy in acute arsenic poisoning. We investigated the use of immunotherapy on the treatment of sodium arsenite toxicity. Female balb/c mice injected with arsanilic acid conjugated to a carrier protein (ovalbumin) were shown to produce antibodies (arsenic reactive serum, ARS) reactive with arsanilic acid and sodium arsenite. Serum was tested for anti-ARS antibodies using a solid phase radioimmunoassay. The antisera bound to ARS conjugated to the synthetic copolymer glutamic acid60 tyrosine30 when diluted as high as 1:4096. Following multiple injections of 100 micrograms of arsanilic acid--ovalbumin compound, mortality on injection with sodium arsenite 0.87 mg/kg i.p. one week later decreased to 0 deaths in 22 pretreated mice vs 9 deaths in 29 untreated mice (31% mortality; p less than .005). No decrease in mortality was noted at higher challenges (1.15 mg/kg) of sodium arsenite. Antisera from pretreated mice was injected 0.1 cc i.p. into 12 week old female balb/c mice followed by an injection of sodium arsenite 0.87 mg/kg i.p. at 10 minutes. Again a protective effect was observed with 0 deaths in 18 mice vs eight deaths in 21 mice (38%; p less than .005). Seventeen additional mice were given an injection of 0.87 mg/kg i.p. of sodium arsenite. After 30 minutes, all mice became symptomatic whereupon antisera 0.1 cc i.p. was given. The one day mortality (2/17, 12%) was possibly lower than the combined control mortality (17/50, 34%; p less than 0.07). There was no change in mortality noted when antisera was administered to mice acutely exposed to 5 mg/kg HgCl2. 
2	Furosemide absorption in patients with cirrhosis. Twelve patients with cirrhosis (seven mild and five severe) were administered intravenous and oral furosemide in random order to assess its absorption and disposition. Total serum clearance (113 +/- 49 ml/min), volume of distribution (11.9 +/- 4.5 L), and elimination half-life (166 +/- 149 minutes) were similar to those reported previously in both healthy control subjects and patients with cirrhosis. Bioavailability of 58% +/- 17% (range, 37% to 82%) was comparable to that of previous studies, and there was no difference between patients with mild and those with severe cirrhosis. In 9 of 12 patients the mean absorption time was longer than the mean residence time determined after intravenous administration (mean for all patients, 203 +/- 86 versus 134 +/- 101 minutes; p less than 0.05), indicating that furosemide followed a "flip-flop" model in these patients. In all patients the mean absorption time was prolonged relative to normal subjects irrespective of the presence of edema. As such, the slower absorption of furosemide in edematous states, such as congestive heart failure and cirrhosis, does not appear to be a consequence of edema per se. Moreover, because similar changes occur in patients with congestive heart failure, it seems that diseases with diverse pathophysiology can slow furosemide absorption. 
1	Clinical review 16: Parathyroid hormone-related proteins: coming of age in the 1990s. The last 3 yr have yielded a fertile harvest of new information on the HHM clinical syndrome and on the novel peptide hormone family responsible for the syndrome. Whereas the clinical riddle enshrouding the HHM syndrome first posed in the early 1940s appears to have been largely solved, a whole new field, concerning the physiological role(s) of PTHRP has opened. The field has evolved rapidly and provides an example of fruitful clinical investigation: the original problem was a clinical one (the HHM syndrome); understanding the clinical disorder led to pursuit of the problem in the laboratory (adenylate cyclase assays, protein purification, molecular cloning, PTHRP synthesis); and observations made in the laboratory have rapidly yielded clinical fruits (PTHRP immunoassays) and opened a new window on normal physiology. 
3	Improving outcomes of analgesic treatment: is education enough? Frequent undertreatment of analgesic-responsive acute pain and chronic cancer pain persists, despite intensive efforts to provide clinicians with information about analgesics. A set of background factors must be addressed in interventions to improve pain treatment: Traditional patterns of clinician and patient interaction on the ward, quality assurance, and drug regulatory practices do not support prompt recognition and treatment of pain. Possible interventions to modify these patterns of daily practice include monitoring and displaying patient pain ratings routinely, making available educational tools to assist optimal drug ordering, encouraging patients to communicate about unrelieved pain, reviewing quality assurance of pain treatment regimens, increasing behavioral research into analgesic prescribing, and selectively modifying narcotics regulatory practices. 
1	Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis. The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement. 
5	Prolonged paralysis following suxamethonium and the use of neostigmine. A case of prolonged neuromuscular block following the administration of suxamethonium is reported. Three hours after administration of suxamethonium, a well defined, recovering phase II block was demonstrated with a T4:T1 ratio of 0.25, and neostigmine was administered. Although the T4:T1 ratio was improved to 0.9, T1 remained at 25% of control, and significant paralysis persisted which responded to administration of cholinesterase. It is concluded that neuromuscular monitoring cannot reliably predict reversibility in such cases and that, even after 3 h, antagonism of prolonged suxamethonium block should commence with cholinesterase, followed by neostigmine if necessary. 
1	Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects. 
4	Peripheral alpha-1 and alpha-2 adrenergic receptors in three models of hypertension in rats: an in vitro autoradiography study. In vitro autoradiography was used to compare peripheral alpha-1 and alpha-2 adrenergic receptor binding in various tissues using [3H]prazosin and [3H]rauwolscine, respectively, in three models of experimental hypertension in rats. Models studied included two-kidney, one-clip hypertension, one-kidney, one-clip hypertension, desoxycorticosterone-salt hypertension, and three normotensive control groups: two-kidney control, one-kidney control and salt-loaded control. Blood pressures at death were significantly higher in all three hypertensive groups compared with normotensive controls, but there were no significant differences among the hypertensive or normotensive groups. Plasma norepinephrine levels were significantly elevated in all three hypertensive groups compared with respective controls, with no significant differences among hypertensive or control groups. In all three hypertensive groups, there were significant reductions in binding of aortic and mesenteric vascular alpha-1 receptors, renal tubular alpha-1 and alpha-2 receptors, and adrenal cortical alpha-2 receptors when compared with respective control groups. Reduced binding of cardiac ventricular alpha-1 and alpha-2 receptors was also found in all hypertensive groups, but not to statistically significant levels. No significant differences in intestinal alpha-1 and alpha-2 receptor binding were detected in either hypertensive or normotensive groups. The results suggest increased peripheral sympathetic activity in all three models of experimental hypertension, which is associated with down-regulation of alpha-1 and alpha-2 receptors in a number of peripheral tissues, especially those that control cardiovascular hemodynamics and fluid and salt balance. There is no evidence of an increase in peripheral alpha receptor binding as has often been found in some models of genetic or spontaneous hypertension. 
3	Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease. BACKGROUND. Creutzfeldt-Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease--10 Libyan Jews from Israel and 1 Libyan Jew from Italy--to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease. METHODS. The prion-protein open-reading frame in peripheral-leukocyte DNA from the Italian patient was amplified with the polymerase chain reaction and sequenced. Allele-specific oligonucleotide hybridization was used to assess a prion-protein codon 200 lysine mutation in the 10 Israeli patients and 37 control subjects. RESULTS. The prion-protein sequence in DNA from the Italian patient revealed a single nucleotide change (G----A) at the first position of codon 200 that resulted in a substitution of lysine for glutamate. This substitution was detected in all 10 Israeli patients, 8 of whom had a positive family history of Creutzfeldt-Jakob disease. One patient was homozygous for the lysine mutation, and her clinical course did not differ from that of the patients heterozygous for the mutation. The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt-Jakob disease. CONCLUSIONS. The codon 200 lysine mutation of the prion-protein gene is consistently present among Libyan Jews with Creutzfeldt-Jakob disease, strongly supporting a genetic pathogenesis of their illness. The similarity of the clinical courses of the patient homozygous for this mutation and the patients heterozygous for it argues that familial Creutzfeldt-Jakob disease is a true dominant disorder. 
4	Transient left ventricular cavitary dilation during dipyridamole-thallium imaging as an indicator of severe coronary artery disease. Transient left ventricular (LV) cavitary dilation during dipyridamole-thallium imaging was reported in 45 of 510 (9%) consecutive patients referred for dipyridamole-thallium imaging. Clinical and hemodynamic effects observed during dipyridamole infusion were not predictive of transient cavitary dilation on the thallium images. Coronary angiography was performed in 32 of the 45 patients: 75% had either left main, 3-vessel or "high-risk" 2-vessel coronary artery disease. Although 25 of 45 patients (56%) with transient cavitary dilation were either asymptomatic or had only grade 1/4 effort angina, 16 of 25 patients (64%) not referred for coronary revascularization sustained a cardiac event during a mean follow-up of 12 months. Most events were cardiac deaths (75%) and 87% of events occurred within 4 months of the test. Noncardiac surgery was performed in 187 of the 510 patients. The postoperative cardiac event rate was 2% in the 101 patients with normal scans or fixed defects, 19% in 75 patients with reversible perfusion defects and 58% in 12 patients with reversible cavitary dilation (p less than 0.0001). Thus, transient LV dilation during dipyridamole-thallium imaging is a marker of severe underlying coronary artery disease, denotes a poor prognosis and predicts a high risk of postoperative cardiac complications in patients who undergo noncardiac surgery. 
1	Distribution and specific identification of papillomavirus major capsid protein epitopes by immunocytochemistry and epitope scanning of synthetic peptides. Monoclonal (MAbs) and polyclonal antibodies were produced against the major capsid protein of detergent-disrupted, purified bovine papillomavirus type 1 (BPV-1). The precise locations of the corresponding epitopes were identified by the reactivity of MAbs and selected polyclonal antibodies with synthetic, overlapping, hexameric peptides corresponding with 95% of the BPV-1 major capsid protein. The topography of these epitopes was determined by reactivity of antibodies with intact (conformational and nonconformational surface epitopes) and disrupted (external or internal nonconformational epitopes) BPV-1 virions. The distribution of epitopes in various papillomaviruses of 13 different species was determined by reactivity of the MAbs and polyclonal sera with productively infected, formalin-fixed papillomas, fibropapillomas, and fibromas. Epitope scanning, using MAbs and polyclonal antisera, resulted in the precise location of BPV-1 hexameric epitopes that could be correlated with their topography on the capsid and distribution in papillomatous lesions of various species. 
3	Familial paroxysmal kinesigenic ataxia and continuous myokymia. A large family with paroxysmal ataxia and continuous myokymic discharges is described. The disorder is of autosomal dominant inheritance. During attacks coordination of movements and balance are disturbed; often a postural tremor of the head and the hands and fine twitching in some of the facial and hand muscles are present. The attacks usually last a few minutes and may occur several times per day. They first appear in childhood and tend to abate after early adulthood. The attacks are frequently precipitated by kinesigenic stimuli similar to those in paroxysmal kinesigenic choreoathetosis. Their occurrence can be reduced or prevented by carbonic anhydrase inhibitors. Between attacks a slight postural tremor and ataxia was found in a few of the elderly affected members. Fine rippling myokymia was obvious in a few and could be detected on close inspection in about half of the adults. Electromyography (EMG) showed myokymic discharges in all affected members. The characteristics and reactivity of this myokymic activity suggest multiple impulse generation in the peripheral nerves. 
2	Tongue atrophy in mixed connective tissue disease. A case is reported of tongue atrophy in a patient with mixed connective tissue disease (MCTD) and major myositic involvement. The case highlights oropharyngeal aspects of MCTD, including inability to wear dentures, dysarthria, and dysphagia. To our knowledge this is the first report of major tongue involvement in myositis as part of MCTD. 
5	A pilot study of intermediate-dose methotrexate and cytosine arabinoside, "spread-out" or "up-front," in continuation therapy for childhood non-T, non-B acute lymphoblastic leukemia. A Pediatric Oncology Group study. One hundred six children with newly diagnosed non-T-, non-B-cell acute lymphoblastic leukemia (ALL) were treated in a Pediatric Oncology Group (POG) pilot study in which six courses of intermediate-dose methotrexate (MTX) and cytosine arabinoside (Ara-C) (1 g/m2 each) were added to a "backbone" of standard continuation therapy. The dose and sequence of MTX/Ara-C administration were based on a preclinical model that demonstrated synergism between MTX and Ara-C. Poor-risk patients (n = 49) were assigned to "up-front" therapy, in which the MTX/Ara-C courses were administered during the initial 15 weeks of remission. Standard-risk patients (n = 57) were assigned to "spread-out" therapy, in which the MTX/Ara-C courses were interspersed at 12-week intervals within continuation treatment. Toxicity after intermediate-dose MTX/Ara-C, principally neutropenia and fever, was judged significant but manageable. Unexpectedly, the incidence of fever and neutropenia less than 500/mm3 was greater after "spread-out" therapy (38%) than after "up-front" therapy (6%). At 4 years, the Kaplan-Meier estimate of event-free survival (EFS) is 71% (+/- 7%) for standard-risk patients and 53% (+/- 8%) for poor-risk patients. The results of this pilot study support the use of intermediate-dose MTX/Ara-C in additional studies. 
3	Differential memory and executive functions in demented patients with Parkinson's and Alzheimer's disease. Selected aspects of verbal memory and executive function were compared in 11 demented Parkinson's disease (PD) patients and 11 Alzheimer's disease (AD) patients with equally severe dementia, with 11 healthy controls matched for age and education. Semantic and episodic memory were impared in all patients compared with controls, but to a relatively greater degree in AD patients than in those with PD. In contrast, demented PD patients were relatively more compromised on executive tasks. These findings, taken in the context of the neuropathological and neurochemical overlap between demented PD and AD patients, suggest that differences in neurobehavioural patterns in patients with these diseases are relative, rather than absolute. 
1	Autologous bone marrow transplantation for high-grade lymphoid malignancy using melphalan/irradiation conditioning without marrow purging or cryopreservation. The Northern Regional Bone Marrow Transplant Group. We report the safety and efficacy of 34 consecutive autologous bone marrow transplant (ABMT) procedures performed in adult patients with high-grade lymphoid malignancy after remission induction therapy. Fifteen patients with acute lymphoblastic leukemia (ALL) and six with high-grade non-Hodgkin's lymphoma (NHL) received pretransplant conditioning with intravenous (IV) melphalan and fractionated total body irradiation (TBI). Thirteen other patients with NHL were conditioned with melphalan alone, having previously received local involved field radiotherapy. Unmanipulated noncryopreserved autologous marrow was reinfused within 48 hours of harvesting. Engraftment occurred in all patients with medians of 10 days of neutropenia (neutrophils less than 0.5 x 10(9)/L), 4-day platelet transfusion requirement, 3 U packed RBC transfusion, and 18 days in hospital posttransplant. There were no procedure-related deaths. Actuarial disease-free survival in the 13 patients with ALL receiving autotransplant early in first remission is 48% with a median follow-up of 3 years. Two other ALL patients who had autotransplants after a period of maintenance therapy also remain in complete remission (CR). These results compare favorably with our 34% disease-free survival (DFS) in 15 allogeneic ALL transplant patients and 21% DFS in 19 patients on standard maintenance after a common induction schedule. No relapses have occurred in the 17 NHL patients transplanted in remission (median follow-up 2 years), but the two NHL patients who developed recurrent disease before ABMT died of progressive disease after temporary responses. We conclude that this method of ABMT results in rapid reengraftment with lack of toxicity and that the conditioning treatment used shows good efficacy against disease. It is applicable in high-grade lymphoid malignancy in first remission, and our results call into question the need for marrow purging in ALL and NHL patients transplanted in first remission. 
1	The use of ketoconazole in ectopic adrenocorticotropic hormone syndrome. The authors report a patient with ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) resulting from small cell lung cancer. Treatment with ketoconazole (KCZ) resulted in significant suppression of serum cortisol levels. The authors confirmed KCZ to be a useful adjunct in the treatment of Cushing's syndrome. 
4	Effect of increased left atrial pressure on breathing frequency in anesthetized dog. Distension or loading of the isolated canine left heart caused reflex tachypnea in prior studies. The object of the present effort was to explore the possibility that this depended primarily on atrial distension. Cardiopulmonary bypass perfusion and ligation of pulmonary veins were used to isolate the left-heart chambers of anesthetized dogs. Simultaneous distension of the beating left atrium and fibrillating ventricle stimulated breathing frequency (f), whereas isolated ventricular distension did not. At other times, intervals of atrial fibrillation were imposed under two different conditions: 1) while the right heart and lungs were bypassed and systemic perfusion was provided by the left ventricle using blood returned to the left atrium by pump and 2) while the ventricles fibrillated and systemic perfusion was supplied directly by the pump. Atrial fibrillation increased left atrial pressure and stimulated f in condition 1. In condition 2, f increased only if fibrillation was associated with a rise in left atrial pressure. Vagal cooling blocked the effect of fibrillation. I conclude that left atrial distension may initiate reflex tachypnea. 
1	Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers. As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration. 
1	Suppression of serum insulin level by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy, nonobese women. Suppression of serum insulin levels with diazoxide is associated with a decrease in serum testosterone and an increase in serum sex hormone-binding globulin in obese women with the polycystic ovary syndrome. To determine whether physiologic insulin levels play a regulatory role in the androgen status of nonobese women with normal menses, the androgen status of five nonobese normal women was assessed on two occasions: during a control study and after 10 days of oral diazoxide (100 mg, three times daily) administration. Insulin release in response to 100 gm oral glucose administration decreased from 108.0 +/- 28.2 to 49.3 +/- 5.2 nmol.min/L (p = 0.05) after diazoxide administration. However, despite suppression of insulin release, diazoxide administration did not affect serum total testosterone (diazoxide, 0.73 +/- 0.10; control, 0.69 +/- 0.11 nmol/L; p = NS) or sex hormone-binding globulin (diazoxide, 79.7 +/- 16.6; control, 70.2 +/- 12.6 nmol/L; p = NS) concentrations. These observations suggest that physiologic insulin levels in nonobese healthy women do not regulate testosterone metabolism and that diazoxide does not exert a direct or independent effect on serum testosterone or sex hormone-binding globulin levels. 
5	Isolated trigeminal sensory loss secondary to a distal anterior inferior cerebellar artery aneurysm: case report. A previously healthy 25-year-old woman suddenly developed right-sided facial numbness and a headache. The neurological examination was within normal limits with the exception of meningismus and right-sided facial sensory loss. A computed tomographic scan and a magnetic resonance imaging study demonstrated an acute hematoma in the right cerebellopontine angle. A 4-vessel cerebral angiogram revealed no abnormalities. Posterior fossa exploration disclosed a large, partially thrombosed, fusiform anterior inferior cerebellar artery aneurysm, which indented the pons at the trigeminal root entry zone. The aneurysm was excised, and the patient made an excellent recovery. She was left with a persistent trigeminal sensory deficit. Anterior inferior cerebellar artery aneurysms are rare lesions that generally present with a cerebellopontine angle syndrome; occasionally, facial sensory loss is also a feature. Isolated trigeminal sensory findings, as illustrated in this case, are extremely unusual in posterior fossa vascular lesions. 
5	Nondiagnosed left main ostial stenosis partly due to the use of 5 French coronary angiographic catheters. Two cases have been reported in which the use of 5 F angiographic catheters is associated with a failure to diagnose an ostial stenosis of the left main coronary artery (LMCA). In both cases, the erroneous diagnosis led to an inappropriate indication for percutaneous transluminal coronary angioplasty (PTCA) on other stenosed vessels, and the ostial left main lesion was unexpectedly discovered when using 8F guiding catheters. It is supposed that the ability of performed 5F catheters to pass easily through an ostial lesion makes detection of such proximal stenosis much more difficult. We suggest that the choice of 5F catheters must be approached with caution when left main disease is potentially expected from the clinical features. 
3	Intraoperative assessment of cerebral ischemia during carotid surgery. One of the problems in carotid surgery is the intraoperative detection of brain ischemia. None of the methods (EEG; stump pressure) applied so far have been successful. Branston et al. (1974) found a threshold relationship between cortical cerebral blood flow and cortical somatosensory evoked potential (SEP). As the local blood flow fell below about 16 ml/100 g/min a progressive reduction occurred in the amplitude of the cortical evoked potential (N20/P25), implying a fundamental failure of neuronal function in the somatosensory cortex. We have monitored cortical SEP (somatosensory evoked potential) during 734 CEA's (carotid endarterectomies) in order to find an index of risk of incipient cerebral ischemia during carotid cross-clamping, to determine the need for shunting and the causes of early irreversible neurologic deficits. In 59 cases evaluation of SEP was not possible because of technical difficulties. During 586 CEA's no alteration of SEP occurred. However, 4 patients had an immediate postoperative neurologic deficit, while the SEP remained normal. Abnormal SEP occurred in 89 cases and in 6 of these an irreversible loss of SEP was seen. These patients awoke with a new neurologic deficit. We found a reversible abnormal SEP in 83 cases. Reversible changes of SEP occurred mainly during carotid clamping. The diagnostic sensitivity of intraoperative SEP monitoring in predicting neurologic outcome was 60% with a specificity of 100%. 
5	Sinus node-atrioventricular node isolation: long-term results with the "corridor" operation for atrial fibrillation The "corridor" operation is designed to restore sinus rhythm to patients with atrial fibrillation by electrically isolating the sinus node, a band of atrial tissue and the atrioventricular (AV) node from the remaining atrial tissue. Nine patients with drug-refractory atrial fibrillation underwent this operation; four patients had chronic atrial fibrillation and five had paroxysmal atrial fibrillation; the mean duration of symptoms was 12 +/- 8 years. Patient ages ranged from 25 to 68 years (mean 48 +/- 12). At preoperative electrophysiologic study, no patient had evidence of an accessory AV pathway or AV node reentry. Sinus node recovery time could not be determined in five patients because of recurrent atrial fibrillation during or before programmed stimulation. At operation the corridor of atrial tissue connecting the sinus and AV nodes was successfully isolated from the remaining left and right atrial tissue in all patients. One patient required early reoperation for recurrent atrial fibrillation before hospital discharge. At the predischarge electrophysiologic study, the corridor remained isolated in all patients except for one patient who had intermittent conduction between the corridor and excluded right atrium. One patient had nonsustained atrial fibrillation and one had atrial tachycardia evident in the corridor. Atypical AV node reentry of uncertain significance was induced in one other patient. Over a total follow-up of 191 patient months (mean 21 +/- 20), seven patients remained free of atrial fibrillation. Two patients had recurrent atrial fibrillation, which in one patient was effectively controlled by a single antiarrhythmic agent. A permanent pacemaker was implanted in four patients for sinus node dysfunction. 
2	Surgical management of nonparasitic cystic liver disease. We report clinical features, surgical management, recurrences, and follow-up study of 12 patients with simple hepatic cyst, 11 patients with polycystic liver disease, and 19 patients with cystadenoma who were surgically treated over a 25-year period. The median age of patients was 48 years, and 37 women and 5 men were in the series. The most common presenting symptom and physical finding were chronic abdominal pain and tenderness in the right upper quadrant. The most commonly associated disease was polycystic kidney disease, which was an associated finding in 5 of the 11 patients with polycystic liver disease (45%). The most valuable diagnostic studies in all groups were computed tomography and ultrasonography. The location of the disease was bilobar in patients with polycystic liver disease, with a right lobe predominance in 18% of patients. The right lobe was also predominant in 83% of patients with simple hepatic cyst and 58% of patients with cystadenoma. Of all solitary cystic lesions in the left lobe, 75% of them were cystadenomas. Of the 66 surgical procedures performed, aspiration was associated with a failure rate of 100%; partial excision, a failure rate of 61%; and total excision and liver resection, a failure rate of 0%. Orthotopic liver transplantation was performed in three patients and was associated with two early deaths. Partial excision relieved symptoms in three patients (43%) with polycystic liver disease. Total excision, enucleation, or liver resection with cyst(s) is the treatment of choice for non-parasitic cystic lesions of the liver. 
4	Blood-pool radionuclide angiography in patients with a Novacor left ventricular assist device. Blood-pool radionuclide angiography was used to investigate the left ventricular function in eight patients who received a Novacor assist device as a bridge-to-cardiac transplantation. Studies were performed during maximal and minimal tolerated assist device flows. The left ventricular ejection fraction, volumes, cardiac output, and the pump ejection fraction were computer-assessed. All patients had severe left ventricular dilation and hypokinesis before insertion of the assist device, with a mean ejection fraction of 18% +/- 4% which improved to 44% +/- 18% (p less than 0.01) during maximal assist device flows, but fell to 25% +/- 15% (p less than 0.01) during minimal flows. The ventricular volumes became normal at maximal assist device flow but increased significantly (p less than 0.05) during minimal flow. The pump was well visualized and had an ejection fraction of 82% +/- 7%. These data indicate that this assist device effectively unloads the left ventricle. The deterioration in ejection fraction following decrease in assist device flow is in keeping with the dependency of these patients on the device to sustain adequate hemodynamics. 
1	The central (intraosseous) calcifying odontogenic cyst: an analysis of 215 cases. This study reviews and analyzes the clinical, radiographic, and histomorphologic features of the 215 cases of central calcifying odontogenic cyst (CCOC) reported in the literature. Based on the present information, a clinicopathologic classification of calcifying odontogenic cyst is proposed. The CCOC is also compared with its peripheral counterpart and the differences discussed. 
4	Doxazosin for the treatment of chronic congestive heart failure: results of a randomized double-blind and placebo-controlled study. In this study we evaluated the effects of once-daily administration of oral doxazosin in patients with chronic congestive heart failure (CHF). After a stabilization period of at least 2 weeks with digitalis and diuretics, 73 patients with chronic CHF were randomized to receive additionally either doxazosin or placebo in double-blind fashion. Patients underwent weekly dose adjustments with increasing doses of doxazosin (1, 2, 4, 8, and 16 mg daily) or placebo for 5 weeks, and 67 were evaluated for 12 additional weeks on maximally tolerated doses of blinded study drugs. Treatment groups were evaluated with respect to symptoms of heart failure, indexes of quality of life and left ventricular function, frequency and type of arrhythmia, adverse events, and mortality rates. Doxazosin (11.9 +/- 0.9 mg) given once daily produced a favorable trend in the investigators' and patients' assessments of symptomatic change. Doxazosin was associated with a significantly higher level of voluntary submaximal exercise and a favorable trend on left ventricular ejection fraction (increase of 9.8% of the baseline value vs 2.7% with placebo; p = NS). During the 3-month steady-dosing period, patients treated with doxazosin had a significant (p less than 0.004) reduction in ventricular arrhythmias and significantly fewer morbid and mortal cardiac events (including episodes of worsening heart failure severe enough to prompt discontinuation of the study, myocardial infarction, and death). Doxazosin was well tolerated, producing no major side effects and only a slightly higher frequency of minor treatment-related side effects compared with placebo (p = NS). 
2	Historical review of pancreaticoduodenectomy. The performance of pancreaticoduodenectomy by Whipple in 1935 demonstrated that the operation was feasible technically and compatible with reasonable function after recovery. From the mid- to late 1940s until the last 10 years, the procedure was condemned by many because of its associated mortality and morbidity. For reasons that are not clear, the risk of pancreaticoduodenectomy in the last 10 years has fallen to less than 10% and in several centers, less than 5%. Postoperative complications have been reduced and blood transfusions are unnecessary in an increasing number of patients. Furthermore, a normal productive life without the need for medication and with no digestive disorder is expected. Seventy-one percent of patients are able to return to their preoperative occupation. 
3	Atrial fibrillation in the elderly: management update. Non-valvular atrial fibrillation is associated with a markedly increased risk of embolic stroke in elderly persons. Evidence is accumulating that anticoagulation with warfarin or aspirin may be effective in reducing this risk. 
3	Rigid fixation of internal orbital fractures. When large portions of the internal orbit are destroyed (two to four walls), standard bone-grafting techniques for immediate and late orbital reconstruction may not yield predictable eye position. Critical bone support is most often deficient inferomedially. CT analysis of orbital volume in cases where eye position was unsatisfactory reveals that displacement of bone grafts is one mechanism of the unsatisfactory result. Other mechanisms include undercorrection and bone-graft resorption. In order to minimize postoperative bone-graft displacement, titanium implants were used to span large defects in the internal orbit to provide a platform for bone-graft support. Twenty-six implants were placed in immediate and 12 were placed in late orbital reconstructions. More reliable bone-graft position resulted. Two late infections have occurred resulting in implant removal in a 3-year period. 
5	Covalent binding of oxidative biotransformation intermediates is associated with halothane hepatotoxicity in guinea pigs. In vivo covalent binding of halothane biotransformation-reactive intermediates to hepatic protein and lipid was examined in association with the subsequent development of hepatic necrosis in the guinea pig. Oxidative halothane biotransformation was inhibited by the use of deuterated halothane, whereas reductive metabolism was enhanced by low inspired oxygen concentrations. Male outbred Hartley guinea pigs (n = 8) were exposed to either 1% (v/v) halothane or deuterated halothane--with a fractional inspired O2 concentration (FIO2) of 0.40 or 0.10--for 4 h. Livers removed from half of the animals immediately after anesthesia were evaluated for organic fluorine bound to protein and lipid. The remaining animals were evaluated for a hepatotoxic response up to 96 h after exposure. Only guinea pigs that received 1% halothane at an FIO2 of 0.40 had centrilobular necrosis develop with significantly increased plasma alanine aminotransferase activities. All other treatment conditions significantly reduced oxidative halothane biotransformation, as indicated by decreased plasma trifluoroacetic acid concentrations. These reductions were associated with a significant decrease in organic fluorine bound to hepatic proteins. An FIO2 of 0.10 during halothane anesthesia significantly enhanced reductive biotransformation, as indicated by plasma fluoride ion concentrations. This was associated with a significant increase in organic fluoride bound to hepatic lipids. Centrilobular necrosis did not develop under these conditions. Thus, covalent binding to subcellular proteins by the trifluoroacetyl acid chloride intermediate generated by oxidative halothane biotransformation is implicated as a mechanism of centrilobular necrosis in guinea pigs. Binding to lipids by reductive pathway generated free radicals does not appear to be involved in production of the lesion. 
1	Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography. Renal ultrasonography was performed in 45,905 adults, including 41,364 without any signs suggesting urinary tract malignancies, 1,667 with microscopic hematuria only and 2,874 with some signs of malignancy. Renal lesions were found in 355 adults (0.858%) in the asymptomatic, 39 (2.3%) in the microscopic hematuria and 75 (2.6%) in the symptomatic groups, respectively. Renal cell carcinoma was found in 35 (7.5%) lesions: 19 (5.4%) in the asymptomatic, none in the microscopic hematuria and 16 (21.3%) in the symptomatic groups. A total of 47 patients, including 12 other renal cell carcinoma patients transferred from related hospitals, was grouped into 28 without and 19 with symptoms. Primary tumor size and clinical stages were significantly smaller and lower, respectively, in the asymptomatic group than in the symptomatic group. Radical nephrectomy was performed in all but 2 asymptomatic patients. The 5-year survival rates after nephrectomy were 94.7 and 60.9% for the asymptomatic and symptomatic groups, respectively (p less than 0.01). The results indicate that ultrasonography is a useful tool to detect low stage asymptomatic renal cell carcinoma at low cost. 
5	Idiopathic sudden sensorineural hearing loss and postnatal viral labyrinthitis: a statistical comparison of temporal bone findings. Although the cause of idiopathic sudden sensorineural hearing loss remains uncertain, a viral origin has been suggested in many cases on the basis of anamnestic microbiologic and pathologic data. Twenty-two temporal bone specimens from 18 patients who during life suffered a sudden partial or complete sensorineural hearing loss were studied. On the basis of clinical data, these cases were assigned to one of three diagnostic categories, and the temporal bones were studied by light microscopy and serial section analysis. The implications of the histopathologic findings for the pathogenesis of idiopathic sudden sensorineural hearing loss are discussed. 
1	Extracolonic malignancies in inflammatory bowel disease. A population-based cohort with inflammatory bowel disease consisting of 4776 patients (3121 with ulcerative colitis and 1655 with Crohn's disease) was followed for 1 to 50 years for the occurrence of malignant neoplasms. Two hundred eighty-three cancers were observed versus 189.1 expected (standardized incidence ratio [SIR] = 1.5, 95% confidence limits [CL] 1.3 to 1.7). One hundred seventy-eight extracolonic cancers were observed versus 168.8 expected (SIR = 1.1, 95% CL 0.9 to 1.2). In Crohn's disease and extensive ulcerative colitis, observed cases were close to those expected but in ulcerative proctitis, the relative risk of extracolonic cancers was close to significantly increased (SIR = 1.3, 95% CL 1.0 to 1.7). Squamous skin cancers after Crohn's disease (SIR = 5.5, 95% CL 2.0 to 11.9) and connective tissue cancers after ulcerative colitis (SIR = 4.0, 95% CL 1.0 to 10.2) were significantly increased. Those having extensive ulcerative colitis at diagnosis had an increased risk of brain cancers (SIR = 2.4, 95% CL 1.0 to 4.6). Patients with extensive ulcerative colitis had lower than expected risk of breast cancer (SIR = 0.4, 95% CL 0.1 to 1.0). 
5	Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy. The epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems. From among over 60 patients with ENS presenting with neurologic manifestations, we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies. Associated brain and neurologic abnormalities included gyral malformations in 12 of 12, mental retardation in 13 of 14, seizures in 16 of 17 (including 9 with infantile spasms), and contralateral hemiparesis in 7 of 12. All had ipsilateral epidermal nevi of the head, and several had ipsilateral facial hemihypertrophy. We concluded that these abnormalities comprise a recognizable neurologic variant of ENS that we believe represents the full expression of primary brain involvement. Several patients also had evidence of acquired brain lesions such as infarcts, atrophy, porencephaly, and calcifications, which are best explained by prior ischemia or hemorrhage. Given repeated observations of blood vessel anomalies in ENS patients, we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions. The same cause may be invoked to explain the wide variety of neurologic symptoms reported in ENS patients without hemimegalencephaly. While the cause of ENS remains unknown, several observations suggest a somatic mutation. 
1	A provider's view of prevention approaches in a prepaid group practice. Kaiser Permanente's health care delivery system and its efforts to integrate public health preventive medicine and curative medicine are described. The author advocates an increased focus on prepaid delivery systems like Kaiser Permanente as the best vehicle to achieve the full promise of health screening, health education, and life-style modification. Because these systems have brought the proper incentives into alignment, prevention and health promotion have become effective tools to achieve cost containment goals. A number of Kaiser Permanente projects are highlighted that demonstrate integration of public health preventive medicine and curative medicine: the Northern California Region's uniform health appraisal examination, which is linked with health education and counseling; the Colorado Region's breast cancer screening program, which is expected to show a higher rate of early breast cancer detection than in the general population; cooperative efforts with two Northern California towns to reduce smoking through a community-wide project; educational theatre programs aimed at early intervention and education of children before high-risk behaviors have become established life-style; and research projects that are possible because of an integrated program. Also, several forces that could endanger integrated systems including cost control practices of employers and insurers, and public policy such as mandating specific benefits, are noted. 
5	The neuromuscular pathology of the Eosinophilia-Myalgia syndrome. The Eosinophilia-Myalgia Syndrome (EMS) is a recently reorganized disorder in patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was severe in four, moderate in two, mild in three and absent in three cases. The lesions contained many eosinophils, T-helper cells, mast cells and activated macrophages. Type 2 myofiber atrophy was present in five cases and in one, this was the only pathologic finding. Severe epineurial inflammation was seen in the three sural nerve biopsies. Indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs (two cases) and neurogenic atrophy (one case). Phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one. Fasciitis was present in three of four skin biopsies and dermal fibrosis in one. 
1	Prosthetic arthroplasty of the knee after resection of a sarcoma in the proximal end of the tibia. A report of sixteen cases. The results of a specific type of prosthetic reconstruction of the knee (total replacement arthroplasty) after resection of a sarcoma of the proximal part of the tibia in sixteen patients were retrospectively reviewed. The diagnosis was stage-IIB osteogenic sarcoma in nine patients, stage-IIB malignant fibrous histiocytoma in three patients, and stage-IB sarcoma of various types in four patients. The length of tibial resection ranged from 100 to 257 millimeters. Of the eleven patients who were available for functional examination (mean duration of follow-up, sixty-three months), three patients had an excellent result, seven had a good result, and one had a fair result. Of the five patients who were not available for functional testing, one who was doing well was lost to follow-up at eighty months, one had died of metastases at sixteen months, and three had had a secondary amputation for infection or for loosening of the prosthesis. 
4	Doppler echocardiographic comparison of the Carpentier and Duran anuloplasty rings versus no ring after mitral valve repair for mitral regurgitation. To compare the hemodynamic results of different anuloplasty techniques of primary valve repair for mitral regurgitation, 122 patients were prospectively studied with Doppler echocardiograms 5 to 10 days after operation. Seventy-seven patients had mitral valve prolapse, 27 had coronary artery disease, 13 patients had rheumatic mitral valve lesions and 5 patients had infective endocarditis. Forty-eight patients received the flexible Duran ring, 46 received the more rigid Carpentier ring and 28 patients received no ring. Doppler echocardiography demonstrated a significant decrease in mitral valve area estimated by the pressure half-time method in patients who received either a Carpentier (2.6 +/- 0.8 cm2) or Duran ring (2.8 +/- 0.8 cm2) when compared with patients who received no ring (3.2 +/- 0.7 cm2) (p = 0.01). No significant differences were observed for peak transmitral diastolic velocity, peak transmitral diastolic gradient, or the grade of mitral regurgitation by color flow Doppler mapping between patients with and without rings. The etiology of mitral disease and concomitant surgical procedures accompanying mitral valve repair did not significantly influence mitral valve area, peak velocity or peak gradient. These data suggest that Carpentier and Duran rings decrease the hemodynamic mitral valve area; however, the decrease in valve area is small and not associated with a clinically important increase in transvalvular gradient. 
1	Elevated insulin receptor content in human breast cancer. The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0.95 + 0.68, P less than 0.001) and in six normal specimens obtained from reduction mammoplasty (0.84 +/- 0.78, P less than 0.001). The insulin receptor content in breast cancer tissues was also higher than in any normal tissue investigated including liver (Pezzino, V., V. Papa, V. Trischitta, A. Brunetti, P.A. Goodman, M.K. Treutelaar, J.A. Williams, B.A. Maddux, R. Vigneri, and I.D. Goldfine, 1989. Am. J. Physiol. 257:E451-457). The insulin receptor in breast cancer retained its ability to both bind insulin and undergo insulin-induced tyrosine kinase activation. Immunostaining of the specimens revealed that the insulin receptor was present in malignant epithelial cells, but was not detected in stromal and inflammatory cells. Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors. 
2	Neuromuscular disease of the gastrointestinal tract. Gastrointestinal motility is the function of gastrointestinal smooth muscle. It is controlled by both the intrinsic and extrinsic nerves of the gastrointestinal tract and, to a lesser degree, the gastrointestinal hormones. Therefore, any abnormality of the above factors, theoretically, can cause gastrointestinal dysmotility. In a clinical situation, commonly seen is gastrointestinal dysmotility caused by either smooth muscle or intrinsic and extrinsic nerves dysfunction. Diseases that cause smooth muscle dysfunction include familial visceral myopathies, nonfamilial visceral myopathies, collagen disease, muscular dystrophies, amyloidosis, thyroid disease, and so on. Diseases that cause enteric nerve dysfunction include familial visceral neuropathies, nonfamilial visceral neuropathies, diabetes mellitus, Chagas' disease, ganglioneuromatosis of the intestine, visceral neuropathy of carcinomatosis, Parkinson's disease, and so on. The patients with neuromuscular disease of the gastrointestinal tract have a wide range of clinical manifestations regardless of the underlying cause. At one end of the spectrum, the patients may be asymptomatic, and at the other end of the spectrum, the patients may have functional obstruction of the gastrointestinal tract. Plain abdominal x-rays, upper gastrointestinal (UGI) and small bowel x-rays, enteroclysis, barium enema, and manometric studies are useful for the work-up of these patients. Enteroclysis is especially helpful in ruling out mechanical obstruction of the small intestine in patients with chronic intestinal pseudo-obstruction. Treatment is mainly symptomatic and supportive. There is no effective drug to improve gastrointestinal motility. Surgery may be helpful in selected cases of severe gastrointestinal dysmotility. 
5	Diffuse sclerosing osteomyelitis of the mandible: a new concept of its etiology. Diffuse sclerosing osteomyelitis of the mandible is a disease of unknown etiology. The clinical and radiographic findings suggest an infectious origin, but bacteriologic and histologic findings do not support this concept. Analysis of clinical symptoms, localization of the condition, and posttreatment findings in a group of 27 patients suggest a chronic tendoperiostitis due to muscular overuse as an etiologic factor in diffuse sclerosing osteomyelitis of the mandible. This hypothesis was supported by the initial results of muscle relaxation treatment in 13 of these patients. 
1	Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors. Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data. 
4	Injuries to the cervical spine causing vertebral artery trauma: case reports. In four patients with lesions of the vertebral artery resulting from cervical spine injury, two were due to unilateral facet dislocation and two to fractures of the dens. There was one arterial occlusion with minor vertebrobasilar symptoms, and an arterial lesion with thrombosis causing embolic occlusion of the basilar artery with lethal outcome. In one patient a fresh fracture of the dens caused dislocation of C1/2 with reversible occlusion of the left and stenosis of the right vertebral artery, resulting in unconsciousness. In a patient with pseudarthrosis of the dens an aneurysm of the vertebral artery could be detected. Cerebellar or cerebral symptoms associated with cervical spine injury should be investigated by vertebral angiography because vertebral arterial injury may be more common than suspected and may simulate traumatic brain damage. 
5	Acute complications of percutaneous transluminal coronary angioplasty for total occlusion. The incidence of major complications after percutaneous coronary angioplasty (PTCA) of a totally occluded artery was assessed retrospectively. A total of 1649 PTCA procedures were analyzed. After exclusion of procedures for acute myocardial infarction or total occlusion that resulted from restenosis, 90 patients were selected. Forty-four patients (49%) had stable angina and 46 (51%) had unstable angina. The estimated duration of occlusion was 87 +/- 78 days in patients with stable angina, as compared with 10 +/- 8 days in patients with unstable angina (p less than 0.001). Abrupt vessel closure during PTCA occurred only in patients with unstable angina (0% versus 17%, p less than 0.05). The major complication rate was 2.5% in the stable angina group, and 20% in unstable angina group (p less than 0.01). This rate was also significantly higher than the complication rate of 8% observed in 442 procedures that were performed during the same period in patients with the unstable angina and nonocclusive stenosis (p less than 0.01). Patients with unstable angina who undergo PTCA of a totally occluded artery represent a subset of high risk for major complications. 
5	Clinical management issues in males with sex chromosomal mosaicism and discordant phenotype/sex chromosomal patterns. The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach. 
5	Alternation of gastric mucosal glycoprotein (lectin-binding pattern) in gastric mucosa in stress. A light and electron microscopic study. Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells. 
1	Prevention and changing demographics. The underserved and cancer. This paper illustrates the complexity of the "cancer control in the underserved" problem, especially as it is affected currently, and will be in the future, by the multiple demographic changes in the United States. It does so by extensively quoting from four rather different articles by authors from a variety of backgrounds in health, management, and economics. Another issue is that although the articles quoted refer mainly to secondary and tertiary prevention, they do apply equally to primary prevention and health promotion. Furthermore, the twin issues of priority and ethnic/cultural differences need to be addressed insofar as they affect health risks, risk reduction efforts, early diagnosis, treatment, and rehabilitation/disability reduction. Finally, the point is made that social and structural change of this magnitude cannot occur in the health care system and society at large without the allocation of discrete private and public sector resources. 
2	Paraileostomy hernia: a clinical and radiological study. Forty-six patients who underwent colectomy with end ileostomy for ulcerative colitis (n = 33) or Crohn's disease (n = 13) have been reviewed for paraileostomy hernia (PIH) formation 1-16 years after surgery. PIH developed in 13 of these patients (28 per cent) and was not related to the original disease or excessive weight gain. Twenty-eight patients underwent limited computed tomography (CT) scanning of the stomal region. Eight of these had a clinically detectable PIH, which was demonstrated on CT. A further two patients had PIH demonstrated on CT which was not detected by clinical examination. The rate of PIH was similar where the stoma emerged lateral to the rectus abdominis muscle (six out of 16 patients, 37 per cent) to where the stoma emerged through the rectus (four out of 12 patients, 33 per cent). Recurrence following operative repair of PIH was common. PIH occurs more frequently than previously supposed. CT can detect PIH and may be useful in evaluating a patient with stoma-related symptoms for occult PIH formation. 
5	Expression of transcobalamin II receptors by human leukemia K562 and HL-60 cells. Plasma membrane receptors for the serum cobalamin-binding protein transcobalamin II (TCII) were identified on human leukemia K562 and HL-60 cells using immunoaffinity-purified human TCII labeled with [57Co]cyanocobalamin. The Bmax values for TCII receptors on proliferating K562 and HL-60 cells were 4,500 and 2,700 per cell, respectively. Corresponding dissociation constants (kd) were 8.0 x 10(-11) mol/L and 9.0 x 10(-11) mol/L. Rabbit TCII also bound to K562 and HL-60 cells but with slightly reduced affinities. Calcium was required for the binding of transcobalamin II to K562 cells. Brief treatment of these cells with trypsin resulted in almost total loss of surface binding activity. After removal of trypsin, surface receptors for TCII slowly reappeared, reaching pretrypsin treatment densities only after 24 hours. Reappearance of receptors was blocked by cycloheximide. TCII receptor densities on K562 and HL-60 cells correlated inversely with the concentration of cobalamin in the culture medium. This suggests that intracellular stores of cobalamin may affect the expression of transcobalamin receptors. Nonproliferating stationary-phase K562 cells had low TCII receptor densities (less than 1,200 receptors/cell). However, the density of TCII receptors increased substantially when cells were subcultured in fresh medium. Up-regulation of receptor expression coincided with increased 3H-thymidine incorporation, which preceded the resumption of cellular proliferation as measured by cell density. In the presence of cytosine arabinoside, which induces erythroid differentiation, K562 cells down-regulated expression of TCII receptors. When HL-60 cells were subcultured in fresh medium containing dimethysulfoxide to induce granulocytic differentiation, the up-regulation of TCII receptors was suppressed. This event occurred well before a diminution of 3H-thymidine incorporation and cessation of proliferation. Thus, changes in the regulation of expression of TCII receptors correlate with both the proliferative and differentiation status of cells. 
5	Molecular evolution of inversions in Drosophila pseudoobscura: the amylase gene region. The amylase region of the third chromosome of Drosophila pseudoobscura has been cloned and localized to cytological band 73A. It is contained within a series of highly polymorphic inversions and serves as a convenient tool for a molecular evolutionary analysis of the inverted gene arrangements. Amylase in D. pseudoobscura is a family of three genes, and some chromosomes have deletions for one or two of them. Two overlapping clones covering 26 kilobases were isolated and used as probes to survey DNA restriction map polymorphism among 28 lines, representing five of the major inversion types found in natural populations, as well as single chromosomes from the closely related species Drosophila persimilis and Drosophila miranda. Restriction-site differences are considerably greater among the various gene arrangements than among chromosomes with the same gene arrangement. Clustering the restriction map haplotypes yielded a dendrogram concordant with the phylogeny generated independently from cytogenetic considerations. The inversion polymorphism is estimated to be about 2 million years old. 
1	Receptor imaging: application to MR imaging of liver cancer. A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors. 
3	Preventing stroke by the modification of risk factors. Epidemiologic research has revealed the major risk factors in cerebrovascular disease. This review will concentrate on three important risk factors: elevated blood pressure, the most common and important, since it is responsible for up to 70% of all strokes; raised cholesterol; and smoking. These factors are important not only because they increase the risk of stroke, but also because they are amenable to modification by drugs, diet, or other interventions. Strategies to avoid stroke can either 1) try to produce substantial reductions, usually with drugs, in the level of the risk factor in the few individuals in the population with high levels (the "high-risk" approach), or 2) try to produce modest reductions in the level of the risk factor in every individual in the population, usually not with drugs but with lifestyle modification (the "mass" approach). The prevention of stroke could best be achieved through continuing medical efforts to deal with high-risk individuals and through political strategies to encourage a healthier lifestyle in the population as a whole. 
4	Results of infrainguinal bypass for limb salvage in patients with end-stage renal disease. Limb salvage in patients with end-stage renal disease (ESRD) is complicated by the diffuse, obstructive, calcific arteriopathy that makes anastomotic technique especially critical. Furthermore, decreased resistance to infection and impaired wound healing produced by host-factor deficiencies such as diabetes mellitus, hypoalbuminemia, uremia, and immunosuppression produce additional obstacles to successful limb salvage. This report summarizes our experience with distal arterial bypass procedures in these patients. A total of 32 bypass procedures were performed for limb salvage in 24 patients (17 diabetic) during a period of 5 years. The operative mortality rate was 6%. During the same period, 635 infrainguinal bypass procedures were performed by the in situ technique in patients without ESRD. Primary bypass patency was comparable in both groups at 24 months (92% vs 90%). In the group with ESRD, overall limb salvage was 83% at 2 years. Life-table analysis of bypass patency and limb salvage was thought not to be appropriate in the population with ESRD beyond 2 years because of the increased mortality rate (38%; 9/24) during this interval. It is important that limb salvage was achieved in diabetic patients with ESRD in the presence of extensive foot gangrene or ischemic ulceration. Revascularization should be considered strongly for limb salvage in all patients in this difficult population. 
5	In vitro model of intestinal crypt abscess. A novel neutrophil-derived secretagogue activity. In order to model crypt abscesses, a histological finding which correlates with disease activity in intestinal inflammation, human polymorphonuclear leukocytes (PMN) were layered onto monolayers of the human intestinal epithelial cell line T84, a crypt-like epithelium which is capable of Cl- secretion. Such PMN-epithelial interaction had no substantial effect on monolayer integrity or function. However, when PMN were stimulated by conditions including those present naturally in the human colonic lumen, monolayers responded with a bumetanide-sensitive short circuit current (Isc) indicative of Cl- secretion, the basis of secretory diarrhea. This Isc response was induced by a neutrophil-derived secretagogue (NDS), which was only active when applied to the luminal surface of monolayers and did not require PMN-epithelial contact. NDS activity is resistant to boiling, acid, and trypsin and passes a 500 nominal mol wt cutoff filter. NDS activity is not secondary to the respiratory burst products O2- or H2O2 and does not appear to be a myeloperoxidase product. We speculate NDS elicited Cl- secretion may contribute to the secretory diarrhea seen in patients with intestinal inflammation and crypt abscesses. 
5	Differential protective effects of halothane and isoflurane against hypoxic and reoxygenation injury in the isolated guinea pig heart. The authors investigated the effects of halothane (HAL) and isoflurane (ISO) on cardiac depression produced by global hypoxia and the recovery of function following reoxygenation is isolated guinea pig hearts perfused with Krebs' solution at constant pressure. Isovolumetric left ventricular systolic (LVSP) and end-diastolic pressures (LVEDP) were measured by placing a saline filled, latex balloon into the left ventricle. Bipolar electrodes were placed in the right atrium and right ventricle for measurements of heart rate (HR), atrioventricular conduction time (AVCT), and determination of the incidence and severity of dysrhythmias occurring during hypoxia and reoxygenation. Hearts were divided into three groups: control (n = 20), halothane (n = 12), and isoflurane (n = 13). All hearts were exposed in sequence to oxygenated perfusate (PO2, 530 mmHg), moderately hypoxic perfusate (PO2, 91 mmHg) for 30 min, and then to oxygenated perfusate for 40 min. Halothane (1%, 0.4 mM) or isoflurane (1.5%, 0.5 mM) were administered 10 min before hypoxia, during hypoxia, and during the first 10 min of reoxygenation. Exposure to halothane and isoflurane before hypoxia produced a 14 and 11% decrease in heart rate, a 32 and 23% increase in AVCT, and a 47 and 28% decrease in LVSP (all P less than or equal to 0.001) for halothane and isoflurane, respectively, and no significant change in LVEDP. During hypoxia, HR decreased and AVCT increased similarly in both groups. Left ventricular systolic pressure (LVSP) decreased sharply with a narrowing of the prehypoxic differences among the groups. In the control and isoflurane groups, LVEDP increased during hypoxia but remained unchanged in the halothane group. 
2	Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis? Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells. 
1	Primary prevention of cancer. The case for comprehensive school health education. Comprehensive school health education plays an important role in the primary prevention of cancer because so many of the health habits relating to cancer and other diseases have their onset early in life. A comprehensive health education program should begin early in life. Such education must be multifactorial from kindergarten through high school, should involve annual health screening, must be assessed annually, and is most effective when coordinated by a full-time health education teacher. Those concerned about the many problems of health behavior in our society should insist that such programs become mandatory in every state in this nation. 
5	Edwards' syndrome after the replacement of cryopreserved-thawed embryos. A case of Edwards' syndrome after the replacement of frozen-thawed embryos is reported. The presence of cardiac abnormalities and limb deformities raised the suspicion of chromosomal abnormality. The diagnosis of trisomy 18 was made by cytogenetic analysis of fetal blood from the umbilical vein. The chromosomal nondisjunction might have been spontaneous or because of freezing and thawing. If it occurred as a result of freezing and thawing, it is more likely that this was at the first cleavage division rather than the second meiotic division because the embryos were frozen at the late pronuclear stage. Unfortunately, there were no karyotypic markers in the couple's chromosomes to time the nondisjunction. The wisdom of using donor oocytes in an ovum donation program from patients with long-standing infertility is questioned. 
3	Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations. Four subjects with thermolabile methylenetetrahydrofolate reductase (MTHFR) were discovered among 16 "obligate" heterozygotes for severe MTHFR deficiency and their family members. All four subjects had less than 25% of normal mean MTHFR specific activity in lymphocyte extracts. Three of them with normal serum folate and cyanocobalamin had intermediate hyperhomocysteinemia, and one with high serum folate and cyanocobalamin had no excessive accumulation of serum homocysteine. The biochemical features in these four subjects are distinguishable from subjects homozygous for the thermolabile MTHFR, whose specific activity is approximately 50% of the normal mean, and from heterozygotes for severe MTHFR deficiency, in whom the enzyme is thermostable and has a specific activity of about 50% of the normal mean. We propose that these four subjects are genetic compounds of the allele for the severe mutation and the allele for thermolabile mutation of the MTHFR gene. It is postulated that subjects with this genetic compound are more susceptible to the development of intermediate hyperhomocysteinemia despite normal folate and B12 levels. Nonetheless, hyperhomocysteinemia due to this compound heterozygosity is correctable by oral folic acid therapy. 
1	Stages of T-cell receptor protein expression in T-cell acute lymphoblastic leukemia. In this study five monoclonal antibodies (MoAbs) to T-cell receptor (TCR) proteins (WT31, alpha F1, beta F1, TCR delta-1 and delta TCS-1) were used to identify discrete maturative stages in 40 cases of T-cell acute lymphoblastic leukemia (T-ALL). These MoAbs reacted exclusively with CD3+ T cells and did not label B-lineage and myeloid cells. In 17 of the 40 T-ALL cases studied the leukemic blasts lacked membrane and cytoplasmic TCR chains (group I). In 12 cases cells did not have membrane CD3/TCR but expressed cytoplasmic TCR proteins heterogenously: nine cases had cytoplasmic TCR beta chains (beta F1+, alpha F1-; group II), one case had cytoplasmic TCR alpha chains (alpha F1+, beta F1-; group III), and two cases were labeled by both alpha F1 and beta F1 MoAbs (group IV). The remaining 11 cases were mCD3+: nine were TCR alpha beta+ (group Va) and two exhibited TCR gamma delta (TCR delta-1+, delta TCS-1+; group Vb). The analysis of the TCR beta, -gamma, and -delta gene configurations in 23 of the 40 T-ALLs showed that: (1) the lack of TCR protein expression was due to the lack of TCR gene rearrangements only in one of nine cases; (2) five of five TCR beta+, TCR alpha- cases studied had germline TCR alpha genes (ie, no detectable TCR delta gene deletions); (3) seven of eight cases with TCR delta gene deletions expressed TCR alpha proteins, whereas in 12 of 20 of the T-ALLs with TCR beta gene rearrangements the synthesis of the corresponding protein occurred; only 2 of 16 cases with rearranged TCR delta genes expressed TCR delta chains. The T-ALL categories identified with anti-TCR MoAbs did not have additional characteristic phenotypic patterns and may correspond to the normal stages of T-cell development more precisely than those defined by other differentiation antigens. 
1	Metastatic carcinoma to the retina. Clinicopathologic findings in two cases. Two cases of metastatic carcinoma to the neuroretina are reported. One patient had an oat cell carcinoma of the lung that was metastatic to the brain and retina; this was confirmed postmortem. The other patient had metastatic breast carcinoma with seeding of tumor cells into the vitreous from a focus of retinal embolism. The diagnosis was confirmed from a vitrectomy specimen. 
1	Progress in psychosocial and behavioral cancer research. The need for enabling strategies. A major component of the Second Workshop on Methodology in Behavioral and Psychosocial Cancer Research was a discussion of enabling strategies, that is, strategies by which future goals and needs in the area of psychosocial and behavioral oncology might be accomplished. This report describes and comments on the discussion that took place at a special plenary session at which representatives from four funding agencies, the American Cancer Society, National Cancer Institute, National Institute of Mental Health, and National Science Foundation, presented their views and their agencies' programs for promoting research in psychosocial and behavioral oncology. It is concluded that much progress has been made in the field and that strategies are in place for ensuring continued progress. However, suggestions are also made for new strategies that might accelerate and broaden that progress. 
3	Hyperprolactinemia increases and hypoprolactinemia decreases tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nuclei, but not the substantia nigra or zona incerta. The effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase (TH) mRNA signal levels were examined in dopaminergic neurons ovariectomized rats. TH mRNA signal levels and relative TH quantity in the arcuate nuclei, zona incerta, and substantia nigra were evaluated by in situ hybridization and immunocytochemistry, respectively. The catalytic activity of TH in the stalk-median eminence (SME) was determined from the in vitro rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine. Chronic administration of bromocriptine (BROMO), a dopamine (DA) agonist, for 3 days reduced circulating rat PRL (rPRL) levels compared to those in the vehicle-treated controls. BROMO treatment decreased TH mRNA signal levels in the arcuate nuclei, the intensity of TH immunostaining in the arcuate-median eminence area, and the rate of DOPA accumulation in the SME. Concomitant administration of ovine PRL (oPRL) reversed the effects of BROMO on TH, resulting in markedly increased TH mRNA signal levels, intensity of TH immunostaining, and rate of DOPA accumulation. Treatment with oPRL by itself for 3 days increased TH mRNA signal levels in the arcuate nuclei and TH activity in the SME, compared to vehicle. Chronic treatment with haloperidol, a DA antagonist, increased circulating levels of endogenous rPRL and increased TH activity in the SME to values similar to those after oPRL treatment. However, in contrast to oPRL, mRNA levels in the arcuate nuclei of haloperidol-treated rats were similar to levels in vehicle-treated animals. To evaluate whether the effect of PRL on TH was species specific, oPRL or rPRL was continuously infused into the jugular vein using an osmotic minipump. TH mRNA levels in the arcuate nuclei were elevated above control levels by either oPRL or rPRL administration. TH mRNA levels in the DA perikarya located in the zona incerta and substantia nigra were not altered by treatment with a DA agonist, a DA antagonist, or PRL. These results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment, respectively, TH mRNA levels in the tuberoinfundibular dopaminergic neurons. The alterations in TH mRNA content probably contribute to the decrease or increase in TH activity associated with hypoprolactinemia or hyperprolactinemia, respectively. 
5	Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors. Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data. 
5	Diclofenac-associated hepatotoxicity Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death. Signs and symptoms developed within several weeks of initiation of drug use and generally resolved 4 to 6 weeks following discontinuation of use of the drug. The only patient rechallenged with the drug developed a recurrence of her hepatic abnormalities. In one patient, fatal, fulminant hepatitis developed despite early withdrawal of the drug. Review of the European literature disclosed three additional fatalities associated with diclofenac therapy. It is unclear whether the incidence of hepatotoxicity is higher with this drug compared with other nonsteroidal anti-inflammatory drugs. Careful patient monitoring is advised, and prompt discontinuation of the drug is suggested when signs or symptoms of liver disease develop. 
3	Microangiopathy in the eosinophilia-myalgia syndrome. The eosinophilia-myalgia syndrome associated with the ingestion of L-tryptophan was recognized in late 1989. We describe our pathologic study of skin, fascial, and muscle biopsies from 21 patients evaluated by light microscopy, histochemistry, and electron microscopy. A perivascular, lymphocytic infiltrate with eosinophils was present in the dermis, fascia, and skeletal muscle. Lymphocytic infiltration of arteries and arterioles was seen. Ultrastructurally, capillary and arteriolar endothelial cell thickening and necrosis was present. This microangiopathy suggests that ischemia may be a contributing factor to the findings in this syndrome. 
5	Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries. A model of proliferative human restenosis was developed in domestic pigs by using deep injury to the coronary arterial media. Metal wire coils were delivered percutaneously to the coronary arteries of 11 pigs with an oversized, high-pressure (14 atm) balloon and were left in place for times ranging from 28 to 70 days. During placement, the balloon expanded the coils and delivered them securely within the arterial lumen. Light microscopic examination of the vessels confirmed fracture of the internal elastic lamina by the coil. An extensive proliferative response occurred in 10 of the 11 pigs and was associated with a luminal area narrowing of at least 50% in all but one pig. The histopathologic features of the proliferative response were identical to those observed in human cases of restenosis after angioplasty. Immunohistochemical studies confirmed the prominence of smooth muscle cells in the proliferative tissue. A similar response was obtained in two of five porcine coronary arteries in which balloon inflation only was performed, without coil implant. This model is practical and inexpensive and closely mimics the proliferative portion of human restenosis both grossly and microscopically. Thus, it may be useful for understanding human restenosis and for testing therapies aimed at preventing restenosis after balloon angioplasty or other coronary interventional procedures. 
1	A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Age, ultrasound score, menopausal status, a clinical impression score and serum CA 125 level were assessed to see how they could best distinguish between patients with benign (n = 101) and malignant (n = 42) pelvic masses. Each criteria used alone provided statistically significant discrimination. The most useful individual criteria were a serum CA 125 level of 30 U/ml (sensitivity 81%, specificity 75%) and an ultrasound score of 2 (sensitivity 71%, specificity 83%). Three criteria could be combined in a risk of malignancy index (RMI) which is simply calculated using the product of the serum CA 125 level (U/ml), the ultrasound scan result (expressed as a score of 0, 1 or 3) and the menopausal status (1 if premenopausal and 3 if postmenopausal). This index was statistically virtually as effective a discriminant between cancer and benign lesions as more formal methods. Using an RMI cut-off level of 200, the sensitivity was 85% and the specificity was 97%. Patients with an RMI score of greater than 200 had, on average, 42 times the background risk of cancer and those with a lower value 0.15 times the background risk. 
5	Biomechanical evaluation of lumbar spinal stability after graded facetectomies. In an in vitro experiment using fresh human lumbar functional spinal units, the effects of the division of the posterior ligaments (consisting of the supraspinous/interspinous ligaments) and graded facetectomies were investigated. The graded facetectomies consisted of unilateral and bilateral medial facetectomies, and unilateral and bilateral total facetectomies. Six kinds of moments were applied and ranges of motion (ROM) and neutral zones (NZ) were determined three-dimensionally by stereophotogrammetric methods. Range of motion was not affected by the division of the supraspinous/interspinous ligaments for all load modes. In flexion, ROM increased slightly after unilateral medial facetectomy. In right axial rotation, ROM increased after left unilateral total facetectomy. Range of motion was not affected, even by bilateral total facetectomies, in extension and lateral bendings. This study suggested that medial facetectomy does not affect lumbar spinal stability, and conversely, total facetectomy, even created unilaterally, makes the lumbar spine unstable. 
4	Inferior vena caval filter thrombi: evaluation with intravascular US. A 20-MHz intravascular ultrasound (US) transducer inside a percutaneously inserted catheter was used to evaluate inferior vena caval (IVC) filters for thrombi in vitro and in vivo. Six different IVC filters were studied with intravascular US in a saline-filled model. Each filter had a characteristic, recognizable US pattern. Experimental thrombi as small as 0.5 cm3 were easily detected. Intravascular US was used clinically 25 times to evaluate the IVC in 23 patients with 24 IVC filters. Positive-contrast cavograms were available for comparison in all 25 cases. In 13 cases, no thrombi were identified in the filter or IVC with either intravascular US or cavography; in five of 12 cases with thrombi, intravascular US and cavography demonstrated the thrombi equally well. In six cases, intravascular US was superior to cavography in detection or delineation of thrombus in the IVC or filter. Intravascular US was considered superior to external duplex US in evaluation of caval thrombi in all 21 cases available for comparison. No complications from intravascular US were noted. 
1	Effects of recombinant human interleukin-3 on human hematopoietic progenitor and precursor cells in vivo. DNA-synthesis rates and concentrations of bone marrow (BM) and peripheral blood (PB) progenitor cells were studied in 22 patients treated with recombinant human interleukin-3 (rhIL3) as part of a clinical phase I/II study. Recombinant hIL3 at doses of 60 to 500 micrograms/m2 was administered by subcutaneous bolus injection for 15 days to 13 patients with solid tumors and preserved hematopoietic function and to nine patients with bone marrow failure, including five with myelodysplastic syndromes. Following treatment with rhIL3, the percentage of actively cycling BM erythroid (BFU-E) and multilineage (CFU-GEMM) progenitors in patients with preserved hematopoietic function increased from 16% to 36% (P less than .05) and from 10% to 40% (P less than .01), respectively. The DNA-synthesis rates of early and late granulocyte macrophage progenitor cells increased from 11% to 26% (CFU-GM day 14; P less than .02) and from 13% to 30% (CFU-GM day 7; P less than .05). There was an increase in BM cellularity from 37% to 58%, and of the myeloid to erythroid ratio from 1.4 to 3.2, while the concentration of marrow progenitors on a per cell basis was unchanged or slightly decreased. The frequencies of blast cells in the BM were unchanged. Mean levels of PB CFU-GM day 14 and CFU-GEMM were 100% and 72% above baseline values after 7 days of rhIL3 but only 25% and 28% above initial levels at the end of treatment. Peripheral blood BFU-E were reduced in the majority of patients with normal marrow after both 7 and 15 days of rhIL3. No augmentation of circulating BFU-E and CFU-GEMM was seen in 5 patients with MDS who had few or no PB BFU-E or CFU-GEMM initially. Total leukocyte, neutrophil, and eosinophil counts increased significantly (P less than .01) in 21 of 22 patients with a peak response after a median of 13 days of rhIL3. While a small increase in reticulocytes was not accompanied by an elevation of the hemoglobin or hematocrit, platelet counts increased by 50% in patients with preserved marrow function. Thus, rhIL3 induces a multilineage response in vivo, apparently by stimulating proliferation of multipotential and lineage-restricted progenitors. It remains to be determined whether this is due to direct or indirect effects on the progenitor cells. 
5	Inflammatory abdominal aortic aneurysm masquerading as occlusion of the inferior vena cava. Inflammatory aneurysms are an uncommon disorder that represent between 5% and 10% of abdominal aortic aneurysms. Their presentation is often variable and may include pain and obstruction of adjacent anatomic structures. This report describes a 68-year-old man who sought treatment after insidious onset of progressive bilateral lower extremity edema over a 6-month period. Noninvasive studies were suggestive of bilateral iliac vein occlusion, and a venogram showed a nearly obstructed vena cava from external compression. A CT scan showed a thick-walled infrarenal abdominal aneurysm. At exploration an inflammatory abdominal aortic aneurysm was found. Because of the presence of dense inflammatory changes surrounding the aneurysm and extending into the pelvis, the surgical procedure of choice was an aortobifemoral bypass graft done with Dacron. The aneurysmal wall was debrided from the vena cava. His postoperative course was uneventful, his edema resolved, and follow-up noninvasive studies were normal. Postoperative venography showed resolution of the extrinsic compression of the vena cava. 
5	Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na(+)-K+ pump inhibition (10 microM ouabain or K(+)-free perfusate) to induce VF. AC stimulation or Na(+)-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na(+)-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM uniformly prevented the initiation of VF due to Na(+)-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM resulted in defibrillation during VF whether induced by AC or Na(+)-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF. 
3	Modern pharmacotherapy of migraine. Rectal ergotamine and naproxen are the major candidates for the ad hoc treatment of migraine attacks; for particularly dramatic episodes, intravenous DHE with prochlorperazine is the author's preference. For long-term stabilization, after simpler measures fail, valproate appears to be a major addition to migraine therapy. 
5	Role of hypoxic drive in regulation of postapneic ventilation during sleep in patients with obstructive sleep apnea. To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level. 
5	Complications of nasotracheal intubation in neonates, infants and children: a review of 4 years' experience in a children's hospital. A computerized database was set up to study the incidence and outcome of complications of nasotracheal intubation in a paediatric hospital. We studied 2953 intensive care admissions over a 4-yr period. The overall complication rate was 8%. Accidental extubation and tube blockage were the most frequent events, accounting for a mean of 3.5% and 2.6% of the complications per year, respectively. Complications were more common in smaller children and there were differences between fields of intensive care. None of the complications was fatal or resulted in serious sequelae. None of the children in the study showed clinical symptoms of acquired subglottic stenosis before discharge from hospital, and none has been readmitted for this condition subsequently. 
5	Superficial femoral artery as inflow for bypass to the proximal popliteal artery. We have obtained long term follow-up on 58 patients in whom the superficial femoral artery was used as a donor site for bypass to the proximal popliteal artery. The indication for the reconstructive procedure was intermittent claudication 36%, rest pain 34%, and gangrene 26%. All patients had angiographic evidence of a patent proximal superficial femoral artery and many had relative indications for short bypass such as limited saphenous vein availability or compromised medical condition. There was a cumulative patency rate of 79% by life table method for the series with a six year follow-up. We have observed that the superficial femoral artery is a satisfactory inflow site for proximal popliteal bypass grafts in selected patients. The procedure can maximize use of a limited segment of vein with minimal operative time and morbidity. Inflow stenosis can be revised or long bypass procedures can be offered in the event of graft failure. 
5	Adenotonsillectomy in children with sickle cell disease. The pediatric patient with sickle cell disease risks having a vasoocclusive episode during adenotonsillectomy under general anesthesia. With proper patient selection and appropriate perioperative management, adenotonsillectomy can be accomplished safely in children with sickle cell disease. We review the management of 10 children with sickle hemoglobinopathies who had adenotonsillectomy. Indications for surgery were recurrent streptococcal infections in four and obstructive sleep apnea in six of these children. No complications resulted from any of these procedures, and the mean length of postoperative hospitalization was 2.4 days. The principal feature of preoperative management was the transfusion of red blood cells to suppress the patient's endogenous erythropoiesis and to reduce the concentration of sickle cell hemoglobin to less than 30%. Though a prospective, multi-institutional clinical trial will ultimately be required to settle the issue of the safest preoperative management of children with sickle cell disease, balancing the risks of transfusion-related complications against anesthesia-related complications, our experience supports the operative safety of hypertransfusion therapy in children with sickle cell disease. 
1	Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem. 
3	Traumatic aneurysm of the superior cerebellar artery: case report and review of the literature. Less than 10% of the 250 reported cases of traumatic intracranial aneurysms have involved the posterior circulation. Traumatic aneurysms of the superior cerebellar artery are extremely rare, with only three cases previously reported. This is the first report of a traumatic superior cerebellar artery aneurysm in which the diagnosis was suggested by computed tomographic scan. The potential for a good outcome suggests the value of early angiography when the history and diagnostic imaging studies suggest the possibility of a traumatic aneurysm. 
5	Transduodenal sphincteroplasty with transampullary septectomy for stenosing papillitis. The papilla of Vater and its sphincter of Oddi, lying at the confluence of the bile and pancreatic ducts in man, have long been suspected as a source of upper abdominal pain. Enlarging the opening of the transpapillary segment of the bile and major pancreatic ducts by using a transduodenal sphincteroplasty with transampullary septectomy resulted in death in a patient with a peripapillary diverticulum and pancreas divisum. Eight-six patients followed for 1 to 10 years experienced a 75% success rate. Thirty-six patients had a marked stenosis of their duct of Wirsung, suggesting that their pain was primarily from the pancreas. The remainder had either a generalized narrowing (40 patients) or a normal (7 patients) papilla. Pain was not satisfactorily resolved in patients with an associated pancreas divisum, chronic pancreatitis, and recurrent episodes of acute pancreatitis with alcoholism. 
4	Angiographic follow-up after placement of a self-expanding coronary-artery stent BACKGROUND. The placement of stents in coronary arteries after coronary angioplasty has been investigated as a way of treating abrupt coronary-artery occlusion related to the angioplasty and of reducing the late intimal hyperplasia responsible for gradual restenosis of the dilated lesion. METHODS. From March 1986 to January 1988, we implanted 117 self-expanding, stainless-steel endovascular stents (Wallstent) in the native coronary arteries (94 stents) or saphenous-vein bypass grafts (23 stents) of 105 patients. Angiograms were obtained immediately before and after placement of the stent and at follow-up at least one month later (unless symptoms required angiography sooner). The mortality after one year was 7.6 percent (8 patients). Follow-up angiograms (after a mean [+/- SD] of 5.7 +/- 4.4 months) were obtained in 95 patients with 105 stents and were analyzed quantitatively by a computer-assisted system of cardiovascular angiographic analysis. The 10 patients without follow-up angiograms included 4 who died. RESULTS. Complete occlusion occurred in 27 stents in 25 patients (24 percent); 21 occlusions were documented within the first 14 days after implantation. Overall, immediately after placement of the stent there was a significant increase in the minimal luminal diameter and a significant decrease in the percentage of the diameter with stenosis (changing from a mean [+/- SD] of 1.88 +/- 0.43 to 2.48 +/- 0.51 mm and from 37 +/- 12 to 21 +/- 10 percent, respectively; P less than 0.0001). Later, however, there was a significant decrease in the minimal luminal diameter and a significant increase in the stenosis of the segment with the stent (1.68 +/- 1.78 mm and 48 +/- 34 percent at follow-up). Significant restenosis, as indicated by a reduction of 0.72 mm in the minimal luminal diameter or by an increase in the percentage of stenosis to greater than or equal to 50 percent, occurred in 32 percent and 14 percent of patent stents, respectively. CONCLUSIONS. Early occlusion remains an important limitation of this coronary-artery stent. Even when the early effects are beneficial, there are frequently late occlusions or restenosis. The place of this form of treatment for coronary artery disease remains to be determined. 
1	Nonpigmented congenital iris stromal cyst. A nonpigmented iris stromal cyst was observed in the right eye of a 6-week-old girl. There was no past history of trauma or use of topical miotics, and the remainder of the ocular examination was normal. The pathophysiology and management of this rare developmental anomaly are controversial. 
2	Treatment of chronic liver disease caused by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid. Deficiency of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, the second enzyme in the sequence that catalyses the synthesis of bile acids from cholesterol, leads to chronic liver disease in childhood as well as to malabsorption of fat and fat soluble vitamins. A 4 year old boy with this condition has been successfully treated by oral administration of a bile acid--chenodeoxycholic acid. He had been jaundiced since birth, grew poorly because of rickets, and had severe pruritus. Plasma transaminase activities were persistently raised. Chenodeoxycholic acid 125 mg twice daily for two months, and then 125 mg daily, cured his jaundice and pruritus, returned his transaminase activities to normal, and eliminated the need for calcitriol for prevention of rickets. On this treatment he has so far remained well for two years. A diagnosis of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency should be considered in any child with unexplained chronic hepatitis or cirrhosis, especially if the liver disease is accompanied by a clinically obvious malabsorption of fat soluble vitamins. A simple colorimetric test of the urine confirms the diagnosis and effective treatment can be started. 
4	An echocardiographic assessment of atrial mechanical behaviour. Relations between movement of the atrioventricular ring and changes in left atrial and ventricular dimensions were studied by echocardiography and compared with apexcardiography and Doppler mitral flow velocity traces in 20 healthy controls and in patients with left ventricular hypertrophy (n = 28) or dilatation (n = 16). During left ventricular systole the atrioventricular ring, a structure common to ventricle and atrium, moved towards the ventricular apex, thus increasing left atrial volume. This action matched pulmonary venous return because it was in phase with the transverse left atrial dimension measured from aortic root to posterior left atrial wall. During early diastole, the mitral ring moved rapidly towards the atrium as transmitral flow accelerated. This requires a force directed from ventricle to atrium, likely to be the result of elastic recoil arising from compression of the ventricular myocardium or stretching of the atrial myocardium during ventricular systole. Two additional mechanisms of ventricular filling with atrial systole were recognised: (a) an increase in ventricular volume as the atrioventricular ring moved upwards and (b) transverse left ventricular expansion by pressure driven transmitral flow. The former is undetectable by Doppler from the apex; it accounted for 10% of ventricular filling in the healthy controls, but for significantly less in those with ventricular dilatation. In left ventricular hypertrophy, left ventricular filling was maintained by both mechanisms compensating for the reduced increase in volume early in diastole. Interactions between the atrium and ventricle are functionally important during ventricular systole, early diastole, and in atrial systole. They are not included in the traditional separation of atrial function into reservoir, conduit, and pump functions. 
5	Extended hepatectomy for hepatocellular carcinoma. The results of extended hepatectomy in 25 patients with hepatocellular carcinoma performed over a 16 year period have been reviewed, analysed and compared with those of 144 patients who underwent lesser liver resection. Five left and 20 right extended hepatectomies were performed for tumours ranging from 3 to 20 cm in diameter. Seventeen (68 per cent) of the patients had non-cirrhotic livers. The major postoperative complications were: haemorrhage in five cases, major bile duct injury in three, subphrenic abscess in two, liver failure in one and wound dehiscence in one. The 30-day (operative) mortality rate was 12 per cent and the median survival duration, including operative mortality, was 9.7 (range 0.2-32.1) months. The survival rate was 46 per cent at 1 year, 33 per cent at 2 years and 22 per cent at 3 years. The morbidity, mortality and survival data of extended hepatectomy were comparable with the results of lesser hepatic resections for hepatocellular carcinoma. We conclude that extended hepatectomy is a worthwhile operation for large hepatocellular carcinomas and a viable alternative to liver transplantation. 
4	Biphasic effects of doxorubicin on the calcium release channel from sarcoplasmic reticulum of cardiac muscle. To define the mechanism of doxorubicin cardiotoxicity, the effects of doxorubicin and caffeine were examined on calcium release channels from cardiac sarcoplasmic reticulum. We found that calcium release from cardiac sarcoplasmic reticulum vesicles was induced by both compounds. When sarcoplasmic reticulum vesicles were incorporated into planar lipid bilayers, calcium-permeable channels were observed. Addition of caffeine (2.5-10 mM) increased channel open probability from less than 0.1% to 40%, and this effect persisted for a mean of 44 minutes. In contrast, doxorubicin (2.5-10 microM) had a biphasic effect; initially, doxorubicin activated the channel, whereas after a mean of 8 minutes, the channel became irreversibly inhibited. Although the degree of channel activation by doxorubicin was concentration dependent, the time needed to inactivate the channel was concentration independent. Pretreatment with dithiothreitol (0.2 mM) prevented doxorubicin-induced channel inactivation, and channel activity persisted for an average of 58 minutes. Dithiothreitol alone did not alter channel open probability. Our results support the hypotheses that 1) the integrity of sulfhydryl groups is important for some aspects of calcium release channel function and 2) activation and inactivation of the channel are separable processes. The biphasic effect of doxorubicin on channel function may also correspond to the clinically observed adverse effects of doxorubicin, a widely used chemotherapeutic agent that, after prolonged usage, causes a dilated cardiomyopathy. 
1	Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment. Extraadrenal retroperitoneal paragangliomas (RP) are uncommon tumors. Because of their rarity, little is known of their natural history or response to treatment. We reviewed 22 patients with RP who were seen at our center between 1949 and 1990. The distribution of male and female patients was nearly equal, and the mean age was 42. Most patients were admitted with pain or a mass, and eight of 22 tumors were functional. No significant difference was noted in duration of symptoms, size of the tumor, or survival between functional and nonfunctional tumors. Eleven of 22 (50%) RP metastasized and were therefore classified as malignant. Five-year and 10-year disease free survival rates were 19% and 19% for tumors not resected and 75% and 45% for those completely resected. Once metastases occurred, the 5-year survival rate was 36%, but no patient survived beyond 76 months. Predictors of survival included complete resection of the tumor but not size or functional status. Although some patients who received chemotherapy or radiotherapy had clinical responses, a survival benefit could not be shown. RP have a high rate of malignant behavior and should be treated aggressively with operation. Late metastases are not uncommon, and prolonged follow-up is necessary. Once metastases have occurred, some patients may have prolonged survival. 
4	Freehand allograft aortic valve replacement and aortic root replacement. Utility of intraoperative echocardiography and Doppler color flow mapping. Seventeen consecutive patients undergoing 20 planned aortic valve replacements with allograft valves at Stanford University Medical Center were studied with intraoperative epicardial echocardiography and Doppler color flow mapping before and after cardiopulmonary bypass. Native aortic valves were replaced in 12 of the 20 patients, and eight patients underwent second aortic valve procedures. In 17 of 20 patients allograft selection was guided by prebypass echocardiographic estimates of annular diameter and/or length of allograft aortic root required. Other prebypass findings included unanticipated severe mitral regurgitation in one patient (which precluded allograft aortic valve replacement), left-to-right shunts in five patients, ascending aortic dissection in one, and aortic root disease necessitating coronary reimplantation or bypass in two. Postbypass echocardiography demonstrated acceptable competency of 18 of 19 allograft valves (mild or no aortic insufficiency). Postbypass echocardiography also documented successful repair of four of five shunts and mild mitral regurgitation in 15 of 19 patients (versus 11 of 19 before bypass). Conclusions: Intraoperative echocardiography-Doppler mapping is a useful adjunct for allograft aortic valve or aortic root replacement; it allows confident selection of appropriate tissue size before aortic cross clamping, which minimizes delay from allograft thawing procedures. It also provides helpful information about the extent of aortic root disease and coronary ostial anatomy before bypass, confirms allograft competency after bypass, and detects accompanying valvular and other hemodynamic lesions before and after allograft valve replacement. 
4	Cardiovascular effects of nicardipine. Nicardipine, a new 1-4 dihydropyridine calcium antagonist, has chemical properties that allow oral and stable intravenous preparations. It is the first intravenous dihydropyridine calcium antagonist available in the United States. Among its drug class it has a unique chemical structure that affords properties useful in the treatment of acute cardiovascular conditions, such as myocardial ischemia, congestive heart failure, hypertension, cerebrovascular disease, and other related disorders. In patients with coronary artery disease, intravenous nicardipine has been found to reduce myocardial oxygen demand by reducing afterload and increasing myocardial oxygen supply through coronary vasodilatation. It enhances left ventricular performance and augments coronary blood flow beyond that required by increased myocardial oxygen consumption. Nicardipine may also offer protection from ischemic injury to the heart and central nervous system. Alone and in combination with other antihypertensive agents, nicardipine has been shown to be effective in the treatment of mild to moderate hypertension. It is safe for use in patients with certain types of conduction disturbances because it does not greatly affect sinoatrial and atrioventricular conduction. Additional advantages for nicardipine's use in the management of acute cardiovascular disorders are its rapid onset and short duration of action. 
5	Retroperitoneal air after routine hemorrhoidectomy. Report of a case. Retroperitoneal air as a complication after routine hemorrhoidectomy has not been reported in the literature. This occurred recently after hemorrhoidectomy in a 34-year-old patient receiving glucocorticoid therapy for rheumatoid arthritis. Adverse steroidal effects of wound healing have been well documented. It is believed that steroid-induced tissue changes contributed to the development of this unique complication. 
4	Changing arteriosclerotic disease patterns and management strategies in lower-limb-threatening ischemia. From January 1, 1974 to December 31, 1989, we treated 2829 patients with critical lower-extremity ischemia. In the last 5 years, 13% of patients had therapeutically significant stenoses or occlusions above and below the groin, while 35% had them at two or three levels below the inguinal ligament. Unobstructed arterial flow to the distal half of the thigh was present in 26% of patients, and 16% had unobstructed flow to the upper third of the leg with occlusions of all three leg arteries distal to this point and reconstitution of some patent named artery in the lower leg or foot. In the last 2 years, 99% of all patients with a threatened limb and without severe organic mental syndrome or midfoot gangrene were amenable to revascularization by percutaneous transluminal angioplasty (PTA), arterial bypass, or a combination of the two, although some distal arteries used for bypass insertion were heavily diseased or isolated segments without an intact plantar arch. Limb salvage was achieved and maintained in more than 90% of recent patient cohorts, with a mean procedural mortality rate of 3.3%. Recent strategies that contributed to these results include (1) distal origin short vein grafts from the below-knee popliteal or tibial arteries to an ankle or foot artery (291 cases); (2) combined PTA and bypass (245 cases); (3) more distal PTA of popliteal and tibial artery stenoses (233 cases); (4) use of in situ or ectopic reversed autogenous vein for infrapopliteal bypasses, even when vein diameter was 3 to 4 mm; (5) composite-sequential femoropopliteal-distal (PTFE/vein) bypasses; (6) reintervention when a procedure thrombosed (637 cases) or was threatened by a hemodynamically significant inflow, outflow, or graft lesion (failing graft, 252 cases); (7) frequent follow-up to detect threatening lesions before graft thrombosis occurred and to permit correction of lesions by PTA (58%) or simple reoperation; and (8) unusual approaches to all infrainguinal arteries to facilitate secondary operations, despite scarring and infection. Primary major amputation rates decreased from 41% to 5% and total amputation rates decreased from 49% to 14%. Aggressive policies to save threatened limbs thus are supported. 
1	The effect of dietary omega-3 fatty acids (fish oil) on azoxymethanol-induced focal areas of dysplasia and colon tumor incidence. MaxEPA (MA), a fish oil high in omega-3 fatty acids, was combined with various levels of corn oil (CO), rich in omega-6 fatty acids, and fed to female CF1 mice. The three fish oil blends with CO and the two CO levels of the diets studied were as follows: 16.0% CO + 4.4% MA (Diet 1); 10.2% CO + 10.2% MA (Diet 2); 4.4% CO + 16.0% MA (Diet 3); 20.4% CO (Diet 4); and 4.4% CO (Diet 5). The diets were provided 2 weeks before weekly subcutaneous injection of saline or azoxymethanol (AOM). Studies of epithelial cell proliferation and the incidence of focal areas of dysplasia (FAD) involved six weekly AOM injections. One week after the last AOM injection and 1 hour before killing, mice were injected with tritiated thymidine (3HTdR). No differences in any proliferative parameters were found among the five groups of saline-treated mice. Among the AOM-treated animals, those fed Diet 3 showed significantly fewer cells per crypt and significantly fewer labeled cells/gland than CO Diets 4 and 5. Additionally, the distribution of S-phase cells in crypts of AOM-treated mice fed Diet 3 most closely resembled that of the saline controls. The greatest alteration in the distribution of proliferative cells was observed in the high-CO diet (Diet 4) and the lowest MA level (Diet 1). Mice fed Diets 2 and 3 had significantly fewer FAD/500 microns of distal colonic serial sections than those fed the high CO diet (Diet 4). Mice involved in chronic tumor incidence studies received only three weekly injections of the same dose of AOM. Regardless of diet, approximately 88% of all tumors arose in the distal colon. A significantly larger tumor-bearing population was observed in both the high-CO Diet 4 and the lowest MaxEPA (MA) diet (Diet 1) compared with the incidence in MA Diets 2 and 3 and the low-CO Diet 5. A diet with a ratio of omega-6 to omega-3 fatty acids of approximately 1.0 apparently prevented the development of an adenoma-type proliferative pattern thereby reducing FAD numbers and subsequent tumor incidence. 
4	Normotensive young men with family histories of hypertension gain weight and decrease their intraerythrocyte sodium content during a 5-year follow-up. Young normotensive men matched for age and body mass index with (n = 16) and without (n = 13) family histories of hypertension were investigated at baseline and after 5 years of follow-up with respect to blood pressure, body weight and intracellular sodium content. Subjects with positive family histories of hypertension increased significantly in body weight (from 81.9 +/- 11.5 kg to 89.5 +/- 11.4 kg, P less than 0.001) compared to subjects with negative family histories of hypertension (from 79.9 +/- 10.8 kg to 80.7 +/- 12.2 kg, NS). Their blood pressure did not differ initially (137 +/- 12/75 +/- 11 mmHg vs. 135 +/- 8/72 +/- 9 mmHg), but was reduced in subjects without family histories of hypertension (to 125 +/- 3/68 +/- 13 mmHg) in the follow-up examination. At follow-up, body mass index showed a positive correlation with blood pressure among subjects with positive family histories of hypertension (r = 0.77, P less than 0.001). At baseline, subjects with hypertensive fathers had significantly higher intraerythrocyte sodium levels than subjects with normotensive parents. At re-examination 5 years later, this difference was no longer present. We conclude that normotensive subjects with positive family histories of hypertension are predisposed to gain weight rather than to show an increase in blood pressure at this age. Normalization of intracellular sodium content, as found in the present study, could be a consequence of this weight gain and the ensuing metabolic adaption. 
3	Observations on the pathophysiology of Nelson's syndrome: a report of three cases. Nelson's syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for Cushing's disease. It is classically defined by cutaneous hyperpigmentation, considerably elevated adrenocorticotropic hormone (ACTH) levels, and an enlarged sella turcica. In this report, we present three cases initially treated by transsphenoidal sellar exploration for Cushing's disease. In two of these cases, remission of hypercortisolism did not occur after the initial pituitary exploration. A microadenomectomy was performed in one case and, in the other, no microadenoma was found. In both, Nelson's syndrome occurred after adrenalectomy. A second transsphenoidal operation and radiotherapy were required to control tumor growth. In another case, transsphenoidal adenomectomy of an ACTH-secreting tumor initially led to a remission of hypercortisolism for 4 years, but recurrent Cushing's disease necessitated adrenalectomy, and again Nelson's syndrome occurred. The documentation of a pre-existing ACTH-secreting basophilic pituitary microadenoma before adrenalectomy, as seen in two of our cases, has not been previously reported, and these observations of "non-classical" courses have major implications for the pathophysiology of Nelson's syndrome. 
5	The importance of congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis. We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer. 
1	Comparison of the conventional method of lymph node staging with a comprehensive fat-clearing method for gastric adenocarcinoma. Discrepant results in long-term survival between United States and Japanese patients with resectable gastric adenocarcinoma may result from more accurate staging in the Japanese series. The authors compared a comprehensive fat-clearing method with the conventional pathology method of lymph node sampling in 11 patients undergoing curative gastrectomy and extended lymphadenectomy at their institution. Comprehensive fat-clearing doubled total lymph node counts (P less than 0.01), identified smaller lymph nodes (P less than 0.001), and identified more histologically involved nodes of significantly smaller size (P less than 0.001). Comprehensive fat-clearing pathologically upstaged 29% of the authors' eligible specimens. Accurate pathologic staging is necessary when comparing Japanese and United States survival data for resectable gastric adenocarcinomas. 
5	Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features. BACKGROUND AND METHODS. We describe a new form of hepatitis, occurring in 10 patients over a period of six years, characterized clinically by manifestations of severe hepatitis, histologically by large syncytial giant hepatocytes, and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids. RESULTS. The patients ranged in age from 5 months to 41 years. The tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five patients and autoimmune chronic active hepatitis in the others. Five patients underwent liver transplantation; the others died. The diagnosis of syncytial giant-cell hepatitis was established pathologically. The liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns, filamentous strands, and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated forms were found in the other two patients. One of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies, probably an anamnestic reaction to previous paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate. CONCLUSIONS. Although further virologic studies will be required for precise classification, we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis. 
1	Influence of chemotherapy administration on monocyte activation by liposomal muramyl tripeptide phosphatidylethanolamine in children with osteosarcoma. The purpose of these studies was to determine whether chemotherapy interfered with the ability of peripheral blood monocytes from patients with osteosarcoma to respond to the liposome-encapsulated activating agent muramyl tripeptide phosphatidylethanolamine (L-MTP-PE). This was done in preparation of designing an adjuvant therapy protocol that includes L-MTP-PE combined with chemotherapy postoperatively for the treatment of primary osteosarcoma. The majority of patients who fail current adjuvant chemotherapy do so while on chemotherapy. Therefore, we believe it is important to combine L-MTP-PE with chemotherapy early in the treatment course rather than waiting until all chemotherapy cycles are completed. The tumoricidal properties of monocytes from patients with osteosarcoma could be activated by L-MTP-PE to levels equal to or greater than those expressed by normal control monocytes. No intrinsic monocyte defect could be demonstrated. Single-agent chemotherapy consisting of cisplatin (CPD), high-dose methotrexate (MTX), Cytoxan (CTX, cyclophosphamide; Bristol-Myers Co, Evansville, IN), or Adriamycin (ADR, doxorubicin; Adria Laboratories, Columbus, OH) did not interfere with this activation process. There was even a suggestion of enhanced activation potential following the administration of ADR. However, when both ADR and CTX were administered together on the same day, profound suppression in monocyte activation was observed. This suppressed function returned to normal by 3 weeks postcombination therapy. We therefore conclude that L-MTP-PE can be combined with ADR, CPD, MTX, or CTX as single agents but recommend that ADR plus L-MTP-PE is the most effective combination. By contrast, we discourage the use of L-MTP-PE when ADR and CTX are given together. 
2	Adenocarcinoma arising in Barrett's esophagus after total gastrectomy A 64-yr-old Japanese male who underwent a partial gastrectomy for a duodenal ulcer at the age of 21, a total resection of the remnant stomach for a stomal ulcer at age 25, and in whom Barrett's esophagus was diagnosed at age 47, was found to have a tumor at the distal esophagus and was operated on by thoracic esophagectomy. The tumor was a well to moderately differentiated adenocarcinoma invading down to the muscularis propria. The entire esophageal mucosa in the resected specimen was lined by columnar epithelium. This tumor was thought to derive from the Barrett's esophageal epithelium. 
4	Parathyroidectomy in chronic renal failure: a nine-year follow-up study. Seventy-three patients with chronic renal failure who underwent parathyroidectomy between March 1978 and April 1987 were reviewed. Thirty-four patients had undergone sub-total parathyroidectomy, and 39 patients had undergone total parathyroidectomy with parathyroid autograft into the forearm. Eight patients showed persistent hyperparathyroidism requiring a second surgical procedure. In all other patients there was highly statistical improvement in parathyroid hormone, total calcium, ionized calcium, alkaline phosphatase and a significant reduction in calcium x phosphate product. Histological evidence of osteitis fibrosa was present in 21 of 22 patients before surgery. Postoperatively, four showed complete resolution and improvement. Three patients developed histological evidence of osteomalacia during the study period. Only four of the 39 patients who underwent total parathyroidectomy with autograft had true recurrent hyperparathyroidism and only two of the 34 patients who underwent sub-total parathyroidectomy had recurrent disease, indicating that there is little to choose between the two techniques in the control of secondary hyperparathyroidism and its subsequent recurrence. In one patient with recurrence of hyperparathyroidism from a forearm parathyroid graft the histological picture was different from that of normal hyperplastic parathyroid tissue. Although it is probable that abnormal parathyroid tissue had been implanted there was no evidence of invasive growth into the forearm muscle. The most striking feature of long term follow-up was the difference in calcium x phosphate product in patients in whom vascular calcification increased compared to those patients with no change or regression of calcification. Mean calcium phosphate product in those patients with progressive vascular calcification was 4.93 for small and medium size vessels and 5.38 for large vessels compared to 4.10 for small and medium vessels and 4.09 for large vessels. In the former case the serum phosphate was 2.00 and 2.17 as compared to 1.75 or 1.73, suggesting that the aim in patients with end stage renal failure maintained by dialysis should be to control the serum phosphate concentration to 1.8 mmol or less and the calcium x phosphate product to less than 4.2. 
4	Comparison of direct and indirect measures of systemic arterial pressure during weightlifting in coronary artery disease. Based on auscultation measurements after exercise, circuit weight training in cardiac patients has been reported to provoke minimal increases in systolic pressure. Direct (brachial artery catheter) and indirect (sphygmomanometry) measures of blood pressure were compared at rest, during lifting with the legs (approximately the fourth, ninth and fourteenth repetition) and during 2 minutes of recovery after lifting with the arms and legs. Subjects performed 15 repetitions of single-arm curl, single-arm military press and single- and double-leg press exercises at 40 and 60% of the maximum load that could be lifted once on a multistation weightlifting apparatus. Indirect measures of systolic pressure at rest were 13% less than those recorded directly (130 +/- 7 vs 149 +/- 8 torr; p less than 0.01); diastolic pressures were similar using either method. This pattern was maintained during lifting with the legs at both intensities, and after exercise with both the legs and the arms. The mean systolic pressure recorded indirectly immediately after exercise was 63 torr (31%) and 76 torr (34%) less than the average peak intraarterial value recorded during leg and arm exercises, respectively. The highest intraarterial pressures were generated during the final repetitions of the set; immediately after the last repetition, both systolic and diastolic pressures rapidly decreased. It is concluded that indirect estimates of systolic pressure are significantly less than true arterial values at rest, and during and after lifting. Moreover, indirect measurements after lifting do not allow accurate conclusions to be drawn about the arterial pressures generated during lifting because of the rapid decrease in pressure that occurs after exercise. 
5	An objective appraisal of the role of computed tomographic (CT) guided drainage of intra-abdominal abscesses. Computed tomographic (CT) guided drainage is an important tool in the treatment of intra-abdominal abscess. Its most important role is in the treatment of small, unilocular, well-placed abscesses. Success rates in our experience diminish considerably in abscesses involving necrotic tumors or those infected with yeast. As is frequently characteristic of new technologic procedures, the initial evaluation of the success rate of the procedure is overly optimistic. The procedure carries a considerable complication rate (13%) and mortality rate (15%). Most importantly, success is usually evident early; within the first 24 to 48 hours. After this length of time, careful evaluation to consider further treatment should be contemplated. 
4	Factors associated with recurrent myocardial infarction within one year after acute myocardial infarction. In a large population of patients (n = 3666) who were discharged from the hospital after acute myocardial infarction and followed up for 1 year, factors associated with recurrent nonfatal (n = 171) or fatal (n = 74) infarction were identified. Also, the effects of combining various end points (recurrent nonfatal or fatal infarction and other cardiac death) in multivariate analyses, a practice common in many small studies that evaluate the predictive-value of various treatments or special tests, was examined. In univariate analyses, patients with nonfatal recurrent infarction did not differ with respect to age or gender from infarct-free survivors, but they more often had a history of previous myocardial infarction, congestive heart failure, angina pectoris, and diabetes; more severe pulmonary congestion was present on chest x-ray during the admission, and a non-Q wave index infarction was more frequent. Patients with either a fatal or nonfatal recurrent infarction had more angina pectoris during follow-up (55% to 60%) compared with 27% in event-free survivors and 31% in patients who died of other cardiac causes in whom this factor could be assessed before death. In multivariate analyses, historical and clinical prognostic factors were ranked differently for fatal or nonfatal reinfarction and other cardiac causes of death; angina pectoris at follow-up was highly related to recurrent infarction (fatal or nonfatal), along with a history of diabetes, and a non-Q wave index infarction. These factors were not independently related to other causes of cardiac death. 
1	Function in athymic nude mice of parathyroid heterografts from patients with primary hyperparathyroidism and secondary hyperparathyroidism. Heterotransplantation of adenomatous parathyroid glandular tissue from humans with primary hyperparathyroidism into athymic nude mice creates a unique animal model of this disease. The mice manifest high concentrations of both midregion/C-terminal human parathyroid hormone and biologically active intact human parathyroid hormone relative to either mice with no implants or mice that received normal human parathyroid tissue. Secretion of these substances is maintained in most mice for at least 9 to 13 months after implantation. In addition, animals that have experienced implantation exhibit other characteristics associated with human primary hyperparathyroidism including relative hypercalcemia and increased renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity. We also measured these parameters in a group of nude mice that received transplantation of a similar mass of hyperplastic parathyroid tissue that was obtained from patients with uremic secondary hyperparathyroidism. Although we hypothesized that the level of human parathyroid hormone secretion from these implants would fall over time in response to the normal host environment, hormone levels remained as high as those in recipients of adenomatous heterografts, even after 9 to 13 months. Moreover, similar biologic effect of the excess parathyroid hormone (i.e., relative hypercalcemia, hyperphosphatasemia, and increased 1,25-dihydroxyvitamin D biosynthesis) were detected. These animal models should prove extremely useful in supplementing our understanding of hyperparathyroid disorder in man. 
4	Noninvasive measurement of renal blood flow with technetium-99m-DTPA in the evaluation of patients with suspected renovascular hypertension If a hypertensive patient with renal artery stenosis (RAS) is to benefit from percutaneous transluminal renal angioplasty (PTRA) in terms of a sustained improvement in blood pressure control, one may postulate a demonstrable reduction in renal blood flow (RBF) to that kidney, reversible by PTRA. In a population of 32 hypertensive patients, RAS was present in 23 of 62 kidneys. Eleven of the 32 patients underwent renal revascularization, of whom 6 showed improvement in blood pressure control at 6 mo, i.e., had renovascular hypertension (RVH). There was no correlation between RBF and angiographic appearances of the renal artery. Furthermore, there was no significant difference between RBF in the stenosed kidneys of the patients with RVH compared with the stenosed kidneys of patients without RVH. Individual kidney RBF was 22% (s.d. 11) higher 1-3 wk after PTRA but the increase did not correlate with clinical outcome. Angiotensin converting enzyme (ACE) inhibition increased RBF by 25% (s.d. 25) of baseline flow before PTRA but the increase did not correlate with clinical outcome. Measurement of RBF is of limited value for the prediction of the long-term blood pressure response following PTRA. 
2	Gross and microscopic changes in the viscera induced by photodynamic therapy applied to the lower abdomen of intact rats. Photodynamic therapy (PDT) is a promising approach to the treatment of cancer. Preferential retention of the photosensitizer by malignant tissue has been considered a hallmark of this treatment modality. However, photosensitivity can be observed in normal, non-neoplastic tissues, and the present study investigated the effects of PDT treatment on the abdomen of intact rats. A circular region (1 cm diameter) on the shaved abdomen of Fischer rats, pretreated 24 h prior with Photofrin II, was irradiated for 30 min at 632 nm. Control animals received either photoradiation or Photofrin II administration. Subsequent lesions were observed in the irradiated skin, its associated abdominal wall, and the underlying gut in rats receiving Photofrin II and laser irradiation. All tissues were not equally sensitive to PDT treatment. Gut lesions were consistently more severe than were skin and abdominal wall injuries. By 24 hr after treatment, the gut manifested a transmural hemorrhagic necrosis, while the irradiated skin and abdominal wall were edematous, with an inflammatory infiltrate in the dermis and around occasional swollen myocytes. These results indicate that superficial lesions induced by PDT may not be reliable indicators of the extent of deeper PDT tissue damage. Further, it may be possible to take advantage of this discrepancy in tissue sensitivity and treat deep tissues through less sensitive superficial tissues. 
4	Nondiagnosed left main ostial stenosis partly due to the use of 5 French coronary angiographic catheters. Two cases have been reported in which the use of 5 F angiographic catheters is associated with a failure to diagnose an ostial stenosis of the left main coronary artery (LMCA). In both cases, the erroneous diagnosis led to an inappropriate indication for percutaneous transluminal coronary angioplasty (PTCA) on other stenosed vessels, and the ostial left main lesion was unexpectedly discovered when using 8F guiding catheters. It is supposed that the ability of performed 5F catheters to pass easily through an ostial lesion makes detection of such proximal stenosis much more difficult. We suggest that the choice of 5F catheters must be approached with caution when left main disease is potentially expected from the clinical features. 
4	Activation of coagulation in acute cardioembolic stroke. The hematologic disorders in patients with acute cardioembolic stroke are not fully understood, and no reliable measures are available to identify patients at high risk for recurrent embolism. We analyzed coagulation and fibrinolytic functions in 22 patients with cardiogenic cerebral embolism less than or equal to 24 hours after onset and in 25 age-matched controls. The levels of antithrombin III, protein C, and alpha 2-plasmin inhibitor were significantly lower in the patients than in the controls (p less than 0.001, 0.02, and 0.05, respectively). In contrast, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer were markedly higher in the patients than in the controls (p less than 0.01 and 0.001, respectively). At the time of admission, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer in the eight patients at high risk for recurrent embolization (one with prodromal embolism, three with intracardiac thrombi, and four with recurrent embolization) were 2.8 and 3.5 times, respectively, higher than those in the 14 patients without recurrence or thrombus formation. The lowest concentration of crosslinked D-dimer in the eight patients at high risk for recurrent embolization was 600 ng/ml on admission. Our results suggest that patients with acute cardioembolic stroke have various degrees of consumption coagulopathy and that the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer can be useful indicators of those who are prone to recurrent embolization during this stage. 
5	Outcome in Mania. A 4-year prospective follow-up of 75 patients utilizing survival analysis. A 4-year follow-up of 75 patients was conducted to investigate outcome after recovery from an episode of mania. Predictors of an unfavorable outcome included poor occupational status prior to index episode, history of previous episodes, history of alcoholism, psychotic features and symptoms of depression during the index manic episode, male gender, and interepisode affective symptoms at 6 months' follow-up. The mortality risk during the follow-up period was 4%. The identification of specific risk factors depended on the definition of outcome and the length of follow-up. 
3	The opposite pupil in herniation. I serially examined the pupil opposite the one already enlarged from transtentorial herniation in 13 patients. The main abnormalities, stereotyped in most patients, were an initially diminished light reaction with a 2.5- to 4-mm-diameter pupil, followed by slight reduction in size, and then reenlargement to greater than original size, all with preserved roundness. Subsequent deterioration varied among patients, but a transitional oval shape was infrequent and oculomotor function was preserved until both pupils were enlarged and fixed. Once the pupil on the side of a mass enlarges, heralding herniation, subsequent deterioration can be appreciated through changes in reactivity and size of the opposite pupil. 
4	Leukoaraiosis, intracerebral hemorrhage, and arterial hypertension. To investigate whether the observed association of leukoaraiosis with intracerebral hemorrhage is direct or mediated by risk factors, we compared 116 patients with intracerebral hemorrhage confirmed by computed tomography and 155 controls without intracerebral hemorrhage, evaluating the prevalence of leukoaraiosis and vascular risk factors. Leukoaraiosis was observed in 21 (18%) of the 116 patients and in 12 (8%) of the 155 controls (p less than 0.01). Only two (6%) of the 31 patients with lobar hemorrhage had leukoaraiosis on computed tomograms, compared with 17 (24%) of the 71 patients with basal ganglionic hemorrhage (p less than 0.05). Leukoaraiosis was significantly correlated with intracerebral hemorrhage after controlling for age and sex by using multiple logistic regression analysis, while the correlation disappeared after controlling for hypertension. Our results indicate that leukoaraiosis is not an independent risk factor for intracerebral hemorrhage. 
3	Magnetic and electrical stimulation of cervical motor roots: technique, site and mechanisms of excitation. Cervical motor roots and the brachial plexus were excited transcutaneously with magnetic (MagStim) and electrical stimulation (ElStim) applied dorsally over the spine and over the supraclavicular fossa (Erb's point). The compound muscle action potentials (CMAPs) from the abductor digiti minimi (ADM) and the biceps muscles (BICEPS) could be evoked with either stimulating technique in all 52 subjects tested. With MagStim over the spinous process C7, greater CMAPs were obtained from ADM (p less than or equal to 0.0001, paired t test) and BICEPS (p less than or equal to 0.005) when the inducing current in the coil as viewed from behind was clockwise for the right arm and vice versa. ElStim with the cathode over C7/T1 and the anode directed cranially provided greater CMAPs from the ADM (p less than or equal to 0.0001) and smaller CMAPs from the BICEPS (p less than or equal to 0.01) than with the inverse polarity. MagStim of the cervical roots provided CMAPs which were smaller from ADM (p less than or equal to 0.0001), and greater from BICEPS (p less than or equal to 0.0001), than ElStim (cathode C7/T1), whereas latencies did not differ significantly (p less than or equal to 0.3). When comparing ElStim and MagStim applied over Erb's point, the former yielded greater CMAPs and 0.5 ms longer latencies from both the ADM and BICEPS (p less than or equal to 0.001). From these data and additional studies in four patients, including direct intraoperative root stimulation in one of them, it is concluded that ElStim and MagStim over the spine excite the motor roots at a similar site, that is, within a few cm outside the intervertebral foramina. 
5	Prognostic factors in alcoholic liver disease. VA Cooperative Study Group. Two hundred eighty-one alcoholic patients were prospectively evaluated by clinical, biochemical, and histologic parameters during a 4-yr period to assess their prognosis. They were stratified into four categories of injury: 1) fatty liver (26 patients), 2) acute alcoholic hepatitis (106), 3) cirrhosis (39), and 4) cirrhosis with superimposed alcoholic hepatitis (111). The rate of survival and variables correlating with survival varied according to the group. At 48 months, 70% of the patients with fatty liver were alive, 58% in the alcoholic hepatitis group, 49% in cirrhosis, and 35% in alcoholic hepatitis superimposed upon cirrhosis. Within group one, deaths were due to causes unrelated to liver disease. In the alcoholic hepatitis group, factors significantly correlating with survival were ascites, alanine amino-transferase levels, grams of alcohol consumed, continuation of alcohol intake, and clinical severity of disease. Survival in patients of group three correlated significantly with prothrombin time and histologic severity score. Patients with combined cirrhosis and alcoholic hepatitis exhibited the worst prognosis, with the most significant predictors of survival being age, grams of alcohol consumed, the ratio of serum aminotransferases (AST:ALT) and the histologic and clinical severity of the disease. Although a different pattern of correlates was observed for each pathologic level of injury, knowledge of the various correlates aids in prognostic assessment. 
2	Malnutrition and carbohydrate malabsorption in children with vertically transmitted human immunodeficiency virus 1 infection. The nutritional needs of children with human immunodeficiency virus infection are poorly understood. Twenty-eight children with vertically transmitted human immunodeficiency virus infection were evaluated for carbohydrate malabsorption using lactose hydrogen breath tests and d-xylose absorption studies. Lactose malabsorption was a common finding in human immunodeficiency virus-infected children and occurred in 8 of 20 patients who had no identifiable enteric pathogen. Lactose malabsorption occurred at an earlier age in human immunodeficiency virus-infected children than in an age-matched group of 45 symptomatic control children (P = 0.02). However, lactose malabsorption was not associated with higher rates of diarrhea or growth failure. Abnormalities in d-xylose absorption were not significantly associated with either diarrhea or growth failure. However, 39% of d-xylose studies (9 of 23) showed abnormal results and were significantly associated with enteric infections (P = 0.004). Abnormalities in small-bowel morphology were found in 4 of 9 children with growth failure, 3 of whom had an enteric infection and low d-xylose absorption. Lactose hydrogen breath testing and d-xylose testing showed carbohydrate malabsorption in 61% of children (17 of 28). This study demonstrates that human immunodeficiency virus-infected children are at risk for malabsorptive disorders, which are not always related to clinical symptoms. We speculate that human immunodeficiency virus may be directly involved in the development of lactose malabsorption. Carbohydrate malabsorption in human immunodeficiency virus-infected children may not be the only factor responsible for growth failure. 
4	Pharmacologic stress imaging. Pharmacologic stress imaging has increasingly been employed as an alternative to exercise imaging for detection of coronary artery disease and risk stratification particularly in patients who are unable to perform adequate exercise. Sensitivity and specificity of thallium 201 scintigraphy using intravenous dipyridamole infusion as a stress for coronary artery disease detection average 85% and 91%, respectively. Dipyridamole imaging is also useful for differentiating between ischemia and scar and identifying patients who have an increased risk for subsequent cardiac events. Dipyridamole imaging is particularly useful for preoperative risk stratification in patients undergoing surgery for peripheral vascular or aortic disease. Dipyridamole imaging is also useful for identifying residual myocardial ischemia after myocardial infarction and detecting restenosis after coronary angioplasty. Adverse side effects of dipyridamole are promptly reversed by aminophylline. Dipyridamole stress can also be employed in association with echocardiography for detection of ischemia-induced regional wall motion abnormalities. 
2	Retrospective application of prognostic indices to pancreatitis discovered at necropsy. Six prognostic indices, which were developed to assess inpatients with acute pancreatitis, were evaluated for possible retrospective application. When applied to a series of 14 cases in whom pancreatitis was first diagnosed at necropsy, the index devised by Jacobs et al was found to be the most useful, because in nine of these cases eight or more of the variables required were available for assessment from the case records. In the other indices evaluated fewer than eight of the required variables were available for retrospective assessment in most cases. Although undiagnosed pancreatitis is probably uncommon as a sole cause of death, the retrospective use of one or more of these indices may help assess the severity of the patient's condition on admission to hospital. 
5	Long-term outcome of massive small bowel resection. The long-term outcome for seven patients 4-17 yr (mean 7.1 yr) after massive small bowel resection, leaving 5-160 cm (mean 86.4) of small bowel, was reviewed. Their mean age at the final enterectomy was 40 yr. Adaptation to foodstuffs and the effects of physiologic alterations and complicating diseases on their return to work were emphasized. More than 3.5 yr after surgery, the patients had adapted to many kinds of foodstuffs, but dietary fat could not be tolerated by three patients. Six patients returned to work an average of 2.7 yr after surgery, but four were obliged to discontinue their work because of rehospitalization for long-term complications. In addition, their working hours were limited, and they could not engage in heavy physical work, owing to physiologic alterations, such as a reduced metabolic state, after massive enterectomy. 
1	An enhancer variant of Moloney murine leukemia virus defective in leukemogenesis does not generate detectable mink cell focus-inducing virus in vivo [published erratum appears in Proc Natl Acad Sci U S A 1991 Jun 1;88(11):5066] Moloney murine leukemia virus (Mo-MuLV) induces T-cell lymphoma when inoculated into neonatal mice. This is a multistep process. Early events observed in infected mice include generalized hematopoietic hyperplasia in the spleen and appearance of mink cell focus-inducing (MCF) recombinants; end-stage tumors are characterized by insertional proviral activation of protooncogenes. We previously showed that an Mo-MuLV enhancer variant, Mo+PyF101 Mo-MuLV, has greatly reduced leukemogenicity and is deficient in induction of preleukemic hyperplasia. In this report, we have examined Mo+PyF101 Mo-MuLV-inoculated mice for the presence of MCF recombinants. In contrast to wild-type Mo-MuLV-inoculated mice, Mo+PyF101 Mo-MuLV-inoculated mice did not generate detectable MCF recombinants. This failure was at least partly due to an inability of the MCF virus to propagate in vivo, since a molecularly cloned infectious Mo+PyF101 MCF virus did not replicate, even when inoculated as a Mo+PyF101 Mo-MuLV pseudotype. These results show that the leukemogenic defect of Mo+PyF101 Mo-MuLV is associated with its inability to generate MCF recombinants capable of replication in vivo. This, in turn, is consistent with the view that MCF recombinants play a significant role in Mo-MuLV-induced disease and, in particular, may play a role early in the disease process. 
4	Comparison of converting enzyme inhibitor and calcium channel blocker in hypertensive glomerular injury. The protective effect of converting enzyme inhibitors in experimental hypertensive glomerular injury is associated with decreased systemic arterial and glomerular capillary pressure. Although calcium channel blockers effectively lower systemic blood pressure, their effect on glomerular capillary pressure and on hypertensive glomerular injury is uncertain. We compared equihypotensive treatment with the calcium antagonist TA 3090 or the converting enzyme inhibitor captopril in post-salt hypertensive Dahl salt-sensitive (DS) rats for up to 5 weeks after five sixths nephrectomy. Before the nephrectomy, all rats demonstrated hypertension (mean 177 mm Hg), proteinuria (mean 175 mg/day), and mild glomerulosclerosis (mean injury score 35). Rats treated with captopril or TA 3090 demonstrated a significant and equivalent decrease in systolic blood pressure compared with untreated rats at 2, 3, and 5 weeks after five sixths nephrectomy; however, only captopril reduced proteinuria. Final proteinuria was actually increased in rats treated with TA 3090 compared with untreated rats. Glomerular injury score was significantly decreased in captopril-treated compared with untreated rats at 2 weeks (33 +/- 9 versus 117 +/- 10, p less than 0.05) and 5 weeks (46 +/- 9 versus 94 +/- 24, p less than 0.05), whereas treatment with TA 3090 delayed but did not prevent progressive glomerular injury (2-week score 35 +/- 7, p less than 0.05 versus untreated; 5-week score 109 +/- 19, p = NS versus untreated). Thus, in hypertensive DS rats after subtotal nephrectomy, treatment with a converting enzyme inhibitor reduced systemic blood pressure, proteinuria, and glomerulosclerosis. However, equihypotensive treatment with a calcium channel blocker did not reduce proteinuria and delayed but did not prevent glomerulosclerosis. Thus, in the rat similar reductions in systemic blood pressure with these two classes of agents have disparate effects on the progression of chronic renal failure. 
5	The deoxyribonucleic acid regions involved in the hormonal regulation of thyroglobulin gene expression. Transcription of the thyroglobulin (TG) gene is stimulated by TSH via cAMP. We have characterized the sequence elements responsible for the hormone-dependent expression of TG gene in rat thyroid FRTL-5 cells using internal deletion and linker-scanning mutants of the minimal TG promoter (-170 basepairs) fused with the bacterial chloramphenicol acetyltransferase reporter gene. The TG gene is regulated by at least two regions located between -165 and -140 bp (TG-III) and between -95 and -65 bp (TG-I) from the transcription initiation site. The intervening region can be deleted without significant effect on the promoter activity. Either of the two regions alone does not promote hormone-dependent transcription. A DNase footprinting assay showed that TG-I and TG-III are the principal protein-binding sites and that the proteins interacting with these two regions are induced by TSH or cAMP. These results suggest that the hormone-dependent expression of TG gene may be achieved by cooperative interaction of the proteins bound to TG-I and TG-III. 
1	Capillary haemangioma presenting as a lung pseudocyst. A girl who developed a lung cyst at 24 hours of age during gentle ventilation for respiratory distress syndrome is reported. Instead of resolving as expected of a pseudocyst it continued to expand. Resection at 1 year of age showed a cyst entirely surrounded by capillary haemangioma. Aspiration of this cyst would have been dangerous. 
4	Mitral valve disruption following percutaneous balloon valvuloplasty. Two cases of massive mitral regurgitation due to mitral valve disruption following percutaneous balloon valvuloplasty are reported. This severe complication occurred in two elderly women with recurrent mitral stenosis after previous surgical commissurotomy. Due to their unstable hemodynamic and clinical condition, both patients underwent emergency valve replacement. At surgery, the commissures appeared fused and heavily calcified; the chordae tendineae thickened, shortened, and fused; and the leaflets presented a large tear with sheared edges. Because the technical aspects of both procedures were unremarkable, the anatomic features of the mitral valve seemed to affect the occurrence of severe mitral regurgitation. Percutaneous balloon valvuloplasty should be therefore applied carefully to patients with prior surgical valvotomy, in whom the structural alterations of the mitral apparatus may predispose to severe valvular damage. 
3	Depressive symptoms following stroke. OBJECTIVE: The primary purpose of this study was to assess the relation of lesion location to mood and vegetative disturbance following stroke. METHOD: Fifty-two inpatients and outpatients who had had single, unilateral strokes were included. Patients with past CNS or psychiatric disorders were excluded. A modified Visual Analogue Dysphoria Scale was used to allow the inclusion of all but the most impaired aphasic patients. Sleep and eating disturbances were measured by using both self-report and nursing assessments. Location of lesions was determined by CT scan and classified according to three dimensions: right-left, dorsal-ventral, and frontal-nonfrontal. RESULTS: On measures of dysphoric mood and sleep disturbance, results indicated significant three-way interactions among the three lesion dimensions. No differences were found with regard to eating disturbance. Greater dysphoria and sleep disturbance were found in subjects with left parietal/occipital, left inferior frontal, right superior frontal, and right temporal lesions than in subjects with lesions in other locations. Depressive symptoms were not associated with functional impairment as measured by activities of daily living, motor strength, or severity of aphasia. CONCLUSIONS: These results support the hypothesis that lesion location is a valid and significant factor in the mixture of influences which may result in a dysphoric mood state following stroke. The relation between the site of the lesion and subsequent depressive symptoms, however, may be more complex than has been reported previously. 
3	Identification of pre- and postcentral gyri on CT and MR images on the basis of the medullary pattern of cerebral white matter. The authors illustrate a new method to identify the pre- and postcentral gyri on computed tomographic (CT) and magnetic resonance (MR) images of the brain on the basis of the pattern of the medullary branches of the cerebral white matter. The most commonly used method to identify the gyri depends on recognition of the central sulcus by surface arrangement of the sulci. The two methods were compared by analysis of CT images of 104 subjects who had normal findings (age range, newborn to 60 years; 57 males and 47 females). The usefulness of the new method was also determined in angiographic studies of nine patients with space-occupying lesions. The method is especially helpful for identification of gyri on the lower level of the centrum semiovale and if space-occupying lesions are present that may result in a blurred depiction of sulci. Since MR imaging depicts the medullary branches more clearly than does CT, this new method should facilitate identification of the gyri with either modality. 
4	Replacement of the aortic valve or root with a pulmonary autograft in children. Between January 1967 and December 1988, 34 patients ranging in age from 3 to 18 years (mean, 14 +/- 3.6 years) underwent replacement of the aortic valve or root with their own pulmonary valve. The indication for operation was left ventricular outflow obstruction in 16 patients (47%), aortic regurgitation in 14 (41%), mixed aortic valve disease in 3 (9%), and failure of a previously implanted aortic homograft in 1 (3%). There were four early deaths, all before 1971, giving a hospital mortality of 11.8% (70% confidence interval, 6% to 20%). Surviving patients have been followed up a cumulative total of 214 patient-years, the longest period of observation being 16 years 8 months. Late mortality was 13.3% (70% confidence interval, 7% to 23%), and 4 other patients required removal of the pulmonary autograft for endocarditis. Actuarial rates at 16 years were 74% +/- 11% for freedom from reoperation on the left ventricular outflow tract, 80% +/- 10% for freedom from reoperation on the right ventricular outflow tract, and 77% +/- 10% for late survival. There was no instance of primary structural degeneration in the pulmonary autograft, and all surviving patients were in New York Heart Association functional class I without medication. This experience demonstrates that the pulmonary autograft can achieve good early and medium-term results in young patients. Should growth potential be realized, it might constitute the ideal biological valve for the left ventricular outflow in children. 
1	Interventional radiology of the biliary tract. Intraductal radiation. One palliative method of treating patients with a high duct cholangiocarcinoma is the use of 192Ir wire. This is placed through the tumor, which has been previously intubated, and delivers a high local dose of radiation. The mean survival time in 30 patients treated with intraductal radiation was 16.8 months, an improvement compared to surgical bypass or endoscopic and radiologic drainage procedures. 
1	Parathyroid hormone-related peptide in plasma of patients with hypercalcemia and malignant lesions We developed and validated a radioimmunoassay for circulating human parathyroid hormone-related peptide (PTHrP), based on a commercial antiserum to the synthetic 1-34 fragment of PTHrP, 125I-Tyr degrees-PTHrP(1-34) as radioligand, and prior extraction of the native peptide from plasma with C-2 cartridges. We determined immunoreactive PTHrP concentrations in plasma samples from 48 healthy persons (mean +/- SD, 3.1 +/- 1.0 pmol/liter; range, less than 2 to 5 pmol/liter), 8 patients with primary hyperparathyroidism, 36 patients with hypercalcemia and a concurrent malignant lesion, and 9 normocalcemic patients with cancer and increased serum levels of carcinoembryonic antigen or prostate-specific antigen. PTHrP was normal in samples from patients with primary hyperparathyroidism (3.2 +/- 1.1 pmol/liter), secondary hyperparathyroidism (2.5 +/- 1.3 pmol/liter), and cancer without hypercalcemia (2.4 +/- 1.0 pmol/liter). In contrast, plasma immunoreactive PTHrP levels were increased (6.0 to 85.0 pmol/liter) in 47% of patients with hypercalcemia and cancer of various types, with or without bone metastatic lesions. Large amounts of PTHrP were also found in conditioned medium from cultured human prostatic carcinoma cells. Thus, PTHrP may be a causative factor for hypercalcemia associated with a malignant lesion in at least half of the cases. Measurement of circulating PTHrP may be of differential diagnostic help in hypercalcemic states. 
5	Preoperative aspirin therapy and reoperation for bleeding after coronary artery bypass surgery. We performed a case-control study to estimate the relative risk of reoperation for bleeding in coronary artery bypass graft patients who had taken aspirin within the 7 days preceding surgery. Comparison of 90 cases of reoperation with 180 matched control subjects gave an estimated odds ratio for reoperation of 1.82 (95% confidence interval, 1.23 to 3.32). Although their preoperative coagulation values were similar, cases used significantly more whole blood (cases, 9.5 +/- 5.2 units; control subjects, 3.0 +/- 2.0 units; median +/- interquartile range), packed red blood cells (cases, 2.1 +/- 4.0 units; control subjects, 0.9 +/- 2.0 units), and platelets (cases, 12.2 +/- 12.0 units; control subjects, 2.9 +/- 4.0 units) than control subjects. Cases had intensive care unit stays of 4.7 +/- 5.7 days (mean +/- SD) vs 2.1 +/- 1.9 days for control subjects and postoperative hospitalizations of 10.9 +/- 8.2 days vs 7.0 +/- 3.2 days for control subjects. We conclude that aspirin exposure within 7 days before coronary bypass surgery is associated with an increased rate of reoperation for bleeding and that reoperation is associated with large increases in transfusion requirements and intensive care unit and hospital stays. 
4	Aortic replacement with composite grafts created with a sutureless intraluminal ringed prosthesis. From 1980 to 1988, 30 patients from a total population of 123 recipients of sutureless grafts (24%) have required aortic reconstruction with a composite ringed graft. Replacement of the ascending aorta was required in 12 patients, of the aortic arch in six patients, of the descending aorta in two patients, of the thoracoabdominal aorta in two patients, and of the abdominal aorta in eight patients. Eight patients (27%) needed an emergency operation at the time of admission. No patients had permanent neurologic or renal deficits. There was no evidence of pseudoaneurysm formation, graft erosion, graft migration, or aortic bleeding in the postoperative period. Two operative deaths (7%) occurred, both in patients undergoing arch reconstruction. Composite grafts can be created that vary in length and shape, incorporate different graft materials, and accommodate the aorta and its branches. The ability to modify the sutureless prosthesis to suit the disease encountered at operation allows the quickest repair with the least chance of anastomotic complication. 
1	Gestational trophoblastic disease of the fallopian tube. Tubal gestational trophoblastic disease (GTD) was diagnosed in 16 (0.8%) of 2,100 women with GTD managed at the New England Trophoblastic Disease Center. Tubal partial mole, complete mole and choriocarcinoma were present in 5, 5 and 6 patients, respectively. Patients with tubal GTD were not clinically distinguishable from those with traditional tubal pregnancies. While only one patient with tubal mole developed metastases, four patients with tubal choriocarcinoma presented with metastases. All the patients achieved complete, sustained remission. 
5	A multifactorial analysis of mortality and morbidity in perforated peptic ulcer disease. Perforated peptic ulcer disease remains a source of considerable morbidity and mortality, and the suggested methods of surgical therapy are diverse. We reviewed the course of 113 patients who were treated surgically and identified 14 factors that influenced the morbidity or mortality rates, or both. Multiple regression analysis showed that the number of coexisting medical conditions, a lower mean blood pressure level and the duration of acute perforation were independent risk factors for death, while age, use of a bronchodilator, a lower mean blood pressure level and the number of coexisting medical conditions correlated positively with all complications. A duodenal site was independently favorable with respect to all complications. The type of operation performed either simple closure, vagotomy and drainage or resection, did not influence morbidity or mortality. The most severely ill patients also did not benefit from any particular type of operation in the short term. Long term results were improved with definitive operation, as measured by the Visick classification and the need for reoperations. Definitive operations are recommended for virtually all patients with perforated peptic ulcer. 
5	Measles-associated diarrhea in hospitalized children in Lima, Peru: pathogenic agents and impact on growth. Because the causes of measles-associated diarrhea are not well known, 0- to 5-year-old children presenting to the hospital with measles-associated diarrhea (cases, n = 77) or acute diarrhea only (controls, n = 77) were compared. Growth and diarrheal morbidity were evaluated for 1 month after acute illness. Campylobacter jejuni was more frequently isolated from cases (31%) than controls (16%; P = .03). Rotavirus was absent in all cases versus 28% of controls (P less than .001). Incidence density for new episodes of diarrhea was significantly greater in cases (6.5 vs. 4.1; odds ratio, 1.6; confidence intervals, 1.09-2.34; P = .01), as was duration of episodes (3 vs. 2 days, P = .02). Both groups showed similar positive cumulative percentage weight gains throughout follow-up. These data support the theory of measles as a risk factor for developing diarrhea. The bacteriologic and virologic findings may reflect the immunologic response of the host to measles infection. 
3	Type I hypersensitivity to rubber. Seven patients with type I hypersensitivity reactions to rubber are reported. Radioallergosorbent testing with crude latex antigen was positive in 6/7 patients. Five patients had coexisting spina bifida, and all had undergone surgery before the development of rubber allergy. Rubber allergy is a new phenomenon that should be in the differential diagnosis of idiopathic anaphylaxis and urticaria. 
1	Treatment selection for carcinoma of the base of the tongue. Between 1974 and 1984, 173 patients were treated for squamous cell carcinoma of the tongue base. Fifty-four patients had T1 or T2 primaries, while 115 patients had T3 or T4 tumors (4 were not staged). Lymph node metastasis was present in 120 patients. Early primary tumors treated with surgery or radiotherapy had a control rate of 83% (5 of 6 tumors) and 89% (40 of 45 tumors), respectively. For advanced primary tumors, definitive radiotherapy produced a local control rate of 55% (42 of 76 tumors), compared with 79% (23 of 29 tumors) for surgery and postoperative radiotherapy. If primary control was obtained, the regional failure rate was less than 10%. Tumor growth patterns were predictive of the response to radiotherapy. The primary control rate at 2 years for 21 patients with exophytic tumors was 84% as opposed to 58% for 62 patients with ulcerative-infiltrative tumors (p = 0.04). Radiotherapy is effective for early stage or exophytic tumors, whereas for advanced or deeply invasive tumors combined therapy enhances local control. 
5	Differential impairment of semantic and episodic memory in Alzheimer's and Huntington's diseases: a controlled prospective study. A controlled prospective study compared the performance of 14 patients with dementia of Alzheimer type (DAT) and 14 patients with Huntington's Disease (HD), who were matched for overall level of dementia, on a battery of semantic and episodic memory tests. The DAT patients were significantly more impaired on measures of delayed verbal and figural episodic memory, and in addition showed a more rapid rate of decline on tests which depend upon the integrity of semantic knowledge (naming, number information, similarities and category fluency). In contrast, the HD patients were significantly worse, and showed a more rapid decline on the letter fluency test, a task especially sensitive to deficiencies in retrieval. The HD patients were also more impaired than DAT patients on a vocabulary test and on copying geometric figures. The observed double dissociations offer compelling evidence that aetiologically distinct forms of dementing illness result in different patterns of cognitive impairment. 
5	Short-term course of corticosteroids in the treatment of resistant ascites complicating schistosomal liver disease. The aim of this work was to evaluate the effect of short-term corticosteroids in resistant ascites complicating schistosomal liver disease after 4 wk or more on standard treatment. Thirty-seven patients were randomly allocated to two groups: Group I (18 patients) was put on 40 mg furosemide and 200 mg spironolactone, in addition to a 15-day, tapering dose of prednisone (15, 10, 5 mg). Group II (19) patients received the same diuretics without steroids, and served as controls. At the end of a 2-wk course of therapy, the mean variations were as follows: body weight in patients in Group I ("cases") decreased by 9.8 kg, compared with 4.3 kg in controls; abdominal girth decreased by 7.4 cm in cases, compared with 3.6 cm in controls; urine output increased by 635.9 ml in cases, compared with 364.6 ml in controls; urinary sodium excretion increased by 16.5 mEq/day in cases, compared with 4.1 mEq/day in controls. These differences between cases and controls were found to be statistically significant (p less than 0.01). On the other hand, there were insignificant differences as regards decrease in blood urea (3.2 g/dl for cases and 2.7 g/dl for controls), decrease in serum creatinine (0.2 mg/dl for both cases and controls), increase in serum albumin (0.3 g/dl in cases and 0.2 g/dl in controls), increase in serum sodium (3.2 mEq/L in cases and 2.7 mEq/L in controls), and increase in serum potassium (0.2 mEq/L in cases and 0.4 mEq/L in controls). We conclude that a short-term course of corticosteroids in conjunction with standard diuretics has proved to be an effective, safe, and economical modality to relieve resistant hepatic ascites. It can be considered a temporary alternative to paracentesis with albumin infusion. 
4	Patient profiling: individualization of hypertension therapy. Although the stepped-care approach remains the cornerstone of antihypertensive therapy, the patient's profile must also be considered. Important issues include the patient's age, race and activity level, potential for hypertensive complications, presence of other diseases, cost of medications and probability of adherence to the recommended drug regimen. Nonpharmacologic treatment based on lifestyle changes is a useful adjunct to drug therapy, but it is not sufficient to control hypertension in most patients. Selection of pharmacologic therapy must be based on a knowledge of each drug's mode of action and side effects, as well as the characteristics of special patient populations. 
4	Atenolol therapy for exercise-induced hypertension after aortic coarctation repair. After successful repair of coarctation of the aorta in childhood, exercise-induced upper body systolic hypertension is well documented. Beta blockade has been shown to reduce the arm/leg gradient in untreated coarctation of the aorta; treatment before coarctation repair has decreased paradoxical hypertension after repair. Ten patients with successful surgical repair of coarctation, defined as a resting arm/leg gradient of less than or equal to 18 mm Hg, were evaluated by treadmill exercise before and after beta blockade with atenolol. Mean age was 5.5 years at repair and 18 at study. At baseline evaluation, systolic blood pressures at termination of exercise ranged from 201 to 270 mm Hg (mean 229 mm Hg). Arm/leg gradients at exercise termination ranged from 30 to 143 mm Hg (mean 84). Follow-up treadmill exercise studies were performed after beta blockade. Upper extremity systolic pressures at exercise termination were normalized in 9 of 10 patients. Maximal systolic blood pressure recorded at exercise termination ranged from 163 to 223 mm Hg (mean 196 mm Hg, p less than or equal to 0.005). Arm/leg gradient at termination of exercise also decreased significantly to a mean of 51 mm Hg (p less than 0.05). No patient had symptoms on atenolol and exercise endurance times were unchanged. The study results in this small series suggest that cardioselective beta blockade can be used to treat exercise-induced upper body hypertension effectively after surgical repair of coarctation. Because a high incidence of premature cardiovascular disease has been well documented after satisfactory surgical repair, the findings are of importance for this group of postoperative patients. 
3	Modulation of the stretch reflex during volitional sinusoidal tracking in Parkinson's disease. Sinusoidal visually-guided wrist tracking, in normal and parkinsonian subjects, was perturbed by torque transients every 90 degrees throughout the movement. Long-latency stretch reflex and volitional EMG amplitude modulations were assessed as functions of the tracking phase. Reflex modulation during tracking, both in wrist flexor and extensor muscles, was found to differ significantly between parkinsonian and normal subjects. In the parkinsonian group, the abnormality consisted of an increased reflex activity during tracking phases in which the muscle was lengthening. At these phases the reflex generated torque is opposite in direction to the volitionally generated torque and the tracking movement. No differences in the unperturbed volitional EMG modulation were observed between groups for this error constrained tracking paradigm. Significant correlations were found between ratings of bradykinesia and the amount of abnormal reflex modulation in the wrist flexor. These data suggest that a component of bradykinesia results from a defective coordination of supraspinal reflex and volitional control systems. 
1	Giant chest wall tumor resulting from tissue reaction to foreign bodies. Three patients are reported in whom chest wall tumors developed 19 to 28 years after thoracoplasty and increased in size with time. The tumors could be removed operatively with good results. All tumors were composed of hematoma and necrotic material, and in all cases they revealed foreign bodies microscopically. Diagnosis and possible etiological factors are discussed. 
1	Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (111In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. 111In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner. 
5	Conditioning prepulse of biphasic defibrillator waveforms enhances refractoriness to fibrillation wavefronts. The mechanism of biphasic waveform defibrillation threshold reduction is unknown. We tested the hypothesis that, during refractory period stimulation, sarcolemmal hyperpolarization by the first pulse of biphasic waveforms facilitates excitation channel recovery, which enhances graded responses produced by the second depolarizing pulse. This prolongs cellular refractoriness to fibrillation wavefronts when compared with a monophasic depolarizing stimulus. Monophasic (10 msec, rectangular wave) or symmetrical biphasic (10 msec, each pulse) current injection S2 stimuli at 1.5 and two times S1 threshold were used to scan the S1 action potential refractory period (S1 cycle length, 600 msec) in myocardial cell aggregates. S2 waveforms were delivered with normal and reversed polarity to test the hyperpolarizing action of biphasic waveforms. Responses to an S3 stimulus, which simulated a potential incoming fibrillation wavefront, were also determined. Results showed that biphasic S2 waveforms produced longer graded responses during and immediately after the S1 refractory period than did corresponding monophasic S2 waveforms. The maximum difference in response duration produced by the biphasic and monophasic waveforms was 58.6 +/- 10.0 msec (p less than 0.001). This maximum difference occurred 10 msec before the end of the S1 refractory period. The longer response durations produced by biphasic S2 also produced longer refractoriness to the S3 stimulus. The maximum difference in total refractoriness to S3 of 51.8 +/- 2.8 msec (p less than 0.002) occurred at the same S1S2 coupling interval as the maximum difference in S2 response duration. Prolonged refractoriness may protect ventricular cells from refibrillation wavefronts and act as the cellular basis for greater biphasic waveform defibrillation efficacy. 
5	Meropenem pharmacokinetics and penetration into an inflammatory exudate. The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose. 
4	The automatic implantable cardioverter-defibrillator: effect of patch polarity on defibrillation threshold. An automatic implantable cardioverter-defibrillator (AICD) was implanted in 40 patients with sudden cardiac arrest (n = 29), sustained monomorphic ventricular tachycardia (n = 10) or recurrent syncope (n = 1) who were unsuitable for direct ablative surgery or had had unsuccessful medical therapy. The effect of patch electrode polarity on the defibrillation threshold was prospectively evaluated. Two large epicardial patches were used. Initial polarity was selected at random. Ventricular fibrillation was induced by direct current and a preestablished defibrillation protocol employed to assess the minimal energy that would reproducibly defibrillate the heart. Nineteen patients had a lower defibrillation threshold with the inferior left ventricular patch as an anode and nine patients had a lower defibrillation threshold with this patch as a cathode. In general, the defibrillation threshold was lower when this patch was used as an anode than when it was used as a cathode (18 +/- 10 versus 22.6 +/- 12.2 J; p less than 0.01). No preoperative variable predicted optimal polarity. Therefore, the effect of patch polarity on defibrillation threshold should be assessed in each patient at the time of AICD implantation so that the safety margin for satisfactory device function can be maximized. 
4	Pathophysiology of ischemic skin flaps: differences in xanthine oxidase levels among rats, pigs, and humans. Oxygen-derived free radicals have been implicated in a variety of diseases and pathologic processes, including ischemia reperfusion injury (IRI). Based on experimental work with rat skin-flap models, the enzyme xanthine oxidase (XO) has been proposed as a major source of free radicals responsible for tissue injury and flap necrosis. The presence of this enzyme is variable within different tissues of a specific species and between species. Xanthine oxidase levels in pig and human skin have not previously been reported. The activity of xanthine oxidase in the skin of rats (N = 16), pigs (N = 7), and humans (N = 8) was measured after varying intervals of ischemia and in the rat also following reperfusion. Control pig and human skin were found to contain minimal enzyme activity, almost 40 times less than that of the rat. In the rat, xanthine oxidase activity was stable throughout a prolonged period of ischemia, and a significant decrease in activity was found after 12 hours of reperfusion (p less than 0.05). In humans, xanthine oxidase activity was unaffected by ischemia time, and in the pig, it did not increase until 24 hours of ischemia (p less than 0.05). The potential sources of free radicals and the mechanism of action of xanthine oxidase and its inhibitor allopurinol in improving flap survival in different species are reviewed. 
4	Controlled trials of antihypertensive drugs in pregnancy. It is taken for granted that severe hypertension in pregnancy should be treated, although the principle has not been formally tested by properly controlled trials. There is less certainty about treating mild to moderate hypertension (140/90 to 169/109 mm Hg). The risk of chronic hypertension in pregnancy depends on that of superimposed preeclampsia, which must be prevented by control of the blood pressure if antihypertensive treatment is to be beneficial. There is not a priori reason why lowering the blood pressure should have this effect. Most of the trials of treatment have been too small to provide conclusive answers. Usually treatment has been started too late to give a realistic expectation of influencing the evolution of superimposed preeclampsia. However, the largest trial of the early use of methyldopa in women with mild chronic hypertension, showed clearly that treatment does not prevent the superimposition of preeclampsia. beta-Adrenergic blocking agents, if used from the second start of the trimester, are associated with a major risk of severe growth retardation and are therefore contraindicated. Methyldopa has the best safety record, which includes long-term follow-up to assess the development of children exposed to methyldopa in utero. The ineffectiveness of antihypertensive drugs in preventing or ameliorating preeclampsia needs to be contrasted with the consistent evidence for the effectiveness of antiplatelet therapy. This is consistent with the increasing evidence that preeclampsia is not primarily, or even necessarily, a hypertensive disease. 
5	Humeral head retroversion in patients with unstable humeroscapular joints. Humeral head retroversion and shoulder rotation in both the frontal and scapular plane were studied in 34 patients with anterior glenohumeral instability. Twenty-two patients had traumatic anterior shoulder dislocations and another 12 patients had nontraumatic dislocations with generalized joint laxity. Patients with traumatic recurrent dislocations had a smaller than normal retroversion angle in the unstable shoulder. The angles were 26 degrees on the dominant side and 23 degrees on the nondominant side compared with 33 degrees and 29 degrees, respectively, in normal shoulders. The stable contralateral shoulder joint was clinically and roentgenographically similar to the normal shoulder. The patients with nontraumatic dislocations had increased rotation and smaller retroversion angles, irrespective of stability in the shoulder joint. The retroversion angles were 18 degrees for unstable shoulders on the dominant side and 15 degrees on the nondominant side. The retroversion angle of the stable contralateral joint in these patients was less in five of eight shoulders. 
1	Pregnancy outcome in hematologic malignancies. By means of a mail questionnaire, information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals. Seven patients conceived while receiving treatment for their neoplasms; in 22 patients, the hematologic disease was diagnosed during pregnancy, and the remaining 27 patients became pregnant after completion of the antineoplastic treatment. When a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population, no increase in the incidence of complications was observed: 64% of the pregnancies went to term, 9% resulted in spontaneous abortion, and 5% resulted in premature births. The observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals. There were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy. In spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed, the data here support the hypothesis that the cytostatic treatment of hematologic malignancies, if deemed necessary, should not be postponed because of pregnancy. Moreover, the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided, especially to those fields involving the pelvic area. 
1	Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody. An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr-labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL. 
4	Spontaneous rupture of an aortic aneurysm into the left renal vein. A diagnostic challenge. Rupture of an aortic aneurysm into a renal vein presents a rare and difficult diagnostic problem. Often, therapy is delayed because the patient is thought to have a urologic problem. In this instance, CT scan provided useful clues leading to the diagnosis of this entity, and its rapid treatment. To our knowledge, this is the first CT scan done in a patient with aorto-renal vein fistula. 
1	Touch and surgical division of the anterior quadrant of the spinal cord. An investigation was carried out to determine whether tactile sensibility was affected by anterolateral cordotomy. There were 65 patients who had cordotomies for painful forms of cancer. Thirty eight had necropsy examination with histological investigation of the spinal cord. No form of mechanoreception was removed in any of the 65 patients and in the majority no forms of tactile sensibility were altered by division of the pathways in the anterolateral and anterior columns. In no case was graphaesthesia affected. Knowledge of joint position and movement and awareness of vibration was normal in 62 of the 65 patients. But information carried by these anterolateral pathways does reach neural levels of consciousness, for with total lesions of the posterior columns, previously reported, touch and pressure are still felt. Itch was removed by division of the anterolateral pathways. Although the posterior columns are essential for discrimination in mechanoreception, discrimination may be disturbed by lesions of the anterolateral pathways, notably two-point discrimination. The evidence on the pathways essential for conveying impulses giving rise to tickle was inconclusive. 
4	Immediate and short-term cardiovascular effects of fosinopril, a new angiotensin-converting enzyme inhibitor, in patients with essential hypertension. Immediate and short-term cardiovascular effects of a new angiotensin-converting enzyme inhibitor, fosinopril, were assessed in 10 patients with mild to moderate essential hypertension. Administration of a 10 mg oral dose of fosinopril reduced mean arterial pressure (p less than 0.001) as a result of a 24% fall in total peripheral resistance (p less than 0.001). Short-term therapy (12 weeks) maintained the decrease in mean arterial pressure (p less than 0.05) by decreasing total peripheral resistance (p less than 0.01), without reflexive cardiac stimulation or expanding intravascular volume. Renal vascular resistance decreased (p less than 0.05) while renal blood flow, glomerular filtration rate and filtration fraction remained unchanged. The response pattern to mental, isometric and orthostatic stress was similarly unchanged. Left ventricular mass diminished by 11% (p less than 0.01); myocardial contractility was unaffected. Afterload was reduced (p less than 0.05), and velocity of circumferential fiber shortening and stroke volume increased (p less than 0.05). Thus, arterial pressure reduction produced by fosinopril was associated with improved systemic and renal hemodynamics and reduced left ventricular mass. 
1	Prophylaxis of aphakic cystoid macular edema without corticosteroids. A paired-comparison, placebo-controlled double-masked study. Prior investigations have reported that topical nonsteroidal anti-inflammatory drug (NSAID) therapy prevents the development of postoperative angiographic signs of angiographic cystoid macular edema (CME). However, these studies include concurrent use of corticosteroids. The current study reports therapeutic efficacy for ketorolac ophthalmic solution (an NSAID) in the prophylaxis of angiographic aphakic CME (ACME) after cataract surgery without concurrent corticosteroids for the first time. Fifty patients with bilateral cataracts were enrolled in this placebo-controlled, paired-comparison, double-masked study. Eleven patients had evidence of angiographic ACME on postoperative day 40. Two of these patients demonstrated bilateral ACME, one patient had ACME in the NSAID-treated eye, and eight patients demonstrated ACME in the placebo-treated eye. This is a statistically significant difference favoring drug treatment. The signs of anterior ocular inflammation were greater in the eyes with ACME. This study suggests prophylactic treatment of ACME may be possible without the risks of concurrent corticosteroid toxicity. In addition, a higher incidence of ACME in black patients (22%) is observed in this study than has been recognized previously. 
5	Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. Recent studies have revealed a role for platelets and the platelet-adhesive proteins, fibronectin and von Willebrand factor (vWF) in platelet-tumor cell interaction in vitro and metastasis in vivo. The present report documents the effect of thrombin treatment of platelets on this interaction in vitro and in vivo. In vitro, thrombin at 100-1,000 mU/ml maximally stimulated the adhesion of six different tumor cell lines from three different species two- to fivefold. As little as 1-10 mU/ml was effective. The effect of thrombin was specific (inhibitable by hirudin, dansyl-arginine N-(3-ethyl-1,5 pentanediyl) amide and unreactive with the inactive thrombin analogue N-P-tosyl-L-phenylchloromethylketone-thrombin and D-phenylalanyl-L-propyl-L-arginine chloromethylketone-thrombin (PPACK-thrombin), and required high-affinity thrombin receptors (competition with PPACK-thrombin but not with N-P-tosyl-L-lysine-chloromethyl-ketone-thrombin). Functionally active thrombin was required on the platelet surface. Binding of tumor cells to thrombin-activated platelets was inhibitable by agents known to interfere with the platelet GPIIb-GPIIIa integrin: monoclonal antibody 10E5, tetrapeptide RGDS and gamma chain fibrinogen decapeptide LGGAKQAGDV, as well as polyclonal antibodies against the platelet adhesive ligands, fibronectin and vWF. In vivo, thrombin at 250-500 mU per animal increased murine pulmonary metastases fourfold with CT26 colon carcinoma cells and 68-413-fold with B16 amelanotic melanoma cells. Thus, thrombin amplifies tumor-platelet adhesion in vitro two- to fivefold via occupancy of high-affinity platelet thrombin receptors, and modulation of GPIIb-GPIIIa adhesion via an RGD-dependent mechanism. In vivo, thrombin enhances tumor metastases 4-413-fold with two different tumor cell lines. 
5	Intraoperative blood pressure. What patterns identify patients at risk for postoperative complications? While monitoring blood pressure is a routine part of intraoperative management, several methods have been proposed to characterize intraoperative hemodynamic patterns as predictors of postoperative complications. In this prospective study of a high-risk population of hypertensive and diabetic patients undergoing elective noncardiac surgery, one objective was to compare different approaches to the assessment of intraoperative hemodynamic patterns to identify those patterns most likely to be associated with postoperative complications. Twenty-one per cent of the 254 patients sustained cardiac or renal complications after operation. Patients with more than 1 hour of greater than or equal to 20-mmHg decreases in mean arterial pressure (MAP) or patients with less than 1 hour of greater than or equal to 20-mmHg decreases and more than 15 minutes of greater than or equal to 20-mmHg increases were at highest risk for postoperative complications. Together these two patterns had a 46% sensitivity rate and a 70% specificity rate in predicting postoperative complications. Using 20% change in intraoperative MAP produced results nearly identical to 20-mmHg changes. When the duration of 20-mmHg changes was accounted for, changes of a greater magnitude (e.g., 40 mmHg) were not significant independent predictors of complications. The use of the mean difference from preoperative MAP was misleading because patients who experienced both high and low MAPs tended to have nearly normal mean MAPs, but high complication rates. The absolute magnitude of intraoperative MAPs, regardless of the preoperative levels, also was evaluated. The overall mean intraoperative MAP was not a significant predictor of complications. Specific intraoperative MAPs (e.g., less than 70 mmHg and more than 120 mmHg) also were evaluated. While neither was a significant predictor, there was a trend for increased complications among patients whose MAPs decreased to less than 70 mmHg. Intraoperative blood pressure should be analyzed in relation to the patient's preoperative blood pressure. Prolonged changes of more than 20 mmHg or 20% in relation to preoperative levels were significantly related to complications. 
5	A study of fatigue in systemic lupus erythematosus. Fifty-nine patients with systemic lupus erythematosus were evaluated by questionnaires, histories, physical examinations and routine laboratory studies in order to better understand their fatigue. The fatigue severity scale (scored from 1 to 7) was used to measure fatigue and yielded a mean score +/- SD of 4.6 +/- 1.5. Fifty-three percent of the patients reported that fatigue was their most disabling symptom. Although perceived as severe, the symptom of fatigue did not correlate significantly with any of the laboratory measures. However, there was a significant correlation between fatigue and the physician's rating of disease activity. Fatigue also correlated significantly with depression which accounted for 21% of the variation in fatigue scores. 
5	Endoscopic variceal ligation in patients who have failed endoscopic sclerotherapy. Endoscopic variceal ligation has been developed as an alternative to endoscopic sclerotherapy. We report a series of 12 men with a history of bleeding esophageal varices who were treated with endoscopic variceal ligation after they had failed sclerotherapy. Hemostasis was achieved in all 10 patients who were bleeding at the time of initial endoscopy and again in those who subsequently re-bled. Over a follow-up period of up to 22 months, varices have been and remain eradicated in five patients; in four others, a reduction in grade was noted before death (two patients), liver transplant, or loss to follow-up (one patient each); two patients died before they could be re-evaluated, while in the remaining patient, no reduction in variceal grade was noted before loss to follow-up. No complication was recorded after 35 endoscopic treatment sessions involving a total of 245 rubber band ligations. Our results indicate that endoscopic variceal ligation may be used with success in patients who fail sclerotherapy. 
4	Transoesophageal echocardiogram may fail to diagnose perioperative myocardial infarction. We report a case in which a 55-yr-old man undergoing aortocoronary bypass was monitored with electrocardiogram and transoesophageal echocardiogram. Intraoperative electrocardiogram and simultaneous ECG recordings using the Holter monitor showed an ST elevation of greater than 2 mm and new Q wave formation in leads AVF and V5 during skin closure. However, the transoesophageal echocardiogram showed no wall motion abnormalities. No significant haemodynamic abnormalities were observed during the period of intraoperative ECG changes. He was treated with nitroglycerin infusion. Confirmation of a perioperative myocardial infarct was documented by postoperative 12-lead ECG and CPK-MB. A post-operative transthoracic echocardiogram showed a hypokinetic left ventricle with an anteroapical infarct. Thus transoesophageal echocardiography failed to detect an apical wall motion abnormality when the probe was placed at the midpapillary level. This limitation can be overcome by periodically obtaining apical views or by using probes with more than one imaging plane. 
4	Mitral valve prolapse. When is it serious? Mitral valve prolapse can best be diagnosed with careful clinical evaluation, including dynamic auscultation. Treatment consists of reassurance, pharmacotherapy for troublesome symptoms, and careful monitoring for signs of complications. Most complications can be either prevented or treated. 
2	Thoracic succussion splash: a new symptom and sign of achalasia. A patient with a "thoracic succussion splash" due to achalasia is described. She noted a splashing or sloshing sensation in her chest related to jogging and bending. On examination a splashing sound could be heard over the mid sternum and the posterior chest when the patient was rocked vigorously back and forth. 
4	Natural evolution of cardiac function, cardiac pathology and antimyosin scan in a murine myocarditis model. Serial technetium-99m radionuclide ventriculograms, indium-111 antimyosin antibody scans and tissue biodistribution studies were performed in C3H/He mice with experimentally induced viral encephalomyocarditis and the results were compared with pathologic assessments of myocardial necrosis. Postinfection ejection fraction decreased on days 10 (20.7 +/- 5.5%, n = 6), 20 (18.6 +/- 15.2%, n = 5), 30 (18.5 +/- 7.7%, n = 5) and 150 (30.0 +/- 18.7, n = 6) (p less than 0.001) in comparison with that in uninfected control mice (63.3 +/- 3.1%, n = 6). In the same group of animals, indium-111 antimyosin antibody scans showed intense positive myocardial accumulation on day 10 (in six of six mice) and only slight accumulation on day 20 (in one of five mice). In the chronic stage, two of five mice on day 30 and two of six mice on day 150 still showed positive uptake. The antimyosin scan myocardium to lung uptake ratio (expressed as mean count density [mean counts/pixel of the region] ratio) increased greatly on day 10 (p less than 0.001 versus values in uninfected control mice) but not subsequently. Biodistribution studies of the indium-111 antimyosin antibody showed that the heart to blood count ratio was significantly higher on day 10 (p less than 0.001 versus values in control mice) but not on days 20, 30 and 150. Pathologic examination showed active and ongoing severe myocardial necrosis with dilated ventricles on day 10. On day 20, there was less active necrosis and healing had appeared to begin. On days 30 and 150, myocardial fibrosis increased. 
5	Flumazenil in ketamine and midazolam anaesthesia. A double-blind, parallel group study using flumazenil and placebo was carried out to determine whether patients who received flumazenil would awake more quickly and whether this drug would reverse the protection conferred by midazolam on the psychic sequelae of ketamine. Fifty female patients were studied. The results showed that there was a significant reduction in awakening time (p = 0.02) and a very significant increase (p = 0.001) in the incidence of dreams in the flumazenil group. 
5	Laser photocoagulation control of diabetic macular oedema without fluorescein angiography. This study included 40 eyes in 22 diabetic patients with focal macular oedema. Laser photocoagulation was directed at decompensated or leaking microvascular lesions clinically detected without using pretreatment fluorescein angiograms. Post-treatment fluorescein angiograms performed after adequate clinical control of disease showed complete resolution of the macular oedema in 25 eyes (62.5%), whereas persistent leakage from microvascular lesions closer than 500 microns from the centre of the foveola was noted in 15 eyes (37.5%). These were clinically detected during the pretreatment examination and were found not to impair or threaten the patient's vision. Our data confirm the clinical impression that fluorescein angiography is not necessary for effective treatment and should be used only if necessary. 
5	Cardiac tamponade and contralateral hemothorax after subclavian vein catheterization. A patient developed life-threatening cardiac tamponade and contralateral hemothorax after insertion of a subclavian catheter in the operating room. Contrast was infused through the catheter, demonstrating its malposition in the pericardial space. Contrast infusion was valuable in evaluating this complication of central line placement. 
5	Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers. Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers. Efficacy was 82% for 1500 mg and 63% for 750 mg. In cured patients taking 750 mg mefloquine, peak plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) were significantly greater than in the patients for whom treatment failed (p less than 0.0005 and p less than 0.01, respectively), and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment. Mefloquine AUC was reduced and variable in the presence of diarrhea. Compared with noninfected volunteers, clinically ill patients displayed a delayed time to reach peak concentration (p less than 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose. Mefloquine AUC was similar in patients with malaria and healthy volunteers. Because plasma levels increased in temporal relationship with clinical illness, mefloquine volume of distribution or clearance (or both) was reduced during the acute phase of illness. 
5	The management of atypical non-cardiac chest pain. Atypical, non-cardiac chest pain is common and disabling, and often persists despite negative medical investigations. Aetiology is disputed and management is difficult. A multi-causal model in which both psychological and physical factors play a part is helpful; a fundamental factor is continued misinterpretation of minor physical symptoms as evidence of heart disease. We report supportive evidence and describe a psychological treatment derived from the model. In a randomized trial, cognitive behavioural methods were effective in reducing chest pain, disability and use of medication, in patients both with and without psychiatric disorder. The clinical implications are discussed. 
5	Spinal anaesthesia in day-care surgery with a 26-gauge needle. We studied 106 day-care surgical patients (52 male) aged 18-70 yr (mean 49.6 yr) who received spinal anaesthesia with a 26-gauge spinal needle. The incidence of headache, back pain and patient acceptability were investigated after operation using a questionnaire. The incidence of postspinal headache was 7.5%, and 11.3% of patients developed back pain. One patient remained in hospital because of hypotension and dizziness. There were no major complications and patient acceptability was almost 100%. We conclude that spinal anaesthesia for day-care surgery is easy to perform and cost effective. 
1	MR imaging of blood-borne liver metastases in mice: contrast enhancement with Fe-EHPG. To determine whether iron(III)ethylenebis-(2-hydrophenylglycine) (Fe-EHPG), a prototype hepatobiliary magnetic resonance imaging agent, can enhance the liver-to-tumor contrast-to-noise ratio (C/N) in models of liver tumors in mice, two types of cell inoculation were used: intrahepatic implantation of M5076 sarcoma and intrasplenic injection of colon tumor (C-26) or M5076 sarcoma. Significant enhancement of the liver-to-tumor C/N and/or improved visualization of small lesions was consistently observed on T1-weighted images obtained after injection of the contrast material. For intrahepatic implants, the C/N on postinjection T1-weighted images was superior to that on T1- and T2-weighted preinjection images. For the C-26 metastatic liver lesions of larger diameter (greater than 5 mm), the C/N on postinjection T1-weighted studies was superior to that on preinjection T1-weighted images but was comparable to that on preinjection T2-weighted images. However, higher C/N after administration of Fe-EHPG improved visualization of medium-sized (3-5 mm) and small (1-3-mm) metastatic lesions in both M5076 and C-26 models. These results demonstrate that MR imaging with appropriate hepatobiliary agents appears promising for early detection of liver metastases. 
3	Chromosome 15 uniparental disomy is not frequent in Angelman syndrome. Genetic imprinting has been implicated in the etiology of two clinically distinct but cytogenetically indistinguishable disorders--Angelman syndrome (AS) and Prader-Willi syndrome (PWS). This hypothesis is derived from two lines of evidence. First, while the molecular extents of de novo cytogenetic deletions of chromosome 15q11q13 in AS and PWS patients are the same, the deletions originate from different parental chromosomes. In AS, the deletion occurs in the maternally inherited chromosome 15, while in PWS the deletion is found in the paternally inherited chromosome 15. The second line of evidence comes from the deletion of an abnormal parental contribution of 15q11q13 in PWS patients without a cytogenetic and molecular deletion. These patients have two maternal copies and no paternal copy of 15q11q13 (maternal uniparental disomy) instead of one copy from each parent. By qualitative hybridization with chromosome 15q11q13 specific DNA markers, we have now examined DNA samples from 10 AS patients (at least seven of which are familial cases) with no cytogenetic or molecular deletion of chromosome 15q11q13. Inheritance of one maternal copy and one paternal copy of 15q11q13 was observed in each family, suggesting that paternal uniparental disomy of 15q11q13 is not responsible for expression of the AS phenotype in these patients. 
5	Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia. Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention. 
4	Spontaneous cerebral embolism from descending thoracic aortic aneurysm--a case report. A case in which an aneurysm of the proximal descending thoracic aorta was the likely source of retrograde cerebral embolism is described. Atherosclerotic disease of the descending thoracic aorta should be considered as an unusual source of cerebral emboli. 
5	Decreased operative risk of surgical treatment of mitral regurgitation with or without coronary artery disease. The consecutive 2 year experience with patients undergoing first-time surgery for mitral regurgitation with and without coronary artery disease was reviewed. From January 1988 to January 1990, 127 patients with pure mitral regurgitation undergoing first-time operation were surgically treated. No other valve lesion, no reoperation and no congenital defects were included. The mean patient age was 62 years with 26% of the patients greater than 70 years. Twenty-six percent of the entire group was in functional class IV. Seventy-five patients received mitral valve repair and 52 underwent mitral valve replacement with a St. Jude or Hancock valve. In patients undergoing mitral valve repair, there was a higher incidence of those greater than 70 years old and of coronary artery disease and in patients undergoing mitral valve replacement there was a higher incidence of functional class IV. The operative mortality rate was 2.3% (3 of 127 patients). No patient failed to be discontinued from cardiopulmonary bypass and all three deaths occurred after mitral valve replacement, with one from complications of chronic renal failure and dialysis. There was no significant difference in patients who either did or did not have a concomitant coronary artery bypass graft and there was no difference related to age or functional class. Postoperative complications occurred in five patients in the valve repair group, including recurrent mitral regurgitation in two necessitating reoperation, and in three patients in the valve replacement group. With newer operative and postoperative management techniques, especially preservation of the papillary muscle annular continuity, the risk of mitral valve surgery, particularly of valve repair, is considerably lower than in previous years. 
2	Colonoscopy without prior preparation in mild to moderate active ulcerative colitis. We evaluated the effect of different types of preparations on the diagnostic yield of colonoscopy (total or limited) in mild to moderate active ulcerative colitis. Our ability to determine the extent of disease and see the mucosa beyond the inflamed areas was assessed in patients receiving no preparation (group A, 72 examinations) and those receiving diphosphosoda enemas (group B, 181 examinations). There were three failures in group A and 11 in group B. In the majority of patients (71% of group A, 83% of group B) the scope could be passed under optimal viewing conditions at least one segment beyond the involved area. In group A the cecum was reached in 16% of the procedures and in group B in 18%. We conclude that in mild to moderate active ulcerative colitis, colonoscopy can be performed without preparation, and still achieve the same results as with preparatory enemas. 
4	Contribution of transesophageal echocardiography to patient diagnosis and treatment: a prospective analysis. The capability of transesophageal (TEE) versus transthoracic (TTE) echocardiography as a diagnostic tool in clinical practice was prospectively examined in 86 consecutive cases. A conclusive diagnosis was possible in 95% with TEE, whereas the same result was achieved in 48% by TTE. Specifically, TEE provided a conclusive diagnosis in 14 of 16 cases of infective endocarditis, while TTE gave this result in 4 of the 16 cases (p less than 0.001). Similarly, TEE allowed a conclusive diagnosis in 11 of 11 instances of aortic dissection, while TTE gave this indication in two cases (p less than 0.001). TEE was similarly effective in eight of eight cases of atrial thrombi, whereas TTE gave the diagnosis in three of eight cases (p less than 0.01). In five subjects with intracardiac masses, TEE gave a conclusive diagnosis in all five, whereas TTE was able to diagnose conclusively in one subject (p less than 0.02). In seven patients with mitral regurgitation, TEE gave the conclusive diagnosis in all seven and TTE was able to provide this information in four (p = NS). TEE was able to provide a conclusive diagnosis in four patients with aortic insufficiency, and TTE gave the same information in two of the four (p = NS). In 14 patients with prosthetic valve dysfunction, TEE gave the diagnosis in 12 and TTE gave it in eight patients (p = NS). Both methods gave a conclusive diagnosis in 13 out of 13 cases of mitral stenosis (p = NS). Also, TEE provided a conclusive diagnosis in eight of eight patients with adult congenital heart disease and TTE gave this information in four (p = NS). 
2	The associated anomalies that determine prognosis in congenital omphaloceles. Cogenital abdominal wall defects such as omphaloceles can be recognized by fetal ultrasonography. To determine whether associated anatomic features may be useful in determining fetal prognosis, a retrospective study was performed over a 5-year period. There were 28 cases of omphalocele; 16 were larger than 5 cm and classified as giant, and the remainder were considered small. Eleven of the 12 infants with small omphaloceles survived with minimal neonatal complications. Ten of the 16 infants with giant omphaloceles died because of associated congenital anomalies. These were congenital heart disease, central nervous system malformations, and diaphragmatic hernias. This review suggests that the prognosis is good when a prenatal diagnosis of giant omphalocele is made and careful fetal ultrasonography, including echocardiography, does not identify heart, central nervous system, or diaphragmatic malformations, even when there is liver herniation into the omphalocele. 
5	Severe anterior segment inflammation following corneal surgery for keratoconus. We present three keratoconus patients who experienced severe anterior segment inflammation, two following penetrating keratoplasty, and one following epikeratoplasty. A favorable response to indomethacin therapy in the second eyes of these patients suggests that the inflammation in the first ones was prostaglandin mediated. 
3	Phenotypic and functional characterization of T cells from patients with myasthenia gravis. A study of cell surface phenotypes of PBL of myasthenia gravis (MG) patients showed that their T cells had a significantly higher percentage of 4B4+ T cells (the helper/inducer subset) than age- and sex-matched controls. The PBL of MG patients proliferated significantly higher than those of normal subjects (NS) in response to the purified alpha chain of the acetylcholine receptor (AChR). Anti-AChR antibody was present in sera of 88% of MG and none of the NS. The PBL B cells from MG only, when cultured with autologous T cells and stimulated with either pokeweed mitogen (69%), or AChR-alpha chain (38%), secreted antibody to AChR-alpha chain, whereas T and B cells alone secreted no antibody. T cells from PBL of MG patients were more readily cloned than T cells of NS, by limiting dilution, in the presence of recombinant IL-2 and in the absence of AChR-alpha chain. About 50% of T cell clones from MG patients, compared to none from NS, proliferated to AChR-alpha chain. This response was HLA-DR restricted. MG T cell clones did not display significant cytotoxic activity, as compared to control T cell clones. Our results indicate that in MG, 4B4+ regulatory T cells play their role in the pathogenesis of MG, not by cytotoxicity, but more likely by their ability to stimulate specific antibody production by B cells. 
2	Diphenylhydantoin-induced hypogammaglobulinemia in a patient infected with human immunodeficiency virus. A case is reported of reversible panhypogammaglobulinemia in a human immunodeficiency virus (HIV)-infected patient. Onset and resolution were temporally correlated with initiation and termination, respectively, of diphenylhydantoin therapy for a possible seizure. A rapid alteration in peripheral T-cell subpopulations was also noted in association with diphenylhydantoin administration. This case is compared with previous reports of diphenylhydantoin-associated hypogammaglobulinemia in non-HIV-infected patients. In addition, the case is discussed with regard to possible deleterious effects associated with the use of diphenylhydantoin as therapy for HIV-associated seizures or as an antiretroviral agent in HIV disease. 
3	Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. The nocturnal secretion of plasma melatonin was determined under dim to dark conditions in eight patients with prospectively confirmed premenstrual syndrome and in eight age- and menstrual cycle phase-matched normal control subjects. Plasma samples for melatonin were collected every 30 minutes from 6 PM to 9 AM during the early follicular, late follicular, midluteal and late luteal phases of the menstrual cycle. Compared with normal controls, patients with premenstrual syndrome had an earlier (phase-advanced) offset of melatonin secretion, which contributed to a shorter secretion duration and a decreased area under the curve. No statistically significant differences were found between women with premenstrual syndrome and normal controls for melatonin onset or peak concentration, or for estradiol or progesterone levels. The data demonstrate that women with premenstrual syndrome have chronobiological abnormalities of melatonin secretion. The fact that these patients respond to treatments that affect circadian physiology, such as sleep deprivation and phototherapy, suggests that circadian abnormalities may contribute to the pathogenesis of premenstrual syndrome. 
5	Ascites not due to congestive heart failure in a fetus with lupus-induced heart block. Hydrops developing in fetuses with lupus-associated heart block has usually been assumed to result from congestive heart failure. We present a case in which fetal ascites associated with complete heart block resolved promptly after administration of betamethasone and prednisone to the mother, who had anti-SSA and who developed clinical lupus erythematosus. This resolution occurred with no demonstrable change in fetal cardiac function. We conclude that an immune mechanism, rather than congestive heart failure, was responsible for the fetal ascites. 
1	Multisurface method of pattern separation for medical diagnosis applied to breast cytology. Multisurface pattern separation is a mathematical method for distinguishing between elements of two pattern sets. Each element of the pattern sets is comprised of various scalar observations. In this paper, we use the diagnosis of breast cytology to demonstrate the applicability of this method to medical diagnosis and decision making. Each of 11 cytological characteristics of breast fine-needle aspirates reported to differ between benign and malignant samples was graded 1 to 10 at the time of sample collection. Nine characteristics were found to differ significantly between benign and malignant samples. Mathematically, these values for each sample were represented by a point in a nine-dimensional space of real variables. Benign points were separated from malignant ones by planes determined by linear programming. Correct separation was accomplished in 369 of 370 samples (201 benign and 169 malignant). In the one misclassified malignant case, the fine-needle aspirate cytology was so definitely benign and the cytology of the excised cancer so definitely malignant that we believe the tumor was missed on aspiration. Our mathematical method is applicable to other medical diagnostic and decision-making problems. 
5	Correlation of APACHE II score, drainage technique and outcome in postoperative intra-abdominal abscess. The APACHE II Score was used to stratify retrospectively severity of illness in 91 patients postoperatively undergoing drainage of intra-abdominal abscesses. The method of initial abscess drainage (percutaneous or operative) was selected by the attending physician. The two groups of patients, those whose initial drainage was performed percutaneously versus operatively were similar with respect to age, sex, abscess location and, most importantly, severity of illness as assessed by the APACHE II score calculated on the day of their abscess drainage. Over-all, the mortality rate was 29 per cent (26 of 91 patients). Only 1.7 per cent of the patients with an APACHE II score of less than 15 died compared with 78 per cent when APACHE II was equal to or more than 15 (p less than 0.0001). Only 8 per cent of patients with APACHE II equal to or more than 15 undergoing percutaneous drainage survived compared with 30 per cent of patients who underwent surgical drainage procedures. While chi-square analysis demonstrated independence between outcome and drainage technique, outcome was dependent upon severity of illness (p less than 0.0005). Paradoxically, despite the attractiveness of a percutaneous technique for abscess drainage in the most ill patients, in this series, a better, although not statistically improved, chance for survival was noted with surgical treatment. We recommend that an objective severity scoring system be used whenever assessing results of treatment of intraabdominal infection and that surgical treatment not be avoided because the patient is considered to be too ill. 
4	Effect of synchronous increase in intrathoracic pressure on cardiac performance during acute endotoxemia. In the anesthetized closed-chest canine model of Gram-negative endotoxemia (n = 10), we tested the hypothesis that the effect of cardiac cycle-specific intrathoracic pressure pulses delivered by a heart rate-(HR) synchronized high-frequency jet ventilator (sync HFJV) on systolic ventricular performance is dependent on the level of preload. To control for HFJV frequency, hemodynamic responses were also measured at fixed frequency within 15% of HR (async HFJV). Biventricular stroke volumes (SV) were measured by electromagnetic flow probes. Measurements were made before (baseline) and 30 min after infusion of 1 mg/kg Escherichia coli endotoxin (serotype 055:B5) and then after 2 mg/kg propranolol at both low (less than 10 mmHg) left ventricular filling pressure (LVFP) and high (greater than 10 mmHg) LVFP. Ventricular function curves, aortic pressure-flow (P-Q) relationships, and venous return (VR) curves were analyzed. We found that endotoxin did not alter VR curves but shifted the aortic P-Q curves to the left with pressure on the x-axis (P less than 0.05). Volume loading increased SV (P less than 0.01) because of a rightward shift of the VR curve. No specific differences occurred with either sync or async HFJV during endotoxin, presumably because of preserved VR and shifted aortic P-Q. The lack of cardiac cycle-specific effects of ITP appears to be due to the selective endotoxin-induced changes in peripheral vasomotor tone that counterbalance any depressed myocardial contractility. 
4	Severe aortic regurgitation as a late complication of temporal arteritis. Two patients with a remote history of pathologically documented giant cell arteritis developed severe regurgitation. The first patient developed severe aortic regurgitation five years after the pathologic documentation of giant cell arteritis of the temporal arteries. Giant cell arteritis involvement of the aortic root was confirmed. The second patient developed aortic regurgitation seven years after pathologic documentation of giant cell arteries of the temporal arteries. Although pathologic confirmation of the aortic root process was not obtained, this case strengthens the clinical association between giant cell arteritis of the temporal arteries and subsequent aortic root dilatation and severe aortic regurgitation. Observation for signs of de novo severe aortic regurgitation is indicated in follow-up of patients with temporal arteritis. 
1	Empiric treatment of fungal infections in the neutropenic host. Review of the literature and guidelines for use. Persistent fever that is refractory to broad-spectrum antibacterials is common in neutropenic patients undergoing induction chemotherapy of acute leukemia. Clinical experience suggests that many of these patients are infected with fungi. Until recently, data supporting the role of empiric antifungal therapy in this setting were limited to small groups of patients or postmortem reports. Evolving evidence in larger patient populations supports data from smaller series: febrile neutropenic patients who have failed to respond to a 4- to 7-day course of broad-spectrum antibacterials may benefit from the early initiation of antifungal therapy. Patients with fungal colonization or pulmonary infiltrates and adult patients who have not received previous fungal prophylaxis may especially benefit from the early use of antifungal drugs. Amphotericin B has been the "gold standard" for empiric antifungal therapy, although the newer azoles may be useful in certain situations. 
5	Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. After nearly 18 years of research, the association between human leukocyte antigens A1-B8-DR3 and autoimmune chronic active hepatitis still provokes debate. The principal reasons for this are disease heterogeneity and racial variation in the distribution of human leukocyte antigens between populations. The aim of the present study was to reexamine the relationship between these antigens and autoimmune chronic active hepatitis in a well-characterized series of patients. Ninety-six outpatients with autoimmune chronic active hepatitis and an additional 14 referred for liver transplantation with end-stage autoimmune chronic active hepatitis were studied. Human leukocyte antigen frequencies were compared with those of 100 racially and geographically matched controls. The A1-B8-DR3 haplotype was present in 38% of patients compared with 11% of controls (chi 2 = 20.6, p less than 0.0005). When all the DR3-positive patients were eliminated, there was a striking secondary association with DR4; 35 (80%) of 44 remaining patients were DR4 positive compared with 31 (39%) of 79 DR3-negative controls (Fisher's exact probability test p = 0.000031, pc = 0.0013). In addition patients with A1-B8-DR3 are seen at a significantly younger age than those without (39.75 yr vs. 48.21 yr, p less than 0.025), relapse more frequently (52% of patients with A1-B8-DR3 relapsed on one or more occasions compared with 34% of patients without this haplotype) and are more frequently referred for liver transplantation. These data indicate for the first time that two genes within the major histocompatibility complex closely linked to the DR3 and DR4 genes independently confer susceptibility to autoimmune chronic active hepatitis. 
2	Surgery for acute and chronic cholecystitis. Cholecystostomy and cholecystectomy remain appropriate and effective therapy for acute and chronic cholecystitis. Cholecystectomy is the gold standard against which all alternative methods of treatment of inflammatory biliary stone disease should be judged. The pathogenesis, diagnosis, and surgical treatment of acute and chronic cholecystitis have been described. Techniques of cholecystostomy, cholecystectomy, and intraoperative cholangiography used by the author have been given. Our results and those generally described in the literature indicate that the overall mortality rate for cholecystectomy, in all age groups, is approximately 0.5%. This rate increases slightly in patients with acute cholecystitis and in those over the age of 65 years. Cholecystectomy remains the most effective and the definitive treatment for acute and chronic cholecystitis. 
1	Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia. Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL. 
5	Salvage of branch vessels during bifurcation lesion angioplasty: acute and long-term follow-up. To evaluate angiographic success, frequency of branch vessel loss and salvage, and long-term outcome, we studied the early and late outcomes of 56 consecutive patients who underwent PTCA of bifurcation lesions, which involved the left anterior descending or left circumflex coronary artery, with stenoses greater than 70% in both the parent and an involved branch vessel. In 35 patients (63%), the PTCA strategy was attempted dilation of both the main vessel and the involved branch vessels using predominantly a double-wire, sequential balloon technique; in 21 (27%) the PTCA attempt was confined to the main vessel alone. Transient angiographic occlusion of the branch vessel occurred in 32% of patients in whom dilation of both vessels was attempted, and in 38% in whom the main vessel alone was dilated (p = NS); 91% of the occluded branch vessels were the salvaged when sequential angioplasty of both vessels had been initially planned, compared to only 38% when the initial strategy had been dilation of the main vessel alone (p less than .05). Predischarge exercise testing showed residual ischemia in 6% of patients who had both vessels successfully dilated, versus 37% in those in whom dilatation was confined to the main vessels (p less than .01). Clinical restenosis, defined as late (greater than 6 weeks) recurrence of angina or a positive exercise test, occurred in 42% of patients who had both vessels successfully dilated. Thus although bifurcation lesion angioplasty frequently results in transient branch vessel loss, these branches can usually be salvaged using a double-wire technique but tend to have a higher late restenosis than conventional single vessel PTCA. 
1	Transfer of secretory proteins from the endoplasmic reticulum to the Golgi apparatus: discrimination between homologous and heterologous transfer in intact heterokaryons. To examine aspects of the transfer of secretory proteins from the endoplasmic reticulum to the Golgi apparatus in situ, heterokaryons were formed between Hep G2 human hepatoma cells and WI-38 human fibroblasts. The cells were appropriately treated with cycloheximide before fusion, which emptied them of their respective secretory proteins, serum albumin for the Hep G2 cells and procollagen I for the WI-38 cells. After fusion was complete, the cycloheximide was washed out, protein synthesis was resumed, and the rates of reappearance of serum albumin and procollagen I in the two separated Golgi apparatuses within each heterokaryon were followed by immunofluorescence microscopy. Serum albumin was found to always reappear first in the Golgi apparatus contributed by the Hep G2 half of the heterokaryon, and procollagen I in the Golgi apparatus of the WI-38 half. These results suggest that the endoplasmic reticulum-to-Golgi apparatus transfer in situ is not simply a stochastic process but is either spatially restricted or exhibits cell-type specificity or both. 
3	Hip pain in late pregnancy. Hip pain in late pregnancy is quite common, and its etiology is rarely established unless acute demineralization occurs. We measured the bone mineral content of both hips in 26 women within 48 hours of delivery. Twelve of 36 densities (33%) were decreased in a group with severe pain when compared to 12 of 120 decreased densities (10%) in the remaining patients (P less than .05). Those data suggest that severe hip pain may be related to a decrease in bone mineral content. 
1	Suprasellar pituitary adenoma arising from the pars tuberalis: case report. A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted. 
5	Superior protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium. Clinical study in comparison with St. Thomas' Hospital solution. The protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium has been assessed in adult patients undergoing heart operations. Postreperfusion recovery of cardiac function and electrical activity was evaluated in 34 patients; 16 received low-calcium, magnesium-free potassium cardioplegic solution (group I) and 18 received St. Thomas' Hospital solution, which is enriched with calcium and magnesium (group II). There were no significant differences between the two groups in age, sex, body weight, and New York Heart Association functional class. Aortic occlusion time (107.3 +/- 46.8 minutes versus 113.6 +/- 44.3 minutes), highest myocardial temperature during elective global ischemia (11.5 degrees C +/- 3.1 degrees C versus 9.3 degrees C +/- 3.2 degrees C), and total volume of cardioplegic solution (44.2 +/- 20.5 ml/kg versus 43.4 +/- 17.6 ml/kg) were also similar in the two groups. On reperfusion, electrical defibrillation was required in four cases (25.5%) in group I and in 15 cases (83.3%) in group II (p less than 0.005), and bradyarrhythmias were significantly more prevalent in group II (6.3% versus 44.4%; p less than 0.05). Serum creatine kinase MB activity at 15 minutes of reperfusion (12.3 +/- 17.0 IU/L versus 42.6 +/- 46.1 IU/L; p less than 0.05) and the dose of dopamine or dobutamine required during the early phase of reperfusion (1.8 +/- 2.5 micrograms/kg/min versus 6.1 +/- 3.3 micrograms/kg/min; p less than 0.0002) were both significantly greater in group II. Postischemic left ventricular function, as assessed by percent recovery of the left ventricular end-systolic pressure-volume relationship in patients who underwent aortic valve replacement alone, was significantly better in group I (160.4% +/- 45.5% versus 47.8% +/- 12.9%; p less than 0.05). Serum level of calcium and magnesium ions was significantly lower in group I. Thus low-calcium, magnesium-free potassium cardioplegic solution provided excellent protection of the ischemic heart, whereas St. Thomas' Hospital solution with calcium and magnesium enabled relatively poor functional and electrical recovery of the heart during the early reperfusion period. These results might be related to differing levels of extracellular calcium and magnesium on reperfusion. 
3	Gait analysis in the treatment of the ambulatory child with cerebral palsy. Surgical treatment of children with cerebral palsy has changed from staged, single joint procedures to comprehensive simultaneous bony and soft-tissue corrections. This regimen of treating multiple joint levels and planes of abnormality is subject to error when based solely on the clinical examination. A more scientific evaluation can be provided by the use of clinical gait analysis. Both preoperative and postoperative analyses provide the clinician with information from which neurologic patterns can be determined and surgical protocols can be judged. 
5	Post-caesarean section analgesia: a comparison of epidural butorphanol and morphine. Epidural butorphanol 1, 2 and 4 mg were compared with morphine, 5 mg, for postoperative analgesia in 92 consenting, healthy, term parturients who had undergone Caesarean section under epidural lidocaine anaesthesia in a randomized double-blind study. Postoperative pain was assessed using a visual analogue scale and recorded with heart rate, blood pressure and respiratory rate. The demographic characteristics, and the incidences of primary and repeat Caesarean sections, were not different among the four treatment groups. At 15, 30, 45 and 60 min after treatment the median pain scores following butorphanol were similar and lower than those following morphine (P less than 0.05). Calculated median percentage pain relief values for butorphanol were higher than morphine at each of these times (P less than 0.05). At 90 min and 2 hr the pain scores and pain relief values were similar. Beyond 45 min the number of patients requesting supplemental medication and dropping out of the study increased progressively in both the butorphanol and morphine treated patients. The attrition profiles for butorphanol were different from morphine (P less than 0.01). The median time in the study was greater than 24 hr for morphine, and 3, 2.5 and 4 hr for butorphanol, 1, 2 or 4 mg, respectively. No patient developed a clinically important change in heart rate or blood pressure, and none experienced a decrease in respiratory rate below 12 breaths.min-1. One of 69 patients (1.4 per cent) who received butorphanol developed pruritus compared with ten (43 per cent) of 23 patients who received morphine. The global assessments of the adequacy of analgesia were indistinguishable between morphine and butorphanol. Epidural butorphanol provides safe, effective postoperative analgesia, has a prompt onset, and a limited duration. 
5	Disability in persons hospitalized with AIDS. This study documents the types and degree of disability seen in persons with AIDS at discharge from acute hospitalization. Based on 37 discharge evaluations using the Functional Independence Measure (FIM), 60% required human assistance in at least one of 18 FIM areas. Thirty-two percent required human assistance in five or more areas. Fifty-one and 38% required human assistance in stair climbing and ambulation, respectively. Feeding and bathing required assistance in about 33% and transferring to tub or shower in 25% of the sample. Increasing disability was associated with longer duration of AIDS diagnosis and increasing lengths of hospital stay (P less than 0.01 and P less than 0.05, respectively). There were individuals who remained nearly functionally independent up to 30 months after an AIDS defining event. The overall variability in function, however, was not significantly different between those with diagnoses less than and greater than 12 months. We conclude that significant physical disability exists in persons with AIDS at discharge from acute hospitalization. Consultation with and intervention by rehabilitation professionals may be helpful in the management of physical disability in this population and setting. 
4	Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats. This study examined the calcium dependency of contractions in arteries from rats made hypertensive by aortic coarctation and in rats with genetic hypertensive (stroke-prone spontaneously hypertensive rats). Mesenteric artery and aortic strips were suspended in tissue baths for isometric force recording and contractions to two drugs were characterized: 1) a phorbol ester, TPA (12-O-tetrade-canoylphorbol-13-acetate), and 2) the calcium channel agonist, Bay K 8644. Thoracic aortae and mesenteric arteries from hypertensive rats were more sensitive to the contractile properties of the protein kinase C activator TPA than comparable arteries from normotensive rats. In thoracic aortae from coarcted rats, the contractile activity of Bay K 8644 was potentiated compared to normotensive values. In the presence of 19.2 mmol/L KCl, responses to Bay K 8644 in thoracic aortae from normotensive rats were potentiated and did not differ from coarcted values. In contrast, contractions to Bay K 8644 and TPA in abdominal aortae obtained below the coarctation were not different from normotensive values. Upon exposure to 26.2 mmol/L KCl, contractions to Bay K 8644 in abdominal aortae were potentiated and those in aortae from coarcted rats did not differ from sham values. Contractile responses to both drugs were blocked by nifedipine and verapamil and responses were attenuated in calcium-free solution. We conclude that calcium channel function and its regulation by protein kinase C contribute to altered vascular reactivity in hypertension. Further, these abnormalities have a pressure dependency, because they did not occur in abdominal aortae from coarcted rats. 
3	Effect of cardiac output reduction on rate of desaturation in obstructive apnea. The nadir of SaO2 during an obstructive apnea is dependent upon the apnea's duration and the rate of fall of saturation (dSaO2/dt). We postulated that a low Q, such as in patients with congestive heart failure with sleep apnea, or a reduction in Q, as seen in some humans during obstructive sleep apnea, might steepen dSaO2/dt. The mechanism postulated was lowering of SvO2 with increased pulmonary capillary blood oxygen uptake and faster depletion of alveolar oxygen. This study examines dSaO2/dt following the onset of apnea in eight spontaneously breathing adult baboons. Nonrepetitive obstructive apneas (30, 45, and 60 seconds) were created by clamping an indwelling cuffed endotracheal tube at the end of expiration. Following baseline measurements, the animals were given a bolus of a rapid-acting beta-adrenergic blocker followed by continuous infusion to reduce cardiac output and to limit the cardiovascular response to obstructive asphyxia. Fiberoptic catheters were used for continuous monitoring of SaO2, SvO2, and cardiac output. Esophageal pressure and relative thoracic gas volume (Respitrace) were monitored to insure equivalence of lung volume at the onset of apnea. Beta-adrenergic blockade reduced resting Q by a mean of 25 percent. The blocked vs unblocked dSaO2/dt was 0.73 vs 0.72 percent/s, 0.76 vs 0.73 percent/s, and 0.70 vs 0.71 percent/s for 30-second, 45-second, and 60-second apneas, respectively. Thus, mean dSaO2/dt for all durations of apneas was unaffected by beta-adrenergic blockade. We concluded that dSaO2/dt is not influenced by limited Q preceding or induced by obstructive asphyxia. 
3	Multiple representations of pain in human cerebral cortex. The representation of pain in the cerebral cortex is less well understood than that of any other sensory system. However, with the use of magnetic resonance imaging and positron emission tomography in humans, it has now been demonstrated that painful heat causes significant activation of the contralateral anterior cingulate, secondary somatosensory, and primary somatosensory cortices. This contrasts with the predominant activation of primary somatosensory cortex caused by vibrotactile stimuli in similar experiments. Furthermore, the unilateral cingulate activation indicates that this forebrain area, thought to regulate emotions, contains an unexpectedly specific representation of pain. 
1	Intraoperative radioimmunodetection of ovarian cancer using monoclonal antibody B72.3 and a portable gamma-detecting probe. To assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer, we used monoclonal antibody B72.3, radiolabeled with 125I, and a hand-held gamma-detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy. B72.3, which recognizes a tumor-associated glycoprotein, TAG 72, was injected 12-29 days preoperatively (intraperitoneally in four cases, intravenously in nine, and by both routes in one). Intraoperatively, the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains. Probe counts were positive in four of seven evaluable patients with histologically confirmed disease. In three of these four patients, the probe detected cancer in specimens interpreted as normal on frozen histologic sections. The probe also identified microscopic cancer in the one patient who had no gross disease. The specificity of the probe was 70%. Preoperative computed tomography was normal in all patients, including those with tumors as large as 3 cm. This pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer. 
2	Neutrophil dysfunction in glycogen storage disease Ib: association with Crohn's-like colitis. Two cases of patients with Crohn's-like colitis and glycogen storage disease Ib have been reported previously. In the current report, chronic inflammatory bowel disease that developed in another adolescent with this glycogenosis is described, thereby corroborating the association. The neutrophil dysfunction observed in glycogen storage disease Ib is the most likely predisposing factor. Neutrophil function was investigated in our patient in an attempt to shed light on the pathogenesis of his intestinal inflammation. The patient displayed reduced neutrophil chemotaxis to zymosan-activated serum, N-formyl-methionine-phenylalanine, and Escherichia coli bacteria-derived factor and reduced intracellular killing of Staphylococcus aureus 502A. Others have found this defective bacteriocidal activity to be caused by impaired oxidative metabolism. The recent recognition of chronic inflammatory bowel disease in glycogen storage disease Ib, as well as in chronic granulomatous disease, suggests that further study of respiratory burst activity of neutrophils in Crohn's disease is warranted. 
4	Effect of coronary occlusion and myocardial viability on myocardial activity of technetium-99m-sestamibi The timing effect of sestamibi administration with respect to the onset of myocardial ischemia and reperfusion was studied in swine. In different groups of animals sestamibi was administered prior to coronary artery occlusion, during occlusion, or 1/2 hour following reperfusion. Sestamibi administered prior to coronary occlusion resulted in an insignificant decrease in 99mTc activity in the ischemic zone. However, infarct zone activity was reduced to 62 +/- 14% of the nonischemic zone. In contrast, administration during coronary occlusion resulted in similar significant reductions of both ischemic and infarct zone activity. Administration of sestamibi during reperfusion resulted in normal ischemic zone activity and markedly reduced activity in the infarct zone. Significantly reduced activity in the infarct zone was found to be independent of the timing of sestamibi administration with respect to the onset of myocardial ischemia and/or reperfusion. Thus, cell viability appears required for uptake and retention of isotope activity. 
1	New active analogues of vitamin D with low calcemic activity. In conclusion, a number vitamin D analogues have been developed that have very low calcemic activity but retain several other properties of 1,25-(OH)2D3, including the ability to differentiate leukemia and skin cells, to enhance the immune response, and to suppress parathyroid hormone levels. Although the mechanism of this selective activity is not yet clear, these analogues may provide new insights into the differences in action of 1,25-(OH)2D3 in various target tissues. Most importantly, the selective action of these analogues may be exploited for the treatment of diseases such as leukemia, psoriasis and hyperparathyroidism. 
1	Recurrent intracaval renal cell carcinoma: the role of intravascular ultrasonography. The presence of extension into the vena cava does not preclude curative resection for extensive renal cell carcinomas. However, preoperative assessment of (1) the proximal extent of the tumor and (2) the degree of adherence within the vena cava is necessary to plan operative strategies. The following report describes the successful use of intravascular ultrasonography in the preoperative evaluation of a patient with recurrent renal cell carcinoma with vena caval extension. 
2	Surgical treatment of hydatid disease of the liver. A 20-year experience. The medical records of 135 consecutive patients (74 women and 61 men) who underwent surgery for hydatid liver disease were reviewed. The patients ranged in age from 4 to 81 years. Twenty-seven patients had undergone previous surgery for hydatid liver disease. Cysts were solitary in 100 patients and multiple in 35 patients. Seventeen patients had concomitant extrahepatic disease. Conservative procedures were used in 71 patients (capitonnage in 50 patients and partial pericystectomy in 21 patients). Radical procedures were used in 64 patients (total pericystectomy in 35 patients, subtotal pericystectomy in 16 patients, and wedge or major liver resection in 13 patients). Operative mortality was 2.2% and morbidity rate was 23.7%. Recurrent disease was found in 13 patients at a mean interval of 3 years from the first operation. Better short- and long-term results were obtained with the use of radical procedures. 
5	Results of infrainguinal bypass for limb salvage in patients with end-stage renal disease. Limb salvage in patients with end-stage renal disease (ESRD) is complicated by the diffuse, obstructive, calcific arteriopathy that makes anastomotic technique especially critical. Furthermore, decreased resistance to infection and impaired wound healing produced by host-factor deficiencies such as diabetes mellitus, hypoalbuminemia, uremia, and immunosuppression produce additional obstacles to successful limb salvage. This report summarizes our experience with distal arterial bypass procedures in these patients. A total of 32 bypass procedures were performed for limb salvage in 24 patients (17 diabetic) during a period of 5 years. The operative mortality rate was 6%. During the same period, 635 infrainguinal bypass procedures were performed by the in situ technique in patients without ESRD. Primary bypass patency was comparable in both groups at 24 months (92% vs 90%). In the group with ESRD, overall limb salvage was 83% at 2 years. Life-table analysis of bypass patency and limb salvage was thought not to be appropriate in the population with ESRD beyond 2 years because of the increased mortality rate (38%; 9/24) during this interval. It is important that limb salvage was achieved in diabetic patients with ESRD in the presence of extensive foot gangrene or ischemic ulceration. Revascularization should be considered strongly for limb salvage in all patients in this difficult population. 
5	Trichothiodystrophy with chronic neutropenia and mild mental retardation. Trichothiodystrophy is a feature of several diseases that consist of characteristic hair shaft abnormalities and a wide spectrum of other developmental defects. Detection of sulfur-deficient hairs identifies this disorder and separates it from other similar ectodermal dysplasias with normal sulfur content. Detection of low sulfur hair syndrome is also important for genetic counseling, because the disease appears to be an autosomal recessive trait. We report a patient with chronic neutropenia, mild mental retardation, and low sulfur content in hair. Our case expands the spectrum of disorders associated with trichothiodystrophy. 
2	Early results of combined electrohydraulic shock-wave lithotripsy and oral litholytic therapy of gallbladder stones at the University of Iowa. One hundred thirty-three patients were entered into a randomized, double-blind, placebo-controlled trial of extracorporeal shock-wave lithotripsy for symptomatic gallstones versus extracorporeal shock-wave lithotripsy plus adjuvant litholytic therapy with ursodeoxycholic acid (UDCA). Six months after lithotripsy, patients receiving placebo were crossed over to UDCA therapy without unblinding the study. One hundred sixteen patients have completed 6 months of follow-up. Five patients were dropped from the study. Nine percent have required cholecystectomy (11 patients with biliary colic and 1 with acute cholecystitis). Ninety-one patients had a solitary stone (64 patients had stones less than or equal to 20 mm and 27 patients had stones greater than 20 mm in diameter), and 25 patients had two to three stones. Fifty percent were retreated. Cumulative stone-free rates at 6, 12, and 18 months were 26%, 39%, and 41%, respectively. At 6 months there was a significant advantage for patients treated with UDCA versus placebo (36% vs 17% were stone free) that had disappeared by 12 months (placebo-treated patients had received 6 months of UDCA). Patients with solitary stones equal to or less than 20 mm in diameter treated with UDCA had stone-free rates at 6, 12, and 18 months of 58%, 58%, and 62%, respectively, versus 27%, 56%, and 50%. The difference was significant only at the 6- month follow-up. Stone-free rates for patients with large solitary stones and multiple stones were very low. Extracorporeal shock-wave lithotripsy is both safe and effective therapy for treatment of symptomatic gallstones in patients with a solitary stone equal to or less than 20 mm in diameter. UDCA markedly improves the efficiency of the procedure and results in a stone-free gallbladder sooner. 
5	Role of cytochrome P-450 in reperfusion injury of the rabbit lung. Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P-450 enzymes are not likely a major source of enhanced O2-. generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder. 
3	Strokes in African-Americans. Hypertension is the most important risk factor for stroke, especially in African-Americans. Improved control of high blood pressure nationwide is a key factor in the recent dramatic decline in stroke frequency, most notably in African-American women. Hypertension control programs must be adequately funded and expanded. African-Americans have a disproportionately high incidence of risk factors for stroke, including hypertension. There is evidence that the cerebral vessels involved in ischemic stroke in African-Americans may differ from those of Caucasians. There is an urgent need for more research on stroke in general, risk factor relations in particular, and mechanisms in the pathogenesis of stroke in African-Americans. 
5	Ventricular arrhythmias after correction of ventricular septal defects: importance of surgical approach. To compare the prevalence of conduction disturbances and ventricular arrhythmias in cases of postoperative ventricular septal defect, 100 patients (50 with repair by right atriotomy, group 1; and 50 with repair by right ventriculotomy, group 2) underwent complete evaluation including an electrocardiogram (ECG) and 24 h ambulatory ECG monitoring. The two groups were comparable except for a shorter follow-up duration (7 +/- 3 versus 12.4 +/- 7 years) and a younger age at evaluation (12.4 +/- 5 versus 16.9 +/- 7 years) in group 1. Complete right bundle branch block was less frequent in group 1 than in group 2 (20% versus 50%, p less than 0.05) but three of the four patients with complete atrioventricular (AV) block detected on ambulatory monitoring were in group 1. Six patients had significant supraventricular arrhythmias, all well tolerated. Ambulatory monitoring revealed significant ventricular arrhythmias (modified Lown grade 2 or higher) in 39 patients, with a lower prevalence in group 1 (30% versus 48%, p = 0.05). No correlation was found between prevalence of ventricular arrhythmias and right ventricular systolic pressure, cardiopulmonary bypass duration, presence of a synthetic patch, previous pulmonary artery banding, presence of complete right bundle branch block and cardiomegaly on chest X-ray film. Prevalence of ventricular arrhythmias increased with follow-up duration, age at evaluation and age at surgery. These were always well tolerated and did not warrant treatment. Thus, right atriotomy reduces the prevalence of right bundle branch block but does not prevent late AV block. Ventricular arrhythmias are frequent after surgical closure of ventricular septal defect whatever the surgical approach and their prevalence is not statistically different from that in postoperative tetralogy of Fallot. 
1	Lack of effect of pregnancy on outcome of melanoma. For The World Health Organisation Melanoma Programme To determine the effect of pregnancy on prognosis in melanoma we investigated 388 women treated for stage 1 primary cutaneous disease during their childbearing years. 85 women had been treated before any pregnancy, 92 during pregnancy, 143 after they had completed all pregnancies, and 68 between pregnancies. Women who had received treatment while pregnant had primary tumours of significantly greater thickness than did those in the other three groups (p = 0.002). Other possible confounding factors (site, age, parity) did not differ between the groups. Once tumour thickness was controlled for, survival rate of women in whom melanoma was diagnosed and treated while they were pregnant did not differ from that in the other three groups. Cox regression analysis showed no differences between the three groups of women who were not pregnant at diagnosis. Women with melanoma should be advised about pregnancy on the basis of thickness and site of tumour and evidence of vascular spread, and not hormonal status. 
1	Differentiation of HL-60 leukemia by type I regulatory subunit antisense oligodeoxynucleotide of cAMP-dependent protein kinase. A marked decrease in the type I cAMP-dependent protein kinase regulatory subunit (RI alpha) and an increase in the type II protein kinase regulatory subunit (RII beta) correlate with growth inhibition and differentiation induced in a variety of types of human cancer cells, in vitro and in vivo, by site-selective cAMP analogs. To directly determine whether RI alpha is a growth-inducing protein essential for neoplastic cell growth, human HL-60 promyelocytic leukemia cells were exposed to 21-mer RI alpha antisense oligodeoxynucleotide, and the effects on cell replication and differentiation were examined. The RI alpha antisense oligomer brought about growth inhibition and monocytic differentiation, bypassing the effects of an exogenous cAMP analog. These effects of RI alpha antisense oligodeoxynucleotide correlated with a decrease in RI alpha receptor and an increase in RII beta receptor level. The growth inhibition and differentiation were abolished, however, when these cells were exposed simultaneously to both RI alpha and RII beta antisense oligodeoxynucleotides. The RII beta antisense oligodeoxynucleotide alone has been previously shown to specifically block the differentiation inducible by cAMP analogs. These results provide direct evidence that RI alpha cAMP receptor plays a critical role in neoplastic cell growth and that cAMP receptor isoforms display specific roles in cAMP regulation of cell growth and differentiation. 
3	Chronic Lyme disease with an expansive granulomatous lesion in the cerebellopontine angle. Expansive granulomatous lesions in the posterior cranial fossa are rare and have not been reported in conjunction with Lyme disease. We report a patient with verified Borrelia burgdorferi infection who developed a tumor in the cerebellopontine angle. Rapid growth of the tumor led to signs of cerebral compression and to hydrocephalus. Surgical intervention was required despite florid meningitis. The histological examination showed inflammatory, nonspecific granulation tissue. The origin of this tissue is almost certainly causally related to the B. burgdorferi infection. Signs of inflammation resolved rapidly after subtotal resection. The clinical, radiological, and biochemical course is documented. This is the first report of an expansive cerebral lesion in the chronic phase of Lyme disease. 
1	Estrogen replacement therapy: is previously treated cancer a contraindication? The benefits of estrogen replacement therapy in preventing vasomotor symptoms, osteoporosis, and cardiovascular disease are well documented. Although estrogen is said to be contraindicated in patients successfully treated for endometrial and breast cancer, there are no data to substantiate this admonition. Experience suggests that it can be used safely in patients treated previously for endometrial cancer. Although there is little or no experience with estrogen use in the woman treated previously for breast cancer, circumstantial evidence suggests that it is not contraindicated in all such cases. Informed consent, patient desires, and risk-benefit considerations must enter into the decision to use estrogen in these patients. 
4	Results and follow-up after percutaneous pulsed laser-assisted balloon angioplasty guided by spectroscopy BACKGROUND. Few data are available on the long-term outcome of patients who undergo laser-assisted balloon angioplasty for recanalization of occluded peripheral arteries. Because the cost of laser angioplasty is high, the value of the method should be carefully analyzed before it can be considered a routine method for recanalization. The purpose of this study was to evaluate the early and late results of laser-assisted balloon angioplasty in patients who could not be recanalized by conventional techniques. METHODS AND RESULTS. Laser angioplasty was performed in 66 patients with total occlusion of the iliofemoral artery in whom mechanical techniques failed to recanalize the obstructed vessel. The system consisted of a pulsed dye laser operated at 480 nm, 2 microseconds/pulse, 5 Hz, 50 mJ/pulse coupled into a 0.021-in. laser catheter. The treatment laser was connected with a diagnostic laser to induce tissue fluorescence for spectroscopic analysis via the same fiber. The treatment laser was emitted only when atheromatous tissue was recognized. After a pilot hole was created by laser emission, dilatation was performed to enlarge the channel. The mean length of occlusion was 8.8 +/- 6.1 cm. The primary success rate was 82%. It did not depend on the length of occlusion but was greater in non-calcified than in calcified lesions (88% versus 71%, p less than 0.03). Complications included seven early reocclusions that could be recanalized and eight perforations without clinical sequelae. At a mean 18-month follow-up, 64% of the laser-treated arteries remained patent. The rate of patency was related neither to the length of the occlusion nor to calcifications but was lower in patients who had early reocclusion (p less than 0.02). CONCLUSIONS. Pulsed dye laser-assisted balloon angioplasty is effective for recanalization of totally occluded arteries that cannot be treated by conventional means. The efficacy is limited by calcifications. The long-term patency rate is acceptable given the severity of the lesions. 
5	Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain. Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging. 
4	Left ventricular pseudoaneurysm complicating mitral valve replacement in a 4-year-old child with acute bacterial endocarditis. A 4-year-old child with acute bacterial endocarditis required mitral valve replacement. A left ventricular pseudoaneurysm developed following surgery. The etiology and diagnosis of this complication are discussed. 
4	Effect of aortic sclerosis on bone mineral measurements by dual-photon absorptiometry. Measurements of the bone mineral content (BMC) of lumbar spine by dual-photon absorptiometry (DPA) are performed mainly in the anteroposterior (AP) projection. Due to superimposition of the abdominal aorta, the BMC measured for patients with aortic calcification usually is too high. To determine the influence of aortic calcifications, DPA scans were performed in the AP-projection on 100 dissected abdominal aortae with different degrees of atherosclerosis placed on a human lumbar spine cast in lucite. The measured values were compared with those obtained in the same projection without the aortae. The average increase of the BMC values relative to the mean for the vertebrae L2 to L4 for aortae with severe complicated lesions, i.e., those containing larger amounts of calcium, was 0.03 g/cm2, with a maximum deviation of 0.09 g/cm2. Aortae with fatty streaks or fibrous plaques did not cause significant increases of the BMC. The mean deviation for aortae with mild complicated lesions, i.e., those containing smaller amounts of calcium, was within the range of instrument precision. 
5	Persistence of monosodium urate crystals and low-grade inflammation in the synovial fluid of patients with untreated gout. Synovial fluid (SF) from 74 asymptomatic knees of patients with gout was analyzed. These patients had never been treated with serum uric acid-lowering agents. SF samples were analyzed for the presence of crystals and for cell counts, using undiluted SF directly in a Niebauer cell counting chamber. Thirty-seven of the aspirated knees had previously been inflamed, and monosodium urate (MSU) crystals were seen in SF aspirates from 36 of them (97%). Of the 37 knees that had never been inflamed, only 8 contained MSU crystals (P less than 0.00001). After reaching the joint, MSU crystals will persist in the SF as long as the serum uric acid level has not been lowered by appropriate treatment. In this situation, analysis of SF is an excellent diagnostic test for the intercritical gout. The mean cell count in the 44 SF samples that contained MSU crystals was 449/mm3 (95% confidence interval 310-589); the mean cell count in the 30 SF without MSU crystals was 64/mm3 (95% confidence interval 34-95) (P less than 0.00002). The SF samples that contained MSU crystals also had a higher percentage of polymorphonuclear leukocytes than those without MSU crystals (P less than 0.002). These data suggest that there is a low-grade inflammation present in the knees of patients with MSU crystals, the consequences of which should be investigated. 
5	Neuropsychological assessment of cognitive functioning in children with epilepsy. The variety of cognitive dysfunctions related to learning disabilities in children with epilepsy have been studied by linking electroencephalogram (EEG) and computerized neuropsychological testing. This showed that "subclinical" discharges impaired performance in 61% of the patients on a simple and a choice reaction time test, although some discharges lasted 1 s only. Neuropsychological investigation of subclinical EEG discharges may help to determine their adverse effect on learning. 
3	Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro. Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells. The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo. Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts. Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve. This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve. 
5	Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia. We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects. 
1	MY7 monoclonal antibody for diagnosis of cutaneous T-cell lymphoma. Infiltrate in cutaneous T-cell lymphomas (CTCLs) is composed mainly of CD4 helper cells with a phenotype very similar to that of benign cutaneous lymphoid infiltrate. MY7 (CD13) is a monoclonal antibody that is normally expressed on peripheral granulocytes and monocytes but also cross-reacts with an antigen expressed on epidermal basal cells. We studied MY7 expression on basal cells of the epidermis and CD4 cell infiltrate in 34 CTCLs, 11 pseudolymphomas, and 29 other benign cutaneous lesions. An indirect immunofluorescence technique with double labeling and an immunoperoxidase technique were used. We found that in benign inflammatory infiltrate, less than 10% of CD4 cells expressed MY7 antigen associated with normal MY7 monoclonal antibody labeling of basal cells, whereas in CTCLs more than 50% of CD4 tumoral cells in dermis expressed MY7 antigens; however, basal cells were MY7 negative. Thus, it is demonstrated that MY7 monoclonal antibody with its double modulation on epidermis (basal cells) and dermis (CD4 cells) has diagnostic value for differentiating CTCLs with CD4+ MY7+ tumor cells in dermis and MY7-negative basal cells from benign inflammatory lesions with CD4+ MY7- cells in dermis and MY7-positive basal cells. This modulation of MY7 labeling could be related to the secretion of epidermal cytokines. 
3	Miller-Fisher syndrome and pontine abnormalities on MRI: a case report. The authors report a patient with Miller-Fisher syndrome in whom MRI of the brain stem showed increased signal density on T2 sequence anterior to the fourth ventricle, on the right and the left. The authors discuss the relation between these MRI abnormalities and some clinical features of the syndrome. The authors believe that the cardinal features of Miller-Fisher syndrome are due to peripheral nervous system dysfunction, but that this does not preclude a possible central nervous system involvement. 
4	Selection of patients with acute myocardial infarction for thrombolytic therapy PURPOSE: To critically review the current recommendations regarding the eligibility of patients with myocardial infarction for thrombolytic therapy. DATA IDENTIFICATION: Relevant studies published from January 1980 to January 1990 were identified through a computerized search of the English-language literature using MEDLINE and by a manual search of the bibliographies of all identified articles. STUDY SELECTION: All randomized, controlled trials of intravenous thrombolysis in acute myocardial infarction and unstable angina were reviewed. Smaller, observational studies and previous review articles were included when relevant to the discussion. DATA EXTRACTION: Key data were extracted from each article, including the proportions of patients eligible for thrombolysis, the reasons for exclusion from thrombolytic therapy, and the clinical outcomes of patients treated and of those excluded from treatment. The validity of certain exclusion criteria was examined using subgroup analysis from the large, randomized mortality trials of intravenous thrombolysis and observations from smaller, nonrandomized studies. RESULTS OF DATA SYNTHESIS: To date, relatively few patients with myocardial infarction have been considered eligible for fibrinolytic therapy. In this group, both early and late mortality have been significantly reduced. Patients excluded from thrombolysis, however, continue to have a high early mortality. The data suggest that the potential benefits of this treatment might be extended to selected high-risk subgroups. In particular, the risk-benefit ratio may favor the inclusion of otherwise healthy elderly patients; certain patients presenting more than 6 hours after the onset of symptoms; and patients with a history of controlled systolic hypertension or brief, nontraumatic cardiopulmonary resuscitation. The data do not support the use of fibrinolytic therapy as primary treatment in patients with unstable angina or suspected myocardial infarction in the absence of confirmatory electrocardiographic changes. CONCLUSIONS: The full potential of thrombolytic therapy to alter the natural history of acute myocardial infarction can only be realized through the continued evaluation of selection criteria and the identification and treatment of the greatest possible number of eligible patients. 
3	Bone scans in the diagnosis of bone crisis in patients who have Gaucher disease [published erratum appears in J Bone Joint Surg [Am] 1991 Jun;73(5):791] Of thirty-four occurrences of bone pain in seventeen children and young adults who had type-I Gaucher disease, twenty-five were finally diagnosed as bone crises. On the basis of a bone scan with technetium-99m methylene diphosphonate, a correct diagnosis of bone crisis was made for twenty-three occurrences, with a sensitivity of 0.92. At the onset of a crisis, the bone scan typically showed decreased uptake of radionuclide at the involved site. After six weeks, a repeat bone scan of the long bones showed a ring of increased uptake surrounding an area of decreased uptake. At six months, the appearance of the bones on the radionuclide scan was normal. 
4	Long-term vascular access via the inferior vena cava. A prospective evaluation of long-term venous access catheters placed via the inferior vena cava was performed to determine their efficacy as well as short- and long-term morbidity. From June 1987 to May 1989, 31 catheters were placed in 26 patients, for a total of 3,503 catheter use days. All catheters were placed via an infraumbilical approach when the more conventional supraumbilical route was technically difficult, dangerous, or impossible to be used. There were a total of 14 complications in 12 episodes (one in every 701 catheter use days), six episodes of catheter occlusion or vessel thrombosis (one in every 583 catheter use days), one catheter malfunction, one episode of cuff erosion through the skin, and one catheter that migrated through the inferior vena cava into the retroperitoneum. These results compared favorably with our experience with long-term catheters of a similar type placed via a supraumbilical approach into the superior vena cava. We conclude that the infraumbilical route for long-term central venous access is safe and technically easy and should be strongly considered in patients in whom venous access via the supraumbilical approach will be technically difficult or have a high likelihood of failure. 
4	Balloon valvuloplasty for critical aortic stenosis in the newborn: influence of new catheter technology. Between 1986 and July 1990, balloon valvuloplasty was attempted in eight newborns (less than 28 days of age) with isolated critical aortic valve stenosis. Balloon valvuloplasty could not be successfully accomplished in any of the three infants presenting before 1989. Since March 1989, when improved catheter technology became available, all five neonates presenting with critical aortic stenosis were treated successfully by balloon valvuloplasty. A transumbilical approach was utilized in all four infants in whom umbilical artery access could be obtained. One newborn who was 25 days of age underwent transfemoral balloon valvuloplasty. Balloon valvuloplasty was immediately successful in all five newborns, as evidenced by a decrease in valve gradient and improvement in left ventricular function and cardiac output. Peak systolic gradient was reduced by 64% from 69 +/- 8 to 25 +/- 3 mm Hg (p = 0.005). Left ventricular systolic pressure decreased from 128 +/- 9 to 95 +/- 9 mm Hg (p = 0.02) and left ventricular end-diastolic pressure decreased from 20 +/- 2 to 11 +/- 1 mm Hg (p = 0.02). Moderate (2+) aortic regurgitation was documented in two infants after valvuloplasty. The time from first catheter insertion to valve dilation averaged 57 +/- 14 min (range 26 to 94) and the median length of the hospital stay was 4 days. With the use of recently available catheters, the transumbilical technique of balloon valvuloplasty can be performed quickly, safely and effectively in the newborn with critical aortic stenosis. It does not require general anesthesia, cardiopulmonary bypass or a left ventricular apical incision and it preserves the femoral arteries for future transcatheter intervention should significant aortic stenosis recur. 
4	Myocarditis simulating acute transmural myocardial infarction. A patient with cardiogenic shock had typical electrocardiographic findings of acute anterior transmural myocardial infarction. Cardiac catheterization revealed normal coronary arteries and severe biventricular failure. Postmortem examination confirmed normal coronary arteries; acute myocarditis, but no evidence for infarction, was found. Electrocardiographic changes of myocarditis may be indistinguishable from acute transmural infarction. In suspected cases, cardiac catheterization should be considered prior to thrombolytic therapy. 
5	Paraplegia after a routine lumbar laminectomy: report of a rare complication and successful management. Arachnoid cysts of the spinal canal are relatively common lesions that may be either intra- or extradural. These cysts are usually asymptomatic but may produce symptoms by compressing the spinal cord or nerve roots. We report a case in which an intradural thoracic arachnoid cyst became symptomatic after a routine decompressive lumbar laminectomy for spinal stenosis. Myelography revealed no abnormality, although magnetic resonance imaging and computed tomography after myelography demonstrated a mass within the posterior aspect of the thoracic spinal canal associated with anterior displacement and compression of the spinal cord. A change in the flow dynamics of the cerebrospinal fluid probably allowed the development of spinal cord compression due to one of the following: expansion of the cyst, decreased cerebrospinal fluid buffer between the cord and the cyst, or epidural venous engorgement. A concomitant and more cephalad lesion such as an arachnoid cyst should be considered when myelopathic complications arise after lumbar surgery. Magnetic resonance imaging and computed tomography after myelography are useful to demonstrate the additional pathological processes. 
4	Supravalvar aortic stenosis: a complication of aortic valve surgery. After a patient had aortic valvotomy and aortotomy for the relief of valvar aortic stenosis supravalvar stenosis developed over the next six years. 
5	The distribution of muscle weakness in upper motoneuron lesions affecting the lower limb. To determine the distribution of weakness in the lower limb after upper motoneuron lesions the strength of 8 muscle groups was measured. Four groups of patients were studied: 22 control subjects, 16 patients with unilateral leg paresis, 4 patients with severe unilateral paralysis and 5 patients with paraparesis. In the testing posture (seated), patients with cerebral upper motoneuron lesions showed no selective loss of power in flexors or extensors on the contralateral side. Gravitational torques were included in the measurements. However, proximal muscles (acting at hip and knee) were significantly less severely affected than more distal muscles (acting at ankle and hallux). At any particular joint, physiological flexors and extensors were affected equally in both the hemiparetic and paraparetic subjects. As in the upper limb (Colebatch and Gandevia, 1989), the strength of muscles on the clinically unaffected side was reduced compared with control subjects, although no muscle groups were especially affected. 
5	A longitudinal study of respiratory symptoms in a community population sample. Correlations with smoking, allergen skin-test reactivity, and serum IgE Chronic cough and/or phlegm, wheeze in the absence of colds, and rhinitis attributed to allergies are three of the most common respiratory symptoms encountered in community populations. In this study, we have determined the prevalence of these complaints in a random population sample (n = 1,109) using standardized questionnaires at two points in time, eight years apart. Cross-sectional prevalence and changes in symptom occurrence have been correlated with smoking status, allergen skin test reactivity, and total serum IgE levels. Our objective was to determine the individual and combined influence of these three variables on symptom prevalence. Initially, 19.2 percent of the population admitted to wheeze, 17.9 percent to cough, and 44.1 percent to allergic rhinitis. Cough and wheeze prevalence changed little over the eight-year period, while rhinitis increased 11 percent by the second survey. The occurrence of chronic cough was strongly correlated with smoking, and was not further influenced by either allergen skin reactivity or IgE level. Conversely, rhinitis prevalence was related to skin test reactivity with no additional association with smoking or IgE level. The occurrence of wheeze in the absence of colds was associated with both smoking and allergen skin reactivity. Among smokers, the prevalence was over 30 percent and was similar in both skin test positive (STP) and skin test negative (STN) individuals. However, on both surveys, STP ex-smokers and nonsmokers had significantly more wheeze than those who were STN. While the prevalence of wheeze in STN nonsmokers was low (6.8 percent), an IgE-wheeze relationship was also suggested on the second survey. In addition to these cross-sectional symptom relationships, changes in either smoking status or allergen skin reactivity during the study period were associated with changes in the prevalence of each symptom. 
4	The health belief model: predicting compliance and dropout in cardiac rehabilitation. We investigated the health belief model and the health locus of control constructs as predictors of group membership (compliers or dropouts) with cardiac rehabilitation and whether they added predictive utility to routinely assessed patient demographics and health behaviors. Questionnaires were completed on entry into the study by 120 patients with coronary artery disease, and by the end of the 6 month program there were 58 compliers and 62 dropouts. Discriminant function analyses were carried out to determine prediction of group membership. The health belief model predicted group membership 64.6% of the time, explaining 5.2% of the variance. Demographics, health behaviors, and health belief model factors accounted for 21.1% of the variance between compliers and total dropouts with group membership correctly predicted 74.4% of the time; avoidable and unavoidable dropout was correctly predicted 84.2% of the time with 56.9% of the variance explained. Health locus of control did not distinguish between compliers and dropouts. The addition of the health belief model provided additional information about compliance with cardiac rehabilitation beyond that explained by demographic and health behavior variables alone, particularly when predicting avoidable/unavoidable dropout. 
5	Electrophysiologic characteristics of manifest and latent retrograde conduction in dogs. Atrioventricular (AV) nodal reentry requires intact retrograde ventriculoatrial (VA) conduction. The purpose of this study was to assess the contribution of various pacing and pharmacologic techniques to uncover VA conduction during apparent unidirectional VA block, and to evaluate the role of several biologic and electrophysiologic factors in concealment of retrograde conduction. Forty healthy dogs underwent catheter-electrophysiologic studies of AV and VA conduction. Group I (20 animals) had intact VA conduction. Group II (six animals) had VA dissociation with ventricular pacing initiated during sinus rhythm, but the presence of VA conduction was confirmed by isoproterenol infusion or by premature ventricular stimulation. In group III (14 animals), the above techniques failed to uncover VA conduction. Eight of 14 group III animals underwent thoracotomy and crushing or freezing of the sinoatrial (SA) node. Ventricular pacing initiated during sinus standstill was associated with 1:1 VA conduction in each experiment. VA conduction time and retrograde Wenckebach cycle length, both in the baseline state and during isoproterenol infusion, were significantly longer in the eight animals in group III than in those in group I. Age, gender, weight, breed, sinus cycle length, and anterograde AV conduction properties were not significantly different between groups I, II, and III. The data suggest that (1) in normal dogs, complete unidirectional VA block probably does not exist; (2) in the presence of anterograde input to the AV node, even sophisticated pacing and pharmacologic maneuvers may fail to uncover the presence of VA conduction; (3) although anterograde input is essential for concealment of VA conduction, the phenomenon is more closely associated with depressed retrograde than with anterograde AV nodal characteristics. 
2	The role of a critical care unit in an epidemic. The role of a critical care unit in life-threatening situations is well established. The management of 52 children with acute gastroenteritis and 22 children with acute paralytic poliomyelitis as part of recent epidemics is described. The solutions to the problems in the critical care management of these 74 victims (out of a total of 6197 patients admitted during the epidemics) are discussed. 
5	Ibuprofen prevents deterioration in static transpulmonary compliance and transalveolar protein flux in septic porcine acute lung injury. The effects of intravenous ibuprofen on measurements of pulmonary function and alveolar capillary membrane permeability to protein in sepsis-induced porcine acute lung injury (ALI) were studied. Young swine (15-25 kg) were anesthetized, cannulated, and ventilated (5 cm H2O PEEP, 0.5 FIO2, and 15 cc/kg tidal volume). Three groups were studied: septic animals (Ps, n = 10) received Pseudomonas aeruginosa for 1 hr IV, controls (C, n = 9) received 0.9% NaCl, and ibuprofen-treated septic animals (Ps + Ibu, n = 7) received ibuprofen 12.5 mg/kg at 0 and 120 min post Ps. Systemic (SAP) and pulmonary (PAP) arterial pressures, PaO2, cardiac index (CI), static lung compliance (CL), EVLW (thermal cardiogreen), and peripheral white blood cell counts (WBC) were measured. Bronchoalveolar lavage (BAL) was performed for protein and % neutrophil (%PMN) content. Results: Ps produced significant (p less than 0.05) decreases in CL, PaO2, SAP, CI, and peripheral WBC and increases in PAP, EVLW, BAL protein, and %PMN's vs. controls. Ibu prevented the early increase in PAP and attenuated the late increase in PAP and EVLW. Ibu also maintained PaO2, CL, BAL protein, and %PMN's in BAL at control levels, but exhibited no significant effect on peripheral leukopenia. These data strongly suggest that ibuprofen administered before and at 120 min after onset of Pseudomonas infusion improves lung compliance and affects neutrophil function sufficiently to significantly ameliorate many of the physiologic derangements in acute sepsis. 
5	Approach to men with urethritis and urologic complications of sexually transmitted diseases. The most important causes of urethritis, and epididymitis in younger men, are C. trachomatis and N. gonorrhoeae. Management of these syndromes requires a thorough sexual history, genital examination, evaluation for objective and laboratory evidence of infection, antimicrobial therapy directed toward the major etiologies, and evaluation and treatment of sexual partners. Treatment of N. gonorrhoeae requires use of a single-dose regimen active against this organism, plus a 7- to 10-day tetracycline regime active against C. trachomatis and nongonococcal urethritis. With recommended regimens, microbiologic failure is infrequent in compliant patients. Recurrent urethritis is frequent, however. The management of patients with persistent or recurrent symptoms requires careful reevaluation of the patient, documentation of urethritis, and re-treatment with antimicrobials if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leukocytes in urethral secretions. Additional treatment beyond this point usually is not indicated, even though a proportion of men will remain symptomatic and some of these will have increased numbers of polymorphonuclear leukocytes in urethral secretions. The most important causes of prostatitis, and epididymitis in older men or men with urethral structural abnormalities, are classical urinary tract pathogens rather than sexually transmitted pathogens. Management of these infections includes documentation of the infection and treatment directed toward the specific pathogen. Men with symptoms of "prostatitis" must be evaluated using both urine and prostatic secretions to document infection and inflammation. The majority of men with such symptoms do not have an infection that can be documented. These men respond poorly to medications. Men with documented chronic bacterial prostatitis require long courses of antimicrobials to effect cure. In some cases, however, the disease is intractable, and chronic suppression with antimicrobials may be necessary. 
4	Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia. The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01). 
4	The role of preoperative radionuclide ventriculography in defining outcome after revascularization of the extremity. Revascularization of the extremity was performed upon 110 patients after preoperative radionuclide ventriculography (RNVG). Mean ejection fraction (EF) was 50 +/- 13 per cent. Ventricular wall motion abnormalities were present in 46 per cent. Revascularization included inflow procedures, such as aortofemoral (n = 25) or extraanatomic bypass (axillofemoral or femorofemoral, n = 11); infrainguinal reconstruction, including femoropopliteal or distal bypass (n = 43), and other procedures to improve perfusion of the limb or correct complications after previous vascular reconstruction upon the extremity (n = 31). Perioperative (30 days) mortality rate was 0.9 per cent and 97.0 per cent of the patients were discharged alive from the hospital. Myocardial infarction (MI) occurred in 3.6 per cent, new ventricular arrhythmia in 1.8 per cent and congestive heart failure in 6.4 per cent of the patients during the perioperative period. During follow-up study (607 +/- 363 days), 7.3 per cent required major amputation, ipsilateral to reconstruction, 5.5 per cent required surgical or angiographic revision for hemodynamic failure of the reconstruction prior to thrombosis and 12.7 per cent thrombosed part or all of the reconstruction. Revascularization failure did not appear to be related to the level of cardiac function. Those with normal (greater than 50 per cent) EF had greater over-all survival by life table analysis than those with EF less than or equal to 50 per cent (p = 0.0006, Mantel-Cox test). Ventricular wall motion abnormalities were associated with reduced over-all survival (p = 0.008, Mantel-Cox test). The presence of angina or previous MI, singularly or in combination, did not have an adverse effect on over-all survival, whereas diabetes (p = 0.0058, Mantel-Cox test) and cigarette smoking (p = 0.0137, Breslow test) were associated with significantly diminished over-all survival. Preoperative RNVG can identify subgroups at a survival disadvantage after revascularization of the extremity in a population in which the presence of angina or previous MI does not predict survival. 
1	Cancer surveillance in ulcerative colitis. During a 13-year period, 213 patients with ulcerative colitis who had no clinical or endoscopic evidence of colonic carcinoma were enrolled in a biopsy surveillance program for dysplasia and carcinoma. The aims of the study were to determine whether such a program could decrease the cancer risk in this group of patients, to determine whether patients with a low risk of carcinoma could be identified, thus enabling them to retain their colon, and to accomplish these goals with a reasonable expenditure of resources. Eighteen patients had dysplasia detected in the initial biopsy specimens; 15 of these patients underwent colectomy, and 7 had unsuspected carcinoma (1 Dukes' stage A, 2 stage B, and 4 stage C). Eleven patients had dysplasia detected during follow-up; 7 of these patients had colectomy, and only 1 patient had carcinoma (Dukes' B). Dysplasia developed in 5 of 20 patients with indefinite changes on initial biopsy samples; 3 of these patients underwent colectomy, and 1 patient had carcinoma (Dukes' B). There was no difference in the prevalence of dysplasia between patients with left-sided disease and patients with extensive disease. With the exception of 2 patients with inadequate surveillance, there has been no clinical evidence of carcinoma in any of the 148 patients whose biopsy results remained negative throughout the study; carcinoma has not developed in any of 175 patients without dysplasia on initial biopsy sample. All 4 patients who died of carcinoma had high-grade dysplasia in their initial colonoscopic biopsy samples. It is concluded that a biopsy surveillance program can be an effective aid in helping control the risk of carcinoma in patients with long-standing ulcerative colitis, that the short-term risk of carcinoma for patients with negative biopsy results is low and colectomy for risk of carcinoma can be deferred in this group, and that patients with extensive and left-sided disease share the same risk of the development of dysplasia. 
1	Polycystic ovary syndrome and bulimia. One hundred fifty-three patients classified as suffering from polycystic ovarian syndrome (PCOS) and 109 patients who were suffering from a clear organic disorder or endocrinopathy received the bulimia investigation test (Edinburgh) (BITE) questionnaire for abnormal eating behaviors. Patients with PCOS showed a significant increase in their mean BITE score for approximately a third had abnormal eating patterns, and 6% have scores suggestive of clinical bulimia compared with only 1% of women in the group with organic endocrinopathies. The work suggests that women with PCOS should be screened for abnormal eating behaviors and raises the possibility that treatment by psychological means should be considered when abnormal eating behaviors are present. 
4	Effects of supplemental oxygen administration in an infant with pulmonary artery hypertension. In patients with pulmonary disease, pulmonary artery hypertension often occurs as a result of pulmonary artery vasoconstriction, primarily from hypoxia and alveolar hypotension. In this report we describe the hemodynamic effects of breathing supplemental oxygen in a child with bronchopulmonary dysplasia and pulmonary artery hypertension. These hemodynamic effects include an improvement in oxygenation, an increase in systemic vascular resistance, and a decrease in the pulmonary vascular resistance. As a direct result of these changes in vascular resistances, alterations of heart rate, cardiac index, stroke volume, aortic pressure, oxygen consumption, and pulmonary artery pressure have been shown to occur. Oxygen is widely used to treat many physiologic conditions. However, during the administration of supplemental oxygen, rarely do we recognize the hemodynamic changes associated with its use. These hemodynamic effects must be clearly understood and appreciated before oxygen administration in any clinical situation. 
5	RAR-alpha gene rearrangements as a genetic marker for diagnosis and monitoring in acute promyelocytic leukemia. Acute promyelocytic leukemias (APLs) are characterized by a translocation that involves chromosomes 15 and 17. The translocation breakpoints have recently been identified and shown to involve the RAR-alpha gene on 17 and myl on 15. Here we report Southern blotting analysis of 26 APLs, including cases with normal karyotypes and atypical morphology, which showed RAR-alpha rearrangements in 92% cases, myl rearrangements in 73%, and either RAR-alpha or myl rearrangements in 100%. Despite a negative clinical and morphologic picture, DNA rearrangement analysis showed that neoplastic promyelocytes persisted in the bone marrow of two patients sampled after induction chemotherapy. Therefore, the RAR-alpha and myl rearrangements provide molecular markers for accurately diagnosing APLs and monitoring the course of the disease during and after chemotherapy. 
4	Role of hemodynamics and vagus nerves in development of fibrin-induced pulmonary edema. The rapid development of pulmonary edema that may occur in the rabbit after the intracisternal injection of a mixture of fibrinogen and thrombin has classically been considered to result from a vagally mediated increase in vascular permeability (G. R. Cameron and S. N. De, J. Pathol. Bacteriol 61: 375, 1949) and to not be dependent on hemodynamic mechanisms. We tested this hypothesis by evaluating the relationship between the degree of pulmonary hypertension and postmortem extravascular lung water content (EVLW) in both nonvagotomized (n = 10) and vagotomized (n = 7) rabbits administered thrombin (0.1 ml, 500 U/ml) and fibrinogen (1 ml, 27 mg/ml) intracisternally. No increase in EVLW was observed in either group unless pulmonary arterial pressure (Ppa) exceeded 25 Torr, and large increases in EVLW were only observed at higher Ppa's. These results thus indicate that some degree of pulmonary hypertension is required for the development of this form of edema. Because the vascular pressure required to produce edema in this model approaches that required to increase pulmonary vascular permeability in the rabbit, a pressure-dependent increase in permeability may be a common characteristic of neurogenic pulmonary edema in this species. Vagotomy had no protective effect but instead appeared to increase the amount of edema development for a given degree of pulmonary hypertension. 
2	Complications of stapled anastomoses in anterior resection for rectal carcinoma: colorectal anastomosis versus coloanal anastomosis. Postoperative results of 48 patients who underwent anterior resection using the EEA-stapler were evaluated. In all but 2 cases the indication for surgery was colorectal carcinoma. In 24 patients an anastomosis was created above the 5 cm level (above the anal verge: colorectal anastomosis) and in 24 at the 0-5 cm level (coloanal anastomosis). There was no perioperative mortality. The only complication observed in the colorectal anastomosis group was one case of late anastomotic stenosis. In the coloanal anastomosis group there were 4 cases with early anastomosis leaks, 3 cases with late stenosis and 5 cases with various degrees of late fecal incontinence, ultimately resulting in a permanent diverting stoma in 5 (10.4%) patients. We conclude that for rectal tumors the EEA-stapled anterior resection provides excellent functional results in most cases. Stapled coloanal anastomoses more often demonstrate various (early and late) complications. Nevertheless in spite of chronic discomfort, many patients still prefer their complaints to a permanent stoma. 
2	Modulatory action of adenosine on gastric function and ethanol-induced mucosal damage in rats. This study examines the gastric effects of adenosine and its antagonist, theophylline, on secretory function, mucosal blood flow, and on ethanol-induced glandular mucosal damage in rats that were fasted for 24 hr before experimentation. The animals were anesthetized with sodium pentobarbitone (50 mg/kg intraperitoneal) and their tracheae cannulated. An ex vivo stomach chamber then was prepared. The luminal bathing solution was collected every 15 min and the concentrations of H+ and Na+ were determined by a pH autotitrator and an ionmeter, respectively. The glandular mucosal blood flow was measured by a laser Doppler flowmeter and the severity of lesions was determined by measuring the hemorrhagic areas. Adenosine administration (2.5 or 7.5 mg/kg, subcutaneous) markedly lowered the H+ and Na+ output but increased the secretory volume and mucosal blood flow in a dose-dependent manner. The same doses of the nucleoside also prevented ethanol-induced mucosal damage. These effects were prevented by pretreatment with theophylline (30 or 60 mg/kg, subcutaneous). Ethanol given alone significantly depressed the H+ and Na+ secretion. Both effects were not modified by adenosine treatment. However, the depressive action of ethanol on mucosal blood flow was prevented by adenosine. These findings indicate that adenosine modulates the physiological function of the stomach. It also directly activates the defensive mechanism of the stomach, which is partially mediated by the improvement of the gastric mucosal blood flow and an increase in the nonacid component of gastric secretion. 
1	Cervical lymph nodes from an unknown primary tumor in 190 patients. Over 10 years, 475 patients with isolated lateral neck masses were evaluated: 190 with lymph nodes from an unknown primary tumor (LNUP), 188 with neck lymphomas, 78 with benign tumors, 10 with sarcomas, and 9 with chemodectomas. This study focused on the patients with LNUP. Only 86 patients were treated with surgery (plus radiotherapy). Other patients were treated with radiotherapy (84) or chemotherapy (13) or had no treatment (7). For the overall population, failures in the neck occurred in 51% of the patients and distant metastases in 27%, while primary tumors appeared in 16%. Survival rates at 3, 5, and 10 years were 27%, 19%, and 7%, respectively, for the overall population and 45%, 35%, and 19%, respectively, for the surgical group. The diagnosis and therapeutic approach had a direct effect on neck control; failure in the neck occurred in 7 of 47 patients (15%) when fine needle aspiration and radical neck dissection with radiotherapy were performed, in 5 of 12 patients (42%) when fine needle aspiration and modified neck dissection with radiotherapy were used, in 5 of 12 patients (42%) when adenectomy diagnosis and radiotherapy treatment were performed, and in 6 of 11 patients (54%) when diagnosis by incisional biopsy was performed prior to admission, despite subsequent radical neck dissection and radiotherapy treatment. In our opinion, panendoscopy and fine needle aspiration should be the first-line diagnostic approach. When cytologic diagnosis proves impossible, the second-line approach must consist of cervical exploration with frozen section examination and excisional biopsy, followed by immediate appropriate treatment. In cases of LNUP, radical neck dissection seems to be preferable. 
5	Long-term follow-up of the ileoanal anastomosis in children and young adults. The purpose of this study was to carry out a long-term study of the ileoanal anastomosis (IAA) in children and young adults, comparing the straight IAA to the J pouch. One hundred twenty-one young people who had undergone IAA were studied, with 114 available for long-term follow-up. One hundred one were 18 years and under. Forty-nine patients had a straight IAA and 72 had a J-pouch reservoir. There were no deaths. After surgery, three children had intraabdominal sepsis and one had pelvic sepsis, but it did not lead to excision of the IAA. The mean stool frequency in all 114 patients was 5.0 +/- 2.5 per day and 1.2 +/- 1.1 at night. The mean number of stools for the straight IAA was 6 per day and 2.1 at night. The mean number of stools for the straight IAA with balloon dilations was 5.8 per day and 1.2 at night, and for the J pouch it was 4 per day and 1 at night. Patients with both the J pouch and straight IAA had good to excellent sensation, with patients with the J pouch always able to distinguish flatus from stool in 87% of patients and almost always in 13%. Daytime continence was very good in both groups. Moderate nighttime loss of stool occurred in 10 patients, 6 with a straight IAA and 4 with a J pouch. Ninety-five percent of the 114 patients were satisfied or very satisfied, with most children with a J pouch very satisfied. The J pouch remains the procedure of choice in young people. 
2	Clinical management of the complications of HIV infection. Patients with advancing HIV infection are subject to a broad range of complications that may challenge the primary care physician. The presence of more than one complication at a time is common. Selected, common complications are discussed, including a discussion of the approach to diagnosis and management. Areas covered include pulmonary, gastrointestinal, ocular, and mucocutaneous complications, as well as lymphadenopathy, the HIV wasting syndrome, and Kaposi's sarcoma. 
1	The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver. The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver. 
5	Capsular genu syndrome. We report 5 patients with unilateral infarct and 1 with hemorrhage limited to the genu of the internal capsule. The most prominent finding was contralateral facial and lingual hemiparesis with dysarthria. Three patients also showed unilateral mastication-palatal-pharyngeal weakness, and 1 had unilateral vocal cord paresis. Mild limb involvement was limited to hand weakness in 4 patients. Our findings suggest that the majority of motor corticopontine and corticocobulbar fibers are located in the genu of the internal capsule. The faciolingual syndrome and its variants are highly suggestive of capsular genu stroke. 
2	The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver. The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver. 
4	Hypertension after operative correction of club-foot deformity. Severe hypertension occurred as a postoperative complication after correction of a club-foot deformity in four children (seven feet) who were between the ages of two and three years and had no history of hypertension. The hypertension subsided slowly after administration of antihypertensive medications or more rapidly after release of the correction that had been obtained operatively. 
4	Carotid endarterectomy for elderly patients: predicting complications OBJECTIVE: To determine whether the complication or death rate from carotid endarterectomy can be predicted from hospital and physician structural variables, such as the hospital's teaching status or the number of endarterectomies done by the surgeon per year. DESIGN: Survey of medical records. After controlling for the severity of the patient's condition on the basis of data in the medical record at the time of the endarterectomy, regression analyses were used to predict the postoperative stroke, heart attack, and 30-day death rate as a function of patient, physician, and hospital characteristics. SETTING: Three geographic areas (states or large parts of states; average population, 3 million) in the United States. PATIENTS: Random sample of 1302 patients 65 years of age or older having carotid endarterectomy in 1981. INTERVENTION: Carotid endarterectomy. MEASUREMENTS AND MAIN RESULTS: Of 1302 patients, 11.3% had a postoperative stroke or heart attack or died within 30 days of the operation. Patient age, race, income, and gender; physician volume, board certification status, and age; and hospital size, for-profit status, ownership, and teaching status were not significantly related to the postoperative complication or death rate. If the surgeon was a graduate of a foreign, but not a Western European or Canadian, medical school, however, the average complication or death rate rose from 10.4% to 19.6% (P less than 0.05). CONCLUSIONS: The effectiveness of carotid endarterectomy depends heavily on its complication rate. Because complications after surgery cannot, in general, be predicted from structural variables, referring physicians cannot rely solely on the surgeon's experience and qualifications when recommending a carotid endarterectomy. The surgeon's and the hospital's actual postoperative complication and death rate should be considered. 
5	Incidence and clinical significance of ST segment elevation after electrical cardioversion of atrial fibrillation and atrial flutter. To study the incidence and clinical significance of postshock ST segment elevations, we recorded 12-lead ECGs immediately after transthoracic direct-current electrical cardioversion in 146 patients with atrial fibrillation or flutter. Among 23 patients (19%), acute ST segment elevations amounted to 1.4 +/- 0.8 mV (mean +/- SD) and occurred after 243 +/- 114 joules (cumulative dose) in the precordial leads only in 14, concomitantly in precordial and inferior leads in two, and in the precordial and anterolateral leads in seven. They normalized within 1.5 +/- 0.8 minutes. Occurrence of ST segment elevation was related to previous pericardiotomy (p less than 0.00001) and age (p = 0.01). Estimation of myocardial enzyme release did not show evidence of myocardial damage. Patients with ST segment elevations had a lower conversion rate (48% versus 76%, p = 0.005). Long-term maintenance of sinus rhythm was also diminished (35% versus 59%, p = 0.03). Results of this study show that postcardioversion ST segment elevation occurs predominantly in postpericardiotomy patients and may be associated with an unfavorable arrhythmia prognosis. 
3	Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy. We examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci. Forty patients were studied prospectively. Spikes were assessed for rates, field, and appearance of new foci. Final localization was determined by surgery, electrocorticography, and seizure onset. Comparison of interictal EEG foci with final localization was made. In 39 patients, slow-wave sleep activated spiking compared with wakefulness. Most patients showed maximal spiking in sleep stages 3 or 4. Restriction of field in rapid eye movement (REM) sleep and wakefulness, and extension of field in slow-wave sleep occurred. New foci appeared in non-rapid eye movement sleep in 53% of patients. Similar but not identical spiking rates, foci, and field distributions were seen in wakefulness and REM sleep. All REM foci were unilateral. Our findings suggest that localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep. 
2	Endoscopic management of chronic organoaxial volvulus of the stomach. Endoscopic correction of the chronic organoaxial volvulus of the stomach was attempted in seven cases of primary and three cases of secondary volvulus. Endoscopic correction was successful in six cases of primary volvulus and one case of volvulus secondary to duodenal carcinoma. This paper describes the details of the technique of endoscopic correction of gastric volvulus, and documentation of correction of the volvulus by barium meal study with a follow-up of 5-26 months. 
5	The prognosis of contact dermatitis. This article reviews the prognosis of contact dermatitis, particularly of occupational contact dermatitis. Most studies document a poor prognosis for occupational and nonoccupational contact dermatitis. The prognoses of occupational and nonoccupational contact dermatitis, irritant contact dermatitis, and allergic contact dermatitis are similar. Only a minority of studies on the prognosis of occupational contact dermatitis have found that a job change by the affected worker leads to clearing of the dermatitis. Dermatologic and nondermatologic factors associated with a poor prognosis are discussed. 
2	Congenital chyloperitoneum as a cause of isolated fetal ascites. Isolated fetal ascites is an unusual prenatal finding and must be differentiated from immune and nonimmune hydrops. This entity is most commonly associated with gastrointestinal and genitourinary anomalies. Fetal chyloperitoneum, however, should be considered as a possible cause. Pulmonary hypoplasia and abdominal dystocia during attempted vaginal delivery are potential complications. We present a case of isolated fetal ascites due to congenital chyloperitoneum. 
3	Pathomechanism, pathogenesis, and results of treatment in cervical spondylotic myelopathy caused by dynamic canal stenosis. In this study, the pathomechanism and pathogenesis of dynamic canal stenosis caused by cervical instability in patients with cervical spondylotic myelopathy and the validity of the concept of instability are clarified by analyzing the results of treatment in 53 cases. In cases of cervical spondylotic myelopathy caused by dynamic canal stenosis, the authors found that the posterior slide of the vertebral body occurs as a result of degeneration in the cervical spine due to aging changes, and that the dynamic sagittal diameter of the spinal canal decreases with an increase of the degree of posterior slide. This is followed by gradual aggravation of the clinical symptoms. Continuous cervical traction was found to be the first choice of treatment. Surgical treatment is indicated in cases in which the traction was ineffective, or even when it was effective, in cases in which the Japanese Orthopaedic Association (JOA) score remained low or when there was a tendency toward rapid aggravation of symptoms. It was demonstrated that the shorter the duration of the myelopathy, the better the results of treatment obtained. A limit of the dynamic sagittal diameter of the spinal canal of 12 mm was considered as valid. 
2	Percutaneous fine-needle aspiration cytologic study of main pancreatic duct stenosis under pancreatographic guidance. When pancreatography shows a stenosis of the main pancreatic duct in patients with normal or inconclusive ultrasound and computed tomography, the exact nature of such stenosis is sometimes difficult to precise before surgical exploration. In such cases, the authors systematically performed a percutaneous fine-needle aspiration cytologic study of the stenosis under pancreatographic guidance. Fifteen patients were referred because of suspected pancreatic malignancy. The tumor markers, carcinoembryonic antigen (CEA) and CA 19-9 were normal in 11 patients and elevated in one patient, whereas only CA 19-9 was elevated in three others. In 14 cases, both the ultrasound and computed tomography did not show any obvious pancreatic mass. The pancreatography was done through endoscopic retrograde cholangiopancreatography (ERCP) (12 patients) or percutaneously in case of failure at ERCP3 and showed a main pancreatic duct stenosis that underwent aspiration by percutaneous fine needle precisely positioned using biplane fluoroscopy. The aspirated material was then smeared on glass slides, air-dried, and stained by Giemsa. In nine of the 15 patients, cytologic study revealed adenocarcinoma. This was confirmed by surgery in five and by progressive deterioration followed by death in four. In six patients, cytologic study gave a nonmalignant result. Chronic pancreatitis was found in five of them, confirmed at surgery in three and based on uneventful follow-up of at least 12 months in two others. In one case, a pancreatic adenocarcinoma not detected by cytologic study was found at surgery. Thus, the sensitivity and specificity of this diagnostic approach were 90% and 100%, respectively. No serious complication was noticed. The authors conclude that when ultrasound and computed tomography are inconclusive, percutaneous fine-needle aspiration cytologic study of main pancreatic duct stenosis under pancreatographic guidance is a safe, simple, and helpful procedure in the investigation of patients with suspected pancreatic malignancy. 
1	Lesions that manifest as medial cheek and nasolabial fold masses. Seventeen cases were collected in which the patient presented with a medial cheek or nasolabial fold mass. Most of these lesions were uncommon, and some were rare. The most reliable differentiating finding was the type of associated bone involvement. The malignancies had bone erosion and as a group could be distinguished from the other masses. Computed tomographic attenuation and magnetic resonance imaging signal intensities were nonspecific and did not allow a definitive diagnosis to be made. The types of pathologic conditions and their sectional imaging findings are reviewed. 
4	Intracoronary adenosine administration during reperfusion following 3 hours of ischemia: effects on infarct size, ventricular function, and regional myocardial blood flow. Previous studies have demonstrated that adenosine significantly enhances myocardial salvage after 90 minutes of regional ischemia. To determine its effect after prolonged ischemia, closed-chest dogs underwent 3 hours of left anterior descending artery occlusion followed by 72 hours of reperfusion. Intracoronary adenosine (3.75 mg/min; at 1.5 ml/min:total volume = 90 ml; n = 10) or an equivalent volume of saline (1.5 ml/min: total volume = 90 ml; n = 9) was infused into the left main coronary artery during the first 60 minutes of reperfusion. Regional myocardial blood flow was assessed serially with microspheres and regional ventricular function was assessed by contrast ventriculography. Infarct size was determined histologically. Light and electron microscopy were utilized to assess neutrophil infiltration and microvascular injury. Adenosine failed to reduce infarct size expressed as a percentage of the area at risk (38.0 +/- 4.9% versus 34.8 +/- 4.6%; p = NS) or to improve regional ventricular function as measured by the radial shortening method (3.2 +/- 1.8% versus 2.2 +/- 3.1%; p = NS) at 72 hours after reperfusion. Vasodilatory effects were not observed in the endo- and midmyocardial regions of the ischemic zone during adenosine administration. This was associated with a similar extent of capillary endothelial changes and neutrophil infiltration in both adenosine-treated and saline control groups. These results suggest that severe functional abnormalities are present in the vasculature after 3 hours of ischemia and that adenosine therapy is ineffective in enhancing myocardial salvage. 
3	Early gastric cancer. Twenty-eight-year experience. A retrospective study of early gastric cancer (60 patients) was performed to evaluate its diagnosis and treatment. Ninety-five per cent of patients presented with nonspecific gastrointestinal symptoms and 53.3% had been treated for presumed benign disease for up to 48 months before diagnosis. Fiberoptic endoscopy detected these lesions more accurately than radiologic examination. The disease-free 5-year survival rate after resection was 76.4%. Survival showed no significant correlation with sex, tumor site, macroscopic appearance, extent of gastric resection, or histopathologic type. Tumors larger than 1.5 cm in diameter, invasion of submucosa, or lymph node metastasis resulted in significantly lower survival rates. Three of eight patients with nodal metastasis survived 5 or more years, including one who had second-echelon deposits. A high index of suspicion may permit more frequent detection. Extended lymphadenectomy (R2) is recommended to achieve the highest possible cure rate. 
5	A model to predict multivessel coronary artery disease from the exercise thallium-201 stress test. PURPOSE: The aim of this study was to (1) determine whether nonimaging variables add to the diagnostic information available from exercise thallium-201 images for the detection of multivessel coronary artery disease; and (2) to develop a model based on the exercise thallium-201 stress test to predict the presence of multivessel disease. PATIENTS AND METHODS: The study populations included 383 patients referred to the University of Virginia and 325 patients referred to the Massachusetts General Hospital for evaluation of chest pain. All patients underwent both cardiac catheterization and exercise thallium-201 stress testing between 1978 and 1981. RESULTS: In the University of Virginia cohort, at each level of thallium-201 abnormality (no defects, one defect, more than one defect), ST depression and patient age added significantly in the detection of multivessel disease. Logistic regression analysis using data from these patients identified three independent predictors of multivessel disease: initial thallium-201 defects, ST depression, and age. A model was developed to predict multivessel disease based on these variables. As might be expected, the risk of multivessel disease predicted by the model was similar to that actually observed in the University of Virginia population. More importantly, however, the model was accurate in predicting the occurrence of multivessel disease in the unrelated population studied at the Massachusetts General Hospital. CONCLUSION: It is, therefore, concluded that (1) nonimaging variables (age and exercise-induced ST depression) add independent information to thallium-201 imaging data in the detection of multivessel disease; and (2) a model has been developed based on the exercise thallium-201 stress test that can accurately predict the probability of multivessel disease in other populations. 
4	Intraoperative blood pressure. What patterns identify patients at risk for postoperative complications? While monitoring blood pressure is a routine part of intraoperative management, several methods have been proposed to characterize intraoperative hemodynamic patterns as predictors of postoperative complications. In this prospective study of a high-risk population of hypertensive and diabetic patients undergoing elective noncardiac surgery, one objective was to compare different approaches to the assessment of intraoperative hemodynamic patterns to identify those patterns most likely to be associated with postoperative complications. Twenty-one per cent of the 254 patients sustained cardiac or renal complications after operation. Patients with more than 1 hour of greater than or equal to 20-mmHg decreases in mean arterial pressure (MAP) or patients with less than 1 hour of greater than or equal to 20-mmHg decreases and more than 15 minutes of greater than or equal to 20-mmHg increases were at highest risk for postoperative complications. Together these two patterns had a 46% sensitivity rate and a 70% specificity rate in predicting postoperative complications. Using 20% change in intraoperative MAP produced results nearly identical to 20-mmHg changes. When the duration of 20-mmHg changes was accounted for, changes of a greater magnitude (e.g., 40 mmHg) were not significant independent predictors of complications. The use of the mean difference from preoperative MAP was misleading because patients who experienced both high and low MAPs tended to have nearly normal mean MAPs, but high complication rates. The absolute magnitude of intraoperative MAPs, regardless of the preoperative levels, also was evaluated. The overall mean intraoperative MAP was not a significant predictor of complications. Specific intraoperative MAPs (e.g., less than 70 mmHg and more than 120 mmHg) also were evaluated. While neither was a significant predictor, there was a trend for increased complications among patients whose MAPs decreased to less than 70 mmHg. Intraoperative blood pressure should be analyzed in relation to the patient's preoperative blood pressure. Prolonged changes of more than 20 mmHg or 20% in relation to preoperative levels were significantly related to complications. 
5	Coronary angioplasty in young adults: initial results and late outcome. The initial and late outcome of coronary angioplasty was studied in 148 patients less than 40 years of age (mean 36.4 +/- 3). Angioplasty was performed on a single vessel in 70% of patients and on multiple vessels in 30%; it was performed on a totally occluded vessel in 20%. Angioplasty was successful in 90.5% of patients, unsuccessful but uncomplicated in 7.4% and complicated by myocardial infarction in 0.7%, emergency bypass surgery in 0.7% and death in 0.7%. At late (mean 3.7 +/- 3 years; range 0.5 to 11.5) follow-up study after successful angioplasty, 94% of patients were alive, 79% were free of angina and 85% had returned to work; late myocardial infarction occurred in 4%. Actuarial survival at 5 years was 95%, and 85% of patients were free from death, infarction or bypass surgery. A second angioplasty was performed in 29 patients (22%) (mean 6.1 +/- 8.4 months) and was successful in 27 (93%), with no deaths. Elective coronary bypass surgery was performed in 8.5% of patients, with perioperative infarction in 9% and no deaths. By univariate analysis, late death was more likely to occur in hypertensive patients (15% versus 2.5%; p less than 0.01) and diabetic patients (21.4% versus 3.6%; p less than 0.01). Cox proportional hazard regression analysis identified hypertension (p = 0.007) and diabetes (p = 0.04) as independent time-related predictors of subsequent death. Thus, early and late results after coronary angioplasty in young adults are favorable, but certain risk factors are important predictors of outcome. Late revascularization procedures (repeat angioplasty or surgery) for restenosis or disease progression are common. 
3	Innervation territories for touch and pain afferents of single fascicles of the human ulnar nerve. Mapping through intraneural microrecording and microstimulation. The peripheral distribution of the fibre content of individual ulnar nerve fascicles supplying skin and muscles of the hand in human volunteers was indirectly mapped by tracing the fields of projected sensation evoked by intraneural electrical microstimulation (INMS) and by tracing receptive fields delineated through intraneural recording of afferent impulse activity elicited by natural stimulation of end organs. Moderate intensity suprathreshold INMS, delivered in cutaneous fascicles, induced nonpainful sensations projecting to stereotyped and coherent areas of skin, the fascicular projected fields (FPFs). Fascicular receptive fields (FRFs) were mapped during microneurographic recording by determining the area of skin which, when activated by light tactile stimuli, elicited afferent neural discharges recorded intraneurally. It was found that at a given electrode position in a skin nerve fascicle, moderate intensity INMS induced nonpainful sensations projecting to a cutaneous field (FPF) that coincides with the FRF, while high intensity INMS induced painful sensations projecting within the cutaneous field of nonpainful sensations. Pain induced by INMS in muscle nerve fascicles was projected to the muscles innervated by that fascicle and, in most instances, to areas beyond the muscular receptive field. The study demonstrates that individual ulnar nerve fascicles, at wrist levels, subserve well-defined cutaneous territories in the hand, and that the area of skin covered by the sum of all ulnar fascicular receptive or projected fields matches the maximal possible cutaneous distribution of the ulnar nerve. Insights of practical relevance regarding clinical expression of fascicular nerve injuries are also brought up by this study. 
1	Clinical trials. Access and reimbursement. Clinical trials continue to play an extremely important role in clinical oncology, but of the nearly 1 million cancer patients diagnosed in the United States each year, only 2.5% (25,000) participate in such trials. Access to clinical trials has been enhanced by the adoption by the NCI of a promotional campaign that involves seminars, dissemination of information to national and local news media, and assisting in making information about clinical trials available to patients and physicians. Factors that hinder accrual of patients to clinical trials include: (1) physicians' concern about losing contact with patients, (2) physicians who feel that "experimental therapy" is not as good as "standard therapy," and (3) the time it takes to discuss and implement clinical trials. Reimbursement for clinical trials has also become a major concern. Who should pay for clinical research? Many insurance companies have been reluctant to pay for "experimental therapy" but will pay for "standard therapy." If this trend continues, the whole concept and organization of clinical trials, i.e., Phase I, II, and III trials, will be greatly hindered. Solutions must be found, and third party payers need to realize that an investment in clinical trials today will decrease the long term costs of state-of-the-art care. 
4	Effects of nicardipine, a calcium antagonist, on myocardial salvage and high energy phosphate stores in reperfused myocardial injury. The current study determined the effectiveness of nicardipine, a 1,4-dihydropyridine calcium antagonist, in preserving reperfused myocardium in a cat model of temporary coronary occlusion and ascertained if replenishment of myocardial phosphate stores during reperfusion as defined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy was indicative of salvage. Twenty open chest, anesthetized cats were studied with use of a snare ligature around the proximal left anterior descending coronary artery, with a coil sutured to the epicardial surface overlying the distribution of the artery. Peak areas of phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP) NMR signals were measured during 1 h of occlusion followed by 1.5 h of reperfusion. Infarct size and jeopardy area were determined in vitro by simultaneous infusion of phthalocyanine blue dye and triphenyltetrazolium chloride into the aorta and the left anterior descending coronary artery, respectively, after 5 h of myocardial reperfusion. Nicardipine-treated and control groups had similar jeopardy area values (41.2 +/- 1.6% versus 47.4 +/- 3.1% of the left ventricle), but infarct area was significantly reduced in the nicardipine-treated group (3.2 +/- 1.1% versus 24.9 +/- 7.5% of jeopardy area, p less than 0.01). High energy phosphate compounds remained markedly altered during reperfusion in both groups. No significant improvement in phosphocreatine or inorganic phosphate recovery was observed in animals pretreated with nicardipine despite an 87% reduction in infarct size. Myocardial ATP was greater during reperfusion in the nicardipine-treated compared with the control group (average over initial 90 min of reperfusion 58 +/- 6% versus 46 +/- 3% of baseline values, p less than 0.05), suggesting improved recovery of ATP. However, the measured levels of high energy phosphate compounds during reperfusion and their ratios did not correlate with infarct size and thus were not predictive of myocardial salvage. 
4	Total left main coronary artery occlusion after aortic aneurysm repair and valve replacement. A 38-year-old woman with complete occlusion of the left main coronary artery secondary to cannulation during aortic valve replacement is presented. The clinical course was characterized by progressive left ventricular dysfunction and congestive heart failure. Recognition of this potential problem when it occurs is important as to institute therapeutic measures which may interrupt a patient's progressive clinical deterioration. 
5	Spinal epidural abscess: an unusual complication of a duodenal ulcer. A 50-year-old man had several months of progressively worse low-back pain associated with constitutional symptoms and a history of retroperitoneal tumor and bleeding duodenal ulcer. Initial evaluation suggested a lumbar spine tumor, but myelography confirmed the presence of an epidural abscess. Further evaluation revealed a duodeno-spinal fistula at the site of the previous duodenal ulcer, which proved to be the cause of the abscess. 
3	Septic arthritis of the C1-C2 lateral facet joint and torticollis: pseudo-Grisel's syndrome. We present the case of a 76-year-old man who experienced the sudden development of fever, rightsided neck pain and stiffness, and torticollis. A soft tissue mass was noted on the right side of his neck, but his head was tilted to the left. Computed tomography scans (with reformatted sagittal and coronal images) of the patient's cervical spine revealed destructive changes of the right lateral masses of C1 and C2 and the clivus, and a well-delineated peridontoid soft tissue mass (confirmed by magnetic resonance imaging). After the second episode of right-sided hemiparesis, he underwent transoral surgical exploration, with anterior decompression and odontoidectomy. Histologic examination of the surgical material revealed granulation tissue, fibrosis, and chronic inflammation, consistent with abscess formation with invasion and compression of the spinal cord and bone. This case suggests that nonreducible rotational head tilt to the side opposite the side of lateral mass collapse should raise the suspicion of a possible infection. 
4	Forearm blood flow response to posture change in the very old: non-invasive measurement by venous occlusion plethysmography. Little is known about the peripheral vascular response to posture change in very elderly people who are vulnerable to the development of orthostatic hypotension. This is due, in part, to the risks of currently utilized invasive vascular monitoring techniques in the elderly population. We studied the forearm vascular response to active standing in 18 healthy young, 10 healthy old, and 19 impaired elderly subjects, using the non-invasive technique of venous occlusion plethysmography. In six subjects this technique was compared to duplex doppler ultrasonography for the measurement of postural changes in forearm blood flow. Forearm blood flow changes determined by venous occlusion plethysmography were 11% larger than doppler measurements, but the two methods strongly correlated (r = 0.90, P less than .001). Mean forearm vascular resistance increased to a significantly greater extent at 1 minute of standing in young subjects than in both groups of old, although the response was quite variable in all groups. Two healthy elderly (20%) and eight impaired elderly (40%) subjects had unexpected forearm vasodilatation at 1 minute of standing. By 3 minutes, forearm vascular resistance had increased by similar amounts in all three groups of subjects. Five impaired elderly and no healthy young or healthy old subjects had orthostatic hypotension, defined as greater than or equal to 10 mm Hg decline in mean arterial blood pressure at 1 or 3 minutes of standing. Forearm vascular resistance changes did not correlate with blood pressure response to standing. Thus, forearm vascular response to 1 minute of active standing is attenuated in many elderly subjects. This abnormality may impair adaptation to orthostatic stress in advanced age. 
5	Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Plasmodium falciparum isolates from 24 Gambian children with cerebral malaria and 57 children with mild forms of the disease were assessed for their ability to form erythrocyte rosettes. All isolates from the children with cerebral malaria were able to form rosettes, whereas those from children with mild forms of the disease did not form rosettes, or had a significantly lower rosetting rate. Plasma of children with cerebral malaria lacked anti-rosetting activity, whereas plasma of children with mild disease could often disrupt rosettes in vitro. A monoclonal antibody to P falciparum histidine rich protein (PfHRP1/KP/KAHRP) disrupted rosettes of many of the isolates in vitro indicating that the rosetting ligand is relatively conserved compared with ligands associated with endothelial cytoadherence. The findings strongly support the hypothesis that erythrocyte rosetting contributes to the pathogenesis of cerebral malaria and suggest that anti-rosetting antibodies protect against cerebral disease. 
5	Aerobic and anaerobic microbiology of acute suppurative parotitis. Aspirates of pus from acute suppurative parotitis were studied for aerobic and anaerobic bacteria. Bacterial growth was present in 23 specimens. A total of 36 bacterial isolates (20 anaerobic and 16 aerobic and facultative) were recovered, accounting for 1.6 isolates per specimen (0.9 anaerobic and 0.7 aerobic and facultative). Anaerobic bacteria only were present in 10 (43%) patients, aerobic and facultatives in 10 (43%), and mixed aerobic and anaerobic flora in 3 (13%). Single bacterial isolates were recovered in 9 infections, 6 of which were Staphylococcus aureus and 3 were anaerobic bacteria. The predominant bacterial isolates were S. aureus (8 isolates), Bacteroides sp. (6 isolates, including 4 Bacteroides melaninogenicus group), and Peptostreptococcus sp. (5). beta-Lactamase-producing organisms were recovered from 11 (73%) of the 15 specimens tested. This study highlights the polymicrobial nature and importance of anaerobic bacteria in acute suppurative parotitis. 
5	Treatment of end-stage chronic obstructive pulmonary disease with double lung transplantation. Six patients with end-stage emphysema (age 44 +/- 2 years) underwent double lung transplantation (Tx) from June 1988 through May 1990. All suffered from severe inanition and required oxygen therapy. The ischemic time was 193 +/- 28 minutes. Post-Tx immune suppression was OKT3 (14 days), cyclosporine (trough levels of 150 +/- 25 ng/ml), azathioprine to keep WBC at 3,000 to 5,000/cu mm (1 to 3.0 mg/kg/day) and following OKT3, a tapering prednisone regimen. Two rejection episodes that occurred in two patients on post-Tx day 5 and 10 were treated with bolus doses of methylprednisolone. The mean hospital stay was 32 +/- 7 days (range, 20 to 69 days). Four patients required treatment of cytomegalovirus (CMV) infection: gastritis (+donor, +recipient) in one and CMV pneumonia in two (+donor, -recipient). A fourth (+donor, -recipient) had right-sided Candida empyema six weeks post-Tx, developed CMV and staphylococcal sepsis, and died 64 days post-Tx. One patient required pyloroplasty eight weeks post-Tx and one patient underwent tracheal suture line repair at eight weeks. During a follow-up of 81 patients months (range, 8 to 24 months), one patient had developed Epstein-Barr viral (EBV) induced lymphoproliferative disease in the lung and one patient had developed EBV lymphoma. Three patients are at work, one is continuing rehabilitation, and one is at home. Double lung Tx offers a definitive benefit to patients with emphysema; however, a prolonged postoperative course can be expected. Viral infections remain serious but treatable problems. 
4	Early scintigraphic detection of experimental myocardial infarction in dogs with technetium-99m-glucaric acid Recent data have generated some interest in technetium-99m-(99mTc) glucaric acid as an in vivo viability marker. We studied 99mTc-glucaric acid retention in canine models of myocardial ischemia (20-min occlusion of the LAD/40-min reperfusion), acute myocardial infarction (MI) (90-min LAD occlusion/3-hr reperfusion), and chronic MI (90-min occlusion and either 48-hr or 10-day reperfusion). Regional myocardial blood flow was measured by radiolabeled microspheres. No preferential uptake of glucaric acid was observed in ischemic but viable myocardium. The compound showed high affinity for necrotic myocardial tissue for several days following injury. The preferential uptake in infarcted tissue disappeared by 10 days following injury. This study shows that 99mTc-glucaric acid acts exclusively as a marker of necrosis in canine models of MI. Technetium-99m-glucaric acid may have clinical utility in early cardiac imaging of myocardial infarction and in differentiating recent from old injuries. 
5	Multicenter registry of angioplasty therapy of cardiogenic shock: initial and long-term survival. This retrospective multicenter study reviews the role of acute percutaneous transluminal coronary angioplasty in the treatment of cardiogenic shock complicating acute myocardial infarction to determine whether early reperfusion affects in-hospital and long-term survival. From 1982 to 1985, 69 patients were treated with emergency angioplasty to attempt reperfusion of the infarct-related artery. Balloon angioplasty was unsuccessful in 20 patients (group 1) and successful in 49 patients (group 2). Initial clinical and angiographic findings in the groups with unsuccessful and successful angioplasty were similar with respect to age (60.5 +/- 2.3 versus 57 +/- 1.8 years), infarct location (65% versus 65% anterior) and gender (65% versus 67% male). Hemodynamic variables in the two groups, including systolic blood pressure (68 +/- 4.3 versus 73 +/- 1.6 mm Hg), left ventricular end-diastolic pressure (24.4 +/- 2.4 versus 27 +/- 1.0 mm Hg) and initial ejection fraction (28.5 +/- 4% versus 32 +/- 2%), were also similar. Twenty-nine patients received thrombolytic therapy with streptokinase; the overall rate of reperfusion was 34%. Group 1 patients had a short-term survival rate of 20%, compared with 69% in group 2 patients (p less than 0.0005). Thirty-eight patients survived the hospital period and were followed up for 24 to 54 months (mean 32.5 +/- 2.4). Five patients (all in group 2) died during follow-up. The long-term incidence rate of congestive heart failure was 19%, arrhythmia 21%, need for repeat angioplasty 17% and coronary artery bypass grafting 26%. Twenty-four month survival was significantly better in group 2 patients (54%) versus group 1 patients (11%, p = 0.003). 
4	Twelve-year incidence of coronary heart disease in middle-aged adults during the era of hypertensive therapy: the Framingham offspring study [published erratum appears in Am J Med 1991 Apr;90(4):537] PURPOSE: To provide information on the incidence of coronary heart disease (CHD) in the offspring of the original cohort from the Framingham Heart Study. PATIENTS AND METHODS: From 1972 to 1974, offspring of the original participants in the Framingham Heart Study underwent a baseline examination for standard cardiovascular risk factors. At entry into the study, these offspring were 30 to 59 years old and free of CHD. They were followed for 12 years, during which time 156 of 1,663 men and 55 of 1,714 women developed CHD. RESULTS: In a multivariate proportional hazards model, CHD was significantly associated with age, lower high-density lipoprotein cholesterol (HDL-C) levels, and number of cigarettes smoked. Fasting glucose levels and low-density lipoprotein cholesterol (LDL-C) were highly associated with CHD in men, but borderline in women, while triglycerides and very-low-density lipoprotein cholesterol were not significantly associated with CHD after adjustment for HDL-C and glucose. Blood pressure medication was used in half of the hypertensive individuals, and systolic pressure was associated with CHD in women only. CONCLUSIONS: This study confirms the importance of the common CHD risk factors of cigarette smoking and LDL-C, and extends the prognostic role of HDL-C in a middle-aged cohort. The impact of blood pressure, with or without use of hypertensive medications, was reduced in this study, and the data suggest that this attenuation was due to successful treatment. 
1	Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial. Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively. 
1	Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification. The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both-sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms. 
1	In vitro activity of LY264826, a new glycopeptide antibiotic, against gram-positive bacteria isolated from patients with cancer. The in vitro activity of LY264826, a novel glycopeptide antibiotic produced by Amycolatopsis orientalis, was compared with those of vancomycin, teicoplanin, and oxacillin against 311 gram-positive clinical isolates from patients with cancer, LY264826 had lower MICs for 90% of isolates (MIC90) than vancomycin for all species tested. It was active against oxacillin-resistant isolates including Staphylococcus aureus (MIC90, 0.5 micrograms/ml), Staphylococcus haemolyticus (MIC90, 2.0 micrograms/ml), Enterococcus spp. (MIC90, 0.5 micrograms/ml), Bacillus cereus (MIC90, 0.25 micrograms/ml), and Corynebacterium jeikeium (MIC90, 0.12 micrograms/ml). For S. aureus, including oxacillin-resistant isolates, the MICs of LY264826 were similar to those of teicoplanin. For coagulase-negative staphylococci, however, LY264826 had MICs that were 4- to 32-fold lower than those of teicoplanin. Against most streptococcal species the activities of LY264826 and teicoplanin were similar. Bactericidal activity against Staphylococcus spp. and most Streptococcus pyogenes isolates was less than or equal to 1 dilution of the MIC. One isolate of S. pyogenes and all Enterococcus faecalis strains tested were tolerant of LY264826, with MBCs greater than or equal to 32-fold greater than the MICs. The addition of 50% human serum resulted in a significant increase in activity only against Staphylococcus epidermidis. Variations in pH from 6.4 to 8.4 and in inoculum from 10(3) to 10(7) CFU/ml did not significantly affect the activity of LY264826. 
2	Expression of class II molecules on intestinal epithelial cells in humans. Differences between normal and inflammatory bowel disease. Expression of class II antigens on human intestinal epithelial cells was assessed using a sensitive avidinbiotin-peroxidase technique. HLA-DR was present predominantly in the normal small bowel with diminished but evident expression in the colon. HLA-DP staining was less prominent, and HLA-DQ was absent. In inflammatory bowel disease the expression of both HLA-DR and HLA-DP was increased, but that for HLA-DQ remained absent, suggesting an inherent defect in the ability of intestinal epithelial cells to express HLA-DQ. In related experiments, an interferon gamma-treated malignant epithelial cell line T84 also failed to stain for HLA-DQ and HLA-DP despite the presence of HLA-DR. Isolated RNAs for all three subclasses of HLA-D were detectable by slot-blot analysis, suggesting that the lack of HLA-DQ expression relates to posttranscriptional defects in intestinal epithelium. These and other differences with conventional class II antigen-positive accessory cells (macrophages/B cells) may help to explain the unique properties of intestinal epithelial cells as antigen-presenting cells. 
3	Differential reading recovery in patients with severe to moderate closed head injury. A differential recovery was seen when alternate forms of a nationally standardized test of Reading Vocabulary, Literal Reading Comprehension and Inferential Reading Comprehension was administered serially to 10 consecutive closed head injury admissions to a university rehabilitation hospital. Inferential Reading Comprehension was the most impaired and had the fastest recovery rate. Subtle cognitive deficits in Inferential Reading Comprehension were detected when Reading Vocabulary was at or better than a twelfth grade level. Maximal recovery of all three reading functions occurred within 4 months after trauma, with most occurring in the first 3 months. The reading recovery pattern parallels the recovery of intelligence scores in the literature. 
5	Mortality in acute stroke with atrial fibrillation. The Italian Acute Stroke Study Group. We compared 211 consecutive patients who had acute ischemic hemispheric stroke and atrial fibrillation with 837 consecutive patients who had stroke without atrial fibrillation. The atrial fibrillation group included a higher frequency of women, older subjects, and those with a severe neurologic deficit, abnormal computed tomogram, and elevated heart rate. The 1-month case-fatality rate in the atrial fibrillation group was 27% while that in the group without atrial fibrillation was 14%. The 6-month case-fatality rates in the two groups were 40% and 20%, respectively. The risk of death attributable to atrial fibrillation, adjusted for the effect of other prognostic factors, was significant at 1 month (relative risk = 1.55) and at 6 months (relative risk = 1.74). The causes of death were equally distributed in the two groups during both the acute and subacute phases. We conclude that atrial fibrillation is a negative prognostic factor in patients hospitalized for acute stroke. Nevertheless, cerebral embolism alone does not completely explain the increase in mortality for stroke patients with atrial fibrillation. Other associated pathogenetic mechanisms must also be taken into account. 
2	Interventional radiology of the biliary tract. Transcholecystic intervention. Diagnostic and therapeutic biliary intervention by percutaneous access to the gallbladder is an important new area in interventional radiology. The anatomy of the gallbladder, biliary tree, and surrounding viscera is reviewed in this article as a preliminary to discussion of the diagnostic techniques of aspiration, cholangiography, biopsy, and the therapeutic techniques of gallbladder drainage and cholelithotomy. Recently there has been a bewildering proliferation of procedures aimed at removal, fragmentation, and dissolution of gallbladder stones. Several of these are discussed in this article. Removal of common bile duct stones by percutaneous cholecystostomy also is discussed. 
2	Mayer-Rokitansky-Kuster-Hauser syndrome with splenosis. A case report. This is the first reported case of simultaneously occurring pelvic splenosis and Mayer-Rokitansky-Kuster-Hauser syndrome. No other congenital or anatomic abnormalities were observed in the patient, and she had no history of abdominal trauma or surgery. Endometriosis was suspected initially during laparoscopy for pelvic pain. After tissue removal at laparotomy, the histologic evaluation established the diagnosis of splenosis. Biopsy at laparoscopy should be considered to confirm the diagnosis in the presence of a congenital anomaly and lesions suspected of being endometriotic. 
5	Percutaneous puncture of a nondeflatable coronary artery angioplasty balloon. We report a case in which a balloon catheter became permanently inflated in a coronary artery saphenous vein bypass graft. While still inflated, the balloon was forcibly withdrawn from the graft into the external iliac artery and successfully deflated via percutaneous puncture using a CHIBA needle. 
2	Granulomatous hepatitis and fever of unknown origin. An 11-year experience of 23 cases with three years' follow-up. Granulomatous hepatitis is a common cause of fever of unknown origin in up to 13% of patients with prolonged fever. Attempts to define an exact etiology of the granulomatous hepatitis frequently does not yield a precise diagnosis, so that the physician must consider empiric treatment. In this paper we retrospectively review 23 patients in whom granulomatous hepatitis was found as part of the initial assessment of fever of unknown origin, and we report on their outcomes after an overall prospective follow-up of 37 months. In 26% a precise diagnosis was established at the time of assessment: Q-fever in three, mycobacterial disease in two, and histoplasmosis in one. In the remaining 74% no etiology was established after 44 months follow-up. Forty-one percent of the idiopathic group resolved spontaneously without therapy, and 18% received short-term prednisone or indomethacin with a favourable outcome. The remaining 41% required long-term prednisone therapy for a mean of 33.1 months, but all have remained afebrile and otherwise healthy after 59.6 months follow-up. We conclude that patients with fever of unknown origin who are diagnosed as having idiopathic granulomatous hepatitis have an excellent prognosis, even the minority who require long-term corticosteroids. 
1	Disposition of cerebral metastases from malignant melanoma: implications for radiosurgery Radiosurgery is becoming more generally available and indications for its use continue to be defined. Cerebral metastases from malignant melanoma are often treated with whole-brain irradiation, but with limited benefit. Innovative treatments, such as radiosurgery, make possible the delivery of doses of radiation that are higher than usual. To determine how many patients might be candidates for radiosurgery, a retrospective analysis of computed tomographic brain scans performed on 41 patients with cerebral metastases from malignant melanoma was undertaken. One-third of these patients were found to have cerebral metastases amenable to a radiosurgical approach, as illustrated radiation dose-volume histograms. Patient and tumor characteristics suggest that this series is represent with cerebral metastases from malignant melanoma. The implications of radiosurgery for normal tissue radiation tolerance and its effects on melanoma are discussed. 
1	Multifocal gastric carcinoma arising from hyperplastic and adenomatous polyps. This paper is a presentation of the unusual case of a 61-yr-old woman operated on for multiple gastric cancers. Two of the cancers were found in the hyperplastic polyps and one in the adenoma. Apart from cancers that arose from these polyps, there were four separate polypoid or flat gastric carcinomas and three other hyperplastic polyps with no signs of malignancy, in this case. The presentation is followed by a detailed discussion focusing on the possible development of carcinoma in gastric hyperplastic polyps in view of the data from the literature. 
4	Effects of heparin versus saline solution on intermittent infusion device irrigation. The purpose of this study was to compare the effectiveness of 1 ml of 0.9% sodium chloride with 10 units of heparin in 1 ml sodium chloride solution, both containing benzyl alcohol, in maintaining patency and reducing the incidence of phlebitis in patients with intermittent infusion devices. The subjects (N = 32) were randomly assigned in a double-blind experimental design. Repeated-measures analysis of variance revealed no significant difference between the groups in phlebitis or patency variables. The results from this controlled study would suggest that 0.9% sodium chloride is as effective as 10 units of heparin in sodium chloride solution in maintaining intermittent infusion device patency and preventing phlebitis. 
4	Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia. The anti-ischemic effects of atenolol and nifedipine were compared in a randomized double-blind crossover manner in 24 patients with stable exertional angina and transient silent ischemia during ambulatory electrocardiographic (ECG) monitoring. Both atenolol and nifedipine were effective (p less than 0.005) in reducing the average number and duration of transient ischemic events, but therapy with atenolol was associated with a significantly greater reduction in the mean number (p less than 0.05) and duration (p less than 0.01) of silent ischemic events. Analyses of the silent ischemic activity during the morning hours revealed that only therapy with atenolol produced a significant reduction in the average duration per patient (139 +/- 54 vs. 1,609 +/- 468 s, p less than 0.01) and in the average duration of silent ischemia per event between 6 AM and 12 noon (62 +/- 21 vs. 208 +/- 24 s, p less than 0.005). There were fewer adverse experiences during therapy with atenolol. These results show that although both atenolol and nifedipine are effective in reducing silent ischemic events, treatment with atenolol is associated with significantly greater efficacy, particularly on the morning surge of silent myocardial ischemia. 
1	Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus. Acute promyelocytic leukemias (APLs) are characterized by a reciprocal balanced translocation that involves chromosomes 15 and 17 [t(15;17)]. We report the isolation and characterization of one of the two reciprocal break sites and demonstrate that the chromosome 17 breakpoint lies within the retinoic acid receptor alpha locus. Nucleotide sequencing of the 15;17 cross-over junction on 15q+ showed that the retinoic acid receptor alpha gene is truncated within its first intron, 370 base pairs upstream from the splicing donor site of exon II. Such a recombination would be expected to generate abnormal RAR alpha mRNA and protein. Southern blot analysis of a number of APLs with chromosome 15- and 17-derived DNA probes revealed similar 15;17 recombinations in the majority of other APLs. Our data are strong evidence that the retinoic acid receptor alpha gene plays a crucial role in the leukemogenesis of APL. 
4	Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen. Forty-seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK)-cell therapy, using a hybrid IL-2 regimen. IL-2 was administered initially by intravenous bolus (10(5) U/kg [Cetus Corp, Emeryville, CA] every 8 hours for 3 days) during the priming phase, and subsequently by continuous infusion (3 x 10(6) U/m2 for 6 days); during this second treatment period, in vitro-generated LAK cells were administered. Despite selection of patients for good performance status (PS) (29, PS 0; 18, PS 1) prior nephrectomy (43 of the 47 patients), and low tumor burden, the response rate was low (two complete [CRs] and two partial responses [PRs], for an overall objective response rate of 9%). Toxicity was comparable to that experienced with the high-dose bolus regimen. These results suggest that the dose and schedule of IL-2 administration may influence the likelihood of response to IL-2 in renal cell carcinoma. 
4	Chronic arterial occlusion with PGE1-resistant skin lesions treated by glycosaminoglycan compound--case reports. The authors report on 2 patients with chronic arterial occlusion in whom the intravenous administration of the glycosaminoglycan compound FPFD 101 was markedly effective. One patient suffered from thromboembolic episodes of the left hand, and the other had peripheral circulatory impairment related to collagen disease. In these patients, the oral administration of anticoagulants and antiplatelet agents in combination with intravenous infusion of prostaglandin E1 was not adequately effective. However, the addition of intravenous injection of FPFD 101 resulted in a marked improvement in their symptoms. FPFD 101, which has an anticoagulant effect and also inhibits platelet aggregation, seems to be useful for the treatment and prevention of chronic arterial occlusion when combined with drugs such as anticoagulants, antiplatelet agents, and vasodilators. 
3	Correlation between essential tremor and migraine headache. The relationship between essential tremor (ET) and migraine was investigated in a prospective study. In a group of 74 ET patients 36.5% had migraine compared with 17.7% of 102 control subjects without tremor. In a group of 58 patients with migraine 17.2% had ET compared with 1.2% of 85 controls without migraine. The prevalence of ET in migraine controls was greater than controls without migraine (22% compared with 1%; p = 0.002). It is concluded that there is an association between essential tremor and migraine. 
5	Acute oculogyric crisis after administration of prochlorperazine. We report a case of acute oculogyric crisis due to prochlorperazine administration in a young black woman with a concomitant viral infection. Neuroleptic medications are the most common cause of drug-induced acute dystonic reactions such as oculogyric crisis. Prochlorperazine is an antiemetic agent with a phenothiazine-type chemical structure and is known to cause dystonic reactions. Drug-induced acute dystonic reactions are most common in young adults and in men. Viral infections may also predispose patients to these adverse reactions. Caution is warranted when this drug is used in patients who have other risk factors for an acute dystonic reaction. 
4	Disseminated Conidiobolus infection with endocarditis in a cocaine abuser. A crack cocaine abuser developed disseminated infection caused by a species of Conidiobolus not known to cause disease in vertebrates. The fungus gained entry via skin abrasions on the lower extremities, spread through the hematogenous route, and caused endocarditis. There was evidence of fungal infection in the lungs, heart, kidneys, skeletal muscles, and brain. An additional complication was extensive rhabdomyolysis, with a marked elevation of creatine kinase of up to 1.2 million U/L. 
5	Recent advance in treatment of Stanford type A aortic dissection. During the period between November 1986 and November 1988, 13 consecutive patients with Stanford type A aortic dissection (8 acute and 5 chronic) were treated as follows: (1) urgent operation for cases with pericardial tamponade or severe heart failure, (2) initial medical treatment followed by elective operation for acute but stable cases or chronic cases, and (3) routine use of open distal anastomosis or selective cerebral perfusion. One patient died during medical treatment: 5 patients were operated on emergently. The remaining 2 acute and 5 chronic cases were operated on electively. There were no operative deaths, neurological disturbances, or late deaths. It is suggested that acute dissection of the ascending aorta requires immediate surgical intervention, especially when the entry is in the ascending aorta. On the other hand, it is also suggested that one could avoid emergency operations in selected cases with retrograde extension of the aortic dissection. 
3	Patellar resurfacing in total knee arthroplasty. Technical errors in patellar resurfacing at the time of total knee arthroplasty (TKA) are responsible for many of the complications that affect the patellofemoral joint. Instability, patellar fracture, and wear of metal-backed patellar implants are significantly affected by errors of patellar resurfacing. A review of 50 TKAs using a condylar prosthesis and a standardized technique for patellar resurfacing was performed to evaluate the accuracy of the technique. The patients were evaluated at a mean of 2.5 years (range, two to five years) after surgery. The Hospital for Special Surgery Knee Score improved from a preoperative mean of 56 to 92 at the last evaluation. The Hospital for Special Surgery Knee Scores were excellent in 92% and good in 8%. The Knee Society Knee Score improved from a preoperative mean of 28 for pain and 49 for function to a last evaluation mean of 96 for pain and 85 for function. None of the patients had symptoms referable to the patellofemoral joint. There were no patellar fractures, dislocations, or instances of implant loosening of the patella. Roentgenograms revealed nine asymmetrically resurfaced patellae and five tilted patellae. There were no patellar subluxations. Patellar thickness was maintained at the preoperative level of 21 mm. Joint-line height was elevated 1 mm. The patellar height was decreased 2 mm from the preoperative height. Using a standard technique, satisfactory clinical results can be achieved, but minor errors in resurfacing and alignment will still occur. 
3	Postnatal epilepsy after EEG-confirmed neonatal seizures. We examined infants whose neonatal seizures were confirmed by randomly recorded ictal EEG tracings to determine the types and frequency of postnatal epilepsy (PNE)--unprovoked, recurring postnatal seizures. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to PNE. Forty infants with EEG-documented neonatal seizures of diverse etiologies were studied. The 27 survivors were followed for a mean of 31 months. PNE developed in 56% (15 of 27) of the cohort. The first seizure appeared at a mean-corrected age of 12.7 months and occurred despite ongoing antiepileptic medication in 60% (9 of 15) of the group. Seizures were classified as infantile spasms or minor motor (7 patients), complex partial (4 patients), or generalized tonic-clonic (4 patients). Perinatal variables that significantly correlated with PNE included the presence of coma but not the age at seizure onset, the estimated gestational age, or Apgar scores. PNE occurred in 68% (13 of 19) of patients with moderately or markedly abnormal EEG backgrounds but in only 25% (2 of 8) without (p = 0.035). There was a strong trend for PNE to develop in patients with greater than 10 electrographic seizures per hour but in only 45% (9 of 20) of infants with fewer seizures (p = 0.058). Several postnatal variables were significantly related to PNE--the presence of cerebral palsy (CP), mental retardation (MR), CP with MR, and follow-up EEGs. PNE occurred in only 27% (3 of 11) of patients without spikes or sharp waves on postnatal EEGs performed at age 3 months but in 100% (3 of 3) of patients with spikes or sharp waves (p = 0.022). 
2	Epidermolysis bullosa acquisita and associated symptomatic esophageal webs. Epidermolysis bullosa acquisita (EBA) is a well-characterized, subepidermal blistering disorder associated with autoimmunity to type VII collagen, which is the collagen localized to anchoring fibrils within the dermoepidermal junction of skin. Although the full clinical spectrum of EBA is still being defined, it is known that the clinical features of EBA may be reminiscent of hereditary dystrophic epidermolysis bullosa, a scarring blistering disease of children that is commonly associated with esophageal stenosis. We describe a patient with EBA who had both an acral-predominant mechanobullous disease akin to dystrophic epidermolysis bullosa and an inflammatory, widespread bullous eruption reminiscent of bullous pemphigoid in association with esophageal webs and dysphagia. Although esophageal involvement is common in dystrophic epidermolysis bullosa, a review of the literature shows that this is the first bonafide case of EBA with symptomatic esophageal disease. 
5	Simplified technique for isolating vascularized rib periosteal grafts. A modified technique for obtaining a vascularized rib periosteal segment utilizing the posterolateral approach is presented. The technique avoids the inclusion of a large muscle cuff or the pleura around the isolated rib segment and therefore minimizes donor-site morbidity and chest complications previously associated with this approach. 
5	Long-term results after atrial correction of complete transposition of the great arteries. This study presents the late results for the first 104 consecutive patients surviving and atrial repair for transposition of the great arteries (TGA) between January 1971 and December 1978 (group 1). Mean follow-up was 12 years (range, 0.1 to 17.7 years). The actuarial survival rate at 18 years was 84.2% (70% confidence limits, 79% to 88%) for simple TGA and 93.7% (70% confidence limits, 84% to 97%) for complex TGA. Nine of the 11 deaths were sudden. Two (2.6%) of the 78 late survivors operated on for simple TGA are in New York Heart Association functional class III or IV versus 4 (26.7%) of the 15 survivors with complex TGA; the other patients are doing very well. To better assess long-term results, we report the findings for randomly obtained electrocardiograms, Holter monitor recordings, radionuclide angiographic studies, and cardiac catheterizations performed in 1987 in a larger group of 159 long-term survivors of atrial repair operated on at Ospedale Riuniti di Bergamo from January 1971 to December 1984 (group 2), which includes all of group 1. The findings confirm that the arterial switch repair is the procedure of choice for complex TGA and that there is a major incidence (approximately 10%) of systemic right ventricular dysfunction and rhythm disturbances after the atrial repair. On the other hand, our late survival rate at 18 years of 84% for simple TGA with 97.5% of the patients in functional class I is a result that should be kept in mind, especially in institutions where the arterial switch is a relatively new approach and presumably is a higher risk to cause early death. 
4	Morphological changes and smooth muscle cell proliferation after experimental excimer laser treatment. BACKGROUND. Little is known about the mechanism(s) in the development of restenosis after excimer laser angioplasty. Thus, the rationale of this study was to determine the time course of intimal and medial smooth muscle cell (SMC) proliferation and histomorphological changes after experimental excimer laser treatment. METHODS AND RESULTS. Laser ablation was performed in the right carotid artery of 34 New Zealand White rabbits after development of a fibromuscular plaque by repeated weak electrical stimulations. The vessels were excised 3, 7, 14, 21, 28, and 42 days after excimer laser treatment. Staining of alpha-actin was used to identify SMCs. In five rabbits (15%), a stenosis of more than 50% of luminal area was due to intimal proliferation of SMCs, and in four other rabbits, a total occlusion was due to organized thrombi. After the initial ablation of the performed plaque (13 +/- 6 intimal SMC layers) a continuous increase of intimal wall thickness was found from 7 +/- 6 SMC layers at 7 days to 28 +/- 5 intimal SMC layers at 28 days after excimer laser ablation (p less than 0.01). After 42 days, no additional increase of intimal thickening occurred. After bromodeoxyuridine labeling, the extent of cell proliferation (percent of cells undergoing DNA synthesis) in the intima and media was determined using a monoclonal antibody against bromodeoxyuridine. Immunohistological quantification of SMC proliferation in the intima revealed a significant increase of cells undergoing DNA synthesis at 3 (p less than 0.05) and 14 (p less than 0.01) days after laser treatment. Medial proliferation of SMCs was delayed and had a significant increase 7 days (p less than 0.05) after intervention. Twenty-one days after laser treatment, SMC proliferation in the intima as well as in the media was normalized. CONCLUSIONS. The proliferative response of SMCs after experimental excimer laser treatment will occur as a dynamic process with a maximum of SMCs undergoing DNA synthesis during 14 days after laser ablation, resulting in an increase of intimal thickening within 4 weeks after laser treatment. The extent of intimal hyperplasia due to SMC proliferation after excimer laser treatment is comparable with the effect of transluminal balloon angioplasty in this experimental model. 
4	Coronary angioplasty following cardiac transplantation: a case report and review of the literature. A 23-year-old man underwent successful percutaneous transluminal coronary angioplasty of a severe stenosis of the left anterior descending artery 25 months after orthotopic heart transplantation. Four months later restenosis of the same lesion was treated by repeat PTCA. Angiography 11 months later showed no restenosis. In selected cases, PTCA may be useful in treating allograft coronary disease. 
5	Caseating hepatic granulomas in Hodgkin's lymphoma. A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver. 
4	Acute hemodynamic effects of intravenous diperdipine, a new dihydropyridine derivative, in coronary heart disease. The acute hemodynamic effects of a new dihydropyridine calcium channel blocker, diperdipine, which is suitable for intravenous administration, were studied by right and left cardiac catheterization in 16 patients with coronary heart disease. Diperdipine markedly reduced systemic vascular resistance and improved stroke index and left ventricular ejection fraction. Mean pulmonary artery and wedge pressures were slightly increased as a possible consequence of enhanced venous return, whereas right atrial and left ventricular end-diastolic pressures were not significantly changed. Nevertheless, an increase in preload was clearly indicated by an augmented left ventricular end-diastolic volume index after administration of diperdipine. Left ventricular contractility, which was estimated by the end-systolic pressure-volume ratio and by dP/dt max was not significantly changed, though analysis of individual data suggests a minimally negative inotropic effect. However, such a minor effect on left ventricular contractility was largely counterbalanced by the marked reduction of afterload, which produced a sharp improvement of stroke index. Enhancement of left ventricular ejection fraction and reduction in systemic vascular resistance were inversely and directly correlated to control values. Overall, diperdipine was well tolerated, but one patient had a major untoward reaction that consisted of an ischemic episode that was possibly related to drug administration. In conclusion, intravenous diperdipine appears to be a potent arteriolar dilating agent that does not affect left ventricular contractility. 
1	Simultaneous hepatoblastoma in identical male twins. Identical male twin infants who in 1987 presented with hepatoblastoma at the age of 7 months are reported. Twin B was admitted for investigation due to enlarged liver and spleen. He was found to have an inoperable hepatoblastoma of fetal type and was treated with chemotherapy and local irradiation. However, 7 months after the chemotherapy the tumor recurred. The asymptomatic twin A was examined because of the known familial cases, and he proved to have an identical tumor. He was successfully radically operated on and 2 years after the chemotherapy is still doing well with no evidence of tumor. As the mother and the maternal grandmother had polyps in the colon, quite probably the hepatoblastomas of the twins were associated with familial adenomatous polyposis. 
5	Donor seropositivity and prednisolone therapy as risk factors for cytomegalovirus infection and disease in cyclosporin-treated renal allograft recipients. We attempted to assess the importance of blood transfusion, donor seropositivity, and prednisolone therapy as risk factors for cytomegalovirus infection in cyclosporin-treated renal allograft recipients. Primary infection was diagnosed in 27 of 86 patients (31 per cent) and recurrent infection in 27 of 79 patients (34 per cent). Receipt of banked blood from unselected donors after transplantation did not increase the incidence of primary infection in the few transfused patients. Kidney donor seropositivity and maintenance prednisolone in addition to cyclosporin were associated with increases in the incidence of primary or recurrent infection, respectively. Cytomegalovirus infection was clinically mild. Presumed bacterial pneumonias occurred in three patients with recurrent cytomegalovirus infection. The absence of severe cytomegalovirus disease probably reflected the minimal use of prednisolone. Matching of seronegative donors with seronegative recipients seemed unjustifiable in cyclosporin-treated renal transplant patients. 
3	Carbon monoxide-induced delayed amnesia, delayed neuronal death and change in acetylcholine concentration in mice. We investigated the interrelationship of delayed amnesia, delayed neuronal death and changes in acetylcholine concentration induced by carbon monoxide (CO)-exposure in mice. In the test for retention of the passive avoidance task, amnesia was observed 5 and 7 days after CO-exposure when the mice were exposed to CO 1 day after training; in the case when the mice were exposed to CO 5 and 7 days before training, amnesia was also observed in a retention test given 1 day after training. The number of pyramidal cells in the hippocampal CA1 subfield was lower than that of the control 3, 5 and 7 days after CO-exposure. But the neurodegeneration in the parietal cortex, area 1, was not observed until 7 days after CO-exposure. The findings indicated that the amnesia and the neuronal death were produced after a delay when the mice were exposed to CO. In addition, the delayed amnesia was closely related to the delayed neuronal death in the hippocampal CA1 subfield. Moreover, [3H]glutamate and [3H]glycine binding sites did not change after CO-exposure but, 7 days after CO-exposure, the concentration of acetylcholine and the binding of [3H]quinuclidinyl benzilate in the frontal cortex and the striatum were found to have significantly changed, but those in the hippocampus did not show significant change. Therefore, we suggest that delayed amnesia induced by CO-exposure may result from delayed neuronal death in the hippocampal CA1 subfield and dysfunction in the acetylcholinergic neurons, in the frontal cortex, the striatum and/or the hippocampus. 
2	Preventing postoperative acute bleeding of the upper part of the gastrointestinal tract. Two hundred and ninety-eight critically ill patients at risk for the development of postoperative stress ulcers and bleeding were randomized into three groups. The first group comprised 85 patients who received meciadanol, a new bioflavonoid, 500 milligrams every six hours through a nasograstric tube; the second group comprised 100 patients who received sucralfate (crushed tablets), 1,000 milligrams every six hours through a nasogastric tube, and the third group comprised 113 patients who received an antacid (Maalox [magnesium aluminum hydroxide gel]) through a nasogastric tube at an initial dose of 15 milliliters every hour. The gastric pH was measured hourly and titrated to a pH greater than or equal to 4.0 in patients in the group receiving the antacid. The gastric pH was measured every two hours in the other two groups. Bleeding in the upper part of the gastrointestinal tract was determined visually (frank blood in gastric contents) or by guaiac testing. Bleeding occurred in seven patients receiving meciadanol, nine receiving sucralfate and six receiving the antacid. The difference in rates of bleeding was not statistically significant. Correlation between the severity of illness index and the development of bleeding was poor, at least in the low and intermediate index range. In contrast, there was a strong correlation between the age of the patient and the development of bleeding. Only one patient younger than 50 years had bleeding develop. Apparently, meciadanol exerts its action by a mechanism other than pH control. It may, therefore, fill an important gap in the ability to prevent postoperative stress ulcers and bleeding. 
3	Changes in quality of care for five diseases measured by implicit review, 1981 to 1986 We measured quality of care before and after implementation of the prospective payment system. We developed a structured implicit review form and applied it to a sample of 1366 Medicare patients with congestive heart failure, acute myocardial infarction, pneumonia, cerebrovascular accident, or hip fracture who were hospitalized in 1981-1982 or 1985-1986. Very poor quality of care was associated with increased death rates 30 days after admission (17% with very good care died vs 30% with very poor care). The quality of medical care improved between 1981-1982 and 1985-1986 (from 25% receiving poor or very poor care to 12%), although more patients were judged to have been discharged too soon and in unstable condition (7% vs 4%). Except for discharge planning processes, the quality of hospital care has continued to improve for Medicare patients despite, or because of, the introduction of the prospective payment system with its accompanying professional review organization review. 
4	Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris. To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil. 
5	Mutations of the ras proto-oncogenes in childhood monosomy 7. ras gene mutations are the most frequent molecular changes found in the preleukemic syndromes of adults and may play a role in initiating these diseases and in their progression to acute leukemia. However, little is known about the incidence or importance of these genetic mutations in childhood myeloproliferative states (MPS). The bone marrow (BM) monosomy 7 syndrome accounts for a large percentage of childhood MPS. Although the duration of the MPS is quite variable, children with monosomy 7 eventually develop acute myeloid leukemia (AML). We investigated 20 children (13 with MPS, 7 with AML) with BM monosomy 7 or 7q- for the presence of ras gene mutations using the polymerase chain reaction and hybridization with mutation-specific oligonucleotides. Mutations of N-ras and K-ras were detected in three children. Two patients carrying a ras mutation were in the myeloproliferative phase, and one had acute leukemia. All three patients with ras mutations either died of their disease or relapsed after BM transplantation as compared with 8 of 17 without ras mutations. However, this difference is not statistically significant (P = .14, not significant). We conclude that ras mutations are observed in childhood monosomy 7, though less frequently than in adult MDS, and may play a limited role in the progression of this disease to acute leukemia. More patients are needed to address the prognostic role of ras mutations in this rare disease. 
1	Vitamin E and cancer prevention. Some animal experiments and human studies suggest that vitamin E may protect against cancer. Serum alpha-tocopherol concentration was studied for its prediction of cancer in a cohort of 36,265 adults in Finland. During a mean follow-up of 8 y, cancer was diagnosed in 766 persons. The levels of serum alpha-tocopherol were determined from stored serum samples (at -20 degrees C) taken from these cancer patients and from 1419 matched control subjects. Individuals with a low level of alpha-tocopherol had about a 1.5-fold risk of cancer compared with those with a higher level. The strength of the association between serum alpha-tocopherol level and cancer risk varied for different cancer sites and was strongest for some gastrointestinal cancers and for the combined group of cancers unrelated to smoking. The association was strongest among nonsmoking men and among women with low levels of serum selenium. The findings agree with the hypothesis that dietary vitamin E in some circumstances protects against cancer. 
1	Pericardial metastasis from testicular seminoma: appearance and disappearance by echocardiography. At the time of initial diagnosis, testicular malignancy is usually limited to the testicle and infradiaphragmatic lymph nodes. Metastases initially follow the retroperitoneal lymph channels and subsequently extend to the supradiphragmatic lymph nodes in the mediastinum and supraclavicular fossa. Testicular metastases to the pericardium are rare and usually asymptomatic. These lesions are most commonly identified at autopsy; therefore, the actual incidence is unknown. The authors report a 32-year-old man with testicular carcinoma, who developed asymptomatic pericardial metastases without concomitant supradiaphragmatic nodal or pulmonary metastases. They review the efficacy of echocardiography in diagnosis and follow up or pericardial metastasis. 
4	Superior protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium. Clinical study in comparison with St. Thomas' Hospital solution. The protective effect of low-calcium, magnesium-free potassium cardioplegic solution on ischemic myocardium has been assessed in adult patients undergoing heart operations. Postreperfusion recovery of cardiac function and electrical activity was evaluated in 34 patients; 16 received low-calcium, magnesium-free potassium cardioplegic solution (group I) and 18 received St. Thomas' Hospital solution, which is enriched with calcium and magnesium (group II). There were no significant differences between the two groups in age, sex, body weight, and New York Heart Association functional class. Aortic occlusion time (107.3 +/- 46.8 minutes versus 113.6 +/- 44.3 minutes), highest myocardial temperature during elective global ischemia (11.5 degrees C +/- 3.1 degrees C versus 9.3 degrees C +/- 3.2 degrees C), and total volume of cardioplegic solution (44.2 +/- 20.5 ml/kg versus 43.4 +/- 17.6 ml/kg) were also similar in the two groups. On reperfusion, electrical defibrillation was required in four cases (25.5%) in group I and in 15 cases (83.3%) in group II (p less than 0.005), and bradyarrhythmias were significantly more prevalent in group II (6.3% versus 44.4%; p less than 0.05). Serum creatine kinase MB activity at 15 minutes of reperfusion (12.3 +/- 17.0 IU/L versus 42.6 +/- 46.1 IU/L; p less than 0.05) and the dose of dopamine or dobutamine required during the early phase of reperfusion (1.8 +/- 2.5 micrograms/kg/min versus 6.1 +/- 3.3 micrograms/kg/min; p less than 0.0002) were both significantly greater in group II. Postischemic left ventricular function, as assessed by percent recovery of the left ventricular end-systolic pressure-volume relationship in patients who underwent aortic valve replacement alone, was significantly better in group I (160.4% +/- 45.5% versus 47.8% +/- 12.9%; p less than 0.05). Serum level of calcium and magnesium ions was significantly lower in group I. Thus low-calcium, magnesium-free potassium cardioplegic solution provided excellent protection of the ischemic heart, whereas St. Thomas' Hospital solution with calcium and magnesium enabled relatively poor functional and electrical recovery of the heart during the early reperfusion period. These results might be related to differing levels of extracellular calcium and magnesium on reperfusion. 
4	Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris. A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05). Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes. 
5	Choroid plexus cysts and chromosomal defects During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts. 
4	Immediate and follow-up results of balloon angioplasty of postoperative recoarctation in infants and children. The purpose of this article is to present immediate and follow-up results of balloon angioplasty of aortic recoarctations following previous surgery in infants and children. During a 45-month period that ended in June 1989, nine infants and children, ages 6 months to 7 years, underwent balloon angioplasty of recoarctation with resultant reduction in peak-to-peak systolic pressure gradient from 52 +/- 20 mm Hg (mean +/- SD) to 16 +/- 8 mm Hg (p less than 0.001) and increase in coarctation segment size from 3.4 +/- 1.4 mm to 6.1 +/- 1.6 mm (p less than 0.01). None required surgical intervention. There were no significant complications. Follow-up catheterization (16 +/- 7 months) data in six children and follow-up clinical (17 +/- 6 months) data in all children were available for review. Both the residual coarctation pressure gradient (6 +/- 6 mm Hg) and coarctation segment size (8.2 +/- 2.4 mm) remain improved (p less than 0.001) when compared with pre-balloon angioplasty values and the pressure gradient fell further (p less than 0.01) when compared with that measured immediately after balloon angioplasty. None developed restenosis, although one child required surgical relief of severe narrowing of isthmus of the aortic arch. None developed aneurysms. On the basis of this experience and that reported in the literature and because of high morbidity and mortality rates associated with repeat surgery for postoperative recoarctation, we recommend balloon angioplasty as the procedure of choice for relief of postoperative recoarctation with significant hypertension. 
2	Urinary tissue factor activity in colorectal disease. Procoagulant activity (PCA) in normal urine has been recognized for over 50 years. Although tissue factor (TF) is produced by certain tumours, and is increased in both tumour-associated macrophages and blood monocytes, the possibility that it might also be increased in urine has not been studied in patients with cancer. We have measured urinary PCA in hospital controls without inflammatory or neoplastic disease (n = 79), in patients with rheumatoid arthritis (n = 8), inflammatory bowel disease (n = 19), colorectal cancer (n = 70) and in patients undergoing colonoscopy (n = 50). Urinary PCA was higher (P less than 0.001) in patients with colorectal cancer and inflammatory bowel disease than controls or patients with rheumatoid arthritis. Fourteen (88 per cent) out of 16 colonoscopy patients subsequently found to have carcinoma or inflammatory bowel disease had levels above the control upper quartile, compared with 8 (24 per cent) out of 34 with normal colonoscopy (P less than 0.001). TF inhibitors confirmed the nature of the PCA and Western blotting studies indicated a urinary TF molecular weight of approximately 38,000. These studies provide further evidence of abnormal haemostasis in malignancy and suggest that determination of urinary TF may provide a useful screening test in patients undergoing colonoscopy. 
4	Efficacy of celiprolol in the elderly hypertensive patient. With the rapidly increasing average age of the population of the Western world, care and treatment of the elderly are becoming increasingly important. Cardiovascular diseases are major causes of death and disability in the elderly; hence, identification of cardiovascular risk factors and effective treatment are essential. Evidence indicates that these risk factors in the elderly are similar to those in the young; namely, high blood pressure, hyperlipidemia, glucose intolerance, hyperfibrinogenemia, obesity, and cigarette smoking. The latter two relate to general patient management, whereas the remainder can be significantly influenced by modern drug therapy such as celiprolol. This drug is a third-generation highly selective beta 1-adrenoceptor antagonist with beta 2-agonist and vasodilatory activity giving a unique and advantageous pharmacologic profile for antihypertensive therapy with particular benefits for the elderly. The impact of therapy with celiprolol on the cardiovascular risk factors in the elderly hypertensive patient is reviewed. 
5	Aerobic and anaerobic microbiologic factors and recovery of beta-lactamase producing bacteria from obstetric and gynecologic infection. Specimens obtained from 736 patients with obstetric and gynecologic infections were studied for aerobic and anaerobic bacteria. Bacterial growth was present in 714 specimens. These included 53 specimens of infected fallopian tubes, 470 of infected endometrium, 94 of infected amniotic fluid, 57 of aspirates of cul-de-sacs in instances of pelvic inflammatory disease, 14 labial and vaginal abscesses and 26 of Bartholyn's cyst abscess. A total of 2,052 isolates (2.9 per specimen), 1,139 anaerobes (1.6 per specimen) and 913 aerobic or facultative (1.3 per specimen) were recovered. The most commonly isolated anaerobic bacteria was Bacteroides species (566 isolates), which included Bacteroides bivius (151), Bacteroides fragilis group (130), Bacteroides melaninogenicus group (110) and Bacteroides ureolyticus (47). Others included an anaerobic gram-positive cocci (391), Clostridium species (48) and Fusobacterium species (36). The most frequently recovered aerobic and facultative bacteria were Lactobacillus species (169), Escherichia coli (85), Neisseria gonorrhoeae (62), Staphylococcus aureus (59) and Group B streptococcus (55). Three hundred and sixty-five (18 per cent) of the isolates recovered from 276 (39 per cent) patients were beta-lactamase producing organisms (BLPO); 222 (61 per cent) anaerobes and 143 (39 per cent) aerobes or facultatives. The most common BLPO were B. fragilis group, B. bivius, B. melaninogenicus, B. disiens, Enterobacteriaceae and S. aureus. These data illustrate the polymicrobial nature and important role of BLPO in obstetric and gynecologic infection. 
4	Postoperative hypertension: a prospective, placebo-controlled, randomized, double-blind trial, with intravenous nicardipine hydrochloride. Nicardipine hydrochloride, a new calcium channel blocker for intravenous use, has been compared with placebo in a prospective, randomized, double-blind trial on postoperative hypertension. Of 175 patients who signed preoperative consent, 24 (13.7%) met entry criteria. Hypertension was significantly better controlled in nicardipine-treated patients compared with those receiving placebo (93% versus 30%, p less than 0.05). All the placebo failures were subsequently successfully treated with nicardipine. There were no significant complications in either group. The authors conclude that nicardipine HC1 is an effective, safe therapy for postoperative hypertension. Further studies are now indicated comparing it with other drugs currently used to treat this condition. 
5	Muscle biopsy for diagnosis of malignant hyperthermia susceptibility in two patients with severe exercise-induced myolysis. Muscle biopsy and in vitro contracture tests for diagnosis of susceptibility to malignant hyperthermia (MH) were performed in two patients who had developed fever and severe myolysis during exercise. MH susceptibility was confirmed in one patient, but in the other, exercise-induced heat stroke proved to be the correct diagnosis. Clinical presentation and epidemiology of exercise-induced MH and its relation to the heat stroke syndrome are discussed. 
4	Orbitozygomatic temporopolar approach for a high basilar tip aneurysm associated with a short intracranial internal carotid artery: a new surgical approach. For two cases of a high basilar tip aneurysm accompanied by a short intracranial internal carotid artery, the orbitozygomatic temporopolar approach consisting of an en bloc fronto-orbitozygomatic temporal craniotomy and temporopolar approach was carried out. On angiograms, the height of the bifurcation of an elongated basilar artery and the length of the intracranial internal carotid artery from the interclinoid line between the anterior and posterior clinoid process were 20 mm and 6 mm in Case 1, and 18 mm and 5 mm in Case 2, respectively. The skin flap was separated subfascially to preserve the frontotemporal branch of the facial nerve. The fronto-orbitozygomatic temporal bone flap was made, and a part of the basal bony structures of the orbital roof, the sphenoid ridge, and the temporal bone were removed. The basilar tip aneurysm could be seen and clipped easily by upward and oblique viewing from below through the wide operative space consisting of the less retracted internal carotid and middle cerebral arteries, the oculomotor nerve, the tentorial hiatus, and the emptied anterior temporal fossa obtained by partial division of the temporal bridging veins. The operative procedure is presented in detail and compared with other surgical approaches that have been described previously. 
3	Fractures of the clivus: classification and clinical features. Fractures of the clival complex were diagnosed in a series of 17 patients admitted to the Maryland Institute for Emergency Medical Services System and the University of Maryland Medical System over a 30-month period. These fractures were divided pathologically into three types based upon their appearance on computed tomography: longitudinal, transverse, and oblique. The mechanisms of injury were similar in all groups, and the Glasgow Coma Scale scores at admission were comparable, regardless of fracture type, in survivors and nonsurvivors. Longitudinal fractures were associated with severe injury to the central nervous system and with brain stem infarction, and 4 of 6 (67%) of these patients died. Transverse fractures of the clival complex were found in 6 patients, 3 of whom (50%) died. All of these patients had fractures of the petrous ridge; 2 of the 3 survivors had multiple cranial nerve deficits, and one patient developed a carotid-cavernous fistula. Of the 5 patients with oblique clival fractures, 2 survived (40%), both of whom had multiple cranial nerve palsies; in addition, one of these patients developed a carotid-cavernous fistula. Using the present generation of computed tomographic scanners, fractures of the clival complex can be reliably diagnosed; they are probably more common than previously believed and can be separated into three groups based on the characteristics on computed tomographic scans and clinical findings. 
2	Perianal abscess and fistula-in-ano in children. The authors present a retrospective review of 40 pediatric patients with perianal abscess and/or fistula-in-ano. The total patient population could be divided clinically into 2 broad groups. The first group consisted of 22 infants younger than 2 years of age, all of whom were males, and 10 of whom presented with recurrences after previous incision and drainage. Of the 14 infants presenting with an abscess, in 12 (85.7 percent), a fistula-in-ano was discovered at surgery. In contrast, in the group of 18 children older than 2 years of age, there were 7 females and 11 males, and fistulas were identified in only 7 of 13 patients (54.8 percent) who presented with abscesses. Surgical treatment consisted of examination under anesthesia and a diligent search for a fistulous tract. Abscesses were primarily saucerized and fistulotomy and cryptotomy of the confluent crypt was performed if a fistulous tract was identified. The only recurrences with this form of treatment occurred in the two immunocompromised patients. 
4	High blood cholesterol in elderly men and the excess risk for coronary heart disease. OBJECTIVE: To determine whether high blood cholesterol is an important risk factor for mortality from coronary heart disease in elderly men. DESIGN: Cohort study with a mean follow-up of 10.1 years. SETTING: A health maintenance organization. PATIENTS: The cohort included 2746 white men 60 to 79 years of age who had no self-reported history of coronary heart disease. MEASUREMENT AND MAIN RESULTS: A total of 260 deaths occurred during 27,842 person-years of follow-up. The relative risk for mortality from coronary heart disease in men 60 to 79 years of age in the highest serum cholesterol quartile was 1.5 (95% CI, 1.2 to 2.0) compared with those in the three lower quartiles combined. The relative risk did not change greatly with age, ranging from 1.4 in men 60 to 64 years of age to 1.7 in men 75 to 79 years of age. However, because mortality from coronary heart disease increased with age, the excess risk for such mortality attributable to elevated serum cholesterol levels increased fivefold over these 20 years, from 2.2 deaths per 1000 person-years to 11.3 deaths per 1000 person-years. CONCLUSIONS: Our results support those of other observational studies in elderly men. If treatment of high blood cholesterol is as effective in reducing cholesterol-related risk for coronary heart disease after 65 years of age as it is in middle-aged men, it might actually produce greater reductions in mortality due to coronary heart disease. A clinical trial is needed to confirm this extrapolation. 
1	Trisomy 13: a new recurring chromosome abnormality in acute leukemia. A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias. 
4	Correlation dimension of heartbeat intervals is reduced in conscious pigs by myocardial ischemia. A reduced standard deviation of RR intervals (SDRR) predicts increased mortality in groups of survivors of myocardial infarction. Like SDRR, the correlation dimension (D2) describes variation within a sampled time series, but uniquely it reveals 1) the epoch's geometric structure and 2) the degrees of freedom of the generator. These unique features may be more sensitive predictors of mortality than SDRR. We developed a new algorithm for estimating D2 (i.e., the "point-D2"), tested it with known data, and found that it had greater accuracy for finite data than other published algorithms. Analysis of RR intervals from eight conscious pigs undergoing acute occlusion of the left anterior descending coronary artery revealed a drop in the point-D2 from a control mean and standard deviation of 2.50 +/- 0.81 to 1.58 +/- 0.64 during the first minute of ischemia (p less than 0.01) and to 1.07 +/- 0.18 during the last minute preceding ventricular fibrillation (p less than 0.01). Partial occlusions (50-90% reduction of coronary blood flow) evoked point-D2 reductions only 25-30% of control (p less than 0.01). The point-D2 means were correlated between pigs with the magnitude of the respiratory sinus arrhythmia (p less than 0.01), but during ischemia this correlation was replaced by one between the standard deviation of the point-D2s and SDRRs. Because the simultaneous reduction in the mean point-D2 and its standard deviation to 1.07 +/- 0.18 occurred in every case, was unique to the few minutes preceding ventricular fibrillation, and never reached these low values during other conditions in which it was reduced, we conclude that the point-D2 may be an accurate prospective predictor of mortality within the individual subject. 
4	Similar time course of ST depression during and after exercise in patients with coronary artery disease and syndrome X. To assess whether the time course of ST segment depression differs in patients with coronary artery disease and patients with angina and normal coronary arteries, the exercise tests of 54 patients with documented coronary artery disease and 25 patients with syndrome X (angina, positive exercise test, no evidence of coronary artery spasm, and normal coronary arteries) were compared. All tests were performed with therapy withheld, using the modified Bruce protocol. In each test, time, heart rate and blood pressure were measured at the onset and at 1 mm of ST segment depression, and at peak exercise. Recovery (return of the ST segment to baseline +/- 0.2 mm) time was also assessed. Peak ST segment depression was similar in coronary artery disease and syndrome X patients (1.5 +/- 0.3 versus 1.6 +/- 0.4 mm). In 42 coronary artery disease patients, ST segment depression developed early (less than or equal to 6 minutes) during exercise; this was associated with a short recovery (less than or equal to 3 minutes) in 17 (40%) and with a long recovery (greater than 3 minutes) in 25 (60%) patients. In 17 patients with syndrome X, ST segment depression developed early; it was associated with a short recovery in six (35%) and with a long recovery in 11 (65%) patients. Late (greater than 6 minutes) onset of ST segment depression was observed in 12 coronary artery disease patients; of these, eight (67%) had a short recovery and 4 (33%) had a long recovery. Late onset of ST segment depression occurred in eight patients with syndrome X; six (75%) had a short recovery and two (25%) had a long recovery. 
3	Otolaryngologic management of patients with subdural empyema. From 1979 to 1988, 17 patients presented to Duke University Medical Center for treatment of subdural empyema. Empyemas were caused by sinusitis in 53% of the patients and by otitis media in 12%. None of those with otologic causes required mastoid drainage, while all patients with sinus infections required sinus drainage. External frontoethmoidectomies were associated with a lower incidence of frontoethmoid re-exploration (P = 0.048), and antrostomies with a lower incidence of maxillary re-exploration (P = 0.111), than were more limited drainage procedures. Sinus drainage performed simultaneously with neurosurgical drainage reduced the incidence of sinus re-exploration (P = 0.167), neurosurgical reexploration (P = 0.048), and length of hospitalization (P = 0.020). 
3	Spirochetal infection of the central nervous system. Four spirochetal diseases frequently involve the central nervous system: syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. In particular, syphilis and Lyme borreliosis are increasing problems. During the spirochetemic phase there is seeding of the nervous system. After a quiescent latent period, there may be late disease flareups producing a variety of neurologic syndromes. Cerebrospinal fluid examination is very helpful in these infections. 
3	Subarachnoid hemorrhage caused by a fungal aneurysm of the vertebral artery as a complication of intracranial aneurysm clipping. Case report. Intracranial aneurysms are an uncommon manifestation of fungal infection. A case is described in which the formation of an aneurysm followed an intracranial intraoperative Aspergillus infection attributable to a long period of preoperative antibiotic medication and immunosuppressive therapy with steroids. 
3	Bacterial meningitis in neonates and children. A high index of suspicion of meningitis is needed when evaluating neonates and young infants because clinical findings can be minimal and are often subtle and nonspecific. Analysis of the CSF constitutes the most effective method to document meningeal bacterial infection, although overlap with normal CSF values can occur, especially in newborns and very young infants. The introduction of highly active third-generation cephalosporins (ceftriaxone, cefotaxime) and their safety and efficacy in treating a broad array of bacterial pathogens that cause meningitis in all age groups has simplified selection of initial antibiotic therapy. In neonates, however, conventional antibiotic therapy with ampicillin and an aminoglycoside is appropriate because of its proven record of safety and efficacy, and because routine use of cephalosporins in the hospital nursery could lead to selection of resistant strains among gram-negative enteric bacilli. Despite the availability of modern intensive care management of infants and children with bacterial meningitis and the advent of potent antibiotics, case fatality rates and morbidity remain high. Because of this, recent research has focused on the complex interaction between bacteria and the host and on means to attenuate the meningeal inflammatory response. The clinical benefits demonstrated recently with the use of dexamethasone therapy in infants and children with bacterial meningitis underscore the importance of anti-inflammatory therapy to reduce audiologic and neurologic sequelae. Future studies of new methods to modulate meningeal inflammation such as the use of monoclonal antibodies directed against cytokines or of agents that interfere with leukocyte-endothelial interactions are indicated. The implication of routine H. influenzae type b immunization in young infants with the conjugated vaccines and optimal intrapartum prophylaxis against group B streptococcal disease in newborns will have an important impact on the incidence of meningitis in infants and children. 
5	Parathyroid hormone secretion and target organ response in experimental acute pancreatitis. To determine changes in parathyroid hormone secretion and target organ response caused by acute pancreatitis before the development of systemic toxic conditions, experimental acute pancreatitis was induced in rats with a choline-deficient, ethionine-supplemented diet. After 7 days, the rats were weighed and bled, and one kidney was assayed for 25-hydroxyvitamin D1 hydroxylase activity. Several manifestations of pancreatitis were observed in rats given the diet: weight loss (from 29.6 to 26.3 g vs that for control rats, from 29 to 52.8 g) and lower dietary intake (15.5 vs 47 g per rat per 7 days). Serum amylase levels fell from 1794 to 350 U/L in rats given the choline-deficient, ethionine-supplemented diet compared with levels of 1800 to 2100 U/L in control rats. The pancreases of rats given the choline-deficient, ethionine-supplemented diet showed degeneration, necrosis, and hemorrhaging. Serum levels of calcium, phosphorus, chloride, and parathyroid hormone did not change significantly throughout the experiment. Renal 25-hydroxyvitamin D1 hydroxylase activity was higher than in control rats (8.9 +/- 0.8 vs 7.6 +/- 0.6 fmol/mg of kidney per minute). Acute pancreatitis in this experimental animal model does not alter serum levels of calcium and parathyroid hormone or reduce target organ responsiveness to the hormone. 
1	Detection of HTLV-I proviral sequences in CD30-positive large cell cutaneous T-cell lymphomas. To investigate the possibility that cutaneous T-cell lymphomas of large cell type may be associated with human T-cell leukemia/lymphoma virus type I infection in nonendemic regions, tissue samples from six cases of large cell cutaneous T-cell lymphoma and four cases of small cell cutaneous T-cell lymphoma were screened for the presence of integrated proviral human T-cell leukemia/lymphoma virus type I DNA. Combined use of Southern blot hybridization and enzymatic DNA amplification revealed human T-cell leukemia/lymphoma virus type I-specific sequences in all cases of large cell cutaneous T-cell lymphoma and in none of the cases of small cell cutaneous T-cell lymphoma. These results suggest that in nonendemic areas, a significant proportion of large cell cutaneous T-cell lymphoma cases are associated with human T-cell leukemia/lymphoma virus type I. 
5	Opioids in cerebrospinal fluid in hypotensive newborn pigs. This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. Closed cranial windows were used to determine pial arteriolar diameter. Periarachnoid cortical and cisterna magna CSF was collected from piglets during normotension and hypotension (systemic arterial pressure decreased from 63 +/- 1 to 33 +/- 1 mm Hg). Opioid profiles were assessed qualitatively by radioreceptor assay, and individual opioids were measured quantitatively by radioimmunoassay. Periarachnoid cortical and cisterna magna CSF methionine enkephalin-, leucine enkephalin-, dynorphin-, and beta-endorphin-like receptor active values all were increased by hypotension. When quantified by radioimmunoassay, periarachnoid cortical CSF values for methionine enkephalin-like immunoreactivity were 1,167 +/- 58 and 2,975 +/- 139 pg/ml for normotension and hypotension, respectively. Periarachnoid cortical CSF radioimmunoassay values for dynorphin-like immunoreactivity were 15 +/- 2 and 28 +/- 2 pg/ml for normotension and hypotension, respectively. When applied topically to the cortical surface, synthetic methionine enkephalin increased pial arteriolar diameter (134 +/- 4, 158 +/- 4, and 163 +/- 4 microns for control, 574 pg/ml [10(-10) M], and 5,740 pg/ml [10(-9) M], respectively). Similarly, topical synthetic leucine enkephalin and dynorphin elicited pial arteriolar dilation. However, beta-endorphin produced arteriolar constriction. Hypotension attenuated methionine and leucine enkephalin-induced dilation and reversed dynorphin-induced dilation to concentration-dependent constriction. beta-Endorphin-induced constriction was not changed by hypotension. Therefore, opioids could contribute to the control of the cerebral circulation during hypotension. 
1	Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases. Between 1979 and 1988, 26 patients with pulmonary metastases from adult soft-tissue sarcomas were treated with Adriamycin (doxorubicin hydrochloride), Cytoxan (cyclophosphamide), and DTIC before metastasectomy. Thirty-eight thoracotomies were performed with postoperative complications in 5 patients (5/38, 13.2%) and one postoperative death (1/38, 2.6%). Two patients had benign lesions at thoracotomy and were excluded from further survival analysis. The median survival of the remaining 24 patients after thoracotomy was 18.5 +/- 5.9 months, and the actuarial 5-year survival was 22%. Five patients (5/24, 21%) achieved a clinically complete response with preoperative chemotherapy, but all had recurrence in the lung and underwent resection of pulmonary metastases. Seven patients (7/24, 29%) achieved a partial response and had residual disease resected at thoracotomy. Twelve patients (12/24, 50%) showed either no change or disease progression while receiving chemotherapy and were referred for resection. Postthoracotomy disease-free survival and postthoracotomy overall survival did not differ significantly between the three groups. One patient in the group showing no change or progression of disease while receiving chemotherapy is alive without recurrence 57 months after initial pulmonary metastasectomy. Chemotherapy can be used for the initial treatment of pulmonary metastases from adult soft-tissue sarcomas. However, survival after resection of pulmonary metastases cannot be accurately predicted based on the clinical response to preoperative chemotherapy. 
5	A palmar dermatosis linked to occult carcinoma of the upper thorax, head and neck: Bazex's syndrome and tripe palm. An unusual, persistent, corregated-to-honeycombed thickening of the palms accompanied by tenderness around the fingernails was found to be a cutaneous marker for internal malignancy. This combination of signs and symptoms has been reported under two clinical entities: Bazex's syndrome and tripe palm. This paraneoplastic syndrome is of interest to head and neck surgeons due to the location of the primary tumor, the site of metastatic disease, and the ability to cure the cutaneous disease by surgical removal of the primary tumor. In our patient, a squamous cell carcinoma of the lung not detectable on chest x-ray presented as a cervical mass accompanied by cutaneous changes on the palms and fingernails. Recognition of the relationship of the dermatologic changes to malignancy of a specific body region eventually led to the detection of the primary tumor. The characteristics of these paraneoplastic syndromes were reviewed in this report. 
5	Left atrial to femoral arterial bypass using the biomedicus pump for operations of the thoracic aorta. Left atrial to left femoral arterial bypass is an approach to operations of the thoracic aorta dating back to the late 1950s. Since that time, various modifications of the basic bypass circuit have evolved. In addition, temporary bypass shunts have also been described in a variety of positions. The goals of bypass of the thoracic aorta regardless of the technique include prevention of distal hypoperfusion, which can lead to paraplegia, limb loss, multiple organ failure, and sometimes death. Recently, there have been reports of the use of the biomedicus centrifugal pump in bypass circuits of the thoracic aorta. Our series, as well as the success of others, using this variation of a traditional bypass circuit of the thoracic aorta, establishes the biopump's capability of minimizing inherent complications in the bypass circuit. 
4	Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina BACKGROUND. Serotonin, a major product of platelet activation, has potent vasoactive effects in animal models, but its role in human coronary artery disease remains largely speculative. METHODS. Using quantitative coronary angiography, we compared the effects of the intracoronary infusion of graded concentrations of serotonin (10(-7) to 10(-4) mol per liter) on coronary vessels in two groups of patients with different clinical presentations of coronary disease (nine with stable angina and five with variant angina), with the effects in a control group of eight subjects with normal vessels on angiography. RESULTS. Normal coronary vessels had a biphasic response to intracoronary serotonin: dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4) mol per liter. Vessels in patients with stable angina constricted at all concentrations, with mean (+/- SEM) maximal decreases in diameter of 23.9 +/- 3.6, 33.1 +/- 3.9, and 41.7 +/- 3.1 percent from base line in proximal, middle, and distal segments at a serotonin concentration of 10(-4) mol per liter. Smooth segments constricted more than irregular segments (42.0 +/- 4.6 vs. 21.1 +/- 1.6 percent). Four patients with stable angina had a marked reduction in collateral filling. All the patients with stable angina had angina during the intracoronary infusion of serotonin, and electrocardiographic changes were noted in six. All the patients with variant angina had angina, electrocardiographic changes, and localized occlusive epicardial coronary-artery spasm at concentrations of 10(-6) (n = 2) or 10(-5) (n = 3) mol per liter. CONCLUSIONS. Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels. Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina. These findings suggest that serotonin, released after the intracoronary activation of platelets, may contribute to or cause myocardial ischemia in patients with coronary artery disease. 
1	Evaluation of the results of oesophagectomy for oesophageal cancer. The long-term results of standard techniques of oesophagectomy were examined in 127 patients with squamous cell carcinoma of the oesophagus. A near-total oesophagectomy with a cervical anastomosis was performed in 93 patients and an oesophagogastrectomy with an intrathoracic anastomosis was carried out in 34 patients. One hundred and eight patients had a curative oesophagectomy and 19 patients had a palliative resection. Eight patients received radiotherapy to the tumour bed. There were 15 deaths in hospital and the overall 5-year survival rate including perioperative deaths was 13.2 per cent. Survival was adversely affected by incomplete excision of macroscopic tumour (P less than 0.001), positive regional lymph nodes (P less than 0.05) and distant lymphatic metastases (P less than 0.02). The 5-year survival rate of patients with tumour invasion beyond the oesophageal wall (T3) and negative nodes was 20 per cent. Postoperative irradiation had no effect on the survival of patients with gross residual tumour. Complete clearance of microscopic tumour was achieved in 50 per cent of patients with T3 tumours and this group did not benefit from adjuvant radiotherapy. Survival in patients undergoing curative oesophagectomy with residual microscopic tumour, however, was significantly improved by irradiation of the tumour bed (P less than 0.01). These results suggest that the survival of patients can be increased significantly by the excision of all gross tumour and by identification of those who will benefit from local radiotherapy. 
4	Metabolic activity in the areas of new fill-in after thallium-201 reinjection: comparison with positron emission tomography using fluorine-18-deoxyglucose. Reinjection of thallium-201 after recording the 3-hr delayed scan often demonstrates improvement in areas of persistent abnormalities. To determine the metabolic activity of these areas, the changes seen on stress/redistribution/reinjection thallium SPECT were compared with PET using fluorine-18-fluorodeoxyglucose (FDG) in 18 patients with coronary artery disease. Of 48 segments showing no redistribution on the delayed scan, the reinjection scan identified new fill-in in 20 segments (42%), all of which demonstrated FDG uptake. In contrast, only 7 of the 28 segments (25%) showing no fill-in after reinjection were PET viable (p less than 0.01). Eleven patients had coronary bypass graft surgery after the radionuclide study. The majority of the segments showing redistribution (87%) and new fill-in after reinjection (65%) improved in wall motion, whereas only eight segments (25%) without new fill-in improved after surgery. Of those without new fill-in, two segments showing PET ischemia improved in wall motion, whereas the remaining six segments showing PET scar did not improve after surgery. Thus, the segments showing new fill-in after reinjection are PET viable myocardium. However, reinjection thallium imaging still underestimates the extent of tissue viability compared to PET imaging. 
1	Intradural chordoma of the tentorium cerebelli. Case report. A rare case of intradural chordoma is described. The literature contains seven examples of intradural extraosseous chordoma, all reported in a ventral location. This is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra- and infratentorial compartments. 
4	Effects of dipyridamole and aminophylline on hemodynamics, regional myocardial blood flow and thallium-201 washout in the setting of a critical coronary stenosis. Experiments were performed to characterize the interaction of intravenous dipyridamole and aminophylline on thallium-201 transport kinetics, regional myocardial blood flow and systemic hemodynamics in the presence of a critical coronary artery stenosis. In 12 dogs with a critical left anterior descending coronary artery stenosis, arterial pressure decreased from a mean value (+/- SEM) of 107 +/- 6 to 94 +/- 3 mm Hg (p less than 0.05) and distal left anterior descending artery pressure decreased from 70 +/- 7 to 55 +/- 4 mm Hg (p less than 0.05) after intravenous administration of dipyridamole (0.25 mg/kg body weight). In the left anterior descending perfusion zone, the endocardial/epicardial flow ratio decreased from 0.70 to 0.36 and the intrinsic thallium washout rate was significantly prolonged. Intravenous aminophylline (5 mg/kg) reversed the dipyridamole-induced systemic hypotension and transmural coronary steal and restored the thallium washout rate to baseline values. In six other dogs, aminophylline alone resulted in no alterations in systemic and coronary hemodynamics or regional myocardial blood flow. As expected, dipyridamole-induced vasodilation and coronary steal were prevented by aminophylline pretreatment. These data show that in a canine model of partial coronary stenosis, systemic hypotension, adverse regional flow effects (coronary steal) and prolonged thallium-201 washout consequent to intravenously administered dipyridamole are promptly reversed by intravenous aminophylline administration. Aminophylline alone had no significant hemodynamic and coronary flow effects. This study provides further insight into the altered thallium kinetics occurring as a consequence of dipyridamole-induced vasodilation and suggests that the prompt reversal of symptoms and signs of ischemia with aminophylline in patients receiving intravenous dipyridamole for clinical imaging studies probably reflects the reversal of transmural coronary steal. 
5	Chromosomal abnormalities in myelodysplastic syndromes and acute myeloid leukemia. Clonal chromosome abnormalities are found in more than half the patients with hematologic malignancies. Karyotype is an independent prognostic factor in these patients. Cytogenetic findings correlate significantly with morphologic, immunologic, and clinical features as well as response to treatment, remission duration, and survival. The number of different cytogenetic abnormalities is enormous; however, many cytogenetic findings frequently occur in a given disease (e.g., abnormalities of 5 or 7 in 75% to 90% of patients with therapy-related AML). Some abnormalities are found only in myeloid malignancies, for example, the t(8;21)(q22;q22) and rearrangements of chromosome 16q22, both of which have a good prognosis. Other abnormalities usually are found in both myeloid and lymphoid malignancies, for example, the t(4;11)(q21;q23) and t(9;22)(q34;q11), both of which have a poor prognosis. The Human Gene Mapping Conferences have compiled much cytogenetic data and produced several interesting correlations in myeloid malignancies: rearrangements of 3q21-26 with myeloid proliferations associated with environmental exposure (similar to abnormalities of 5q, 7q, 12p, and 17q), aberrations of 12p, 11q13 and 11q23 with both myeloid and lymphoid disorders, and the lack of myeloid involvement and abnormalities of chromosomes 14 and 18. In conclusion, cytogenetic analysis of neoplastic cells at diagnosis for patients with MDS, AML, and SAML is required for appropriate diagnosis and treatment. The use of chromosome abnormalities to separate patients into high- and low-risk groups eventually may allow us to be more effective in selecting curative therapy. 
5	Chest pain in teenagers. When is it significant? Chest pain in teenagers often has no obvious organic cause. Onset of symptoms with an emotionally stressful situation may indicate psychogenic chest pain. The differential diagnosis also includes cardiac, musculoskeletal, gastrointestinal, and respiratory disorders. Routine testing generally does not help to establish a diagnosis and may even do harm by reinforcing a patient's unspoken fear of serious illness. Most teenagers with chest pain have no such illness, and symptoms usually resolve without therapy. An important role for primary care physicians is to provide support during evaluation and follow-up. 
3	Aqueductal (pencil) glioma presenting as neurogenic pulmonary edema: a case report. A case of neurogenic pulmonary edema due to hydrocephalus, without initial neurological deficit, is described. Computed tomography demonstrated a ring enhancing lesion in the tectum of the mesencephalon obstructing the aqueduct of Sylvius. The lesion, on autopsy, was a rare mesencephalic glioma described in the literature as a "pencil glioma" of the aqueduct. 
4	Selective prolongation of QRS late potentials by sodium channel blocking antiarrhythmic drugs: relation to slowing of ventricular tachycardia. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial (ESVEM) Investigators. Sodium channel blocking antiarrhythmic drugs have preferential effects on diseased, slowly conducting myocardium, and slowing of tachycardia caused by these drugs may result primarily from further prolongation of conduction time in slowly conducting tissue. In patients with sustained ventricular tachycardia, late potentials detected by signal-averaged electrocardiography (ECG) are thought to arise from slowly conducting ventricular myocardium. This study tested the hypothesis that sodium channel blocking drugs selectively prolong the late potential, or terminal low amplitude signal, portion of the signal-averaged QRS complex and that prolongation of the late potential would correlate with slowing of ventricular tachycardia. Fifty-six drug trials in 32 patients with spontaneous and inducible ventricular arrhythmias were studied. Prolongation of the late potential (11 +/- 15 ms) was significantly greater than prolongation of the initial portion of the QRS complex (4 +/- 9 ms) (p = 0.01). Selective prolongation of the late potential by drugs resulted in significantly greater QRS prolongation detectable by signal-averaged ECG than by standard ECG (p less than 0.0001). In 40 trials in which ventricular tachycardia remained inducible during drug therapy, the increase in induced tachycardia cycle length correlated strongly with the increase in late potential duration (p = 0.005) but not with change in the initial portion of the QRS complex. These data suggest that in patients with ventricular tachycardia, sodium channel blocking antiarrhythmic drugs have preferential effects on slowly conducting tissue and that drug effect on slowly conducting tissue contributes to prolongation of ventricular tachycardia cycle length. 
4	Use of magnetic resonance imaging in the diagnosis of cortical blindness in pregnancy. Magnetic resonance imaging (MRI) may be helpful in the assessment of eclampsia and preeclampsia with central nervous system symptomatology such as cortical blindness. We describe a rare case of complete binocular blindness postpartum with no other neurologic deficits, in which MRI abnormalities were undetected on computed tomography. The better soft-tissue discrimination of MRI may visualize important but subtle lesions which ultimately may help to explain the underlying pathophysiologic mechanism in such cases. 
1	Primary adenocarcinoma of the urinary bladder. A clinicopathologic analysis of 72 cases. Adenocarcinomas account for approximately 2% of primary epithelial malignancies of the urinary bladder. The clinicopathologic features of 72 cases treated at one institution are reported; 22 cases were evaluated immunohistochemically. Twenty-four tumors were urachal and 48 nonurachal. The cases were analyzed according to their stage at presentation, histologic type, and mucin staining; they were tested immunohistochemically to determine their reaction to carcinoembryonic antigen, Leu-M1, prostate-specific antigen, and prostatic acid phosphatase. Tumor stage was a highly significant predictor of outcome (P = 0.001). Nonurachal tumors tended to have a worse outcome than urachal, but the difference was not statistically significant (P = 0.07). Histologic type was not a significant predictor of outcome (P = 0.10). For adenocarcinoma of the urinary bladder, stage was the most significant predictive factor; separating urachal from nonurachal tumors was important, but mucin histochemistry and immunohistochemistry did not help in this distinction. On occasion, a few tumors may react with some polyclonal antibodies to prostate-specific antigen; thus these results must be interpreted with caution. In these instances, the possibility of using highly sensitive and specific monoclonal antibodies such as the one employed in this study should be considered. 
4	Diagnosis and evaluation of renovascular hypertension. Indications for therapy. Renovascular hypertension is caused by two distinct conditions with different causes, fibromuscular dysplasia and atheroma. Diagnosis of the former is both simpler and more rewarding, whereas atheromatous lesions of the renal artery may be secondary to essential hypertension. It is therefore important to establish existence of functional renal ischemia as well as an anatomical lesion. Universal screening of all hypertensive patients is not recommended because of the relatively low prevalence of the disease and insufficient accuracy of available screening tests. When renovascular hypertension is clinically suspected, an oral captopril test is the most reliable office screening test. After this, digital subtraction angiography with renal vein renins or captopril renography are appropriate steps. However, the latter procedure, while promising, requires further evaluation. Duplex scanning of the renal arteries also comes into this category. Arteriography is done last, so that if renal ischemia is indicated, angioplasty can be attempted at the same time as arteriography. 
3	Concomitant neurocysticercosis and brucellosis. A young Mexican woman had headache and left arm weakness develop shortly after immigrating to the United States. A solitary cerebral cysticercus was found at surgery, but, instead of the expected finding of clear fluid, the cyst contained pus from which Brucella melitensis was cultured. Although the patient had no signs or symptoms suggestive of brucellosis, agglutination studies revealed IgM and IgG antibodies consistent with active brucellosis. Clinicians should be alert to the possibility of multiple infections in immigrants from countries where parasites and bacteria that are uncommon in the United States are endemic. 
5	Influence of untreated chronic plastic iridocyclitis on intraocular pressure in leprosy patients. The intraocular pressures of a total of 286 eyes of patients with lepromatous and borderline lepromatous leprosy who never had regular ophthalmological care or local eye treatment were measured. The patients were categorised according to the type of leprosy they had, and the eyes were categorised as without or with chronic plastic iridocyclitis. In patients with lepromatous and borderline lepromatous types of leprosy the intraocular pressure was significantly lower in eyes with chronic plastic iridocylitis 10.1 (3.6) mmHg than in both unaffected eyes 11.0 (3.2) mmHg and control eyes 13.5 (2.5) mmHg. It has been shown that chronic plastic iridocyclitis which remains untreated for years results in a lower intraocular pressure than normal. 
1	Prognostic implications of DNA histogram, DNA content, and histologic changes of regional lymph nodes in patients with lung cancer. Forty-six cases of resected lung cancer, including 20 cases at Stages I and II and 26 cases at Stage III (N2), were subdivided into two groups: a good prognosis group with a longer survival period and a poor prognosis group in which the patients died earlier of the cancer. From paraffin-embedded lymph node tissues of these patients, the authors examined DNA histogram pattern and DNA content, using flow cytometry, and histologic hyperplasia of germinal center and paracortical area; they also evaluated their correlation with the prognosis. In the good prognosis group at Stages I and II, paracortical hyperplasia (PH) of the lymph nodes was observed significantly more frequently. In the good prognosis group at Stage III, the incidence of PH, G2M phase in the DNA histograms, and DNA content were all significantly higher. DNA content was positively correlated with the grade of PH. 
1	Expression of major histocompatibility complex class II antigens and interleukin-1 by epithelial cells of Warthin's tumor. The immunoreactivity for class II antigens of the major histocompatibility complex and interleukin-1 (IL-1) in Warthin's tumor (WT) cells was studied. In addition to macrophages, dendritic cells, and capillary endothelia, the luminal tumor cells and some keratinocytes in the metaplastic squamous foci exhibited immunoreactivity for both class II antigens and IL-1. The distribution of the class II antigens in the luminal tumor cells was limited to their basolateral membrane. These data, together with previous findings, strongly suggest that the luminal tumor cells of WT introduce the luminal antigen to the underlying lymphoid tissue and, thus, act as an antigen-presenting cell. 
4	Determinants and significance of diltiazem plasma concentrations after acute myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. A total of 1,975 plasma diltiazem concentrations were obtained from 1,067 patients enrolled in a multicenter secondary intervention study of diltiazem after acute myocardial infarction. To evaluate the determinants and significance of diltiazem concentrations in this patient population, we related drug concentrations to a variety of clinical variables recorded on the case history forms. Multiple linear regression analysis showed that (1) time from the last drug dose, (2) drug dose taken, (3) patient height (an index of lean body weight), and (4) patient age were important determinants of plasma concentration. For an equivalent dose, plasma diltiazem concentrations in a 75-year-old patient were about double those of a 25-year-old patient. Total weight and drug dose prescribed did not significantly affect plasma concentrations. Whereas drug concentrations were higher (p = 0.01) among patients with left-sided heart failure, they were not altered by renal dysfunction, hepatic disease or beta blockers. Diltiazem concentrations were a significant determinant of diastolic arterial pressure (p less than 10(-9), but neither systolic pressure nor heart rate were significantly related to diltiazem concentration. The overall incidence of adverse experiences was not related to drug concentrations, but the occurrence of second- and third-degree atrioventricular block in the coronary care unit and the need for a temporary pacemaker were substantially higher among patients with a drug concentration greater than 150 ng/ml (7.4 and 1.9%, respectively) than among patients with lower concentrations (2.6% for atrioventricular block, 0.3% for pacemaker; p = 0.02 for each). The risk of atrioventricular block was particularly increased by high diltiazem concentrations in the face of acute inferior infarction. These results suggest that diltiazem's pharmacologic and clinical effects in a large population are concentration-related, and that the consideration of patient size, age, and left ventricular function in selecting a diltiazem dose may allow for effective drug therapy with a reduced likelihood of adverse effects. 
1	Limitation of transcatheter arterial chemoembolization using iodized oil for small hepatocellular carcinoma. A study in resected cases. The radiologic and histologic findings are presented of the resection of 14 small hepatocellular carcinomas (HCC), less than 2 cm in maximum diameter, after transcatheter arterial chemoembolization (TCE) using iodized oil. The effect of TCE on small HCC depended on the morphologic type of the tumors. When no extracapsular invasion of tumor cells occurred, TCE was extremely effective against encapsulated tumors. However, in nine of the 14 resected specimens, viable tumor cells remained in or around the tumor. The authors suggest that small HCC are not always curable with TCE alone and that a multi-disciplinary approach is necessary for patients with small HCC. 
4	Bronchiolar morphology after systemic arterial interruption. To assess ischemic lesions as a factor in obliterative bronchiolitis after lung transplantation, the authors severed the left bronchial arteries of 15 dogs, together with the left stem bronchus, the latter being immediately reanostomosed. They examined the bronchioles at weekly interfals up to three and a half months. On the week chosen each dog was anesthetized, totally heparinized, and exsanguino-perfused with saline. Just after heart arrest, the thoracic aorta was injected with a barium solution until this white medium appeared in the bronchial arteries. The heart-lung blocs were excised en bloc, submitted to soft-tissue x ray, fixed, and then sliced to 1 cm. Corresponding right and left 5-mm-thick samples of these slices were prepared for contact microradiography followed by histologic 5-to-20-micron-thick, stained, correlated specimens. For two weeks the left bronchial arteries remained empty, but there was no necrosis or edema. Between two and four weeks barium solution appeared in the bronchial arteries, and the bronchiolar epithelium had become multistratified. Later the left bronchiangiogram became similar to the right, but there were more folds of the mucosa and a little submucosal fibrosis. These studies provide proof that no significant ischemic lesions occurred during repermeation of the bronchiolar vascular bed. Ischemia, if existent, is not a significant factor in obliterative bronchiolitis. 
3	Laparoscopic ventrosuspensions. A review of 72 cases. Laparoscopic ventrosuspension is simple to perform after diagnostic laparoscopy. Serious postoperative complication is unlikely. However, patient follow-up over 6 months has not confirmed the usefulness of laparoscopic ventrosuspension in the management of deep dyspareunia or pelvic pain in association with a retroverted uterus. The success rate of laparoscopic ventrosuspension at 6 months varies from 18.6% to 46.5%. The prior use of a Hodge pessary does not predict the success of laparoscopic ventrosuspension. 
4	Infective endocarditis and an embolomycotic aneurysm in a 25-month-old child. Infective endocarditis in young children is uncommon, especially where there is no underlying structural heart disease. While septic embolization in adults occurs in up to 43% of the cases of endocarditis, there is little data on systemic embolization in cases of children. We present an unusual case of a 25-month-old child with infective endocarditis and an embolomycotic aneurysm treated by mitral valve replacement and aortoiliac reconstruction. 
4	Retinal arterial macroaneurysms: risk factors and natural history. A case control study was conducted to identify the systemic and ocular risk factors for retinal arterial macroaneurysms. Forty-three patients with 52 photographically confirmed macroaneurysms were located. Forty-three age-matched, race-matched concurrent control patients were also identified. The patients with macroaneurysms had decreased visual acuity (p less than 0.0001) and a higher prevalence of hypertension (p = 0.037), female sex (p = 0.099), and retinal vein occlusions (p = 0.055) than controls. In patients with both a macroaneurysm and venous occlusion there was a 12.0 times higher prevalence of macroaneurysms in the area of retina drained by the occluded vein (p less than 0.05). Common findings associated with macroaneurysms included retinal haemorrhage (81% of patients), retinal exudate (70%), vitreous haemorrhage (30%), macular involvement (30%), and distal arteriolar narrowing (26%). Arteriolar occlusion occurred spontaneously (8%) or after laser photocoagulation (16%). 
4	Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study. To determine whether associations of elevated resting pulse rate with CHD incidence or death in white men are independent of other risk factors and whether such associations exist for women and blacks, data were examined from the NHANES I Epidemiologic Follow-up Study. Over a follow-up period of 6 to 13 years, elevated RR for CHD incidence were found for older white men with baseline pulse greater than 84 beats/min compared with less than 74 beats/min after controlling multiple risk factors (RR = 1.37, 95% CL 1.02, 1.84). Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also elevated for white men with elevated pulse rate independent of other risk factors. CHD incidence was increased in white women with elevated pulse rate. Risks of death from all causes, cardiovascular diseases, and noncardiovascular diseases, were also elevated for white men with elevated pulse rate independent of other risk factors. CHD incidence was increased in white women with elevated pulse rate. Risk of death from all causes and cardiovascular diseases was elevated in black men and women with elevated pulse rate. Risk of death from noncardiovascular disease was elevated in black men with elevated pulse rate. The association with cardiovascular death was particularly striking in black women, even after adjusting for baseline risk factors (RR 3.03, 95% CL 1.46, 6.28). Further studies are needed to assess associations of pulse rate with CHD in blacks and to elucidate mechanisms in all groups. 
5	Achieving pH control in the critically ill patient: the role of continuous infusion of H2-receptor antagonists. Stress-related gastric mucosal damage is a common occurrence in intensive care unit (ICU) patients. Because of the significant morbidity and mortality associated with this mucosal damage, many ICU patients routinely receive prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs). Gastric acid secretion occurs in a circadian pattern, with late afternoon and evening surges. H2RAs by continuous infusion may control this uneven pattern of secretion more effectively than H2RAs given by bolus injection. More studies are needed to identify the target ICU population for prophylactic treatment. 
5	Managing prostatitis in the elderly. Bacterial prostatitis is primarily a disease of elderly men, and it is the most common urinary tract infection seen in this age group. Urosepsis from prostatitis or prostatic abscess occurs less frequently than with urological manipulation, but must always be considered in elderly men with prostatitis. This article focuses on the diagnosis and antibiotic treatment of bacterial prostatitis in the elderly. 
1	Esthesioneuroblastoma with intracranial extension. The authors present five cases of olfactory neuroblastoma with intracranial extension operated on in the Department of Neurosurgery in collaboration with otorhinolaryngologists. This tumor is most frequently reported as growing inside the nasal cavities, and it can extend to the paranasal sinuses. Cases presenting initially as intracranial tumors have been infrequently reported. At present, histological diagnosis of this tumor is aided by the use of electron microscopy and immunocytochemistry. Total resection combined with radiation therapy remains the most satisfactory treatment. 
4	Assay of serum cardiac myosin heavy chain fragments in patients with acute myocardial infarction: determination of infarct size and long-term follow-up. To evaluate the correlation between myosin heavy chain release and the necrosis mass, serum levels of myosin heavy chain fragments were determined serially in 55 patients with acute myocardial infarction. Eight of these patients were successfully treated with thrombolytic agents: the others were not treated. The same myosin titration was applied to the sera of 25 dogs with an experimental myocardial infarction. Six of the dogs were successfully treated with thrombolytic agents. The time courses of the myosin concentrations are typical and monophasic for all patients with a noncomplex myocardial infarction. The values for the kinetic parameters of myosin release are comparable to those previously reported. We have now determined that cumulative myosin release significantly correlates with cumulative creatine kinase (CK), CK-MB, and lactate dehydrogenase release, as well as with thallium-201 distribution, as determined for different patient groups. Thrombolytic treatment does not seem to qualitatively upset myosin kinetics. The results obtained in dogs with or without thrombolysis conclusively indicate that myosin release is a quantitative index of the necrosis mass. From a practical point of view, a few serial determinations of serum levels of myosin heavy chains are enough to estimate the necrosed mass in patients with acute myocardial infarction. More generally, serum myosin titration could be useful in detecting any cardiac disturbance involving myocardial injury resulting in membrane leakage of cardiac cells. 
1	Vimentin expression appears to be associated with poor prognosis in node-negative ductal NOS breast carcinomas. Vimentin expression in tumors from 83 node-negative and 112 node-positive patients with infiltrative ductal not otherwise specified (NOS) breast carcinomas has been compared with 5-year survival. For node-negative, but not for node-positive patients, there was a significant inverse relation between vimentin expression and survival. Five-year survival of node-negative patients with vimentin-positive tumors was significantly worse compared with vimentin-negative tumors (P less than 0.0001). In the node-negative group, only 36% of patients with vimentin-positive tumors but 82% of patients with vimentin-negative tumors survived 5 years. Tumors of all eight node-negative patients with ductal NOS cancer who died in the first 27 months expressed vimentin. Multivariate analysis of the node-negative group showed a strong correlation of vimentin expression and overall survival, but weak and not significant correlation between histologic grade or size and overall survival at 5 years. Thus vimentin expression seems to be a strong indicator of poor prognosis in node-negative ductal NOS breast carcinomas. 
1	Trends in female breast cancer in Connecticut and the United States. Trends for female breast cancer were examined by age, period and cohort for the years 1950-1984 in U.S. mortality. Connecticut mortality and Connecticut incidence. Birth cohort patterns were evident for all three sets of data. The results confirm a continuing increase in invasive breast cancer by providing evidence of a strong birth cohort pattern, over a time series of 90 years of birth cohorts. This trend appears to be real for the most part because of the cohort patterns and because there is minimal underdetection in data obtained by autopsy and blind biopsy. Secondly, when cohort modeling is applied to breast cancer mortality, there is an indication of a modest decline in recent breast cancer mortality (in the face of an apparent long-term increase), which suggests that control of breast cancer mortality may have developed in recent decades, perhaps through earlier detection and improved treatment. Finally, in contrast with a prior report, there is little evidence for a clinically important difference in time trend between pre- and postmenopausal breast cancer. 
4	Late effects of treatment for Wilms' tumor. A report from the National Wilms' Tumor Study Group. The National Wilms' Tumor Study (NWTS) was initiated in 1969. One of its objectives was to modulate treatments according to risk factors to minimize the number and severity of treatment-related short-term and long-term iatrogenic complications. The NWTS has therefore incorporated a Long Term Follow-up Study (LTFS) within its framework to monitor late effects. The LTFS is confined to relapse-free survivors alive 5 years or longer after initial surgery, and data are collected using specifically designed forms. A total of 787 patients registered on NWTS-1 or NWTS-2 (1969 to 1979) were eligible, of whom 680 (86%) were available for analysis regarding musculoskeletal, cardiovascular, and neuropsychologic status, and the presence of benign and malignant tumors. Patients with early-stage disease who were treated with radiation had scoliosis reported, along with other musculoskeletal abnormalities (32 versus 2), nearly seven times as often as did the members of the cohort population who did not undergo radiation (35 of 57 versus 5 of 53, respectively). The difference in cardiovascular problems recorded in survivors who did and did not receive Adriamycin (Adria Laboratories, Columbus, OH) (2.4 versus 1.1 per 100-person years at risk) had borderline statistical significance (P = 0.06). No excess in neuropsychologic events was reported for those given the neurotoxin vincristine. When considering patients with disease of all stages, all 5 second malignant tumors occurred in the 623 patients who underwent radiation (RT patients); benign tumors were also more frequent in RT patients than in those patients who did not undergo radiation (41 of 486 or 8% versus 4 of 194 or 2%). Continuing study of this unique body of patients is needed, especially for those given Adriamycin, because of the known long interval needed for latent cardiomyopathy to become clinically manifest in some patients. 
5	IL-2-PE40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. A number of different immunotherapeutic reagents are currently being developed to target IL-2R for the treatment of leukemia, graft rejection, and certain autoimmune diseases. Previously, we have shown that IL-2-PE40, a chimeric protein composed of human IL-2 linked to the N-terminus of a truncated form of Pseudomonas exotoxin (PE), could effectively kill a variety of cell lines in vitro expressing either low, intermediate, or high affinity IL-2R. Here, we demonstrate that IL-2-PE40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of EL4J murine thymoma cells transfected with the p55 murine IL-2R. The transfected line, EL4J-3.4, expresses 1,000 to 3,000 high affinity IL-2R. Survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post-tumor injection in both athymic nude and C57BL/6 mice. Similarly, the growth of an aggressive s.c. solid tumor could also be inhibited. Extension of survival was not achieved either by using the truncated toxin alone not attached to IL-2 or by using an IL-2-PE40Asp553 mutant lacking a functional toxin. Survival extension was not caused by IL-2 activated NK or other host effector mechanisms as IL-2-PE40 was unable to prevent the receptor-negative EL4J parental line from forming a lethal ascites or a solid tumor. Thus, IL-2-PE40 is a potent, specific cytolytic reagent that may prove useful in the arsenal of anti-IL-2R immunotherapeutics. 
4	Reliability of death certificate diagnoses. Consistency between death certificates and clinical records from 5 general hospitals in Kuwait was studied for 470 deaths with the following underlying or associated causes: hypertensive (HYP), ischaemic heart diseases (IHD), cerebrovascular diseases (CVD) and diabetes mellitus (DM). Direct causes were not considered since they are of little interest analytically. Only deaths with definite or most probable ascertainment were included. One cardiologist, who was provided with the WHO criteria and relevant documents on death certification, independently reviewed the records. To test the reviewer's bias and the reliability of his judgement, an adjudication process was effected by having one senior cardiologist re-review a random subsample of 140 records. The two reviewers showed good agreement. Specific diagnoses criteria for deciding the underlying cause of death in multiple morbid conditions by the reviewer were followed. Due to possible reviewer bias, we aimed at measuring the difference between initial certifiers and the reviewer rather than measuring the diagnostic accuracy of initial certifiers in reference to the reviewer. The agreement index kappa showed poor agreement between original and revised certificates. The original certificates under-estimated CVD as an underlying cause of death by 69.2%, DM by 60%, IHD by 33.5% and HYP by 31.8% in our sample. Associated causes were also consistently under-estimated by initial certifiers as compared with the reviewer. This bias calls for basing mortality statistics in Kuwait on hospital death committees' reports rather than on initial certifier death certificates, use of multiple-causes of death instead of one underlying cause and adequate training of the medical profession on the value and process of death certification. 
1	Definitive mandibular replacement using reconstruction plates. Mandibular defects following radical cancer surgery continue to provide challenges to head and neck surgeons. Twenty-seven patients with advanced oral cancer underwent primary mandibular replacement with metal reconstruction plates without the use of bone. Twenty-one patients (78%) had successful reconstruction with primary soft tissue healing. Six patients required removal of the plate in the postoperative period. Two of these patients had their reconstruction plates replaced as a secondary procedure following soft tissue healing. Thus, 23 of 27 patients (85%) had final mandibular reconstruction and were followed for an average of 19 months. Functional and cosmetic results were satisfactory. For patients with advanced disease, this technique compares favorably with microvascular transfer in terms of operating time and donor defect. Despite problems with plate exposure, the initial and overall success rates of 78% and 85%, respectively, make the use of these plates a reasonable choice for immediate reconstructive needs in patients with difficult tumors. 
3	Intracranial hypertension in relation to memory functioning during the first year after severe head injury. The relationship between intracranial hypertension and residual memory deficit after closed head injury was evaluated using the 6-month and 1-year neurobehavioral outcome data obtained by the Traumatic Coma Data Bank. Intracranial pressure was analyzed using the percentage of time that it exceeded 20 mm Hg and the maximum value recorded during the first 72 hours after injury. Memory measures included recall of word lists, prose recall, and visual memory for designs that were obtained 6 months (n = 149) and 1 year (n = 132) after injury. Intracranial hypertension occurred in more than half of the Traumatic Coma Data Bank cohort who met the criteria for the neurobehavioral follow-up study. Linear regression analysis disclosed an effect of elevated intracranial pressure on some, but not all, measures of memory at 6 months, whereas the results were negative for the 1-year follow-up examination. We conclude that the elevation of intracranial pressure exerts little if any effect on later memory functioning, and that any effect it does have diminishes over 1 year in survivors of severe head injury. 
3	Xenon-enhanced computed tomographic measurement of cerebral blood flow in patients with chronic subdural hematomas. We compared clinical symptoms with extent of brain shift on computed tomographic (CT) scans and quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced CT scans in 10 patients with chronic subdural hematomas. Five patients had only headache and minimal or no brain shift on a CT scan. The other five had hemiparesis and/or mental disturbance in addition to headache and moderate or severe brain shift on a CT scan. The mean hemispheric CBF decreased about 7% in patients with headache and about 35% in patients with hemiparesis and/or mental disturbance. It decreased also on the side without the hematoma. The CBF reduction was always more pronounced in the putamen and thalamus than in the cortex. On the contrary, the cortex CBF was mostly preserved or even elevated in both groups of patients. We speculate that CBF reduction in patients with a chronic subdural hematoma occurs initially in central cerebral areas like the basal ganglia and thalamus, and then extends to the entire hemisphere including the cortex as brain compression and displacement progress. Central cerebral area involvement might be more responsible for clinical symptoms than the cortex. 
2	Scintigraphic measurement of oropharyngeal transit in man. Scintigraphic studies of the oropharyngeal transit of a liquid bolus were performed in 15 healthy controls, 12 patients with symptoms of oral-pharyngeal dysphagia, and 13 patients with neuromuscular disease, who did not have dysphagia. Gamma camera imaging of the head, neck, and upper thorax was undertaken, in the lateral projection, during the swallowing of the radiolabeled bolus of water. Inspection of summed images permitted the selection of regions of interest (ROI) to represent the mouth, pharynx, and upper esophagus. Transit times between each ROI were calculated and compared. Significant prolongation of bolus transit time between the mouth and esophagus was present in both patients with and without dysphagia (0.59 +/- 0.38 sec and 0.33 +/- 0.7 sec; mean +/- SD, respectively) compared with controls (0.26 +/- 0.04 sec P less than 0.001, P less than 0.01, respectively, Mann-Whitney U test). Repeat studies in 25 individuals indicated that the transit measurements were more reproducible between swallows in normal subjects than in patients with symptoms. Deglutitive scintigraphy provides a noninvasive technique for the quantitative study of swallowing and its disorders. 
3	Refractory hypoglycemia secondary to topical salicylate intoxication. We describe a case of severe refractory hypoglycemia secondary to topical salicylate intoxication. A 72-year-old man with psoriasis and end-stage renal disease was treated with a topical cream containing 10% salicylic acid. The patient presented with encephalopathy and subsequently developed hypoglycemia refractory to infusions of large amounts of glucose. A serum salicylate concentration was elevated at 3.2 mmol/L. Emergent hemodialysis was accompanied by rapid lowering of serum salicylate concentration and resolution of refractory hypoglycemia. Salicylate is well absorbed across normal and diseased skin. Salicylate markedly impairs gluconeogenesis and increases glucose utilization, resulting in hypoglycemia. To our knowledge, this is the first article on hypoglycemia due to the application of topical salicylate. 
5	Coronary collateral recruitment: functional significance and relation to rate of vessel closure. Studies in animals and humans have demonstrated the anatomic presence and functional significance of coronary collaterals. The extent of collateralization varies among species and among individuals. Collateral vessels are usually adequate for preserving resting regional and global ventricular function in the face of coronary obstruction. During stress, however, collateral supply may be inadequate. Collateral development is a time-dependent process during both the initial occlusion and following transient reflow and reclosure. Therefore when a previously collateralized coronary occlusion is recanalized and then recloses, the extent of the resulting collateral recruitment will depend, at least in part, upon the period of reflow between the two occlusions. The longer the reflow period, the less enhanced will be the collateralization. This is illustrated in the cases presented and has also been demonstrated in animal studies. The exact mechanisms for this recurrent collateral recruitment need further study. 
5	Early inappropriate secretion of antidiuretic hormone after trans-sphenoidal pituitary adenomectomy. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a rare but life-threatening complication of trans-sphenoidal pituitary adenomectomy. It has previously only been described as a late phenomenon. We report an early presentation within the first week. The pathophysiology, clinical features and treatment are discussed. 
1	Intrarectal ultrasonography in rectal cancer staging and in the evaluation of pelvic disease. Clinical uses of intrarectal ultrasound. Accurate preoperative staging of a rectal cancer patient may impact heavily on subsequent management. This study attempts to evaluate the accuracy of intrarectal ultrasonography (IRUS) in staging rectal cancers compared to clinical and pathologic examination. In addition the accuracy of IRUS was assessed in a group of patients with uncertain pelvic-perirectal disease after a negative physical examination. In a prospective manner, 52 cancer patients were staged with digital exam and IRUS. Accuracy rates were 48% and 83%, respectively, compared to pathologic evaluation in assessing wall penetration, and IRUS identified positive lymph nodes in 12 of 17 cases. In patients with pelvic disease, IRUS corresponded with pathologic diagnosis in 15 of 17 cases and revealed new information in 6 patients. Intrarectal ultrasonography appears to be the most accurate imaging technique for staging rectal cancers and demonstrates promise in the evaluation of perirectal-pelvic disease. 
1	Significance and treatment of positive margins or seminal vesicle invasion after radical prostatectomy. The periprostatic soft-tissue involvement described in the older urologic literature differs from that now recognized; a much "earlier" pathologic stage C is being identified. Apparent microscopic extension of the cancer to the margin of the specimen yields an approximately 25% risk of local recurrence. Postoperative radiation apparently is effective in reducing this risk, and if patients are properly selected, such treatment is well tolerated. Whether adjuvant radiation affects overall survival is not known. New observations on pathologic extension of the disease need to be refined. 
4	CR leads in cardiac emergencies. A preliminary study. The purpose of this study was to find a set of simplified electrocardiographic (ECG) leads that would be useful in cardiac emergencies. In 27 ambulatory cardiac patients and in 15 patients admitted to the hospital, we found that ECG records obtained with six bipolar CR leads were, in most respects, similar to records obtained previously in the same patients with six V leads. Records obtained with two abdominal-upper extremity leads, tested as possible alternatives to limb leads 2 and 3, were quite similar to records obtained with leads 2 and 3 in patients with an inferior wall infarction. Records obtained with leads CR7, CR8, and CR9 in a patient with a posterior wall infarction revealed a QS pattern that was not seen in the conventional 12-lead hospital record. In patients with anterolateral and inferior myocardial infarctions and in patients with unstable angina, the diagnostic patterns recorded with 11 bipolar leads described in this report were identical to patterns recorded with 12-lead ECGs. Although a larger number of observations, including patients with arrhythmias, would be required to reach a definitive conclusion, our results provide preliminary evidence that cardiac potentials may be adequately analyzed by using only two electrodes, using CR and abdominal leads, in succession. The technique described in this report, in which the reference electrode is attached to the right arm, and the exploring electrode is moved successively over nine preselected chest sites and over the umbilicus, can be completed in less than 3 minutes in a given patient, and provides records that are comparable to those obtained with the conventional 12-lead system. 
4	Long-term results of catheter ablation of idiopathic right ventricular tachycardia Ten consecutive patients with recurrent episodes of symptomatic, idiopathic, sustained monomorphic ventricular tachycardia (VT) originating in the right ventricle underwent an attempt at catheter ablation of the ventricular tachycardia. There were seven women and three men, with a mean age of 39 +/- 14 years (+/- SD). None of the patients had any evidence of structural heart disease. The VT had a left bundle branch block configuration and an inferior axis in each patient, and the mean cycle length was 313 +/- 75 msec. Based on the methods of induction of the VT and the response of the VT to verapamil, the VT mechanism was presumed to be reentry in six patients, triggered activity in three patients, and catecholamine-sensitive automaticity in one patient. Sites for ablation were guided by pace mapping, and an appropriate target site was identified in the right ventricular outflow tract in each patient. From one to three shocks of 100-360 J (mean total, 336 +/- 195 J) were delivered from a defibrillator between the tip of the ablation catheter (cathode) and a patch electrode on the anterior chest (anode). An electrophysiology test 7-9 days after ablation demonstrated that VT was still inducible in only one patient, who was treated with amiodarone. One other patient had a recurrence of VT 3 weeks after ablation and was treated with verapamil. Eight of 10 patients were not treated with antiarrhythmic medications and have had no episodes of symptomatic VT during 15-68 months of follow-up (mean follow-up, 33 +/- 18 months). There were no acute or long-term complications. 
1	The use of L-dopa and carbidopa in metastatic malignant melanoma. A combination of L-dopa and carbidopa was given orally to 17 patients with metastatic melanoma. Maximum tolerated oral doses were given, up to 4 grams daily. No response was seen in 15 patients evaluable for response. Toxicity was considerable, with seven of 17 patients (41%) stopping treatment because of unacceptable gastrointestinal toxicity or postural hypotension. Contrary to previous anecdotal reports, there was no evidence that L-dopa/carbidopa treatment resulted in accelerated progression of metastatic melanoma. Orally administered L-dopa/carbidopa is ineffective as therapy for advanced melanoma when maximum tolerated doses are used. 
1	Benign cystic teratoma manifested as an umbilical hernia. We have reported a case of dermoid tumor manifested as an umbilical hernia. Resection led to complete recovery. 
1	Management of primary nonrenal parenchymal malignancies with vena caval thrombus. We report our experience with the management of 7 primary nonrenal parenchymal malignancies with vena caval tumor thrombus. Included are 3 cases of adrenal cortical carcinoma and 1 each of transitional cell carcinoma, embryonal cell testicular carcinoma, pheochromocytoma and primary small cell carcinoma of the lung with metastases to the kidney. Surgical treatment and followup are presented, as well as a review of the literature. An aggressive surgical approach is warranted because prolonged survivals free of disease are possible. 
5	A comparison of induction and maintenance therapy for acute nonlymphocytic leukemia in childhood: results of a Pediatric Oncology Group study. Two hundred fifty-six children with previously untreated acute nonlymphocytic leukemia (ANLL) were evaluated on a Pediatric Oncology Group (POG) phase III randomized trial of both induction and continuation chemotherapies. Induction therapy compared vincristine, cytarabine, and dexamethasone (VADx) with daunorubicin, cytarabine, and thioguanine (DAT). The complete remission (CR) rate using DAT was superior (82% v 61%, P = .02). Postremission therapy consisted of either "standard" two-cycle therapy or a more intensive four-cycle regimen given for 2 years. Overall, there was no difference in outcome for patients randomized to either continuation regimen. The overall complete continuous remission rate (CCR) for the "best" induction/continuation therapy combination at 2 years was .50 (SE = .06), at 3 years was .35 (.04), and at 4 years was .34 (.05). Analysis of selected clinical and laboratory parameters demonstrated differences in induction responses favoring DAT induction but did not impact eventual disease-free survival. There were two subgroups of patients who responded better to four-cycle continuation therapy. These were patients with French-American-British (FAB) M1/M2 (2-year CCR was .20 v .44, P = .01) and patients older than 10 years at diagnosis (.32 v .62, P = .004). 
5	Adjunctive use of beta-adrenergic blockers, calcium antagonists and other therapies in coronary thrombolysis. The availability of thrombolytic agents for use in the treatment of acute myocardial infarction is an important step in the management of a common, often debilitating, and potentially lethal disorder. However, despite the proven benefits of coronary thrombolysis, the importance of adjunctive treatment modalities is being increasingly recognized. Beta-adrenergic blockers, calcium antagonists, nitrates, magnesium, and angiotensin-converting enzyme inhibitors each exert favorable cardiovascular properties that may offer additional benefits. Clinical trials combining thrombolytic and adjunctive pharmacologic agents offer hope for further advances in the treatment of acute myocardial infarction. 
4	Angiographic contrast media interference with laser-induced fluorescence excitation and detection in atherosclerotic human coronary arteries. Laser-induced fluorescence has been used in conjunction with angiography for laser angioplasty guidance. The effect of radiopaque contrast media on the excitation and detection of arterial fluorescence has not been previously reported. Accordingly, fluorescence emission spectra from human coronary artery necropsy specimens (n = 7) during excitation with pulsed excimer laser excitation (308 nm) was examined before and after the addition of three different contrast media, sodium and meglumine diatrizoate, sodium and meglumine ioxaglate, and iopamidol. A decrease in overall fluorescence intensity was observed at all wavelengths for each contrast agent examined. The decrease in intensity of fluorescence emission was more marked at wavelengths less than 410 nm than at wavelengths above 425 nm. Similar effects were observed for contrast media diluted with whole blood. Absorption spectra for all three contrast media demonstrated absorption in the ultraviolet centered around 240 nm. We conclude that preferential absorption in the ultraviolet range by contrast media interferes with the excitation and detection of laser-induced fluorescence; use of visible light excitation may obviate interference with laser-induced fluorescence analysis of plaque. 
2	The role of sphincteroplasty for fecal incontinence reevaluated: a prospective physiologic and functional review. Sixteen female patients (mean age 54.1 years; range 34-74 years) with a 9.8-year (range 1-25 years) history of incontinence to solid stool underwent overlapping sphincteroplasty with internal sphincter imbrication without fecal diversion. All patients were prospectively evaluated with preoperative anorectal manometry, electromyography, and pudendal nerve motor latency assessment, postoperative anorectal manometry, and preoperative and postoperative functional evaluation. Mean and maximal resting pressures increased from 30 mm Hg and 49 mm Hg preoperatively to 40 mm Hg and 57 mm Hg, respectively, postoperatively. Likewise, mean and maximal squeeze pressures increased from 27 mm Hg and 48 mm Hg preoperatively to 39 mm Hg and 73 mm Hg, respectively, postoperatively (P less than 0.01). Furthermore, anal canal high pressure zone length was increased by sphincteroplasty from a mean of 0.9 cm (range 0-3 cm) to a mean of 2.1 cm (range 1-4 cm). These objective physiologic improvements correlated well with subjective functional improvement. Subjectively, functional outcome was rated by patients as excellent in 38 percent, good in 38 percent, fair in 19 percent, and poor in only 5 percent of cases. Overlapping sphincteroplasty with internal sphincter imbrication improves both the anal sphincter physiologic profile and fecal continence. 
5	Italian experience of voice restoration after laryngectomy with tracheoesophageal puncture. This report concerns 102 cases of tracheoesophageal puncture performed as a means of secondary voice restoration after total laryngectomy, in 70 patients proving unable to learn esophageal speech and as a treatment of choice in a further 32 cases. Complications arose in 21 cases but were generally minor and could be overcome. Results were favorable in 45 of 70 and 29 of 32 cases, respectively. The method was considered effective, particularly when supported by the patient's determination to learn a verbal communication method. 
2	Transient renal acidification defect during acute infantile diarrhea: the role of urinary sodium. We studied urinary acidification daily during the hospital course of 16 infants with acute gastroenteritis and metabolic acidosis. Urine pH value on admission was higher than 5.5 in 14 (87%) patients. We hypothesized that inappropriate urinary acidification was due to sodium deficiency and inadequate sodium delivery to the distal nephron. Forty-one urinary samples were collected during metabolic acidosis. The mean pH of 24 urine samples with sodium concentration less than 10 mmol/L was significantly higher than the pH of 17 samples with sodium concentration greater than 10 mmol/L (6.04 +/- 0.06 vs 5.19 +/- 0.1; p less than 0.001). The urine ratios of titratable acid to creatinine and of total acidity to creatinine were significantly higher in urine samples containing more sodium (p less than 0.02), whereas the ammonium/creatinine ratio was not. After administration of furosemide or correction of the sodium deficit, appropriate acidification was observed. We conclude that impaired urinary acidification is frequently found during metabolic acidosis in infants with acute gastroenteritis and results from a sodium deficit rather than from transient distal renal tubular acidosis. 
5	Intra-arterial urokinase as the initial therapy for acutely ischemic lower limbs Acute ischemia of the lower limb remains a significant risk to both life and limb. Mortality rates of approximately 10-30% and amputation rates of the same magnitude in the survivors are repeatedly reported despite advances in medical and surgical techniques. Our experience, which utilized percutaneous intra-arterial thrombolysis as the initial treatment in 72 instances (63 patients), has resulted in a markedly lower mortality rate of 1.6% and a lower amputation rate of 8.5% in the survivors. Careful categorization by clinical degree of ischemia indicates that 82% of the cases were either threatened or irreversible limb ischemia. The initial treatment with thrombolysis did not preclude subsequent prompt surgical treatment when necessary; in these cases, thrombolysis promoted improved surgical results (100%) when it was successful. It markedly reduced the need for urgent surgery, usually simplified the subsequent surgical approach, diminished the overall need for surgery, and often accomplished a successful outcome alone (31%). Significant bleeding was not noted during subsequent surgical procedures and was noted in only 2.8% of the cases. Confirmation of these results and further improvements in technique might justify the use of an initially high-dose urokinase transcatheter infusion regimen as the initial treatment of choice for acute lower-limb ischemia. 
5	Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. 110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation. 
2	Nonmucous glycoproteins as pronucleating agents. Cholesterol crystallization-promoting factors probably play an important role in the pathogenesis of gallstone disease. We have isolated one of the factors involved by using lectin-affinity chromatography. A potent promoting activity binds to concanavalin A-Sepharose. The activity is heat labile and sensitive to digestion by glycosidase but remarkably insensitive to proteases. The concanavalin A-binding pronucleator affects cholesterol solubilization in model bile in two ways. It induces a shift of cholesterol and phospholipid from the micellar to the vesicular phase but also interacts directly with cholesterol-phospholipid vesicles. The concanavalin A-binding protein fraction contains at least two different promoting factors with gel permeation molecular weights of about 150 kD and 5 kD, respectively. The higher molecular weight activity could be assigned to a protein with an apparent molecular weight of 130 kD. Concanavalin A-binding-promoting activity was present in bile from both patients with and without stones, indicating that it is a normal constituent of bile. However, the activity was strongly increased in bile from patients with multiple cholesterol gallstones, suggesting that it could play a key role in gallstone formation in these patients. 
4	Antihypertensive effectiveness of nifedipine gastrointestinal therapeutic system in the elderly. The Modern Approach to the Treatment of Hypertension (MATH) Study Group. The Modern Approach to the Treatment of Hypertension (MATH) trial was conducted to determine the therapeutic safety and efficacy of the once-a-day nifedipine gastrointestinal therapeutic system (GITS) formulation in a large and diverse cohort of patients with mild-to-moderate hypertension. One of the goals of the MATH study was to evaluate the clinical utility of nifedipine GITS in elderly hypertensives. This analysis compares the safety and efficacy of nifedipine GITS in elderly patients (greater than or equal to 65 years of age) and nonelderly patients (adults less than 65 years of age). A total of 222 elderly and 933 nonelderly patients from 127 centers were evaluated. Following a 2 week placebo washout phase, patients were titrated over 1 to 6 weeks on nifedipine GITS 30 to 180 mg/day, increasing in 30 mg increments to achieve goal blood pressure, defined as sitting diastolic blood pressure of less than 90 mm Hg and a 10 mm Hg decrease from baseline. Therapy was maintained at the optimal dose for an additional 12 weeks. Hemodynamic and laboratory parameters were assessed at baseline and at the final treatment visit. Baseline parameters were comparable between patient groups except for systolic blood pressure, which was significantly greater in the elderly compared with nonelderly patients (164 +/- 18 v 150 +/- 14 mm Hg, respectively, P less than .0001). After 12 weeks of therapy with nifedipine GITS, sitting and standing systolic and diastolic blood pressure was significantly decreased from baseline for both elderly and nonelderly patients. 
1	Cystic tumors of the pancreas. New clinical, radiologic, and pathologic observations in 67 patients. Within a 12-year period we treated 67 patients (49 women, 18 men; mean age, 61 years) with cystic neoplasms of the pancreas, including 18 serous cystic adenomas, 15 benign mucinous cystic neoplasms, 27 mucinous cystadenocarcinomas, 3 papillary cystic tumors, 2 cystic islet cell tumors, and 2 cases of mucinous ductal ectasia. Mean tumor size was 6 cm (2 to 16 cm). In 39% the patients had no symptoms, and in 37% the lesions had been misdiagnosed as a pseudocyst. Computed tomography was useful for detection, for distinguishing the microcystic subgroup of serous cystadenoma, and for showing rim calcification (all 7 cases were malignant) but was not reliable for distinguishing neoplasm from pseudocyst, serous from mucinous tumors, or benign from malignant. Arteriography showed hypervascularity in 4 of 10 serous adenomas, 3 of 11 mucinous carcinomas, and 1 of 1 papillary cystic tumors. Endoscopic pancreatography showed no communication with the cyst cavity in 37 of 37 cases of cystic neoplasms but opacified the ectatic ducts in 2 of 2 cases of mucinous ductal ectasia. Stenosis or obstruction of the pancreatic duct indicated cancer. The tumor was resected by distal pancreatectomy in 25 patients, by proximal resection in 29, and by total pancreatectomy in one, with no operative deaths. Forty-four per cent of the tumors were malignant. In 10 cases the tumor was unresectable because of local extension or distant metastases, and those patients died at a mean of 4 months. Seventy-five per cent of those resected for cure are alive without evident recurrence. Because the epithelial lining of the tumor was partially (5% to 98%) absent in 40% to 72% of cases of the major tumor types, and the mucinous component comprised only about 65% of mucinous cystadenoma lining, misdiagnoses on frozen and even permanent sections were made. Mitoses and histologic solid growth correlated with malignancy. Neuroendocrine elements were seen in 87% of benign and 47% of malignant mucinous tumors. It is recommended that the terms macrocystic and microcystic be abandoned in favor of the histologic designations serous and mucinous. Incomplete examination of the cyst wall can be misleading, however. It is suggested that mucinous ductal ectasia be recognized separately from cystic tumors and that all of these lesions be resected, with the possible exception of asymptomatic confirmed serous cystadenomas. 
3	Relative effects of brain and non-brain injuries on neuropsychological and psychosocial outcome. Based on the 242 consecutive surviving head injury cases and 132 general trauma cases, this study examined the contribution of brain and non-brain injuries to cognitive and psychosocial outcome 1 month postinjury. The study also examined the relationships among various head injury severity indices. The head injury severity indices were all correlated but patients with Glasgow Coma Scale scores in the mild range had broadly ranging scores on the other head injury severity indices (Abbreviated Injury Scale and time to follow commands). Neuropsychological outcome was related to brain injury severity, but was not independently influenced by severity of other systems injuries. Psychosocial outcome related to both brain and non-brain injuries independently. When evaluating trauma outcome, it is important to consider the contributions of both brain and other system injuries. 
2	Does paramedic-base hospital contact result in beneficial deviations from standard prehospital protocols? We reviewed written and audio records of paramedic-base hospital radio contact to determine whether care differed from that suggested in standard prehospital care protocols. Records of all 659 contacts for seizure, syncope, abdominal pain, or altered mental state during 1987 (28.4% of all contacts) were scored for the use of standard therapies (such as intravenous access, oxygen, naloxone hydrochloride) and unanticipated therapies (intubation, nitroglycerin). Cases that involved unanticipated treatments were reviewed to determine whether they could have been prospectively identified by simple clinical findings. Standard therapies were used in the majority of patients. Unanticipated therapies were administered to 13 patients, all of whom had abnormal vital signs, diaphoresis, respiratory distress, or a second prominent symptom. Data suggest that protocols could replace radio contact for most patients and that the few who might benefit from radio contact can be easily identified. A 90% reduction in radio contacts in Los Angeles county could save $3 million each year. 
4	Dipyridamole magnetic resonance imaging: a comparison with thallium-201 emission tomography. Limitation of space and motion artefact make magnetic resonance imaging during dynamic exercise difficult. Pharmacological stress with dipyridamole can be used as an alternative to exercise for thallium scanning. Forty patients with a history of angina and an abnormal exercise electrocardiogram were studied by dipyridamole thallium myocardial perfusion tomography and dipyridamole magnetic resonance wall motion imaging with a cine gradient refocused sequence. Images for both scans were obtained in the oblique horizontal and vertical long axis and short axis planes before and after pharmacological stress with dipyridamole. The myocardium was divided into nine segments for direct comparison of perfusion with wall motion. Segments were assessed visually into grades--normal, hypokinesis or reduced perfusion, and akinesis or very reduced perfusion. After dipyridamole there were reversible wall motion abnormalities in 24 (62%) of 39 patients with coronary artery disease and 24 (67%) of 36 patients with reversible thallium defects. The site of wall motion deterioration was always the site of a reversible thallium defect. Thallium defects affecting more than two segments were always associated with wall motion deterioration but most single segment thallium defects were undetected by magnetic resonance imaging. There was a significant correlation between detection of wall motion abnormality, the angiographic severity of coronary artery disease, and the induction of chest pain by dipyridamole. There were no significant differences in ventricular volume or ejection fraction changes after dipyridamole between the groups with and without detectable reversible wall motion changes but the normalised magnetic resonance signal intensity of the abnormally moving segments was significantly less than the signal intensity of the normal segments. 
4	Follow-up results of balloon angioplasty of native coarctation in neonates and infants. The purpose of this study is to present intermediate-term results of balloon angioplasty of native aortic coarctation in neonates and infants less than 1 year of age. During a 60-month-period that ended in January 1990, 19 infants ages 3 days to 12 months (median, 2.5 months), underwent balloon angioplasty of native coarctation with resultant reduction in peak-to-peak systolic pressure gradient from 39 +/- 12 mm Hg (mean +/- SD) to 11 +/- 7 mm Hg (p less than 0.001) and increase in coarctation segment size from 2.2 +/- 0.8 mm to 4.7 +/- 1.0 mm. None required immediate surgical intervention. Thirteen of the 19 (68%) had severe associated cardiac defects. There was one death (5%) 2 days after balloon angioplasty, and it was related to associated cardiac defect. One infant was lost to follow-up. It is too soon to restudy one infant. The remaining 16 infants had clinical (36 +/- 18 months) and catheterization (12 +/- 4 months) follow-up data. The residual coarctation gradient (22 +/- 15 mm Hg) and coarcted segment size (4.4 +/- 1.6 mm) remain improved (p less than 0.01) when compared with pre-balloon angioplasty values. Five of the 16 (31%) infants (four were neonates at the time of balloon angioplasty) had evidence for recoarctation (defined as gradient greater than 20 mm Hg) and underwent surgical resection (two) or repeat balloon angioplasty (three), all with success. None developed aneurysms. 
3	Acute subdural hematoma: morbidity, mortality, and operative timing. Traumatic acute subdural hematoma remains one of the most lethal of all head injuries. Since 1981, it has been strongly held that the critical factor in overall outcome from acute subdural hematoma is timing of operative intervention for clot removal; those operated on within 4 hours of injury may have mortality rates as low as 30% with functional survival rates as high as 65%. Data were reviewed for 1150 severely head-injured patients (Glasgow Coma Scale (GCS) scores 3 to 7) treated at a Level 1 trauma center between 1982 and 1987; 101 of these patients had acute subdural hematoma. Standard treatment protocol included aggressive prehospital resuscitation measures, rapid operative intervention, and aggressive postoperative control of intracranial pressure (ICP). The overall mortality rate was 66%, and 19% had functional recovery. The following variables statistically correlated (p less than 0.05) with outcome; motorcycle accident as a mechanism of injury, age over 65 years, admission GCS score of 3 or 4, and postoperative ICP greater than 45 mm Hg. The time from injury to operative evacuation of the acute subdural hematoma in regard to outcome morbidity and mortality was not statistically significant even when examined at hourly intervals although there were trends indicating that earlier surgery improved outcome. The findings of this study support the pathophysiological evidence that, in acute subdural hematoma, the extent of primary underlying brain injury is more important than the subdural clot itself in dictating outcome; therefore, the ability to control ICP is more critical to outcome than the absolute timing of subdural blood removal. 
1	Human basophils express interleukin-4 receptors. Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed. 
5	The interspinous method of posterior atlantoaxial arthrodesis. Thirty-six patients underwent C1-2 posterior wiring and fusion procedures over a 5-year period for unstable C-2 fractures (eight cases), unstable atlas-axis combination fractures (six cases), rheumatoid C1-2 instability (14 cases), os odontoideum (four cases), traumatic C1-2 ligamentous instability (three cases), or instability secondary to a C-2 tumor (one case). In each case, the atlantoaxial arthrodesis utilized sublaminar wire at C-1 and incorporated an iliac-crest strut-graft positioned between the posterior arches of C-1 and C-2, held in place by securing wire around the base of the spinous process of the axis. Follow-up examination was performed in all patients after a mean postoperative duration of 33.7 months. The technical aspects and clinical merits of this fusion procedure, which led to a 97% union rate (one nonunion) and minimal morbidity and mortality rates, are presented. 
1	Diagnostic accuracy and appropriateness of care for seborrheic keratoses. A pilot study of an approach to quality assurance for cutaneous surgery In 1985 there were more than 40 million visits for ambulatory surgical procedures in the United States. Although benign cutaneous lesions are among the most frequent conditions to receive surgical treatment in ambulatory settings, their treatment is seldom subject to peer review. In this pilot study we assessed diagnostic accuracy and appropriateness of care using information available from the surgical pathology laboratory. We assessed these two measures of physician performance for 527 seborrheic keratoses removed by 133 clinicians affiliated with four different institutions. Overall, a correct preoperative diagnosis was provided in only 49% of cases. Dermatologists had the highest diagnostic accuracy (61% vs 35% for all other physicians). An appropriate procedure for the actual pathological diagnosis was performed in only 50% of cases. Lesions with a correct preoperative diagnosis were more than eight times more likely to receive appropriate care. Our data suggest that many clinicians fail to note a correct diagnosis of common cutaneous lesions before surgical removal, and many patients are treated with procedures that are more invasive than necessary for the final pathological diagnosis. Because the approach used in this pilot study relies on data already available, it has promise as a low-cost method of monitoring the quality of care of ambulatory surgery. 
5	Choreoathetosis after deep hypothermia without circulatory arrest In 8 of 758 patients undergoing an intracardiac operation under cardiopulmonary bypass and hypothermia, choreoathetosis developed 3 to 7 days postoperatively. Before the onset of choreoathetosis, varying degrees of neurological dysfunction were noted. Electroencephalography and neuroimaging failed to detect any responsible functional or structural changes. Six patients are alive 1 to 3 years postoperatively, and their condition is improving. Two patients died of aspiration or sepsis. All patients were grouped based on factors identified as being possibly causative: depth of hypothermia, cooling time, flow rate, and repeated hypothermia. The incidence of choreoathetosis was significantly different in group A (rectal temperature greater than 25 degrees C) compared with group B (rectal temperature less than or equal to 25 degrees C) (0/295 versus 8/463; p = 0.02). Based on cooling time, the incidence of choreoathetosis was significantly different in group B1 (cooling time less than 1 hour) compared with group B2 (cooling time greater than or equal to 1 hour) (1/220 versus 7/243; p = 0.05). Based on flow rate during cooling, group B2 was further divided into the low-flow group (less than 1,500 mL.min-1.m-2) and the high-flow group (greater than or equal to 1,500 mL.min-1.m-2). Although not significant, the incidence of choreoathetosis was higher in the high-flow group (6/153 versus 1/90; p = 0.22). In group B patients having reoperation, the incidence of choreoathetosis was higher than in patients operated on for the first time (5/54 versus 3/409; p less than or equal to 0.0001). 
3	Intradural chordoma of the tentorium cerebelli. Case report. A rare case of intradural chordoma is described. The literature contains seven examples of intradural extraosseous chordoma, all reported in a ventral location. This is the first reported case of a primary intradural chordoma distant from the clivus and involving both the supra- and infratentorial compartments. 
1	The gastrin hypothesis. Implications for antisecretory drug selection. Newer potent and long-acting inhibitors of acid secretion, such as the proton pump inhibitor omeprazole, are becoming available for general use. These drugs promise to control acid-peptic disease effectively in patients who do not respond adequately to conventional short-acting H2-receptor antagonists. The safety of chronic administration of these drugs has come into question, however. Lifelong profound inhibition of acid secretion in rats induced by superpotent inhibitors of acid secretion or subtotal fundectomy is associated with the development of carcinoid tumors of enterochromaffin-like (ECL) cells in the gastric corpus. Available evidence supports a role of gastrin, which becomes chronically elevated in animals subjected to prolonged and profound hypochlorhydria. In humans, hypergastrinemic states such as Zollinger-Ellison syndrome and atrophic gastritis are associated with an increased risk of ECL-cell carcinoid tumors. Such observations have raised concern that humans may also be susceptible to carcinoid tumor formation in response to potent inhibitors of acid secretion. To date, however, no cases of carcinoid tumor have been attributed to the use of omeprazole in humans. If achlorhydric doses are not used, significant hypergastrinemia can be avoided while effectiveness of treatment is maintained. Such measures should minimize any risk of ECL-cell carcinoid tumors in humans taking potent long-term antisecretory drugs. 
2	The Baltimore experience with laparoscopic management of acute cholecystitis. Laparoscopic cholecystectomy has rapidly emerged as a popular alternative to traditional laparotomy and cholecystectomy. Acute cholecystitis has been considered to be a relative or absolute contraindication to laparoscopic surgery. After gaining extensive experience in laparoscopic biliary tract surgery, this procedure was attempted in 15 patients with acute cholecystitis. All patients were operated on within 72 hours of admission. In five patients, the laparoscopic procedure was converted to an open laparotomy; in one patient, a localized abscess was found, and in the other four patients, extensive inflammation and edema precluded a safe dissection of the vascular and ductal structures. Laparoscopic cholangiography was performed in 14 patients and proved valuable in demonstrating the ductal anatomy. Patients were discharged an average of 2.7 days after the laparoscopic procedure. Laparoscopic cholecystectomy may be safely performed by experienced surgeons in patients with acute cholecystitis. To ensure a low complication rate, a low threshold for converting the procedure to an open laparotomy must be maintained if the ductal and vascular anatomy cannot be safely demonstrated. 
4	Extrahepatic portal vein aneurysm associated with a tortuous portal vein. Portal vein aneurysm is rare and its etiology is controversial. A case of extrahepatic portal vein aneurysm associated with an unusually tortuous portal vein is described. Real-time ultrasonography showed anechoic masslike lesions at the porta hepatis communicating with the superior mesenteric vein and intrahepatic portal branches. This suggested the presence of two saccular portal vein aneurysms, 27 x 21 mm and 21 x 13 mm in size. Magnetic resonance imaging and portal venography confirmed the portal vein aneurysms and an unusually tortuous portal vein curving caudally between them. The liver was histologically normal and there was no evidence of portal hypertension. It is speculated that these portal vein aneurysms may have been congenital and that the associated tortuous portal vein might have been secondary to hemodynamic changes in the portal venous system. 
3	Early-onset dementia and extrapyramidal disease: clinicopathological variant of Gerstmann-Straussler-Scheinker or Alzheimer's disease? A case of progressive dementia and extrapyramidal signs beginning at age 29, with a ten year course until death, is presented. Necropsy examination showed an assortment of plaque types (including striatal plaques), neurofibrillary tangles, granulovacuolar degeneration, and depigmentation of the substantia nigra and locus ceruleus. This case had pathological features found in both Gerstmann-Straussler-Scheinker disease and in Alzheimer's disease. While somewhat similar to several other cases with features of both diseases, it differs in the presence of dystonia and striatal plaques. Although such cases may be difficult to categorize at present, they must be considered in the differential diagnosis of early onset dementia. 
5	Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). Traditional concepts of impermeability of the bladder have centered around unique cellular tight junctions and ion pumps. However, recent data from our laboratory have shown that the bladder epithelium in animals and humans relies primarily on its surface glycosaminoglycans to maintain its impermeability. This study demonstrates the first disease associated with an epithelial dysfunction of the bladder, that is a leaky epithelium. The study consisted of 31 normal subjects and 56 individuals with interstitial cystitis. Interstitial cystitis patients were shown to have a leaky epithelium by placing a solution of concentrated urea into the bladder and measuring the absorption. The normal subjects absorbed 4.3% in 45 minutes, while the interstitial cystitis patients absorbed 25% (difference is highly significant, p less than 0.005). Interstitial cystitis patients with Hunner's ulcers (10) had a 34.5% absorption rate, while those without ulcers absorbed 22.8% (46). This difference also was highly significant (p = 0.002) and supports the concept that patients with ulcers have clinically worse disease. 
5	Observer variability in the scoring of colpophotographs. Colposcopy and cervicography are accepted tools for assessing the cervix for an atypical transformation zone. We studied the validity of the colpophotograph as a measurement tool by determining the agreement of experienced colposcopists using colpophotographs of 50 women. Interobserver agreement was generally fair to good (kappa greater than or equal to 0.40) for the presence of the squamocolumnar junction and the area of ectopia but it was poor (kappa less than 0.40) for the area, border, and color characteristics of an atypical transformation zone. Intra-observer agreement was fair to good for the color characteristics of an atypical transformation zone, but it was poor for the area and border characteristics. We conclude that observer agreement studies should play a role in the validation of methods used in the visual diagnosis of cervical intraepithelial neoplasia. Considerable lack of agreement in reporting cytologic findings is a well-known problem, and lack of agreement might be an even bigger problem in reporting colposcopic findings. 
1	Synchronous carcinoma of the colon and rectum. Reports on the incidence of synchronous carcinoma of the colon and rectum have varied from 2 to 11 per cent. The variability is a result of a lack of uniformity in criteria of diagnosis, differences in the population studied and differences in time period used. In this study, we evaluated the incidence and distribution of synchronous lesions during a recent time period before the use of colonoscopy became widespread. We reviewed the records of all patients with newly diagnosed adenocarcinoma of the colon and rectum who were operated upon at our institution between 1976 and 1981. In a total group of 1,000 patients of which 52 per cent were men, there were 54 patients or 5.4 per cent who had synchronous carcinomas. The group of patients with synchronous carcinomas were older than the group with nonsynchronous carcinomas (72.4 versus 68.8 years). There was also a higher incidence of associated benign polyps in the group with synchronous carcinomas (70 versus 30 per cent for a nonsynchronous carcinomas). The anatomic distribution of carcinomas of the colon and rectum in the group with synchronous lesions (111 in total) revealed a higher percentage of carcinomas located on the right side (29.7 versus 22.5 per cent), although the difference did not reach statistical significance. Synchronous carcinomas were located in nonadjacent segments of the colon in 37 per cent. There was no difference in stage between the groups with and without synchronous carcinomas. The preoperative identification of synchronous lesions by either colonoscopy or barium enema is important for the proper treatment of patients with carcinoma of the colon and rectum. Failure to locate these tumors may lead to the demise of the patient. 
1	Cessation of treatment in advanced cancer. A major responsibility for all physicians, but particularly for oncologists, is to recognize the time when active antitumor treatment ceases to have a rational basis. The decision to treat or not to treat at any stage of disease requires an analysis of "the legitimate aims of therapy." We have acquired the ability to cure or prolong survival in an increasing proportion of patients with several types of cancer. For patients who fail to achieve those results and for those with tumors that are rarely amenable to specific therapy, the choice of less surely effective therapy is an option; the patient must participate in the decision, armed with as much information and insight as possible, for conventional and experimental treatment. A distinction must be made between specific antitumor therapy and palliative measures for which cessation is never an option. Happily, cessation of treatment must also be considered when therapy has been so successful that the patient has achieved complete remission. At what point may treatment be discontinued without the danger of relapse? These issues are rarely crisply defined, but primary concern for the patient and careful analysis of the available data can lead to appropriate value judgements. 
4	Effects of diltiazem on the functional recovery of the myocardium at organ and cellular level during prolonged hypothermic ischemic cardiac arrest. The effectiveness of diltiazem on the functional recovery of the heart, calcium (Ca++) uptake and binding, Ca++ ATPase of cardiac sarcoplasmic reticulum (SR), and MB fraction of creatine kinase (MBCK) of coronary sinus blood was investigated after one and a half hours of reperfusion following three hours of ischemic cardiac arrest. The dogs were divided into three groups: group I, sham bypass; group II, cold crystalloid cardioplegia; and group III, cold crystalloid cardioplegia with diltiazem. There was a decrease in aortic pressures left ventricular pressure development (dp/dt), left ventricular work index (LVWI), total systemic vascular resistance (TSVR), and left ventricular systolic pressure (LVSP) in the sham bypass group. There was a decrease in cardiac index (CI), LVWI, and mean right atrial pressure (mRAP) and an increase in TSVR and pulmonary vascular resistance (PVR) in group II as compared with group I. Although there was a tendency for a decrease in the indices of myocardial contractility in group II, they were not significantly different from those in group I. The indices of myocardial contractility, CI, and LVWI in group III were slightly higher than in group II, but they were not significantly different from each other. The values for calcium uptake by SR in groups II and III were similar but significantly lower than those in group I. Calcium binding in group III was significantly lower than that in group I. Calcium ATPase of SR in the three groups were similar. Although MBCK increased in all the groups, the increases were not significantly different among the three groups. The results of this study indicate that cold crystalloid cardioplegia with diltiazem was not better than cold crystalloid alone in preserving the cardiac contractility and cellular function during prolonged ischemic cardiac arrest. However, the cardiac function in terms of cardiac index was better preserved with diltiazem. 
5	Results of contemporary radical cystectomy for invasive bladder cancer: a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. We reviewed 261 patients who underwent a radical operation at a single institution as definitive treatment of invasive bladder cancer to evaluate the survival and accuracy of the tumor, nodes and metastasis system in characterizing the prognosis. Between January 1979 and June 1987 the 261 evaluable patients underwent 1-stage radical cystectomy with pelvic node dissection and urinary diversion. No chemotherapy and/or radiation therapy was given before or after the operation. The postoperative mortality rate was 1.8%. The over-all staging error between clinical and pathological stages was as high as 44%. The over-all actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A significant difference in the survival (p less than 0.002) was observed in stage pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those extending throughout the bladder wall (pT3b, 15%). A careful evaluation of transitional cell involvement of the prostate in stage pT4a cancer led to the identification of 2 different patterns: 1) contiguous when a bladder tumor extended directly into the prostate through the bladder wall and 2) noncontiguous when a bladder tumor and a transitional cell carcinoma of the prostate were found simultaneously. These patterns had completely different (p less than 0.05) survival rates (6 versus 37%). The patients with high grade tumors had a worse prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p less than 0.005). The over-all 5-year survival of patients with positive nodes was 4% in comparison with 60% of those without nodal involvement (p less than 0.001). Despite current optimal surgical treatment, nearly 50% of all patients with invasive bladder cancer continue to die. The need for a modification of the current tumor, nodes and metastasis tumor classification to provide the clinician a more reliable staging system for planning treatment modalities is indeed mandatory. 
3	Magnetic resonance imaging of the head and spine: effective for the clinician or the patient? OBJECTIVES--To test how the results of magnetic resonance imaging influence clinicians' diagnoses and management plans for patients with cranial and spinal problems and to assess changes in the quality of life of these patients. DESIGN--Survey of patients undergoing cranial and spinal magnetic resonance imaging with questionnaires about diagnoses and intended management plans before and after imaging and quality of life questionnaires at the time of imaging and again four months later. SETTING--Regional magnetic resonance imaging and spectroscopy unit. SUBJECTS--100 consecutive patients referred for cranial imaging in early 1989; 100 similar patients referred for spinal imaging. MAIN OUTCOME MEASURES--Changes in clinicians' leading diagnoses after magnetic resonance imaging and their confidence in these diagnoses; changes in intended management plans; assessment of the contribution to the future management of the patient; changes in patients' quality of life. RESULTS--Magnetic resonance imaging altered the clinicians' leading diagnoses in 35 of 169 (21%) cases. The clinicians became more confident about their leading diagnoses in 90 of 167 (54%). There was a change in management plan in 113 of 182 (62%). The clinicians considered that magnetic resonance imaging made an important contribution to management in 119 of 162 (73%) patients. Overall, the patients' quality of life was unchanged at the four month assessment. CONCLUSIONS--Magnetic resonance imaging of patients with cranial and spinal problems influences clinicians' diagnoses and management plans, but the quality of life of these patients remains unchanged. 
4	Daytime hypertension in obstructive sleep apnea. Prevalence and contributing risk factors. We examined the prevalence of daytime hypertension in a modern sample of patients with obstructive sleep apnea (OSA) and assessed the relative risk factors contributing to the development of hypertension in this disorder. Daytime hypertension was present in 92 (45 percent) of 206 male and female patients with OSA. Stepwise logistic regression revealed that only age and body mass index (BMI) were predictors of hypertension in this population. A subsample of 152 male patients with OSA was then compared to 904 men identified from a geographically and ethnically similar general population. When one controlled for age and BMI, the prevalence of hypertension in the two groups was the same except for those aged 25 to 44 years who were markedly obese (BMI greater than 31 kg/m2). In this group, 47 percent of the patients with OSA were hypertensive vs 26 percent of control subjects (p less than 0.05). Our data suggest that the high prevalence of hypertension in OSA is primarily related to age and the excess obesity seen in these patients. In morbidly obese young patients with OSA, factors directly related to OSA may also be contributing to the development of hypertension. With increasing age, other competitive risks may obscure any independent effect that OSA may exert. 
1	Overall mortality and cancer mortality around French nuclear sites Higher than expected mortality from leukaemia has been observed in the population under age 25 living around Sellafield and Dounreay, nuclear reprocessing plants in the United Kingdom. We report the results of a similar study for the population residing around nuclear sites in France. The number of leukaemia deaths was 58, comparable to the 62 in control areas, and slightly less than the 67 expected from national mortality statistics. Twelve deaths due to Hodgkin's disease were observed around nuclear sites; this is about twice the number of Hodgkin's deaths observed in control areas and twice the number expected from national mortality statistics. This observation must, however, be interpreted in light of the fact that several causes of deaths were studied, increasing the play of chance. 
1	Choroid plexus tumors in the breast cancer-sarcoma syndrome. Choroid plexus neoplasms are rare epithelial tumors of the central nervous system. A carcinoma of the choroid plexus occurred in a child from a family with the breast cancer-sarcoma syndrome (Li-Fraumeni or SBLA syndrome), an inherited condition characterized by the development of diverse neoplasms (sarcoma, breast cancer, brain tumors, leukemia, adrenal cortical carcinoma, and others). Choroid plexus carcinomas were identified in two kindreds previously reported with the syndrome. The literature contains reports of choroid plexus neoplasms occurring in families and in individuals with multiple primary tumors. Choroid plexus neoplasm may be a manifestation of the inherited proclivity to tumor development in the breast cancer-sarcoma syndrome. 
1	Cancer in relatives of survivors of childhood sarcoma. Relatives of 88 long-term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li-Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected, 23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition. An increased cancer risk and exceptional requirement for disease screening appear to be confined to first-degree relatives of a small fraction of children with sarcoma, notably probands with second cancers. 
4	Intrapericardial infusion of 5-fluorouracil. An unusual complication of a Hickman catheter. Venous access devices (VAD) have become an important tool in the management of patients with cancer. Multiple complications can occur as a consequence of insertion of a VAD. The authors report a case of a Hickman catheter perforating the wall of the superior vena cava into the pericardium, resulting in accidental intrapericardial infusion of 5-fluorouracil (5-FU). Pericarditis and cardiac arrhythmias developed, but the patient did not have cardiac tamponade. She recovered from the event without apparent chronic cardiac dysfunction. 
3	Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection. We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy. 
2	Treatment of obstructive pneumatosis coli with endoscopic sclerotherapy: report of a case. The case of an 86-year-old man with cardiac and pulmonary failure, in whom pneumatosis cystoides intestinalis caused segmental obstruction of the sigmoid colon is described. The patient was treated with endoscopic puncture and sclerotherapy of the cyst walls in four sessions, giving endoscopic and radiologic regress of the lesions and symptomatic relief. 
1	High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma. The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach. 
3	Severe cerebral and systemic necrotizing vasculitis developing during pregnancy in a case of systemic lupus erythematosus. We describe a fatal case of systemic lupus erythematosus (SLE) developing cerebral and systemic necrotizing vasculitis during pregnancy. The patient was discovered to have SLE at 14 weeks' gestation. Although the symptoms disappeared without treatment with corticosteroid in the 2nd trimester, she presented with meningoencephalitis due to vasculitis in the 3rd trimester. Polyarteritis nodosa (PAN)-like necrotizing vasculitis of the small muscular arteries and arterioles, with acute and healing lesions in the leptomeninges, brain parenchyma and visceral organs was observed at postpartum autopsy. PAN-like vasculitis in the central nervous system is quite rare in SLE. This case is also suggestive in terms of the influence of pregnancy on the activity of SLE. 
5	Femorofemoral bypass: a profile of graft failure. We have reviewed our experience with 71 patients who had a femorofemoral bypass for unilateral iliac artery occlusion or stenosis. We analyzed morbidity, mortality, initial relief of symptoms, early patency, and long-term primary and secondary patency; and we attempted to identify the cause of graft failure. The overall hospital mortality after operative repair was 4%. One-year survival was 84% and 2-year survival was 81%. Early patency was 98.5% at 1 month, late patency was 91% at 1 year and 82% at 5 years. The major cause of graft failure was inadequate run-off and outflow disease progression. 
2	Effect of V1-vasopressin receptor blockade on arterial pressure in conscious rats with cirrhosis and ascites. Angiotensin II blockade with saralasin in human cirrhosis with ascites is associated with a significant reduction in arterial pressure, indicating that endogenous angiotensin II plays an important role in the maintenance of systemic hemodynamics in this condition. The aim of the current study was to investigate whether vasopressin also contributes to the maintenance of arterial pressure in cirrhosis with ascites. The study was performed using three groups of cirrhotic rats with ascites and three groups of control animals. The administration of d(CH2)5Tyr(Me)AVP, a selective antagonist of the vascular effect of vasopressin, to 10 cirrhotic rats induced a significant reduction in mean arterial pressure (from 94 +/- 4 to 85 +/- 4 mm Hg; P less than 0.001) and a significant increase in plasma renin activity (from 24.3 +/- 4.9 to 34.3 +/- 5.9 ng/mL.h; P less than 0.02) and plasma norepinephrine concentration (from 1474 +/- 133 to 2433 +/- 253 pg/mL; P less than 0.01). Similar results were observed following saralasin administration in a second group of 5 cirrhotic rats [mean arterial pressure decreased from 97 +/- 4 to 85 +/- 5 mm Hg (P less than 0.0001); and plasma renin activity and norepinephrine concentration increased from 18.4 +/- 5.8 to 40.3 +/- 5.7 ng/mL.h (P less than 0.02) and from 1383 +/- 70 to 2312 +/- 334 pg/mL (P less than 0.05), respectively]. The simultaneous blockade of angiotensin II and vasopressin in a third group of cirrhotic rats resulted in a significantly greater reduction of mean arterial pressure (from 97 +/- 6 to 74 +/- 6 mm Hg; P less than 0.05). No changes in arterial pressure were observed in the three groups of control rats. These findings indicate that endogenous vasopressin is as important as angiotensin II in the maintenance of arterial pressure in cirrhotic rats with ascites and support the contention that arterial hypotension is the initial event leading to the stimulation of the renin-angiotensin system and vasopressin in this animal model of cirrhosis. 
3	Magnetic resonance imaging for ineffectual tarsal tunnel surgical treatment. Tarsal tunnel syndrome (TTS) is an entrapment neuropathy caused by compression of the posterior tibial nerve beneath the ankle flexor retinaculum. Treatment of TTS consists of surgical release of the retinaculum. The failure rate is 10%-20%. Magnetic resonance (MR) imaging was used to evaluate a patient with an unsatisfactory response. MR imaging demonstrated incompleteness of the surgical release of the flexor retinaculum. 
2	Monomicrobial nonneutrocytic bacterascites: a variant of spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is diagnosed when (a) the ascitic fluid culture is positive, (b) the ascitic fluid neutrophil count is greater than or equal to 250 cells/mm3 and (c) there is no evident intraabdominal surgically treatable source for infection. Few details are available regarding the variant of ascitic fluid infection in which the culture grows bacteria (pure growth of a single type of organism), but the neutrophil count is less than 250 cells/mm3. In this prospective study of 138 episodes of culture-positive spontaneously infected ascites detected in 105 patients, 44 (31.9%) were episodes of "monomicrobial nonneutrocytic bacterascites" compared with 94 (68.1%) episodes of spontaneous bacterial peritonitis. Seventeen patients had both types of infection. The infection-related mortality and hospitalization mortality were similar between the two groups. Patients with bacterascites appeared to have less severe liver disease. In 62% of bacterascites episodes in which a second paracentesis was performed before any treatment the fluid spontaneously became sterile without development of ascitic fluid neutrocytosis. Thirty-eight percent of patients with bacterascites (who underwent a second paracentesis before treatment was started) progressed to spontaneous bacterial peritonitis--sometimes within a few hours. The concentration of the chemoattractant C5a was not decreased in the ascitic fluid of the bacterascites patients; this excludes ascitic fluid C5a deficiency as the explanation of the lack of neutrocytosis. Monomicrobial nonneutrocytic bacterascites is a common variant of ascitic fluid infection that may resolve without treatment or may progress to spontaneous bacterial peritonitis. 
4	Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension. Patients with untreated hypertension have been shown to be resistant to insulin-stimulated glucose uptake and are more hyperinsulinemic and hypertriglyceridemic than matched groups of patients with normal blood pressure. In addition, insulin resistance, hyperinsulinemia, and hypertriglyceridemia have been demonstrated in spontaneous hypertensive rats and in Sprague-Dawley rats fed a fructose-enriched diet. The defect in insulin-stimulated glucose uptake in these experimental models can also be shown at the cellular level. Experimental interventions that prevent insulin resistance or hyperinsulinemia from developing in fructose-fed rats also greatly attenuate the increase in blood pressure. Since endogenous hyperinsulinemia and hypertriglyceridemia have been identified as factors that increase the risk of coronary artery disease (CAD), it is likely that they contribute to the increased prevalence of CAD in hypertensive patients. Antihypertensive treatment may have exacerbated these metabolic abnormalities, which could help explain why it has been difficult to show that lowering blood pressure decreases the risk of CAD. These observations raise the possibility that abnormalities of carbohydrate and lipoprotein metabolism may play a role in both the etiology and clinical course of hypertension. 
5	Effects of 1.32-micron Nd-YAG laser on brain thermal and histological experimental data. Considering that the 1.32-microns Nd-YAG laser should have physicothermal properties close to those of the CO2 laser, a series of experiments were conducted on rat cortex (N = 51). Three laser wavelengths were compared: CO2 laser (10.6 microns), 1.06-microns Nd-YAG, and 1.32-microns Nd-YAG lasers. For each shot, temperature measurements were recorded with an infrared thermographic videocamera. The digitized signals were figured as thermal profiles and temperature developments. Ninety-five shots were correctly studied and analyzed: CO2, N = 29; 1.06-microns Nd-YAG, N = 20; 1.32-microns Nd-YAG, N = 46. The histological lesions produced by these three lasers were compared on animals killed 24 hours (N = 20), 8 days (N = 20), and 30 days (N = 5) after the laser impacts. For equivalent densities of energy, the depth of cortical necrosis was comparable for the CO2 laser (200-250 microns) and the 1.32-microns Nd-YAG laser (210-260 microns) whatever the date of death; the 1.06-microns Nd-YAG laser shots were responsible for much more important damage (400-550 microns). Because of its important absorption in water and nervous tissue, the authors consider the 1.32-microns Nd-YAG laser most suitable for neurosurgery, particularly because it is conducted through optic fibers, and therefore is easy to handle during neurosurgical procedures. 
1	Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma. Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. 
1	Isolated calcaneal metastasis in a patient with endometrial adenocarcinoma. A 55-year-old woman with a history of Stage IA endometrial adenocarcinoma, previously treated with surgery and intracavitary radiation therapy, had an isolated calcaneal metastasis. Normal radiographs led to a delay in the diagnosis of her relapse. An ankle computed tomographic scan finally identified a mass, and the surgical biopsy specimen confirmed the diagnosis. This is the first reported case of an isolated calcaneal metastasis in endometrial adenocarcinoma to the authors' knowledge. 
4	Percutaneous support devices for high risk or complicated coronary angioplasty. Indications for coronary angioplasty have expanded to include patients with unstable acute ischemic syndromes, severe multivessel coronary artery disease and impaired left ventricular function. Several mechanical approaches have been developed as adjuncts to high risk coronary angioplasty to improve patient tolerance of coronary balloon occlusion and maintain hemodynamic stability in the event of complications. These percutaneous techniques include intraaortic balloon counterpulsation, anterograde transcatheter coronary perfusion, coronary sinus retroperfusion, cardiopulmonary bypass, Hemopump left ventricular assistance and partial left heart bypass. The intraaortic balloon pump provides hemodynamic support and ameliorates ischemia by decreasing myocardial work; it may be inserted for periprocedural complications or before angioplasty in patients with ischemia or hypotension. Anterograde distal coronary artery perfusion may be accomplished passively through an autoperfusion catheter or by active pumping of oxygenated blood or fluorocarbons through the central lumen of an angioplasty catheter. Synchronized coronary sinus retroperfusion produces pulsatile blood flow via the cardiac veins to the coronary bed distal to a stenosis. Both perfusion techniques limit development of ischemic chest pain and myocardial dysfunction in patients undergoing prolonged balloon inflations. Percutaneous cardiopulmonary bypass provides complete systemic hemodynamic support which is independent of intrinsic cardiac function or rhythm and has been employed prophylactically in very high risk patients before coronary angioplasty or emergently for abrupt closure. These and newer support devices, while associated with significant complications, may ultimately improve the safety of coronary angioplasty and allow its application to those who would otherwise not be candidates for revascularization. 
5	An in vitro evaluation of an artificial heart. Interactions between human blood and the Penn State Artificial Heart were examined in vitro to study the effects of various operating conditions on the hematologic response. A dual-loop recirculating flow system that accommodated human blood was developed and blood was subjected for 3 hr to various operating conditions known to alter fluid mechanics in the artificial ventricle. The operating conditions investigated were: 60 beats/min at 50% systolic duration, 60 beats/min at 30% systolic duration, and 90 beats/min at 50% systolic duration. Quantification of plasma free hemoglobin provided a direct indicator of hemolysis in the flow system. Platelet number and beta-thromboglobulin levels were monitored to investigate thrombotic activity, and levels of complement 3a were measured to examine complement system activation. The system was effective in demonstrating the relative hemolytic properties of the operating conditions. Ninety beats/min induced 37% more hemolysis than 60 beats/min at 50% systolic duration, and 50% systolic duration induced 32% more hemolysis than 30% systolic duration at 60 beats/min. There were no statistically significant changes in either platelet number or beta-thromboglobulin levels during the 3 hr recirculation period. Increases were seen in complement 3a levels, but these appeared to be surface-induced and not sensitive to the different operating conditions. These studies demonstrate the usefulness of the flow system in examining the relative hemolytic properties of the artificial ventricle, and suggest that bulk turbulent stresses may play a more important role than laminar wall shear stresses in mediating blood damage in this artificial ventricle. 
4	Human dose-response relationship for decompression and endogenous bubble formation. The dose-response relationship for decompression magnitude and venous gas emboli (VGE) formation in humans was examined. Pressure exposures of 138, 150, and 164 kPa (12, 16, and 20.5 ft of seawater gauge pressure) were conducted in an underwater habitat for 48 h. The 111 human male volunteer subjects then ascended directly to the surface in less than 5 min and were monitored for VGE with a continuous-wave Doppler ultrasound device over the precordium or the subclavian veins at regular intervals for a 24-h period. No signs or symptoms consistent with decompression sickness occurred. However, a large incidence of VGE detection was noted. These data were combined with those from our previously reported experiments at higher pressures, and the data were fit to a Hill dose-response equation with nonlinear least-squares or maximum likelihood routines. Highly significant fits of precordial VGE incidences were obtained with the Hill equation (saturation depth pressure at which there is a 50% probability of detectable VGE [D(VGE)50] = 150 +/- 1.2 kPa). Subclavian monitoring increased the sensitivity of VGE detection and resulted in a leftward shift [D(VGE)50 = 135 +/- 2 kPa] of the best-fit curve. We conclude that the reduction in pressure necessary to produce bubbles in humans is much less than was previously thought; 50% of humans can be expected to generate endogenous bubbles after decompression from a steady-state pressure exposure of only 135 kPa (11 ft of seawater). This may have significant implications for decompression schedule formulation and for altitude exposures that are currently considered benign. These results also imply that endogenous bubbles arise from preexisting gas collections. 
5	Major cross-country differences in risk of dying for people with IDDM. Diabetes Epidemiology Research International Mortality Study Group. OBJECTIVE: Little is known concerning global differences in the risk of premature death for individuals developing youth-onset insulin-dependent diabetes mellitus (IDDM). The Diabetes Epidemiology Research International Study was developed to examine the mortality patterns of four population-based cohorts of IDDM cases from Allegheny County, Pennsylvania (n = 1000), Finland (n = 5146), Israel (n = 681), and Japan (n = 1428). RESEARCH DESIGN AND METHODS: All subjects were diagnosed as having diabetes, were less than 18 yr old at onset, were taking insulin at the time of hospital discharge, and were diagnosed between 1 January 1965 and 31 December 1979. The living status as of 1 January 1985 was determined. RESULTS: Overall, there were 182 deaths. Life-table analysis revealed that at 20-yr duration of diabetes, 5.5% of the cohort had died in Allegheny County in contrast to only 3.1% in Finland and 4.6% in Israel (P less than 0.01). Follow-up for an additional 3 yr in the United States and Finland revealed major differences in the 30- to 39-yr age-group, with 3.9 times greater premature mortality in the U.S. cohort compared with the Finnish group (overall mortality 2.3 vs. 0.6%, respectively). The Japanese cohort was developed in a somewhat different manner than the other three; therefore, the populations of the U.S., Finland, and Israel were reconfigured to make them directly comparable to that of Japan. The Japanese cohort exhibited markedly higher age-adjusted mortality rates (n/100,000 person-yr of diabetes) than the other three (Japan 681, U.S. 230, Finland 171, and Israel 131). CONCLUSIONS: These data indicate that young adult IDDM subjects are at an increased risk of premature death, there are differences in the mortality risk across countries, and both the U.S. and Japan have the major problem of an apparently excessive premature death rate among young people who have diabetes. 
4	Fatal fungal pericarditis after cardiac surgery and immunosuppression. The cases of two patients with fulminant pericarditis after cardiac surgery are reported. Both fungal infections developed after rethoracotomy for open-chest cardiac resuscitation and high-dose glucocorticoid treatment. Although the time course of both infections from the inoculation of fungi during rethoracotomy and immunosuppression with glucocorticoids to the lethal outcome was strikingly similar, histopathologic studies disclosed the disparate character of the two fungal pathogens responsible: the yeast Candida albicans and the angiotropic mold Aspergillus fumigatus. 
3	Differential diagnosis of mut and cbl methylmalonic aciduria by DNA-mediated gene transfer in primary fibroblasts. Methylmalonic aciduria can be caused by mutations in the gene encoding the methylmalonyl coenzyme A mutase apoenzyme (mut) or genes required for the provision of cofactor B12 (cbl). The mut and cbl forms are classically differentiated by somatic cell complementation. We describe a novel method for differential diagnosis of mut and cbl methylmalonic aciduria using DNA-mediated gene transfer of a methylmalonyl CoA mutase cDNA clone. Gene transfer of a functional methylmalonyl CoA mutase cDNA clone into mut fibroblasts reconstitutes holoenzyme activity measured by metabolism of [14C]-propionate in culture. Identical gene transfers into cbl fibroblasts have no effect. This method is used for the differential diagnosis of mut and cbl genotypes in cells from patients with a clinical diagnosis of methylmalonic aciduria and is shown to be a facile, sensitive, and specific method for genetic diagnosis. This work establishes the principle of using DNA-mediated gene transfer to identify the genotype of diseases which can result from mutations at several different genetic loci. This type of differential genotypic diagnosis will be particularly important for establishing the applicability of somatic gene therapy in individual patients. 
4	Isolated lung transplantation for pulmonary fibrosis. The peri-operative anaesthetic management of 11 patients with pulmonary fibrosis undergoing single-lung transplantation is presented. Intra-operative problems, the early postoperative phase of recovery and intensive care, and other incidents in which general anaesthesia was required for the management of complications, are featured. Results, both short- and long-term, are mentioned. Major intra-operative events that cause concern appear to be related to the severity of the presenting illness and the development of respiratory failure. Others have reported the development of intra-operative cardiac failure. All cases were successfully managed operatively using conventional one-lung anaesthesia, although resort to partial cardiopulmonary bypass may have been indicated in some. The indications and attitudes to utilising cardiopulmonary bypass in the evolution of techniques for facilitating single-lung transplantation are reviewed. 
5	Mild hypothermic intervention after graded ischemic stress in rats. We investigated the effect of mild (34 degrees C) postischemic hypothermia on hippocampal neuronal damage in 43 rats as a function of the duration of forebrain ischemia. Two temperatures and two durations were investigated. In two normothermic groups ischemia lasted 8 (n = 15) and 12 (n = 10) minutes, respectively. In two hypothermic groups ischemia lasted 8 (n = 9) and 12 (n = 9) minutes, respectively, and was followed immediately by the lowering and maintenance of rectal temperature to 34 degrees C for 2 hours. Seven days after the ischemic insult, the rats were sacrificed and the brains were prepared for histologic analysis; the percentage of necrotic neurons among the total neuronal population in selected CA1/2 sectors of the hippocampus was determined. There was a significant decrease in the percentage of necrotic neurons in the central (77.5% versus 55.5%, p = 0.006) and lateral (62.5% versus 38.9%, p=0.005) areas and in the overall CA1/2 sector of the hippocampus (71.8% versus 52.2%, p = 0.008) for the 8-minute hypothermic group compared with the 8-minute normothermic group. In contrast, no differences were detected in any area of the hippocampus between the 12-minute normothermic and the 12-minute hypothermic groups (p = 0.29-0.49). Our data indicate that mild postischemic whole-body hypothermia ameliorates neuronal survival when ischemia lasts 8 minutes but not 12 minutes. 
5	Intravascular laser therapy of acute myocardial infarction. The efficacy of a new method of treatment, endovascular blood irradiation with He-Ne laser, developed by the authors, was studied in 295 patients with primary acute transmural myocardial infarction (MI). Twenty-four-hour Holter monitoring findings before and after laser irradiation suggested the possibility of preventing sudden death in the acute period of MI owing to the high anti-arrhythmic efficacy of the method with respect to high-grade ventricular arrhythmias. Precodial ECG mapping and serial determination of blood enzyme activities (CPK and MB-CPK) showed that irradiation performed within the first hours of MI development contributed to effective limitation of the infarction area and restricted the spread of the area of myocardial ischemic damage. 
2	Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial OBJECTIVE: To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: United States Army hospital in Egypt. PARTICIPANTS: United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded. INTERVENTIONS: All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo. MEASUREMENTS: Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common. MAIN RESULTS: After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19). CONCLUSIONS: In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe. 
1	The potential role of postoperative hepatic artery chemotherapy in patients with high-risk hepatomas. The relationship between operative findings of hepatoma and the postoperative prognosis was studied to clarify indications for adjuvant hepatic arterial chemotherapy after hepatectomy. The results of adjuvant hepatic arterial chemotherapy using 0.4 mg/kg of doxorubicin and 0.12 mg/kg of mitomycin C and infusion of 5-fluorouracil were reported. One hundred sixty patients who had undergone hepatectomy for hepatoma were studied. In the operative findings of hepatoma, with a surgical margin of less than 10 mm, intrahepatic metastasis, tumor embolus in the second or more proximal branch of the portal vein, or lack of capsule formation related to the prognosis were the risk factors for recurrence. In 132 patients with these risk factors the survival rate of 19 patients with adjuvant arterial chemotherapy was significantly higher than for the 113 patients without it. Adjuvant hepatic arterial chemotherapy thus may be an effective therapy and should be studied prospectively in patients undergoing hepatectomy for high-risk hepatoma. 
5	Hot spots for growth hormone gene deletions in homologous regions outside of Alu repeats. Familial growth hormone deficiency type 1A is an autosomal recessive disease caused by deletion of both growth hormone-1 (GH1) alleles. Ten patients from heterogeneous geographic origins showed differences in restriction fragment length polymorphism haplotypes in nondeleted regions that flanked GH1, suggesting that these deletions arose from independent unequal recombination events. Deoxyribonucleic acid (DNA) samples from nine of ten patients showed that crossovers occurred within 99% homologous, 594-base pair (bp) segments that flanked GH1. A DNA sample from one patient indicated that the crossover occurred within 454-bp segments that flanked GH1 and contained 274-bp repeats that are 98% homologous. Although Alu repeats, which are frequent sites of recombination, are adjacent to GH1, they were not involved in any of the recombination events studied. These results suggest that length and degree of DNA sequence homology are important in defining recombination sites that resulted in GH1 deletions. 
4	Mechanical cardiopulmonary support for refractory cardiogenic shock. From February 1982 to February 1990, 38 patients (30 male patients and 8 female patients) ranging in age from 10 to 78 years (mean 49.4 years) have been supported with arteriovenous extracorporeal membrane oxygenation (ECMO) at St. Louis University Medical Center as a resuscitative system for cardiac arrest or cardiogenic shock. All patients were unresponsive to conventional resuscitative measures including an intraaortic balloon pump in 25 patients. Patients were resuscitated in the intensive care unit, cardiac catheterization laboratory, or the emergency department. Diagnosis varied from acute myocardial infarctions (12 patients), ischemic disease (15 patients), end-stage cardiomyopathy (7 patients), congenital heart disease (3 patients), or postoperative cardiac transplant graft rejection (1 patient). Three patients could not be resuscitated with ECMO because of low flow, but the remaining 35 (92%) achieved hemodynamic stability with ECMO flows greater than 2 L/min/m2. Duration of support ranged from 0.5 to 130 hours (mean 28 hours). Twenty-four patients were successfully weaned from ECMO support after coronary artery bypass (five patients), cardiac transplantation (two patients), or ventricular assist device insertion (eight patients), or with inotropic support (nine patients). Of the 14 patients not weaned, three were inadequately resuscitated, two had percutaneous transluminal coronary angioplasty while receiving ECMO, and nine were not candidates for further intervention. Nine (24%) patients were discharged and are long-term survivors. Our results indicate that resuscitative ECMO is useful for intervals of 12 to 24 hours and can best be applied with (1) patients younger than 60 years of age; (2) patients having acute events (failed percutaneous transluminal coronary angioplasty) amenable to surgical intervention; and (3) candidates for cardiac transplantation who could be switched to more sophisticated devices within 12 to 24 hours of ECMO insertion. With these criteria, ECMO, when used as a resuscitative system, can result in increased survival in selected patients with refractory cardiogenic shock or cardiac arrest. 
2	Bacteriologic findings with ectopic pregnancy. The fallopian tubes and peritoneum of 27 patients were cultured at the time of salpingotomy/salpingectomy to determine if active tubal infection was the cause of post-operative temperature elevations. Infection was documented in six patients (22%). Previous exposure to Chlamydia trachomatis was documented with 2 endocervical cultures and 17 serum specimens positive for IgG antibody. The culture results, however, did not correlate with the postoperative febrile morbidity. 
3	Maxillofacial surgery and nasal CPAP. A comparison of treatment for obstructive sleep apnea syndrome Nasal continuous positive airway pressure (CPAP) is the primary therapy for obstructive sleep apnea syndrome (OSAS). Recent reports have indicated, however, that there is a small but significant number of failures related to patient compliance. Primary surgical treatment, which has been uvulopalatopharyngoplasty (UPPP), has declined because of poor results. A reviewed of UPPP failures has shown that while UPPP eliminated palatal obstruction, it failed to eliminate base of tongue obstruction. Maxillofacial surgery has been reported as treatment of OSAS by correcting base of tongue obstruction. Thirty patients with severe OSAS were evaluated to compare nasal CPAP and maxillofacial surgery. The goal was to determine if our surgical protocol was as effective as nasal CPAP. All patients initially underwent baseline diagnostic polysomnography to document OSAS. A nasal CPAP study was performed to determine the appropriate positive end-expiratory pressure. The patients in this study were using nasal CPAP, but they found it unacceptable as long-term treatment and elected surgery. Maxillofacial surgery consisted of maxillary, mandibular, and hyoid advancement. Polysomnography was performed six months following surgery and compared with the night 2 CPAP results. The parameters included in the investigation were the respiratory disturbance index (RDI), lowest SaO2, number of SaO2 falls below 90 percent, total sleep time (TST), REM sleep percent, stage 3-4 sleep percent, and wake after sleep onset. The mean RDI before treatment was 72.0 (SD 25.7). After completing therapy, the RDI from surgery and CPAP was 8.8 (SD 6.0) and 8.6 (SD 4.1), respectively. The mean low SaO2 prior to treatment was 61.0 (SD 13.5), and the CPAP results and postsurgical results were 86.2 (SD 5.5) and 86.1 (SD 4.2), respectively. An analysis of variance was used to examine the results, and there was no statistical difference between nasal CPAP and surgery for all respiratory variables. 
1	Cyclophosphamide and ifosfamide combination as neoadjuvant chemotherapy for locally advanced nonsmall-cell lung cancer: a meta-analytic review. Twenty-three patients with marginally resectable and unresectable non-small-cell lung cancer (stages IIIA and IIIB) were treated by neoadjuvant chemotherapy. All patients received three cycles of preoperative chemotherapy with two alkylating agents, cyclophosphamide 2.5 g/m2 intravenously (i.v.) and ifosfamide 3.5 g/m2 i.v., mesna 12 g/m2 was given additionally to prevent drug hematuria. Six of 23 patients (26%) had partial response. Of the seven patients who underwent thoracotomy, two were completely resected, but with macroscopic residual disease. Mean time to progression for the whole group was 7 months. Fifteen patients had progression of disease, with local metastases only in six, and distant metastases in eight. After administering 52 chemotherapy cycles, cyclophosphamide-ifosfamide doses were cut down, as eight of 16 patients required hospitalization for fever during neutropenia nadirs. This two-alkylating (non-cisplatin) regimen, unlike cisplatin-based regimens, was ineffective, and further trials are not recommended. 
5	Mucosal intussusception to avoid ascending cholangitis. Many methods have been devised to prevent ascending cholangitis following Kasai's hepatic portoenterostomy for biliary atresia. To investigate the effectiveness of mucosal intussusception in preventing ascending cholangitis, 20 mongrel dogs were randomized to undergo Roux-en-Y cholecystjejunostomy and common bile duct ligation with or without mucosal intussusception. Aeromonas hydrophila was instilled into the gastrointestinal tract. Bacterial cultures were grown from samples taken from the gallbladders and lower jejunum, and blood chemistry and barium studies were performed. The barium studies showed satisfactory lack of reflux in all ten dogs with mucosal intussusception. Only two of them had positive cultures for Aeromonas from the gallbladder 3 days after bacterial instillation into the jejunum. All ten dogs in the control group had positive cultures for Aeromonas from the gallbladder. Our results showed that the mucosal intussusception group had a significantly lower rate of recovery of organisms from the gallbladder compared with the control group when the organisms were instilled into distal intestine (P less than 0.05). The method is worthy of clinical trial as a means of preventing or treating ascending cholangitis. 
1	A report on radiation-induced gliomas. Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy. 
5	Variceal rebleeding after portosystemic shunting. Strategies and solutions to a vexing problem. The purpose of this review was to discuss an approach to the treatment of recurrent bleeding from esophageal or gastric varices after portosystemic shunt. From our own clinical experience, as well as that of others, it appears that re-establishment of portal decompression should offer the best chance at long-term survival. Luckily, innovations in angiographic technique have allowed attainment of this goal without the inordinate risk of an operative procedure. However, not all patients' situations will be amenable to such treatment. For some of them, operative decompression of the portal venous system can be carried out in an anatomic area previously untouched. For those patients in whom no decompression is possible, direct endoscopic treatment of the varices will offer an alternative, albeit temporizing, approach. 
3	Detecting lower motor neuron dysfunction of the pharynx and larynx with electromyography. This study assessed the utility of clinical electromyography (EMG) for detecting lower motor neuron (LMN) or upper motor neuron (UMN) dysfunction affecting the intrinsic muscles of the larynx and pharynx. Twenty-nine subjects were examined; their clinical diagnoses included perioperative nerve injury, cerebral infarction, and lateral medullary infarction. Resting activity, motor unit action potential (MUAP) morphology, and MUAP recruitment were evaluated in every case. Medical records (excluding EMG data) were analyzed for clinical evidence of LMN or UMN dysfunction in the intrinsic muscles of the larynx and pharynx. The diagnosis of LMN dysfunction rested on clinical data consistent with cranial nerve injury, poliomyelitis, Wallenberg syndrome, or unilateral bulbar palsy. Criteria for UMN dysfunction included previous cerebral (not brainstem) infarction or mass lesion or the presence of hemiparesis. Electromyographic abnormalities were significantly associated with LMN dysfunction (p less than .05), but they were not significantly associated with UMN dysfunction. Of the parameters tested, MUAP recruitment was the most sensitive (82%) and specific (92%). 
1	Use of monoclonal antibody KP1 for identifying normal and neoplastic human mast cells. The monoclonal antibody KP1 (CD68) was used to stain normal and neoplastic monocytes and macrophages in routinely processed, paraffin wax embedded tissue: mast cells also exhibited strong, consistent cytoplasmic immunoreactivity. Light microscopic findings were corroborated by electron microscopical and immunocytochemical findings. The predominant sites of immunoreactivity were the specific intracytoplasmic granules of the mast cells. All mast cell subtypes--that is, normal and reactive mast cells, such as those in lymph nodes exhibiting chronic non-specific lymphadenitis, and malignant or neoplastic mast cells in various types of mastocytosis--reacted with this antibody. This finding is of diagnostic importance, because mast cell proliferation could be mistaken for histiocyte proliferation. It also supports the hypothesis that mast cells derive from the bone marrow. 
1	Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study. Of 2947 children with acute lymphocytic leukemia (ALL), treated during three consecutive studies of the Pediatric Oncology Group (1974-1986), 52 (1.8%) had Down's Syndrome (DS). Comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count, racial distribution, sex ratio, platelet count, incidence of mediastinal mass, lymphadenopathy or hepatosplenomegaly, or percentage of blood or bone marrow blasts for children with ALL with or without Down's Syndrome (DS-ALL or NDS-ALL, respectively). However, children with DS-ALL were slightly older at the time of presentation and had higher hemoglobin values. The relative frequency of each major immunophenotype (early pre-B, pre-B, T, or B) was also comparable for patients with or without DS. For this report, treatment regimens were categorized as either conventional (no consolidation therapy) or intensive. Cox regression analysis revealed that the presence of DS, a higher leukocyte count, black race, or age older than 10 years was independently associated with a poorer event-free survival (EFS) for children treated with conventional chemotherapy. However, for the cohort of children who received intensive chemotherapy, DS was no longer an independent risk factor. In fact, event-free survival (EFS) was markedly improved to a level comparable with that observed in the children diagnosed as having NDS-ALL. On the other hand, serious toxicity, requiring interruption of treatment, was significantly more frequent in the intensively treated children with DS compared with similarly treated patients with NDS-ALL, although deaths resulting from toxicity occurred infrequently. 
1	Fractionated high dose rate versus low dose rate regimens for intracavitary brachytherapy of the cervix. I. General considerations based on radiobiology. Intracavitary brachytherapy at low dose rate (LDR), often with the addition of external-beam radiotherapy, has long been considered the treatment of choice for carcinoma of the cervix, maximizing acute damage in the treatment volume, whilst minimizing late effects. In recent years, primarily for reasons of convenience and cost, there has been a move towards treatments involving a few fractions at high dose rate (HDR). Using data from cells of human origin cultured in vitro, we make estimates of the doses that, delivered in 2-12 HDR fractions, produce tumour control and early effects equivalent to intracavitary treatments at LDR. We also show that, for situations where the normal-tissue dose responsible for late effects is significantly smaller than the tumour dose, HDR schemes may be devised which, while yielding early killing comparable with that of LDR, should not result in worse late effects. We suggest that this scenario probably applies to treatment of carcinoma of the cervix. 
5	Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine. 
5	The Indian experience with hypertrophic pyloric stenosis. A study of 58 consecutive Indian infants operated for congenital hypertrophic pyloric stenosis revealed an accentuated male predominance in the incidence of the disease and far less preoperative hemetemesis as compared to that in their Western counterparts. 'Pyloric tumor' was palpable in 89% of cases. Only 34.5% of these infants were first born. Postoperative vomiting occurred in 13.8% of patients and wound sepsis was not encountered. Air contrast radiography confirmed the diagnosis in clinically doubtful cases. 
4	Quincke's edema, revisited. Angioneurotic edema involving the uvula is sometimes referred to as Quincke's edema. The term angioneurotic edema describes several closely related diseases manifested by recurrent, acute edema of the skin or mucosa. We report a case of uvular edema secondary to food allergy, treated successfully with steroids. A short review of angioneurotic edema and its management is also presented. 
1	Evaluation of tumor progression by repeated fine needle biopsies in prostate adenocarcinoma: modal deoxyribonucleic acid value and cytological differentiation. Repeated fine needle aspiration biopsies of the prostate were taken during a period of 24 months or more from 84 patients with untreated prostate cancer. Serial followup regarding modal deoxyribonucleic acid values and cytological differentiation of the tumor cells was possible in 72 and 78 patients, respectively. During followup the modal deoxyribonucleic acid values in the tumor cells changed towards an increased aneuploidy in 17 patients and the cytological differentiation decreased in 18. These findings of a change in modal deoxyribonucleic acid values and cytological differentiation of prostate cancer cells during the course of untreated patients support the concept of a gradual dedifferentiation of prostate cancer. 
1	Hypersensitivity reactions to epipodophyllotoxins in children with acute lymphoblastic leukemia. The incidence, clinical characteristics, and outcome of hypersensitivity reactions to teniposide (VM-26), etoposide (VP-16), or both were determined in 108 children with acute lymphoblastic leukemia (ALL) treated with a contemporary regimen of intensive multiagent chemotherapy. Fifty (46%) of the 108 patients had one or more hypersensitivity reactions. The risk of any child having an initial reaction over the cumulative dose range studied was 52% (95% confidence limits, 41% and 63%) for VM-26, compared with 34% (95% confidence limits, 24% and 44%) for VP-16. The risk of having an initial reaction to VM-26 or VP-16 was clearly related to the cumulative dose. This risk peaked at 1500 to 2000 mg/m2 for VM-26 and at 2000-3000 mg/m2 for VP-16. All reactions were Type 1 reactions according to the Gell and Coombs classification, characterized by urticaria, angioedema, flushing, rashes, or hypotension, and 86% of reactions were of Grade 1 or 2 severity according to standard criteria. There was no evidence of increasing clinical severity on repeated rechallenge with premedication, and no deaths occurred. The findings suggested that hypersensitivity reactions to epipodophyllotoxins in children with ALL are more common than previously reported, but only rarely constitute dose-limiting toxicity. 
1	Expression of blood-group antigen A--a favorable prognostic factor in non-small-cell lung cancer. BACKGROUND. New prognostic factors are needed to guide the treatment of patients with non-small-cell lung cancer. We evaluated the prognostic value of altered expression of ABH blood-group antigens, which has been implicated in the multistep process of carcinogenesis and tumor progression. METHODS. The presence of blood-group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 164 patients who underwent curative surgery for non-small-cell lung cancer from 1980 through 1982. Monoclonal antibodies were used to detect the A and B antigens, and Ulex europaeus agglutinin I to detect H antigen. RESULTS. Survival of the 28 patients with blood type A or AB who had primary tumors negative for blood-group antigen A was significantly shorter than that of the 43 patients with antigen A-positive tumors (P less than 0.001) and of the 93 patients with blood type B or O (P = 0.002). The respective median survival times were 15, 71, and 39 months. Disease progressed significantly earlier in the 28 patients with tumors negative for blood-group antigen A than in the antigen A-positive patients (P less than 0.001). Expression of blood-group antigen B or H in tumor cells did not correlate with survival. Cox proportional-hazards regression analysis showed that expression of blood-group antigen A in tumor cells added significantly to the prediction of overall survival provided by other known prognostic factors among the patients with blood type A or AB (P = 0.004). CONCLUSIONS. Expression of blood-group antigen A in tumor cells is an important favorable prognostic factor in patients with non-small-cell lung cancer. This variable needs to be considered in the design of future trials of therapy. 
4	Adult open heart surgery in New York State. An analysis of risk factors and hospital mortality rates This study analyzes data from New York State's new Cardiac Surgery Reporting System, which contains information about cardiac preoperative risk factors, postoperative complications, and hospital discharge. The purposes of the study were to determine the set of significant clinical risk factors and to identify cardiac surgical centers most likely to have serious quality-of-care problems. Significant risk factors for in-hospital death were age, gender, ejection fraction, previous myocardial infarction, number of open heart operations in previous admissions, diabetes requiring medication, dialysis dependence, disasters (acute structural defect, renal failure, cardiogenic shock, gunshot), unstable angina, intractable congestive heart failure, left main trunk narrowed more than 90%, and type of operation performed. Four of the 28 hospitals had significantly higher mortality rates than expected, given the risk factors of their patients. Subsequent site visits and medical record reviews confirmed that these facilities had high percentages of quality-of-care problems among cases resulting in mortality. 
5	Hypothalamic or central obesity is associated with an early rise in plasma insulin concentration. Insulin levels in a 7-year-old boy with hyperphagia and obesity following an episode of meningoencephalitis were studied sequentially during the course of progressive weight gain. High fasting insulin levels (1183 pmol/L) and strikingly high insulin release in response to glucose (7892 pmol/L) were found within weeks of the onset of the illness. The abnormality in insulin secretion occurred prior to the marked weight gain. Hyperinsulinemia was not accompanied by hypoglycemia. Early hyperinsulinemia may be a primary event in the development of hyperphagia and obesity following hypothalamic injury. 
5	Treatment of Fournier's gangrene with adjunctive hyperbaric oxygen therapy. Fournier's gangrene is a devastating infection and often is associated with a high morbidity and mortality. Surgical debridement and antibiotics are the cornerstones of therapy. This case describes the use of hyperbaric oxygen as an adjunct in the treatment of Fournier's gangrene. 
5	Pulmonary-renal syndrome with "triad" involvement due to small vessel vasculitis. We describe the clinical course and morphologic findings of a 22-year-old woman presenting with a systemic disease that included nasal ulceration, hemoptysis and rapidly progressive renal failure. Biopsies of nasal septum and lung revealed small vessel leukocytoclastic angiitis while renal biopsy showed a diffuse crescentic glomerulonephritis. Immunosuppressive therapy resulted in remission of clinical symptoms and resolution of glomerulonephritis as documented in a followup biopsy. Although her clinical presentation with triad organ involvement strongly suggested Wegener's granulomatosis, this case illustrates that other varieties of vasculitis may mimic Wegener's granulomatosis. 
5	Postischemic seizures and necrotizing ischemic brain damage: neuroprotective effect of postischemic diazepam and insulin. Insulin has recently been shown experimentally to modify ischemic brain damage when administered either before or after the episode of ischemia. In controlled studies in the rat, high doses of insulin (greater than or equal to 8 IU/kg) result in seizures and early death. The present study was undertaken to determine whether diazepam, a potent, centrally penetrating GABAmimetic, alone or in combination with insulin, could mitigate postischemic seizures or regional selective neuronal necrosis and infarction. Forebrain ischemia was induced in rats for 10 1/2 minutes by carotid clamping and hypotension. The animals were observed clinically until elective perfusion-fixation and quantitative pathologic examination at 1-week recovery. Diazepam, either alone or with insulin, reduced regional brain necrosis and reduced the seizure rate. Insulin alone also led to reduced regional necrosis. However, the combination of diazepam plus insulin yielded the greatest proportion of undamaged brains in the hippocampus, thalamus, and midbrain. In the neocortex, the diazepam-only group showed the greatest number of normal hemispheres. Hypothalamic infarction was eliminated by all three treatments. Seizures per se were associated with increased damage in the cerebral cortex, thalamus, and brainstem, irrespective of treatment group. The findings indicate that ischemic brain necrosis can be mitigated by diazepam and insulin treatment begun in the immediate postischemic period. 
5	Snoring (I). Daytime sleepiness in regular heavy snorers. Fifteen men, mean (means) age 44 years, were investigated. Their means body mass index was 21.9 kg/m2, and all of them had a respiratory disturbance index below 5 and had good nocturnal oxygen saturation. The subjects were monitored several nights both with and without the following devices: a tight-fitting facial mask, a pneumotachometer, and an esophageal balloon. They were also monitored with and without nasal continuous positive airway pressure. The Multiple Sleep Latency Test was administered after three of the experimental nights (after the baseline nights and after the second nasal CPAP night). Determination of short EEG arousals during nocturnal sleep, which lasted 2 to 10 s, was performed. The relationship between short EEG arousals, the esophageal pressure nadir, and airflow decrease was investigated. We also determined the relationship between clinical reporting of decrease in daytime alertness and MSLT results, and the relationship between MSLT results and the frequency of EEG arousals. The monitoring indicated that heavy snorers may present significant increase in Pes nadir with abrupt decrease in flow leading to EEG arousals. The frequency at which EEG arousals occur has an impact on MSLT scores. Nasal CPAP improves MSLT scores and eliminates these respiration-related EEG arousals. Some heavy snorers without obstructive sleep apnea syndrome may be at risk of having a decrease in daytime alertness. 
1	Lithiumogenic disorders of the thyroid and parathyroid glands as surgical disease. Little notice has been paid in the surgical literature to problems with psychoeffective lithium, which by interfering with adenylate cyclase affects thyroid and parathyroid function, causing hypercalcemia, hyperparathyroidism, and hypothyroidism. Seven patients with lithiumogenic hyperparathyroidism occurring after years of lithium therapy underwent treatment and manifested osteoporosis (n = 2), hypertension (n = 2), nephrolithiasis (n = 1), coma (n = 1), rising hypercalcemia (n = 1), goitrous myxedema (n = 4), nephrogenic diabetes insipidus (n = 2), renal failure (n = 2), and hyperlipidemia (n = 1). Disease-directed parathyroidectomy (without morbidity) was curative. Unique laboratory findings included normal serum phosphorus and reduced urinary calcium and cyclic adenosine monophosphate values. Three separate cases of thyroid carcinoma after long-term lithium therapy were also treated, being preceded by myxedema (n = 2) and concurrent with hyperparathyroidism (n = 1). There has been only one previous report of lithium-associated thyroid carcinoma. All patients taking lithium should undergo surveillance for thyroid and parathyroid dysfunction and neoplasia, and appropriate surgical and medical treatment should be considered in each situation. Although hyperparathyroidism may be reversible with lithium discontinuance, such therapy may be obligatory for patient well-being, thus dictating parathyroidectomy. 
5	Reperfusion inhibits elevated splanchnic prostanoid production after hemorrhagic shock [published erratum appears in Ann Surg 1991 Feb;213(2):91] The effect of reperfusion following hemorrhagic shock on splanchnic prostanoid release was studied. Anesthetized male rats were bled to a mean arterial blood pressure of 30 mmHg for 30 minutes and either killed or treated with shed blood for 60 minutes and then killed. The superior mesenteric arterial bed was cannulated and perfused in vitro with oxygenated Krebs. Collected venous effluent (up to 180 minutes) was analyzed for 6-keto-PGF1 alpha (PGI2 metabolite), PGE2, PGF2 alpha, and thromboxane B2 by radioimmunoassay in shock, shock plus reperfusion, and sham groups. The major prostanoid released was 6-keto-PGF1 alpha and was three times higher in the shock group compared to the sham group (p less than 0.05). Reperfusion of shed blood abolished the increase in 6-keto-PGF1 alpha found in the shock group (p less than 0.05). These data show that the attempt of the rat splanchnic bed to compensate for hemorrhagic shock by increasing release of PGI2 (potent vasodilator) was abolished during reperfusion of blood. 
1	Radical resection for carcinoma of the ampulla of Vater. One hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed. Frequent clinical findings included jaundice (67%), significant (greater than 10%) weight loss (42%), and anemia (27%). Eighty-seven patients (84%) underwent a subtotal pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy. The postoperative mortality was 5.7% (six patients), and reoperation for postoperative complications was required in six patients. The 5- and 10-year survival rates were 34% and 25%, respectively. Eight patients died of tumor recurrence more than 5 years after resection. Patient survival was significantly impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor grade, and the epithelium of origin. In a multivariate analysis, only microscopic lymphatic invasion significantly reduced patient survival. Radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma. 
4	Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B BACKGROUND AND METHODS. The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). RESULTS. The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent). In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent. By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; P less than 0.005). Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions. Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77). CONCLUSIONS. In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events. 
2	A case of group B streptococcal pyomyositis The group B streptococcus is an opportunistic pathogen that causes a variety of serious infections including bacteremias, puerperal sepsis, and neonatal meningitis. Group B streptococcal infections of muscle are rare. We report here an unusual case of group B streptococcal pyomyositis. Pyomyositis arises predominantly from infections caused by Staphylococcus aureus and, occasionally, Streptococcus pyogenes. Because of the rarity of pyomyositis in temperate climates, the common lack of localizing signs or symptoms, and the frequently negative blood cultures, considerable delay often precedes the diagnosis of pyomyositis; in fact, the infection has been initially misdiagnosed as muscle hematoma, cellulitis, thrombophlebitis, osteomyelitis, or neoplasm. Diagnosis may be greatly aided by radiologic techniques that can demonstrate the sites of muscle enlargement and the presence of fluid collections. The response to antibiotics is usually rapid, but resolution of the infection may require aspiration of deeply situated muscle abscesses. This report describes a diabetic patient with an unusual presentation of pyomyositis that mimicked an acute abdomen. 
5	Surgical results of intrathoracic gastric volvulus complicating hiatal hernia. From 1981 to 1988, 138 patients with hiatal hernia were treated surgically at our centre. Twenty-one (mean age 76.6 years, 17 women, four men) had an associated intrathoracic gastric volvulus. Eleven patients (mean age 73.2 years), of whom eight were asymptomatic, had an elective procedure. Ten patients (mean age 80.3 years) had emergency surgery, six for acute complications of the volvulus (five cases of strangulation and one of perforated ulcer) and four because of other, unrelated causes of acute abdomen. There were four deaths after operation, all in the emergency surgery group. Four other patients had significant morbidity, all in the emergency group. In the elective cases, all hernias were easily reduced. In one emergency case a gastrotomy was necessary for decompression, and in another gastrectomy was necessary because of gastric gangrene. Our results indicate the need for elective intervention when intrathoracic gastric volvulus is first diagnosed. 
4	Changes in haemostasis after stopping the combined contraceptive pill: implications for major surgery. OBJECTIVE--To investigate the changes in haemostasis in the three months immediately after stopping the combined contraceptive pill. DESIGN--Prospective randomised study. SETTING--Family planning centre in London. SUBJECTS--24 women aged 35-45 investigated before, during, and after six months' use of combined oral contraceptives containing 30 micrograms ethinyl oestradiol together with the progestogens desogestrel or gestodene. MAIN OUTCOME MEASURES AND RESULTS--Blood samples were taken immediately before and after six months of oral contraceptive use and one, two, four, six, eight, and 12 weeks after the pill had been stopped. During the six months of oral contraceptive use the plasma concentration of factor X and fibrinogen increased and that of antithrombin III decreased. Between two and six weeks after stopping the pill a rebound phenomenon occurred with plasma concentrations of antithrombin III increasing (mean change from baseline at two weeks 0.06 IU/l and at six weeks 0.10 IU/l) and fibrinogen decreasing (0.26 g/l change at two weeks and 0.40 g/l at six weeks). Factor X concentrations fell gradually and the values at eight weeks were not significantly different from those found before the combined pill was started. CONCLUSION--The combined pill should be stopped at least four weeks before major surgery, which carries the risk of postoperative thrombosis, to allow the potentially prothrombotic haemostatic changes that occur during its use to be corrected. 
5	Prevalence of acute mountain sickness in the Swiss Alps. OBJECTIVE--To assess the prevalence of symptoms and signs of acute mountain sickness of the Swiss Alps. DESIGN--A study using an interview and clinical examination in a representative population of mountaineers. Positive symptoms and signs were assigned scores to quantify the severity of acute mountain sickness. SETTING--Four huts in the Swiss Alps at 2850 m, 3050 m, 3650 m, and 4559 m. SUBJECTS--466 Climbers, mostly recreational: 47 at 2850 m, 128 at 3050 m, 82 at 3650, and 209 at 4559 m. RESULTS--In all, 117 of the subjects were entirely free of symptoms and clinical signs of acute mountain sickness; 191 had one or two symptoms and signs; and 158 had more than two. Those with more than two symptoms and signs were defined as suffering from acute mountain sickness. At 4559 m 11 climbers presented with high altitude pulmonary oedema or cerebral oedema, or both. Men and women were equally affected. The prevalence of acute mountain sickness correlated with altitude: it was 9% at 2850 m, 13% at 3050 m, 34% at 3650 m, and 53% at 4559 m. The most frequent symptoms and signs were insomnia, headache, peripheral oedema, and scanty pulmonary rales. Severe headache, vomiting, dizziness, tachypnoea, and pronounced pulmonary rales were associated with other symptoms and signs and therefore characteristic of acute mountain sickness. CONCLUSION--Acute mountain sickness is not an uncommon disease at moderately high altitude--that is, above 2800 m. Severe headache, vomiting, dizziness, tachypnoea, and pronounced pulmonary rales indicate severe acute mountain sickness, and subjects who suffer these should immediately descend to lower altitudes. 
5	Fast short-tau inversion-recovery MR imaging. To enhance the versatility of the short-tau inversion-recovery (STIR) sequences, the authors determined a range of repetition time (TR) and inversion time (TI) combinations that suppress signal intensity from fat by study of both patient and phantom images. To make fast STIR images, variations in the following pulsing conditions were studied with use of an interactive computer program: decreasing the TR, limiting the number of excitations, and limiting the number of phase-encoding steps. The authors found that (a) STIR imaging need not be time consuming, (b) fat suppression can be accomplished at shorter TR by using shorter TI, and (c) short-TR fast STIR imaging is sensitive to enhancement with gadopentetate dimeglumine. 
1	Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma [published erratum appears in J Clin Oncol 1991 May;9(5):893] Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors. Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype. In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms. Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P less than .0001). None of the eight patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site. Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup. 
1	Induction of donor-type chimerism in murine recipients of bone marrow allografts by different radiation regimens currently used in treatment of leukemia patients. Three radiation protocols currently used in treatment of leukemia patients before bone marrow transplantation (BMT) were investigated in a murine model (C57BL/6----C3H/HeJ) for BM allograft rejection. These include (a) a single dose of total body irradiation (8.5 Gy TBI delivered at a dose rate of 0.2 Gy/min), (b) fractionated TBI (12 Gy administered in six fractions, 2 Gy twice a day in 3 days, delivered at a dose rate of 0.1 Gy/min, and (c) hyperfractionated TBI (14.4 Gy administered in 12 fractions, 1.2 Gy three times a day in 3 days, delivered at a dose rate of 0.1 Gy/min). Donor-type chimerism 6 to 8 weeks after BMT and hematologic reconstitution on day 12 after BMT found in these groups were compared with results obtained in mice conditioned with 8 Gy TBI delivered at a dose rate of 0.67 Gy/min, routinely used in this murine model. The results in both parameters showed a marked advantage for the single dose 8.5 Gy TBI over all the other treatments. This advantage was found to be equivalent to three- to fourfold increment in the BM inoculum when compared with hyperfractionated radiation, which afforded the least favorable conditions for development of donor-type chimerism. The fractionated radiation protocol was equivalent in its efficacy to results obtained in mice irradiated by single-dose 8 Gy TBI, both of which afforded a smaller but not significant advantage over the hyperfractionated protocol. This model was also used to test the effect of radiation dose rate on the development of donor-type chimerism. A significant enhancement was found after an increase in dose rate from 0.1 to 0.7 Gy/min. Further enhancement could be achieved when the dose rate was increased to 1.3 Gy/min, but survival at this high dose rate was reduced. These results demonstrated indirectly that dose rate affects the expression of host-type pluripotent stem cells, the progeny of which appear 3 to 6 weeks after treatment with 8 Gy TBI delivered at a dose rate of 0.1 Gy/min, but which are eradicated if radiation is delivered at a dose rate of 1.3 Gy/min. 
2	The effects of vitamin K on the generation of des-gamma-carboxy prothrombin (PIVKA-II) in patients with hepatocellular carcinoma. The clinical significance of des-gamma-carboxy prothrombin (PIVKA-II) in hepatocellular carcinoma (HCC) was investigated in 112 patients with and without vitamin K administration. The positivity rate of PIVKA-II was significantly decreased in patients receiving vitamin K (28.5%), compared with those without vitamin K administration (54.5%, p less than 0.05). The plasma levels of vitamin K derivatives [phylloquinone (VK1), menaquinone-4 (MK4), and menaquinone-7 (MK7)] measured were not decreased in patients with HCC, but were significantly increased in MK4 and VK1 + MK4 + MK7. The amount of PIVKA-II in plasma did not correlate with the plasma levels of vitamin K derivatives. However, PIVKA-II was decreased by the administration of vitamin K, and all of the six patients with more than 5.0 ng/ml of VK1 + MK4 + MK7 were within normal limits, whereas half of 32 patients with less than that had abnormal levels of PIVKA-II. Thus, it was suggested that PIVKA-II was not elevated due to vitamin K deficiency, but might result from the impaired metabolism or availability of vitamin K in the tumor. Therefore, PIVKA-II should be measured without vitamin K administration. 
2	Exocrine pancreatic function in chronic liver diseases. To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity. 
5	A denaturated venous homograft as an alternative material for shunts and other reconstructions in congenital cardiac surgery. A human venous homograft "Varivas R", in clinical use for 10 years for vascular access loops and femoropopliteal bypasses, has been used since December 1985 as a material for aortopulmonary shunts and other reconstructive procedures in congenital heart surgery. For this purpose vein segments 5 cm length, varying in diameter from 4 up to 10 mm by steps of 1 mm, were obtained. Our experience with Varivas is limited to 59 patients. Of 47 infants, 18 received a left, and 25 a right sided aortopulmonary shunt, 9 had bilateral aortopulmonary shunts, 2 right ventricle pulmonary conduits, 1 a pulmonary-pulmonary conduit, 3 interrupted aortic arch reconstructions and 4 a central aortopulmonary shunt, 1 with confluence reconstruction, 3 recidives of coarctation a patch repair. Among 11 adults 6 received coronary bypass and 6 others vascular reconstructions. In contrast to other artificial graft materials, the vein material offers easy manipulation similar to the daily routine of handling fresh vein material offers easy manipulation similar to the daily routine of handling fresh vein grafts in coronary surgery. The appropriate diameter sizes match better the infants anatomy, without the risk of kinking and/or anastomosis displacement. Peroperatively it was possible to confirm patency by electromagnetic flow measurement and the postoperative examinations were done by colour Doppler echocardiography. We had to reoperate upon 4 infants because of early thrombosis; on 1 infant for stenosis of the graft and on another 5 for late thrombosis. In an attempt to extend the indications for "inoperable" pulmonary hypoplasia/atresia we were not able to keep the shunt open in 4 infants. 
4	Atrial fibrillation and left atrial enlargement: cause or effect? In a blinded controlled study, 58 consecutive patients with definite left atrial enlargement (M-mode dimension of at least 45 mm) were followed up after 1-2 years. The aim of the study was to examine the following: (a) the prospective risk of developing atrial fibrillation (AF); and (b) the effect of the heart rhythm on the left atrial size. Of 36 patients in sinus rhythm, one developed paroxysmal AF and one developed persistent AF during a median follow-up period of 20 months. Thus the incidence of new AF was 5% per year. Eighteen patients died before scheduled echocardiographic follow-up, but in the remaining subjects the left atrial dimension did not change significantly: the median increment was 1 mm in 20 patients who sustained sinus rhythm vs 2 mm in 16 patients with chronic AF (P greater than 0.05). Although left atrial dilatation may cause AF and vice versa, this study demonstrated that the incidence of new AF is low, despite the fact that the left atrial dimension is substantially increased. Similarly, AF per se does not appear to have any major impact on the left atrial dimension. 
4	Medical management of acute traumatic rupture of the aorta. Surgical reconstruction is the treatment for acute traumatic aortic rupture and should be accomplished immediately in most patients. In patients in whom concomitant injuries or the development of life-threatening complications preclude safe and successful aortic reconstruction, pharmacological intervention to reduce the risk of free aortic rupture may be considered. Surgical reconstruction can then be more safely performed under controlled elective circumstances. 
3	The deja vu experience: remembrance of things past? The deja vu experience is a common phenomenon, occurring in pathological as well as nonpathological conditions. It has been defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. The authors discuss the epidemiologic data, clinical features, and etiology of the phenomenon of deja vu. They also review the different hypotheses on the psychopathogenesis of the deja vu experience and introduce an explanation based on the hologram as a mnestic model. 
3	Effects of head trauma from motor vehicle accidents on Parkinson's disease. During 1 year we monitored changes in clinical disability scores in 10 patients with Parkinson's disease (PD) who sustained head trauma from motor vehicle accidents. Disability significantly increased immediately after trauma, but returned to baseline levels in subsequent weeks. These patients' signs deteriorated over the subsequent year, but this decline was equivalent to that of a matched control group with PD who did not have a motor vehicle accident or trauma. Based on these data, we conclude that trauma or stress caused by motor vehicle accidents can transiently exacerbate parkinsonian dysfunction without causing persistent increased disability or an alteration in disease course. 
1	Renal cell carcinoma associated with sarcoidlike tissue reaction. A 60-year-old man was referred to our institution with the diagnosis of sarcoidosis. Because of several months' complaint of right flank pain and weight loss, the patient had consulted his local physician. After an extensive workup revealed only cholelithiasis, he underwent a cholecystectomy for presumed chronic cholecystitis. At the time of operation, biopsy of several liver nodules and peripancreatic nodes revealed noncaseating granulomas, consistent with sarcoidosis. On initial examination at our institution, the patient had microhematuria. A chest roentgenogram demonstrated multiple pulmonary nodules, an abdominal computed tomographic scan showed an indeterminate left renal mass, and magnetic resonance imaging of the spine revealed abnormal signals in the body of T-12. Open-lung biopsy showed an adenocarcinoma with clear cell features, likely of renal origin. The patient was diagnosed as having a metastatic renal carcinoma associated with a sarcoidlike tissue reaction. Although noncaseating granulomas have been reported in association with other malignant lesions, to our knowledge this is the first report of such an association with renal carcinoma. In addition, this case illustrates several points. First, sarcoidosis is a multisystem disorder with protean extrapulmonary manifestations. In fact, all our patient's findings could have been attributed to sarcoidosis. Second, noncaseating granulomas occur with many types of processes, including infections, chemical exposures, and, as in this case, neoplasms. Thus, noncaseating granulomas are not pathognomonic for sarcoidosis. Third, sarcoidosis is a clinical diagnosis that cannot be based on histologic findings alone. 
5	Allergen-induced increase in airway responsiveness and inflammation in mild asthma. The relationship between airway responsiveness to methacholine and inflammatory cells in bronchoalveolar lavage (BAL) was determined in patients with history of rhinitis and/or mild bronchial asthma either at baseline (10 patients) or 3-4 h after allergen inhalation challenge (11 patients). At baseline, airway responsiveness did not correlate with any BAL cell population. When data obtained after allergen challenge were included in the analysis, 44% of the variability of airway responsiveness was explained by a multiple regression model with BAL eosinophils as a directly correlated (P = 0.002) independent variable and with BAL macrophages as an inversely correlated (P = 0.045) independent variable. Changes in airway responsiveness after allergen challenge were predicted (82% of variance explained) by a model with BAL eosinophils and BAL lymphocytes as directly correlated (P = 0.0002 and P = 0.03, respectively) independent variables. We conclude that, in stable asymptomatic asthma, baseline airway responsiveness does not correlate with the presence in the airways of inflammatory and immunoeffector cells that can be recovered by BAL. Nevertheless the allergen-induced increase in airway responsiveness is associated with an influx of eosinophils and lymphocytes in the bronchial lumen. 
5	Leukemias of indeterminant lineage. Two biologically and clinically important forms of acute leukemia have been described. Evidence suggests that both undifferentiated acute leukemia and many types of hybrid leukemia arise from relatively fewer differentiated cells than do the more straightforward acute leukemias. Clinical correlations suggest that patients with these leukemias may have a poorer prognosis, although some findings may be associated with an improved prognosis. More data in which multiple techniques are applied to the same leukemic cells are clearly needed. Patients with certain types of hybrid leukemias may be suitable candidates for more aggressive forms of chemotherapy or, possibly, combinations of therapy directed at cells of both lineages. 
3	32-gauge spinal catheters through 26-gauge needles Small diameter intrathecal catheters potentially combine the certainty of intrathecal injection and the advantage of repeatability, without the risk of a high incidence of headache after dural puncture. We report problems placing such catheters. 
4	Lovastatin. Warfarin interaction. Two patients who developed hypoprothrombinemia and bleeding due to lovastatin-warfarin drug interaction are described. Because of the wider use of lovastatin and warfarin, heightened clinical awareness of this potentially serious interaction must be publicized. Therefore, prothrombin time should be monitored diligently when warfarin is prescribed to patients receiving lovastatin. 
5	Lack of association between keratoconus, mitral valve prolapse, and joint hypermobility. The authors enrolled 95 patients with keratoconus and 96 matched controls in a cross-sectional study to determine if mitral valve prolapse and hypermobile joints occur with greater frequency in individuals with keratoconus than in individuals without keratoconus. The hypothesis that keratoconus may not be a distinct eye disease, but a nonspecific sign representing a more generalized systemic disorder, possibly a mild collagen tissue abnormality, was considered. M-mode and two dimensional echocardiography and cardiac auscultation detected no statistically significant difference in the prevalence of mitral valve prolapse in patients with keratoconus compared with controls. Formal, systematic examination of five joints also failed to detect a statistically significant difference in the prevalence of hypermobile joints in keratoconus patients and controls. However, as an ancillary finding, a significantly higher proportion of patients with keratoconus was found to have a history of hay fever than was the case with controls. 
5	Role of new antiplatelet agents as adjunctive therapies in thrombolysis. Coronary thrombolysis is the treatment of choice for patients with acute Q-wave myocardial infarcts who have no contraindications to such therapy. However, the time required for thrombolysis and the possibility of reocclusion of the infarct-related artery remain problematic. Herein are described experimental animal studies and clinical evaluations in which attempts have been made to develop adjunctive therapies that, when coupled with available thrombolytic interventions, might shorten the time to thrombolysis and delay or prevent reocclusion. From the studies conducted to date, it is clear that a combined thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist and heparin shorten the time to thrombolysis and delay or prevent coronary artery reocclusion in experimental canine models with copper coil-induced coronary artery thrombi. A monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor coupled with tissue plasminogen activator (t-PA) and heparin also shortens the time to thrombolysis and delays or prevents reocclusion in experimental canine models. Thrombin inhibitors, including heparin and synthetic inhibitors, given with t-PA and aspirin, appear to shorten the time to thrombolysis and delay or prevent coronary artery reocclusion in experimental canine models. Aspirin coupled with intravenous streptokinase reduces mortality in patients with presumed acute myocardial infarction, and a combination of heparin and t-PA results in infarct-artery patency more frequently than t-PA without heparin. Data from these studies are encouraging with regard to the possibility of developing effective and relatively safe thrombolytic regimens that shorten the time to thrombolysis and delay or prevent coronary artery reocclusion. 
2	Acute lower respiratory tract infections in hospitalized patients with diarrhea in Dhaka, Bangladesh. This study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection (ALRI) and diarrhea in Dhaka, Bangladesh, and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens. The most common manifestations of ALRI were pneumonia (374 cases), bronchiolitis (12 cases), and tracheobronchitis (11 cases). The majority (77%) of the illnesses were in children less than 2 years of age, and 88% of the children were malnourished. A respiratory tract pathogen was identified in 30% of the patients, and a diarrheal pathogen was identified in 34%. The overall case-fatality rate in children with ALRI and diarrhea was 8%. The case-fatality rate was 14% in children with bacterial pneumonia and diarrhea, 3% in those with viral pneumonia and diarrhea, and 14% in malnourished children with shigellosis and ALRI. The most common respiratory tract pathogens were respiratory syncytial virus, Streptococcus pneumoniae, influenza viruses, and Haemophilus influenzae type b. 
1	Delayed reconstruction following Mohs' chemosurgery for skin cancers of the head and neck. The case records of 52 patients with 55 cutaneous neoplasms treated by Mohs' chemosurgery and subsequently reconstructed by plastic surgeons were reviewed to determine if delay between resection and reconstruction adversely affected the outcome of reconstruction. Reconstruction was performed from 5 to 61 days after Mohs' chemosurgery for 45 basal cell carcinomas and 10 other cutaneous neoplasms. There were no complications during the interval between resection and reconstruction. Following reconstruction, minor wound complications occurred in 6% of patients; there were no major complications. Microscopic examination of the re-excised wound revealed residual disease in 2 of 45 cases of basal cell carcinoma and 0 of 10 other cutaneous malignancies. Both patients with residual basal cell carcinomas (i.e., false-negative margins after Mohs' surgery) had presented to the Mohs' surgeon with recurrent tumors. During a follow-up period of 3 months to 3 years after complete resection, recurrent tumor developed in 2 of 45 cases of basal cell carcinoma and 3 of 8 cases of squamous cell carcinoma. Delayed reconstruction, usually 5 to 20 days after Mohs' chemosurgery, can be performed without significant morbidity. Re-excision of the Mohs' chemosurgical wound for pathologic examination can detect residual disease and may be especially indicated for large recurrent wounds. 
4	Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs The purpose of the present study was to examine subendocardial flow and function during graded coronary pressure reduction to determine the effect of tachycardia on the lower autoregulatory pressure limit (critical coronary pressure) in unanesthetized dogs. During atrial pacing at a rate of 200 beats/min, subendocardial flow measured by radioactive microspheres averaged 1.55 +/- 0.34 ml/min/g and remained unchanged as pressure was reduced over the autoregulatory plateau from 84 +/- 10 to 59 +/- 7 mm Hg. Further reductions in coronary pressure to below a critical coronary pressure of approximately 60 mm Hg were associated with concomitant reductions in subendocardial flow and the endocardial-epicardial flow ratio during tachycardia. Although regional function remained constant over the autoregulatory plateau, there was a rightward shift of the coronary pressure-function relation during ischemia in response to a steady-state increase in rate from 100 to 200 beats/min. Reductions in regional wall thickening began when coronary pressures reached 38 +/- 7 mm Hg at a heart rate of 100 beats/min and 61 +/- 6 mm Hg at a heart rate of 200 beats/min (p less than 0.005). Similar critical coronary pressure values were obtained for subendocardial segment shortening. Relations between subendocardial flow and myocardial function measured by both transmural wall thickening and subendocardial segment shortening were linear during pacing at a heart rate of 200 beats/min with relative reductions in wall thickening related to reductions in subendocardial flow on a nearly one-to-one basis. The results of this study demonstrate that there is a shift in the lower limit of subendocardial autoregulation during tachycardia as manifest by the onset of subendocardial ischemia at a higher distal coronary artery pressure. The shift in critical coronary pressure relates to an increase in resting flow requirements due to increased demand and diminished subendocardial vasodilator reserve at any given coronary pressure secondary to a reduction in the time available for diastolic subendocardial perfusion during tachycardia. 
5	Reference ranges for lymphocyte subsets. A comparison of standard vs rapid whole-blood lysis techniques. Reference ranges for lymphocyte subsets may vary with processing techniques, monoclonal reagents, or analytic methods. We compared reference ranges obtained for T- and B-lymphocyte subsets by means of standard manual whole-blood lysis with a wash step vs a rapid, no-wash whole-blood lysis system. Both techniques demonstrated reference ranges similar to those in previous literature reports. The ranges established with standard and rapid lysis were similar when antibodies directed to the same cluster designation were used. Although slight statistical differences in relative percentages of CD2 and CD3 lymphocytes were observed, these differences were probably not clinically significant. These data indicate that the rapid technique provides a standardized method for enumerating T and B lymphocytes in peripheral blood. 
5	Development of a special care unit for chronically critically ill patients. Intensive care units (ICUs) are recognized as one of the most expensive services provided by hospitals. Within these ICUs are a growing population of patients whose stays are extensively prolonged because of complications or underlying chronic health conditions that are exacerbated by a critical illness. These patients can be described as "chronically critically ill" and are costly to hospitals both in terms of actual dollars and in terms of the burden of care to nurses and physicians. This article describes the creation of a special care unit (SCU) designed specifically to meet the needs of chronically critically ill patients. The SCU environment is composed of a physical design that accommodates limited technology and care aimed at family involvement and rehabilitation, a case management practice model, and a shared governance management model. This structure is in contrast to traditional ICU environments, which include physical layouts that allow for high technology and close monitoring of patients, a primary nursing delivery system, and a bureaucratic management model. A research project to compare the effects of the SCU with the effects of the traditional ICUs on nurse and patient outcomes is described. 
4	Percutaneous extraction of fractured guidewire from distal right coronary artery. The incidence of retained hardware components in the coronary artery tree is likely to parallel the growing number and types of percutaneous coronary revascularization procedures being performed. Management has extended from the conservative option of simply leaving behind the retained components to the more aggressive approach of surgical removal. A percutaneous method is described herein which offers the interventional cardiologist an alternative method of managing patients with retained wire fragments contained entirely in the coronary artery. 
4	Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood BACKGROUND. Cardiotoxicity is a recognized complication of doxorubicin therapy, but the long-term effects of doxorubicin are not well documented. We therefore assessed the cardiac status of 115 children who had been treated for acute lymphoblastic leukemia with doxorubicin 1 to 15 years earlier in whom the disease was in continuous remission. METHODS. Eighteen patients received one dose of doxorubicin (45 mg per square meter of body-surface area), and 97 received multiple doses totaling 228 to 550 mg per square meter (median, 360). The median interval between the end of treatment and the cardiac evaluation was 6.4 years. Our evaluation consisted of a history, 24-hour ambulatory electrocardiographic recording, exercise testing, and echocardiography. RESULTS. Fifty-seven percent of the patients had abnormalities of left ventricular afterload (measured as end-systolic wall stress) or contractility (measured as the stress-velocity index). The cumulative dose of doxorubicin was the most significant predictor of abnormal cardiac function (P less than 0.002). Seventeen percent of patients who received one dose of doxorubicin had slightly elevated age-adjusted afterload, and none had decreased contractility. In contrast, 65 percent of patients who received at least 228 mg of doxorubicin per square meter had increased afterload (59 percent of patients), decreased contractility (23 percent), or both. Increased afterload was due to reduced ventricular wall thickness, not to hypertension or ventricular dilatation. In multivariate analyses restricted to patients who received at least 228 mg of doxorubicin per square meter, the only significant predictive factors were a higher cumulative dose (P = 0.01), which predicted decreased contractility, and an age of less than four years at treatment (P = 0.003), which predicted increased afterload. Afterload increased progressively in 24 of 34 patients evaluated serially (71 percent). Reported symptoms correlated poorly with indexes of exercise tolerance or ventricular function. Eleven patients had congestive heart failure within one year of treatment with doxorubicin; five of them had recurrent heart failure 3.7 to 10.3 years after completing doxorubicin treatment, and two required heart transplantation. No patient had late heart failure as a new event. CONCLUSIONS. Doxorubicin therapy in childhood impairs myocardial growth in a dose-related fashion and results in a progressive increase in left ventricular afterload sometimes accompanied by reduced contractility. We hypothesize that the loss of myocytes during doxorubicin therapy in childhood might result in inadequate left ventricular mass and clinically important heart disease in later years. 
4	A multicenter study of doxazosin in the treatment of essential hypertension in France. This study was designed to assess the efficacy and tolerance of doxazosin in patients with mild, moderate, or severe essential hypertension in a general practice setting. Ninety-six adults of a mean age of 55 1/2 years took part in the 14-week study, consisting of a placebo phase (2 weeks), a dose-adjustment phase with doxazosin (8 weeks), and a maintenance phase (4 weeks). Doxazosin, at a final mean daily dose of 3.4 mg, produced a significant (p less than 0.05) reduction in blood pressure at all points of measurement during the study. The mean change in sitting blood pressure at the end of treatment was -15.4/-15.8 mm Hg. Of the 85 patients who could be categorized as a success or failure, 78 (92%) were considered a therapeutic success; 78 (89%) of the 88 efficacy-evaluable patients demonstrated an improvement in the severity category of their hypertension. Treatment with doxazosin produced a reduction in serum cholesterol (-3.1%) and triglyceride (-3.8%) levels, although these changes did not attain statistical significance. The calculated probability of developing coronary heart disease in 10 years (according to the Framingham equation) was significantly (p less than 0.001) reduced by 22%, from 16.7 chances per 100 (baseline) to 14.3 chances per 100 (final visit). Twenty-six patients (27.1%) reported side effects that were possibly related to treatment, the most prevalent of which were vertigo (7.3%) and headache (6.3%). In four (4.2%) patients the dose of doxazosin was reduced and two (2.1%) were withdrawn prematurely. The investigator's assessments of tolerance was reduced and two (2.1%) were considered to be excellent or good in 85 (88%) patients. 
1	Rehabilitation of physically disabled dentists: a model for a vocationally specific rehabilitation program. A unique collaborative program whose goal is to facilitate the return of disabled dentists to active dental practice is described. This approach includes comprehensive interdisciplinary evaluation and remediation, and it has succeeded in revealing previously undiagnosed impairments which should be considered in the formulation of a rehabilitation plan. A case report illustrates the process. This program can serve as a model for similar programs addressing the needs of other disabled health care professionals. 
2	Intussusception and the diagnostic value of testing stool for occult blood. A retrospective review was performed to determine the diagnostic value of testing for occult blood in stool of children suspect for intussusception. Ninety-six children had barium enema studies for suspected intussusception. Of the 57 children who had barium enema confirmed intussusception, 29 did not have history or physical findings of gross blood per rectum. Stool was tested for occult blood in 16 of these 29 patients, and 12 (75%) were positive. In comparison, three (20%) of the children who did not have intussusception had stool positive for occult blood. Stool with occult blood was significantly associated with intussusception (P less than .002). The only other clinical factor significantly associated with intussusception was abdominal mass (P less than .02). Vomiting, episodic irritability, poor feeding, abdominal pain and lethargy were not significantly different in the two groups. In conclusion, the authors suggest stool testing for occult blood when evaluating children who present with nonspecific signs and symptoms supportive of intussusception. 
4	Pulmonary resection combined with cardiac operations. Surgical management of patients with concomitant critical cardiac disease and resectable lung lesions is controversial. During a 7-year period (1982 to 1988), 21 patients underwent combined cardiac and pulmonary operations. Patients had cardiac symptoms only; the lung lesions were found on preoperative chest roentgenograms. The pathological diagnosis was established in only 2 of the patients before operation. All underwent concurrent pulmonary resection during cardiac operations requiring extracorporeal circulation. The pulmonary operations included 17 wedge resections and four lobectomies. The final diagnoses in 8 patients with stage I non-small cell lung cancer included epidermoid carcinoma (4), adenocarcinoma (3), and bronchoalveolar carcinoma (1). Postoperatively, 1 patient required a permanent pacemaker and 1 patient died. The actuarial survival at 5 years for all patients who underwent combined procedures was 95%. The 5-year survival for the 8 patients with lung cancer was 88% compared with 100% for those with benign pulmonary pathology (p = 0.172). This experience suggests that combining pulmonary resection with cardiac operations is safe and offers a favorable prognosis to a select group of patients. 
1	Regional chemotherapy for colorectal liver metastases: a phase II evaluation of targeted hepatic arterial 5-fluorouracil for colorectal liver metastases. The results of systemic chemotherapy in patients with liver metastases from colorectal cancer remain dismal. Regional chemotherapy has been advocated as a method of improving the delivery of cytotoxic drugs to tumour, while minimizing systemic toxicity. The use of vasoactive agents to redistribute arterial blood flow towards tumour, and of biodegradable microspheres to slow tumour blood flow, have also been suggested as methods of further improving tumour exposure to drug. We present 21 patients who received intrahepatic arterial chemotherapy for colorectal liver metastases. Combined treatment (angiotensin II, albumin microspheres and 5-fluorouracil) was administered 4-6 weekly, and bolus 5-fluorouracil was given in the intervening weeks. Toxicity was minimal. Responses were seen in seven patients. Fewer than half of the deaths were from liver metastases; a quarter of the patients died from non-cancer-related causes. Survival was prolonged in the treated group compared with historical controls. These results suggest that this regimen has activity in patients with colorectal liver metastases. 
1	Expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas. The expression of ABH and Lewis antigens has been studied in a series of pulmonary carcinomas, in areas of squamous metaplasia, and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies. All respiratory epithelial cells can express antigens, with the exception of glandular serous cells. The expression of AB antigens is rather homogeneous, while Lewis antigens are expressed in a more irregular pattern, alternating positively stained cells with negatively stained cells in the same microscopic field. The expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms. Metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas. The most significant findings are the deletion of A antigen and the strong expression of Le antigen. Pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas. The most important findings are the deletion of AB antigens and the strong expression of Le(y) antigen. 
1	Preoperative endoscopic diagnosis of fibroepithelial polyp of the renal pelvis: a case report and review of the literature. Benign fibroepithelial polyps of the renal pelvis are rare, with only 9 cases described previously in the literature. We report an additional case and suggest how nephrectomy may be avoided. 
1	Molecular surgery of the basement membrane by the argon laser. Although the argon laser is used successfully to weld a number of different tissues, the underlying chemical and cellular mechanisms for this process are not precisely defined. Consequently, a biochemical model has been developed in vitro using the well-defined extracellular matrix from the murine Engelbreth-Holm-Swarm (EHS) sarcoma. Control and experimental samples of EHS basement membranes were irradiated with a Trimedyne argon laser at 500-3,000 Joules/cm2 at 0 degrees C. The samples were diluted into cold phosphate-buffered saline and allowed to gel at 35 degrees C. The time course of the gelation reaction was followed in a spectrophotometer at 360 nm. Irradiation reduced the absorbance 7.5-15% compared to controls and was independent of the dilution over a 10-fold range. Gelation was also measured by determining the amount of protein by the Bradford assay that could be collected by centrifugation at 10,000g for 10 minutes. Argon-irradiated samples had 30-40% less protein in the precipitate than the controls. The addition of 5 mM beta-mercaptoethanol to the EHS extract blocked the effect of the laser on the gelation reaction. In addition, when gelation was carried out in the absence of calcium and magnesium, there were no differences between laser-treated samples and controls. The basement membrane proteins were separated by electrophoresis through polyacrylamide gels under denaturing plus reducing or denaturing and non-reducing conditions. No differences in the polypeptide composition were noted between irradiated and control samples using either Coomassie- or silver-staining techniques. 
1	Exposure histories in acute nonlymphocytic leukemia patients with a prior preleukemic condition. A subset of patients with acute nonlymphocytic leukemia (ANLL) have evidence of a myelodysplastic syndrome (MDS), low infiltrate leukemia, or other preleukemic condition that may be present for several months before onset of disease. The hypothesis that these conditions act as markers for environmentally induced cancer was examined in 270 ANLL patients, 46 with a preleukemic phase and 224 with an acute onset. Although the effects of previously identified risk factors (male sex, age older than 50 years, prior cytotoxic therapy) were demonstrated, no associations with common environmental conditions (cigarette smoking, alcohol use, occupations with exposure to chemicals or radiation) were present with the exception of hobbies involving potential chemical exposure, odds ratio (OR) and 95% confidence intervals = 4.2 (1.4 to 12.3) and self-reported exposure to pesticides, OR = 10.2 (1.8 to 63.1). These may be chance associations although a previous case-control study of MDS reported similar findings. 
1	The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer. A rational approach to the local treatment of intraductal breast cancer continues to generate considerable debate. However, the finding of an invasive component in intraductal breast cancer is widely regarded as an appropriate indication for axillary node dissection as part of the local treatment and staging of this disease. Despite this view, the natural history of patients with intraductal breast cancer with foci of microinvasion is poorly defined. Between 1965 and 1988, 41 patients with this pathologic finding of intraductal carcinoma with foci of microinvasion were seen at the UCLA Medical Center. Twenty-three patients presented with mammographic abnormalities, while 17 patients presented with a palpable mass. One patient presented with Paget's disease of the nipple. Thirty-three patients underwent axillary node dissection as part of their local treatment. No lymph node metastases were identified. The median follow-up in 37 patients was 47 months. There have been no local recurrences and no deaths from recurrent breast cancer. Intraductal breast cancer associated with microinvasion appears to be an extremely favorable lesion with minimal risk of nodal metastases. 
5	Interaction of two different disorders in the beta-globin gene cluster associated with an increased hemoglobin F production: a novel deletion type of G gamma + (A gamma delta beta)zero-thalassemia and a delta zero-hereditary persistence of fetal hemoglobin determinant. We report two different disorders of the beta-globin gene cluster segregating in a Belgian family: a novel deletion that results in G gamma + (A gamma delta beta)zero-thalassemia (thal) and a heterocellular hereditary persistence of foetal hemoglobin of the Swiss type linked to a delta degree-thal gene (delta degree-HPFH). Heterozygosity for the heterocellular HPFH brings about a moderate (3.4% to 8.24%) increase of hemoglobin (Hb) F having a G gamma/A gamma ratio of 4:1, whereas carriers of the G gamma + (A gamma delta beta)zero-thal deletion show in their peripheral blood a considerably higher (15%) percentage of Hb F. Both defects interact in the compound heterozygotes for G gamma + (A gamma delta beta)zero-thal and delta zero-HPFH producing a further increase (up to 24%) of fetal Hb consisting entirely of G gamma chains. Molecular characterization of the G gamma + (A gamma delta beta)zero-thal by means of Southern analysis showed that the deletion spans about 50 kb, removing the 3' end of the A gamma-gene, the psi beta-, delta-, and beta-genes. A number of possible mechanisms leading to the overproduction of Hb F in HPFH and G gamma + (A gamma delta beta)zero-thal will be discussed. 
1	The diagnosis and definition of hepatic malignancies by use of arterial enhanced computerized tomographic scanning. Axial computerized tomography is a useful tool in the evaluation of either primary or metastatic hepatic neoplasms. An adjunct to this technique is visceral arterial enhanced computerized tomography (AECT). To determine the effectiveness of this modality, bolus intravenous enhanced computerized tomography scans and AECT were compared and correlated to operative findings. Fifty-four consecutive patients were evaluated by AECT and bolus intravenous enhanced computerized tomography over a 30-month period (May 1986 to August 1989) for suspected primary or metastatic hepatic malignancies. Forty-four patients (81%) had hepatic lesions. Fifty-two percent (23 of 44 patients) of the metastatic tumors were from colonic or rectal primary lesions, and 20% were hepatocellular primary lesions. The remainder of the lesions were metastases from a variety of primary lesions. When studies were compared, 34% of the patients (15 of 44 patients) differed in either the location or total number of lesions noted. The lesions of three of the 15 patients (20%) were determined unresectable on the basis of AECT. Of the remaining patients, planned resections were revised in seven patients to either lesser or greater procedures. The number of lesions found at laparotomy equaled the number found by AECT in all but two cases. AECT caused no complications. AECT improved our ability to identify and localize primary and metastatic lesions of the liver. This technique offers the advantage of preoperative definition of the hepatic arterial and portal venous anatomy. 
4	Evolution of human cardiac myocyte dimension during prolonged mechanical support. In animal models using left ventricular assist systems over long time periods, myocardial cellular atrophy has been reported, raising concern that prolonged clinical use of such systems might lead to deterioration in left ventricular function. At the University of Pittsburgh, long-term clinical use of the Novacor (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.) left ventricular support system for patients awaiting heart transplants has allowed study of the effects of long-term mechanical support on human subjects. This study determined that cardiac myocyte dimension is initially greater in patients with end-stage cardiac disease who require support rather than in patients with the same disease who do not require such support. Although myocyte dimension does decrease within a few days of the inception of support, this decrease merely brings cell size closer to the values usual in patients with chronic end-stage cardiac disease, and no further shrinkage is observed. Thus the Novacor left ventricular assist system does not appear associated with left ventricular atrophy, and its long-term use may not be detrimental to left ventricular function. 
4	Time of onset of supraventricular tachyarrhythmia in relation to alcohol consumption. It is widely believed but has never been proved that idiopathic supraventricular tachyarrhythmias beginning during or after weekends or winter holidays are frequently alcohol-related ("holiday heart" syndrome). The time of arrhythmia onset was therefore studied in relation to self-reported ethanol consumption and results of a screening test for alcoholism (CAGE questionnaire) in 289 patients aged less than 65 years admitted for supraventricular tachyarrhythmias. There were 102 patients having an etiologically idiopathic arrhythmia with a known time of onset. Among them, but not among those with disease-related arrhythmias, patients with arrhythmic episodes beginning on Saturdays or on Sundays were more often chronic alcohol abusers (9 of 19, 47%) than either patients with episodes beginning from Mondays through Fridays (18 of 83, 22%; p = 0.040) or control subjects from the out-of-hospital population (8 of 66, 12%; p = 0.002). In multivariate analysis, the time of arrhythmia onset was related to the CAGE response (G2 = 6.0, p = 0.014) but not to the most recent ethanol use. However, the increased frequency of problem drinkers among patients with weekend-onset idiopathic arrhythmias was only relative, and resulted from a decreased number of abstainers and non-problem drinkers. No conspicuous clustering of alcohol-related arrhythmias was seen after New Year's or May Day. Thus, although the present study confirms an association between heavy drinking and idiopathic arrhythmias beginning during weekends, it shows that the question may be of a relative rather than an absolute overrepresentation. The term holiday heart may also be somewhat misleading since no postholiday accumulation of alcohol-related arrhythmias was found. 
3	A novel treatment for ischemic intracranial hypertension in cats. There is no accepted efficacious treatment for ischemic cerebral edema. We show in a cat model of focal cerebral ischemia that infarct volume can be reduced (p less than 0.05) by ventriculocisternal perfusion with an oxygenated fluorochemical emulsion (bis-perfluorobutylethylene). An accompanying effect of such ventriculocisternal perfusion is a reduction in intracranial pressure. At 18 hours following the start of the perfusion, there was a significant (p less than 0.05) difference in intracranial pressure between nonperfused controls (mean 11.4 [range 2.3-23.0] torr, n = 6) and cats perfused with an oxygenated nutrient solution not containing fluorochemical (mean 11.3 [range 3.0-29.0] torr, n = 8) or animals perfused with the oxygenated fluorochemical emulsion (mean 2.21 [range 0-3.5] torr, n = 7). Perfusion with this oxygenated fluorochemical emulsion warrants further study as a treatment for elevated intracranial pressure. 
3	Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension. 
5	Development of multiple necrotizing enteritis induced by a tumor necrosis factor-like cytokine from lipopolysaccharide-stimulated peritoneal macrophages in rats. We report the development of an animal model of multiple necrotizing enteritis (MNE) in rats. When rats were injected directly with a culture supernatant of lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages into the abdominal aorta, the overt pathologic lesions of MNE developed within 30 minutes after injection. The rats showed an elevated level of blood fibrinogen degradation product content even 30 minutes after injection. Furthermore the rats that were pretreated intravenously with heparin sulfate did not develop MNE, indicating the acute disturbances of blood microcirculation in the intestine. Multiple necrotizing enteritis was developed also by the injection with recombinant tumor necrosis factor (rTNF) but rarely was observed with even a high dose of recombinant interleukin-1 (rIL-1) or platelet-activating factor (PAF). The supernatant was cytotoxic in vitro to TNF-susceptible LM and many other cells but was less cytotoxic to the TNF-resistant LR line. Partial purification of the supernatant suggested that the supernatant contained a cytokine that has biochemical features of TNF. Furthermore polyclonal anti-TNF antibody could inhibit not only the cytotoxicity in vitro but also MNE development in vivo by this factor. These data strongly indicate that MNE possibly could be caused by a TNF-like cytokine produced by macrophages that are stimulated by the endotoxin. 
4	Role of oxygen free radicals in ischemic and reperfused myocardium. In recent years there has been considerable interest concerning the role of oxygen radicals in myocardial ischemia and reperfusion injury. The sequential univalent reduction of oxygen gives rise to very reactive intermediate products. Normally, the tissue concentration of these intermediate products of oxygen is limited and the aerobic myocardium survives because of the existence of a delicate balance between the generation of the various oxidants and the maintenance of the antioxidant defense mechanism. Several possible sources have been identified for the production of active oxygen species after ischemia and reperfusion and these sources may be mutually interactive. The ability of scavengers of oxygen free radicals, including vitamin E, to improve mechanical, mitochondrial, and sarcoplasmic reticulum function in animal models of ischemic-reperfusion injury also suggests that oxygen free radicals are partly responsible for myocardial damage in these models, although caution in the interpretation of these data is necessary. 
3	Brain stem tuberculoma in adult patients: diagnosis and treatment. A consecutive series of six adult patients ranging in age from 29 to 53 years is presented. The clinical and radiological features in each patient are described. Attention is drawn to the features demonstrated on computed axial tomography. In only one patient, the first encountered, was surgical excision undertaken and histological verification obtained. One patient died before any form of treatment could be instituted. The remaining four patients were treated with antituberculous chemotherapy alone and their progress monitored by sequential computed tomography. The excellent response and good outcome in this conservatively treated group are documented. 
5	Research and policy directions. Salt and blood pressure. The relation between dietary intake of sodium chloride and blood pressure levels remains controversial. The critical questions concern whether there is a susceptible subgroup at risk of elevated blood pressure because of sodium chloride consumption. If there is such a subgroup, what is its size and how can it be identified? Further clinical trials are needed to determine the long-term effects of sodium chloride reduction on blood pressure. The risk of disease, including stroke and coronary heart disease, is linear with blood pressure levels. A small change in blood pressure can have a relatively large impact on disease, even within the normal range of blood pressure. 
1	Local reactions to radioiodine in the treatment of thyroid cancer. PURPOSE: To compare the rate of local complications resulting from radioiodine ablation of thyroid cancer in patients with a residual intact thyroid lobe to that in patients who had more extensive surgical treatment prior to radioiodine administration. PATIENTS AND METHODS: We retrospectively studied 59 patients who had received 131I between 1979 and 1989. The patients were divided into two groups, depending on the extent of their previous surgical thyroid excision. Group 1 comprised 10 patients with a lobectomy or hemithyroidectomy before the ablative radioiodine dose, and Group 2 comprised 49 patients with more extensive thyroid excision (near-total or subtotal thyroidectomy) before the radioiodine treatment. RESULTS: Sixty percent of the 10 patients in Group 1 experienced some degree of neck pain or tenderness following radioiodine ablation of their residual thyroid. In one case, the local reaction was very severe and accompanied by the development of transient hyperthyroidism. There was only a 6% local complication rate in the patients who had undergone more extensive thyroid excision before ablative therapy (p less than 0.001), and none had a severe reaction. CONCLUSIONS: Patients with only unilateral surgical excision before radioiodine therapy have a higher rate of local complications than do patients treated with more extensive surgery prior to radioiodine ablation. If radioiodine is to be employed in such patients, they should be informed of this possible complication. Since evidence supports a dose effect in the pathogenesis of the complications, we recommend using a dose of less than 30 mCi for the initial ablation in these patients even though it may be necessary to repeat this dose to complete thyroid ablation. 
5	Herniation of the antral membrane through an extraction site. Report of a case. A case of herniation of the antral membrane through a recent extraction site is presented. The lesion was initially diagnosed as a tumor by the referring dentist. Oroantral fistulas are not an uncommon finding after dental extractions. It is rare, however, to see herniation of the antral membrane with large polyps extending through the fistula into the oral cavity. A search of the literature revealed only two other such cases. Surgical removal of the polyps and closure of the oroantral fistula by means of a buccal sliding flap technique is discussed. 
5	Transcranial electrical motor evoked potentials as a prognostic indicator for motor recovery in stroke patients. Transcranial electrical motor evoked potentials (MEP) were examined in 33 patients within three days after stroke. Normal values for MEP and motor central conduction time (CCT) were obtained in 46 healthy controls whose MEPs were evaluated during slight voluntary muscle contraction and at rest. Two months later 23 patients were re-examined clinically and electrophysiologically. Motor function change was correlated with MEP results. Two months after stroke the patients with normal or prolonged CCT had an improved motor function compared with those with absent CCT. MEP may be a valuable prognostic indicator in the acute stage of paralytic stroke for recovery of motor function. 
5	Hyaluronan in pleural effusions and in serum. It has been suggested that a high level of hyaluronan (hyaluronic acid, HYA) in pleural fluid is an indicator of malignant mesothelioma. In 78 consecutive patients with pleural effusion of various causes the HYA concentration was measured in pleural fluid samples and in serum. Nine patients had malignant pleural mesothelioma, and in three of them the HYA level in pleural fluid was 100 mg/l or more. In 42 patients with effusions due to metastatic malignancy, the mean HYA in the pleural fluid was 75 mg/l, and in five the HYA level was above 100 mg/l. Cardiac insufficiency caused the effusion in 11 patients, of whom two had a level above 100 mg/l in pleural fluid. Four patients had a serologically confirmed viral infection and had HYA levels in pleural fluid of 8, 157, 335, and 554 mg/l, respectively. One patient had postinfectious effusion with an HYA level in pleural exudate of 748 mg/l, the highest in this investigation. Two patients had benign asbestos pleural effusions, and both had high pleural HYA levels (256 and 490 mg/l, respectively). The serum HYA values were much lower than in the pleural fluid, namely from 15 to 480 micrograms/l; the levels were independent of the levels in the pleural fluid. Thus, a high level of HYA in pleural fluid is not specific for mesothelioma but can occur in other malignant or benign diseases, and a low level does not exclude mesothelioma. 
1	The child with recurrent solid tumor. A significant percentage of relapse occurs in children with solid tumors despite advances in treatment. This article discusses reasons for failure of primary therapy, evaluation of the relapsed patient, treatment of the relapsed patient, as well as questionable cancer therapies and therapy cessation. 
1	Literacy and laryngectomy: how should one treat head and neck cancer in patients who cannot read or write? The entire population of otolaryngologists and radiation oncologists (N = 192) in active practice in the state of North Carolina were surveyed to assess their level of awareness of illiteracy among adults in the United States and to determine whether these physicians consider illiteracy in the treatment decision process for patients with head and neck cancer. Excluding respondents who did not treat patients with head and neck cancer and physicians practicing outside of the state of North Carolina, the response rate was 115 of 182, or 63%. Only 26% of respondents were able to estimate correctly the prevalence of illiteracy in the US adult population. Forty-one percent of respondents, however, stated that they did consider their patient's ability to read and/or write before making treatment recommendations for head and neck cancer. This survey and accompanying literature review suggest that physicians perceive illiteracy as a problem that may have a significant impact on patients with head and neck cancer, but lack the data needed to enable them to quantify the effect of illiteracy on treatment outcome. The study reported is the first step in examining ways in which illiteracy might negatively affect patient outcomes. 
1	Skeletal manifestations of ectopic or inappropriate endocrine and metabolic syndromes. A variety of tumors and nontumorous lesions were used to illustrate some of the biologic, clinical, and pathologic aspects of inappropriate or ectopic endocrine and metabolic syndromes that have musculoskeletal repercussions. It is clear, both from the discussion and case material, that many mechanisms of ectopic endocrine syndromes have yet to be clarified. Elaborate techniques are available for hormonal estimations, but their routine use is prohibitively expensive and relatively unrewarding. Cells of a given lesion may be functionally heterogeneous or may fail to elaborate active products in substantial amounts. Different cells may produce similar peptides, while the same cells can produce more than one. Despite these difficulties, recognition of ectopic endocrine syndromes remains crucial to diagnosis and patient management, and thus corroboration or correlation must often rest on a cruder basis. In fact, the clinical significance of basic laboratory data, e.g., PTH elevation, may vary, as PTH may be immunoreactive but biologically inactive. As another example, hypercalcemia associated with myeloma may be variously related to coexistent hyperparathyroidism, renal disease, dehydration, or humoral osteolysis. Therefore, roentgenographic evidence of bone destruction or skeletal stigmata of hyperparathyroidism imbues laboratory data with greater significance. Paraneoplastic syndromes are of particular concern to the radiologist, as multiple systemic manifestations, occurring either synchronously or metachronously, may suggest the presence of an underlying or unifying lesion or even of a specific type of neoplasm. They may precede detection of neoplasms by months to years and can develop at any time during their course. Paraneoplastic syndromes may, furthermore, parallel the course of a lesion and be used as indicators of remission or recurrence. Conversely, those unassociated with overt symptoms possess endocrine markers that can reinforce sometimes silent skeletal stigmata. Familiarity with representative secretory products influencing the musculoskeletal system per se may often clarify seemingly innocuous and sometimes asymptomatic skeletal findings. Alert imagers may, therefore, detect, infer, or suspect particular syndromes when they present in a specific sequence or mosaic. Conversely, when apprised of their existence, imagers should know where their related effects may be sought or anticipated. Such relationships, sometimes serendipitously discovered, may be valuable assets in clinical diagnosis and patient management in both suspected and unsuspected cases. 
4	Quinapril in chronic heart failure. Angiotensin converting enzyme inhibitors are now firmly established in the treatment of patients with chronic heart failure (CHF). Their beneficial acute and chronic hemodynamic effects are not associated with reflex tachycardia or drug tolerance. Angiotensin converting enzyme inhibitors produce symptomatic improvement and improve exercise capacity in all grades of heart failure. They also improve the prognosis of patients with severe heart failure. Quinapril is a recently introduced, nonsulfhydryl ACE inhibitor, whose intermediate half-life makes it well-suited for the treatment of patients with CHF. The acute and chronic hemodynamic effects of quinapril are similar to those of other ACE inhibitors. In a large, multicenter, randomized, placebo-controlled study of 225 patients with mild to moderate CHF, 10 to 40 mg/day quinapril significantly improved clinical status and exercise capacity in a dose-related manner. The incidence of side effects did not differ significantly from that of placebo. The initial studies with quinapril are promising and warrant further clinical investigation of this compound. 
5	Six year follow up of infants with bacteriuria on screening. OBJECTIVE--To determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria, renal growth, and renal damage. DESIGN--Prospective six year follow up of infants with bacteriuria on screening in an unselected infant population. SETTING--Paediatric outpatient clinic. PATIENTS--50 Infants (14 girls, 36 boys) with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of Gothenburg. INTERVENTIONS--Children with asymptomatic bacteriuria and normal findings on initial urography were untreated, although other infections were treated. MAIN OUTCOME MEASURES--Culture of urine and determination of C reactive protein concentration every six weeks for the first six months after diagnosis, every three months from six months to two years, and every six months between two and three years; thereafter yearly urine culture. Evaluation of renal concentrating capacity with a desmopressin test; radiological examination, including first and follow up urography and micturition cystourethrography without antibiotic cover; and measurement of renal parenchymal thickness and renal surface area. RESULTS--Of the original 50 infants, 37 (12 girls, 25 boys) were followed up for at least six years. Two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed; the others remained free of symptoms. 45 Infants were untreated; the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight. Recurrences of bacteriuria were observed in 10 of the 50 children, of whom one had pyelonephritis. No child had more than one recurrence. At follow up urography in 36 of the 50 children (9 girls, 27 boys) after a median of 32 months no child had developed renal damage. First samples tested for renal concentrating capacity showed significantly higher values than those from a reference population (mean SD score 0.50, 95% confidence interval 0.21 to 0.79; p less than 0.001), but the last samples showed no significant difference (mean SD score 0.08, -0.24 to 0.40; p greater than 0.05). CONCLUSIONS--Mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended. 
3	Myxomatous cyst of the brachial plexus. Case report. The case of a myxomatous cyst of the brachial plexus is presented. The clinical course is reported, and the frequency of the lesion, diagnostic workup, histopathology, and surgical therapy are discussed. 
5	Early diagnosis and surgical intervention of acute aortic dissection by transesophageal color flow mapping. To determine whether transesophageal color Doppler echocardiography (TEE) is useful for the early diagnosis and surgical intervention in acute aortic dissection, 57 serial patients with acute aortic dissection were examined. These patients were evaluated by TEE with either the single-plane probe (39 patients) or the biplanar probe (18 patients) just after admission. The intimal flap was detected in all patients, and there were 18 patients with type A dissection and 39 patients with type B dissection. The entry was visualized in 83% of type A dissection cases and in 90% of type B dissection cases. In two of 18 patients examined with the biplanar probe technique, the entry was detected in the longitudinal view only. Emergency operations were performed in 18 patients with type A dissection and in 10 patients with ruptured type B dissection. Twenty-nine of 39 patients with type B dissection were treated conservatively. The operative mortality rate of patients with type A dissection was 22%, and that of patients with ruptured type B dissection was 60%. The major advantage of TEE is its ease of application at the bedside or in the operating room, which allows immediate and accurate diagnosis of acute aortic dissection for emergency surgical intervention. Biplanar TEE provides additional acoustic windows, ease of spatial orientation, and more accurate visualization of entry. TEE is a useful and powerful diagnostic tool for acute aortic dissection, and by using this method, one may achieve a more rapid and aggressive surgical approach for patients with acute aortic dissection. 
3	Neurologic complications of the tryptophan-associated eosinophilia-myalgia syndrome. A case of tryptophan-associated eosinophilia, central nervous system complications, and multiple white matter lesions by magnetic resonance imaging is presented. Eosinophilia regardless of its cause should be included within the differential of patients exhibiting periventricular white matter lesions. 
5	Mandibular reconstruction with composite microvascular tissue transfer. Microvascular free tissue transfer has provided a variety of methods of restoring vascularized bone and soft tissue to difficult defects created by tumor resection and trauma. Over 7 years, 26 patients have undergone 28 free flaps for mandibular reconstruction, 15 for primary squamous cell carcinoma of the floor of the mouth or tongue, 7 for recurrent tumor, and 6 for other reasons [lymphangioma (1), infection (1), gunshot wound (1), and osteoradionecrosis (3)]. Primary reconstruction was performed in 19 cases and secondary in 9. All repairs were composite flaps including 12 scapula, 5 radial forearm, 3 fibula, 2 serratus, and 6 deep circumflex iliac artery. Mandibular defects included the symphysis alone (7), symphysis and body (5), symphysis-body-ramus condyle (2), body or ramus (13), and bilateral body (1). Fourteen patients had received prior radiotherapy to adjuvant or curative doses. Eight received postoperative radiotherapy. All patients had initially successful vascularized reconstruction by clinical examination (28) and positive radionuclide scan (22 of 22). Bony stability was achieved in 25 of 26 patients and oral continence in 24 of 26. One complete flap loss occurred at 14 days. Complications of some degree developed in 22 patients including partial skin necrosis (3), orocutaneous fistula (3), plate exposure (1), donor site infection (3), fracture of reconstruction (1), and fracture of the radius (1). Microvascular transfer of bone and soft tissue allows a reliable reconstruction--despite previous radiotherapy, infection, foreign body, or surgery--in almost every situation in which mandible and soft tissue are absent. Bony union, a healed wound, and reasonable function and appearance are likely despite early fistula, skin loss, or metal plate or bone exposure. 
4	Primary varicose veins: topographic and hemodynamic correlations. This study was conducted to correlate the clinical presentations of uncomplicated primary varicose veins with the topographic and anatomic source of reflux (escape points). One-hundred sixty-three patients with primary varicose veins (144 females, 19 males; 96 unilateral, 67 bilateral) in 230 involved limbs were examined. The origin and extent of venous reflux was traced with Doppler ultrasound. Three distinct groups were recognized. Group I. Typical saphenous varicosities with junctional escapes occurred in 164 (71.3%). Sapheno-femoral junction (SFJ) incompetence in 147, and sapheno-popliteal junction (SPJ) incompetence in 17 limbs. Group II. Atypical saphenous varicosities with non-junctional escapes occurred in 51 (22.17%) limbs. In 5 limbs, no escape was detected. Twenty-two limbs had escapes localized in the main perforators: mid-thigh perforator 17, upper calf 2, distal ankle in 3. Twenty-four limbs had their escapes in the auxiliary perforators: abdomino-pelvic 17, and circumflex iliac/external epigastric, 7 limbs. Group III. Non saphenous (lateral venous system) varicosities occurred in 15 (6.52%) limbs. Based on physical examination alone, 55 limbs would possibly have undergone unnecessary ankle to groin stripping and 83 limbs an unnecessary SFJ ligation. Doppler US is an essential diagnostic tool that can accurately map the origin and extent of the venous reflux. The obtained hemodynamic information will permit more selective, multimodal therapy and avoid the indiscriminate, often unnecessary stripping of the entire saphenous system in all cases of primary varicose veins. 
2	Pemoline-associated hepatic injury. Among 100 cases of hepatic injury attributed to the administration of pemoline, 43 had sufficient accompanying information to permit analysis. All but two patients were less than 20 years old, and 80% were less than 12 years old. Males predominated the study. Injury appeared as early as 1 week or as late as greater than 1 year of taking the drug. The injury was uniformly hepatocellular as judged by the high values for aminotransferases and by death in massive necrosis in one patient. Mechanism was judged to be idiosyncratic, and the idiosyncrasy was probably metabolic rather than immunologic. 
1	Recent life change and large bowel cancer. Data from the Melbourne Colorectal Cancer Study. In a large, population based, epidemiological study of colorectal cancer, The Melbourne Colorectal Cancer Study, several etiological factors were investigated. Persons' recent life changes, as well as the degree of upset they experienced as a result of these changes, were included. Interviews with 715 histologically confirmed new cases of colorectal cancer occurring over a 12-month period in Melbourne, Australia, and with 727 age and sex matched community controls were conducted. As one of the methods of assessing any effect of recall bias, 179 hospital controls were also investigated. Major illness or death of a family member, major family problems and major work problems were found to be significantly more common for cases over the 5 years preceding diagnosis compared to controls. Cases also reported being significantly more upset with their recent life changes than did controls. No significant differences in results were found between males and females, or between colon cancer and rectal cancer patients. Although the possibility of recall bias, was not completely controlled for in this study, it was probably not an important factor in explaining case-control differences. Recent life changes, and their perceptions, may have significance in the development of large bowel cancer. 
3	ACTH therapy in infantile spasms: relationship between dose of ACTH and initial effect or long-term prognosis. The relationship between the dose of ACTH and the initial effect was investigated in 41 children with infantile spasms. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and electroencephalographic abnormalities. The relationship between the dose of ACTH and long-term prognosis was investigated in 29 patients. There was no relationship between the daily or total ACTH dosage, provided the dose was greater than 0.015 mg (0.6 IU)/kg/day, and the outcome of seizures and electroencephalographic abnormalities; however, ACTH 0.04-0.06 mg (1.6-2.4 IU)/kg/day and a total ACTH dose of 1.1-1.5 mg (44-60 IU)/kg resulted in better mental development than smaller doses of ACTH. Side effects of ACTH increased with dosage. Too small or too large a dose of ACTH does not lead to better mental development. The proper dose of ACTH should be used with careful attention to potential side effects. 
5	Prognostic factors in acute renal failure following aortic aneurysm surgery. This study analyses the prognostic factors associated with survival in 70 patients who developed acute renal failure following surgery for an aortic aneurysm. Forty-nine patients (70 per cent) had surgery for a ruptured aortic aneurysm and 21 patients (30 per cent) had an elective procedure. Fifty-nine patients received haemodialysis. Thirty-three patients (47 per cent) survived the episode of acute renal failure. Six of these thirty-three patients died within three months of recovering from acute renal failure, giving an overall survival of 27/70 (39 per cent). A stepwise logistic regression analysis showed that the following factors significantly adversely affected survival: a need for inotropic support, ventilation for more than three days and age over 65 years. A model developed using these variables provided a basis for predicting outcome. 
2	Colon interposition for esophageal disease: histologic finding of colonic mucosa after a follow-up of 5 months to 15 years. Thirty-six patients, subjected to colon interposition for benign esophageal disease or carcinoma of the esophagus or gastric cardia, were studied by endoscopy for signs of mucosal disease in the interposed colon. Five months to 15 yr (mean 57 months) after the operation, endoscopic finding of the interposed colon was macroscopically normal in 28 patients. Signs of inflammation, including hyperemia or hyperemia and friability, were observed in seven patients. Histologic specimens obtained at endoscopy were examined microscopically, and the findings were compared with those seen in the preoperative graft. In two patients, chronic inflammatory changes were observed in the graft mucosa, consisting of mononuclear cell infiltration of the lamina propria accompanied by crypt dilatation and deformation. In one of these patients, the inflammation was in the proximal third of the graft, and it was also seen at the endoscopy. In the remaining 34 patients, the graft mucosa was microscopically comparable to normal. The alterations were unexpectedly few and mild considering the marked change in the location and function of the colonic segment. 
1	Immunohistochemical differentiation of basal cell epithelioma from cutaneous appendages using monoclonal anti-glycoprotein antibody TNKH1. Its application in Mohs' micrographic surgery. TNKH1, which was primarily developed to detect differentiated melanocytic tumor cells, was found to recognize basal keratinocytes of hair follicle and some basal keratinocytes of human epidermis. Thus, TNKH1 decorated the basal cells of following structures: epidermis (39 of 54, only part of each specimen [OPES]), upper hair follicle (one of 24, OPES), lower hair follicle (21 of 21, very high rate of each specimen [VHES]), sebaceous duct (14 of 15, VHES), sebaceous gland (ten of 14, germinative cells near duct), eccrine duct (three of 19, OPES). Epithelial tumors, considered to be derived from or differentiating toward hair follicle such as trichilemmoma (one of one, VHES) and basal cell epithelioma (BCE) (32 of 32, VHES) were labeled not only in the peripheral cells but in their entirety. On the other hand, epidermal tumors, such as seborrheic keratosis (ten of 11, OPES), actinic keratosis (two of three, OPES), and squamous cell carcinoma (one of two, OPES), showed an irregular peripheral basal cell staining as in normal epidermis. The apocrine sweat apparatus and eccrine secretory portion were negative. Eccrine ductal tumors such as syringoma (two tested), eccrine acrospiroma (one), and eccrine carcinoma (two) were TNKH1 negative. Taking advantage of this total labeling of BCE versus peripheral labeling of the hair follicle, the authors could distinguish BCE tissue from other structures clearly. Among confusing structures the upper hair follicle and the eccrine duct were excluded easily because of their negative staining with TNKH1. The lower hair follicle was TNKH1 positive but only in the outer basal layer, whereas the BCE was TNKH1 positive in its entire basaloid cells. The result indicated that TNKH1 will be a useful antibody in Mohs' micrographic surgery. 
2	Malignant potential of juvenile polyposis coli. Report of a case and review of the literature. Juvenile polyps of the colon and rectum traditionally have been viewed as being benign inflammatory or harmartomatous lesions without potential for malignant change. The authors report a case of adenocarcinoma developing in a patient with sporadic juvenile polyposis. Juvenile polyposis was diagnosed in the patient at age 4 years. He underwent subtotal colectomy at age 6 years. At age 12, he underwent a proctectomy and a Swenson pull-through because of adenomatous changes in the rectal stump. At age 19 surveillance endoscopy revealed invasive cancer in a juvenile polyp. 
5	Local antibiotic delivery in the treatment of bone and joint infections. Antibiotics can be delivered locally via an implantable pump to treat bone and joint infections. This is a completely closed system, and the pump is refilled percutaneously at intervals based on its flow rate. The use of this method is described in three specific clinical situations: (1) resistant osteomyelitis (patients with persistent infections despite previous therapy), (2) acutely infected arthroplasties (symptomatic for less than six weeks), and (3) chronically infected arthroplasties (patients infected more than six weeks). In all three clinical situations, hospitalization time was shortened, and high local and low systemic levels of antibiotic were obtained. There was only one incident of side effects to the antibiotic used. This method has been successful in obtaining long-term suppression of infection in 30 of 42 patients with resistant osteomyelitis, 30 of 37 patients with acutely infected arthroplasties, and seven of ten patients with chronically infected arthroplasties. The complication unique to this method of therapy is pump-site and catheter-site infections. This occurred in three patients with recalcitrant osteomyelitis and three patients with acutely infected arthroplasties. 
2	Comparison of shunt fraction estimation using transcolonic iodine-123-iodoamphetamine and technetium-99m-pertechnetate in a group of dogs with experimentally-induced chronic biliary cirrhosis. Portosystemic shunt fraction estimation using transcolonic iodine-123-iodoamphetamine (IMP) has been previously validated relative to portal vein macroaggregated albumin injections using an experimental model of cirrhosis. Transcolonic technetium-99m-pertechnetate (TcO4-) has been proposed as an alternative tracer to IMP to study portal circulation in cirrhotic patients. We compared shunt fraction estimates from paired transcolonic IMP and TcO4- studies performed on a group of dogs before and after common bile duct ligation surgery. Pertechnetate over-estimated shunt fraction in 6/7 postoperative studies relative to IMP. A good correlation between the two methods was demonstrated, however, the slope of the regression line was substantially less than 1.0 with TcO4- values reaching 100% at IMP shunt values of approximately 60%. This apparent inability to accurately assess high shunt flows may limit the quantitative aspects of TcO4- studies on patients with severe portosystemic shunting. 
4	Mechanical circulatory support as a bridge to transplantation: current status of total artificial heart in 1989 and determinants of survival. Since April 1986, 40 total artificial hearts (TAH) were implanted as a bridge to transplantation in our institution. In an attempt to identify factors affecting survival of TAH recipients we reviewed our experience over 1000 days of mechanical support. There was no postoperative bleeding requiring surgery nor were there any clinical episodes of thromboembolic complications. Over a total functioning period greater than 3 years there were no mechanical failures in the driving system but one artificial ventricle had to be replaced because of mechanical dysfunction. Infections and multiple organ failure were the primary causes of morbidity and mortality during mechanical support. When the patients who underwent staged transplantation (no. 17) were compared with those who died during mechanical support (no. 23) there were no differences in TAH driving mode or hemodynamic variables between the groups. Although preoperative pulmonary, hepatic and renal functions were found to be similar between the groups, there were significant differences in the early evolution (3 days) of hepatic and renal functions following TAH implant (p less than 0.01). Urinary output was found to be the earliest variable discriminating recovery and survival (p less than 0.01). Finally, univariate analysis indicated age (less than 40 vs greater than 40 years) and modality of cardiac decompensation (acute vs chronic) as the most important factors affecting survival after TAH implantation. Since young patients (less than 40 years of age) with acute decompensation were successfully transplanted in 82% of cases while 100% of older patients with chronic decompensation died before or after transplantation, TAH should be advised in young patients with acute or chronic heart failure and in selected older candidates with recent, acute cardiac failure. 
4	Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. This study was designed to determine the morphological correlate of chronic heart failure. Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis. Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen. The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed that desmin was localized at the Z lines. In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged. Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts. Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells. Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells. About one third of all cells showed moderately severe changes, and the remaining cells were normal. Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis. We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure. 
4	Short-term changes in renal function, blood pressure, and electrolyte levels in patients receiving cyclosporine for dermatologic disorders. We compared the changes in renal function, blood pressure (BP), and concentrations of serum potassium, magnesium, and urate (uric acid) in two groups of patients not given transplants. Group 1, comprising 21 psoriatic patients, was treated with 14 mg/kg per day of oral cyclosporine for 4 weeks in a prospective, placebo-controlled study; group 2, comprising 28 patients with diverse cutaneous diseases, was given 6 mg/kg per day of oral cyclosporine for 1 to 3 months in a prospective, open-labeled study. Renal function (determined by serum urea nitrogen [SUN] and creatinine levels and urinalysis), BP, serum electrolyte levels (potassium and magnesium), and urate level were measured weekly for the first 4 weeks in both groups, and then, after 2 and 3 months of therapy, in group 2 only. During the first 4 weeks in group 1 patients, there were significant increases in values of SUN, creatinine, BP, potassium, and urate, and a significant decrease in the serum magnesium value. When data for the two groups were combined, the changes from pretherapy values in each of the above measures (except systolic BP) during the first 4 weeks correlated significantly with cyclosporine trough levels. In group 2, the changes that occurred in the first 4 weeks in the SUN value, SUN/creatinine ratio, and BP were magnified over the subsequent 8 weeks of treatment. In the combined group for the first 4 weeks of therapy, duration of therapy, independent of cyclosporine trough levels, correlated with changes in SUN, creatinine, and urate levels, but not with changes in the potassium or magnesium level or in BP. We conclude that the cyclosporine blood level was a better discriminant than cyclosporine dosage in the analysis of renal dysfunction and hypertension in these patients. 
3	Bronchial mucus hypersecretion in acute quadriplegia. Macromolecular yields and glycoconjugate composition. In acute quadriplegia we have noted that about one in five patients develops unexplained production of markedly excessive and tenacious bronchial mucus. Spontaneous recovery from mucus hypersecretion usually occurs within weeks to months. Mucus samples collected from 12 patients have been found to be abnormal. Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical ultracentrifuge analysis showed the mucus to contain considerable epithelial glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate compositions were characteristic of the GP from hypersecretory bronchial mucus such as in chronic bronchitis and cystic fibrosis. In five patients studied after recovery from hypersecretion, there tended to be relatively less GP. The mucus samples contained a high density glycoconjugate (GC): this had sugars of GP but also reacted positively with a monoclonal antibody to keratan sulfate. Its amino acid composition was different from that of GP: threonine was lower and glycine was higher than in GP. In mucus from one patient who died, chondroitin sulfate ABC and hyaluronic acid were identified as well. This suggests proteoglycans are involved in the pathophysiology of mucus hypersecretion. The sudden onset and spontaneous recovery of hypersecretion suggests that it is not due to gland hypertrophy. We speculate that in acute quadriplegia it is due to disturbed neuronal control of bronchial mucus gland secretion, perhaps related to initial disappearance and later reappearance of peripheral sympathetic nervous system tone. 
4	Angioplasty of occluded coronary arteries: use of thin shaft balloon over-the-wire system without pre-dilatation. A retrospective review was done on 13 consecutive patients who underwent PTCA of totally occluded coronary arteries using a recently released thin shaft balloon over-the-wire angioplasty system. Balloon size was determined by the closest fit to the arterial size and used without predilatation techniques. This technique was initially successful in 12 patients with only 2 clinically insignificant episodes of distal embolization and one probable early reclosure. Using thin shaft angioplasty systems, balloon dilatation of totally occluded coronary arteries can be done safely with a single balloon in many cases resulting in simplified procedures and economic benefits. 
4	Atrial fibrillation after stroke in the elderly. To examine the relationship between atrial fibrillation and mortality after stroke, we studied 186 men and 167 women from the Waikato Stroke Registry whose mean age was 75.2 +/- 7.5 years. Twenty-three percent (82 of 353) had atrial fibrillation or flutter on their admission electrocardiogram. This group differed significantly from that with sinus rhythm in three respects: 1) They were older (p less than 0.01); 2) they had more severe current stroke deficit as evidenced by lower limb power (p less than 0.05) and Mini-Mental State Score (p less than 0.001), higher incidence of homonomous hemianopia (p less than 0.05), and lower incidence of lacunar syndrome stroke (p less than 0.001); and 3) they had a significantly higher incidence of cardiomegaly and congestive heart failure (p less than 0.01). Functional outcome was insignificantly better in the group with sinus rhythm. During a mean follow-up period of 18 months, mortality was significantly higher in the group with atrial fibrillation (p = 0.001). Proportional hazards modeling, however, showed that the apparently poorer survival in those patients with atrial fibrillation could be explained by factors other than cardiac rhythm, such as age, Mini-Mental State Score, level of consciousness, and interstitial edema on admission chest radiograph. Thus, atrial fibrillation was not an independent predictor of survival after stroke. 
2	The effect of posterior rectopexy on fecal continence. A prospective study. Twenty-three patients with rectal prolapse or intussusception were studied to specifically focus on the effect of posterior rectopexy on fecal continence, anal pressure, and rectal capacity. Before operation, five patients were fully continent (A), 10 were continent for solid stools (B) and eight patients were fully incontinent (C). Group A remained fully continent; continence was regained nine times in group B and in group C, three patients regained full continence, two became continent for solid stools, three patients remained incontinent. Other symptoms such as constipation, false urgency, and a feeling of incomplete evacuation were not beneficially influenced by rectopexy. The patients' continence status was correlated to anorectal manometry and rectal capacity measurement. In group B, incremental pressure (P = squeeze - basal P) increased significantly (P less than 0.02) as well as incremental volume (V = maximum tolerated volume - volume of first sensation) (P less than 0.05). We conclude that, by an increase of incremental anal pressure and incremental rectal volume, posterior rectopexy offers an 83 percent chance of regaining full continence, or a major improvement, and a 17 percent chance of stabilization of fecal incontinence. 
3	Neurodevelopmental outcome of children with evidence of periventricular leukomalacia on late MRI. Fifteen children, 8 months of age or older, from a neonatal follow-up program underwent magnetic resonance imaging and neurologic, cognitive, and language evaluations. Magnetic resonance imaging findings in all children included increased white matter signal on T2-weighted images and ventricular enlargement adjacent to regions of abnormal white matter. The extent of degree of abnormal white matter signal and the degree of sulcal prominence were variable. Twelve children had cerebral palsy; 5 children, 4 of whom had cerebral palsy, manifested significant sensory impairments. The median score on cognitive testing was 89; only 2 children exhibited severe-to-profound cognitive disability. Cognitive scores were stable on retesting. The degree of motor disability was correlated with the extent of white matter signal abnormality; however, cognitive outcome was not related to the extent and degree of white matter signal abnormality or to the degree of sulcal prominence. Despite the association of a major handicapping condition and periventricular leukomalacia, cognitive and language functioning may be relatively spared. 
2	The management of pseudomyxoma peritonei. The management of nine patients with pseudomyxoma peritonei was reviewed. Aggressive surgical resection of tumor is the standard of treatment, with many patients requiring multiple laparotomies. Chemotherapy, including the use of cisplatin is not effective. Long-term nutritional support provides a better quality of survival for select patients. 
2	Binding to human jejunum of serum IgA antibody from children with coeliac disease. Jejunal histology and the presence of serum IgA antibodies (JAB) binding to human jejunum in vitro were studied in 139 children with severe malabsorptive symptoms. Among 33 children with confirmed coeliac disease (ESPGAN criteria), 13 (93%) of 14 sampled before starting on a gluten-free diet had JAB, none of 21 sampled had JAB while on a gluten-free diet of long duration, and 90% of 30 sampled during gluten challenge had JAB. 53 children had severe jejunal villous atrophy (probable coeliac disease): 71% of those younger than 2 years and 94% of those aged 2-18 years had JAB during gluten intake. JAB could not be detected in 53 disease control patients (normal jejunal histology) and in 3 coeliac disease patients with selective IgA deficiency. Simultaneous determination of antigliadin (AGA) and antiendomysium (EMA) levels, and gliadin and tissue absorption studies, showed that JAB and AGA are different, whereas JAB and EMA are probably identical. IgA JAB could be the target-organ-related autoantibodies in coeliac disease. 
1	Pulmonary hypertension five years after left pneumonectomy for adenoid cystic carcinoma. We report the findings in a patient with shortness of breath due to pulmonary hypertension five years after left pneumonectomy. Mediastinal recurrence of an incompletely resected and slowly growing adenoid cystic carcinoma of the left main bronchus had encased the right main pulmonary artery. 
1	The role of attitudes, beliefs, and personal characteristics of Italian physicians in the surgical treatment of early breast cancer. The influence of Italian physicians' attitudes, beliefs, and personal characteristics on medical decision making is examined in the case of surgical treatment of early breast cancer. Responses to a mail survey of 657 physicians from different specialties were analyzed comparing doctors recommending a radical procedure (9%) to those preferring a conservative procedure for younger patients only (25%), and those considering conservative surgery the treatment of choice regardless of patients' age (66%). The findings suggest that the likelihood of physicians' preferring a conservative procedure is influenced by their specialty and the extent to which they feel that a patient should have a role in the treatment decision more than by differences in the beliefs of treatment outcomes. Only preferences of the small group indicating radical surgery as the sole admissible treatment can be accounted for by ignorance or distrust of results of recent trials. These findings suggest that other than scientific factors guide many doctors in their decision making; they may help to explain why the diffusion of research results into clinical practice is often disappointingly slow. 
2	A comparison in vitro of human and rabbit distal colonic muscle responses to inflammatory mediators. The present study compared in vitro the motor responses of human and rabbit distal colonic longitudinal and circular muscle to acetylcholine, histamine, leukotrienes B4 and D4, and prostaglandins E2 and F2 alpha. The active and passive mechanical properties of these muscles were also evaluated. All muscle types were contracted by acetylcholine and histamine. Longitudinal muscle from both species was contracted by prostaglandin E2 and prostaglandin F2 alpha, although rabbit muscle was more sensitive. Prostaglandin E2 relaxed the majority of both human and rabbit circular muscle preparations that were studied. Prostaglandin F2 alpha first relaxed and then contracted circular muscle from both species. Leukotriene B4 had no effect on any tissue studied. Leukotriene D4 caused transient relaxations in a proportion of all muscle types, but the relaxations were not concentration-related. Contractile responses did not differ under isotonic recording conditions, but relaxations were much more clearly defined. Based on experiments using atropine, phentolamine and propranolol, and pyrilamine or tetrodotoxin, it was concluded that the responses of both human and rabbit distal colonic muscles to these inflammatory mediators have a similar pharmacological basis. All muscle types exhibited low passive tension and developed active tension in the range 0.8-1.2 Lo. These data strongly support the belief that after the onset of an induced colitis, the rabbit colon has value as a predictive model for the study of inflammatory mediator-induced colonic motility changes in humans. 
5	Definitive mandibular replacement using reconstruction plates. Mandibular defects following radical cancer surgery continue to provide challenges to head and neck surgeons. Twenty-seven patients with advanced oral cancer underwent primary mandibular replacement with metal reconstruction plates without the use of bone. Twenty-one patients (78%) had successful reconstruction with primary soft tissue healing. Six patients required removal of the plate in the postoperative period. Two of these patients had their reconstruction plates replaced as a secondary procedure following soft tissue healing. Thus, 23 of 27 patients (85%) had final mandibular reconstruction and were followed for an average of 19 months. Functional and cosmetic results were satisfactory. For patients with advanced disease, this technique compares favorably with microvascular transfer in terms of operating time and donor defect. Despite problems with plate exposure, the initial and overall success rates of 78% and 85%, respectively, make the use of these plates a reasonable choice for immediate reconstructive needs in patients with difficult tumors. 
3	Neuropsychological assessment of cognitive functioning in children with epilepsy. The variety of cognitive dysfunctions related to learning disabilities in children with epilepsy have been studied by linking electroencephalogram (EEG) and computerized neuropsychological testing. This showed that "subclinical" discharges impaired performance in 61% of the patients on a simple and a choice reaction time test, although some discharges lasted 1 s only. Neuropsychological investigation of subclinical EEG discharges may help to determine their adverse effect on learning. 
1	Portal vein resection with a new antithrombogenic catheter. Curative resection of pancreatic and hepatobiliary tumors is rarely possible because of local invasion, especially into the portal vein. We developed a new antithrombogenic catheter using a heparinized hydrophilic polymer to allow portal vein bypass during resection of tumors invading the portal vein. Pancreatectomy or hepatectomy accompanied by portal vein resection was performed for pancreatic or hepatobiliary cancer, with an intraoperative shunt from the superior mesenteric vein to the femoral vein or from the superior mesenteric vein to the intrahepatic portal vein through the umbilical vein or the hepatic hilar portal vein. Use of the shunt prevented stasis in the superior mesenteric vein and hepatic ischemia even during prolonged occlusion of the portal vein, and portal vein resection was performed in 81 patients with hepatobiliary and pancreatic disease with greater safety and ease. 
4	The role of chronotropic impairment during exercise after the Mustard operation. To better understand the role of chronotropic impairment on exercise performance after the atrial switch (Mustard) operation, 20 patients who had undergone this operation for uncomplicated d-transposition of the great arteries exercised to maximal volition using a 1 min incremental treadmill protocol. Heart rate, oxygen consumption, carbon dioxide production and minute ventilation were monitored continuously. Two-dimensional echocardiograms were obtained before testing to calculate the right ventricular inflow volume indexed to body surface area. All patients achieved maximal aerobic capacity based on their ventilatory patterns and respiratory exchange ratio. Maximal heart rate was reduced (175 beats/min; 87% of predicted for age) and maximal oxygen consumption was decreased (31 ml/kg per min; 75% of predicted for age and gender). There was no correlation between maximal oxygen consumption and maximal heart rate. Right ventricular volume index, however, had a significant inverse correlation with maximal heart rate (r = -0.62, p less than 0.005). There was no correlation between right ventricular volume index and heart rate at rest. These results suggest that decreased maximal oxygen consumption in patients after the Mustard procedure is not a result of chronotropic impairment. Right ventricular dilation may be a compensatory response to chronotropic impairment. 
4	The costs of prevention. A prevention program is cost-effective if it yields more health benefits than do alternative uses of health care resources. Some prevention programs meet this standard: either they actually save more health care resources than they utilize, or their net costs per healthy year of life gained are lower than those of alternatives such as curative or palliative medicine. Other prevention programs, however, are less cost-effective than are medical treatments for the same disease. One lesson for public policy is that generalizations about the cost-effectiveness of "prevention" are unwise. Another lesson is that prevention programs should not be subjected to a higher standard than other health programs: they should not be expected to save money, but they should be expected to yield improved health at a reasonable price. 
4	Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study. A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland. 
2	Proximal gastric vagotomy: follow-up at 10-20 years. From August 1969 to December 1989, 600 patients had elective proximal gastric vagotomy for duodenal ulceration with an operative mortality of 0.2 per cent. Of these, 372 patients had surgery over 10 years ago. Three hundred and forty-two patients survived for more than 10 years and, in a prospective study, 305 were reviewed, forming the basis of this 10-20-year follow-up report. Forty-six (15 per cent) have had recurrent ulceration; 80 per cent of these developed symptoms within 5 years and no patient has had recurrence after 13 years. Although 29 patients required reoperation for recurrent ulceration, the current patient satisfaction rate for Visick grades I and II is 92 per cent. Only two patients required reoperation because of gastric stasis. It is concluded that proximal gastric vagotomy is a safe and satisfactory first choice operation for duodenal ulceration. 
5	Dietary deficiency of antioxidants exacerbates ischemic injury in the rat kidney. We examined the effects of dietary deficiency of vitamin E and selenium on the ischemia-reperfusion model of renal injury in the rat. Deficient diets imposed for six weeks on three-week-old weanling rats led to no significant differences in body weights, serum creatinine, GFR, RBF, TmPAH or urinary total protein excretory rates prior to ischemia. Twenty-four hours after one hour of ischemia, animals on the deficient diet demonstrated more markedly impaired GFR, RBF, TmPAH and urine to plasma creatinine concentrations and an increased renal failure index. Tubular damage was more severe injury in the deficient animals. Lipid peroxidation, 15 minutes after the release of the ischemic clamp, was increased in the deficient animals. We confirmed the effects of our dietary manipulation in impairing the oxidant scavenging system in the deficient animals since glutathione peroxidase activity was reduced to less than 5% in the basal state, and this striking reduction persisted following ischemia. Plasma vitamin E concentrations were also markedly depressed in the deficient diets. This dietary deficiency also worsened the course of acute renal injury and was accompanied by 50% mortality compared to 0% mortality in the control animals. Thus, dietary deficiency of vitamin E and selenium led to greater structural and functional renal impairment and increased lipid peroxidation following ischemia. These data provide support for the role of reactive oxygen species in mediating ischemia-reperfusion injury. 
3	"Pseudospasticity" in Guillain-Barre syndrome. We report a woman with Guillain-Barre syndrome who developed a flexion posture of the right arm and hand resembling upper motor neuron dysfunction. EMG demonstrated that involuntary peripherally generated continuous motor unit discharges caused the posture. 
5	Influence of bone mineral density on the fixation of thoracolumbar implants. A comparative study of transpedicular screws, laminar hooks, and spinous process wires. Posteriorly directed load to failure testing of four different types of spinal implants was performed in individual T5 to S1 vertebra harvested from seven fresh-frozen human cadaveric spines. The implants tested were: 1) Drummond spinous process wires, 2) Harrington laminar hooks, 3) Cotrel-Dubousset transpedicular screws, and 4) Steffee VSP transpedicular screws. The ultimate failure of each implant was compared with the bone mineral density of each vertebra to determine which implants, if any, were particularly advantageous in osteoporotic vertebrae. Before biomechanical testing, the spines were analyzed in vitro by dual photon absorptiometry to determine the bone mineral densities (gm/cm2) of each vertebra. The mean tensile loads to failure for each of the implants tested were as follows: Cotrel-Dubousset transpedicular screws: 345 Newtons; spinous process wire/button: 382 Newtons; Steffee transpedicular screws: 430 Newtons; and laminar hooks: 646 Newtons. The difference between the loads to failure for laminar hooks and the other implants was significant (P less than 0.05) using one-way analysis of variance. The overall correlation coefficient for bone mineral density with ultimate load to failure was 0.30 (P less than 0.001). The correlation coefficients were 0.47 (P less than 0.001) for spinous process wires alone; 0.096 (not significant) for laminar hooks alone; 0.37 (P less than 0.001) for Cotrel-Dubousset pedicle screws; and 0.48 (P less than 0.001) for Steffee pedicle screws. Of the four different implants tested, laminar hooks were most resistant to failure from posteriorly directed forces. 
3	A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. BACKGROUND AND METHODS. In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS. Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS. In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection. 
5	Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event. 
1	Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas. 
1	Potent selective inhibition of 7-O-methyl UCN-01 against protein kinase C. UCN-01 is a staurosporine-related compound that was isolated from the culture broth of Streptomyces sp. and shows potent and selective inhibitory activity against protein kinase C. Cellular inhibitory activity of UCN-01 against protein kinase C and cytotoxicity of UCN-01 were compared with those of staurosporine. When the mechanism of inhibitory activity was investigated in vitro, UCN-01 as well as staurosporine inhibited the activity of the catalytic domain of protein kinase C. In spite of direct inhibition against the catalytic domain of protein kinase C, cytotoxicity of UCN-01 was much lower than that of staurosporine. In addition, UCN-01 showed more selective inhibitory activity against protein kinase C than did staurosporine because of the sole structural difference at C-7. Therefore, a series of 7-O-alkyl derivatives of UCN-01 was synthesized and investigated. Interestingly, one of the compounds, the beta-methoxy derivative, showed 3-fold greater potency and 17-fold more selective inhibitory activity against protein kinase C than did UCN-01. 
5	Thyroiditis. Acute, subacute, and chronic. Inflammatory diseases of the thyroid are collectively the commonest thyroid disorder. Individually, they range from the rare case of acute bacterial thyroiditis to the other end of the spectrum, the even rarer Riedel's thyroiditis. Relatively common thyroid inflammatory diseases include the subacute thyroiditis syndromes. Of particular interest to endocrinologists is that both subacute granulomatous (painful) thyroiditis and subacute lymphocytic (painless) thyroiditis are very similar in terms of clinical course, although most likely have different etiologies. Nevertheless, their similarities suggest the possibility that there may be etiologic heterogeneity for the syndromes. From a clinical standpoint, it is essential to differentiate subacute painless thyroiditis from Graves' disease, because these two disorders also may mimic each other, yet only Graves' disease requires specific therapy. Chronic lymphocytic (Hashimoto's) thyroiditis, the commonest of the thyroiditides, presents with goiter and either hyperthyroidism (uncommon), hypothyroidism (common), or euthyroidism (most common). When L-T4 therapy is used in the treatment of Hashimoto's thyroiditis, the physician must be alert to the possibility of excess thyroid hormone administration. Sensitive TSH measurements help to avoid this therapeutic pitfall. 
5	Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response. Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation. 
5	Observer reliability in detecting surreptitious random occlusions of the monaural esophageal stethoscope. The esophageal stethoscope is used often during anesthesia to monitor ventilation and cardiac function. Deficiencies in observer vigilance may limit the effectiveness of this monitoring instrument. The aim of this study was to determine how long it took for an observer to detect a surreptitiously occluded monaural esophageal stethoscope in the setting of clinical anesthesia. During routine anesthesia, where an esophageal stethoscope was in use, a computer-guided device would artificially, silently, and at random time intervals, occlude the stethoscope tubing. Personnel using the stethoscope noted when they perceived the absence of stethoscope sounds. We studied 320 stethoscope occlusions in 32 patients. The time between stethoscope occlusion and detection was 34 +/- 59 seconds (mean +/- SD). Eighty-seven percent of detections were made in less than 60 seconds. However, 13% of detections were delayed for more than 60 seconds, and 2.3% for more than 240 seconds. While anesthesia personnel using an esophageal stethoscope could detect most stethoscope occlusions, failure to appreciate such episodes occurred in a small but significant number of cases. This suggests that the esophageal stethoscope has some definite limitations as a continuous monitor and that other monitoring techniques, such as oximetry, capnography, and ventilator disconnect alarms, as well as visual/tactile inspection of the patient, should be used as well. 
5	Postnatal epilepsy after EEG-confirmed neonatal seizures. We examined infants whose neonatal seizures were confirmed by randomly recorded ictal EEG tracings to determine the types and frequency of postnatal epilepsy (PNE)--unprovoked, recurring postnatal seizures. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to PNE. Forty infants with EEG-documented neonatal seizures of diverse etiologies were studied. The 27 survivors were followed for a mean of 31 months. PNE developed in 56% (15 of 27) of the cohort. The first seizure appeared at a mean-corrected age of 12.7 months and occurred despite ongoing antiepileptic medication in 60% (9 of 15) of the group. Seizures were classified as infantile spasms or minor motor (7 patients), complex partial (4 patients), or generalized tonic-clonic (4 patients). Perinatal variables that significantly correlated with PNE included the presence of coma but not the age at seizure onset, the estimated gestational age, or Apgar scores. PNE occurred in 68% (13 of 19) of patients with moderately or markedly abnormal EEG backgrounds but in only 25% (2 of 8) without (p = 0.035). There was a strong trend for PNE to develop in patients with greater than 10 electrographic seizures per hour but in only 45% (9 of 20) of infants with fewer seizures (p = 0.058). Several postnatal variables were significantly related to PNE--the presence of cerebral palsy (CP), mental retardation (MR), CP with MR, and follow-up EEGs. PNE occurred in only 27% (3 of 11) of patients without spikes or sharp waves on postnatal EEGs performed at age 3 months but in 100% (3 of 3) of patients with spikes or sharp waves (p = 0.022). 
1	Kaposi's sarcoma of the colon in a young HIV-negative woman with Crohn's disease. We report a case of isolated colonic Kaposi's sarcoma in a 36-year-old HIV-negative woman with refractory Crohn's disease of the colon and perineum following 11 months' treatment with azathioprine. The clinical features of this case are quite different from those classically described in Kaposi's sarcoma. Among the known risk factors, iatrogenic immunosuppression would appear to be the most probable. 
5	Multifocal colitis associated with an epidemic of chronic diarrhea. An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea. 
3	Extracranial repair of cerebrospinal fluid fistulas: technique and results in 37 patients. Although neurosurgeons have traditionally preferred intracranial repair for the management of cerebrospinal fluid (CSF) fistulas, this approach is associated with the complications of a craniotomy, anosmia, and a high incidence of recurrent fistulas. Extracranial repair, on the other hand, produces no central nervous system morbidity, preserves olfaction, and is associated with a low incidence of recurrence. Although there have been several reports of extracranial repair of CSF fistulas by otorhinolaryngologists, this approach has received scant mention in the neurosurgical literature. We report here our experience with 37 patients with CSF rhinorrhea or otorrhea who underwent extracranial repair. The etiology of the fistula was postoperative in 22, traumatic in 6, and spontaneous in 9. The fistulas were repaired using one of four techniques: external ethmoid-sphenoid in 18 patients, transmastoid in 9, transseptosphenoid in 7, and osteoplastic frontal sinusotomy in 3. In 32 of the 37 patients (86%) the fistulas were successfully repaired with the initial procedure. Of the 5 patients requiring a second operation, the fistula was successfully closed in 4 for an overall success rate of 97%. Complications were few and consisted of a transient facial paresis in a patient undergoing transmastoid repair and one death from meningitis. The authors conclude that because of low morbidity and mortality and a high success rate in closing fistulas, extracranial repair is the preferred technique for the operative management of CSF rhinorrhea and otorrhea. 
5	Clinical outcome of seriously ill surgical patients with intra-abdominal infection depends on both physiologic (APACHE II score) and immunologic (DTH score) alterations. The delayed-type hypersensitivity (DTH) response and the APACHE II score in 118 patients with surgical infections were measured prospectively and related to outcome. Logistic regression analysis generated the equation: [formula: see text]. The risk assessment as calculated by this model was compared to that using the APACHE II system alone in a separate group of 354 patients. There was an improvement in the predictive capacity of the APACHE II + DTH equation compared to APACHE II alone, as shown by a better fit of expected and observed deaths, an improved Goodman-Kruskal G statistic, and a larger area under the receiver operating characteristic curve. It is concluded that the DTH response (a broad marker of immunocompetence) is an independent prognostic factor in surgical patients and can be used in combination with the APACHE II score (a measure of acute physiology) to estimate better the outcome of surgical patients. 
3	Stroke recurrence within 2 years after ischemic infarction. We prospectively studied stroke recurrence in 1,273 patients with ischemic stroke who were entered into the Stroke Data Bank. Median follow-up was 13 months. The 2-year cumulative recurrence rate among these patients was 14.1%. Age, sex, race, history of hypertension, atrial fibrillation, or transient ischemic attacks, and stroke location were not associated with a higher risk of stroke recurrence. Patients with an elevated blood pressure, an abnormal initial computed tomogram, or a history of diabetes mellitus were at a higher risk of stroke recurrence. In contrast, patients with an infarct of unknown cause were at a lower risk of stroke recurrence than patients with a defined stroke mechanism, such as lacune, embolism, or atherosclerosis. A multivariate model suggests that patients at the lowest risk for stroke recurrence have a low diastolic blood pressure, no history of stroke, no history of diabetes mellitus, and an infarct of unknown cause. 
1	Helicobacter pylori and Zollinger-Ellison syndrome. Helicobacter pylori (previously Campylobacter pylori) is almost invariably associated with chronic duodenal ulcer disease. The relationship between H. pylori infection and duodenal ulcer in Zollinger-Ellison syndrome is unknown. We investigated the frequency of H. pylori infection in Zollinger-Ellison syndrome and also what effect H. pylori infection had on gastric function in patients with Zollinger-Ellison syndrome. H. pylori infection was diagnosed based on a specific serologic (ELISA) assay based on high-molecular-weight cell-associated proteins of H. pylori. We studied 20 patients with Zollinger-Ellison syndrome; 15 men and 5 women ranging in age from 24 to 71 years, median age 51. Six Zollinger-Ellison syndrome patients had H. pylori infection compared to 100 consecutive patients with chronic recurrent duodenal ulcer disease (P less than 0.05). Pretreatment basal acid output in Zollinger-Ellison syndrome patients ranged from 7.9 to 95.0 mmol/hr, median 35.2. Pentagastrin-stimulated maximal acid output ranged from 8.5 to 132 mmol/hr; median 52.7. Acid secretion was lower in the H. pylori-infected patients than the uninfected patients (BAO 24.5 +/- 6.5 vs 45.4 +/- 6.6, and MAO 44.3 +/- 11.8 vs 67.9 +/- 10.7, for H. pylori infected vs uninfected patients, respectively). The difference in BAO was statistically significant (P less than 0.05). The present results indicate that H. pylori is not a major contributing factor in duodenal ulcer associated with Zollinger-Ellison syndrome. The association of a reduced BAO with H. pylori suggests that these findings may be related. 
5	Acute pelvic inflammatory disease after surgical sterilization. STUDY OBJECTIVE: Physicians are very cognizant of the possibility of pregnancy after surgical sterilization, but the potential for acute pelvic inflammatory disease (PID) is thought to be rare. This study was undertaken to determine if upper tract PID occurred more frequently than previously reported in patients remote from surgical sterilization. DESIGN: Retrospective review of hospitalized patients with the primary discharge diagnosis of PID. SETTING: Urban, university hospital. PARTICIPANTS: Three hundred sixty-four hospitalized patients with the primary discharge diagnosis of PID over a six-year study period. MEASUREMENTS AND MAIN RESULTS: Patients' age; gynecologic histories and diagnoses; and laboratory, clinical, and surgical findings were noted. Twenty-three cases of acute PID were identified in 21 patients previously sterilized (6%). Nine of the 23 cases had systemic toxicity warranting surgical evaluation; 18 of the 23 cases were admitted from the emergency department. Mean statistical characteristics of the study group were age, 27.3 +/- 0.8 (SE) years; time interval from sterilization, 49.8 +/- 7.4 months; WBC 15,000 +/- 1,200; and temperature, 38.0 +/- 0.2 C. CONCLUSION: We conclude that acute PID may occur more frequently than previously reported in patients with prior surgical sterilization. An increased awareness of this entity is warranted. 
1	DNA aneuploidy in follicular thyroid neoplasia. The potential value of DNA aneuploidy, in distinguishing benign from malignant follicular thyroid neoplasms, was studied. The nuclear DNA content of 65 follicular thyroid neoplasms (52 adenomas and 13 carcinomas) was determined by flow cytometric analysis of paraffin embedded material; in 58 cases preparations were technically satisfactory. In 22 follicular neoplasms DNA analysis was also performed on fresh material obtained by fine needle aspiration of surgical specimens. Cell cycle analysis was performed on both fresh and fixed specimens. An aneuploid DNA profile was found on analysis of fixed tissue in eight of 45 (18 per cent) follicular adenomas and four of 13 (31 per cent) follicular carcinomas. DNA aneuploidy was also found in six of the 22 (27 per cent) fresh preparations from follicular adenomas. The frequency of DNA aneuploidy in apparently benign and malignant follicular neoplasms was similar. Follicular thyroid neoplasia are best regarded as a single entity with a low incidence of local and distant spread. All follicular neoplasia are therefore best excised. 
1	Post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. Is it necessary to resect all residual masses? A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequential operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and alpha-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high. 
1	Methionine dependency of malignant tumors: a possible approach for therapy When methionine (Met), an essential amino acid, was substituted for by its precursor homocysteine (Hcy) in the culture medium, normal cells such as fibroblasts proliferated normally. In contrast, many tumor cells failed to grow or grew at a lower rate. Met dependency is acquired simultaneously with cell transformation, as observed with HBL 100, a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number, and NIH/3T3 (J10), a mouse fibroblast line transformed by transfection with the human HRAS oncogene. A relationship was observed between Met dependency and metastatic potential of the RMS-21, RMS-S4T, and RMS-J1 sublines derived from RMS-0, a rat rhabdomyosarcoma cell line: the higher the metastatic potential of the cell line, the higher the concentration of Met required to maintain its proliferation. Met-independent cells derived from the RMS-0 line, obtained by a progressive decrease of Met in the culture medium lost their tumorigenicity when injected into rats fed with Met-deprived diets. In addition, the in vitro motility of RMS-S4T tumor cells, a marker of metastatic capability, decreased in Met-free Hcy-complemented (Met- Hcy+) medium. Similarly, RMS-0 tumor cells, preincubated in a Met- Hcy+ culture medium for 24 hours, evidenced a decreased capacity to form lung colonies when injected into syngeneic rats: the median number of lung colonies was 27 and 3 (P less than .05) for cells cultivated in Met+ Hcy- and Met- Hcy+ media, respectively. An amino acid-defined mixture reproducing casein composition was used as a protein source in the diets fed to RMS-J1 tumor-bearing rats. Dietary substitution of Hcy for Met (i.e., met deprivation) resulted in decreased tumor growth (from 44.4 +/- 1.0 to 40.6 +/- 1.4; P less than .05) and prevention of metastatic spread (from 37 to 0; P less than .05). In conclusion, exogenous Met can be substituted for Hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro. Therefore, this defect of cancerous versus normal cells could be used for a therapeutic purpose. 
3	Cognitive deficits in children: adaptive behavior and treatment techniques. Impaired cognitive functioning impedes the development of age-appropriate adaptive behavior, thus adding to the burdens of many children with epilepsy. Detailed neuropsychological assessment can identify the underlying ability-related impairments that contribute to the adaptive behavior deficiencies evidenced, particularly in the home and school settings. This information can serve as the basis for a multidisciplinary treatment plan tailored to individual needs. Ideally, the need for such a treatment plan should be perceived early in childhood, so that it can be developed and applied preventively. The same remedial principles also apply in older children and are here set out in detail. 
4	Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle BACKGROUND. At any given perfusion pressure, coronary reserve is expressed by the difference between autoregulated and maximally vasodilated flow. In hypertension the raised coronary resistance reduces the steepness of the pressure-flow relationship at maximal vasodilatation. In the presence of cardiac hypertrophy the line of autoregulated flow becomes higher. For these reasons coronary reserve is reduced and the point at which baseline flow approaches the maximal achievable flow might be shifted to a higher perfusion pressure. Thus, any reduction below this elevated and critical value of pressure would lower the coronary flow. METHODS AND RESULTS. The investigated patients were normotensive (controls, nine) and hypertensive with normal (group I, seven) or augmented LV mass index because of concentric LV hypertrophy (group II, eight). All had effort-induced angina and angiographically normal left epicardial branches. Flow in the great cardiac vein was measured by thermodilution in the baseline and during stepwise (5 mm Hg every 5 minutes) decrease of the coronary perfusion pressure with a titrated nitroprusside i.v. infusion; perfusion pressures of 60 mm Hg in the controls and 70 mm Hg in the hypertensives were taken as end points. Baseline flow averaged 102 ml/min in normotensives, 104 ml/min in hypertensive group I and 148 ml/min in hypertensive group II. At the end points flow was similar to baseline in the controls and group I. In group II coronary flow started to decline and myocardial O2 extraction started to slightly but significantly rise at perfusion pressures of 90-80 mm Hg; at the end point flow was reduced by 26% (p less than 0.01 from baseline). The perfusion patterns did not seem to be related to the changes in tension-time index and heart rate. CONCLUSIONS. The association of high blood pressure (reduced ability of the coronary arterioles to dilate) and hypertrophy of the myocardium (augmented baseline coronary flow) may shift the point of exhaustion of coronary reserve to a higher perfusion pressure and make the myocardium vulnerable to treatment-induced relative hypertension. 
2	Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure. We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients. 
3	Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain. We report a case of epidural haematoma following a steroid injection into the cervical epidural space. The complication occurred on the seventh such injection over a 2 year period for chronic spinal pain. Surgical decompression over the seventh cervical and the upper 3 thoracic vertebrae was required to alleviate the symptoms of paralysis and anaesthesia. The patient subsequently required skin grafting to the surgical site and two trans-urethral resections of the prostate gland during his 6 week hospital admission. He made a full recovery. 
1	Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. The leukemogenic membrane glycoprotein (gp55) encoded by Friend spleen focus-forming virus appears to bind to erythropoietin receptors (EpoR) sto stimulate erythroblastosis [Li, J.-P., D'Andrea, A.D., Lodish, H.F. & Baltimore, D. (1990) Nature (London) 343, 762-764]. To directly compare the effects of gp55 with erythropoietin (Epo), we produced retrovirions that encode either gp55, Epo, or EpoR. After infection with EpoR virus, interleukin 3-dependent DA-3 cells bound 125I-labeled Epo and grew without interleukin 3 in the presence of Epo. These latter cells, but not parental DA-3 cells, became factor-independent after superinfection either with Epo virus or with Friend spleen focus-forming virus. In addition, Epo virus caused a disease in mice that mimicked Friend erythroleukemia. Although Fv-2r homozygotes are susceptible to all other retroviral diseases, they are resistant to both Epo viral and Friend viral erythroleukemias. These results indicate that both gp55 and Epo stimulate EpoR and that the Fv-2 gene encodes a protein that controls response to these ligands. However, the Fv-2 protein is not EpoR because the corresponding genes map to opposite ends of mouse chromosome 9. These results have important implications for understanding signal transduction by EpoR and the role of host genetic variation in controlling susceptibility to an oncogenic protein. 
5	The surgical pathologist's role in liver transplantation. Liver transplantation has become an option in treating a wide variety of diseases. The surgical pathologist, as a member of the transplantation team, is increasingly involved in the evaluation of allograft dysfunction. Interpretation of the liver allograft biopsy specimen requires integration of clinical history, biochemical data, and histologic patterns of a wide variety of lesions, including harvesting injury, vascular thrombosis, rejection, infection, and recurrent disease. This article reviews the varied histologic appearances of the more common forms of liver allograft injury, the contexts in which they arise, and their distinction from one another. 
4	Relation between three-dimensional geometry of the inflow tract to the orifice and the area, shape, and velocity of regurgitant color Doppler jets: an in vitro study. The relation between three-dimensional geometry of the inflow tract to the orifice and the area, shape, and velocity of regurgitant jets was studied in a pulsatile in vitro color Doppler flow model. A 2.5 MHz transducer connected to a diagnostic ultrasound machine was placed in a water tank facing pulsatile jets (duration, 0.5 second) obtained by a calibrated injector. Flow rate from 6 to 52 ml/sec were tested through a 5 mm diameter circular orifice. Four different three-dimensional inflow tract geometries were compared: (A) sharp-edged, (B) Venturi (funnel), (C) converging conical, and (D) diverging conical. Mean velocities of jets were measured by continuous-wave Doppler echocardiography. Driving pressures were also measured by means of a fluid-filled catheter. Two observers independently digitized contours of maximal color jet areas by computer system from two separate sets of experiments. Results are given as the mean values of the four measurements for each parameter. Jet areas were correlated to flow rate, with no difference from A through D. The shape (eccentricity) of jets was different between A and B (p less than 0.05), between B and D (p less than 0.01), and between C and D (p less than 0.01). The shape of jets was correlated with flow rate, continuous-wave velocity, and pressure gradient in B, C, and D but not in A. Measured pressure gradients and estimated gradients by continuous-wave Doppler echocardiography were similarly correlated from A through D. 
1	Comparative ophthalmologic studies on children and adults with craniopharyngiomas. The subjects of the study are 74 patients with craniopharyngiomas treated at the Clinic of Neurosurgery, Bulgarian Medical Academy, within the period 1960-1989. Fifty of the patients are children and 24 adults. The diagnosis of all patients is made on the base of clinical, X-ray and histological studies. The ophthalmologic state was studied in all patients, prior to operation, via routine methods. Reduced visual acuity was established in 69.6% of the children and 81.8% of the adults. The presence of congestive optic papilla was diagnosed in 22% of the children and 12.5% of the adults. Optic atrophy was established in 62.5% of the adults and 52% of the children. Various defects in the visual field were established in 67.7% of the children and 81.8% of the adults with the predomination of bitemporal defects. The use of highly informative conventional and modern X-ray methods is recommended in all patients suspected of compression of the visual pathways. 
5	Strong association of HLA-DRw9 in Chinese patients with recurrent oral ulcers. The frequency of HLA-DR and -DQ antigen occurrence was investigated in 80 Chinese patients with recurrent oral ulcers and 107 matched healthy control subjects of the same ethnic group. No significant differences in the presence of HLA-DQ antigens were found. However, the HLA-DRw9 antigen occurs more frequently in patients with recurrent oral ulcers (p less than 0.0001, corrected p less than 0.005) and may be considered as a genetic marker of the disease in the Chinese population. 
3	Naloxone and spinal fluid drainage as adjuncts in the surgical treatment of thoracoabdominal and thoracic aneurysms. Forty-seven patients who were treated for thoracoabdominal or thoracic aneurysms over a 5 1/2-year period were analyzed for neurologic deficit risk. Patients were divided into two groups for analysis. Twenty-four patients, who were treated from January 1984 to December 1986, did not undergo spinal fluid drainage or naloxone administration (group A). Twenty-three patients, who were treated from January 1987 to August 1989, had spinal fluid drainage (group B); 12 patients in this group also received naloxone as an intravenous drip at 1 microgram/kg/hr for 48 hours after surgery. Permanent neurologic deficits occurred in seven (29%) group A patients but in only one (4%) group B patient, who did not receive naloxone (p less than 0.03). The first two group B patients to receive naloxone showed complete reversal of neurologic deficits on waking from anesthesia. This significant reduction in neurologic deficit was associated with an increased 1-year survival rate (72% in group A, 91% in group B). We conclude that the use of naloxone and spinal fluid drainage reduces the incidence of neurologic deficit that is associated with repair of thoracoabdominal and thoracic aortic aneurysms. This reduction in neurologic deficit is associated with improved survival in the long term. The observed reversal of postoperative neurologic deficits with naloxone implicates opiates as a major factor in the pathophysiology of spinal cord ischemia. 
5	Optimal escort for interhospital transport of pediatric emergencies. The charts of 130 seriously ill or injured children transported to tertiary level intensive care were examined to determine the incidence of secondary insults incurred, as a function of escort training. Of all insults incurred, approximately 8% occurred with specialized pediatric transport escorts who were accompanied by a tertiary care physician (Group III, n = 52); 20% with specialized pediatric transport escorts alone (Group II, n = 44); and 72% with escorts who had not received specialized pediatric transport training (Group I, n = 34). Based on our results, we recommend that all transport coordinators review the qualifications and experience of their transport team members and all potential escorts to assess their ability to provide optimal care for the children they transport, particularly during long journeys, transfer by air, and when serious illness or injury is involved. 
5	Inflammatory response in retrieved noncemented porous-coated implants. One hundred forty-six noncemented porous-coated hip and knee implants retrieved from 97 patients were evaluated histologically for the type, amount, and anatomic distribution of tissue ingrowth. The degree of inflammatory cell infiltrate present was also evaluated and the predominant cell type was identified. An inflammatory infiltrate was present in the components of 21 of 97 patients (22%). In 16 of the 21 cases the infiltrate was lymphocytes and histiocytes with a minor population of plasma cells. One of the remaining five cases had a predominately plasma cell reaction, and the other four had significant populations of plasma cells. Vascular proliferation was observed in nine of the 21 cases. Bone ingrowth was present in ten of the 21 cases. A 38% incidence of removal for persistent pain was present in cases with an inflammatory infiltrate. Seventeen of 87 patients (20%) with cobalt-chromium devices and four of ten patients (40%) with titanium devices were identified as having an inflammatory infiltrate. The origin of the inflammatory infiltrate is unclear. All patients with inflammatory infiltrates had noninfected implants, which were not loose roentgenographically or clinically at the time of removal. Hypersensitivity and allergic responses to metal ions may produce such infiltrates. It is impossible, however, in the present study to definitively determine the etiology of the infiltrates. 
2	Anorectal surgery in the HIV+ patient: update. Anorectal surgery in HIV+ patients historically has been viewed with a great deal of nihilism. Advances in medical therapy and better understanding of unique pathophysiologic processes have afforded the colorectal surgeon the ability to treat better and sometimes cure the anorectal complications of AIDS. We present a series of 75 consecutive surgical procedures (1-year accrual) on HIV+ (40) and CDC AIDS (22) patients. Surgical procedures, perioperative T cell counts, and outcome will be presented; 53 percent of procedures resulted in complete healing of anal wounds; 30 percent resulted in partial healing with symptomatic relief; 17 percent resulted in symptomatic relief or tissue diagnosis without appreciable wound healing. The healing rate was significantly higher in the HIV+ group (69 percent) compared to the AIDS group (26 percent). Perioperative T cell counts did not have predictive value on outcome. No patients suffered significant unexpected morbidity, mortality, or incontinence. Pathophysiologic mechanisms of several disease processes unique to HIV+ patients and data from our ongoing investigation using RNA hybridization are presented. 
4	Comparison of the antihypertensive effects of delapril and enalapril. The angiotensin converting enzyme (ACE) inhibitors delapril and enalapril were compared in a double-blind, randomized, parallel study. The population included 142 patients with essential hypertension who were treated with delapril and 140 treated with enalapril. At the end of a 2 week initial placebo period, the diastolic blood pressure of these patients ranged from 95 to 115 mm Hg in the sitting position. After this placebo period, randomization took place. Patients in the delapril group received 15 mg of the drug twice daily. Treatment with enalapril was started with a daily dose of 10 mg. If the diastolic blood pressure did not fall to less than or equal to 90 mm Hg or at least by 15 mm Hg after 2 weeks of treatment, the doses of the ACE inhibitors were doubled. After another 2 weeks, 25 mg hydrochlorothiazide daily was added if the target level of diastolic blood pressure was not reached. Both drugs caused a similar decrease of systolic and diastolic blood pressure. The antihypertensive effect of both ACE inhibitors was increased by the addition of the diuretic. The frequency and severity of side effects were similar in the two groups of patients. It is concluded from this study that delapril and enalapril do not differ in antihypertensive efficacy nor in safety. 
1	Recreational sun exposure in Puerto Rico: trends and cancer risk awareness. Persons who sunbathe or engage in other activities at the beach are exposed to large amounts of UV radiation. Four hundred seven adults who visited the beaches of Puerto Rico were surveyed to determine their knowledge about the risks of sun exposure and to evaluate sunscreen use. The group consisted of 195 year-round Puerto Rican residents and 212 tourists. Ninety-five percent believed that the sun can cause skin cancer, although only half of the subset who lived all year in Puerto Rico believed that they personally received enough exposure to be at risk. The majority of the group (83%) understood the meaning of the sun protection factor numbers, although 35% used either nothing or a nonscreening oil. Half of Puerto Rican residents rarely or never used sunscreen protection while sunbathing. When sunscreen was used, the most important factor sought was given as sun protection factor (64%), followed by a perceived ability to aid in tanning (26%). 
1	An analysis of the results of mammographically guided biopsies of the breast. Three hundred and fifty-three women underwent 358 biopsies of the breast for nonpalpable mammographic lesions during a five year period. Cancer was identified in 95 (27 per cent). Mammographic findings in the patients with cancer were calcifications only (54 per cent), a mass (27 per cent), a mass with calcifications (15 per cent), an asymmetric distortion (1 per cent) and an asymmetric distortion with calcifications (3 per cent). Cancer was identified in 29 per cent of the biopsies done for calcifications, 20 per cent of those done for a mass with calcifications, 6 per cent of those done for an asymmetric distortion and 38 per cent of those done for an asymmetric distortion with calcifications. Forty-nine per cent of the mammographically suspicious calcifications were cancer, while 100 per cent of the indeterminate calcifications were benign. Forty-five per cent of the spiculated masses were cancerous, while only 3 per cent of the circumscribed masses were malignant. For those patients with carcinoma undergoing axillary lymph node dissection, 13 per cent had one or more positive nodes. A strategy for increasing the effectiveness of mammographically guided biopsies of the breast is presented. 
3	Capsular genu syndrome. We report 5 patients with unilateral infarct and 1 with hemorrhage limited to the genu of the internal capsule. The most prominent finding was contralateral facial and lingual hemiparesis with dysarthria. Three patients also showed unilateral mastication-palatal-pharyngeal weakness, and 1 had unilateral vocal cord paresis. Mild limb involvement was limited to hand weakness in 4 patients. Our findings suggest that the majority of motor corticopontine and corticocobulbar fibers are located in the genu of the internal capsule. The faciolingual syndrome and its variants are highly suggestive of capsular genu stroke. 
3	mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. We studied two related infants with a fatal mitochondrial disease, affecting muscle in one and liver in the other. Quantitative analysis revealed a severe depletion of mtDNA in affected tissues. This genetic abnormality was also observed in muscle of an unrelated infant with myopathy and in muscle and kidney of a fourth child with myopathy and nephropathy. Biochemistry, immunohistochemistry, and in situ hybridization showed that the depletion of mtDNA in muscle fibers was correlated with a respiratory chain defect and with lack of mitochondrially translated proteins. Although the differential tissue involvement in these infants suggests mtDNA heteroplasmy, sequence analysis of mtDNA replication origins did not reveal any abnormality that could account for the low copy number. 
2	Ondansetron: a new entity in emesis control. Nausea and vomiting are serious problems for patients receiving cancer chemotherapy. Dopamine receptor and cholinergic receptor antagonism have been the target mechanism for agents used to combat drug-induced nausea and vomiting; more recently, blockade of serotonin receptors has been used for this indication. Current therapies are limited by extrapyramidal adverse effects, as well as drowsiness, sedation, respiratory depression, and cardiac effects. Ondansetron is an investigational serotonin antagonist that has documented effectiveness for cancer chemotherapy-induced emesis. Ondansetron appears to be well tolerated, with the possible exception of headaches and transient increases in liver enzymes. No extrapyramidal toxicities have been reported with this agent. While ondansetron looks promising, further studies are needed to fully define its role as an antiemetic. 
4	Stroke volume during submaximal exercise in endurance-trained normotensive subjects and in untrained hypertensive subjects with beta blockade (propranolol and pindolol). The effect of beta-adrenergic blockade on stroke volume (SV) at increasing submaximal exercise intensities was studied in 12 endurance-trained normotensive and 12 untrained hypertensive (diastolic blood pressure greater than 95 mm Hg) men, aged 18 to 34 years. Subjects were assigned to each of 3 treatments in a double-blind, randomized order: placebo, propranolol (80 mg twice daily) and pindolol (10 mg twice daily) for 10 days, with a period of 48 to 60 hours from the initial dose to the first treadmill test and a 4-day washout period between drugs. Cardiac output was measured using the carbon dioxide rebreathing method and SV was calculated from cardiac output and heart rate as follows: SV = cardiac output/heart rate. Cardiac outputs were estimated at rest and while walking on a treadmill at 25, 45, 60 and 75% of the subject's previously determined maximal oxygen uptake (VO2max). No significant differences were found in cardiac output between either of the drugs and placebo at rest, or at any of the 4 rates of work. Propranolol significantly increased SV above placebo values (p less than 0.05) for both trained and untrained groups at the intensities of 45, 60 and 75%. Significant differences in SV were found between pindolol and placebo only at the intensities of 60 and 75% in the trained group. Contrary to expectations, SV showed no indication of a plateau with propranolol in the trained subjects throughout the 4 different exercise intensities, whereas a plateau was established under placebo conditions by 45% of VO2max in both trained and untrained subjects. These results suggest that both trained and untrained hypertensive persons can exercise with beta-adrenergic blockade at submaximal levels without compromised cardiac function. 
4	Chylous ascites should suggest constrictive pericarditis even in a patient with cirrhosis. Chylous ascites, a milky, high triglyceride fluid is usually found in patients with lymphatic obstruction from malignancy. We describe a patient with cirrhosis who developed constrictive pericarditis and chylous ascites. Long-standing portal hypertension compounded by elevated central venous pressure provided several pathophysiologic contributions to the formation of the chylous ascites. Chylous ascites even in a cirrhotic requires prompt assessment for conditions leading to elevated central venous pressure. 
2	"Spontaneous sump syndrome": Successful treatment by duodenoscopic sphincterotomy. "Sump syndrome" is a rare complication of side-to-side choledochoenterostomy operations which develops in the distal, nonfunctioning limb of the common bile duct where lithogenic bile, gastrointestinal contents, and debris accumulate. We report here a patient who developed spontaneous sump syndrome as a result of the formation of choledochoduodenal fistula, and who presented with multiple pyogenic liver abscesses. The patient's symptoms and liver abscesses resolved completely after treatment by endoscopic sphincterotomy and antibiotics. This case demonstrates that sump syndrome may occur spontaneously, that it can be a cause for pyogenic liver abscess formation, and that it may be treated effectively by endoscopic sphincterotomy. 
5	Acute respiratory failure and pulmonary thrombosis in leukemic children. Acute respiratory failure (ARF) in an 11-year-old child with pre-T acute lymphoblastic leukemia (ALL) at the beginning of induction therapy was observed, connected with a pulmonary thrombosis and not with an infective origin. A systematic search for this pathology identified six other children with the same pulmonary complication, five of whom where in the early phase of acute nonlymphoblastic leukemia (ANLL) and one in induction therapy for ALL in marrow relapse. At the beginning of the symptomatology, all children presented severe hypoxia and hypercapnia, with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement. In all patients the arteriography and nuclear imaging studies confirmed the diagnosis. The causes of the thrombi could be connected with neoplastic emboli after cell lysis and/or with the vascular damage resulting from antiblastic therapy. Intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children. 
5	Can concomitant restriction be detected in adult men with airflow obstruction? A reduction in lung volume is used to diagnose physiologic restriction in the pulmonary function tests of patients with lung disease. Airflow obstruction is commonly associated with hyperinflation of static lung volume. Because restriction and obstruction exert opposite effects on lung volumes, we questioned whether the lack of hyperinflation of static lung volumes could indicate the presence of concomitant restriction in patients with airflow obstructive ventilatory defects. To assess this, we evaluated by pulmonary function tests and chest roentgenograms of 58 patients with airflow obstruction (group 1), 18 of whom then sustained various types of resection for lung cancer (group 2) as a type of superimposed restriction. We selected 80 percent of predicted as the lower limit of "normal" frequently used by clinical pulmonary function laboratories. Despite a statistically significant decrease in total lung capacity (p less than 0.05) for the postpneumonectomy patients, when the static lung volume measurements of the patients with resection were evaluated, no one lung volume showed a consistent reduction sufficient to detect the superimposed restriction in all these patients. Using 80 percent of predicted as "normal," 61 percent of our patients with airflow obstruction and superimposed restriction would have been missed. We conclude that it is clinically difficult, based on only static lung volume measurements alone, to detect restriction superimposed on the hyperinflation of airflow obstruction unless these lung volumes are reduced to below accepted "normal" limits. 
4	Interatrial shunt flow profiles in newborn infants: a colour flow and pulsed Doppler echocardiographic study. Interatrial shunt flow profiles in 36 normal term infants were examined serially by colour flow and pulsed Doppler echocardiographic techniques from within an hour of birth to four or five days after birth. Shunt flow across the foramen ovale was detected in 33 normal infants (92%) within an hour of birth (mean 40 minutes). The occurrence of interatrial shunting decreased with age, but a shunt signal was still detected in 17 infants (47%) on the fourth or fifth day of life, by then the ductus arteriosus had already closed in all the normal infants. The direction of interatrial shunt flow was predominantly left-to-right, but in 64% there was a coexistent small right-to-left shunt in diastole within an hour of birth; by four to five days it was found in 19%. In the six patients with persistent fetal circulation the direction of the interatrial shunt flow was predominantly right-to-left with biphasic peaks in diastole and systole at the early stage of the disease, and the period of right-to-left shunt flow during each cardiac cycle was significantly longer than that in normal infants examined within 1 hour of birth. In all patients the ductus closed before the foramen ovale. At the time of ductal closure in all patients with persistent fetal circulation right-to-left shunt flow was seen during diastole and its period was still prolonged. These findings suggest that interatrial shunting, predominantly left-to-right, is common in normal newborn infants. 
5	Adrenal insufficiency in the cancer patient: implications for the surgeon. Aspects of acute and chronic adrenal insufficiency of interest to surgeons who treat cancer patients are reviewed. Clinical features and the management of both primary and secondary types are considered with reference to classification, aetiology, diagnosis and treatment. Specifically considered are the management of patients with Addison's disease and metastases. Prompt recognition and treatment of adrenal insufficiency can avert potentially life-threatening situations. 
5	Verbal memory impairment correlates with hippocampal pyramidal cell density. Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures. 
5	Electrical pacing for dynamic treatment of unilateral vocal cord paralysis. Experiment in long-denervated muscle. In order to explore the possibility of clinical application of laryngeal pacing as a treatment for unilateral vocal cord paralysis, we examined the reactivity of atrophic muscle to electrical stimulation in dogs whose recurrent laryngeal nerves were damaged by crushing, dissection followed by resuturing, or a 3-cm neurectomy. The threshold level to induce enough vocal cord adduction reached the maximum at 2 weeks after nerve injury, decreased with time, and never surpassed 7 V in each case. On the basis of results of these preliminary probings, laryngeal pacing was conducted on a dog 15 months after resection of the laryngeal nerve. Adduction of the paralyzed vocal cord for synchrony with the intact cord was achieved by 7 V of electrical stimulation of the thyroarytenoid muscle that was triggered by signals from the cricothyroid muscle. 
2	Surgical correction of hydrothorax from diaphragmatic eventration in children on peritoneal dialysis. Continuous ambulatory peritoneal dialysis (CAPD) is frequently used in the pediatric age group for reversible and end-stage renal failure. Most pediatric patients tolerate this therapy with few complications. Approximately 2% of children, however, develop massive unilateral hydrothorax. This major complication usually results in the discontinuation of peritoneal dialysis in all forms and the institution of hemodialysis. Occult diaphragmatic defects account for most adult and pediatric patients who develop this complication. Three pediatric patients receiving CAPD complicated by massive hydrothorax are described. All patients were successfully treated by thoracotomy and repair of the diaphragmatic eventration with an immediate return to CAPD. This is the first report of successful therapy of this kind in children. A review of the cause, diagnosis, and treatment of massive hydrothorax developing during CAPD therapy is presented. 
1	Lack of late skin necrosis in man after high-dose irradiation using small field sizes: experiences of grid therapy. Out of a total of 437 patients with superior vena caval syndrome or advanced malignancy, given single-dose grid radiotherapy, four survived to 7 years. The dose to the skin under each of the 77 holes in the grid was approximately 58 Gy. The lack of skin necrosis in the total of 308 skin circles of 1 cm diameter among these survivors, compared with known necrosis rates in larger irradiated areas, implies that there is a marked field-size effect for late necrosis in small areas of irradiated skin. 
4	Coronary angioplasty after coronary bypass surgery: initial results and late outcome in 422 patients. From 1978 to 1988, coronary angioplasty was performed in 422 patients with prior coronary artery bypass surgery (264 patients with native coronary artery angioplasty and 158 patients with graft angioplasty). Angioplasty was successful in 84%, unsuccessful but uncomplicated in 11% and complicated by one or more major cardiac events in 5% (myocardial infarction 5%, emergency bypass surgery 2% and death 0.2%). Follow-up data were obtained in 99% of 356 patients with successful angioplasty. At a mean of 33 +/- 26 months, 92% were alive, 73% had improvement in angina and 61% were free of angina. One or more of the following late events occurred in 67 patients (19%): myocardial infarction (6%), elective reoperation (13%) and cardiac death (6%). Repeat angioplasty was performed in 27%, with a success rate of 89% and no deaths. Initial success rates were equal in native vessel versus graft angioplasty, but late outcome was less favorable with the latter because of a higher rate of infarction (11% versus 4%, p less than 0.05) and need for reoperation (19% versus 10%, p less than 0.05). The initial success rate was higher in vein grafts less than 1 year old compared with grafts 1 to 4 years or greater than 4 years after operation (92% versus 85% versus 83%, respectively) and adverse late events were less frequent after angioplasty in recent vein grafts (less than 1 year 13%, 1 to 4 years 35%, greater than 4 years 29%; less than 1 versus greater than 1 year, p less than 0.05). 
3	Distribution of three alpha-chain beta-hexosaminidase A mutations among Tay-Sachs carriers. DNA from 176 carriers of the Tay-Sachs gene was tested for the presence of the three mutations most commonly found among Ashkenazi Jews: the so-called insertion, splice junction, and adult mutations. Among 148 Ashkenazi Jews tested, 108 had the insertion mutation, 26 had the splice junction mutation, five had the adult mutation, and nine had none of the three. Among 28 non-Jewish carriers tested, most of whom were obligate carriers, four had the insertion mutation, one had the adult mutation, and the remaining 23 had none of the three. 
5	Role of membrane proteins in monosodium urate crystal-membrane interactions. II. Effect of pretreatments of erythrocyte membranes with membrane permeable and impermeable protein crosslinking agents. Intact, human erythrocytes were pretreated with membrane permeable, dimethyl adipimidate (DMA) and dimethyl suberimidate (DMS) and membrane impermeable 3,3' dithiobis (sulfosuccinimidylpropionate) (DTSSP) protein crosslinking agents and incubated with monosodium urate monohydrate (MSUM) crystals. The percent inhibition of lysis values for pretreated cells relative to untreated cells were determined. All 3 agents caused a concentration dependent inhibition of MSUM induced hemolysis that was not due to a decrease in MSUM binding to the pretreated membranes. It was proposed that the inhibition of lysis was due to crosslinking of integral and cytoskeletal membrane proteins, resulting in a reduced mobility of the proteins, inhibition of lateralization of integral proteins into aggregates and decreased "pore" formation in the membrane. 
5	Otogenic Fusobacterium necrophorum meningitis. A case of meningitis secondary to acute suppurative otitis media in a previously healthy child is reported. The only organism isolated from blood after aerobic and prolonged anaerobic culture was identified as Fusobacterium necrophorum. Complete recovery followed treatment with surgery and prolonged antibiotic therapy. The role of anaerobes in the development of meningitis, the isolation and identification of Fusobacterium necrophorum, the clinical presentations of F. necrophorum infection and the choice of antibiotics in the treatment of these infections are discussed. 
4	Prevalence and association of asteroid hyalosis with systemic diseases. We performed a cross-sectional study of 12,205 patients, which identified 101 patients (0.83%) with asteroid hyalosis. These patients were examined for associated systemic and ocular conditions. Diabetes mellitus was found in 29 of the patients with asteroid hyalosis (29%), as compared to ten of 101 (10%) control subjects (P = .0007). An increased prevalence of systemic arterial hypertension (61 of 101 [60%] patients with asteroid hyalosis compared with 29 of 101 [29%] control subjects; P = .0001) and atherosclerotic vascular disease (30 of 101 [30%] patients with asteroid hyalosis compared with 13 of 101 [13%] control subjects; P = .006) was also discovered in the asteroid hyalosis group. Additionally, patients with asteroid hyalosis were found to be more hyperopic than control subjects (P = .009). 
4	Relief of tracheal compression by aortopexy. We have performed aortopexy in 12 children with tracheal compression. Six infants had compression secondary to a vascular anomaly (group 1), and the other 6 had previous repair of esophageal atresia (group 2). Eleven of the 12 children are alive after a mean follow-up of 36 months. In group 1, 1 patient died and 3 patients (50%) experienced recurrent respiratory distress. Five infants sustained a major postoperative complication, and the average postoperative hospital stay was 25 days. In group 2, however, aortopexy was uniformly successful. There were no deaths, no postoperative complications, and no cases of postoperative respiratory distress, and the mean postoperative hospital stay was only 10 days. For children with reflex apnea after repair of esophageal atresia, aortopexy is lifesaving and can be performed with minimal morbidity and mortality. Great caution is indicated in children with tracheal compression from other causes. 
5	Leukotriene synthesis inhibition and receptor blockade do not inhibit hypoxic pulmonary vasoconstriction in sheep. Several lines of evidence suggest that leukotrienes may be mediators of hypoxic pulmonary vasoconstriction (HPV). However, the effect of leukotriene inhibition on HPV remains controversial. The present study investigated the effect of leukotriene synthesis inhibition and receptor blockade on HPV in the halothane-anesthetized sheep. After initial baseline measurements, the pulmonary pressor response to 15 min of global hypoxia (FIO2 = 0.13) was measured. A second set of baseline measurements was obtained and the sheep then received the combined cyclooxygenase/lipoxygenase inhibitor BW755C, the selective lipoxygenase inhibitor U60257, or the leukotriene receptor antagonist LY171883. Hemodynamic measurements were obtained after drug administration and during a subsequent hypoxic challenge (FIO2 = 0.13). Initial hypoxic challenge increased pulmonary artery pressure 68% and increased pulmonary vascular resistance 104%. Pulmonary hemodynamics after recovery from hypoxia were similar to initial baseline values. Drug administration had no significant hemodynamic effect. Hypoxic challenge after drug administration resulted in a pulmonary pressor response identical to the initial hypoxic challenge. Because leukotriene synthesis inhibition and receptor blockade did not alter the response to hypoxia, we conclude that leukotrienes are not obligatory mediators of HPV. A critical review of the literature supports a modulatory rather than an obligatory role for leukotrienes in HPV. 
3	Duplex scanning of normal or minimally diseased carotid arteries: correlation with arteriography and clinical outcome. This study evaluated the role of duplex scanning in the management of patients with normal or minimally diseases carotid arteries. Carotid duplex scans were interpreted according to previously established criteria and considered normal when pulsed Doppler spectral waveforms showed laminar flow or only minor flow disturbances. Normal flow patterns were noted by duplex scanning in 100 carotid bifurcations of 72 patients who also underwent carotid arteriography. Neurologic symptoms (amaurosis fugax, transient ischemic attack, or stroke) were present in relation to 23 arteries and absent in relation to 77 arteries. On the 23 symptomatic sides arteriography was interpreted as normal in eight, 1% to 15% stenosis in 14, and 16% to 40% stenosis in one. For the 77 asymptomatic sides, arteriography showed normal vessels in 15, 1% to 15% stenosis in 43, and 16% to 40% stenosis in 19. One symptomatic patient was treated by carotid endarterectomy for an irregular 1% to 15% stenosis. None of the asymptomatic lesions were in the range of 80% to 99% stenosis, which would justify endarterectomy for asymptomatic disease. Clinical follow-up for a mean interval of 28 months on 20 of the 22 symptomatic patients not undergoing surgery revealed no strokes and transient recurrent symptoms in two patients. Assuming that the single operation in this study was indicated, duplex scanning correctly identified lesions not requiring carotid endarterectomy in 96% (22/23) of the symptomatic patients. A normal duplex scan also predicted a benign clinical outcome without operation. Duplex scanning can reliably exclude surgically treatable carotid bifurcation lesions in asymptomatic patients, and endarterectomy is rarely indicated in symptomatic patients with normal duplex scan results. This study supports a nonoperative therapeutic approach for most patients with neurologic symptoms and a normal carotid duplex scan on the appropriate side. 
1	Clinicopathological features of elevated lesions of the duodenal bulb. We present here our findings on patients with an elevated lesion of the duodenal bulb. All these patients were treated in our clinics between the years 1984 and 1988. These lesions were present in 36 of 8,802 patients who underwent upper gastrointestinal pan-endoscopy. Two patients had a duodenal carcinoma, 2 an adenoma, and 1 a Brunner's gland adenoma. There were 15 with a hyperplastic polyp, 3 with a heterogenic gastric mucosa, 3 with Brunner's gland hyperplasia, 6 with duodenitis, and 4 with regenerative mucosa. Among these 36 lesions, only 69% (25 lesions) were evident on the upper gastrointestinal X-ray series. Adenoma and Brunner's gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa. Both duodenal carcinomas were detected by endoscopic biopsy and were resected. Histologically, these lesions were limited to the submucosal layer and were of the non-pedunculated polypoid form, but there were no other characteristic endoscopic features, in comparison with other elevated lesions. Thus, upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion. 
1	Rhabdomyosarcomas in the head and neck: MR imaging evaluation. To determine the typical magnetic resonance (MR) signal intensity characteristics of rhabdomyosarcomas, short repetition time (TR)/short echo time (TE) (T1-weighted) and long TR (proton density and T2-weighted) images of 13 patients with rhabdomyosarcomas of the head and neck were retrospectively reviewed. Seven patients received gadopentetate dimeglumine injections. The most common MR appearance was that of a homogeneous mass, hyperintense to both muscle and fat on long TR/long TE images and isointense or minimally hyperintense to muscle on short TR/short TE images. All lesions of the patients who received gadopentetate dimeglumine enhanced markedly. Two lesions had intratumoral hemorrhage, and six were markedly heterogeneous in signal intensity. Similar MR signal intensity patterns have been described for lymphomas and nasopharyngeal carcinomas. The forte of MR imaging lies in its ability to delineate precisely the extent of the rhabdomyosarcoma. 
4	The prophylactic use of octreotide in a patient with ovarian carcinoid and valvular heart disease. This case report describes the use of octreotide, a long-acting somatostatin analogue, in the management of a patient with an ovarian carcinoid tumour and severe cardiac valvular disease. This patient underwent laparotomy and tumour resection without complication. Anaesthesia was induced with midazolam, fentanyl, and vecuronium, and maintained with isoflurane as well as additional fentanyl and vecuronium. However, we feel that it was the use of octreotide that prevented a life-threatening crisis intraoperatively, and recommend its use in patients with carcinoid syndrome undergoing anaesthesia and surgery. 
4	Long-term clinical results with the Ionescu-Shiley pericardial xenograft. From 1977 to 1987, 829 Ionescu-Shiley pericardial valves (Shiley, Inc., Irvine, Calif.) were implanted in 766 patients at the University of Ottawa Heart Institute. There were 476 patients who had aortic valve replacement, 234 who had mitral valve replacement, and 44 who had double valve replacement. The standard-profile design was used in 508 patients and the low-profile design in 321 patients. Follow-up was obtained for 97% of patients, with calculation of event-free probabilities. At 10 years the overall probability of freedom from structural failure was 48% +/- 7% after aortic valve replacement, 44% +/- 15% after mitral valve replacement, and 79% +/- 11% after double valve replacement. Although at 5 years the probability of failure was statistically lower with the low-profile design, this favorability was lost by 6 years. Freedom from structural failure was only 47% +/- 7% for the standard-profile valve at 10 years. Thus the probability of freedom from reoperation was only 46% +/- 7% after aortic valve replacement, 39% +/- 6% after mitral valve replacement, and 65% +/- 20% after double valve replacement at 10 years. Thromboembolism occurred in 69 patients, for a predicted freedom from this complication at 10 years of 79% +/- 3% after aortic, 73% +/- 7% after mitral, and 96% +/- 4% after double valve replacement. There were 31 cases of endocarditis. The 10-year predicted freedom from endocarditis, therefore, was 86% +/- 3% after aortic, 98% +/- 1% after mitral, and 97% +/- 1% after double valve replacement. A total of 221 operative and late deaths were recorded in this series. Prosthetic valve failure accounted for 27% of late deaths. The 10-year survival rates were estimated to be 56% +/- 5% (aortic valve replacement), 54% +/- 6% (mitral valve replacement), and 51% +/- 8% (double valve replacement). We concluded that the Ionescu-Shiley pericardial xenograft provides less than optimal clinical performance and its use has been discontinued. 
5	Itraconazole in opportunistic mycoses: cryptococcosis and aspergillosis. Striking results were obtained with oral itraconazole therapy in two opportunistic mycoses. Of 28 patients with cryptococcal meningitis, 18 achieved complete responses, including 16 of 24 patients with acquired immunodeficiency syndrome. Other manifestations of cryptococcosis were similarly responsive. In aspergillosis 12 of 15 patients responded, including 8 of 10 immunocompromised hosts. These patients included those with invasive pulmonary disease (4/5), skeletal disease (2/2), pleural disease (1/2), and pericardial, sinus, mastoid, hepatosplenic, or nail disease (1/1). These results with itraconazole compare favorably to conventional (parenteral) therapy, and toxicity was minimal. This suggests that comparative trials are now in order. 
1	Tyrosine-rich crystalloids in a polymorphous low-grade adenocarcinoma. A polymorphous low-grade adenocarcinoma with tyrosine-rich crystalloid deposits is reported. The literature is reviewed, and diagnostic and histogenetic implications of this finding are discussed. 
3	Streptococcus bovis meningitis: report of 2 cases. We describe 2 cases of Streptococcus bovis meningitis and review the 9 cases previously reported. This microorganism is a rare cause of meningitis in which there are no distinctive clinical or laboratory features. The Gram stain of the CSF is usually negative. Ten of the 11 cases had some underlying disease or comorbid condition that predisposed to S bovis infection: gastrointestinal disorder, endocarditis, CSF leak, polymyalgia rheumatica, and mandibular block. Treatment with high-dose penicillin is usually adequate. 
1	Third ventricle cavernous angioma: report of two cases. Cavernous angioma arising in the third ventricle is an extremely rare disease. We have reviewed five cases previously reported, as well as our own two cases, and discuss the clinical characteristics of and surgical approach to cavernous angioma at this site. The bifrontal craniotomy and interhemispheric translamina terminalis approach minimize the damage to the brain and allow for an approach to the third ventricle in a wide operative field with minimal compression of the brain itself. We have found this approach to be suitable for surgery on angiomas of the anterior half of the third ventricle. 
5	Partial characterization of Chlamydia trachomatis isolates resistant to multiple antibiotics. In vitro susceptibility testing was done on urogenital isolates of Chlamydia trachomatis from five patients, four of whom were suspected treatment failures. At least one isolate from each patient was resistant to tetracycline at concentrations greater than or equal to micrograms/ml, although less than 1% of a population of organisms showed high-level resistance. Fully resistant populations selected by passage through 8 micrograms/ml tetracycline either died or lost their resistance on further passage in antibiotic-free medium. Relatively large inocula were required to demonstrate resistance, and morphology of inclusions was altered at high tetracycline concentrations. The observed resistance may be a new characteristic of the organism or merely newly recognized. Isolates resistant to tetracycline were resistant to doxycycline, erythromycin, sulfamethoxazole, and clindamycin but sensitive to rifampin, ciprofloxacin, and ofloxacin. Thus, resistance to tetracycline, erythromycin, and clindamycin occurs in C. trachomatis and may be a factor in some treatment failures. 
4	Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis [published erratum appears in Proc Natl Acad Sci U S A 1991 Apr 1;88(7):2967] The gene coding for plasminogen has been compared with several abnormal genes from Japanese patients by the polymerase chain reaction and DNA sequence analysis. Two types of abnormal genes coding for plasminogen were identified in these patients. In the type I mutation, a guanosine in GCT coding for Ala-601 near the active-site histidine was replaced by an adenosine resulting in ACT coding for threonine. This mutation was also shown by the loss of a cleavage site for Fnu4HI endonuclease, a restriction enzyme that recognizes GCTGC but not ACTGC. In the type II mutation, a guanosine in GTC coding for Val-355 was replaced by a thymidine resulting in TTC coding for phenylalanine. This change was readily shown by digestion with Ava II endonuclease, a restriction enzyme that recognizes GGTCC and not GTTCC. The type I mutation has been found to be identical to a plasminogen variant identified in Japanese patients by amino acid sequence analysis and also detected by isoelectric focusing, whereas the type II mutation is a unique amino acid substitution in the connecting region between the third and fourth kringles in plasminogen. DNA sequence analysis also revealed that the abnormal genes carry several silent nucleotide substitutions located primarily within introns and 5' and 3' flanking regions. 
5	Biobehavioral factors in Cardiac Arrhythmia Pilot Study (CAPS). Review and examination. The behavioral studies component of the multicenter Cardiac Arrhythmia Pilot Study (CAPS) was designed to examine the relation of biobehavioral factors and frequency of ventricular premature complexes (VPCs), efficacy of antiarrhythmic therapy, and disease end points in a study population that had experienced recent myocardial infarction and significant ventricular ectopy. Biobehavioral factors included both psychosocial (depression, anxiety, social support, type A behavior, mood, defensiveness, and anger expressiveness) and psychophysiological (heart rate and blood pressure reactivity to a videogame stressor) variables. Data were collected at baseline and at 3-, 6-, 9-, and 12-month follow-ups. Of the 502 patients enrolled in CAPS, 353 participated in the behavioral studies component. At baseline, assessments of psychosocial variables revealed the CAPS study population to be generally similar to other heart disease populations, and no relation between these variables and psychophysiological reactivity or arrhythmias was found. At follow-up among patients assigned to the placebo condition, biobehavioral variables were not related to levels of VPCs or VPC suppression. Cox regression analyses revealed that type B behavior, depression, and reduced heart rate reactivity were associated with increased clinical events, even after controlling for baseline left ventricular ejection fraction, myocardial infarction before the qualifying event, use of beta-blockers, use of digitalis, Q wave of qualifying myocardial infarction, and presence of unsustained ventricular tachycardia on baseline electrocardiogram. It is hypothesized that the relation among reduced heart rate reactivity, depression, and clinical events is mediated by diminished cardiac vagal tone. 
4	Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10(-8) M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3 +/- 4.1% vs 6.8 +/- 1.3%, P less than 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls. 
2	Gracilis muscle transposition for faecal incontinence. Transposition of the gracilis muscle for faecal incontinence was performed in 13 patients. Six gained satisfactory continence, four were improved, two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre-existing colostomy. Anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmHg (range 5-63 mmHg), whereas maximum squeeze pressure increased from a median of 38 mmHg (range 5-79 mmHg) to 59 mmHg (range 10-143 mmHg) (P = 0.041) which was, however, significantly lower than 130 mmHg (range 81-236 mmHg) in the control group. All patients who benefited from the operation had an increase in maximum squeeze pressure. The ability to retain a viscous fluid in the rectum was measured in seven patients, four of whom had gained satisfactory continence and three of whom had improved continence. They were able to retain a median volume of 200 ml (range 50-225 ml) without leakage compared with 325 ml (range 250-400 ml) in the control group. These patients could retain the maximum amount of viscous fluid for 5-8 min, whereas all control subjects could do so for more than 15 min. It is concluded that, although gracilis transposition never results in normal continence, acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed. 
4	Lateral medullary infarction: prognosis in an unselected series. We describe the acute and long-term prognosis in 43 patients with lateral medullary infarction (LMI) collected from a population-based stroke registry from 1982 to July 1988. Mean age was 63.9 years and median time of follow-up was 33 months. In the acute phase, 5 patients (11.6%) died from respiratory and cardiovascular complications and 2 new strokes occurred, both in the posterior circulation. During follow-up, recurrent vertebrobasilar territory strokes occurred in only 2 patients (a rate of 1.9% per year). The mechanisms of stroke were vertebral artery (VA) branch occlusion, causing a medial medullary syndrome, and basilar artery thrombosis propagating from a contralateral, distal VA stenosis. In the acute phase of LMI, respiratory and cardiovascular events, presumably caused by autonomic dysfunction related to the lateral medullary lesion, are the major hazards. Recurrent posterior circulation strokes were uncommon during follow-up. 
4	Role of angioplasty in myocardial infarction management strategies: a review. The role of angioplasty in acute myocardial infarction has been extensively studied in the past few years. Although angioplasty in some circumstances can be the primary reperfusion intervention, logistic problems and the excellent results of intravenous thrombolytic therapy have resulted in postlytic angioplasty being the preferred use of this interventional strategy. Clinical trials of this strategy have not supported its routine use, however, and a much more selective application of postthrombolytic coronary artery dilation is advocated at this time. 
5	The osteogenetic potential of fracture haematoma. Subperiosteal and intramuscular transplantation of the haematoma. We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential. 
5	Proliferation characteristics of human colorectal carcinomas measured in vivo. The cell proliferation kinetics of 100 human colonic and rectal adenocarcinomas have been studied in vivo by bromodeoxyuridine infusion and multiparameter flow cytometry. A total of 97 patients, three with synchronous tumours, consented to receive a single bolus dose of 250 mg between 2.4 and 16 h before curative or palliative surgery. By this method, the ploidy pattern, the total and aneuploid labelling indices (LI), the S phase duration (Ts) and the potential doubling time (Tpot) can be estimated. Of the tumours 48 were diploid and 52 were aneuploid. The mean and median total LI of 100 tumours were 9.0 per cent (range 0.7-22.2 per cent). The mean aneuploid LI was 12.1 per cent (median 12.0 per cent, range 2.0-25.5 per cent), and was significantly higher than the total LI (P = 0.01). The labelling index alone is not a sufficient indicator of proliferation, because the Ts also varies within and between tumours. The intertumour range of the Ts varied from 4.0 to 28.6 h. The mean was 14.1 h and the median was 13.1 h. The mean Tpot was 5.9 days (median 3.9 days) with a range of 1.7-21.4 days. No correlation was found between any kinetic parameters and the Dukes' classification or histological classification. The correlation between proliferation and prognosis will be established in due course. 
1	The cancer experience in the Framingham Heart Study cohort. The almost 40-year records of The Framingham Heart Study (FHS) cohort were reviewed to establish the cancer experience of this noninstitutionalized group of white subjects. Diagnoses were confirmed from pathology and laboratory reports and clinical notes. Age-specific incidence rates were compared with Connecticut Surveillance, Epidemiology, and End Results (SEER) data. Among the 5209 subjects, 1201 malignancies were confirmed. Median age at diagnosis was 69 for men and 65 for women. Lung, prostate, skin, and colon accounted for more than half of men's cancers; breast, colon, and skin made up half of the women's. FHS and Connecticut SEER rates matched closely, with the same primary tumor sites appearing commonly in both groups. Thus, the FHS cohort should provide a fair database for analysis of risk factors in cancer incidence, as it has done in cardiovascular diseases. 
3	Hemorrhagic pituitary adenomas: clinicopathological features and surgical treatment. Forty-five (9.9%) of 453 pituitary adenomas operated on between January 1973 and November 1988 demonstrated hemorrhagic changes at surgery: 24 had a blood collection, 12 had a blood collection associated with hemorrhagic necrosis, and 9 had hemorrhagic necrosis. Thirteen patients (28.9%) experienced the acute symptoms of pituitary apoplexy, whereas another 32 had an "asymptomatic" hemorrhage, that is, the clinical course was comparable to an uncomplicated adenoma. Nineteen tumors (42.2%) showed marked suprasellar extension, 8 (17.8%) showed moderate extension, and 11 (24.5%) showed slight extension; another 2 (4.4%) were laterosellar and 5 (11.1%) were intrasellar. Invasive behavior was present in 32 cases (71.1%) and this may suggest another hypothesis to explain the pathogenesis of tumoral hemorrhage. The incidence of hemorrhagic complications in invasive adenomas with marked suprasellar extension was particularly impressive; therefore, we do not suggest preoperative bromocriptine treatment in this type of tumor. Two of 14 patients operated on by the transcranial route died after surgery, whereas there was no operative mortality in the 31 patients operated on by the transsphenoidal route. It proved advantageous to operate as early as possible, even during the acute phase of pituitary apoplexy. The transsphenoidal approach gave the best results, but to achieve satisfactory late results multidisciplinary treatment was necessary, namely, postoperative radiotherapy in 23 patients, bromocriptine in 12, and endocrine replacement therapy in almost all. In an average follow-up period of 6.2 years, 5 (11.1%) symptomatic recurrences were observed. 
1	Giant benign mesenchymoma of the breast. The term mesenchymoma refers to a group of mixed tumors that are composed of two or more mesenchymal elements, excluding fibrous tissue, not ordinarily found together within the same tumor. Mesenchymomas occur most commonly in the renal and perirenal regions with rare occurrence in the breast. We describe what to our knowledge is the first report of a giant benign mesenchymoma of the breast. The clinical presentation, course, and treatment of a patient with this condition is discussed. Clinicians should be aware that benign mesenchymomas may involve the breast and simulate a malignant breast neoplasm. 
4	Pheochromocytoma in the pediatric age group: the prostate--an unusual location. Pheochromocytomas of the prostate are rare, with only 3 cases in adults reported in the literature. We present the case of an 8-year-old boy with a pheochromocytoma of the prostate and a second tumor in the region of the left internal iliac artery. 
5	Mechanical myocardial actuation during ventricular fibrillation improves tolerance to ischemia compared with cardiopulmonary bypass. Direct mechanical ventricular actuation (DMVA) is a unique non-blood-contacting biventricular assist device that provides circulatory support during ventricular fibrillation without demonstrating adverse effects on the myocardium. The purpose of this study was to assess the preservation of myocardial energy stores and myocardial responses to ischemia after circulatory support during ventricular fibrillation with direct mechanical ventricular actuation versus cardiopulmonary bypass. Twenty adult mongrel dogs were randomized to receive circulatory support with either cardiopulmonary bypass or direct mechanical ventricular actuation. After 4 hours of ventricular fibrillation, hearts were defibrillated and left ventricular transmural biopsies were obtained. Hearts were then excised and subjected to 90 minutes of normothermic total ischemia. Serial biopsies were obtained at 15-minute intervals to determine regional depletion of high energy phosphates. The time-to-peak ischemic contracture was recorded by using needle-tipped Millar catheters placed in the left ventricular endocardium, epicardium, septum, and right ventricle. Time-to-peak ischemic contracture of the endocardium (62.6 +/- 1.4 vs. 58.8 +/- 1.0 minutes, p less than 0.05) and septum (61.1 +/- 6.9 vs. 46.9 +/- 6.2 minutes, p less than 0.004) were significantly prolonged after direct mechanical ventricular actuation versus cardiopulmonary bypass, respectively. Similar trends were noted in the epicardium and right ventricular regions; however, these differences were not statistically significant. Left ventricular adenosine triphosphate (ATP) levels were better preserved after direct mechanical ventricular actuation (22 +/- 1.5 mumols/g dry wt) compared with cardiopulmonary bypass (17 +/- 1.9 mumols/g dry wt). The depletion of left ventricular endocardium ATP during normothermic ischemia was significantly delayed after direct mechanical ventricular actuation compared with cardiopulmonary bypass. 
2	The symptom sensitivity index: a valuable additional parameter in 24-hour esophageal pH recording. Twenty-four-hour esophageal pH monitoring is useful for the quantitative measurement of gastroesophageal reflux and for the demonstration of a temporal relationship between symptoms and reflux. The symptom index, a numerical score, was developed to quantify the association between symptoms and reflux. Because the symptom index primarily assesses the specificity of a patient's reflux symptoms, we propose to refer to this score as the symptom specificity index. Because of certain limitations of this score, we developed and evaluated a new score, the symptom sensitivity index, that quantifies the subject's sensitivity for reflux. Fifty-two consecutive patients, referred to our laboratory for ambulatory 24-h pH recording were studied. Beside the conventional reflux variables, both indexes were calculated. Although a statistically significant correlation between the indexes was found, discordance between the specificity and sensitivity indexes was seen in 17 patients (33%). Based on the findings in this study we advocate that the symptom sensitivity index should be used, in addition to the symptom specificity index, and incorporated in future pH studies to optimalize the interpretation of the results. 
4	Vitamin C and cardiovascular risk factors. The concept that ascorbic acid (vitamin C) supplementation protects against coronary heart disease developed in the late 1970s when vitamin C intakes in industrialized nations were lower than at present. Supplementation was then shown to lower plasma total cholesterol and, among some elderly men, to raise high-density lipoprotein cholesterol. However, among people in initially good vitamin C nutriture, these effects are usually not seen. In five populations of essentially healthy people, blood pressure has been found to correlate negatively with vitamin C status. Recently, in a placebo-controlled, double-blinded study, extra ascorbic acid for 6 wk was observed to lower systolic and pulse pressure in a small group of borderline hypertensive subjects. 
1	Technetium-99m-methylene diphosphonate (MDP) uptake in a sympathetic effusion: an index of malignancy and a review of the literature. We report a patient with a sympathetic pleural effusion secondary to T-cell lymphoma that accumulated the bone imaging agent, Technetium-99m-methylene diphosphonate (99mTc-MDP). This case is significant in that malignant cells were not present on three cytologic examinations of the pleural fluid or multiple pleural biopsies. We also present a review of the published literature on pleural effusions that accumulate bone tracers. We conclude that pleural effusions that accumulate 99mTc-MDP should be considered malignant or secondary to a malignancy and further work-up is essential even if the cytologic exam of the pleural fluid is unremarkable. 
5	Dislocation after total hip arthroplasty. Causes and prevention. In this prospective study, a technique of positioning the acetabulum by bony landmarks of the pelvis in the standing position was developed using a standing lateral preoperative roentgenogram with the X-ray tube centered over the trochanter. Since 1984, 441 total hip arthroplasties (THAs) were done through the posterior approach with a 1.14% dislocation rate through 1988 and no dislocations in 1989. To prevent impingement and dislocation, it was determined that the safest range for cup position was 30 degrees-50 degrees abduction and 20 degrees-40 degrees flexion from the horizontal. To measure postoperative cup position, a standing true lateral roentgenogram of the operated hip allowed direct measurement of cup flexion and was reproducible within 10 degrees. No special instruments are necessary for this technique, which can be used with any THA system. 
5	Epidemiology of acute respiratory tract infections among young children in Kenya. The epidemiology of acute respiratory tract infection (ARI) was investigated in a rural community 80 km north of Nairobi, Kenya. This research was conducted prospectively on 250 families with 470 children less than 5 years of age who were contacted every 8 days during the 3-year study. The yearly incidence of respiratory tract infections decreased from 5.2 to 3.4 during the study; less than 5% of these infections involved the lower respiratory tract. The incidence was inversely related to age, and the illnesses were generally mild and brief in length. Fifteen children died during the study period. The precise causes of death are unknown, but respiratory infections possibly played a role in most cases. This study emphasizes the importance of determining the risk factors responsible for unusually severe morbidity and high mortality in children with ARI in developing countries. 
5	Senile dementia and healthy aging: a longitudinal CT study. Volumetric indexes of cerebral atrophy obtained by using computed tomography (CT) were measured longitudinally in patients with senile dementia of the Alzheimer type (SDAT) and in healthy elderly control subjects. Measurements were made three times over a 51-month period. Of the original 44 patients with SDAT, five were available for CT examination at the last time of assessment (51 months); in contrast, 41 of the original 58 control subjects were still available for study at 51 months. As a group, scans of SDAT subjects showed greater atrophy than those of control subjects in all volumetric indexes at each time of testing and demonstrated greater progression of atrophy during the study period. However, the overlap of indexes between the patients with SDAT and the control subjects indicates that CT data cannot be used alone to predict the presence or progression of dementia in individual cases. 
1	Systemic therapy in metastatic colorectal cancer. Fluorouracil-based chemotherapy regimens have been utilized in metastatic colorectal cancer for more than 30 years. Early attempts at defining an optimal treatment schedule and use in combination with other drugs failed to significantly improve results. In contrast, the clinical effectiveness of fluorouracil has been improved by continuous infusion administration and modulation with folinic acid. Both approaches have increased the response rate compared with results achieved with traditional bolus schedules; the effect on survival has been less significant. Unfortunately, expense and, in some instances, toxicity have also been increased, which detracts from their overall usefulness. Clinical studies that evaluate fluorouracil chemotherapy in combination with biological-response modifiers are ongoing and will be areas of intense research during the next few years. 
4	Diagnostic echocardiographic features of the sinus venosus defect. To establish the diagnostic criteria for a sinus venosus atrial septal defect cross sectional echocardiograms, cineangiograms, and surgical notes of all patients with this diagnosis seen at the Children's Hospital of Pittsburgh between 1986 and 1988 were reviewed. Seven patients were identified. In each the extent of the atrial septum and the nature of the junction of the superior vena cava with the atria were evaluated echocardiographically from the subcostal position. All had overriding of the superior vena cava and abnormally connected right pulmonary veins. Six patients had undergone cardiac catheterisation and cineangiography. Five patients underwent surgical repair. The operative findings were consistent with the expected morphology in all five, and these features were additionally confirmed in a specimen from the cardiopathological museum. Therefore, the basic anatomical feature of a superior sinus venosus interatrial communication is a biatrial connection of the superior vena cava. This, together with anomalous drainage of the right sided pulmonary veins, results in an interatrial communication outside the confines of the true atrial septum. Overriding of the superior vena cava across the upper rim of the oval fossa is suggested as the pathognomonic diagnostic feature that can clearly be demonstrated echocardiographically from the subcostal position. In essence the lesion is an interatrial communication rather than an atrial septal defect. 
1	Popliteal artery occlusion caused by cystic adventitial disease: successful treatment by urokinase followed by nonresectional cystotomy. Preoperative diagnosis of an occluded popliteal artery caused by cystic adventitial disease allowed use of urokinase to successfully dissolve secondary thrombosis. Subsequent non-resectional adventitial cystotomy and evacuation of cyst contents allowed lasting restoration of a patent arterial lumen and return of normal distal pulses. This nongrafting technique may serve as a model for future patients with occluded arteries caused by this condition. 
1	Usefulness of epidurally evoked cortical potential monitoring during cervicomedullary glioma surgery. This report describes a patient with an intramedullary ependymoma at the region of the cervicomedullary junction in whom there was an abolition of somatosensory evoked potentials following median nerve stimulation. During intraoperative monitoring of cortical potentials elicited by epidural cervical cord stimulation, the tumor was removed. Posterior epidural stimulation appeared to depolarize more ascending fibers than did stimulation of a single peripheral nerve. We recommend that, in cases of operations in this vital area, epidurally evoked cortical potentials be monitored intraoperatively. 
5	Natural history of progressive ischemic stroke in a population treated with heparin Data on the acute natural history of progressive stroke with or without heparin treatment are limited. To define the acute course of patients treated with heparin for progressive stroke, we examined the charts of 69 such patients identified through the Cornell Neurology Database from October 1979 to June 1985. Analysis included determining whether further clinical deterioration or hemorrhagic complications were associated with readily identifiable clinical or laboratory variables. Twenty-five patients (36%) continued to deteriorate while receiving heparin, another two (3%) worsened due to intracerebral hemorrhage, and a total of 10 patients (14%) had bleeding complications. No clinical features or heparin dosing regimens distinguished the patients likely to benefit from heparin. Clinical progression or hemorrhage did not correlate with the level of anticoagulation as measured by the average heparin dose per day or the mean partial thromboplastin time. Without unequivocal evidence demonstrating heparin's ineffectiveness for progressive stroke, many clinicians managing such patients will continue to use heparin. Our results suggest that this decision should not be governed by such clinical features as a patient's age or sex or by the vascular distribution of the stroke. Furthermore, frequent measurement of and overzealous efforts to adjust the partial thromboplastin time may be unnecessary since it does not correlate with outcome. 
5	Decreased protein binding of salicylates in Kawasaki disease. Because patients with Kawasaki disease have low serum concentrations of salicylates despite high doses, and because the free (unbound) drug is responsible for the pharmacologic effects of salicylates, we assessed salicylate protein binding in patients with Kawasaki disease. During the acute phase of the disease, protein binding of salicylate in 36 children with Kawasaki disease was 73 +/- 12%, significantly lower than during the subacute phase (90.4 +/- 8.7%; p less than 0.0005). Mean serum albumin concentration was 29.2 +/- 6.4 gm/L during the acute phase and 36.7 +/- 7.8 gm/L during the subsequent subacute phase (p less than 0.005). Salicylate protein binding was affected independently by both serum albumin and total salicylate levels. During the acute phase of Kawasaki disease, children had an average twofold increase in free salicylate compared with normoalbuminemic control subjects. A nomogram has been devised to derive free salicylate levels from the known total salicylate and serum albumin concentrations. 
4	Single lung transplantation for primary pulmonary hypertension. Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation-perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension. 
5	Xenon-enhanced computed tomographic measurement of cerebral blood flow in patients with chronic subdural hematomas. We compared clinical symptoms with extent of brain shift on computed tomographic (CT) scans and quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced CT scans in 10 patients with chronic subdural hematomas. Five patients had only headache and minimal or no brain shift on a CT scan. The other five had hemiparesis and/or mental disturbance in addition to headache and moderate or severe brain shift on a CT scan. The mean hemispheric CBF decreased about 7% in patients with headache and about 35% in patients with hemiparesis and/or mental disturbance. It decreased also on the side without the hematoma. The CBF reduction was always more pronounced in the putamen and thalamus than in the cortex. On the contrary, the cortex CBF was mostly preserved or even elevated in both groups of patients. We speculate that CBF reduction in patients with a chronic subdural hematoma occurs initially in central cerebral areas like the basal ganglia and thalamus, and then extends to the entire hemisphere including the cortex as brain compression and displacement progress. Central cerebral area involvement might be more responsible for clinical symptoms than the cortex. 
3	Noradrenergic abnormalities in the central nervous system of seizure-naive genetically epilepsy-prone rats. Norepinephrine (NE) concentrations were measured in 15 discrete areas of the central nervous system of two types of genetically epilepsy-prone rats (GEPRs) and in nonepileptic controls. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had extensive abnormalities in brain NE concentration. Deficits of equal magnitude in GEPR-3s and GEPR-9s were found in the spinal cord, midbrain minus the inferior colliculus, inferior colliculus, hypothalamus, amygdala, hippocampus, occipital + parietal cortex, frontal cortex, and olfactory septum. Because both types of GEPRs share these deficits and share seizure susceptibility, we hypothesize that these areas are candidates for regulation of seizure susceptibility in GEPRs. In addition, because GEPR-9s have more severe seizures than GEPR-3s and because GEPR-9s had greater NE deficits in several brain areas (cerebellum, pons-medulla, thalamus, and possibly the temporal cortex and olfactory bulbs), we hypothesize that these areas may be important in regulation of seizure severity in GEPRs. All animals used in these experiments had been protected from seizure-provoking stimuli and were naive to seizures. Because the abnormalities in NE concentration were present in seizure-predisposed animals that were protected from seizures, we conclude that these abnormalities are important components of the seizure-predisposition characteristic of GEPRs and do not result from seizure experience. 
1	Murine erythroleukemia cell line GM979 contains factors that can activate silent chromosomal human gamma-globin genes. We introduced a normal chromosome 11 into GM979 murine erythroleukemia cells by fusing them with Epstein-Barr virus-transformed lymphocytes from a normal individual. In contrast to previous data obtained with other murine erythroleukemia cells, we detected activation of human chromosomal gamma-globin genes in GM979 cells. GM979, unlike previously used murine erythroleukemia cell lines, expresses murine embryonic globin in addition to adult globin. While all the hybrids expressed gamma- and beta-globin, they displayed a wide range of gamma-globin expression in relation to that of beta-globin. No correlation, however, was found in quantitative expression between murine embryonic globin and human gamma-globin in these hybrids, suggesting that the two globins are regulated independently, at least in this cell line. These data indicate that gamma-globin genes from normal, nonerythroid chromosomes are not irreversibly silenced, and they can be activated by a positive trans factor(s) present in GM979 cells. 
3	Antimigraine treatment for slit ventricle syndrome. Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures. 
3	Area of lateral ventricles measured on cranial ultrasonography in preterm infants: association with outcome. The association between measurements of lateral ventricle area (determined by serial ultrasound scans) and outcome was studied in 70 preterm neonates of 33 weeks' gestation or less. The study group was subdivided into four groups according to cranial ultrasonographic findings at 2 weeks postnatal age: group A (n = 15) had isolated periventricular/intraventricular haemorrhage; group B (n = 20) had periventricular/intraventricular haemorrhage and dilated ventricles; group C (n = 24) had periventricular/intraventricular haemorrhage and periventricular leukomalacia with or without dilated ventricles; and group D (n = 11) had isolated periventricular leukomalacia. Eighty seven preterm infants with no evidence of intracranial disease and good neurodevelopmental outcomes at 2 years formed the control group. A poor outcome was observed in infants in group B, C, and D, particularly in those who had persistent dilated ventricles at 6 weeks postnatal age and extensive periventricular leukomalacia. There was no difference in outcome between group A and controls. During the first six weeks of life ventricular area growth velocities were significantly higher in groups B, C, D, compared with normal controls and group A. We suggest that persistent ventricular dilatation at this early stage carries a bad prognosis, which is the result of atrophy of the brain. 
5	Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats. Post-resectional hyperplasia is the phenomenon in which residual small bowel increases in size and absorptive capacity after segmental enterectomy. This experiment studied the effect of somatostatin analogue therapy on the development of two structural parameters of post-resectional hyperplasia in rats subjected to 40% proximal small bowel resection. Octreotide acetate-treated rats failed to develop increased villus height (902 +/- 50 microns) relative to saline-treated rats (1,103 +/- 98 microns). Augmentation of residual intestinal weight was also significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5 mg/cm). We conclude that somatostatin analogue treatment during the early postoperative period does impair the growth of residual bowel in rats. These findings raise concern regarding the use of this drug for postoperative patients who have undergone massive small bowel resection in whom the process of post-resectional adaptation may be critical to allow sustenance with enteral nutrition. 
4	Comparative effects of overweight on cardiovascular risk in younger versus older men. The relation of age and body mass index (BMI) to atherosclerosis risk factors was examined in 357 men. Older (greater than or equal to 45 years) men had higher (p less than 0.01) systolic and diastolic blood pressures, fasting cholesterol and glucose, and 1-hour glucose and insulin levels. Fasting insulin and triglyceride levels were not significantly different between the 2 age groups. Although older men (n = 170) had greater values for several risk factors, overweight (BMI greater than 25.5 kg/m2) increased risk factors more in men younger than 45 years (n = 187). In younger men, those with higher BMIs had a greater prevalence, respectively, of blood pressure greater than 140/90 mm Hg (35.2 vs 11.2%, p less than 0.0001), cholesterol greater than 200 mg/dl (53.5 vs 29.3%, p less than 0.001), fasting triglycerides greater than 150 mg/dl (38.0 vs 10.3%, p less than 0.0001), 1-hour glucose greater than 160 mg/dl (15.5 vs 5.2%, p less than 0.05), fasting insulin greater than 11 microU/ml (28.2 vs 5.2%, p less than 0.0001), and 1-hour insulin greater than 110 microU/ml (28.2 vs 9.5%, p less than 0.001). In contrast, among older men, the prevalence of elevated blood pressure, cholesterol, triglycerides and glucose values was not significantly greater in the subgroup with high BMI. However, elevations of fasting (19.6 vs 6.4%, p less than 0.05) and 1-hour insulin (29.3 vs 11.5%, p less than 0.01) values were more common among older men with higher BMIs. 
2	Dysphagia and esophageal motor dysfunction in gastroesophageal reflux are corrected by fundoplication. Abnormalities in esophageal peristaltic function and acid clearance appear to be responsible for prolonged esophageal acid exposure, a major determinant of the reflux esophagitis and esophageal stricture. We evaluated esophageal motility by manometry in 50 healthy controls and in 35 symptomatic reflux patients before, within 6 months, and 1 year after Nissen fundoplication. Preoperative motility was analyzed in relation to the presence or absence of both nonobstructive dysphagia and erosive esophagitis. We found that (a) preoperative dysphagia was related more to peristaltic dysfunction than to esophagitis; (b) peristaltic wave amplitude and duration were significantly lower than control values in patients with reflux, without correlation to degree of esophagitis or lower esophageal sphincter hypotension; (c) dysphagia ceased in most patients after antireflux surgery at the same time that normal motility was restored independently of lower esophageal sphincter pressure increments. These results suggest that motility disturbances are an important cause of dysphagia in reflux disease, and that reflux is the cause of, rather than the consequence of, peristaltic dysfunction. 
1	Expectant management of localized prostatic cancer. Seventy-five patients with clinical Stage B histologically proven prostatic cancer accumulated over a 40-year period and receiving no therapy for at least 1 year after histologic diagnosis were retrospectively reviewed. Twenty-nine patients had Stage B1 lesions, 37 had B2, and nine had B3 lesions; median follow-up for these patients was 124, 120, and 96 months, respectively. Five ultimately received pelvic lymph node dissection with iodine-125 implantation, 23 had transurethral resection of the prostate, and 18 had endocrine therapy. Of those tumors which progressed, 18 of 19 (95%) B1, 26 of 29 (90%) B2, and four of four (100%) B3 lesions demonstrated local progression first. Six of 29 (21%) B1, 17 of 37 (46%) B2, and two of nine (22%) B3 tumors developed recognized distant metastasis. Actuarial survival at 15 years was 67%, 39%, and 63% for patients with B1, B2, and B3 lesions, respectively. These data indicate the varied and potentially protracted course of patients with clinical Stage B prostatic cancer. 
5	Exercise thallium-201 imaging in complete left bundle branch block and the prevalence of septal perfusion defects. To determine the prevalence of septal defects in a generalized referral population, the records of 93 consecutive patients with complete left bundle branch block (BBB) who underwent symptom-limited treadmill exercise testing with thallium-201 myocardial imaging over a 3-year period were reviewed. Segmental analysis of the planar thallium-201 images was performed in a blinded fashion with agreement by consensus. Computerized quantitative analysis of the images also was independently performed, and was correlated with the visual interpretations. Forty-seven patients (51%) had normal images, and 46 (49%) had defects of greater than or equal to 2 segments. In the abnormal studies, only 13 patients (14% of the total population) had septal defects, while a much higher number of patients, 33 (39%), had inferior or apical defects, or both. Coronary angiography was performed in 6 patients with septal defects: Significant narrowing of the left anterior descending coronary artery was found in 4 patients, a narrowed right coronary artery was found in 1, and normal coronary arteries were seen in the other patient. In conclusion, whereas previous studies have suggested a high percentage of false-positive septal defects in patients with left BBB, this study demonstrates a low prevalence (14%) of septal defects in a large population of unselected patients presenting for exercise thallium-201 imaging. Therefore, exercise thallium-201 imaging remains a useful procedure for evaluating patients with complete left BBB. 
5	Pharmacokinetics of famotidine after intravenous administration in liver disease. The pharmacokinetics of famotidine were studied after the administration of a single intravenous dose of 20-mg to seven normal volunteers, six patients with chronic hepatitis, 14 patients with compensated cirrhosis, and seven patients with decompensated cirrhosis. The plasma terminal elimination half-life of famotidine was significantly prolonged and famotidine total body clearance was significantly reduced in patients with decompensated cirrhosis, whose creatinine clearance was 57.2 +/- 6.7 ml/min/1.48 m2, but these changes were not significant in patients with chronic hepatitis (creatinine clearance: 109.2 +/- 10.5 ml/min/1.48 m2) or in patients with compensated cirrhosis (creatinine clearance: 72.2 +/- 26.5 ml/min/1.48 m2 in comparison with normal volunteers. The total volume of distribution at steady state was not significantly different between the normal volunteers and the three groups of patients. Famotidine total body clearance showed a weak but significant correlation with the creatinine clearance (r = 0.66, p less than 0.001), serum albumin level (r = 0.51, p less than 0.01), and serum total bilirubin level (r = 0.36, p less than 0.05), which suggested that the reduction in clearance was due in part to the concomitant renal impairment, as well as hepatic dysfunction in these patients. In conclusion, famotidine total body clearance was reduced in decompensated cirrhosis, indicating that the dose schedule requires modification in patients with this condition. 
4	Estimating left ventricular filling pressure during positive end-expiratory pressure in humans. In the critically ill, accurate measurements of left ventricular (LV) filling pressure using pulmonary artery occlusion pressure (Ppao) are important for diagnostic and therapeutic purposes. In patients receiving positive end-expiratory pressure (PEEP), Ppao may not reflect LV filling pressure because of elevated pericardial pressure (Ppc). It has been proposed that in humans, Ppc and right atrial pressure (PRA) are equal, so that referencing Ppao to PRA may improve the assessment of LV filling pressure when Ppc is elevated. Similarly, it has also been shown in the dog that nadir Ppao immediately after airway disconnection from PEEP (nadir Ppao), accurately reflects LV filling pressure when LV filling pressure is greater than or equal to 10 mm Hg. We examined methods of estimating LV filling pressure using Ppao measurements under conditions in which increases in Ppc were the primary determinants of differences in the two measurements. Using left atrial pressure (PLA) relative to Ppc, called transmural PLA (PLAtm), as LV filling pressure, we compared the accuracy of Ppao, nadir Ppao, and Ppao relative to PRA to reflect PLAtm in 15 postoperative cardiac surgery patients in whom an air-filled pericardial balloon catheter and a left atrial catheter were inserted during surgery. PEEP was sequentially increased from zero to 15 cm H2O. We found that PRA always exceeded Ppc (p less than 0.01) and increased less with PEEP than did Ppc (p less than 0.05). At less than or equal to 5 cm H2O PEEP, both Ppao and nadir Ppao were similar to each other and to PLAtm. 
4	The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease. Plasma homocyst(e)ine (the sum of free and bound homocysteine, homocystine, and the mixed disulfide homocysteine-cysteine, expressed as homocysteine) levels were determined by high performance liquid chromatography in 214 patients with symptomatic (claudication, rest pain, gangrene, amputation) lower extremity arterial occlusive disease and/or symptomatic (stroke, cerebral transient ischemic attacks) cerebral vascular disease and in 103 control persons. Mean plasma homocyst(e)ine was significantly higher in patients than in controls (14.37 +/- 6.89 nmol/ml vs 10.10 +/- 2.16, p less than 0.05). Thirty-nine percent of patients (83 of 214) had plasma homocyst(e)ine values greater than control mean + 2 standard deviations. Plasma homocyst(e)ine values were contrasted to age, male sex, diabetes, hypertension, smoking, renal failure, and plasma cholesterol. No difference was found in the incidence and/or level of any of these risk factors when patients with normal plasma homocyst(e)ine were compared to those with elevated plasma homocyst(e)ine, both by univariate and multivariate analysis. Patients with elevated plasma homocyst(e)ine were more likely to demonstrate clinical progression of lower extremity disease and of coronary artery disease, but not of cerebral vascular disease than were patients with normal plasma homocyst(e)ine, and the rate of progression was more rapid (p = 0.002). Progression of lower extremity disease as assessed in the vascular laboratory was also more common in patients with elevated plasma homocyst(e)ine (p = 0.01). We conclude that elevated plasma homocyst(e)ine is an independent risk factor for symptomatic lower extremity disease or cerebral vascular disease or both. Symptomatic patients with lower extremity disease and with elevated plasma homocyst(e)ine also appear to have more rapid progression of disease. 
4	Visual evoked potential monitoring of optic nerve function during surgery. A study was made with intra-operative flash--visual evoked potentials (VEP) monitored using a fibre-optic/contact lens photo stimulator in 57 patients undergoing intra-orbital surgical procedures with potential risk to the optic nerve. The VEPs recorded under enflurane and nitrous oxide anaesthesia did not differ significantly in latency or amplitude from the pre-operative recordings. Transient abolition of the VEP was seen under many circumstances and did not correlate with the outcome of surgery, but absence of a previously normal VEP for more than four minutes during surgical manipulation within the orbit did show a correlation with post operative impairment of vision. The technique provides early warning to the surgeon of threats to the integrity of the optic nerve. 
3	Missed injuries. The trauma surgeon's nemesis. The multiply injured trauma patient presents a diagnostic and therapeutic challenge: that of discovering all injuries while simultaneously proceeding with resuscitation and maintaining life. Many factors involved in the initial resuscitation of the multiply injured patient, such as altered level of consciousness, hemodynamic instability, or inexperience and diagnostic oversight, may lead to missed injuries. Injuries may be missed at any stage of the management of the trauma patient, including intraoperatively, and may involve all regions of the body. Established protocols in the initial management of the multiply injured patient, such as the primary and secondary surveys of the Advanced Trauma Life Support Course, will minimize the chance of missing immediately life-threatening injuries in the emergency department. A careful intraoperative approach must be used in all patients, but especially in those with hemodynamic instability, so that all areas are examined for possible injury, rather than concentrating simply on what is known to be injured. Use of the tertiary survey, a careful re-examination of the multiply injured trauma patient, especially when he or she awakes, will help detect injuries missed during the initial evaluation. Injuries will be missed. Rather than dismissing these as occurrences that happen only to the inexperienced or incompetent, one should approach the multiply injured trauma patient with both special alertness and the humility necessary to search for diagnostic oversights. This approach will lead to early discovery of missed injuries and will minimize the consequences. 
5	Progressive coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension: report of two cases. Two cases of neurological deterioration and coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension and invasion of the 3rd ventricle are presented. Emergency ventricular shunting led to prompt neurological improvement, which, supplemented by radiation therapy, allowed long-term amelioration of symptoms. Three possible explanations for this complication are offered: 1) traction of the attached 3rd ventricle into the decompression site, causing increased obstructive hydrocephalus, 2) vasopressin release by surgical manipulation of the pituitary stalk and circumventricular organs causing cerebral edema, and 3) edema in the residual tumor secondary to surgical manipulation causing further hydrocephalus. Subsequent patients with similar clinical and imaging criteria will have a planned perioperative ventricular shunting procedure performed. 
1	Hepatic vein reconstruction for preserving remnant liver function. Hepatic malignancies often infiltrate to the major hepatic vein. Recently, we performed hepatic resection combined with hepatic vein reconstruction for preserving remnant liver function in three such patients. One patient had a saphenous vein graft. Postoperative liver function of the patients who underwent hepatic vein reconstruction was compared with those of eight patients who underwent hepatic resection of segments VII and VIII. The right hepatic vein in four of them was resected and in the remaining four was preserved by skeletalization using an ultrasonic aspirator. Although four patients with right hepatic vein resection showed severe lowering of liver function after surgery, the postoperative course of patients with preservation or reconstruction of the right hepatic vein maintained good liver function. Liver regeneration of three patients with hepatic vein reconstruction was good on computed tomography. Besides this report, to our knowledge, there is no other report of hepatic vein reconstruction for preserving the remnant liver function. Problems with hepatic resection combined with hepatic vein reconstruction are discussed. We conclude that hepatic vein reconstruction is one of the means for extending indication of the malignant tumor resection of the liver. 
5	Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans. Iron catalysis is involved in oxygen-derived free radical generation and subsequent lipid peroxidation, which have been reported to occur during cardiopulmonary bypass in humans. We assessed the effects of the iron chelator deferoxamine on the susceptibility of circulating low density lipoproteins (LDLs) to induced peroxidation in 20 adult patients (10 controls and 10 treated) undergoing cardiopulmonary bypass for coronary or valve procedures. Deferoxamine was given both intravenously (30 mg/kg body wt, starting 30 minutes before bypass and extending for the next 4 hours) and as an additive to the cardioplegic solution (250 mg/l). Blood samples were taken from both atria before and immediately after the end of cardiopulmonary bypass. Plasma lipid peroxidation was assessed by measuring spectrophotometrically the thiobarbituric acid reactive substances (TBARS) content of selectively isolated LDLs after their exposure to a peroxidizing agent. Before cardiopulmonary bypass, the right and left atrial blood values of LDL-TBARS were not significantly different between the two groups. Cardiopulmonary bypass resulted in a lipid peroxidation of significantly greater magnitude in control than in treated patients. Postbypass right atrial values for LDL-TBARS (expressed in mumol/mmol LDL-phospholipids) were 45.7 +/- 17.2 (mean +/- SEM) in control patients and 6.9 +/- 2.9 in treated patients (p less than 0.02), whereas in the left atrial blood, LDL-TBARS yielded values of 62.7 +/- 20.5 and 10.3 +/- 3.9, respectively (p less than 0.01). 
3	Bicarbonate-buffered lidocaine-epinephrine-hyaluronidase for eyelid anesthesia. A double-masked, randomized clinical trial was conducted to determine if subcutaneous eyelid injections of a bicarbonate-buffered lidocaine-epinephrine-hyaluronidase mixture were less painful than unbuffered injections. Twenty-one patients received both buffered (pH = 7.4) and unbuffered (pH = 4.6) injections. After each injection, patients recorded pain on a scale of 0, "no pain," to 10, "severe pain." Mean pain score for buffered injections was 2.0 versus 4.1 for unbuffered injections (P = 0.0003). Seventeen (81%) of 21 patients ranked the buffered injection less painful. Use of a bicarbonate-buffered lidocaine-epinephrine-hyaluronidase mixture is effective in making ophthalmic anesthesia less painful. 
4	Stress echocardiography and the human factor: the importance of being expert. The aim of this study was to evaluate how the diagnostic accuracy of a stress echocardiographic procedure, such as a dipyridamole echocardiography test, depends on the specific experience of the physician interpreting the test. Recordings of 50 consecutive dipyridamole echocardiographic tests were selected for the first part of the study. They were analyzed by 20 experienced echocardiographers with different backgrounds in stress echocardiography: 10 beginners (less than 20 stress studies interpreted with trained staff) and 10 experienced observers (greater than or equal to 100 stress studies performed). Diagnostic accuracy (true positive + true negative/total number of tests) versus the angiographic reference standard (greater than 70% coronary stenosis of at least one major coronary artery) was 62 +/- 6% for beginners and 85 +/- 3% for experienced observers (p less than 0.0001). In the second part of the study, 10 observers (5 beginners and 5 experienced observers) evaluated 2 different sets of 50 dipyridamole echocardiographic test studies before and after the training of the beginners. Before training, the accuracy of beginners was lower than that of experienced observers (61 +/- 7% versus 85 +/- 3%; p less than 0.001). After training, the accuracy gap was closed (83 +/- 3% versus 86 +/- 2%; p = NS). Therefore, interpretation of stress echocardiographic tests by an echocardiographer without specific training severely underestimates the diagnostic potential of this technique. One hundred stress echocardiographic studies are more than adequate to build the individual learning curve and reach the plateau of diagnostic accuracy that the test can yield. 
1	Maffucci's syndrome with bilateral cartilaginous tumors of the cerebellopontine angle. Maffucci's syndrome is characterized by the combination of multiple enchondromas (Ollier's disease) and hemangiomatosis. These hemangiomas develop in the subcutaneous tissue and form red-blue tumors dispersed over the whole body. Intracranial involvement is rare, making a preoperative radiological diagnosis and differentiation from other tumors rather difficult. The radiological characteristics and successful removal of the intracranial part of a chondrosarcoma of the cerebellopontine angle in a case of Maffucci's syndrome are reported in this paper. 
5	Sudden cardiac death while wearing a Holter monitor. The Holter tapes of 61 patients (46 men, mean age +/- standard deviation 65 +/- 11 years) with sudden cardiac death while being monitored were analyzed. Thirty-eight patients were known to have coronary artery disease, 5 had cardiomyopathy, and 7 had aortic valve disease. Etiology remained unknown in 11 patients. Mean New York Heart Association functional class was 2.5 +/- 0.7. Thirty patients had received antiarrhythmic drugs and 32 had received digitalis. Sudden death occurred at rest in 73%. In the hours before death, repetitive ventricular arrhythmias were found in 50 patients (82%), with atrial fibrillation in 34%. Patients with bradyarrhythmic death (18%) had less complex ventricular activity compared to patients with tachyarrhythmic death (p less than 0.01). Lethal arrhythmias--monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, torsades de pointes, primary ventricular fibrillation, and 1:1 conducting atrial tachycardia--were found in 26 (43%), 15 (25%), 5 (8%), 3 (5%), and 1 patient, respectively. The coupling interval of the final ventricular tachycardia correlated inversely with the initial frequency of ventricular tachycardia (p less than 0.05). For patients with tachyarrhythmic death, an increase of heart rate within the last 3 hours was noted (83 vs 89 beats/min, p less than 0.05). Ventricular premature complexes and the proportion of patients with greater than 2 couplets and greater than 2 triplets increased significantly only within the last hour before death. 
5	Gastroesophageal reflux in infants. Clinically significant gastroesophageal reflux occurs in one in 500 infants. Symptoms resolve in 60 to 80 percent of infants by 18 months of age. Thickened formula and position changes are often recommended. Medication and surgical intervention may be needed in refractory cases. 
5	A reevaluation of heparin requirements for cardiopulmonary bypass. We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators. An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour. In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds. The mean total heparin administered was 41,000 units in group I and 25,000 units in group II. Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass. No significant difference in any of these coagulation parameters was observed between the groups. The performance of the oxygenators was similar in both groups, with no evidence of thrombosis. Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance. 
5	Complications of stapled anastomoses in anterior resection for rectal carcinoma: colorectal anastomosis versus coloanal anastomosis. Postoperative results of 48 patients who underwent anterior resection using the EEA-stapler were evaluated. In all but 2 cases the indication for surgery was colorectal carcinoma. In 24 patients an anastomosis was created above the 5 cm level (above the anal verge: colorectal anastomosis) and in 24 at the 0-5 cm level (coloanal anastomosis). There was no perioperative mortality. The only complication observed in the colorectal anastomosis group was one case of late anastomotic stenosis. In the coloanal anastomosis group there were 4 cases with early anastomosis leaks, 3 cases with late stenosis and 5 cases with various degrees of late fecal incontinence, ultimately resulting in a permanent diverting stoma in 5 (10.4%) patients. We conclude that for rectal tumors the EEA-stapled anterior resection provides excellent functional results in most cases. Stapled coloanal anastomoses more often demonstrate various (early and late) complications. Nevertheless in spite of chronic discomfort, many patients still prefer their complaints to a permanent stoma. 
4	Nitrendipine-induced gingival hyperplasia. First case report. Drug-induced gingival hyperplasia is well documented within the literature. It has been associated with phenytoin, cyclosporine, and calcium channel blocking agents. Nitrendipine is an experimental calcium channel blocking agent that also appears to cause the side effect of drug-induced gingival hyperplasia. The clinical and histologic presentation of this side effect and possible biochemical mechanisms of pathogenesis are discussed. 
4	Angioplasty from the contralateral approach: use of a guiding catheter and coaxial angioplasty balloons. An 8-F guiding catheter has been developed for use with coaxial angioplasty balloon catheters in angioplasty of the femoral artery from the contralateral approach when antegrade puncture of the ipsilateral femoral artery is not possible. The catheter may be used for angioplasty of the femoral artery bifurcation and the superficial femoral artery and for arterial stenoses in patients with renal transplants. 
5	Vasal injuries during childhood and their effect on subsequent fertility. Thirty subfertile males had testicular obstruction following inguinal or pelvic surgery in childhood. All 13 patients with bilateral obstruction were azoospermic and 6 had developed antibodies to spermatozoa. Of 17 patients with unilateral obstruction, 11 had oligozoospermia and 6 had normal sperm counts: all had high titres of antibodies to spermatozoa (a significant difference from the men with bilateral obstruction). This indicates that male infertility can result from vasal or epididymal injuries in childhood due either to the obstruction itself or its immunological consequences. Following corrective surgery and prednisolone treatment for the antibodies, where appropriate, 5/17 patients with unilateral blocks and 1/11 with bilateral blocks successfully produced pregnancies. 
3	Soluble interleukin-2 receptors in cerebrospinal fluid from individuals with various neurological disorders. Soluble interleukin-2 (IL-2R) levels in the cerebrospinal fluid (CSF) were studied in infectious, inflammatory, degenerative, and neoplastic disorders to evaluate their usefulness as a marker for the presence of activated T cells, thus indicating an inflammatory process. CSF from control subjects and patients with stationary, progressive, and treated multiple sclerosis (MS); aseptic meningitis; lymphoid and nonlymphoid central nervous system (CNS) tumors; Alzheimer's disease, as well as serum from MS patients and control subjects were studied for levels of soluble IL-2R. A significant increase in CSF IL-2R levels was observed in patients with MS, meningitis, and lymphoid CNS tumors; the MS group showed the highest values. CSF from individuals with Alzheimer's disease and from patients with nonlymphoid tumors did not show significantly elevated values. Serum IL-2R levels were significantly higher in MS patients than in control subjects, but there was no significant correlation between individual serum and CSF IL-2R levels. This study suggests the presence of activated T-lymphocytes in the CNS of patients with MS. 
2	Overt hepatic encephalopathy precipitated by zinc deficiency. Encephalopathy in liver disease may be unresponsive to protein restriction, lactulose, and neomycin. Zinc supplements have been reported to improve psychometric performance in liver cirrhosis, but the importance of zinc deficiency in overt hepatic encephalopathy has not yet been clearly established. A patient with severe recurrent hepatic encephalopathy was studied to determine the relation between her signs of encephalopathy and zinc deficiency. The study included a period in which zinc deficiency was artificially induced by oral histidine. An episode of overt encephalopathy occurred that was identical to earlier episodes and responded to oral zinc. The study showed an association between encephalopathy and zinc deficiency by successive zinc depletion and supplementation regimens. Long-term zinc supplementation improved severe recurrent hepatic encephalopathy and therefore the quality of life. 
4	Simultaneous transesophageal atrial pacing and transesophageal two-dimensional echocardiography: a new method of stress echocardiography The diagnostic use of exercise echocardiography has been widely reported. However, transthoracic exercise echocardiography is inadequate in up to 20% of patients because of poor image quality related to exercise. In an attempt to overcome these limitations, a system was developed in which transesophageal echocardiography is combined with simultaneous transesophageal atrial pacing by means of the same probe. In a prospective study, transesophageal echocardiography was performed before, during and immediately after maximal atrial pacing in 50 patients with suspected coronary artery disease. Results of transesophageal stress echocardiography were considered abnormal when new pacing-induced regional wall motion abnormalities were observed. Correlative routine bicycle exercise testing was carried out in 44 patients. Cardiac catheterization was performed in all patients. The success rate in obtaining high quality diagnostic images was 100% by transesophageal echocardiography. All nine patients without angiographic evidence of coronary artery disease had a normal result on the transesophageal stress echocardiogram (100% specificity). Thirty-eight of 41 patients with coronary artery disease (defined as greater than or equal to 50% luminal diameter narrowing of at least one major vessel) had an abnormal result on the transesophageal stress echocardiogram (93% sensitivity). The sensitivity of the technique for one, two or three vessel disease was 85%, 100% and 100%, respectively, compared with 44%, 50% and 83%, respectively, for bicycle exercise testing; the 12 lead electrocardiogram (ECG) during rapid atrial pacing showed a sensitivity of 25%, 64% and 86%, respectively. Thus, rapid atrial pacing combined with simultaneous transesophageal echocardiography is a highly specific and sensitive technique for the detection of coronary artery disease. Ischemia-induced wall motion abnormalities were detected earlier than observed ECG changes. The technique appears to be particularly suited to patients who are unable to perform an active stress test or those with poor quality transthoracic echocardiograms. 
1	Inhibition by 1,25 dihydroxyvitamin D3 of chemically induced erythroid differentiation of K562 leukemia cells. The physiologically active form of vitamin D, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], was found to inhibit erythroid differentiation of human leukemic K562 cells. Differentiation was induced by 1 mumol/L arabinocytosine (Ara-C), 40 mumol/L tiazofurin, 1 mumol/L aphidicolin, or 1 mumol/L hydroxyurea, and was monitored daily by the appearance of hemoglobin in an increasing proportion of cells. Pretreatment for 48 hours with 2.4 x 10(-8) mol/L 1,25(OH)2D3, a concentration that is also optimal for induction of monocytic differentiation of HL-60 cells, reproducibly inhibited subsequent induction of erythroid differentiation by all of the above inducers, and modified the morphologic changes that Ara-C produced in these cells. The inhibition of hemoglobinization was approximately 50% irrespective of the degree of differentiation produced by the various inducers, but growth inhibition associated with exposure to the inducers was not affected by 1,25(OH)2D3. Similar inhibition of differentiation by 1,25(OH)2D3 was observed in mouse erythroleukemia cells MEL-D1B treated with 5 mmol/L hexamethylenebisacetamide. The inhibitory effect of 1,25(OH)2D3 on erythroid differentiation of K562 cells was abrogated by cyclohexamide (20 micrograms/mL), an inhibitor of protein synthesis. The mRNA for 1,25(OH)2D3 receptor (VDR) was detected in K562 cells, and was downregulated by a 96-hour exposure to 1,25(OH)2D3 or a 48-hour exposure to Ara-C. The presence of VDR mRNA suggests a physiologic role for 1,25(OH)2D3 in K562 cells that are precursors of erythroid cells. This role is perhaps to shift the pathways of differentiation from the erythroid to the monocytic lineage. 
3	Antecedent medical diseases in patients with amyotrophic lateral sclerosis. A population-based case-controlled study in Rochester, Minn, 1925 through 1987. Odds ratios (ORs) were estimated for the prevalence of antecedent endocrine, metabolic, or vascular diseases among 45 patients with amyotrophic lateral sclerosis from the Rochester, Minn, population compared with 90 control subjects matched for sex, year of birth, period of observation, and residence. Hypertension occurred less frequently in male patients with amyotrophic lateral sclerosis (4%) than in control subjects (30%; OR = .10). Because of small population size, no conclusions can be drawn with respect to the following antecedent conditions: thyroid disease (OR = 1.61), coronary artery disease (OR = .58), obesity (OR = .52), diabetes (OR = 1.00), cerebrovascular disease (OR = .21), and peripheral vascular disease (OR = 1.23). The heterogeneity of antecedent thyroid disease makes it highly unlikely that any specific thyroid lesion is causally associated with most cases of amyotrophic lateral sclerosis. Hypertension may be a marker for protective factors against the development of amyotrophic lateral sclerosis in men. 
5	Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences. This study compares the metabolism and functional responses of adult and immature hearts to a standard ischemic insult. Ten adult dogs (25 to 27 kg) and 10 puppies (6 to 10 weeks old) underwent 45 minutes of aortic clamping on bypass. Preoperative and postoperative ventricular performance (Starling curves), biochemical factors, and water content were measured. Global ischemia in adults produced a 30% mortality rate (3/10) and low output syndrome in survivors (33% recovery of stroke work index). Conversely, all puppies survived and stroke work index returned to 85% of control, with less edema developing (0.4% versus 2% water gain, p less than 0.05). Puppies expended comparable glycogen stores but used more glutamate (15.4 versus 8.6 mumol/gm dry weight), produced more alanine (18.9 versus 6.4 mumol, p less than 0.05), succinate (19 versus 8.2 mumol, p less than 0.05), and malate (2.6 versus 0.15 mumol, p less than 0.05) during ischemia, and recovered better postischemic aerobic metabolism (410 versus 255 nmol tissue pyruvate, p less than 0.05). We conclude that tolerance of immature hearts to ischemia is related to amino acid utilization by transamination and increased substrate level phosphorylation, as occurring in diving mammals, suggesting retention of intrautero adaptive mechanisms. 
1	Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin. Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer. 
5	Short stature, mental retardation, and hypoparathyroidism: a new syndrome. Eight children (four boys and four girls) with extreme failure to thrive, dysmorphic features, developmental delay, hypoparathyroidism, and abnormal skeletal survey were studied. They were the products of seven consanguinous marriages, two of the patients being brothers. In the remaining six families, a further four children had affected siblings who had died in infancy. When assessed the children were aged 0.47-12.8 years; SD scores were less than -2 for height, weight, and head circumference in all patients. The children had identical facies with deep set eyes, depressed nasal bridge with beaked nose, long philtrum, thin upper lip, micrognathia, and large floppy earlobes. They were all developmentally retarded. The following abnormalities were found on investigation: hypocalcaemia in all (of whom six of seven had hypoparathyroidism), medullary stenosis and other skeletal survey defects in seven of the eight children, and reduced numbers of T cell subsets in four of four tested. We believe that these children represent a new, as yet undescribed genetically determined syndrome. 
2	Clinicopathological features of elevated lesions of the duodenal bulb. We present here our findings on patients with an elevated lesion of the duodenal bulb. All these patients were treated in our clinics between the years 1984 and 1988. These lesions were present in 36 of 8,802 patients who underwent upper gastrointestinal pan-endoscopy. Two patients had a duodenal carcinoma, 2 an adenoma, and 1 a Brunner's gland adenoma. There were 15 with a hyperplastic polyp, 3 with a heterogenic gastric mucosa, 3 with Brunner's gland hyperplasia, 6 with duodenitis, and 4 with regenerative mucosa. Among these 36 lesions, only 69% (25 lesions) were evident on the upper gastrointestinal X-ray series. Adenoma and Brunner's gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa. Both duodenal carcinomas were detected by endoscopic biopsy and were resected. Histologically, these lesions were limited to the submucosal layer and were of the non-pedunculated polypoid form, but there were no other characteristic endoscopic features, in comparison with other elevated lesions. Thus, upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion. 
2	Mallory-Weiss syndrome after cardiopulmonary resuscitation. We report hematemesis from Mallory-Weiss tears after successful cardiopulmonary resuscitation (CPR). A computer search of the English language literature disclosed only 3 similar cases, and we review them. This complication of CPR may occur more frequently than recognized and should be prevented by careful technique. 
4	Usefulness of color-flow Doppler in diagnosing and in differentiating supracristal ventricular septal defect from right ventricular outflow tract obstruction. Color-flow Doppler is used for special localization of cardiac flows. The transeptal jet in supracristal ventricular septal defect (VSD) is directed toward the pulmonary valve and is often difficult to distinguish from the right ventricular (RV) outflow tract flow. Pulsed- and continuous-wave Doppler can misread the VSD jet as a stenotic lesion in the RV outflow tract. This study describes the color-flow Doppler characteristics of supracristal VSD and determines if color-flow Doppler can differentiate supracristal VSD jets from RV outflow tract flow. The study group comprised 28 patients ranging in age from 3 days to 23 years (mean 6.4), with catheter-diagnosed supracristal VSD in 14, isolated pulmonary valve stenosis in 10 and RV infundibular obstruction in 4. The echocardiographic Doppler and color-flow Doppler data of all patients were reviewed without knowledge of catheterization diagnosis. In all patients with supracristal VSD, color-flow Doppler revealed an abnormal transeptal jet directed toward the pulmonary valve that occurred 5 to 10 ms before RV outflow tract flow was identified. VSD and RV outflow tract jet could be differentiated by pulsed- and continuous-wave Doppler alone in 10 of 14 patients (71%). In 4 patients, differentiation was possible only with color-flow Doppler and electrocardiographic gating. Associated aortic regurgitation, or a fistula, or both, were detected in 6 patients. Pulsed- and continuous-wave Doppler with or without color-flow Doppler correctly identified the level of obstruction in all patients with RV outflow tract lesions (14 of 14). Supracristal VSD jet occurs in early systole and is directed toward the pulmonary valve. 
1	Selection of therapy for stage III breast cancer. Locally advanced breast cancer is a heterogenous group including both operable and inoperable lesions. Local surgery or radiation alone produces poor survival rates, indicating micrometastases at diagnosis. Systemic chemotherapy as part of multimodality regimens has increased the length and rate of disease-free survival. 
5	Leukemia initiated by hemopoietic stem cells expressing the v-abl oncogene. We report a mouse model with which to study leukemogenesis initiated by a specific genetic change introduced into a primary lymphoid-myeloid pluripotent stem cell. Fetal liver hemopoietic cells were infected with a high titer of helper-free Abelson murine leukemia virus (A-MuLV) and were used to reconstitute lethally irradiated mice. Two weeks later, progenies of a single primitive hemopoietic stem cell carrying a specifically integrated A-MuLV proviral DNA could be detected in both colony-forming units in spleen and myeloid colony-forming cells in the bone marrow. Beginning at 3 weeks after transplantation, the recipients developed elevated leukocyte counts, splenomegaly, and increase of blast cells in the peripheral blood. Multiple clones of A-MuLV-infected cells were infused into each recipient. However, in the same animal, DNA extracted from various affected organs and from factor-independent lymphoid and myeloid immortalized cells all contained an identical, specifically integrated proviral genome. The A-MuLV-infected stem cells differentiated into various lineages of hemopoietic cells. Our data show that the expression of the v-abl oncogene in a primary lymphoid-myeloid hemopoietic stem cell directly initiates leukemogenesis by stimulating factor-independent growth. The monoclonal-type disease development seen in these animals may require the occurrence of an additional genetic event. 
3	Evaluation of minor head trauma in children younger than two years. The recent medical literature emphasizes the limitations of skull films in the evaluation of minor head trauma. However, the emergency medicine literature places little emphasis on the particular risks in children younger than 2 years old with blunt head injury. These children have immature bone and unfused sutures that may increase risk of cranial injury and delayed complications. A case is presented to illustrate this point. Unlike severe head trauma, where evaluation is directed toward computed tomography, the literature continues to be controversial regarding the indications for skull radiographs and computed tomography in minor head trauma. The authors recommend a low threshold for radiographic imaging in blunt heat injuries in children younger than 2 years. 
3	Spinal cord inhibitory mechanisms in Parkinson's disease. We studied two spinal cord inhibitory mechanisms, recurrent (Renshaw) inhibition and reciprocal inhibition, in seven patients with asymmetric Parkinson's disease in order to determine their contribution to the pathogenesis of rigidity. Recurrent inhibition, studied in the leg, did not differ from that found in normal subjects. All three periods of reciprocal inhibition, studied in the forearm, were present but reduced in magnitude compared with those observed in normal subjects. The arms, whether more symptomatic or less symptomatic, gave similar results. The diminution of all three periods of reciprocal inhibition is similar to the findings in patients with dystonia and is apparently indicative of an abnormal supraspinal influence on spinal mechanisms in these two disorders of basal ganglia function. 
5	Anterior cruciate ligament reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts. Two year results in thirty-six patients [published erratum appears in Am J Sports Med 1991 May-Jun;19(3):272] Thirty-six of 44 patients (82%) who underwent ACL reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts were evaluated at least 2 years postoperatively. A detailed subjective evaluation using the Lysholm scale was recorded as well as a functional evaluation using the Tegner activity scale. All of the patients received a detailed physical examination that included testing with the KT-1000 ligament arthrometer and the Cybex dynamometer. Complete chart reviews and radiographic evaluations were also obtained. Only 17 patients were considered to be functionally successful and performing at their desired activity level. The average KT-1000 showed a side-to-side difference of 5.9 mm at 30 pounds for the successful group and 7.9 mm for those who had functional failure. The Lysholm scores were 91.6/100 versus 61.1/100 in the failures. Eight patients (22%) at repeat surgery were noted to have complete dissolution of the graft. Large femoral cysts were noted radiographically in all of these patients. It was concluded that freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts have a high failure rate and cannot be recommended for ACL reconstruction. 
5	Growth and spread of hepatocellular carcinoma. A review of 240 consecutive autopsy cases. All 240 consecutive cases of hepatocellular carcinoma (HCC) that underwent autopsy at the National Cancer Center Hospital (Tokyo, Japan) between September 1962 and August 1986 were reviewed. Among these cases, 162, for which photographs of cut surfaces of the primary tumors were available, were grossly classified using a combination of both Eggel's classification and our own into three major types, i.e., nodular, massive, and diffuse as described by Eggel (Eggel H, Beitr Pathol Anat 1901; 30:506-604), and three subgroups of nodular type, i.e., single nodular type (type 1), single nodular type with extranodular growth (type 2), and contiguous multinodular type (type 3) by our classification (Kanai T et al., Cancer 1987; 60:810-819). Seventy-eight cases were classified as nodular type, comprising seven cases of type 1, 61 cases of type 2, and ten cases of type 3. Sixty-seven and 17 cases were classified as massive and diffuse type, respectively. Of the 78 nodular-type tumors, 59 measured less than 10 cm, whereas 64 of 67 massive-type tumors were 10 cm or more in size. The incidence of intrahepatic and extrahepatic tumor spread of HCC was significantly higher for tumors measuring more than 5 cm. As to the relationship between macroscopic type and tumor spread, the frequency of spread was lowest for type 1 tumors, and high for the other types. Intrahepatic metastasis was detected in 28.6% of type 1, 93.4% of type 2, 100% of type 3, and 98.5% of massive-type tumors. Lymph node metastasis was detected in 14.3% of type 1, 24.6% of type 2, 70% of type 3, 38.8% of massive-type and 52.9% of diffuse-type tumors. Hematogenous extrahepatic metastasis was detected in 14.3% of type 1, 47.5% of type 2, 70% of type 3, 74.6% of massive-type and 82.4% of diffuse-type tumors. It appears that not only primary tumor size but also its macroscopic type has an important influence on the growth and spread of HCC. 
3	Fulminant hepatitis after lisinopril administration. A case of fulminant hepatitis in a patient taking lisinopril for 5 weeks for arterial hypertension is reported. Jaundice, fever, myalgia, and marked increase in serum aminotransferase activities occurred after 2 weeks of treatment. Continuation of lisinopril administration for 3 weeks after the onset of jaundice was associated with the development of grade III encephalopathy and a marked decrease in prothrombin and proaccelerin levels. This case strongly suggests that lisinopril may induce acute hepatitis and that continuation of the treatment after the onset of jaundice can lead to life-threatening hepatic failure. 
3	Impairment of sequences of memory-guided saccades after supplementary motor area lesions. Different paradigms of saccades were recorded electro-oculographically in 2 patients with infarction affecting the left supplementary motor area. Saccades made toward visual targets (visually-guided saccades) or away from them (antisaccades) were normal in both patients. Memory-guided saccades, made to the remembered position of a flash occurring 2 seconds before, were preserved in 1 patient and only slightly impaired in the other. However, sequences of two or three memory-guided saccades were severely impaired in both patients. It has previously been reported that the supplementary motor area plays an important role in programming sequential limb movements. Our data suggest that this area plays a similar role in the control of sequential eye movements. 
5	Interleukin-6 mRNA and protein increase in vivo following induction of acute thrombocytopenia in mice. Induction of experimental thrombocytopenia in rodents results in the enhancement of megakaryocytic growth and differentiation. Interleukin-3 (IL-3) and IL-6, cytokines with a broad spectrum of biologic activities, stimulate megakaryocytopoiesis in vitro. To determine if expression of these factors might increase in response to experimental thrombocytopenia, we measured steady-state levels of IL-3 and IL-6 mRNA following rabbit antiplatelet serum (APS) injection. Groups of mice were injected intravenously with 0.2 mL APS while control animals received rabbit antilymphocyte serum (ALS), normal rabbit serum (NRS), or phosphate-buffered saline (PBS). At various times up to 72 hours after injection mice were exsanguinated and splenectomized. Platelet counts in the experimental animals were less than 12% of controls. Splenic RNA was hybridized in solution to 32P-UTP-labeled cRNA probes for IL-3 and IL-6. RNase-resistant hybrids were resolved on denaturing gels and visualized autoradiographically. IL-3 hybrids were undetectable at all time points tested, irrespective of the film exposure time or specific activity of the probe. Conversely, IL-6 hybrids were easily visualized and showed peak expression at 1.5 to 2.0 hours. By 3 hours, IL-6 mRNA had returned almost to the level of the controls. Similar results were observed in the bone marrow, although maximal IL-6 mRNA in that tissue was observed 4 hours following APS administration. To determine if this mRNA increment was associated with a concomitant increase in bioactive protein, serum was tested for its ability to stimulate IL-6-dependent B9 cells. At 1.75 hours following injection, experimental animals showed a small but significant increment in IL-6 activity compared with controls (200 +/- 30 U/mL IL-6 compared with 129 +/- 17 U/mL in ALS-injected controls, 106 +/- 17 U/mL in NRS-injected controls and 84 +/- 17 U/mL in PBS-injected controls). The data show that IL-6 mRNA and bioactive protein increase in response to acute immunothrombocytopenia, while no increment in IL-3 is detectable. These results suggest that IL-6 may play a role in the physiologic response to acute immunothrombocytopenia. 
2	Crack-related perforated gastropyloric ulcer. Cocaine is a potent topical vasoconstrictor that causes nasal mucosal and dermal ulceration. Use of the purified cocaine derivative "crack" has reached epidemic proportions in large cities. In 18 months we operated on 24 patients with perforated peptic ulcers. Five of the patients were young (27-38 years) male crack users without prior history of gastric symptoms who presented with a perforated gastric ulcer related to smoking crack. Three had had symptoms for only 1-5 days before admission. All five were afebrile, had a rigid abdomen, normal leukocyte count, and free intraabdominal air upon radiography. Five other age-matched, non-crack-using patients served as case controls. Their duration of symptoms was 1-24 months, they had elevated leukocyte counts on admission, and, in contrast to the crack users, four of these patients had duodenal perforations. The clinical presentation of the crack smokers and the unusual localization of the perforations imply different pathogenetic mechanisms than are commonly seen in perforated ulcer disease. With increasing abuse of crack, greater numbers of patients with this new complication may be expected to present to emergency services in urban areas. 
4	Nitrous oxide does not alter infarct volume in rats undergoing reversible middle cerebral artery occlusion. This experiment was designed to determine if nitrous oxide alters neurologic and pathologic outcome from temporary focal cerebral ischemia in spontaneously hypertensive rats deeply anesthetized with a barbiturate. Two groups of rats were given intravenous methohexital such that a stable EEG pattern of burst suppression was achieved. In one group of rats (n = 11), the lungs were mechanically ventilated with 70% N2O/30% O2, and in the other group (n = 10), ventilation was done with 70% nitrogen/30% O2. The middle cerebral artery was then occluded for 2 h, during which time mean arterial pressure, blood gases, hematocrit, plasma glucose, and head temperature were held constant between groups. The total doses of methohexital administered were similar in both groups as were the plasma methohexital concentrations immediately prior to onset of ischemia. After reperfusion of the middle cerebral artery, the animals were allowed to awaken. Neurologic evaluations were performed prior to ischemia and at 24 and 96 h postischemia. Cerebral infarct volume was measured at 96 h postischemia using triphenyl tetrazolium chloride staining and computer imaging techniques. There were no neurologic differences between the N2O and nitrogen groups at any experimental interval although both groups exhibited deficits at both 24 and 96 h postischemia relative to preischemic values. The two groups also had nearly identical cerebral infarct volumes (N2O = 231 +/- 97 mm3; nitrogen = 226 +/- 75 mm3; mean +/- SD). 
1	Fatal disseminated mycobacterial infection following intravesical bacillus Calmette-Guerin. We describe a fatal case of disseminated mycobacteriosis after intravesical bacillus Calmette-Guerin immunotherapy. We summarize the prior safety record of this therapeutic modality, discuss local and systemic pathophysiological mechanisms by which dissemination might have occurred, and review the reported clinical experience with antituberculous chemotherapy for significant bacillus Calmette-Guerin infection. Finally, we offer suggestions for prophylaxis of certain patients with a history of exposure to intravesical bacillus Calmette-Guerin. 
3	Acute oculogyric crisis after administration of prochlorperazine. We report a case of acute oculogyric crisis due to prochlorperazine administration in a young black woman with a concomitant viral infection. Neuroleptic medications are the most common cause of drug-induced acute dystonic reactions such as oculogyric crisis. Prochlorperazine is an antiemetic agent with a phenothiazine-type chemical structure and is known to cause dystonic reactions. Drug-induced acute dystonic reactions are most common in young adults and in men. Viral infections may also predispose patients to these adverse reactions. Caution is warranted when this drug is used in patients who have other risk factors for an acute dystonic reaction. 
5	Full recovery after a chloroquine suicide attempt. The nonfatal case of a 20 year-old woman who ingested 6 grams of chloroquine in a suicide attempt is reported. After initial ventricular fibrillation, she rapidly developed a pulmonary edema with cardiogenic shock. She was successfully treated with diazepam, epinephrine, dobutamine and mechanical ventilation. Plasma chloroquine levels showed an initial peak of 36 micrograms/mL. The patient was discharged fully recovered after 19 days. The interaction between chloroquine and diazepam is discussed, as is the need for careful management of epinephrine therapy. 
2	Immune competent cells of regional lymph nodes in colorectal cancer patients: I. Flow cytometric analysis of lymphocyte subpopulation. Lymphocyte subpopulations of the regional lymph nodes in 20 colorectal cancer patients were measured by flow cytometry to analyze nodal lymphocytes phenotypically. Eleven patients with cholelithiasis were used as controls. Comparison of lymphocyte subpopulations between colorectal cancer and control groups revealed a significantly increased rate of Leu-12+ cells in the cancer patients. Furthermore, a significant increase of Leu-3a+ Leu-8- cells and a significant decrease of Leu-3a+ Leu-8+ cells were also found in the paracolic nodes of the cancer patients. However, Leu-2a+ Leu-15- cells were not different between the both groups. Meanwhile, in the cancer patients, the rates of Leu-4+, Leu-3a+, and Leu-3a+ Leu-8- cells were higher in the paracolic nodes compared with the intermediate nodes. Additional investigation of the correlation between clinicopathological features of the tumors and lymphocyte subpopulations, showed that Leu-12+ cells were related to the tumor size and Leu-2a+ 15- cells related to the histopathological type. The foregoing results indicate that the rates of both B and helper T cells, which may specifically participate in the antibody production, increase in the regional lymph nodes of colorectal cancer patients. 
3	The disabled driver: an unmet challenge. A survey was undertaken to determine if driving impairment secondary to a disabling injury is addressed in state licensing laws and training programs. In 35 states drivers submit voluntarily to reevaluation after disabling injuries, but no provision is made for reporting such individuals. Only 15 states authorize physicians to report impaired drivers, and only seven require such reporting. Based on a survey of licensing bureaus in the capital or a major city of every state, clerks (who are likely to be the source of information to injured persons) are generally not aware of reporting requirements and supervisors are only slightly better informed. Of the 100 rehabilitation centers surveyed, only 36 provided on-site training for disabled drivers. Voluntary submission for reevaluation after head injury does not often occur. Despite being asked to do so, none of the 35 head injured patients, followed up to two years post-onset, sought reevaluation, although 21 had resumed regular driving. Two of the 21 were involved in subsequent traffic accidents. Common guidelines need to be established across states to ensure reevaluation of individuals with disabling conditions, delivery of accurate information concerning licensing, and availability of training programs. 
3	Cluster headache: the effect of low oxygen saturation The present study concerns the possible relationship between hypoxia and the generation of cluster headache attacks. Fifteen controls and 25 cluster headache patients were studied. The patients were allocated into two groups according to cluster headache stage, i.e. cluster or remission period. During the tests, all the subjects were asked to inhale 12% oxygen (88% N2) for 30 min, and the decreasing oxygen saturation (SaO2%) was monitored. Patients in the remission period showed nearly the same decrement of SaO2% as controls. At the end of the test, patients in the bout showed significantly less reduction of SaO2% than the controls. In 5 patients, the test was carried out both in and outside the cluster periods. The tendency to less decrement in oxygen saturation in the cluster phase was as marked with this comparison, but the difference between the groups was not significant, probably partly due to the low number of tests carried out. Only one patient got a typical attack. It seems that hypoxia of this magnitude per se is not the cause of attacks. The different pattern with respect to SaO2% following 12% O2 inhalation in cluster headache may be due to an abnormality in central regulation and/or chemoreceptor sensitivity. 
1	The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis. A prospective, double-blind study compared the effectiveness of sucralfate suspension with diphenhydramine syrup plus kaolin-pectin in reducing severity and pain of radiation-induced oropharyngeal mucositis. Fourteen patients who received at least 4600 cGy to the oral cavity used one of the mouth rinses four times a day, beginning at 1600 cGy. Data were collected on daily perceived pain and helpfulness of mouth rinse, weekly mucositis grade, weight change, and interruption of therapy. Analysis of data revealed no statistically significant differences between the two groups in any parameter. A retrospective review of 15 patients who had received at least 4600 cGy radiation to the oropharynx but had not used a daily mouth-coating rinse, was compared with the study group. Comparison of the two groups suggested that consistent daily oral hygiene and use of a mouth-coating agent will result in less pain and may reduce weight loss and interruption of radiation because of severe mucositis. 
3	Reverse coitus: mechanism of urethral injury in male partner. Reverse coitus, a rarely used sexual position, makes the male urethra more vulnerable to injury from the pubic arch and symphysis pubis of the female partner. Severe pain, bleeding and immediate detumescence were observed in 3 patients. The lesion usually occurred at the fossa navicularis, responded well to conservative management and did not hinder micturition. Potency has been well preserved in all 3 patients. 
4	Central retinal artery obstruction in herpes zoster ophthalmicus and cerebral vasculopathy. We present a case of acute central retinal artery obstruction in association with Herpes zoster ophthalmicus and delayed cerebral vasculopathy. Retinal vascular obstruction is rare in zoster, and its occurrence during postherpetic cerebral vasculopathy has not been reported previously to our knowledge. The syndrome of delayed cerebral vasculopathy is discussed as is its possible relationship to central retinal artery obstruction. 
5	Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma. Severe gastrointestinal dysmotility is a newly recognized paraneoplastic syndrome that occurs with small-cell lung carcinoma. Thirty-four patients with small-cell carcinoma, of whom 5 had chronic intestinal pseudoobstruction and 29 had no digestive symptoms, were studied serologically. Four of the 5 patients with gut dysmotility had immunoglobulin G antibodies reactive with neurons of the myenteric and submucosal plexuses of jejunum and stomach in an indirect immunofluorescence assay. Antibodies of this type were not found in any of the 29 patients who had no gut dysmotility, nor were they found in patients with chronic idiopathic intestinal pseudoobstruction (n = 8), ovarian cancer (n = 20), or epilepsy (n = 4) or in normal subjects (n = 9). In 4 of the patients with paraneoplastic pseudoobstruction, antibodies in highly diluted serum (1:4000-1:8000) bound selectively to nuclei and cytoplasm of neuronal elements in the gut. This novel autoantibody activity suggests that intestinal pseudoobstruction occurring in patients with small-cell carcinoma may have an autoimmune basis. From a clinical standpoint, serological testing offers a simple means for determining which patients with gut dysmotility syndromes may have associated small-cell carcinoma, thereby enabling earlier diagnosis and treatment of the tumor. 
1	Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. One hundred and two benign, mature ovarian teratomas and two immature, malignant teratomas were karyotyped and scored for centromeric heteromorphisms as part of an ongoing project to determine the chromosomal karyotype and the genetic origin of ovarian teratomas and to assess their utility for gene-centromere mapping. Karyotypic analysis of the benign cases revealed 95 46,XX teratomas and 7 chromosomally abnormal teratomas (47,XXX, 47,XX,+8 [two cases], 47,XX,+15, 48,XX,+7,+12 91,XXXX,-13 [mosaic], 47,XX,-15,+21,+mar). Our study reports on the first cases of tetraploidy and structural rearrangement in benign ovarian teratomas. The two immature cases had modal chromosome numbers of 78 and 49. Centromeric heteromorphisms that were heterozygous in the host were homozygous in 65.2% (n = 58) of the benign teratomas and heterozygous in the remaining 34.8% (n = 31). Chromosome 13 heteromorphisms were the most informative, with 72.7% heterozygosity in hosts. The cytogenetic data indicate that 65% of teratomas are derived from a single germ cell after meiosis I and failure of meiosis II (type II) or endoreduplication of a mature ovum (type III); 35% arise by failure of meiosis I (type I) or mitotic division of premeiotic germ cells (type IV). 
2	Safety and efficacy of laparoscopic cholecystectomy. A prospective analysis of 100 initial patients Laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy. However its safety, efficacy, and morbidity have yet to be fully evaluated. During the first 6 months of 1990, we performed 100 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 8% (8 of 100 patients; 4 major, 4 minor). There were 81 women and 19 men, with a mean age of 46.1 years (range, 17 to 84 years). All patients had a preoperative history consistent with symptomatic biliary tract disease, and most had proved gallstones by sonography. This included four patients with acute cholecystitis. Mean operating time improved significantly from month 1 to month 6 (122 +/- 45.4 minutes versus 78.5 +/- 30 minutes, respectively), indicating a rapid learning curve. Mean hospital stay was 27.6 hours, reflecting a policy of overnight stay. Postoperative narcotic requirements were limited to oral or no medications in more than 70% of patients. A regular diet was tolerated by 83% of the patients by the morning following the procedure. Median time of return to full activity was 12.8 +/- 6.8 days after operation. In addition analysis of the hospital costs of these 100 cases demonstrates a modest cost advantage over standard open cholecystectomy (n = 58) (mean, $3620.25 +/- $1005.00 versus $4251.76 +/- $988.00). There was one minor bile duct injury requiring laparotomy and t-tube insertion, two postoperative bile collections, and one clinical diagnosis of a retained stone that passed spontaneously. Four patients required conversion to open cholecystectomy because of technical difficulties with the dissection. Although there is a significant learning curve, laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk. Laparoscopic cholecystectomy should be performed by surgeons who are trained in biliary surgery and knowledgeable in biliary anatomy, and, as with all operations, it should be performed with meticulous attention to technique. 
3	Standard v lightweight wheelchair propulsion in spinal cord injured patients. Twenty-six male SCI subjects (six quadriplegics, eight "high paraplegics," and 12 "low paraplegics") propelled both standard and lightweight wheelchairs at a "sprint pace" (Sp) for 400 feet, and at a "duration pace" (Du) for four continuous minutes. Pulse, blood pressure and respirations were measured before and after each trial, and V was calculated. Appropriate training and rest periods were given; order of wheelchair testing was randomized. A questionnaire was later administered. Variations in pulse, systolic blood pressure, and respirations were significant between myelopathic levels (P less than 0.01), but were not affected by the type of wheelchair used. Quadriplegic V was less (P less than 0.01) than that of either paraplegic group for Sp and Du trials; for Sp, lightweight wheelchair V is faster (P less than 0.01) than standard wheelchair V for all groups. 
4	Five-year results of coronary bypass grafting for patients older than 70 years: role of internal mammary artery. Despite numerous references to the superiority of the internal mammary artery (IMA) over the saphenous vein for myocardial revascularization, its role in the elderly is still in question. From January 1984 through December 1988, 1,081 patients older than 70 years (mean age, 74.9 years) underwent bypass grafting, 354 (33%) receiving left IMA grafts based on the surgeon's preference and 727 (67%) receiving vein grafts only. Selection bias resulted in a higher incidence of known risk factors (such as cardiomegaly, arrhythmias, left ventricular failure, wall motion abnormalities, and preoperative combined New York Heart Association/Canadian Cardiovascular Association functional class IV) in patients in whom the IMA was not used. However, unstable angina, acute myocardial infarction, left ventricular dysfunction, and left main disease were not contraindications for using IMA grafts. The operative mortality rate was significantly lower in IMA patients (2.8% versus 7.6%). The actuarial 5-year survival rate (standard error) was higher in patients with IMA grafts, 89% (3%) versus 78% (2%), and postoperative functional class improved to a greater extent in IMA patients (87% of patients were in classes I and II). Arrhythmias and myocardial infarction were significant causes of late death only in patients with vein grafts. When patients are older than 70 years, patient selection factors clearly play an important role in the differential results between patients in whom the IMA is used and patients in whom vein grafts are used. As in younger patients, excellent results can be achieved in the elderly. 
1	Interferon alpha and etretinate combination treatment of cutaneous T-cell lymphoma. Eleven patients suffering from cutaneous T-cell lymphoma (mycosis fungoides) were treated with recombinant interferon alpha-2A in combination (seven patients) or alone. Two patients, one in combined treatment, went into clinical complete remission, and five experienced partial remission. Two patients progressed during therapy, and two were nonevaluable because they stopped treatment early due to side effects. Dosages of interferon were from 3 to 36 million units daily for 3 months, and thereafter 3 times weekly. Etretinate (0.7 mg/kg) was given orally. The study showed that recombinant interferon alpha-2A in combination with etretinate or alone can induce remission of cutaneous T-cell lymphoma. 
3	Orocaecal transit time in Duchenne muscular dystrophy. Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility. 
3	Infection during chronic epidural catheterization: diagnosis and treatment. A potentially serious complication of long-term epidural catheterization in cancer patients is infection. The early signs of infection were studied in 350 patients in whom long-term epidural catheters were inserted. Three areas of the catheter track were found to be involved; exit site and superficial catheter track infection, and epidural space infection. The authors identified the early signs of infection in each area and the progress of the infection from the deep track to include the epidural space in four of these patients. All 19 patients who developed deep track or epidural infections were successfully treated with antibiotics and catheter removal. None of the patients required surgery for spinal cord decompression. Catheters were replaced in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. It was concluded that use of long-term epidural catheterization is associated with a definable epidural infection rate. The use of epidural opioid analgesia is an effective and safe means of obtaining pain relief for terminally ill patients when patients are monitored for possible infection and receive prompt treatment when the diagnosis is established. 
2	Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment. 
4	Treatable complications in undiagnosed cases of autosomal dominant polycystic kidney disease. In a study to determine the proportion of unrecognised cases and the prevalence of treatable complications of autosomal dominant polycystic kidney disease (ADPKD), 46 probands were identified through genetics and renal clinics in Melbourne, Australia. 321 offspring of the probands who were older than 15 years and had not been previously diagnosed as having ADPKD were identified. 68 (21%) had ultrasound evidence of polycystic kidney disease. Of this previously undiagnosed group, 25 (37%) had one or more treatable complications at the time of diagnosis. The complications included 20 cases of hypertension (diastolic blood pressure 95 mm Hg or above), 7 cases of impaired renal function (serum creatinine 0.12 mmol/l or above), and 4 cases of bacterial urinary tract infection. 8 people had several complications. ADPKD has an important treatable component which is not being treated in a substantial proportion of affected individuals, because the disease is not being diagnosed despite the presence of a positive family history. 
5	Is primary repair of gastroschisis and omphalocele always the best operation? Optimal surgical management of neonates with gastroschisis and omphalocele remains controversial. Suggested benefits of primary fascial closure include earlier return of gastrointestinal function, decreased hospital stay, less sepsis, less risk of postoperative intestinal obstruction and fistulae, and lower mortality. Between 1978 and 1989, 40 neonates with gastroschisis or omphalocele underwent repair. Primary fascial repair was performed in 30 children, 18 of whom had a gastroschisis and 12 of whom had an omphalocele. Ten children had staged repair with the use of a silastic silo; seven of these had a gastroschisis and three an omphalocele. Comparison between the groups was made regarding birth weight, days on the ventilator before and after surgery, days to first feeding, days in the hospital after surgery, postoperative complications, and survival. There was no significant difference in birth weight, days on the ventilator, days to first feeding, and postoperative days in the hospital. There were nine complications in nine patients (30%) with primary repair and four complications in two patients (20%) with staged repair. Two infants died after primary repair (6.7%), and one (10%) died after staged closure. It was concluded that silastic silo repair and primary fascial closure are both acceptable alternatives. Primary closure is attractive whenever possible to avoid additional operations. 
5	Acute coronary artery occlusion during and after percutaneous transluminal coronary angioplasty. Frequency, prediction, clinical course, management, and follow-up [published erratum appears in Circulation 1991 Jul;84(1):446] BACKGROUND. Acute coronary artery occlusion after percutaneous transluminal coronary angioplasty (PTCA) continues to remain a serious complication despite significant improvement in operator performance and technological advancements. This retrospective study was performed to ascertain the frequency, predictive variables, management, and outcome of acute coronary artery occlusion. METHODS AND RESULTS. The study was based on data from 1,423 consecutive patients who underwent an elective coronary angioplasty between January 1986 and December 1988. Acute coronary artery occlusion occurred in 104 patients (7.3%). Acute occlusion developed during the dilatation procedure in 80 patients (5.6%) and within 24 hours after the procedure in 24 patients (1.7%). Four clinical and 14 angiographic variables predictive for acute coronary artery occlusion were analyzed in these 104 patients with a complicated procedure and were compared with those in 104 representative patients with successful attempts. Multivariate analysis found three independent predictive variables: unstable angina, multivessel disease, and complex lesions. The overall clinical outcome after management of acute coronary artery occlusion including immediate repeat dilatation (95 patients), use of intracoronary streptokinase (34 patients), or autoperfusion catheter (12 patients) was successful (reduction of lumen diameter to less than 50%, no death, no myocardial infarction [MI], and no emergency surgery) in 42 patients (40%), was a failure without major complication in four patients (4%), and was a failure with major complication (death, MI, and emergency surgery) in 58 patients (56%). The overall mortality rate was 6% (six patients), the overall MI rate was 36% (37 patients), and emergency bypass surgery was required in 30% of patients (31 patients). At 6 months' follow-up of 42 patients with successful management, recurrent angina pectoris due to restenosis occurred in 10 patients (24%), and a late MI occurred in one patient (3%). At 6 months' follow-up of 56 survivors with unsuccessful management (development of MI or need for emergency bypass surgery), recurrent angina occurred in nine patients (16%), and cardiac death in two patients (4%). However, the majority of patients in both groups were either symptom free or had mild angina pectoris. CONCLUSION. Acute coronary artery occlusion during PTCA is often unpredictable, but its frequency is higher in patients with unstable angina, multivessel disease, and complex lesions. Despite immediate redilatation, use of intracoronary streptokinase, and emergency bypass surgery, PTCA is associated with a high mortality and morbidity. 
1	Combination therapy for anaplastic giant cell thyroid carcinoma. Since 1981, 20 patients with anaplastic giant cell carcinoma of the thyroid have been prospectively treated according to a combination regimen of chemotherapy and external beam radiation therapy. Two types of chemotherapy were used every 4 weeks, depending on the patient's age. For those younger than 65 years, a combination of doxorubicin (60 mg/m2) and cisplatin (90 mg/m2) was given, and for older patients mitoxantrone (14 mg/m2) was used. Radiotherapy was carried out between Day 10 and Day 20 of the first four cycles of chemotherapy. It delivered 17.5 Gy in 7 fractions to the neck and the superior mediastinum. Survival exceeding 20 months was observed in three patients. Complete neck tumor response was observed in five patients, among whom four had undergone previous operations. No response was seen in distant metastases, which were the cause of death in 14 patients. These treatment modalities are effective in some patients, both in terms of survival and of local control, avoiding death from local invasion. Gross tumor resection should be performed whenever possible but should not delay the commencement of this protocol. Toxicity was high and remains the main limiting factor. 
4	End diastolic flow velocity just beneath the aortic isthmus assessed by pulsed Doppler echocardiography: a new predictor of the aortic regurgitant fraction. End diastolic flow velocity just beneath the aortic isthmus was measured within 72 hours of cardiac catheterisation by pulsed Doppler echocardiography in 30 controls and 61 patients with aortic regurgitation. The end diastolic flow velocity was determined at the peak R wave on a simultaneously recorded electrocardiogram. In all controls there was no reverse flow at the end diastole beneath the aortic isthmus. In patients with aortic regurgitation the end diastolic flow velocity correlated well with the angiographic grade of regurgitation (r = 0.81) and regurgitant fraction (r = 0.82). The mean (SD) values were 6.3 (5.2), 12.2 (4.3), 22.1 (5.7), and 34.3 (9.3) cm/s for patients with regurgitant fraction of less than 20%, between 20% and 40%, between 41% and 60%, and greater than 60%, respectively. An end diastolic flow velocity of greater than 18 cm/s predicted a regurgitant fraction of greater than or equal to 40% with a sensitivity of 88.5% and a specificity of 96%. The study suggests that the pulsed Doppler derived end diastolic flow velocity is a useful index in the routine non-invasive assessment of the severity of aortic regurgitation. 
5	Balloon dilatation versus surgical revision of infra-inguinal autogenous vein graft stenoses: long-term follow-up. Although infra-inguinal autogenous vein graft stenoses may be treated by balloon dilatation (PTA) or surgical revision, the optimal approach is undefined. Over the last 7 years 24 PTA procedures were performed on 37 vein graft stenoses in 19 grafts. Graft stenoses were diagnosed from 2 to 72 (mean = 17.3) months after implantation. PTA was successfully completed in 23 (96%) of the 24 procedures including 18 (95%) of the primary, and 5 (100%) of the secondary procedures. Recurrent vein graft stenosis or graft thrombosis developed in 12 (67%) grafts from 3 to 47 (mean = 12.5) months after primary PTA. Long-term patency after primary PTA was 69% at 6, 29% at 12, and 22% at 36 months; secondary patency was 81% at 6, 45% at 12, and 27% at 36 months. During the same period vein graft stenosis in 7 fem-pop and 2 fem-tib grafts were surgically revised with an initial success rate of 100%, and 2 (22%) complications. Four (44%) of these grafts occluded from 1-17 (mean 6.2) months after repair, yielding a primary 5-year patency of 62%. Although vein graft stenosis may be safely, effectively, and repeatedly treated with PTA, long-term durability appears to be superior after surgical revision. 
3	Normeperidine-induced seizures in hereditary coproporphyria. Seizures are common in acute exacerbations of hepatic porphyria, even though the etiology is not identified in most cases. We have reported a case of normeperidine-induced seizures in a patient with hereditary coproporphyria. Although meperidine is commonly used for pain control during acute attacks in these patients, this report suggests that meperidine is not a good analgesic choice in porphyria. Normeperidine-induced seizures in patients with porphyria may be treated by withdrawal of meperidine therapy and selective use of anticonvulsants. 
3	Adjuvant chemotherapy for primary lymphoma of the central nervous system. Ten immunocompetent patients with primary non-Hodgkin's lymphoma of the central nervous system were treated by the neuro-oncology service at the University of California at San Francisco (UCSF). After undergoing surgery for biopsy or removal of their tumors, these patients (group 1) received irradiation with hydroxyurea followed by adjuvant chemotherapy with the combination of procarbazine, lomustine (CCNU), and vincristine. The outcome of treatment in this group was compared with that in three other groups of patients with primary CNS lymphoma: patients treated at the UCSF Cancer Research Institute who underwent surgery and radiation therapy (RT) (group 2); patients described in the literature who had surgery and RT (group 3); or patients described in the literature who had surgery, RT, and chemotherapy (group 4). Median and quartile survival times were greater in patients who received adjuvant chemotherapy (group 1, 30 and 50 months; group 4, 20 and 25 months) than in patients who did not receive chemotherapy after RT (group 2, 13 and 20 months; group 3, 15 and 24 months). These results suggest that adjuvant chemotherapy is useful in the treatment of primary CNS lymphoma. 
1	Segregation analysis of breast cancer from the cancer and steroid hormone study: histologic subtypes The segregation pattern of breast cancer in white families from the Cancer and Steroid Hormone Study was investigated. Families were categorized into four groups based on the histologic type of breast cancer in the probands:ductal cancer, lobular cancer, adenocarcinoma, and medullary cancer. The ductal cancer sample was further split into a premenopausal-proband and a postmenopausal-proband subset. Results for six complex segregation analyses are presented; the findings suggest heterogeneity in the transmission of breast cancer. For all analyses, there was no evidence for a multifactorial component in the mixed model, ie, a major locus plus other transmission, genetic and/or cultural. Interpretation of the medullary cancer, adenocarcinoma, and lobular cancer analyses does not permit discrimination among the major locus models. Segregation of breast cancer in the entire ductal sample was consistent with autosomal recessive transmission. In the ductal subanalyses, a recessive gene was sufficient to explain the breast cancer distribution when the proband had postmenopausal breast cancer. In contrast, when the proband had premenopausal breast cancer, the transmission model was consistent with a dominant major gene, with sporadic cases of disease. 
1	New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia. A new and rare type of Bcr/Abl junction between exon C3 of the 3' portion of the Bcr gene and Abl exon 2 has been identified in the leukemic cells of two Ph1-positive chronic myelogenous leukemia patients in chronic phase. This is the fourth type of Bcr/Abl junction so far identified in Ph1-positive hematologic malignancies and is a consequence of an unusual breakpoint position on chromosome 22 that falls approximately 20 kb downstream of the major breakpoint cluster region (bcr) of the Bcr gene. The new hybrid mRNA is 540 base pairs (bp) longer than that expressed by the K562 cell line and could codify for a Bcr/Abl protein carrying 180 additional aminoacids with respect to the larger P210 protein so far identified. The hematologic phenotype expressed by the two patients carrying this unusual type of Bcr/Abl rearrangement does not significantly differ from that commonly seen in chronic myelogenous leukemia. 
1	Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures. Malignant strictures of the extrahepatic bile ducts are difficult to distinguish from benign strictures, particularly in patients with primary sclerosing cholangitis. Because attempts at diagnosing small cancers with fine-needle aspiration biopsy are not possible in the absence of an associated mass lesion and because the sensitivity of exfoliative biliary cytology is controversial, brush cytology has been used as a potential means of establishing a specific diagnosis of bile duct carcinoma. Herein we report our experience with this technique when performed on 65 patients over a 5-yr period. Each had at least one brushing. Thirty-seven were found to have bile duct carcinoma and 28 were found to have benign strictures. Of these 37, the first brushing was positive for malignancy in 15 (40%), whereas four (11%) had cells suspected but not diagnostic of malignancy. Thirteen patients with bile duct carcinoma whose initial brushings were negative for malignancy had second brushings. Of these, five (38%) had malignant cells, whereas three (24%) yielded suspicious cells. Three of the eight whose first two brushings were negative for malignancy were found to have malignant cells on the third brushing. In contrast, of the 28 patients with benign strictures, malignant cells were never found. However, in two patients, suspicious cells were reported with the first but not the second brushing. A single negative or suspicious cytological finding decreased the probability of bile duct carcinoma to 43%. Two and three sequential negative tests reduced the probability to 32% and 0%, respectively. 
1	A randomized control trial of two cervical spatulas The sampling efficacy of the Ayre and Rocket cervical spatulas was compared in a randomized controlled trial involving 533 women who were attending a colposcopy clinic either for investigation of cytological abnormality or for review after treatment of CIN. Smears were compared with respect to the presence of cytological abnormality and two types of normal cervical epithelial cells (endocervical and immature metaplastic cells) which are considered indicators of adequate cytological sampling. Smears taken with the Rocket spatula were significantly less likely to contain immature metaplastic cells (95% CI on difference in proportion; 5-30%), but more likely to contain endocervical cells (95% CI 16-36%). No significant difference was found in the proportion of smears containing one or other type of indicator cell or in the yield of abnormal smears. It is concluded that the Rocket spatula offered no advantage when used in these circumstances. This study illustrates how spurious conclusions of sampling efficacy can be drawn if only one type of indicator cell is used as an endpoint. 
5	Persistent hepatitis B virus following interferon alfa therapy and liver transplantation. A 44-year-old man with chronic hepatitis B virus infection and cirrhosis was treated with recombinant human interferon alfa for 67 days immediately before orthotopic liver transplantation and immunoprophylaxis with hyperimmune globulin to hepatitis B virus in the peritransplant period. Dot blots for hepatitis B virus DNA demonstrated marked reduction in viremia after 41 days of interferon alfa treatment. Southern analysis for hepatitis B virus in liver showed a pronounced decrement in actively replicating forms in the explant, although hepatic infection was still detectable. After liver transplantation, tests for serum hepatitis B virus DNA and hepatitis B surface antigen remained negative. The patient died 32 days after transplantation of causes unrelated to hepatitis B virus. DNA isolated from liver and other visceral organs at autopsy showed infection of the engrafted liver and the persistence of monomeric relaxed circular forms of hepatitis B virus DNA in pancreas, kidney, and spleen. Thus, graft reinfection occurred despite aggressive antiviral therapy and immunoprophylaxis combined with liver transplantation. Existing viral serological markers appear insufficiently sensitive to assess residual infectivity. 
1	Long-term vascular access via the inferior vena cava. A prospective evaluation of long-term venous access catheters placed via the inferior vena cava was performed to determine their efficacy as well as short- and long-term morbidity. From June 1987 to May 1989, 31 catheters were placed in 26 patients, for a total of 3,503 catheter use days. All catheters were placed via an infraumbilical approach when the more conventional supraumbilical route was technically difficult, dangerous, or impossible to be used. There were a total of 14 complications in 12 episodes (one in every 701 catheter use days), six episodes of catheter occlusion or vessel thrombosis (one in every 583 catheter use days), one catheter malfunction, one episode of cuff erosion through the skin, and one catheter that migrated through the inferior vena cava into the retroperitoneum. These results compared favorably with our experience with long-term catheters of a similar type placed via a supraumbilical approach into the superior vena cava. We conclude that the infraumbilical route for long-term central venous access is safe and technically easy and should be strongly considered in patients in whom venous access via the supraumbilical approach will be technically difficult or have a high likelihood of failure. 
5	Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence. 
5	Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. To investigate the incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection, a prospective follow-up study was conducted in two consecutive groups of patients. Group I consisted of 984 patients (859 men and 125 women) with biopsy-proven chronic type B hepatitis, whereas group II consisted of 1,598 asymptomatic chronic carriers (998 men and 600 women) with normal serum aminotransferase activity. During a mean follow-up period of 4.0 +/- 2.3 yr, 19 patients (1.9%) of group I cleared HBsAg from their serum, whereas 35 patients (2.2%) in group II did so in a mean follow-up period of 2.7 +/- 1.4 yr. The annual incidence of delayed serum HBsAg clearance was 0.5% in group I and 0.8% in group II (p less than 0.02). The cumulative probability of HBsAg clearance was also higher in group II than in group I (p less than 0.007). Antibodies to HBsAg developed in 9 patients (47.4%) with chronic hepatitis and in 11 (31.4%) asymptomatic carriers who cleared serum HBsAg. Those who were HBeAg negative and those older than 40 at entry and those who exhibited cirrhosis during follow-up had a higher incidence of delayed HBsAg clearance. Gender, initial histological changes and hepatitis delta virus infection did not influence the occurrence of HBsAg clearance. Serum HBV DNA was not detectable by slot-blot hybridization but was still detectable by polymerase chain reaction in serum specimens collected within 1 yr of HBsAg clearance. Liver biopsy performed later in 10 patients showed no significant hepatitis activity or tissue HBV DNA, HBsAg or HBcAg. 
1	Wound healing complications in soft tissue sarcoma management: comparison of three treatment protocols. A prospective, nonrandomized comparison of three treatment protocols was undertaken in 45 patients with soft tissue sarcoma designated preoperatively as being at high risk of wound healing complications. All patients underwent complete resection of the gross tumour mass (5 with positive and 40 with negative microscopic margins). Fourteen patients received postoperative adjuvant irradiation (group I), 16 preoperative irradiation (group II), and 15 preoperative irradiation and vascularized tissue transfer to the surgical bed after resection (group III). Major wound healing complications (defined as complications requiring at least 1 further surgical procedure) were lower in group III patients (chi-square = 5.57, P less than 0.03), as was the mean postoperative hospital stay (P less than 0.02, analysis of variance), and the mean number of secondary surgical procedures. Multivariate analysis showed that the only variable influencing length of stay was the use of tissue transfer. Careful intraoperative assessment of the adequacy of resection is essential prior to performing vascularized tissue transfer to ensure that tumour contamination of the donor site is avoided. Since this study is a nonrandomized clinical trial using sequential distribution of patients to the treatment groups, the data should be considered as preliminary, rather than definitive, evidence of the efficacy of vascularized tissue transfer. 
4	Coronary artery disease in Chinese males without hypercholesterolaemia The aim of this study was to determine the frequency of various metabolic risk factors for coronary artery disease (CAD) in 246 male patients studied over a 2-year period. CAD was diagnosed on the basis of a history indicative of angina pectoris, an electrocardiogram diagnostic of myocardial ischaemia, and a positive coronary angiogram. Thirty-eight per cent of this population had diabetes, hypertension or both. Of the remaining individuals, 39% had a plasma cholesterol concentration greater than 5.2 mmol l-1, whereas 23% had a cholesterol concentration less than 5.2 mmol l-1. Plasma lipid and lipoprotein levels of a non-smoking subset of those subjects with a total cholesterol concentration less than 5.2 mmol l-1 were compared with values of a matched group of individuals who did not have significant vessel disease as revealed by angiography. The results of these investigations indicated that patients with CAD and a plasma cholesterol concentration less than 5.2 mmol l-1 exhibited an increase in plasma triglyceride concentration and a decrease in plasma HDL-cholesterol concentration. Since these subjects were not diabetic, hypertensive or hypercholesterolaemic, it is suggested that the observed changes in triglyceride and HDL metabolism made a major contribution to the CAD in these individuals. 
4	Oxygen supply and utilization relationships. A reevaluation. The relationship between oxygen transport (TO2) and oxygen consumption (VO2) has been studied in patients with a number of acute and chronic disorders. Many of these patients have been shown to have a linear relationship between these two variables over a wide range of TO2, which has been considered as evidence of pathologic supply dependency. This supply dependency contrasts with animal studies that have clearly demonstrated a biphasic relationship between TO2 and VO2. This review of the available data concerning the relationship between oxygen transport and supply under conditions of increased oxygen requirements and reduced oxygen transport suggests the possibility that the observed interaction in patients may, in many cases, represent the normal physiologic behavior of the system rather than an abnormal manifestation of impaired oxygen extraction. 
1	Spontaneous rupture of hepatocellular carcinoma: a review of 172 Japanese cases. The spontaneous rupture of a primary hepatocellular carcinoma (HCC) accounts for 10% mortality of HCC patients in Japan. Because this problem occurs much less frequently in western countries, it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a HCC. In an effort to advance the general knowledge of this disease and clarify a selection for its treatment, we review 172 cases of spontaneous rupture of a HCC reported in the Japanese literature. The chief complaint of the patients was sudden epigastralgia or right hypochondriac pain. Abdominal paracentesis was positive in 86% of the patients. Liver failure was the cause of death in 42% of the patients. Therefore, it is important to evaluate liver reserve quickly. In addition, emergency hemostatic procedures must be implemented to avoid hemorrhagic shock. Although two-stage hepatectomy was performed in only 12% of the cases, these had the highest survival rates. Consequently, this is the procedure of choice for the treatment of spontaneous rupture of a HCC. 
4	Intraoperative peripheral Nd:YAG laser-assisted thermal balloon angioplasty: short-term and intermediate-term follow-up. Laser-assisted thermal balloon angioplasty was performed in 48 arteries (iliac, superficial femoral, and popliteal). Indications for surgery were limb salvage (25%), rest pain (38%), and claudication (38%). Patients were categorized into three groups: lesions less than 5 cm, greater than 5 to 10 cm, or greater than 10 cm in length. Demographic characteristics, risk factors, and outcome measures were compared by use of Fisher's exact test and Student's t test. The time for vascular patency failure was compared by use of a standard Kaplan-Meier survival analysis for the three groups. Initial failure to recanalize was noted in 14% in lesions less than 5 cm, 40% in lesions greater than 5 to 10 cm, and 73% in lesions greater than 10 cm. The overall success rate was 38%, with a mean follow up of 1 year. The less than 5 cm lesion group had a significantly higher rate of overall success (59%, p = 0.005) than the other two groups combined. The greater than 10 cm lesion group did significantly worse (9%) than the other two groups combined (p = 0.028). Patients in the less than 5 cm group had significantly longer patency than the other two groups (p less than 0.01). Iliac lesions had a higher overall success rate (73%) than superficial femoral and popliteal artery lesions (35%) (p = 0.038). In conclusion, the widespread application of laser-assisted thermal balloon angioplasty cannot be justified without further long-term clinical and laboratory investigation. Conversely, the potential of this technique should not be dismissed out of hand. Proper patient selection, length and nature of the lesion to be treated, and the appropriate forms, doses, and method of delivery of laser energy, remain to be defined. 
4	Sudden death during empiric amiodarone therapy in symptomatic hypertrophic cardiomyopathy. Amiodarone is reported to improve symptoms and to prevent sudden death in patients with hypertrophic cardiomyopathy (HC). Amiodarone treatment (loading dose 30 g given over 6 weeks; maintenance dose 400 mg/day) was prospectively evaluated in 50 patients with HC in whom the drug was initiated because of symptoms refractory to conventional drug therapy (calcium antagonists and beta blockers). Twenty-one (42%) patients had ventricular tachycardia (VT) during Holter monitoring. Amiodarone significantly and often markedly improved the patients' New York Heart Association functional class status (from 3.3 to 2.7 at 2 months, p less than 0.001) and treadmill exercise duration (p less than 0.001). Eight patients, however, died (7 suddenly) during a mean follow-up period of 2.2 +/- 1.8 years. Of the 7 sudden deaths, 6 occurred within 5 months of initiation of treatment. The 6-month and 1- and 2-year survival rates were 87, 85 and 80%, respectively. The survival rate of patients with VT was significantly worse than that of patients without VT (61 vs 97% at 2 years; p less than 0.01). Sudden death occurred despite abolition of VT on Holter monitoring. Amiodarone increased left ventricular peak filling rate by radionuclide angiography in 20 of 33 patients (61%) (p less than 0.01). Decrease in peak left ventricular filling rate within 10 days of amiodarone therapy (8 of 33 patients) was associated with subsequent sudden death (p less than 0.04). 
3	The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography. We have studied regional cerebral blood flow changes in 6 patients after their recovery from a first hemiplegic stroke. All had a single well-defined hemispheric lesion and at least a brachial monoparesis that subsequently recovered. Each patient had 6 measurements of cerebral blood flow by positron tomography with 2 scans at rest, 2 during movement of fingers of the recovered hand, and 2 during movement of fingers of the normal hand. When the normal fingers were moved, regional cerebral blood flow increased significantly in contralateral primary sensorimotor cortex and in the ipsilateral cerebellar hemisphere. When the fingers of the recovered hand were moved, significant regional cerebral blood flow increases were observed in both contralateral and ipsilateral primary sensorimotor cortex and in both cerebellar hemispheres. Other regions, namely, insula, inferior parietal, and premotor cortex, were also bilaterally activated with movement of the recovered hand. We have also demonstrated, by using a new technique of image analysis, different functional connections between the thalamic nuclei and specific cortical and cerebellar regions during these movements. Our results suggest that ipsilateral motor pathways may play a role in the recovery of motor function after ischemic stroke. 
5	L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat. Tryptophan-associated eosinophilia-myalgia syndrome (L-TRP-EMS) is a newly described syndrome which occurred in epidemic fashion in the United States in the summer and fall of 1989. Epidemiologic data has linked the syndrome to intake of L-tryptophan (L-TRP) from one specific manufacturer, but the precise etiologic compound(s) must be established by replication of the syndrome in an appropriate animal model. In this study, implicated L-TRP, United States Pharmacopeia (USP) grade L-TRP, or vehicle was administered by gavage in a blinded fashion for 38 d to female Lewis rats at doses comparable with those ingested by patients who developed the eosinophilia-myalgia syndrome. Animals receiving implicated L-TRP, but not those receiving USP grade L-TRP or vehicle, developed histologic signs consistent with fasciitis and perimyositis, specific pathologic features of human L-TRP-EMS. Peripheral blood eosinophilia was not observed. Hypothalamic corticotropin releasing hormone mRNA levels were lower and plasma corticosterone levels tended to be lower in the animals that received implicated L-TRP. Plasma L-kynurenine was higher in both L-TRP-treated groups compared to the vehicle-treated animals. The female Lewis rat is known to be susceptible to a wide variety of inflammatory diseases. Identification of specific inflammatory changes in this rat following exposure to implicated L-TRP indicates that this animal model will be important in subsequent investigations into the etiology, pathogenesis, and treatment of human L-TRP-EMS. 
2	Parathyroid hormone-like peptide in normal and neoplastic mesothelial cells. Mesothelioma has not been commonly reported as a cause of hypercalcemia of malignancy. We have studied a patient with malignant mesothelioma and hypercalcemia in association with elevated plasma concentrations of parathyroid hormone-like peptide (PLP). Immunohistochemical analysis of the tumor and seven of eight other mesotheliomas that were not associated with hypercalcemia revealed the presence of PLP cytoplasmic immunopositivity. PLP immunopositivity was also detected in normal and reactive mesothelial cells. The results of these studies suggest that PLP immunoreactivity is common in normal and neoplastic mesothelial cells and raises the possibility that PLP production may play a role in the pathogenesis of hypercalcemia associated with mesothelioma. 
4	Hemodynamic efficacy of rapid saline infusion and dobutamine versus saline infusion alone in a model of cardiac rupture. Despite recent reports describing survival after cardiac rupture, the effectiveness of circulatory support while awaiting definitive surgical treatment is controversial. To assess the efficacy of volume expansion and pharmacologic support in cardiac tamponade due to cardiac rupture, a model of hemorrhagic cardiac tamponade was developed and treatment with rapid saline infusion and dobutamine was compared with rapid saline infusion alone in 15 closed chest dogs. A right ventricular wound of reproducible size was produced by deflating an aortic valvuloplasty balloon that had previously been passed by way of the internal jugular vein into the pericardial space and through a stab wound in the right ventricular free wall. Hemodynamic values were compared at baseline, during tamponade and after a rapid infusion (1 liter at 100 ml/min) of either saline solution alone or saline solution plus dobutamine (20 micrograms/kg per min). Atrial and pericardial pressures increased significantly in both groups. Mean arterial pressure, cardiac output and stroke volume increased with combined saline and dobutamine infusion to values similar to those at baseline (91 +/- 19%, 114 +/- 43% and 94 +/- 37% of baseline, respectively). In contrast, saline infusion alone caused a small increase in cardiac output but failed to significantly increase mean arterial pressure or stroke volume (76.8 +/- 14.2%, 55 +/- 18% and 51 +/- 17% of baseline, respectively). Combined rapid infusion of saline solution and dobutamine infusion has a more beneficial hemodynamic effect and may be more effective than rapid saline infusion alone in resuscitating patients with hemorrhagic cardiac tamponade due to cardiac rupture. 
5	Haemorrhagic shock encephalopathy and sudden infant death In 2 pairs of non-identical twins, haemorrhagic-shock encephalopathy syndrome developed in 1 co-twin while the other died of sudden infant death syndrome. The twin pairs were aged 3 and 4 months, respectively, and no cause was identified. We suggest that stress protein deficiency may underlie both syndromes. 
5	Accidental poisoning with a superwarfarin compound (brodifacoum) in a child. The "superwarfarin" compounds are 4-hydroxy derivatives of coumarin that have increased activity and a longer duration of action than the parent compound. The superwarfarins are used widely in the United States as rodenticides and are effective against warfarin-resistant strains of rats. A chronic accidental ingestion of one of these products, brodifacoum, by a 7-year-old child who had bleeding and laboratory evidence suggestive of a vitamin K-related coagulopathy is reported. The bleeding manifestations were severe and prolonged, requiring 13 months for normalization of coagulation times. With a negative history of ingestion and despite clinical suspicion, documentation of superwarfarin poisoning was hampered by the lack of readily available assays for these compounds, even from the manufacturers. Brodifacoum was also identified in rat feces from the family home. This finding raises the concern of poisoning not only from ingestion of brodifacoum particles themselves, but also from a fecal-oral route. A review of the literature is presented and the implications of this case for the practicing physician are discussed. 
5	The management of retinal detachments associated with choroidal colobomas by vitreous surgery. We used vitreous surgery to treat seven patients (eight eyes) with complicated retinal detachments associated with choroidal colobomas. All eyes had large choroidal colobomas and no evidence of peripheral retinal breaks. Small, atrophic breaks were detected in five of the eyes and were located in the base of the coloboma in four of the five eyes. Adjunctive surgical techniques were necessary and included cyanoacrylate retinopexy in four eyes, silicone oil tamponade in five eyes, and retinectomy in two eyes. Retinal reattachment was ultimately attained in seven of the eight eyes. The number of surgical procedures ranged from one to five, with an average of three. Postoperative visual acuity of the eyes that underwent anatomically successful procedures ranged from 20/100 to light perception. Proliferative vitreoretinopathy was the most frequent cause of redetachment, occurring in six of the eight eyes. 
1	Growth and spread of hepatocellular carcinoma. A review of 240 consecutive autopsy cases. All 240 consecutive cases of hepatocellular carcinoma (HCC) that underwent autopsy at the National Cancer Center Hospital (Tokyo, Japan) between September 1962 and August 1986 were reviewed. Among these cases, 162, for which photographs of cut surfaces of the primary tumors were available, were grossly classified using a combination of both Eggel's classification and our own into three major types, i.e., nodular, massive, and diffuse as described by Eggel (Eggel H, Beitr Pathol Anat 1901; 30:506-604), and three subgroups of nodular type, i.e., single nodular type (type 1), single nodular type with extranodular growth (type 2), and contiguous multinodular type (type 3) by our classification (Kanai T et al., Cancer 1987; 60:810-819). Seventy-eight cases were classified as nodular type, comprising seven cases of type 1, 61 cases of type 2, and ten cases of type 3. Sixty-seven and 17 cases were classified as massive and diffuse type, respectively. Of the 78 nodular-type tumors, 59 measured less than 10 cm, whereas 64 of 67 massive-type tumors were 10 cm or more in size. The incidence of intrahepatic and extrahepatic tumor spread of HCC was significantly higher for tumors measuring more than 5 cm. As to the relationship between macroscopic type and tumor spread, the frequency of spread was lowest for type 1 tumors, and high for the other types. Intrahepatic metastasis was detected in 28.6% of type 1, 93.4% of type 2, 100% of type 3, and 98.5% of massive-type tumors. Lymph node metastasis was detected in 14.3% of type 1, 24.6% of type 2, 70% of type 3, 38.8% of massive-type and 52.9% of diffuse-type tumors. Hematogenous extrahepatic metastasis was detected in 14.3% of type 1, 47.5% of type 2, 70% of type 3, 74.6% of massive-type and 82.4% of diffuse-type tumors. It appears that not only primary tumor size but also its macroscopic type has an important influence on the growth and spread of HCC. 
4	Estimation of Reynolds stresses within the Penn State left ventricular assist device. Fluid velocities were measured using a two-component laser Doppler anemometery (LDA) system at 129 locations within a Plexiglas model of a 70 cm3 Penn State electric Left Ventricular Assist Device (LVAD). The LVAD was driven by a pulsatile piston pump acting on an attached segmented polyurethane diaphragm. Bjork-Shiley tilting disc valves were used to provide unidirectional flow through the inlet and outlet ports. A seeded blood analog fluid, which matched the kinematic viscosity of blood at high shear rates and the refractive index of Plexiglas, was used to make the measurements. At each location, 250 instantaneous velocity realizations were collected at eight instances during the pump cycle. The maximum Reynolds shear and normal stresses were calculated for each pump cycle time and location after filtering the data. The results reveal that the highest Reynolds shear and normal stresses occur in the near wall region just proximal to the aortic valve during diastole, and reach values of 5,300 dynes/cm2 and 10,800 dynes/cm2, respectively. The elevated turbulent stresses are observed during the period of regurgitant flow through the aortic valve, with peak stress values arising during the period of peak regurgitant flow. This supports the hypothesis that a regurgitant turbulent jet is formed near the wall of the prosthetic aortic valve and may be contributing to blood damage. 
2	A hepatocellular carcinoma of massive arterioportal shunts without tumor stain treated with CDDP two-route chemotherapy--a case report. Massive arterioportal shunts without tumor vessels or tumor stain are sometimes encountered in advanced cases of liver cirrhosis. Massive arterioportal shunts without tumor stain that responded well to intensive chemotherapy with cis-diamminedichloroplatinum II are reported. 
5	Insulin resistance and compensatory hyperinsulinemia: role in hypertension, dyslipidemia, and coronary heart disease. Resistance to insulin-stimulated glucose uptake and hyperinsulinemia may play a central role in the cause and clinical course of patients with non-insulin-dependent diabetes mellitus, high blood pressure, abnormalities of lipoprotein metabolism, and coronary heart disease. This article summarizes the evidence in support of this general hypothesis. 
3	Protecting the vasculature: an eye toward the future. Although calcium antagonists were originally developed for use in the management of patients with angina pectoris, they are now used in the management of other cardiovascular disorders, including hypertension. More recently, the calcium antagonists have been under investigation for their potential protective role in atherosclerosis. Coupled with these new possibilities for therapeutic use are the development of new, long-acting, tissue-specific calcium antagonists. Amlodipine belongs to this group, and although it is a dihydropyridine-based calcium antagonist, its pharmacologic profile differs from that of other dihydropyridine-based calcium antagonists. Differences include: different pH optimum for receptor binding, different rates of association and dissociation, and differences in allosteric interaction with the diltiazem and verapamil binding sites. Amlodipine, when given orally to rabbits receiving a high-cholesterol diet, reduces atheroma formation. Evidence of its ability to protect the vasculature is provided by its ability to significantly increase (p less than 0.001) survival in stroke-prone hypertensive rats. 
4	Arrhythmias in patients with CHF. Should they be treated? Ventricular arrhythmias are a major cause of death in patients with congestive heart failure. Dr Ellenbogen and his associates discuss the current thinking, based on recent studies, concerning use of antiarrhythmic agents to prevent sudden cardiac death in these patients. As they point out, the proper antiarrhythmic therapy may be crucial to long-term survival. 
1	Consistent involvement of the bcr gene by 9;22 breakpoints in pediatric acute leukemias. To investigate the relationship of bcr-abl fusion mRNAs with childhood acute lymphoblastic leukemias (ALL), we examined 27 pediatric Philadelphia chromosome (Ph1)-positive acute leukemias using a reverse polymerase chain reaction (PCR) procedure. In cells from 24 leukemias, single bcr-abl PCR products were detected that corresponded to breakpoints in the minor breakpoint cluster region (mbcr in intron 1 of the bcr gene) associated with production of the P190 fusion protein. Cells from the three remaining leukemias contained breakpoints in the major breakpoint cluster region (Mbcr) as shown by PCR and Southern blot analyses. These three leukemias also contained low levels of the mbcr PCR product that may have resulted from alternative splicing of the bcr-abl precursor RNA. A screen of 35 additional leukemias from patients who failed therapy before day 180 (induction failures or early relapses) found one case with unsuccessful cytogenetics to express Mbcr-abl RNA. All four children with Mbcr breakpoints had white blood cell levels in excess of 250,000 at presentation (compared with 2 of 24 with mbcr breakpoints) and two had hematologic and clinical features suggestive of chronic myelogenous leukemias (CML) in lymphoid blast crisis. Our results indicate that in Ph1-positive pediatric leukemias, all 9;22 breakpoints occur in one of the two known breakpoint cluster regions in the bcr gene on chromosome 22. The reverse PCR reliably detected all patients with cytogenetic t(9;22) and is capable of detecting additional Ph1-positive leukemias that are missed by standard cytogenetics. Furthermore, the Mbcr-type breakpoint, associated with production of p210, can be seen in childhood leukemias presenting either as clinical ALL or as apparent lymphoid blast crisis of CML, suggesting that t(9;22) breakpoint locations do not exclusively determine the biologic and clinical features of pediatric Ph1-positive ALL. 
4	Effect of antihypertensives on sexual function and quality of life: the TAIM Study OBJECTIVE: To evaluate treatment of mild hypertension using combinations of diet and low-dose pharmacologic therapies. DESIGN: Multicenter, randomized, placebo-controlled clinical trial. SETTING: Three university-based tertiary care centers. PATIENTS: Patients (697) 21 to 65 years of age with diastolic blood pressure between 90 and 100 mm Hg as well as weight between 110% and 160% of ideal weight. INTERVENTION: Patients were stratified by clinical center and race and were randomly assigned to one of three diets (usual, low-sodium and high-potassium, weight loss) and one of three agents (placebo, chlorthalidone, and atenolol). MEASUREMENTS: Changes in measures of sexual problems, distress, and well-being after 6 months of therapy were analyzed. MAIN RESULTS: Low-dose chlorthalidone and atenolol produced few side effects, except in men. Erection-related problems worsened in 28% (95% CI, 15% to 41%) of men receiving chlorthalidone and usual diet compared with 3% (CI, 0% to 9%) of those receiving placebo and usual diet (P = 0.009) and 11% (CI, 2% to 20%) of those receiving atenolol and usual diet (P greater than 0.05). The weight loss diet ameliorated this effect. The low-sodium diet with placebo was associated with greater fatigue (34%; CI, 23% to 45%) than was either usual diet (18%; CI, 10% to 27%; P = 0.04) or weight reduction (15%; CI, 7% to 23%; P = 0.009). The low-sodium diet with chlorthalidone increased problems with sleep (32%; CI, 22% to 42%) compared with chlorthalidone and usual diet (16%; CI, 8% to 24%; P = 0.04). The weight loss diet benefited quality of life most, reducing total physical complaints (P less than 0.001) and increasing satisfaction with health (P less than 0.001). Total physical complaints decreased in 57% to 76% of patients depending on drug and diet group, and were markedly decreased by weight loss. CONCLUSION: In general, low-dose antihypertensive drug therapy (with chlorthalidone or atenolol) improves rather than impairs the quality of life; however, chlorthalidone with usual diet increases sexual problems in men. 
5	Colonic lipoma as a source of massive hemorrhage. Report of a case. Colonic lipomas are a rare source of massive lower gastrointestinal bleeding requiring operative intervention. A case of massive hemorrhage from cecal lipomatosis is presented. The methods of preoperative diagnosis and treatment are discussed. 
2	Surgical results of intrathoracic gastric volvulus complicating hiatal hernia. From 1981 to 1988, 138 patients with hiatal hernia were treated surgically at our centre. Twenty-one (mean age 76.6 years, 17 women, four men) had an associated intrathoracic gastric volvulus. Eleven patients (mean age 73.2 years), of whom eight were asymptomatic, had an elective procedure. Ten patients (mean age 80.3 years) had emergency surgery, six for acute complications of the volvulus (five cases of strangulation and one of perforated ulcer) and four because of other, unrelated causes of acute abdomen. There were four deaths after operation, all in the emergency surgery group. Four other patients had significant morbidity, all in the emergency group. In the elective cases, all hernias were easily reduced. In one emergency case a gastrotomy was necessary for decompression, and in another gastrectomy was necessary because of gastric gangrene. Our results indicate the need for elective intervention when intrathoracic gastric volvulus is first diagnosed. 
5	Roles of beta 1- and beta 2-adrenoceptors in the mechanism of halothane myocardial sensitization in dogs. The authors investigated the comparative roles of beta 1- and beta 2-adrenoceptors in myocardial sensitization by halothane in dogs. The arrhythmogenic dose (AD) of isoproterenol was determined in the presence of various doses of phenylephrine during halothane anesthesia in dogs, and the influences of 1-metoprolol (beta 1-antagonist) and ICI-118,551 (beta 2-antagonist) on the AD were examined. In the presence of 1-metoprolol, the AD of isoproterenol was significantly greater than the control, but in the presence of ICI-118,551, the AD of isoproterenol was lower. Blood pressure during the arrhythmias was higher in the presence of ICI-118,551 than that in controls. In addition, the AD of ritodrine (beta 2-agonist) was also determined at various doses of phenylephrine. The interaction between phenylephrine and ritodrine in inducing arrhythmias showed hyperbolic isoboles. However, 1-metoprolol completely inhibited the occurrence of arrhythmias induced by ritodrine and phenylephrine. The results suggest that myocardial beta 1-adrenoceptors play an essential role in the genesis of arrhythmias during halothane anesthesia in dogs, whereas beta 2-adrenoceptors do not. 
5	The role of a critical care unit in an epidemic. The role of a critical care unit in life-threatening situations is well established. The management of 52 children with acute gastroenteritis and 22 children with acute paralytic poliomyelitis as part of recent epidemics is described. The solutions to the problems in the critical care management of these 74 victims (out of a total of 6197 patients admitted during the epidemics) are discussed. 
4	Strokes in Asians and Pacific-Islanders, Hispanics, and Native Americans. Stroke in Asian and Pacific-Islander populations remains the principal cause of death among adults, but its incidence in the United States approximates that of Caucasians. Although controversial, uncontrolled hypertension in certain population groups (e.g., northern Japanese) and high dietary saturated fat in others (e.g, Pacific-Islanders) are believed to be responsible for the high stroke incidence rates. The recent reduction in stroke frequency rates in these areas is thought to be the result of better hypertension control. In the Ni-Hon-San Study, the level of hypertension and its frequency were similar in Hawaii and Japan, but ischemic infarction and intracerebral hemorrhage were less frequent in Hawaii. Reduced meat and fat intake may contribute to small vessel disease in Japan. Stroke is the third major cause of death among Hispanic-Americans and Native Americans, yet there is a paucity of information, especially about stroke, in subgroups of these populations. There is also considerable ignorance and controversy about risk factors for stroke in these populations. The need for additional research is urgent. 
4	Sinistral (left-sided) portal hypertension. Between 1953 and 1988, 21 patients with splenic vein thrombosis (SVT), 12 of whom had sinistral portal hypertension (SPH) were treated at our institution. SVT was identified at autopsy in nine patients. Twelve additional patients presented with SPH: bleeding esophageal varices, SVT and normal hepatic function. SVT was caused by pancreatic neoplasm (5), chronic pancreatitis (5), and pancreatic pseudocyst (2). SVT was diagnosed by splanchnic angiography, splenoportography, computerized tomography, and ultrasonography. Gastric varices were diagnosed by endoscopy (10) and barium swallow (2). Splenectomy was performed as primary therapy in 10 patients. Three of these 10 had en block distal pancreatectomy. Two high-risk patients had splenic artery embolization, one as a prelude to splenectomy performed 48 hours later and the other as definitive therapy. One splenectomized patient continued to bleed. No further bleeding occurred in 10 splenectomized patients in follow-up from 1 week to 14 years. Sinistral portal hypertension is a clinical syndrome of splenic vein thrombosis caused by pancreatic pathology and manifests as bleeding gastric varices in patients with a patent portal vein and normal hepatic function. Splanchnic arteriography is necessary for accurate diagnosis. Splenectomy is the effective treatment of choice. 
5	Sequential connection of flaps: a logical approach to customized mandibular reconstruction. Microsurgery has improved the success rate for reconstruction of composite defects in the head and neck. Restoration of mandibular continuity alone is not adequate for reconstruction. Replacement of the oral lining with thin tissue is necessary to improve tongue mobility and to set the stage for later dental restoration. There is currently no ideal osteocutaneous free flap that provides unlimited length of bone, can undergo multiple osteotomies to produce the proper curve to the reconstructed mandible, and provides thin skin for oral lining. Combining free flaps can take advantage of the strengths of the individual donor sites and eliminate some of the problems with current osteocutaneous flaps. In six patients, a fibular osseous free flap was combined with either a radial forearm flap or a lateral arm flap to provide bone and oral lining in reconstruction of mandibular composite defects. In these selected patients, the fibula provided the blood supply for the second free flap, which was placed sequentially. The distal peroneal vessels were used to anastomose to the radial forearm vessels or the lateral arm pedicle. This approach allows the surgeon to customize the defect by improving both the functional and aesthetic aspects of reconstruction and is of use in cases where vascular access is limited, such as following head and neck surgery and radiation. 
1	Topographic classification, clinical characteristics, and diagnostic delay of cancer of the larynx/hypopharynx in Torino, Italy. The case series of a population-based case-control study of laryngeal and hypopharyngeal cancers in Torino, Italy, included 281 men with clinical and anamnestic data. Two hundred fifteen, 28, and 38 cancers originated from the endolarynx, epilarynx, and hypopharynx, respectively. Regions invaded by the tumor were divided into 26 subsites. A classification based on the number of invaded subsites was proposed, which agreed well with the T classification of the TNM system. Cancers originating from the hypopharynx invaded more subsites than cancers from the endolarynx, and among the latter, supraglottic were more invasive than glottic lesions. The number of invaded subsites was strongly associated with nodal involvement. Among symptoms at onset of disease and at diagnosis, patients with endolaryngeal lesions reported dysphonia and dyspnea more frequently, and patients with lesions from other regions had a higher prevalence of dysphagia, odynophagia, otalgia, and adenopathia. Clinical and epidemiologic results of this study suggest considering the endolarynx, epilarynx, and hypopharynx as separate anatomic entities. Diagnostic delay was not associated with tumor size and showed a negative trend with involvement of cervical lymph nodes, suggesting that stage at diagnosis is due to intrinsic differences in tumor aggressiveness. 
1	Zollinger-Ellison syndrome. Relation to Helicobacter pylori-associated chronic gastritis and gastric acid secretion. Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion. 
3	An early description of slowly progressive aphasia. Slowly progressive aphasia without generalized dementia has become an important issue of present-day neuropsychological research. Historically, credit for the first description is usually given to Pick. Another German-speaking author who has published a vivid description of a pertinent cases is Pick's contemporary, Max Rosenfeld. This author has also observed a patient with slowly progressive spatial disorientation and visual recognition deficit, and he has discussed these patients in a remarkably modern way in the context of partial atrophy of the brain. 
5	Differences in glycolytic capacity and hypoxia tolerance between hepatoma cells and hepatocytes. Viability, glycolytic capacity and energy metabolism under anaerobic conditions were studied in the hepatoma cell lines HTC, FU5 and HepG2 and in rat and human hepatocytes using glucose and fructose as glycolytic precursors. During 6 hr of anaerobic incubation without additional substrate, viability decreased rapidly in FU5 and HTC cells, whereas viability of HepG2 cells was not significantly affected. In all tumor cells, 10 mmol/L glucose prevented hypoxic cell injury almost completely. Lactate formation from glucose was about five times higher than in hepatocytes under these circumstances. ATP content of the tumor cells remained almost constant under anaerobic conditions in the presence of glucose. Ten millimoles per liter of fructose diminished glycolysis in the hepatoma cells compared with glucose, ranging from 87% reduction in HTC cells to 43% reduction in HepG2 cells. Accordingly, ATP content decreased rapidly in the FU5 and slowly in the HepG2 cells. Viability was strongly diminished in the HTC and FU5 cells in the presence of fructose, whereas in the HepG2 cells no effect of fructose on viability was detectable. In contrast to the hepatoma cells, rat and human hepatocytes exhibited higher rates of anaerobic glycolysis in the presence of fructose and thus were able to maintain their viability under these conditions. These differences in glycolytic capacity, energy metabolism and hypoxia tolerance of hepatoma cells compared with hepatocytes may be used for the treatment of liver cancer by isolated liver perfusion and ex situ revision of the organ. 
3	Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease. Facioscapulohumeral disease (FSHD), an inherited neuromuscular disorder, is characterized by progressive wasting of specific muscle groups, particularly the proximal musculature of the upper limbs; the primary defect in this disorder is unknown. We studied a patient with FSHD to determine whether the mitochondrial respiratory chain was functionally abnormal. Muscle biopsy revealed fiber atrophy with patchy staining for oxidative enzymes. Electron microscopy of a liver section showed many enlarged mitochondria with paracrystalline inclusions. Decreased oxidation of the respiratory substrates-alanine and succinate-in skin fibroblasts suggested a deficiency of complex III of the electron-transport chain; cytochrome c oxidase activity (complex IV) was in the normal range. Biochemical analysis of liver supported the fibroblast data, since succinate oxidase activity (electron-transport activity through complexes II-IV) was reduced, whereas complex IV activity was normal. Furthermore, analysis of the cytochrome spectrum in liver revealed typical peaks for cytochromes cc1 and aa3, whereas cytochrome b (a component of complex III) was undetectable. Southern blot analysis of fibroblast mtDNA revealed no major deletions or rearrangements. Our study provides the first documentation of a specific enzyme-complex deficiency associated with FSHD. 
5	Use and misuse of oral therapy for diarrhea: comparison of US practices with American Academy of Pediatrics recommendations. To determine how closely US pediatricians follow the 1985 American Academy of Pediatrics Committee on Nutrition's recommendations on oral therapy for acute diarrhea, a questionnaire was administered to four groups: New England private practitioners, pediatricians from 27 states attending a postgraduate course, representatives of departments of pediatrics at US schools of medicine, and housestaff at Boston Children's and Massachusetts General hospitals. The responses from departments of pediatrics and housestaff were not significantly different from those of community practitioners in most categories. The reported rate of use of glucose-electrolyte solutions recommended by the American Academy of Pediatrics was not different from the use of nonphysiologic, high-osmolar, low-salt solutions such as sodas and juices. The usage rate for glucose-electrolyte solutions meeting the American Academy of Pediatrics-recommended carbohydrate-to-sodium ratio of less than 2:1 was less than 30%. Other findings included the general lack of agreement on the use of a single type of therapy and the common use of oral therapy only for mild or no dehydration. Although the American Academy of Pediatrics recommends that feeding be reintroduced in the first 24 hours of a diarrheal episode, the majority of respondents withhold feeding until the second day or later. These findings indicate that educational programs on oral therapy during acute diarrhea are needed in the United States. 
1	Imaging of adult central nervous system primary malignant gliomas. Staging and follow-up. A classification and staging system for primary adult gliomas was proposed. This system uses the high signal intensity found on proton density or T2-weighted magnetic resonance (MR) scans at the site of the tumor and surrounding edema (including infiltrating tumor). 
5	Hyposensitivity to vasopressin in patients with hepatitis B-related cirrhosis during acute variceal hemorrhage. It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18 +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p greater than 0.05). 
2	Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity. 
1	An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs. 
4	Effects of occupied and unoccupied bed making on myocardial work in healthy subjects. Strict bed rest prescribed after acute myocardial infarction provides rest for the heart in an effort to lessen myocardial work. However, bed rest has been implicated as a threat to physical and psychosocial well-being. Nurses must question whether activities associated with bed rest, such as bed making by hospital personnel while the patient is occupying the bed, actually require less myocardial work than out-of-bed activities. In this study we examined cardiovascular function of 22 healthy individuals, 10 (45.5%) men and 12 (54.5%) women ranging in age from 34 to 69 years (mean 48 years), during occupied (side to side method) and unoccupied (patient up to chair) bed making. Cardiac output, heart rate, stroke volume, systolic blood pressure, diastolic blood pressure, mean arterial pressure, total peripheral resistance, and the ratio of preejection period to left ventricular ejection time were measured by using an impedance cardiograph and vital signs monitor. Although differences between these measurements during the two bed making procedures were statistically significant (p less than 0.001), they were not deemed clinically significant for healthy subjects because they represent transient reflexive responses to posturally induced changes in venous return rather than substantial increases in myocardial work. When the goal is minimal myocardial energy expenditure, making the bed when it is unoccupied may offer a sound alternative to making an occupied bed. 
3	A family study of Gilles de la Tourette syndrome. Previous studies have demonstrated that Gilles de la Tourette syndrome (TS) is a familial disorder and that chronic tics (CT) and obsessive compulsive disorder (OCD) appear to be etiologically related to the syndrome. In the present study we report the results from a study of 338 biological relatives of 86 TS probands, 21 biologically unrelated relatives of adopted TS probands, and 22 relatives of normal subjects. The 43 first-degree relatives of the adopted TS and normal probands constituted a control sample. The rates of TS, CT, and OCD in the total sample of biological relatives of TS probands were significantly greater than in the relatives of controls. In addition, the morbid risks of TS, OCD, and CT were not significantly different in families of probands with OCD when compared to relatives of probands without OCD. These findings provide further evidence that OCD is etiologically related to TS. 
5	One-stage repair of colovaginal fistula complicating acute diverticulitis. Fourteen patients with colovaginal fistula secondary to sigmoid diverticulitis were seen between 1964 and 1988. Thirteen had undergone prior hysterectomy. Three different operative approaches were used. Three patients were treated with colostomy alone; one died and the fistula persisted in one. Five patients underwent staged procedures. One patient died of complications after the second stage of a planned three-stage procedure. Four patients underwent a two-stage procedure (fistula takedown, colectomy with colostomy and colostomy closure), all with good results. Six patients were treated with one-stage fistula takedown, colectomy and primary anastomosis, without major complication. We advocate this as the procedure of choice and emphasize the following principles of epidemiology and management: 1) colovaginal fistula complicates diverticulitis in elderly women usually following hysterectomy; this association may be a factor in etiology; 2) vaginography is useful in diagnosis; and 3) planned one-stage repair is the best surgical approach. 
4	Role of prostanoids in renin-dependent and renin-independent hypertension. We investigated the role of prostanoid-mediated pressor mechanisms in setting the level of blood pressure in renin-dependent and renin-independent models of hypertension in unanesthetized rats. Intravenous administration of a blocker of thromboxane A2/prostaglandin endoperoxide receptors, SQ29548 (2 mg/kg bolus injection plus 2 mg/kg/hr for 3 hours), reduced from 162 +/- 4 to 144 +/- 5 mm Hg (p less than 0.05) the blood pressure of rats with aortic coarctation-induced hypertension at 7-14 days after coarctation when plasma renin activity is greatly increased. In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity. The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin. We attribute the hypotensive effect of SQ29548 to interference with pressor mechanisms that depend on activation of thromboxane A2/prostaglandin endoperoxide receptors and suggest that such prostanoid-mediated mechanisms are operational and contribute to an increase in blood pressure in angiotensin-dependent forms of hypertension. Also prostanoid-mediated vasodepressor mechanisms are operational in the early phase of aortic coarctation-induced hypertension since the blood pressure of rats pretreated with SQ29548 was increased by the subsequent administration of indomethacin. Accordingly, the blood pressure of rats with aortic coarctation-induced hypertension is influenced by the interplay of prostanoid-mediated pressor and vasodepressor mechanisms. 
1	Pathologic features of sharp curettings in complete hydatidiform mole. Predictors of persistent gestational trophoblastic disease. The medical records and pathologic specimens were reviewed from 33 patients with complete molar pregnancy at Brigham and Women's Hospital between 1980 and 1989. Two pathologists (D.R.G. and R.W.R.) reviewed all slides from the original sharp curettage to identify pathologic features that may be associated with persistent gestational trophoblastic tumor (GTT). The pathologic features evaluated were implantation site, presence of myometrium, presence of villi, presence and degree of atypia in cytotrophoblast, syncytiotrophoblast and intermediate trophoblast, presence of fibrinoid, presence of implantation site inflammatory cells, volume of tissue and area of trophoblastic tissue. Only one pathologic feature, fibrinoid deposits, identified in sharp curettings was associated with the development of persistent GTT. While 12 (48%) of 25 patients who attained remission without chemotherapy had fibrinoid deposits, only 1 (12.5%) of 8 patients who developed persistent GTT had them (P less than .10). 
5	Mechanisms controlling growth of hepatocytes in primary culture. Mature hepatocytes in primary culture express most of the functions and hormonal responsiveness seen in normal liver studied in vivo. The growth of hepatocytes in culture is regulated by various growth factors. We have identified a hepatocyte growth factor that is isolated from rat platelets. We found that rat platelets also contain a growth inhibitor, transforming growth factor-beta which is secreted as a latent molecule. Its latency is due to its binding with a masking protein. Growth of hepatocytes is also suppressed by interleukin-1 (IL-1) and IL-6. Moreover, the growth and functions of liver cells in culture are regulated reciprocally by cell density: at higher cell density liver-specific functions are expressed and growth is suppressed, whereas the opposite situation is observed at lower cell density. In contrast, neonatal hepatocytes in culture grow autonomously without a requirement for added hormones. This autonomous growth is due to an autocrine mechanism in which the cells secrete one or more growth factors into the culture medium. However, this autonomous growth ceases one week after birth at a time when the cells begin to express differentiated characteristics. Based upon these data, the mechanisms of liver regeneration, differentiation, and hepatocarcinogenesis are discussed. 
4	Thrombotic vasculopathy associated with cryofibrinogenemia. Cryofibrinogenemia refers to the presence of cold-precipitable plasma proteins associated with a variety of disorders, including malignancies, inflammatory processes, and thrombohemorrhagic phenomena. Few cases of essential or primary cryofibrinogenemia are reported. We report a case in a 48-year-old man of essential cryofibrinogenemia and hemorrhagic necrosis of the ears and of the upper and lower extremities. Histopathologic studies demonstrated extensive eosinophilic thrombi in the dermal vasculature, with minimal inflammation and no vasculitis. Cryofibrinogenemia should be considered in the investigation of patients with otherwise unexplained cold intolerance and dermal thrombosis associated with minimal or no inflammation. 
5	New isotopic technique for detecting prosthetic arterial graft infection: 99mTc-hexametazime-labelled leucocyte imaging. Early and accurate detection of prosthetic arterial graft infection is important because this serious complication of vascular surgery carries high morbidity and mortality rates. This report describes the use of a new method of isotopic imaging to detect graft infection using 99mTc-hexametazime-labelled leucocytes. Seventeen patients with potentially infected arterial grafts were imaged in addition to routine investigations but were managed according to our normal surgical practice. 99mTc-imaging was positive in eight patients with proven graft infection and falsely positive in one patient with a groin haematoma (89 per cent specificity). There were no false negatives (100 per cent sensitivity) after an average follow-up of 6 months (range 3-9 months). This technique has proved a reliable and rapid method of confirming graft infection. 
2	Small bowel phytobezoar mimicking presentation of Crohn's disease. A case of small bowel phytobezoar formed from unusual ingested vegetation is described. The patient presented with recurrent subacute obstruction and a right iliac fossa mass mimicking the presentation of Crohn's disease. None of the usual gastrointestinal disorders that predispose to bezoar formation were present. The phytobezoar passed spontaneously following small bowel enema and colonoscopy. It is possible that relaxation of the gut secondary to the antispasmodics administered at investigation or the physical disturbance during these procedures enabled migration through the ileocecal valve. Antispasmodics may be of use in the conservative management of bezoars obstructing otherwise normal bowel. 
5	The prolonged burner syndrome. Over the course of a single football season, six players evaluated by the medical staff had burners that displayed a prolonged neurologic recovery. These players were examined and subsequently evaluated with isokinetic testing and electrodiagnostic studies to elucidate better the short-term natural history of the prolonged burner syndrome. Evidence of muscular weakness at 72 hours postinjury best correlated with positive electrodiagnostic findings. No correlation was found between the initial physical examination findings and the results of electrodiagnostic testing. Isokinetic strength evaluation demonstrated many relative strength differences that were difficult to discern with manual muscle testing. The return of a player to athletic competition following this injury should largely be based on the clinical examination. 
3	A limited diagnostic investigation for obstructive sleep apnea syndrome. Oximetry and static charge sensitive bed. A simplified sleep apnea investigation consisting of combined oximetry and respiration movement monitoring was compared with conventional polysomnography. These two types of recordings were performed simultaneously during one night in 77 patients with suspected obstructive sleep apnea syndrome (OSAS). A static charge sensitive bed (SCSB) was used in the simplified recording because it provides a comfortable and reliable means of recording respiration movements. Periods of obstructive apneas gave a diamond-shaped periodic respiration movement pattern in the SCSB, usually accompanied by repetitive oxygen desaturations. The average number of desaturations greater than or equal to 4 percent per sleeping hour was termed the oxygen desaturation index (ODI) and compared with the apnea index (AI). In the whole population they were well correlated (p less than 0.0001, R2 = 0.41), but in individual cases there were considerable discrepancies. Patients with periodic respiration movements less than 18 percent of total sleeping time and ODI less than 2 never had AI greater than or equal to 5, whereas patients with periodic respiration greater than 45 percent and ODI greater than 6 always had AI greater than or equal to 5. Fifty-one of the 77 patients fulfilled these criteria. A bradycardia response to apneas was absent in 29 percent of patients with AI greater than or equal to 5. A combination of respiration movement and oximetry recording thus seems to give sufficient information to confirm or negate a diagnosis of OSAS in a majority of patients with clinical symptoms. In borderline patients, further investigations should be performed. 
2	Adenocarcinoma of the appendiceal stump. We have reported the case of a 58-year-old woman with nonspecific abdominal complaints in whom barium enema and subsequent colonoscopy showed a 3 cm lobulated adenocarcinoma within a villous adenoma arising from the appendiceal stump. Because such appendiceal malignancies have no specific clinical signs, symptoms, or radiologic features, preoperative diagnosis is extremely difficult, and colonoscopy may be required to clarify radiologically demonstrated irregularities. 
5	Hospital setting and fetal death during labor among women at low risk. Intrapartum fetal death in low-risk women at term is a rare obstetric outcome. This is difficult to study because few data sets contain an adequate number of cases for meaningful analysis. This study used data from the 1980 National Natality Survey and National Fetal Mortality Survey, merged with an American Hospital Association annual survey for the same year, to determine whether the frequency of intrapartum fetal death in low-risk women varied by the hospital setting for birth. Stratified analysis was used to assess the relation of level of hospital for delivery with intrapartum fetal death, with control for potential confounding factors. As the level of available perinatal technology decreased, the frequency of intrapartum fetal death increased (odds ratio, 2.0 for Level II and 3.3 for Level I, as compared with Level III hospitals). Even when early neonatal deaths were considered, perinatal mortality remained lowest at Level III facilities (odds ratio, 1.6 for Level II and 2.7 for Level I, as compared with Level III hospitals). The components of intrapartum surveillance that are most effective in the reduction of perinatal mortality have not been identified. 
4	Tightening the screw: statutory and legal supervision of interhospital patient transfers. A federal statute governing the transfer of indigent patients from Medicare-enrolled hospitals was first enacted in 1986. Review of the statutory and other legal controls over interhospital transfers is precipitated by its recent amendment and the fining of a Texas physician for transferring a high-risk obstetric patient without following the statutory guidelines. These events are part of a pattern of increasing regulation of the practice of medicine. Physicians and hospital administrators responsible for hospital transfer policies should be aware of regulatory developments. Hospitals contemplating transfer of patients must develop transfer policies that comply with governing law, including state law. A transfer policy should provide guidelines as to when a patient is "stable for transfer". Patients may not be transferred unless a physician can certify that delay attendant to transfer will not be detrimental. Furthermore, the policy should specify the procedures to be followed to effect a transfer and any documentation that the physician will have to complete. 
4	Cerebral air embolism treated by pressure and hyperbaric oxygen. We used pressure and hyperbaric oxygen to treat 2 patients with cerebral air embolism, occurring as the result of invasive medical procedures, and neither suffered any permanent damage detectable by clinical examination and MRI. This outcome contrasts with reports of infarct and disability among untreated victims of air embolism. 
5	Ulcerative colitis and giant cell arteritis associated with sensorineural deafness Sensorineural deafness is rarely associated with both ulcerative colitis and giant cell arteritis. A patient is described in whom acute sensorineural deafness occurred in association with episcleritis, ulcerative colitis and clinical features suggesting giant cell arteritis. 
1	Deletion of the human retinoblastoma gene in primary leukemias. As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study. 
5	Tracheotomy in the first year of life. Much has been written concerning complications of pediatric tracheotomies, but few studies have reviewed the complication rates of tracheotomies performed in the first 12 months of life. We reviewed the records of 60 patients who underwent tracheotomy in the first year of life between 1976 and 1988. This study includes 30 full-term infants and 30 premature infants, 16 of whom were very low birth weight preterm infants (less than or equal to 32 weeks' gestation and less than 1,500 g birth weight). Overall complication rates were 3% intraoperative, 13% early postoperative, and 38% late postoperative. The early postoperative complication rate in preterm infants was nearly double that of full-term infants. The late postoperative complication rate of patients undergoing tracheotomy for airway obstruction was more than double that of patients requiring tracheotomy for pulmonary indications. Duration of tracheotomy, however, was felt to be the most important factor in the development of a late postoperative complication. 
4	Elderly men with histories of heavy drinking: correlates and consequences. Recognition that the physical, psychological and social consequences of substance abuse may persist throughout the life span has led to increased study of the impact of lifetime drinking habits on the elderly. We examined the characteristics of elderly men with self-reported histories of having ever been heavy drinker (H+) in a population-based (N = 1,155, mean age = 73.7 years) longitudinal survey of community-dwelling elders; 10.4% of the men reported that they had been heavy drinkers at some time during their lives. H+ men were younger and less educated than non-heavy drinkers (H-) or never drinkers (N). Mortality was higher among H+ men who were current drinkers than among H- or N men. H+ men reported more major illnesses, poorer self-perceived health status, more physician visits, more depressive symptoms, lower levels of life satisfaction and smaller social networks than did H- or N men. Self-reported ability to perform activities of daily living and instrumental activities of daily living was poorest among H+ men, who also scored the lowest on a mental status examination. Thus, a history of having ever been a heavy drinker is predictive of widespread impairments in physical, psychological and social health and functioning among elderly men. 
2	Clinical evaluation of plasma abnormal prothrombin (des-gamma-carboxy prothrombin) in hepatobiliary malignancies and other diseases. Des-gamma-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist-II (PIVKA-II) was measured in the plasma of patients with primary hepatocellular carcinoma and those with various other hepatobiliary and pancreatic diseases. DCP levels were determined by enzyme immunoassay (E-1023), using an anti-DCP monoclonal antibody. Forty-two of the 91 patients (46.2%) with hepatocellular carcinoma had abnormally elevated levels of DCP, whereas only one of the 24 patients with hepatic cirrhosis showed a slight increase. An increase was also observed in some patients with obstructive jaundice. There was no correlation between plasma levels of DCP and those of serum alpha-fetoprotein (AFP). In most patients with hepatocellular carcinoma, plasma DCP levels normalized after curative surgical resection. Plasma DCP levels were not related to the plasma concentration of vitamin K in the patients with hepatocellular carcinoma. Plasma DCP determination may be useful in the diagnosis and postoperative monitoring of the response of hepatocellular carcinoma. 
1	Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. A cDNA clone for human catechol-O-methyltransferase (hCOMT; S-adenosyl-L-methionine:catechol O-methyltransferase; EC 2.1.1.6) was isolated from a human hepatoma cell line (Hep G2) cDNA library by hybridization screening with a porcine cDNA probe. The cDNA clone was sequenced and found to have an insert of 1226 nucleotides. The deduced primary structure of hCOMT is composed of 271 amino acid residues with the predicted molecular mass of 30 kDa. At its N terminus it has a hydrophobic segment of 21 amino acid residues that may be responsible for insertion of hCOMT into the endoplasmic reticulum membrane. The primary structure of hCOMT exhibits high homology to the porcine partial cDNA sequence (93%). The deduced amino acid sequence contains two tryptic peptide sequences (T-22, T-33) found in porcine liver catechol-O-methyltransferase (COMT). The coding region of hCOMT cDNA was placed under the control of the cytomegalovirus promoter to transfect human kidney 293 cells. The endogenous COMT activity, which was approximately 9.98 units per mg of protein in the untransfected cells, increased to 206 units per mg of protein upon transfection with a plasmid containing the COMT cDNA. The COMT activity of recombinant protein was inhibited competitively (IC50 = 700 nM) by the selective COMT inhibitor Ro 40-7592. An anti-COMT monoclonal antibody recognized, on immunoblots, a major polypeptide with apparent molecular mass of 29 kDa, in reasonable agreement with the predicted molecular mass. The recombinant hCOMT was shown by immunoblot analysis to be mainly associated with the membrane fraction. RNA blot analysis revealed one COMT mRNA transcript of 1.4 kilobases in Hep G2 poly(A)+ RNA. 
4	Rarity of preclinical alcoholic cardiomyopathy in chronic alcoholics less than 40 years of age. Preclinical alcoholic cardiomyopathy, myocardial damage in the absence of overt congestive heart failure in chronic alcoholics, is well characterized at necropsy, but attempts to identify such a clinical entity before death have produced conflicting results. Studying subjects only at rest, the inclusion of older alcoholics and limitations of noninvasive techniques may explain some of the disagreement. To determine if preclinical alcoholic cardiomyopathy could be identified independent of the aforementioned limitations, 25 asymptomatic chronic alcoholics aged less than 40 years (mean 34), each of whom had consumed a minimum of 1 pint of whiskey or one 6-pack of beer greater than or equal to 5 days per week for greater than or equal to 5 years, underwent radionuclide ventriculography for measurements of systolic and diastolic function at rest, peak supine exercise and during recovery, and echocardiography for assessment of chamber size, wall thickness and left ventricular mass. Red blood cell levels of selenium and thiamine were measured to determine whether abnormalities were present in these 2 potential mediators of alcoholic cardiomyopathy. For comparison, an age-matched group of healthy control subjects was also studied. For alcoholics and control subjects at rest, mean ejection fraction (67 +/- 7% vs 71 +/- 6%) and diastolic peak filling rate (3.4 +/- 0.6 vs 3.3 +/- 0.6 end-diastolic volumes per second [EDV/s]) were similar. 
4	Assessment of ventricular function with an ambulatory left ventricular function monitor. Changes in ventricular function caused by activities of daily living, including standing, walking, stair climbing, and mental stress, were evaluated using a radionuclide device that recorded left ventricular function on a beat-by-beat basis. The ambulatory monitor was positioned over the patient's left ventricle after a gated blood pool scan. Monitoring revealed a 10% increase of left ventricular ejection fraction from baseline to brisk walking, an 18% increase during stair climbing, and a 6% increase with mental stress. In some subjects, however, the increase in ejection fraction during mental stress exceeded that during exercise. 
2	Recurrence of Crohn's disease after resection. Recurrent Crohn's disease develops in most patients after surgical resection if the patient is followed for sufficient time. This review examines various aspects of recurrent Crohn's disease. It is concluded that Crohn's disease is a diffuse condition of the gastrointestinal tract and that radical resection of Crohn's disease does not prevent recurrence. Assorted factors thought to be associated with recurrence are examined and the relevance of these factors to the surgeon treating Crohn's disease is discussed. 
5	Identification of herpes simplex virus DNA in lesions of erythema multiforme by the polymerase chain reaction. An association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme. In rare cases, the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme. To investigate further the association between erythema multiforme and herpes simplex virus, we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme. In this study herpes simplex virus DNA was detected in 11 of 31 biopsy specimens of erythema multiforme; six additional cases showed equivocal amplification results, which is suggestive of low amounts of viral DNA. Seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls: all were positive for herpes simplex virus DNA. Viral DNA was not detected in control biopsy specimens from skin excised for unrelated conditions. These studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme. The polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes-associated erythema multiforme. Furthermore, the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence. 
5	Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. Saponins were purified from Quillaja saponaria Molina bark by silica and reverse phase chromatography. The resulting purified saponins were tested for adjuvant activity in mice. Several distinct saponins, designated QS-7, QS-17, QS-18, and QS-21, were demonstrated to boost antibody levels by 100-fold or more when used in mouse immunizations with the Ag BSA and beef liver cytochrome b5. These purified saponins increased titers in all major IgG subclasses. To determine optimal dose in mice for adjuvant response, QS-7 and QS-21 were tested in a dose-response study in intradermal immunization with BSA in mice; for both of these purified saponins, adjuvant response (determined by stimulation of ELISA titers to BSA) neared maximum at doses of 5 micrograms and was shown to plateau up to the highest dose tested, 80 micrograms. These purified saponins vary considerably in their toxicity, as assessed by lethality in mice; the main component, QS-18, being the most toxic. Saponins QS-7 and QS-21 showed no or very low toxicity in mice, respectively. None of these saponins stimulated production of reaginic antibodies. The monosaccharide composition of these saponins showed similar but distinct compositions with all four containing fucose, xylose, galactose and glucuronic acid. Predominant differences were observed in the quantities of rhamnose, arabinose, and glucose. Monomer m.w. (determined by size exclusion HPLC) were determined to range from 1800 to 2200. 
5	Surgical therapy of the eyelids in patients with facial paralysis. Patients with facial paralysis have a degree of lagophthalmos and paralytic ectropion. We present our experience in the surgical management of 25 consecutive patients treated for these problems. Paralytic lagophthalmos was corrected using gold weights inserted into the upper eyelid. The advantages and disadvantages of this surgical technique are reviewed. Medial canthoplasty and lateral canthoplasty were performed to rectify paralytic ectropion. Ancillary procedures included browpexy, upper-lid blepharoplasty, and temporalis sling. The results were excellent in 23 of 25 patients and good in the remaining two. After a minimum of 6 months' follow-up, there were no complications. The authors believe that the above procedures will yield consistently excellent cosmetic and functional results in patients with paralysis of the eyelids. 
5	Subcutaneous and mediastinal emphysema associated with hypersensitivity pneumonitis. We report a rare case of a patient in whom severe subcutaneous and mediastinal emphysema occurred in association with summer-type hypersensitivity pneumonitis and in whom overdistention or disruption of alveoli with obliteration of the respiratory bronchioles was revealed on open lung biopsy. This case suggests that obstructive bronchiolitis with hypersensitivity pneumonitis is an etiologic factor of mediastinal emphysema. 
4	Blue rubber bleb nevus syndrome with oral hemangiomas. A case of blue rubber bleb nevus syndrome with oral hemangiomas is reported. Attention is directed to this syndrome because, although rare, it is usually associated with oral lesions. The blue rubber bleb nevus syndrome should always be considered a possibility in patients with oral hemangiomas and bluish skin nodules. 
4	Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators. Thrombolytic therapy has been shown to improve clinical outcome when administered early after the onset of symptoms of acute myocardial infarction; the mechanism of benefit is believed to be reestablishment and maintenance of coronary artery patency. Anistreplase is a second generation thrombolytic agent that is easily administered and has a long duration of action. To compare anistreplase (30 units/2-5 min) and therapy with the Food and Drug Administration-approved regimen of intravenous streptokinase (1.5 million units/60 min), a randomized, double-blind, multicenter patency trial was undertaken in 370 patients less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset. Coronary patency was determined by reading, in a blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes) and later (18-48 hours; mean, 28 hours) after beginning therapy. Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 = 73%) therapy, and overall patency patterns were similar, although patent arteries showed "complete" (grade 3) perfusion more often after anistreplase (83%) than streptokinase (72%) (p = 0.03). Similarly, residual coronary stenosis, determined quantitatively by a validated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02). In patients with patent arteries without other early interventions, reocclusion risk within 1-2 days was defined angiographically and found to be very low (anistreplase = 1/96, streptokinase = 2/94). Average coronary perfusion grade was greater, and percent residual stenosis was less, at follow-up than on initial evaluation and did not differ between treatment groups. Enzymatic and electrocardiographic evolution was not significantly different in the two groups. Despite rapid injection, anistreplase was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean differential fall in blood pressure. In-hospital mortality rates were comparable for anistreplase and streptokinase (5.9%, 7.1%). Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other serious bleeding events and adverse experiences occurred uncommonly and with similar frequency in the two groups. Thus, for the end points of our study (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400 WORDS). 
5	Iatrogenic contamination of multidose vials in simulated use. A reassessment of current patient injection technique. An investigation of the potential spread of iatrogenic infections through contaminated multidose vials was performed. Contamination of a multidose vial was hypothesized to occur after a single syringe is used to inject an infected patient with medication, and the same syringe subsequently is used to withdraw additional medication from the multidose vial. If the contaminated multidose vial is used for another patient, an iatrogenic infection may be spread. Laboratory study of this injection technique found that viral plaque-forming units could be transmitted to a multidose vial in this manner. A survey of 100 fellows of the American Academy of Dermatology from the United States found that 24% of the respondents used this potentially unsafe procedure. The potential for iatrogenic spread of the human immunodeficiency virus and hepatitis B virus is described. Recommendations to avoid patient infection are made. 
3	Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot. Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important. 
4	Hepatic giant cavernous hemangioma with microangiopathic hemolytic anemia and consumption coagulopathy. We describe a case of hepatic giant cavernous hemangioma with both microangiopathic hemolytic anemia (MAHA) and consumption coagulopathy, but without thrombocytopenia, which was completely cured by surgical resection of the tumor. The patient was a 54-yr-old Japanese woman whose chief complaint was right upper abdominal discomfort. Angiography and dynamic computed tomography revealed typical findings of hepatic cavernous hemangioma. The patient also had hematological disorders. At surgery, we performed an atypical right lobectomy to preserve as much normal liver tissue as possible. The patient has been well, with no related complaints or abnormal laboratory findings, 5 yr since her operation. This case indicates that giant cavernous hemangioma of the liver should be considered in the differential diagnosis of MAHA, and if surgical treatment is adequate, hematological abnormalities may be eliminated. 
4	Doppler echocardiographic assessment of changes in pulmonary artery pressure associated with vasodilating therapy in patients with congestive heart failure. Transpulmonic pressure gradient and pulmonary artery pressures can be estimated from the Doppler pulmonary regurgitant flow velocities by applying the simplified Bernoulli equation. In this study, continuous-wave Doppler echocardiography was used to assess changes in pulmonary regurgitant flow velocities associated with administration of vasodilators in 10 patients with congestive heart failure. M-Mode echocardiographic parameters such as left ventricular end-systolic and end-diastolic dimension and fractional shortening did not change with administration of vasodilators. Pulmonary regurgitant flow velocity at end diastole decreased from 1.9 +/- 0.6 to 1.3 +/- 0.3 m/sec (p less than 0.01), and Doppler-estimated transpulmonic pressure gradient at end diastole decreased from 16 +/- 11 to 8 +/- 4 mm Hg (p less than 0.01). Doppler-estimated transpulmonic pressure gradient at end diastole was compared with catheterization-determined pulmonary arterial end-diastolic pressure before and after administration of vasodilators in three patients, and there was a good agreement between these measurements. Thus noninvasive and sensitive assessment of the effect of vasodilators on pulmonary arterial end-diastolic pressure in patients with congestive heart failure is possible with continuous-wave Doppler echocardiographic measurement of pulmonary regurgitant flow velocities. 
4	Thrombus in a natural left ventricle during left ventricular assist: another thromboembolic risk factor. Systemic thromboembolism is one of the serious complications during use of a left ventricular assist system (LVAS). The authors' original LVAS has excellent antithrombogenicity to reduce this risk, but thrombus formation in a natural left ventricle (LV) is another risk factor for systemic embolization. We used our LVAS in 22 patients. Of these, LV wall motion was studied in 15, and a smoke-like echo disclosed thrombus in the LV in eight. When LVAS sufficiently supported the systemic circulation, LV wall motion was irregular upon closure of the aortic valve. Upon recovery of LV function and decrease of LVAS flow, the smoke-like echo diminished and LV thrombus decreased in one, but LV thrombus remained unchanged or increased in seven. Systemic administration of antithrombotic agents had an unclear effect. Seven of eight patients with LV thrombus on echo died during or after LVAS. In these seven, a high incidence of LV thrombus (71%), and systemic embolism to the brain (29%) or kidney (86%), were revealed at necropsy. We subsequently used local heparinization to prevent LV thrombus formation. One patient with a smoke-like echo had no evidence of LV thrombus or systemic embolism. During LV assist, careful management of the LVAS, and intra-LV heparinization should be considered to reduce the risk of thrombus formation in the natural LV. 
3	Idiopathic intracranial hypertension. A prospective study of 50 patients. Management of patients with idiopathic intracranial hypertension (IIH) should be based on the presence and progression of visual loss. To characterize the clinical course of IIH more completely, we monitored the clinical status, especially visual function, in 50 consecutive newly-diagnosed patients over a period of 2 to 39 months (average follow-up 12.4 months). The mean age at onset of symptoms was 31 (range 11-58) yrs; 46 (92%) were women and 47 (94%) were obese (mean weight 90 kg). Common symptoms were headache (92%), transient visual obscurations (72%) and intracranial noises (60%); 13 of the patients (26%) initially had complaints of sustained visual loss. There was visual loss as determined by Goldmann perimetry in 96% and by automated perimetry in 92%. Contrast sensitivity testing was abnormal in 50% and Snellen acuity in 22%. Two patients (4%) became blind in both eyes. The Goldmann visual field grade improved in 60% of patients but visual function deteriorated in 5 (10%). Deterioration of visual field grade was significantly associated only with weight gain during the year before diagnosis. Visual loss in patients with IIH is common and is often reversible. Patients should be evaluated by perimetry using an appropriate strategy and contrast sensitivity testing, along with careful examination of the optic discs. 
2	Delayed presentation of intrapericardial diaphragmatic hernia, an unusual cause of colon obstruction. The earliest symptoms of diaphragmatic hernia may not appear until viscera incarcerate in it years after the causal injury. The most unusual site for a diaphragmatic hernia to occur is through the central tendon of the diaphragm into the pericardium. We present the case of a 43-year-old man who suffered a bowel obstruction when the transverse colon and omentum became incarcerated in the intrapericardial diaphragmatic hernia. The defect presumably resulted from blunt chest and abdominal trauma received 15 years earlier. The delayed presentation of intrapericardial diaphragmatic hernia is reviewed, and recommendations for evaluation and treatment are made. 
1	A randomized study of methanol-extraction residue of bacille Calmette-Guerin as postsurgical adjuvant therapy of uveal melanoma. A randomized controlled clinical trial of methanol-extracted residue of bacille Calmette-Guerin adjuvant treatment of posterior uveal melanoma was undertaken. Of 113 patients, 34 patients received adjuvant immunotherapy and 79 patients received no treatment. No difference in survival was observed between the adjuvant-treated group and the control group of patients. This study found that the size of the tumor was a highly significant risk factor for death caused by metastasis of uveal melanomas. The standard deviation of the nucleolar area of the neoplastic cells was a significant risk factor, even though patients with tumors composed of Callender's spindle-type cells were not included in the study. 
4	Effect of ischemia induced by middle cerebral artery occlusion on superoxide dismutase activity in rat brain. Acute cerebral ischemia increases the generation of free radicals, causing cell damage, and theoretically may decrease the activity of the scavenging enzyme superoxide dismutase. To investigate the role of superoxide dismutase in cerebral ischemia, we used a model of middle cerebral artery occlusion in rats. In this model an infarct is produced in the pyriform and frontoparietal cortices, extending into the lateral basal ganglia. We measured superoxide dismutase activity by using the xanthine oxidase cytochrome c reduction assay in these areas of rat brains. Tissue samples were analyzed 20 minutes, 2, 6, or 24 hours, or 7 days after middle cerebral artery occlusion and 2 or 24 hours or 7 days after sham operation (n = 8-10 at each time). There was no significant change in superoxide dismutase activity relative to control values in any brain area at any time up to 24 hours after surgery. However, 7 days after middle cerebral artery occlusion a significant decline in superoxide dismutase activity, to 55%-68% (p less than 0.05) of that in unoperated controls, was observed in all brain areas. Our results do not support an important role for changes in the activity of endogenous superoxide dismutase during the acute phase of cerebral ischemia. However, the decrease in superoxide dismutase activity 7 days after ischemia could indicate ongoing additional damage to peri-infarct tissue. 
1	Parascapular free flaps for head and neck reconstruction. We report our experience with single-stage, primary reconstruction of the head and neck in 29 consecutive patients using parascapular free flaps. The commonest indications were for craniofacial defects (9), oropharyngeal soft tissue defects (10), and combined mandibular and soft tissue losses (4). Ablative surgery was performed for squamous carcinoma (22), melanoma (2), and malignant fibrous histiocytoma (2). Seven patients died of recurrent disease during a 3 1/2 year follow-up. Seven patients are alive with recurrence. Flap complications included total loss (2) due to unsalvageable microvascular thrombosis, wound breakdown with oropharyngeal fistula (2), mandibular osteomyelitis (1), trismus (2), neck contracture (1), and donor site wound dehiscence (1). The overall success of this reconstruction was 93%. Primary wound healing was the general rule with lower morbidity than with other reconstructive techniques. The flap is thin, pliable, and conforms well to three-dimensional defects. The lateral border of the scapula can be incorporated on the same vascular pedicle for single-stage mandibular reconstruction. No muscle is sacrificed, and the posterior donor defect is an added advantage. The parascapular flap is our first choice for reconstruction of major defects in the head and neck. 
2	Helicobacter pylori infection in pernicious anemia: a prospective controlled study. Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process. 
5	Use of H2-receptor antagonists in children. H2-receptor antagonists (H2RAs) have evolved into the mainstay of anti-acid therapy for pediatric patients, replacing antacids and other modes of therapy. Much of the experience and data used for therapeutic decisions in children, however, have been extrapolated from adult studies. Ranitidine and cimetidine have been studied most extensively in the adult and pediatric populations. Both raise gastric pH and achieve other therapeutic endpoints; however, cimetidine appears to have a greater frequency of both adversed effects and drug interactions. H2RAs are the preferred agents for prevention of stress ulcers, ulcer disease, and reflux esophagitis in the pediatric population. 
4	Effects of fish oil supplements in NIDDM subjects. Controlled study. The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy. 
3	Isolation of sequences that span the fragile X and identification of a fragile X-related CpG island [published erratum appears in Science 1991 Apr 26;252(5005):494] Yeast artificial chromosomes (YACs) were obtained from a 550-kilobase region that contains three probes previously mapped as very close to the locus of the fragile X syndrome. These YACs spanned the fragile site in Xq27.3 as shown by fluorescent in situ hybridization. An internal 200-kilobase segment contained four chromosomal breakpoints generated by induction of fragile X expression. A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males. This CpG island may indicate the presence of a gene involved in the clinical phenotype of the syndrome. 
1	Long-term adjuvant therapy of high-risk malignant melanoma with interferon alpha 2b. Fifty-three high-risk melanoma patients in stage I and 15 patients in stage II were treated after standard surgical intervention with adjuvant therapy with recombinant interferon alpha-2b (rIFN alpha 2b) therapy for a total period of 20 months. Concomitant patients (stage I, n = 82; stage II, n = 33) with identical stages and prognostic factors without adjuvant therapy were used to evaluate the efficacy of rIFN alpha 2b therapy. No difference in 5-year relapse incidence and overall survival rates could be detected. However, it appears that patients of both stage I and stage II benefit from long-term adjuvant rIFN alpha 2b therapy, because during the treatment period (20 months), the incidence of relapses was lower in comparison to controls. After stopping treatment the incidence of relapse is equal in treated and control groups. According to the results of our study, we suggest using continuous low-dose rIFN alpha 2b therapy for adjuvant treatment of malignant melanoma. 
3	Clinical value of magnetic resonance imaging for cervical myelopathy. The magnetic resonance imaging (MRI) findings in 115 cases of cervical myelopathy, 121 cases of cervical radiculopathy, and 64 cases of neck pain with no neurologic deficit were prospectively studied to investigate the clinical value of MRI for cervical myelopathy. The MRI findings in the T1-weighted sagittal projection were classified into four groups according to the degree of the compressed deformities of the cervical cord. The degree of compression of the cervical cord on MRI findings showed a significant correlation with the severity of myelopathy, the anteroposterior diameter of the spinal column, and the degree of compression of the dural tube in the myelograms (P less than 0.01). Fifty-one patients of cervical myelopathy had undergone both preoperative and postoperative MRI. Of these, the spinal canal of 47 patients that was well decompressed was recognized according to plain computed tomography (CT). However, 24 (51%) of these 47 patients showed on MRI a deformity in the spinal cord amounting to cord atrophy. The correlation between the clinical function of the spinal cord and the recovery of the cord deformity on MRI at the operative levels was accurately investigated in 34 patients who had no cord deformities in the adjacent intervertebral levels. Twenty patients with cord atrophy had slightly poor clinical results, although no significant difference was found between these 20 and 14 patients with recovery in the cord deformities. From these results, it was evident that T1-weighted MRI is useful in the accurate diagnosis of compression myelopathy, in accurately deciding the level of the disease focus, and in the accurate assessment of the surgical results. 
1	Bladder outlet obstruction due to pelvic lipoma: computerized tomography, magnetic resonance imaging and radiographic evaluation. We report an unusual case of long-standing bladder outlet obstruction due to pelvic lipoma in a 31-year-old white man. The mass was evaluated by plain film, computerized tomography and magnetic resonance imaging. The differential diagnosis of fat-containing extraperitoneal pelvic masses is discussed. 
4	LVAS pump performance following initiation of left ventricular assistance. Prevention of disturbed flow (e.g., flow stasis) and consequent thrombosis in heart pumps is based upon design characteristics determined during laboratory bench tests. These tests employ optimal filling and emptying characteristics, such as the full-fill to complete empty mode in the Novacor left ventricular assist system. Filling characteristics of the Novacor LVAS were examined during the first 48 hours after implantation in 14 patients. Fill volume of the pump was reduced in pathologic states, such as cardiac tamponade, and following the initiation of right ventricular mechanical circulatory support. In addition, multiple regression analysis revealed that right ventricular function measured by the amount of inotropic support required, the right ventricular ejection fraction, and the total pulmonary resistance, significantly predicted left ventricular assist pump fill volume during the first 48 hours of support. Flow visualization simulating these clinical conditions of incomplete filling suggest inadequate valve washing, particularly around the inlet valve and its conduit, which may predispose to thrombus formation. 
4	Left atrial to femoral arterial bypass using the biomedicus pump for operations of the thoracic aorta. Left atrial to left femoral arterial bypass is an approach to operations of the thoracic aorta dating back to the late 1950s. Since that time, various modifications of the basic bypass circuit have evolved. In addition, temporary bypass shunts have also been described in a variety of positions. The goals of bypass of the thoracic aorta regardless of the technique include prevention of distal hypoperfusion, which can lead to paraplegia, limb loss, multiple organ failure, and sometimes death. Recently, there have been reports of the use of the biomedicus centrifugal pump in bypass circuits of the thoracic aorta. Our series, as well as the success of others, using this variation of a traditional bypass circuit of the thoracic aorta, establishes the biopump's capability of minimizing inherent complications in the bypass circuit. 
5	Aberrant origin of the right coronary artery as a potential cause of sudden death: successful anatomical correction. A man with an aberrant right coronary artery and haemodynamically important prolapse of the mitral valve was successfully resuscitated. The aberrant right coronary artery was thought to be a possible cause of the cardiopulmonary arrest in this patient. Both lesions were corrected at a single operation. 
2	Primary cytomegalovirus infection and gastric ulcers in normal host. A 42-year-old woman presented with epigastric pain and vomiting. Upper gastrointestinal endoscopy revealed three gastric ulcers. Histologic examination of biopsies from the ulcers showed cytomegalovirus inclusion bodies. The appearance of IgM antibodies to cytomegalovirus indicated a recent and primary infection. Stored serum from her last pregnancy 17 months previously contained no cytomegalovirus antibodies. A thorough evaluation of her immune system revealed no abnormality. We are aware of only two other cases where seroconversion was documented in normal hosts. Cytomegalovirus infections in the gastrointestinal tract of normal hosts are very unusual but a common cause of morbidity in immunocompromised hosts. We believe that cytomegalovirus may have a role in the pathogenesis of gastrointestinal lesions in nonimmunocompromised patients. 
4	Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients Histopathologic examination was performed in 20 patients undergoing antemortem coronary angioplasty. Thirty-four lesions were dilated and the interval between coronary angioplasty and death ranged from several hours to 4 years. Intimal proliferation of smooth muscle cells, as a major cause of restenosis, was observed in 83% to 100% of 28 lesions examined 11 days to 2 years after coronary angioplasty. In 20 lesions examined within 6 months, proliferating smooth muscle cells were predominantly of the synthetic type and there was abundant extracellular matrix substance chiefly composed of proteoglycans. In eight lesions examined between 6 months and 2 years, contractile type smooth muscle cells were dominant and extracellular matrix was composed chiefly of collagen. In three lesions examined after 2 years, evidence of antemortem coronary angioplasty was hardly identifiable and these lesions were almost indistinguishable from conventional atherosclerotic plaque. These temporal changes in histologic pattern provide a pathologic background for clinical reports that restenosis is predominantly found within 6 months after coronary angioplasty. Morphometric analysis revealed that the extent of intimal proliferation was significantly greater in lesions with evidence of medial or adventitial tears than in lesions with no or only intimal tears. 
1	Treatment of relapsed non-Hodgkin's lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation. Combination chemotherapy is capable of curing many patients with newly diagnosed intermediate- and high-grade non-Hodgkin's lymphomas (NHL), but treatment of relapsed NHL remains problematic. Bone marrow transplantation (BMT) offers the best chance for disease-free survival, but interim chemotherapy is often necessary while awaiting BMT, especially for patients with bulky disease. We report here 39 patients (median age, 44 years) who failed primary therapy with doxorubicin-based regimens and subsequently were treated with one to six cycles of dexamethasone, 40 mg intravenous (IV) every day on days 1 to 4, cisplatin 100 mg/m2 by continuous infusion on day 1, and cytarabine 2 g/m2 IV every 12 hours x two doses on day 2 (DHAP) before the planned BMT. Histologies included 16 diffuse large-cell, six diffuse mixed, five diffuse small-cleaved, four lymphoblastic, and eight other. Twenty-eight patients had stage IV disease, 13 had B symptoms, and 20 had an elevated lactate dehydrogenase (LDH). Patients had been treated with a median of three previous chemotherapy regimens. Sixty-one percent of patients had high tumor burdens according to the MD Anderson criteria. Objective responses to DHAP were seen in 26 patients (67%) including nine complete responses (CRs) (23%) and 17 partial responses (PRs) (44%), and responses lasted a median of 7.5 months. Myelosuppression was the major toxicity, but there were no treatment-related deaths. To date, 17 patients have undergone subsequent BMT with a projected 3-year disease-free survival of 15%. We conclude that the DHAP regimen is effective short-term salvage therapy for relapsed NHL patients, but the long-term prognosis of multiply relapsed patients remains poor. 
4	Six year follow up of a consecutive series of patients presenting to the coronary care unit with acute chest pain: prognostic importance of the electrocardiogram In a retrospective 6 year follow up data were obtained for 536 of 566 (95%) consecutive patients admitted to a coronary care unit with acute chest pain. Their diagnoses were acute myocardial infarction in 290 (54%), myocardial ischaemia in 164 (31%), pericarditis in 16 (3%), and non-cardiac in 66 (12%). Six year mortality was 36%, 24%, 0%, and 16% respectively. In patients with acute myocardial infarction a higher mortality rate during follow up was associated with a higher than average age, a higher than average creatine kinase, previous myocardial infarction, Q wave infarction, and the presence of reciprocal changes. The presence of reciprocal changes was associated with higher than average concentration of serum creatine kinase, indicating more extensive infarction. Infarction complicated by ventricular fibrillation or left bundle branch block was associated with a higher death rate. The electrocardiogram recorded at the time of acute myocardial infarction contains much useful prognostic information. 
4	Potential complications of high-dose epinephrine therapy in patients resuscitated from cardiac arrest Adults resuscitated from nontraumatic cardiac arrest who received intravenous epinephrine in doses chosen by the treating physician and who survived at least 6 hours were studied to determine if high-dose epinephrine produced more complications than standard-dose. A total of 68 patients were enrolled and evaluated for postresuscitation complications attributable to epinephrine, using a two-tailed t test, and contingency analysis. The 33 patients receiving high-dose epinephrine and 35 patients receiving standard-dose epinephrine were similar in demographics and variables known to affect outcome. There was no difference in potential complications between groups except serum calcium, which was 1.97 mmol/L (SD, 0.20) in the high-dose epinephrine group and 2.10 (SD, 0.20) in the standard-dose group. Hospital discharge rates (18% in the high-dose vs 30% in the standard-dose group) and neurological status on discharge were not significantly different. High-dose epinephrine did not produce increased direct complications in this cardiac arrest population compared with standard-dose epinephrine. 
1	Parotid duct communicating with a labial pit and ectopic salivary cyst. Labial pits are usually described as blind epidermal invaginations of lip mucosa with occasional drainage of minor salivary gland secretions. A case of an aberrant parotid duct in communication with both a unilateral, commissural labial pit and an interposed salivary cyst is presented. A 7-year-old boy who had experienced lifelong clear drainage from a congenital pit at his right oral commissure developed fever, pain, and a submucosal mass of the right cheek over a 6-week period. A preoperative sialogram through the pit demonstrated a communication between the oral commissure fistula, an intervening salivary cyst, and a proximal tract from the cyst to the parotid gland. An en bloc resection of the pit, fistula tract, and cyst was performed through a transoral approach. The dissection was medial to the buccinator muscle. There has been no recurrence of the cyst after 1 year follow-up. A description of labial pits and parotid duct anomalies is presented; however, to our knowledge, this combination of anomalies has not been previously described. 
5	Autoimmune chronic active hepatitis in a family. A positive family history of autoimmune disease is common among patients with autoimmune chronic active hepatitis, but usually autoimmunity is directed at organs other than the liver. We document for the first time the multiple occurrence of autoimmune chronic active hepatitis in a family. Out of a sibship of seven, three sisters developed this, one sister developed coeliac and autoimmune thyroid disease, one sister showed serological signs of autoimmunity, while the two brothers were well with no signs of autoimmunity. HLA typing showed that in association with the female sex DR3 seems to be more important than B8 in conferring susceptibility to autoimmune chronic active hepatitis, at least in this family. 
1	Endometrioma. An intra-abdominal troublemaker. A ten-year review of intestinal and abdominal wall endometriomas is reported. Seven cases of intestinal and two cases of abdominal wall endometriomas are presented. Symptoms were varied but a majority had some gynecologic complaint. In this select group of patients, preoperative investigations did not assist in establishing the diagnosis. All patients underwent surgery and coexisting inflammatory bowel disease was present in two patients. This review suggests that endometrioma of the intestine requires a high index of suspicion for diagnosis and that danazol does not appear to be effective treatment for these patients. 
5	Cortical atrophy and cognitive performance in infantile nephropathic cystinosis. A group of children and adolescents with infantile nephropathic cystinosis underwent cognitive testing and were examined for cortical atrophy using magnetic resonance imaging or computed tomography. Ten of 11 patients demonstrated cortical atrophy. A consistent pattern of lower cognitive performance was found in patients with greater atrophy; however, only the relationship between atrophy and short-term memory approached statistical significance. In addition, evidence for greater impairment of visual memory than of other cognitive functions was observed. This latter observation did not appear to be related to the degree of atrophy. 
2	Relief of tracheal compression by aortopexy. We have performed aortopexy in 12 children with tracheal compression. Six infants had compression secondary to a vascular anomaly (group 1), and the other 6 had previous repair of esophageal atresia (group 2). Eleven of the 12 children are alive after a mean follow-up of 36 months. In group 1, 1 patient died and 3 patients (50%) experienced recurrent respiratory distress. Five infants sustained a major postoperative complication, and the average postoperative hospital stay was 25 days. In group 2, however, aortopexy was uniformly successful. There were no deaths, no postoperative complications, and no cases of postoperative respiratory distress, and the mean postoperative hospital stay was only 10 days. For children with reflex apnea after repair of esophageal atresia, aortopexy is lifesaving and can be performed with minimal morbidity and mortality. Great caution is indicated in children with tracheal compression from other causes. 
1	In vivo incorporation of [9,10(-3)H]-palmitate into a rat metastatic brain-tumor model. Lipid metabolism of an intracerebrally implanted brain tumor and normal brain was investigated in awake Fischer 344 rats using intravenously injected [9,10(-3)H]-palmitate as a probe. A suspension of Walker 256 carcinosarcoma cells (250 cells in 5 microliters medium), with or without 1% low-melting-point agar, was implanted into the caudate nucleus of rats 8 to 9 weeks old. Control animals received an intracerebral injection without tumor cells. Seven days after implantation, awake rats were infused intravenously for 5 minutes with [9,10(-3)H]-palmitate (6.4 mCi/kg). The rats were killed 20 minutes after initiation of the infusion and coronal brain slices were obtained for quantitative autoradiography and light histological study. Tumor cell masses were histologically well demarcated from the surrounding brain tissue. Tumor tissue incorporation of [9,10(-3)H]-palmitate was heterogeneous, ranging on average from 3.1- to 6.1-fold greater than in the corresponding contralateral brain. In addition, incorporation corresponded to regional tumor cell density. The incorporation rate constant of [9,10(-3)H]-palmitate in tumor was significantly increased compared to control brain and was independent of tumor size. Necrotic areas within tumors showed no incorporation of radiolabeled palmitate. Brain surrounding the tumors and control injection sites showed reactive gliosis, and possessed 30% greater incorporation of [9,10(-3)H]-palmitate than contralateral normal brain. These results suggest that [9,10(-3)H]-palmitate can be used to image brain tumors in vivo, measuring turnover and/or synthesis of tumor and brain lipid. 
5	Acute and chronic bioeffects of single and multiple doses of piezoelectric shockwaves (EDAP LT.01). Piezoelectric second generation lithotriptors are an established means of administering extracorporeal shockwave lithotripsy (ESWL) enabling treatment to be performed without anaesthesia or analgesia, but higher shockwave doses and multiple or staged treatment are frequently required. The bioeffects of this modality of ESWL, therefore, require further assessment. Seven experimental groups of adult male rabbits were treated using the EDAP LT.01 in order to determine the acute and chronic bioeffects of clinical dose, excess dose, divided excess dose, high frequency and multiple treatment (X10) piezoelectric shockwaves (PSW). Renal function was measured before and after treatment using mercaptoacetyltriglycine (MAG 3) scans. Gross and histological morphological changes were assessed at one and 30 days following application of PSW. Application of single clinical dose PSW was not associated with any significant functional or morphological renal injury. Excess dose PSW caused transient gross renal contusion, which resolved in the majority of animals with no persistent microscopic abnormality. Divided excess dose PSW resulted in no gross or microscopic damage. High frequency PSW was associated with mild histological abnormality. Multiple PSW treatments caused small discrete fibrotic lesions in all cases, without any change in renal function. 
5	Treatment of aggressive keratoacanthomas by radiotherapy. Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas. 
1	Partial nephrectomy for renal cell carcinoma: indications, results and implications. Of 52 patients who underwent partial nephrectomy for tumor 44 were found to have renal cell carcinoma. The indications for this parenchyma-sparing procedure were categorized according to the initial status of the contralateral kidney and included bilateral tumors or tumor in a solitary kidney in 16 patients (mandatory indications), unilateral carcinoma with compromise of the contralateral kidney by a benign disease process in 9 (relative indications) and small peripheral tumor with a normal contralateral kidney in 19 (elective indications). There were 4 recurrences that accounted for 3 deaths, all in patients with mandatory indications. All patients who underwent partial nephrectomy for relative or elective indications were without definite evidence of recurrent disease at last followup (over-all mean 36 months). Our results suggest that conservative surgery can often provide effective and advantageous therapy for renal cancer and we encourage further consideration of the role of partial nephrectomy as an alternative to radical nephrectomy in selected patients with small peripheral tumors and normal contralateral kidneys. 
5	Long-term psychosocial adjustment to coronary artery disease. Personality hardiness, which has been conceptualized as a potential internal resource facilitating stress resistance, was examined in conjunction with Type A behavior, perceived family cohesion and adaptability, and sociodemographic and medical variables to assess the independent differential correlations of these factors with long-term psychosocial adjustment to coronary artery disease. One hundred twenty-eight patients completed the third generation Hardiness Scale, together with questionnaires measuring Type A behavior, perceived family cohesion and adaptability, and psychosocial adjustment to illness. The results showed that personality hardiness was the most salient correlate of psychosocial adjustment. High hardiness scores were associated with good adjustment to the various life domains. Angina severity accounted for the variance in social domains, but not the psychologic distress domain. Type A behavior, both dimensions of perceived family dynamics, and the sociodemographic variables did not have a significant role in explaining the variance in psychosocial adjustment. We conclude that personality hardiness could serve as a valid indicator of long-term psychosocial adjustment in patients with coronary artery disease. 
2	Circadian esophageal motor function in patients with gastroesophageal reflux disease. Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated. 
4	Infrainguinal revascularization for limb salvage in patients with end-stage renal disease. We studied the efficacy of infrainguinal bypass for limb salvage in patients with end-stage renal disease. The patency of 42 femoropopliteal and femorodistal bypasses, performed for limb salvage in 37 patients with end-stage renal disease, was assessed with Doppler ultrasonography and dye tests. Patency rates and limb salvage were determined by life-table analysis. Average age was 45 years (range, 28 to 61 years); 23 of the 37 were men. Twenty-three patients had diabetes mellitus, and 16 were smokers. Bypass procedures were done in 32 instances while the patients were maintained with chronic hemodialysis and in five instances with peritoneal dialysis; in five instances the patients had had successful renal transplantation. Indications for revascularization included pain at rest, nonhealing ulcer, or distal gangrene. Femoropopliteal bypass was done in 32 limbs; 10 were more distal procedures. Reversed saphenous vein was the conduit in 30 cases; prosthetic material was used in the remainder. Autogenous material was used in all distal bypasses. Four patients required graft revision during the initial hospitalization, but none thereafter. Two patients died within the operative period, nine within 18 months of operation. Nine major operations were required. Three-month cumulative graft patency was achieved in 41 cases and corresponding limb salvage in 33 cases; 18-month patency was achieved in 34 cases and overall limb salvage in 33 cases. Success of limb salvage most closely correlated with preoperative ankle-brachial ratio and level of bypass required. 
4	A lethal complication of papaverine-induced priapism. A large series of patients was treated for impotence with intracorporeal injections of papaverine and phentolamine with no major complications and no deaths reported. We report on a 45-year-old black man with advanced multiple sclerosis who died after such therapy. When the first self-administered injection of phentolamine and papaverine failed to produce an adequate erection the patient injected a second dose that resulted in priapism and death of massive pulmonary embolism. 
5	Capillary leakage in inflammation. A study by vascular labeling. The local injection of pure inflammatory mediators induces venular leakage. To test the effect of endogenous mediators from dying tissue on vascular leakage, the authors devised an experimental model simulating an infarct, whereby living vessels would be exposed to fragments of organs undergoing aseptic necrosis. Tissues from donor rats were implanted aseptically in the cremasteric sac. Control rats were implanted with materials deemed to be as close as possible to nonirritating: boiled tissues and spheres of Teflon or glass. At different points the rats were injected intravenously with carbon black and killed an hour later. Whole cremaster mounts showed that vascular labeling was strictly venular up to 8 hours, mixed with capillary labeling between 12 and 24 hours, and mainly or exclusively capillary at 48 hours. Histology showed an acute inflammatory infiltrate in the labeled areas. A similar but weaker labeling pattern accompanied by milder inflammation was seen in controls. These results indicate that the vascular leakage in aseptic inflammation is biphasic, first venular, then capillary; and that the capillary phase is induced by the inflammatory reaction itself, possibly through a form of diffuse angiogenesis. 
4	Antibodies directed against neutrophils (C-ANCA and P-ANCA) are of distinct diagnostic value in systemic vasculitis. In a prospective study, sera from over 700 patients with suspected vasculitis, including over 200 patients undergoing renal biopsy, were examined for antibodies to neutrophil cytoplasmic antigen (ANCA). An indirect immunofluorescence assay on ethanol fixed human neutrophils identified two types of autoantibody: C-ANCA, which produces diffuse cytoplasmic staining and P-ANCA, which produces an artefactual nuclear/perinuclear staining pattern. The diagnosis of patients in whom ANCA of either form was found was established following case note review according to defined diagnostic criteria. Forty of 45 patients whose sera contained C-ANCA at a titre of greater than or equal to 1/40 satisfied the diagnostic criteria for Wegener's granulomatosis or microscopic polyarteritis. Twelve of 30 patients with P-ANCA at a titre of greater than or equal to 1/40 were also classified as having one of these disorders. Seventeen of the remaining 18 patients had immune-mediated disorders with deep organ damage. Of 47 ANCA-positive patients who underwent renal biopsy, 21 had glomerulonephritis associated with Wegener's glomerulonephritis and a further 22 had a necrotizing or crescentic glomerulonephritis. Ethanol fixation is important for discrimination of C-ANCA and P-ANCA. C-ANCA are highly specific for Wegener's granulomatosis and microscopic polyarteritis. In patients undergoing renal biopsy, the presence of these antibodies is highly specific for a necrotizing or crescentic glomerulonephritis. 
1	Primary central nervous system T-cell lymphoma. Case report. Primary central nervous system (CNS) T-cell lymphoma is extremely rare. The present case report provides immunocytochemical evidence for a cerebellar CNS T-cell lymphoma. The patient underwent surgery followed by radiation therapy and is alive and well 36 months postoperatively. The clinical and pathological features of primary CNS T-cell lymphoma as well as diagnostic measures and treatment options are discussed, together with a compilation of all previous case reports of primary CNS T-cell lymphomas. 
5	Aspiration pneumonia and the laryngeal mask airway A case of aspiration pneumonia is reported after the use of a laryngeal mask airway in a young woman undergoing an elective cholecystectomy. The case illustrates the hazards of regurgitation with the laryngeal mask airway and the need for further evaluation when used with controlled mechanical ventilation. 
4	Value of carvedilol in congestive heart failure secondary to coronary artery disease. Despite considerable interest in the use of beta-blocking agents in congestive heart failure (CHF), their clinical application is limited because of their negative inotropic effects. Beta blockers with vasodilating properties may have the advantage of overcoming this, however. Carvedilol, a beta-blocking agent with vasodilating properties, was evaluated in 17 patients with chronic CHF secondary to ischemic heart disease with a resting left ventricular ejection fraction less than or equal to 45%, who were being maintained on diuretics. Exercise testing, radionuclide ventriculography, and right-sided cardiac catheterization were performed and intraarterial blood pressure measured before and after 8 weeks of carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood pressure were both reduced by chronic therapy. Mean +/- standard deviation exercise time improved from 4.3 +/- 1.6 to 7.1 +/- 2.7 minutes (p less than 0.0001), as did resting left ventricular ejection fraction, from 27 +/- 9 to 31 +/- 11% (p less than 0.02). Pulmonary arterial wedge pressure fell from 19 +/- 7 mm Hg to 12 +/- 5 mm Hg (p less than 0.001) and total systemic vascular resistance from 1,752 +/- 403 to 1,497 +/- 310 dynes/s/cm-5/m2 (p less than 0.02). Stroke volume index improved also, from 31 +/- 6 ml to 40 +/- 6 ml (p less than 0.0005). These hemodynamic changes were mediated partly by vasodilation, diminished myocardial oxygen demand and reduction of sympathetic overactivity in the failing heart. These data suggest that carvedilol may have beneficial effects in patients with chronic CHF secondary to coronary artery disease. 
1	Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients, a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin. 
2	Pharmacokinetics of famotidine after intravenous administration in liver disease. The pharmacokinetics of famotidine were studied after the administration of a single intravenous dose of 20-mg to seven normal volunteers, six patients with chronic hepatitis, 14 patients with compensated cirrhosis, and seven patients with decompensated cirrhosis. The plasma terminal elimination half-life of famotidine was significantly prolonged and famotidine total body clearance was significantly reduced in patients with decompensated cirrhosis, whose creatinine clearance was 57.2 +/- 6.7 ml/min/1.48 m2, but these changes were not significant in patients with chronic hepatitis (creatinine clearance: 109.2 +/- 10.5 ml/min/1.48 m2) or in patients with compensated cirrhosis (creatinine clearance: 72.2 +/- 26.5 ml/min/1.48 m2 in comparison with normal volunteers. The total volume of distribution at steady state was not significantly different between the normal volunteers and the three groups of patients. Famotidine total body clearance showed a weak but significant correlation with the creatinine clearance (r = 0.66, p less than 0.001), serum albumin level (r = 0.51, p less than 0.01), and serum total bilirubin level (r = 0.36, p less than 0.05), which suggested that the reduction in clearance was due in part to the concomitant renal impairment, as well as hepatic dysfunction in these patients. In conclusion, famotidine total body clearance was reduced in decompensated cirrhosis, indicating that the dose schedule requires modification in patients with this condition. 
1	Three staged approach to the surgical management of renal cell carcinoma extending into the right atrium. Case report. Left renal cell carcinoma extending into the right atrium was treated by angioinfarction, removal of right atrial tumour using cardiopulmonary bypass and ten days later abdominal radical nephrectomy and inferior vena cava thrombectomy. Twenty four months later the patient remains well with no evidence of tumour recurrence. 
1	Familial multiple desmoplastic trichoepitheliomas. A kindred with familial multiple desmoplastic trichoepitheliomas is described. Desmoplastic trichoepitheliomas should be added to the group of lesions that indicate an inherited pattern when they occur as multiple primary tumors. The implications for nosologic status and treatment of desmoplastic trichoepitheliomas are considered. 
2	Endosonography of peri-anal and peri-colorectal fistula and/or abscess in Crohn's disease. Transcolorectal endosonography (ES) was performed in 36 patients with Crohn's disease suspected clinically to have a fistula or abscess. A hypoechoic or anechoic duct-like lesion immediately adjacent to the anorectal lumen compatible with a fistula was found in 32 patients. A communication between the fistulous tract and adjacent structures such as the skin, anal canal, or vagina was detected in all 32 patients. An anechoic cavity adjacent to or communicating with the fistula was visualized in 29 of the 36 patients. A fistula was visualized in the remaining seven patients with no evidence of an abscess. This anechoic cavity compatible with an abscess was surgically confirmed in 14 of 17 patients. We judged the extent and configuration of the abnormalities to be more clearly visualized by ES when results were compared with fistulography in five patients. There were no ES complications, and we conclude that ES is the preferred diagnostic procedure in patients with peri-rectal pathology because of the low risk of bacterial dissemination and low incidence of patient discomfort. Utilizing ES after non-surgical treatment was successful in 19 patients for documentation of the response to therapy. 
1	Pelvic resections: the Rizzoli Institute experience. Materials, methods, and techniques of pelvic resections are discussed. Results, including the complications of nerve damage, infection, and vascular, visceral, and reconstructive complications are tabulated. 
4	Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization. 
3	What practicing physicians in North Carolina rate as their most challenging geriatric medicine concerns. We recently surveyed a random sample of 500 physicians in family practice, general practice, and internal medicine in North Carolina, to discover their most challenging geriatric concerns. Using a three-stage survey technique, respondents were asked to answer two open-ended questions about the most challenging geriatric problems they face and what specific geriatric content areas would attract their participation in an educational program. They were then asked to rank 34 topics on which they would like more information. A total of 242 responses were received for a 55% response rate (63 of the 500 were undeliverable). Responses indicated that physicians are more concerned with management than diagnosis and revealed considerable evidence of empathy and concern. The top three topics had to do with the management of dementia, multiple problems, and depression. Approximately 25% of physicians consider problems of financing health care as among the most challenging problems. 
5	Improvement of septic syndrome after administration of recombinant human growth hormone (rhGH)? Twenty patients with generalized sepsis were studied prospectively to evaluate the effects of recombinant human growth hormone (rhGH) administration. Five patients had developed sepsis after major abdominal surgery, 15 patients after multiple trauma with head injury (HTI-ISS 38 +/- 2 and Glasgow Coma Scale 4 +/- 1). The urea production rate (UPR) could be significantly reduced by the intramuscular administration of 1.5 IU of rhGH/kg bodyweight (BW) per day (UPR day: 5, 62 +/- 6.7 gm/d vs. UPR day: 10, 42.6 +/- 5.9 gm/d). The catabolic index of Bistrian (BI) was significantly lower after rhGH therapy on day 10 compared to day 5. IGF-1 increased significantly after the administration of rhGH. The nitrogen balance, however, did not become positive, despite the administration of rhGH. The changes in sepsis were estimated by the scoring system according to Elebute and Stoner on days 3, 5, 7, 10, and 13. In those patients who were available for post-treatment evaluation the parameters had returned to baseline values after the withdrawal of rhGH. Results indicate that this therapy might ameliorate the nitrogen intake, but has no influence on the course of sepsis. Compared to previously published results in nonseptic patients, the somatomedin inhibitors as well as the split-products of the complement system and the metabolites of arachidonic acid may have been responsible for this weak effect of rhGH and IGF-1 in septicemia. 
5	Application of pulsed and continuous wave 1.32 and 1.06 microns wavelengths of the Nd:YAG laser in the canine tracheobronchial tree: a comparative study. Previous investigations have shown good clinical potential for the use of the 1.32 microns wavelength Nd:YAG laser because its soft tissue absorption is better than that of the 1.06 microns wavelength Nd:YAG laser. The 1.32 microns wavelength Nd:YAG laser has an absorption coefficient in water that is 10 times higher than the 1.06 microns wavelength Nd:YAG laser. A comparative in vivo study of laser soft tissue effects was performed by using the 1.32 microns wavelength and the 1.06 microns wavelength Nd:YAG lasers in a pulsed wave (PW) mode and continuous wave (CW) mode using a non-contact endoscopic delivery system. A standard 5 mm mucosal lesion was made in the canine tracheobronchial tree down to the level of the perichondrium. Soft tissue and cartilage effects were examined by light and scanning electron microscopy, acutely, 1 week and 2 weeks after operation, and a comparison was made between the different laser modalities. To create similar lesions, higher energy was required when using the 1.06 microns wavelength Nd:YAG laser. Soft tissue injury was greater with the 1.06 microns wavelength in CW mode, and no cartilage damage occurred in the PW mode. Soft tissue and cartilage repair after 1 and 2 weeks was better with the 1.32 microns wavelength laser. In comparison, the CO2 laser and the contact Nd:YAG laser proved to be more precise cutting tools than the 1.32 microns wavelength or the 1.06 microns wavelength Nd:YAG lasers. Both Nd:YAG laser wavelengths were useful for coagulation and vaporization of tissues and blood vessels. More studies are needed to determine the effect of the new 1.32 microns wavelengths on endotracheal tumors. 
5	Single lumen ileum with myectomy: a possible alternative to the pelvic reservoir in restorative proctocolectomy. An alternative procedure to construction of a pelvic ileal reservoir was assessed which avoids the need for a pouch, while providing an adequate rectal substitute and good continence. Thirty-six female adult beagles were allotted randomly to undergo total colectomy with (a) ileo-anal anastomosis alone, (b) ileo-anal anastomosis with two 15 cm myectomies, (c) ileo-anal anastomosis and myectomy with an ileo-ileal valve, or (d) ileo-anal anastomosis with a duplicated J pouch. The animals were studied before operation and at 4-weekly intervals for 20 weeks after operation. Mortality rates were similar. Ileal compliance was increased significantly by myectomy from 0.64 ml/mmHg (median, interquartile range 0.49-0.78) after ileo-anal anastomosis alone to 1.65 mmHg (1.16-1.93), P less than 0.01, an increase which was maintained. Ileal capacity was also increased both by myectomy and by the J pouch: ileo-anal anastomosis = 85 ml (75-100 ml), ileo-anal anastomosis and myectomy = 139 ml (116-156 ml), ileo-anal anastomosis and myectomy and ileo-ileal valve = 125 ml (range 85-145 ml), ileo-anal anastomosis and J pouch = 130 ml (range 75-165 ml) (P less than 0.01). Bowel function in the other three groups was markedly superior to ileo-anal anastomosis alone. Mean transit time was significantly less after ileo-anal anastomosis, 5.2 h (2.6-8.2 h) than after both ileo-anal anastomosis and myectomy, 10.5 h (9.6-13.9 h), P less than 0.05 and ileo-anal anastomosis and J pouch, 11.0 h (8.4-13.0 h), P less than 0.05, but addition of an ileo-ileal valve did not produce a further increase in transit time, 12.9 h (range 10.5-14.5 h), P = n.s. Myectomy of single lumen ileum may be a useful alternative to a pelvic ileal reservoir in restorative proctocolectomy. 
5	False aneurysm formation of the great arteries after arterial switch operation. An infant with simple transposition of the great arteries underwent a two-staged arterial switch operation, after which mediastinal infection occurred. Continuous irrigation with povidone-iodine solution was performed for 10 days. After that, the patient experienced life-threatening hemorrhage three times. At the time of the second hemorrhage, greater omental transfer was performed. On postoperative day 109, false aneurysm was recognized, having developed from both great arteries. Successful repair was performed on postoperative day 110. 
5	Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes. Microencapsulation of cells within synthetic semipermeable membranes is a novel technique that enables the transplantation of cell cultures without the need for immunosuppression. We have previously shown that transplanted isolated encapsulated hepatocytes can provide sufficient short-term metabolic support to improve the survival of animals with galactosamine-induced fulminant hepatic failure. Here we have demonstrated the feasibility of isolated encapsulated hepatocyte transplantation in providing long-term metabolic liver support in Gunn rats. Gunn rats have a congenital inability to conjugate bilirubin and thus exhibit lifelong hyperbilirubinemia. We studied the feasibility of isolated encapsulated hepatocyte transplantation in restoring this specific liver function. Free hepatocytes, isolated from male Wistar rats, were microencapsulated with collagen within a trilayered sodium alginate-poly-L-lysine-sodium alginate membrane using techniques developed in our laboratory. A total of 45 Gunn rats underwent intraperitoneal transplantation with free hepatocytes (5 x 10(7], isolated encapsulated hepatocytes (5 x 10(7], control (empty) microcapsules or no transplant (untreated controls). Serum bilirubin levels were monitored daily for 10 days after transplantation, and subsequent weekly samples were obtained for up to 1 mo. Microcapsules were studied by light and electron microscopy 1 mo after transplantation. During the first week after transplantation, the mean maximum reduction in serum bilirubin levels for the isolated encapsulated hepatocytes, free hepatocytes and control microcapsule transplanted groups was 45.7%, 18.6% and 14.3%, respectively. For up to 1 mo thereafter the mean reduction in serum bilirubin levels in these respective groups was 34.8%, 13.5% and 3.3%. 
5	Admissions to the intensive care unit after complications of anaesthetic techniques over 10 years. 2. The second 5 years Compared with the first 5 years there was a 19% increase in general anaesthetics, a 171% increase in local and (or) sedation techniques and a 9% increase in obstetric epidurals with no increase in anaesthetic staffing. In this second 5-year period, 46 patients were admitted to the Intensive Care Unit as a result of a complication of an anaesthetic technique. These patients represented 1 in 2371 anaesthetic techniques carried out in the District compared with the previous 5 years where the incidence was 1 in 1543. Seven patients died (15.2%). The complication was considered to be wholly or partially avoidable in 14 instances (30.4%). Four of these subjects died. 
1	Amphotericin B vs high-dose ketoconazole for empirical antifungal therapy among febrile, granulocytopenic cancer patients. A prospective, randomized study. We compared high-dose ketoconazole (800 mg/kg per day, orally) with amphotericin B (0.5 mg/kg per day, intravenously) for empirical antifungal therapy in a prospective, randomized study of persistently or recurrently febrile granulocytopenic cancer patients. Among 97 patients eligible for empirical antifungal therapy, 20 (21%) of these patients were ineligible for randomization to ketoconazole treatment because of their inability to tolerate oral medications. Among 72 patients eligible for randomization, 64 were assessable (32 in each arm of the study). Five of six patients with proved fungal infections who were randomized to receive ketoconazole treatment required crossover to amphotericin B treatment because of progressive infection. The conditions of three of these five patients improved after receiving amphotericin B. The frequency of transaminase elevation was higher in those receiving ketoconazole, while the frequency of azotemia was higher in those receiving amphotericin B. Bioavailability of ketoconazole was unpredictable. Amphotericin B remains the drug of choice for empirical antifungal therapy in granulocytopenic patients; whereas, lack of a parenteral formulation, ineffectiveness against proved mycoses, and unreliable bioavailability preclude high-dose ketoconazole from being an appropriate compound for this purpose. 
4	Hormone replacement therapy. How to select the best preparation and regimen. Hormone replacement therapy is a mainstay of preventive healthcare for the maturing female population. Estrogen deficiency that comes with menopause can have serious effects and is especially important in light of the increasing life expectancy of women. Various estrogen and progesterone preparations are available, and their best application requires understanding of the different potencies and metabolic effects. Daily maintenance therapy without a drug-free interval is becoming the standard method of the 1990s. No doubt the future will bring even better delivery regimens. 
1	Mastectomy following preoperative chemotherapy. Strict operative criteria control operative morbidity. The surgical morbidity associated with aggressive preoperative chemotherapy in 106 patients with advanced primary breast cancer who had chemotherapy followed by mastectomy was examined. These patients were compared with a group of 91 consecutive patients who had mastectomy without preoperative chemotherapy. Strict operative criteria were used to determine the timing of mastectomy following chemotherapy. Wound infection rates were no different in the preoperative chemotherapy group compared to the mastectomy-alone groups (7% versus 4%; p = 0.62). The incidence of wound necrosis was similar (11% versus 6%; p = 0.29). Seroma formation was decreased significantly in the preoperative chemotherapy group compared to the mastectomy-alone group (15% versus 28%; p = 0.04). Intensive preoperative chemotherapy did not delay the reinstitution of postoperative treatment (30% versus 20%; p = 0.27). However, when delay in instituting postoperative chemotherapy was more than 30 days, there was a significant decrease in overall survival rate (p = 0.04). This study provides evidence that intensive preoperative chemotherapy and mastectomy can be performed without increased morbidity. Furthermore it is important to institute systemic chemotherapy within 30 days of mastectomy to achieve maximum survival. 
4	Comparative clinical pharmacology of calcium channel blockers. Calcium channel blockers are effective antihypertensive agents, both as initial monotherapy and in combination with other antihypertensive agents. These drugs are also effective in the treatment of chronic, stable angina, variant angina and supraventricular arrhythmias. Drugs in this class have different affinities for calcium channels in vascular smooth muscle, cardiac muscle, cardiac sinus and atrioventricular node. They are all useful in hypertension and angina, but only verapamil and diltiazem are also useful in the control of heart rate and supraventricular arrhythmias. Nimodipine may control vascular spasm following subarachnoid hemorrhage. Calcium channel blockers have also been used in the treatment of migraine headache and Raynaud's phenomenon. 
5	Effects of spermatic vascular division for correction of the high undescended testis on testicular function. Orchiopexy with division of the spermatic artery and veins is a commonly used technique for correcting the high undescended testis, although the longterm results have not been clearly defined. The left spermatic artery and veins of 22 adult Wistar albino rats were divided while preserving the vessels associated with the vas and cremaster muscle (DT). A sham operation was performed on the left testicle of six additional rats (ST). At 3 weeks postoperatively, both testes from all rats were removed. All testes were viable and bled when incised, although bleeding was considerably reduced in testes with DT. Mean testicular weights after DT were 1,061 +/- 423 mg compared with 1,634 +/- 125 mg for ST rats (p less than 0.02) and 1,508 +/- 119 mg for contralateral testes. The mean tubular diameter after DT was 220 +/- 37 mu compared with 303.1 +/- 10.7 mu for ST testes (p less than 0.02). The testicular biopsy score based upon the morphology of the spermatic tubules was 4.46 +/- 3.32 for DT testes and 8.65 +/- 0.23 for ST testes (p less than 0.02) compared with 8.38 +/- 0.18 for contralateral testes and an absolute normal value of 10. No morphologic abnormalities were observed in the contralateral unoperated testes from any of the rats. The contralateral testes in 12 additional rats were removed before DT. The mean testosterone values in these rats with one testicle was 1.43 +/- 0.75 ng/mL. Three weeks after DT, testosterone values were 0.19 +/- 0.31 ng/mL (p less than 0.01). It is concluded that division of the main spermatic artery and vein in rats produces testicular atrophy with spermatogenic arrest and interstitial cell dysfunction. Although collateral blood flow to the testis may be demonstrated, tissue perfusion is inadequate for normal spermatogenesis and endocrine function. 
1	Petrosal sinus sampling: technique and rationale. Bilateral simultaneous sampling of the inferior petrosal sinuses is an extremely sensitive, specific, and accurate test for diagnosing Cushing disease and distinguishing between that entity and the ectopic ACTH syndrome. It is also valuable for lateralizing small hormone-producing adenomas within the pituitary gland. The inferior petrosal sinuses connect the cavernous sinuses with the ipsilateral internal jugular veins. The anatomy of the anastomoses between the inferior petrosal sinus, the internal jugular vein, and the venous plexuses at the base of the skull varies, but it is almost always possible to catheterize the inferior petrosal sinus. In addition, variations in size and anatomy are often present between the two inferior petrosal sinuses in a patient. Advance preparation is required for petrosal sinus sampling. Teamwork is a critical element, and each member of the staff should know what he or she will be doing during the procedure. The samples must be properly labeled, processed, and stored. Specific needles, guide wires, and catheters are recommended for this procedure. The procedure is performed with specific attention to the three areas of potential technical difficulty: catheterization of the common femoral veins, crossing the valve at the base of the left internal jugular vein, and selective catheterization of the inferior petrosal sinuses. There are specific methods for dealing with each of these areas. The sine qua non of correct catheter position in the inferior petrosal sinus is demonstration of reflux of contrast material into the ipsilateral cavernous sinus. Images must always be obtained to document correct catheter position. Special attention must be paid to two points to prevent potential complications: The patient must be given an adequate dose of heparin, and injection of contrast material into the inferior petrosal sinuses and surrounding veins must be done gently and carefully. When the procedure is performed as outlined, both inferior petrosal sinuses can be catheterized in more than 98% of patients. The complication rate is low, and the theoretical risk of major morbidity or death is less than 1% (neither has yet occurred, to our knowledge). The most common complication is groin hematoma. 
4	Comparison of myocardial imaging with iodine-123-iodophenyl-9-methyl pentadecanoic acid and thallium-201-chloride for assessment of patients with exercise-induced myocardial ischemia. Iodine-123-iodophenyl-9-methyl-pentadecanoic acid [( 123I]MPDA) and thallium-201 (201Tl) were sequentially injected in 11 patients during exercise-induced myocardial ischemia. Simultaneous dual-energy planar images were obtained at 5 min, 3 and 5 hr. All studies were concordantly either positive (8/11) or negative (3/11) by both radionuclides. Exact agreement for segmental uptake was 93%, 94% and 94% for 5-min, 3- and 5-hr images, respectively. Exact agreement for defect reversibility by 3 and 5 hr were 95% and 92%. The initial defect contrasts and myocardial-to-lung ratios were similar by both agents but myocardial-to-liver ratio was lower by [123I]MPDA at 5 min, which became similar to 201Tl at 5 hr. Normal percent myocardial clearances of both agents were comparable and significantly higher than those in defect zones. Thus [123I]MPDA is suitable for myocardial imaging and correlates closely with 201Tl for initial postexercise myocardial uptake and defect reversibility. Defect reversibility appears to result from differential myocardial clearance from normal and ischemic regions. 
3	The risk for systemic vascular diseases and mortality in patients with central retinal vein occlusion. In this cross-sectional study, the authors evaluated 197 patients diagnosed with central retinal vein occlusion (CRVO) at the Wilmer Ophthalmological Institute between 1980 and 1985 to determine the risk of systemic disease and mortality. Complete follow-up information for mortality was obtained in 191 (97%). National Health Interview Survey (NHIS) patients and Wilmer cataract patients formed two comparison groups. The prevalence of hypertension was significantly elevated in the CRVO cases when compared with both comparison groups (P less than 0.03, 0.005). The prevalence of diabetes mellitus was increased in CRVO cases in comparison with the NHIS group (P less than 0.005). The prevalence of cerebrovascular or cardiovascular disease was the same for all three groups, as was overall mortality. Mortality was not increased in CRVO cases as compared with United States mortality rates. 
5	Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment. In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment. 
1	Equal parental origin of chromosome 22 losses in human sporadic meningioma: no evidence for genomic imprinting. Inactivation of tumor suppressor genes can occur either by mutation at the gene locus or by loss of part or all of the chromosome region containing the gene. The latter is most frequently detected by DNA markers as loss of heterozygosity in the tumor tissue. In several reports, the paternal homologue was preferentially retained in embryonal tumors associated with loss of particular chromosomal regions, suggesting genomic imprinting of the corresponding tumor suppressor loci. To explore the generality of these findings and the possible role of genomic imprinting in adult tumors of the nervous system, we have determined the parental origin of chromosome 22 loss in sporadic meningioma. Of nine cases studied, five tumors retained the maternally derived chromosome 22 homologue while four retained the paternally derived chromosome 22. Thus, in contrast to the embryonal tumors, the meningioma locus on chromosome 22 is inactivated by random mutation in sporadic adult meningiomas. 
4	The De Vega tricuspid annuloplasty. Perioperative mortality and long term follow-up. One hundred and fifty-three patients undergoing De Vega tricuspid annuloplasty, with or without other associated cardiac procedures between January, 1979, and June, 1987, were evaluated. There were 136 hospital survivors. The follow-up was 98.1% complete for a mean of 3.7 years/patient. Operative mortality was 11.1%; preoperative NYHA class and length of CPB were significant risk factors of perioperative mortality. The actuarial survival of operative survivors at 9 years was 73.5 +/- 11.8%. There were 7 late cardiac deaths among a total of 12 late deaths. Eleven patients required reoperation (2.1 +/- 0.6% patient-year). In seven patients it was necessary for recurrence of tricuspid regurgitation; six of these had also a mitral prosthesis malfunction or a periprosthetic leak. Residual tricuspid regurgitation was judged as mild, moderate or severe in 29.9%, 11.9% and 4.3% of the patients respectively. De Vega tricuspid annuloplasty is the method of choice for mild and moderate tricuspid insufficiency; in selected cases, with a more severe degree of regurgitation, better results could be achieved with a different surgical approach. 
1	Biliary and pancreatic metastases of breast carcinoma: is surgical palliation indicated? Obstructive jaundice developed in a patient concomitantly with the diagnosis of breast carcinoma. Abdominal exploration disclosed a metastatic tumor in the head of the pancreas, the distal bile duct, and the gallbladder. A cholecystectomy and choledochojejunostomy were performed and later, because of intestinal obstruction, the patient underwent gastrojejunostomy. Pathological examination demonstrated metastatic lobular carcinoma of breast with strongly positive staining for estradiol. Additional hormonal therapy has been given to the patient since the operation. The patient is alive 16 months after the diagnosis of her disease. This case suggests that a vigorous diagnostic approach should be adopted in every jaundiced patient with metastatic breast cancer in order to exclude causes of jaundice other than diffuse metastatic involvement of the liver. Patients with extrahepatic biliary metastasis should be treated by aggressive surgical treatment, combined with systemic therapy which can offer them significant palliation and better survival. 
5	A rodent model of cirrhosis, ascites, and bacterial peritonitis. We sought to develop a rodent model of spontaneous bacterial peritonitis and report here the preliminary results of carbon tetrachloride-induced cirrhosis in which ascites and bacterial peritonitis predictably develop. Of 41 rats that survived the initial carbon tetrachloride toxicity, 38 (92.7%) developed cirrhosis with ascites. Of these 38, 21 (55.3%) developed 24 episodes of ascitic fluid infection without iatrogenic colonization. No surgically treatable source of infection was identified at autopsy in any rat; therefore, the infections were presumed to be "spontaneous." Eight (50%) of the 16 rats with culture-positive ascitic fluid at postmortem examination also had spontaneous pleural fluid infection with the same organism. Escherichia coli and Proteus sp. were the organisms most commonly isolated. This rodent model of cirrhosis with ascites appears to be the first high-yield animal model of spontaneous bacterial peritonitis. Ascitic fluid infection in these rats resembles ascitic fluid infection in humans. This model will allow further investigation of the mechanisms of pathogenesis of ascitic fluid infection and provide insight into the prevention and treatment of spontaneous bacterial peritonitis and pleural fluid infection in patients with cirrhosis. 
4	Subarachnoid hemorrhage of unknown etiology: early prognostic factors for long-term functional capacity. Forty-one patients suffering subarachnoid hemorrhage (SAH) of unknown etiology were re-investigated at an average of 91 months after the bleed to determine functional capacity. Nineteen patients were performing at their previous level of work, five were employed part-time, and four could not work due to the SAH. Five patients showed a moderate disability in activities of daily living but were not dependent on help, one patient was severely disabled, and two had died. There was one rebleed. Early prognosis of an unfavorable outcome was possible on the basis of three clinical variables on admission: a history of hypertension, a Hunt and Hess grade of greater than II, and the presence of focal neurological deficits. In addition, the presence of an organic mental syndrome at discharge was identified as a predictive factor for reduced functional capacity later on. Other clinical variables in the acute stage, including sex, age, history of headache, interval between SAH and admission, impaired consciousness, and cognitive deficits, were not related to a limited functional level. Residual neurological deficits and the Glasgow Outcome Scale score on discharge were also not predictive of restrictions in global functions evaluated by means of the Karnofsky Performance Scale status at follow-up review. 
2	Long-term results of the Belsey Mark IV antireflux operation in relation to the severity of esophagitis A retrospective analysis of the results of the Belsey Mark IV operation has been conducted, relating these to the degree of esophagitis present preoperatively. Analysis of 89 patients showed a 91.7% success rate in patients without esophagitis. Good results diminished steadily as the severity of esophagitis increased, giving 76.5%, 75%, 66.7%, and 50% success rates for first-, second-, third-, and fourth-degree esophagitis, respectively. We believe that shortening of the esophagus is an important factor in this. Shortening is obvious in third- and fourth-degree esophagitis but subtle in first- and second-degree esophagitis. We conclude that the Belsey operation is adequate for patients without esophagitis, but for patients with any degree of esophagitis more effective reflux control is needed. 
1	Effect of closing dead space on incidence of seroma after mastectomy. Seromas are a significant cause of morbidity after modified radical mastectomy. The effect of closing dead space by suturing skin flaps to underlying muscle combined with early removal (48 hours postoperatively) of closed suction drains on formation of the seroma was evaluated prospectively in 37 patients. Thirty-three underwent modified radical mastectomy for invasive carcinoma while four underwent total mastectomy with a level 1 axillary dissection for multifocal intraductal carcinoma. Seromas occurred in three, all were minor, two required one aspiration only and one required two aspirations. Two were seromas of the lower flap while one was an axillary seroma. Except for one patient who had a wound hematoma develop, no other instances of morbidity were noted. Closing dead space by suturing skin flaps to underlying muscle combined with early removal of closed suction drains is associated with a low incidence of seroma formation after mastectomy. Use of this technique has important economic and clinical implications for patients who had mastectomy. 
3	Anterior acromioplasty for treatment of the shoulder impingement syndrome. Between 1975 and 1979, anterior acromioplasty was performed in 65 patients with 66 involved shoulders. The procedure appears to be safe and reasonably effective. Of the 65 patients in this study, 50 had chronic tendon inflammation with fibrosis, and 16 also had a small supraspinatus tendon tear. These 16 had rotator cuff repairs. Twenty-six patients were also treated with distal clavicle excision, and seven had tenodesis of the long head of the biceps brachii. The average age of the patients was 50 years (range, 23-75 years). All patients were followed for an average of eight years (range, three to 13 years). At final evaluation, no or slight pain was present in 77% of the shoulders: 39 of 50 without tendon tearing and 12 of 16 with tendon tearing and repair. Active shoulder abduction averaged 167 degrees. Ninety-two percent returned to employment, including 18% with some job modification. Eighty-six percent returned to recreational athletics, 20% with some modification of activities. Seven patients had additional surgical treatment. The progression of rotator cuff disease is not always prevented, but the need for subsequent shoulder treatment generally decreases. 
5	Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. We evaluated the outcome in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS) associated with histologically verified small-cell carcinoma (SCC). Thirteen patients received specific tumor therapy (chemotherapy, radiation therapy, or resection) and most also received pharmacologic and immunologic treatment for LEMS. Seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement (1 patient being in complete remission at 7 years); in 3 of 11 improvement was transient. An EMG index of disease severity (compound muscle action potential amplitude in abductor digiti minimi) was significantly increased at final follow-up (p less than 0.01; n = 11). A pretreatment amplitude greater than 3.0 mV was a good prognostic sign. We conclude that a combined treatment approach in SCC-LEMS usually results in neurologic improvement. 
5	Pleuropulmonary manifestations of hepatic amebiasis Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess. 
3	Progress report of the Stroke Prevention in Atrial Fibrillation Study. The Stroke Prevention in Atrial Fibrillation Study recently found and reported (SPAF Investigators, N Engl J Med, 1990;322:863-868) a beneficial effect of both warfarin and aspirin compared with placebo in the primary prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Among warfarin-eligible patients, the event rates were 1.6%/yr for those receiving active antithrombotic therapy (warfarin or aspirin) and 8.3%/yr for those receiving placebo (p less than 0.00005) (risk reduction 81%, 95% confidence interval 56-91). Ironically, we did not find a beneficial effect of aspirin in warfarin-ineligible patients. On the basis of these results, the study has been reshaped to directly compare these two antithrombotic agents. Insight into the apparent aspirin unresponsiveness noted in some patients also is being sought. Interpretation of the preliminary results and the reshaping of the study have been made more complex by the continued blinding of the investigators to certain portions of the data. Presented is an account of the study from its inception through its recent redesign. 
1	Choroid plexus cysts and chromosomal defects During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts. 
5	Behavioral modification of colonic function. Can constipation be learned? We challenged the two hypotheses: first, that defecation can be suppressed for an extended time, and second, if so, that this has an effect on upper colonic motility. Thus we studied 12 male volunteers with conditions of identical nutrition and patterns of physical activity over a two-week period, where one week with normal defecation and one week with voluntary prolonged suppression of defecation followed each other in randomized order. Frequencies of defecation, stool weights, total and segmental colonic transit times (using radiopaque markers) were compared. Frequency of defecations and stool weights were lower during suppressed defecation [8.9 +/- 0.66 vs 3.7 +/- 0.41 (mean +/- SE) bowel movements per week, P = 0.003, and 1.30 +/- 0.09 vs 0.98 +/- 0.13 kg/week, P = 0.01]. Total transit times were increased from 28.8 +/- 4.4 to 53.1 +/- 4.3 hr, P = 0.004. Segmental transit times were increased in the rectosigmoid (from 8.83 +/- 3.6 to 32.1 +/- 5.6 hr, P = 0.04) and right hemicolon (from 14.5 +/- 0.9 hr to 19.7 +/- 1.5 hr, P = 0.02) by suppression of defecation. We conclude that defecation habits may induce changes in colonic function such as those seen in constipation and that functional anorectal outlet obstruction may, probably by reflex mediation, affect the right colon. 
3	Selective spatial attention in patients with visual extinction. The present study was designed to verify the attentional performance of patients with parietal lesions in the experimental condition in which they had to pay attention to 3 spatial positions located on the left, on the right and directly above the fixation stimulus (Experiment 1) and to only 1 of the 3 spatial positions at a time (Experiment 2). Twelve patients (6 subjects with right parietal lesions and 6 subjects without neurological deficits) participated in the experiment. The results of Experiment 1 showed that in patients with right parietal lesions the speed and accuracy of response to horizontally aligned stimuli increased gradually from right to left, whereas the control group showed only the effect due to the different retinal eccentricities of the 3 stimuli, that is, responses to central stimuli were faster and more accurate than responses to left and right stimuli. The results of Experiment 2 showed that both the neurological and control groups were faster to respond to central than to left and right stimuli, and that the neurological group was faster to respond to right than left stimuli, whereas no difference in RTs between two visual fields was obtained in the control group. Furthermore, when the patients had to respond to 3 spatial locations aligned horizontally (Experiment 1), the speed and accuracy of response to the right stimulus were the same as when they had to focus attention on it (Experiment 2). These results showed that the focus of attention in patients with visual extinction is on the rightmost stimulus and that the increased attention to the right is accompanied by a decreased attention to the left. 
1	Retroviral transformation of cerebral microvascular endothelial cells: macrophage-like and microvascular endothelial cell properties. We report that L-cell-conditioned medium (LCM) transforms porcine cerebral microvascular (PCMV) endothelial cells into cells with macrophage-like properties. LCM is known to contain both cytokine(s) and the L-cell virus, a murine retrovirus found in the L929 cell and LCM. Our evidence suggests that both LCM cytokine(s) and the L-cell virus are involved in this PCMV endothelial cell transformation. Criteria for transformation include focus formation, decreased serum requirements for growth, changes in morphology including nonadherence, propagation in suspension culture, and a decreased growth response to stimulation with a known endothelial cell mitogen. Macrophage-like characteristics of this transformed cell, designated as RVTE, include pinocytosis of low-density lipoprotein, Fc receptor-mediated phagocytosis, phagocytosis of bacteria and zymosan, the expression of macrophage enzyme markers, and constitutive production of colony-stimulating factor 1. However, the transformed cell retains several properties of the nontransformed cell including the expression of FVIII:RAg and in vitro self-organization into capillary-like structures. Cloning of RVTE cells clearly shows that both macrophage-like and cerebral microvascular endothelial cell properties are present in the same cell. During self-organization, nontransformed cells express morphologic and functional characteristics classically associated with the macrophage. These findings suggest that some brain capillary pathophysiologies could involve macrophage-like cerebral microvascular endothelial cells. Furthermore, the "reticuloendothelial" phenotypic repertoire expressed by this transformed cerebral microvascular endothelial cell may show that the cerebral capillary endothelial cell in vivo is derived from a hematopoietic and/or phagocytic precursor. 
4	Tilt test for diagnosis of unexplained syncope in pediatric patients. Thirty-five teenage patients with a history of presyncope or syncope underwent a passive head-up tilting to reproduce symptoms of syncope. If tilting alone did not induce syncope, isoproterenol infusion was given to increase heart rate to 150 to 160 beats per minute. In 80% of patients with a history of syncope, identical symptoms could be reproduced during tilting: an abrupt fall in blood pressure combined with profound nodal bradycardia, ranging from 32 to 86 beats per minute. These symptoms were quickly reversed by returning the patient to the supine position. For patients with frequent occurrences of syncope, especially when there was a history of trauma sustained during these episodes, a therapeutic regimen of either beta blockers or 9 alpha-fluorocortisol was begun. The mechanisms of this common cause of syncope in childhood is neurocardiogenic in response to venous pooling and catecholamine-induced tachycardia. The tilt test is an excellent and cost-effective test for the workup of unexplained syncope in childhood. 
1	Metastatic tumors of the umbilicus: a review 1830-1989. Umbilical metastases from known and unknown primary cancers are rare. The eponym "Sister Mary Joseph's nodule" has been used by generations of physicians. The first reports of this clinical sign were from Walshe in 1846. A review of the literature revealed 265 cases from then until 1989. Only 85 cases of umbilical metastasis from unknown primary tumors were found. This review should help us to focus on the common and uncommon primary sites in the diagnosis of patients with this finding. A single case report and the work-up for the hidden primary tumor are described. 
3	Glossopharyngeal schwannoma: review of five cases and the literature. Glossopharyngeal schwannomas are rare tumors in spite of the fact that acoustic schwannomas account for 8%-10% of intracranial tumors. There have been 23 reported cases in the literature. This report of five cases is the largest series of these tumors. The presentation, radiological workup, operation, and long-term postoperative results will be presented, along with a review of the literature. 
5	Failure of transluminal angioplasty in the treatment of myointimal hyperplasia of the internal carotid artery: case report. Recurrent stenosis of the carotid arteries after a carotid endarterectomy for atherosclerosis can occur as a result of myointimal hyperplasia. This condition was treated by percutaneous transluminal angioplasty. Excellent dilatation of the vessel lumen was documented after balloon dilatation. A 6-month follow-up angiographic study, however, demonstrated recurrent high-grade stenosis at the same level in both carotid arteries. Presumably, the failure of percutaneous transluminal angioplasty and the treatment of myointimal hyperplasia of the internal carotid artery results in the same condition after the original endarterectomy, that is, additional myointimal hyperplasia. 
4	Correction of truncus arteriosus with truncal valvar stenosis or insufficiency using two homografts. Surgical correction of truncus arteriosus requires the creation of right ventricular to pulmonary artery continuity and closure of the ventricular septal defect. A variety of conduits have been used including valved and nonvalved. Despite a significant incidence of truncal valvar stenosis and insufficiency, this valve has seldom been replaced. We present 4 cases of truncus arteriosus with truncal valvar stenosis or insufficiency that were repaired using two valved homografts: one to create the pulmonary outflow tract and the other to replace the abnormal truncal valve. Two of these patients are doing well after 4 months. Another child survived the operation and did well for 2 months when she died suddenly. The last child died 14 hours postoperatively from low cardiac output syndrome secondary to diabetic hypertrophic cardiomyopathy. When truncal valvar abnormalities are present, the primary repair of truncus arteriosus in an infant should include replacement of the truncal valve. Total correction can be successfully achieved using two valved homografts, resulting in long-term palliation and freedom from thromboembolic events and the use of anticoagulants. 
5	A dentofacial deformity associated with incontinentia pigmenti: report of a case. A case of IP in a 16-year-old girl has been presented. This patient manifested classic ectodermal and mesodermal anomalies. We present this case to illustrate a rare etiologic factor in the development of dentofacial deformities that can be treated in the conventional manner. 
4	The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study. Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug. 
1	Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory. The ability of rIL-4 to trigger host reactivity against both a chemically induced fibrosarcoma (CE-2) and a spontaneous adenocarcinoma (TS/A) of BALB/c mice was studied. Daily local s.c. administration around tumor draining lymph nodes of 10 injections of progressive amounts (0.00001 to 1000 pg/day) of rIL-4 induced appreciable inhibition of the growth of both tumors after a dose-response survival curve peaking at 0.1 pg/day. Inasmuch as rIL-4 has no direct antitumor activity, as shown by in vitro tests, host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition (LATI). LATI, in fact, is abolished when recipient mice are sublethally irradiated or treated with cyclosporin A, or when the reactivity of CD4+ lymphocytes is suppressed, whereas it is not affected by anti-asialo GM1 antibody. The morphologic data show that rIL-4 LATI rests on the recruitment of several cell reaction mechanisms, among which those that are nonspecific seem to predominate. rIL-4 LATI also leads to a state of long lasting and specific immune memory: the growth of a second contralateral tumor challenge is significantly impaired after LATI. This immune memory takes place after LATI of both the poorly immunogenic CE-2 fibrosarcoma and the TS/A adenocarcinoma, previously classed as nonimmunogenic on the basis of immunization-protection tests. In the latter case, adoptive transfer experiments show that Thy-1+ lymphocytes and, in particular, the CD4 cell-depleted T lymphocyte subpopulation, are responsible for the immune memory. Finally, the ability of rIL-4 to trigger LATI is greater than that of the most effective doses of rIL-2, rIL-1 beta, and IFN-gamma, whereas its association with rIL-1 beta induces a more effective immune memory. 
4	Can heart failure be prevented, delayed, or reversed? A review of the clinical course of chronic heart failure demonstrates that current outcomes remain highly unsatisfactory both in mortality and perhaps more important in morbidity. The extraordinary satisfactory functional responses seen in patients who undergo cardiac transplantation clearly identify the primary cause as the status of the heart itself, whatever the pathophysiologic adjustments of the neuroendocrine system, and interventions of the wide variety of drugs. Since donor hearts are unlikely to be available even from younger sufferers of these clinical syndromes, prevention must be the hallmark. Protection of the viability of myocytes, such as in acute myocarditis and acute infarction, is essential. Myocardial collagen undergoes continual synthesis, and production is greatly stimulated in the presence of hypertrophy caused by increased wall stress. It is possible that excess collagen is intimately involved with diastolic ventricular dysfunction, but that this may be a reversible process if the collagen-producing stimulus is removed. Thus reduction in wall stress and reversibility of ventricular hypertrophy appear to be promising directions. However, to limit the catastrophic effects of chronic heart failure, early recognition of the precursors of these syndromes, prevention of progression, and surgical intervention in valvular heart disease at an optimal point in time are essential. 
5	Anal ulcerations due to cytomegalovirus in patients with AIDS. Report of six cases. Lesions due to cytomegalovirus (CMV) are frequent in the immunocompromised patient. This is particularly the case in patients with AIDS, where the colon and rectum are the regions most often involved. The authors report six cases of anal ulcerations due to CMV in patients with AIDS. These lesions, confirmed histologically, were either isolated or associated with other localizations. Treatment is based on specific antiviral agents but resistance and recurrence can occur. The current report underlines the importance of histologic examination of anal lesions in HIV-infected subjects. 
1	Endothelin-like immunoreactivity in human breast cyst fluid. Immunoreactive endothelin has been detected in 21 of 43 samples of breast cyst fluid (21 cases; 3.5 +/- 0.6 pmol/l, mean +/- SEM. Other 22 cases; not detectable, less than 0.5 pmol/l). Fast protein liquid chromatographic analysis of the immunoreactive endothelin of pooled breast cyst fluid showed two immunoreactive peaks; one in the void volume and the other in the position of endothelin-1. It is probable that endothelin-1 is produced by the epithelial cells lining breast cysts, but significance of the presence of endothelin-1 in breast cyst fluid remains to be elucidated. 
5	Treatment of osteonecrosis of the femoral head by drilling and muscle-pedicle bone grafting. Sixty-one patients with 68 osteonecrotic femoral heads, at different stages of development, were treated surgically; their average age was 36 years. Necrosis followed a fracture in 43 hips and traumatic dislocation in three. It was idiopathic in 14, cortisone-induced in seven and associated with gout in one. The operation of multiple drilling, curettage of the necrotic bone and muscle pedicle bone grafting was performed in all. Cheilectomy of the superolateral part of the femoral head and adductor tenotomy were added in cases of advanced necrosis. Of the several types of muscle pedicle used, tensor fasciae latae anteriorly and quadratus femoris posteriorly were preferred. Full weight-bearing was not permitted for five to six months. The follow-up period varied from three to 12 years. Hip pain was regularly relieved and abduction and rotation of the joints were improved. Those with post-traumatic or idiopathic necrosis did better than those with cortisone-induced necrosis. 
5	Lidocaine local anesthesia for arthroscopic knee surgery. Forty-five patients were evaluated during knee arthroscopy performed using local anesthesia produced by lidocaine with epinephrine to determine the dose-response relationship for operative analgesia. Serum lidocaine concentrations were also measured. Patients were randomized prospectively to receive 20 mL of 0.5%, 1.0%, or 1.5% lidocaine with epinephrine intraarticularly. Intraoperative discomfort was measured by verbal response on an 11-point linear pain scale. Pain scores were significantly higher in patients receiving 0.5% lidocaine during the first 45 min of surgery (P = 0.03). After 45 min, pain scores continued to be higher in the 0.5% lidocaine group than in the 1.0% or 1.5% groups, but the differences were not statistically significant. Ninety-four percent of patients in the 1.5% lidocaine group were willing to repeat this anesthetic technique for surgery compared with 83% of those in the 1.0% lidocaine group and 75% of those in the 0.5% lidocaine group (P greater than 0.05). The duration of postoperative analgesia was similar in all groups. Serum lidocaine concentrations before and 15, 30, 60, and 120 min after instillation of lidocaine were highest in the 1.5% lidocaine group with a peak concentration of 278 ng/mL. No patient had symptoms of lidocaine toxicity. We recommend that lidocaine concentrations of 1.0% or 1.5% be used when 20 mL is instilled intraarticularly for knee arthroscopy based on patient comfort and absence of lidocaine toxicity. 
1	Treatment of spinal cord compression by epidural malignancy in childhood. Epidural spinal cord compression by a malignant tumor is a rare occurrence in children. Both the tumors involved and the extent of involvement of the vertebral column are different in children and adults. Often, the epidural tumor in a child is identified before significant spinal canal compromise has occurred, and these children frequently can be managed by radiation therapy and/or chemotherapy. There is a group of children, however, who have severe spinal canal encroachment by a tumor, as evidenced by a near complete or complete block on myelography. In this study, we report a group of patients with severe spinal cord compression, as documented by imaging studies. We compared the results of a decompressive laminectomy and subtotal tumor resection followed by adjuvant therapy with the results obtained with radiation therapy and/or chemotherapy alone. Thirty-three patients met the criteria for inclusion in the study. Twenty-six were treated with a laminectomy and adjuvant therapy, and 7 were treated without surgical intervention. With surgical therapy, 25 of 26 epidurals were either improved or stable, whereas 4 of 7 nonsurgical patients deteriorated. Especially notable was a decrease in pain in the operative patients immediately after their procedure. There was no surgical mortality or morbidity. The results of this study indicate that children with severe spinal cord compression as evidenced by a near complete or complete block on myelography or filling of 50% or more of the spinal canal on magnetic resonance imaging are best treated by a combination of surgical decompression and tumor removal followed by adjuvant therapy. 
5	Results and complications of angioplasty in fibromuscular disease. Percutaneous transluminal angioplasty (PTA) was used to treat 66 patients with 85 renal artery stenoses due to fibromuscular dysplasia. The hypertension was refractory to medical management in 46 patients, and the initial success rate was 100%. Clinical follow-up has been obtained in all patients, who were followed for as long as 121 months. The recurrence rates were 8% of lesions and 10% of patients. Cumulative patency rate predicted for 10 years was 87.07%. The mean systolic pressure decreased by 52 mm Hg and the mean diastolic pressure decreased by 35 mm Hg in response to treatment. Twenty-six patients (39%) were cured, 39 (59%) were classified as improved, and one (2%) did not respond to PTA. Fourteen of the patients also had elevated blood urea nitrogen and creatinine levels. Renal function was improved in 86% of the patients and stabilized in 14% of the patients. Analysis of the long-term results suggests that PTA should be the initial treatment for choice of patients with fibromuscular dysplasia in the renal arteries. 
4	The iris in Williams syndrome. Forty three children with Williams syndrome and 124 control subjects had their eyes photographed. The photographs were examined by three ophthalmologists and four geneticists of varying experience. A stellate pattern was noted more often in the irides of patients with Williams syndrome (51%) than in those of the control subjects (12%), and was more difficult to detect, or was absent, in heavily pigmented irides. We conclude that the stellate pattern is of diagnostic importance, particularly if the pattern is carefully defined and the clinician is experienced. 
5	Plasma vasoactive intestinal polypeptide concentration determination in patients with diarrhea. Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course. 
2	Association of autoimmune hepatitis with HLA-Bw54 and DR4 in Japanese patients. Human leukocyte antigen-D region-related alleles (human leukocyte antigen DR and DQ) and human leukocyte antigen class I alleles were typed serologically in 31 Japanese patients with autoimmune hepatitis. These patients had increased serum levels of AST and IgG, high titers of autoantibodies, no history of blood transfusion and were negative for HBsAg and antibodies to HBc. Three hundred eighty-six healthy subjects and 30 patients with cryptogenic chronic hepatitis served as control groups. The frequency of DR4 was significantly higher in autoimmune hepatitis patients (90.3%) than in healthy subjects (38.6%) and in cryptogenic chronic hepatitis patients (30%). The frequency of Bw54 was significantly higher in autoimmune hepatitis patients (45.2%) than in healthy subjects (10.9%). The risk to DR4-positive subjects for autoimmune hepatitis was 14.8 relative to healthy subjects. Two of 31 patients (6.5%) with autoimmune hepatitis were positive for antibody to hepatitis C virus; both clearly satisfied criteria for autoimmune hepatitis and both had Bw54 and DR4. This study revealed a highly significant association of autoimmune hepatitis with human leukocyte antigen Bw54 and DR4 in Japanese patients. Among the DR4-positive patients with autoimmune hepatitis, no significant differences were seen between those positive or negative for Bw54 with regard to clinical or laboratory data, relapse of disease or efficacy of prednisolone. Thus human leukocyte antigen class II alleles contribute to susceptibility and resistance to autoimmune hepatitis in Japanese patients, with distinct racial differences from those in white patients. 
5	Nasal reconstruction with articulated irradiated rib cartilage. Nasal structural reconstruction is a formidable task in cases where there is loss of support to both the nasal dorsum and tip. A multitude of surgical approaches and materials have been used for the correction of the saddle-nose deformity with varying degrees of success. Articulated irradiated rib cartilage inserted through an external rhinoplasty approach was used to reconstruct nasal deformities in 18 patients over a 6-year period. Simultaneous use of a midline forehead flap to reconstruct the overlying soft tissue was required in four cases. Follow-up ranged from 1 to 6 years (mean, 2.8 years). Results were rewarding in most cases with marked improvement in nasal support and airway. Revision and/or replacement secondary to trauma or warping of the graft was required in four cases. None of the patients exhibited infection, extrusion, or noticeable resorption. A description of the surgical technique, review of all the cases, and recommendation for continued use of this graft material are discussed. 
5	A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club. BACKGROUND AND METHODS. The Southern Surgeons Club conducted a prospective study of 1518 patients who underwent laparoscopic cholecystectomy for treatment of gallbladder disease in order to evaluate the safety of this procedure. RESULTS. Seven hundred fifty-eight operations (49.9 percent) were performed at academic hospitals, and 760 (50.1 percent) at private hospitals. In 72 patients (4.7 percent) the operation was converted to conventional open cholecystectomy; the most common reason for the change was the inability to identify the anatomy of the gallbladder as a result of inflammation in the region of this organ. A total of 82 complications occurred in 78 (5.1 percent) of the patients; this is comparable with the rates of 6 to 21 percent that have been reported for conventional cholecystectomy. Overall, the most common complication was superficial infection of the site of insertion of the umbilical trocar. A total of seven injuries to the common bile duct or the hepatic duct occurred during the operation, for a rate of 0.5 percent. Four of the seven injuries were simple lacerations, which were repaired after conversion to conventional cholecystectomy. The incidence of bile-duct injury in the first 13 patients operated on by each surgical group was 2.2 percent, as compared with 0.1 percent for subsequent patients. No complications were attributed directly to either cautery or laser-surgical technique, and similar numbers of complications occurred in academic and private hospitals. The mean hospital stay for the entire group was 1.2 days (range, 6 hours to 30 days). CONCLUSIONS. The results of laparoscopic cholecystectomy compare favorably with those of conventional cholecystectomy with respect to mortality, complications, and length of hospital stay. A slightly higher incidence of biliary injury with the laparoscopic procedure is probably offset by the low incidence of other complications. 
1	Oral manifestations of HIV infection and their management. I. More common lesions. Oral lesions are common at all stages of HIV infection. This first of two articles reviews the clinical features and pathogenesis of common oral manifestations of HIV disease (candidiasis, hairy leukoplakia, Kaposi's sarcoma, and HIV-related periodontal disease) and considers current treatment measures. 
5	Chronic anal fissure. A new method of treatment by anoplasty. Chronic anal fissure is a common condition usually treated by maximal anal dilatation or lateral subcutaneous sphincterotomy. The following method is based on a common surgical principal; to widen a stenosed tube a longitudinal incision is made across the stenosed area and this is sutured transversely as in pyloroplasty. This method of anoplasty is simple and appears to have no resultant complications. Further studies are necessary before its value can be established compared to the presently accepted methods of treatment. 
2	Recurrence of duodenal ulcer and elevated serum pepsinogen I levels in smokers and nonsmokers. We determined serum pepsinogen I (PG I) levels by radioimmunoassay in 472 patients with duodenal ulcer and 141 normal subjects to investigate whether serum PG I levels were related to cigarette smoking, and in 225 patients to determine whether the recurrence of duodenal ulcer was related to serum PG I levels or cigarette smoking. Serum PG I levels were not influenced by cigarette smoking in either patients with duodenal ulcer or normal subjects. The recurrence rate of duodenal ulcer not under maintenance therapy was significantly higher in hyperPG I patients than in normoPG I patients, regardless of their smoking habits. Only in hyperPG I patients was the recurrence rate in smokers higher than in nonsmokers. Patients under maintenance therapy showed similar results. Multilogistic regression indicated that hyperPG I had a greater effect than cigarette smoking on ulcer recurrence. These findings indicate that serum PG I levels are not influenced by smoking, and the important characteristic in patients with recurrent duodenal ulcers is the increased serum PG I levels. 
1	Nonrandom chromosomal abnormalities in primary uveal melanoma. We report on 14 cases of clonal chromosomal anomalies in patients with primary uveal melanoma. An increased dosage of chromosome 8 or of parts of the long arm of chromosome 8 (8q) were detected in eight patients (57%). The smallest multiplied area of 8q appeared to be the region 8q2.1----qter. Monosomy of chromosome 3 was seen in six patients (43%), five of which were associated with anomalies of chromosome 8. Increased dosage of parts of chromosome 8q and loss of heterozygosity of chromosome 3, or the combination of both, seemed to be nonrandom for uveal melanoma and may distinguish it genetically from cutaneous malignant melanoma. Anomalies of chromosome 6, mostly resulting in additional material of 6p or a deletion of 6q, were found in six patients (43%). These anomalies, which seem to be common features of cutaneous malignant melanoma, were considered secondary rather than primary changes in uveal melanoma, since they were present only in subclones in most cases. Loss of the Y chromosome, restricted to tumor cells, was detected in four male patients, and loss of one X chromosome was detected in a female patient. 
3	Antiepileptic drugs, cognitive function, and behavior in children: evidence from recent studies. The effects of antiepileptic drugs (AEDs) on cognitive function and behavior in children are reviewed on the basis of published studies. Individual AEDs have been shown to differ--the deleterious effects of phenytoin generally contrasting with the relatively minimal effects of valproate and carbamazepine. Some of the differences between results may be attributed to the psychological tests used and to age differences. However, there appears to be a dissociation between AEDs that affect higher cognitive function, e.g., phenytoin, and those mainly affecting motor function, e.g., carbamazepine, which appears to increase speed of performance, AEDs should be prescribed with care in children with epilepsy, taking account of their differing effects on cognitive function and behavior. 
5	Squamous metaplasia of the peritoneum. The capacity of the peritoneal serosa to undergo metaplasia to mullerian-type epithelium is well recognized. We report a case of squamous metaplasia of the peritoneum that was studied by light microscopy. Immunohistochemical techniques, and electron microscopy. The pathogenesis of peritoneal squamous metaplasia is obscure, but may be a response to chronic irritation. 
2	Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test. The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration. 
2	Audit of results of operations for infantile pyloric stenosis in a district general hospital Because of the proposal that infants with hypertrophic pyloric stenosis should only be treated by surgeons with an interest in paediatric surgery, we carried out a retrospective study to audit our experience in a district general hospital. Forty six infants over a five year period underwent pyloromyotomy. There were no deaths, and 36 infants (78%) made uneventful recoveries. Perforation of the duodenal mucosa occurred during the operation in 11 patients, and eight complications developed in six of these infants. There were seven wound infections, and two patients had vomiting that lasted four days or longer after their operations. There were no long term feeding problems. The results of this study show that such patients can be successfully treated in district general hospitals, and three areas merit special attention: meticulous surgical technique, the use of prophylactic antibiotics, and early graduated feeding. 
5	Emergency department diagnosis of ectopic pregnancy. STUDY OBJECTIVES: To assess the accuracy of the history and physical examination as compared to the addition of serum progesterone screening for ectopic pregnancy in women presenting to the emergency department. DESIGN: Prospective, consecutive case series, N = 2,157. SETTING: ED of the Regional Medical Center at Memphis, a publicly subsidized, 450-bed acute care hospital staffed by residents and faculty of the University of Tennessee, Memphis. TYPE OF PARTICIPANTS: All ED patients with a positive urine pregnancy test treated between January 1 and December 31, 1988. INTERVENTIONS: Screening history, physical examination, and serum progesterone (P) and quantitative human chorionic gonadotropin (hCG) titer. MEASUREMENTS: All discharged patients were given follow-up appointments within two weeks; those found to have a P less than 25 ng/mL were called to return for repeat hCG and transvaginal ultrasound. MAIN RESULTS: One hundred sixty-one of 2,157 patients (7.5%) with a positive urine pregnancy test were found to have an ectopic pregnancy. All but five had a P of less than 25 ng/mL (sensitivity, 97%); four of these were admitted for immediate surgery because of symptoms. Overall, the ED physician detected 89 of 161 ectopics (55.3%) on initial presentation, 53 (60%) of which were ruptured at the time of surgery. Seventy-two patients (44.7%) who were discharged but later found to have an ectopic pregnancy had benign clinical presentations, including 41 with vaginal bleeding. There were no statistically significant differences in the presenting symptoms of patients with unruptured ectopics compared with normal intrauterine pregnancies. All but one of the 72 discharged patients were noted the following day to have a progesterone of less than 25 ng/mL and contacted to return. Eight of these were found to have a ruptured ectopic at the time of surgery. Only 91 of 161 patients (56.5%) with ectopic pregnancy acknowledged one or more clinical risk factors on follow-up questioning. CONCLUSION: The standard history and physical examination, including those performed by gynecologic specialists, are insufficiently sensitive for early detection of unruptured ectopic pregnancy. EDs with a high incidence of ectopic pregnancy should strongly consider implementation of a universal progesterone screening program to decrease unnecessary patient morbidity and the risk of mortality from undiagnosed ectopic pregnancy. 
4	Treatment of hypertension in the elderly: effects on blood pressure, heart rate, and physical fitness. The subjects were 36 hypertensive patients aged 61 to 79 years (mean, 66 years). After a placebo run-in period of one month, each patient was randomly assigned to two months of treatment with 100 mg of metoprolol, 50 mg of captopril, or 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride daily, or placebo. The doses were doubled if diastolic pressure was above 95 mm Hg after one month of treatment. Blood pressure, heart rate, and physical fitness (endurance during a standard cycle ergometer exercise) were measured and side effects assessed after each two-month treatment period. Mean blood pressures were significantly lower after treatment with metoprolol (154/92 mm Hg), captopril (157/92 mm Hg), and hydrochlorothiazide-amiloride (152/91 mm Hg) than after placebo (170/101 mm Hg). Heart rate was significantly lower after treatment with metoprolol (64 beats/minute) than after placebo (77 beats/minute). Exercise endurance was lower after treatment with metoprolol (498 seconds) and hydrochlorothiazide-amiloride (519 seconds) than after placebo (529 seconds) and higher after captopril (541 seconds). More patients reached the target exercise work load after captopril than after the other treatments. No patients withdrew from treatment because of side effects or abnormal laboratory test results. All three active treatments benefited the elderly hypertensive patients and did not lower their physical fitness. Captopril appeared to be more effective than the other two treatments. 
2	Small bile duct abnormalities in sarcoidosis. We report four patients with hepatic involvement of sarcoidosis manifested primarily by bile duct depletion. The patients developed fever, weight loss, anorexia, a markedly elevated alkaline phosphatase, and mildly abnormal serum levels of aspartate aminotransferase. Endoscopic retrograde cholangiopancreatography showed slight intrahepatic irregularities but were not diagnostic of sclerosing cholangitis. Liver biopsy showed predominantly bile duct depletion, ranging from an estimated 10-100% absence of bile ducts in portal areas, which correlated with the degree of fibrosis. The degree of bile duct depletion is useful as a histological marker in patients with sarcoid liver disease. Steroids improve symptoms, but do not inhibit the development of "ductopenia.". 
5	A detachable balloon procedure for a traumatic internal carotid-internal jugular fistula: report of a case A case of a traumatic fistula between the internal carotid artery and the internal jugular vein is reported. The fistula was treated by detachable balloon occlusion and clipping of the internal carotid artery. 
1	Familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex. A 55-year-old man with cerebellar ataxia and steatocystoma multiplex was found to have reduced serum concentrations of total cholesterol, betalipoprotein and apolipoprotein B. Computed tomography revealed atrophy of the cerebellum and brain stem. Of the six family members examined, four had hypobetalipoproteinaemia, and one had mild ataxia. Similar skin lesions were noted in five male relatives. This case represents a rare combination of familial hypobetalipoproteinaemia, cerebellar ataxia and steatocystoma multiplex. 
5	Long-term results following surgical management of aortic graft infection. Between January 1970 and June 1988, a total of 45 patients with aortic prosthetic graft infection underwent removal of the infected aortic prosthesis. In addition, 36 of these patients also underwent revascularization via an extra-anatomic bypass. We analyzed the early and long-term results with respect to survival, limb salvage, freedom from infection, and extra-anatomic graft patency. The 30-day mortality was 24% (11/45), and the amputation rate was 11% (8/73). During a mean follow-up of 36 months (range, 2 to 144 months), 80% (24/30) of the patients remained free of infection and are considered cured. Infection in the extra-anatomic bypass graft was the most common cause of recurrent sepsis and the leading cause of late amputations (four of seven). By life-table methods, 1-year survival was 63% and 5-year survival was 49%. Limb salvage rates at 1 and 5 years were 79% and 66%, respectively. The primary patency rate of extra-anatomic bypass was 43% at 3 years, with the secondary patency rate improved to 65%. These early and late results are in marked contrast to the natural history of untreated aortic graft infection. Nonetheless, a perioperative mortality rate of 24%, a 5-year limb loss rate of 33%, and 3-year graft thrombosis rate of 35% are testimony to the serious nature of aortic graft infection and the need to develop better methods to prevent this complication. 
2	Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence. 
2	Liver pathology in morbidly obese patients with and without diabetes. The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty-three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status. 
5	Effect of indecainide in patients with left ventricular dysfunction. Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 +/- 32 mg; half of the responders achieved achieved efficacy at serum drug concentration greater than or equal to 600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p less than 0.04) and inversely related to creatinine clearance (r = 0.74, p less than 0.05) and ejection fraction (r = 0.71, p less than 0.02). Indecainide prolonged mean PR and QRS intervals (p less than 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r = 0.80, p less than 0.001) and QRS (r = 0.66, p less than 0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects. 
5	In vivo incorporation of [9,10(-3)H]-palmitate into a rat metastatic brain-tumor model. Lipid metabolism of an intracerebrally implanted brain tumor and normal brain was investigated in awake Fischer 344 rats using intravenously injected [9,10(-3)H]-palmitate as a probe. A suspension of Walker 256 carcinosarcoma cells (250 cells in 5 microliters medium), with or without 1% low-melting-point agar, was implanted into the caudate nucleus of rats 8 to 9 weeks old. Control animals received an intracerebral injection without tumor cells. Seven days after implantation, awake rats were infused intravenously for 5 minutes with [9,10(-3)H]-palmitate (6.4 mCi/kg). The rats were killed 20 minutes after initiation of the infusion and coronal brain slices were obtained for quantitative autoradiography and light histological study. Tumor cell masses were histologically well demarcated from the surrounding brain tissue. Tumor tissue incorporation of [9,10(-3)H]-palmitate was heterogeneous, ranging on average from 3.1- to 6.1-fold greater than in the corresponding contralateral brain. In addition, incorporation corresponded to regional tumor cell density. The incorporation rate constant of [9,10(-3)H]-palmitate in tumor was significantly increased compared to control brain and was independent of tumor size. Necrotic areas within tumors showed no incorporation of radiolabeled palmitate. Brain surrounding the tumors and control injection sites showed reactive gliosis, and possessed 30% greater incorporation of [9,10(-3)H]-palmitate than contralateral normal brain. These results suggest that [9,10(-3)H]-palmitate can be used to image brain tumors in vivo, measuring turnover and/or synthesis of tumor and brain lipid. 
2	Incidence and prevalence of ulcerative colitis in the upper Galilee, Northern Israel, 1967-1986. An epidemiological study of ulcerative colitis was performed in the Upper Galilee, Israel, over a 20-yr period (1967-1986). The average annual incidence of ulcerative colitis was 2.23 per 100,000 population, and the prevalence on December 31, 1986, was 44.58 per 100,000. Considering the fact that strict steps were taken to include only definite cases, these figures are probably an underestimation. An increase of the average annual incidence from 0.88 in the period 1967-1976 to 3.79 in 1977-1986 was found. When the data were stratified according to ethnic groups, the highest average annual incidence and the highest point prevalence was found in Israeli-born Jews (6.9 and 138.2 per 100,000 population, respectively). When Jewish residence patterns were compared, the highest average annual incidence and point prevalence were found among Kibbutz members (5.52 and 110.39, respectively), and the lowest (1.94 and 38.76) among Moshav inhabitants. There were 10 Arab patients with an average annual incidence of 0.96 and a point prevalence of 19.27. There were 25 women and 28 men (female:male ratio of 0.89). Among the Jews, the female:male ratio was 1.04. Peak incidence was found in the 25- to 34-yr-old range. No second peak was noticed. Anemia was demonstrated in 66.6% of the women and 27.5% of the men in our study. We suggest that the increase in UC incidence and prevalence in Israeli and Asia/africa-born Jew and in Arabs in the Upper Galilee points toward environmental factors in the etiology of this disease. 
3	Middle cerebral artery strokes causing homonymous hemianopia: positron emission tomography. Eight patients were evaluated with 18F-fluorodeoxyglucose positron emission tomography between 3 and 30 days after isolated stroke involving the middle cerebral artery territory that caused homonymous hemianopia. Diffuse hypometabolism was present throughout the damaged cerebral hemisphere, even in cortical areas not obviously ischemic by clinical examination or neuro-imaging. Glucose metabolism in primary and association visual cortex of the damaged hemisphere was decreased by more than 47% (p less than 0.01). Metabolism in the undamaged hemisphere was less profoundly affected, but significant decrements were found in calcarine (40%; p less than 0.01) and lateral occipital cortex (35%; p less than 0.05). 
5	Prognostic significance of serosal invasion in carcinoma of the stomach. Two hundred and seventy-seven patients with advanced carcinoma of the stomach invading the serosa were studied with regard to the relationship between the length of the serosal invasion (LSI) and prognosis, with a division made between expanding and infiltrative types of tumors. Among patients with expanding types of tumors, five year survival rates were 40 per cent in patients with LSI less than 4.0 centimeters, 33 per cent in patients with LSI 4.1 to 6.0 centimeters and 13.0 per cent in patients with LSI more than 6.0 centimeters. Among those patients with infiltrative types of tumors, those with less than 2.0 centimeters of LSI had a better prognosis (five year survival rate of 53 per cent), whereas those patients with a LSI more than 2.0 centimeters had a very poor prognosis (five year survival rate of less than 20 per cent) and the significant LSI on prognosis was found to be 2.0 centimeters. Involvement of the lymph node and metastasis to the liver were not affected by LSI, whereas the rates of peritoneal dissemination and direct invasion to neighboring organs increased with an increase in LSI. Knowledge of these factors facilitates the planning of postoperative treatment. 
2	The Munich Gallbladder Lithotripsy Study. Results of the first 5 years with 711 patients. OBJECTIVE: To evaluate the long-term results of three types of shock wave treatment in patients with radiolucent gallbladder stones. DESIGN: Cohort study. SETTING: Single-center trial. PATIENTS: Of 5824 patients with gallstones, 19% were eligible; 711 patients were treated. INTERVENTIONS: Patients received extracorporeal shock wave lithotripsy as well as adjuvant therapy with bile acids. RESULTS: Lithotripsy was done in three ways, using a water-tank lithotriptor (group A), a water-cushion lithotriptor at low energy levels (group B), and a water-cushion lithotriptor at high energy levels (group C). The rate of complete fragment clearance 9 to 12 months after lithotripsy was done differed significantly among the three groups: Among patients with single stones of 20 mm or less in diameter, the rate of fragment clearance for group A was 76%; for group B, it was 60%; and for group C, it was 83% (P = 0.03). Among patients with single stones of 21 to 30 mm, the rate of fragment clearance for group A was 63%; for group B, it was 32%; and for group C, it was 58% (P less than 0.005). Among patients with two or three stones, the rate of fragment clearance for group A was 38%; for group B, it was 16%; and for group C, it was 46% (P = 0.01). Patients with fragments of 3 mm or less 24 hours after lithotripsy was done showed a higher probability of fragment disappearance than did those with larger fragments (P less than 0.001). The clearance rate was higher in patients who were compliant than in those who were noncompliant with bile acid therapy (P less than 0.001). Adverse effects included liver hematoma in 1 patients, biliary pain attacks in 253 patients (36%), mild biliary pancreatitis in 13 patients (2%), and cholestasis in 7 patients (1%). Elective cholecystectomy was done in 16 patients (2%), and endoscopic sphincterotomy was done in 4 patients (1%). CONCLUSIONS: The rate of complete disappearance of stones after shock wave therapy depends on the size and the number of the initial stones, the diameter of the largest fragment, and the mode of shock wave treatment. Adjuvant therapy with bile acids appears to be important for complete fragment clearance. 
1	A randomized trial comparing two methods of cold knife conization with laser conization. In a randomized study, 62 women were submitted to cold knife conization with application of Sturmdorf sutures, 60 to cold knife conization without sutures, and 61 to laser conization. Early hemorrhage occurred in 1.6, 13.3, and 6.6% of women, respectively (P less than .05), and late hemorrhage in 15.3, 3.6, and 11.7%, respectively. Considering early and late hemorrhage together, there was no significant difference among the three treatment groups. Dysmenorrhea tended to be more common after application of Sturmdorf sutures, as it was reported by 27.8, 13.2, and 14.3% of patients, respectively, but the difference was not statistically significant. Dysmenorrhea occurred in 13% of the cases with a cone height of 20 mm or less and in 26% of the cases with a cone height greater than 20 mm (P less than .05). Endocervical cells were present significantly more often after sampling with a cytobrush than with a cotton swab (P less than .0001), whereas the method of conization had no influence. In smears obtained with a cytobrush, endocervical cells were present in 88.0, 84.9, and 82.5% of the cases; in smears obtained with a cotton swab, endocervical cells were present in 46.6, 57.7, and 54.5%, respectively. We conclude that cold knife conization without Sturmdorf sutures is about equal to laser conization in overall complications, but the laser is preferable for outpatient treatment because of a lower frequency of early hemorrhage. Sturmdorf sutures should be avoided. Smears at follow-up should be taken with a cytobrush and a wooden spatula. 
4	Left ventricular passive diastolic properties in chronic mitral regurgitation. BACKGROUND. In chronic mitral regurgitation, the myocardium responds to the increased filling volume by geometric alteration and eccentric hypertrophy. This study was designed to evaluate the effects of a pure volume overload on left ventricular diastolic chamber and myocardial properties and to assess the relation of passive diastolic function to systolic ejection performance. METHODS AND RESULTS. By use of simultaneous cineangiography and left ventricular micromanometry, left ventricular passive diastolic stiffness was evaluated in nine normal controls (group 1), 14 patients with chronic mitral regurgitation and a normal ejection fraction (greater than or equal to 57%, group 2), and 13 patients with mitral regurgitation and a reduced ejection fraction (less than 57%, group 3). Passive diastolic function was evaluated by using a three-constant elastic model. Left ventricular chamber properties were represented by the relation of pressure to volume; myocardial properties were evaluated by relating myocardial midwall stress to midwall strain. The constant of left ventricular chamber stiffness was decreased in group 2 compared with controls (p less than 0.05) but it was normal in group 3. The constant of myocardial stiffness was increased in group 3 compared with groups 1 and 2 (p less than 0.01). Among patients with mitral regurgitation, there was a significant inverse relation between ejection fraction and the constant of myocardial stiffness (r = -0.83). CONCLUSIONS. The chronic adaptation to volume overload in chronic mitral regurgitation tends to decrease left ventricular chamber stiffness. Patients with mitral regurgitation and a depressed ejection fraction demonstrated diastolic myocardial dysfunction. Compromised diastolic function in patients with chronic mitral regurgitation and reduced systolic performance may contribute to the clinical manifestations of congestive heart failure. 
5	Vascular abnormalities in epidermal nevus syndrome. We report a patient with epidermal nevus syndrome and right hemispheric infarct and review 3 others with neurologic manifestations best explained by ischemia or hemorrhage. Each had a significant vascular abnormality such as occlusion or blood vessel dysplasia. None had hemimegalencephaly. We hypothesize that underlying vascular dysplasia is the cause of the neurologic lesions in these patients. 
1	Keratin subsets in spindle cell sarcomas. Keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins. The presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone-fixed frozen sections. Results revealed that keratins 8 and 18 were present in a high number of tumors: 9 of 9 synovial sarcomas, 5 of 7 leiomyosarcomas, 5 of 5 malignant schwannomas, and 1 of 4 undifferentiated spindle cell sarcomas. In addition to keratins 8 and 18, the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19. Also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution, but desmoplakin was absent in other spindle cell sarcomas. Furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas. In contrast, keratins 7, 13, and 19 were practically absent in leiomyosarcomas, malignant schwannomas, and undifferentiated spindle cell sarcomas. The widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells, previously described in cultured transformed fibroblasts. The presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas. 
5	Surgical treatment of hydatid disease of the liver. A 20-year experience. The medical records of 135 consecutive patients (74 women and 61 men) who underwent surgery for hydatid liver disease were reviewed. The patients ranged in age from 4 to 81 years. Twenty-seven patients had undergone previous surgery for hydatid liver disease. Cysts were solitary in 100 patients and multiple in 35 patients. Seventeen patients had concomitant extrahepatic disease. Conservative procedures were used in 71 patients (capitonnage in 50 patients and partial pericystectomy in 21 patients). Radical procedures were used in 64 patients (total pericystectomy in 35 patients, subtotal pericystectomy in 16 patients, and wedge or major liver resection in 13 patients). Operative mortality was 2.2% and morbidity rate was 23.7%. Recurrent disease was found in 13 patients at a mean interval of 3 years from the first operation. Better short- and long-term results were obtained with the use of radical procedures. 
2	Albumin absorption and protein secretion by the gallbladder in man and in the pig. To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders. 
1	Cutaneous angiolipoleiomyoma. We describe eight cases of cutaneous angiolipoleiomyoma, a rare tumor previously reported only once under the term cutaneous angiomyolipoma. Clinically, the tumors were acquired, solitary, asymptomatic nodules that were always acral in location. Patients' ages ranged from 33 to 77 years (median 52.6 years); the male/female ratio was 7:1. Signs of tuberous sclerosis or renal angiomyolipoma were absent in all cases. Histologically, the tumors were subcutaneous, well circumscribed, and composed of smooth muscle, vascular spaces, connective tissue, and mature fat. In some tumors the fat was the predominant component, and in others smooth muscle predominated. Elastic tissue stains revealed that some blood vessels had developed an elastic lamina whereas other blood vessels lacked it. Additional histologic features occasionally observed included vascular thrombi, glomus bodies, and focal mucin deposition. 
2	Regulation of insulin-like growth factor II gene expression by hepatitis B virus in hepatocellular carcinoma. In this study we investigated the regulation of insulin-like growth factor II gene expression to explain a role for this growth factor in concert with hepatitis B virus involvement in the development of hepatocellular carcinoma from cirrhosis. Sections of normal liver and tumor and non-tumor-bearing liver disease tissue were hybridized in situ with [35S]-labeled insulin-like growth factor II oligonucleotide probe. Parallel sections were tested for presence of insulin-like growth factor II polypeptide using immunohistochemistry. To investigate a possible role for hepatitis B virus in insulin-like growth factor II gene expression in hepatocellular carcinoma, results were analyzed against patient seropositivity for hepatitis B virus. Levels of insulin-like growth factor II transcripts in normal liver (n = 4) sections and in those from non-tumor-bearing individuals (n = 10) were so low that specific signal was not detectable above homogeneous tissue background. In contrast, 4 of 8 (50%) of the sections of hepatocellular carcinoma arising from cirrhosis or noncirrhotic chronic liver disease with hepatitis B virus involvement showed increased expression of insulin-like growth factor II messenger RNA transcripts. Up-regulation was observed in cell foci in the hepatocellular regions of the surrounding cirrhotic lobular cells and the fibrous septa. Numerous cell foci were observed in patch distribution in the tumor areas. The level of insulin-like growth factor II messenger RNA transcripts in sections of hepatocellular carcinoma arising from cirrhotic and noncirrhotic tissues obtained from patients seronegative for hepatitis B virus was similar to that of normal liver. 
5	The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. T-associated maternal effect (Tme) is the only known maternal-effect mutation in the mouse. The defect is nuclear-encoded and embryos that inherit a deletion of the Tme locus from their mother die at day 15 of gestation. There are many genomically imprinted regions known in the mouse genome but so far no imprinted genes have been cloned. The Tme locus is absent in two chromosome-17 deletion mutants, Thp and the tLub2, and its position has been localized using these deletions to a 1-cM region. We report here that the genes for insulin-like growth factor type-2 receptor (Igf2r) and mitochondrial superoxide dismutase-2 (Sod-2) are absent from both deletions. Probes for these genes and for plasminogen (Plg) and T-complex peptide 1 (Tcp-1) were used in pulsed-field gel mapping to show that Tme must lie within a region of 800-1,100 kb. We also demonstrate that embryos express Igf2r only from the maternal chromosome, and that Tcp-1, Plg and Sod-2 are expressed from both chromosomes. Therefore Igf2r is imprinted and closely linked or identical to Tme. 
5	Progressive coronary luminal narrowing after cardiac transplantation. Accelerated coronary disease is a major factor limiting long-term survival in cardiac transplant recipients. Coronary angiography was obtained a mean of 5.1 weeks posttransplantation and annually thereafter. Replicate projections recorded after nitroglycerine administration were quantitated using computer-assisted edge detection. Five hundred and fifteen coronary segments in 25 patients having 1-year follow-up and 353 segments in 18 patients reaching 2-year follow-up were compared with baseline angiograms. Significant change was defined as +/- 0.10 mm, equal to 3.8% change in diameter based on three standard deviations obtained from estimation of measurement error. Mean coronary diameter fell from 2.44 +/- 0.26 mm at baseline to 2.21 +/- 0.34 mm (p less than 0.001) at 1-year follow-up. This rate of diameter decline was 20-fold more rapid during the initial posttransplantation year than the rate of change of visually normal segments in nontransplant patients with coronary atherosclerosis elsewhere. There was no significant drop in mean diameter between the first and second year in those patients who had second-year studies. Decrease in absolute diameter for vessels greater than 2.9 mm significantly exceeded diameter reduction for smaller vessels but did not differ when considered as a ratio of vessel diameter. In 21 of 25 patients, mean coronary diameter reduction exceeded the three-standard deviation threshold at their last angiogram, but only two of these patients had visually detectable transplant coronary disease. 
3	Cervical spine diastematomyelia in adulthood. Adult cervical diastematomyelia is a rare malformation and is usually associated with posterior element anomalies. A case of isolated cervical diastematomyelia, which was initially thought to be a herniated cervical disc, is described. Diagnosis and surgical management are discussed. 
3	Retrograde transurethral balloon dilation of prostate: innovative management of abacterial chronic prostatitis and prostatodynia. Retrograde transurethral balloon dilatation (RTBD) of the prostate recently has been suggested as alternative therapy for patients with benign prostatic hyperplasia (BPH). Seven patients with documented functional urinary outlet obstruction at the level of the bladder neck or prostatic urethra underwent RTBD of prostate. Each patient had a classic diagnosis of abacterial chronic prostatitis or prostatodynia based on history, physical examination, and localization cultures. Prior to RTBD of prostate, patients underwent cystoscopy, voiding cystourethrogram, urodynamic and uroflow studies. RTBD of prostate was done as an outpatient procedure requiring intravenous sedation or general anesthesia. Dilation was performed with a 25-mm urethroplasty balloon catheter inflated at 3.5 atm of pressure for twenty minutes. Improvement in voiding symptomatology was noted in all patients and graded numerically (0-10 scale), with ten indicating normal voiding. Follow-up to date ranges from one to five months. This technique may have promise as a treatment option in patients with abacterial chronic prostatitis and prostatodynia. 
5	Zollinger-Ellison syndrome. Relation to Helicobacter pylori-associated chronic gastritis and gastric acid secretion. Since Helicobacter pylori infects the gastric mucosa in most patients with chronic duodenal ulcer, infection with this organism has been implicated in the pathogenesis of this common disease. We postulated that if H. pylori is pathogenic in the usual type of duodenal ulcer, it should be less common when duodenal ulcer has another, specific etiology, such as Zollinger-Ellison syndrome. Gastric mucosa was compared from 18 patients with proven Zollinger-Ellison syndrome (17 of whom had had duodenal ulcer disease) and 18 controls with chronic duodenal ulcer without such a diagnosis. All subjects, who were matched for age and sex, had undergone elective gastric resections. Gastric tissues were stained by hematoxylin-eosin and Giemsa and were reviewed by an experienced pathologist who was unaware of the diagnosis. The frequency of H. pylori in patients with Zollinger-Ellison syndrome (8/18) was lower than in controls with duodenal ulcer (16/18; P less than 0.02). Moreover, chronic antral gastritis scores were higher in patients with duodenal ulcer (P less than 0.01). In Zollinger-Ellison syndrome, peak acid output was lower in patients positive (median 22 meq/30 min) compared to those negative for H. pylori (median 32 meq/30 min; P less than 0.02) but serum gastrin was correspondingly lower in patients positive for H. pylori (P less than 0.05). H. pylori infection appears to be more frequent when duodenal ulceration is not associated with another etiology, such as acid hypersecretion in Zollinger-Ellison syndrome. H. pylori infection in Zollinger-Ellison syndrome may also be associated with decreased gastric acid secretion. 
5	Percutaneous transvesical chorionic villus sampling: an alternative approach to the retroverted uterus. In 458 consecutive chorionic villus sampling (CVS) procedures, we observed a significant influence of uterine position upon sampling efficacy. Compared with anteverted (N = 243) or axial (N = 149) locations, the retroverted uterus (N = 66) was associated with a lower mean sample weight per aspiration (22, 18, and 15 mg, respectively; P less than .01) and a greater frequency of multiple-pass procedures (23, 31, and 52%, respectively; P less than .0001). To improve sampling efficiency in selected cases of uterine retroversion, we adopted a transvesical approach. When compared with transabdominal or transcervical techniques, transvesical CVS had the highest single-pass success rate (33, 33, and 60%, respectively). Only one in 30 transvesical cases required three placental passes, compared with nine of 36 retroverted uteri sampled by either transabdominal or transcervical techniques (P less than .05). The mean transvesical sample weight was 18.7 mg; at least 10 mg was retrieved in all cases. Post-procedure bleeding occurred in four instances and an additional patient suffered a spontaneous loss at 16 weeks' gestation. Aneuploidy was found in four of 30 biopsy specimens, and the remaining pregnancies either have delivered at term (N = 18) or are continuing (N = 7). Our preliminary experience suggests that selected use of this CVS method may improve sampling efficiency without increasing the incidence of complications. 
5	New insights into the causes of cancer. Recent advances in molecular biologic analysis have led to major new insights concerning the genetic mechanisms underlying the development of cancer. This article examines the current state of our understanding of the genetic basis underlying the possible mechanisms of carcinogenesis and metastasis. The nature of the genetic lesions found in some cancer-causing genes, cancer-inhibiting genes, growth factor genes, and metastasis genes is discussed, as is the impact that these may have on clinical oncology. 
5	Three-dimensional analysis of 61 human endolymphatic ducts and sacs in ears with and without Meniere's disease. We used light microscopy and computerized graphic reconstruction techniques to examine the endolymphatic duct and sac in 20 pairs of bones from patients with Meniere's disease and 21 bones from controls. The diameters of the endolymphatic duct and the proximal portion of the vestibular aqueduct were significantly smaller in Meniere's disease ears than in controls. Graphic reconstructions showed the Meniere's sacs to be smaller and to have fewer tubular epithelial structures in the intraosseous portion than in the control ears. The median volume of the sac in the Meniere's disease side was substantially lower than in the contralateral ear. The width of the external aperture of the vestibular aqueduct was significantly smaller in Meniere's disease ears than in controls. These findings indicate that the size not only of the vestibular aqueduct but also of the sac is reduced in Meniere's disease. The results may suggest that the endolymphatic sac is pathologically changed in Meniere's disease and that a reduced resorptive capacity of a small endolymphatic sac could result in endolymphatic hydrops. 
1	Modified technique of Pringle's maneuver in resection of the liver. Crushing of the hepatic parenchyma with hepatic clamps to minimize blood loss during resection of the liver leads to mechanical damage of hepatocytes. Pringle's maneuver may precipitate liver failure by hepatic warm ischemia as well. Therefore, we controlled bleeding from the surface of the resection by using light compression on the hepatic parenchyma with a band while applying a hepatic arterial clamp at the hepatic hilus. This vascular control method can be done because the portal pressure is about one-tenth of the hepatic artery pressure and provides an efficient and harmless transection of the liver. 
4	Hepatocellular carcinoma with tumor thrombus extending into the right atrium: report of a successful resection with the use of cardiopulmonary bypass. Hepatocellular carcinoma with a tumor thrombus extending into the right atrium has been considered beyond the reach of resection. These patients usually die within a short period because of pulmonary embolism, heart failure, or cancer progression. The only treatment is hepatic resection with removal of the tumor thrombus. A 38-year-old woman underwent left lobectomy with removal of the tumor thrombus with the use of cardiopulmonary bypass. The patient had an uneventful course and is doing well 15 months after surgery, without signs of recurrence. We have proved that hepatic resection with removal of a tumor thrombus extending into the right atrium can be carried out successfully. The next problem is whether the lives of these patients can be prolonged by this operation. 
2	Small intestinal transit in the portal hypertensive rat. The purpose of this study was to determine the effects of portal hypertension on gastrointestinal transit. Portal hypertension was induced in a group of 15 rats by the staged portal vein ligation technique. A control group of 15 rats underwent a sham operation. Ten days later, a 51Cr-labeled Krebs' buffer solution was instilled into the duodenum and the distribution or radioactivity along the length of the small intestine was determined after 15, 30, and 60 minutes. Portal hypertension was consistently established in the study group; splenic pulp pressure (mm Hg, mean +/- SD, portal hypertensive vs. control) was 20.0 +/- 3.9 vs. 12.7 +/- 3.9, P less than 0.002. Various measures of intestinal transit revealed delayed transit in the portal hypertensive group. Retention of radioactivity in the most proximal quartile of the intestine was greater [percentage retained (portal hypertensive vs. control) was 57.9 +/- 17.3 vs. 31.2 +/- 15.3, P less than 0.02, 49.1 +/- 15.5 vs. 28.3 +/- 4.8, P = 0.03, and 42.4 +/- 17.6 vs. 29.0 +/- 8.8, P = 0.08, at 15, 30, and 60 minutes, respectively] and the geometric mean of transit was located more proximally (P less than 0.02) at each study interval in the portal hypertension group. It was concluded that portal hypertension is associated with delayed intestinal transit. This abnormality could predispose to bacterial overgrowth and contribute to altered digestion and absorption. 
1	Intracranial chordoma in a preadolescent. Case report. Chordomas are rare tumors derived from notochord remnants occurring primarily in the sacrum, clivus, and cervical regions. Exceptionally, these tumors occur in children, though usually in the sacrum. Eight cases of clivus chordoma have been described in preteenagers. In this report, a clival chordoma with unusual radiologic features is described in an 11-year-old boy. The literature regarding this entity is reviewed. 
5	Correlation between laboratory findings and clinical outcome after restorative proctocolectomy: serial studies in 20 patients with end-to-end pouch-anal anastomosis. Clinical function and anorectal physiological function were assessed and correlated in 20 patients with ulcerative colitis before restorative proctocolectomy and 3, 7, and 12 months after operation. The entire anal sphincter was preserved by means of a stapled pouch-anal anastomosis. Before operation, the median resting anal pressure was 79 cmH2O (interquartile range 70-89 cmH2O), the rectoanal inhibitory reflex was present in all patients and anorectal 'sampling' was noted in 16 of 20 patients. Three months after operation, resting anal pressure was 68 cmH2O (range 50-87 cmH2O) (P less than 0.001), the reflex was present in only three patients (P less than 0.001) and sampling was observed in one patient. After 7 months, resting anal pressure was 76 cmH2O (range 64-89 cmH2O), the reflex was present in 11 patients and sampling was observed in nine patients. At 12 months, resting anal pressure was 84 cmH2O (range 66-94 cmH2O), the reflex was present in 19 patients and sampling was observed in 17 patients. The compliance and capacity of the reservoir increased significantly. Ability to discriminate flatus from faeces was associated with return of the rectoanal reflex and sampling. 
3	Stroke rehabilitation: a geropsychological perspective. Rehabilitation medicine and geriatric medicine are similar in their concern for functional improvement in the face of chronic medical conditions. Although many patients served by rehabilitation medicine fall within the geriatric age range, a knowledge of normal aging does not necessarily inform clinical decision making or research practices in rehabilitation. Using stroke as an example of a disorder affecting primarily geriatric patients and requiring the technology of rehabilitation, ways in which age might affect assessment of outcome are examined. Three areas dealing with conceptual and methodologic issues--depression, neurochemical interventions, and family--are highlighted. The final section outlines recommendations for research on rehabilitation outcome of geriatric stroke patients. 
2	A case of severe pancytopenia caused by ibuprofen. We here present the case of a patient with severe neutropenia, haemolytic anaemia and thrombocytopenia associated with long-term use of ibuprofen. The blood parameters rapidly normalized when the drug was discontinued, and no further treatment, except for a short course of antibiotics, was required. 
4	Arterial revascularization by laser angioplasty: first Italian experiences. Eighty-seven laser angioplasty procedures were performed on 85 patients (73 men and 12 women). In the first phase (54 patients) a broad selection process included long occlusions (23.9 cm avg) and vessels with heavy calcification; in the second phase (31 patients) the authors treated vessels with shorter occlusions (10 cm avg) and less calcific. The primary success rate, based on number of procedures (73.5% overall) was 69% in the first phase but reached 81.3% in the second phase. There were 14 perforations (16%), 8 dissections (9.4%), and 4 peripheral emboli (4.7%). Six-month follow-up shows that the Winsor index maintained its initial improvement in 76.5% of all patients, or 62% in just the long occlusions. These data and a review of the cases suggest that no more of 10-20% of patients with claudication in lower extremities can be treated by laser angioplasty; the authors consider ideal candidates those patients who noncalcific lesions in the common iliac or superficial femoral arteries at the III medium level with obstructions shorter than 8 cm and good runoff. 
4	Ulcerative colitis and giant cell arteritis associated with sensorineural deafness Sensorineural deafness is rarely associated with both ulcerative colitis and giant cell arteritis. A patient is described in whom acute sensorineural deafness occurred in association with episcleritis, ulcerative colitis and clinical features suggesting giant cell arteritis. 
1	An unusual organoid tumor. Alveolar soft part sarcoma or paraganglioma? The histogenesis of alveolar soft part sarcoma (ASPS) is a subject of continued debate. Although many recent reports suggest a muscle origin, others advocate a neuroendocrine derivation. A tumor in the chest wall of a 16-year-old woman was diagnosed and treated as ASPS. The light microscopic, electron microscopic, and immunohistochemical findings showed features of both ASPS and paraganglioma. In addition, this lesion was positive for antibody to glucagon, a characteristic of neither ASPS nor paraganglioma, although seen in a few gangliocytic paragangliomas. This case demonstrates the need for continued inquiry into the histogenesis of ASPS. 
3	Genetic cause of a juvenile form of Tay-Sachs disease in a Lebanese child. Abnormality in the beta-hexosaminidase alpha gene underlying the clinical phenotype of a Lebanese patient with a juvenile form of Tay-Sachs disease has been studied. Clinical features were progressive spasticity, ataxia, and cognitive decline. The protein coding sequence of several beta-hexosaminidase alpha-chain complementary DNAs isolated by polymerase chain reaction was completely normal except for a G-to-A transition at nucleotide position 1511 within exon 13, which resulted in substitution of the normal arginine 504 (CGC) with histidine (CAC). Although the patient was from a first-cousin marriage, she was heterozygous for this mutation. The abnormality in the other allele, which is carried by the father, was not identified, except that it is neither of the two mutations responsible for the infantile Jewish Tay-Sachs disease. Biosynthetic and immunoprecipitation studies in cultured fibroblasts showed synthesis of the alpha-chain precursor, but the mature form of the alpha-subunit was not detected. 
4	Morphological observations late (greater than 30 days) after clinically successful coronary balloon angioplasty. This report describes clinical, morphological, and histological findings late (1.6-24.1 months [average, 8.2 months]) after clinically successful coronary balloon angioplasty in 20 necropsied patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 (70%) of patients, including six patients with sudden coronary death. Of the 20 patients, 14 (70%) had cardiac causes of death and six (30%) had noncardiac causes of death. Two major subgroups of histological findings were observed: 1) intimal proliferation (60%) and 2) atherosclerotic plaques only. Of the eight sites with atherosclerotic plaques only, six were eccentric lesions and two were concentric lesions. No morphological evidence of previous angioplasty injury (cracks, breaks, or tears) was observed in the eight patients with atherosclerotic plaques only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphological findings at angioplasty restenosis sites, specific treatment strategies for coronary artery balloon angioplasty restenosis are proposed. 
2	Prognosis of Wilsonian chronic active hepatitis. Twenty of 320 patients with Wilson's disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis. 
3	Limited selective posterior rhizotomy for the treatment of spasticity secondary to infantile cerebral palsy: a preliminary report. A limited selective posterior rhizotomy was performed on 30 children suffering from spasticity secondary to infantile cerebral palsy. As opposed to standard techniques that stimulate and divide the dorsal rootlets from L2 to S1, we dissected L4, L5, and S1 dorsal roots through an L5 to S1 laminectomy. Eight to 12 rootlets from each root were electrically stimulated with two unipolar electrodes (pulse width, 50 microseconds; 10-50 V). The muscle responses were observed visually and registered by electromyography. Those rootlets associated with an abnormal motor response as evidenced by sustained muscular contraction or by prolonged electromyographic response were divided. Spasticity was scored from 0 to +. The muscular groups assessed were those involved in the flexion of the shoulder, elbow and wrist in the upper limbs, and those involved in flexion and adduction of the hip, flexion of the leg, and plantar flexion in the lower limbs. The patients were assessed 1 week before and 6 months after the operation. Reduction of spasticity was observed in all the muscular groups, and all the patients presented functional improvement of motor abilities. These preliminary results indicate that a limited procedure that reduces the extension of the laminectomy and the length of the operation could be effective for treating spasticity secondary to infantile cerebral palsy. 
5	Reconstruction of mandibular defects in irradiated patients. In this prospective study, mandibular reconstruction using titanium plates was evaluated in 31 patients treated between July 1988 and January 1990. Sixteen patients had prior surgery; 13 had prior radiotherapy. In 11 patients, prior radiation and surgery had failed. Sixteen patients received postoperative radiotherapy either in standard or accelerated fractions. Twelve patients had complications of either intraoral (8), extraoral (5), or combined (1) plate exposure or fistula formation (2). Factors significantly related to complications were poor nutrition, accelerated radiation, and recurrence. Sixty-one percent of all patients healed uneventfully. When patients with complications secondary to recurrence who subsequently died were excluded, the success rate was 73%. Only one patient had an unacceptable result that produced a cosmetic and functional deformity despite secondary repair. 
4	Influence of dietary cod liver oil on fatty acid composition of plasma lipids in human male subjects after myocardial infarction. A randomized crossover study was carried out to investigate the fatty acid profile and concentrations of plasma lipids in male patients with myocardial infarction (MI) who supplemented their diet with 20 ml cod liver oil daily for 6 weeks. Subjects were divided into two groups, A and B. Group A received cod liver oil daily for 6 weeks after hospital discharge, but none for the subsequent 6 weeks. Group B did not start taking cod liver oil until 6 weeks after hospital discharge, and they then took cod liver oil for 6 weeks. Diet, medication or smoking habits were kept as constant as possible during the study. During the period of cod liver oil intake, eicosapentaenoic acid (20:5 (n-3), EPA) and docosahexaenoic acid (22:6 (n-3), DHA) increased significantly in phospholipids (PL), triglycerides (TG) and cholesterol esters (CE), whereas linoleic acid (18:2 (n-6), LA), dihomo-gamma-linolenic acid (20:3 (n-6), DHGLA) and arachidonic acid (20:4 (n-6), AA) were significantly decreased in phospholipids. The plasma level of TG was significantly decreased during the cod liver oil intake. Total cholesterol, high density lipoprotein (HDL) cholesterol, and levels of apolipoproteins A1 and B were not affected by cod liver oil in these MI patients. 
5	Use of immunoelectron microscopy to show Ebola virus during the 1989 United States epizootic. A filovirus, serologically related to Ebola virus, was detected by "post-embedment" immunoelectron microscopical examination of MA-104 cells. These had been infected by inoculation with serum samples obtained during the 1989 epizootic in cynomolgus monkeys (Macaca fascicularis), imported from the Philippines and maintained at Reston, Virginia, USA, a primate holding facility. The immunoelectron microscopy method, when used in conjunction with standard transmission electron microscopy (TEM) of infected cells, provided consistent results and was simple to perform in this epizootic. It is concluded that immunoelectron microscopy is potentially useful in the direct immunological diagnosis of Ebola and related filoviral infections (such as Marburg) in clinical samples obtained from those with acute infection. 
5	Recurrent thoracic outlet syndrome. Recurrent symptoms develop in 15% to 20% of patients undergoing either first rib resection or scalenectomy for thoracic outlet syndrome. Over the past 22 years 134 operations for recurrence were performed in 97 patients. Four operations were used: transaxillary first rib resection (26); supraclavicular first rib resection with neurolysis (15); scalenectomy with neurolysis (58); and brachial plexus neurolysis (35). Complications included temporary plexus injury (0.7%), temporary phrenic palsy (3.7%), and permanent phrenic palsy (1.4%). The combined primary success rate of all four operations for recurrence was 84% in the first 3 months. This fell to 59% at 1 to 2 years; 50% at 3 to 5 years; and 41% at 10 to 15 years. No significant difference was found in results between the four operations used for recurrence. When recurrence was caused by trauma the results of reoperations were better than when recurrence was spontaneous. The primary success rates of three initial operations for thoracic outlet syndrome were compared to their secondary success rates (improved after reoperation). By use of life-table methods, reoperation improved the 5- to 10-year success rate of transaxillary first rib resection from 69% to 86% and for scalenectomy from 69% to 84%. Reoperation is successful in most cases of recurrent thoracic outlet syndrome and better when recurrence is the result of a neck injury. 
1	Preferential mitogenic activity for myoblast-like cells can be extracted from uterine leiomyoma tissues. The presence of mitogen(s) in leiomyoma extracts stimulating cells with the fibroblast, myoblast, and osteoblast phenotype was documented. Mitogenic activity in leiomyoma extracts was acid stable and sensitive to tryptic digestion. Reverse-phase high-performance liquid chromatography successfully separated mitogen(s) with preferential activity for myoblast cells from mitogens with a broad type of cell specificity and from inhibitors. This leiomyoma-derived preferential activity for myoblasts was absent in identically treated myometrial and endometrial extracts. This suggests that leiomyoma-derived substances with preferential growth factor activity for myoblast-like cells may play a role in the pathophysiologic characteristics of uterine leiomyomas. 
5	Congenital cyst of common bile duct: an unusual cause of obstructive jaundice. Congenital cysts, sometimes referred to as nonparasitic biliary cysts, are not unusual findings in the liver parenchyma, but they have not been previously described in the common bile duct. This clinical report describes a 41-year-old woman with obstructive jaundice that was caused by congenital cysts. The patient had obstruction of the middle portion of the common bile duct; therefore the major differential diagnostic considerations were cholangiocarcinoma, cancer of the pancreas, or true biliary cysts. Congenital cysts, retention cysts, and neoplastic cysts cannot be differentiated from other true cysts preoperatively. Diagnosis can only be established by microscopic examination after surgical excision. 
4	Surgical correction of recurrent venous ulcer. Seventy-six limbs from 46 patients with comparable superficial and deep venous valve incompetence underwent surgical correction for recurrent venous ulcers of the leg that were refractory to various modes of nonsurgical and surgical treatments. A follow-up of 10 to 73 months (mean = 37 months), revealed the venous ulcer healed with perforator ligation and saphenous vein stripping in 14 of 33 (44%), stripping plus valvuloplasty 17 of 21 (80%), stripping plus vein transposition 11 of 14 (78%) and stripping plus valve transplantation 6 of 8 (75%). In patients with incompetent deep venous valve and perforators, the disassociation of the superficial from the deep venous system (stripping) plus correction of the deep venous valvular incompetence (valvuloplasty, transposition or valve transplant) produced superior results in the treatment of recurrent venous ulcer when compared to perforator ligation and saphenous vein stripping alone (p less than 0.005). Adjunctive usage of elastic stockings and intermittent compression pneumatic boots in the perioperative period was helpful in controlling leg swelling and promoting wound healing. 
5	Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity. Anaemia is an important factor in the response of some human tumours to radiotherapy. The outcome is also influenced by whether the treatment is given in air or high pressure oxygen (HPO). The present study examined the relationship between anaemia and tumour response to radiation given in air or HPO in C3H mice transplanted with a mammary adenocarcinoma using a growth delay assay to assess the radiation response. Chronic anaemia was induced by the use of a low iron diet and was characterized by a significant reduction in host haematocrit and whole blood viscosity. In addition, anaemia was associated with a right shift in the oxyhaemoglobin dissociation curve and an increase in the volume doubling time of the tumour; but there was no change in the concentration of 2,3-diphosphoglycerate in the red cells. Radiation studies with these anaemic mice demonstrated that the tumour radiosensitivity was decreased when treatment was given in air. HPO was successful in overcoming the increased radioresistance associated with anaemia. This result suggested that tumours grown in anaemic mice have a higher hypoxic fraction than those grown in control mice. Changes in host physiology with chronic anaemia may contribute to the benefit seen with HPO but such alterations per se may be inadequate to maintain tumour oxygenation when treatment is given in air. 
4	Spontaneous regression of cardiomyopathy in a patient with the acquired immunodeficiency syndrome. Cardiac involvement is common in patients with the acquired immunodeficiency syndrome (AIDS) and, when symptomatic, it portends a poor prognosis. We present a case of marked spontaneous regression of cardiomyopathy in a patient with AIDS. To our knowledge, this is the first reported case of spontaneous recovery of ventricular function in an AIDS patient. 
4	Relation between beta-adrenergic blocker use, various correlates of left ventricular function and the chance of developing congestive heart failure. The Multicenter Diltiazem Post-Infarction Research Group. This study examined the relations among beta-adrenergic blocker use, various correlates of left ventricular function and the chance of developing congestive heart failure in patients after myocardial infarction. The study was performed with the placebo group of the Multicenter Diltiazem Post-Infarction Trial. Ejection fraction data were available in 1,084 patients; of these, 557 were receiving a beta-blocker and 527 were not. In addition to ejection fraction, other correlates of left ventricular function included the presence or absence of pulmonary rales, chest X-ray film evidence of pulmonary congestion and the presence of an S3 gallop. Beta-blocker use was less frequent in patients with an ejection fraction less than 30%, rales, an S3 gallop and pulmonary congestion on chest X-ray film. Twenty-one percent of patients with an ejection fraction less than 30%, 42% of patients with rales, 28% of patients with an S3 gallop and 28% of patients with pulmonary congestion were receiving beta-blocker therapy. For every correlate of left ventricular function, the chance of developing congestive heart failure was greater in patients with diminished left ventricular function than in those without. For each level of left ventricular function, the chance of developing congestive heart failure requiring treatment was greater in patients not taking a beta-blocker. 
5	Vaginal bleeding in childhood and adolescence. Vaginal bleeding in early childhood, regardless of its duration and quantity, is always of clinical importance. This article discusses the examination of the child and adolescent and reviews the various causes of vaginal bleeding in these patient groups. 
3	Respiratory muscle involvement in nemaline myopathy. A boy who had experienced generalized muscle weakness and hypotonia since early infancy was diagnosed as having nemaline myopathy on the basis of muscle biopsy at 3 years of age. At 8 years of age, he developed severe respiratory failure and required respiratory support during sleep. Because of recurrent pneumothorax, he underwent thoracic surgery, at which time biopsy specimens were obtained from the respiratory and truncal muscles. The histologic findings of the respiratory muscles included marked variation in fiber size with a notable increase in fibrous tissue, type 2 fiber deficiency, elevated acid phosphatase activity, and a disorganized intermyofibrillar network. The findings from the truncal muscles were similar to those of the biceps brachii muscle: little variation in fiber size, numerous nemaline bodies in all fibers, and type 1 fiber predominance. The preferential damage to the respiratory muscles was probably responsible for the sudden onset of severe respiratory failure. 
4	Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity. The purpose of the present study was to characterize the effects of xamoterol in the human myocardium. In the presence of forskolin or milrinone, xamoterol increased isometric force of contraction, contraction velocity, and relaxation velocity in isolated, electrically driven preparations from human myocardium, but had no effect alone. There was no difference in the effect of xamoterol between right atrial myocardium and left ventricular myocardium from nonfailing (NF), moderately failing (NYHA II-III), and severely failing (NYHA IV) human hearts. The positive inotropic and lusitropic effects of isoprenaline were reduced depending on the severity of heart failure in left ventricular myocardium (i.e., NF greater than NYHA II-III greater than NYHA IV). In the presence of norepinephrine, xamoterol produced negative inotropic effects similar to those of the beta-adrenoceptor antagonists pindolol and propranolol. Xamoterol alone had no effects on force of contraction, whereas pindolol and propranolol markedly reduced contractile force. In NYHA class IV, isoprenaline stimulated adenylate cyclase about twofold but xamoterol, like pindolol or propranolol, had no effect. Experiments with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, showed that the positive inotropic and lusitropic effects of xamoterol were mediated by beta 1-adrenoceptors. Consistently, xamoterol had a selectivity of 13.8 at beta 1-adrenoceptors as measured in radioligand binding experiments. It is concluded that xamoterol acts as a beta 1-adrenoceptor antagonist with a selectivity of 13.8 in human ventricular myocardium. The compound has an intrinsic sympathomimetic activity, as it produces beta 1-adrenoceptor-mediated positive inotropic and lusitropic effects in the presence of forskolin. The beneficial effects of xamoterol in patients with heart failure could be due to prevention of the detrimental effects of norepinephrine such as beta 1-adrenoceptor downregulation of an increase of Gi (inhibitory guanine-nucleotide binding protein). 
4	Effect of abrupt mitral regurgitation after balloon valvuloplasty on myocardial load and performance. The concept that mitral regurgitation masks myocardial dysfunction by reducing afterload and augmenting ejection performance has not been well established in humans. The effect of abruptly produced mitral regurgitation on left ventricular loading and performance was therefore evaluated in five patients who developed this complication after an otherwise successful percutaneous balloon mitral valvuloplasty. Mitral valve area by Gorlin formula calculated with forward flow increased from 0.92 +/- 0.14 to 2.75 +/- 0.82 cm2. Mean left atrial pressure did not decrease (19 +/- 4 to 19 +/- 6 mm Hg). The size of the left atrial V wave relative to mean left atrial pressure (peak V - mean left atrial pressure) increased from 7 +/- 4 to 19 +/- 6 mm Hg. Angiographic mitral regurgitation increased from 0+ or 1+ to greater than 3+ in each patient and regurgitant fraction increased from 0.23 +/- 0.11 to 0.55 +/- 0.09 (p less than 0.01). End-diastolic volume increased modestly from 148 +/- 15 to 159 +/- 15 ml (p = NS). Heart rate increased from 54 +/- 5 to 71 +/- 8 beats/min (p less than 0.05), which may have prevented further increases in preload by shortening the filling period. End-systolic stress decreased by 32% from 277 +/- 34 to 188 +/- 52 kdyn/cm2 (p less than 0.01) as a result of a 25% decrease in end-systolic pressure from 121 +/- 8 to 91 +/- 7 mm Hg and a 16% decrease in end-systolic volume from 67 +/- 13 to 56 +/- 8 ml (p = NS). 
5	How long can a coronary reperfusion catheter be placed in acute coronary occlusion following failed transluminal coronary angioplasty? A case report. A coronary reperfusion catheter (CRC) is designed to preserve antegrade coronary flow when abrupt coronary closure occurs during percutaneous transluminal coronary angioplasty (PTCA). Insertion of the catheter to an occluded coronary artery for a few hours has been reported to be effective for myocardial salvage: however, it is unknown how long the catheter can be kept in place without causing extension of myocardial ischemia. The authors experienced a case in which the CRC was kept in place for twenty-four hours for anticoagulant therapy of an occluded coronary artery following failure of PTCA. This case suggests that adequate anticoagulant therapy can prolong the period during which a CRC can be kept in place if emergency coronary bypass surgery cannot be performed immediately after failure of coronary angioplasty. 
4	Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event. 
5	The role of infections in the rheumatic diseases: molecular mimicry between bacterial and human stress proteins? Infections can cause or exacerbate the rheumatic diseases in several ways, including immune cross-reactivity between bacterial heat shock proteins and similar proteins in normal human tissues. This may lead to autoimmunity in rheumatoid arthritis and systemic lupus. In addition, increased activation of the gene regulating the synthesis of a heat shock protein has been found in scleroderma fibroblasts. As an infection-induced model for other rheumatic diseases, rheumatic fever (RF), with its well-established link to prior group A streptococcal infection, will be revisited. The lessons learned from RF and other rheumatic diseases directly linked to infection will be applied to ankylosing spondylitis, rheumatoid arthritis, Sjogren's syndrome and polymyositis, for which a mounting body of circumstantial evidence suggests a probable infectious cause. The interplay of genetic susceptibility and infection with particular organisms and the implications of this new information for present and future therapy of the rheumatic diseases will also be presented. 
2	Warner-Lambert/Parke-Davis Award lecture. Pathobiology of the intestinal epithelial barrier. The major route of passive permeation across intestinal epithelia is paracellular. The intercellular tight junction lies in and serves as the rate-limiting barrier in this paracellular pathway. Once viewed as static, it is now clear that the structure and permeability of the tight junction is highly dynamic. Not only may inflammatory events (cytokines, neutrophil transmigration) reversibly effect the tight junction but this key barrier also is regulated by physiologic events such as activation of absorptive cell Na(+)-nutrient cotransporters. Such physiologic regulation of the junction is of major importance to the absorption of nutrients via parcellular solvent drag. 
5	Genetics of common diseases of adulthood. Implications for prenatal counseling and diagnosis. Genetic factors play an important role in the development of many common diseases of adulthood that result in early morbidity and mortality. Prevention of these disorders and their sequelae is best established through early detection and early intervention. Although it may be feasible to screen the entire population for some disorders (e.g., hypertension), this approach would be expensive and impractical for others (e.g., colon cancer). The family history provides an inexpensive and convenient method of identifying families at risk for premature diseases of adulthood. Family screening for a disorder should be recommended if there is increased risk for the disorder among family members, if screening methods are available to detect the condition at an early age or preclinical stage, and if early intervention will alter the course of the disease. For many disorders screening and intervention can prevent the occurrence of clinical disease. The prenatal counseling session affords an ideal setting for identifying families at risk for diseases of adulthood with major genetic components. By reviewing the family history, key family members can be identified and investigated, in order to establish a specific genetic diagnosis. At-risk relatives can then be counseled and screened for the disorder preclinically and premorbidly. The screening and intervention available for a disease depends on the nature of the disorder, our understanding of its physiology and etiology, and our current technology. The disorders discussed earlier are typical of conditions of adulthood that are influenced strongly by genetic factors, especially when they appear in younger adults. Atherosclerosis, colon cancer, and diabetes are complex phenotypes. Each can be caused by single-gene defects, but commonly the genetics are more complex. Empiric data help to establish the risk to an individual in the latter cases. In all three examples, early detection should lead to treatment, which can prevent more serious sequelae: by treating the dyslipidemia, coronary artery disease can be prevented; by removing the benign polyp, malignant cancer can be avoided; and when impaired glucose tolerance is detected, diet and exercise can prevent or delay frank diabetes and its complications. The complete evaluation of individuals at risk for disorders such as those in Table 1 and their families can be a complicated task. Referral to a center experienced in the genetics of common diseases often may be necessary.(ABSTRACT TRUNCATED AT 400 WORDS). 
2	Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis. Recently the formation of bile acid glucosides has been described as a novel conjugation mechanism in vitro and in vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 +/- 0.03 mumol/24 hr (mean +/- S.E.M.)-in the range of bile acid glucuronide excretion (0.41 +/- 0.06 mumol/24 hr; mean +/- S.E.M.). A gas chromatography-mass spectrometry-characterized trihydroxy bile acid glucoside of still-unknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 +/- 0.13 mumol/24 hr (mean +/- SEM), yet significantly lower than bile acid glucuronide excretion (1.53 +/- 0.13 mumol/24 hr; mean +/- SEM; p less than 0.001). In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation. The data establish the composition and quantity of urinary bile acid glucosides in healthy controls and cholestasis and constitute a quantitative comparison with another glycosidic conjugation reaction, bile acid glucuronidation. 
4	Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit. BACKGROUND. The limiting effect of ischemic preconditioning on infarct size has been reported in canine hearts, which contain considerable amounts of xanthine oxidase, a free radical-producing enzyme. Furthermore, a recent study suggested that free radicals generated during preconditioning may contribute to the cardioprotective effect of preconditioning. The present study examined 1) whether preconditioning limits infarct size in rabbits, which, like humans, lack myocardial xanthine oxidase and 2) whether the cardioprotective effect of PC is mediated by free radicals. METHODS AND RESULTS. A branch of the circumflex coronary artery in rabbits was occluded for 30 minutes and then reperfused for 72 hours. Myocardial infarct size and area at risk were determined by histology and fluorescent particles, respectively. Five groups were studied: an untreated control group, a preconditioned group (PC group), a high-dose superoxide dismutase (SOD)-treated preconditioned group (high-dose SOD-PC group), a low-dose SOD-treated preconditioned group (low-dose SOD-PC group), and a SOD-plus-catalase-treated preconditioned group (SOD/CAT-PC group). Preconditioning was performed with four episodes of 5 minutes of ischemia and 5 minutes of reperfusion. The free radical scavengers (30,000 units/kg SOD for high-dose SOD-PC group, 15,000 units/kg SOD for low-dose SOD-PC group, and 30,000 units/kg SOD plus 55,000 units/kg catalase for SOD/CAT-PC group) were infused intravenously over 60 minutes starting 20 minutes before preconditioning. Infarct size as the percentage of area at risk was 45.1 +/- 3.5% (mean +/- SEM) in the control group (n = 11), 13.3 +/- 3.0% in the PC group (n = 12), 9.7 +/- 1.8% in the high-dose SOD-PC group (n = 8), 11.9 +/- 2.2% in the low-dose SOD-PC group (n = 6), and 9.6 +/- 2.3% in the SOD/CAT-PC group (n = 6) (p less than 0.05 versus control for the last four values). The differences in infarct size as the percent of area at risk among the PC, high-dose SOD-PC, low-dose SOD-PC, and SOD/CAT-PC groups were not significant. CONCLUSION. Ischemic preconditioning delays ischemic myocardial necrosis regardless of myocardial xanthine oxidase content. Free radicals are unlikely to have a major role in the mechanism of the preconditioning in rabbits. 
3	Isolation of a complementary DNA clone encoding an autoantigen recognized by an anti-neuronal cell antibody from a patient with paraneoplastic cerebellar degeneration. We isolated a complementary DNA clone encoding a 52-kd protein recognized by an anti-neuronal cell antibody in serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. The recombinant protein expressed in prokaryotic cells was specifically recognized by the anti-neuronal cell antibody from the patient, and its molecular weight was identical to that of antigenic proteins in the cerebellum. The deduced protein consisted of 450 amino acids dominated by hydrophilic residues, the calculated relative molecular mass was 51,238, and the predicted value of the isoelectric point was 4.99. This complementary DNA sequence and the deduced protein sequence have not been reported previously, and the sequences showed no homologies with the complimentary DNA or the amino acid sequences in the GenBank, EMBL, or NBRF databases, including the complementary DNA for a 34-kd cerebellar protein (CDR34) that is recognized by an anti-Purkinje cell antibody. Unexpectedly, the transcript of this gene was detected not only in the cerebellum and the brain stem but also in an extraneural tissue, the intestine. 
5	Transient left ventricular cavitary dilation during dipyridamole-thallium imaging as an indicator of severe coronary artery disease. Transient left ventricular (LV) cavitary dilation during dipyridamole-thallium imaging was reported in 45 of 510 (9%) consecutive patients referred for dipyridamole-thallium imaging. Clinical and hemodynamic effects observed during dipyridamole infusion were not predictive of transient cavitary dilation on the thallium images. Coronary angiography was performed in 32 of the 45 patients: 75% had either left main, 3-vessel or "high-risk" 2-vessel coronary artery disease. Although 25 of 45 patients (56%) with transient cavitary dilation were either asymptomatic or had only grade 1/4 effort angina, 16 of 25 patients (64%) not referred for coronary revascularization sustained a cardiac event during a mean follow-up of 12 months. Most events were cardiac deaths (75%) and 87% of events occurred within 4 months of the test. Noncardiac surgery was performed in 187 of the 510 patients. The postoperative cardiac event rate was 2% in the 101 patients with normal scans or fixed defects, 19% in 75 patients with reversible perfusion defects and 58% in 12 patients with reversible cavitary dilation (p less than 0.0001). Thus, transient LV dilation during dipyridamole-thallium imaging is a marker of severe underlying coronary artery disease, denotes a poor prognosis and predicts a high risk of postoperative cardiac complications in patients who undergo noncardiac surgery. 
5	The "all-autogenous" tissue policy for infrainguinal reconstruction questioned. In 33% of patients referred for infrainguinal reconstruction for limb-threatening ischemia (mean preoperative ankle-arm index [AAI] = 0.26), no suitable autogenous reconstruction was possible. In 40% of cases, intraoperative pre-bypass contrast arteriography was necessary to identify a graftable tibial or pedal artery. The results of polytetrafluoroethylene (PTFE) and autogenous bypasses were compared after 1 to 3 years. After 1 year, patency was 85% and 67% for autogenous and PTFE bypasses, respectively. Limb salvage was 90% for autogenous bypass and 70% for PTFE bypass. Cumulative patency rates at 3 years were 80% for autogenous and 57% for PTFE grafts. Graft surveillance with duplex scanning and AAI was valuable in detecting failing grafts. For both types of reconstruction, secondary procedures were required to maintain patency. We attribute the excellent results with PTFE in part to long-term aspirin and warfarin therapy. In cases of combined superficial femoral and severe infra-popliteal occlusive disease, PTFE bypass is an excellent alternative when no autogenous conduit is available. 
4	Natural history of moderate aortic stenosis. The natural history of severe, symptomatic aortic stenosis has been well documented. However, the natural history of moderate aortic stenosis remains poorly understood. Therefore, a group of 66 patients was identified who had a diagnosis of moderate aortic stenosis at the time of cardiac catheterization (aortic valve area 0.7 to 1.2 cm2) and who did not have surgical therapy during the 1st 180 days after cardiac catheterization. During a mean follow-up period of 35 months, 14 patients died of causes attributed to aortic stenosis and 21 underwent aortic valve replacement. The estimated probability for remaining free of any complication of aortic stenosis at the end of the first 4 years was 59%. Symptomatic patients with decreased ejection fraction or hemodynamic evidence of left ventricular decompensation were at greater risk for these complications. It is concluded that patients with moderate aortic stenosis are at significant risk for the development of complications. 
1	Endosalpingosis as a cause of chronic pelvic pain. Endosalpingosis, a condition characterized by ectopic oviduct epithelium, is diagnosed histologically by the appearance of benign ciliated and nonciliated columnar cells in an abnormal location. Endosalpingosis is typically without symptoms. Our unusual case report shows symptomatic endosalpingosis first seen with chronic pelvic pain. Various aspects of this disease will also be discussed. 
1	Mucocelelike tumor of the breast associated with atypical ductal hyperplasia or mucinous carcinoma. A clinicopathologic study of seven cases. We studied seven patients with mucocelelike tumors of the breast, known to be benign lesions that may be confused with mucinous carcinomas of the breast. All patients had a palpable mass. Microscopically, the most striking feature was the cystic character of the lesion. The epithelial lining of the cysts was usually flat or cuboidal to low columnar, and mucin pools frequently appeared near the ruptured cysts. Three mucocelelike tumors contained a microscopic focus of mucinous carcinoma. The other tumors had areas of atypical ductal hyperplasia containing abundant intraluminal mucinous materials. The mucin was composed predominantly of neutral and nonsulfated acid mucins whose character was identical to that of those in mucinous carcinoma. Because all mucocelelike tumors in our series were associated with either atypical ductal hyperplasia or carcinoma and because some mucocelelike tumors may indeed be early mucinous carcinomas of the breast, we recommend examination of the entire specimen and careful clinical follow-up. 
4	Echocardiographic assessment of doxazosin on left ventricular mass in patients with essential hypertension. A single daily dose of doxazosin taken during a 12-week period produced a significant reduction in blood pressure and left ventricular mass index in patients with mild or moderate hypertension. The systolic shortening coefficient was also increased and a trend in the improvement of ejection fraction, rate of circumferential fiber shortening, systolic contraction time, and preejective/ejective ratio was observed. No change in heart rate was recorded and no patients had side effects. The serum lipid profile was modified favorably, particularly with regard to the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio. By producing a reduction in blood pressure and left ventricular mass while favorably modifying the serum lipid profile, doxazosin produced a beneficial change in the overall coronary heart disease risk profile. 
2	Use of the pudendo-anal reflex in the treatment of neurogenic faecal incontinence. An electrical stimulator has been devised to treat neurogenic faecal incontinence caused by pudendal nerve neuropathy and works on the basis of repeated stimulation of the pudendo-anal reflex arc. Although conduction in the pudendo-anal reflex arc may be prolonged, and is so in neurogenic faecal incontinence, it must be shown to be present before the method can be used. This stimulation results in an immediate rise in the pressure in the anal canal and a significant increase in the electromyographic activity of the external anal sphincter. Maintenance of the stimulus over a two month period raised the mean resting pressure significantly in the anal canal and increased the reflex and voluntary responses of the external anal sphincter to coughing and squeezing actions respectively. The length of the sphincter was not affected. There was widening of the mean motor unit potential duration, though this was not significant. The resting electromyogram was enhanced after the course of treatment, indicating greater spontaneous activity in the external sphincter. The changes led to seven of the eight patients studied becoming continent at the end of the treatment. 
3	Clinical features and natural history of von Hippel-Lindau disease The clinical features, age at onset and survival of 152 patients with von Hippel-Lindau disease were studied. Mean age at onset was 26.3 years and 97 per cent of patients had presented by aged 60 years. Retinal angioma was the first manifestation in 65 patients (43 per cent), followed by cerebellar haemangioblastoma (n = 60, 39 per cent) and renal cell carcinoma (n = 15, 10 per cent). Overall, 89 patients (59 per cent) developed a cerebellar haemangioblastoma, 89 (59 per cent) a retinal angioma, 43 (28 per cent) renal cell carcinoma, 20 (13 per cent) spinal haemangioblastoma and 11 (7 per cent) a phaeochromocytoma. Renal, pancreatic and epididymal cysts were frequent findings but their exact incidence was not accurately assessed. Mean age at diagnosis of renal cell carcinoma (44.0 +/- 10.9 years) was significantly older than that for cerebellar haemangioblastoma (29.0 +/- 10.0 years) and retinal angioma (25.4 +/- 12.7 years). The probability of a patient with von Hippel-Lindan disease developing a cerebellar haemangioblastoma, retinal angioma or renal cell carcinoma by age 60 years was 0.84, 0.7 and 0.69, respectively. A comprehensive screening protocol for affected patients and at-risk relatives is presented, based on detailed analysis of age at onset data for each of the major complications. Median actuarial survival was 49 years, with renal cell carcinoma the leading cause of death. 
4	Metabolic considerations in the choice of therapy for the patient with hypertension. The objective of treating patients with hypertension is not simply to reduce blood pressure but rather to prevent the associated morbidity and mortality. Recent assessments of clinical trials have shown that while the risk of stroke is consistently lower with antihypertensive therapy, the same degree of success has not been demonstrated for coronary artery disease (CAD). Although there are many explanations of why we have not done as well in preventing CAD, one possibility is that the therapy used in clinical trials, primarily thiazide diuretics and beta-adrenoreceptor blockers, has increased the patient's risk of developing coronary atherosclerosis or lethal arrhythmias. Four classes of antihypertensive agents are recommended for initial therapy--thiazide diuretics, beta-adrenoreceptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium entry blockers. The metabolic effects of thiazide diuretics include electrolyte disturbances (hypokalemia, hypomagnesemia, and hyponatremia), dyslipidemia (increased triglycerides), abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance), and hyperuricemia. beta-Adrenoreceptor blockers have many of the same metabolic adverse reactions. beta-Adrenoreceptor blockers without intrinsic sympathomimetic activity (ISA) also cause dyslipidemias (lowered high-density lipoprotein cholesterol and increased triglycerides) and abnormalities of glucose metabolism (hyperglycemia, hyperinsulinemia, and peripheral insulin resistance). beta-Adrenoreceptor blockers with ISA and third-generation beta-blockers with selective partial agonist activity (celiprolol and dilevalol) do not cause dyslipidemia and to date do not appear to induce abnormalities in glucose metabolism. ACE inhibitors may decrease triglycerides and increase high-density lipoprotein cholesterol, and captopril may improve insulin sensitivity. Calcium entry blockers are metabolically neutral. 
1	The Cancer Prevention Reminder System. The Cancer Prevention Reminder System is a computer-based system designed to increase the delivery of periodic health maintenance procedures. The program provides printed reminders that identify patients' overdue procedures, prints summary reports of the percentage of patients who are eligible and overdue for a procedure, and prints mailing labels for patients. We performed a randomized, controlled trial in which the effects of computer-based reminders were compared with those of two other interventions among residents in a university-based group practice. 
5	Hyperkalemia in acute glomerulonephritis due to transient hyporeninemic hypoaldosteronism. Transient hyperkalemia has been reported to occur in patients with acute glomerulonephritis, but the pathogenetic mechanism has not been investigated systematically. We studied the mechanism of hyperkalemia (5.7 to 6.7 mmol/liter) in four men with post-infectious glomerulonephritis. All four patients had clinical findings consistent with acute glomerulonephritis (edema, hypertension, proteinuria, hematuria, and an elevated ASO titer) and a renal biopsy performed in three of the patients confirmed the diagnosis. In comparison to normal subjects (N = 18), plasma aldosterone (5.4 +/- 1.6 vs. 22.8 +/- 2.6 ng/dl, P less than 0.005) and plasma renin activity (0.3 +/- 0.2 vs. 4.3 +/- 0.6 ng/ml/hr, P less than 0.005) were reduced. Hyperkalemia resolved within one to two weeks in two patients as the nephritis resolved and diuresis ensued, and aldosterone and renin levels obtained at follow-up visits were normal. Hyperkalemia persisted despite furosemide-induced diuresis in the other two patients, but resolved with fludrocortisone treatment. Thus, hyperkalemia in patients with acute glomerulonephritis is a manifestation, in part, of hyporeninemic hypoaldosteronism. It is ameliorated by mineralocorticoid therapy and improves spontaneously with resolution of the glomerulonephritis. 
2	Retained intrahepatic stones: treatment with piezoelectric lithotripsy combined with stone extraction. Extracorporeal shock wave lithotripsy (ESWL) was performed in 11 patients with oriental cholangiohepatitis and intrahepatic stones associated with segmented strictures of intrahepatic ducts. All patients had previously undergone biliary surgery and basket extraction via a T-tube tract at the time of lithotripsy. The indication for ESWL was failure of, or anticipated difficulty with, basket extraction of the stones via a T-tube tract. A piezoelectric lithotriptor was used in all procedures. The average total number of shock waves administered was 29,756 (range, 10,000-61,395). The average number of treatment sessions was 3.1 (range, 1-6); the number of shock waves used in a single session ranged from 10,000 to 15,000 with a frequency of five shots per second and 30%-50% power. In six patients, the stones were successfully fragmented and completely removed; in three of the others of the stones were fragmented and removed. The overall success rate, including complete (54%) and incomplete (27%) success, was 82%. Difficulty in targeting stones, and severe strictures and deformities of intrahepatic ducts, were the factors responsible for failure. No significant complications were observed. 
5	Radiculomegaly of canines and congenital cataracts--a syndrome? Radiculomegaly of single teeth is very uncommon. Our survey indicates that the canine tooth is most frequently affected. Although illustrated in a number of texts of dental anatomy, there is a lack of detailed case reports. 
5	Isolation of a novel tumor protein that induces resistance to natural killer cell lysis. The human metastatic tumor cell line CAP-2, produces a soluble factor that induces resistance to NK lysis of K-562 susceptible leukemia cell line, and does not inhibit the cytotoxic capacity of effector cells. The use of sequential HPLC, hydrophobic interaction chromatography, and reverse phase chromatography, coupled with cytotoxic assays, resulted in the isolation and separation to homogeneity of a novel protein responsible for this biologic activity. Size estimation studies based on TSK HPLC columns showed that this protein has a mass of 8 to 12 kDa. The amino acid composition analysis of the CAP-2 protein calculated from HPLC chromatograms shows that this protein contains around 108 amino acids. Subsequent gas phase sequence analysis, however, was hampered because the N terminus of this protein was blocked and therefore unsuitable for sequencing by Edman degradation. The functional studies showed that the NK lysis-resistance activity of the CAP-2 protein is mediated by interaction with and nonspecific binding to NK target cells. The lymphokine-activated killer and macrophage-mediated cytotoxicity and mitogen-induced proliferation is not affected. Unexpectedly, the CAP-2 protein appears to be mitogenic to its own cell line. Thus, the induction of NK lysis-resistance and the mitogenic activity showed by CAP-2 protein could contribute to the tumor growth and metastatic establishment. 
4	Intra-aortic balloon pump for combined myocardial contusion and thoracic aortic rupture. The coexistence of myocardial contusion and thoracic aortic injury is probably more common than recognized following rapid deceleration multisystem trauma. This report describes the successful application of intra-aortic balloon counterpulsation in a critically injured patient requiring emergent repair of a thoracic aortic tear complicated by ventricular failure due to cardiac contusion. 
3	Dysgeusia, gustatory sweating, and crocodile tears syndrome induced by a cerebellopontine angle meningioma. Facial nerve involvement in cerebellopontine angle tumors, both during their development and after excision, may be expressed in irreversible dysfunction of the parasympathetic pathways. The exact location of the lesion along the efferent nerve fibers can be established through evaluation of the functional level of those organs supplied by the cholinergic motor secretory components. This report deals with a female patient in whom peripheral facial palsy developed shortly after removal of a right cerebellopontine angle meningioma. She had slight facial asymmetry and deafness in the right ear and complained of prandial flush and sweating of the right malar area. Occult ipsilateral hyposalivation and hypolacrimation were diagnosed. In patients with seventh and ninth cranial nerve pathoses, evaluation of the end organs that are supplied by their associated autonomous nerve fibers is mandatory to prevent late ocular and oral sequelae. 
5	Patterns of chromosomal breakpoint locations in Burkitt's lymphoma: relevance to geography and Epstein-Barr virus association. We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5' region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations. 
4	Obstruction of mechanical heart valve prostheses: clinical aspects and surgical management. One hundred patients (32 male) aged 5 months to 82 years (median 32 years) underwent 106 surgical procedures for 112 mechanical prosthetic valves obstructed by a thrombus (n = 61) or pannus (n = 7), or both (n = 44), between January 1, 1980 and December 31, 1989. The position of the obstructed prosthesis was aortic in 51 patients (48%), mitral in 49 (46%) and both aortic and mitral in 6 (6%). The types of obstructed prosthetic valves were Bjork-Shiley (n = 51), St. Jude (n = 41) and Medtronic-Hall (n = 20). The time interval between valve replacement and obstruction ranged from 6 weeks to 13 years (median 4 years). Of 63% of patients in whom coagulation variables were available at the time of obstruction, 70% were receiving inadequate anticoagulant therapy. In 63% of the procedures the patient was in New York Heart Association functional class IV. Two patients underwent preoperative thrombolysis with incomplete results. Operative procedures included valve replacement (n = 81), valve declotting and excision of pannus (n = 23) and aortic valve replacement and mitral valve declotting (n = 2). The early mortality rate was 12.3% (13 patients), and there was no difference between surgery for mitral prostheses (12.2%) versus aortic prostheses (13.7%). The perioperative mortality rate was 17.5% (11 of 63 patients) in patients in functional class IV and 4.7% (2 of 43 patients) in those in functional classes I to III (p less than 0.05). For valve replacement, the mortality rate was 12% (10 of 81 patients) and for declotting of the prosthesis 13% (3 of 23 patients). 
4	Venous dysfunction of late pregnancy persists after delivery. Pregnancy is associated with DVT, pelvic thrombophlebitis, and lower extremity varicosities. Pelvic venous compression by the gravid uterus is blamed. A prospective controlled study using plethysmography was performed. Venous capacitance and outflow were measured at term, and at 1 week, 6 weeks and 3 months following delivery. Results show decreased venous capacitance and venous outflow at term pregnancy, no improvement 1 week after delivery, modest improvement at 6 weeks, and dramatic statistically significant improvement in both parameters by 3 months. The persistence of venous dysfunction for several weeks after delivery indicates that changes in venous function at term pregnancy are largely the result of factors other than pelvic venous compression by the gravid uterus. 
4	Clinical results of axillobifemoral bypass using externally supported polytetrafluoroethylene Seventy-six axillobifemoral grafts with externally supported polytetrafluoroethylene prostheses were performed since 1983. The indications for operation were absolute (aortic sepsis) in 20 (26%) patients and relative (excessive operative risk or technical difficulty) in 56 (74%) patients. The life-table primary patency for these operations at 4 years follow-up (mean follow-up, 2 years, 4 months) was 85%. We conclude that the patency results achieved in this patient series are sufficiently satisfactory to warrant use of axillobifemoral grafts in an expanded number of patients with high operative risk and need for bypass of aortoiliac occlusive disease. 
5	Long-term results of catheter ablation of idiopathic right ventricular tachycardia Ten consecutive patients with recurrent episodes of symptomatic, idiopathic, sustained monomorphic ventricular tachycardia (VT) originating in the right ventricle underwent an attempt at catheter ablation of the ventricular tachycardia. There were seven women and three men, with a mean age of 39 +/- 14 years (+/- SD). None of the patients had any evidence of structural heart disease. The VT had a left bundle branch block configuration and an inferior axis in each patient, and the mean cycle length was 313 +/- 75 msec. Based on the methods of induction of the VT and the response of the VT to verapamil, the VT mechanism was presumed to be reentry in six patients, triggered activity in three patients, and catecholamine-sensitive automaticity in one patient. Sites for ablation were guided by pace mapping, and an appropriate target site was identified in the right ventricular outflow tract in each patient. From one to three shocks of 100-360 J (mean total, 336 +/- 195 J) were delivered from a defibrillator between the tip of the ablation catheter (cathode) and a patch electrode on the anterior chest (anode). An electrophysiology test 7-9 days after ablation demonstrated that VT was still inducible in only one patient, who was treated with amiodarone. One other patient had a recurrence of VT 3 weeks after ablation and was treated with verapamil. Eight of 10 patients were not treated with antiarrhythmic medications and have had no episodes of symptomatic VT during 15-68 months of follow-up (mean follow-up, 33 +/- 18 months). There were no acute or long-term complications. 
1	Malignant fibrous histiocytoma of soft tissue. A population-based epidemiologic and prognostic study of 137 patients. Epidemiology and prognosis were analyzed in a consecutive, population-based series of 137 patients with malignant fibrous histiocytoma of soft tissue in the extremities and trunk wall, with a complete follow-up of minimum 3 years. All but one patient were treated by surgery in 28 cases combined with adjuvant radiotherapy or chemotherapy. The annual incidence was 0.42/10(5). The ratio men to women was 1.1. The median age was 64 years (range, 22 to 87 years). The thigh was the most common location. The median size was 6 cm. Superficial tumors constituted 43% and were smaller than deep-seated tumors. Eighty-three tumors were storiform-pleomorphic, 53 were myxoid, and one was of inflammatory type. The myxoid tumors were smaller and more often superficial. The cumulative 5-year survival rate for all patients was 0.7, but differed markedly between the histologic types; it was 1.0 in patients with myxoid tumors and 0.5 in patients with storiform-pleomorphic tumors. In the 77 patients with storiform-pleomorphic tumors without metastases at presentation, only tumor size larger than 10 cm and tumor necrosis independently impaired survival. The 23 patients who had none of these risk factors had a 5-year survival rate of 0.8. 
5	Sudden blindness after thermocoagulation of the trigeminal ganglion. Sudden blindness during percutaneous thermocoagulation of the gasserian ganglion occurred in a 72-year-old woman with trigeminal neuralgia. Considered a safe procedure, we highlight the possibility of this serious complication which was probably due to direct damage of the optic nerve. 
4	Dependence of Doppler echocardiographic transmitral early peak velocity on left ventricular systolic function in coronary artery disease. The influence of systolic function on pulsed Doppler echocardiographic transmitral flow velocity patterns was assessed before and after postextrasystolic (PES) potentiation in 12 normal subjects (control group) and in 25 patients with previous healed myocardial infarction (MI) group. Simultaneous high-fidelity left ventricular pressure measurements were performed in all patients. A programmed single-coupled right ventricular extrasystole was induced during echocardiographic and subsequent cineangiocardiographic recordings. Adequate angiograms for volumetric analysis in both baseline and PES beats were obtained in 23 patients (7 in the control group and 16 in the MI group). PES potentiation of contraction was more pronounced in the MI group than in the control group. PES changes in ejection fraction, stroke volume and end-systolic volume were significantly greater in the MI group than in the control group (11 vs 5%, p less than 0.005; 15 vs 5 ml/m2, p less than 0.005; and -13 vs -4 ml/m2, p less than 0.01, respectively). In contrast, PES potentiation prolonged the time constants of left ventricular pressure decline derived from exponential curve fits with a zero (Tw) and non-zero (Tb) asymptote pressure in the MI group to the same extent as in the control group (4 vs 5 ms, difference not significant [NS], and 9 vs 11 ms, NS, respectively). In the PES beat, peak E velocity remained unaltered (48 vs 49 cm/s, NS) in the control group, whereas it increased significantly (p less than 0.0001) from 47 to 51 cm/s in the MI group. 
3	Eosinophilic fasciitis associated with tryptophan ingestion. A manifestation of eosinophilia-myalgia syndrome. Recently, the ingestion of tryptophan has been associated with eosinophilia-myalgia syndrome, which is characterized by eosinophilia, myalgias, and several less consistently reported findings. We treated 13 patients who exhibited clinical features of eosinophilic fasciitis who were taking high-dose tryptophan before the onset of clinical symptoms. Twelve patients exhibited eosinophilia, with eosinophil counts ranging from 0.13 to 0.88. The remaining patient was taking oral corticosteroids when her eosinophil count was determined. Eight patients complained of myalgias. Other symptoms included arthralgias, pruritus, cutaneous burning, weakness, fever, rashes, malaise, edema, muscle spasms, and alopecia. 5-Hydroxyindoleacetic acid levels were elevated in four of the eight urine specimens that were tested. Our findings suggest that previously diagnosed cases of eosinophilic fasciitis may represent variants of tryptophan-associated eosinophilia-myalgia syndrome. Derangements in the metabolism of tryptophan may play a role in sclerotic diseases. 
1	Factor XIIIa in nodular malignant melanoma and Spitz naevi. The distribution of factor XIIIa-positive dermal dendritic cells was studied in a series of nodular malignant melanomas and compared with that seen in Spitz naevi. Two patterns of distribution were recognizable: (a) diffusely spread through the tumour and (b) located mainly at the periphery of the tumour. These did not correlate with the diagnosis of melanoma or Spitz naevus and the distribution appeared to be a function of growth pattern of the tumour. The diffuse pattern was the most common regardless of diagnosis and the distribution of factor XIIIa-positive cells is the same in malignant melanoma and Spitz naevi. 
5	Augmentation mentoplasty using Mersilene mesh. Many different materials are available for augmentation mentoplasty. However, the optimal implant material for chin implantation has yet to be found. During the past several years, a number of experienced surgeons have turned to the use of Mersilene mesh. Mersilene mesh is a non-absorbable Dacron polyester fiber that can be conformed easily into layers to achieve tailored dimensions and shape. At the McCollough Plastic Surgery Clinic PA, Birmingham, Ala, 277 patients over a 10-year period underwent chin augmentation with Mersilene mesh implants. The material provides excellent tensile strength, durability, and surgical adaptability. The overall complication rate was 3.2% (nine patients); infection rate, 2.5% (seven patients); and removal secondary to infection, 1.7% (five patients). Based on this 10-year experience, Mersilene mesh remains our material of choice for chin augmentation. 
5	Helicobacter pylori in dyspeptic patients in Kuwait. Two hundred and four patients, mainly Arabs, attending for upper gastrointestinal endoscopy at the gastroenterology clinic in Mubarak Al-Kabeer Hospital, Kuwait, were examined for evidence of infection with Helicobacter pylori and associated inflammation. Biopsy specimens of antrum, body, and duodenum; gastric juice; and antral mucosal brushings were investigated by microbiological, cytological, and histopathological methods. Clinical conditions diagnosed at endoscopy included gastritis, gastric ulcer, duodenitis and duodenal ulcer, but half the patients had endoscopically normal gastric and duodenal mucosae. H pylori was detected by one or more of the procedures in at least one specimen from 197 (96.6%) of the patients. Histological and cytological analysis showed equal sensitivity, but bacteriological culture was less reliable. The proportion of positive cases was high, compared with other reported series, which may have been accounted for by the variety of diagnostic techniques used in this study, the selected population (all with gastrointestinal symptoms) or genetic or environmental predisposing factors peculiar to the sample population. 
4	Preservation of oscillations in postocclusive reactive hyperemia. Oscillations in skin blood flow (SkBF) during postocclusive reactive hyperemia are believed to be due to locally mediated events in the microcirculation. We characterized the activity of these oscillations in nine healthy young men who underwent 0, 10, and 40 Torr of lower body negative pressure (LBNP). Postocclusive SkBF was estimated in both forearms simultaneously in a stable thermal environment with laser-Doppler velocimetry. Periodic behavior of SkBF was characterized by frequency-domain power spectral analysis. LBNP at 40 Torr increased heart rate, decreased forearm blood flow, and decreased postocclusive SkBF amplitude but did not change the periodicity of SkBF in the frequency response range that is characteristic of postischemic SkBF oscillations (0.11 +/- 0.04 Hz). We observed that LBNP did not alter the frequency response of the postocclusive SkBF as quantified in the periodogram, even though the amplitude of the SkBF was markedly diminished as a part of the general decrease in arm blood flow. We found inferential evidence for a disseminated common pacemaker mechanism that performs similarly at distant sites. We conclude that the LBNP baroreflex-mediated modulation of SkBF reduces the amplitude but does not change the frequency behavior of postocclusive SkBF. We propose on the basis of our findings that the preservation of vasomotion suggests that this phenomenon is an adaptation to the ischemic changes induced by disruption of blood flow. 
5	Tuberculous tenosynovitis of the wrist. Two case reports. Tuberculosis was first described in 1756 by Acrel in a case report. Subsequent reports of musculoskeletal tuberculosis documented the uncommon occurrence of hand and wrist involvement. The two cases presented here demonstrate the difficulty in eradicating the organism even with modern regimens of chemotherapy. Intraoperative Gram's stain and frozen sections were useful to rule out other etiologies. Firm diagnosis must be established by tissue culture. The first case appeared cured after thorough initial debridement and had no recurrence for 36 years. While recurrences are common in patients treated with debridement alone, most appear within one year after the index procedure. The amount of time that elapsed in this case is unusual and serves as a sobering reminder that tuberculosis may recur at a time distant from the initial procedure. The second patient had tuberculosis diagnosed elsewhere and was treated twice with antituberculous chemotherapy. Although the first course of therapy for six months may have been inadequate, the second course with multiple drugs for 18 months would certainly be considered adequate; yet he had a recurrence in his wrist eight months after completing treatment. These two cases illustrate the fastidious nature of the Mycobacterium tuberculosis organism and the need for a combined treatment protocol of meticulous surgical debridement and combined chemotherapy. 
3	Clinical and electrographic effects of acute anticonvulsant withdrawal in epileptic patients. We retrospectively investigated the effects of acute antiepileptic drug (AED) withdrawal on seizure symptomatology--including frequency, clinical features, and electrical onset--by studying 35 patients during evaluation for epilepsy surgery. The highest risk for both partial and secondary generalized seizures occurred during absent or subtherapeutic, and not during rapidly falling, AED levels. AED withdrawal had minimal effect on clinical symptomatology or electrographic onset. 
4	Anatomic correlations of the long-axis views in biplane transesophageal echocardiography. The number of views obtainable during transesophageal echocardiography (TE) has been limited by the fixed position of the transducer at the end of the probe. This has confined standard TE studies to short-axis tomography of the heart and aorta. Recently, a biplane TE probe has become available that is capable of both long- and short-axis imaging. This study prospectively assessed the application of the long-axis plane of the biplane probe in providing complementary long-axis views in ambulatory patients. Six standard long-axis views could be obtained and were compared with corresponding anatomic sections to illustrate anatomic relations and facilitate structure identification. The long-axis views provide a better appreciation of the 3-dimensional nature of cardiac anatomy and function, especially in demonstrating the relation of vertically aligned structures. 
5	Stiff-man syndrome. Stiff-man syndrome (Moersch-Woltman syndrome) is a rare disorder of motor function characterized by involuntary stiffness of axial muscles and superimposed painful muscle spasms, which are often induced by startle or emotional stimuli. The standard treatment has been benzodiazepines. An association has been reported between stiff-man syndrome and epilepsy, insulin-dependent diabetes, and a variety of organ-specific autoimmune disorders. Antibodies directed against glutamic acid decarboxylase and against pancreatic islet cells have been detected in the serum and cerebrospinal of patients with stiff-man syndrome. These findings suggest that stiff-man syndrome may be an autoimmune disease. Preliminary reports indicate that patients with stiff-man syndrome have a favorable response to plasma exchange and corticosteroid therapy. 
1	Features distinguishing secondary achalasia from primary achalasia. Eighteen patients with cancer-induced or secondary achalasia (SA) were compared to 421 patients with idiopathic or primary achalasia (PA). The aim of the study was to detect any differences in clinical presentation between the two groups. Mean age of patients with SA was 57.1 (range 15-78) and 47.1 (range 1-90) in patients with PA (p = 0.02). Three patients with SA were 15, 24, and 36 yr old, respectively. Symptom frequency was comparable in SA versus PA. Mean duration of symptoms in SA was 4.5 months, with 15 of the 18 patients experiencing symptoms for six months or less. Weight loss occurred in 88.2% of patients with SA and 57.3% of patients with PA (p less than 0.05). Cancer was at the gastroesophageal junction in 16 patients, duodenum in one, and breast in one. Endoscopy showed tumor in 12 (67%). The esophagram was suspicious for tumor in only 25%. We conclude that patients with SA are older, more likely to lose weight, and have a short duration of symptoms. However, SA may occur in younger patients, and endoscopy with biopsy is necessary in any newly diagnosed case of achalasia. 
4	A technique for improving accuracy of the pulmonary artery diastolic pressure as an estimate of left ventricular end-diastolic pressure. Pulmonary artery diastolic pressure (PAD) is often used to estimate left ventricular end-diastolic pressure (LVEDP) when artifact, respiratory variation, or technical difficulties make the wedge pressure difficult to identify on the waveform. To determine which point on the PAD waveform best estimated LVEDP, we performed studies in 100 adults undergoing routine diagnostic cardiac catheterization. During normal spontaneous respiration, simultaneous recordings of the electrocardiogram, PAD, and LVEDP were obtained. Three end-expiratory measurements of PAD were recorded: at the lowest point on the waveform (PAD), at 0.04 seconds (PAD 0.04), and at 0.08 seconds (PAD 0.08) after the onset of the QRS complex. The PADs were correlated with LVEDP by linear regression. PAD 0.08 correlated best with LVEDP (r = 0.88, standard error of the estimate [SEE] = 3.6 mm Hg) whereas PAD 0.04 and PAD correlated slightly less strongly (r = 0.86, SEE = 4.0 mm Hg; r = 0.82, SEE = 4.4 mm Hg respectively). Therefore, when the wedge pressure is not easily determined, PAD 0.08 may be the best point on the waveform to use when attempting to estimate LVEDP in the clinical setting. 
1	Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index). The 17 patients with nonmetastatic cancer were followed from the first cycle of chemotherapy to cancer recurrence; subsequent to six cycles of chemotherapy, all of these patients except one were rendered clinically disease-free through surgery and/or radiation. The end point was defined as either local/regional recurrence or metastasis. Strong P-glycoprotein-positive staining in a majority of tumor cells (the N+/I+ phenotype) was significantly correlated with no initial response to chemotherapy (P less than .02) and with a shorter progression-free survival (P less than .02). Thus, the pretreatment evaluation of P-glycoprotein expression may be of prognostic value in patients with locally advanced breast cancer. 
1	Giant intradiploic epidermoid tumor of the occipital bone: case report. The authors describe a case of a giant intradiploic epidermoid cyst of the occipital bone with an intracranial extension in the posterior fossa and no signs of neurological involvement. The lesion started as a painless lump under the scalp. Roentgenographic and computed tomographic findings led to a correct diagnosis, and the complete removal of the cyst was accomplished, despite its large size. The total removal of these cysts is associated with a good prognosis. 
5	Chronic pain--assessment of orthopedic physical therapists' knowledge and attitudes. Orthopedic physical therapists' knowledge of pain mechanisms and methods of pain management and their attitudes toward working with patients with benign chronic pain were studied. A random sample of 500 members of the American Physical Therapy Association's Section on Orthopaedics received by mail a 36-item questionnaire. Statistical analysis of scores, using frequencies, means, and correlations was performed on the 119 (23.8%) usable returns. All but 4% of the respondents preferred to work with patients who are not likely to have chronic pain. Seventy-two percent believed their entry-level education in pain management and theory was very inadequate or less than adequate to deal with an orthopedic patient population. Pain knowledge scores were low (35.8 out of 46 points), and the scores on positive attitudes toward treating patients with benign chronic pain were lower (20.5 out of 36 points). The study suggests specific deficiencies in orthopedic physical therapists' knowledge of clinical pain mechanisms and management and potentially undesirable attitudes toward treating patients with chronic pain. 
4	Dapsone is an effective therapy for the skin lesions of subacute cutaneous lupus erythematosus and urticarial vasculitis in a patient with C2 deficiency. The deficiency of second component of complement (C2d) is the most common hereditary complement deficiency. Patients with C2 deficiency are frequently associated with an auto-immune disease process, in particular, systemic lupus erythematosus (LE)-like syndrome and/or vasculitic syndrome or bacterial infections. C2d has been associated with the LE subset of subacute cutaneous LE (SCLE), the presence of anti-Ro (SSA) antibodies, and the human leukocyte antigen (HLA) types A10, B18, DR2. We describe the clinical, serologic and immunogenetic data in a patient with manifestations of Sjogren's syndrome who developed urticarial vasculitis and photosensitive annular SCLE which were effectively treated with oral dapsone. Our case illustrates the dynamic nature of LE. 
3	Prognostic significance of conjugate eye deviation in stroke patients. We prospectively studied the prognostic significance of conjugate eye deviation in 80 patients with acute stroke and compared the 3-month mortality and disability of these patients to those of the Tilburg epidemiological study of stroke. Mortality of patients with conjugate eye deviation was higher (41%) than for the general stroke population (34%), but this difference was not statistically significant (p less than 0.179). Looking at mortality and disability together, we found the outcome of patients with conjugate eye deviation to be significantly worse (p less than 0.001). Deviation of the eyes occurred more frequently to the right (65%) than to the left (35%). In the patient group with eye deviation to the left, mortality was significantly higher (64%, p less than 0.001) than in the group with eye deviation to the right (25%); only two patients of the former group (n = 28) could return home. Compared to the Tilburg epidemiological study of stroke, the group with eye deviation to the left did significantly worse, both for mortality alone (p less than 0.001) and for mortality and disability together (p less than 0.001). The group with eye deviation to the right did significantly worse only for mortality and disability together (p less than 0.01). Our results indicate that conjugate eye deviation is a prognostic factor for poor short-term mortality and disability in stroke patients, especially when the eyes are deviated to the left. 
5	Psychological reaction to hospitalization and illness in the emergency department. Each personality type presents with different methods of coping. Physicians should be aware of the impact on a patient's psychological functioning and ability to cope with illness and hospitalization, to understand and more effectively manage the patient. The physician must try to assess the patient's baseline personality from their past and present behavior. Establishing a good physician-patient relationship is important as a source of information about behavior of patients and how they will respond to their illness. Depending on the specific personality type, each patient will respond differently to the stress of illness. The effort of the emergency physician to identify personality types will aid in medical management of the patient and enable the physician to help each patient cope effectively with the illness and the hospitalization. The specific issues that seem to be threatening to traumatized patients include the following: helplessness, humiliation, blurring of body image, and gaps in memory filled with distortions. The traumatized patient experiences an altered state of consciousness which is either due to a physiologic cause or an emotional cause. Emotional causes are usually based on defensive dissociation. People who have been in an auto accident characteristically report loss of memory of the intense pain that the accident produces initially. Oftentimes, the core experience for the traumatic patient is not somatic, it is unconscious. The interesting feature is that so many patients do not remember the accident. The mind seems to be filled with all kinds of distortions and irrelevant and perhaps totally inconsistent fantasies, such as imprisonment, confinement, or deathlike experiences. Some report that they are being incarcerated, others recall being in a featureless cubicle with no contact with the normal world in which there are no windows, no pictures, no flowers. Others remember only being surrounded by masked, hatted, uniformed wardens who are standing over them with nasogastric tubes, intravenous lines, Foley catheters, arterial blood gases, subclavians, and dermal cut-downs. This is an overwhelming nightmare that can be relieved only by the empathic and caring physician and emergency department staff. The stress of medical illness and/or hospitalization can be overwhelming for some patients and is usually followed by some form of psychological response. Current understanding of the psychological impact of illness is based upon psychological defenses, coping mechanisms, and individual personality. It is the ability of the emergency physician to identify defenses, coping skills and personality types that will aid him or her in the medical management of the patients in their time of illness and hospitalization. 
5	Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease. There is little information concerning the prevalence and clinical correlates of increased pulmonary thallium-201 uptake during dipyridamole thallium-201 stress imaging. Accordingly, the clinical characteristics and quantitative thallium-201 findings were correlated with quantitative lung/heart thallium-201 ratio in 87 patients undergoing dipyridamole thallium-201 stress testing. Nineteen patients (22%) had an elevated ratio (greater than 0.51). These patients were more likely to have had an infarction, to be taking beta blockers, and have a lower rate-pressure product after dipyridamole administration than those with a normal ratio (p less than 0.03). An elevated ratio was associated with a greater likelihood of initial, redistribution and persistent defects, as well as left ventricular cavity dilatation on thallium-201 imaging (p less than 0.05). In addition, the number of myocardial segments demonstrating initial, redistribution and persistent defects was also greater in patients with increased ratios (p less than 0.03). Multivariate analysis demonstrated that the presence of redistribution and left ventricular cavity dilatation were the most significant correlates of lung/heart thallium-201 ratio. It is concluded that the prevalence of increased lung/heart thallium-201 ratio with dipyridamole thallium-201 stress imaging is similar to that seen with exercise stress imaging. As with exercise thallium-201 imaging, increased pulmonary thallium-201 uptake may be a marker of functionally more significant coronary artery disease. 
4	Crico-tracheal disruption and common carotid artery occlusion: a case of blunt trauma. A case of blunt trauma to the neck is presented. While driving an all terrain vehicle (ATV), a 20-yr-old male was struck across the anterior neck by a cord suspended between two poles. Initial findings were suggestive of an isolated laryngeal injury; 48 hours later, however, a dense left hemiplegia became manifest. A CT scan demonstrated a large right frontoparietal cerebral infarct, and an angiogram confirmed occlusion of the right common carotid artery. Intractable cerebral oedema developed, and the patient died five days after the initial insult. Such injuries should alert the clinician to the possibility of major vascular injury, and if suspected, angiography is warranted. 
5	Usefulness of fecal alpha 1-antitrypsin clearance and fecal concentration as early indicator of postoperative asymptomatic recurrence in Crohn's disease. The aim of this study was to evaluate in Crohn's disease the possible usefulness of alpha 1-antitrypsin clearance and fecal concentration in the early detection of postoperative asymptomatic recurrence. Eleven adult patients with small bowel Crohn's disease undergoing elective resection were enrolled in the study and prospectively followed for one year. Three, six, and 12 months after surgery the alpha 1-antitrypsin clearance and fecal concentration were measured, and the disease activity was assessed. All patients were free of active symptoms throughout the study. One year after surgery small bowel radiology was performed in all patients. Radiographic evidence of recurrent macroscopic disease was found in five of the 11 patients. Three months after surgery both alpha 1-antitrypsin clearance and fecal concentration were significantly lower (P less than 0.01) than before surgery. There was no difference at this time between patients with recurrence and those with no recurrence. In patients with recurrence both alpha 1-antitrypsin clearance and fecal concentration significantly increased at six months in comparison with the values at three months (P less than 0.02). Both measurements were significantly higher at six and 12 months in this group of patients than in those with no recurrence and in normal controls (P less than 0.01). At six and 12 months alpha 1-antitrypsin clearance was above the upper normal limit in all patients with recurrence. We conclude that fecal alpha 1-antitrypsin clearance is a noninvasive, inexpensive, sensitive marker of asymptomatic recurrence in CD patients who are under regular supervision after surgery. 
5	Changes in anxiety among abstinent male alcoholics. Symptoms of anxiety are prevalent features of alcoholics seeking treatment. In the present study levels of state anxiety among male primary alcoholics (with no preexisting major psychiatric disorders) were examined 3 times per week during inpatient treatment for alcoholism and again at 3 months following treatment. The 171 male alcoholics also completed the trait scale of the State Trait Anxiety Inventory upon admission to an inpatient program and at 3 months following treatment. Results indicate that recently detoxified males experience multiple anxiety symptoms, with 40% reporting significantly elevated levels of state anxiety at admission (greater than or equal to 75th percentile). By the second week of treatment state anxiety scores typically returned to the normal range although symptoms continued to decrease significantly with each week of continued abstinence. Elevated levels of anxiety symptoms were more common among primary alcoholics with a history of panic episodes or generalized anxiety disorder symptoms. While abstainers and relapsers did not differ in level of anxiety observed during treatment, the relapsers report significantly higher state and trait anxiety scores at follow-up. 
5	Passage of a colon 'cast' after anoabdominal rectal resection. Report of a case. The authors report a case of the passage of a total colonic J-pouch "cast" per anus after anoabdominal rectal resection and colonic J-pouch-anal anastomosis. This occurred without development of cuff abscess and was not due to occlusion of the inferior mesenteric artery. This was successfully treated, with preservation of anal function, with resection of the colonic J-pouch by transanal approach. 
2	Intraoperative fine needle aspiration cytology of pancreatic lesions. The aim of the present study was to demonstrate the practicality of intraoperative fine needle aspiration (FNA) cytology of pancreatic lesions in 43 patients. The indication for performing this procedure was to determine the nature of pancreatic masses. Conclusive cytologic diagnoses were reached in 41 patients who represent the present study. On the basis of histologic findings in 30 cases (73.2%) and on clinical findings in 11 cases (26.8%), a final diagnosis of malignant pancreatic disease (MPD) was established in 31 and of benign pancreatic disease (BPD) in 10 patients. Among the 31 cases with MPD, the cytologic diagnosis was correct in 30 patients and falsely negative in one patient. Among 10 patients with BPD, all the cytologic finding were reported as benign. The sensitivity and specificity and positive and negative predictive values for cytologic findings were 96.8%, 100%, 100%, and 90.9%, respectively. The diagnostic accuracy of FNA cytology was 97.6%. No complications followed the procedure. We conclude that intraoperative FNA cytology of pancreatic lesions is a simple, safe, highly sensitive, and specific tool in differentiating benign from malignant pancreatic lesions. This procedure should be carried out in any patient with pancreatic mass incidentally found at laparotomy or in a patient undergoing surgery because of suspected nonmetastasizing MPD in whom repeated imaging guided FNA failed to demonstrate malignancy. 
4	Comparison of frequency of late potentials in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy with advanced congestive heart failure and their usefulness in predicting sudden death. Signal-averaged electrocardiograms were obtained in 62 consecutive patients with advanced congestive heart failure (CHF) undergoing evaluation for possible heart transplantation to determine if late potentials: (1) provide unique information compared to assessment of ventricular ectopic activity on ambulatory electrocardiogram, and (2) identify a subgroup of CHF patients with higher sudden death risk. Patients with a history of cardiac arrest or sustained ventricular tachycardia were excluded. CHF was due to old myocardial infarction in 40 patients and idiopathic dilated cardiomyopathy in 22 patients. Late potentials were present in 16 of 40 (40%) patients with old infarction but in only 3 of 22 (14%) patients with nonischemic CHF (p = 0.03). Twenty-four-hour ambulatory electrocardiograms were obtained in 34 patients (55%). Total ventricular ectopic activity and repetitive forms of ectopy were similar in patients with and without late potentials. Nine patients died suddenly, 9 had nonsudden death, 15 underwent heart transplantation and 29 were alive and well after a mean follow-up of 218 +/- 154 days. At 1 year, the actuarial risk of death was 37% and of sudden death was 20%. Sudden death risk was 12% in patients with late potentials versus 21% in those without (p = 0.73). Thus, the incidence of the arrhythmia substrate producing late potentials depends on the CHF etiology. The signal-averaged electrocardiogram and ambulatory electrocardiogram provide independent information for possible risk assessment in CHF. However, late potentials are poor predictors of sudden death risk when CHF is advanced, possibly due to the heterogeneity of causes of sudden death--ventricular tachycardia being only 1 of many possible mechanisms. 
5	Insensitivity of noninvasive tests to detect coronary artery vasculopathy after heart transplant. Obstructive coronary artery vasculopathy can be a major problem after cardiac transplant. The use of noninvasive tests to detect coronary artery vasculopathy was studied in 73 consecutive patients after heart transplant. Angiographically or autopsy-proved coronary artery disease was noted in 19 consecutive patients (26%) followed prospectively for 2.5 +/- 1.3 years (mean +/- standard deviation). Patients underwent yearly surveillance echocardiographic, rest/exercise-gated wall motion, oral dipyridamole thallium, ambulatory electrocardiographic monitor and angiographic studies. Positive test results were defined by decrease in ejection fraction, wall motion abnormality, failure to increase ejection fraction, lack of systolic blood pressure increase, and ischemic ST changes at maximal exercise (or on ambulatory monitor). Wall motion abnormalities and depressed ejection fraction on echocardiography were also abnormal studies as were fixed or reversible perfusion defects on thallium scan. Angiograms were considered positive when 50% luminal narrowing was observed and autopsy coronary artery vasculopathy was defined as cross-sectional coronary obstruction greater than or equal to 70%. No procedure that was examined proved to be a sensitive noninvasive detector of heart transplant coronary artery vasculopathy. All except ambulatory electrocardiographic monitoring had positive predictive values less than 50%. Interestingly, of the techniques evaluated, echocardiography was most sensitive (53%). The poor predictive ability of noninvasive testing in this population may be due to the fact that these tests are designed to detect effects of ischemia rather than coronary obstruction alone. Use of these particular noninvasive modalities routinely after heart transplant to detect coronary artery vasculopathy should be reconsidered because of their low sensitivity and predictive value when used as a surveillance screen. 
4	Cardiopulmonary perfusion and cerebral blood flow in bilateral carotid artery disease The fear of cerebral complications after cardiopulmonary bypass in patients with heart disease and severe carotid artery disease has led many authors to suggest combined approaches in these patients. The pathogenetic mechanism for stroke is based partly on the stenotic narrowing of the carotid artery. A diameter reduction of 75% is frequently considered hemodynamically significant and indicative of an increased risk for neurological morbidity. We studied the cerebral blood flow in 7 patients undergoing coronary artery bypass grafting who also had severe bilateral carotid disease. The results were compared with the results in 17 patients without carotid disease who had bypass grafting. The cerebral blood flow was measured by xenon 133 washout technique before, during, and after cardiopulmonary bypass with moderate hypothermia. Acid-base regulation was according to the alpha-stat theory, and blood pressure was kept greater than 50 mm Hg. The cerebral blood flow levels (mL.100g-1.min-1) before, during, and after cardiopulmonary bypass in the study group (30 +/- 11, 31 +/- 8, 47 +/- 20) (mean +/- standard deviation) were almost identical to those in the control group (30 +/- 11, 28 +/- 8, 47 +/- 12). The cerebral blood flow levels for the left and right hemispheres in the group with carotid disease were comparable and within normal ranges. In 2 patients, slight differences were noted between hemispheres, and this finding may indicate an increased risk for ischemia. These patients, however, did not show any signs of postoperative deficit. The flow limitations of critical carotid stenoses do not seem to imply a risk for cerebral hypoperfusion if cardiopulmonary perfusion is performed in a controlled manner. 
4	Cellular immunodeficiency in protein-losing enteropathy. Predominant reduction of CD3+ and CD4+ lymphocytes. Cellular immunological abnormalities were studied in a patient with protein-losing enteropathy associated with constrictive pericarditis. Analysis of lymphocyte subpopulations in peripheral blood showed lymphopenia with a decrease of CD3+ and CD4+ T cells, whereas CD8+ lymphocytes, B cells and NK cells were within the normal range. Fecal loss of lymphocytes as a cause of lymphopenia was evidenced by a marked excretion of 111-indium-labeled peripheral blood mononuclear cells via stool. Proliferative responses against several mitogens were severely reduced as was in vitro IgG production. Delayed-type hypersensitivity reaction against a variety of antigens was absent. Vaccination with tick-borne encephalitis virus, used for primary immunization, and with the recall antigen tetanus toxoid resulted in a blunted antibody response. After pericardectomy, the severity of enteric protein loss declined, serum immunoglobulin levels returned to the normal range, and total lymphocytes and CD3+ and CD4+ counts increased but remained low even 12 months after surgery. Fecal loss of lymphocytes was found to be reduced after pericardectomy, but was higher than that seen in a disease control patient with active inflammatory bowel disease. In vitro immunoglobulin production returned to normal, DTH could be demonstrated against purified protein derivative and proteus antigen, but mitogen-driven blastogenic response of lymphocytes remained low. Revaccination with tick-borne encephalitis and tetanus toxoid antigens seven months after surgery resulted in a dramatic increase of serum levels of antibodies against both antigens, comparable to that seen in healthy control individuals. 
3	Seizures in the alcoholic patient. The First International Symposium on Alcohol and Seizures (September 1988, Washington, DC) convened experts from North America and Europe to discuss the basic and clinical research findings in this field. Most of the observations communicated at this symposium are included in this article. Emergency physicians are familiar with the alcoholic patient who presents during or after a seizure(s). This familiarity must not obscure the fact that a significant minority of these patients will have an underlying process that can cause morbidity or mortality if the unsuspecting physician does not have an organized and methodic approach to the evaluation and management of the seizing alcoholic patient. Status epilepticus should be evaluated and treated in a similar fashion, whether or not the patient is an alcoholic. Otherwise, almost without exception, there are nuances and controversies with respect to the evaluation and management of the alcoholic patient with a seizure(s), from the indications for CT scan, to the proper role of sedatives and anticonvulsants, and the need for admission. The emergency physician must remain a patient advocate. The great majority of alcoholic patients with seizures who require admission can be treated satisfactorily at the hospital of presentation. 
4	Elevated plasma beta-endorphin levels in patients with congestive heart failure Recent experimental studies show that the opioid system is important to the pathophysiology of cardiovascular impairment in congestive heart failure. Plasma beta-endorphin levels were measured in 37 patients with congestive heart failure and compared with those of 21 age- and gender-matched normal subjects. The relation of plasma beta-endorphin levels and cardiac function at rest and exercise capacity was assessed in 17 of the patients with dilated cardiomyopathy. Exercise capacity was determined by symptom-limited maximal treadmill exercise with expired gas analysis. Plasma beta-endorphin levels were elevated and correlated with the patients' New York Heart Association functional cardiac status (control: 14.0 +/- 4.4 pg/ml; class II: 17.9 +/- 3.6 pg/ml; class III: 28.3 +/- 8.8 pg/ml; class IV: 46.7 +/- 14.6 pg/ml, mean +/- SD). No relation was found between plasma beta-endorphin levels and left ventricular systolic performance as assessed by M-mode and Doppler echocardiography. Plasma beta-endorphin levels were negatively correlated with cardiac output determined by Doppler echocardiography and positively correlated with systemic vascular resistance (r = -0.733, r = 0.747, respectively, both p less than 0.001), but not correlated with calf blood flow as measured by a plethysmography. A good correlation was found between plasma beta-endorphin levels at rest and exercise capacity. The correlations with peak oxygen consumption, anaerobic threshold, and peak rate-pressure product were r = -0.721, -0.672, and -0.674, respectively (p less than 0.01). The data show that plasma beta-endorphin levels are elevated in patients with congestive heart failure and reflect, to some degree, the severity of the disease. 
3	Nontropical pyomyositis as a cause of subacute, multifocal myalgia in the acquired immunodeficiency syndrome. We report a case of nontropical pyomyositis in a patient with acquired immunodeficiency syndrome and disseminated Mycobacterium avium infection, in which severe myalgia was the presenting symptom over several weeks. Multifocal muscle lesions were identified by gallium scanning and magnetic resonance imaging techniques. The epidemiology, possible pathogenesis, clinical features, diagnostic imaging, and therapy are reviewed. Early suspicion of nontropical pyomyositis in severely immunocompromised patients with "cryptic" myalgia is recommended. 
3	Causes of death in the elderly and their changing pattern in Hisayama, a Japanese community. Results from a long-term and autopsy-based study. The causes of death for the elderly were prospectively studied in Hisayama, Japan, a rural community. We compared 1,621 subjects, aged 40 years or over, recruited in 1961, and 2,053 subjects recruited in 1974. Each cohort was studied in a follow-up that lasted 10 years; they had autopsy rates of 82.1% and 86.1% during each 10-year period, respectively. The most common causes of death for those aged 70 years or over were cerebrovascular disease, malignant neoplasms, and pneumonia. Deaths due to cerebrovascular disease tended to decrease in the recent cohort, but the proportion of decline was more prominent in cases aged 40 to 69 years. There was a sex difference in the changing pattern of mortality from heart diseases including ischemic heart disease. Deaths by both heart diseases and ischemic heart disease increased in the more recent cohort of aged women, whereas they decreased in the aged men. Pneumonia was an important cause of death for the elderly in both cohorts. Deaths due to "senility" were rare, being only 1% of the deceased aged 70 or over. With prolonged lifespan, especially for women, the impact of atherosclerosis and its related disorders on the recent Japanese aged population appears to have increased. 
1	Clinicopathologic characteristics of adenosquamous carcinoma of the lung. Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants. 
4	Value of ventricular electrogram recordings in the diagnosis of arrhythmias precipitating electrical device shock therapy. An antitachycardia pacemaker-cardioverter-defibrillator that is capable of storing ventricular electrograms before and after delivery of device shock therapy was implanted in 16 patients. Three of the patients experienced out-of-hospital device shock therapy preceded by minimal symptoms. Although limitations of electrogram analysis exist and are discussed, careful analysis and registration of electrograms during all supraventricular and ventricular rhythms observed during in-hospital testing served as an important reference for subsequent arrhythmia diagnosis. By analyzing the electrogram rate and RR interval stability and configuration, a definitive diagnosis was established in all three patients (atrial fibrillation, polymorphic ventricular tachycardia and rate-sensing lead disruption, respectively). Thus, the ability to store ventricular electrograms before shock therapy represents a major advance in the management of patients who receive an electrical device to treat ventricular tachyarrhythmia. 
4	Captopril-induced cholestatic jaundice. I have reported a case of captopril-induced cholestatic jaundice. This drug is being used with increasing frequency, so it is important that physicians recognize this adverse effect. Captopril-induced jaundice resolves after cessation of captopril therapy. 
1	Survival after groin dissection for malignant melanoma. Groin dissection was performed in 158 patients with malignant melanoma (superficial dissection, 76 patients; radical dissection, 82 patients). Of 63 patients with palpable nodes, 57 patients (90%) had histologic involvement. Of 93 patients with nonpalpable nodes, 31 patients (33%) had histologically positive nodes. The 5-year survival rate for patients with histologically negative nodes (n = 69) was 77%; the 5-year survival rate for patients with histologically positive nodes (n = 89) was 43%. The respective 5-year disease-free survival rates were 72% and 34%. Of 57 patients with palpable, positive inguinal nodes, 21 patients (37%) had involvement of the deep nodes. Of 31 patients with nonpalpable, histologic involvement of the inguinal nodes, six patients (19%) had or developed involvement of the deep nodes. One of two patients with uncertain clinical status of the nodes preoperatively had positive deep nodes. In prophylactic node dissection, frozen section of the inguinal group of the nodes does not provide a reliable method, because of sampling errors, in determining microscopic involvement of the nodes and in deciding whether a superficial or radical groin dissection is to be done. For patients with positive nodes the 5-year survival rate was 48% when only the inguinal group was involved and was 28% when both inguinal and deep nodes were involved; the respective 5-year disease-free survival rates were 39% and 20%. Survival after therapeutic groin dissection may partly depend on the thoroughness of the procedure. Patients who have positive, deep nodes and who are undergoing an incontinuity dissection of the inguinal, iliac, and obturator nodes have an appreciable 5-year survival rate. 
2	Pancreatic response to percutaneous biliary drainage: a prospective study. To evaluate the effects of percutaneous biliary drainage (PBD) on the pancreas, serum amylase levels were measured for 7 consecutive days after PBD and compared with baseline values in 50 patients who underwent a total of 53 PBD procedures. Of the 45 patients with normal baseline serum amylase levels, 12 patients (24%) developed postprocedural hyperamylasemia without clinical symptoms and five patients (10%) developed postprocedural hyperamylasemia with clinical signs of pancreatitis. Five patients who presented with elevated baseline serum amylase levels demonstrated decreases into the normal range after placement of stents without initiation of bowel rest or liquid diet. The level of biliary obstruction proved insignificant, as did the nature of the obstructing disease, in determining which patients would experience hyperamylasemia or pancreatitis after PBD. It is concluded that the frequency of pancreatic insult from PBD may be more common than previously reported and that patient susceptibility is not dependent on the level of biliary obstruction or the nature of the disease. 
3	Neuroanatomy of fragile X syndrome: the posterior fossa. The occurrence and specificity of posterior fossa abnormalities as measured from magnetic resonance images of the brain were investigated in a group of 14 males with fragile X syndrome and comparison groups consisting of 17 males with other causes of developmental disability and 18 males with normal IQs. The size of the posterior cerebellar vermis was significantly decreased and the fourth ventricle significantly increased in the group of males with fragile X syndrome compared with males in both comparison groups. These neuroanatomical abnormalities appeared to be secondary to hypoplasia rather than atrophy. 
5	Helicobacter pylori infection in pernicious anemia: a prospective controlled study. Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process. 
2	Crohn's disease and pregnancy. Seventy-eight pregnancies in 50 patients were reviewed to evaluate the effects of Crohn's disease on the outcome of pregnancy and the influence of the pregnancy on the course of Crohn's disease. Overall, 21 pregnancies (27 percent) had abnormal outcomes including spontaneous abortions (9), infants small for gestational age (6), premature infants (5), and infants who developed respiratory distress (1). Eight (50 percent) patients with active disease compared with 13 (21 percent) patients with inactive disease at conception had abnormal outcomes (P less than 0.05). During pregnancy 15 (55 percent) with active disease and 6 (12 percent) with inactive disease had an abnormal outcome (P less than 0.001). Neither medical nor surgical treatment, independent of disease activity, appeared to affect the outcome adversely. Eighteen of 73 (25 percent) patients with quiescent or mild disease relapsed, and seven of 16 patients with some disease activity improved (44 percent). Of 34 patients on medication, nine relapsed (27 percent), and of 39 patients not on medication, nine relapsed (24 percent) (P = N.S.). These results suggest that the outcome of pregnancy is not adversely affected by Crohn's disease. However, patients with active disease at conception and/or during the pregnancy have poorer outcomes independent of the use of medication or requirement of surgery. Neither pregnancy nor medications taken affect the course of the disease. 
5	Injury biomechanics of the human cervical column. In this study, the authors have developed a technique to replicate clinically relevant traumatic cervical spine injuries and determined the injury biomechanics. Because of the importance of compressive forces in neck injuries, this research was conducted using compression as the primary load vector. Six fresh human cadaveric head-neck complexes were prepared by fixing the distal end in methylmethacrylate. Tests were done with varying loading rates to include quasistatic and dynamic conditions. For quasistatic experiments, the proximal end was fixed to the piston of the testing device. In dynamic tests, the cranium was unconstrained, and to maintain stability, the effects of the spinal musculature were simulated by means of pulleys, deadweights, and springs in the anterior and posterior parts of the head-neck complex. Quasistatic tests conducted at a rate of 2.0 mm/sec produced cervical spine trauma at forces ranging from 1.7 to 2.3 kN, with deformations ranging from 2.2 to 3.7 cm. The specimens were deep-frozen at the level of injury, preserving the local deformation of the tissues to enable a detailed evaluation immediately after the injury. Dynamic tests conducted at velocities of 3.2 to 5.7 m/sec resulted in impact injuries at one level of the head-neck complex. The applied forces at the vertex were considerably higher than those recorded at the distal end. The failure deformations for both the quasistatic (2.2-3.7 cm) and dynamic (1.7-3.2 cm) tests, however, were found to be similar, suggesting that the human head-neck complex is a deformation-sensitive structure. 
4	Physical examination and echo Doppler study in the assessment of femoral arterial complications following cardiac catheterization. Femoral arterial complications following cardiac catheterization have been well recognized. The development of an inguinal mass in these patients can represent a simple hematoma, a pseudoaneurysm, or an arteriovenous fistula. The utility of the physical examination in diagnosing these complications was assessed by using the echo Doppler study for comparison. This study shows that any single clinical sign should not be used in isolation, but a constellation of physical findings can suggest the correct diagnosis. 
1	Nuclear grading of breast carcinoma by image analysis. Classification by multivariate and neural network analysis. The use of nuclear grade as a prognostic indicator for breast carcinoma has been limited by interobserver variability. Advances in image analysis and automated cell classification offer one approach to this problem. The authors used the CAS-100 (Cell Analysis System. Elmhurst, IL) system to measure and analyze nuclear morphometric and texture features of cytologic preparations from 35 breast carcinomas (well, moderate, and poorly differentiated) as well as benign lesions. Morphometric and Markovian texture feature data from breast cancer nuclei of various grades comprised a training set, which was then used to establish classification criteria by multivariate (Bayesian) analysis and to train a neural network system. Both systems were tested for the ability to classify the nuclear grade of individual nuclei. There was good agreement between computer classification and the grade assigned by human observer to individual nuclei using either Bayesian or neural network analysis. Thirty-one unknown cases, which were assigned an overall grade by an observer, were then analyzed by computer, and an overall grade assigned based on the grade of nucleus most frequently present. Using this method, both classification systems were able to assign a "correct" grade to low-grade lesions (approximately 70% correct) more often than to high-grade tumors (approximately 20%). Difficulty in computer assignment of high-grade tumors was explained by nuclear heterogeneity in these tumors (i.e., although the percentage of high-grade nuclei was increased compared with that of low-grade tumors, high-grade nuclei frequently did not predominate). The authors present this study to demonstrate the feasibility of using image analysis as an objective means of nuclear grading. Further studies will be needed to establish criteria for assigning overall nuclear grade based on computer analysis of imaging data. 
2	Which clinical variables predict an abnormal double-contrast barium enema result? OBJECTIVE: To determine the relations among patient history, symptoms, objective indicators, and abnormal double-contrast barium enema results in outpatients. PATIENTS AND SETTING: Seven hundred and ninety-four patients receiving care in a large multispecialty medical group. DESIGN: Physicians completed a form before ordering a double-contrast barium enema, listing information about patient history, symptoms, and objective findings, including the results of a complete blood count, stool hemoccult, and sigmoidoscopy. MEASUREMENTS AND MAIN RESULTS: Outcome measures were colon cancer and any abnormal finding. The results of 18.6% of the barium enemas were abnormal. The most frequent positive findings were of polyps (8.8%) and colon cancer (2.9%). Over 50% of the barium enemas were ordered solely on the basis of symptoms, yet there was no statistical correlation between symptoms and colon cancer or any positive finding. Using logistic regression, four variables were shown to be significant predictors of colon cancer (P less than 0.05): abnormal sigmoidoscopy, iron deficiency anemia, positive stool hemoccult results, and relevant history. The respective odds ratios of these variables were 3.76 (95% CI, 2.89 to 4.90); 2.86 (CI, 2.13 to 3.74); 1.87 (CI, 1.46 to 2.39); and 1.91 (CI, 1.44 to 2.52), respectively. In a patient without any of these indicators, the predicted probability of having colon cancer was only 0.7%. In a patient with at least two objective indicators, the probability of having colon cancer was greater than 15%. CONCLUSIONS: Symptoms without objective indicators or pertinent risk factors do not correlate with an abnormal double-contrast barium enema result. Objective indicators are useful predictors of an abnormal barium enema result, particularly when looking for colon cancer. 
4	IgG and IgA antibodies to the collagen-like region of C1q in rheumatoid vasculitis. We investigated the presence of IgG and IgA antibodies to C1q in serum samples from 80 patients with rheumatoid arthritis (RA), 31 patients with rheumatoid vasculitis, and 80 healthy controls. IgG and IgA antibodies to C1q, as measured by enzyme-linked immunosorbent assay, were found in less than 5% of the sera from RA patients and from healthy controls. In contrast, IgG and IgA antibodies to C1q were found in 29% and 61%, respectively, of the sera from patients with rheumatoid vasculitis. The occurrence of IgA antibodies to C1q has not been previously demonstrated. These results also demonstrate that IgG antibodies to C1q do not occur exclusively in systemic lupus erythematosus patients: Sera of patients with rheumatoid vasculitis frequently contain IgG or IgA antibodies to C1q, which contribute to immune complex formation. 
3	Steroids induce acetylcholine receptors on cultured human muscle: implications for myasthenia gravis. Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. We show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. Our results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also to a direct effect on muscle. We propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications. 
1	Fine-needle aspiration biopsy of head and neck lesions. The case records of 213 fine-needle aspiration biopsies (FNAB) of head and neck masses performed on 209 patients over a 3-year period were reviewed to assess the diagnostic accuracy and safety of this technique in comparison with surgical histologic examination. Cytologic diagnoses based on FNAB were compared with histologic diagnoses in 110 patients who underwent surgery. Based on cytology alone, 40.3% of the lesions were reported as malignant, 45.1% as benign, and 14.6% as indeterminant. A specific cytologic diagnosis was made in 85.5% of the cases. Cytologic diagnoses concurred with surgical histologic diagnoses 90% of the time. Fine-needle aspiration biopsy was found to have a false-positive rate of 0.5% and a false-negative rate of 2.3%. The sensitivity and specificity of FNAB in determining a malignant diagnosis were 81.1% and 99%, respectively. Positive and negative predictive values were calculated at 98.9% and 82.8%, respectively. Diagnostic rate, sensitivity, and negative predictive value increased consistently throughout the study period, indicating that the diagnostic accuracy of FNAB improved with experience. 
5	Carcinoma of the pancreas: a retrospective review. Eighty-five patients with adenocarcinoma of the pancreas were reviewed in order to evaluate the efficacy of our methods of diagnosis and treatment. The most useful diagnostic test was percutaneous transhepatic cholangiography (PTC) with a diagnostic rate of 96%. Pancreaticoduodenectomy (Whipple procedure) and total pancreatic resection were performed in 13 and 2 patients, respectively. The remaining 50 patients underwent various palliative drainage procedures. Twenty patients did not undergo operation for various reasons. The primary tumor was found in the head of the pancreas in 50 patients (59%), the body in 6 patients (7%), and in the tail in 8 patients (9%). Postoperative complications, including sepsis, bleeding, intra-abdominal abscesses, and anastomotic leaks, occurred in 37% of the patients. There were one operative and 9 postoperative deaths. The average survival for those patients undergoing surgical intervention was 6 months. There were no 5-year survivors. 
5	Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. The reversibility of hepatic fibrosis was investigated in an experimental model of extrahepatic cholestasis in the rat after common bile duct ligation for 2 weeks, followed by bilioduodenal anastomosis for 3 weeks. Bile duct ligation resulted in a transitory marked elevation in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin during the first 3 days. Then these levels decreased to threefold, twofold, and 100-fold the normal values, respectively, during the following 4 weeks. Histologic examination of the liver disclosed extensive bile duct proliferation and the formation of periportal fibrosis, with only slight inflammation and necrosis. The distribution of the major components of the hepatic extracellular matrix was analyzed 2 weeks after bile duct ligation, using the indirect immunoperoxidase method. Fibrous septa were found to be strongly stained for collagens I, pro-III, III and IV, fibronectin, and laminin. The most intense staining was found in enlarged periportal areas, collagen IV and laminin being particularly abundant around newly formed bile ducts. These changes paralleled high steady-state levels of alpha 1(I) and alpha 1(IV) collagen and B2 chain laminin mRNAs. Relief of the obstruction for 2 weeks resulted in a shift in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin toward normal values. A dramatic resorption of bile duct proliferations and periportal fibrosis were observed. Three weeks after bile duct repermeabilization, immunohistochemical study showed that the pattern of distribution of extracellular matrix components was almost normal, except for collagen IV, which remained abundant in the sinusoids when compared with the normal liver. In parallel, the steady-state B2-chain laminin mRNA level became lower than in cholestatic livers, whereas alpha 1(I) and alpha 1(IV) mRNAs were almost undetectable. These results show that hepatic fibrosis induced by experimental extrahepatic cholestasis in rat disappears in less than 3 weeks after relief of bile duct obstruction, suggesting that an active degradation of matrix protein occurs, except for collagen IV in the sinusoid. 
1	Carcinosarcoma of the lung with hypertrophic pulmonary osteoarthropathy. Carcinosarcoma of the lung is a rare malignancy. Endobronchial and parenchymal variants are classically described. Clinicopathological features are often related to anatomical location, as is the case for most lung neoplasms. This case report details the surgical management of a carcinosarcoma in a patient seen with pulmonary osteoarthropathy. 
1	Diagnosis of noninfective cardiac mass lesions by two-dimensional echocardiography. Comparison of the transthoracic and transesophageal approaches. This study was conducted in 46 patients with cardiac thrombi, 15 patients with atrial myxomas, and 32 patients with other cardiac or paracardiac tumors. Diagnoses were subsequently proven by surgery, autopsy, computed tomography, magnetic resonance imaging, or angiography in all patients. All patients underwent precordial and transesophageal two-dimensional echocardiography to assess the various mass detection rates. Atrial myxomas and predominantly left-sided cardiac tumors were identified by both echocardiographic techniques with comparable detection rates. Left ventricular apical thrombi were detected more frequently by precordial echocardiography. In contrast, transesophageal echocardiography was superior in visualizing left atrial appendage thrombi, small and flat thrombi in the left atrial cavity, thrombi and tumors in the superior vena cava, and masses attached to the right heart and the descending thoracic aorta. These data indicate that transesophageal echocardiography leads to a clinically relevant improvement of the diagnostic potential in patients in whom cardiac masses are suspected or have to be excluded in order to ensure the safety of clinical procedures. 
1	CD34 antigen expression in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. One characteristic of Philadelphia chromosome (Ph')-positive acute leukemia is the occasional presence of both lymphoid and myeloid features in the same leukemia. This phenomenon supports the theory that this subtype of acute leukemia arises from lymphoid-myeloid stem cell, pluripotent progenitors. Very few reports, however, describe the immunophenotype, especially CD34 antigen, of Ph'-positive acute lymphoblastic leukemia (ALL). It has been shown that CD34, the human progenitor cell antigen, is found on 1% or less of normal human bone marrow cells, approximately 30% of acute leukemias, and multipotent progenitor cells; CD34 is not found on normal peripheral blood cells. A high frequency of CD34 expression was found in children with Ph'-positive ALL: CD34 was positive for all six patients tested, and one had an acute mixed-lineage leukemia. These findings suggest the involvement of a pluripotent stem cell in Ph'-positive ALL. 
1	Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1. A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver. 
5	Endoscopic management of chronic organoaxial volvulus of the stomach. Endoscopic correction of the chronic organoaxial volvulus of the stomach was attempted in seven cases of primary and three cases of secondary volvulus. Endoscopic correction was successful in six cases of primary volvulus and one case of volvulus secondary to duodenal carcinoma. This paper describes the details of the technique of endoscopic correction of gastric volvulus, and documentation of correction of the volvulus by barium meal study with a follow-up of 5-26 months. 
3	Syncope and presyncope associated with probable adverse drug reactions. The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications. 
5	The impact of quitting smoking on symptoms of chronic bronchitis: results of the Scottish Heart Health Study. Scotland has high rates of death from diseases of the respiratory system and high rates of smoking, especially among women. Data on self reported smoking and prevalence of chronic cough and chronic phlegm among 10,359 men and women aged 40-59 years were obtained from the Scottish Heart Health Study. Overall, current cigarette smokers had rates of chronic cough and chronic phlegm four to five times those of never smokers after standardisation for age (32.3% v 6.5% for men and 24% v 5.5% for women for chronic cough; 31% v 8.3% for men and 21% v 5.5% for women for chronic phlegm). Ex-smokers' symptom rates were a little above those of never smokers and were significant for chronic cough among women and chronic phlegm among men. Men had higher symptom rates than women and this was true for smokers, ex-smokers, and never smokers. The higher rates among men could not be explained by higher cotinine concentrations. Tests to detect "deceivers" among ex-smokers and never smokers using biochemical validation suggested that 87 (1.5%) respondents were in fact smoking; they were excluded from analyses. There were substantially lower rates of chronic cough and chronic phlegm within a year of stopping smoking, and two to four years after stopping 89-99% of the difference between current smokers and never smokers was accounted for (99% and 93% for men and women with chronic cough, 96% and 89% for men and women with chronic phlegm). Even 10 years after stopping, rates of symptoms among ex-smokers remained a little above those of never smokers (except for women with chronic phlegm), though these differences were not statistically significant. Former heavy smokers continued to have rates of chronic cough and chronic phlegm that were higher than those of former light and moderate smokers (though not significantly so). These are cross sectional data, but they emphasise the importance for chronic bronchitis symptoms of giving up cigarette smoking, though the amount previously smoked continues to exert a small influence. 
5	Hyaline ring granuloma: a distinct oral entity. Hyaline ring granuloma (HRG) is a distinct oral entity. In this study, 64 cases from the literature are analyzed and two new cases are reported. The lesions could be classified by location as central hyaline ring granuloma (42%) and peripheral hyaline ring granuloma (53%). Radiographically, a radiolucent area irregularly outlined by well-formed trabeculae of bone was found in central HRG, and a poorly defined erosion at the crest of the alveolar ridge was often found in peripheral HRG. Occasionally, the lesion occurred in the connective tissue wall of cysts (5%). The etiology of this condition is controversial, but most lesions were in edentulous areas and most patients had a history of tooth extraction or other trauma. The majority of cases (83%) occurred in the mandible, usually posterior to the premolar. The mean age of patients at diagnosis was 43 years, and the male/female ratio was 1.9:1. Pain was not a symptom, although local discomfort, such as recurrent swelling and tenderness, was noted in many cases. Hyaline rings with giant cell inclusions are the significant features for histopathologic diagnosis. HRG is treated by curettage or surgical excision, care being taken to remove the entire lesion. The removal of a peripheral HRG in an edentulous jaw should be followed by careful smoothing of the bone surface, since the lesion tends to infiltrate and is not well demarcated. Recurrence, probably due to incomplete excision, is uncommon. 
5	Voltage criteria of left ventricular hypertrophy in sudden and nonsudden coronary artery disease mortality: the Italian section of the Seven Countries Study. It is unclear whether sudden or nonsudden death can be predicted independently from other risk factors for coronary artery disease (CAD). Therefore, this investigation was undertaken to measure 12-lead QRS voltage sum, a recently proposed (Am J Cardiol 1985;55:485-494) index of left ventricular (LV) hypertrophy, and its ability to predict either subsequent sudden (less than 2 hours) or nonsudden CAD death during 20 to 23 years of follow-up in 1,588 middle aged men (40 to 61 years old) from 2 cohorts of the Italian section of the Seven Countries Study who were free of demonstrable CAD (at entry examination in 1962). The Sokolow-Lyon and the modified Sokolow-Lyon indexes, 2 standard electrocardiographic methods to detect LV hypertrophy were also measured and compared. During follow-up, 67 patients died suddenly and 87 died a nonsudden CAD death. In the Cox proportional-hazards model, age, mean blood pressure, heart rate, body mass index, cholesterol, physical activity, smoking habit, ST-T alterations (Minnesota codes 4.1 to 4.3 together with 5.1 to 5.3) and the 3 electrocardiographic indexes, all measured at the time of enrollment into the study, were included. The 12-lead QRS voltage sum retained significant and independent relation to sudden death (t = 2.00); Sokolow-Lyon index entered the Cox solution for nonsudden CAD death but the association was inverse (t = -2.10). ST-T alterations were significantly associated only with nonsudden CAD death (t = 2.19). Thus, in addition to several known risk factors, measurement of 12-lead QRS voltage sum in middle-aged men without clinical evidence of heart disease may help identify subjects at an increased risk of sudden death; nonsudden CAD death is predicted by Sokolow-Lyon index and by ST-T alterations. The usefulness of these indexes needs to be tested in different populations. 
5	Left ventricular pseudoaneurysm with hemoptysis. A 53-year-old man who had previously undergone resection of a left ventricular aneurysm was admitted because of hemoptysis. Preoperative evaluation with computed tomographic scan and cardiac catheterization demonstrated a pseudoaneurysm of the inferior ventricular wall measuring 16 cm in diameter with protrusion into the left hemithorax. The neck of the pseudoaneurysm was a defect in the ventricular wall extending from the base of the mitral valve annulus to the insertion of the posterior papillary muscle. Operative repair was performed using an albumin-coated, low-porosity Dacron patch. 
3	Cerebral blood flow in progressive aphasia without dementia. Case report, using 133xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography. We report a case of progressive aphasia without clinical signs of intellectual or behavioral impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset. 
1	Anionic complex-carbohydrate units of human thyroglobulin. Human thyroglobulin (hTG) contains sulfate in chondroitin 6-sulfate chains and in complex carbohydrates. In this study the sulfate-containing complex carbohydrates were characterized by the number of sulfate and sialic acid residues that they contain. Samples of normal and nodular thyroid tissue were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified from the tissues and the media. Complex carbohydrates were enzymatically removed from hTG. Subsequent analysis on an HPLC anion exchange column at pH 2.2 separated the carbohydrate units according to their number of negative charges. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing peaks were identified by their shift to lower charge after treatment with neuraminidase. Peaks corresponding to sialic acid-free carbohydrate units with one to four sulfates were identified. Also, carbohydrate units with two and three negative charges containing both sulfate and sialic acid were present. In the nodular tissue of one patient there were more sulfated units with higher charge, especially units containing sialic acid. In this patient the proportion of sulfated polyvalent units with sialic acid was 22.4% for normal and 64.6% for nodular tissue. No difference in the composition of the charged units between the tissues and their corresponding media was seen, making it unlikely that the sulfate-containing carbohydrates play a role in hTG release. It is concluded that hTG contains complex carbohydrate units with up to four sulfate groups and units with both sulfate and sialic acid. In some patients, the sulfate-containing anionic carbohydrate units of hTG from normal and nodular thyroid tissue are different. 
5	Bilateral phrenic nerve palsy associated with open-heart surgery. The incidence of phrenic nerve palsy after open-heart surgery has been estimated at 10%, but it is usually unilateral and does not cause symptoms. Bilateral phrenic nerve injury after coronary artery bypass surgery is a rare complication. This case report describes a patient who developed bilateral phrenic nerve palsies and required prolonged ventilatory support. Denervation of both hemidiaphragms was documented by needle electromyography four weeks after bypass surgery. The patient required total ventilatory support for three months and partial ventilatory support for an additional three months. This case demonstrates the usefulness of electromyographic screening for documentation and prognostication after phrenic nerve injury. The cause of the lesion was unclear, but hypothermia and stretch were leading hypotheses. This patient developed the phrenic nerve palsies despite using a cardiac insulation pad. 
3	Progressive coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension: report of two cases. Two cases of neurological deterioration and coma after the transsphenoidal decompression of a pituitary adenoma with marked suprasellar extension and invasion of the 3rd ventricle are presented. Emergency ventricular shunting led to prompt neurological improvement, which, supplemented by radiation therapy, allowed long-term amelioration of symptoms. Three possible explanations for this complication are offered: 1) traction of the attached 3rd ventricle into the decompression site, causing increased obstructive hydrocephalus, 2) vasopressin release by surgical manipulation of the pituitary stalk and circumventricular organs causing cerebral edema, and 3) edema in the residual tumor secondary to surgical manipulation causing further hydrocephalus. Subsequent patients with similar clinical and imaging criteria will have a planned perioperative ventricular shunting procedure performed. 
3	Vertebrobasilar occlusion following minor trauma in an 8-year-old boy. An 8-year-old boy developed seizures and coma 2 days after a trivial bicycle accident. Computed tomography failed to show pathology. Magnetic resonance imaging of the head showed infarction of the pons and right cerebellum. Angiography showed occlusion of the right vertebral and basilar arteries. Minor traumatic injuries to the cervical spine may result in vertebrobasilar occlusion. The neurologic manifestations of this disorder and emergency department diagnosis and management are discussed. 
2	A coproporphyria-like syndrome induced by glipizide. A 49-year-old man with a 1-month history of episodic, severe abdominal pain sought medical attention. The patient's history was remarkable for type II diabetes, for which glipizide therapy had been initiated 2 months earlier. No other medications were being taken at the time the paroxysms of pain began. During the episodes of pain, both examination of the abdomen and abdominal roentgenograms revealed normal findings. Initial assessment, including ultrasonography and computed tomographic scanning of the abdomen, upper gastrointestinal and colon roentgenograms, and esophagogastroduodenoscopy, revealed no cause of the pain. Empiric trials of famotidine, sucralfate, and antacids failed to relieve the pain. Both urine and fecal specimens collected after an attack demonstrated substantially increased coproporphyrins. The glipizide regimen was discontinued; 2 months later, the stool coproporphyrins had decreased to normal levels. At follow-up more than 1 year later, the patient had had no recurrence of abdominal pain. Although other orally administered hypoglycemic agents and other sulfa compounds have been reported to precipitate acute attacks of porphyria, to our knowledge this is the first such case associated with glipizide. We suggest that glipizide be added to the list of medications to be avoided in patients with porphyria. 
1	Human immunodeficiency virus-induced immunosuppression: a risk factor for human papillomavirus infection. In a group of 92 women with genital condylomata, 15 (16.3%) human immunodeficiency virus-positive patients were found, whereas no case was detected in a control group of 100 women. The relative risk was greater than 19.28. Human immunodeficiency-positive status was associated with other parameters: lower age and parity, major frequency of induced abortions, and sexually transmitted diseases. Thus although human immunodeficiency-positive status seems to be a true risk factor in relation to the altered immunologic state, an indirect association cannot be discarded. Such patients should be screened closely for human papillomavirus infection and cervical cancer. Among human immunodeficiency-positive women, a more resistant behavior of human papillomavirus-associated lesions was detected (recurrence-persistence of 41.7% versus 12%), a fact that might also be in relation to the immunodepressed status. 
2	Delayed pharyngoesophageal perforation: a complication of anterior spine surgery. Stabilization of the cervical spine is often accomplished via an anterior cervical approach. Bone grafts and/or plates and screws are used to achieve stabilization. Injuries to the pharynx and esophagus are known complications in anterior exposure of the cervical spine. These injuries are manifest in the early postoperative period. Reports of late perforations are very rare. We present four cases of delayed injury to the pharynx and esophagus that resulted in abscess or fistula. We postulate that graft displacement with resulting erosion was responsible for these serious complications. Postoperative odynophagia in patients who undergo anterior cervical fusion warrants evaluation of the bone graft location. Early surgical intervention and repair may decrease prolonged morbidity in these patients. 
4	Effects of inosine on glycolysis and contracture during myocardial ischemia. The effects of inosine (INO) on substrate metabolism and rigor formation in ischemic myocardium were examined in isolated rabbit hearts. Metabolite content was assessed in tissue extracts by chemical analysis and in the whole heart by 13C and 31P nuclear magnetic resonance spectroscopy. In ischemic hearts metabolizing either [3-13C]pyruvate or [1-13C]glucose, 1 mM INO increased both total and 13C-labeled alanine content; lactate content was unaffected. At 3 minutes of ischemia, tissue alanine was 1.81 +/- 0.11 microM/g wet wt (mean +/- SEM) in hearts perfused with pyruvate+INO versus 1.23 +/- 0.15 microM/g wet wt in hearts perfused with pyruvate alone (p less than 0.05). INO reduced tissue glycogen during ischemia in pyruvate-perfused hearts. Tissue alanine content in ischemic hearts that were supplied glucose+INO (1.29 +/- 0.13 microM/g wet wt) was greater than in ischemic hearts supplied glucose alone (0.65 +/- 0.14 microM/g wet wt). Alanine was found to originate from pyruvate and was a glycolytic end product in glucose-perfused hearts. INO raised the [3-13C]alanine/[3-13C]lactate ratio in ischemic, intact hearts (glucose = 0.24 +/- 0.07 versus glucose+INO = 0.60 +/- 0.09; pyruvate = 0.49 +/- 0.08 versus pyruvate+INO = 0.89 +/- 0.08). At 7 minutes of ischemia, ATP content fell to 70 +/- 3% with glucose+INO versus 58 +/- 5% with glucose alone. Rigor (stone heart) was delayed from 14.7 +/- 1.3 to 23.2 +/- 1.6 minutes with INO. INO did not change ATP content in ischemic hearts that were supplied pyruvate but delayed rigor (pyruvate = 9.9 +/- 1.2 minutes; pyruvate+INO = 15.6 +/- 1.0 minutes), possibly at the expense of glycogen. Supplemental glucose improved the effectiveness of INO with pyruvate to preserve ATP (pyruvate+glucose = 42 +/- 6%; pyruvate+glucose+INO = 72 +/- 6%) and further delayed rigor (pyruvate+glucose = 13.3 +/- 1.5 minutes; pyruvate+glucose+INO = 20.3 +/- 1.8 minutes). Glucose metabolism supported improved energetic and contractile states in ischemic hearts treated with INO. Thus, cardioprotection of the ischemic heart by INO was associated with preservation of functional integrity and improved energy production due to increased glycolytic activity. Activation of glycolysis in the presence of INO was accommodated by augmented alanine production without the additional accumulation of lactate. 
1	Cystic adenoma of the pigmented ciliary epithelium. Clinical, pathologic, and immunohistopathologic findings. A 51-year-old white man was found to have a deeply pigmented mass in the ciliary body and peripheral choroid of his right eye with an associated vitreous hemorrhage. Although the tumor appeared to be a ciliochoroidal melanoma, a melanocytoma and adenoma of the pigment epithelium also were considered in the differential diagnosis. The tumor was removed by a large partial lamellar sclerocyclochoroidectomy. Results of histopathologic evaluation showed a cystic adenoma of the pigmented ciliary epithelium. To the authors' knowledge, this was the first immunohistopathologic study of this tumor. Results of the study showed marked immunoreactivity for low molecular weight cytokeratins, vimentin, and S-100 protein. These immunohistochemical studies are consistent with the origin of this tumor from pigment epithelial cells. 
2	Treatment of severe colitis in Behcet's syndrome with thalidomide (CG-217). A 35-year-old male patient, known in our department since 1979 on account of a severe and complete Behcet's syndrome, was treated with thalidomide (CG-217) as a final pharmacological measure to avoid colectomy during a severe attack of Behcet colitis. Prior to the administration of thalidomide, the patient had been treated for 7 weeks with full parenteral nutrition and high doses of steroids intravenously without a satisfactory effect on the colitis. Treatment with sulphasalazin was unsuccessful because of a decreasing number of platelets on this drug. After a few days on thalidomide, 300 mg given once daily at bedtime, the patient's stools were normalized and without reaction for blood, his oral ulcers and pleural effusion disappeared, and his steroid doses could be reduced. Gradually he was put on oral nutrition again, and his rectal mucosa became normalized. The dose of thalidomide was reduced to 200 mg, and then to 100 mg daily when the patient was discharged from hospital, less than 3 weeks after institution of the drug treatment. After 5 months as an out-patient his condition is still satisfactory and without symptoms of his former disease. Thalidomide has previously been reported to be of value in treatment of Behcet's syndrome, but to my knowledge never with such a dramatic effect on a severe colitis as reported in this case. 
2	Intussusception encephalopathy: an underrecognized cause of coma in children. Intestinal intussusception is a common cause of bowel obstruction in infancy and early childhood. Typically the presenting signs and symptoms are referable to the abdomen. On occasion the most prominent presenting feature is depressed level of consciousness. We describe 3 patients who presented with coma associated with intussusception. 
3	Plasma homocyst(e)ine levels in men with premature coronary artery disease. Plasma homocyst(e)ine (that is, the sum of free and bound homocysteine and its oxidized forms, homocystine and homocysteine-cysteine mixed disulfide) levels were determined in 170 men (mean age +/- SD 50 +/- 7 years) with premature coronary artery disease diagnosed at coronary angiography and in 255 control subjects clinically free of coronary artery disease (mean age 49 +/- 6 years). Patients with coronary artery disease had a higher homocyst(e)ine level than control subjects (13.66 +/- 6.44 versus 10.93 +/- 4.92 nmol/ml, p less than 0.001). High density lipoprotein (HDL) cholesterol levels were lower (32 +/- 10 versus 46 +/- 13 mg/dl, p less than 0.001) and triglycerides levels were higher (193 +/- 103 versus 136 +/- 106 mg/dl, p less than 0.001) in the coronary disease group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels were not significantly different between patients with coronary disease and control subjects. The presence of hypertension, smoking or diabetes mellitus did not significantly alter homocyst(e)ine levels in the patient or the control group. Patients who were not taking a beta-adrenergic blocking drug (n = 70) had a nonsignificantly higher homocyst(e)ine level than did patients taking this class of drugs (n = 100) (14.67 +/- 8.92 versus 12.95 +/- 3.77 nmol/ml, p = 0.087). By design, none of the control subjects were taking a beta-blocker. No significant correlations were observed between homocyst(e)ine and age, serum cholesterol, LDL cholesterol, HDL cholesterol or triglyceride levels. It is concluded that an elevated plasma homocyst(e)ine level is an independent risk factor for the development of premature coronary atherosclerosis in men. 
1	Atrial fibrillation with cardiac tamponade as the initial manifestation of malignant pericarditis This article describes the case of a 72-year-old woman with cardiac tamponade and atrial fibrillation as the initial manifestation of a lymphoid malignancy. The pathogenesis of cardiac tamponade, various diagnostic modalities, and therapy of this condition are reviewed. 
3	Optic nerve gliomas and meningiomas. Optic nerve gliomas are benign astrocytic neoplasms that primarily affect children. The ultimate prognosis for vision is poor. For lesions confined to the optic nerves, long-term survival is excellent, but with involvement of the chiasm and especially of the hypothalamus or third ventricle, prognosis falls significantly. For this group, no form of therapy has proven to be of any benefit. Optic sheath meningiomas are neoplasms arising from arachnoid cap cells. They primarily affect middle-aged adults. Like gliomas, the prognosis for vision is poor, but unlike gliomas, prognosis for life is excellent. 
5	Munchausen syndrome by proxy documented by discrepant blood typing. The authors describe a case of Munchausen syndrome by proxy, a form of child abuse, documented by use of routine blood bank serologic procedures. While immunohematologic testing has been used in the legal arena to resolve issues of disputed paternity and to investigate instances of criminal acts, the authors believe this to be the first documented application to this clinical disorder. 
3	Limitations of electroencephalographic monitoring in the detection of cerebral ischemia accompanying carotid endarterectomy. An analysis was undertaken of 458 consecutive carotid endarterectomies performed over 6 years with the patient under general anesthesia and with electroencephalographic monitoring. Seventy patients (15%) had electroencephalographic changes suggestive of ischemia with carotid clamping and had shunts placed. Ischemic encephalographic changes occurred in 26% of patients with an occluded contralateral carotid artery, 21% of patients with a prior stroke history, and 12% of patients with no stroke history and a patent contralateral carotid artery. Nineteen strokes (4.1%), nine transient deficits (2.0%), and one death (0.2%) occurred in the 458 endarterectomies in this experience. Ten of the 19 strokes and five of nine transient deficits were immediately apparent when patients awoke from anesthesia. Five of 10 patients with immediate strokes and all five patients with immediate transient deficits had no ischemic electroencephalographic changes during the procedure. Two other patients with immediate strokes initially had ischemic electroencephalographic changes after carotid clamping that reversed with increased blood pressure or shunting. Therefore 7 of 10 patients with immediate strokes and all 5 patients with immediate transient deficits had electroencephalographs unchanged from baseline at completion of the procedure, and thus deficits not manifest by operative electroencephalographic changes developed. Our data do not support the tenet that electroencephalographic monitoring will always predict neurologic deficits accompanying carotid endarterectomy. 
1	Obstructing carcinoma of the cecum. Carcinoma of the cecum, the third most common location for malignancy of the large bowel, was examined with attention centered upon cecal cancers producing obstruction. Reviewing 136 patients revealed 11 obstructing lesions (8.1%) presenting as distal small bowel obstructions. The mean age of the patients was 74 years. All but one patient had resection for cure which consisted of a right hemicolectomy with ileotransverse colostomy. There was no operative mortality or significant morbidity. Bowel obstruction due to cecal carcinoma is an infrequent occurrence arising in elderly patients and carries a poor survival rate due to advanced disease at the time of diagnosis and treatment. 
4	Anomalous origin of the left coronary artery from the pulmonary artery. Surgical alternatives depending of the age of the patient. Four cases of anomalous origin of the left coronary artery from the pulmonary artery, three of which were operated upon in our Centre, are presented. An aortocoronary bypass with reversed autologous saphenous vein was carried out in both of the children; and in the adult, the anomalous ostium was closed from the interior of the pulmonary artery. After 84, 72, and 4 months of evolution, respectively, they were found to be asymptomatic, the mitral insufficiency had disappeared and the venous graft remained patent. In this paper, the clinical form of presentation, diagnostic possibilities and surgical treatment are analysed. 
5	Visual evoked potential monitoring of optic nerve function during surgery. A study was made with intra-operative flash--visual evoked potentials (VEP) monitored using a fibre-optic/contact lens photo stimulator in 57 patients undergoing intra-orbital surgical procedures with potential risk to the optic nerve. The VEPs recorded under enflurane and nitrous oxide anaesthesia did not differ significantly in latency or amplitude from the pre-operative recordings. Transient abolition of the VEP was seen under many circumstances and did not correlate with the outcome of surgery, but absence of a previously normal VEP for more than four minutes during surgical manipulation within the orbit did show a correlation with post operative impairment of vision. The technique provides early warning to the surgeon of threats to the integrity of the optic nerve.